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WEIGHT CONTROL AND SLIMMING INGREDIENTS IN FOOD TECHNOLOGY

Susan S. Cho

A John Wiley & Sons, Inc., Publication

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WEIGHT CONTROL AND SLIMMING INGREDIENTS IN FOOD TECHNOLOGY

Susan S. Cho

A John Wiley & Sons, Inc., Publication

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Edition first published 2010
C 2010 Blackwell Publishing Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical, and Medical business to form Wiley-Blackwell. Editorial Office 2121 State Avenue, Ames, Iowa 50014-8300, USA For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book, please see our website at www.wiley.com/wiley-blackwell. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee codes for users of the Transactional Reporting Service are ISBN-13: 978-0-8138-1323-3/2010. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Library of Congress Cataloging-in-Publication Data Weight control and slimming ingredients in food technology / [edited by] Susan Sungsoo Cho. p. ; cm. Includes bibliographical references and index. ISBN 978-0-8138-1323-3 (hardback : alk. paper) 1. Weight loss preparations. 2. Functional foods. 3. Dietary supplements. I. Cho, Sungsoo. [DNLM: 1. Overweight–prevention & control. 2. Dietary Supplements. 3. Food. 4. Overweight–diet therapy. 5. Weight Loss. WD 210 W4193 2010] RM222.2.W2968 2010 613.2 5–dc22 2009031847 A catalog record for this book is available from the U.S. Library of Congress. R Set in 11/13 pt Times by Aptara
Inc., New Delhi, India Printed in Singapore

1 2010

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Contents Contributors

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Preface

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Introduction Part I

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Lipids based ingredients

Chapter 1

Conjugated Linoleic Acid David J. Cai

Chapter 2

Appetite Suppression Effects of PinnoThinTM (Korean Pine Nut Oil) Corey E. Scott

Chapter 3

Sucrose Fatty Acid Ester (Olestra) John C. Peters

Chapter 4

The Effects of a Novel Fat Emulsion r / FabulessTM ) on Energy Intake, Satiety, (Olibra
Weight Loss, and Weight Maintenance Rick Hursel and Margriet Westerterp-Plantenga

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Part II Protein based ingredients Chapter 5

Chapter 6

The Role of Dairy Products and Dietary Calcium in Weight Management Lisa A. Spence, and Raj G. Narasimmon Gelatin—A Versatile Ingredient for Weight Control Klaus Flechsenhar and Eberhard Dick

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Chapter 7

Chapter 8

Chapter 9

Contents

α-Lactalbumin in the Regulation of Appetite and Food Intake Arie G. Nieuwenhuizen, Ananda Hochstenbach-Waelen, and Margriet Westerterp-Plantenga The Effects of Casein-, Whey-, and Soy Protein on Satiety, Energy Expenditure, and Body Composition Margriet Veldhorst, Anneke van Vught, and Margriet Westerterp-Plantenga Soy Peptides and Weight Management Cristina Mart´ınez-Villaluenga and Elvira Gonz´alez de Mej´ıa

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Part III Functional components Chapter 10

Chapter 11

Chapter 12

The Effects of Caffeine and Green Tea on Energy Expenditure, Fat Oxidation, Weight Loss, and Weight Maintenance Rick Hursel and Margriet Westerterp-Plantenga Mechanisms of (−)-Epigallocatechin-3-Gallate for Antiobesity Hyun-Seuk Moon, Mohammed Akbar, Cheol-Heui Yun, and Chong-Su Cho Capsaicin Astrid J.P.G. Smeets and Margriet Westerterp-Plantenga

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201

Part IV Fiber based ingredients Chapter 13

r , Resistant Dextrin, in Satiety Control NUTRIOSE
Susan S. Cho and Iris L. Case

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Chapter 14

Fiber and Satiety Susan S. Cho, Iris L. Case, and Stephanie Nishi

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Appendix

Global Suppliers of Ingredients for Weight Control

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Index

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Contributors Mohammed Akbar, PhD (11) Laboratory of Molecular Signaling National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda, MD USA David J. Cai, PhD (1) Cognis Corp. Nutrition and Health LaGrange, IL USA Iris L. Case, BS (13, 14) NutraSource Clarksville, MD USA

Eberhard Dick (6) Food Application, GELITA AG Uferstraße, Eberbach Germany Klaus Flechsenhar, MD (6) Senior Manager Medical Affairs Research and Development GELITA AG Uferstraße, Eberbach Germany Elvira Gonz´alez de Mej´ı a, PhD (9) Department of Food Science and Human Nutrition University of Illinois Urbana, IL USA

Chong-Su Cho, PhD (11) Research Institute for Agriculture and Life Sciences, and School of Ananda Hochstenbach-Waelen, Agricultural Biotechnology PhD student (7) Seoul National University, Seoul Department of Human Biology South Korea Nutrition and Toxicology Research Institute Susan S. Cho, PhD (13, 14) Maastricht (NUTRIM) NutraSource Maastricht University, Maastricht Clarksville, MD The Netherlands USA vii

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Rick Hursel, MSc (4, 10) Dept. of Human Biology Maastricht University 6200 MD Maastricht The Netherlands Cristina Mart´ınez-Villaluenga, PhD (9) Department of Food Science and Human Nutrition University of Illinois Urbana, IL 61801, USA Hyun-Seuk Moon, PhD (11) Laboratory of Molecular Signaling National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda, MD USA Raj G. Narasimmon, PhD (5) Vice President, Product Research Dairy Management Inc. Rosemont, IL USA Arie G. Nieuwenhuizen, PhD (7) Department of Human Biology Nutrition and Toxicology Research Institute Maastricht (NUTRIM) Maastricht University, Maastricht The Netherlands Stephanie Nishi, BS (14) University of Toronto Toronto, Canada

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John C. Peters, PhD (3) P&G Nutrition Science Institute The Procter & Gamble Company Cincinnati, OH USA Dr. Corey E. Scott, PhD (2) Nutrition Manager Lipid Nutrition, B.V. Astrid J.P.G. Smeets, PhD (12) Maastricht University Medical Center Maastricht The Netherlands Lisa A. Spence, PhD, RD (5) American Dietetic Association Chicago, IL, USA Anneke van Vught, MSc (8) Nutrition and Toxicology Research Institute Maastricht (NUTRIM) Maastricht University Medical Centre Maastricht, The Netherlands. Margriet Veldhorst, MSc (8) Maastricht University Medical Centre Maastricht, The Netherlands.

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Prof. Dr. Margriet Westerterp-Plantenga, PhD (4, 7, 8, 10, 12) Department of Human Biology Nutrition and Toxicology Research Institute Maastricht (NUTRIM) Maastricht University, Maastricht The Netherlands

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Cheol-Heui Yun, PhD (11) Research Institute for Agriculture and Life Sciences, and School of Agricultural Biotechnology Seoul National University, Seoul South Korea

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Preface The incidence of obesity is rising at alarming rates throughout the world. In the United States, it has become a public health epidemic. Some estimates indicate that 1.1 billion individuals are overweight worldwide (WHO, 2009). Food manufacturers are responding to this epidemic by developing low-calorie, low-fat foods and incorporating into these foods ingredients that actively promote body weight reduction and control. The identification of ingredients that promote weight management should be actively pursued and done so, based on credible science. Numerous ingredients are available with varying levels of scientific evidence supporting a weight management potential. These ingredients range from wellresearched ones, such as novel fat emulsion, sucrose polyester, alginate, guar gum, resistant starches, green tea polyphenols, protein from dairy sources, and conjugated linolenic acid, to ingredients, such as Hoodia gordonii and capsaicin, that have only limited available data to support their possible role in weight management. In this book, each chapter presents data on efficacy, mechanism of action, and safety of the various ingredients. Current and potential food applications for these ingredients are provided as well. This book offers the most up-to-date information and research findings for each ingredient. Information on the global sources of these new and innovative materials is also included. This book will be useful to those in food manufacturing responsible for product development, as well as to nutritionists and other health professionals who have an interest and responsibilities in the weight management of their clients.

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Introduction Currently, over 60% of the U.S. population are overweight or obese (CDC, 2009). The condition is widespread across all states and demographic groups in the United States. Children are not immune from this disturbing trend. Obesity prevalence among 4-year-old U.S. children (mean age 52.3 months) was 18.4% in 2005 (Anderson and Whitaker, 2009). The prevalence of overweight and obesity has steadily increased among some sex and age groups of preschool children since 1971–1974. More than 10% of 4- and 5-year-old girls were overweight in 1988 through 1994 compared with 5.8% in 1971 through 1974 (Ogden et al., 1997). Other countries, both developed and underdeveloped, are also observing this trend. In the United Kingdom, the percentage of overweight adults is 51%, in Russia 54%, in Germany 50%, in Brazil 36%, and in China 15% (WHO, 2009). Weight gain and obesity are risk factors for type 2 diabetes, gallbladder disease, hypertension, coronary heart disease, osteoarthritis, and certain cancers (Nguyen et al., 2008). Analysis of NHANES 1999–2004 revealed that increasing body mass index is associated with an increase in the prevalence of hypertension (18.1% for normal weight to 52.3% for obesity class 3), diabetes (2.4% for normal weight to 14.2% for obesity class 3), dyslipidemia (8.9% for normal weight to 19.0% for obesity class 3), and metabolic syndrome (13.6% for normal weight to 39.2% for obesity class 3). With normal-weight individuals as a reference, individuals with obesity class 3 had an adjusted odds ratio of 4.8 (95% CI 3.8–5.9) for hypertension, 5.1 (95% CI 3.7–7.0) for diabetes, 2.2 (95% CI 1.7–2.4) for dyslipidemia, and 2.0 (95% CI 1.4–2.8) for metabolic syndrome (Nguyen et al., 2008). These findings have important public health implications for the prevention of obesity. Major causes for increased overweight and obesity prevalence are increased calorie intakes and sedentary lifestyles. In the past two decades, caloric intake has risen significantly and physical activity has dramatically xiii

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declined. Fiber intake is low, but the consumption of energy-dense foods, snacks, and drinks has increased. Researchers reported that energy density of foods was associated with diet quality and body weight (Kant et al., 2008). Food manufacturers are responding to this epidemic by developing the foods which may help consumers better manage their satiety and body weight. The identification of ingredients that promote weight management should be actively pursued. Numerous ingredients have been claimed for their efficacy for satiety and/or weight management. In this book, each chapter offers comprehensive thoughts on various ingredients. This book reviews the most relevant satiety clinical studies on various ingredients including conjugated linoleic acid high-amylose corn starches (HACS), sucrose polyester, novel fat emulsions, and Korean pine nut oil. Although these ingredients have been shown to impact satiety, careful consideration has to be given to the exact clinical protocol, dosing regime, and specific delivery form. Even within each class of macronutrients, variable degrees of efficacy and potency were noted. In addition to macronutrients, this book covers other functional ingredients such as green tea, coffee, and capsaicin. We would like to thank all researchers in nutrition and weight management who made this book possible. Susan Cho

References Anderson SE, Whitaker RC. Prevalence of obesity among US preschool children in different racial and ethnic groups. Arch Pediatr Adolesc Med 2009;163:344–348. CDC. Available online at http://www.cdc.gov/datastatistics. 2009. Kant AK, Andon MB, Angelopoulos TJ, Rippe JM. Association of breakfast energy density with diet quality and body mass index in American adults: National Health and Nutrition Examination Surveys, 1999– 2004. Am J Clin Nutr 2008;88:1396–1404. Nguyen NT, Magno CP, Lane KT, Hinojosa MW, Lane JS. Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with obesity: findings from the National Health and Nutrition Examination Survey, 1999 to 2004. J Am Coll Surg 2008;207:928–934.

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Introduction

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Ogden CL, Troiano RP, Briefel RR, Kuczmarski RJ, Flegal KM, Johnson CL. Prevalence of overweight among preschool children in the United States, 1971 through 1994. Pediatrics 1997;99:E1. WHO. Available online at http://www.who.int/en. 2009.

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PART I

Lipid based ingredients

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CHAPTER 1

Conjugated Linoleic Acid David J. Cai, PhD

Abstract As consumers are becoming more educated about the importance of improving body composition not just weight loss, that is, preserving and increasing lean muscle mass while reducing body fat at the same time, public interest for functional ingredients, such as conjugated linoleic acids (CLAs), that can deliver such benefits is also growing. Research findings indicate that CLA may be useful in improving human health in controlling body fat gain and enhancing lean body mass. Functional foods that are developed with such ingredients could encourage healthier consumer attitudes toward body image and weight loss. The chapter reviews current research on mechanism, safety and effectiveness, regulatory details, and product development issues of CLA. These details provide food developers, marketers, academic researchers, and health professionals an overview of CLA and its application in functional foods.

Introduction The current focus of the weight management category has steered away from typical stimulants-based concepts, which have been the basis for the products of the past. New trends include insulin management, appetite control, and optimal body composition (reduce body fat reduction and increase lean muscle mass). Consumers are becoming more educated about overall body composition, not just weight loss; they are learning about the importance of preserving and increasing lean muscle mass while reducing body fat at the same time. Preventing fat regain is another area of focus 3

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H3C

c 9,t 11 O OH

H3C

t10,c12 O

Figure 1.1. Chemical structure of the two primary CLA isomers of Tonalin TG 80 (provided by Cognis GmbH).

especially for yo-yo dieters. Functional foods that are developed to target fat and retain lean body mass could encourage healthier attitudes toward body image and weight loss. A recently published meta-analysis study along with other studies put conjugated linoleic acid (CLA) to the spotlight as the candidate for a healthier weight management aid. In the meta-analysis, the authors concluded that CLA could enhance overall health by effectively reducing body fat, maintaining or increasing lean muscle mass, and potentially preventing weight and fat regain commonly experienced by adults, especially yo-yo dieters (Whigham et al., 2007). Although this effect is modest, it could be important if accumulated over time, especially in an environment where continuous weight gain is the norm in the adult population. The following paragraphs provide an overview of CLA and its application in functional foods.

Background CLA is found primarily in dairy products and ruminant meat as a result of bacterial biohydrogenation of linoleic acid in the rumen. CLA is a collective term for many modified forms of linoleic acid that are resulted from double bonds occurring in different locations along the fat molecules. The cis-9,trans-11-CLA (c9,t11-CLA) and trans-10,cis-12-CLA (t10,c12CLA) are the two most bioactive isomers (see Fig.1.1) (Pariza et al., 2001) whereas the cis-9,trans-11 isomer is also the predominant form in whole fat dairy products and ruminant meat accounting for more than 90% of CLA intake in the diet (Bhattacharya et al., 2006). The estimated human intake of CLA from the U.S. diet is approximately 200 mg/day (Ritzenthaler et al., 2001).

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In addition to the bacterial biodehydrogenation in ruminant animals, CLA can also be produced commercially from safflower oil, such as the r
Tonalin CLA manufactured by Cognis GmbH (Monheim, Germany). The high-quality CLA consists of approximately equal amounts of the c9,t11 (40%) and t10,c12 isomers (40%) with less than 2% of other isomers. It is produced by chemical isomerization of safflower linoleic acid under alkaline conditions. CLA appears to have effects on the function of body based on its two most bioactive isomers. The c9,t11- and t10,c12-CLA isomers either act alone or in concert to produce their effects. In vitro and animal studies indicated that the t10,c12 isomer is solely responsible for the reduction of body fat gain while c9,t11-CLA enhances growth and feed efficiency in young rodents (reviewed in Ritzenthaler et al., 2001). In other cases, the isomers act together to induce an effect (Ip et al., 2002). This may be due to the fact that the mixed isomers seem to involve additive biochemical pathways or multiple interactions with numerous metabolic signaling pathways, which results in the superiority of the isomer blend (Ritzenthaler et al., 2001).

Absorption and Metabolism The general metabolic fate of CLA is considered to be similar to that of linoleic acid (Banni, 2002). Like most fatty acids, CLA is well absorbed across the gastrointestinal mucosa. It is also widely distributed throughout the body, metabolized via oxidation and desaturation and extensively excreted from the body in expired air, and lesser amounts in urine and feces (S´eb´edio et al., 2003). Both isomers may also be oxidized in the β-oxidation pathway.

Mechanism for Decreasing Body Fat Mass The exact mechanism through which CLA is able to decrease body fat mass is yet not clear. However, it does appear that CLA has two main sites of action: the adipocytes that are the principal site of fat storage, and the skeletal muscle cells that are the principal site of fat burning (reviewed in Ritzenthaler et al., 2001 and Pariza et al., 2001). Studies have shown that CLA inhibits the activity of lipoprotein lipase (LPL) and stearoyl-CoA desaturase, and stimulates the breakdown of stored fat in the adipocytes (lipolysis) (Choi et al., 2000; Gavino et al., 2000; Park et al., 1997). LPL is the enzyme that transfers dietary fat after a meal into

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Lipid based ingredients

the adipocytes for storage. By inhibiting the LPL activities, CLA could reduce lipid uptake into adipocytes (Park et al., 1997, 1999). The t10,c12CLA isomer may also affect the number of newly formed adipocytes by reducing preadipocyte differentiation (Brown et al., 2003; Kang et al., 2003), or existing number of adipocytes by increasing adipocyte apoptosis or programmed cell death (Evans et al., 2000; Fischer-Posovszky et al., 2007; Hargrave et al., 2002; LaRosa et al., 2006; Tsuboyama-Kasaoka et al., 2000). Other evidence demonstrated that carnitine palmitoyltransferase (CPT) activity is increased with CLA. The increased CPT activity in skeletal muscle cells enhances the rate of fatty acid transport into the mitochondria and results in an increased β-oxidation (Park et al., 1997). This may explain the enhancement of oxygen consumption and energy expenditure reported in CLA-fed OLETF rats (Nagao et al., 2003) and more recent in human studies (Close et al., 2007). In summary, it is likely that CLA decreases body fat mass through four possible actions: 1. Decreasing the amount of fat that is stored after eating (decreases LPL). 2. Increasing the rate of fat breakdown in fat cells (lipolysis) and the rate of fat burning in the mitochondria (CPT and ß-oxidation). 3. Reducing proliferation and differentiation of preadipocytes to mature adipocytes. 4. Decreasing the total number of fat cells (apoptosis). The mechanisms are supported mostly by data from animal studies and in vitro studies using cultured mouse adiposities, human adipocytes, and modified markers of differentiation as well as cultured human preadipocytes (reviewed in Ritzenthaler et al., 2001). CLA may also decrease muscle protein breakdown, reduce the release of proinflammatory cytokines, and improve insulin-stimulated glucose transport (energy supply) into muscle that results in maintained or even increased muscle mass (Henriksen et al., 2003).

Body Fat Reduction by CLA Introduction CLA had been shown to reduce body fat and increase lean body mass in several species of animals, including chicken, mice, rats, and pigs (Ritzenthaler et al., 2001). In addition to extensive animal data, over 30

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clinical studies investigating doses from 0.7 to 6.8 g/day of the 50:50 mixture in over 1,700 human subjects for periods of 12 weeks to 2 years have been published. Many clinical studies have shown that CLA improves body composition with or without combination with exercise and in lean, overweight, and even obese subjects. For example, a long-term study demonstrated a 9% decrease in body fat in overweight subjects following 1-year supplementation with CLA without additional exercise (Gaullier et al., 2004, 2005). A recent study demonstrated its effect in overweight subjects during holiday period (Watras et al., 2006). Another recent study further demonstrated that the body fat reduction mainly occurs in waist and leg area suggesting a body-shaping benefit (Gaullier et al., 2007) and is effective for both men and women subjects. Although a few studies used up to 6.8 g of CLA mixture/day (Kreider et al., 2002; Steck et al., 2007), the most common dosage is about 3.2 g of active CLA-mixed isomers per day either as free fatty acids or as triglycerides. While several studies showed significant reductions in body fat and/or other parameters of body composition, there are others that did not find such benefits. To fully understand why there is inconsistency in CLA study outcomes, it is critical to take into consideration the key factors to the quality and outcome of CLA studies: 1. Quality of testing material 2. Suitable methods for measuring body composition 3. Study design includes random, double-blind design with adequate number of subjects. Other design factors include suitable dosage and study duration.

Quality of Testing Material The quality of material is critical to clinical study outcomes. A CLA material containing high amount of less bioactive CLA isomers would certainly hamper the body fat reduction effect of the c9,t11- and t10,c12-CLA isomers (Gaullier et al., 2002). High-quality CLA-mixed isomers are usually manufactured under patented technology and process. In the case of r
Tonalin CLA, manufactured by Cognis GmbH, the raw material used is food grade safflower oil rich in linoleic acid (C18:2 c9,c12) and containing very few other polyunsaturated fatty acids. The high linoleic acid then goes through isomerization to form CLA under a nitrogen atmosphere in order to limit oxidation. By carefully optimizing the reaction conditions, only the

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Technical-grade CLA c 9,t 11 CLA c9,t 11 CLA

65

t 10,c12 CLA

t 10,c12 CLA

70

min

65

70

min

Figure 1.2. Comparison of GC–MS profile of unpatented and patented CLA products (provided by Cognis GmbH).

c9,t11- and t10,c12-CLA isomers are formed in a 1:1 ratio. Conventional deodorization and/or bleaching stages in accordance with cGMP are performed to further improve the quality of the final CLA product. The finished product contains >80% of c9,t11- and t10,c12-CLA isomers with <2% of other isomers. The Tonalin CLA is produced according to FDA GMP regulations and the production of GRAS substances. A CLA product manufactured using nonpatented process and under less-controlled condition would contain less c9,t11- and t10,c12-CLA isomers, but more other CLA isomers that may not be bioactive (Fig.1.2).

Body Composition and Body Weight The effect of CLA is mainly on reducing body fat and improving body composition that may not necessarily be accompanied by weight loss. An optimal body composition is more critical to long-term health than just weight loss. In fact, obesity is more a definition of having excessive body fat rather than having excessive body weight. Although body weight is an important health risk indicator, the amount of body fat, especially the abdominal fat, is more directly related to diseases. This is because lipids released from visceral fat could enter the portal vein and circulate to the

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liver resulting in higher total cholesterol and LDL cholesterol. Maintaining a healthy body fat percentage, 14–20% for men and 17–24% for women, can reduce risk and help prevent the onset of these conditions. Because body weight does not reflect percentage of body fat mass and lean mass, a muscular, lean person could have body mass index (BMI) over 30 (a criterion for being obese) even though he has high amount of muscle mass and low amount of body fat. Therefore, body composition is a much better indicator of overall health and fitness than body weight alone.

Comparing Methods for Measuring Body Fat Body composition can be measured by several methods from simple often less accurate to more accurate but often more costly and complicated. The simple, less expensive, but less accurate methods include: 1. Calipers (anthropometry–skinfold measurements): The method is based on the assumption that the subcutaneous fat reflects a constant proportion of the total body fat. 2. Near-infrared interactance (NIR): This method is based on studies that show optical densities are linearly related to subcutaneous and total body fat. 3. Bioelectrical impedance (BIA): This method measures electrical signals as they pass through the fat, lean mass, and water in the body. The more expensive and more accurate methods include: 1. Hydrodensitometry weighing (underwater weighing): This method measures whole-body density by determining body volume. Body fat percentage is calculated from body density using standard equations (either Siri or Brozek). 2. Dual energy X-ray absorptiometry (DEXA): A very accurate method, DEXA is based on a three-compartment model that divides the body into total body mineral, fat-free soft (lean) mass, and fat tissue mass. It measures the amount of photon energy absorbed by the bone, lean mass, and fat mass. 3. Total body electrical conductivity (TOBEC): This method is based on lean tissue being a better conductor of electricity than fat. 4. Air displacement pletismography (Bod Pod): This method is based on the same principle as underwater weighing, but it measures how much air is displaced instead of water.

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5. Four-compartment model: This is so far the most accurate body composition method. It incorporates measurements from DXA, underwater weighing, and 18 O stable isotope into Selinger’s four-compartment equation to calculate the criterion for body fat mass (Watras et al., 2006). The methods to measure body composition could affect the CLA study outcome significantly. For example, in comparison to DXA, BIA is known (Newton et al., 2006) to underestimate body fat in obese subjects while showing a systematic overestimate of fat-free mass. In Berven et al. (2000), the Norwegian research group investigated the effect of 3-month supplementation with 3.4 g CLA/day in 60 overweight and obese subjects, but did not find significant differences between treatments, but only a trend (0.9 kg reduction of body fat). The body composition was measured using BIA. Two other studies using BIA methods investigated 3 g CLA supplementation in lean and overweight/obese subjects over 8 weeks and 12 months, respectively, also failed to detect any differences in body fat reduction (Noone et al., 2002; Whigham et al., 2004). Interestingly, when the same Norwegian group (Blankson et al., 2000) used DXA in a similar designed study, they were able to detect a significant body fat reduction by CLA supplementation. The superiority of the DXA method is further supported by later findings of the Norwegian group (Gaullier et al., 2004, 2005) in which after 12 months of supplementation with 3.4 g CLA/day, subjects experienced a significant reduction of body fat mass of 2.4 kg (−9%) whereas subjects receiving the placebo did not show these changes. Because methods involving DXA have been accepted as one of the most accurate methods to detect body fat reduction, the following review of CLA clinical studies focuses on studies conducted with DXA or equally accurate methods.

Review of Clinical Studies of CLA on Body Composition Long-Term Studies The longest study duration reported was a 24-month study in which a 12-month multicenter, double-blind, randomized, and placebo-controlled

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study was followed by a 12-month open-label follow-up study. In the first study, 180 overweight (BMI 25–30) volunteers received 3.4 g CLA/day either as free fatty acid (Tonalin 80 FF, 4.5 g oil) or as triglycerides (Tonalin 80 TG, 4.5 g oil), or 4.5 g olive oil as the control group. Mean body fat mass in the CLA groups regardless of the forms was >8%, lower than that in the placebo group. This loss of body fat coincided with a slight increase of lean body mass (0.6 kg) and a reduction of body weight (−1.6 kg) whereas subjects receiving the placebo did not show these changes (Gaullier et al., 2004). In the follow-up study, 125 overweight (BMI 25–30) volunteers from both CLA group and the initial placebo group received 3.4 g CLA/day (given as Tonalin 80 TG). Subjects who lost body fat mass in year 1 did not lose further body fat, but were able to prevent fat regain. Subjects from the initial placebo group lost body fat mass significantly in the second year after they were given CLA supplement (Gaullier et al., 2005). The authors concluded that long-term supplementation with CLA reduced body fat mass (BFM) in healthy overweight adults and helped prevent fat regain. A recent long-term study was conducted in 120 subjects who were put on energy restriction diet over a period of 8 weeks and investigated if CLA supplementation (3.4 g/day) for 1 year would prevent body weight and body fat regain. Although the differences on body fat regain did not reach statistical significance, the authors found that CLA group regained less body fat (2.1 kg with CLA vs. 2.7 kg with placebo) and more lean body mass (Larsen et al., 2006). A recent randomized, double-blind CLA study using the fourcompartment model method found that giving 40 healthy, overweight subjects 3.2 g CLA/day or placebo (safflower oil) for 6 months, the CLA supplementation significantly reduced body fat (−1.0 kg; p < 0.05) and weight gain during a period that included the holiday season (November to January). The placebo group, however, gained weight and body fat during the same period (Watras et al., 2006). In a follow-up study, the research group discovered that fat oxidation was increased significantly during sleep (15%) compared to baseline in the CLA group, while it was decreased in the placebo group (−22%) (Close et al., 2007). Furthermore, the total energy expenditure during sleep was also increased in the CLA group. The results may explain partially the body fat reduction effect of CLA in the holiday study. The four-compartment model method is a combination of a few existing accurate methods, thus, making it the most accurate method so far to measure body composition. This method is able to detect even subtle change in body composition.

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In Exercise Subjects with BMI < 25 CLA not only has effect on body fat reduction in overweight or obese subjects, the same effect was demonstrated in lean subjects as well. An earlier study investigated the effect of CLA supplementation (1.8 g/day) upon body fat in healthy, lean humans over 12 weeks (Thom et al., 2001). In this placebo-controlled double-blind study, all 20 subjects (age 18–39 years) performed a standardized physical exercise for 90 minutes, three times per week. While the placebo group experienced no changes in body composition, the CLA-treated group reduced BFM from 22% to 17.5%. The number of subjects, however, was relatively small. Another study evaluated whether CLA supplementation during resistance training affects body composition, strength, and/or general markers of catabolism and immunity (Kreider et al., 2002). In a double-blind and randomized study, 23 experienced, resistance-trained subjects were matched according to body mass and training volume and randomly assigned to supplement their diet with 6 g CLA/day versus placebo for 4 weeks. Although some statistical trends were observed with moderate to large effect sizes, CLA supplementation did not significantly affect (p > 0.05) changes in total body composition parameters, or general markers of catabolism and immunity during training. Unfortunately, the study duration was too short and the number of subjects was too small to observe any significant effects. In a recent longer duration study, 76 subjects were randomized to receive 5 g CLA/day or placebo for 7 weeks while performing resistance training three times per week. The CLA group had greater increases in lean tissue mass and greater losses of fat mass by maintaining the resting metabolic rate (RMR) while RMR decreased in the placebo group. Additionally, supplementation with CLA lessened the catabolic effects of training (measured as myofibrillar protein degradation, 3-MH). This finding suggests that CLA might be most effective if combined with physical exercise (Pinkoski et al., 2006). In Subjects with BMI > 25 Kamphuis et al. (2003aa, 2003bb) tested the hypothesis that CLA might reduce the regain of body fat and body weight in overweight adults who had undergone weight loss. All subjects received a very low calorie diet for 3 weeks followed by a 13-week intervention period during which they ate ad libitum but were given CLA (1.8 or 3.6 g) or placebo each day. The subjects consuming CLA (either dose level) significantly gained

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lean mass, but not fat mass comparing to the controls, and a significantly enhanced RMR. Interestingly, measures of appetite, feelings of fullness and satiety were also increased while feelings of hunger were decreased by CLA ingestion. In another clinical study (Blankson et al., 2000) with overweight and obese subjects, BFM was reduced by 5.7% after 3 months of supplementation with CLA (3.4 g/day). The reduction in BFM was accompanied by a proportional increase in lean body mass and an improved overall feeling of well-being. Higher dosages of CLA were tested, but did not result in greater effects upon body composition. In a recent study, 48 healthy obese subjects of both genders were randomized to receive placebo, 3.2 g CLA/day, or 6.4 g CLA/day for 12 weeks. Subjects were instructed to maintain their current diet and exercise routines throughout the study period. Although no significant difference on body fat was found between two groups, lean body mass was increased significantly by 0.64 kg in the 6.4 g of CLA group/day (p < 0.05) after 12 weeks of intervention (Steck et al., 2007).

Body Shaping and CLA A new study recently demonstrated that CLA may have body-shaping effect by losing fat in certain areas of body. In a randomized, doubleblind, placebo-controlled study (Gaullier et al., 2007), 83 overweight and obese subjects (BMI 28–32 kg/m2 ) took 3.4 g of a 50:50 CLA mixture or placebo (olive oil) per day for 6 months; CLA significantly decreased BFM at month 3 (−0.9%, p < 0.05) and at month 6 (−3.4%, p < 0.05) compared to placebo. The reduction in fat mass was mostly in the legs (−0.8 kg, p < 0.001), and in women (−1.3 kg, p ≤ 0.05) with BMI over 30 (−1.9 kg, p < 0.05), compared to placebo. Waist/hip ratio was also decreased significantly (p < 0.05) compared to placebo. Lean body mass was increased (+0.5 kg, p < 0.05) within the CLA group. All changes were independent of diet and/or physical exercise.

CLA Efficacy in Foods The body fat reduction benefits of CLA began to draw mainstream food manufacturers to launch functional foods in an attempt to solve the widespread obesity problem. Since 2004, there are a few CLA-enriched functional foods that have been launched in Europe. One of the most successful examples is from a Spanish firm Asturiana. Asturiana has launched

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a series of CLA-fortified dairy and fruit products in Spain since 2004 and has accomplished over 47 million Euros annual sales since then. It is important to study the efficacy of CLA in food matrix because of any potential synergy or interaction between CLA and food components. A recent study confirmed that CLA in foods is as effective as it is in supplement forms (Laso et al., 2007). Sixty healthy subjects of both genders (BMI 25–35 kg/m2 ) were randomized to receive a placebo or 500 mL milk supplemented with 3 g CLA for 12 weeks. Total fat mass was decreased significantly among subjects with a BMI ≤ 30 kg/m2 in the CLA-fortified milk group (∼2%, p = 0.01) while no changes were detected in the placebo group. Trunk fat mass showed a trend toward reduction (∼3%, p = 0.05). The authors concluded that supplementation of milk with 3 g CLA over 12 weeks results in a significant reduction of fat mass in overweight but not in obese subjects. In a smaller study, 31 overweight subjects were given CLA-fortified milk (with or without 3 g CLA, respectively) in combination with programmed physical activity (60 minutes each time, four times a week) for a total duration of 4 months (Nazare et al., 2007). The group receiving 3 g CLA/day decreased BMI (p < 0.0001), and subcutaneous fat mass measured by anthropometry (p < 0.002) and the total fat mass measured by air displacement pletismography (Bod Pod) (p < 0.0001) in comparison to the placebo group (the physical activity level was identical). Another recent study using CLA-fortified yogurt, however, failed to find a significant body fat reduction effect in 44 healthy subjects even though the basal energy expenditure increased significantly in the CLA group (+5 kJ/kg fat-free mass/day on day 98 vs. day 0, p = 0.03) suggesting a potential fat burning effect of CLA (Villegas et al., 2007). The subjects were randomly assigned to consume daily either a 50:50 CLA-mixed isomer (3.76 g/day) supplemented yogurt or a placebo yogurt for 98 days. Meta-Analysis and Summary Despite some inconsistent results on body fat reduction, the totality of the evidence suggests a moderate body fat reduction by CLA mixture confirmed by a recent meta-analysis study (Whigham et al., 2007). The meta-analysis study collected and analyzed 18 eligible CLA studies that were longitudinal randomized, double-blind, placebo-controlled human clinical trials using validated body composition measurements. The researchers concluded that among participants given 3.2 g/day, CLA produces a significant but modest reduction of fat mass of 0.2 pounds a week or 0.8 pounds a month compared to participants in the placebo group.

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Although this effect is modest, it could be important if accumulated over time, gradual weight gain is the norm in the adult population. In summary, when the high-quality CLA-mixed isomers were used in proper designed studies with adequate number of subjects, there was an indication of significant BFM reduction relative to placebo controls regardless of delivery vehicle. This effect was observed in both short-term and long-term studies and in various subject populations. More importantly, the fat reduction seems to occur in waist and leg areas where the accumulation of fat is the most detrimental to health. Although further evidence is needed, the potential of this benefit by CLA on long-term health is too important to be ignored. Furthermore, CLA may be most effective in reducing fat mass and increasing lean mass when combined with enhanced physical activity. CLA intake was not always associated with significant reductions in body weight, which is consistent with data from animal studies.

Safety Evaluation of CLA-Mixed Isomers A large number of published studies—including traditional toxicology studies and extensive human trials—have assessed the safety of CLA (50:50 mixture). CLA is the subject of 32 clinical studies in which the 50:50 mixture of isomers was evaluated. A comprehensive review of the clinical data has demonstrated that consumption of 50:50 CLA isomers at levels up to 6 g/day for up to 1 year (Larsen et al., 2006; Whigham et al., 2004) and 3.4 g/day for up to 2 years (Gaullier et al., 2004, 2005, 2007) is safe and has no significant effects on cardiovascular parameters (lipid metabolism, markers of inflammation, and markers of oxidative stress), insulin sensitivity and glucose, and milk fat deposition (Cognis GmbH, 2007). Although most consumers for CLA products are expected to be adults, the safety evaluation has considered potential use among children and did not find any potential adverse effects among children at the recommended use level. Pre-clinical data have demonstrated an absence of significant toxicological, mutagenic, or reproductive and developmental effects. Subchronic and chronic studies in rats demonstrate that CLA at 2,433 and 2,728 mg/kg body weight/day for males and females, respectively, for periods of 13 weeks to 18 months, produce no significant adverse effects. Reproductive and developmental toxicity studies in rats and pigs demonstrate a lack of adverse effects on maternal food consumption and body weight, litter size, or offspring growth and development following exposure to CLA

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(0.25–2% in the diet, equivalent to 250–500 mg/kg body weight/day) throughout gestation, lactation, and/or during the postweaning period. In vitro assays demonstrate an absence of mutagenicity or genotoxicity (reviewed in Ritzenthaler et al., 2001, Cognis GmbH, 2007, and Campbell and Kreider, 2008). Based on the clinical data, toxicological data, and the history of dietary consumption of CLA, an expert panel concluded in 2007 that estimated consumption of 50:50 CLA isomers is safe within the meaning of the FDA regulations for use as a food ingredient at levels of up to 1.5 g CLA per serving, with expected use of approximately 2 servings per day (Cognis GmbH, 2007). FDA agreed with the expert panel’s conclusion in July 2008 and issued no-question letter to the petitioners, one of which is Cognis GmbH (FDA, 2008); thus, Cognis’ CLA-mixed isomers achieved the so-called FDA-notified GRAS status.

Regulatory Status Labeling Commercial CLA can be labeled as CLA or conjugated linoleic acid. CLA is not considered as trans fat according to FDA rulings (68 Fed. Reg. 41433, 41462, 2003). Because commercial high-quality CLA oil, such as the Tonalin CLA TG80, is derived from highly refined natural safflower oil, it is also exempt from allergen labeling requirement. CLA is fatty acid; thus, the calorie calculation for nutrition labeling is based on its fat content. In the case of Cognis’ Tonalin CLA, the TG 80 (100% fatty acids) = 9 kcal/g, 60 WDP (80% fatty acids) = 7 kcal/g, 35 WDP (67% fatty acids) = 6 kcal/g.

Claims The claims on CLA’s effect on body composition were documented by several patents and licensed to a couple of CLA manufacturers, such as Cognis GmbH, the manufacturer of Tonalin CLA. The following structure function claims can be used for either foods or dietary supplements: Clinical and laboratory research indicates that Tonalin CLA r helps reduce body fat, r maintains lean body mass,

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r improves body composition, r increases lean body mass, r enhances lean body mass.

Application of CLA in Functional Foods Cognis’ CLA is FDA GRAS. It is intended for use in specific foods within the following general food categories: beverages and beverage bases, grain and pasta products, milk and milk products, and processed fruits and fruit juices. Specifically, these food applications are as follows: r r r r r r r r

Coffee creamers (only for Cognis’ Tonalin CLA) Chocolate (only for Cognis’ Tonalin CLA) Milk-based and fruit-based beverages Soy milk beverages Meal-replacement beverages and bars Milk and flavored milk products Yogurt products Fruit juice products

The level to be added into foods is at a level of up to 1.5 g CLA per labeled serving and up to 2 servings a day as a total recommended daily intake of 3 g CLA/day.

CLA Forms There are a variety of CLA forms available from major suppliers for nearly any type of food applications. For instance, Cognis offers the r
Tonalin range of CLA products in multiple concentrations and forms to meet a wide range of formulation requirements, such as 80% triglyceride or free fatty acids oil, 60% encapsulated water dispersible powder, and 35% acid-stable water dispersible powder. Additionally, a customized wet emulsion form is available for beverage applications. Table 1.1 lists the product forms available at Cognis GmbH. When CLA oil used, it can replace existing fat or oil in food formula. If developers need to blend the CLA with other dry ingredients, a powder form is more appropriate. When CLA powder is used, food manufacturers must list in the ingredient statement any carriers contained in powders (i.e., gum arabic, maltodextrin).

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Table 1.1.

The different forms of CLA producta

CLA Product Forms r


Tonalin TG 80

r


Tonalin 35 WDP

r


Tonalin 40 WDP

r


Tonalin 60 WDP

a Provided

Description

Food Applications

78–84% as CLA triglyceride, transparent, colorless to slightly yellow liquid at room temperature with characteristic taste/odor 32–38% CLA cold water dispersible powder, fine, free flowing, cold water dispersible white powder with characteristic taste/odor, gum acacia as carrier 37–42% CLA water dispersible powder, fine, free flowing, cold water dispersible white to off-white powder with characteristic taste/odor, modified food starch derived from waxy maize as carrier 53–62% CLA water dispersible powder, fine, free flowing, cold water dispersible, white to off-white powder with characteristic taste/odor, milk powder as carrier

Oil-based food products, spreads, dairy, dressings

Cloudy beverages, baked goods, dairy, cereals, bars

Dry powder mixes, powdered drink mixes, formulas as chewable tablet and two piece capsules Dairy beverages, yogurts, baked goods, cereals, bars

by Cognis GmbH.

Stability CLA, in general, is very stable and is not impacted by heat treatment and/or acid environments. The stability of CLA has been monitored by following the fatty acid profile, c9,t11 and t10,c12 isomer distribution, color (Hazen or Gardner), acid value, peroxide value, glyceride composition, and nonlipid components under a variety of storage conditions (e.g., plastic, steel, and glass containers). For storage of greater than 1 month, CLA should be stored in the dark in an air-free environment and not exposed to elevated temperatures (>25◦ C) or strong odors. Under the appropriate storage conditions, CLA triglycerides oil was completely stable in airtight steel drums over 24 months. In addition, CLA is an

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anhydrous system and will not support microbial growth. CLA is stable in various food matrices (orange juice, milk, yogurt, and nutrition bars) and following pasteurization and ultrahigh temperature (UHT) treatment. As far as interaction with other ingredients is concerned, the avoidance of pro-oxidants is recommended.

Sensory Impact CLA is a bland tasting product with a slight characteristic flavor that can be masked by various flavoring agents. When used and handled in accordance with suppliers’ recommendations, the impact on sensory characteristics should be minimal.

References Villegas JA, Rom´an JL, Gonz´alvez ABM, Luque A. Effect of physical activity and ingestion of CLA enriched milk on health overweight subjects. Rev Esp Obes 2007; 5 (2): 109–118. Banni S. Conjugated linoleic acid metabolism. Curr Opin Lipid 2002; 13 (3): 261–266. Berven G, Bye A, Hals O, Blankson H, Fagertun H, Thom E, Wasstein J, Gudmundsen O. Safety of conjugated linoleic acid (CLA) in overweight or obese human volunteers. Eur J Lipid Sci Technol 2000; 102: 455–462. Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G. Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem 2006; 17 (12): 789–810. Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr 2000; 130, 2943–2948. Brown JM, Boysen MS, Jensen SS, Morrison RF, Storkson J, Lea-Currie R, Pariza M, Mandrup S, McIntosh MK. Isomer-specific regulation of metabolism and PPAR γ signaling by CLA in human preadipocytes. J Lipid Res 2003; 44: 1287–1300. Campbell B, Kreider RB. Conjugated linoleic acids. Curr Sports Med Rep 2008; 7 (4): 237–241.

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Choi Y, Kim YC, Han YB, Park Y, Pariza MW, Ntambi JM. The trans10,cis-12 isomer of conjugated linoleic acid downregulates stearoylCoA desaturase 1 gene expression in 3T3-L1 adipocytes. J Nutr 2000; 130 (8): 1920–1924. Close RN, Schoeller DA, Watras AC, Nora EH. Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep. Am J Clin 2007; 86: 797–804. Cognis GmbH. GRAS notification dossier. GRN 232. 2007. Evans M, Geigerman C, Cook J, Curtis L, Kuebler B, McIntosh M. Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes. Lipids 2000; 35 (8): 899– 910. FDA. FDA response letter to GRN 232. 2008. Fischer-Posovszky P, Kukulus V, Zulet MA, Debatin KM, Wabitsch M. Conjugated linoleic acids promote human fat cell apoptosis. Horm Metab Res 2007; 39 (3): 186–191. Gaullier JM, Breven G, Blankson H, Gudmondsen O. Clinical trial results support a preference for using CLA preparations enriched with two isomers rather than four isomers in human studies. Lipids 2002; 37: 1019–1025. Gaullier JM, Halse J, Hoivik HO, Hoye K, Syvertsen C, Nurminiemi M, Hassfeld C, Einerhand A, O’Shea M, Gudmundsen O. Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese. Br J Nutr 2007; 97 (3): 550–560. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr 2004; 79 (6): 1118–1125. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O. Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans. J Nutr 2005; 135: 778– 784. Gavino VC, Gavino G, Leblanc MJ, Tuchweber B. An isomeric mixture of conjugated linoleic acids but not pure cis-9, trans-11-octadecadienoic

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acid affects body weight gain and plasma lipids in hamsters. J Nutr 2000; 130: 27–29. Hargrave KM, Li C, Meyer BJ, Kachman SD, Hartzell DL, Della-Fera MA, Miner JL, Baile CA. Adipose depletion and apoptosis induced by trans-10, cis-12 conjugated linoleic Acid in mice. Obes Res 2002; 10 (12): 1284–1290. Henriksen EJ, Teachey MK, Taylor ZC, Jacob S, Ptock A, Kramer K, Hasselwander O. Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat. Am J Physiol 2003; 285 (1): E98–E105. Ip C, Dong Y, Ip MM, Banni S, Carta G, Angioni E, Murru E, Spada S, Melis MP, Saebo A. Conjugated linoleic acid isomers and mammary cancer prevention. Nutr Cancer 2002; 43 (1): 52– 58. Kamphuis MM, Lejeune MP, Saris WH, Westerterp-Plantenga MS. Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects. Eur J Clin Nutr 2003a; 57 (10): 1268–1274. Kamphuis MM, Lejeune MP, Saris WH, Westerterp-Plantenga MS. The effect of conjugated linoleic acid supplement after weight loss on body weight regain, body composition, and resting metabolic rate in overweight subjects. Int J Obes Relat Metab Disord 2003b; 27 (7): 840– 847. Kang KH, Liu W, Albright KJ, Park Y, Pariza MW. trans-10,cis12 CLA inhibits differentiation of 3T3-L1 adipocytes and decreases PPAR gamma expression. Biochem Biophys Res Comm 2003; 303 (3): 795–799. Kreider RB, Ferreira MP, Greenwood M, Wilson M, Almada AL. Effects of conjugated linoleic acid supplementation during resistance training on body composition, bone density, strength, and selected hematological markers. J Strength Cond Res 2002; 16 (3): 325– 334. LaRosa PC, Miner J, Xia Y, Zhou Y, Kachman S, Fromm ME. Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis. Physiol Genomics 2006; 27 (3): 282– 294.

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Larsen TM, Toubro S, Gudmundsen O, Astrup A. Conjugated linoleic acid for 1y does not prevent weight or body fat regain. Am J Clin Nutr 2006; 83: 606–612. Laso N, Bruque E, Vidal J, Ros E, Arnaiz JA, Carne X, Vidal S, Mas S, Deulofeu R, Lafuente A. Effect of milk supplementation with conjugated linoleic acid (isomers cis-9, trans-11 and trans-10, cis-12) on body composition and metabolic syndrome components. Br J Nutr 2007; 11: 1–8. Nagao K, Wang YM, Inoue N, Han SY, Buang Y, Noda T, Kouda N, Okamatsu H, Yanagita T. The 10trans, 12cis isomer of conjugated linoleic acid promotes energy metabolism in OLETF rats. Nutrition 2003; 19 (7–8): 652–656. Nazare JA, de la Perriere AB, Bonnet F, Desagne M, Peyrat J, Maitrepierre C, Louche-Pelissier C, Bruzeau J, Goudable J, Lassel T, Vidal H, Laville M. Daily intake of conjugated linoleic acid- enriched yoghurts: effects on energy metabolism and adipose tissue gene expression in healthy subjects. Br J Nutr 2007; 97 (2): 273–280. Noone EJ, Roche HM, Nugent AP, Gibney MJ. The effect of dietary supplementation using isomeric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects. Br J Nutr 2002; 88: 243– 251. Newton RL, Jr, Alfonso A, York-Crowe E, Walden H, White MA, Ryan D, Williamson DA. Comparison of body composition methods in obese African-American women. Obesity 2006; 14 (3): 415–422. Pariza MW, Park Y, Cook ME. The biologically active isomers of conjugated linoleic acid. Prog Lipid Res 2001; 40 (4): 283–298. Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW. Effect of conjugated linoleic acid on body composition in mice. Lipids 1997; 32 (8): 853–858. Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW. Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 1999; 34 (3): 235–241. Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk JB, Facci M, Farthing JP and Zello GA. The effects of conjugated linoleic acid supplementation during resistance training. Med Sci Sports Exerc 2006; 38/2: 339–348.

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Ritzenthaler KL, McGuire MK, Falen R, Shultz TD, Dasgupta N, McGuire MA. Estimation of conjugated linoleic acid intake by written dietary assessment methodologies underestimates actual intake evaluated by food duplicate methodology. J Nutr 2001; 131 (5): 1548–1554. S´eb´edio JL, Chardigny JM, Beredeaux O. Metabolism of conjugated linoleic acids. In: S´eb´edio JL, Christie WW, Adlof R (eds.). Advances in Conjugated Linoleic Acid Research, Vol. 2. AOCS Press, Champaign, IL, 2003, pp. 259–266. Steck S, Chalecki A, Miller P, Conway J, Austin G, Hardin J, Albright C, Thuillier P. Conjugated linoleic acid supplementation for 12 weeks increases lean body mass in obese humans. J Nutr 2007; 137: 1188–1193. Thom E, Wadstein J, Gudmundsen O. Conjugated linoleic acid reduces body fat in healthy exercising humans. J Int Med Res 2001; 29: 392–396. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 2000; 49 (9): 1534–1542. Watras AC, Buchholz, AC, Close RN, Zhang Z, Schoeller, DA. The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain. Int J Obes 2006; 31 (3): 481–487. Whigham LD, O’Shea M, Mohede IC, Walaski HP, Atkinson RL. Safety profile of conjugated linoleic acid in a 12-month trial in obese humans. Food Chem Toxicol 2004; 42 (10): 1701–1709. Whigham LD, Watras AC, Schoeller DA. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Am J Clin Nutr 2007; 85: 1203–1211.

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CHAPTER 2

Appetite Suppression Effects of PinnoThinTM (Korean Pine Nut Oil) Dr. Corey E. Scott, PhD

Abstract The use of natural appetite suppressants to affect satiety and food intake may be an effective strategy to help reduce worldwide weight gain and obesity trends. PinnoThinTM is a natural oil pressed from Korean pine nuts, which is uniquely high in pinolenic acid and works as an appetite suppressant. In randomized, placebo-controlled, double-blind clinical trials, PinnoThinTM triglyceride (TG) or the natural metabolite free fatty acid (FFA) form has shown the ability to significantly increase key satiety hormones cholecystokinin (CCK) and glucagonlike peptide-1 (GLP-1), significantly reduce ad libitum food intake, and affect self-reported feelings of satiety (visual analogue scales). PinnoThinTM TG can be incorporated easily into liquid foods, such as flavored milk or yogurt, and is also available in a powdered form, which can be incorporated into other food matrices. Given its noted effects on satiety, PinnoThinTM can be a promising food ingredient or supplement to help promote weight management via appetite suppression.

Introduction As worldwide obesity rates continue to rise, it is imperative to develop key strategies that are both effective and applicable to the general population to help prevent weight gain. Two prominent factors that can 25

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contribute to weight gain are a lack of physical exercise and a surplus of energy intake. Estimations of energy balance suggest that an increase in daily caloric intake of 50–100 kcal more than energy expenditure can result in a yearly increase in body weight of 1–2 kg, contributing to the development of obesity (Brown et al., 2005). One strategy to reduce the amount of excess energy and food intake that can lead to weight gain is via the use of natural ingredients that can regulate appetite. Human appetite is controlled by a complex feedback system that regulates hunger, satiety, and satiation. Hunger can be defined as the desire for food intake whereas satiation is the signal to terminate food intake. Satiety is defined as the time period between meals in which there is no food intake. Feelings of hunger, satiation, and satiety are all regulated by the nervous and the hormonal system (Wynne et al., 2005). When food is consumed and digested, several key gastrointestinal hormones are released to alert the brain of the presence of food in the gut and to eventually reduce food intake. Key satiety hormones that regulate food intake are cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), ghrelin, and peptide tyrosine tyrosine (PYY) (Ballantyne, 2006; Burton-Freeman et al., 2004; de Graaf et al., 2004; Degen et al., 2001; Greenman et al., 2004; Gutzwiller et al., 2004; Verdich et al., 2001). CCK is released in the proximal small intestine (duodenum) into the bloodstream in response to fatty acids and protein (Burton-Freeman et al., 2004) (Fig. 2.1).

Appetite

CCK GLP-1 PYY

Figure 2.1. Activity of satiety hormones CCK, GLP-1, and PYY to decrease appetite.

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CCK release has long been associated with effects on appetite with higher concentrations producing more effects on appetite (Beglinger and Degen, 2004; Burton-Freman et al., 2002; Degen et al., 2001; Drewe et al., 1992; Gutzwiller et al., 2004; Hildebrand et al., 1998; Hopman et al., 1985; Lieverse et al., 1994). In addition, infusions of exogenous CCK in humans have been shown to reduce food intake and enhance satiety (Geary et al., 1992; Greenough et al., 1998; Gutzwiller et al., 2000; Kissileff et al., 1981). GLP-1 and PYY also work to decrease appetite and are released in the distal small intestine (ileum) of the gut when carbohydrates and fats are present (Ballantyne, 2006; de Graaf et al., 2004; Frost et al., 2003; Greenman et al., 2004; Kong et al., 1999; Lavin et al., 1998; Ranganath et al., 1996; Thomsen et al., 2003; Verdich et al., 2001). Similar to CCK infusions in humans, exogenous GLP-1 infusions have been shown to significantly reduce food intake at ad libitum meals by decreasing hunger and enhancing satiety (Flint et al., 1998, 2001; Gutzwiller et al., 1999a, 1999b; Halton and Hu, 2005; Naslund et al., 1998, 1999). Ghrelin is produced by the stomach and opposes the actions of CCK and GLP-1 as it induces hunger and increases appetite (Greenman et al., 2004). The roles of macronutrients (fats, carbohydrates, and proteins) in appetite suppression via satiety hormone release have been extensively studied. Of these, it has been suggested that protein and fiber-rich foods produce strong satiety responses (Halton and Hu, 2005; Slavin, 2005). Fat intake releases satiety hormones CCK and GLP-1, which can affect satiety despite there being a relationship between high fat intake and increased weight gain (Blundell et al., 1995). This apparent contradiction may be explained in part by the type of fat that is consumed. The effects of fats on satiety and food intake are related to chain length and degree of saturation (number of double bonds). In nature, fats exist as forkshaped molecules that consist of three fatty acids bound to a glycerol backbone. When fats are ingested, the triglyceride is broken down by lipases yielding free fatty acids (FFAs) (Fig. 2.2). FFAs trigger the release of satiety hormones, more so than triglycerides (Little et al., 2007). It has been demonstrated that long-chain FFA (greater than 14 carbons) produced greater effects on hunger and plasma CCK levels than medium-chain FFA (12–14 carbons) (Feinle et al., 2001). In addition, only fatty acids with chain lengths ≥ 12 carbons are capable of releasing significant amounts of CCK (Beglinger and Degen, 2004; Burton-Freman et al., 2002). Moreover, duodenal infusions of FFA of a chain length of 12 carbons produced more potent effects on food intake, appetite expression, and CCK and GLP-1 release compared with a FFA

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Lipid based ingredients O HO

O

O

H2C O O

Lipase

HC O O

HO Free fatty acids

H2C O Triglyceride

H3C

O

+

HC O H3C

Monoglyceride

Figure 2.2. Enzymatic hydrolysis of triglycerides into free fatty acids and a monoglyceride during human digestion.

of chain length of C10 (Feltrin et al., 2004). In terms of saturation and effects on appetite, polyunsaturated fatty acids (PUFAs, fats with one or more double bonds) exert a stronger effect on appetite expression than monounsaturated (MUFA, fats with one double bond) and saturated (SFA, fats with no double bonds) (Lawton et al., 2000). GLP-1 release is also affected by the degree of saturation and is released by MUFA rather than SFA in response to high-fat meals (Thomsen et al., 1999, 2003). Thus, selective intakes of oils containing longer chain fats with high degrees of unsaturation can have implications for appetite regulation and long-term weight management (Halford, 2007). One such oil with a high concentration of long-chain PUFA that may influence satiety hormones is PinnoThinTM . PinnoThinTM is a natural oil pressed from Korean pine nuts (Pinus Koraiensis). Korean pine nut oil is derived from the nuts of the native Korean pine tree. This tree grows in Korea, Japan, Siberia, and China (Manchuria). Pine nuts consist of about 60% oil by weight and have long been widely consumed in popular dishes and as condiments in many geographical areas. Pine nut oil consists of 92% of PUFAs and MUFAs, mainly pinolenic acid (C18:3), linoleic acid (C18:2), and oleic acid (C18:1) (Wolff et al., 2000) (Fig. 2.3). PinnoThinTM is unique in that it contains a large concentration of pinolenic acid, which makes up approximately 14% of the total fatty acids, whereas other pine nuts contain approximately 1–2% of pinolenic acid (Wolff et al., 2000). The high concentration of PUFA and the uniquely high content of pinolenic acid lead to the hypothesis that PinnoThinTM intake can reduce appetite by an induction of satiety hormones. In peer-reviewed, published human clinical studies (Hughes et al., 2008; Pasman et al., 2008), PinnoThinTM supplementation has shown the ability

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O HO Oleic acid O HO Linoleic acid O HO Pinolenic acid

Figure 2.3. Unsaturated fatty acids found in PinnoThinTM .

to influence satiety and food intake and can be an integral part of weight management.

Effects of PinnoThinTM on In Vitro CCK Release PinnoThinTM was first evaluated for its effects on releasing the satiety hormone CCK in cell culture. PinnoThinTM and several other common fatty acids such as capric acid (C10), oleic acid (C18:1), linoleic acid (C18:2), α-linoleic acid (C18:2), and oil from Italian stone pine nut (oleic, linoleic, and pinolenic (1.2%)) were added to a well-established murine enteroendocrine tumor cell line, STC-1, at 50 µM concentrations for 60 minutes and evaluated for the release of CCK (Pasman et al., 2008). PinnoThinTM produced the greatest release in CCK (493 pg/mL), and as expected, capric acid, a small-chain fatty acid, which is more quickly absorbed in the human body and elicits a poorer CCK response, produced the least (46 pg/mL) (Fig. 2.4). Oleic, linoleic, and α-linoleic acids produced similar amounts of CCK relative to each other, which were 145, 138, and 124 pg/mL, respectively, but much lower than that of PinnoThinTM . Italian stone pine nut oil produced a very small amount of CCK in this evaluation, which was 62 pg/mL. The fatty acid profile of PinnoThinTM and Italian stone pine nuts are similar although PinnoThinTM is much more concentrated in pinolenic acid, which may suggest the large differences in the observed in vitro CCK release.

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CCK release (pg/mL)

500

400

300

200

100

0 PinnoThin

Italian stone pine nut

Oleic acid

Linoleic acid Alpha linoleic Capric acid acid

Figure 2.4. The effects of PinnoThinTM and other fatty acids on CCK release from STC-1 cell lines.

In Vivo Effects of PinnoThinTM on Satiety Hormones and Subjective Measures of Satiety (VAS) The observation that PinnoThinTM increased in vitro CCK to a greater extent than many other commonly consumed fats in the diet led to the hypothesis that PinnoThinTM may increase satiety hormones and affect appetite feelings in humans. For this study, 18 overweight, postmenopausal women were chosen to participate in a randomized, double-blind, placebocontrolled, crossover trial (Pasman et al., 2008). The volunteers had a median BMI of 27.4 kg/m2 , median age of 55 years, and median weight of 76.7 kg. The volunteers reported to the laboratory after an overnight fast and a cannula was inserted in the forearm in an antecubital vein for blood sampling. Each of the volunteers consumed a light breakfast consisting of two pieces of white bread with marmalade and no additional fat and each received 3 g of PinnoThinTM TG (triglyceride), 3 g of PinnoThin FFA (natural metabolite FFA form), or 3 g of olive oil (placebo) in the form of softgel capsules that they consumed with the breakfast and a glass of water.

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After capsules and breakfast were taken, blood was sampled to measure satiety hormones CCK, GLP-1, Ghrelin, and PYY at t = 0, 30, 60, 90, 120, 180, and 240 minutes after start of breakfast. Appetite sensations were evaluated using visual analogue scales (VASs) for “hunger,” “fullness,” “desire to eat,” and “prospective food consumption” (Flint et al., 2000; Stubbs et al., 2000). The VASs consisted of horizontal lines, with each end expressing the most positive or negative sensation (i.e. I am not hungry at all/I am extremely hungry). Subjects drew a vertical line on the horizontal line corresponding to their appetite sensation. These procedures were followed for each treatment on three test days, with a washout period of 1 week between treatments. With respect to the effects of PinnoThinTM on satiety hormones, CCK release was significantly higher with PinnoThinTM FFA than with placebo at 30, 90, 120, and 180 minutes (Fig. 2.5).

pmol/L

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1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0

* **

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12 10 8 6 4 2 0

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Figure 2.5. The effects of PinnoThinTM FFA •, PinnoThinTM TG
, and olive oil placebo  on CCK and GLP-1 release. * indicates p < 0.05 for PinnoThinTM FFA, ** indicates p < 0.05 for PinnoThinTM TG.

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CCK release was also significantly higher at 60 and 120 minutes with PinnoThinTM TG compared with placebo. The CCK area under the curve (AUC) for PinnoThinTM FFA was 60.3% higher and for PinnoThinTM TG 22.0% higher than the CCK AUC for placebo (p < 0.0001). The overall response curves for CCK were significantly different between the treatments. The maximal concentration (Cmax ) reached for PinnoThin FFA was 2.0 ± 0.43 pmol/L; for PinnoThinTM TG, 1.45 ± 0.23 pmol/L; and for placebo, 1.08 ± 0.15 pmol/L (p < 0.01). The other satiety hormone studied, GLP-1 (Fig. 2.5), also showed overall different response curves between treatments. GLP-1 release was significantly higher using PinnoThinTM FFA than using placebo at 60 minutes (p < 0.05). GLP-1 AUC was 25.1% higher after the PinnoThinTM FFA than with placebo (p < 0.01). GLP-1 release takes place in the distal colon whereas CCK release takes place in the first parts of the small intestine that suggests why GLP-1 release took longer than CCK release. The effects of PinnoThinTM TG on GLP-1 release were similar to placebo. Similar effects on ghrelin were observed with PinnoThinTM FFA, PinnoThinTM TG, and placebo. At 60, 180, and 240 minutes, the PYY concentrations after PinnoThinTM FFA was higher than placebo and the AUC was 16.2% higher for PinnoThinTM FFA versus placebo (p < 0.01). There were no significant effects of PinnoThinTM TG on PYY release versus placebo. Regarding VAS scoring, “prospective food consumption” at 30 minutes was 36% lower for PinnoThinTM FFA compared to placebo (p < 0.01) (Fig. 2.6). This study showed that PinnoThinTM can influence satiety in humans by increasing the release of hormones that regulate appetite and affecting subjective measures of satiety such as VAS scores (prospective food intake). From this study, both forms of PinnoThinTM showed efficacy, with the natural metabolite PinnoThinTM FFA showing greater efficacy in releasing satiety hormones and influencing VAS scores. This is consistent with other studies showing that FFA triggers the release of CCK (Cox et al., 2004; Guimbaud et al., 1997; Hildebrand et al., 1998). Also, this study found effects with only 18 people and perhaps a larger population may have yielded greater differences in VAS scores and satiety hormones. Although effects of PinnoThinTM were shown for key satiety hormones, CCK and GLP-1, a consistent effect of PinnoThinTM on PYY and ghrelin hormones was not found. A lack of an effect of fat intake on ghrelin was also reported by Poppitt and coworkers (Poppitt et al., 2006) showing that high-fat meals and fatty acid saturation levels had no differential effect on ghrelin levels in healthy men.

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70

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* *

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0 0

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90

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Minutes

Figure 2.6. The effects of PinnoThinTM FFA •, PinnoThinTM TG
, and olive oil placebo  on prospective food intake. * indicates p < 0.05 for PinnoThinTM FFA.

The Effects of PinnoThinTM on Ad Libitum Food Intake Given the previous study that PinnoThinTM can increase satiety hormones and also affect subjective satiety scores (VAS) in humans, a study was performed to evaluate the effects of PinnoThinTM administration on subsequent ad libitum (at will) food and caloric intake (Hughes et al., 2008). For this evaluation, 42 nonsmoking, healthy overweight women (median BMI of 27.4 kg/m2 , median age of 33.8 years, median weight of 73.9 kg) were included in a double-blind, placebo-controlled, crossover study and randomized to receive five treatments, placebo (olive oil), 2 g PinnoThinTM TG, 4 g PinnoThinTM TG, 6 g PinnoThinTM TG, and 2 g PinnoThinTM FFA (natural metabolite) administered as softgel capsules. On each test day, participants came into the study site where they consumed a fixed-load breakfast (496 kcal) consisting of cereal, milk,

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Study day

8:30 am Fixed breakfast

1:00 pm Ad libitum lunch

5:00 pm Ad libitum supper

12:30 pm PinnoThin capsules

Figure 2.7. Food-intake study design.

white bread toast, orange juice, and a hot drink. Three and a half hours later and 30 minutes prior to the ad libitum lunch, six capsules containing either the placebo oil or doses of PinnoThinTM were provided with 200 mL water to the volunteers. After 30 minutes, an ad libitum lunch consisting of several different food choices such as sandwich items, pizza, and dessert items was served with water. The volunteers were instructed to consume as much as they liked from the choice of foods offered, taking as long as they wished, and signaling when they had finished. Four hours later, participants returned and were served a hot ad libitum evening meal consisting of a pasta dish. Similar to the lunch meal, volunteers were asked to consume as much as they desired, taking as long as they wished and signaling when they had finished. The study design is outlined in Fig. 2.7. The study found that the PinnoThinTM FFA intake before lunch was associated with a reduction in the amount of food and energy intake at the lunch meal. Two grams of PinnoThinTM FFA significantly reduced intake of food by 9% at the lunch meal (347.9 g PinnoThinTM vs. 380.2 g olive oil placebo, p = 0.029) (Fig. 2.8). Furthermore, caloric intake at lunch was reduced by 7% (656.2 kcal PinnoThinTM vs. 706.1 kcal olive oil placebo, p = 0.09), which corresponds to roughly a 50-kcal reduction. Although this reduction narrowly missed statistical significance most likely due to lack of power, a reduction of 50 kcal is physiologically relevant. Brown et al. (2005) have suggested that the average weight gain in a female population equates with an energy imbalance of only 10–40 kcal/day. No effects were seen for food or caloric intake at the dinner meal for the PinnoThinTM FFA versus the placebo (530.2 g and 1,024.2 kcal vs. 521.4 g and 1,002.4 kcal, respectively; p = ns) indicating that the volunteers did not compensate for the reduced caloric and food intake observed at lunch. The effects on food intake of PinnoThinTM TG at the doses tested were similar to that of olive oil, although PinnoThinTM FFA in the natural

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Food intake (g)

400 375

*

350 325

Caloric intake (kcal)

300 Placebo

PinnoThin FFA

Placebo

PinnoThin FFA

750 700 650 600 550

Figure 2.8. The effects of PinnoThinTM FFA on food intake (g) and caloric intake (kcal) during an ad libitum lunch. * denotes statistical difference (p < 0.05)

metabolite form was efficacious at 2 g.The lack of a significant effect for the PinnoThinTM TG may be explained by the timing of the administration rather than dosage. PinnoThinTM can affect satiety by increasing the release of satiety hormones CCK and GLP-1 (Pasman et al., 2008). In order to trigger the release of satiety hormones, PinnoThinTM TG must first be metabolized into FFA. In a previous study using both PinnoThinTM TG and PinnoThinTM FFA, the peak release in CCK took longer for the TG compared to the FFA (60 minutes rather than 30 minutes) (Pasman et al., 2008). In this food-intake study, the PinnoThinTM TG was administered 30 minutes prior to the ad libitum lunch and not 60 minutes where a peak increase in CCK by PinnoThinTM TG has been previously observed (Pasman et al., 2008). This study showed that the natural metabolite form of PinnoThinTM , PinnoThinTM FFA can reduce food and caloric intake in healthy overweight women. The lack of significant effects of PinnoThinTM TG on food intake remains unclear and more research is needed to determine how PinnoThinTM TG affects satiety. Future studies are underway in larger groups of people using various food applications that may make

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PinnoThinTM TG more bioavailable and produce stronger effects on satiety and food intake. In other studies, FFA release from PinnoThinTM TG has been observed in in vitro digestion models and also in plasma isolated from individuals who had consumed a beverage containing 3 g of PinnoThinTM TG (unpublished data). Thus, FFA from PinnoThinTM TG are bioavailable and may require sufficient time before a meal to affect food intake.

Food Applications PinnoThinTM is available as a natural oil in triglyceride form and can be applied to a wide range of food products. The recommended dosage of PinnoThinTM for satiety benefits is 3 g per serving. Extensive tests with PinnoThinTM have been performed to test the effect of several standard processing steps including homogenization, UHT treatment, pasteurization, sterilization, baking, extrusion, molding, fermentation, and acidification. These processing steps do not affect PinnoThinTM in concentration and sensory parameters. PinnoThinTM can also be taken as a supplement in a softgel form. For food products, PinnoThinTM is most recommended for liquid food products such as flavored milk, yogurt, and beverages, and for products such as dressings and other fat-based products such as fat spreads. PinnoThinTM has also been successfully applied to bakery products including cookies and nutritional bars. Incorporating PinnoThinTM in food products can be done by replacing or by mixing the existing fat phase with PinnoThinTM . In aqueous solutions, it may be useful to add PinnoThinTM as an emulsion. Emulsions can be made by adding the oil phase (PinnoThinTM and/or others) to the water phase (e.g., water, yogurt, milk) under continuous mixing followed by homogenization. After homogenization, a heat treatment can be applied to extend the shelf life of the product. PinnoThinTM is also available as a microencapsulated powder containing 60% PinnoThinTM TG. This product can be used in instant products such as powdered shakes, meal replacer shakes, and so on. The PinnoThinTM powder is also recommended for food products with relatively low water activities such as nutritional bars, cookies, bread, instant powders, and so on. The stability of PinnoThinTM in food products is comparable to other PUFAs. PUFAs are most sensitive to oxidation. Oxidation of fats can have a negative impact on the quality of the final product, such as formation of

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off-flavors, discoloring, change in texture, and formation of free radicals. It is best to avoid the following factors where possible, such as exposure to oxygen, heat, light, and transition metals. PinnoThinTM contains mixed tocopherols to increase the stability of the oil.

History of Pine Nut Consumption Pine nuts have long been constituent parts of the diets of many cultures, particularly in the Mediterranean and Asian regions, and they are now also consumed very widely outside these geographical areas. To date, no published studies are known or available, which shows that daily human exposure to Korean pine nut oil is unsafe and causes adverse events. Historical use of pine nut oil in foods, at levels of up to 7.5 g/day, has not been associated with adverse events. In addition, pine seeds are commonly used in a variety of foods including breads, ice cream, and cookies, and so an exposure could potentially exceed 7.5 g/day. PinnoThinTM has been tested in two human clinical studies with up to 6 g doses with no reported adverse events versus a placebo oil.

Conclusion PinnoThinTM is an all-natural appetite suppressant that has been clinically shown to affect satiety. In human clinical studies, PinnoThinTM significantly increased satiety hormones that play an essential role in appetite suppression. The effects of PinnoThinTM were further confirmed in a subsequent human trial, which showed that PinnoThinTM FFA can reduce food and caloric intake. Taken together, the effects of PinnoThinTM on satiety can play a key role in the overall strategy for weight management.

References Ballantyne GH. Peptide YY (1–36) and peptide YY (3–36). Part I: distribution, release and actions. Obes Surg 2006;16:651–658. Beglinger C, Degen L. Fat in the intestine as a regulator of appetite—role of CCK. Physiol Behav 2004;83:617–621. Blundell JE, Cotton JR, Delargy H, Green S, Greenough A, King NA, Lawton CL. The fat paradox: fat-induced satiety signals versus high-fat over-consumption. Int J Obes 1995;19:832–835.

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Brown WJ, Williams L, Ford JH, Ball K, Dobson AJ. Identifying the energy gap: magnitude and determinants of 5-year weight gain in midage women. Obes Res 2005;13:1431–1441. Burton-Freeman B, Davis PA, Schneeman BO. Interaction of fat availability and sex on postprandial satiety and cholecystokinin after mixed-food meals. Am J Clin Nutr 2004;80:1207–1214. Burton-Freman B, Davis PA, Schneeman BO. Plasma cholecystokinin is associated with subjective measures of satiety in women. Am J Clin Nutr 2002;76:659–667. Cox JE, Kelm GR, Meller ST, Randich A. Suppression of food intake by GI fatty acid infusions: roles of celiac vagal afferents and cholecystokinin. Physiol Behav 2004;82:27–33. de Graaf C, Blom WA, Smeets PA, Stafleu A, Hendriks HF. Biomarkers of satiation and satiety. Am J Clin Nutr 2004;79:946–961. Degen L, Matzinger D, Drewe J, Beglinger C. The effect of cholecystokinin in controlling appetite and food intake in humans. Peptides 2001;22:1265–1269. Drewe J, Gadient A, Rovati LC, Beglinger C. Role of circulating cholecystokinin in control of fat-induced inhibition of food intake in humans. Gastroenterology 1992;102:1654–1659. Feinle C, Rades T, Otto B, Freid M. Fat digestion modulates gastrointestinal sensations induced by gastric distension and duodenal lipids in humans. Gastroenterology 2001;120:1100–1107. Feltrin KL, Little TJ, Meyer JH, Horowtiz M, Smout AJPM, Wishart J, Pilichiewicz AN, Rades T, Chapman IM, Fienle-Bisset C. Effects of intraduodenal fatty acids on appetite, antopyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length. Am J Physiol 2004;287:R524–R533. Flint A, Raben A, Astrup A, Holst J. Glucagon like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998;101:515–520. Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord 2000;24: 38–48.

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Flint A, Raben A, Ersbø´ ll AK, Holst JJ, Astrup AA. The effect of physiological levels of glucagon like peptide 1 on appetite, gastric emptying, energy and substrate metabolism in obesity. Int J Obes 2001;25:781–792. Frost GS, Brynes AE, Dhillo WS, Bloom SR, McBurney MI. The effects of fibre enrichment of pasta and fat content on gastric emptying, GLP-1, glucose, and insulin responses to a meal. Eur J Clin Nutr 2003;57:293–298. Geary N, Kissileff HR, Pi-Sunyer FX, Hinton V. Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men. Am J Physiol 1992;262:R975–R980. Greenman Y, Golani N, Gilad S, Yaron M, Limor R, Stern N. Ghrelin secretion is modulated in a nutrient- and gender-specific manner. Clin Endocrinol 2004;60:382–388. Greenough A, Cole G, Lewis J, Lockton A, Blundell JE. Untangling the effects of hunger, anxiety and nausea on food intake during intravenous cholecystokinin octapeptide (CCK-8) infusions. Physiol Behav 1998;65:303–310. Guimbaud R, Moreau JA, Bouisson M, Durand S, Escourrou J, Vaysse N, Frexinos J. Intraduodenal free fatty acids rather than triglycerides are responsible for the release of CCK in humans. Pancreas 1997;14:76– 82. Gutzwiller J-P, Degen L, Matzinger D, Prestin S, Beglinger C. Interaction between GLP-1 and CCK-33 in inhibiting food intake and appetite in men. Am J Physiol Regul Integr Comp Physiol 2004;287:R562–R567. Gutzwiller J-P, Drewe J, Goke B, Schmidt H, Rohrer B, Lareide J, Beglinger C. Glucagon like peptide promotes satiety and reduced food intake in patients with diabetes mellitus. Am J Physiol 1999a;276: R1541–R1545. Gutzwiller J-P, Drewe J, Ketterer S, Hildebrand AK, Beglinger C. Interaction between CCK and a preload on reduction of food intake is mediated by CCK-A receptors in humans. Am J Physiol 2000;279:R189–R195. Gutzwiller J-P, Goke B, Drewe J, Hildebrand P, Ketterer S, Handschin D, Winterhalder R, Conen D, Beldlinger C. Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 1999b;44:81–86.

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Halford JCG. What’s new in the appetite suppressant field. A nutritional and behavioural perspective. Agro Foods Industry Hi-Tech. Anno 18—No. 5 September/October 2007. Halton TI, Hu FB. The effects of high protein diets on thermogenesis, satiety and weight loss. A critical review. J Am Coll Nutr 2005;23:373–385. Hildebrand P, Petrig C, Buckhardt B, Ketterer S, Lengsfeld H, Fleury A, Hadvary P, Belinger C. Hydrolysis of dietary fat by pancreatic lipase stimulated cholecystokinin releases. Gastroenterology 1998;114:123–129. Hopman WPM, Jansen JB, Lamers CB. Comparative study of the effects of equal amounts of fat, protein, and starch on plasma cholecystokinin in man. Scand J Gastroenterol 1985;20:8437. Hughes GM, Boyland EJ, Williams NJ, Mennen L, Scott C, Kirkham TC, Harrold JA, Keizer HG, Halford JC. The effect of Korean pine nut oil (PinnoThin) on food intake, feeding behaviour and appetite: a double-blind placebo-controlled trial. Lipids Health Dis 2008;7:6. Kissileff HR, Pi-Sunyer X, Thornton J, Smith GP. C-terminal octapeptide of cholecystokinin decreases food intake in man. Am J Clin Nutr 1981;34:154–160. Kong M-F, Chapman I, Goble A, Wishart J, Wittert G, Morris H, Horowitz M. Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects. Peptides 1999;20:545–551. Lavin JH, Wittert GA, Andrews J, Yeap B, Wishart JM, Morris HA, Morley JE, Horowitz M, Read NW. Interaction of insulin, glucagonlike peptide 1, gastric inhibitory polypeptide, and appetite in response to intraduodenal carbohydrate. Am J Clin Nutr 1998;68: 591–598. Lawton CL, Delargy HJ, Brockman J, Smith FC, Blundell JE. The degree of saturation of fatty acids influences post-ingestive satiety. Br J Nutr 2000;83:473–482. Lieverse RJ, Jansen JBMJ, Masclee AAM, Rovati LC, Lamers CBHW. Effect of a low dose of intraduodenal fat on satiety in humans: studies using the type A cholecystokinin receptor antagonist loxiglumide. Gut 1994;35:501–505. Little TJ, Russo A, Meyer JH, Horowitz M, Smyth DR, Bellon M, Wishart JM, Jones KL, Feinle-Bisset C. Free fatty acids have more potent effects

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on gastric emptying, gut hormones, and appetite than triacylglycerides. Gastroenterology 2007;133(4):1124–1131. N¨aslund E, Barkeling B, King N, Gutniak M, Blundell JE, Holst JJ, R¨ossner S, Hellstr¨om PM. Energy intake and appetite are suppressed by glucagon like peptide 1 (GLP-1) in obese men. Int J Obes 1999;23:304–311. N¨aslund E, Gutniak M, Skogar S, R¨ossner S, Hellstr¨om PM. Glucagon-like peptide 1 increase the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr 1998;68:525–530. Pasman WJ, Heimerikx J, Rubingh CM, Van Den Berg R, O’Shea M, Gambelli L, Hendriks HF, Einerhand AW, Scott C, Keizer HG, Mennen LI. The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women. Lipids Health Dis 2008;7:10. Poppitt SD, Leahy FE, Keogh GF, Wang Y, Mulvey TB, Stojkovic M, Chan YK, Choong YS, McArdle BH, Cooper GJ. Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men. Eur J Clin Nutr 2006;60:77–84. Ranganath LR, Beety JM, Morgan LM, Wright W, Howland R, Marks V. Attenuated GLP-1 secretion in obesity: cause or consequence? Gut 1996;38:916–919. Slavin JL. Dietary fibre and body weight. Nutrition 2005;21:411–418. Stubbs RJ, Hughes DA, Johnstone AM, Rowley E, Reid C, Elia M, Stratton R, Delargy H, King N, Blundell JE. The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br J Nutr 2000;84: 405–415. Thomsen C, Rasmussen O, Losen T, Holst JJ, Fenselau S, Schrezenmeir J, Hermansen K. Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects. Am J Clin Nutr 1999;69:1135–1143. Thomsen C, Storm H, Holst JJ, Hermansen K. Differential effects of saturated and monounsaturated fats on postprandial lipemia and glucagonlike peptide 1 responses in patients with type 2 diabetes. Am J Clin Nutr 2003;77:605–611.

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Verdich C, Flint A, Gutzwiller JP, Naslund E, Beglinger C, Hellstrom PM, Long SJ, Morgan LM, Holst JJ, Astrup A. A meta-analysis of the effect of glucagon-like peptide-1 (7–36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 2001;86:4382–4389. Wolff RL, P´edrono F, Pasquier E, Marpeau AM. General characteristics of Pinus spp. seed fatty acid compositions, and importance of delta5olefinic acids in the taxonomy and phylogeny of the genus. Lipids 2000;35(1):1–22. Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005;184:291–318.

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CHAPTER 3

Sucrose Fatty Acid Ester (Olestra) John C. Peters, PhD

Abstract Despite 20 years of mounting evidence concerning the implications of eating too much fat, people still consume more than the recommended amount. While nutrition experts agree that the optimal method for reducing fat in the diet is to replace high-fat foods with low-fat choices, the reality is that most people find it difficult to eliminate foods containing fat from their everyday meals and snacks. For more than 30 years, scientists and researchers at The Procter & Gamble Company have been working with a fat substitute known as olestra (brand name Olean). Although olestra looks, cooks, and tastes like conventional fat, it is not broken down by the body. In 1996, FDA approved olestra as a replacement for up to 100% of the conventional fat in savory snacks. Because the olestra molecule can be manipulated for application in a wide variety of food formulations, it is an ideal choice for eliminating all fat, and thus all calories from fat, in some foods or for blending with dietary fat for reducing calorie content. In addition to its potential impact on weight control, olestra has been shown to have a positive impact on cardiovascular and metabolic risk factors and may also provide a therapeutic approach for reducing levels of fat-soluble environmental contaminants in the body such as dioxin. Reduce total fat intake to 30% or less of calories. Reduce saturated fatty acid intake to less than 10% of calories and the intake of cholesterol to less than 300 mg daily. The intake of fat and cholesterol can be reduced by substituting fish, poultry without skin, lean meats, and low- or nonfat dairy products for fatty meats and whole-milk dairy products; by choosing 43

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more vegetables, fruits, cereals, and legumes; and by limiting oils, fats, egg yolks, and fried and other fatty foods. Diet and Health: Implications for Reducing Chronic Disease Risk Committee on Diet and Health, National Research Council National Academies Press, 1989

Since the United States National Research Council issued its 1989 landmark report, Diet and Health: Implications for Reducing Chronic Disease Risk, dietary fat has been a primary focus among nutrition and health professionals worldwide, and consumers have struggled to follow the council’s now ubiquitous “30% of calories” recommendation for fat intake. In its earliest incarnation, consumer interest in low-fat eating was driven primarily by the link between dietary fat and cardiovascular disease. Over time, as research showed that not all dietary fat is “bad for the heart,” consumer focus shifted to the impact of dietary fat on weight, and the spotlight shifted from fat as a risk factor for clogged arteries to fat as a risk factor for eating too many calories. Despite 20 years of mounting evidence concerning the implications of eating too much fat, however, people still consume more than the recommended amount. Although the percentage of calories from total fat decreased from 36.9% to 32.8% for men and from 36.1% to 32.8% for women between 1971–1974 and 1999–2000, Americans are still consuming more than their healthy share of fat. In fact, the decrease in percentage of calories from fat is attributed to an increase in total calories consumed; absolute fat intake in grams has actually increased (Table 3.1). Making any dietary change is a complex process. Research shows that reducing fat in the diet is one of the most difficult behaviors to sustain (American Dietetic Association, 2006; Drewnowski and Rolls, 2005). While nutrition experts agree that the optimal method for reducing fat in the diet is to replace high-fat foods with low-fat choices such as whole grains, fruits, and vegetables, the reality is that most people find it impossible—and undesirable—to eliminate foods containing fat from their everyday meals and snacks. Table 3.1. Mean energy intake among adults and percentage of calories from fat among adults during 1971–2000 Men

Women

Time Frame

Kilocalories per Day

Percentage of Kilocalories from Fat

Kilocalories per Day

Percentage of Kilocalories from Fat

1971–1974 1976–1980 1988–1994 1999–2000

2,450 2,439 2,666 2,618

36.9 36.8 33.9 32.8

1,542 1,522 1,798 1,877

36.1 36.0 33.4 32.8

Source: Wright et al., 2004.

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Although overconsumption of particular fatty acid compositions has known health risks, fat is also vital to human growth and development and key to certain physiological processes. In addition, fat imparts important functional and sensory qualities to food, including flavor, softness, chewiness, smoothness, and creaminess. Fat helps maintain moisture in food, influences food stability for storage, creates structure in baked goods, and helps transmit the heat that creates crsipiness. Fat also carries, enhances, and release flavor. Because fat performs so many diverse and complex functions in food, it is difficult to eliminate or replace it in whole foods and in food formulations without affecting function and consumers’ number one criterion for food choice, taste. Almost two decades ago, the U.S. Department of Agriculture challenged food manufacturers to develop at least 5,000 reduced-fat products by the year 2000. This goal was easily met and surpassed by 1995 (International Food Information Council, 2000). What these early products lacked in fat, however, they often made up for in added salt and sugar in an effort to preserve flavor. Nevertheless, taste and texture remained an issue for consumers. Taste continues to rule consumer food choice today, but as the quest for overall wellness and the desire for healthful food become mainstream, the demand for flavorful reduced-fat foods that can be seamlessly incorporated into everyday eating is increasing rapidly.

The Evolution of Olestra For more than 30 years, scientists and researchers at The Procter & Gamble Company (P&G), a multinational consumer products company based in Cincinnati, Ohio, have been working with a fat substitute known as olestra (brand name Olean). P&G chemists created olestra, a sucrose polyester, through a multistep process that combines two naturally occurring substances, sucrose and vegetable oil (soybean or cottonseed). The result is a proprietary cooking oil/shortening that adds no fat, no calories, no transfat, and no cholesterol to food yet maintains the properties of normal fat flavor, texture, mouthfeel, and thermal stability. Although olestra looks, cooks, and tastes like conventional fat, it is not broken down by the body. While the typical fat molecule is composed of three fatty acid chains attached to a glycerol core, the olestra molecule is composed of six to eight fatty acid chains attached to sucrose core. Like the insoluble fiber in apples, corn, and bran, olestra is impossible for gastrointestinal enzymes to digest (Fig. 3.1). Because other fat replacers mimic only one or two functions of fat, they must be mixed and matched into “systems” in order to replace conventional fat in foods. Olestra, however, is a fat; therefore, it does not have to be combined with other replacers in order to be effective. Olestra can be made

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Figure 3.1. Olestra molecule.

from fatty acids derived from different types of vegetable oil and can be tailored to replace conventional fat in various foods. In the early 1970s, P&G began meeting with the U.S. Food and Drug Administration (FDA) to discuss using olestra in foods. Because olestra is a novel food ingredient, it required FDA approval as a food additive. In 1987, P&G filed a petition with the FDA. The agency’s 22-member Food Advisory Committee subsequently reviewed approximately 100 animal and 40 human studies, including more than 40 tightly controlled clinical studies in more than 5,000 men, women, and children, plus an additional 55 sensory or preference studies in more than 20,000 people. (See www.olean.com/default.asp?p=prof&id=sc for a guide to olestra studies.) With the depth and breadth of this scrutiny—which covered areas such as nutritional and gastrointestinal effects, weight management, drug interactions, toxicology biomarkers for cancer, heart disease, and allergic reaction—olestra became one of the most studied food ingredients of all time. In 1996, FDA approved olestra as a replacement for up to 100% of the conventional fat in savory snacks such as potato chips, tortilla chips, cheese puffs, and crackers. Because olestra holds up under the high temperature of frying, it imparts the same taste and texture as conventional frying oil—a benefit other fat replacers cannot claim. Some nutrition experts questioned why P&G chose to “make a bad food good” by replacing the fat in a snack such as potato chips. The answer

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rests in the simple reality of consumer behavior: Despite the high amount of unhealthy dietary fat in potato chips, people enjoy them, eat a lot of them, and are loathe to give them up no matter what health authorities recommend. Thus, potato chips are a good target for reducing fat and calories in the American diet. In granting P&G’s petition, FDA required that products containing olestra carry a label informing consumers that after eating olestracontaining snacks, some people may experience temporary digestive effects, and that vitamins A, D, E, and K have been added to the product to compensate for the possibility that in the presence of olestra, not all of the fat-soluble vitamins present in the food would be absorbed. In 2003, FDA authorized removal of this information label, and in the following year, FDA approved olestra for use in microwave popcorn. In 2007, P&G submitted a GRAS notification to FDA that provided data supporting olestra’s use in prepackaged ready-to-eat cookies.

The Role of Olestra in Weight Prevention, Loss, and Maintenance Health experts around the world agree that obesity has become a serious global issue. High blood pressure, heart attack and stroke, type 2 diabetes, gallbladder disease, and certain cancers have been linked directly to obesity (American Dietetic Association, 2006; Drewnowski and Rolls, 2005). Research indicates that the path to obesity is paved with foods high in fat. Not only are high-fat foods energy dense, but calorie for calorie, dietary fat is thought to be less satiating than protein or carbohydrate and thus promotes overeating. In addition, excess dietary fat is more easily stored as body fat (Bray et al., 2002; Hill, 2006; Peters, 2003). Consuming foods in which some of all of the dietary fat has been replaced is one way to help reduce the amount of fat and hence the number of calories consumed. To fully appreciate the potential impact of reduced-fat food on weight prevention, loss, and maintenance, it is necessary to understand three core concepts: volume/weight versus calories consumed, energy density, and compensation. Research by Barbara Rolls and others has shown that over the course of several days, people tend to eat a consistent weight/volume of food rather than a certain number of calories (Rolls et al., 2005). Theoretically, if the weight of food eaten remains the same over time, but the calories in that volume food are reduced, the appetite should be satisfied with fewer

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calories. Typically, the body does not notice differences in calorie intake unless it is losing weight, in which case it will trigger a primitive defensive mechanism to prevent the threat of perceived starvation. The number of calories (amount of energy) in a given volume of food such as a cubic centimeter is called energy density. Practically speaking, on a label, this concept is expressed as calories per gram. When a food is low in energy density, more of that food can be consumed without contributing calories to the diet. At one end of the spectrum of food components, water (including the water intrinsic in fruits and vegetables) has the most impact on energy density because it adds weight (volume) without adding calories. At the other end of the spectrum, fat has the greatest impact on energy density because among the macronutrients, fat adds the most calories per unit of volume—9 kcal/g versus only 4 kcal/g for carbohydrate and protein. Rolls and others have also demonstrated that when the energy density of a given weight of food is lowered, even by as much as 30%, individuals do not notice the decrease and report levels of hunger and satiety (fullness) similar to what they experience in their normal diet—because they have consumed the same weight/volume of food as usual. Thus, it is not surprising that higher energy density diets are associated with higher energy (calorie) intakes and that energy density has a stronger impact on energy intake than does any one macronutrient (Rolls et al., 2005). Because lower fat diets generally have a lower energy density, however, fat reduction can be an effective strategy for reducing calorie intake as long as fat calories are exchanged for foods that are naturally low in energy density—fruits, vegetables, and whole grains—or for foods that contain an ingredient such as olestra that has been modified to deliver all the taste and texture benefits of natural fat without the calories. For example, on average, every person in America eats 21 pounds of salted snacks per year. Those snacks contain nearly 6 pounds—more than 22,800 calories—of fat. As a nation, Americans eat more than 5.6 billion pounds of salted snacks per year. In these snacks, they consume about 774,000 tons of fat, or more than 6 trillion calories. If only 10% of these people ate snacks made with olestra instead of full-fat snacks, Americans would avoid 77,400 tons of fat and more than 600 billion calories in a single year. A 1-ounce serving of potato chips fried with olestra contains only 70 calories and 0 g of fat versus 150 calories and 10 g of fat in regular chips (Table 3.2). Since olestra has been available, consumers have purchased more than 5 billion servings of olestra products, saving more than 130 million pounds of body fat.

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Table 3.2. The impact of olestra Full Fat Potato Chips (28 g) Fat/serving kcal/serving Tortilla Chips (28 g) Fat/serving kcal/serving Cheese Curls (28 g) Fat/serving kcal/serving

100% Olestra

10 g 150 8g 150

0g 70

% Reduction 100 55

1 g from corn 90

85 40

>1 70

85 45

10 160

Source: The Procter & Gamble Company.

Dieting versus “Lifestyling” Although numerous diets are available to help people lose weight in the short term, successful weight-loss maintenance and the prevention of the weight gain associated with aging require a permanent change in lifestyle. For example, dietary fat reduction is a popular weight-loss strategy, but long-term compliance with any diet that restricts food is too challenging for most people. As James Hill and others have demonstrated, food restriction is not only contrary to human biology but also creates counterproductive metabolic changes (Hill, 2006). According to data from the 5,000-plus-member National Weight Control Registry (www.nwcr.ws), however, incorporating fat-modified foods into the diet is a strategy frequently used by people who are successful with weight maintenance. Not all mimetics and substitutes used to replace dietary fat can withstand the high heat of frying or baking and not all are as flavorful as natural fat. In addition, some fat replacers still contain calories—sometimes more than the number of calories found in carbohydrate and protein. Olestra, however, can be used at high temperature, mimics the taste and texture of “real” fat, and adds no calories. Human studies reviewed in a 2001 issue of Critical Reviews in Food Science and Nutrition and in a 2002 issue of Obesity Reviews have shown the short-term and long-term effects of a sucrose polyester such as olestra on energy intake and satiety in adults and children (Eldridge et al., 2002; Stubbs, 2001). For example: r When olestra was used to reduce fat from approximately 40% of

energy to 30% of energy over a 10-week period, the body did not metabolically detect the lost fat. Study subjects using olestra barely

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compensated for the lost energy. Subjects consuming a traditional reduced-fat diet, however, experienced greater energy compensation (Roy et al., 2002). r In a 9-month randomized clinical trial of healthy obese men, a diet in which olestra was substituted for one-third of dietary fat (resulting in a diet with 33% total fat, but only 25% metabolizable fat) was compared with diet having 33% and 25% calories from fat without olestra. Subjects on the olestra diet lost more weight and more body fat than did those in the other two groups (Bray et al., 2002; Lovejoy et al., 2003). These studies suggest an important role for olestra in allowing people to have access to good-tasting foods that normally would be restricted on a weight-loss diet and thus improving short- and long-term diet compliance.

Olestra’s Potential Food Applications Olestra can be used to modify the energy density of food wherever intrinsic fat is present. Removing just 1–2 g of fat from the typical diet each day would prevent the 1- to 2-pound annual weight gain experienced by the average adult (Hill, 2006; Hill et al., 2003). Because the olestra molecule can be manipulated for application in a wide variety of food formulations, it is an ideal choice for eliminating all fat, and thus all calories from fat, in some foods or for blending with dietary fat for reducing calorie content. When P&G first introduced olestra, its use in savory snacks such as chips and then microwave popcorn was aimed at eliminating fat from indulgent foods, thus making it easier for people to enjoy these items and still cut down on calories. As olestra technology has progressed, P&G scientists have been successful in lowering fat calories while preserving taste and texture by using olestra oil, shortening, and fat blends in a wide variety of products (Table 3.3).

Other Health Considerations In addition to its potential impact on weight prevention, loss, and maintenance, olestra has been shown to have a positive impact on cardiovascular and metabolic risk factors such as cholesterol level, blood pressure, and fasting insulin. In one study, “consumption of a low-fat diet containing olestra for 9 months produced significant improvement in cardiovascular risk factors” such as the reduction LDL (bad) cholesterol and triglyceride

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Table 3.3. Olestra fat/oil replacement formulation matrix Applications Capable Today Baked Goods Dough Cookies Cakes Pie crusts Biscuits Frying Chips French fries Doughnuts Fried meats/fish Other Confectionary coatings Popcorn

Olestra Oil

Olestra Blends

Olestra Shortening

X

X X X X

X X X X X

X X X X

X X X X

X

Formulations: Fast Development Dairy Ice cream Processed cheese Cheddar Mozzarella Cream cheese Spreads Mayonnaise X Peanut butter Margarines X Other Fillings/icings Confections/candy Prepackaged direct fat substitute X Formulations: More Development Needed Dairy Custard/pudding Cottage cheese Milk Yogurt Cream Other Sauces/gravies Meats/sausage Source: The Procter & Gamble Company.

X X X X X

X

X X X

X X X X X TBD TBD

X

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levels, and increased HDL (good) cholesterol. The researchers attribute these results to weight loss, which occurred because the study subjects using olestra were able to adhere to their low-fat diets for 9 months (Patterson et al., 2000; Roy et al., 2002). In another study, researchers demonstrated that just a single meal containing olestra can have a positive effect on the resiliency of blood vessels (Cook et al., 2000). Olestra also may provide a therapeutic approach for reducing levels of fat-soluble environmental contaminants in the body such as dioxin (Geusau et al., 1999; Moser and McLachlan, 1999). In addition, olestra may assist in ridding the body of fat-soluble organochlorines released into the blood stream by adipose tissue during weight loss. Organochlorines, which are found in substances such as lubricants and coolants for electrical appliances and in insecticides such as DDT, resist degradation and are stored in fat cells. They have been associated with cancer as well as immune system and thyroid disorders (Pelletier et al., 2003).

References American Dietetic Association. Position of the American Dietetic Association: fat replacers. J Am Diet Assoc 2006;106(2):266–275. Bray GA, Lovejoy JC, Most-Windhauser M, Smith, SR, Volaufova J, Denkins Y, de Jonge L, Rood J, Lefevre M, Eldridge AL, Peters JC. A 9-mo randomized clinical trial comparing fat-substituted and fatreduced diets in healthy obese men: the Ole Study. Am J Clin Nutr 2002;76: 928–934. Cook B, Cooper D, Fitzpatrick D, Smith, S, Tierney D. The influence of a high fat meal compared to an olestra meal on coronary artery endothelial dysfunction by rubidium (RB)-82 positron emission tomography (PET) and on post prandial serum triglycerides. Clin Positron Imaging 2000;4:150. Research chosen for presentation to the media at the 12th Annual International PET Conference, October 18, 2000, Washington, DC. Drewnowski A, Rolls BJ. How to modify the food environment. J Nutr 2005;135:898–899. Eldridge AL, Cooper DA, Peters JC. A role for olestra in body weight management. Obesity Rev 2002;3:17–25.

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Geusau A, Tschachler E, Meixner M, Sandermann S, Papke O, Wolf C, Valic E, Stingl G, McLachlan M. Olestra increases faecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Lancet 1999;354(9186):1255– 1267. Hill JO. Understanding and addressing the epidemic of obesity: an energy balance perspective. Endocrine Rev 2006;27:750–761. Hill JO, Wyatt HR, Reed GW, Peters JC. Obesity and the environment: where do we go from here? Science 2003;299:853–855. International Food Information Council. IFIC review: uses and nutritional impact of fat reduction ingredients. 2000. Available online at www.ific.org/publications/reviews/upload/Uses-Nutritional-Impactof-Fat-Reduction-Ingredients.pdf. Lovejoy JC, Bray GA, Lefevre M, Smith SR, Most MM, Denkins YM, Volaufova1 J, Rood JC, Eldridge, AL, Peters JC. Consumption of a controlled low-fat diet containing olestra for 9 months improves health risk factors in conjunction with weight loss in obese men: the Ole
Study. Int J Obesity 2003;27:1242–1249. Moser GA, McLachlan MS. A non-absorbable dietary fat substitute enhances elimination of persistent lipophilic contaminants in humans. Chemosphere 1999;39(9):1513–1521. Patterson RE, Kristal AR, Peters JC, Neuhouser ML, Rock CL, Cheskin LJ, Neumark-Sztainer D, Thornquist MD. Changes in diet, weight, and serum lipid levels associated with olestra consumption. Arch Intern Med 2000;160:2600–2604. Pelletier C, Imbeault P, Tremblay A. Energy balance and pollution by organochlorines and polychlorinated biphenyls. Obes Rev 2003;4(1):17–24. Peters JC. Dietary fat and body weight control. Lipids 2003;38:123–127. Rolls BJ, Drewnowsk A, Ledikwe JH. Changing the energy density of the diet as a strategy for weight management. J Am Diet Assoc 2005;105:S98–S103. Roy HJ, Most MM, Sparti A, Lovejoy JC, Volaufova J, Peters JC, Bray GA. Effect on body weight of replacing dietary fat with olestra for two or ten weeks in healthy men and women. J Am Coll Nutri 2002;21(3):259– 267.

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Stubbs RJ. The effect of ingesting olestra-based foods on feeding behavior and energy balance in humans. Crit Rev Food Sci Nutr 2001;41(5):383–386. Available online at http://dx.doi.org/10.1080/ 20014091091850. Wright JD, Kennedy-Stephenso J, Wang CY, McDowell MA, Johnson CL. Trends in intake of energy and macronutrients—United States, 1971–2000. Morb Mortal Wkly Rep 2004;53(4):80–82.

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CHAPTER 4

The Effects of a Novel Fat R / Emulsion (Olibra
FabulessTM) on Energy Intake, Satiety, Weight Loss, and Weight Maintenance Rick Hursel, MSc, and Prof. Dr. Margriet Westerterp-Plantenga, PhD

Abstract As obesity is becoming a major problem in the developed countries, scir / ence tries to find strategies for weight loss and weight maintenance. Olibra
TM Fabuless is an example of such a strategy. This fat emulsion can replace milk fat, and through its physicochemical properties, it may increase satiety. Shortr /FabulessTM has a suppressive effect on the term studies have shown that Olibra
appetite ratings and that it enhances satiety. Only the studies from Burns et al. reported an actual lowering effect on energy intake. They also showed that there is a r /FabulessTM on energy intake. No effect was seen dose-response effect of Olibra
considering energy intake on the long term, but the fat emulsion did contribute to weight maintenance in a long-term study by Diepvens et al., due to decreased r /FabulessTM has been feelings of hunger. The observed satiating effect of Olibra
suggested to be the result of the ileal brake mechanism. This ileal brake initiates a feedback loop that inhibits upper gut motility (to slow gastric emptying and 55

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intestinal transit) in response to nutrients in the distal small intestine, which cause r /FabulessTM components are entirely natural and no satiety signals. The Olibra
study recorded any side effects.

Introduction The prevalence of obesity has increased worldwide during the past few decades (Seidell, 1998). Obesity is a major causative factor for a number of diseases, including coronary heart disease, hypertension, noninsulindependent diabetes mellitus, pulmonary dysfunction, and certain types of cancer (Stunkard, 1996). Obesity develops when the equilibrium between energy intake (EI) and energy expenditure (EE) shifts toward a positive energy balance. Treatment of obesity is beneficial in that weight loss reduces the risk for mortality and morbidity. Even modest weight loss, such as 5–10% of the initial body weight, has beneficial health effects (Goldstein, 1992). Body weight loss and prevention of body weight (re)gain can be achieved by reducing EI and/or increasing EE, or promoting fat oxidation. r is a novel fat emulsion consisting of a mixture of fractionated Olibra
palm oil (40%) and fractionated oat oil (2.5%) in water. The emulsion r corresponds to can be incorporated into yogurts, whereby 5 g of Olibra
about 2 g of milk fat, the common fat in yogurts (Diepvens et al., 2007). r , may have Fats with different physicochemical properties, such as Olibra
different effects on satiety (Burns et al., 2000). r is an example of an active ingredient that aims to promote Olibra
reduction of EI by promoting and maintaining satiety. R Efficacy of Olibra


Short-Term Experiments Burns et al. were the first to report the effects of a novel fat emulsion, also r . In their initial study, they investigated the short-term known as Olibra
r on the dietary intakes of nonobese subjects, especially effects of Olibra
energy and macronutrient intakes (Burns et al., 2000). Subjects received either yogurt with the novel fat emulsion or yogurt that contained normal dairy fat. Results showed that EI was significantly decreased (13.9% reduction in EI, p > 0.001; EI: 6.67 ± 2.1 MJ after test yogurt compared to 7.75 ± 1.8 MJ after placebo yogurt) at a meal, 4 hours postconsumption of r compared to the control yogurt. Fat (18.9%), carthe yogurt with Olibra
bohydrate (10.1%), and protein (12.1%) intake were significantly reduced

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after the test yogurt compared to the placebo yogurt, with the strongest reduction in fat intake. Subjects also ate a smaller amount of food after the intervention with the novel fat emulsion (Burns et al., 2000). These results indicate that subjects were more satiated 4 hours postconsumption of the test yogurt compared to the control yogurt. Appetite was rated with visual analogue scales (VASs, in mm). Subjects reported that they felt r containing yogurt and that they ate less more satiated after the Olibra
for the remainder of the day (till 21:00 hour) following the control yogurt (Burns et al., 2000). Whether these obtained results are also applicable in obese subjects remained unknown from this study. It was expected that obese subjects would respond differently because they have an increased preference for high-fat foods, although these foods are less satiating in obese subjects (Lawton et al., 1993). In a subsequent study, Burns et al. conducted a study that was comparable to the first one. In addition to the nonobese subjects participating in the previous study, they also included overweight and obese subjects. They extended the observation of the subjects from 4 to 8 hours postconsumption. It was shown that, in comparison with a yogurt containing normal r significantly milk fat, consumption of a 200-g yogurt containing Olibra
decreased EI in normal weight and overweight subjects, at a meal 4 and 8 hours later, and in obese subjects 8 hours postconsumption, and that the decreased intake persisted for the rest of the day (Burns et al., 2001). However, the magnitude of the responses observed 4 hours postconsumption were not as significant in the overweight (27.6% reduction in EI, p < 0.05; EI: 4.43 ± 0.38 MJ after test yogurt compared to 6.12 ± 0.47 MJ after placebo yogurt) and obese group (13.1% reduction in EI, ns; EI: 4.56 ± 0.41 MJ after test yogurt compared to 5.25 ± 0.44 MJ after placebo yogurt) compared to the nonoverweight group (30.2% reduction in EI, p < 0.05; EI: 3.82 ± 0.29 MJ after test yogurt compared to 5.38 ± 0.34 MJ after placebo yogurt). Furthermore, despite reduced subsequent EI, contradictory results were seen in hunger and satiety recordings (Burns et al., 2001). It was speculated by Burns et al. that the lower response of the obese r may have been caused because subjects to the yogurt containing Olibra
of a lower dose (expressed relative to body weight) (Burns et al., 2001). The same research group investigated this hypothesis and they revealed that relative to the control yogurt, mean EIs (2 g: 21% reduction in EI, EI: 5.83 ± 1.91 MJ; 4 g: 25% reduction in EI, 5.60 ± 1.89 MJ; 6 g: 30% reduction in EI, 5.24 ± 1.91 MJ compared to control yogurt 7.42 ± 1.89 r in subjects MJ, p > 0.05) were reduced with an increasing dose of Olibra
with normal weight and overweight (Burns et al., 2002). A larger effect after the test yogurt was seen in females in contrast to males, which can

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be explained by higher body weight in male subjects. Males received a lower dose relative to their body weight (Burns et al., 2002). There were no significant differences regarding satiety and appetite ratings between control and different dosages (Burns et al., 2002). r on appetite Diepvens et al. also studied the short-term effects of Olibra
and food intake (Diepvens et al., 2008), since results, as obtained by Burns et al., had not been confirmed by other studies, thus far (Burns et al., 2000, 2001, 2002). Consequently, the aim of this study was to assess the effect r versus placebo in the short term by investigating the possible of Olibra
r in junior-normal weight and senior-overweight groups, effects of Olibra
on appetite ratings and EI 4 hours later, in similar groups as in the Burns studies. No difference was seen in food intake (test: 467.6 ± 114.3 g; placebo: 450.1 ± 90.7 g) between the test yogurt and the placebo yogurt, r emulsion did at lunch 4 hours postconsumption. However, the Olibra
exert a suppressive effect on appetite ratings in the short term (Diepvens et al., 2008). Nevertheless, this was not sufficient to reduce EI. Less food was eaten in the junior-normal weight group compared to the senioroverweight group, which can be subscribed to the higher bodyweight of the latest. As explained before, the dosage may have been insufficient for this group. There might be a possibility that the emulsion prevents overeating, but this could not be confirmed by this study (Diepvens et al., 2008).

Long-Term Experiments After the positive effects of the short-term studies by Burns et al., it r has any long-term effects as well. was time to reveal whether Olibra
r emulsion during Logan et al. investigated the effects of the Olibra
r , 3 weeks. Subjects received either 200 g yogurt, containing 5 g Olibra
or the control that was 5 g of milk fat. On day 1, 8, and 22, food intake 4 hours postconsumption of the yogurts was assessed (Logan et al., 2006). In contrast to some short-term studies, no long-term effects were found r containing yogurt (day 1, EI: 5.04 ± 1.54 after consuming the Olibra
MJ after test yogurt compared to control yogurt EI: 5.06 ± 1.54 MJ, ns; day 8, EI: 4.92 ± 1.40 MJ after test yogurt compared to control yogurt EI: 5.22 ± 1.67 MJ, ns; day 22, EI: 5.02 ± 1.57 MJ after test yogurt compared to control yogurt EI: 5.06 ± 1.46 MJ, ns). There was neither on day 1, 8, or 22 a significant difference in mean energy, macronutrients, or amounts of food eaten 4 hours postconsumption. The appetite ratings also failed to result in any significant effects (Logan et al., 2006).

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Logan et al. came up with several explanations for the results of their study. The eating environment during lunch, for instance, was more sociable compared to the results of previous studies, which can influence food intake. People tend to overeat when the ambience is more sociable (Stroebele and De Castro, 2004). Another reason may be the period in which the study was conducted, August and November. People are more prone to overeat during autumn and winter compared to summer and spring (Shahar et al., 2001). In another long-term study, Diepvens et al. assessed a possible weight r maintenance (after a very low energy diet) by consumption of Olibra
up till 18 weeks. Hunger ratings, satiety-related hormones, resting energy expenditure (REE), and body composition were assessed as well (Diepvens et al., 2007). After the weight-loss period, the subjects in the r containing yogurt, showed no significant test group, who ate the Olibra
increase in weight (1.2 kg (15.5%) regain, ns) in contrast with the subjects who ate the control yogurt (3.0 kg (40.3%) regain, p > 0.05) (Figs. 4.1 and 4.2) Glugacon-like peptide-1 (GLP-1) values were significantly increased at 180 minutes postconsumption of the test yogurt at week 25 compared to week 1. In week 25, a significant difference was found between both groups, in that the test group was less hungry 4 hours after the yogurt compared with the placebo group (Diepvens et al., 2007). REE

84

Olibra Placebo

82

Body weight (kg)

80 78 76 74 *

72 70 68 8

2

26

Week

Figure 4.1. During weight maintenance, there was significant body weight r regain in the placebo group (p < 0.001), but not in Olibra
group. * indicates p < 0.001 regain (kg) in placebo group (ANOVA repeated measures). (After Diepvens et al., 2007.)

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Percentage of weight regain

p=0.05 50 40 30 20 10 0 Olibra

Placebo

r Figure 4.2. Regain as percentage of weight loss was lower with Olibra
as compared to placebo yogurt. Two-factor ANOVA repeated measures. (After Diepvens et al., 2007.)

was significantly increased in the test group in week 25 compared to week 7, but the same occurred in the placebo group as well. The increased REE in both groups might be a consequence of the increase in fat-free mass (FFM), as FFM is the main determinant of REE. For this reason, REE was corrected for FFM and results showed that the increase in REE could not r . fully be attributed to the increase in FFM, but also to the effect of Olibra
After the correction, where REE was expressed as a function of FFM, REE was significantly increased in the test group and not in the placebo group. An FFM sparing effect occurred that prevented a lowered REE as fat mass (FM) decreased more in the test group compared to the placebo group, which was also shown by a decreased weight circumference in the test group (Diepvens et al., 2007). Eventually, this group did not regain as much weight as the placebo group, after the period of weight loss, due to a decreased feeling of hunger and an increase in REE. Another explanation r might be that participants in for the weight-maintenance effect of Olibra
the weight-maintenance study had to eat the yogurt twice a day instead of once, as in the other long-term study where the effect on EI was assessed r was higher here, (Diepvens et al., 2007). The dose of consumed Olibra
which had been proven to be of influence by Burns et al. (Burns et al., 2002).

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Mechanisms of Action r The observed effect of Olibra
has been suggested to be the result of the ileal brake mechanism (Burns et al., 2000, 2001, 2002). This ileal brake, for which fat is the most important trigger, initiates a feedback loop that inhibits upper gut motility (to slow gastric emptying and intestinal transit) in response to nutrients in the distal small intestine (Maljaars r to increase satiety can be attributed to et al., 2007). The ability of Olibra
the physicochemical properties of the emulsion. The palm oil core of the relatively small emulsion particles is covered by hydrophilic galactolipids derived from the fractionated oat oil. Due to this particular combination of triglyceride oils, resulting in delayed digestion compared to the milk fat particles, (partly) undigested particles may penetrate more distal parts of the small intestine, where sensors will detect unabsorbed fat and send satiety signals (e.g., GLP-1, CCK, PYY) to the brain. This delayed gastric emptying may evoke an indirect satiety effect (Welch et al., 1985, 1988) whereby possible inhibition of food intake is not preceded by differences in appetite ratings. However, a direct satiating effect of ileal fat perfusion without a preceding meal (Maljaars et al., 2007) was also observed; so the appetite pattern after consumption of the palm oil and fractionated oat oil may not be completely predictive for EI thereafter.

Safety The FabulessTM components are entirely natural and no study recorded any side effects. Burns et al. measured the adverse effects and gastrointestinal complaints in their subjects. They reported that the subjects did not experience any adverse effects or discomfort after the consumption of the novel fat emulsion, even not with increasing dosages (Burns et al., 2000, 2001, 2002).

Food/Supplement Applications r FabulessTM (formerly known as Olibra
) has many applications in dairy products, as the structure and composition of dairy are particularly suited to this ingredient. When administered to dairy products, the novel fat emulsion appears to enhance texture as dairy products containing FabulessTM are perceived as creamier and fuller. FabulessTM has also been launched in the form of a supplement concept. A small bottle containing the

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effective daily dose of FabulessTM offers a convenient solution for weight management, as it is supposed to reduce EI.

Patent Activities Document ID: U.S. Patent 6517883 European Patent EP0994655 Title: Satiety product Assignee: LTP Lipid Technologies Provider AB

Information on Global Suppliers After DSM (The Netherlands) gained a main interest in LTP Lipid Technologies Provider AB (Sweden), and with this the exclusive right r , they introduced the first dairy product for the production of Olibra
TM with Fabuless , “ActifControl,” in Italy. Subsequently, a dairy product with FabulessTM was launched in Portugal under the brand name “Adagio Versus.” Campina launched “Optimel Control” with FabulessTM in The Netherlands. Supplements with FabulessTM are also launched in Belgium, Spain, United Kingdom (Slimthru), United States, and Turkey.

References Burns AA, Livingstone MB, Welch RW, Dunne A, Reid CA, Rowland IR. The effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-overweight, overweight and obese subjects. Int J Obes Relat Metab Disord 2001;25:1487–1496. Burns AA, Livingstone MB, Welch RW, Dunne A, Robson PJ, Lindmark ´ Rowland IR. Short-term effects of yoghurt L, Reid CA, Mullaney U, containing a novel fat emulsion on energy and macronutrient intakes in non-obese subjects. Int J Obes Relat Metab Disord 2000;24:1419– 1425. Burns AA, Livingstone MB, Welch RW, Dunne A, Rowland IR. Doseresponse effects of a novel fat emulsion (Olibra) on energy and macronutrient intakes up to 36 h post-consumption. Eur J Clin Nutr 2002;56:368–377.

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Diepvens K, Soenen S, Steijns J, Arnold M, Westerterp-Plantenga M. Long-term effects of consumption of a novel fat emulsion in relation to body-weight management. Int J Obes (Lond) 2007;31:942–949. Diepvens K, Steijns J, Zuurendonk P, Westerterp-Plantenga M. Shortterm effects of a novel fat emulsion on appetite and food intake. Physiol Behav 2008,95:114–117. Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord 1992;16:397–415. Lawton CL, Burley VJ, Wales JK, Blundell JE. Dietary fat and appetite control in obese subjects: weak effects on satiation and satiety. Int J Obes Relat Metab Disord 1993;17:409–416. Logan CM, McCaffrey TA, Wallace JM, Robson PJ, Welch RW, Dunne A, Livingstone MB. Investigation of the medium-term effects of Olibratrade mark fat emulsion on food intake in non-obese subjects. Eur J Clin Nutr 2006;60:1081–1091. Maljaars J, Peters HP, Masclee AM. Review article: the gastrointestinal tract: neuroendocrine regulation of satiety and food intake. Aliment Pharmacol Ther 2007;26(Suppl 2):241–250. Seidell JC. Dietary fat and obesity: an epidemiologic perspective. Am J Clin Nutr 1998;67:546S–550S. Shahar DR, Yerushalmi N, Lubin F, Froom P, Shahar A, Kristal-Boneh E. Seasonal variations in dietary intake affect the consistency of dietary assessment. Eur J Epidemiol 2001;17:129–133. Stroebele N, De Castro JM. Effect of ambience on food intake and food choice. Nutrition 2004;20:821–838. Stunkard AJ. Current views on obesity. Am J Med 1996;100:230–236. Welch I, Saunders K, Read NW. Effect of ileal and intravenous infusions of fat emulsions on feeding and satiety in human volunteers. Gastroenterology 1985;89:1293–1297. Welch IM, Sepple CP, Read NW. Comparisons of the effects on satiety and eating behaviour of infusion of lipid into the different regions of the small intestine. Gut 1988;29:306–311.

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Protein based ingredients

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CHAPTER 5

The Role of Dairy Products and Dietary Calcium in Weight Management Lisa A. Spence, PhD, RD, and Raj G. Narasimmon, PhD

Abstract Overweight and obesity are global public health concerns. Excess body fat increases the risk of premature death, coronary heart disease, type 2 diabetes, hypertension, stroke, some types of cancer, and other debilitating conditions. The cause of overweight and obesity is multifactorial and successful prevention or treatment depends on multiple actions. Although attention has focused primarily on reducing energy (calorie) intake and/or increasing energy expenditure (physical activity), a promising beneficial role for dietary calcium and dairy products in weight management has emerged. Overall, the body of scientific evidence including human, clinical, observational, animal, and cellular studies supports a relationship between the consumption of dairy foods and weight management. While consumption of dairy foods has been shown to exert a greater impact than calcium alone, studies continue to examine the mechanism to explain this phenomenon, which appears to be multifactorial and may involve bioactive components found in dairy foods. While there is more to learn about dairy food consumption’s impact on weight management, the Dietary Guidelines recommend 3 servings of low-fat and fat-free milk or equivalent milk products (e.g., cheese, yogurt) daily as part of a healthy diet and stresses the importance of balancing calories consumed from foods and beverages with calories expended to achieve and maintain a healthy body weight.

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Introduction Overweight and obesity are global public health concerns (Wang and Lobstein, 2006; WHO, 2000). In the United States, statistics indicate that more than 66% of adults are overweight or obese and 17% of children aged 2–19 years are overweight (Ogden et al., 2006). If current trends continue, nearly half of the children in North and South America will be overweight by 2010 (Wang and Lobstein, 2006). Excess body fat increases the risk of premature death, coronary heart disease, type 2 diabetes, hypertension, stroke, some types of cancer, and other debilitating conditions. Because of these health outcomes, as well as the adverse economic consequences of overweight and obesity, numerous government programs are focused on obesity prevention. The cause of overweight and obesity is multifactorial and successful prevention or treatment depends on multiple actions. Although attention has focused primarily on reducing energy (calorie) intake and/or increasing energy expenditure (physical activity), a promising beneficial role for dietary calcium and dairy products in weight management has emerged. Several review articles have been published summarizing the observational and clinical data published to date and elucidating the mechanism of action (Barr, 2003; Heaney, 2003; Heaney et al., 2002; Major et al., 2008; Parikh and Yanovski, 2003; Schrager, 2005; St-Onge, 2005; Teegarden, 2003, 2005; Trowman et al., 2006; Zemel, 2001, 2002, 2003a, 2003b, 2005). One such review indicated that each 300 mg increase in calcium intake was associated with about 1 kg less body fat in children and as much as 3 kg lower weight in adults. These researchers also reported that increasing calcium intake by 2 servings of dairy products (600 mg calcium) per day could reduce the risk of being overweight by as much as 70% (Heaney, 2003). A recent review by Major et al. (2008) presented information by experts in the field of calcium/dairy and weight loss during a 2007 symposium. The review integrates current developments in calcium-related obesity research focusing on the effects of calcium and dairy consumption on (1) body weight, (2) adiposity, (3) weightloss intervention outcome, (4) lipid–lipoprotein profile, and (5) the risk of developing metabolic syndrome. Moreover, the review discusses the potential molecular mechanisms that explain the effects of dairy and calcium, such as increased adipocyte calcium concentrations and changes in lipolysis, lipogenesis, calcium intake and fat cell apoptosis, calcium intake and UCP2 expression, calcium intake on satiety, and calcium intake and fecal fat excretion.

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This chapter reviews the current scientific evidence, including human clinical interventions, observational studies, and animal research that has explored the relationship between the consumption of dairy foods and weight management as well as plausible mechanisms by which dairy products may favorably affect body weight, body fat, and lean mass. The chapter also addresses food application and patent activities.

Scientific Evidence on Efficacy and Mechanism of Action Randomized Clinical Trials Controlled feeding studies in humans are considered the “gold standard” for interventions and have provided the strongest evidence for a beneficial role of dairy foods and calcium on body weight and body fat. Since 1998, there have been several published reports (Bowen et al., 2005; Eagan et al., 2006; Gunther et al., 2005a; Harvey-Berino et al., 2005; Major et al., 2007; Summerbell et al., 1998; Thompson et al., 2005; Wagner et al., 2007; Zemel et al., 2004, 2005a, 2005b, 2009) of randomized trials designed to evaluate the effects of calcium and/or dairy product consumption on body weight and fat loss under caloric restriction in obese and overweight adults or changes in body composition under caloric maintenance in obese and normal-weight adults as the primary outcome. Some human studies (Boon et al., 2005a; Cummings et al., 2006; Gunther et al., 2005b; Jacobsen et al., 2005; Lorenzen et al., 2007; Melanson et al., 2005) have been conducted to compare the effect of increased calcium or dairy product consumption on energy expenditure, substrate oxidation, thermic effect of food, and/or fecal fat excretion to understand the mechanism by which calcium or dairy products may impact body weight and composition. In many of these studies, overweight or obese adults (males, females, Caucasians, African Americans) who followed moderately reducedcalorie diets for 12 or 24 weeks, and increased consumption of dairy foods from 1 serving or less per day (inadequate calcium) to ≥3 servings per day (adequate calcium), experienced enhanced body weight and/or body fat loss, reduced abdominal (trunk) obesity, and minimal loss of lean body mass compared to those consuming little or no dairy foods. Moreover, the intake of dairy foods had a substantially greater effect on both weight and fat loss compared to an equivalent amount of calcium alone.

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Importantly, three physiological and dietary conditions were common in those studies showing favorable weight-loss effects of dairy/calcium. First, all study subjects were obese or overweight. Second, the subjects’ habitual calcium intakes were inadequate (<600 mg/day). Third, all subjects consumed moderately reduced-calorie diets to induce weight loss (i.e., 500 kcal/day less than required to maintain weight). These studies indicate that the impact of dairy foods on augmenting body weight and body fat loss depends on factors such as calorie intake, baseline calcium or dairy food intake, and initial body weight (i.e., overweight or normal weight). Studies of Body Weight and Body Composition Several studies (Summerbell et al., 1998; Zemel et al., 2004, 2005a, 2005b, 2009) reported greater body weight and/or fat loss in obese and/or overweight adults consuming dairy products and/or calcium as part of an energy restriction protocol. In contrast, other published studies reported no significant differences between dietary groups in body weight and fat loss under energy restriction in overweight and obese adults consuming low or moderate versus adequate dairy diets nor with calcium supplementation, nor within high-protein diets utilizing dairy products (Bowen et al., 2005; Harvey-Berino et al., 2005; Major et al., 2007; Thompson et al., 2005; Wagner et al., 2007). One published study (Gunther et al., 2005a) in normal-weight women showed no effect of dairy product consumption on body composition under energy balance conditions after 1 year. However, in the same women followed for an additional 6 months, those who continued to consume higher dairy/calcium diets had reduced fat mass compared to women consuming low-dairy/low-calcium diets (Eagan et al., 2006). The following provides details from studies, which used both energy restriction and energy balance plus dairy foods and/or calcium as part of a balanced diet to investigate impact on body weight and composition. Zemel et al. (2004) reported on 32 obese adults maintained for 24 weeks on a calorie-restricted diet, with macronutrients maintained at average U.S. levels across all treatment groups, that increasing dietary elemental calcium significantly enhanced body weight (p < 0.01) and body fat (p < 0.01) loss compared to a low-calcium/low-dairy diet. Consumption of dairy products (milk, cheese, yogurt) at recommended intakes of 3 servings per day exerted a substantially greater effect compared to the elemental calcium-rich group (p < 0.01) (Fig. 5.1). In addition, the dairy group exhibited a significant improvement in glucose tolerance, a 44% decrease in plasma insulin levels (p < 0.01), and a modest reduction in systolic

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0

Body fat reduction (%)

−2 −4 −6 −8 −10 −12 −14 −16

p < 0.01 p < 0.01 Low calcium

High calcium

High dairy

Figure 5.1. Effects of high-calcium and high-dairy diets on body fat reduction. (From Zemel et al., 2004.)

blood pressure (p < 0.02) compared to the other two groups. A similarly designed multicenter trial (Zemel et al., 2009) of 68 overweight and obese adults maintained for 12 weeks on a calorie-restricted diet reported that elemental calcium-rich diet exerted no significant effects on weight loss or body composition compared to a low-calcium diet. However, the diet providing equivalent calcium supplied from 3 servings per day of milk, cheese, and yogurt resulted in augmented weight loss (p = 0.07), fat loss (p < 0.025), trunk fat (p < 0.05), and waist circumference (p < 0.025) compared to the low-calcium diet and the elemental calcium-rich diet. A study of 34 obese adults maintained for 12 weeks on a calorierestricted diet that included 3 servings per day of yogurt resulted in enhanced body weight and body fat loss (p < 0.005), waist circumference (p < 0.001), and trunk fat (p < 0.001) compared to a low-calcium/lowdairy calorie-restricted diet (Zemel et al., 2005b). Further evidence comes from a 24-week study in 29 obese African American adults on calorierestricted diets including 3 servings per day of dairy foods (milk, yogurt, and cheese), which resulted in approximately twofold greater (p < 0.01) body weight and fat loss compared to a low-calcium/low-dairy diet (Zemel et al., 2005a). Additionally, the diet of 3 servings of dairy foods per day produced greater trunk fat loss (p < 0.01) and reduced loss of lean mass (p < 0.001) compared to the low-calcium/low-dairy diet.

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In contrast to the above studies, Harvey-Berino et al. (2005) reported no significant difference in weight or body fat loss under caloric restriction (increased exercise expenditure plus energy restriction) between subjects who consumed 3 servings per day of dairy foods (milk, cheese, and yogurt) versus those who consumed less than 1 serving per day. Based on reported daily energy intake and expenditure, subjects consuming 3 servings per day of dairy foods were in a more positive energy balance (less caloric restriction), but still lost equivalent amounts of body weight and fat as subjects consuming little or no dairy foods. Thompson et al. (2005) investigated the impact of moderate (2 servings per day) versus adequate calcium or dairy intakes (4 servings per day) with caloric restriction in obese adults and found no significant difference in weight or body fat loss between groups. The subjects consuming the greater amounts of dairy foods consumed approximately 150 kcal/day more compared to the subjects consuming lower amounts of dairy foods per day (p = 0.034). Therefore, comparable loss in body weight and fat loss were achieved at a higher energy intake for the subjects consuming higher amounts of dairy foods. In a 15-week study of calcium and vitamin D supplementation, Major et al. (2007) reported no differences in weight and body fat loss in overweight and obese women supplemented with 1,200 mg/day Ca and 400 IU/day vitamin D compared to the placebo group; both groups had an energy-restricted diet (700 kcal/day less than needed to maintain weight). However, the consumption of calcium plus vitamin D during this weightloss intervention did enhance the beneficial effect of body weight loss on lipid and lipoprotein profiles in these women compared to the placebo. Wagner et al. (2007) examined the effects of increased calcium intake (either supplemental calcium as calcium lactate and calcium phosphate or nonfat milk) on body weight, body fat, and markers of bone health in premenopausal adult women following a calorie-restricted diet for 12 weeks; no differences were observed in body weight and body fat among the groups consuming near-adequate calcium intakes versus high calcium intakes. In a randomized, parallel arm study, Bowen et al. (2005) compared the effects of two high-protein diets differing in dietary calcium and protein source on weight loss and body composition during 12 weeks of energy restriction in 50 healthy, overweight adults. The study diets, high dairy protein/high calcium (2,400 mg/day) and high mixed protein/low calcium (500 mg Ca/day), were matched for energy and macronutrients at 34% protein, 41% carbohydrate, and 24% fat as energy. There were no significant differences in weight, body fat, or lean mass after 12 weeks between the groups, and improvements in fasting insulin, lipids, and blood pressure were independent of the dietary group.

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A few studies have assessed dairy consumption’s effect on body composition changes when energy intake was maintained. Zemel et al. (2005a) reported that for 34 obese African American adults maintained for 24 weeks on a weight maintenance diet that included 3 servings per day of dairy foods (milk, cheese, and yogurt) resulted in enhanced body fat (p < 0.01) and trunk fat losses (p < 0.01) with an increase in lean mass (p < 0.04) compared to a low-calcium diet. Additionally, there was a decrease in insulin (p < 0.04) and a reduction in systolic pressure in subjects consuming 3 servings of dairy foods per day, while there were no significant changes in those in the low-dairy group. Gunther et al. (2005a) reported no significant effect after 1 year of dairy inclusion in the diet on body composition in 155 healthy normal-weight young women, aged 18–30 years. Subjects were randomized to a control group (subjects’ habitual dairy/calcium intake providing ∼800 mg calcium/day), medium dairy (1,000–1,100 mg calcium/day), or high dairy (1,300–1,400 mg/day). The two dairy groups were instructed to substitute low-fat dairy products for other foods to achieve the desired calcium levels and to maintain caloric intake. A portion of this cohort (n = 51) was (Eagan et al., 2006) followed for an additional 6 months after the completion of 1-year intervention with an assessment of body composition (body fat, lean mass) using DXA. The high-dairy group maintained a calcium intake at 1,027 ± 380 mg/day at 18 months compared with the control group that continued their usual intake at 818 ± 292 mg/day (p = 0.02). When controlling for baseline BMI in a regression analysis, mean calcium intake over the 18 months predicted a negative change in fat mass (p = 0.04). Authors concluded that increased dietary calcium intakes through dairy products may prevent fat mass accumulation in young, healthy, normal-weight women. Studies of Energy Expenditure, Substrate Oxidation, and Fecal Excretion Several clinical trials have assessed potential mechanisms of action by which calcium and dairy foods may regulate the use of fat calories by the body leading to lower body weight and fat. Increased consumption of calcium and dairy foods may stimulate calorie utilization through increased fat oxidation or may reduce the availability of fat calories to the body through decreased absorption of fat or increased satiety (leading to decreased food intake). Melanson et al. (2005) reported an increased 24-hour fat oxidation during energy deficit (diet plus exercise) compared to a low-calcium diet during energy deficit as well as compared to high- and low-dairy diets

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under energy balance conditions in 19 healthy, overweight adults maintained for 7 days on an isocaloric calcium-rich diet supplied from 2 to 3 servings per day of dairy foods. A study in 19 normal-weight women (aged 18–30 years) (Gunther et al., 2005b) reported that high dietary calcium intake (1,000–1,400 mg/day) from dairy foods consumed over 1 year was associated with greater postprandial fat oxidation after both a high and a low-calcium meal compared to low dietary calcium intake (<800 mg/day). Jacobsen and colleagues (2005) investigated the effects of low- and high-calcium intakes mainly from low-fat dairy foods in both highand normal-protein diets on 24-hour energy expenditure, fat oxidation, and fecal fat excretion in 10 healthy, nonobese adults under eucaloric conditions in a randomized crossover study with each dietary treatment fed for 1 week. The calcium intake had no effect on 24-hour energy expenditure or fat oxidation, but fecal fat excretion increased approximately 2.5-fold during the high-calcium, normal-protein diet and fecal energy excretion was significantly greater compared to the other two diets (p < 0.05). The authors speculate that the differences in fecal fat excretion between the high-calcium, normal-protein and high-calcium, high-protein diets may be due to greater calcium binding to dietary protein in the upper gastrointestinal track in the high-calcium, higher protein diet rather than calcium binding to dietary fat and being excreted as was observed in the high-calcium, normal-protein diet. The short-term increase in dietary calcium along with the normal protein intake increased fecal fat and energy excretion by ∼350 kJ/day, which may explain the mechanism by which high-calcium diets produces weight loss, and indicates that dietary protein level may be important. Boon et al. (2005a) examined the effects of dietary calcium intake on energy and substrate metabolism and adipose tissue enzyme mRNA expression in 12 healthy, nonobese men receiving three isocaloric diets for 1 week, which were high calcium/high dairy, high calcium/low dairy, and low calcium/low dairy in a randomized crossover design. Neither 24-hour energy expenditure nor fat oxidation was significantly affected by dietary treatment. Expression of genes involved in the lipolytic and lipogenic pathways did not differ significantly between dietary treatments. Cummings et al. (2006) investigated the acute effects of different sources of calcium on diet-induced thermogenesis, substrate oxidation, nonesterified fatty acids (NEFAs), and glycerol (both surrogate markers of lipolysis), over a 6-hour postprandial period in eight overweight and obese adults in a randomized crossover study. The treatments included breakfast meals either low in dairy calcium and vitamin D, high in nondairy

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calcium (calcium citrate) but low in vitamin D, or high in dairy calcium and vitamin D. The amount of calcium but not the source of calcium acutely impacted outcomes; that is, the high-calcium meal increased postprandial fat oxidation and led to less suppression of NEFAs compared to the low-calcium meal. Lorenzen et al. (2007) examined the effect of calcium intake on postprandial fat metabolism and appetite in a randomized crossover design of meals including dairy (high, medium, and low) or supplemental calcium. Calcium from dairy significantly reduced postprandial lipidemia likely due to reduced fat absorption compared to supplemental calcium. Neither source of calcium impacted appetite sensation, energy intake at the subsequent meal, or on the postprandial responses of several hormones involved in satiety. The clinical trials to date support the notion that diets including 3 servings per day of dairy foods, high in calcium and a good source of protein, enhance body weight and body fat loss by targeting the fat compartment during energy restriction in obese and overweight individuals. As mentioned previously, three important elements are apparent in the weight-loss studies: (1) caloric deficit is maintained; (2) baseline intakes of calcium and dairy are inadequate and an appropriate control group with inadequate intakes is compared to a test group with adequate intake; (3) individuals are obese and overweight adults. While consumption of dairy foods has been shown to exert a greater impact than calcium alone, studies continue to examine the mechanism to explain this phenomenon that appears to be multifactorial. The enhanced loss of body weight and body fat in obese and/or overweight individuals with the consumption of an adequate calcium diet from dairy foods versus elemental calcium suggests the involvement of bioactive components associated with dairy foods (e.g., calcium, protein, ACE inhibitory peptides). However, further research is necessary to identify the specific components of dairy responsible for these observations.

Observational Studies and Secondary Analyses of Clinical Trials Although observational or epidemiological studies do not prove a cause and effect relationship, they help generate hypothesis or critical questions. As with all observational studies, there are typical limitations (i.e., limited sample sizes, unable to determine causation, etc.). Several observational studies, including cross-sectional analysis of national databases

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(NHANES, CSFII), prospective studies (Quebec Family Study, the Heritage Family Study, the Coronary Artery Risk Development in Young Adults Study, the Tehran Lipid and Glucose Study, and the Portuguese Health Interview Study), and retrospective secondary analyses of clinical trials, not originally designed to study body weight, have examined the impact of increased dairy food consumption or increased calcium in the diet on changes in body weight or body fat (Albertson et al., 2003; Azadbakht et al., 2005; Bailey et al., 2007; Boon et al., 2005b; Brooks et al., 2006; Buchowski et al., 2002; Caan et al., 2007; Davies et al., 2000; Gonzalez et al., 2006; Heaney et al., 2002; Hess et al., 2008; Jacqmain et al., 2003; Lin et al., 2000; Liu et al., 2005; Loos et al., 2004; Lovejoy et al., 2001; Marques-Vidal et al., 2006; McCarron et al., 1984; Melanson et al., 2003; Mirmiran et al., 2005; Murakami et al., 2006; Newby et al., 2003, 2004; Ochner and Lowe, 2007; Pereira et al., 2002; Rajpathak et al., 2006; Reid et al., 2005; Rosell et al., 2006; Shahar et al., 2007; Shapses et al., 2004; Zemel et al., 2000). A statistically significant inverse relationship has been reported between calcium/dairy product intake and body weight/fat in many of these studies. The effects have been observed across multiple ages and ethnicities, predominantly in females but some studies have included males. The available data on children and adolescents are limited compared to adults with mainly cross-sectional and prospective studies (and only a few randomized clinical trials) investigating this relationship; however, the data demonstrate either an inverse or neutral relationship between dairy and/or calcium and body weight and body fat in children and adolescents (Barba et al., 2005; Barr, 2007; Berkey et al., 2005; Cadogan et al., 1997; Carruth and Skinner, 2001; Chan et al., 1995; DeJongh et al., 2006; Fiorito et al., 2006; Lappe et al., 2004; Lorenzen et al., 2006; Moore et al., 2006; Novotny et al., 2004; Phillips et al., 2003; Rockell et al., 2005; Skinner et al., 2003; Volek et al., 2003). In contrast, some observational studies have reported that dietary calcium or dairy food intake is not associated with changes in body weight including the Health Professionals Follow-up Study (men) and in a study of pre- and postmenopausal women. Inconsistencies in findings from observational studies may be explained by several factors such as level and/or range of calcium or dairy foods consumed, baseline body weight or body fatness, energy intake, and methods used to assess dietary intake and body weight or body fat. Both longitudinal prospective studies and cross-sectional studies have demonstrated an inverse association between dairy and/or calcium and body weight and/or body fat. Pereira and colleagues (2002) examined the association between dairy intake and incidence of insulin resistance

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syndrome (IRS) adjusting for confounding lifestyle and dietary factors in a 10-year cumulative incidence observational population-based prospective study (CARDIA) consisting of general community sample from four U.S. metropolitan areas of 3,157 black and white adults aged 18–30 years. Overweight participants who consumed the most dairy products had an approximately 70% lower incidence of IRS than those who consumed few dairy products. Increased dairy food intake was equally beneficial to African Americans and Caucasians, and both reduced-fat and full-fat versions were effective. Risk of weight gain over 10 years was 67% lower in those who consumed the most dairy foods versus the least. Authors concluded that dietary patterns characterized by increased dairy consumption have a strong inverse association with IRS among overweight adults and may reduce risk of type 2 diabetes and CVD. Liu et al. (2005) examined the associations between dairy, calcium, and vitamin D intake and the prevalence of metabolic syndrome in over 10,000 middle-aged or older women, who were free of cardiovascular disease, cancer, or diabetes, and who never used postmenopausal hormones. In age- and calorie-adjusted analyses using multiple logistic regression models, comparing different dietary intake levels of calcium and vitamin D, higher intakes of total, dietary, and supplemental calcium were significantly and inversely associated with the prevalence of metabolic syndrome. Similarly, a strong inverse relationship between intakes of dairy products and metabolic syndrome was also observed. After adjustment for lifestyle and dietary factors, the multivariable odd ratios comparing the highest with the lowest intake categories were 0.66 (p < 0.0001) for total dairy products and 0.85 (p = 0.05) for total milk intake. Furthermore, consumption of both high-fat and low-fat dairy products were associated with a lower prevalence of metabolic syndrome. Dietary vitamin D was inversely associated with prevalence of metabolic syndrome but was not independent of total calcium intake. Specifically, the component of metabolic syndrome, abdominal obesity measured by waist circumference, was significantly reduced in those with higher calcium intakes, and the number of women with BMI ≥ 30 was reduced. Results suggest that calcium and dairy product consumption may be associated with lower prevalence of the metabolic syndrome in middle-aged and older women. Jacqmain et al. (2003) performed a cross-sectional study, using data from adults in the Quebec family study of 235 men and 235 women divided into three groups on the basis of their daily dietary calcium intake: <600 mg, 600–1,000 mg, and >1,000 mg. After controlling for age, socioeconomic status and other dietary variables (daily energy intake, percentage dietary fat, dietary protein), women consuming <600 mg

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of calcium/day had greater body weight, BMI, percentage body fat, fat mass, waist circumference, and abdominal adipose tissue than those consuming 600 mg calcium or more (p < 0.05). No significant differences were found for men. Correlations between calcium intake and body composition measurements, adjusted for the same factors as above, were significant only for women. These adjusted correlations were significant for calcium intake and percentage body fat (p < 0.1), fat mass, BMI, and waist circumference (all p < 0.05). Dairy foods provided about 62% of the calcium in women’s diets, compared to about 60% in the diets of men. Several studies that were designed for outcomes other than body weight, that is, skeletal end points, have been reevaluated to assess the relationship between dairy and/or calcium and body weight and/or body fat. Davies et al. (2000) reevaluated five clinical trials (four observational, 1 RCT), originally designed to determine skeletal end points, to determine the association of calcium intake and body weight. The odds ratio for being overweight for calcium below the median intake was 2.25 (p < 0.02). These results indicate that a 100-mg increase in calcium intake may result in a 0.82 kg/year decrease in body weight in young women, 0.038 kg/year in middle-aged women, and 0.052 kg/year in older women. Further evaluation of these data suggest that if calcium was consumed at recommended levels, the prevalence of overweight and obesity might be reduced by 60–80% (Heaney, 2003). The Women’s Health Initiative clinical trial, a randomized, double-blinded, placebo-controlled trial that was designed to study the effects of calcium plus vitamin D supplementation on the incidence of hip fracture and colorectal cancer in over 36,000 postmenopausal women demonstrated a modest but significant attenuation of postmenopausal weight gain in the supplemented group compared to the placebo group. Notably, this benefit was only evident in women whose baseline calcium intake was suboptimal, as treatment effects were only seen in the women with baseline calcium intakes less than 1,200 mg/day. In contrast, other studies designed for skeletal end points did not see significant associations of calcium and body weight. Shapses et al. (2004) analyzed data from three separate 25-week RCTs, originally designed to investigate the effects of calcium supplementation (1 g/day) on bone health during weight loss in 100 pre- and postmenopausal women reporting no significant differences in body weight and fat between calcium supplemented and control groups. Reid and colleagues (2005) reported the effects of 1 g/day calcium supplementation on body weight and blood pressure in normal-weight women from a study originally designed for skeletal end points. There were no differences in weight or body composition between

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the control and calcium supplement groups, but those receiving calcium supplements did experience less increase in blood pressure. Furthermore, when data were analyzed adjusting for baseline intakes of calcium, the treatment effect of calcium on blood pressure was larger and did persist for those with baseline calcium intakes less than 600 mg/day. Lin et al. (2000) examined the effects of calcium intake on changes in body composition during a 2-year exercise intervention in 54 normalweight young women. Total calcium and dairy calcium per kilocalories were negatively related to change in body weight and body fat. Thus, as calcium intake per energy intake (mg/kcal) increased, there was a decrease in body weight and body fat. These researchers concluded that the effect of calcium was specific to dairy calcium because total calcium and dairy calcium, when adjusted for energy, predicted changes in body weight and body fat whereas nondairy calcium did not. A study by Bailey et al. (2007) examined the role of calcium consumption on body weight and fat in the absence of caloric restriction. Specifically, moderately obese, sedentary males (n = 20) and females (n = 30) were subjected to a moderately intensive exercise routine (45 minutes per day, 5 days per week) while consuming food ad libitum for 9 months. The results showed that calcium consumption was associated with weight change (r = −0.47) and body fat (r = −0.53) in men but not in women. The authors conclude that weight and fat loss associated with moderate exercise can be improved by higher intakes of calcium in men. Ochner and Lowe (2007) conducted a retrospective analysis to study the effects of dietary calcium and energy intake on changes in body weight for 18 months following a weight-loss regimen. In 103 overweight or obese women, after controlling for energy intake, the only nutrient examined that predicted weight regain was calcium. Thus, the authors concluded that the results indicate that dietary calcium may oppose weight regain and reduce the effect of greater energy intake that occurs following a weight-loss intervention. Melanson and colleagues (2003) reported on a cross-sectional study in which 35 nonobese, healthy adults completed a 24-hour stay in a wholeroom calorimeter. Acute total and dairy calcium intake were positively correlated with fat oxidation over 24 hours (r = 0.38 and 0.35, respectively, p < 0.05), while habitual calcium intake (total or dairy) was not related to 24-hour oxidation. Further statistical modeling showed that both acute and habitual total calcium were predictors of 24-hour fat oxidation; acute and habitual dairy calcium was not. These data support the hypothesis that high calcium intakes promote lipolysis and protect against fat mass accumulation.

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In summary, numerous observational studies or secondary analyses have examined the impact of increased dairy food consumption or increased calcium in the diet on changes in body weight or body fat. In most of the studies, a statistically significant negative relationship was reported between calcium/dairy product intake and body weight/fat. In general, the effect appears relatively robust as seen across multiple ages and ethnicities.

Animal Models and In Vitro Studies Exploring Potential Mechanisms Several rodent models have been utilized to assess the effects of calcium and dairy intake on body weight and fat. Some studies have used transgenic mice that overexpress the agouti gene specifically in adipocytes (aP2-agouti) to assess the impact of increased dairy intake on weight gain, weight loss, and body fat alterations (Bultman et al., 1992; Shi et al., 2001a; Zemel et al., 2000). Data from these studies indicate that in this transgenic model, increasing dietary calcium intake attenuates diet-induced adiposity by modulating adipocyte intracellular calcium and thereby coordinately regulating lipogenesis and lipolysis. Additionally, dietary calcium facilitates reduction of adipose tissue mass and body weight by modulating energy metabolism, serving to reduce energy storage and increased thermogenesis. Sun and Zemel (2004) reported that high-calcium diets elicit a shift in energy partitioning and reduction of weight gain during refeeding, with dairy calcium sources exerting markedly greater effects. Studies in other animal models have also demonstrated an effect of high dietary calcium on body fat. Papakonstantinou and colleagues (2003) demonstrated in male Wistar rats that a high-calcium, high dairy protein diet decreases body weight and fat content due to a lower digestible energy intake caused by increased fecal lipid. Parra et al. (2008) examined the effects of calcium on body weight and fat in wild-type, C57BL/J6J mice. Calcium intake was able to attenuate body weight and body fat gain under a high-fat diet condition. Additionally, following weight gain, the increased calcium accelerated weight loss in the mice consuming a normal-fat diet. In both instances, there was no difference in food intake. Calcium intake decreased the expression of various proteins involved in calcium signaling, which could reduce cytosolic calcium levels in adipocytes contributing to diminished fat accretion. This result supports results obtained in the agouti mouse model and further supports the hypothesis that intracellular calcium levels regulate lipolysis and lipogenesis. In contrast, Zhang and Tordoff

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(2004) reported no effects of calcium manipulations on energy intake, body weight, or carcass fat content, and no relation between calciotropic hormones and body weight in rodent models fed normal- or high-energy density diets. In addition to the animal model studies, in vitro studies have been conducted in human fat cells to help elucidate a plausible mechanism of dietary calcium-induced reductions in adiposity (Shi et al., 2001b, 2002; Xue et al., 2001). In general, elevations in 1,25-(OH)2 -D that occur in response to low-calcium diets may stimulate adipocyte Ca2+ influx and thereby increase adiposity. 1,25-(OH)2 -D has been shown to stimulate Ca2+ influx and sustained increases in steady-state intracellular Ca2+ in human adipocytes. Moreover, treatment of human adipocytes with 1,25(OH)2 -D resulted in a coordinated activation of fatty acid synthase (FAS) and inhibition of lipolysis. Consequently, suppression of 1,25-(OH)2 -D with high-calcium diets would be anticipated to reduce adipocyte intracellular Ca2+ , inhibit FAS, and activate lipolysis, thereby exerting and antiobesity effects. This concept is summarized in Fig. 5.2. In addition to this mechanism, other mechanisms have been hypothesized including reduced fat absorption via calcium’s binding of dietary fat in the gut and a possible calcium suppressing effect on appetite.

Ca2+ 1,25-(OH)2-D

mVDR

−

−

[Ca2+]i

Lipolysis and fat oxidation

−

Dietary calcium

RXR

nVDR

FAS

DR-3 UCP2

+

Nucleus

de novo lipogenesis

Core temperature Fat oxidation

Adipocyte

Other dairy components

Figure 5.2. A summary of the mechanism of calcium modulation of adiposity. (Adapted from Shi et al., 2002 and Zemel, 2003b.)

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Summary of Scientific Evidence The body of scientific evidence including clinical, observational, animal, and cellular studies supports a relationship between the consumption of dairy foods and weight management. The clinical studies to date demonstrate that diets including 3 servings per day of dairy foods, high in calcium and a good source of protein, enhance body weight and/or fat loss in obese and overweight individuals when calories are restricted and dairy/calcium intakes are increased from inadequate to adequate. While consumption of dairy foods has been shown to exert a greater impact than calcium alone, studies continue to examine the mechanism to explain this phenomenon, which appears to be multifactorial and may involve bioactive components found in dairy foods (e.g., calcium, protein, branch chain amino acids, ACE inhibitory peptides). Most observational data either from cross-sectional data sets, prospective studies, or secondary analysis of clinical trials indicate a statistically significant inverse relationship between dairy intake/calcium intake and body weight and body fat loss. Animal studies have demonstrated an important role of increased dairy intake on decreasing body weight and body fat during overconsumption, during energy restriction, and refeeding. Further research is necessary to identify the specific components of dairy responsible for these observations.

Food Application The 2005 Dietary Guidelines for Americans, issued jointly by the U.S. Department of Health and Human Services and the U.S. Department of Agriculture, recommend 3 servings of low-fat and fat-free milk or equivalent milk products (e.g., cheese, yogurt) daily as part of a healthy diet. The Guidelines recommend balancing calories consumed from foods and beverages with calories expended to achieve and maintain a healthy body weight. Additionally, the Guidelines advise that adults and children do not need to avoid milk and milk products because of concerns about weight gain. Dairy products such as milk, yogurt, and cheese serve as functional ingredients found in a variety of food products. Additionally, dairy components such as whey protein and nonfat dry milk are used in food applications. The following section provides general information on dairy products and components as well as some specific industry utilizations of dairy components for weight management.

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Milk provides good to excellent sources of nine essential nutrients, making it one of the most nutrient-dense foods. Each serving of milk provides 10% or more of the recommended daily intake for calcium, vitamin D (if fortified), protein, potassium, vitamin A, vitamin B12, riboflavin, and phosphorus. It is a functional ingredient utilized in a variety of food products, ranging from baked goods and confections to salad dressings. Yogurt is produced by adding specific cultures of lactic acid producing bacteria to fluid dairy products to convert some lactose into lactic acid. The aroma, body, and flavor of yogurt vary depending on the type of culture and milk, amount of milk fat and nonfat milk solids, fermentation process, and the temperature used in production. The nutritional and caloric contents of yogurts are similar to those of the fluid milks from which they are made. Each is an important source of calcium, riboflavin, and protein. Cheese is a concentrated dairy food made from milk, which is obtained by draining the whey after coagulation of casein, the major milk protein. Cheese is made from whole, 2%, 1%, or fat-free, or combinations of these milks. Each cheese has a distinct texture and flavor profile due to the different ingredients and processes employed during the making and aging of cheese. Natural and process cheese can be utilized as a base for dips, a flavorful complement to foods such as pasta or potatoes, a seasoning for vegetables, meats, sauces, and as a filling in desserts and bakery products. Average nutrient values for cheese vary due to the differences in manufacturing processes and standards of identity. Cheese provides calories, high-quality protein, vitamins, and minerals, such as calcium, phosphorus, and zinc. Nonfat dry milk is made by removing moisture from pasteurized nonfat milk. The resulting powder contains not more than 1.5% milk fat and is a versatile and important ingredient in many food formulations. Most nonfat dry milk used as an ingredient is spray dried. Whey is the watery portion of milk that remains after cheesemaking, which contains lactose, minerals, vitamins, protein, and traces of milk fat. The most valuable component of whey is its protein, which delivers both enhanced functionality and nutrition to many formulations. Whey protein, as a high-quality dairy protein, has been shown to stimulate protein synthesis after resistance exercise (Tipton et al., 2004) and gains in muscle mass (Burke et al., 2001; Cribb et al., 2007). Many foods contain whey protein such as dairy-based beverages, yogurt, nutrition and energy bars, ready-to-drink beverages, powder for smoothies and shakes, beverage mixes, and meal replacements.

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Some food applications are already on the market touting the benefit of dairy components for weight management. One example is a product from Glanbia Nutritionals, Prolibra, which contains intact whey proteins, peptides, and minerals. The product is a partially hydrolyzed whey protein isolate, whey mineral complex that is high in protein and low in fat. Glanbia’s suggested application for the ingredient includes ready-to-drink beverages, powdered beverage mixes, bars, snacks, and dairy products. This product has been used in a double-blind, placebo-controlled clinical trial of 12 weeks demonstrating a greater body fat loss and greater lean mass preservation with the consumption of Prolibra compared to the control beverage within a calorie-reduced diet in obese adults. Both the control and treatment groups lost weight, but there was a trend for greater weight loss in the Prolibra group (Frestedt et al. 2008). Based on these clinical results, Glanbia touts the product’s features and functions as a high protein, low fat, excellent source of calcium, clean flavor profile product that promotes fat loss. A patent is pending for use of the product in weight-loss applications clinically proven to reduce fat and maintain lean body mass. Glanbia also produces Thermax, a heat-stable whey protein for ready-to-drink, low-acid beverages claiming benefits that include nutritional, sports/performance, and weight loss. This product is heat stable at neutral pH, soluble over a wide pH range and has excellent nutrition value with mild flavor.

Patent Activities The original patent protecting the use of dietary calcium and dairy foods in weight management and obesity prevention and treatment was issued to Zemel et al. in 2002 (U.S. Patent 6,384.087), and additional patents protecting specific applications of whey and dairy components are presently pending. Patents for the same claims have been issued to this group by China (Patent #ZL0181078.7, issued 2007), Australia (Patent #2001288707, issued 2007), and New Zealand (Patent # 525004, issued 2008), and are presently pending in Canada, the European Union, Mexico, Japan, and Korea. These claims have been licensed to Dairy Management, Inc. (U.S.); sublicenses are available from this organization. Additionally, U.S. patent applications (US 2003/0165574 A1, US 2005/0106218 A1, and US 2007//0128252 A1) have been filed by Glanbia Nutritionals for a nutritional supplement containing milk mineral and protein for treatment of body weight conditions.

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Summary Overall, the body of scientific evidence including clinical, observational, animal, and cellular studies supports a relationship between the consumption of dairy foods and weight management. Many clinical studies have focused on dairy foods, as milk, yogurt, and cheese, or calcium supplementation to investigate the impact of dairy and/or calcium consumption on body weight and body composition. While consumption of dairy foods has been shown to exert a greater impact than calcium alone, studies continue to examine the mechanism to explain this phenomenon, which appears to be multifactorial and may involve bioactive components found in dairy foods (e.g., calcium, protein, branch chain amino acids, ACE inhibitory peptides). Dairy protein may impact satiety, thermogenesis, and the preservation of lean muscle mass. Branched chain amino acids, which are concentrated in whey protein, specifically leucine, play a regulatory role in signaling protein synthesis and have been implicated in weight management (Layman, 2003). ACE inhibitory peptides derived from milk proteins may influence lipogenesis in the adipocyte tissue (Zemel and Herweyer, 2007). Thus, many components of dairy may be acting synergistically to impact body weight and body composition. Further research is necessary to identify the specific components of dairy responsible for these observations. While there is more to learn about dairy food consumption’s impact on weight management, the 2005 Dietary Guidelines recommend 3 servings of low-fat and fat-free milk or equivalent milk products (e.g., cheese, yogurt) daily as part of a healthy diet and stresses the importance of balancing calories consumed from foods and beverages with calories expended to achieve and maintain a healthy body weight.

References Albertson AM, Good CK, Holschuh NM, Eldridge EL. The relationship between dietary calcium intake and body mass index in adult women: data from the continuing survey of food intake by individuals, 1994–1996. FASEB J 2003;17:A289. Azadbakht L, Mirmiran P, Esmaillzadeh A, Azizi F. Dairy consumption is inversely associated with the prevalence of the metabolic syndrome in Tehranian adults. Am J Clin Nutr 2005;82(3):523–530.

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18:21

Printer Name: Yet to Come

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Bailey BW, Sullivan DK, Kirk EP, Hall S, Donnelly JE. The influence of calcium consumption on weight and fat following nine months of exercise in men and women. J Am Coll Nutr 2007;26(4):350–355. Barba G, Troiano E, Russo P, Venezia A, Siani A. Inverse association between body mass and frequency of milk consumption in children. Br J Nutr 2005;93(1):15–19. Barr SI. Calcium and body fat in peripubertal girls: cross-sectional and longitudinal studies. Obesity 2007;15(5):1302–1310. Barr SI. Increased dairy product or calcium intake: is body weight or composition affected in humans? J Nutr 2003;133:245S–248S. Berkey CS, Rockett HRH, Willett WC, Colditz GA. Milk, dairy fat, dietary calcium, and weight gain. Arch Pediatr Adolesc Med 2005;159:543–550. Boon N, Hul GB, Viguerie N, Sicard A, Langin D, Saris WH. Effects of 3 diets with various calcium contents on 24-h energy expenditure, fat oxidation, and adipose tissue message RNA expression of lipid metabolism-related proteins. Am J Clin Nutr 2005a;82(6):1244–1252. Boon N, Koppes LL, Saris WH, Van Mechelen W. The relation between calcium intake and body composition in a Dutch Population: The Amsterdam Growth and Health Longitudinal Study. Am J Epidemiol 2005b;162(1):27–32. Bowen J, Noakes M, Clifton PM. Effect of calcium and dairy foods in high protein, energy-restricted diets on weight loss and metabolic parameters in overweight adults. Int J Obes 2005;29(8):957–965. Brooks BM, Ranganathan R, Nicklas TA, Yang S-J, Berenson GS. Association of calcium intake, dairy product consumption with overweight status in young adults (1995–96): The Bogalusa Heart Study. J Am Coll Nutr 2006;25(6):523–532. Buchowski MS, Semenya J, Johnson AO. Dietary calcium intake in lactose maldigesting intolerant and tolerant African-American women. J Am Coll Nutr 2002;21:47–54. Bultman SJ, Michaud EJ, Woychik RP. Molecular characterization of the mouse agouti locus. Cell 1992;71:1195–1204. Burke D, Chilibeck P, Davison K, Candow D, Farthing J, Smith-Palmer T. The effect of whey protein supplementation with and without creatine

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monohydrate combined with resistance training on lean tissue mass and muscle strength. Int J Sport Nutr Exerc Metab 2001;11(3):349–364. Caan B, Heuhouser M, Aragaki A, Lweis CB, Jackson R, LeBoff MS, Margolis KL, Uwaifo G, Whitlock MD, Wylie-Rosett J, Lacroix A. Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain. Arch Intern Med 2007;167(9):893–902. Cadogan, J, Eastell R, Jones, N, Barker, ME. Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial. Br Med J 1997;315:1255–1260. Carruth BR, Skinner JD. The role of dietary calcium and other nutrients in moderating body fat in preschool children. Int J Obes 2001;25:559– 566. Chan G, Hoffman K, McMurry M. Effects of dairy products on bone and body composition in pubertal girls. J Pediatr 1995;126(4):551–556. Cribb P, Williams A, Stathis C, Carey M, Hayes A. Effects of whey isolated, creatine, and resistance training on muscle hypertrophy. Med Sci Sports Exerc 2007;39(2):298–307. Cummings NK, James AP, Soares MJ. The acute effects of different sources of dietary calcium on postprandial energy metabolism. Br J Nutr 2006;96(1):138–144. Davies KM, Heaney RP, Recker RR, Lappe JM, Barger-Lux MJ, Rafferty K, Hinders S. Calcium intake and body weight. J Clin Endocrinol Metab 2000;85:4635–4638. DeJongh ED, Binkley TL, Specker BL. Fat mass gain is lower in calciumsupplemented than in unsupplemented preschool children with low dietary calcium intakes. Am J Clin Nutr 2006;84:1123–1127. Eagan MS, Lyle RM, Gunther CW, Peacock M, Teegarden D. Effect of 1-year dairy product intervention on fat mass in young women: 6-month follow-up. Obesity 2006;14(12):2242–2248 Fiorito LM, Ventura AK, Mitchell DC, Smiciklas-Wright H, Birch LL. Girls’ dairy intake, energy intake, and weight status. J Am Diet Assoc 2006;106:1851–1855. Frestedt JL, Zenk JL, Kuskowski MA, Ward LS, Bastian ED. A wheyprotein supplement increases fat loss and spares lean muscle in obese subjects: a randomized clinical study. Nutr Metab 2008;5(8).

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88

18:21

Printer Name: Yet to Come

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Gonzalez AJ, White E, Kristal A, Littman AJ. Calcium intake and 10-year weight change in middle-aged adults. J Am Diet Assoc 2006;106:1066–1073. Gunther CW, Legowski PA, Lyle RM, McCabe GP, Eagan MS, Peacock M, Teegarden D. Dairy products do not lead to alterations in body weight and fat mass in young women in a one year intervention. Am J Clin Nutr 2005a;81(4):751–756. Gunther CW, Lyle RM, Legowski PA, James JM, McCabe LD, McCabe GP, Peacock M, Teegarden D. Fat oxidation and its relation to serum parathyroid hormone in young women enrolled in a 1-y dairy calcium intervention. Am J Clin Nutr 2005b;82:1228–1234. Harvey-Berino J., Gold B.C., Lauber R., Starinski A. The impact of calcium and dairy product consumption on weight loss. Obes Res 2005;13(10):1720–1726. Heaney RP. Normalizing calcium intake: projected population effects for body weight. J Nutr 2003;133:268S–270S. Heaney RP, Davies KM, Barger-Luz J. Calcium and weight: clinical studies. J Am Coll Nutr 2002;21:152S–155S. Hess CJ, Shaw SE, Carothers L. Association of calcium intake and adiposity in postmenopausal women. J Am Coll Nutr 2008;27(2):260– 266. Jacobsen R., Lorenzen J.K., Toubro S., Krog-Mikkelsen I., Astrup A. Effect of short-term high dietary calcium intake on 24-h energy expenditure, fat oxidation, and fecal fat excretion. Int J Obes 2005;29(3):292–301. Jacqmain M, Doucet E, Despres JP, Bouchard C, Tremblay A. Calcium intake, body composition, and lipoprotein-lipid concentrations in adults. Am J Clin Nutr 2003;77:1448–1452. Lappe JM, Rafferty KA, Davies KM, Lypaczewski G. Girls on a highcalcium diet gain weight at the same rate as girls on a normal diet: a pilot study. J Am Diet Assoc 2004;104:1361–1367. Layman DK. The role of leucine in weight loss diets and glucose homeostasis. J Nutr 2003;133:261S–267S. Lin YC, Lyle RM, McCabe LD, McCabe GP, Weaver CM, Teegarden D. Dairy calcium is related to changes in body composition during a

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two-year exercise intervention in young women. J Am Coll Nutr 2000;19:754–760. Liu S, Song, Y, Ford, ES, Manson, JE, Buring, JE, Ridker PM. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middleaged and older U.S. women. Diabetes Care 2005;28:2926–2932. Loos R, Rankinen T, Leon A, Skinner J, Wilmore J, Rao DC, Bouchard C. Calcium intake is associated with adiposity in black and white men and white women of the HERITAGE family study. J Nutr 2004;134:1772–1778 Lorenzen JK, Molgaard C, Michaelsen KF, Astrup A. Calcium supplementation for one year does not reduce body weight or fat mass in young girls. Am J Clin Nutr 2006;83:18–23. Lorenzen JK, Nielsen S, Holst JJ, Tetens I, Rehfeld JF, Astrup A. Effect of dairy calcium or supplementary calcium intake on postprandial fat metabolism, appetite, and subsequent energy intake. Am J Clin Nutr 2007;85:678–687. Lovejoy JC, Champagne CM, Smith SR, deJonge L, Xie H. Ethnic differences in dietary intakes, physical activity, and energy expenditure in middle-aged, premenopausal women: the Healthy Transitions study. Am J Clin Nutr 2001;74:90–95. Major GC, Alarie F, Dore J, Phouttama S, Tremblay A. Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations. Am J Clin Nutr 2007;85(1):54–59. Major GC, Chaput JP, Ledoux M, St-Pierre S, Andersen GH, Zemel MB, Tremblay A. Recent developments in calcium-related obesity research. Obes Rev 2008;9(5):428–445. Marques-Vidal P, Goncalves A, Dias CM. Milk intake is inversely related to obesity in men and in young women: data from the Portuguese Health Interview Survey 1998–1999. Int J Obes 2006;30(1):88–93. McCarron DA, Morris CD, Henry HJ, Stanton JL. Blood pressure and nutrient intake in the United States. Science 1984;224(4656):1392–1398. Melanson EL, Donahoo WT, Dong F, Ida T, Zemel MB. Effect of low- and high-calcium dairy-based diets on macronutrient oxidation in humans. Obes Res 2005;13:2102–2112.

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Melanson EL, Sharp TA, Schneider J, Donahoo WT, Grunwald GK, Hill JO. Relation between calcium intake and fat oxidation in adult humans. Int J Obes 2003;27:196–203. Mirmiran P, Esmaillzadeh A, Azizi F. Dairy consumption and body mass index: an inverse relationship. Int J Obes 2005;29(1):115–121. Moore LL, Bradlee ML, Gao D, Singer MR. Low dairy intake in early childhood predicts excess body fat gain. Obesity 2006;14:1010–1018. Murakami K, Okubo H, Sasaki S. No relation between intakes of calcium and dairy products and body mass index in Japanese women aged 18 to 20 y. Nutrition 2006;22:490–495. Newby PK, Muller D, Hallfrisch J, Andres R, Tucker KL. Food patterns measured by factor analysis and anthropometric changes in adults. Am J Clin Nutr 2004;80:504–513. Newby PK, Muller D, Hallfrisch J, Qiao N, Andres R, Tucker KL. Dietary patterns and changes in body mass index and waist circumference in adults. Am J Clin Nutr 2003;77:1417. Novotny R, Daida YG, Acharya S, Grove JS, Vogt TM. Dairy intake is associated with lower body fat and soda intake with greater weight in adolescent girls. J Nutr 2004;134:1905–1909. Ochner CN, Lowe MR. Self-reported changes in dietary calcium and energy intake predict weight regain following a weight loss diet in obese women. J Nutr 2007;137(10):2324–2328. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006;295:1549. Papakonstantinou E, Flatt WP, Huth PJ, Harris RB. High dietary calcium reduces body fat content, digestibility of fat, and serum vitamin D in rats. Obes Res 2003;11(3):387–394. Parikh SJ, Yanovski JA. Calcium intake and adiposity. Am J Clin Nutr 2003;77:281–287. Parra P, Bruni G, Palou A, Serra F. Dietary calcium attenuation of body fat during high-fat feeding in mice. J Nutr Biochem 2008;19(2):109–117. Pereira MA, Jacobs DR, Van Horn L, Slattery ML, Katashov AI, Ludwig DS. Dairy consumption, obesity, and the insulin resistance syndrome in young adults: the CARDIA study. JAMA 2002;287(16):2081–2089.

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Phillips SM, Bandini LG, Cyr H, Cloclough-Douglas S, Naumova E, Must A. Dairy food consumption and body weight and fatness studied longitudinally over the adolescent period. Int J Obes 2003;27:1106– 1113. Rajpathak SN, Rimm EB, Rosner B, Willett WC, Hu FB. Calcium and dairy intakes in relation to long-term weight gain in US men. Am J Clin Nutr 2006;83:559–566. Reid IF, Horne A, Mason B, Ames R, Bava U, Gamble GD. Effects of calcium supplementation on body weight and blood pressure in normal older women—A randomized controlled trial. J Clin Endocrinol Metab 2005;90(7):3824–3829. Rockell JEB, Williams SM, Taylor RW, Grant AM, Jones IE, Goulding A. Two-year changes in bone and body composition in young children with a history of prolonged milk avoidance. Osteoporos Int 2005;16(9):1016–1023. Rosell M, H˚akansson NN, Wolk A. Association between dairy food consumption and weight change over 9 y in 19 352 perimenopausal women. Am J Clin Nutr 2006;84(6):1481–1488. Schrager S. Dietary calcium intake and obesity. J Am Board Fam Pract 2005;18(3):205–210. Shahar DR, Abel R, Elhaynay A, Vardi H, Fraser D. Does dairy calcium intake enhance weight loss among overweight diabetic patients? Diabetes Care 2007;30(3):185–189. Shapses SA, Heshka S, Heymsfield SB. Effect of calcium supplementation on weight and fat loss in women. J Clin Endocrinol Metab 2004;89(2):632–637. Shi H, DiRienzo D, Zemel MB. Effects of dietary calcium on adipocyte lipid metabolism and body weight regulation in energyrestricted aP2-agouti transgenic mice. FASEB J 2001a;15:291– 293. Shi H, Norman AW, Okarmura WH, Sen A, Zemel MB. 1α,25 dihydroxyvitamin D3 modulates human adipocyte metabolism via nongenomic action. FASEB J 2001b;15:2751–2753. Shi H, Norman AW, Okamura WH, Sen A, Zemel MB. 1 alpha, 25dihydroxyvitamin D3 inhibits uncoupling protein 2 expression in human adipocytes. FASEB J 2002;16(13):1808–1810.

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Skinner JD, Bonds W, Carruth BR, Ziegler P. Longitudinal calcium intake is negatively related to children’s body fat indexes. J Am Diet Assoc 2003;103:1626–1631. St-Onge MP. Dietary fats, teas, dairy, and nuts: potential functional foods for weight control? Am J Clin Nutr 2005;81(1):7–15. Summerbell CD, Watts C, Higgins JPT, Garrow JS. Randomized controlled trial of novel, simple, and well supervised weight reducing diets in outpatients. Br Med J 1998;317:1487–1489. Sun X, Zemel MB. Calcium and dairy products inhibit weight and fat regain during ad libitum consumption following energy restriction in Ap2-agouti transgenic mice. J Nutr 2004;134:3054–3060. Teegarden D. Calcium intake and reduction in weight or fat mass. J Nutr 2003;133:249S–251S. Teegarden D. The influence of dairy product consumption on body composition. J Nutr 2005;135(12):2749–2752. Thompson WG, Rostad Holdman N, Janzow DJ, Slezak JM, Morris KL, Zemel MB. Effect of energy-reduced diets high in dairy products and fiber on weight loss in obese adults. Obes Res 2005;13(8):1344– 1353. Tipton K, Elliott T, Cree M, Wolf S, Sanford A, Wolfe R. Ingestion of casein and whey protein result in muscle anabolism after resistance exercise. Med Sci Sports Exerc 2004;36(12):2073– 2081. Trowman R, Dumville JC, Hahn S, Torgerson DJ. A systematic review of the effects of calcium supplementation on body weight. Br J Nutr 2006;95:1033–1038. Volek JS, Gomez AL, Scheett TP, Sharman MJ, French DN, Rubin MR, Ratamess NA, McGuigan MM, Kraemer WJ. Increasing fluid milk favorably affects bone mineral density responses to resistance training in adolescent boys. J Am Diet Assoc 2003;103:1353– 1356. Wagner G, Kindrick S, Hertzler SM, DiSilvesto RA. Effects of various forms of calcium on body weight and bone turnover markers in women participating in a weight loss program. J Am Coll Nutr 2007;26(5):456–461.

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Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 2006;1:11. World Health Organization. Obesity: preventing and managing the global epidemic, WHO Technical Report Series No. 894. Worth Health Organization, Geneva, 2000. Xue B, Greenberg AG, Kraemer FB, Zemel MB. Mechanism of intracellular calcium inhibition of lipolysis in human adipocytes. FASEB J 2001;15(13):2527–2529. Zemel MB. Calcium modulation of hypertension and obesity: mechanisms and implications. J Am Coll Nutr 2001;20:428S–435S. Zemel MB. Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications. J Am Coll Nutr 2002;21:146S– 151S. Zemel MB. Mechanisms of dairy modulation of adiposity. J Nutr 2003a;133:252S–256S. Zemel MB. Role of dietary calcium and dairy products in modulating adiposity. Lipids 2003b;38:139–146. Zemel MB. The role of dairy foods in weight management. J Am Coll Nutr 2005;24(Suppl. 6):537S–546S. Zemel MB, Herweyer A. Role of branched chain amino acids and ACE inhibition in the anti-obesity effect of milk. FASEB J 2007;21: 538.11. Zemel MB, Richards J, Milstead A, Campbell PJ. Effects of calcium and dairy on body composition and weight loss in African-American adults. Obes Res 2005a;13(7):1218–1225. Zemel MB, Richards J, Russell A, Milstead A, Gehardt L, Silva E. Dairy augmentation of total and central fat loss in obese subjects. Int J Obes 2005b;29(4):341–347. Zemel MB, Shi H, Greer B, DiRienzo D, Zemel PC. Regulation of adiposity by dietary calcium. FASEB J 2000;14:1132–1138. Zemel MB, Teegarden D, Van Loan M, Schoeller DA, Matkovic V, Lyle RM, Craig BA. Dairy-rich diets augument fat loss on an energy-restricted diet: A multicenter trial. Nutrients 2009;1:83– 100.

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Zemel MB, Thompson W, Milstead A, Morris K, Campbell P. Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults. Obes Res 2004;12(4):582–590. Zhang Q, Tordoff MG. No effect of dietary calcium on body weight of lean and obese mice and rats. Am J Physiol Regul Integr Comp Physiol 2004;286(4):R669–R677.

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CHAPTER 6

Gelatin—A Versatile Ingredient for Weight Control Klaus Flechsenhar, MD, and Eberhard Dick

Abstract In industrialized countries all over the world, there is a growing population of overweight and obese subjects. This rise of an obesity epidemic is due to the overabundance of food that is easily available for individuals living in affluent societies. As overweight and obesity are invariably associated with a range of health problems, such as musculoskeletal diseases and cardiovascular morbidity and mortality, the scope of this twenty-first century epidemic with an ever-increasing number of individuals being affected by the metabolic syndrome may well exceed the resources of most health care systems. Health care professionals, originating both from academia and industry, are therefore obliged to think about therapeutic approaches how to fight the battle against this ever-growing epidemic. Decreasing the calorie content of food items would be one potential solution. Studies on nutrition have shown that replacing fat by protein exerts a more pronounced effect on weight loss than replacing fat by carbohydrates. As collagenous peptides and gelatin represent, chemically speaking, highly purified proteins that are at the same time versatile agents in the manufacturing process in the food industry, a wide range of food products can be created that are both delicious in taste and beneficial in regard to their health aspects.

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Introduction Since the beginning of this millennium, there have been more individuals in our world who are well nourished and overweight than people who are malnourished and who constantly face problems arising from poverty and famine. Thus, in modern societies of the so-called developed world in terms of public health, aspects of overweight, obesity, and the metabolic syndrome prevail. This enormous rise in the development of metabolic disorders such as diabetes and cardiovascular morbidity and mortality is viewed by medical experts as the scourge of the twenty-first century, which has meanwhile taken on epidemic proportions. There is a broad consensus that it requires a joint effort by academia and industry to fight the battle against this ever-growing health problem. One way of offering solutions to this troubling issue is to develop nutritional products that are calorie reduced, but that still offer the same pleasure in eating as traditional high-energy, high-fat products do. In this chapter, the authors attempt to describe the biochemical background of an overconsumption of food and the occurrence of health problems that result from an abundance of nutritional products. We also try to give an overview of studies that highlight the benefits of eating highprotein diets, and finally we provide an outline of what products such as gelatin or collagenous proteins can actually achieve in terms of creating new foods and the health benefits associated with these.

Some Facts about Nutrition In order to maintain our body weight, we need to ingest 30 kilocalories (kcal) per kilogram (kg) of body weight per day. This means that for a 70-kg individual, the daily energy requirements are equivalent to 2,100 kcal. Nutritionists recommend that 50% of the calorie intake should be consumed as carbohydrates, 15% as proteins, and 35% as fat. A 70-kg individual consuming less than 2,100 kcal a day will lose weight. If that individual consumes more than 2,100 kcal, he or she will gain weight. Furthermore, in order to maintain fluid homeostasis, an individual has to ingest 40 mL of fluid per kg of body weight per day, which accounts for daily fluid requirements of 2,800 mL for a 70-kg individual. The figures above represent simple numbers of fundamental biochemical facts and requirements (Flechsenhar and Reinhold, 1998), which make human life possible.

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In the past, people had to cope with scarcity of food and with famine. Today, in Western societies, where food is easily accessible for everyone, there is a mushrooming problem of overweight and obesity resulting from an abundance and overavailability of convenience products, ready-to-eatmeals, and highly-processed, high-fat fast food. The average American ingests between 3,100 and 3,500 kcal a day, and this means that only onethird of the U.S. population can actually be considered to be of normal weight, with the remaining two-thirds being either overweight or obese (Hedley et al., 2004; Kahn et al., 2006). This overconsumption of food in modern society is also often combined with a sedentary lifestyle. As Asian populations are beginning to adopt typical Western diets, similar trends in obesity can nowadays also be observed in countries such as India and China.

The Obesity Epidemic—An Analysis from the Medical Perspective In subjects whose weight does not change over time, there is a balance between consumption of food, that is, ingestion of calories, and energy expenditure. If a person consumes more calories than can actually be burned by physical activity, then there is a net gain in weight. Any excessive food intake—be it either carbohydrates, amino acids, fat, or alcohol—is bound to be metabolized into acetyl-coenzyme A and then reassembled into fatty acids that are stored in adipose tissue. In fact, there are two distinct reservoirs of adipose tissue: fat can either be stored in the abdominal cavity or in the form of a subcutaneous layer. As adipose tissue and, consequently, body mass increase, there will also be an increase in the number of β-pancreatic cells, in an effort to maintain normal glucose levels. However, as body mass continues to increase, this process can no longer cope at some stage, causing the release of insulin to become insufficient. Furthermore, insulin receptors on the cell surfaces become refractory to the action of insulin. This state of insulin resistance also induces a specific form of dyslipidemia. As the enzyme lipoprotein-lipase is insulin dependent, the clearance of triacylglycerolrich lipoproteins will inevitably decrease. Moreover, impaired lipolysis of triglyceride-rich lipoproteins leads to reduced concentrations of highdensity lipoproteins (HDLs). The level of low-density lipoproteins (LDLs) may be unremarkable, but, as the activities of both cholesterol ester transfer protein and hepatic lipase are increased, this entails the generation of small dense LDL particles that are known to be particularly atherogenic.

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As nonesterified fatty acids are known to be toxic to β-cells, there will be a decrease in the release of insulin that aggravates the insulin-deficient situation, leading to the full-blown clinical situation of diabetes mellitus. Thus, the association of a high body mass index, insulin resistance (leading to elevated glucose serum levels), dyslipidemia (leading to high triglyceride and low HDL cholesterol concentrations), and hypertension is commonly known as the metabolic syndrome. Apart from those purely biochemical disruptions such as hyperglycemia and hyperlipidemia, the metabolic syndrome is also known to be associated with an increased level of inflammation, with adipose tissue secreting tumor necrosis factor α and interleukin 6 (Berg et al., 2004). This overexpression of cytokines in adipose tissue also results in the increased systemic release of C-reactive protein, von Willebrand factor, and plasminogen activator inhibitor 1 that accounts for a state of hypercoagulability in the affected body. Thus, it is easy to see why the diagnosis of the metabolic syndrome is invariably associated with elevated cardiovascular morbidity and mortality, which clinically translates into a higher incidence of myocardial infarction and a higher prevalence of congestive heart failure. As more and more individuals in affluent societies become overtly obese, the occurrence of the metabolic syndrome is reaching epidemic proportions worldwide.

Therapeutic Options Individuals suffering from the metabolic syndrome are—from the pathophysiological point of view—trapped in a vicious cycle. Insulin must be regarded as an anabolic hormone. In healthy individuals, it inhibits gluconeogenesis in the liver and lipolysis in adipose tissue. As the metabolic syndrome is characterized by the fact that insulin receptors do not adequately respond to the action of insulin, more and more glucose is synthesized in hepatocytes, aggravating the diabetic situation, and more and more free fatty acids are released, worsening the state of dyslipidemia. As the ingestion of energy-dense food aggravates the metabolic disorder, one option to treat people with the metabolic syndrome is to make them lose weight, that is, to cut back on calories and to increase the level of physical exercise. One way to reduce calories is to replace fat with carbohydrates or protein. As 1 g of fat yields 9 kcal and 1 g of carbohydrates or protein merely yields 4 kcal, one can save on calories by offering the same amount of food.

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Layman et al. carried out a dietary study (Layman et al., 2003) and demonstrated that, by reducing the amount of fat in a diet and by increasing either the quantity of carbohydrates or protein, study participants significantly lost body weight throughout the study period. In that particular trial, researchers recruited 24 women whose age ranged from 45 to 56 years and whose body mass index was greater than 26 kg/m2 . Study participants were randomized to follow one of two types of lowfat diet, corresponding to a total energy intake of 1,690 kcal/day. Both groups received approximately 50 g of fat a day. One group of subjects followed a carbohydrate-rich diet, consisting of 239 g of carbohydrates and 68 g of protein, while the other group was assigned to another more protein-rich diet made up of 125 g of protein and 171 g of carbohydrates. When the two groups of subjects were followed up for 10 weeks, weight loss did not differ significantly between the two groups: It was 7.53 ± 1.44 kg for the group receiving the high-protein diet and 6.96 ± 1.36 kg for the group following the more carbohydrate-based diet, but, interestingly enough, there was a significant difference between the two groups when the changes in body composition were expressed as the ratio of fat/lean loss. Over the 10-week period, the group ingesting the highprotein diet achieved a ratio of fat/lean loss of 6.36 ± 0.85, whereas the group consuming the carbohydrate-rich diet had a ratio of fat/lean loss of 3.92 ± 0.79 (p < 0.05), a finding that suggests a more pronounced effect of a protein-based diet in regard to effective loss of adipose tissue mass. In another clinical study (Skov et al., 1999), Skov et al. recruited 65 healthy overweight and obese individuals, 50 women and 15 men, who were randomized into three groups. One group was asked to follow a high-protein diet, another group was put on a high-carbohydrate diet, and a third group (control group) did not receive any recommendations for their dietary habits. After a follow-up of 6 months, it became apparent that the high-protein diet group had lost substantially more weight (8.9 kg) than had the high-carbohydrate diet group (5.1 kg) (p < 0.001). Those figures translated into a loss in fat mass of 7.6 kg versus 4.3 kg. Moreover, the high-protein diet significantly decreased fasting plasma triglycerides and free fatty acids. Why is it that a protein-based diet exerts a more pronounced effect on weight loss than does a carbohydrate-based diet? There are two separate explanations that can be found in standard textbooks of biochemistry and in the current literature. The first explanation lies in the fact that there is a distinct difference between metabolizable energy and net metabolizable energy. According

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to the laws of thermodynamics, both 1 g of carbohydrates and 1 g of protein yield 4 kcal. However, in the human body, carbohydrates—after being transformed into acetyl-CoA—are directed toward oxidative phosphorylation in the mitochondria, whereas amino acids—in order to be metabolized—need to be submitted to the urea cycle, which is a pathway that consumes energy. That may be the reason why, in terms of net metabolizable energy, 1 g of carbohydrates yields 3.82 kcal, whereas 1 g of protein yields 3.1 kcal (Livesey, 2001). Another explanation why a protein-based diet exerts a more pronounced effect on weight loss in obese subjects compared to a carbohydrate-based diet may reside in endocrinological phenomena of the gastrointestinal tract. Physiologically, the consumption of food is regulated by the hypothalamus, a mechanism that is mediated by the melanocortin and the neuropeptide Y systems. The Y2 receptor, an integral part of those systems in the brain, has an inhibitory role. Peptide YY (PYY), which is released in the gastrointestinal tract, usually binds to the Y2 receptor, thus producing an effect of satiety in the hypothalamus. Interestingly, PYY is released upon ingestion of food, and the secretion of PYY is enhanced, when proteins are ingested. This means that the oral consumption of protein may lead to a premature feeling of satiety, which inevitably entails a marked decrease in the consumption of calories in normal-weight and obese subjects. This phenomenon could be observed in both animal and human studies (Batterham et al., 2002, 2006). Therefore, as the ingestion of protein-rich diets results in a marked loss of adipose tissue—and this effect is more pronounced than what can be achieved with the ingestion of carbohydrates—the consumption of protein in addition to that phenomenon also entails an increase in the mass of muscle tissue. This means that insulin sensitivity improves in the long run, thus counterbalancing the deleterious effects of the metabolic syndrome (Katsanos et al., 2006). Of course, another way of building up muscular mass would be to adhere to a regular exercise program. Walking or running 3 miles a day would result in an energy expenditure of roughly 300 kcal, which—after 30 days—would total 9,000 kcal of energy expenditure, which would be equivalent to the loss of 1 kg of fat or adipose tissue after 1 month of regular exercise. It is common knowledge that, with the constraints everyday life imposes on average people in our modern societies, exercise programs are difficult to implement. The individuals who would be most likely to benefit from such an exercise program, that is, obese subjects, are the ones who would also be most unlikely to stick to it, as they tend

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to be handicapped by joint pain or dyspnea on exertion, which again are a result of overweight.

Technological Properties of Gelatin and the Usefulness of Implementing Collagenous Proteins Thus, if we focus on the field of nutrition, an efficient way of making overweight or obese subjects lose weight is to offer them a diet that is reduced in fat and that is—according to the biochemical findings mentioned above—high in protein. Ingredients that have been shown to be versatile agents in the food industry, that is, replacing fat with protein, are collagenous products, the most important of which is gelatin. Gelatin is the ingredient that, when ingested, meets both requirements: It creates satiety, making individuals consume less calories, and with equal amounts of food being served—as far as volume is concerned—the caloric density of gelatin is much lower than that of traditional nutritional products. The raw material that gelatin or gelatinous products originate from is the skin or hide split of animals slaughtered for meat production, or the bones of those animals. Gelatin, however, produced from bone chips, in terms of material being used for the food industry, must be regarded as exceptional. All these materials contain a protein that is adequate for nutrition, namely, collagen. Various types of collagen can be found in animals. In fact, collagen is—strictly speaking—the essential protein forming the body of mammals, including humans, building up connective tissue, including the skeleton. Based on these distinct types of raw material, a number of products can be manufactured by using a variety of industrial processes. Gelatin is the best known among these products. Processes such as cleansing, grinding, extraction, hydrolysis in combination with subsequent drying and milling—just to name a few—result in three groups of products: edible collagen, edible gelatin, and collagenous peptides. All these products are based on the protein fraction of the raw materials mentioned above. Due to the production process, the protein fraction is isolated from all other constituents of the raw materials. Furthermore, they are hydrolyzed to a significant extent. In summary, chemically speaking, all these products are highly purified proteins. Again, when added to regular

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food, these products induce satiety in the human body and, physically, they help reduce the energy content of food. From the metabolic point of view, the composition of amino acids in collagenous proteins is not perfectly suited to human biochemistry because collagen does not contain the amino acid tryptophan and as its cysteine and methionin content is rather low. In order to increase their nutritional value, collagenous proteins should be mixed with other proteins such as milk proteins. In the food industry, collagenous peptides have traditionally been used to increase the protein content of certain products. Based on the fact that collagenous proteins are highly hydrolyzed, and that they have reduced technological functionality, they exert little effect on the sensory properties of food and therefore can always be used to increase the protein content of food products. Collagen and, in particular, gelatin can be characterized in two ways from the perspective of functionality. First, the protein is capable of forming thermoreversible hydrous gels, which means that large amounts of water can be bound in food, thus modifying its texture. Second, it is capable of forming and stabilizing foam. From these two properties, we can derive two ways to reduce oral intake of calories, that is, increase the water content of food and also increase the volume of food by adding air (Houlton, 2007). As far as the increase in water content is concerned, a variety of products are available on the market. The most popular products in this regard are low-fat butter and low-fat margarine. Huge amounts of water are used in the manufacture of these products. In order to maintain the consistency, structure, and spreadability of the low-fat butter and low-fat margarine, water is gelled with gelatin, thus creating the characteristic texture and flavor of the regular products that are not fat reduced. There are various dressings and different types of mayonnaise that are produced in almost identical ways by making use of gelatin or gelatin hydrolysate, which are available in supermarkets or food stores (Table 6.1). In the meat-producing industry, gelatin has traditionally been used in order to bind large quantities of water. A good example of this type of manufacturing process is the existence of aspic-preserved products, that is, meat products that in relation to other products have a considerably lower calorie content. Functional proteins are also commonly used by the meat-producing industry. This, in most cases, is collagenous protein or partially hydrolyzed protein that has not yet reached the same degree of solubility as gelatin. These proteins are usually used for the production of

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Table 6.1. Ingredients per 100 g of serving Traditional Dressing (Available on the Market) Energy (kcal) Protein (g) Carbohydrates (g) Fat (g) Water (%)

230 1.6 8.2 21.2 68

Dressing As Produced by GELITA 86 3.0 4.8 5.6 80

boiled sausage. This production process therefore results in an increase in the binding of water and, consequently, a decrease in the content of energy. These products, when adequately prepared, can also be used in industrial sectors that are not necessarily related to the meat-producing industry. That way, viscous pastes can be created, which, across a wide range of temperatures, maintain comparatively constant viscosity and which are not characterized by the rubber-like, long texture of gelatin. The use of such collagenous proteins that have the capacity to expand in volume or the use of the chemical effect of coacervation in order to generate insoluble mixtures makes it possible to create two-phase water-in-water systems (Roller and Jones, 1996). These systems genuinely have the potential to generate a creamy, fat-like mouth-feeling, which is analogous to a fat-inwater emulsion. In order to achieve the desired effect, it is necessary for collagen to have a sufficiently low particle size that would be equivalent to the lipid droplets of an oil-in-water emulsion. Those types of collagen can also be used in order to reduce the percentage of fat in an emulsion, that is, to cut down on calories without compromising on flavor or texture (Table 6.2). The high water-binding capacity of those proteins can achieve a higher water content in these products. Sensory properties and functionality are considered to be equivalent to those of the traditional regular products (Figs. 6.1 and 6.2). Putting into practice appropriate technology may result in the generation of products, resembling cheese, which can be used as toppings for pizza, cheeseburgers or similar food items (Table 6.3). That way, collagenous proteins open up new promising avenues for the development of calorie-reduced products that still convey the full scope of mouth-feeling to the consumer.

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Protein based ingredients r Table 6.2. Composition of GELITA
mayonnaise in percentage of ingredients r Composition of GELITA
Mayonnaise

Collagen particles Saccharose Starch Citric acid Sodium chloride (salt) Spices Brandy Water Mustard Vinegar Oil

1.12% 1.75% 1.85% 0.25% 1.60% — 0.45% 80.50% 2.70% 0.80% 8.98%

Figure 6.1. A delicious dessert that is created by using gelatin to expand the volume of the serving, thus generating a texture that resembles an oil-in-wateremulsion.

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Figure 6.2. The gelling properties of gelatin entail improved spreadability and lower viscosity of margarine.

There are foams that are manufactured on the basis of gelatin that open up new options for increasing the volume per serving. Whipped cream can be produced with the aid of soda siphons, a technique that is also feasible in restaurants or people’s homes to generate espumas, that is, mashed vegetables or juices, that due to the effect of gelatin, adopt the shape of foam. Those items can generally be served as starters. However, these techniques can also be used for the creation of desserts with mousse for instance, a sweet dish that has already become established as an integral part of that particular product range (Table 6.4). r Table 6.3. Comparison of a traditional cheese product versus the GELITA
product

Collagen particles Sodium caseinate Cheese Starch Fat Processed cheese Sodium chloride (salt) Water Dry mass Fat within the dry mass

Traditional Product

Preparation of the r Product with the GELITA
Addition of Collagen

— 3.50% 38.50% 3.50% 11.00% 1.50% 0.75% 41.25% 43.20% 51.60%

10.50% — 17.00% 1.50% 10.00% 1.50% 1.50% 58.00% 33.70% 44.30%

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Table 6.4. Ingredients of two types of chocolate dessert per 100 mL of serving Chocolate Cream Energy (kcal) Protein (g) Carbohydrates (g) Fat (g)

171 3.5 18.2 9.3

Mousse 143 3.7 17.2 6.6

As far as the production of meat and sausages is concerned, it is nowadays possible to manufacture products that are equivalent to foam and whose shape is stabilized by gelatin (Fig. 6.3). This technology could easily be put into practice. However, it is seldom used for the production of meat products, whereas it is widely used for the creation of a variety of cheese products.

Conclusion Overweight, obesity, and the development of the metabolic syndrome are growing health issues in the twenty-first century. Thus, industry ought

Figure 6.3. In this sausage, gelatin or collagenous proteins fulfill the purpose of increasing the water content and decreasing the calorie content of the product.

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to participate in the search for ways to implement a healthier lifestyle that is accessible to millions of consumers. As we have seen, making use of proteins, in particular collagenous proteins, for the manufacture of nutritional products is an option for creating new products that are healthy from the biochemical and metabolic perspective, and that help to reduce the energy content of food. Using the functional properties of collagenous proteins also enables the production of calorie-reduced food. This technology increases the water content of those products and achieves a larger volume per serving. Making use of the functional properties of collagenous proteins has already resulted in a variety of products on the market, which would not have been feasible without the addition of edible collagen, hydrolyzed collagen, or gelatin. In conclusion, what it really takes is a zest for creative design and unconventional thinking to come up with a novel range of calorie-reduced nutritional products. Such fat-reduced and energy-reduced products boast properties that incite nutritional experts’ and clinical investigators’ interest in terms of being “functional ingredients” that also render them interesting in view of the upcoming political issue of “health claims.”

References Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. Gut hormone PYY3–36 physiologically inhibits food intake. Nature 2002;418:650–654. Batterham RL, Heffron H, Kapoor S, Chivers JE, Chandarana K, Herzog H, LeRoux CW, Thomas EL, Bell JD, Withers DJ. Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab 2006;4:223–233. Berg AH, Lin Y, Lisanti MP, Scherer PE. Adipocyte differentiation induces dynamic changes in NF-kappaB expression and activity. Am J Physiol Endocrinol Metab 2004;287:E1178–E1188. Flechsenhar K, Reinhold L. Parenteral nutrition in general surgery. In: Adolph M, Behrendt W, Jauch KW, Kemen M, Kreymann G, Schuster HP (eds.). New Aspects in Clinical Nutrition. Bibliomed, Germany, 1998.

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Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. JAMA 2004;291:2847–2850. Houlton S. Matter of convenience. International Food Ingredients No 5, 2007. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840–846. Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab 2006;2292(2):E381–E387. Layman DK, Boileau RA, Erickson DJ, Painter JE, Shiue H, Sather C, Christou DD. A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women. J Nutr 2003;133(2):411–417. Livesey G. A perspective on food energy standards for nutrition labelling. Br J Nutr 2001;85:271–287. Roller S, Jones SA. Handbook of Fat Replacers. CRC Press, Boca Raton, FL, 1996, pp. 252–263. Skov AR, Toubro S, Roenn B, Holm L, Astrup A. Randomized trial on protein versus carbohydrate in ad libitum fat reduced diet for the treatment of obesity. Int J Obes 1999;23(5):528–536.

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CHAPTER 7

α-Lactalbumin in the Regulation of Appetite and Food Intake Arie G. Nieuwenhuizen, PhD, Ananda Hochstenbach-Waelen, PhD student, and Prof. Dr. Margriet Westerterp-Plantenga, PhD

Abstract The monoamine neurotransmitter serotonin plays a role in the regulation of human appetite and food intake, as it is supported by the anorectic effects of various serotonergic drugs. Serotonin is synthesized from its precursor, the amino acid l-tryptophan. Studies in laboratory animals and humans have shown that supplementation with l-tryptophan, the biological precursor of serotonin, reduces food intake. A few naturally occurring proteins or peptides contain relatively high levels of tryptophan, such as the milk-derived peptide α-lactalbumin. These peptides may therefore be useful in controlling appetite or food intake. When subjects consumed a breakfast containing either α-lactalbumin or casein as the sole protein source, voluntary energy intake of a subsequent lunch was lower after the α-lactalbumin-containing breakfast. However, it seems unlikely that the high levels of tryptophan fully account for the satiating properties of α-lactalbumin. Thus, the naturally occurring peptide, α-lactalbumin, may help to reduce appetite and food intake; however, its mechanism of action remains to be elucidated.

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Serotonin in the Regulation of Appetite and Food Intake Serotonin (5-hydroxytryptamine) is a monoamine that is produced and secreted in the body by various cell types, including the endocrine enterochromaffin (EC) cell and neuronal cells (Gershon and Tack, 2007). The latter indicates a role of serotonin as a neurotransmitter. Serotonergic neurons are found peripherally (e.g., in the myenteric plexus (Gershon and Tack, 2007)) as well as centrally. In the brain, the principal source of brain serotonin is neurons that originate in the raphe nuclei and project to various brain areas, including the hypothalamus (Ugrumov, 1997). The essential role of the hypothalamus in the regulation of appetite and food intake (Berthoud and Morrison, 2008) may suggest a role of brain serotonin in these processes. Indeed, rat studies show that infusion of low dosages of serotonin in several nuclei of the hypothalamus (including the paraventricular, ventromedial, and suprachiasmatic nucleus) inhibits energy intake, in particular the intake of carbohydrates (Leibowitz and Alexander, 1998). Pharmacological serotonergic agents, such as d-fenfluramine, also suppress food intake both in laboratory animals (Blundell, 1986; Leibowitz and Alexander, 1998) and in humans (Halford et al., 2007; Toornvliet et al., 1996), further supporting a role for serotonin in the regulation of appetite and food intake.

The Role of L-Tryptophan in Brain Serotonin Synthesis Like the other two main monoamine neurotransmitters (i.e., dopamine and norepinephrine), serotonin is also endogenously synthesized from one single amino acid. More precisely, dopamine and norepinephrine are synthesized from l-tyrosine and serotonin from l-tryptophan (Wurtman and Fernstrom, 1975). In contrast to l-tyrosine, l-tryptophan cannot be produced by the human body (e.g., through conversion from other amino acids), and is therefore considered to be an essential amino acid. This means that circulating l-tryptophan can originate only from tissue pools or from the diet. The initial biosynthetic step in the production of serotonin involves hydroxylation of l-tryptophan to 5-hydroxytryptophan (5-HTP) (Fernstrom, 1985; Wurtman and Fernstrom, 1975). This process is catalyzed by the enzyme tryptophan hydroxylase, localized within serotonin-producing

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cells, and is believed to be the rate-limiting step in serotonin synthesis (Fernstrom, 1985; Wurtman and Fernstrom, 1975). Subsequently, 5-HTP is decarboxylated to produce serotonin, which is catalyzed by the enzyme l-amino acid decarboxylase. Interestingly, serotonin seems to exert only a weak negative feedback on its own synthesis (Millard et al., 1972). Ample scientific data indicate that the rate of neuronal serotonin synthesis is influenced by local availability of its precursor, l-tryptophan. For instance, oral administration of a physiological dosage of l-tryptophan to rats resulted in an increase both in plasma and CSF tryptophan concentrations, which was associated with an increase in brain serotonin production (Fernstrom, 1983; Wurtman and Fernstrom, 1975). Thus, it seems that circulating l-tryptophan regulates brain l-tryptophan availability and, subsequently, brain serotonin production. It should be noted, however, that the transport of l-tryptophan across the blood–brain barrier is not solely depending on l-tryptophan concentrations in the peripheral circulation. It is now well established that l-tryptophan is transported to the brain through a transporter that is functional related to the sodium-independent amino acid transport system L, but with a higher affinity for amino acids than the peripheral L-type amino acid transporters (Ruddick et al., 2006). This transporter also facilitates the transport of other large neutral amino acids (LNAA)—valine, leucine, isolaucine, tyrosine, and phenylalanine—across the blood–brain barrier, all in a competitive manner (Fernstrom, 1983, 1985; Ruddick et al., 2006; Wurtman and Fernstrom, 1975; Wurtman and Wurtman, 1988). Thus, transport of l-tryptophan across the blood–brain barrier, and, hence, brain serotonin synthesis may not only depend on plasma l-tryptophan concentrations, but also on the plasma ratio of l-tryptophan to the sum of the other LNAA (Fig. 7.1).

Dietary Amino Acid Interventions to Increase Serotonin Precursor Availability L-Tryptophan

and 5-HTP

Oral administration of l-tryptophan to rats increased both plasma and CSF concentrations of this amino acid, as well as brain serotonin (Wurtman and Fernstrom, 1975), implying that l-tryptophan supplementation may be an interesting nutritional tool to affect appetite and food intake. Indeed, l-tryptophan administration to rats decreased food intake

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Brain capillary L-Tryptophan

LNAA

L-type amino acid transporter L-Tryptophan

Neuron L-Tryptophan

5-HTP

Serotonin

Serotonin

Figure 7.1. Schematic drawing of brain l-tryptophan transport and serotonin synthesis. LNAA: large neutral amino acids; 5-HTP: 5-hydroxytryptophan.

(Blundell, 1986; Latham and Blundell, 1979). Limited human data seem to extend the anorectic effects of l-tryptophan also to our species (Cavaliere and Medeiros-Neto, 1997; Silverstone and Goodall, 1986). In ten obese subjects, both 2 and 3 g of l-tryptophan consumed 1 hour prior to a plated meal significantly reduced caloric intake (in particular, carbohydrate intake) when compared to placebo (lactose) (Cavaliere and Medeiros-Neto, 1997). A lower dosage of 1 g was ineffective. 5-HTP, the product of l-tryptophan hydroxylation, reflects another biological precursor for serotonin. Synthesis of serotonin from 5-HTP bypasses the rate-limiting step in the conversion of l-tryptophan to serotonin, that is, hydroxylation of l-tryptophan. For this reason, 5-HTP is frequently used as a tool to increase serotonin production (Birdsall, 1998). In obese subjects, 900 mg/day of 5-HTP for 12 weeks (the first 6 weeks were without diet description; during the second 6 weeks, a 5,040 kJ/day diet was advised) resulted in increased weight loss when compared with a placebo-treated group (Cangiano et al., 1992). This was associated with a reduction in carbohydrate intake and an increase in early satiety (Cangiano et al., 1992). All together, these data show that both serotonin precursors, l-tryptophan and 5-HTP, affect appetite and/or food intake, emphasizing the role of serotonin in human eating behavior. However, the use of l-tryptophan and 5-HTP in food supplements was seriously challenged by the 1989 outbreak of eosinophilia-myalgia syndrome (EMS) in the United States that was associated with the use of dietary supplements containing l-tryptophan. Even though later studies related the occurrence of

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EMS to the presence of several contaminants in the l-tryptophan preparations (Varga et al., 1993), the safety of isolated l-tryptophan and related compounds as a food supplement is under ongoing debate.

α-Lactalbumin The natural source of l-tryptophan in our body is dietary protein. Still, in rats, a diet containing natural protein or a complete mixture of amino acids failed to increase brain serotonin (Wurtman and Fernstrom, 1975). This is explained by the fact that most dietary proteins also contain the LNAA that compete with l-tryptophan for transport across the blood–brain barrier. Indeed, increasing the amount of protein in the diet of normal subjects resulted in higher plasma concentrations of l-tryptophan, but in a lower plasma ratio of l-tryptophan to LNAA (Fernstrom, 1985). In contrast, dietary carbohydrates do seem to enhance the plasma ratio of l-tryptophan to LNAA as well as brain l-tryptophan and serotonin concentrations, which is mimicked by insulin administration (Fernstrom, 1985; Wurtman and Fernstrom, 1975; Wurtman and Wurtman, 1988). This effect of carbohydrates (and insulin) may be explained by the observation that insulin specifically lowers the plasma levels of LNAA, but not of l-tryptophan, thereby increasing the l-tryptophan/LNAA ratio (Wurtman and Wurtman, 1988). Nevertheless, it should be noted that dietary protein sources differ markedly in their tryptophan as well as their LNAA content, and therefore may distinctly affect plasma l-tryptophan concentrations or plasma l-tryptophan/LNAA ratio, hence, brain serotonin synthesis. This may in part determine the satiating properties of dietary protein: Dietary proteins have repeatedly shown to be the most satiating of all macronutrients (Lejeune et al., 2006; Poppitt et al., 1998; Smeets et al., 2008; Veldhorst et al., 2008; Weigle et al., 2005), with marked differences in satiating properties between different protein sources (Borzoei et al., 2006; Bowen et al., 2006; Hall et al., 2003; Lang et al., 1998, 1999; Uhe et al., 1992; Veldhorst et al., 2008). In particular, the milk peptide, α-lactalbumin, contains high levels of tryptophan, and has been shown to increase plasma tryptophan concentrations and plasma tryptophan/LNAA ratio when ingested alone (Markus et al., 2000, 2002), or as part of a meal (Beulens et al., 2004). At the other end of the spectrum, collagen hydrolysate, or gelatin, contains very low levels of tryptophan and is even used as an experimental approach to induce central serotonin depletion in laboratory animals (Lieben et al., 2004) as well as in humans (Evers et al., 2005).

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–

Alpha-lactalbumin 10% Gelatin 10%

– –

Gelatin+TRP 10%

*

– – – –

Figure 7.2. Changes in subjective ratings of hunger, as assessed by visual analogue scales, after ingestion of a custard based on α-lactalbumin or gelatin with or without TRP addition. * indicates p < 0.05 for α-lactalbumin versus gelatin+TRP, and for α-lactalbumin versus gelatin. (Adapted from Nieuwenhuizen et al., 2009.)

Recent studies in our laboratory explored the satiating properties of α-lactalbumin, when consumed as part of a normal meal. When 24 subjects consumed a “normal” breakfast (containing 10 energy% protein, 55 energy% carbohydrate, and 35 energy% fat) with α-lactalbumin being the sole protein source, the energy intake during a subsequent ad libitum lunch, offered 180 minutes after breakfast, was about 20% lower than when other, more common dietary proteins (e.g., casein or soy) were the protein source in the preceding breakfast (Veldhorst et al., 2009). In order to attribute these effects of α-lactalbumin to its high tryptophan content, we compared the effects of α-lactalbumin on appetite with gelatin and gelatin with added l-tryptophan (Nieuwenhuizen et al., 2009). This study showed that ingestion of a breakfast containing α-lactalbumin as the only protein source results in a more prolonged suppression of hunger than a breakfast containing gelatin (Fig. 7.2). However, the slower recurrence of hunger after the α-lactalbumin-containing breakfast is unlikely to be due to its high tryptophan content, as addition of tryptophan to gelatin to the same levels present in α-lactalbumin did not affect subjective ratings of hunger or satiety. Also, there were no differences in plasma ratio of l-tryptophan to LNAA between the three breakfasts, implying that the differences in satiating properties between α-lactalbumin and gelatin are not likely to be related to differences in brain serotonin synthesis. Therefore, other biological mechanisms should be involved in the relatively strong appetite-suppressing effect of the milk peptide,

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α-lactalbumin. Plasma responses of GLP-1 and ghrelin, a “satiety” and “hunger” hormone, respectively, which are implicated to play a role in the regulation of appetite and energy intake (Dhillo and Bloom, 2004), were similar for an α-lactalbumin and a gelatin-containing breakfast (Nieuwenhuizen et al., 2009), indicating that these hormones are not involved in the differences in hunger rates between those breakfasts. This is in accordance with recent studies showing that the increased satiety after a high-protein meal compared to a nonprotein meal is not mediated by changes in circulating ghrelin and/or GLP-1 concentrations (Lejeune et al., 2006; Moran et al., 2005; Smeets et al., 2008). Therefore, the satiating properties of dietary protein, in general, are likely to be mediated by a more complex set of mechanisms, and this may even be protein specific, as has recently been suggested (Veldhorst et al., 2008).

Conclusion The monoamine neurotransmitter, serotonin, is involved in the regulation of human appetite and food intake. As serotonin production in the brain is depending on the plasma availability of its precursor, l-tryptophan, or, more precisely, the plasma ratio of l-tryptophan to LNAA, dietary interventions modulating l-tryptophan availability may affect appetite and/or food intake. Potential interventions include administration of l-tryptophan or another serotonin precursor, 5-HTP. α-lactalbumin, a milk-derived peptide, is relatively rich in l-tryptophan, and has been shown to increase the plasma ratio of l-tryptophan to LNAA following ingestion. Accordingly, recent studies show that this peptide is more satiating than other more common dietary proteins (Nieuwenhuizen et al., 2009; Veldhorst et al., 2008, 2009). However, it seems unlikely that the high levels of tryptophan fully account for the outstanding satiating properties of α-lactalbumin. In conclusion, the naturally occurring peptide, α-lactalbumin, may help to reduce appetite and food intake; however, its mechanism of action remains to be elucidated.

References Berthoud HR, Morrison C. The brain, appetite, and obesity. Annu Rev Psychol 2008;59:55–92. Beulens JW, Bindels JG, de Graaf C, Alles MS, Wouters-Wesseling W. Alpha-lactalbumin combined with a regular diet increases plasma TrpLNAA ratio. Physiol Behav 2004;81(4):585–593.

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Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev 1998;3(4):271–280. Blundell JE. Serotonin manipulations and the structure of feeding behaviour. Appetite 1986;7(Suppl.):39–56. Borzoei S, Neovius M, Barkeling B, Teixeira-Pinto A, Rossner S. A comparison of effects of fish and beef protein on satiety in normal weight men. Eur J Clin Nutr 2006;60(7):897–902. Bowen J, Noakes M, Clifton PM. Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake. J Clin Endocrinol Metab 2006;91(8):2913–2919. Cangiano C, Ceci F, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Antonucci F, Rossi-Fanelli F. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992;56(5):863–867. Cavaliere H, Medeiros-Neto G. The anorectic effect of increasing doses of l-tryptophan in obese patients. Eat Weight Disord 1997;2(4):211– 215. Dhillo WS, Bloom SR. Gastrointestinal hormones and regulation of food intake. Horm Metab Res 2004;36(11–12):846–851. Evers EA, Tillie DE, Van Der Veen FM, Lieben CK, Jolles J, Deutz NE, Schmitt JA. Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers. Psychopharmacology (Berl) 2005;178(1):92–99. Fernstrom JD. Dietary effects on brain serotonin synthesis: relationship to appetite regulation. Am J Clin Nutr 1985;42(Suppl. 5):1072–1082. Fernstrom JD. Role of precursor availability in control of monoamine biosynthesis in brain. Physiol Rev 1983;63(2):484–546. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 2007;132(1):397–414. Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE. Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs 2007;67(1):27–55.

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Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr 2003;89(2):239–248. Lang V, Bellisle F, Alamowitch C, Craplet C, Bornet FR, Slama G, Guy-Grand B. Varying the protein source in mixed meal modifies glucose, insulin and glucagon kinetics in healthy men, has weak effects on subjective satiety and fails to affect food intake. Eur J Clin Nutr 1999;53(12):959–965. Lang V, Bellisle F, Oppert JM, Craplet C, Bornet FR, Slama G, Guy-Grand B. Satiating effect of proteins in healthy subjects: a comparison of egg albumin, casein, gelatin, soy protein, pea protein, and wheat gluten. Am J Clin Nutr 1998;67(6):1197–1204. Latham CJ, Blundell JE. Evidence for the effect of tryptophan on the pattern of food consumption in free feeding and food deprived rats. Life Sci 1979;24(21):1971–1978. Leibowitz SF, Alexander JT. Hypothalamic serotonin in control of eating behavior, meal size, and body weight. Biol Psychiatry 1998;44(9):851–864. Lejeune MP, Westerterp KR, Adam TC, Luscombe-Marsh ND, Westerterp-Plantenga MS. Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber. Am J Clin Nutr 2006;83(1):89–94. Lieben CK, van Oorsouw K, Deutz NE, Blokland A. Acute tryptophan depletion induced by a gelatin-based mixture impairs object memory but not affective behavior and spatial learning in the rat. Behav Brain Res 2004;151(1–2):53–64. Markus CR, Olivier B, de Haan EH. Whey protein rich in alphalactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects. Am J Clin Nutr 2002;75(6):1051– 1056. Markus CR, Olivier B, Panhuysen GE, Van Der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF, de Haan EE. The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects

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raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress. Am J Clin Nutr 2000;71(6):1536–1544. Millard SA, Costa E, Gal EM. On the control of brain serotonin turnover rate by end product inhibition. Brain Res 1972;40(2):545–551. Moran LJ, Luscombe-Marsh ND, Noakes M, Wittert GA, Keogh JB, Clifton PM. The satiating effect of dietary protein is unrelated to postprandial ghrelin secretion. J Clin Endocrinol Metab 2005;90(9):5205–5211. Nieuwenhuizen AG, Hochstenbach-Waelen A, Veldhorst M, Westerterp KR, Engelen MPKJ, Brummer RJM, Deutz NE, Westerterp-Plantenga MS. Acute effects of breakfasts containing alpha-lactalbumin, or gelatin with or without added tryptophan, on hunger, ‘satiety’ hormones and amino acid profiles. Br J Nutr 2009;101:1859–1866. Poppitt SD, McCormack D, Buffenstein R. Short-term effects of macronutrient preloads on appetite and energy intake in lean women. Physiol Behav 1998;64(3):279–285. Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA. Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med 2006;8(20):1–27. Silverstone T, Goodall E. Serotoninergic mechanisms in human feeding: the pharmacological evidence. Appetite 1986;7(Suppl.):85–97. Smeets AJ, Soenen S, Luscombe-Marsh ND, Ueland O, WesterterpPlantenga MS. Energy expenditure, satiety, and plasma ghrelin, glucagon-like peptide 1, and peptide tyrosine-tyrosine concentrations following a single high-protein lunch. J Nutr 2008;138(4):698– 702. Toornvliet AC, Pijl H, Hopman E, Elte-de Wever BM, Meinders AE. Serotoninergic drug-induced weight loss in carbohydrate craving obese patients. Int J Obes Relat Metab Disord 1996;20(10):917–920. Ugrumov MV. Hypothalamic monoaminergic systems in ontogenesis: development and functional significance. Int J Dev Biol 1997;41(6):809–816. Uhe AM, Collier GR, O’Dea K. A comparison of the effects of beef, chicken and fish protein on satiety and amino acid profiles in lean male subjects. J Nutr 1992;122(3):467–472.

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Varga J, Jimenez SA, Uitto J. l-tryptophan and the eosinophilia-myalgia syndrome: current understanding of the etiology and pathogenesis. J Invest Dermatol 1993;100(1):97S–105S. Veldhorst M, Smeets A, Soenen S, Hochstenbach-Waelen A, Hursel R, Diepvens K, Lejeune M, Luscombe-Marsh N, Westerterp-Plantenga M. Protein-induced satiety: effects and mechanisms of different proteins. Physiol Behav 2008;94(2):300–307. Veldhorst MA, Nieuwenhuizen AG, Hochstenbach-Waelen A, Westerterp KR, Engelen MP, Brummer RJ, Deutz NE, Westerterp-Plantenga MS. A breakfast with alpha-lactalbumin, gelatin, or gelatin + TRP lowers energy intake at lunch compared with a breakfast with casein, soy, whey, or whey-GMP. Clin Nutr 2009;28:147–155. Weigle DS, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, Purnell JQ. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr 2005;82(1):41–48. Wurtman RJ, Fernstrom JD. Control of brain monoamine synthesis by diet and plasma amino acids. Am J Clin Nutr 1975;28(6):638–647. Wurtman RJ, Wurtman JJ. Do carbohydrates affect food intake via neurotransmitter activity? Appetite 1988;11(Suppl. 1):42–47.

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The Effects of Casein-, Whey-, and Soy Protein on Satiety, Energy Expenditure, and Body Composition Margriet Veldhorst, MSc, Anneke van Vught, MSc, and Prof. Dr. Margriet Westerterp-Plantenga, PhD

Abstract Relatively high-protein diets have come into focus as having the potential to act on the different metabolic targets regulating body weight, via (i) an increased postprandial and postabsorptive satiety, (ii) preservation of fat-free body mass, and (iii) a lower energy efficiency due to increased thermogenesis. Casein, whey, and soy are three important protein sources of the diet that have been shown to be more satiating than controls such as carbohydrates or water. When protein types are compared with each other, whey seems to be more satiating than casein or soy. Consumption of casein, whey, or soy induces changes in specific hormones but every type of protein has its own mechanism inducing satiety, mainly dependent on amino acid content. In the longer term, additional to the satiety effect, a sustained energy expenditure in negative energy balance and a fat-free mass sparing effect, possibly induced by changes in the somatotropic axis, may be responsible for the weight maintenance after weight-loss effects of high-protein diets. Again, amino acid composition is of major importance as the mechanism through which protein may influence energy expenditure and body composition. Long-term consumption of high-protein diets may have adverse effects on the 121

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kidneys and on blood pressure in at-risk populations such as diabetics or those with existing renal disease. In healthy individuals, relatively high protein intake does not seem to have serious adverse effects.

Background Overweight and obesity are rapidly growing into a threat with epidemic proportions and are the result of a positive energy balance, which arises when energy intake exceeds energy expenditure. The solution for the problem of overweight and obesity in humans is body weight maintenance after body weight loss. Conditions for successful weight maintenance are (i) sustained satiety despite a negative energy balance, (ii) sustained basal energy expenditure despite body weight loss due to (iii) sparing of fatfree mass, since fat-free mass is the main determinant of basal energy expenditure. In the context of research on prevention and treatment of overweight and obesity, relatively high-protein diets have come into focus as having the potential to act on the different metabolic targets regulating body weight. High protein intake has been shown to play a role during weight loss as well as during weight maintenance thereafter through (i) an increased postprandial and postabsorptive satiety, (ii) preservation of fat-free body mass, and (iii) a lower energy efficiency due to increased thermogenesis. A hierarchy has been observed for the satiating properties of the three different macronutrients protein, carbohydrate, and fat, with protein being the most satiating and fat the least. A dose-dependent satiating effect of protein offered acutely, that is, in a single meal, has been shown in subjects who are in energy balance and are weight stable. In addition, persistent protein-induced satiety has been shown when a high-protein diet was given for 24 hours up to several days. Usually mixed proteins are used, for instance from meat, fish, plants, or dairy products. In terms of satiating properties, however, it is important to distinguish between types of protein since differences have been shown between different types of protein. This chapter focuses on the comparison of the acute meal-induced and mediumterm diet-induced satiating properties of three different types of protein, that is, casein, whey, and soy. In addition, other factors through which protein plays a role in weight loss and weight maintenance are discussed.

Types of Protein Casein, whey, and soy are three important protein sources of the diet; together they make up a large part of the total daily protein intake. Casein

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and whey are derived from milk or other dairy products; soy is a vegetable protein source that is derived from soybeans.

Casein Casein is an important part of milk protein; it comprises ∼80% of the protein content of bovine milk. It is considered as a “slow” protein because it coagulates in the stomach and delays gastric emptying.

Whey Whey protein is the other primary source of milk protein; ∼20% of milk protein is whey. The components of whey include β-lactoglobulin, α-lactalbumin, and glycomacropeptide (GMP). Whey is a popular dietary protein supplement suggested to provide immune modulation, improved muscle strength and body composition, and to prevent cardiovascular disease and osteoporosis. In comparison with casein, it is considered as a relatively “fast” protein and therefore has been suggested to induce satiety quickly. The bioactive peptide GMP has been suggested to decrease food intake.

Soy Despite being a vegetable protein, soy is considered as a complete protein since it contains all essential amino acids. Soy-containing diets are suggested to have health promoting effects, such as lowering of cholesterol and protective effects against obesity, diabetes, and kidney disease.

Short-Term Effects of Casein, Whey, and Soy on Satiety Casein, whey, and soy have been shown to be more satiating than controls such as water or carbohydrates, and there are several studies that have compared the satiating properties of these types of protein with each other. There are a few methods to determine effects on satiety, including measurement of (i) appetite ratings, (ii) orexigenic and anorexigenic hormones, amino acids, and/or other metabolites, and (iii) ad libitum food intake.

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Methods to Determine Satiety Appetite ratings are measured with visual analogue scales asking questions like “How hungry do you feel?” “How satiated do you feel?” “How full do you feel?” and “How is your desire to eat?” Subjects are instructed to rate themselves on a 100-mm horizontal line anchored with “not at all” and “extremely.” Orexigenic and anorexigenic hormones that are involved in appetite regulation and that are often measured are ghrelin, glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY), and insulin. The third method to measure effects on satiety is to offer subjects an ad libitum meal after a previous, subject-specific fixed meal, and instruct them to eat till they are comfortably full. The amount of food consumed from the ad libitum meal has to be measured and provides information on the satiety induced by the previous fixed meal relative to a previous control meal.

Effects of Casein, Whey, and Soy on Satiety When casein and whey were at breakfast as 1.7 MJ with 48 g of one of the protein types, there was a reduced desire to eat after the whey breakfast compared with the casein breakfast (Hall et al., 2003). In a similar experiment, however, these results could not be replicated; no differences between casein and whey in breakfasts, with respect to subsequent appetite ratings, appetite regulatory hormones, or ad libitum food intake, were observed (Bowen et al., 2006b). Whey and soy reduced ad libitum food intake to the same extend 3 hours after a 1.1 MJ liquid consumption with 50 g whey or soy. In addition, no differences in postprandial ghrelin, GLP-1, insulin, and CCK concentrations were observed (Bowen et al., 2006a). Drinks with 45–50 g whey or soy decreased food intake 1 hour later compared with control (Anderson et al., 2004). Also, no difference was observed after the casein or soy treatment in subsequent satiety, 24-hour energy- or macronutrient intakes, or postprandial glucose and insulin concentrations after a lunch of 5.2 MJ with 22% of energy from protein with ∼65% of the protein from casein or soy (Lang et al., 1998). A casein-rich lunch, however, delayed glucose and insulin responses for 1.5 hours compared with soy, but there were only weak and inconsistent effects on hunger and satiety ratings and no effects on 24-hour energy- or macronutrient intakes (Lang et al., 1999). Whey was more satiating than casein or soy when offered in a breakfast with 10% of energy from one of

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70 Casein

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Figure 8.1. Satiety after a breakfast with either casein-, whey-, or soy protein. (Adapted from Veldhorst et al., 2007.)

the single protein types, whereas there were no differences in satiety between protein types at the level of 25% of energy from protein. Although whey was more satiating than casein or soy at the level of 10% of energy from protein, there was no effect on energy intake 3 hours after breakfast (Veldhorst et al., 2007). GMP has been shown to increase pancreatic secretion of digestive peptides (Beucher et al., 1994; Pedersen et al., 2000); nevertheless, pure GMP in a beverage with 0.4% or 2.0% GMP had no effect on energy intake of subjective satiety ratings (Gustafson et al., 2001). The presence or absence of GMP in whey also had no remarkable effect on subsequent satiety, food intake, or CCK release (Burton-Freeman, 2007). In another experiment, however, GMP as part of whey in a breakfast lowered subsequent energy intake at lunch with ∼10% compared with a breakfast with whey without GMP (Veldhorst et al., 2008b) (Fig. 8.1).

Explanations for Differences in Results Differences in results between experiments comparing the satiating properties of different types of protein may have several reasons. First of

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all, the protein content of the preload or the meal is of major importance. In the above-mentioned experiments, protein content ranged from 10 energy% to >90 energy%. A high level of protein, being the most satiating macronutrient, induces an elevated satiety response making it impossible to distinguish between types of protein. Furthermore, not all proteins that were used in the experiments were pure proteins; sometimes a mixture of proteins was tested. The most important factor when studying the effects of different types of protein on subsequent food intake, however, is the timing of a test meal. Effects on energy intake can only be observed if the test meal is offered at a sensitive and relevant moment in time. Differences in energy intake should not occur too early, because of the irrelevance of a meal at that moment in a normal, free-living condition, nor too late, since differences in appetite ratings or hormones have then become extinguished. What the most sensitive moment in time is can be different for different types of protein, and should be tested beforehand in each different condition.

Conclusion Although there are different results reported in literature, one may conclude that whey is more satiating than casein however without any significant effects on food intake. GMP as a whey fraction does seem to reduce food intake compared with whey without GMP. Differences between effects of soy and casein or soy and whey consumption are less pronounced.

Long-Term Effects of Casein, Whey, and Soy Several studies have found a continuously higher satiety throughout the day after a high-protein versus a normal-protein diet, for instance, in the energy balance controlled condition of a respiration chamber (WesterterpPlantenga et al., 1999a). But also in a situation of negative energy balance, a high-protein diet has been found to induce a sustained satiety (Lejeune et al., 2006; Westerterp-Plantenga et al., 2006). Energy expenditure has been shown to be increased after a high-protein diet for 36 hours compared with a high-fat diet (Lejeune et al., 2006; Westerterp-Plantenga et al., 1999a) as well as in comparison with a normal diet (Lejeune et al., 2006). Although casein, whey, and soy are highquality proteins containing essential amino acids, consumption of only

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one type of protein is difficult. Therefore, there have hardly been any studies comparing the effects of casein, whey, or soy on satiety, energy expenditure, or body composition in the medium or long term. In one experiment, casein and soy both induced a significant weight loss when they were offered in a shake three times a day as part of a 16-week energyrestricted diet for obese women, but there were no differences in weight loss or loss of fat mass between casein and soy (Anderson et al., 2007).

Mechanisms of Action Mechanisms that may contribute to the increased satiety of a highprotein meal or diet are (i) increases in concentrations of certain hormones or metabolites (i.e., amino acids), (ii) increases in energy expenditure, and (iii) changes in the somatotropic axis leading to beneficial changes in body composition. Differences in satiating properties between different types of protein can therefore be attributed to protein-specific characteristics regarding, for instance, amino acid content, rate of absorption, and the ability to induce changes in certain hormones or metabolites.

Changes in Concentrations of Hormones or Metabolites Coinciding with the increased satiety after a breakfast with whey compared with casein, there were increased concentrations of the amino acids leucine, lysine, tryptophan, isoleucine, and threonine. These amino acids may play a role in the satiating effect of whey (Veldhorst et al., 2007, 2008a). Moreover, the faster gastric emptying and absorption of whey resulting in higher postprandial excursions of amino acids compared with casein is suggested to induce an increased satiety (Hall et al., 2003). This is in line with the amino static theory from Mellinkoff that states that a larger rise in plasma amino acids increases satiety (Mellinkoff et al., 1956). The slower digestion of casein may also induce reduced or retarded hormone responses, as was the case in comparison with soy (Lang et al., 1999). Consumption of a meal with casein, whey, or soy protein lead to changes in hormones such as insulin, GLP-1, or ghrelin, which, in some cases, were different between the different types of protein (Veldhorst et al., 2008a). These changes in hormones, however, were not related to changes in satiety and are a physiological response to the presence of nutrients but

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do not necessarily have a direct relation with feelings of satiety (Smeets et al., 2008; Veldhorst et al., 2008a).

Energy Expenditure A high-protein-diet-induced satiety has been shown to be related to elevated energy expenditure (Lejeune et al., 2006). Increased energy expenditure implies increased oxygen consumption and an increase in body temperature both leading to feeling deprived of oxygen and thus promote satiety (Westerterp-Plantenga et al., 1999b, 2006). Energy expenditure is different due to different protein types and is mediated by digestion rate and ATP costs of postprandial protein synthesis. Taking into account the stoichiometry of amino acid catabolism and urea synthesis, the energy expenditure to produce ATP varies per amino acid and hence also per type of protein (Westerterp-Plantenga et al., 2006).

Body Composition In the longer term, dietary protein has been shown to have a positive effect on body composition; increasing the level of protein increased lean body mass and reduced body fat (Jean et al., 2001). During weight maintenance, protein intake is characterized by a fat-free mass sparing effect and fat mass reducing effect (Westerterp-Plantenga et al., 2004). The effect of dietary protein on body composition may be mediated by the somatotropic effects of protein and of some amino acids in particular. The somatotropic axis, that is, growth hormone (GH)/insulin-like growth factor-1 (IGF-1 axis), plays an important role in muscle mass synthesis (Flakoll et al., 2004), regulation of the fat distribution and reducing fat mass (Bengtsson et al., 1992). Dietary protein, for instance soy, as well as some amino acids, particularly arginine and lysine, have been shown to stimulate the somatotropic axis (Bengtsson et al., 1992; Hoppe et al., 2004; van Vught et al., 2008a, 2008bb). Studies suggest that the amino acid composition is crucial in understanding the mechanism through which protein may influence GH and IGF-1 production in relation to body composition. Milk protein, for instance, increases IGF-1 concentrations in children, whereas vegetable proteins or meat proteins do not show an effect on IGF-1 (Hoppe et al., 2004). Recently, associations were found between intakes of the specific amino acids arginine and arginine in combination with lysine and the development of fat-free mass and fat mass in children. Arginine alone or

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FFM

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Figure 8.2. Influence of protein and the amino acids arginine (ARG) and lysine (LYS) on fat-free mass (FFM) and fat mass (FM), via growth hormone (GH) and insulin growth factor 1 (IGF-1).

combined with lower amounts of lysine reduced fat mass gain, and arginine combined with high lysine stimulated the fat-free mass development (van Vught et al., 2008c). The interaction between the amino acids suggest that the effects of proteins on body composition may consist of the available amount and combination of specific amino acids (Fig. 8.2).

Conclusion Overall, it can be concluded that every type of protein has its own mechanism inducing satiety, mainly dependent on amino acid content. Consumption of casein, whey, or soy induces changes in certain hormones, but these changes do not necessarily have a direct relation with satiety. In the longer term, additional to the satiety effect, a sustained energy expenditure in negative energy balance and sparing of fat-free mass possibly induced by changes in the somatotropic axis may be responsible for the weight maintenance after weight-loss effects of high-protein diets.

Safety Long-term consumption of high-protein diets may have adverse effects on the kidneys and on blood pressure, especially in at-risk populations such as diabetics or those with existing renal disease. In healthy individuals, relatively high protein intake does not seem to have serious adverse effects (Eisenstein et al., 2002). Different amino acids may have opposing effects on the kidneys and blood pressure, dependent on whether they are involved in

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gluconeogenesis and/or ureagenesis or whether they are acidifying. Amino acids involved in gluconeogenesis and/or ureagenesis may have a blood pressure lowering effect, whereas acidifying amino acids may have a blood pressure raising effect. Subjects with subclinical renal injury, low renal functional mass, or obesity-related conditions will be more susceptible to the blood pressure raising effects than others (Veldhorst et al., 2008a).

Food Supplement Applications Casein, whey, and soy are often used, alone or in combination with each other, as protein source in nutritional supplement products to enhance sports performance and building muscle mass. In health stores and on the internet, numerous products can be found that are claimed to be helpful for people who want to increase their muscle mass and muscle strength. Moreover, some companies offer soy protein as a food supplement that is suggested to be beneficial for weight loss, because of less hunger and better glycemic control. Combinations of casein, whey, and/or soy are used in weight-loss products and diets to enhance satiety and thereby reduce food intake.

Patent Activities There are some patents on the protein content of body weight control products, for instance, patent MXPA04008476 entitled “Compositions and methods for treatment of body weight conditions with milk minerals and casein fractions” or patent FR2889067 entitled “Using protein fraction from whey for control of body weight, e.g. to promote slimming, comprises β-lactoglobulin, and α-lactalbumin at specified ratio.”

Information on Global Suppliers Casein and whey protein are supplied by the dairy industry with numerous companies offering different forms of casein or whey. Soy protein is, among others, supplied by The Solae Company and The Central Soya Company.

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References Anderson JW, Fuller J, Patterson K, Blair R, Tabor A. Soy compared to casein meal replacement shakes with energy-restricted diets for obese women: randomized controlled trial. Metabolism 2007;56:280–288. Anderson GH, Tecimer SN, Shah D, Zafar TA. Protein source, quantity, and time of consumption determine the effect of proteins on short-term food intake in young men. J Nutr 2004;134:3011–3015. Bengtsson BA, Brummer RJ, Eden S, Rosen T, Sjostrom L. Effects of growth hormone on fat mass and fat distribution. Acta Paediatr Suppl 1992;383:62–65; discussion 66. Beucher S, Levenez F, Yvon M, Corring T. Effects of gastric digestive products from casein on CCK release by intestinal cells in rat. J Nutr Biochem 1994;5:578–584. Bowen J, Noakes M, Clifton PM. Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake. J Clin Endocrinol Metab 2006a;91:2913–2919. Bowen J, Noakes M, Trenerry C, Clifton PM. Energy intake, ghrelin, and cholecystokinin after different carbohydrate and protein preloads in overweight men. J Clin Endocrinol Metab 2006b;91:1477– 1483. Burton-Freeman BM. Glycomacropeptide (GMP) is not critical to wheyinduced satiety, but may have a unique role in energy intake regulation through cholecystokinin (CCK). Physiol Behav 2007;93(1–2):379– 387. Eisenstein J, Roberts SB, Dallal G, Saltzman E. High-protein weight-loss diets: are they safe and do they work? A review of the experimental and epidemiologic data. Nutr Rev 2002;60:189–200. Flakoll P, Sharp R, Baier S, Levenhagen D, Carr C, Nissen S. Effect of beta-hydroxy-beta-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women. Nutrition 2004;20:445–451. Gustafson DR, McMahon DJ, Morrey J, Nan R. Appetite is not influenced by a unique milk peptide: caseinomacropeptide (CMP). Appetite 2001;36:157–163.

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Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr 2003;89:239–248. Hoppe C, Udam TR, Lauritzen L, Molgaard C, Juul A, Michaelsen KF. Animal protein intake, serum insulin-like growth factor I, and growth in healthy 2.5-y-old Danish children. Am J Clin Nutr 2004;80:447–452. Jean C, Rome S, Mathe V, Huneau JF, Aattouri N, Fromentin G, Achagiotis CL, Tom´e D. Metabolic evidence for adaptation to a high protein diet in rats. J Nutr 2001;131:91–98. Lang V, Bellisle F, Alamowitch C, Craplet C, Bornet FRJ, Slama G, Guy-Grand B. Varying the protein source in mixed meal modifies glucose, insulin and glucagon kinetics in healthy men, has weak effects on subjective satiety and fails to affect food intake. Eur J Clin Nutr 1999;53:959–965. Lang V, Bellisle F, Oppert JM, Craplet C, Bornet FR, Slama G, Guy-Grand B. Satiating effect of proteins in healthy subjects: a comparison of egg albumin, casein, gelatin, soy protein, pea protein, and wheat gluten. Am J Clin Nutr 1998;67:1197–1204. Lejeune MP, Westerterp KR, Adam TC, Luscombe-Marsh ND, Westerterp-Plantenga MS. Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber. Am J Clin Nutr 2006;83:89–94. Mellinkoff SM, Frankland M, Boyle D, Greipel M. Relationship between serum amino acid concentration and fluctuations in appetite. J Appl Physiol 1956;8:535–538. Pedersen NL, Nagain-Domaine C, Mahe S, Chariot J, Roze C, Tome D. Caseinomacropeptide specifically stimulates exocrine pancreatic secretion in the anesthetized rat. Peptides 2000;21:1527–1535. Smeets AJ, Soenen S, Luscombe-Marsh ND, Ueland O, WesterterpPlantenga MS. Energy expenditure, satiety, and plasma ghrelin, glucagon-like peptide 1, and peptide tyrosine-tyrosine concentrations following a single high-protein lunch. J Nutr 2008;138:698–702. van Vught AJ, Nieuwenhuizen AG, Brummer RJ, Westerterp-Plantenga MS. Effects of oral ingestion of amino acids and proteins on the somatotropic axis. J Clin Endocrinol Metab 2008a;93:584–590.

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van Vught AJ, Nieuwenhuizen AG, Brummer RJ, Westerterp-Plantenga MS. Somatotropic responses to soyprotein alone and as part of a meal. Eur J Endocrinol 2008b;159(1):15–18. van Vught JAH, Heitmann B, Nieuwenhuizen AG, Veldhorst MAB, Brummer RJM, Westerterp-Plantenga MS. Associations between dietary protein and 6y-change in body composition among normal and overweight 9y old boys and girls (EYHS). ECO 2008, Geneva, 2008c. Veldhorst MAB, Nieuwenhuizen AG, Hochstenbach-Waelen A, Westerterp KR, Engelen MPKJ, Brummer R-JM, Deutz NEP, WesterterpPlantenga MS. Effects of high or normal casein-, soy-, or whey with or without GMP- protein breakfasts on satiety, ‘satiety’ hormones, and plasma amino acid responses. Appetite 2007;49:336. Veldhorst M, Smeets A, Soenen S, Hochstenbach-Waelen A, Hursel R, Diepvens K, Lejeune M, Luscombe-Marsh N, Westerterp-Plantenga M. Protein-induced satiety: effects and mechanisms of different proteins. Physiol Behav 2008a;94:300–307. Veldhorst MAB, Nieuwenhuizen AG, Hochstenbach-Waelen A, Westerterp KR, Engelen MPKJ, Brummer R-JM, Deutz NEP, WesterterpPlantenga MS. Effects of casein-, soy-, whey with or without GMP-, alpha-lactalbumin, or gelatin with or without added tryptophan- protein breakfasts on energy intake. Int J Obes 2008b;32:S142. Westerterp-Plantenga MS, Lejeune MP, Nijs I, van Ooijen M, Kovacs EM. High protein intake sustains weight maintenance after body weight loss in humans. Int J Obes Relat Metab Disord 2004;28:57–64. Westerterp-Plantenga MS, Luscombe-Marsh N, Lejeune MP, Diepvens K, Nieuwenhuizen A, Engelen MPKJ, Deutz NEP, Azzout-Marniche D, Tome D, Westerterp KR. Dietary protein, metabolism, and body-weight regulation: dose-response effects. Int J Obes (Lond) 2006;30(Suppl. 3):S16–S23. Westerterp-Plantenga MS, Rolland V, Wilson SA, Westerterp KR. Satiety related to 24 h diet-induced thermogenesis during high protein/carbohydrate vs high fat diets measured in a respiration chamber. Eur J Clin Nutr 1999a;53:495–502. Westerterp-Plantenga MS, Westerterp KR, Rubbens M, Verwegen CR, Richelet JP, Gardette B. Appetite at “high altitude” [Operation Everest III (Comex-’97)]: a simulated ascent of Mount Everest. J Appl Physiol 1999b;87:391–399.

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CHAPTER 9

Soy Peptides and Weight Management Cristina Mart´ınez-Villaluenga, PhD, and Elvira Gonzalez ´ de Mej´ıa, PhD

Abstract In this chapter, the authors relay available scientific information regarding the role of soy peptides or soy hydrolysates on weight management. Proposed mechanisms include (a) regulation of satiety and food intake; (b) decrease lipid absorption and modulation of lipid metabolism; (c) increased thermogenesis and energy expenditure; and (d) inhibition of adipogenesis. Although there is not enough clinical information to claim a clear benefit of soy peptides on obesity, there is evidence to suggest that some soy peptides may have a future as regulators of adiposity and satiety. These two properties may have an impact on weight management.

Introduction Obesity is a major contributor to the burden of chronic disease and disability in developed and developing countries. Despite public health education, the prevalence of obesity continues to increase and more than 30% of adults in the United States are obese (Odgen et al., 2007). The use of most drugs developed to date is limited by unacceptable adverse reactions or the potential for abuse during long-term pharmacotherapy (Ioannides-Demos et al., 2006). Therefore, new therapeutics to reduce body weight with minimal adverse reactions will be beneficial. In recent years, high-protein diets gained widespread popularity before scientific 135

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Protein based ingredients Intestinal tract

Dietary proteins

Epithelial cells

Inside the body

Resistant dietary proteins

Proteins

Resistant oligopeptides

Peptides

Proteinases Oligopeptides

Hydrolyzed

Peptidases Di(tri)peptides

Resistant di(tri)peptides

Peptides and amino acids Di(tri)peptides

Hydrolyzed

Peptidases Amino acids

Amino acids

Amino acids Metabolized

Figure 9.1. Bioactive peptides are liberated from dietary proteins and can display bioactivity in the small and large bowel (Adapted from Shimizu, 2004.)

evidences on their safety or efficacy were fully understood. Dietary proteins are hydrolyzed to amino acids and peptides in the gastrointestinal tract, and consequently different chain lengths and amino acid sequences are generated as intermediates. Figure 9.1 presents a simplified diagram of the absorption of food-derived peptides. These peptides have important roles in the intestinal tract before being absorbed because they can modulate nutrient absorption in the intestines. The understanding of the performance of dietary peptides in the intestine is vital for designing functional foods with physiological functions (Shimizu, 2004). Peptides are absorbed directly from the intestine by peptide-specific transport systems (Takamatsu, 2006). A peptide-specific transporter was cloned and characterized as a H+ -coupled transporter of oligopeptides named PepT1 (Fei et al., 1994). It displays broad substrate specificity, unlike amino acid transporters. These studies clearly show that peptides are absorbed with their intact primary structures (Chun et al., 1996; Ihara et al., 1990). Thus, it is thought that in the intestine, peptide transporters constitute a major mechanism for absorption of the products of protein digestion (Brandsch et al., 2008; Fei et al., 1994). Peptides are unique components of living organisms and appear in many biological capacities, nutritional activities, and fermentation processes. Many types of biologically active peptides in the body, such as hormones, participate in inter- and intracellular communication and activities.

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Research to determine the physiological function of dietary peptides, and thus their health benefits, are markedly increasing. Recent in vitro and in vivo studies have shown that, in addition to soy protein and isoflavones, peptides derived from soy protein have biological activities against obesity through different mechanisms. To be considered “bioactive,” a dietary peptide should impart a measurable biological effect at a physiologically realistic level and this “bioactivity” has to have the potential to positively affect health (M¨oller et al., 2008). Processing methods using enzymes, acids, and heating are used for protein hydrolysis to produce peptides. In particular, enzyme hydrolysis has the advantage of high-sequence specificity, low energy cost, and avoidance of generating undesirable compounds. Soy peptides may be also produced by fermentation of soybean in which protein hydrolysis takes place by microbial proteases. This is a suitable method of producing soy peptides for food applications, especially for health purposes. In this chapter, we provide an overview of the most up-to-date experimental evidence on efficacy, mechanisms of action, safety, and food applications of soy peptides in weight management.

Efficacy and Mechanisms of Action of Soy Peptides in Weight Management A number of studies in cell lines, animals, and humans support the evidence concerning the potential relationship between soy peptides and weight loss. The mechanisms whereby soy peptides have an impact on weight loss are still under study. Several lines of evidence suggest that soy peptides may affect satiety and food intake (Foltz et al., 2008; Jang et al., 2008; Nishi et al., 2003a, 2003b; Rho et al., 2007; Takenaka et al., 2000b), lipid absorption and lipid metabolism (Aoyama et al., 2000a; Cho et al., 2007; Jang et al., 2008; Lovati et al., 2000; Takenaka et al., 2000a; Yang et al., 2007), energy expenditure and thermogenesis (Claessens et al., 2007; Vaughn et al., 2008), and inhibition of adipogenesis (Kim, 2007; Kim et al., 2007). Table 9.1 summarizes the antiobesity effects and proposed mechanisms of action for soy peptides/hydrolysates.

Soy Peptides May Help Weight Control by Suppressing Food Intake It is believed that the mechanism of action of soy peptides is to regulate food intake by inducing satiety through the activation of opioid and

138

Black soybean hydrolysis by protease for 5 hours; ultrafiltration (MWCO 3 and 10 kDa), gel filtration chromatography and RP-HPLC Tryptic–chymotryptic digestion of genetically modified proglycinin

Black soy peptide (Ile-Gln-ASn)

Tryptic–chymotryptic digestion of glycinin A5 A4 B3

Black soybean protein hydrolysis by protease for 5 hours

Black soy peptides

Takenaka et al. (2000a)

Takenaka et al. (2000b)

Suppression of food intake

Lipid lowering effect by reducing cholesterol absorption and increasing fecal bile excretion

Kim et al. (2007)

Inhibition of adipogenesis in 3T3-L1 preadipocytes

Jang et al. (2008), Rho et al. (2007) Jang et al. (2008)

Kim (2007)

Nishi et al. (2003b)

Nishi et al. (2003a)

Reference

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Peptide from proglycinin A1a B1b (LPYPR) Peptide from glycinin A5 A4 B3 (LPYPR)

β-Conglycinin hydrolysis by alcalase from B. licheniformis at pH 8.0, 50◦ C for 3 hours Synthesis; protease hydrolysis for 5 hours

β-Conglycinin hydrolysates Black soy peptides

Suppression of food intake through stimulation of CCK1 R and secretion of CCK in vivo Suppression of food intake through secretion of CCK and inhibition of gastric emptying in vivo Inhibition of lipid accumulation and adiponectin induction in 3T3-L1 adipocytes Suppression of food intake through leptin-like signaling in the hypothalamus in rodents Lipid lowering effect through activation of the phosphorylation of 5 AMP-activated protein kinase (AMPK) and inhibition of ACC phosphorylation in rats

Synthesis; hydrolysis by pepsin pH 1.8 and trypsin pH 8.0 at 37◦ C for 10 minutes Pepsin hydrolysis at pH 1.8, 37◦ C for 10 minutes

Mechanism of Action

Preparation

β-Conglycinin peptides and hydrolysates β-Conglycinin hydrolysates

Material

Table 9.1. Antiobesity effects and potential mechanisms of action reported for soy peptides/hydrolysates

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Soy protein concentrate (CroksoyR 70) hydrolysis by pepsin-trypsin; ultrafiltration using cutoff membranes of 3,000 and 1,000 kDa Isolated soy protein hydrolysis by alkaline (APR68) and neutral protease (NPR68) from B. amyloliquefaciens FSE-68

Soy protein hydrolysate

Soy protein hydrolysates

Soy protein hydrolysates Soy protein isolate hydrolysis by alcalase from B. licheniformis at pH 8, 50◦ C for 3 hours

Drinks containing soy protein hydrolysate (0.4 g protein hydrolysate per kg of body weight) Soy protein isolate hydrolysis by alcalase from B. licheniformis at pH 8, 50◦ C for 3 hours Quest International, The Netherlands

Soy protein hydrolysates

Kim (2007)

Inhibition of adipogenesis through overexpression of pref-1 factor in 3T3-L1 preadipocytes Suppression of food intake through stimulation of CCK1 R and secretion of CCK in vitro Reduction of body weight and food intake by increasing energy expenditure and thermogenesis in rats

Vaughn et al. (2008)

Foltz et al. (2008)

Claessens et al. (2007)

Yang et al. (2007)

Cho et al. (2007)

Lovati et al. (2000)

Aoyama et al. (2000a)

Increase of energy expenditure and thermogenesis in humans

Lipid lowering effect by reducing cholesterol absorption and increasing fecal bile excretion in mice Cholesterol lowering effect; reduced synthesis of intracellular cholesterol by upregulation of LDL-R transcription in human liver cell line Cholesterol lowering effect; reduced synthesis of intracellular cholesterol by upregulation of LDL-R transcription in human liver cell line Decrease lipid accumulation in the liver and hypolipidemic effects by enhancing excretion and inhibiting absorption of lipids in rats

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Soy protein hydrolysates

Soybean acid-precipitated protein hydrolysis by pepsin at pH 2, 37◦ C for 24 hours

Soy protein hydrolysate

Soy protein hydrolysates

Soy protein isolate hydrolysis by protease from Bacillus subtillis (Hynute-D1)

Soy protein hydrolysate

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cholecystokinin (CCK) receptors in the gut (Pupovac and Anderson, 2002). In vitro studies support the evidence that soy peptides increase markers of satiety and reduce energy intake, which directly may impact weight loss. Foltz et al. (2008) demonstrated that soy hydrolysates (Quest International, The Netherlands) at low concentrations (10 mg/L) stimulated the release of satiety hormones such as CCK from STC-1 enteroendocrine cells up to 2.1-fold, which in turn activated CCK1 receptor (CCK1 R). Furthermore, soy hydrolysates stimulated CCK1 R-expressing cells and may mediate satiety at least in part, by direct receptor stimulation. In summary, this study demonstrated the potential importance of selected short-chain peptides to act in a dual mode on dietary satiety signaling. In another investigation, in vivo intraduodenal infusion of β-conglycinin hydrolysates inhibited food intake of rats in a dose-dependent manner and this suppression was abolished by intravenous injection of devazepide, a selective peripheral CCK receptor antagonist (Nishi et al., 2003a). The arginine residues in the protein structure was shown to be responsible for CCK release through direct action on the intestinal cells. Regarding the relationship between arginine and binding activity to brush border membrane, synthetic model peptides with one arginine (GGGRGGG and GGGGGGR) showed no activity. The binding activity of synthetic peptides containing two arginine residues depended on the position of the arginine residues. GGRGRGG, GRGGRGG, and GRGGGRG can bind to the brush border membrane while GGGRRGG cannot. GRGRGRG, a synthetic peptide containing three arginine residues had stronger binding ability (Nishi et al., 2003b). Comparing several arginine fragments of βconglycinin on their abilities to bind to the intestinal cell component, the fragment from 51 to 63 of the β subunit of β-conglycinin was found to have the highest binding affinity, also affecting food intake in rats (Nishi et al., 2003b). Soybean β-conglycinin pepsin hydrolysates not only suppressed food intake but also inhibited gastric emptying by direct action on CCK secretion, which contributed to reduction of food intake (Nishi et al., 2003b). Other in vivo studies demonstrated the potential antiobesity activity of a novel peptide mixture called black soy peptide (BSP) derived from black soybean (Jang et al., 2008; Rho et al., 2007) through leptin-like signaling in the hypothalamus. This peptide mixture did not contain a significant amount of isoflavones, and small-size peptides (<10 Kda) composed of more than 80% of BSP. Short- and long-term effects of BSP were evaluated in induced obese rodents fed a high-fat (HF) diet without or with BSP (2%, 5%, and 10% of energy) for 4 weeks (Rho et al., 2007), 13 weeks, or 8 weeks in combination with exercise (Jang et al., 2008). Rodents fed

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an HF diet with BSP (2%, 5%, or 10%) for 4 or 13 weeks gained less body weight than rodents fed HF diet without BSP, concurrent with inhibition of total food intake in a dose-dependent manner. In addition, the antiobesity and fat reduction effects of black soy protein increased when combined with low-intensity exercise. Jang et al. (2008) could detect a specific hepta-peptide (IPPGVPY in BSP at 50 µg/g) in plasma at 30 minutes after oral administration of BSP (1 g) in rats, suggesting that peptides in the BSP mixture might be absorbed as intact molecules. Body weight regulation of BSP has been related to a major signaling pathway such as JAK2-dependent STAT3 activation (Jang et al., 2008). The leptin-mediated STAT3 phosphorylation pathway in the hypothalamus is a major cellular mechanism among the multiple pathways involved in suppressing food intake and promoting energy expenditure (Bates and Myers, 2003; Spiegelman and Flier, 2001). Induction of hypothalamic STAT3 phosphorylation by BSP was demonstrated in leptin-deficient ob/ob mice, suggesting that anorectic effect of soy peptides is through leptin receptor and activation of leptin-like signaling in the hypothalamus at a concentration as low as 1 µg/mL. Some anorectic peptides have been also identified to exert antiobesity activity through decreasing food intake, fat body mass, and body weight. One example is a Leu-Pro-Tyr-Pro-Arg peptide from soybean glycinin A5A4B3 subunit (Takenaka et al., 2000a, 2000b).

Soy Peptides May Reduce Adiposity by Inhibiting Lipid Absorption and Regulation of Lipid Metabolism There is in vivo evidence that consumption of soy peptides can reduce serum total cholesterol, LDL cholesterol, and triglycerides as well as hepatic cholesterol and triglycerides (Aoyama et al., 2000a, 2000b; Cho et al., 2007; Jang et al., 2008; Takenaka et al., 2000a; Yang et al., 2007). Studies in animals indicate that soy peptide ingestion exerts its lipid lowering effect by reducing intestinal cholesterol absorption and increasing fecal bile acid excretion, thereby reducing body fat accumulation, hepatic cholesterol content, and enhancing removal of LDL (Aoyama et al., 2000a, 2000b; Takenaka et al., 2000a). Yang et al. (2007) demonstrated the hypolipidemic effects of nondialyzed soy protein hydrolysate (NSPH) in rats fed a cholesterol-rich diet. After a 12-week experimental period, the NSPH groups had a significant lower plasma concentration of total cholesterol, triglycerides, and LDL-cholesterol compared with the casein

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group. Moreover, fecal excretion of neutral steroids and nitrogen compounds was significantly higher in NSPH group than that in the casein group. An in vitro study also showed that NSPH, compared with casein, decreased cholesterol micellar solubility. These results suggested that NSPH may decrease lipid accumulation in the liver and have a hypolipidemic effect by enhancing excretion and inhibiting absorption of lipids. Some studies have demonstrated the effectiveness of feeding mixtures containing soy peptides, l-carnitine, and Garcinia cambogia extract on body weight and lipid metabolism in obese rats fed a HF diet (Kim et al., 2005; Park et al., 2006). Results suggested that this mixture was effective in reducing body and adipose tissue weight, probably due to the modulation of lipid metabolism and the increased fecal excretion of lipids. Kim et al. (2003) investigated the effect of combination of a functional beverage (containing Garcinia cambogia 300 mg, l-carnitine 20 mg, and soy peptides 1,000 mg) and exercise in body composition and biochemical metabolic profile in humans. Eighty-one healthy volunteers (69 females aged 19–50 years and 12 males aged 19–55 years), who maintained their body weight stable at 23 or higher BMI and 25% or higher body fat for the past 3 months, were recruited for the study. The research design was a randomized, double-blind, placebo-controlled parallel group design. All participants were given 12-week programmed-exercise, which was performed three times a week. One bottle (100 mL) of test or placebo solution was given daily, 30 minutes before each session of programmed exercise. At the end of 4, 8, and 12 weeks, approximately 2.0%, 3.0%, and 3.5% losses of body weight were observed, respectively, in the test group (p < 0.01) and 0.3% 0.7%, and 1.6%, respectively, in the placebo group (p > 0.05). In conclusion, the combination of the functional beverage, which contained Garcinia cambogia, l-carnitine and soy peptides, and exercise had a synergistic effect on reducing body fat. Dietary soy peptides have also been shown to directly affect hepatic cholesterol metabolism and LDL receptor activity. Lovati et al. (2000) demonstrated in vitro that trypsin plus pepsin CroksoyR 70 peptides, without isoflavone components, showed a marked upregulation of LDL receptor versus controls. Similarly, Cho et al. (2007) demonstrated that soy peptides can effectively stimulate LDL-R transcription, in a human liver cell line, and that dietary upregulation of the LDL-R transcription by soybean may be consequent to an enhanced catabolism or a reduced synthesis of intracellular cholesterol. Soy oligopeptide mixtures (200–5,000 Da) have also been shown to be useful as apolipoprotein B (Apo B), the structural protein of LDL secretion inhibitors in HepG2 cells, for treatment of

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obesity and other lifestyle diseases. Based on these results, a storagestable beverage containing this mixture in freeze-dried powder form was also formulated (Inoue et al., 2004). Jang et al. (2008) demonstrated that BSP may have an impact in body weight and hypotriglyceridemic effect through activation of the phosphorylation of 5 AMP-activated protein kinase (AMPK) followed by acetylCoA carboxylase (ACC) phosphorylation inhibition. AMPK functions as a sensor of the intracellular energy state and is activated by exercise, adiponectin, leptin, and sympathetic outflow (Carling, 2004). A long-term dietary soy peptides intervention study significantly increased plasma adiponectin when mice were fed high doses of BSP (10%) in the diet. Adiponectin has received attention because it decreases the concentration of plasma triglycerides and free fatty acids primarily through the activation of AMPK (Yoon et al., 2006). In skeletal muscle cells, activated AMPK increases fatty acid oxidation through the influx of long-chain fatty acids into the mitochondria.

Soy Peptides May Reduce Body Weight by Increasing Energy Expenditure and Thermogenesis Increased postprandial thermogenesis results in greater energy utilization, which in turn may contribute to a reduction in body weight. Proteins, including soy hydrolysates, have a higher postprandial thermic effect than carbohydrates or fat and therefore could be more effective in weight reduction. Vaughn et al. (2008) investigated the effect of soy hydrolysates on body weight and food intake in adult rats receiving intracerebroventricular injections of soy hydrolysates (100 µg/ µL) three times weekly for 2 weeks. The hydrolysates caused a significant body weight reduction (p < 0.001) without reducing food intake. It was speculated that peptides in the soy hydrolysate may act by mechanisms that regulate energy metabolism and thermogenesis. A main reason for the difference in the thermic effects of foods higher in protein compared with those higher in carbohydrates or fats may be attributable to the fact that the body has no storage capacity for protein, and thus it needs to be immediately metabolically processed (Hu, 2005). The synthesis of proteins, the high ATP cost of peptide bond synthesis, and the high cost of urea production and gluconeogenesis are possible reasons for the higher thermic effect of protein (Mikkelsen et al., 2000; Robinson et al., 1990).

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The interaction between the consumption of soy protein hydrolysates and carbohydrates on thermogenesis and hormonal secretion has also been tested. Claessens et al. (2007) reported the effect of soy protein hydrolysates, with and without a carbohydrate pre- and afterload, on energy metabolism and hormonal secretion in eight healthy nonobese subjects. In all cases, 0.4 g protein and/or carbohydrate per kilogram of body weight were tested. Soy hydrolysate consumption led to a higher diet-induced thermogenesis than a carbohydrate load. Thermogenesis induced by soy protein hydrolysate combined by a carbohydrate pre- or afterload also increased energy expenditure. The larger diet-induced thermogenesis, after protein consumption than after carbohydrate, may be related to the glucagon response that is induced by protein but not by carbohydrates. Glucagon is a regulatory response to hypoglycemia. In this regard, glucagon stimulates glucose output by increasing liver glyconeolysis and gluconeogenesis (Jiang and Zhang, 2003), and insulin. Furthermore, when soy protein hydrolysate consumption was followed by a carbohydrate load, it did not result in a rise in plasma glucose concentration. This may be probably due to the fact that peptides elevated plasma insulin levels before the carbohydrate load consumption. Therefore, soy peptides ingestion may have other additional health benefits as preventing plasma glucose increase when carbohydrates are ingested after proteins. The relative contribution of fat and carbohydrates on postprandial energy expenditure when consuming soy protein has been investigated in experimental animals. Ishibara et al. (2003) compared the effects of feeding a soybean peptide isolate diet on the oxidation of dietary carbohydrate and lipids in type II diabetic mice. When diabetic mice were fed a restricted diet, postprandial energy expenditure was higher in the soy peptide group than in the casein group. The authors suggested that the difference in energy expenditure between the groups was due to an increase in postprandial carbohydrate oxidation promoted by the soybean peptide.

Soy Peptides May Reduce Adiposity through Inhibition of Adipogenesis Adipogenesis is a process through which a fibroblast, first becomes a preadipocyte, then a multilocular adipocyte, and, finally, a mature (unilocular) adipocyte (Fernyhough et al., 2005). During the maturation process of adipocytes, the increase in lipid mass caused by increase in size of adipocytes is termed hypertrophy. Hypertrophy in adipose tissue occurs

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in response to weight gain due to excess calorie intake. Increase of body weight produces increase in number of adipocytes termed as hyperplasia. There are limited data from in vitro experiments analyzing the specific effects of soy peptides on adipose tissue development (adipogenesis). Results from our laboratory showed the effectiveness of soy peptides on adipogenesis including proliferation of preadipocytes, hypertrophy of adipocytes, expression of preadipocyte factor-1 (pref-1), adiponectin, and lipid accumulation using the Swiss mouse 3T3-L1 cell line as a model (Kim, 2007). Preadipocytes and mature adipocytes were incubated with soy protein isolate hydrolysate (SH), β-conglycinin hydrolysate (BCH), and commercial purified soy peptides (SPP). Figure 9.2 presents the inhibitory effect of soy products on proliferation of preadipocytes. Hydrolyzed β-conglycinin (BCH) inhibited preadipocytes in a dosedependent manner (IC50 , 455 µM) (Fig. 9.2a). Alcalase-hydrolyzed soy protein isolate (SH) also showed a clear dose response (IC50 , 700 µM)

Inhibition (%)

100

–0.5

75 50 25

0.0

C B A

292 (b)

Inhibition (%)

Inhibition (%)

80 70 60 50 40 30 20 10 0

0.5

583 µM

1.0

1.5

2.0

Log (µM)

(a)

1167

80 70 60 50 40 30 20 10 0 –10 (c)

C

C

B B A 0.25

1.44

2.52

4.66

6.99

mM

Figure 9.2. Inhibitory effect of soy hydrolysate products on preadipocyte proliferation measured by cell viability MTS assay after 72 hours of treatment. (a) Inhibitory effect of alcalase-hydrolyzed β-conglycinin (BCH), IC50 = 455 µM. (b) A dose-response inhibitory effect of alcalase-hydrolyzed soy protein isolates (SH), IC50 = 700 µM (c) A dose-response inhibitory effect of soy-purified peptides (SPP), IC50 = 2.3 mM (different letters indicate significant differences, p < 0.05). Error bars indicate standard deviation.

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B

3.0 2.5 2.0 1.5 1.0

A

0.5 0.0 SPP

SH

Figure 9.3. Fold increase in pref-1 (60 kDa) by soy-purified peptides (SPP, 2.3 mM) and alcalase soy hydrolysates (SH, 700 µM).

(Fig. 9.2b). Figure 9.2c shows the inhibitory effect by SPP (IC50 , 2.3 mM). In our study, it was found that β-conglycinin hydrolysate showed the highest inhibition of preadipocyte proliferation with the least amount of protein, which implied that this protein may have a key role in adipogenesis. Figure 9.3 presents the increase in the expression of pref-1 (60 kDa), in preadipocytes exposed to IC50 values of SPP (2.3 mM), SH (700 µM), for 72 hours in comparison to their controls. Several biomarkers are involved during adipogenesis and some are specific to preadipocytes, which include pref-1. Pref-1 is a regulator of adipogenesis due to its role in adipocyte differentiation (Wang et al., 2006). Pref-1 is a transmembrane protein of 385 amino acids (60 kDa) that can exist in multiple membrane forms. Overexpression of pref-1 is known to decrease fat mass, reduce expression of adipocyte markers, and lower adipocyte-secreted factors, such as adiponectin (Lee et al., 2003). Figure 9.4 presents the evaluation of lipid accumulation and adiponectin expression in 3T3-L1 adipocytes treated with β-conglycinin hydrolysates. Adiponectin is a 30 kDa protein composed of 244 amino acids and is one of the adipocytes-specific hormones (Maeda et al., 1996). Adiponectin improves insulin sensitivity and regulates metabolism of lipids and glucose (Berg et al., 2001; Druce et al., 2004). Several studies have found that induction of adiponectin decreases body weight, plasma triglycerides, and fatty acid oxidation (Nedvidkova et al., 2005; Qi et al., 2004; Yamauchi et al., 2003). The most interesting aspect of this hormone is that its level decreases in an obese individual and, thus, its absence is closely related to obesity (Buemann et al., 2006; Hu et al., 1996).

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60 10 µM

100 µM

40 30 20 10 0

Adiponectin expression (fold increase vs. control)

Lipid accumulation inhibition (%) versus control

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10 µM

1.5 1.0 0.5 0.0

Beta-conglycinin hydrolysate (a)

100 µM

2.0

Beta-conglycinin hydrolysate (b)

Figure 9.4. β-conglycinin hydrolysates inhibit lipid accumulation (a), and induce adiponectin expression (b) in 3T3-L1 adipocytes. Error bars indicate standard deviation.

In summary, soy hydrolysates have the capacity to inhibit in vitro adipogenesis by upregulation of preadipogenic pref-1 factor. In addition, our data suggest that β-conglycinin hydrolysate may have an impact on weight loss by induction of adiponectin expression and inhibition of lipid accumulation in adipose tissue. In vitro studies are not a direct approach to obesity treatment. However, offering the understanding of the mechanism of action and the potential for in vivo studies may show benefits in the management of obesity. Kim et al. (2007) identified a tripeptide, Ile-Gln-Asn, from black soybean hydrolysate as adipogenesis inhibitor in 3T3-L1 preadipocytes, having IC50 value of 14 µg protein/mL. These results were confirmed with a synthetic tripeptide.

Food Applications of Soy Peptides for Weight Control Based on the antiobesity activity of soy and soy peptides, various foods and beverages have been developed. For example, a soy protein meal replacement formula (Scan Diet) has been found effective for weight loss and fat mass reduction in obese subjects (Allison et al., 2003). Other products include antiobesity formulas containing proteins, water-soluble fibers and gelatins, mineral, vitamins, and soy peptides (Fujita, 2000; Inoue et al., 2004; Son and Bang, 1999). A sugar-free coffee containing soybean

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protein hydrolysate was also developed (Miura, 2002). This beverage contained oligopeptides with three to six amino acid residues prepared by enzymatic hydrolysis of soybean protein. Ingestion of this kind of sugar-free coffee for 8 weeks led to a 4–7% body weight reduction in human volunteers. Soybean peptides have also been used as body fat decreasing agents in foods. It has been observed in humans that body fat, serum glycerides and cholesterol can be decreased by peptides without decreasing body proteins (Inaba et al., 2002). Although all these findings are encouraging, clinical studies are needed to assess the true contribution of soy peptides to weight management. Current data suggest that soy peptides may have the potential ability to prevent obesity but results must be carefully interpreted and additional evidence is needed before making firm conclusions concerning the effect of soy peptides on weight loss. Although soy protein/peptides may be considered as good as other protein sources for promoting weight loss, a suggestive body of evidence indicates that soy foods confer additional benefits (Cope et al., 2008).

Safety of Soy Peptides Peptides are normally generated during protein digestion in the gastrointestinal tract. Because soy hydrolysates and fermented soybean products have been safely used as food for years without apparent harmful effects, the risk of toxicity caused by peptides formed during these processes is practically nil. Although peptides can be absorbed into the blood, there have been no reports about toxic effects of soybean peptides to date. An additional concern about the safety of proteins is their allegenicity. To date, 34 soybean proteins have been identified as allergens (Farrp Allergen Protein Database, 2008; Xiang et al., 2008). However, enzymatic hydrolysis is the predominant method for reducing allergenicity of proteins. The best examples of food products that are processed to render them less allergenic are hydrolyzed infant formulas (FDA, 2005). Song et al. (2008b) showed that hydrolyzed soybean ingredients exhibited negligible IgE immunoreactivity to soy proteins and peptides using different human plasma samples from subjects reporting previous soybean allergies. Soy-hydrolyzed ingredients are produced by means of heat denaturation and/or enzymatic hydrolysis, sometimes in combination with ultrafiltration or high pressure. The additional ultrafiltration step is able to eliminate most residual immunodominant peptides (Song et al., 2008b). Lee et al. (2007) reported that peptic and chymotryptic hydrolyzed fragments of 11S

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globulin, of less than 20 kDa, were no immunoreactive to IgE in human plasma. Fermentation process has been investigated with regard to its potential on production of hypoallergenic products (Frias et al., 2008; Song et al., 2008a). Hydrolysis of soy proteins into peptides by microbial enzymes may undergo destruction of both conformational and linear epitopes, consequently reducing or eliminating the antigenicity of soy proteins. Fermentation conditions such as particle size, microorganism used, and extent of fermentation may have different impact on reduction of soybean immunoreactivity (Frias et al., 2008; Song et al., 2008a). In sum, due to the production and chemical nature of the peptides, it is highly unlikely that these products are allergenic.

Information of Global Suppliers Consumers are becoming more health conscious about the impact of their lifestyle and diet on their health. This has resulted in a rapid expansion of the healthy eating market, covering everything from organic through more conventional products that are lower in fat, calories, or sugar. Soy-based products include energy bars, soymilk, frozen and refrigerated meat alternatives, cold cereal, frozen entrees, cheese and yogurt, cookies, spreads, bread, energy drinks. These products may contain bioactive peptides or they can be produced during GI digestion. Some of the product claims include lower cholesterol, improved gut health, improved immune system, improve memory, improve eyesight, and even better complexions. Table 9.2 presents a list of soy products and their suppliers that include soy peptides in the formulas. Few of them present a health claim related to weight management. More research is needed to find out the benefits of these peptides added as ingredients to functional foods. Other applications may be in dietetic foods, personal care products, fortified foods, dietary supplements among others. Industrial scale production of hydrolyzed products that would contain peptides are currently in the areas of (a) infant nutrition for easy digestion; (b) clinical nutrition to improve immune status; and (c) sports nutrition to improve muscle recovery.

Conclusions Numerous bioactive peptide fragments with different physiological activities related to obesity have been identified in soy hydrolysates and

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References

Reduced calories Improve metabolic syndrome (GRAS in United States)

Calpis, Japan CBC Co. Ltd., Japan

Kibun Food Chemiha, Tokyo, Japan Kibun Food Chemiha, Tokyo, Japan

Sapple-Daizu Peptide, amino acid 5,900

Fine-soy peptide supplement

Kibun Food Chemiha, Tokyo, Japan

Not specified

Not specified

Not specified

www.kibunfc.co.jp

www.kibunfc.co.jp

www.kibunfc.co.jp

www.kibunfc.co.jp

http://duqing.en.ecplaza .net

Beijing, China

www.cocacolajapan.co.jp

Chuo-ku, Tokyo, Japan

Shibuya-ku, Tokyo, Japan

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Powerade soy peptide drink, 4,000 mg Coca Cola Japan, Tokyo, Japan of soy peptide Dou Dou CHU sweetened black soy milk Dou Dou Chu, Beijing, China Not specified added with soy peptides 2.0 g protein/100 g Soy oligopeptides Heze Roc International Co., Ltd., Not specified China Soy peptide soy milk fortified with Kibun Food Chemiha, Tokyo, Not specified 1,800 mg of soy peptide Japan

Karada Mame Latte Soy milk drink with soy peptides Touchi, fermented black soybean extract 55% protein

Daizu Peptide Nysankin (soy peptide lactic Calpis-Ajinomoto-Danon, Tokyo, Regulates GI Tokyo, Japan acid bacteria), 1,000 mg of Japan conditions and soy peptide regains and sustains energy level

Soy Products

Table 9.2. Products that contain soy peptides, suppliers, and health claims

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Oriental style noodles soy peptides, soybean sauce, 9 g protein/120 g

Soy peptide energy-recovery beverages, 8,000 mg of soy peptide

Yakult, Korea

Not specified

Energy-recovery beverage promotes energy enhancing to body and brain

Not specified

Not specified

Osotsoa, Thailand Shandong Duqing Inc., China Toraku/Soyafarm (Kobe), Japan

Not specified

Osoth Inter Lab, Thailand

Socho-gu, Seoul, South Korea

Chenji Industrial District, Heze, Shandong, China www.the-peptide.com

Bangkok, Thailand

Chonburi, Thailand

Minato-ku Tokyo, Japan

Chou-ku, Tokyo, Japan

Chou-ku Tokyo, Japan

New Jersey, U.S.

Asia, Eastern Asia, Japan

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Energy bar

Morinaga, Tokyo, Japan

Weider recover bar with 4,000 mg soy peptides, 7.7 g protein/58 g Soy peptide drink Peptein, 5% peptides from soy protein, 4 g protein/100 mL Soy peptide drink, Paptein

Slim down, weight control

Meiji Seika Kaisha

Not specified

Meiji Seika Kaisha, Tokyo, Japan

Diet and collagen bar 15 g soy protein 16 g protein/45 g

Reduced carbohydrates

Life services supplements

Keto bar, Lemon chiffon bar, 24 g protein/bar 65 g, soy protein isolate, hydrolyzed protein Aqua soy protein 100 added with soy peptides 67% protein

Not specified

KYOWA HAKKO KOGYO Co. Ltd., Japan

SOY PEPTIDE CSPHP Kyowa Super Soy

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soy-fermented products. The activities of bioactive peptides have been demonstrated, but their molecular mechanism of action is not yet clear. Furthermore, the investigations have been focused mainly on in vitro studies and on animal models. Human clinical studies are limited or nonexisting. Bioactive peptides are released from protein by either food processing or GI digestion. Indirect evidence also suggests that these peptides can be absorbed by the gastrointestinal system, thus exerting their action on specific target organs. The effective plasma levels of bioactive peptides are unknown and need to be determined. It is also important to discover new peptides and their physiological functions in soy hydrolysates and fermented foods. The identification of these compounds will contribute toward a better understanding of the role of soy on obesity and the development of new functional ingredients with slimming characteristics. More work is needed on processing technologies to make bioactive peptides more available to consumers.

References Allison DB, Gadbury G, Schwartz LG, Murugeasn R, Kraker JL, Heshka S, Fontaine KR, Heimsfield SB. A novel soy-based meal replacement formula for weight loss among obese individuals: a randomized controlled clinical trial. Eur J Clin Nutr 2003;57:514–522. Aoyama T, Fukui K, Nakamori T, Hashimoto Y, Yamamoto T, Takamatsu K, Sugano M. Effect of soy and milk whey protein isolates and their hydrolysates on with reduction in genetically obese mice. Biosci Biotechnol Biochem 2000a;64:2594–2600. Aoyama T, Fukui K, Takamatsu K, Hashimoto Y, Yamamoto T. Soy protein isolate and its hydrolysate reduce body fat of dietary obese rats and genetically obese mice (Yellow KK). Nutrition 2000b;16:349–354. Bates SH, Myers Jr MG. The role of leptin receptor signaling in feeding and neuroendocrine function. Trends Endocrinol Metab 2003;14:447– 452. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocytesecreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001;7:947–953. Brandsch M, Knutter I, Bosse-Doenecke E. Pharmaceutical and pharmacological importance of peptide transporters. J Pharm Pharmacol 2008;60:543–585.

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Buemann B, Astrup A, Pedersen O, Black E, Holst C, Toubro S, Echwald S, Holst JJ, Rasmussen C, Sørensen TI. Possible role of adiponectin and insulin sensitivity in mediating the favorable effects of lower body fat mass on blood lipids. J Clin Endocrinol Metab 2006;91:1698–1704. Carling D. The AMP-activated protein kinase cascade: a unifying system for energy control. Trends Biochem Sci 2004;29:18–24. Cho S-J, Juillerat MA, Lee C-H. Cholesterol lowering mechanism of soybean protein hydrolysate. J Agric Food Chem 2007;55:10599–10604. Chun H, Sasaki M, Fujiyama Y, Bamba T. Effect of peptide chain length on absorption and intact transport of hydrolysed soybean peptide in rat intestinal everted sac. J Clin Biochem Nutr 1996;21:131–140. Claessens M, Calame W, Siemensma AD, Sari WHM, van Baak MA. The thermogenic and metabolic effects of protein hydrolysate load in healthy male subjects. Metab Clin Exp 2007;56:1051–1059. Cope MB, Erdman JW, Allison DB. The potential role of soyfoods in weight and adiposity reduction: and evidence-based review. Obes Rev 2008;9(3):219–235. Druce MR, Small CJ, Bloom SR. Minireview: gut peptides regulating satiety. Endocrinology 2004;145:2660–2665. FDA US Food and Drug Administration, Center for Food Safety and Applied Nutrition. Approaches to establish thresholds for major food allergens and for gluten in food. 2005. Available online at http://www.cfsan.fda.gov/˜ dms/alrgn.html. Fei YJ, Kanai Y, Nussberger S, Ganapathy V, Leibach FH, Romero MF, Singh SK, Boron WF, Hediger MA. Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 1994;368:563–566. Fernyhough ME, Bucci LR, Hausman GJ, Antonio J, Vierck JL, Dodson MV. Gaining a solid grip on adipogenesis. Tissue Cell 2005;37:335–338. Foltz M, Ansems P, Schwarz J, Tasker MC, Lourbakos A, Gerhardt CC. Protein hydrolysates induce CCK release from enteroendocrine cells and act as partial agonist of the CCK1 R. J Agric Food Chem 2008;56:837–843. Food allergy Research and Resource Program (FARRP). Searchable protein database: Soybean. 2008. Available online at http://www. allergenonline.com/db sort.asp.

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19:40

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Frias J, Song YS, Mart´ınez-Villaluenga C, Gonz´alez de Mej´ıa E, VidalValverde C. Immunoreactivity and amino acid content of fermented soybean products. J Agric Food Chem 2008;56:99–105. Fujita T. Soya proteins, water-soluble fibers and gelatins, basic aminoacids, and/or basic peptides as compositions for prevention of obesity. Jpn Kokai Tokkyo Koho, JP 2000001440 A2 7, 2000, p. 5. Hu FB. Protein, body weight and cardiovascular health. Am J Clin Nutr 2005;82:242S–247S. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:10697–10703. Ihara M, Miyanomae T, Kido Y, Kishi K. Effects of soy protein on nutritional state and small intestinal function in short-bowel and methotrexate treated rats. Nutr Sci Soy Protein Jpn 1990;11:108–112. Inoue N, Nagao K, Kan SY, Yanagida A, Nakamori T, Furuta H. Acidic amino acid-rich oligopeptide mixtures, their enzymic manufacture, and apolipoprotein B secretion inhibitors containing them. Jpn Kokai Tokkyo Koho, JP 2003–98101 20030401, 2004, p. 12. Inaba H, Sakai K, Ota A. Body fat decreasing agents containing peptides and glutamine, and food compositions containing them. Jpn Kokai Tokkyo Koho, JP 2002020312 A2 23, 2002, p. 5. Ioannides-Demos LL, Proietto J, Tonkin AM, McNeil JJ. Safety of drug therapies used for weight loss and treatment of obesity. Drug Saf 2006;29:277–302. Ishibara K, Oyaizu S, Fushiki T, Yasumoto KA. Soybean peptide isolate diet promotes postprandial carbohydrate oxidation and energy expenditure in type II diabetic mice. J Nutr 2003;133:752–757. Jang E-H, Moon J-S, Ko JH, Ahn C-W, Lee H-H, Shin J-K, Park C-S, Kang J-H. Novel black soy peptides with antiobesity effects: activation of leptin-like signaling and AMP-activated protein kinase. Int J Obes 2008;32:1161–1170. Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 2003;284:E671–E678. Kim HJ, Bae IY, Ahn C-W, Lee S, Lee HG. Purification and identification of adipogenesis inhibitory peptide from black soybean protein hydrolysate. Peptides 2007;28:2098–2103.

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Kim KS, Jung JH, Song CH, Sung BJ. The effects of combination of functional beverage (Garcinia cambogia, l-carnitine and soy peptide) and exercise on the improvement of body fat. J Appl Pharmacol 2003;11:99–108. Kim LM. Soy and Tea Components Inhibit In Vitro Adipogenesis. Master Thesis, University of Illinois, Urbana, IL, 2007, p. 120. Kim YJ, Jun H-S, Park I-S, Kim M, Lee J, Lee K, Park T. Effect of treadmill exercise training and dietary intake of Garcinia cambogia extract, soy peptide and l-carnitine mixture on body weight reduction in rats fed high-fat diets. Korean Nutr Soc 2005;38:626–636. Lee HW, Keum EH, Lee SJ, Sung DE, Chung DH, Lee SI, Oh S. Allergenicity of proteolytic hydrolysates of the soybean 11S globulin. J Food Sci 2007;72:C168–C172. Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul SH. Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). J Clin Invest 2003;111:453–461. Lovati MR, Manzoni C, Gianazza E, Arnoldi A, Kurowska E, Carroll KK, Sirtori CR. Soy protein peptides regulate cholesterol homeostasis in Hep G2 Cells. Nutr Metab 2000;130:2543–2549. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose-specific collagenlike factor, apM1 (adipose most abundant gene transcript 1). Biochem Biophys Res Commun 1996;221:286–289. Mikkelsen PB, Toubro S, Astrup A. Effect of fat-reduced diets on 24 h energy expenditure: comparisons between animal protein, vegetable protein, and carbohydrate. Am J Clin Nutr 2000;72:1135– 1141. Miura H. Nonsugar beverages and diet compositions containing soybean protein hydrolysates. Jpn Kokai Tokkyo Koho JP 2002010764 A2 15, 2002, p. 4. M¨oller NP, Scholz-Ahrens KE, Roos N, Schrezenmeir J. Bioactive peptides and proteins from foods: indication for health effects. Eur J Nutr 2008;47:171–182. Nedvidkova J, Smitka K, Kopsky V, Hainer V. Adiponectin, an adipocytederived protein. Physiol Res 2005;54:133–140.

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Nishi T, Hara H, Asano K, Tomita F. The soybean beta-conglycinin beta 51–63 fragment suppresses appetite by stimulating cholecystokinin release in rats. J Nutr 2003a;133:2537–2542. Nishi T, Hara H, Tomita F. Soybean beta-conglycinin peptone suppresses food intake and gastric emptying by increasing plasma cholecystokinin levels in rats. J Nutr 2003b;133:352–357. Odgen CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology 2007;132:2087–2102. Park J-Y, Lee H-S, Kim J, Lee J-H, Lee K-P, Kim M-S, Kim Y. Effect of feeding mixture of soybean peptides, l-carnitine and Garcinia Cambogia on body weight and lipid metabolism in rats. J Food Sci Nutr 2006;11:210–217. Pupovac J, Anderson GH. Dietary peptides induce satiety via cholecystokinin- A and peripheral opioid receptors in rats. J Nutr 2002;132:2775–2780. Qi Y, Takahashi N, Hileman SM, Patel HR, Berg AH, Pajvani UB, Schere PE, Ahima RS. Adiponectin acts in the brain to decrease body weight. Nat Med 2004;10:524–529. Rho SJ, Park S, Ahn C-W, Shin J-K, Lee HG. Dietetic and hypocholesterolaemic action of black soy peptide in dietary obese rats. J Sci Food Agric 2007;87:908–913. Robinson SM, Kaccard C, Persaud C, Jackson AA, Jequier E, Schutz Y. Protein turnover and thermogenesis in response to high-protein and high-carbohydrate feeding in men. Am J Clin Nutr 1990;52:72–80. Shimizu M. Food-derived peptides and intestinal function. Biofactors 2004;21:43–47. Son HK, Bang SM. A dietary composition for weight loss. Pacific Co., Ltd., S. Korea, KR 96–44612 19961008, 1999. Song YS, Frias J, Mart´ınez-Villaluenga C, Vidal-Valverde C, Gonz´alez de Mejia E. Immunoreactivity reduction of soybean meal by fermentation, effect on amino acid composition and antigenicity of commercial soy. Food Chem 2008a;180:571–581. Song YS, Mart´ınez-Villaluenga C, Gonz´alez de Mejia E. Quantification of human IgE immunoreactive soybean proteins in commercial soy ingredients and products. J Food Sci 2008b;doi: 10.1111/ j.1750–3841.2008.00848.x

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Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell 2001;104:531–543. Takamatsu K. Soy peptides as functional food material. In: Sugano M (ed.). Soy and Health and Disease Prevention. CRC Press, Boca Raton, FL, 2006, pp. 235–249. Takenaka Y, Nakamura F, Yoshikawa M. Study on lipid metabolism regulation by a low molecular weight peptide derived from soybean protein. Jpn J 2000a;3:105–109. Takenaka Y, Utsumi S, Yoshikawa M. Introduction of enterostatin (VPDR) and related sequence into soybean proglycinin A1a B1b subunit by sitedirected mutagenesis. Biosci Biotecnol Biochem 2000b;64:2731–2733. Vaughn N, Rizzo A, Doane D, Beverly JL, Gonzalez de Mejia E. Intracerebroventricular administration of soy protein hydrolysates reduce body weight without affecting food intake in rats. Plant Foods Hum Nutr 2008;63:41–46. Wang Y, Kim KH, Kim JH, Sul HS. Pref-1, a preadipocyte secreted factor that inhibits adipogenesis. J Nutr 2006;136:2953–2956. Xiang P, Baird LM, Jung R, Zeece MG, Markwell J, Sarath G. P39, a novel soybean protein allergen, belongs to a plant-specific protein family and is present in protein storage vacuoles. J Agric Food Chem 2008;56:2266–2272. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003;423:762–769. Yang S-C, Liu S-M, Yang H-Y, Lin Y-H, Chen J-R. Soybean protein hydrolysate improves plasma and liver lipid profiles in rats fed highCholesterol diet. J Am Coll Nutr 2007;26:416–423. Yoon MJ, Lee GY, Chung JJ, Ahn YH, Hong SH, Kim JB. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p 38 mitogen-activated protein kinase, and peroxisome proliferators activated receptor a. Diabetes 2006;55:2562–2570.

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Functional Components

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CHAPTER 10

The Effects of Caffeine and Green Tea on Energy Expenditure, Fat Oxidation, Weight Loss, and Weight Maintenance Rick Hursel, MSc, and Prof. Dr. Margriet Westerterp-Plantenga, PhD

Abstract Overweight and obesity, caused by an imbalance between energy intake and energy expenditure, represent a rapidly growing threat to the health of populations in an increasing number of countries worldwide. Natural food products such as caffeine and green tea, which also contains caffeine, are being studied as possible thermogenic agents that have the ability to increase diet-induced thermogenesis. It has been shown that green tea and caffeine enhance energy expenditure and fat oxidation over 24 hours as well as in the long term. In several long-term studies, it was shown that green tea and caffeine contributed to weight loss or helped maintaining weight after a period of weight loss. The main mechanism of action consists of the inhibition of two key enzymes that help regulate the sympathetic nerve system. Green tea inhibits the catechol-O-methyltransferase, which usually degrades noradrenalin, and caffeine inhibits phosphodiesterase that hydrolyses cAMP to AMP. Due to the inhibition of these enzymes, the sympathetic nerve system is constantly activated, and ultimately this leads to an increase in energy expenditure and fat oxidation. Green tea and caffeine are natural products that are safe to use and consume, although there is a limit to the amount of caffeine a person can consume per day. 161

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Introduction Overweight and obesity represent a rapidly growing threat to the health of populations in an increasing number of countries (“Obesity,” 2000). The ultimate cause of obesity is an imbalance between energy intake and energy expenditure (EE) (Stunkard, 1996). A negative energy balance is needed to produce weight loss and can be achieved by either decreasing intake or increasing expenditure. Classical weight-loss programs, such as low-fat diets, behavioral modification, and exercise, often fail to achieve a long-term maintenance of weight loss (Pasman et al., 1999; Wadden et al., 1988). Because of these low success rates, the stimulation of EE (or the prevention of its decline during dieting) by the use of natural herbal nutrients such as green tea and caffeine has attracted interest. Green tea is consumed primarily in China, Japan, and a few countries in North Africa and the Middle East (Graham, 1992; Weisburger, 1997). Tea is made from the leaves of Camellia sinensis L. species of the Theaceae family, green tea being the nonoxidized, nonfermented product. As a consequence of this, it contains high quantities of several polyphenolic components such as epicatechin, epicatechin gallate, epigallocatechin, and, the most abundant and probably the most pharmacologically active, epigallocatechin gallate (Kao et al., 2000a). From caffeine, that is also present in green tea, it has been reported that it has thermogenic effects and can stimulate fat oxidation in vitro, in part via sympathetic activation of the central nervous system (Dulloo et al., 1992). In humans, caffeine has been shown to stimulate thermogenesis and fat oxidation (Astrup et al., 1990; Bracco et al., 1995; Dulloo et al., 1989). Green tea extracts, containing caffeine and catechin-polyphenols, have been reported to have an effect on body weight (Chantre and Lairon, 2002; Kao et al., 2000a) and EE (Dulloo et al., 1999, 2000). The fact that green tea stimulates thermogenesis cannot be completely attributed to its caffeine content because the thermogenic effect of green tea is greater than that of an equivalent amount of caffeine (Dulloo et al., 1999).

Efficacy of Green Tea and Caffeine Short-Term Experiments Green Tea In a short-term human study epigallocatechin gallate plus caffeine (EGCG/caffeine), (90/50 mg), caffeine (50 mg), or placebo capsules were

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consumed three times daily on three different occasions (Dulloo et al., 1999). Relative to the placebo and to the caffeine alone, treatment with the green tea extract resulted in a significant increase in 24-hour EE (4% = 328 kJ) and fat oxidation, suggesting that green tea has thermogenic properties beyond that explained by its caffeine content per se (Borchardt and Huber, 1975). Rudelle et al. conducted a similar study in which 3 servings of a 250 mL thermogenic beverage per day (during 3 days), containing 94 mg EGCG and 100 mg caffeine, were consumed. Twenty-four-hour EE was significantly increased with 4.6% (= 445.2 kJ) after the thermogenic beverage (Rudelle et al., 2007). In another short-term study, subjects took two capsules of 150 mg EGCG a day, for 3 days. On day 3, 24-hour EE was measured, which was increased with a magnitude similar to the short-term study of Dulloo et al. In a Japanese study by Komatsu et al., subjects increased their EE over 2 hours with 4% (= 49.5 kJ) after a beverage containing 161 mg caffeine and 156 mg EGCG (Komatsu et al., 2003). These observations were confirmed by determining 24-hour EE using respiratory chambers and giving the subject different dosages of green tea (Berube-Parent et al., 2005). No significant difference was seen between the different doses of EGCG (Berube-Parent et al., 2005). Comparing all short-term studies, the increase in 24-hour EE was doubled in the latter (24-hour EE = 750 kJ), probably due to the difference in the amount of caffeine (200 vs. 50 and 100 mg three times daily) since the amount of EGCG was, besides the Japanese study, the same (±300 mg daily) (Berube-Parent et al., 2005). Although the previous studies showed a short-term thermogenic effect of green tea and caffeine, a recent study by Belza et al. could not retrieve similar results for green tea. They did find that caffeine increased the EE over 4 hours with 6% (= 72 kJ). No significant effects of both thermogenic agents on energy intake were found (Belza et al., 2009). Caffeine While consuming the same breakfast, normal-weight subjects presented a greater thermic effect over 3 hours, when it was accompanied with a caffeinated coffee (8 mg/kg body weight) in comparison to a decaffeinated coffee (Acheson et al., 1980). Moreover, EE was increased by 16% over a 2-hour period with caffeinated (100 mg) compared to decaffeinated coffee (Hollands et al., 1981). In accordance with this effect, an increase in basal metabolic rate by 3–4% was seen after consumption of a single oral dose of 100 mg caffeine in nine lean and nine postobese subjects (Dulloo et al., 1989). A linear, dose-dependent stimulation of thermogenesis, which lasted longer than 3 hours after administration of 100, 200, or 400 mg oral

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caffeine, was observed in subjects with a habitual caffeine intake of less than 200 mg/day (Astrup et al., 1990). In 20 female subjects (10 lean and 10 obese), an increase in thermogenesis was seen with 4 mg/kg caffeine five times a day but this increase was smaller in the obese (4.9 ± 2.0%) than in the lean subjects (7.6 ± 1.3%). The thermogenic effect of caffeine was prolonged even overnight, which may suggest a possible long-term effect of caffeine (Bracco et al., 1995).

Long-Term Experiments Green Tea When investigating the effect of a green tea extract (375 mg catechins from which 270 mg EGCG and 150 mg caffeine/day, divided over four capsules) on body weight with 70 overweight subjects, body weight was decreased by 4.6% and waist circumference by 4.5% after 3 months, which is substantial since the study had an open uncontrolled design (Chantre and Lairon, 2002). In accordance with this observation, Japanese studies showed that the long-term (12 weeks) administration of tea catechins in a dose of 400–700 mg/day reduced body fat and body fat parameters (Hase et al., 2001; Kozuma et al., 2005; Nagao et al., 2001, 2005, 2007; Tsuchida et al., 2002). Harada et al. demonstrated that after a 12-week administration of a 350-mL tea beverage a day (592.2 mg), EE and dietary fat oxidation were increased (Harada et al., 2005). Furthermore, a recent Japanese study observed that the daily consumption of 340 mL tea containing 576 mg catechins for 24 weeks reduced body fat ratio and waist circumference compared to the control group, who had a daily consumption of 340 mL tea with 75 mg catechins (Matsuyama et al., 2008). In the Netherlands, 104 overweight/moderately obese subjects were followed after a very-low-energy diet (2.1 MJ/day) of 4 weeks, during a weight maintenance period of 13 weeks in which subjects received placebo or green tea (caffeine/catechins: 104/573 mg/day) (Kovacs et al., 2004). Body weight regain and the rate of regain were not significantly different between the green tea and placebo group. Significantly, stronger body weight maintenance after weight loss was shown by post hoc analysis, that is, 16% body weight regain in the habitually low-caffeine consumers versus 39% in the habitually high-caffeine consumers relative to habitual caffeine consumption (Kovacs et al., 2004). From a follow-up study, it was concluded that habitual high caffeine intake was associated with a significant greater weight loss (6.7 vs. 5.1 kg) and relatively higher thermogenesis

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95

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Figure 10.1. Body weight (BW) of men (n = 23) and women (n = 53) over time. Month 1: after the VLED; month 4: after 3-month follow-up; CL, habitual low caffeine intake; CH, habitual high caffeine intake; GT, green tea during follow-up; P, placebo during follow-up. * p < 0.01, at month 1: group (pooled high caffeine intake groups vs. pooled low caffeine intake groups) × time (twofactor repeated measures ANOVA). * p < 0.01, at month 4: group (low caffeine intake group receiving green tea vs. all other groups) × time (four-factor repeated measures ANOVA). (After Westerterp-Plantenga et al., 2005.)

and fat oxidation, while green tea was associated with greater weight maintenance in habitual low-caffeine consumers, supported by relatively greater thermogenesis and fat oxidation (Westerterp-Plantenga et al., 2005) (Figs. 10.1 and 10.2). Thus, the effect of green tea may partly depend on habitual caffeine intake. In 46 females following a low-energy diet combined with green tea (caffeine/catechins 225/1,125 mg/day) or placebo supplementation during 12 weeks, with caffeine intake being standardized at 300 mg/day, resting EE as a function of fat-free mass and fat mass did not decrease significantly over time when green tea was ingested independently of habitual caffeine intake. On the other hand, the decrease in resting EE was significant in the placebo group (Diepvens et al., 2005). However, this did not imply a significant difference in body weight loss between the green tea and placebo

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Functional Components 0.875 RQ 0.85 RQ CL, P 0.825 RQ CL, GT RQ CH, P

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Figure 10.2. RQ of men (n = 23) and women (n = 53) over time. Month 1, after the VLED; month 4, after 3-month follow-up; CL, habitual low caffeine intake; CH, habitual high caffeine intake; GT, green tea during follow-up; P, placebo during follow-up. * p > 0.01, at month 1: group (pooled high caffeine intake groups vs. pooled low caffeine intake groups) × time (two-factor repeated measures ANOVA). * p > 0.01, at month 4: group (low caffeine intake group receiving green tea vs. all other groups) × time (four-factor repeated measures ANOVA). (After Westerterp-Plantenga et al., 2005.)

group (Diepvens et al., 2005). Moderate use of caffeine is likely to make the green tea supplement ineffective (Westerterp-Plantenga et al., 2005). In a recent long-term weight-loss study from Thailand, obese people that consumed the green tea intervention (100 mg EGCG and 87 mg caffeine/day) lost significantly more weight within 12 weeks compared to the placebo group (2.7 vs. 2.0 kg) that ate the similar standardized meals during the entire study. REE was significantly increased after 12 weeks of green tea supplementation, which led to the body weight reduction (Auvichayapat et al., 2008). Caffeine Although caffeine seems to increase thermogenesis in the short term, greater weight loss was not achieved when consuming caffeine in comparison to a placebo in obese subjects in the long term (Pasman et al., 1997; Tremblay et al., 1988). The observation that a habitually high (>300 mg/day) caffeine intake group receiving a green tea–caffeine combination did not show greater body weight maintenance after body weight loss than

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a habitually high-caffeine group receiving placebo leads to the suggestion that sensitivity to caffeine may be lost over time (Westerterp-Plantenga et al., 2005). Increased SNS activity has been shown to lead to a decrease in energy intake (Bray, 1993). In men (but not in women), caffeine consumption (300 mg) appeared to reduce energy intake (by 22%) (Tremblay et al., 1988). Moreover, a positive relationship between satiety and daily caffeine intake, in men and women, was shown (Westerterp-Plantenga et al., 2005). Lopez-Garcia et al. studied the effect of caffeine on longterm weight change in a prospective study. In their cohort, they found that people who increased the caffeine consumption over 12 years gained less weight than those who decreased the caffeine consumption (Lopez-Garcia et al., 2006). Thus, caffeine may influence both EE and energy intake.

Mechanisms of Action Catechins in green tea inhibit the enzyme catechol-O-methyltransferase (COMT) that is present in almost every tissue and degrades catecholic compounds such as norepinephrine (NE) (Dulloo et al., 1999; WesterterpPlantenga et al., 2005). COMT decreases the hydrophilicity by methylation, followed by sulfation and glucuronidation to make the excretion in urine and bile possible (Shixian et al., 2006). NE cannot be degraded through the inhibition of COMT and consequently the sympathetic nerve system (SNS) will be stimulated continuously due to the presence of NE, which attaches to β-adrenoceptors and causes an increase in EE and fat oxidation (Diepvens et al., 2007; Westerterp-Plantenga et al., 2006). The SNS plays an important role in the regulation of energy homeostasis but the above-described phenomenon does not always appear equally clear in all ethnic groups. For instance, studies with Asian subjects seem to report more positive results than studies with Caucasian subjects. This may be caused by differences in relevant enzyme activity, causing differences in sensitivity for these ingredients. In that respect, Hodgson et al. (2006) stated that there is a wide variability in flavonoid O-methylation, a major pathway of flavonoid metabolism, by the enzyme COMT. The interindividual variability of the activity of COMT could vary as much as threefold (Hodgson et al., 2006). Moreover, there is evidence that there is a difference in COMT enzyme activity between ethnic groups (Palmatier et al., 1999). Asian populations have a higher frequency of the thermostable, high-activity enzyme, COMTH allele (Val/Val polymorphism) than the Caucasian populations. The Caucasian populations have a higher frequency of the thermolabile, low-activity enzyme, COMTL allele

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(Met/Met/Val polymorphism) (Palmatier et al., 1999). Fifty percent of Caucasians are homozygous for the COMTL allele (25%) and COMTH allele (25%). The other 50% is heterozygous (Met/Met polymorphism) (Palmatier et al., 1999). This may explain the difference in sensitivity to interventions with green tea–caffeine mixtures, and why, in some studies with Caucasian subjects, no effect was seen after ingestion of green tea. As caffeine is also present in green tea, its effect will also take place after green tea consumption. Caffeine affects the thermogenesis by inhibiting the enzyme phosphodiesterase. This enzyme degrades intracellular cyclic amino mono phosphate (cAMP) (Diepvens et al., 2007; Westerterp-Plantenga et al., 2006). Phosphodiesterase usually hydrolyses cAMP to AMP, but after consumption of caffeine, cAMP concentration rises and SNS activity will be increased and inactive hormone-sensitive lipase (HSL) will be activated, which promotes lipolysis (Acheson et al., 2004). The SNS activity and lipoysis are dependent on cAMP, because cAMP activates the protein kinase A (Belza et al., 2007). Besides the inhibition of phosphodiesterase, caffeine also affects the thermogenesis through the stimulation of substrate cycles such as the Cori cycle and the FFA-triglycreride cycle (Diepvens et al., 2007; Westerterp-Plantenga et al., 2006). Caffeine is a methylxanthine, which has a thermogenic impact. In the Cori cycle, lactate moves from the muscles to the liver where it will be converted into pyruvate. The pyruvate will be converted to glucose by the enzyme lactate dehydrogenase and circulate back to the muscles via the blood (Diepvens et al., 2007; Westerterp-Plantenga et al., 2006). Acheson et al. showed that FFA turnover and lipid oxidation are increased after the consumption of caffeine but that it requires a large increase in FFA turnover to have a small increase in lipid oxidation. Nonoxidative lipid turnover, the hydrolysis and reesterification of triacylglycerol, is greater than the increase in oxidative lipid disposal (Acheson et al., 2004). They also found that caffeine antagonizes the inhibitory effects of adenosine on lipolysis via adenylyl cyclase. Nonadrenergic thermogenic mechanisms can also be involved, as caffeine antagonizes the ryanodine receptor, the calcium ion release channel of sarcoplasmatic reticulum in skeletal muscle that for instance increases glycolysis and ATP turnover after stimulation (Acheson et al., 2004). Catechins and caffeine inhibit two enzymes, which interrupt the pathway of NE-activated thermogenesis (Kao et al., 2000b). As SNS activity is determined by the concentration of NE, more NE means a higher activity and increased EE. SNS activity regulates the resting metabolic rate, which is the largest component of the daily EE. NE makes it possible to increase the usage of ATP through ion pumping and substrate cycling

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(Diepvens et al., 2007). The rate of mitochondrial oxidation is also involved in the increased thermogenesis due to the poor coupling of ATP synthesis, which leads to heat production. Catechins also have a direct effect on the gene expression of different uncoupling proteins (UCPs) that influence the thermogenesis with the production of heat (Klaus et al., 2005). Gene expression of the UCPs also increases when cAMP activates the protein kinase A, after the inhibition of phophodiesterase by caffeine (Lowell and Spiegelman, 2000). The protein kinase A stimulates HSL, which increases the concentration of free fatty acids by the conversion of triglycerides. UCP activity will be enhanced through this (Lowell and Spiegelman, 2000). The increase in EE is accompanied by a change in substrate oxidation as Dulloo et al. showed an increase in fat oxidation after the supplementation of green tea (Dulloo et al., 1999). Another mechanism is triggered by the tea catechins that block the nuclear factor-κ B (NFκB) activation by inhibiting the phosphorylation of IκB (Yang et al., 2001). NFκB is an oxidative stress sensitive transcription factor that regulates the expression of several genes, which are important in cellular responses such as inflammation and growth (Yang et al., 2001). NFκB is no longer able to inhibit the peroxisome proliferator activated receptors (PPARs) that are important transcription factors for lipid metabolism (Murase et al., 2002). The mRNA expression of lipid-metabolizing enzymes such as acyl-CoA oxidase (ACO) and medium-chain acyl-CoA dehydrogenase (MCAD) is upregulated. ACO is a peroxisomal β-oxidation enzyme and MCAD is a mitochondrial β-oxidation enzyme in the liver (Murase et al., 2002). The upregulation of these lipid-metabolizing enzymes makes it clear that β-oxidation activation after the supplementation of tea catechins is enhanced followed by an increase in fat oxidation.

Safety of Caffeine and Green Tea Administration Caffeine appears to be a safe thermogenic agent for weight control. In adults, the short-term lethal dose for caffeine is estimated at 5–10 g/day (either intravenously or orally), which is equivalent to 75 cups of coffee, 125 cups of tea, or 200 cola beverages (Curatolo and Robertson, 1983). Long-term ingestion of caffeine has been suggested to have some minor adverse effects on human health. Astrup et al. (1990) observed only small and insignificant changes in blood pressure and pulse rate after 100 and

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200 mg caffeine. In contrast, 400 mg caffeine significantly increased systolic and diastolic blood pressure by an average value of 6.3 mm Hg. Furthermore, after 400 mg caffeine, significantly more subjects reported side effects such as palpitation, anxiety, headache, restlessness, and dizziness compared with placebo (Astrup et al., 1990). Robertson et al. (1978) administrated 250 mg oral caffeine to nine subjects who were not used to coffee. Systolic blood pressure increased 10 mm Hg 1 hour after caffeine consumption. Heart rate showed a decrease after the first hour followed by an increase above baseline after 2 hours (Robertson et al., 1978). However, in a subsequent study that examined the chronic effects of caffeine ingestion (150 mg/day for 7 days), tolerance to these effects was developed after 1–4 days (Robertson et al., 1981). Thus, no long-term effects of caffeine on blood pressure, heart rate, or plasma rennin activity were demonstrated. Furthermore, in the short term, Bracco et al. (1995) did not find a significantly altered heart rate during the day after 4 mg caffeine per kg body weight was consumed five times daily. Accordingly, the use of caffeine is relatively safe, as it is quite certain that, although acute caffeine consumption may alter some cardiovascular variables, chronic ingestion of caffeine has little or no health consequences. Green tea has been widely consumed in China and Japan for many centuries and is regarded as safe. A possible side effect of green tea consumption is a minor increase in blood pressure as seen by BerubeParent et al. (2005). They observed a nonsignificant increase (7 mm Hg) in 24-hour systolic blood pressure accompanied by a significant increase (5 mm Hg) in 24-hour diastolic blood pressure. No increase in heart rate was seen (Berube-Parent et al., 2005). This small short-term increase in blood pressure induced by green tea might be neglected since systolic blood pressure, diastolic blood pressure, and heart rate were not affected by green tea in other short-term (Dulloo et al., 1999) or long-term research (Chantre and Lairon, 2002; Diepvens et al., 2005).

Food/Supplement Applications Caffeine and green tea are known to enhance fat oxidation and EE, which makes them excellent (slimming) ingredients for people who want to lose weight or maintain their weight. These ingredients are also known to have a positive effect on one’s health as the antioxidants protect against different types of cancer, cardiovascular diseases, and neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s. They are also

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offered as capsules and powders and for instance used by athletes to enhance their performances, as they can give them an energy boost.

Patent Activities 1. Document ID: WO2003090673A2 Title: COMPOSITIONS AND METHODS FOR PROMOTING WEIGHT LOSS, THERMOGENESIS, APPETITE SUPPRESSION, LEAN MUSCLE MASS, INCREASING METABOLISM AND BOOSTING ENERGY LEVELS, AND USE AS A DIETARY SUPPLEMENT IN MAMMALS Assignee: RTC RES & DEV LLC 2. Document ID: WO2007056133A2 Title: HERBAL COMPOSITION FOR WEIGHT MANAGEMENT Assignee: INDFRAG LTD 3. Document ID: WO2007101349A1 Title: COMPOSITIONS AND METHODS FOR INCREASING ADIPOSE METABOLISM, LIPOLYSIS OR LIPOLYTIC METABOLISM VIA THERMOGENESIS Assignee: HHC FORMULATIONS LTD 4. Document ID: WO2008006082A2 Title: ENERGY ENHANCING FORMULATION Assignee: BARRON JON 5. Document ID: WO2008028268A1 Title: DIET SUPPLEMENT FOR CAUSING WEIGHT LOSS COMPRISING CISSUS QUANDRANGULANS, GREEN TEA AND CAFFEINE Assignee: MULTI FORMULATIONS LTD 6. Document ID: US20020192308A1 Title: Method and composition for controlling weight

Information on Global Suppliers Green tea and caffeine (coffee, soft drinks, energy drinks) are available in every supermarket worldwide. Capsules and powders are also available in commercial stores and on the internet. One of the world’s leading companies in green tea is the Japanese Kao Corporation. Nestl´e is a big company that deals with caffeine as it exploits the world’s largest coffee brand.

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References Acheson KJ, Gremaud G, Meirim I, Montigon F, Krebs Y, Fay LB, Gay LJ, Schneiter P, Schindler C, Tappy L. Metabolic effects of caffeine in humans: lipid oxidation or futile cycling? Am J Clin Nutr 2004;79:40–46. Acheson KJ, Zahorska-Markiewicz B, Pittet P, Anantharaman K, Jequier E. Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals. Am J Clin Nutr 1980;33:989–997. Astrup A, Toubro S, Cannon S, Hein P, Breum L, Madsen J. Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers. Am J Clin Nutr 1990;51:759–767. Auvichayapat P, Prapochanung M, Tunkamnerdthai O, Sripanidkulchai BO, Auvichayapat N, Thinkhamrop B, Kunhasura S, Wongpratoom S, Sinawat S, Hongprapas P. Effectiveness of green tea on weight reduction in obese Thais: a randomized, controlled trial. Physiol Behav 2008;93:486–491. Belza A, Frandsen E, Kondrup J. Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects. Int J Obes (Lond) 2007;31:121–130. Belza A, Toubro S, Astrup A. The effect of caffeine, green tea and tyrosine on thermogenesis and energy intake. Eur J Clin Nutr 2009;63(1):57–64. Berube-Parent S, Pelletier C, Dore J, Tremblay A. Effects of encapsulated green tea and Guarana extracts containing a mixture of epigallocatechin3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men. Br J Nutr 2005;94:432–436. Borchardt RT, Huber JA. Catechol O-methyltransferase. 5. Structure– activity relationships for inhibition by flavonoids. J Med Chem 1975;18:120–122. Bracco D, Ferrarra JM, Arnaud MJ, Jequier E, Schutz Y. Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women. Am J Physiol 1995;269:E671–E678. Bray GA. Food intake, sympathetic activity, and adrenal steroids. Brain Res Bull 1993;32:537–541.

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Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine 2002;9:3–8. Curatolo PW, Robertson D. The health consequences of caffeine. Ann Intern Med 1983;98:641–653. Diepvens K, Kovacs EM, Nijs IM, Vogels N, Westerterp-Plantenga MS. Effect of green tea on resting energy expenditure and substrate oxidation during weight loss in overweight females. Br J Nutr 2005;94:1026–1034. Diepvens K, Westerterp KR, Westerterp-Plantenga MS. Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol 2007;292:R77–R85. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 1999;70:1040–1045. Dulloo AG, Geissler CA, Horton T, Collins A, Miller DS. Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am J Clin Nutr 1989;49:44–50. Dulloo AG, Seydoux J, Girardier L. Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition? Metabolism 1992;41:1233–1241. Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord 2000;24:252–258. Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med 1992;21:334–350. Harada U, Chikama A, Saito S, Takase H, Nagao T, Hase T, Tokimitsu I. Effects of long-term ingestion of tea catechins on energy expenditure and dietary fat oxidation in healthy subjects. J Health Sci 2005;51:248–252. Hase T, Komine Y, Meguro S, Takeda Y, Takahashi H, Matsui Y, Inaoka S, Katsuragi Y, Tokimitsu I, Shimasaki H, Itakura H. Anti-obesity effects of tea catechins in humans. J Oleo Sci 2001;50:599–605.

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Hodgson JM, Puddey IB, Burke V, Croft KD. Is reversal of endothelial dysfunction by tea related to flavonoid metabolism? Br J Nutr 2006;95:14–17. Hollands MA, Arch JR, Cawthorne MA. A simple apparatus for comparative measurements of energy expenditure in human subjects: the thermic effect of caffeine. Am J Clin Nutr 1981;34:2291–2294. Kao YH, Hiipakka RA, Liao S. Modulation of endocrine systems and food intake by green tea epigallocatechin gallate. Endocrinology 2000a;141:980–987. Kao YH, Hiipakka RA, Liao S. Modulation of obesity by a green tea catechin. Am J Clin Nutr 2000b;72:1232–1234. Klaus S, Pultz S, Thone-Reineke C, Wolfram S. Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation. Int J Obes (Lond) 2005;29:615–623. Komatsu T, Nakamori M, Komatsu K, Hosoda K, Okamura M, Toyama K, Ishikura Y, Sakai T, Kunii D, Yamamoto S. Oolong tea increases energy metabolism in Japanese females. J Med Invest 2003;50:170– 175. Kovacs EM, Lejeune MP, Nijs I, Westerterp-Plantenga MS. Effects of green tea on weight maintenance after body-weight loss. Br J Nutr 2004;91:431–437. Kozuma K, Chikama A, Hishino E, Kataoka K, Mori K, Hase T, Katsuragi Y, Tokimitsu I, Nakamura H. Effect of intake of a beverage containing 540 mg catechins on the body composition of obese women and men. Prog Med 2005;25:185–197. Lopez-Garcia E, van Dam RM, Rajpathak S, Willett WC, Manson JE, Hu FB. Changes in caffeine intake and long-term weight change in men and women. Am J Clin Nutr 2006;83:674–680. Lowell BB, Spiegelman BM. Towards a molecular understanding of adaptive thermogenesis. Nature 2000;404:652–660. Matsuyama T, Tanaka Y, Kamimaki I, Nagao T, Tokimitsu I. Catechin safely improved higher levels of fatness, blood pressure, and cholesterol in children. Obesity 2008;16(6):1338–1348. Murase T, Nagasawa A, Suzuki J, Hase T, Tokimitsu I. Beneficial effects of tea catechins on diet-induced obesity: stimulation of lipid

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catabolism in the liver. Int J Obes Relat Metab Disord 2002;26:1459– 1464. Nagao T, Hase T, Tokimitsu I. A green tea extract high in catechins reduces body fat and cardiovascular risks in humans. Obesity (Silver Spring) 2007;15:1473–1483. Nagao T, Komine Y, Soga S, Meguro S, Hase T, Tanaka Y, Tokimitsu I. Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men. Am J Clin Nutr 2005;81:122–129. Nagao T, Meguro S, Soga S, Otsuka A, Tomonobu K, Fumoto S, Chikama A, Mori K, Yuzawa M, Watanabe H, Hase T, Tanaka Y, Tokimitsu I, Shimasaki H, Itakura H. Tea catechins suppress accumulation of body fat in humans. J Oleo Sci 2001;50:717–728. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000;894 (i–xii): 1–253. Palmatier MA, Kang AM, Kidd KK. Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles. Biol Psychiatry 1999;46:557–567. Pasman WJ, Saris WH, Muls E, Vansant G, Westerterp-Plantenga MS. Effect of exercise training on long-term weight maintenance in weightreduced men. Metabolism 1999;48:15–21. Pasman WJ, Westerterp-Plantenga MS, Saris WH. The effectiveness of long-term supplementation of carbohydrate, chromium, fibre and caffeine on weight maintenance. Int J Obes Relat Metab Disord 1997;21:1143–1151. Robertson D, Frolich JC, Carr RK, Watson JT, Hollifield JW, Shand DG, Oates JA. Effects of caffeine on plasma renin activity, catecholamines and blood pressure. N Engl J Med 1978;298:181–186. Robertson D, Wade D, Workman R, Woosley RL, Oates JA. Tolerance to the humoral and hemodynamic effects of caffeine in man. J Clin Invest 1981;67:1111–1117. Rudelle S, Ferruzzi MG, Cristiani I, Moulin J, Mac´e K, Acheson KJ, Tappy L. Effect of a thermogenic beverage on 24-hour energy metabolism in humans. Obesity (Silver Spring) 2007;15:349–355.

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Shixian Q, VanCrey B, Shi J, Kakuda Y, Jiang Y. Green tea extract thermogenesis-induced weight loss by epigallocatechin gallate inhibition of catechol-O-methyltransferase. J Med Food 2006;9:451–458. Stunkard AJ. Current views on obesity. Am J Med 1996;100:230–236. Tremblay A, Masson E, Leduc S, Houde A, Despres JP. Caffeine reduces spontaneous energy intake in men but not in women. Nutr Res 1988;8:553–558. Tsuchida T, Itakura H, Nakamura H. Reduction of body fat in humans by long-term ingestion of catechins. Prog Med 2002;22:2189–2203. Wadden TA, Stunkard AJ, Liebschutz J. Three-year follow-up of the treatment of obesity by very low calorie diet, behavior therapy, and their combination. J Consult Clin Psychol 1988;56:925–928. Weisburger JH. Tea and health: a historical perspective. Cancer Lett 1997;114:315–317. Westerterp-Plantenga M, Diepvens K, Joosen AM, Berube-Parent S, Tremblay A. Metabolic effects of spices, teas, and caffeine. Physiol Behav 2006;89:85–91. Westerterp-Plantenga MS, Lejeune MP, Kovacs EM. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes Res 2005;13:1195–1204. Yang F, Oz HS, Barve S, de Villiers WJ, McClain CJ, Varilek GW. The green tea polyphenol (−)-epigallocatechin-3-gallate blocks nuclear factor-kappa B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol 2001;60:528–533.

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Mechanisms of (−)Epigallocatechin-3-Gallate for Antiobesity Hyun-Seuk Moon, PhD, Mohammed Akbar, PhD, Cheol-Heui Yun, PhD, and Chong-Su Cho, PhD

Abstract It has long been recognized that obesity is major risk factor for numbers of disorders including diabetes, hypertension, and heart diseases. For these, adipocytes play a central role in maintaining lipid homeostasis and energy balance in vertebrates by storing triacylglycerols (TGs) and releasing free fatty acids (FFAs) in response to changes in energy demands. Last few years, numerous studies regarding green tea catechins (GTCs) are reported to exhibit a variety of biological activities including cancer prevention and cardiovascular health. Furthermore, the obesity-preventive effects of green tea and its main constituent especially (−)-epigallocatechin-3-gallate (EGCG) are widely supported by results from epidemiological, cell culture, animal, and clinical studies. In this review, the biological activities and multiple mechanisms of EGCG in vitro and in vivo studies including animal models and clinical observations are explained.

Introduction Adipocytes and Obesity It is well known that adipocytes play a critical role in maintaining lipid homeostasis and energy balance by either storing triacylglycerols (TGs) or 177

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releasing free fatty acids (FFAs) dependent on changes of energy demands (Fruhbeck et al., 2001). In the industrialized countries, obesity becomes a major risk factor for numbers of disorders such as diabetes, hypertension, and heart disease (Farmer and Auwerx, 2004; Kelly and Goodpaster, 2001; Lee et al., 2005; Lewis et al., 2002). Also, several lines of evidence have suggested that TG accumulation in skeletal muscles and pancreatic islets is causally related to the insulin resistance together with pancreatic β-cell dysfunction in obese patients (Kelly and Goodpaster, 2001; Lewis et al., 2002). The development of obesity can be characterized by an increased number of fat cells and the contents of lipids due to the processes so called mitogenesis and differentiation, which are regulated by genetic, endocrine, metabolic, neurological, pharmacological, environmental, and nutritional factors (Farmer and Auwerx, 2004; Lewis et al., 2002; Unger and Zhou, 2001). Accordingly, an understanding of the mechanism by which particular nutrients affect the mitogenesis of preadipocytes and their differentiation to adipocytes would help to understand, and therefore prevent the initiation and progression of obesity and its associated diseases (Unger and Zhou, 2001).

Green Tea After water tea is the second most widely consumed beverages in the world, and its origins date back thousands of years (Rusznyak and SzentGyorgyi, 1936). Green tea, prepared by drying fresh tea leaves, contains a number of bioactive components, including polyphenols, caffeine, amino acids, and other trace compounds such as lipids and vitamins (Safe, 2001). It has been suggested that the health-promoting effects of green tea are mainly attributed to its polyphenol content (Roberts, 1953; Rusznyak and Szent-Gyorgyi, 1936; Safe, 2001). In fact, green tea is a rich source of polyphenols, especially flavanols and flavonols, which represent approximately 30% of dry weight of its fresh leaf (Ahmad and Mukhtar, 1999; Lin et al., 1999; Roberts, 1953; Safe, 2001). Catechins are the predominant form of the flavanols and mainly comprised epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC) (Ahmad and Mukhtar, 1999; Roberts, 1953). Not only they have unique chemical structures (Fig.11.1) and are major ingredients of unfermented tea (Hung et al., 2005) but they have been also found to possess widespread biological functions and health benefits (Chung et al., 2003; Kong et al., 2000; Lambert and Yang, 2003; Mukhtar and Ahmad, 2000; Riemersma et al., 2001). Recently, it is becoming clear that

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OH 4´

OH

5´

R1

B HO

O

7

2

A 5

3

OR2

G=galloyl:

OH

OH C

C

OH

O OH

(−)Epicatechin (EC) (−)Epigallocatechin (EGC) (−)Epicatechin-3-gallate (ECG) (−)Epigallocatechin-3-gallate (EGCG)

R1

R2

g/mol

H OH H OH

H H G G

290 306 442 458

Figure 11.1. Structures of four major green tea catechins. Differences among these catechins occur in the number of hydroxyl groups, the presence of a galloyl group, and the molecular weight (Hung et al., 2005; reprinted with permission).

many of the aforementioned beneficial effects of green tea were attributed to its most abundant catechin, EGCG (Ahmad and Mukhtar, 1999; Lin et al., 1999; Roberts, 1953). Indeed, it has been shown that EGCG lowers the incidence of various cancers (Ahmad and Mukhtar, 1999; Lin et al., 1999; Mitscher et al., 1997; Roberts, 1953), collagen-induced arthritis (Yang and Wang, 1993), oxidative stress-induced neurodegenerative disease (Haqqi et al., 1999), and streptozotocin-induced diabetes (Mendel and Youdim, 2004). Also, it has been clearly demonstrated that EGCG or EGCG-containing green tea extract reduces food uptake, lipid absorption, and blood TGs, cholesterol, and leptin levels, as well as stimulating energy expenditure, fat oxidation, high-density lipoprotein (HDL) levels, and fecal lipid excretion (Safe, 2001; Song et al., 2003).

The Aim of This Review During the last decades, the obesity-preventive effects of green tea and its main compound EGCG are widely supported by results from epidemiological, preclinical, and clinical studies. This review focuses on in vitro

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and in vivo studies investigating the antiobesity effects of green tea or isolated green tea components and attempts to explore the underlying mechanisms. The possible relevance of each of the proposed mechanism on human obesity prevention is also discussed. The mechanisms for antiobesity discussed in this review may possibly be utilized in the further research and therapeutic treatment of patients with obesity and its related disease.

Antiobesity Mechanisms of EGCG Antiadipogenic Effect of EGCG via Extracellular Signal-Regulated Kinase (ERK)-Dependent Signaling Pathway Mitogen-activated protein kinases (MAPKs) are serine/threoninespecific protein kinases composed of extracellular signal-related kinases (ERK) and c-Jun-N-terminal kinases (JNK) and p38 that respond to extracellular stimuli (e.g., mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis. The activation of MAPK results in regulation of gene expression by phosphorylation of a variety of transcription factors and modification of their transcriptional efficiencies in a variety of cell types (Pearson et al., 2001). Importantly, in adipocytes, both ERK and JNK can phosphorylate peroxisome proliferator-activated receptor γ (PPARγ), which results in repression of its transcriptional activation potential and adipogenesis (Ahmad and Mukhtar, 1999). In relation to this action, EGCG has been proposed to serve as signal elements in several types of cells where EGCG may regulate cell growth (Ahmad and Mukhtar, 1999; Yang and Wang, 1993) and may modulate the mitogenic and adipogenic signalings of IGF-I in 3T3-L1 preadipocytes (Levites et al., 2002). In addition, the antiadipogenic effect of EGCG appears to be important not only in reducing adipocyte differentiation (hypertrophy) but also in inhibiting adipocyte proliferation (hyperplasia), suggesting that ERK1/2, enzymes that involved in the control of cell cycle, is required for these inhibitory effects (Hung et al., 2005). Supporting this hypothesis, Hung et al. (2005) reported that EGCG induced a decrease in phosphorylated ERK1/2 in 3T3-L1 preadipocytes but did not alter the total levels of MEK1, ERK1/2, p38, phospho-p38, JNK, or phospho-JNK (Fig.11.2), suggesting that EGCG acts specifically on a phosphorylation of the ERK1/2. This contention is also partially supported

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Figure 11.2. Effects of EGCG on ERK1/2, phospho-ERK1/2 and MEK1 in 3T3-L1 preadipocytes (day 3). (a) Time-dependent effect of EGCG at 50 µM was observed. (b) Dose-dependent effect of EGCG was observed after 4 hours of treatment. (c) EGCG at 50 µM altered MEK1 activity as indicated by decreased phospho-ERK1/2, which was dependent on the growth phases of cells after 4 hours of treatment. Day 1, the day when cells were plated; latent, day 3; log-phase, day 5 (confluent). The kinases were measured by Western blot analysis and then expressed after normalization to β-actin. Data are expressed as mean ± SE from triplicate determinations. In some data, SE bars are too small to be seen. * indicates p < 0.05 when compared to the control (Hung et al., 2005; reprinted with permission).

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by the fact that exposure (24 or 48 hours) to EGCG induced a decrease in the phosphorylated ERK1/2 of preadipocytes without altering total levels of MEK1 or ERK1/2 proteins (Levites et al., 2002).

Antiadipogenic Effect of EGCG via Resistin (RSTN)-Modulated Adipogenesis Adipokines, mainly produced by adipocytes, are active participants in the regulation of inflammation (Arner, 2005). Among them, resistin (RSTN), known as an adipocyte-specific secretory factor (ADSF), is implicated to modulate insulin resistance in rodents (Adeghate, 2004). Interestingly, RSTN is expressed in white adipose tissue in mouse, but mainly in leukocytes in human. Steppan et al. reported that RSTN has an inhibitory effect on insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes (Steppan et al., 2001). Recent study suggested that intracellular RSTN protein significantly decreased in the presence of 100 µM EGCG 3 hours after treatment, whereas the release of the RSTN protein has no significant change (Liu et al., 2006), suggesting that EGCG may modulate the distribution of RSTN protein.

Antiadipogenic Effect of EGCG via Cyclin-Dependent Kinase 2 (CDK 2)-Dependent Signaling Pathway It has been shown that EGCG downregulated adipocyte differentiation through the CDK2 signaling pathway (Hung et al., 2005). These results suggested that the antimitogenic effect of EGCG on 3T3-L1 preadipocytes is dependent on the ERK MAPK and cyclin-dependent kinase 2 (CDK2) pathways and is likely mediated through decreases in their activities. Also, Wu et al. reported that the apoptotic effect of EGCG on 3T3-L1 preadipocytes is dependent on the Cdk2 and caspase-3 pathways and is likely mediated through alterations in their activities (Wu et al., 2005), suggesting that decreases in Cdk2 activity by EGCG may be due to its effect on this particular member of the CKI family. However, there are very limited studies between EGCG and CDK. In vivo study suggested that CDK2 activity can be regulated by the association of stimulatory proteins such as cyclin E (Morgan, 1995). Hence, more investigations are needed to clarify whether the production of cyclin E protein and its association

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with CDK2 can be altered by EGCG and thereafter resulting decreases in CDK2 activity.

Antiadipogenic Effect of EGCG via Activation of AMP-Activated Protein Kinase (AMPK) AMPK is known to play an important role in energy homeostasis by coordinating number of effectors responses in ATP-depleting metabolic states such as ischemia/reperfusion, hypoxia, heat shock, oxidative stress, and exercise (Kemp et al., 2003; Morgan, 1995). Moreover, AMPK promotes oxidation of fatty acid and inhibits lipid synthesis in cells through phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) activity (Jaleel et al., 2006; Shaw et al., 2004; Xie et al., 2006). The persistent activation of AMPK has been shown to be linked to p53-dependent cellular senescence, suggesting its role as an intrinsic regulator of the cell cycle (Jones et al., 2005). Moreover, AMPK cascades have emerged as novel targets for the treatment of obesity and type II diabetes (Luo et al., 2005; Meisse et al., 2002; Song et al., 2002). Hwang et al. (2005) suggested that several naturally occurring compounds including EGCG or capsaicin have potential antiobesity effects by activation of AMPK and inhibition of adipocyte differentiation in 3T3-L1 cells. This result indicated that AMPK activation is necessary for the inhibition of adipocyte differentiation by EGCG and capsaicin. Furthermore, Collins et al. reported that EGCG suppresses hepatic gluconeogenesis through ROS, CaMKK, and AMPK (Collins et al., 2007). Hence, the mechanism that affects AMPK regulation after EGCG treatment could be a promising target for the development of strategies to treat obesity.

Antiadipogenic Effect of EGCG via Regulation of Reactive Oxygen Species (ROS) Generally, ROS has been suggested as upstream molecules of AMPKactivated signals (Collins et al., 2007; Giakoustidis et al., 2008; Kemp et al., 2003; Meng et al., 2008; Qanungo et al., 2005; Yao et al., 2008). In fact, Hwang et al. reported that genistein inhibits adipocyte differentiation and the induction of adipocyte apoptosis through the activation of AMPK paralleled with the generation of ROS, and this effect was similar to that of EGCG treatment (Hwang et al., 2005). Therefore, one of the AMPK activation mechanisms was suspected to be ROS, which was supported by

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reports that various therapeutic effects in naturally occurring compounds were mediated by the release of ROS (Qanungo et al., 2005). Hwang et al. have shown that genistein induced ROS generation significantly, which led to AMPK activation, and these effects were abolished by its inhibitor, NAC (5 mM) treatment (Hwang et al., 2005). These results indicate that ROS is necessary for AMPK activation in the inhibitory process of adipocyte differentiation by phytochemicals in 3T3-L1 cells. Recent study also showed that EGCG at relatively low and nontoxic concentration (equal or less than 1 µM) inhibited glucose production by hepatic gluconeogenesis mediated by AMPK activation through Ca2+ /calmodulin-dependent protein kinase kinase (CaMKK) and ROS (Giakoustidis et al., 2008). Meng et al. investigated EGCG for its antiaging effect on human diploid fibroblasts (HDF). In this study, HDF treated with EGCG at 25 and 50 µM for 24 hours dramatically increased catalase, superoxide dismutase (SOD)1, SOD2, and glutathione peroxidase gene expressions and their enzyme activities. Furthermore, these activities appeared to be necessary to protect HDF against hydrogen peroxide (H2 O2 )-induced oxidative damage, accompanied with decreased accumulation of intracellular ROS and well-maintained mitochondrial integrity (Meng et al., 2008).

Antiadipogenic Effect of Green Tea via Inhibition of Lipogenic Enzymes GTCs are known to possess antilipogenic activity (Kao et al., 2006). They can inhibit the activity and/or expression of lipogenic enzymes, such as ACC, fatty acid synthase (FAS), malic enzyme (ME), glucose-6phosphate dehydrogenase (G6PDH), glyceol-3-phosphate dehydrogenase (G3PDH), and stearoyl-CoA desaturase-1 (SCD-1) (Table 11.1) (Ahmad and Mukhtar, 1999; Crespy and Williamson, 2004; Kao et al., 2006; Lin et al., 1999). ACC involves the rate-limiting step in fatty acid synthesis for catalyzing the conversion of acetyl-CoA to malonyl-CoA (Kimura et al., 1983). When ECG or EGCG from green tea was incubated with rat liver ACC, they (with Ki of 310 µM) inhibited the activity of ACC (Kimura et al., 1983). However, such activity was not observed when (+)-catechin, EC or EGC, was used. A recent report also showed that EGCG supplementation downregulates ACC mRNA expression in obese mice (Ahmad and Mukhtar, 1999). It has also been reported that when EGCG was incubated with chicken FAS, the second enzyme to catalyze the conversion of malonyl-CoA to fatty acyl-CoA, it inhibited FAS activity with an IC50 of 52 µM (Wang

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Table 11.1. EGCG inhibition of lipid-related enzymes in cell-free systemsa Enzymes Lipogenic enzymes ACC Aromatase FAS Lanosterol 14α-demethylase Oxidosqualene: lanosterol cyclase Squalene epoxidase Lipolytic enzymes GLb PL Oxidoreductase Glycyrhizin-binding lipoxygenase Lipoxygenase Type 1 5α-reductase Type 2 5α-reductase Others COMT

IC50 (µM) 310 60 52 >100 >100 0.7 10 0.34–11 10 10 15 74 0.2

Sources: Kao et al., 2006; reprinted with permission. a Activity and expression of some enzymes that have been found to be affected by tea catechins in cell or animal systems include ACC, FAS, ME, G6PDH, G3PDH, SCD1, acyl-CoA oxidase, medium-chain acyl CoA dehydrogenase, UCP2, UCP3, fatty acid translocase, carnitine palmitoyltransferase, and HSL. b The unit is expressed as milligrams of green tea extract per gram of tributyrin substrate.

and Tian, 2001). Generally, inhibitory activity of FAS by EGCG depends on reversible fast-binding inhibition and irreversible slow-binding inactivation (Wang and Tian, 2001). Because FAS shows high levels of activity in LNCaP human prostate cancer cells, EGCG treatment at 100 µM for 24 hours inhibited 52% FAS activity (Brusselmans et al., 2003). In addition, EGCG is reported to suppress FAS mRNA and protein levels in MCF-7 breast cancer cells suggested that EGCG signaling may be involved in the downregulation of the EGF receptor and its downstream Akt and Sp-1 proteins (Yeh et al., 2003). Moreover, a decrease in the expression of hepatic ME and G6PDH, which generate NADPH for fatty acid biogenesis, has also been observed in obese mice when treated with EGCG (Ahmad and Mukhtar, 1999). Furthermore, the activity and expression of G3PDH involving a step in TG biosynthesis are decreased by EGCG treatment (Mochizuki and Hasegawa, 2004). Also, it was found that gene expression of SCD1, utilized for the synthesis of monounsaturated fatty

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acids by liver and adipose tissue, was suppressed in EGCG-treated obese mice (Ahmad and Mukhtar, 1999). Overall, green tea, EGCG in particular, appears to reduce fatty acid and TG synthesis by inhibiting lipogenic enzymes, and this may explain its hypolipidic effects.

Antiadipogenic Effect of Green Tea via Downregulation of Adipocyte Marker Proteins and Its Target Genes Generally, the enforced expression of PPARγ and C/EBPα stimulates adipogenesis in NIH 3T3 fibroblasts, suggesting the essential role of these transcription factors in regulating adipogenesis (Chu et al., 1995; Dalei and Lazar, 1997). In fact, PPARγ2 and C/EBPα are found almost exclusively in the adipose tissue and have been linked to the adipocyte differentiation (Hwang et al., 1997), which could play a crucial role both in the induction of adipose-specific genes and in the manifestation of the mature adipose phenotype. Furthermore, the combined expression of PPARγ and C/EBPα has synergistic effects in promoting fat cell conversion in myoblasts (Brown et al., 2003; Moon et al., 2006), indicating that they are very important for fat accumulation. Also, these transcription factors coordinate the expression of genes involved in creating and maintaining the adipocyte phenotype, including aP2 (Chu et al., 1995). The aP2, a member of intracellular lipid binding protein family, is involved in the formation of atherosclerosis predominantly through the direct modification of cholesterol trafficking and inflammatory responses in the macrophages (Chu et al., 1995; Dalei and Lazar, 1997). By contrast, it was demonstrated that EGCG significantly downregulated the expression of adipocyte maker genes during adipocyte differentiation (Yang and Wang, 1993), indicating that the negative impact of EGCG on adipogenesis was accompanied by the reduction of PPARγ2 protein in 3T3-L1 cells coincide with the attenuation of C/EBPα expression. Because PPARγ is one of the key transcription factors in the induction of adipogenesis and lipid accumulation (Brown et al., 2003; Moon et al., 2006), EGCG-induced downregulation of PPARγ expression is likely to suppress the lipid accumulation and adipocyte differentiation (Haqqi et al., 1999; Kao et al., 2000; Mendel and Youdim, 2004; Song et al., 2003). On the other hand, TG hydrolysis proportionally released glycerol and FFA from adipocytes, and the glycerol release caused the lipolysis in the adipocytes (Moussalli et al., 1986). Certain natural compounds such as conjugated linoleic acid (CLA) and forskolin-induced lipolysis in adipocyte models (Wolfram et al., 2006b).

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In fact, we previously reported that CLA had an antiadipogenic effect and induced lipolysis in 3T3-L1 cells (Moon et al., 2006). It is to note from another study that GTCs strongly reduced adipocyte differentiation but did not induce lipolysis (Wolfram et al., 2006a), indicating that the antiadipogenic effects of EGCG have no direct relation with changes of lipolysis.

Insulin-Potentiating Activity by Green Tea In addition to the antiadipogenic effects of EGCG on adipocyte marker protein expression, Wu et al. reported that, after 12 weeks of green tea supplementation, the fasting plasma glucose and insulin levels in the green tea group were significantly lower than those in the control group (Wu et al., 2004). As shown in Fig. 11.3, during the 2 hours following glucose ingestion, no difference was seen in the plasma glucose levels between the two groups. However, the plasma insulin levels of the group fed with green tea at all time points were significantly (p < 0.05) lower than those in the control group. In fact, the AUCs for plasma glucose and insulin were 336

Control Green tea

(b) 50 Plasma insulin (µU/mL)

Plasma glucose (mg/dL)

(a) 250 200 150 100

* 50

40 30 20

*

*

10

* *

* 0

0 0

30

60

90 120 150

Time (min)

0

30

60

90 120 150

Time (min)

Figure 11.3. Changes in plasma levels of glucose (a) and insulin (b) in rats in response to an oral glucose tolerance test (2 g of glucose/kg of BW) performed after 12 weeks with or without green tea supplementation. Values are shown as the mean ± SD. * indicates p < 0.05 when compared to the control group (Wu et al., 2004; reprinted with permission).

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± 11 mg h/dL and 38 ± 10 µU h/mL, respectively, in the group fed with green tea, whereas 346 ± 13 mg h/dL and 60 ± 18 µU h/mL, respectively, in the control group. No significant difference was found between the two groups in the AUC for plasma glucose (p = 0.260); however, the AUC for insulin in the group fed with green tea was significantly lower (p = 0.004) than the control group, demonstrating that the green tea causes increase of insulin sensitivity. These results indicated that green tea supplementation in the form of regular tea infusion could increase insulin sensitivity by increasing the glucose uptake. It is believed that the beneficial effects of green tea are due to the polyphenols, the principal active ingredients. It provides the protection against oxidative damage and antibacterial, antiviral, anticarcinogenic, and antimutagenic activities; however, it may also increase insulin activity (Wu et al., 2004). Several compounds found in green tea were also shown to enhance insulin activity, for instance, EGCG as the greatest activity, followed by ECG, tannins, and theaflavins (Anderson and Polansky, 2002; Carobbio et al., 2004; Wu et al., 2004). Supporting these results, Anderson et al. reported that the insulinpotentiating activity in green and oolong tea was mainly due to EGCG (Table 11.2) (Anderson and Polansky, 2002). These data demonstrated that the increased insulin together with its activity of the tea leaves is predominantly due to the presence of the active ingredient EGCG. Insulin secretion by pancreatic β cells is stimulated by glucose, amino acids, and other metabolic fuels (Carobbio et al., 2004). Li et al. reported that EGCG does not affect glucose-stimulated insulin secretion under high-energy conditions when glutamate dehydrogenase (GDH) is fully inhibited. They also showed that EGCG acts in an allosteric manner independent of their antioxidant activity and that the β-cell

Table 11.2. Insulin activity ratios of fractions from Oolong teaa Fraction Time (minutes) 2.5–6 6–13 13–20 20–23 23–28

Insulin Activity Ratio

Fraction Time (minutes)

Insulin Activity Ratio

1.5 1.2 1.3 4.5 1.0

38–44 44–47 47–52 52–60 60–68

1.1 0.9 1.3 1.4 1.3

Sources: Anderson et al., 2002; reprinted with permission. a Fractions were collected as described for the chromatogram. Individual fractions were concentrated by rotoevaporation to 0.5 mL and diluted fivefold in water prior to assay.

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stimulatory effects are directly correlated with glutamine oxidation (Li et al., 2006).

Epidemiological Observation of Green Tea and Clinical Studies Although some epidemiological studies have failed to provide clearcut evidence for a link between tea consumption and body weight (Kono et al., 1996), several studies have shown that tea intake is associated with decreased serum concentrations of total cholesterol and lipoprotein. For example, Tokunaga et al. reported that green tea consumption was inversely associated with serum levels of total cholesterol and LDL, but not with body weight index, HDL, and TG (Tokunaga et al., 2002). In another study with men over 40 years of age, higher levels of green tea consumption were associated with a proportional increase of HDL coincide with a proportional decrease of LDL and serum concentrations of total cholesterol and TG, but not with the body weight index (Imai and Nakachi, 1995). In a recent clinical study, green tea extract containing 25% EGCG exerted reduction of body weight (4.6%) and waist circumference (4.5%) in moderately obese patients 3 months after treatment (Chantre and Lairon, 2002). Also, Nagao et al. (2005) reported that the subjects who ingested one bottle of oolong tea containing 690 mg GTCs/day for 12 weeks had a lower body weight, body weight index, waist circumference, body fat mass, and subcutaneous fat area than did the subjects who ingested one bottle of oolong tea containing 22 mg catechins/day (Table 11.3). These early studies indicated the beneficial effects of GTCs to reduce body weight. Also, Nakagawa et al. clearly demonstrated that when 18 healthy Japanese men were given a green tea extract containing 254 mg, their plasma level of EGCG reached 0.27 nM in 1 hour after administration, while plasma phospholipids, total cholesterol, and TG did not change. However, the plasma phatidycholine hydroperoxide level decreased from 74 pM in controls compared to 45 pM in EGCG-treated subjects, suggesting that tea catechins are as effective as antioxidants (Nakagawa et al., 1999). It is to note that there are controversial observations on the regulation of energy expenditure and fat oxidation by green tea in human. In fact, according to a respiratory chamber study, ten healthy men had a green tea extract that contains 50 mg caffeine and 90 mg EGCG at breakfast,

190

Weight (kg)b,c Control group GTE group BMI (kg/m2 )b,c Control group GTE group Waist (cm)b–d Control group GTE group Hip (cm)b Control group GTE group Body fat mass (kg)b,c Control group GTE group Lean body mass (kg)b Control group GTE group 72.9 ± 1.3 72.6 ± 1.7 24.7 ± 0.4 24.4 ± 0.4 86.7 ± 1.1 86.6 ± 1.4 95.9 ± 0.7 97.0 ± 0.9 18.8 ± 0.9 19.2 ± 0.9 54.1 ± 0.7 53.4 ± 1.0

25.0 ± 0.4 24.9 ± 0.4 87.8 ± 1.1 87.9 ± 1.4 97.0 ± 0.8 97.4 ± 0.9 19.5 ± 1.0 19.7 ± 0.8 54.3 ± 0.7 54.2 ± 1.1

Four Weeks

73.8 ± 1.3 73.9 ± 1.8

Initial

53.9 ± 0.7 54.1 ± 1.1

18.8 ± 1.0 18.0 ± 0.9

95.8 ± 0.8 96.0 ± 1.1

53.7 ± 0.7 53.2 ± 1.0

18.8 ± 1.1 18.3 ± 0.9

95.8 ± 0.8 96.1 ± 1.1

86.2 ± 1.2 84.5 ± 1.3

24.6 ± 0.4 24.1 ± 0.4

72.5 ± 1.4 71.5 ± 1.7

Twelve Weeks

−0.6 ± 0.3 −1.0 ± 0.4

−0.7 ± 0.3 −1.4 ± 0.3

−1.1 ± 0.3 −1.3 ± 0.3

−1.6 ± 0.4 −3.4 ± 0.5

−0.4 ± 0.1 −0.8 ± 0.2

−1.3 ± 0.3 −2.4 ± 0.5

Change at Twelve Weeks

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86.6 ± 1.1 85.5 ± 1.3

24.6 ± 0.4 24.3 ± 0.4

72.7 ± 1.4 72.2 ± 1.7

Eight Weeks

Table 11.3. Changes in anthropometric variables and body composition after consumption of either control or high-catechin beverages for 12 weeksa

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26.2 ± 1.5 25.9 ± 1.8 246.4 ± 12.7 232.1 ± 9.9 84.5 ± 5.0 73.2 ± 5.3 161.9 ± 11.0 158.8 ± 8.3

25.3 ± 1.3 26.3 ± 1.6 254.2 ± 13.1 246.3 ± 11.2 88.9 ± 6.5 79.2 ± 5.4 165.3 ± 10.7 167.1 ± 8.7

167.3 ± 11.0 158.7 ± 7.9

87.0 ± 5.2 73.0 ± 5.3

254.3 ± 13.6 231.7 ± 11.1

25.7 ± 1.4 24.6 ± 1.5

−4.1 ± 4.1 −16.7 ± 3.0

−2.4 ± 2.7 −10.1 ± 4.0

−6.7 ± 5.8 −26.7 ± 6.0

−1.3 ± 0.7 −3.3 ± 0.7

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Sources: Nagao et al., 2005; reprinted with permission. a All values are x ± SEM. GTE, green tea extract; TFA, total fat area; VFA, visceral fat area; SFA, subcutaneous fat area. Control group, n = 18; GTE group, n = 17. The initial values did not differ significantly between groups. Data from weeks 0, 4, 8, and 12 were compared by using two-factor repeated-measures ANOVA with time and group. b Significant effect of time from week 0 to week 12, p < 0.01. c Significant time-by-group interaction, p < 0.05. d Significant differences between groups for change at 12 weeks (unpaired t test): p < 0.01. e Significant differences between groups for change at 12 weeks (unpaired t test): p < 0.05. f Control group, n = 18 at initial measurement and 12 weeks; n = 17 at 4 and 8 weeks.

Skinfold thickness (mm)b,e Control group 27.0 ± 1.5 GTE group 27.9 ± 1.8 TFA (cm2 )b,f Control group 261.0 ± 12.7 GTE group 258.4 ± 11.0 VFA (cm2 )b,f Control group 89.3 ± 5.8 GTE group 83.1 ± 5.7 SFA (cm2 )b,c,e,f Control group 171.7 ± 10.7 GTE group 175.3 ± 8.2

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lunch, and dinner (Dulloo et al., 1999). The results showed that EGCGcontaining green tea extracts that contain caffeine are more potent than caffeine alone at stimulating 24-hour energy expenditure and fat oxidation and urinary norepinephrine excretion. However, in another study involving 104 overweight and moderately obese male and female subjects, ages of 18–60 years and BMI of 25–35 kg/m2 , the level of green tea extracts that contained caffeine (104 mg/day) and EGCG (323 mg/day) were given for 13 weeks was not associated with weight maintenance after a 7.5% body weight loss in very low energy diet subjects (Kovacs et al., 2004). This study also showed that habitual caffeine consumption affected weight maintenance in the green tea treatment. In addition, these clinical observations indicated that long-term, but not short-term, oral consumption of green tea appeared to reduce the body weight and/or fat. The difference in regulating body weight from these studies may be attributable to the protocols employed, the purity of green tea extracts, the period of administration, the percentage of the caffeine, and the physiological condition of the subjects.

Summary and Future Direction Obesity is associated with high blood cholesterol and a high risk for developing diabetes and cardiovascular diseases. Therefore, the management of body weight and obesity is increasingly recognized as a key factor to maintain healthy cholesterol profiles and to reduce cardiovascular risk. Several drugs are tested and used to treat obese-related metabolic diseases in association with the possibility of preventing body fat accumulation. Increasing interest in the health benefits of tea has led to the addition of tea extracts in dietary supplements and functional foods among these substances of interest. Especially, EGCG is known to have a beneficial effect on human health that reduced adipocyte differentiation and decreased TG levels. However, epidemiologic evidence regarding the effects of tea consumption on obesity-related disease is conflicting. This is an important area for future investigations, as it would provide further insight on precise mechanism of EGCG during adipogenesis in the patients. Although more studies are required to examine the effects and mechanisms of EGCG in animals and humans, the antiadipogenic effect of EGCG on adipocyte differentiation seems sounding and promising therapeutic treatment against obesity. Also, the various mechanisms discussed in this review could be utilized in the treatment of obesity using EGCG.

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Acknowledgments We are grateful to Dr. Dehua Cao at LMS/NIAAA/NIH for providing the information of green tea.

References Adeghate E. An update on the biology and physiology of resistin. Cell Mol Life Sci 2004;61:2485–2496. Ahmad N, Mukhtar H. Green tea polyphenols and cancer: biologic mechanisms and practical implications. Nutr Rev 1999;57:78–83. Anderson RA, Polansky MM. Tea enhances insulin activity. J Agric Food Chem 2002;50:7182–7186. Arner P. Resistin: yet another adipokine tells us that men are not mice. Diabetologia 2005;48:2203–2205. Brown JM, Boysen MS, Jensen SS, Morrison RF, Storkson J, LeaCurrie R, Pariza M, Mandrup S, McIntosh M. Isomer-specific regulation of metabolism and PPARgamma signaling by CLA in human preadipocytes. J Lipid Res 2003;44: 1287–1300. Brusselmans K, Schruver ED, Heyns W, Verhoeven G, Swinnen JV. Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells. Int J Cancer 2003;106:856–862. Carobbio S, Ishihara H, Fernandez-Pascual S, Bartley C, Martin-DelRio R, Maechler P. Insulin secretion profiles are modified by overexpression of glutamate dehydrogenase in pancreatic islets. Diabetologia 2004;47:266–276. Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine 2002; 9:3–8. Chu R, Madison LD, Lin Y, Kopp P, Rao MS, Jameson JL, Reddy JK. Thyroid hormone (T3) inhibits ciprofibrate-induced transcription of genes encoding beta-oxidation enzymes: cross talk between peroxisome proliferator and T3 signaling pathways. Proc Natl Acad Sci USA 1995;92:11593–11597.

P1: SFK/UKS P2: SFK c11 BLBS044-Cho October 15, 2009

194

8:11

Printer Name: Yet to Come

Functional Components

Chung FL, Schwartz J, Herzog CR, Yang YM. Tea and cancer prevention: studies in animals and humans. J Nutr 2003;133:3268S–3274S. Collins QF, Liu HY, Pi J, Liu Z, Quon MJ, Cao W. Epigallocatechin3-gallate (EGCG), a green tea polyphenol, suppresses hepatic gluconeogenesis through 5
-AMP-activated protein kinase. J Biol Chem 2007;282:30143–30149 Crespy V, Williamson G. A review of the health effects of green tea catechins in in vivo animal models. J Nutr 2004;134:3431S–3440S. Dalei S, Lazar MA. Peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein alpha, and cell cycle status regulate the commitment to adipocyte differentiation. J Biol Chem 1997;272:21473–21478. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 1999;70:1040–1045. Farmer SR, Auwerx J. Adipose tissue: new therapeutic targets from molecular and genetic studies–IASO Stock Conference 2003 report. J Obes Rev 2004;5:189–196. Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrel MA. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab 2001;280;E827–E847. Giakoustidis AE, Giakoustidis DE, Koliakou K, Kaldrymidou E, Iliadis S, Antoniadis N, Kontos N, Papanikolaou V, Papageorgiou G, Atmatzidis K, Takoudas, D. Inhibition of intestinal ischemia/repurfusion induced apoptosis and necrosis via down-regulation of the NF-kB, c-Jun and caspace-3 expression by epigallocatechin-3-gallate administration. Free Radic Res 2008;42:180–188. Haqqi TM, Anthony DD, Gupta S, Ahmad N, Lee MS, Kumar GK, Mukhtar H. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl Acad Sci USA 1999;96:4524–4529. Hung PF, Wu BT, Chen HC, Chen YH, Chen CL, Wu MH, Liu HC, Lee MJ, Kao YH. Antimitogenic effect of green tea (−)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways. Am J Physiol Cell Physiol 2005;288:C1094–C1108.

P1: SFK/UKS P2: SFK c11 BLBS044-Cho October 15, 2009

8:11

Printer Name: Yet to Come

Mechanisms of (−)-Epigallocatechin-3-Gallate

195

Hwang CS, Loftus TM, Mandrup S, Lane MD. Adipocyte differentiation and leptin expression. Annu Rev Cell Dev Biol 1997;13:231–259. Hwang JT, Park IJ, Shin JI, Lee YK, Lee SK, Baik HW, Ha JH, Park OJ. Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun 2005;16:694–699. Imai K, Nakachi K. Cross sectional study of effects of drinking green tea on cardiovascular and liver diseases. Br Med J 1995;32: 3615–3619. Jaleel M, Villa F, Deak M, Toth R, Prescott AR, Van Aalten DM, Alessi DR. The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation. Biochem J 2006;394:545–555. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Thompson CB. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005;18:283–293. Kao YH, Chang HH, Lee MJ, Chen CL. Tea, obesity, and diabetes. Mol Nutr Food Res 50:2006; 188–210. Kao YH, Hiipakka RA, Liao S. Modulation of endocrine systems and food intake by green tea epigallocatechin gallate. Endocrinology 2000;141:980–987. Kelly DE, Goodpaster BH. Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance. Diabetes Care 2001;24:933–941. Kemp BE, Stapleton D, Campbell DJ, Chen ZP, Murthy S, Walter M, Gupta A, Adams JJ, Katsis F, Van Denderen B, Jennings IG, Iseli T, Michell BJ, Witters LA. AMP-activated protein kinase, super metabolic regulator. Biochem Soc Trans 2003;31:162–168. Kimura Y, Okuda H, Okuda T, Yoshida T, Hatano T, Arichi S. Studies on the activities of tannins and related compounds of medicinal plants and drugs. III. Effects of various tannins and related compounds on adrenocorticotropic hormone-induced lipolysis and insulin-induced lipogenesis from glucose in fat cells. (2). Chem Pharm Bull 1983;31:2501– 2506. Kong AN, Yu R, Chen C, Mandlekar S, Primiano T. Signal transduction events elicited by natural products: role of MAPK and caspase pathways in homeostatic response and induction of apoptosis. Arch Pharm Res 2000;23:1–16.

P1: SFK/UKS P2: SFK c11 BLBS044-Cho October 15, 2009

196

8:11

Printer Name: Yet to Come

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Kono S, Shinchi K, Wakabayashi K, Honjo S, Todoroki I, Sakurai Y, Imanishi K, Nishikawa H, Ogawa S, Katsurada M. Relation of green tea consumption to serum lipids and lipoproteins in Japanese men. J Epidemiol 1996;6:128–133. Kovacs EMR, Lejeune MPGM, Nijs I, Westerterp-Plantenga MS. Effects of green tea on weight maintenance after body-weight loss. Br J Nutr 2004;91:431–437. Lambert JD, Yang CS. Cancer chemopreventive activity and bioavailability of tea and tea polyphenols. Mutat Res 2003;523:201–208. Lee WJ, Koh EH, Won JC, Kim MS, Park JY, Lee KU. Obesity: the role of hypothalamic AMP-activated protein kinase in body weight regulation. Int J Biochem Cell Biol 2005;37:2254– 2259. Levites Y, Amit T, Youdim MBH, Mandel S. Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol (−)-epigallocatechin 3-gallate neuroprotective action. J Biol Chem 2002;277:30574–30580. Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocrinol Rev 2002;23:201–209. Li C, Allen A, Kwagh J, Doliba NM, Qin W, Najafi H, Collins HW, Matschinsky FM, Stanley CA, Smith TJ. Green tea polyphenols modulate insulin secretion by inhibiting glutamate dehydrogenase. J Biol Chem 2006;281:10214–10221. Lin JK, Liang YC, Lin-Shiau SY. Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem Pharmacol 1999;58:911–915. Liu HS, Chen YH, Hung PF, Kao YH. Inhibitory effect of green tea (−)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway. Am J Physiol Endocrinol Metab 2006;290:E273–E281. Luo Z, Saha AK, Xiang X, Ruderman NB. AMPK, the metabolic syndrome and cancer. Trends Pharmacol Sci 2005;26:69–76. Mendel S, Youdim MB. Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med 2004;37:304–317.

P1: SFK/UKS P2: SFK c11 BLBS044-Cho October 15, 2009

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Mechanisms of (−)-Epigallocatechin-3-Gallate

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Meisse D, Van de Casteele M, Beauloye C, Hainault I, Kefas BA, Rider MH, Foufelle F, Hue L. Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal kinase activation and apoptosis in liver cells. FEBS Lett 2002;526:38–42. Meng Q, Velalar CN, Ruan R. Effects of epigallocatechin-3-gallate on mitochondrial integrity and antioxidative enzyme activity in the aging process of human fibroblast. Free Radic Biol Med 2008;44:103210–103241. Mitscher LA, Jung M, Shankel D, Dou JH, Steele L, Pillai SP. Chemoprotection: a review of the potential therapeutic antioxidant properties of green tea (Camellia sinensis) and certain of its constituents. Med Res Rev 1997;17:327–365. Mochizuki M, Hasegawa N. Stereospecific effects of catechin isomers on insulin induced lipogenesis in 3T3-L1 cells. Phytother Res 2004;18:449–450. Moon HS, Lee HG, Seo JH, Chung CS, Kim TG, Kim IY, Lim KW, Seo SJ, Choi YJ, Cho CS. Down-regulation of PPARgamma2-induced adipogenesis by PEGylated conjugated linoleic acid as the pro-drug: attenuation of lipid accumulation and reduction of apoptosis. Arch Biochem Biophys 2006;456:19–29. Morgan DP. Principles of CDK regulation. Nature 1995;374:131–134. Moussalli C, Downs RW, May JM. Potentiation by glucose of lipolytic responsiveness of human adipocytes. Diabetes 1986;35:759–763. Mukhtar H, Ahmad N. Tea polyphenols: prevention of cancer and optimizing health. Am J Clin Nutr 2000;71:1698–1702. Nagao T, Komine Y, Soga S, Meguro S, Hase T, Tanaka Y, Tokimitsu I. Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men. Am J Clin Nutr 2005;81:122–129. Nakagawa K, Ninomiya M, Okubo T, Aoi N. Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans. Agric Food Chem 1999;47:3947–3973. Pearson G, Robinson F, Gibson TB, Xu BE, Karandikar M, Berman K, Cobb MH. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrinol Rev 2001;22:153– 183.

P1: SFK/UKS P2: SFK c11 BLBS044-Cho October 15, 2009

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8:11

Printer Name: Yet to Come

Functional Components

Qanungo S, Das M, Haldar S, Basu A. Epigallocatechin-3-gallate induces mitochondrial membrane depolarization and caspase-dependent apoptosis in pancreatic cancer cells. Carcinogenesis 2005;26:958–967. Riemersma RA, Rice-Evans CA, Tyrrell RM, Clifford MN, Lean ME. Tea flavonoids and cardiovascular health. QJM 2001;94:277–282. Roberts EAH. Separation of tea polyphenols on paper chromatograms. J Sci Food Agric 1953;3:193–198. Rusznyak S, Szent-Gyorgyi A. Maturation of megaloblasts in bone marrow cultures. Nature 1936;138:27. Safe S. Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor–Sp1 interactions. Vitam Horm 2001;62:231–252. Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, Cantley LC. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA 2004;101:3329–3335. Song XM, Fiedler M, Galuska D, Ryder JW, Fernstrom M, Chibalin AV, Wallberg-Henriksson H, Zierath JR. 5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulinresistant diabetic (ob/ob) mice. Diabetologia 2002;45:56–65. Song EK, Hur H, Han MK. Atherosclerotic lesion development in hypercholesterolemic Japanese quail following probucol treatment: a biochemical and morphologic evaluation. Arch Pharmacol Res:Seoul 2003;26:559–563. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 2001;409:307–312. Tokunaga S, White IR, Frost C, Tanaka K, Kono S, Tokudome S, Akamatsu T, Moriyama T, Zakouji H. Green tea consumption and serum lipids and lipoproteins in a population of healthy workers in Japan. Ann Epidemiol 2002;12:157–165. Unger RH, Zhou YT. Lipotoxicity of beta-cells in obesity and in other causes of fatty acid spillover. Diabetes 2001;50:S118–S121. Wang X, Tian W. Green tea epigallocatechin gallate: a natural inhibitor of fatty-acid synthase. Biochem Biophys Res Commun 2001;288: 1200–1206.

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Wolfram S, Raederstorff D, Preller M, Wang Y, Teixeira SR, Riegger C, Weber P. Epigallocatechin gallate supplementation alleviates diabetes in rodents. J Nutr 2006a;136:2512–2518. Wolfram S, Wang Y, Thielecke F. Anti-obesity effects of green tea: from bedside to bench. Mol Nutr Food Res 2006b;50:176–187. Wu BT, Hung PF, Chen HC, Huang RN, Chang HH, Kao YH. The apoptotic effect of green tea (−)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the Cdk2 pathway. J Agric Food Chem 2005;53:5695–5701. Wu LY, Juan CC, Ho LT, Hsu YP, Hwang LS. Effect of green tea supplementation on insulin sensitivity in Sprague–Dawley rats. J Agric Food Chem 2004;52:643–648. Xie Z, Dong Y, Zhang M, Cui MZ, Cohen RA, Riek U, Neumann D, Schlattner U, Zou MH. Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells. J Biol Chem 2006;281:6366–6375. Yang CS, Wang ZY. Tea and cancer. J Natl Cancer Inst 1993;85:1038–1049. Yao K, Ye P, Zhang L, Tan J, Tang X, Zhang Y. Epigallocatechin gallate protects against oxidative stress-induced mitochondria-dependent apoptosis in human lens epithelial cells. Mol Vis 2008;14:217–223. Yeh CW, Chen WJ, Chiang CT, Lin-Shiau SY, Lin JK. Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects. Pharmacogenomics J 2003;3:267–276.

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Capsaicin Astrid J.P.G. Smeets, PhD, and Prof. Dr. Margriet Westerterp-Plantenga, PhD

Abstract Capsaicin is a major pungent principle present in a variety of capsicum fruits such as hot peppers. In rats, capsaicin increases catecholamine secretion from the adrenal medulla, mainly through activation of the sympathic nervous system. As a result of β-adrenergic stimulation, capsaicin may increase in thermogenesis. In addition, animal studies showed that the administration of capsaicin favors an increase in lipid oxidation and a decrease in body fat mass. In lean human subjects, the addition of capsaicin to a meal increased diet-induced thermogenesis, increased fat oxidation, reduced hunger, and prospective food consumption before a subsequent ad libitum meal, and reduced energy, protein, and fat intake during a subsequent ad libitum meal. Capsaicin treatment, during a 3-month weight maintenance after weight-loss period, attenuated the increase in RQ and the decrease in fat oxidation compared to placebo treatment. Furthermore, tended resting EE as a function of FFM to be increased in the capsaicin group, compared with placebo. Summarized, these observations suggest that capsaicin can realistically be considered as a functional agent that could help preventing a positive energy balance and obesity.

Introduction Research has been focusing on specific food components, which may have favorable effects on weight loss, weight maintenance, and metabolism. Certain spices and herbs are used to give flavor to foods and drinks without adding calories. Moreover, consumption of spiced 201

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foods or herbal drinks may lead to greater thermogenesis and in some cases to greater satiety. Therefore, it is suggested that these ingredients can realistically be considered as functional agents that could help preventing a positive energy balance and obesity. Capsaicin (8-methyl-Nvanillyl-6-nonenamide) is a major pungent principle present in a variety of capsicum fruits such as hot peppers, which are plants belonging to the genus Capsicum (Govindarajan and Sathyanarayana, 1991). Capsaicin is widely consumed as a food additive throughout the world, particularly in South East Asian and Latin American countries. The capsaicin content of hot red peppers ranges from 0.1% to 1.0% (Govindarajan and Sathyanarayana, 1991). Capsaicin is present in large quantities in the placental tissue (which holds the seeds), the internal membranes and, to a lesser extent, the other fleshy parts of the fruits of plants in the genus Capsicum. Contrary to popular belief, the seeds themselves do not contain any capsaicin, yet the highest concentration of capsaicin can be found in the white pith around the seeds. The amount of capsaicin is often indicated by the number of Scoville heat units (SHU). A more accurate method to measure the amount of capsaicin is high-performance liquid chromatography (HPLC). This identifies and measures the heat-producing chemicals expressed in ASTA pungency units. Numerous animal studies have shown that capsaicin can increase the activity of central nervous system with a consequent stimulation of β-adrenergic receptors. In addition, animal studies showed that the administration of capsaicin favors an increase in lipid oxidation and a decrease in body fat mass. Capsaicin is perceived as a hot substance (Rolls et al., 2003). Because the ingestion of hot substances can lead to an increase in body temperature, feedback mechanisms are activated to lower body temperature, such as blood vessel dilatation and sweating. The greater heat loss, due to blood vessel dilatation and sweating, after capsaicin ingestion may contribute to higher thermogenesis. Accordingly, these observations suggest that capsaicin can realistically be considered as a functional agent that could help preventing a positive energy balance and obesity.

Efficacy In a series of human studies, Yoshioka et al. showed an increase in diet-induced thermogenesis and a decrease in respiratory quotient (RQ) immediately after a meal to which red pepper (capsaicin) was added,

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implying a shift in substrate oxidation from carbohydrate to fat oxidation (Yoshioka et al., 1995, 1998, 1999, 2001). Consumption of a breakfast with capsaicin caused an immediate increase in diet-induced energy expenditure in Japanese males (Yoshioka et al., 1995). This increase was caused by β-adrenergic stimulation since β-adrenergic blockade abolished this increase in diet-induced energy expenditure (Yoshioka et al., 1995, 2001). In 13 Japanese female subjects, addition of red pepper to the experimental meals increased postprandial energy expenditure and lipid oxidation as well (Yoshioka et al., 1998). These subjects were submitted to the four following experimental conditions at breakfast time: (1) High-fat meal; (2) High-fat meal + red pepper; (3) High-carbohydrate meal; (4) High-carbohydrate meal + red pepper. The results showed that red pepper supplementation increased both postprandial diet-induced thermogenesis and lipid oxidation. Interestingly, this stimulating effect was more pronounced after the high-fat breakfast (Fig. 12.1). Belza et al. studied the thermogenic effect of a combination of capsaicin, green tea extract (catechins and caffeine), tyrosine, and calcium after a 7-day treatment (Belza and Jessen, 2005). Energy expenditure was increased by 160 kJ/day by the combination of combination of capsaicin, green tea extract (catechins and caffeine), tyrosine, and calcium as compared to placebo, whereas the enterocoated preparation of the combined bioactive components had no such effect. The lack of effect of the enterocoated preparation suggests that a local action of capsaicin in the gastric mucosa is a prerequisite for exerting the thermogenic effect. Additionally, the effects of capsaicin on feeding behaviors and subsequent food consumption have been studied. Red pepper ingested in a standardized meal test was found to reduce hunger level and prospective food consumption before a subsequent ad libitum meal. Moreover, the results showed that protein and fat intake was decreased during this subsequent ad libitum meal (Yoshioka et al., 1999). In a second study, Yoshioka et al. served an isocaloric appetizer, containing a sauce with or without red pepper, which was followed by an ad libitum meal and a snack several hours later (Yoshioka et al., 1999). Total energy intake was significantly lower after the ingestion of the standardized appetizer. In addition, the results of this study showed that there was a significant negative association between energy intake and the change in low-frequency/highfrequency heart interval ratio, which indicates that capsaicin can increase SNS activity. Furthermore, red pepper in combination with caffeine consumption significantly reduced the cumulative ad libitum energy intake and increases energy expenditure over 24 hours in eight Caucasian male

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Lipid oxidation (mg/min)

(a) 100

75

50

25

0

(b)

Diet composition effect Diet composition × time interaction RP effect RP × time interaction

Meal 30

0

60 90 120 150 Time after meal ingestion (min)

180

210

6 A

∆ Lipid oxidation (g)

5 B 4

BC C

3 2 1 0

HF HF-RP HC HC-RP

Figure 12.1. (a) Lipid oxidation measured for 210 minutes following ingestion of experimental meals: (···◦···), high fat; (···•···), high fat plus red pepper (RP); (-ρ-), high carbohydrate; (-π-), high carbohydrate plus RP. Values are mean for 13 subjects, with their standard errors represented by vertical bars. Three-way ANOVA revealed that postprandial lipid oxidation was significantly modified by time, diet composition, RP, diet composition × time interaction, and RP × time interaction. (b) Change in lipid oxidation following high-fat (HF) and highcarbohydrate (HC) meals with and without RP. Values are means for 13 subjects, with their standard errors represented by vertical bars. A, B, C mean values not sharing a common letter were significantly different, p < 0.05. (After Yoshioka et al., 1998).

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15

24 EI MJ/day

* #

*

10

* #

* 24-h EI Capsaicin juice 24-h EI placebo juice

5

24-h EI Capsaicin capsule 24-h EI placebo capsule

0 Men

Women

Figure 12.2. Average daily energy intake over 2 days (MJ/day) in men and women (n = 24; 35 ± 10 years; BMI: 25.0 ± 2.4 kg/m2 ), with capsaicin ingestion 30 minutes before each meal, in tomato juice versus plain tomato juice or in capsules versus placebo capsules, swallowed with tomato juice. * indicates p < 0.01 (capsaicin vs. placebo). # indicates p < 0.05 (capsaicin in juice vs. capsaicin in capsule). (After Westerterp-Plantenga et al., 2005).

subjects (Yoshioka et al., 2001). Westerterp-Plantenga et al. studied the relative oral and gastrointestinal contribution to the effects of capsaicin on food intake or macronutrient selection (Westerterp-Plantenga et al., 2005). Red pepper (0.25% capsaicin; 80,000 Scoville Thermal Units) or placebo was offered in either tomato juice or two capsules, swallowed with tomato juice 30 minutes before each meal. Both oral and gastrointestinal exposure to capsaicin increased satiety and reduced energy and fat intake; however, the stronger reduction with oral exposure indicates that also a sensory effect of capsaicin plays a role (Fig. 12.2). Concerning this sensory effect, Yoshioka et al. hypothesized that the observed effects of red pepper involve a feeling of spiciness (Yoshioka et al., 2004). The subjects ingested a placebo, a moderate or a maximal tolerable dose of red pepper in a soup or in a capsule at the beginning of a meal. Red pepper lowered subsequent energy intake in a dose-dependent manner. Moreover, the maximal tolerable dose of red pepper in the soup suppressed fat intake compared with the placebo. The capsules with the maximal tolerable dose tended to decrease fat intake compared with the placebo condition; this effect was very similar to the soup with the maximal tolerable dose. Consequently, the authors suggested that the effects of red pepper on energy and macronutrient intake do not occur in the mouth.

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Further studies related to red pepper and food intake in overweight, obese, and postobese individuals will be required.

Mechanism of Actions The stimulatory effect of pungent principles such as capsaicin is likely due to the involvement of a transient receptor potential vanilloid receptor 1 (TRPV1)-linked thermogenic mechanism (Eldershaw et al., 1994). This vanilloid receptor is expressed in sensory neurons, the brain, and various nonneuronal tissues, and is also involved in the pain pathway (Caterina et al., 2000; Szallasi, 2005). Heat, protons, and vanilloids can activate the TRPV1 receptor (Szallasi, 2005). Capsaicin has been reported to increase thermogenesis by enhancing catecholamine secretion from the adrenal medulla in rats, mainly through activation of the sympathic nervous system (SNS) (Kawada et al., 1986, 1988; Watanabe et al., 1987, 1988). The increase in thermogenesis induced by capsaicin is due to β-adrenergic stimulation (Yoshioka et al., 1995). Both animal and human studies showed that the increase in thermogenesis is abolished after administration of β-adrenergic blockers such as propranolol (Kawada et al., 1986; Watanabe et al., 1988). Because of its stimulating effects on the SNS, capsaicin may influence both energy expenditure and energy intake with respect to the regulation of energy balance. Possible SNS involvement in thermogenesis is suggested by the observation that, during the infusion of nor-epinephrine or epinephrine, thermogenesis increased significantly (Kurpad et al., 1994; Simonsen et al., 1992). Furthermore, SNS activity is reciprocally related to food intake (Bray, 1993). SNS activity is diminished in obese (prone) subjects, and during negative energy balance. Capsaicin may counteract this by stimulating SNS activity.

Safety The acute toxicity of capsaicin has been determined in several animal species (Glinsukon et al., 1980). The relatively low toxicity induced by oral dosage of capsaicin appears to be associated with gastrointestinal enzyme activity. The likely mechanism of lethal effects of capsaicin has not been elucidated, but is considered to involve respiratory paralysis. A 4-week feeding study by Jang et al. revealed that diets containing 0.5–10%

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of ground capsicum fruit is relatively nontoxic at the doses tested (Jang et al., 1992). Ingestion of capsaicin in large subchronic doses has been reported to cause histopathological and biochemical changes including acute erosion of gastric mucosa and hepatic necrosis (Agrawal and Bhide, 1988; Lee, 1963; Monsereenusorn et al., 1982; Schneider et al., 1956). The long history of use as a food additive/component without any indication of deleterious health effects suggests that the potential risks to humans from both dietary and occupational exposure are negligible.

Food/Supplement Applications Capsaicin is the spicy component of hot, sweet, and bell peppers, which are plants belonging to the genus Capsicum. Commercially available capsules (range 9,000–40,000 Scoville Heat Units), often sold as “Cayenne pepper,” contain capsaicin extracts from natural sources.

Patents In addition to numerous patents on capsaicin application in the field of pain relief, several patents on the application of capsaicin in the field of obesity have been filed. Most of these patents describe the composition of a mix of compounds, including capsaicin, which is claimed to suppress appetite or stimulate metabolism.

Research Findings Weight Control Lejeune et al. tested capsaicin for its potential to facilitate weight maintenance in a postobese state. Obese individuals were subjected to either a placebo or a capsaicin (135 mg/day) treatment for 3 months after having experienced a moderate weight loss by energy restriction (Lejeune et al., 2003). During weight regain, the increase in RQ was smaller in the capsaicin group, so the decrease in fat oxidation was smaller compared with placebo. The net fat oxidation (g/h) after weight maintenance was also higher in the capsaicin group compared with placebo. Furthermore tended resting EE as a function of FFM to be increased in the capsaicin group, compared with placebo. In a recent study, Belza et al. studied the effects of a combination of tyrosine, capsaicin, catechines, and caffeine on thermogenesis and body fat loss in overweight and obese subjects (Belza et al.,

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2007). Subjects that had lost >4% of their initial weights after a 4-week hypocaloric diet were randomized to receive either placebo or bioactive supplement in a double-blind, 8-week intervention. The bioactive supplement increased thermogenesis more than placebo, and the effect was maintained after 8 weeks and accompanied by a slight reduction in body fat mass. These results suggest that capsaicin in combination with other bioactive components may support weight maintenance after a hypocaloric diet.

Food Applications Weight Control The extreme pungency of capsaicin and the possible burning feeling in the stomach may limit its intake on the long term. Therefore, capsaicin analogues with no pungency, such as CH-19 Sweet, a nonpungent cultivar of red pepper, may be an alternative. Ohnuki et al. observed that CH-19 Sweet enhanced adrenalin secretion, increased oxygen consumption, and suppressed fat accumulation in rats similarly to capsaicin (Ohnuki et al., 2001a). In humans, CH-19 Sweet increased oxygen consumption, suggesting increased thermogenesis (Inoue et al., 2007; Ohnuki et al., 2001b).

Suppliers Commercially available capsules containing capsaicin can be purchased online: www.nutraceutical.com www.nutrasanus.com www.naturesway.com

References Agrawal RC, Bhide SV. Histopathological studies on toxicity of chilli (capsaicin) in Syrian golden hamsters. Indian J Exp Bio1 1988;26:377–382. Belza A, Frandsen E, Kondrup J. Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects. Int J Obes (Lond) 2007;31(1):121–130.

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Belza A, Jessen AB. Bioactive food stimulants of sympathetic activity: effect on 24-h energy expenditure and fat oxidation. Eur J Clin Nutr 2005;59(6):733–741. Bray GA. Food intake, sympathetic activity, and adrenal steroids. Brain Res Bull 1993;32:537–541. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, PetersenZeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000;288:306–313. Eldershaw TP, Colquhoun EQ, Bennett KL, Dora KA, Clark MG. Resiniferatoxin and piperine: capsaicin-like stimulators of oxygen uptake in the perfused rat hindlimb. Life Sci 1994;55:389–397. Glinsukon T, Stitmunnaithum V, Toskulkao C, Buranawuti T, Tangkrisanavinont V. Acute toxicity of capsaicin in several animal species. Toxicon 1980;18(2):215–220. Govindarajan VS, Sathyanarayana MN. Capsicum–production, technology, chemistry, and quality. Part V. Impact on physiology, pharmacology, nutrition, and metabolism; structure, pungency, pain, and desensitization sequences. CRC Crit Rev Food Sci Technol 1991;29:435–474. Inoue N, Matsunaga Y, Satoh H, Takahashi M. Enhanced energy expenditure and fat oxidation in humans with high BMI scores by the ingestion of novel and non-pungent capsaicin analogues (capsinoids). Biosci Biotechnol Biochem 2007;71(2):380–389. Jang JJ, Devor DE, Logsdon DL, Ward JM. Food Chem Toxicol 1992;3:783–787. Kawada T, Sakabe S, Watanabe T, Yamamoto M, Iwai K. Some pungent principles of spices cause the adrenal medulla to secrete catecholamine in anesthetized rats. Proc Soc Exp Biol Med 1988;188:229–233. Kawada T, Watanabe T, Takaishi T, Tanaka T, Iwai K. Capsaicin-induced beta-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization. Proc Soc Exp Biol Med 1986;183:250–256. Kurpad AV, Khan K, Calder AG, Elia M. Muscle and whole body metabolism after norepinephrine. Am J Physiol 1994;266:E877–E884. Lee SO. Korean J Intern Med 1963;6:383–395.

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Lejeune MPGM, Kovacs EMR, Westerterp-Plantenga MS. Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects. Br J Nutr 2003;90:1–10. Monsereenusorn Y, Kongsamut S, Pezalla PD. Capsaicin—a literature survey. CRC Crit Rev Toxicol 1982;10:321–339. Ohnuki K, Haramizu S, Oki K, Watanabe T, Yazawa S, Fushiki T. Administration of capsiate, a non-pungent capsaicin analog, promotes energy metabolism and suppresses body fat accumulation in mice. Biosci Biotechnol Biochem 2001a;65(12):2735–2740. Ohnuki K, Niwa S, Maeda S, Inoue N, Yazawa S, Fushiki T. CH-19 sweet, a non-pungent cultivar of red pepper, increased body temperature and oxygen consumption in humans. Biosci Biotechnol Biochem 2001b;65(9):2033–2036. Rolls ET, Verhagen JV, Kadohisa M. Representations of the texture of food in the primate orbitofrontal cortex: neurons responding to viscosity, grittiness, and capsaicin. J Neurophysiol 2003;90:3711–3724. Schneider MA, Deluca V, Gray SJ. Am J Gastroenterol 1956;26:722–726. Simonsen L, Bulow J, Madsen J, Christensen NJ. Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue. Am J Physiol 1992;263:E850–E855. Szallasi A. Piperine: researchers discover new flavor in an ancient spice. Trends Pharmacol Sci 2005;26:437–479. Watanabe T, Kawada T, Kurosawa M, Sato A, Iwai K. Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats. Am J Physiol 1988;255:E23–E27. Watanabe T, Kawada T, Yamamoto M, Iwai K. Capsaicin, a pungent principle of hot red pepper, evokes catecholamine secretion from the adrenal medulla of anesthetized rats. Biochem Biophys Res Commun 1987;142:259–264. Westerterp-Plantenga MS, Smeets A, Lejeune MP. Sensory and gastrointestinal satiety effects of capsaicin on food intake. Int J Obes 2005;29:682–688. Yoshioka M, Doucet E, Drapeau V, Dionne I, Tremblay A. Combined effects of red pepper and caffeine consumption on 24 h energy balance in subjects given free access to foods. Br J Nutr 2001;85:203–211.

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Yoshioka M, Imanaga M, Ueyama H, Yamane M, Kubo Y, Boivin A, St-Amand J, Tanaka H, Kiyonaga A. Maximum tolerable dose of red pepper decreases fat intake independently of spicy sensation in the mouth. Br J Nutr 2004;91(6):991–995. Yoshioka M, Lim K, Kikuzato S, Kiyonaga A, Tanaka H, Shindo M, Suzuki M. Effects of red-pepper diet on the energy metabolism in men. J Nutr Sci Vitaminol 1995;41:647–656. Yoshioka M, St-Pierre S, Drapeau V, Dionne I, Doucet E, Suzuki M, Tremblay A. Effects of red pepper on appetite and energy intake. Br J Nutr 1999;82:115–123. Yoshioka M, St-Pierre S, Suzuki M, Tremblay A. Effects of red pepper added to high-fat and high-carbohydrate meals on energy metabolism and substrate utilization in Japanse women. Br J Nutr 1998;80:503–510.

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CHAPTER 13 R NUTRIOSE
(Resistant Dextrin) in Satiety Control Susan S. Cho, PhD, and Iris L. Case, BS

Abstract r NUTRIOSE
or resistant dextrin (RD) is a water-soluble polymer that is largely resistant to digestion and absorption in the small intestine, and fermented in the colon, thus meeting the classification for dietary fiber. RDs can r FB) or maize starch (RDbe made from either wheat starch (RD; NUTRIOSE
r r

corn; NUTRIOSE FM). NUTRIOSE is considered as GRAS (generally recognized as safe) ingredients. RDs are well tolerated at a dose of 45 g/day. It has been estimated that the small intestine digestibility of RD is 15% and that more than 75% of RD is fermented in the human gastrointestinal tract. The net energy value of RD was determined to be 2.1 kcal/g, which is in agreement with the caloric value estimated for other soluble dietary fibers. A recent study in r enhanced overweight Chinese volunteers indicated that 34 g of NUTRIOSE
higher satiety as compared to a maltodextrin placebo, the result of which lowered r group over a period of the caloric intake and body weight of the NUTRIOSE
3 months. This soluble fiber is slowly digested in the small intestine that induces low glycemic and insulinemic responses. RD can be used in foods and beverages to provide desirable sensory properties as well as various health benefits such as prebiotic effects, satiety management, intestinal regularity, and glycemic control.

Introduction r NUTRIOSE
is a water-soluble polymer derived from enzymatically hydrolyzed starch heated at high temperature and adjusted to a low

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moisture level in the presence of an acid catalyst (Lefranc-Millot, 2008). The dextrin obtained is purified with activated carbon and demineralized by exchange resins. Afterward, the product is chromatographed, and the r high molecular weight fraction is retained and spray dried. NUTRIOSE
is resistant to digestion and absorption in the small intestine; thus, it is classified as RD. In addition to the typical starch α-1,4 and α-1,6 glucosidic linkages, the presence of α-1,2 and α-1,3 glycosidic linkages makes RDs resistant to the hydrolysis by human alimentary enzymes. Thus, the r or RD can be made from RDs are classified as dietary fiber. NUTRIOSE
r r
FM). either wheat starch (NUTRIOSE FB) or corn starch (NUTRIOSE
r
NUTRIOSE FB is a mixture of glucose polymers with degrees of polymerization in a range of 12–25 (mean 18). The number-average molecular weight is approximately 2,480 (range 2,000–4,000 Da) and the weightaverage molecular weight is about 5,344 (range 4,000–6,000 Da). RD can be used in various processed foods and beverages to provide desirable sensory properties as well as various health benefits including limited glycemic response and intestinal regularity. This soluble fiber has a very low hygroscopicity, as it maintains its free flowing, powder nature at an 80% relative humidity (24 hours, 20◦ C) before clumping occurs. RD is stable in high-temperature processing conditions, including sterilization and ultrahigh temperature treatment. RD is stable in highly acidic conditions as well as large-scale shear processes such as extrusion. RD does not significantly add viscosity to formulations and it is not readily fermented by bacterial strains typically found in milk products; thus, it can be used in dairy products designed for fiber supplementation and prebiotic effects.

Safety r NUTRIOSE
and dextrins are considered as “GRAS” (Wils et al., 2008). The safety of RS was reviewed by the U.S. FDA in 1990 to be classified as dextrins (21 CFR Section 184.1444). The joint FAO/WHO Expert Committee on Food Additives (JECFA) has also recognized the safety of dextrins and has allocated an “acceptable daily intake (ADI) not specified” for white and yellow dextrins (JECFA, 1974). Data from an acute toxicity study, a 90-day feeding study, mutagenicr FB is ity tests, and human clinical trials indicate that NUTRIOSE
safe and well tolerated for human use (Pasman et al., 2006; Vermorel et al., 2004; Wils et al., 2008). It was also found that RD did not affect the

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absorption and binding properties of various minerals, such as magnesium and calcium (Vermorel et al., 2004). An acute oral toxicity study with a fixed dose of 2,000 mg/kg indicated that the lethal dose (LD50 ) of RD was greater than 2,000 mg/kg (Wils et al., 2008). The 90 days feeding study revealed no treatment-related adverse effects when RD was given to rats at a level of 5% in the diet for 13 weeks (Wils et al., 2008). No mortality and no behavior modification of significance occurred during the study. No diarrhea or soft feces as well as no ophthalmological abnormalities were observed during the study. The no-observable adverse effect levels (NOAELs) were established by the highest tested doses: 4.4 g/kg body weight (BW) day in males and 6.5 g/kg BW/day in females. This low toxicity is consistent with the similar low toxicity reported for RD originated from corn starch (Okuma and Wakabayashi, 2001). An Ames test revealed that RD induced no mutagenic activity in the five Salmonella typhimurium strains tested (Wils et al., 2008). In vitro mammalian cell mutation assays at the TK locus in L5178y mouse lymphoma cells showed that there was no mutagenic potential of RD. There was no significant increase in the mean number of induced mutants at any dose tested as shown in the assays with and without metabolic activation. In addition, RD produced no significant variation in the number of large or small colony mutants relative to the solvent control with and without metabolic activation. The results of safety studies on other RDs are also relevant to those of RD. In a rat feeding experiment, the LD50 of corn-based RD was found to be over 40 g/kg BW, the maximum dosage in the acute toxicity study (Wakabayashi et al., 1992). In rats fed 10% RD (derived from corn) in water for 5 weeks, no harmful effects were observed on internal organs such as the pancreas, kidney, and liver. Furthermore, there is no evidence of mutagenicity caused by the consumption of corn-based RD (Wakabayashi et al., 1992). Corn-based RD was found to have no adverse effects on mineral metabolism as measured by mineral binding properties in an in vitro experiment (Nomura et al., 1992). The demonstrated safety data on r FB and other types of RDs are mutually supportive. NUTRIOSE


Safety Studies in Humans Various researchers reported that RD was well tolerated up to 45 g a day in both short term (van den Heuvel et al., 2005) and longer term (Pasman et al., 2006), with no negative effects found for gastrointestinal

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parameters. At the end of the study, there was no significant difference in gastrointestinal complaints for the different treatments. This indicates that after 4–5 weeks consumption, habituation to the dose of RD had likely occurred (Pasman et al., 2006). High daily dosages of 60 and 80 g caused mild bloating and increased flatulence in some subjects, but no diarrhea was reported (van den Heuvel et al., 2005, 2005). Compared with a placebo, flatulence occurred more frequently over the 7-day period when 30, 60, or 80 g/day of RD was tested (p < 0.05). On days 6–7, 60 and 80 g/day of RD produced a high frequency of flatulence and bloating (p < 0.05), and 60 g RD decreased the frequency of defecation (p < 0.05). None of the doses of RD resulted in diarrhea.

Digestibility Pasman et al. (2006) reported a small intestine digestibility of 15%, with the range of 8.7–19%, for this RD. More than 87% of RD is considered to be digested or fermented in the human gastrointestinal tract (van den Heuvel et al., 2005). van den Heuvel et al. (2005) reported that the fecal residue of RD nonlinearly increased with the dose. In this study, it was calculated that about 2% of 10 g/day RD and 13% of 80 g/day RD were recovered in the feces, assuming a constant excretion of RD in feces per 24 hours (van den Heuvel et al., 2005). Vermorel et al. (2004) estimated that the apparent digestibility of the RD was 90.8% and that approximately 76% of the RD was fermented. A daily dose of over 30 g of RD increased the concentration of αglucosidase. The α-glucosidase activity, whose activity has been shown to improve the fermentation of RD leading to short-chain fatty acids (SCFAs) and lactic acids that are a source of energy for tissues. A daily dose of over 10 g RD/day increased β-glucosidase activity in a dose-dependent manner. An increase in β-glucosidase may be beneficial for health by releasing flavonoids, which are known to promote antioxidative, anticarcinogenic, and immune stimulatory effects (Wollowski et al., 2000). Rat and in vitro experiments indicate that only 85% of RD reaches the colon (Vermorel et al., 2004), where it is fermented by the bacterial flora. RD recovered in feces as polymerized glucose represented the nondigested and nonfermented part of RD. Supplementation of RD increased wet and dry stool outputs by 45% and 70%, respectively (Vermorel et al., 2004), probably due to increased dry matter (DM) output (38%) and increased water output (62%). However, van den Heuvel et al. (2005) reported that

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supplementation with 10–15 g of RD decreased wet and dry weight of feces without changing the percentage DM. Thicker feces were observed during the past 24 hours on 15 g/day of RD as the amount of fecal water probably decreased. A decreased level of fecal water may be due to high SCFAs absorption that often accompanies high water and salt absorption. The fecal pH in RD-treated groups was decreased from 6.6 (day 1) to 6.1 (day 35), indicating increased fermentation while the placebo group maintained a pH range of 6.5–6.6 during the test period (Vermorel et al., 2004). The pH remained stable from day 21 onward for all groups. The total sum of the SCFAs (acetate, propionate, butyrate, and isoforms of SCFAs) did not show changes in concentration due to time or study substance.

Fermentation The colonic effects and the production of SCFAs, as contributors to the daily energy supply, are key factors in providing a long-lasting energy supply of RD. van den Heuvel et al. (2005) studied the fermentation of RD by a breath hydrogen excretion test. This test was carried out on the last day of 10 or 15 g/day of RD or placebo treatment. As compared with the baseline, breath hydrogen excretion levels before breakfast significantly increased. However, there was no overall difference between the areas under the curve (AUC) among treatments, except from the points 270 and 300 minutes after ingestion. The absence of an overall significant difference in AUC attributable to RD may be due to a relatively small dose of RD (2.5 or 3.0 g) in each meal and/or the large variations in measurement data.

Caloric Value Direct determination of net energy value (NEV) of fibers is difficult, mainly because they are consumed in small quantities, and thus induce small differences in energy expenditure. Digestible energy value (DEV), metabolizable energy value (MEV), and NEV are generally estimated from measurements of fiber fermentability, breath tests, and hypotheses on gas, microbial mass and volatile fatty acids (VFAs) production, and efficiency of VFA energy utilization. In the study of Vermorel et al. (2004), the NEV of the tested RD was estimated using three prediction equations as outlined in Livesey (1992, 2001). First, the MEV of the tested RD was estimated from its

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metabolizable energy content, assuming that hydrogen and methane energy losses accounted for 5% of the fermented carbohydrate (CHO) energy, and fermentation heat also accounted for 5%. VFA energy was estimated as “Estimated ME Glucose energy (GE)” (derived from enzymatic digestion). The efficiencies of GE and VFA energy utilization are estimated at 1 and 0.85, respectively, to produce Equation (1). NEV = (Gross energy × Enzymatic digestibility (ED)) +(VFA energy × 0.85)

(13.1)

Secondly, the carbohydrate substitutes method was used: The enzymatically digested fraction is assumed to produce glucose used with an energetic efficiency of 1. Fermentable carbohydrates are assumed to supply 8 kJ NE/g to result in Equation (2). NEV = (Gross energy × Enzymatic digestibility) +(Fermentable CHO × 8)

(13.2)

Third is the minimal methodology for net ME. The apparent digestibility of fermentable carbohydrates is used to estimate VFA production, assuming that 65% of actually “fermented energy” is recovered as VFA. The efficiency of ME utilization from fermentable carbohydrates is assumed to be 0.76 to yield Equation (3). NEV = (GE × ED) + (Fermentable CHO ×Unavailable CHO digestibility × 0.65 × 0.76) (13.3) From these three methods, NEVs of RD were estimated to be 8.7, 8.9, and 11.4 kJ/g DM in healthy young men (Vermorel et al., 2004). In this study, ten healthy young men were fed for 31-day period a maintenance r diet supplemented with either placebo (dextrose) or the NUTRIOSE
(100 g DM/day) in a crossover design. After a 20-day adaptation period, food intake was determined for 11 days using the duplicate meal method, and feces and urine were collected for 10 days for further analyses. The r was 14.1 (SD 2.3) kJ/g DM, 14% less ME value of the NUTRIOSE
than the tabulated values of sucrose and starch. NEV of RD (mean of 2.0 kcal/g) estimated by Vermorel et al. (2004) is in agreement with the caloric value estimated for soluble dietary fibers (Livesey, 1992). These studies indicate that soluble dietary fibers may have a positive impact on the total daily energy expenditures through the colonic fermentations and the viscosity of the gut contents. Moreover, RD, used as a bulking agent to easily replace fat or carbohydrates, allows obtaining food with lower overall caloric value.

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Satiety During and immediately after eating, afferent information provides the major control over appetite (Blundell, 1999). Physiological events are indeed triggered in responses to the ingestion of food and form the inhibitory processes which stop eating and then prevent the reoccurrence of eating until another meal is triggered. These physiological events are termed “satiety signals”. Satiation is the process that leads to the termination of food intake. Termination of the period of satiety leads to the resurgence of the feeling of hunger and a consequent resumption of the food-intake cycle (Blundell, 1999). It appears that RD has a more powerful satiating effect in subjects as compared to a maltodextrin placebo. During a recent study, with no energy restriction (ad libitum diet) but in which energy intakes were recorded, overweight Chinese volunteers r or 17 g malreceived beverages containing either 17 g NUTRIOSE
todextrin (placebo), twice daily, for 12 weeks. It was observed that 34 g of RD enhanced higher satiety than did maltodextrin (Roquette Group, 2008). In this study, significant decreases in body weight (p < 0.0001), body mass index (p < 0.0001), body fat (p < 0.0001), and hunger (p < 0.001) associated with a decrease in caloric intake (p < 0.001) were measured throughout the study in the RD group. Abdominal scans indicated a significant reduction of waist circumference in the RD group while no changes were observed in the placebo group (p < 0.001). The authors concluded that RD supplementation significantly decreased the feeling of hunger and expression of some biological markers of metabolic syndrome, including body weight than did maltodextrin. van den Heuvel et al. (2005) also investigated the effects of RD supplementation to usual diets, meals contained similar amounts of energy to their habitual breakfast or dinner, on satiety and energy intakes. In this study, subjects (average BMI = 22.3 kg/m2 ) ate standard breakfast, lunch, and afternoon snacks that were not designed for energy restriction. Hunger and satiety were measured just before breakfast (time point 0) and at 30, 60, 90, 120, 150, 180, 240 (just before lunch), 270, and 480 minutes. Feelings of hunger and satiety were rated by a 10 cm visual analogue scale (VAS), such as appetite for a meal, appetite for something sweet, appetite for something savory, satiety (fullness), and feeble/weak with hunger) on day 7 of treatment. Only the AUC of the rating on “feeble or weak with hunger” was lower on day 7 of the treatment with 15 g/day of RD compared to 15 g/day of the placebo (p = 0.04). No other significant differences in satiety scores were found. Also, an increasing dose of RD did not affect food habits as compared with the placebo. The findings from

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these studies suggest that RD may have a satiating effect in subjects with energy-unrestricted diets.

Body Fat Control in Animals It has been proposed that RD reduced the body fat content in animals by moderating postprandial glucose levels and by lowering insulin secretion (Okuma and Wakabayashi, 2001). Wakabayashi et al. (1991) reported that RD (5%) supplementation to a high-sucrose diet for 8 weeks did not induce an increase in body fat, whereas a high-sucrose diet alone increased the body fat in rats. A 110-day-old broiler chicken study reported a similar trend (Wakanabe et al., 1993). Supplementation of 5% RD-corn to a diet reduced the total body fat content, the fat content in the liver (from 27% to 17%) and other internal organs in broiler chickens.

Glycemic Response and Satiety The rate of absorption of the RD at the different stages of the gastrointestinal tract plays a major role in determining its metabolic effect. This soluble fiber is slowly digested in the small intestine (15% of the ingested dose evaluated in vitro; Vermorel et al., 2004), which induces a low glycemic response (GR = 25) and a low insulinemic response (IR = 13) (Donazzolo et al., 2003). As compared to glucose, the low insulinemic response of the RD contributes to a greater feeling of satiety. Incorporation of this RD into foods such as pasta, biscuits, and syrups significantly reduced the glycemic response of a meal (Lefranc-Millot, 2008; Lefranc-Millot et al., 2006). Peak glycemia was 7.6 mmol/L for glucose and 5.3 mmol for the pasta containing RD. Mean AUC for RD pasta was significantly lower than that of glucose (42.0 vs. 123.6, p < 0.01). Syrups made with RD elicit a glucose response of only 10% of the equivalent product made with sugar when used in a fruit drink (Lefranc-Millot et al., 2006). Mean AUC for RD biscuits was significantly lower than that of glucose (66.6 vs. 137.0, p < 0.01). Several researchers have reported that low glycemic index (GI) foods enhance higher satiety responses than high glycemic foods. GI corresponds to the incremental area under the blood response curve measured over 2-hour time of a 50-g CHO portion of a test food expressed as percentage of the response to the same amount of CHO from a reference food (usually glucose) consumed by the same subject (FAO/WHO, 1988). Because lowGI foods are characterized by a slower rate of digestion and absorption,

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prolonged feedback (likely through satiety signals) to the hunger/satiety center in the brain is probably due to continuous stimulation of nutrient receptors in the gastrointestinal tract. In a study with 26 males (mean BMI = 23.4 ± 2.2 kg/m2 ), Pasman et al. (2003) reported that consumption of a simple CHO breakfast resulted in higher glucose and insulin levels at 30 minutes after breakfast consumption. Satiety scores were higher after complex CHO breakfast consumption for the first 90 minutes after intake. Warren et al. (2003) reported that low-GI foods eaten at breakfast have a significant impact on food intake at lunch. This study investigated the effect of three test breakfasts—low-GI, low-GI with 10% added sucrose, and high-GI—on ad libitum lunch intake, appetite, and satiety. Lunch intake was lower after low-GI and low-GI with added sucrose breakfasts compared with lunch intake after high-GI and habitual breakfasts (which were high-GI): highGI versus low-GI = 145 ± 54 kcal; high-GI versus low-GI plus sucrose = 119 ± 53 kcal; low-GI plus sucrose versus low-GI = 27 ± 54 kcal. Lunch intake after the low-GI breakfast and the low-GI breakfast with added sucrose was also significantly lower than that after the habitual breakfast: low-GI versus habitual = −109 ± 75 kcal; low-GI plus sucrose versus habitual = −83 ± 75 kcal; high-GI versus habitual = 36 ± 75 kcal. At lunchtime, hunger ratings were greater after the high-GI breakfast compared with the other two test breakfasts on two of the three experimental days. Prelunch satiety scales were inversely related to subsequent food intake. Based on time to request additional food, a prolongation of satiety was observed after the low-GI meal replacement as compared to high-GI meal replacement (Ball et al., 2003). There are reports that both high-GI and low-GI carbohydrates were shown to suppress appetite and food intake but the time courses were different (Anderson et al., 2002; Rogers and Blundell, 1989; Woodend and Anderson, 2001). High-GI carbohydrates induced an early short-term satiating effect. There was an inverse association between the blood glucose response and the subjective appetite and food intake in the 1 hour after consumption of isovolumetric preloads of carbohydrates (Anderson et al., 2002). One hour after their consumption, high-GI carbohydrates (glucose, polycose, and sucrose) more effectively suppressed food intake than did low-GI carbohydrates (amylose, amylopectin, and a fructose–glucose mixture). The early satiating effect of high-GI carbohydrates was also confirmed by other investigators (Rogers and Blundell, 1989; Woodend and Anderson, 2001). However, low-GI foods showed higher satiety than did high-GI foods at 2–6 hours after the ingestion (Anderson et al., 2002).

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Summary r NUTRIOSE
is a soluble fiber, derived from corn or wheat, that is r can function as a bulking agent and is well classified as RD. Nutriose
tolerated in humans, with a dose of 45g/day showing no side effects. Studies show that RD reduces glycemic and insulinemic responses, which is associated with satiety control. Recent studies indicate that dietary supplementation of RD may aid in satiety control. Several clinical studies have demonstrated the prebiotic nature of RD. RDs can be used in food formulations targeting satiety management. In addition, RD can be used in functional foods designed for limiting glycemic and insulinemic responses, fortifying diets in fiber, prebiotic effects, or intestinal regularity.

References Anderson GH, Catherine NL, Woodend DM. Inverse association between the effect of carbohydrates on blood glucose and subsequent short-term food intake in young men. Am J Clin Nutr 2002;76:1023–1030. Ball SD, Keller KR, Moyer-Mileur LJ. Prolongation of satiety after low versus moderately high glycemic index meals in obese adolescents. Pediatrics 2003;111(3):488–494. Blundell JE. The control of appetite: basic concepts and practical implications. Schweiz Med Wochenschr 1999;129:182–188. Donazzolo Y, Pelletier X, Cristiani I, Wils D. Glycemic and insulinemic r FB in healthy subjects. Proceedings of the indexes of NUTRIOSE
Dietary Fibre Conference. Noordwijkerhout, The Netherlands, 2003, p. 53. FAO/WHO. Carbohydrates in human nutrition. Report of a Joint FAO/WHO Expert Consultation (Rome, 14–18 April 1997). FAO Food and Nutrition Paper 66. 1988. JECFA Joint Expert Committee of Food Additives (JECFA) Dextrins (WHO Food Additive Series 17). 1974. r 06: a useful soluble dietary fibre for added Lefranc-Millot C. NUTRIOSE
nutritional value. Nutr Bull 2008;33:234–239.

Lefranc-Millot C, Wils D, Henry J, Lightowler H, Saniez-Degrave M-H. r
r , a sugar alcohol, NUTRIOSE a resistant dextrin, and MALTISORB


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two key ingredients for healthy diets and obesity management. Obes Rev 2006;7(Suppl. 2):269. Livesey G. Energy values of dietary fibre and sugar alcohols for man. Nutr Res Rev 1992;5:61–84. Livesey G. A perspective on food energy standards for nutrition labelling. Brit J Nutr 2001;85:271–287. Nomura M, Ohashi M, Nishigawa T, Kubota M, Ohkuma K, Nakajima Y, Abe H. Effect of dietary fibers on the diffusion of glucose and metal ions through cellulose membrane. J Jpn Soc Clin Nutr 1992;13:141–147 (in Japanese). Okuma K, Wakabayashi S. Fibersol-2: a soluble, non-digestible, starch derived dietary fiber. In: McCleary BV, Prosky L (eds.). Advanced Dietary Fiber Technology. Blackwell Science, Malden, MA, 2001, pp. 509–523. Pasman WJ, Blokdijk VM, Bertina FM, Hopman WP, Hendriks HF. Effect of two breakfasts, different in carbohydrate composition, on hunger and satiety and mood in healthy men. Int J Obes Relat Metab Disord 2003;27(6):663–668. Pasman WJ, Wils D, Saniez MH, Kardinaal A. Long-term gastror FB in healthy men. Eur J Clin intestinal tolerance of NUTRIOSE
Nutr 2006;60(8):1024–1034. Rogers P, Blundell JE. Separating the actions of sweetness and calories: effects of saccharin and carbohydrates on hunger and food intake in human subjects. Physiol Behav 1989;6(45):1093–1099. Roquette Group. Effects of Dietary Supplementation with the Soluble r
Fiber NUTRIOSE on weight management in healthy young adult men. Nutritional Study Abstract No. 3, 2008. van den Heuvel EG, Wils D, Pasman WJ, Bakker M, Saniez MH, Kardinaal AF. Short-term digestive tolerance of different doses of r FB, a food dextrin, in adult men. Eur J Clin Nutr NUTRIOSE
2005;58(7):1046–1055. Vermorel M, Coudray C, Wils D, Sinaud S, Tressol JC, Montaurier C, Vernet J, Brandolini M, Bouteloup-Demange C, Rayssiguier Y. Energy r
value of a low-digestible carbohydrate, NUTRIOSE FB, and its impact on magnesium, calcium and zinc apparent absorption and retention in healthy young men. Eur J Nutr 2004;43:344–352.

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Wakabayashi S, Satouchi M, Nogami Y, Ohkuma K, Matsuoka A. Effect of indigestible dextrin on cholesterol metabolism in rat. J Jpn Soc Nutr Food Sci 1991;44:471–478 (in Japanese). Wakabayashi S, Satouchi M, Ueda Y, Ohkuma K. Acute toxicity and mutagenicity studies of indigestible dextrin, and its effect on bowel movement of the rat. J Food Hyg Soc Japan 1992;33:557–562 (in Japanese). Wakanabe O, Fujinaka K, Uchiyama K, Katta Y, Okuma K. Effects of galacto-oligosaccharides and indigestible dextrin on fat accumulation in broiler. Jpn J Poult Sci 1993;30:35 (in Japanese). Warren JM, Henry CJ, Simonite V. Low glycemic index breakfasts and reduced food intake in preadolescent children. Pediatrics 2003;112(5):e414. Wils D, Scheuplein RJ, Deremaux L, Looten P. Safety profile of a food dextrin: acute oral, 90-day rat feeding and mutagenicity studies. Food Chem Toxicol 2008;46:3254–3261. Wollowski I, Rechkemmer G, Pool-Zobel BL. Protective role of probiotics and prebiotics in colon cancer. Am J Clin Nutr 2000;73:451S–455S. Woodend DM, Anderson GH. Effect of sucrose and safflower oil preloads on short term appetite and food intake of young men. Appetite 2001;37(3):185–195.

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CHAPTER 14

Fiber and Satiety Susan S. Cho, PhD, Iris L. Case, BS, and Stephanie Nishi, BS

Abstract Dietary fiber has received much support from leading scientific authorities for the role it plays in satiety control. The USDA Dietary Guidelines for Americans state that high fiber content of foods, in particular whole grains, helps “you feel full with less calories.” The National Academy of Sciences Food and Nutrition Board also recognizes the satiety benefits of dietary fiber stating that high-fiber diets delay stomach emptying, which increases the amount of time for energy and nutrients to get absorbed from the digestive tract. Fibers tend to show good correlation to satiety but results are variable most likely due to the diverse physicochemical and gastrointestinal transit behavior of these materials. This chapter reviews the most relevant satiety clinical studies with a focus on fibers and hydrocolloids. This chapter will also address the definitions of satiation and satiety, clinical methods for measuring satiety, and physiological mechanisms of appetite regulation and control of food intakes.

Definition of Satiation and Satiety Satiation and satiety are often confused as the same physiological response, but they are in fact distinctly different phases of appetite regulation. The distinction between satiation and satiety is important to fully appreciate the key positive and negative processes based on palatability that drive food intake (appetite), and secondarily a negative feedback loop 227

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coming mainly from the gastrointestinal tract that triggers the body to stop eating. Satiation is the response to food during the course of eating and eventually brings the period of eating to an end (Stubbs et al., 1995); it represents the point where negative feedback equals positive feedback. Satiation is generally defined by the quantitation of the eating episode, that is, volume, weight, or caloric intake of food associated with a specific meal. Hunger declines as satiation develops and usually reaches its lowest point at the end of a meal. Satiety, on the other hand, is a more indirect physiological response (a negative feedback process) and is much longer in duration than satiation. Technically, it is defined as the state in which further eating is inhibited; it arises as a consequence of food ingestion and follows the end of an eating episode. The intensity of satiety is measured by the duration of time that elapses until eating is recommenced, or by the amount consumed at the next meal.

Clinical Methods for Satiety Measurements Although there is no universally standardized methodology for satiety testing, most studies either use subjective visual analogue scale (VAS) scores, direct measurements of food intake, or a combination of both. Typically, these studies present one of several test meals of varying nutrient content to each subject on several occasions (Porrini et al., 1995). At certain time points following the consumption of the test meals, subjective satiety ratings are measured repeatedly. Most of these subjective tests employ VAS scores that are usually 100 or 150 mm in length, to assess hunger, satiety, fullness, prospective food consumption, and palatability of the meals. Subjects are asked the questions, such as “how hungry do you feel?” “how satisfied do you feel?”, “how full do you feel?”, “how much do you think you can eat?”, and so on (Willis et al., 2009). When food-intake metrics are required, test subjects are given free access to food and are instructed to eat until they feel comfortably full. Food intakes (FI) and/or energy intakes (EI) are then assessed. The timing of these ad libitum food intakes vary from 1 to 8 hours post preload, but certain studies have monitored food intake well into the next day (Nilsson et al., 2008). The majority of these investigations used a crossover design where subjects received both test meals on separate occasions and thus acted as their own control. In some experiments, plasma concentrations of glucose, lactate, and satiety related gut hormones were determined concomitantly. Covert manipulation assessed the physiological effects of nutrients or foods. Volume and differences between preloads should not be apparent

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(Stubbs, 1999; Stubbs et al., 1995). Overt manipulation assesses interaction of and differences between preloads. Thus, differences between preloads should be apparent through labeling and sensory properties, and so on. In addition to subjective measures of satiety and food or EI, gastric emptying (GE) has been used to predict satiety. From a practical perspective, satiety and FI appear to be the most relevant measures of satiety. Since FI metrics is a direct measurement, it is generally more reliable than the subjective VAS scoring.

Regulation of Satiety and FI by the Central Nervous System Food intake (FI) is regulated mainly by the central nervous system. Due to the complexity of feeding behavior, many areas of the brain are involved in regulation of FI (Heijboer et al., 2006). The hypothalamus consists of several areas that play a role in regulating FI including the arcuate nucleus, the paraventricular nucleus, the lateral hypothalamic area, the ventromedial nucleus, and the dorsomedial nucleus. The arcuate nucleus is very important for food regulation; it contains neural circuits that receive and integrate cues pertaining to the body’s nutritional status (L´opez et al., 2007b). The arcuate neurons then modulate other hypothalamic nuclei to adapt the body’s behavior and metabolism to the specific environmental conditions. The arcuate nucleus of the hypothalamus produces both orexigenic peptides (agouti-related protein and neuropeptide Y) and anorectic peptides (α-melanocyte-stimulating hormone and cocaine- and amphetaminerelated transcript) (Dhillo, 2007). The lateral hypothalamus also produces orexigenic peptides (melanin-concentrating hormone and orexins). Other hypothalamic factors implicated in appetite regulation include the endocannabinoids, brain-derived neurotrophic factor, nesfatin-1, AMPactivated protein kinase, mammalian target of rapamycin protein, and protein tyrosine phosphatase (Dhillo, 2007). These circulating factors affect FI by signaling to the hypothalamus and/or brainstem; signals from neurons, hormones, and nutrients are sensed by neuronal systems and influence the individual’s level of satiety (Heijboer et al., 2006; Stubbs, 1999).

Short-Term FI The hypothalamus regulates both long-term and short-term intake (Anderson et al., 2006). Gastrointestinal responses to food ingestion

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activate many of the regulation signals. These signals are transmitted to feeding centers in the brain, primarily via the vagus nerve resulting in a short-term decrease in FI. Regulation of short-term FI is dictated mainly by food signals arising from both preabsorptive action in the gut and postabsorptive metabolism. 1. Preabsorptive signals: The ingestion of food and the passage of the subsequent digestive products through the gastrointestinal tract prior to absorption produces signals that are integrated with long-term energy signals to control FI (Anderson et al., 2006). Nutrients stimulate the release of gastrointestinal hormones that act directly on receptors in the vagus nerve and in the brain. Mechanoreceptors, osmoreceptors, and chemoreceptors in the stomach and the small intestine are involved in this process. a. Ileal brake: Under normal physiological situations, undigested nutrients can reach the ileum. When this occurs, the ileum slows distal movement of luminal contents. This phenomenon has been termed “ileal brake” (Dobson et al., 1999). This brake mechanism ensures that the transit of the undigested nutrients through the rest of the ileum is slowed to optimize nutrient digestion and absorption. The ileal brake mechanism has been shown to reduce FI and increase satiety levels. Glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) are known to be ileal brake activators. b. Gastric emptying: Slower GE is associated with increased satiety (Slavin and Green, 2007). Many factors contribute to the rate of GE of a meal, including the physical state, temperature, volume, osmolality, caloric content of the meal, and hormonal interactions. Solid foods are emptied more slowly from the stomach than are liquid; increased volume accelerates the initial rate of GE, and solutions of high osmolality slow GE. Several hormones affect GE; for example, GE is slowed by GLP-1 (Anderson et al., 2006). 2. Postabsorptive signals: Digested nutrients in circulation stimulate satiety centers in the brain by endocrine and metabolic actions to generate postabsorptive satiety signals (Anderson et al., 2006). These signals could inform the brain about the nutritional status and elicit adaptive homeostatic changes in energy intake and expenditure. About 70 years ago, it was proposed that the central nervous system sensed circulating levels of metabolites such as glucose, lipids, and amino acids, and modified feeding behavior according to the levels of those molecules. This proposal has led to the formulation of the glucostatic, lipostatic, and aminostatic hypotheses (L´opez et al., 2007a).

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3. Gut hormones related to satiety: The gut is a source of numerous peptides that contribute to the regulation of satiety, FI, and overall nutrient metabolism. After food is consumed, the digestion and absorption of nutrients are associated with increased secretion of multiple gut peptide hormones that act on distant target sites to promote the efficient uptake and storage of energy (Drucker, 2007). These peptide hormones are synthesized by enteroendocrine cells located in the epithelium of the stomach, small bowel, and large bowel and are maintained at low basal levels in the fasting state (Drucker, 2007). Gut hormones activate neural circuits, primarily the vagus nerve and hypothalamus, which communicate with peripheral organs, including the liver, muscle tissue, adipose tissue, and islets of Langerhans in the pancreas, to coordinate overall EI and assimilation. GLP-1 is a 30-amino-acid hormone that is released from L cells in the intestinal mucosa after ingestion of food (Meier and Nauck, 2005). Sustained GLP-1 receptor activation is associated with satiety and weight loss. GLP-1 is secreted within minutes of nutrient ingestion and inhibits gastrointestinal motility and secretion, acting as part of the “ileal brake” mechanism. GLP-1 is also involved in the slowing of GE and potentiating all steps of insulin biosynthesis (Meier and Nauck, 2005). Thus, GLP-1 has a critical role in FI and glycemic control (Huda et al., 2006). Decreased GLP-1 secretion is observed in subjects with type 2 diabetes, suggesting that GLP-1 may play a role in the pathogenesis or control of type 2 diabetes. Exercise has been shown to increase the acute GLP-1 response to a liquid meal (from 52% to 78%; p = 0.02) in adolescents (Chanoine et al., 2008). Fasting GLP-1 concentrations and postprandial GLP-1 responses were lower in overweight adolescents, compared to normal-weight adolescents (Chanoine et al., 2008). PYY, a 36-amino-acid peptide, is secreted primarily by the L cells in the intestinal mucosa of the ileum and large intestine (Ueno et al., 2008). Release of PYY is influenced by calorie intake as well as meal composition. Higher plasma concentrations are seen following isocaloric meals of fat compared with meals of protein or carbohydrate. In animal studies, PYY release is also stimulated by gastric acid and cholecystokinin (CCK) secretion, and by infusion of bile acids into the ileum or colon. PYY is released into the circulation in response to FI, rising to a plateau 1–2 hours after food ingestion and remaining elevated for up to 6 hours. When the presence of nutrients in the distal small intestine stimulates PYY secretion, motility and secretion are slowed in the upper small intestine, an action that contributes to the “ileal brake.” Repeated administration

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of PYY (3–36) reduces appetite, EI, and body weight in both humans and animals. PYY may have a physiological role in eating behavior, in particular in mediating the satiating effects of dietary protein (Coll et al., 2007). PYY is also involved in regulating insulin secretion and glucose homeostasis. There are reports that fasting and postprandial PYY levels are decreased in obese subjects (Grudell and Camilleri, 2007) and that overweight subjects have a relative deficiency of postprandial PYY release that is associated with reduced satiety (Coll et al., 2007). Ghrelin, an acylated upper gastrointestinal peptide, is the only known orexigenic hormone (Cummings, 2006). The octanoylated 28-amino-acid peptide is produced and secreted by cells within the oxyntic glands of the stomach (Coll et al., 2007). Ghrelin mRNA expression and peptide secretion are increased by weight loss, fasting, and insulin-induced hypoglycemia (Coll et al., 2007). Peripheral administration of ghrelin stimulates appetite, FI, and decreases fat utilization. Compared to other macronutrients, the ingestion of lipids suppresses ghrelin poorly. Cholecystokinin is released from the gastrointestinal tract by the local action of digested food (Beglinger and Degen, 2004). Cholecystokinin functions as a positive feedback signal to stimulate digestive processes and as a negative feedback signal to limit the amount of food consumed during an individual meal (Beglinger and Degen, 2004). Cholecystokinin was shown to induce satiety by interacting through CCK-1 receptors located in specialized regions of the hindbrain (Chandra and Liddle, 2007).

Long-Term FI The adiposity-related hormones, such as leptin, ghrelin, and insulin have been recognized as having a major influence on mediating the longterm regulation of FI (Coll et al., 2007). Leptin enters the central nervous system by crossing the blood–brain barrier and binding to hypothalamic leptin receptors and thus acts to suppress FI (Klok et al., 2006). Conversely, ghrelin crosses the blood–brain barrier and stimulates FI by acting on several classical body weight regulatory centers, including the hypothalamus, hindbrain, and mesolimbic reward system. Insulin affects neuropeptides in the hypothalamus involved in regulating FI and energy expenditure (Heijboer et al., 2006). 4. Other physiological factors affecting satiety: Aging is associated with a physiological decline in FI (Morley, 2001), which involves both peripheral and central mechanisms. Altered hedonic qualities of food

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occur due to alterations in taste and smell that accompany aging. A decline in adaptive relaxation of the fundus of the stomach and an increased rate of antral filling appear to play a role in the early satiation seen in many older persons. Cholecystokinin levels are increased with aging and older persons are more sensitive to the satiating effects of this gut hormone (Morley, 2001). The decline in testosterone levels in aging males leads to increased leptin levels, which may lead to a greater decline in FI in the older male.

Mechanism of Dietary Fiber Actions Pereira and Ludwig (2001) summarized physiologic mechanisms by which dietary fiber affects satiety and body weight regulation. Three main factors, intrinsic, hormonal, and colonic effects of dietary fiber, satiation and/or satiety. First, soluble, viscous fibers delay GE by forming a gel matrix (Howarth et al., 2001). Delayed GE increases the time permitted for absorption of energy and nutrients from the digestive tract (IOM, 2002), which in turn promotes a feeling of fullness and delayed return of appetite. Second, there is evidence that the effect of fermentable dietary fibers on satiety may be mediated through the colonic production of short-chain fatty acids (SCFA) (Hamer et al., 2008). It has also been hypothesized that SCFA produced in the large intestine can influence upper gut motility and satiety (Cherbut, 2003). Butyrate has been shown to increase the expression of PYY and proglucagon in vitro in rat epithelial cells, as well as increase PYY release, but not the expression of GLP-1, in the isolated colon of animals (Cherbut et al., 1998; Longo et al., 1991). Enteroendocrine L cells containing PYY in the human large intestine express the SCFA receptor, GPR43. Thus, activation of the SCFA receptor GPR43 may play a role in this effect on satiety (Karaki et al., 2008). However, human evidence remains limited and most evidence originates from rat studies (Hamer et al. 2008). Finally, fiber increases chewing, which limits intake by promoting the secretion of saliva and gastric juice. This results in an expansion of the stomach and increased satiety (Howarth et al., 2001). In addition, dietary fibers alter the response and actions of gut hormones such as GLP-1 and CCK. Howarth et al. (2001) and Pereira and Ludwig (2001) summarized the effects of dietary fiber on hunger, satiety, energy intake, and body weight. Most studies with controlled energy intake have reported an increase in

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satiety after meals and a decrease in subsequent hunger with an increased dietary fiber diet or meal. Studies with ad libitum energy intake indicated that an additional 14 g/day of fiber resulted in an average of 10% decrease in energy intake and an average weight loss greater than 1.9 kg following approximately 3.8 months of intervention. The effects of increasing dietary fiber were more notable in obese individuals (Pereira and Ludwig, 2001; Slavin, 2005; Slavin and Green, 2007). Many dietary fibers promote satiety and decrease FI; however, not all fibers are equivalent in this regard given the extreme variance in viscosity, solubility in the gut, fermentation profiles, and hormonal responses. Soluble and fermentable fibers such as psyllium, pectin, alginate, guar gum, and barley fibers represent a diverse class of hydrocolloids that enhance satiety presumably due to gastric thickening effects that subsequently delay emptying (Adam and Westerterp-Plantenga, 2005a, 2005b; Delargy et al., 1997; Nilsson et al., 2008). On the other hand, fibers with low viscosities, such as soy fiber and oat hull fiber, showed no effect on satiety (Bouin et al., 2001; Weickert et al., 2005, 2006b).

Authoritative Statements Related to Fiber and Satiety The most current edition of the Dietary Guidelines for Americans (USDA, 2005) reported that high fiber content of foods was inversely associated with weight gain and/or body mass index (BMI). Other scientific bodies have issued several authoritative statements as follows: Foods low in fat and high in naturally occurring fiber appear to induce satiety in humans at lower levels of caloric intake than do high fat, low fiber foods. (Surgeon General’s Report, 1988) Overweight people should increase their physical activity and reduce their caloric intake, and people with a family history of obesity should avoid calorically dense foods and select low-fat foods. (NAS Diet and Health Report, 1989) There are two kinds of fiber: insoluble fiber, which exerts its effects primarily in the digestive system, and soluble fiber, which has effects on substances in the blood stream. Diets high in both kinds of fiber tend to be bulky, and since fiber itself does not contribute calories, foods high in fiber tend to contain fewer calories in the same volume of food. These characteristics of high-fiber diets may help assuage hunger and thus contribute to weight loss. (NAS Eat for Life, 1992)

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Based on these authoritative statements, a structure function claim for fiber and satiety control may be justified. However, any food formulation targeting satiety control should be based on the review of individual ingredients recognizing that there are significant variations among fiber ingredients in the regulation of satiety. The following section provides a review of individual fiber ingredients.

Review of Fiber Ingredients Psyllium Psyllium mucilage is obtained from the coat of psyllium seeds (also called plantago or fleas seeds) by mechanical milling/grinding of the outer layer of these seeds. Psyllium has a gel-forming property in aqueous solutions. This gel-forming fraction of the alkali-extractable polysaccharides is composed of arabinose, xylose, and traces of other sugars (Singh and Chauhan, 2009). As shown in Table 14.1, all of the studies using more than 7 g of psyllium fiber showed positive effects on controlling satiety (Bergmann et al., 1992; Delargy et al., 1997; Nguyen et al., 1982; Rigaud et al., 1998; Stevens et al., 1987; Turnbull and Thomas, 1995). For example, psyllium (10.8 g) significantly delayed GE from the third hour after consumption of a meal and increased the sensation of satiety and decreased hunger at the sixth hour following the meal (Bergmann et al., 1992). However, two studies employing less than 5 g of psyllium showed no effects on measures of satiety (Table 14.2; Bianchi and Capurso, 2002; Frost et al., 2003).

Guar Gum Guar gum is a high molecular weight natural polymer that consists of a polymannan backbone with single galactose unit side chains, and is highly soluble and viscous in aqueous solutions (Chauhan et al., 2009). As shown in Tables 14.3 and 14.4, 11 out of the 16 studies on guar gum ingestion reported increased satiety (Adam and Westerterp-Plantenga, 2005a, 2005b; Chow et al., 2007; Ellis et al., 1981; French and Read, 1994; Heini et al., 1998; Hoad et al., 2004; Kovacs et al., 2002; Krotkiewski, 1984; Lavin and Read, 1995, Pasman et al., 1997). Five studies found no effect of guar gum on measures of satiety (Table 14.4; Kovacs et al., 2001; Mattes, 2007; Morgan et al., 1993; O’Donovan et al., 2005; van

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Water (200 mL) and VAS, fat placebo (20 g intake granules with 200 mL water)

Standard meal—40 g VAS, GE CHO, 23 g lipid, 21 g protein

20 g Plantago ovate (20 g granules with 200 mL water)

10.8 g psyllium supplementation

15 g psyllium addition to base liquid GE

VAS, EI, GE

6.9 g placebo—15 minutes before the test meal (450 kcal: 21 g protein, 40 g CHO, and 23 g lipid) Base liquid: 24 g lactose in 480 mL water or 480 mL 2.5% low fat milk

7.4 g psyllium before the test meal

Measurement

Control

Test Diet

Table 14.1. Studies reporting positive effects of psyllium Results

Reference

Plantago ovate had a significantly higher fullness at 1 hour postmeal. Total fat intake was significantly lower in g/day and as a percentage of energy on the day of the meal after Plantago compared with water 12 healthy subjects; Psyllium significantly 6 hours delayed GE from the third hour after a meal. It

The addition of psyllium or cellulose modestly delayed GE at approximately 30 minutes

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2 healthy subjects and 1 lactose malabsorber; 50 minutes

14 healthy subjects. Psyllium reduced hunger Rigaud et al., VAS—4 hours; feelings and EI; no effect on 1998 GE—200 minutes GE

Design

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22 g psyllium Low-fiber cereal with VAS, EI (soluble 17.5 g 3 g fiber insoluble 4.2 g) or wheat bran (WB: insoluble fiber) were incorporated into breakfast cereals

increased the sensation of satiety and decreased hunger at the sixth hour after the meal 16 healthy males; The psyllium breakfast ad libitum intake: produced a greater 1.5–7 hours after suppression of snack intake breakfast; dietary than the control breakfast, record–24 hours but smaller suppression than the WB breakfasts. Psyllium reduced hunger and voluntary EI (NS) compared with the WB much later in the day (9.5–13.5 hours after breakfast) 12 females; 2 Psyllium gum and weeks intervention combination supplements significantly decreased intake of digestible energy by 153 and 115 kcal/day, respectively First study—12; Psyllium produced greatest volunteers; second satiety 13.5 hours after study—16 breakfast volunteers; 24 hours

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White bread and one 70 g egg yolk

2 soluble (guar gum and ispaghula) and 1 insoluble fibers (microcrystalline cellulose); 5 g each Pasta with 1.7 g psyllium enrichment served with a tomato sauce GE

Measurement

Results

10 healthy subjects; No change in GE or the 4 hours incremental area under the curve for GLP-1

10 healthy subjects; Dietary fibers did not 24 hours significantly change GE.

Design

Frost et al., 2003

Bianchi and Capurso, 2002

Reference

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Pasta containing 50 g GE and of available postprandial carbohydrate GLP-1

Control

Test Diet

Table 14.2. Studies reporting no significant effects of psyllium

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99 overweight and GG resulted in a 27.1% Chow et al., 2007 obese subjects with increase in fullness, a 15.8% NIDDM; 4 hours decrease in prospective consumption, and a 14.2% decrease in hunger in the

Commercial nutrition VAS control bars (CH; 6.4 g fiber)

300 kcal lunch consisting of GG-containing nutrition bars (9.1 g fiber)

(Continued)

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Adam and WesterterpPlantenga, 2005b

Adam and WesterterpPlantenga, 2005a

36 normal-weight subjects; 2 hours

Satiety was increased in normal-weight subjects compared with OW subjects in the GG condition at 30 (p = 0.02) and 60 (p = 0.04) minutes. GLP-1 concentrations were significantly increased after GG at 30 and 60 minutes compared with W in both groups Postprandial plasma GLP-1 concentrations after GG were significantly increased. Deltasatiety was significantly related to DeltaGLP-1 (W)

A galactose (50 g)/ Water (250 mL) and VAS, GLP-1 GG (2.5 g) load (836 the standard breakfast kJ) and a standard (W) breakfast

Reference

28 overweight/obese (OW) and 30 normal-weight subjects; 2 hours

Results

Water (250 mL) and VAS, GLP-1 the standard breakfast (W)

Design

A galactose (50 g)/ GG (2.5 g) load and a standard breakfast

Measurement

Control

Test Diet

Table 14.3. Studies reporting positive effects of guar gum (GG)

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240

Control

A 325-mL sweetened, VAS, GE milk-based meal-replacer beverage

Two types of alginates, which gel weakly or strongly on exposure to acid, compared with GG; 1% each

VAS, CCK, leptin

25 obese females. 5 weeks intervention; measurement up to 2 hours postmeal 12 volunteers; up to 4 hours

8 males; 50 minutes

VAS, GE

A 3.3 MJ (800 kcal) formula

11 nondiabetic subjects; 2 hours

Design

VAS

Measurement

French and Read, 1994

Ellis et al., 1981

Reference

Compared with the control meal, strong-gelling alginate and guar meals increased fullness and decreased hunger

Hoad et al., 2004

No changes in fasting blood Heini et al., 1998 levels of CCK and leptin and VAS scores

3% GG delayed the GE of the low-fat soup; the small delays in the return of hunger and decline of fullness were significantly correlated with the GE

Significant increases in satiety attributed to 100–150 g guar/kg bread

120–240 minutes postlunch areas under the curve (AUC) compared to CH

Results

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20 g fiber from GG

Bread supplemented Bread alone with GG at three levels (50, 100, and 150 g/kg) 3% guar gum was High- and low-fat added to high- and soups with 0 g guar low-fat soups

Test Diet

Table 14.3. (Continued)

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VAS, EI, GE

VAS, EI

2% GG in a 250-mL, A 250-mL, 30% 30% glucose drink glucose drink; 0 g GG

20–40 g GG supplementation

Pasman et al., 1997

Lavin and Read, 1995

Daily hunger ratings Krotkiewski, recorded for up to 10 weeks 1984 showed that GG reduced hunger significantly better than commercially available bran taken in the same way

Satiety before the third Kovacs et al., meal was higher with SSM 2002 with GG compared to SSM without GG. Meal pattern, general appetite, and total EI were similar for all treatments

GG reduced the ratings for hunger and desire to eat and an increase in ratings for fullness and satiety. No changes in EI from the test meal and GE Obese women who Mean EI decreased had lost weight; 1 significantly from 6.7±0.4 week MJ to 5.4±0.2 MJ daily after GG supplementation. No changes in satiety ratings

10 healthy males; up to 3.5 hours after the drinks

Obese subjects; up to 10 weeks

15 overweight males; 2 week

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0 g GG supplementation

VAS

SSM and a solid meal VAS, EI (947 kJ)

20 g GG a day (10 g Bran supplement supplement twice daily)

2.5 g GG addition to a semisolid meal (SSM)

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Test meals containing GIP, GE 100 g carbohydrate

No effect on GE

GG addition to a semisolid had no effect on appetite, hunger and desire to eat as well as EI No significant treatment effects in self-reported appetitive sensations over each 5-hour postloading period. 4 g guar added glucose infusion (intraduodenal) —attenuated GLP-1 and GIP responses in elderly

Results

6 healthy nonobese GG and SBF lowered subjects; postprandial GIP levels. 200 minutes No effect on GE

8 males; 180 minutes

A standard semisolid test meal containing 0g

GE

8 healthy older subjects; 120 minutes after infusion

25 healthy overweight adults; 5 hours

Intraduodenal glucose GLP-1, GIP infusion (3 kcal/min)

VAS

55 g breakfast bar with and without 3.9 g alginate/bar

28 overweight males; 2 weeks

Design

Morgan et al., 1993

van Nieuwenhoven et al., 2001

O
Donovan et al., 2005

Mattes, 2007

Kovacs et al., 2001

Reference

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Intraduodenal glucose infusion (3 kcal/min) with guar gum (4 g) for 1 hour A standard semisolid test meal containing 2.5 g, 3.5 g, or 4.5 g of GG Test meals with 10 g GG, 10 g soybean–cotyledon fiber, 10 g SBF, or 5 g glucomannan

VAS, EI

A low-energy SSM and a solid meal

Addition of modified guar gum (GG) to a low-energy semisolid meal 55 g breakfast bar (3.9 g GG/bar or 7% w/w)

Measurement

Control

Test Diet

Table 14.4. Studies reporting no significant effects of guar gum

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Nieuwenhoven et al., 2001). Overall, guar gum tended to promote satiety, most likely due to its gel-forming properties. As an ingredient, guar gum is relatively easy to handle and is a fairly low-cost substance in the hydrocolloid category.

Alginate Alginate is a linear polysaccharide, whose monomers are mannuronic and guluronic acids, and has a gel-forming property, especially in the presence of calcium ion (Panouill´e and Larreta-Garde, 2009). A review of three studies on alginate indicates that alginate consistently promotes satiety probably through its gel-forming capacity, which contributes to slower GE (Table 14.5; Hoad et al., 2004; Paxman et al., 2008; Pelkman et al., 2007). Minimum level necessary to decrease EI appears to be 1.5 g/dose. Paxman et al. (2008) randomly assigned 68 normal-weight adults (an average age of 24.6) to either an alginate beverage (1.5 g of alginate/day) or an 18.2 g dose of SlimFast (Unilever) for 7 days. The alginate beverage group had a significant 7% reduction in daily EI (equivalent to about 135 kcal/day). The test beverage was composed of 1.5 g sodium alginate (Protanal from FMC BioPolymer, with a guluronate content of 65–75%), 0.7 g calcium carbonate, 2.8 g glucono-delta-lactone, 0.5 g sodium bicarbonate, 0.05 g malic acid, 0.24 g vanilla flavor, and 7 g fructose. The composition is reportedly patented under patent number WO2007039294. Although this carboxylic polymer can contribute to increased viscosity in the gastrointestinal tract by either acid-induced gelation or via calcium induced cross-linking (with coingestion of calcium), high material cost, sour taste, and difficult handling properties may limit food uses of alginate as a source of dietary fiber.

Oat β-Glucan Oat β-glucan consists of a mixture of β-(1,3) and β-(1,4)-glycosidic bonds, and has been known to lower blood cholesterol and glucose levels due to its viscosity, which is affected by concentration and molarity (Wood, 2004). Despite the high viscosity of oat β-glucan, two studies on oat β-glucan have reported no effects on satiety (Table 14.6; Hlebowicz et al., 2008; Juntunen et al., 2002).

244

Beverage with 0 g GG or alginate

1.0 g or 2.8 g beverage alginate-pectin formulations were tested Two types of alginates, which gel weakly or strongly on exposure to acid, compared with GG; 1% each A strong-gelling sodium alginate formulation VAS, EI

Measurement

Placebo

EI

Results

Reference

68 healthy subjects; Alginate formulation 7 days reduced EI

Paxman et al., 2008

29 healthy subjects. In women in the lower 50th Pelkman et al., week percentile of rigid restraint, 2007 GG reduced EI by 12% during the day and by 22% for the evening snack 12 volunteers Compared with the control Hoad et al., 2004 meal, strong-gelling alginate and guar meals increased fullness and decreased hunger

Design

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A 325-mL sweetened, Intragastric milk-based gelling, GE meal-replacer beverage

Control

Test Diet

Table 14.5. Studies reporting positive effects of alginate

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White-wheat bread (WWB)

Wholemeal rye bread containing oat β-glucan concentrate or dark durum wheat pasta (95.6 g fiber from wheat), or whole-kernel rye bread

Reference

20 healthy subjects; No effect on GE and Juntunen et al., 3 hours GLP-1 2002

Results

VAS, GE rate 12 healthy subjects; No effect on GE rate Hlebowicz et al., 90 minutes and satiety 2008

GE, GLP-1, GIP

Measurement Design

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Extruded muesli product based Extruded muesli on 4 g oat β-glucan product with 0 g oat β-glucan

Control

Test Diet

Table 14.6. Studies reporting no significant effects of oat β-glucan

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Fiber based ingredients

Barley Barley and wheat are commonly used grains in diets. All the studies employing >62 g barley/dose consistently produced a positive impact on satiety (Table 14.7; Granfeldt et al., 1995; Liljeberg et al., 1999; Kaplan and Greenwood, 2002; Nilsson et al., 2008). However, as shown in Table 14.8, less than 50 g of barley had little effect on satiety (Keogh et al., 2007; Kim et al., 2006). Thus, it appears that barley exhibits a dose–response relationship in terms of satiety. Barley consists of two major fiber components: β-glucan and amylose. The results from studies on barley, HACS, and oat β-glucan suggest that the high amylose present in barley may have contributed to enhanced satiety effects.

Wheat and Wheat Bran As shown in Table 14.9, wholemeal wheat is also known to be effective in enhancing satiety (Grimes and Gordon, 1978; Holt and Miller, 1994; Holt et al., 1995). A satiety index (SI) score (approximately 160) of wholemeal bread was higher than that of white pasta (approximately 120), muesli (approximately 100), white bread (100), or croissant (approximately 35) (Holt et al., 1995). Studies report that whole-grain oat cereal and whole-wheat cereal have comparable satiety effects as measured by EI and VAS (Berti et al., 2005; Saltzman et al., 2001). However, durum wheat and processed wheat fiber neither promote gut hormonal gastric inhibitory polyreptide (GIP) responses nor slow GE (Table 14.10; Juntunen et al., 2002; Weickert et al., 2005, 2006b). A limitation of comparing these studies is that different end point measurements were assessed, which may partly contribute to the inconsistencies in the findings between various researchers. Wheat bran was effective in promoting satiety when wheat bran cereals were compared with low-fiber cereals (Table 14.11; Delargy et al., 1995, 1997; Hlebowicz et al. 2008; Levine et al., 1989). Although, wheat bran showed no efficacy when it was incorporated into other forms of diet (Table 14.12; Beck et al., 1986; Morgan et al., 1993; Sandstrom et al., 1983; Stevens et al., 1987). The data indicate that food form is another important factor determining the satiety effects of fiber ingredients. Wheat showed comparable satiety effects when compared with chickpeas (Pittaway et al., 2007) or rye (Heinonen et al., 2007).

Soy Fiber, Oat Hull Fiber, and Sugar Beet Fiber Soy fiber, oat hull fiber, and sugar beet fiber (SBF) are not viscous in aqueous solutions (Howarth et al., 2001; Weickert et al., 2005). Oat hull

VAS

The highest satiety score was associated with the barley breakfast

Results

All barley products elicited higher satiety scores when compared with WWB 15 healthy subjects. The evening meal with Measured second HBB bread resulted in a meal effects higher satiety score (AUC no I. IAUC 180 minutes) after the standardized breakfast with after all other evening meals

10 health subjects; 4 hours after breakfast; 3 hours after second meal 10 healthy subjects; 2 hours

Design

(Continued)

Nilsson et al., 2008

Granfeldt et al., 1995

Liljeberg et al., 1999

Reference

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50 g available starch–-WWB

50 g available CHO; white bread

WWB (50 g starch) VAS

Bread with 60% barley flour; bread with barley flour + barley flakes (containing 17% β-glucan) 79.1 and 90.2 g normal and high-amylose barley flour (porridge; 50 g available CHO) WWB with ordinary barley (OB), high-amylose barley (HAB), enriched barley β-glucan (HBB) or 100 g HACS (RS), or WWB with the same amount of RS and also with DF from barley (RS+DF)

Measurement

Control

Test Diet

Table 14.7. Studies reporting positive effects of barley

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Control Iso-CHO (Available CHO 46.6 g) nonenergy placebo drink

Test Diet

Barley, glucose drink, or potatoes

Table 14.7. (Continued)

VAS, FI

Measurement 10 healthy subjects; 120 minutes postingestion period, followed by consumption of an ad libitum lunch

Design

Reference

Potatoes increased satiety Kaplan and the most, followed by Greenwood, barley, then glucose, 2002 which trended toward greater satiety than placebo. Potatoes led to less hunger than placebo and less prospective consumption than the other three foods Potatoes and barley led to greater fullness than glucose and placebo

Results

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Wheat containing meal; 5 g fiber, 25 g available CHO

30 g barley cereal, 8 g fiber, 19 g available CHO

VAS, FI

19 overweight subjects; 150 minutes

14 healthy women consumed a test breakfast. Crossover. 10 hours

Measurement Design

Reference

The ingestion of 1–2 g of β-glucan did not change VAS ratings, which rate their hunger, fullness, satisfaction, and thirst, at timed intervals

Kim et al., 2006

Meal type did not affect any Keogh et al., variable measured by the 2007 VAS. Ad libitum FI over the next 10 hours was reduced by 23% (9.6 vs. 11.0 MJ, p < 0.05) after the wheat-containing meals compared to the barley-containing glycaemic index meals

Results

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2 g, 1 g, or 0 g β-glucan Isocaloric test meals: VAS (50 g or 25 g barley) a glucose solution or from barley wheat, a wheat–barley mixture (1 g β-glucan), or barley (2 g β-glucan)

Control

Test Diet

Table 14.8. Studies reporting no significant effects of barley

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250

Compared the amount eaten to reach fullness

Grimes and Gordon, 1978

Wholemeal bread required less quantity than white bread to reach fullness

VAS

10 healthy subjects; 120 minutes

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VAS

WWB

Reference

Wholemeal wheat bread

Results

Meals with fine wholemeal flour

Design

Meals with whole grains, cracked grains, or coarse wholemeal flour

Measurement

101 g of wholemeal bread Holt et al., 1995 resulted in a higher SI score (approximately 160) than white pasta (approximately 120), muesli (approximately100), white bread (100), or croissant (approximately 47) The fine flour meal had the Holt and Miller, lowest satiety response 1994 (AUC: 231.4 +/−31.6) and the whole grain meal had the highest response

Control

101 g wholemeal Isoenergetic 1,000 kJ A satiety index 11–13 subjects; 120 bread (240 kcal) servings of (SI) score minutes 38 foods separated into six food categories

Test Diet

Table 14.9. Studies reporting positive effects of wholemeal wheat

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GLP-1, GIP

VAS, GLP-1, GIP

Bread with 10.5 g wheat White bread fiber

Bread with 10.5 g wheat White bread fiber or 10.5 g oat fiber

Measurement GE, GLP-1, GIP

Control

Dark durum wheat pasta WWB (95.6 g fiber from wheat), whole-kernel rye bread, or wholemeal rye bread containing oat β-glucan concentrate

Test Diet

Results

20 healthy subjects; No effect on GE, GIP, and 3 hours GLP-1 responses, except for GLP-1 responses to the rye bread containing oat β-glucan concentrate, which were lower after the consumption of rye breads and pasta than after consumption of WWB 14 healthy women; GIP at 180 minutes— 5 hours significantly lower after wheat fiber, GLP-1—no effect 14 healthy women; No effect on GLP-1; no 5 hours effect in hunger scores. Postprandial responses of PYY and ghrelin were blunted after the intake of wheat fiber

Design

Table 14.10. Studies reporting no significant effects of wholemeal wheat or wheat fiber

Weickert et al., 2006b

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Weickert et al., 2005

Juntunen et al., 2002

Reference

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Bran flakes with sour milk

Corn flakes or oat flakes with sour milk

First experiment— 12 healthy; second experiment—16 subjects; 24 hours GE rate, VAS 12 healthy subjects, 90 minutes

VAS

Delargy et al., 1995

Bran flakes slowed the GE Hlebowicz et al., rate when compared to oat 2008 flakes and corn flakes. No effect on satiety

WB produced greatest satiety shortly after consumption

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Breakfast cereal with Comparison of 20 g fiber from wheat psyllium versus WB bran or psyllium

Levine et al., 1989

Reference

WB cereal reduced Delargy et al., short-term hunger ratings 1997 (1.5 hours), no significant effect of breakfast type on total day EI.

16 healthy subjects; ad libitum EI was assessed at 1.5 hours (snack) after breakfast, later in the day (food box), and the following day

Low-fiber cereal and cereal with psyllium

VAS, EI

14 healthy subjects; Fiber cereals reduced FI 6 hours without the perception of feeling less hungry

Results

Low-fiber cereal plus VAS, FI milk and orange juice

Design

57 g All Bran, Fiber One, Shredded Wheat, and other breakfast cereals Cereal breakfast with wheat bran (22 g fiber; 18.1 g insoluble and 3.8 g soluble)

Measurement

Control

Test Diet

Table 14.11. Studies reporting positive effects of wheat bran

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4 g/day fiber control

Crackers containing psyllium gum, wheat bran, or a combination of the two fiber sources (23 g fiber/day)

Results

12 females; 2 weeks

No effect on EI

Basal levels of the three hormones were not affected by bran ingestion. WB decreased GIP response to the test meal only 10 constipated The FI was generally patients in geriatric satisfactory and decreased ward, 6–12 weeks in only two women on bran treatment 6 volunteers; Wheat bran—no effect on 200 minutes GIP or GE

5 healthy men; 7 weeks

Design

Stevens et al., 1987

Morgan et al., 1993

Sandstr¨om et al., 1983

Beck et al., 1986

Reference

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EI

GIP, GE

100 g CHO meal

Comparing 10 g wheat bran, 10 g SBF, 10 g guar gum, and 10 g soy fiber and 5 g glucomannan

GIP, gastrin, vasoactive intestinal polypeptide (VIP) FI, 5-day food records after 6 and 12 weeks

0 g WB

Wheat bran addition to normal diet; 20 g/day

Measurement

Ordinary or low-phytate 0 g WB wheat bran addition to their diet; 20 g/day

Control

Test Diet

Table 14.12. Studies reporting no significant effects of wheat bran

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Fiber based ingredients

fiber has become an important food ingredient due to its high fiber content (about 90%). The results of two studies using oat hull fiber suggest that this food ingredient has little effect on satiety; oat hull fiber accelerated GIP responses without affecting hunger scores or GLP-1 and PYY responses (Table 14.13; Hlebowicz et al., 2008; Weickert et al., 2005, 2006a, 2006b; Zarling et al., 1994). Similarly, studies on soy fiber showed no effect on GE (Table 14.14; Bouin et al., 2001; Morgan et al., 1993; Zarling et al., 1994). Gastric emptying and gastric acid secretion in healthy adults were unaffected when a supplementation of an enteral diet with 7.5 g soy polysaccharides (500 kcal, 250 mL/h) was consumed (Bouin et al., 2001). Morgan et al. (1993) also reported that 10 g of soy fiber in a test meal containing 100 g carbohydrates had no effect on GIP response and GE. A study employing a mixture of soy fiber and oat hull fiber (28.8 g/day, 10 days) showed no effect on GE in medically stable residents of a chronic care facility (Zarling et al., 1994). The end points employed in the studies on soy fiber are GE and/or gut hormones, not actual satiety. It may be premature to conclude that soy fiber does not have satiety effects; thus, more studies are needed. It appears that sugar beat fiber does not have a significant inpact on satiety (Table 14.15).

Inulin, Oligofructose (OF), and Polydextrose Cani et al. (2006) reported that supplementation of 16 g OF/day for 2 weeks increased short-term satiety measures. In this study, subjects completed two 2-week experimental phases during which they received either 16 g of OF (8 g with breakfast and 8 g with dinner) or a placebo (maltose) (Table 14.16). During breakfast, OF significantly increased satiety compared to placebo treatment, but without affecting other measures of satiety. After lunch, no significant differences were observed between treatment periods. At dinner, OF significantly increased satiety and reduced hunger (p = 0.04) and prospective food consumption. The EI at breakfast and lunch were significantly lower after OF treatment than after placebo treatment. Total daily EI was 5% lower during OF than the placebo period. Archer et al. (2004) reported that supplementation of 24 g inulin/day induced a lower EI during the test day, even though it had no effect on satiety at the breakfast. The authors suggested that a late postabsorptive satiety effect may be related to the fermentation of inulin. However, two studies on inulin showed no effect on GE (Table 14.17; Den Hond et al., 2000; Geboes et al., 2003). Differences between inulin and OF may be partly explained by the fact that long-chain inulin is largely fermented in the

White bread

White bread

Bread enriched with 10.5 g oat fiber

Bread enriched with 10.5 g oat fiber, 10.8 g wheat fiber, or 10.4 g RS subgroups Fiber-enriched bread (white bread enriched with 31.2 g oat fiber/day)

Oat flakes with sour milk

Corn flakes with sour milk

14 healthy women; 5 hours

5 hours

Design No effect on hunger scores and postprandial responses of PYY and ghrelin

Results

Oat fiber was associated with earlier GIP responses; no effect on GLP-1 Plasma ghrelin, 17 overweight or No effect on plasma and obese subjects with ghrelin, and adiponectin adiponectin, normal glucose concentrations, as well body weight metabolism; as substrate utilization 72 hours and body weight GE 10 medically stable No effect on GE. Oat resident patients; 10 fiber increased fecal days intervention; energy 140 minutes postmeal GE rate, VAS 12 healthy subjects, No effect on satiety or 90 minutes satiety

GIP, GLP-1

VAS, PYY, gherlin

Measurement

Hlebowicz et al., 2008

Zarling et al., 1994

Weickert et al., 2006b

Weickert et al., 2005

Weickert et al., 2006a

Reference

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Enteral nutritional Enteral nutritional formula with a mixture formula of a 50% soy and 50% oat fiber (28.8 g/day)

White bread

Control

Test Diet

Table 14.13. Studies reporting no significant effects of oat fiber

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Enteral nutritional Enteral nutritional formula with a mixture formula of a 50% soy and 50% oat fiber (28.8 g/day)

10 medically stable resident patients; 10-day intervention; 140 minutes postmeal

6 healthy nonobese subjects; 200 minutes

12 healthy volunteers; 3 hours

Design

Bouin et al., 2001

Reference

No effect on GE. A mixture of soy fiber and oat fiber increased fecal energy

Zarling et al., 1994

Soy fiber, SBF, and Morgan et al., wheat bran had no effect 1993 on GIP concentrations and GE

No significant effect on GE and gastric acid secretion

Results

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GE

GIP, GE

Test meals containing 100 g carbohydrate

Test meals with 10 g soybean–cotyledon fiber (Fibrim), 10 g guar gum, 10 g SBF, or 5 g glucomannan

Measurement GE

Control

Enteral diet with soy Enteral diet with polysaccharide fiber or 0 g fiber mixed fiber from pea and inulin

Test Diet

Table 14.14. Studies reporting no significant effects of soy fiber

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PYY GIP, GE

GIP, GE

Hormonal responses

0g Test meals containing 100 g carbohydrate

Test meals containing 100 g carbohydrate

No fiber

40 g Fibrex, 27 g DF daily Test meals with 10 g SBF, 10 g soybean–cotyledon fiber, 10 g guar gum, or 5 g glucomannan Test meals with 10 g SBF, 10 g soybean–cotyledon fiber, 10 g guar gum, or 5 g glucomannan

Measurement

Control

Test Diet

Table 14.15. Studies reporting no significant effects of SBF

3 hours

SBF increased GIP response

SBF increased GIP response

SBF increased GIP response

No changes in PYY

Results

Hagander et al., 1986

Morgan et al., 1990

Hagander et al., 1989 Morgan et al., 1993

Reference

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6 healthy nonobese subjects

12 NIDDM subjects; 8 weeks 6 healthy nonobese subjects

Design

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Maltodextrin

Standard enteral formula

OF-Raftilose P95 (8 g twice daily—once at breakfast and once at dinner)

Enteral formula with pea-fiber (10 g/L) and FOS (5 g/L) EI, VAS

VAS

VAS

Measurement

Results

11 healthy subjects; Consumption of the 14 days pea-fiber/FOS formula resulted in higher mean fullness 33 men; VAS— Inulin reduced EI 285 minutes; EI— without changing the 24 hours satiety responses

10 persons; 2 weeks OF treatment increased satiety following breakfast and dinner, reduces hunger and prospective food consumption following dinner

Design

Archer et al., 2004

Whelan et al., 2006

Cani et al., 2006

Reference

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Half the fat of a full-fat A full-fat sausage sausage patty is patty replaced with inulin or with lupin-kernel fiber

Control

Test Diet

Table 14.16. Studies reporting positive effects of and inulin

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Table 14.17. Studies reporting no significant effects of and inulin Test Diet

Control

Measurement Design

Results

15 g inulin/day

Sucrose

GE

No effect on Den Hond GE et al., 2000

Test meal Test meal with 5 or with 0 g 10 g inulin inulin (Raftilin HP)

GE

6 healthy subjects; 2 weeks Healthy subjects; 180 minutes plus

Reference

No effect on Geboes GE et al., 2003

distal colon, whereas OF is fermented in the proximal colon. Thus, inulin may not be able to produce the same effect as OF in terms of GLP-1 (Cani et al., 2006). Polydextrose showed inconsistant effects (Table 14.18; King et al., 2005; Willis et al., 2009).

Resistant Starches (RS) Starches and degradation products of starch that resist enzymatic digestion in the small intestine are classified as RS (Finocchiaro et al., 2009). Such indigestible materials pass to the large intestine where they can be fermented and act as a fiber in the body. RS are typically classified into four fractions: RS1 through RS4 . Where RS1 is physically inaccessible or digestible and can be found in seeds or legumes and unprocessed whole grains; RS2 occurs in a natural granular form, for instance uncooked potato and high-amylose corn; RS3 is formed when starch-containing foods are cooked and cooled such as in bread or retrograded high-amylose corn; and RS4 are starches that have been manufactured or chemically modified to resist digestion (Sajilata et al., 2006). High-amylose corn starch (HACS) and ingredients prepared from this starch are examples of natural RS (RS2 and RS3) and have been the focus of substantial research including many of the following selected studies. As shown in Table 14.19, studies based on isocaloric comparisons of RS and placebo tend to show positive effects of RS on satiety (Qu´ılez et al., 2007; van Amelsvoort and Weststrate, 1992; Willis et al., 2009). Satiety effects were weakened when placebo was replaced with an equal weight of HACS resulting in a lower caloric content of the RS group (Table 14.20; Anderson et al., 2002; Weststrate and van Amelsvoort, 1993).

260

Preload-yogurt

Control VAS, EI

Measurement

Results

Reference

20 healthy subjects; Polydextrose muffin had Willis et al., 2009 3 hours the least impact on satiety (less than the control muffin)

15 healthy subjects; When the energy content King et al., 2005 1.5 hours of the yogurt preloads were accounted for, there was a significant suppression of energy intake for P (yogurt + 25 g polydextrose) compared with C (p = 0.002). The XP yogurt (yogurt + 12.5 g xylitol and 12.5 g polydextrose) induced a significantly stronger satiating effect

Design

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No significant effects High-fiber muffin Isocaloric low-fiber VAS enriched with muffin (1.6 g polydextrose, corn fiber;178 kcal) bran, RS or barley β-glucan with oat fiber (8.0–9.6 g fiber; 174–177 kcal)

Positive effects Preload-yogurt containing 12.5 g xylitol, 12.5 g polydextrose (P), 12.5 g xylitol plus 12.5 g polydextrose (XP)

Test Diet

Table 14.18. Studies reporting effects of polydextrose

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VAS

VAS

Isocaloric low-fiber muffin (1.6 g fiber;178 kcal)

100 g pastas, 19% E from protein, 23% fat, 53% polysaccharides

Bread—50 g available CHO

High-fiber muffin enriched with Hi maize RS(RS2 RS3), polydextrose, corn bran, or barley β-glucan with oat fiber (8.0–9.6 g fiber; 174–177 kcal) 20% of wheat flour was replaced by 70% or >75% high amylose—(24.5% of CHO); or regular corn starch 40% of flour was replaced by HACS in low-calorie muffins (6.3 g fiber; 102 g serving size vs. 1.5–2.7 g fiber control)

Measurement

Control/Diet

Amount Fed

Table 14.19. Studies reporting positive effects of RS

The satiety response of low-calorie (HACS) muffins (SI = 100) was similar to bread (SI = 100) and higher than plain muffins (SI = 52: p = 0.02).

Fullness/satiety score was higher after high-amylose meals

Subjects were more satisfied after eating RS or corn bran than after polydextrose.

Results

(Continued)

Qu´ılez et al., 2007

Hospers et al., 1994

Willis et al., 2009

Reference

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14 healthy or overweight subjects; 2 hours

16 healthy males; 3 hours

20 volunteers; 3 hours

Design

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262

Control/Diet

60 g fiber from RS ingredient (100 g Novelose 260)

VAS

Measurement

Low RS GLP-1 diet-supplemented with 40 g waxy-maize starch

Hot mixed lunch in which Low-amylose diet Amylose:Amylopectin (Am:Ap = 0:100) (Am:Ap) was 45:55

Amount Fed

Table 14.19. (Continued)

10 healthy subjects. Low-fiber diet for 24 hours, then meal tolerance test (MTT) the following morning

24 healthy males; 6 hours

Design

van Amelsvoort and Weststrate, 1992

Reference

Plasma GLP-1 during Robertson et al., the MTT rose from a 2003 mean basal level of 11 pmol/L to reach a mean peak concentration of 42 pmol/L after 1 hour. There was no effect of preceding diet on the plasma GLP-1 excursion

High-amylose meals induced more satiety up to 6 hours postprandially.

Results

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50 g available starch—WWB

WWB with ordinary barley (OB), high-amylose barley (HAB), enriched barley β-glucan (HBB) or 100 g HACS (RS), or WWB with the same amount of RS and also with DF from barley (RS+DF) VAS, FI

VAS

Measurement

14 healthy subjects

15 healthy subjects; measured second meal effects

Design

Carbohydrates with a high GI (glucose, polycose, and sucrose) suppressed subjective appetite and FI in the short term, but those with a low GI (amylose and amylopectin) did not.

RS may have slightly better satiety scores than WWB. The evening meal with HBB bread resulted in a higher satiety score (IAUC 180 minutes) after the standardized breakfast with after all other evening meals

Results

(Continued)

Anderson et al., 2002

Nilsson et al., 2008

Reference

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Compared with Beverages amylopectin, polycose, a containing 75 g fructose–glucose CHO mixture, sucralose, and glucose

Control/Diet

Test Diet

Table 14.20. Studies reporting no significant effects of RS

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264

Pasta containing RS

Normal pasta

EE, VAS, Ghrelin, GLP-1, PYY

30 subjects; 3 hours after lunch

24 healthy males; up to 4 weeks

0g supplementation

RS supplementation had no acute effect on substrate utilization, appetite feelings, and gut-derived hormones.

Consumption of 30 g/ day RS2 and RS3 had little influence on appetite and FI

No systematic effect of amylose content on appetite or fullness ratings

Results

Smeets et al., 2008

de Roos, 1995

Weststrate and van Amelsvoort, 1993

Reference

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VAS, FI

22 healthy males; 4 hours after breakfast and 6 hours after lunch

Breakfast with a VAS low-amylose starch. Pizza lunch with 25.5 g common maize starch

Design

40 g CHO (14 g amylose) at breakfast and 46 g CHO (16 g amylose or 25 g high-amylose maize starch) at lunch (pizza) 30 g RS/day

Measurement

Control/Diet

Test Diet

Table 14.20. (Continued)

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The study conducted by Willis et al. (2009) compared several fibers, including commercial RS ingredients derived from HACS. Their results suggested that all fibers do not influence satiety equally and that natr r 260 and Novelose
330) was the ural RS (a mixture of HiMaize
most effective in enhancing short-term satiety among the various fibers tested. In this study, 20 healthy subjects, aged 18–65 years, consumed either a low-fiber control muffin (1.6 g) or one of four high-fiber muffins (8.0–9.6 g fiber), which contained nearly identical macronutrient content (175 kcal). The test supplements were corn bran, barley β-glucan with oat fiber, polydextrose, or HACS. On the morning of each test, subjects completed a previously validated 100 mm VAS to assess hunger and appetite (baseline). Additional VAS were completed at 15, 30, 45, 60, 120, and 180 minutes after consumption of muffins. At 45 minutes, subjects were more significantly satisfied after eating a muffin with HACS (p = 0.0009) or corn bran (p = 0.0118) than a muffin with polydextrose or the control muffin. Subjects were significantly less hungry at 180 minutes after consuming either HACS (p = 0.0009) or barley with oat fibers (p = 0.024) than after consuming polydextrose. Similarly, subjects felt more satisfied after either HACS (p = 0.004) or corn bran (p = 0.028) than polydextrose. As previously mentioned, and as indicated in Table 14.19, RS has been shown to have positive effects on satiety (Qu´ılez et al., 2007; van Amelsvoort and Weststrate, 1992). Mechanisms by which RS may promote satiety include the effect of fermentation and resulting butyrate production, reduced glycemic and insulinemic responses, and possibly gut viscosity (Hamer et al., 2008). Several studies have suggested RS fermentation was the key trigger indicating satiety (Bird et al., 2007). Breath hydrogen, an indicator of colonic fermentation, also correlated positively with satiety (r = 0.27; p < 0.01) and inversely with GE rate (r = −0.23; p < 0.05) (Nilsson et al., 2008). Other studies demonstrated that RS also plays a role in reduction of postprandial blood glucose and insulin responses, which may be linked to increased satiety (Anderson et al., 2002; Behall et al., 2006; Bornet et al., 2007; Noakes et al., 1996; Qu´ılez et al., 2007; Robertson et al., 2003, 2005; van Amelsvoort and Weststrate, 1992).

Conclusions All dietary fibers are not the same. It appears that viscous fibers such as psyllium, guar gum, and alginate are effective in promoting satiety.

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However, the effect of increasing the feeling of satiety still needs to be proven for insoluble, nonviscous fibers such as oat fiber, soy fiber, and SBF. The feelings of satiety produced by certain fiber ingredients have been acknowledged by authoritative bodies, including the potential health benefits resulting from the effect of fiber on satiety, such as the implication it has for weight control. Therefore, based on the scientific evidence, a structure function claim for general fiber in relation to its ability to control satiety may be justified. However, claims for individual fiber ingredients should be established based on findings specific to the particular ingredients since all dietars fibers are not the same.

References Adam TC, Westerterp-Plantenga MS. Glucagon-like peptide-1 release and satiety after a nutrient challenge in normal-weight and obese subjects. Br J Nutr 2005a;93:845–851. Adam TC, Westerterp-Plantenga MS. Nutrient-stimulated GLP-1 release in normal-weight men and women. Horm Metab Res 2005b; 37:111–117. Anderson GH, Aziz A, Abou Samra R. Physiology of food intake regulation: interaction with dietary components. Nestle Nutr Workshop Ser Pediatr Program 2006;58:133–143. Anderson GH, Catherine NL, Woodend DM, Wolever TM. Inverse association between the effect of carbohydrates on blood glucose and subsequent short-term food intake in young men. Am J Clin Nutr 2002;76:1023–1030. Archer BJ, Johnson SK, Devereux HM, Baxter AL. Effect of fat replacement by inulin or lupin-kernel fibre on sausage patty acceptability, post-meal perceptions of satiety and food intake in men. Br J Nutr 2004;91(4):591–599. Beck B, Villaume C, Bau HM, Gariot P, Chayvialle JA, Desalme A, Debry G. Long-term influence of a wheat-bran supplemented diet on secretion of gastrointestinal hormones and on nutrient absorption in healthy man. Hum Nutr Clin Nutr 1986;40:25–33. Beglinger C, Degen L. Fat in the intestine as a regulator of appetite—role of CCK. Physiol Behav 2004;83:617–621.

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Fiber and Satiety

8:28

Printer Name: Yet to Come

267

Behall KM, Scholfield DJ, Hallfrisch JG, Liljeberg-Elmst˚ahl HG. Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women. Diabetes Care 2006;29:976– 981. Bergmann JF, Chassany O, Petit A, Triki R, Caulin C, Segrestaa JM. Correlation between echographic gastric emptying and appetite: influence of psyllium. Gut 1992;33:1042–1043. Berti C, Riso P, Brusamolino A, Porrini M. Effect on appetite control of minor cereal and pseudocereal products. Br J Nutr 2005;94:850–858. Bianchi M, Capurso L. Effects of guar gum, ispaghula and microcrystalline cellulose on abdominal symptoms, gastric emptying, orocaecal transit time and gas production in healthy volunteers. Dig Liver Dis 2002;34:S129–S133. Bird AR, Vuaran M, Brown I, Topping DL. Two high-amylose maize starches with different amounts of resistant starch vary in their effects on fermentation, tissue and digesta mass accretion, and bacterial populations in the large bowel of pigs. Br J Nutr 2007;97:134–144. Bodinham BL, Frost GS, Robertson MD. The acute effects of resistant starch on appetite and satiety. Proceedings of the Nutrition Society (2008), 67 (OCE), E157– University of Surrey, Guildford, Surrey. Bornet FR, Jardy-Gennetier AE, Jacquet N, Stowell J. Glycaemic response to foods: impact on satiety and long-term weight regulation. Appetite 2007;49:535–553. Bouin M, Savoye G, Herve S, Hellot MF, Denis P, Ducrotte P. Does the supplementation of the formula with fibre increase the risk of gastrooesophageal reflux during enteral nutrition? A human study. Clin Nutr 2001;20:307–312. Cani PD, Joly E, Horsmans Y, Delzenne NM. Oligofructose promotes satiety in healthy human: a pilot study. Eur J Clin Nutr 2006;60(5):567–572. Chandra R, Liddle RA. Cholecystokinin. Curr Opin Endocrinol Diabetes Obes 2007;14:63–67. Chanoine JP, Mackelvie KJ, Barr SI, Wong AC, Meneilly GS, Elahi DH. GLP-1 and appetite responses to a meal in lean and overweight adolescents following exercise. Obesity (Silver Spring) 2008;16:202–204.

P1: SFK/UKS P2: SFK c14 BLBS044-Cho October 15, 2009

268

8:28

Printer Name: Yet to Come

Fiber based ingredients

Chauhan K, Chauhan GS, Ahn JH. Synthesis and characterization of novel guar gum hydrogels and their use as Cu2+ sorbents. Bioresour Technol 2009;100(14):3599–3603. Cherbut C. Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract. Proc Nutr Soc 2003;62:95–99. Cherbut C, Ferrier L, Roze C, Anini Y, Blotti`ere H, Lecannu G, Galmiche JP. Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am J Physiol 1998;275(6 Pt 1): G1415–G1422. Chow J, Choe YS, Noss MJ, Robinson KJ, Dugle JE, Acosta SH, Garleb KA. Effect of a viscous fiber-containing nutrition bar on satiety of patients with type 2 diabetes. Diabetes Res Clin Pract 2007;76:335– 340. Coll AP, Farooqi IS, O’Rahilly S. The hormonal control of food intake. Cell 2007;129:251–262. Cummings DE. Ghrelin and the short- and long-term regulation of appetite and body weight. Physiol Behav 2006;89:71–84. Delargy HJ, Burley VJ, O’Sullivan KR, Fletcher RJ, Blundell JE. Effects of different soluble: insoluble fibre ratios at breakfast on 24-h pattern of dietary intake and satiety. Eur J Clin Nutr 1995;49:754–766. Delargy HJ, O’Sullivan KR, Fletcher RJ, Blundell JE. Effects of amount and type of dietary fibre (soluble and insoluble) on short-term control of appetite. Int J Food Sci Nutr 1997;48:67–77. Den Hond ED, Geypens B, Ghoos Y. Effect of high performance chicory inulin on constipation. Nutr Res 2000;5:731–736. de Roos N, Heijnen ML, de Graaf C, Woestenenk G, Hobbel E. Resistant starch has little effect on appetite, food intake and insulin secretion of healthy young men. Eur J Clin Nutr 1995;49:532–541. Dhillo WS. Appetite regulation: an overview. Thyroid 2007;17:433–445. Dobson CL, Davis SS, Chauhan S, Sparrow RA, Wilding IR. The effect of oleic acid on the human ileal brake and its implications for small intestinal transit of tablet formulations. Pharm Res 1999;16:92–96. Drucker DJ. The role of gut hormones in glucose homeostasis. J Clin Invest 2007;117:24–32.

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Fiber and Satiety

8:28

Printer Name: Yet to Come

269

Ellis PR, Apling EC, Leeds AR, Bolster NR. Guar bread: acceptability and efficacy combined. Studies on blood glucose, serum insulin and satiety in normal subjects. Br J Nutr 1981;46:267–276. Finocchiaro T, Birkett A, Okoniewska M. Resistant starch. In: Cho S, Samuel P (eds.). Handbook of Fiber Ingredients. Taylor Francis/CRC Press, Boca Raton, FL, 2009, pp. 205–246. French SJ, Read NW. Effect of guar gum on hunger and satiety after meals of differing fat content: relationship with gastric emptying. Am J Clin Nutr 1994;59:87–91. Frost GS, Brynes AE, Dhillo WS, Bloom SR, McBurney MI. The effects of fiber enrichment of pasta and fat content on gastric emptying, GLP-1, glucose, and insulin responses to a meal. Eur J Clin Nutr 2003;57:293–298. Geboes KP, Luypaerts A, Rutgeerts P, Verbeke K. Inulin is an ideal substrate for a hydrogen breath test to measure the orocaecal transit time. Aliment Pharmacol Ther 2003;18(7):721–729. Granfeldt Y, Drews A, Bj¨orck I. Arepas made from high amylose corn flour produce favorably low glucose and insulin responses in healthy humans. J Nutr 1995;125:459–465. Grimes DS, Gordon C. Satiety value of wholemeal and white bread. Lancet 1978;8:106. Grudell AB, Camilleri M. The role of peptide YY in integrative gut physiology and potential role in obesity. Curr Opin Endocrinol Diabetes Obes 2007;14:52–57. Hagander B, Asp NG, Efendic S, Nilsson-Ehle P, Lungquist I, Schersten B. Reduced glycemic response to beet-fibre meal in non-insulin-dependent diabetics and its relation to plasma levels of pancreatic and gastrointestinal hormones. Diabetes Res 1986;3(2):91–96. Hagander B, Asp NG, Ekman R, Nilsson-Ehle P, Schersten B. Dietary fibre enrichment, blood pressure, lipoprotein profile and gut hormones in NIDDM patients. Eur J Clin Nutr. 1989;43(1): 35–44. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 2008;27:104–119.

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270

8:28

Printer Name: Yet to Come

Fiber based ingredients

Heijboer AC, Pijil H, Van Den Hoek AM, Havekes LM, Romijn JA, Corssmit EPM. Gut-brain axis: regulation of glucose metabolism. J Neuroendocrinol 2006;18:883–894. Heini AF, Lara-Castro C, Schneider H, Kirk KA, Considine RV, Weinsier RL. Effect of hydrolyzed guar fiber on fasting and postprandial satiety and satiety hormones: a double-blind, placebo-controlled trial during controlled weight loss. Int J Obes Relat Metab Disord 1998;22:906–909. Heinonen MV, Karhunen LJ, Chabot ED, Toppinen LK, Juntunen KS, Laaksonen DE, Siloaho M, Liukkonen KH, Herzig KH, Niskanen LK, Mykk¨anen HM. Plasma ghrelin levels after two high-carbohydrate meals producing different insulin responses in patients with metabolic syndrome. Regul Pept 2007;138(2–3):118–125. Hlebowicz J, Darwiche G, Bj¨orgell O, Alm´er LO. Effect of muesli with 4 g oat beta-glucan on postprandial blood glucose, gastric emptying and satiety in healthy subjects: a randomized crossover trial. J Am Coll Nutr 2008;27:470–475. Hoad CL, Rayment P, Spiller RC, Marciani L, Alonso Bde C, Traynor C, Mela DJ, Peters HP, Gowland PA. In vivo imaging of intragastric gelation and its effect on satiety in humans. J Nutr 2004;134:2293– 2300. Holt SH, Miller JB. Particle size, satiety and the glycaemic response. Eur J Clin Nutr 1994;48:496–502. Holt SH, Miller JC, Petocz P, Farmakalidis E. A satiety index of common foods. Eur J Clin Nutr 1995;49:675–690. Hospers JJ, van Amelsvoort JMM, Weststrate JA. Amylose-to amylopectin ration in pastas affects postprandial glucose and insulin responses and satiety on males. J Food Sci 1994;59:1144–1149. Howarth NC, Saltzman E, Roberts SB. Dietary fiber and weight regulation. Nutr Rev 2001;59:129–139. Huda MS, Wilding JP, Pinkney JH. Gut peptides and the regulation of appetite. Obes Rev 2006;7:163–182. Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. National Academy Press, Washington, DC, 2002.

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Fiber and Satiety

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271

Juntunen KS, Niskanen LK, Liukkonen KH, Poutanen KS, Holst JJ, Mykk¨anen HM. Postprandial glucose, insulin, and incretin responses to grain products in healthy subjects. Am J Clin Nutr 2002;75:254–262. Kaplan RJ, Greenwood CE. Influence of dietary carbohydrates and glycaemic response on subjective appetite and food intake in healthy elderly persons. Int J Food Sci Nutr 2002;53:305–316. Karaki S, Tazoe H, Hayashi H, Kashiwabara H, Tooyama K, Suzuki Y, Kuwahara A. Expression of the short-chain fatty acid receptor, GPR43, in the human colon. J Mol Histol 2008;39(2):135–142. Keogh JB, Lau CW, Noakes M, Bowen J, Clifton PM. Effects of meals with high soluble fibre, high amylose barley variant on glucose, insulin, satiety and thermic effect of food in healthy lean women. Eur J Clin Nutr 2007;61:597–604. Kim H, Behall KM, Vinyard B, Conway JM. Short term satiety and glycemic responses after consumption of whole grains with various amounts of beta glucan. Cereal Foods World 2006;51:29–33. King NA, Craig SA, Pepper T, Blundell JE. Evaluation of the independent and combined effects of xylitol and polydextrose consumed as a snack on hunger and energy intake over 10 d. Br J Nutr 2005;93:911–915. Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 2006;8:21–34. Kovacs EM, Westerterp-Plantenga MS, Saris WH, Goossens I, Geurten P, Brouns F. The effect of addition of modified guar gum to a low-energy semisolid meal on appetite and body weight loss. Int J Obes Relat Metab Disord 2001;25:307–315. Kovacs EM, Westerterp-Plantenga MS, Saris WH, Melanson KJ, Goossens I, Geurten P, Brouns F. The effect of guar gum addition to a semisolid meal on appetite related to blood glucose, in dieting men. Eur J Clin Nutr 2002;56:771–778. Krotkiewski M. Effect of guar gum on body-weight, hunger ratings and metabolism in obese subjects. Br J Nutr 1984;52:97–105. Lavin JH, Read NW. The effect on hunger and satiety of slowing the absorption of glucose: relationship with gastric emptying and postprandial blood glucose and insulin responses. Appetite 1995;25:89–96.

P1: SFK/UKS P2: SFK c14 BLBS044-Cho October 15, 2009

272

8:28

Printer Name: Yet to Come

Fiber based ingredients

Levine AS, Tallman JR, Grace MK, Parker SA, Billington CJ, Levitt MD. Effect of breakfast cereals on short-term food intake. Am J Clin Nutr 1989;50:1303–1307. Liljeberg HG, Akerberg AK, Bj¨orck IM. Effect of the glycemic index and content of indigestible carbohydrates of cereal-based breakfast meals on glucose tolerance at lunch in healthy subjects. Am J Clin Nutr 1999;69:647–655. Longo WE, Ballantyne GH, Savoca PE, Adrian TE, Bilchik AJ, Modlin IM. Short-chain fatty acid release of peptide YY in the isolated rabbit distal colon. Scand J Gastroenterol 1991;26:442– 448. L´opez M, Lelliott CJ, Vidal-Puig A. Hypothalamic fatty acid metabolism: a housekeeping pathway that regulates food intake. Bioessays 2007a;29:248–261. L´opez M, Tovar S, V´azquez MJ, Williams LM, Di´eguez C. Peripheral tissue–brain interactions in the regulation of food intake. Proc Nutr Soc 2007b;66:131–155. Mattes RD. Effects of a combination fiber system on appetite and energy intake in overweight humans. Physiol Behav 2007;90:705–711. Meier JJ, Nauck MA. Glucagon-like peptide 1 (GLP-1) in biology and pathology. Diabetes Metab Res Rev 2005;21:91–117. Morgan LM, Tredger JA, Shavila Y, Travis JS, Wright J. The effect of non-starch polysaccharide supplementation on circulating bile acids, hormone and metabolite levels following a fat meal in human subjects. Br J Nutr 1993;70:491–501. Morgan LM, Tredger JA, Wright J, Marks V. The effect of soluble- and insoluble-fibre supplementation on post-prandial glucose tolerance, insulin and gastric inhibitory polypeptide secretion in healthy subjects. Br J Nutr 1990;64(1):103–110. Morley JE. Decreased food intake with aging. J Gerontol A Biol Sci Med Sci 2001;56:81–88. National Academy of Sciences. Diet and health: implications for reducing chronic disease risk. Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, DC. 1989.

P1: SFK/UKS P2: SFK c14 BLBS044-Cho October 15, 2009

Fiber and Satiety

8:28

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National Academy of Sciences. Eat for Life. Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, DC. 1992. Nguyen KN, Welsh JD, Manion CV, Ficken VJ. Effect of fiber on breath hydrogen response and symptoms after oral lactose in lactose malabsorbers. Am J Clin Nutr 1982;35:1347–1351. Nilsson AC, Ostman EM, Holst JJ, Bj¨orck IM. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast. J Nutr 2008;138:732–739. Noakes M, Clifton PM, Nestel PJ, Le Leu R, McIntosh G. Effect of high-amylose starch and oat bran on metabolic variables and bowel function in subjects with hypertriglyceridemia. Am J Clin Nutr 1996;64:944–951. O’Donovan D, Feinle-Bisset C, Chong C, Cameron A, Tonkin A, Wishart J, Horowitz M, Jones KL. Intraduodenal guar attenuates the fall in blood pressure induced by glucose in healthy older adults. J Gerontol A Biol Sci Med Sci 2005;60:940–946. Panouill´e M, Larreta-Garde V. Gelation behaviour of gelatin and alginate mixtures. Food Hydrocolloids 2009;23:1074–1080. Pasman WJ, Saris WH, Wauters MA, Westerterp-Plantenga MS. Effect of one week of fibre supplementation on hunger and satiety ratings and energy intake. Appetite 1997;29:77–87. Paxman JR, Richardson JC, Dettmar PW, Corfe BM. Daily ingestion of alginate reduces energy intake in free-living subjects. Appetite 2008;51:713–719. Pelkman CL, Navia JL, Miller AE, Pohle RJ. Novel calcium-gelled, alginate-pectin beverage reduced energy intake in nondieting overweight and obese women: interactions with dietary restraint status. Am J Clin Nutr 2007;86:1595–1602. Pereira MA, Ludwig DS. Dietary fiber and body-weight regulation. Observations and mechanisms. Pediatr Clin North Am 2001;48:969–980. Pittaway JK, Ahuja KD, Robertson IK, Ball MJ. Effects of a controlled diet supplemented with chickpeas on serum lipids, glucose tolerance, satiety and bowel function. J Am Coll Nutr 2007;26(4):334–340.

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Porrini M, Crovetti R, Testolin G, Silva S. Evaluation of satiety sensations and food intake after different preloads. Appetite 1995;25:17–30. Qu´ılez J, Bull´o M, Salas-Salvad´o J. Improved postprandial response and feeling of satiety after consumption of low-calorie muffins with maltitol and high-amylose corn starch. J Food Sci 2007;72:S407–S411. Rigaud D, Paycha F, Meulemans A, Merrouche M, Mignon M. Effect of psyllium on gastric emptying, hunger feeling and food intake in normal volunteers: a double blind study. Eur J Clin Nutr 1998;52:239–245. Robertson MD, Bickerton AS, Dennis AL, Vidal H, Frayn KN. Insulinsensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin Nutr 2005;82:559– 567. Robertson MD, Currie JM, Morgan LM, Jewell DP, Frayn KN. Prior short-term consumption of resistant starch enhances postprandial insulin sensitivity in healthy subjects. Diabetologia 2003;46:659– 665. Sajilata MG, Singhal RS, Kulkarni PR. Resistant starch—a review. Comp Rev Food Sci Food Safety 2006;5:1–17. Sandstr¨om B, Andersson H, Bosa´eus I, Flakheden T, Goransson H, Melkersson M. The effect of wheat bran on the intake of energy and nutrients and on serum mineral levels in constipated geriatric patients. Hum Nutr Clin Nutr 1983;37:295–300. Saltzman E, Moriguti JC, Das SK, Corrales A, Fuss P, Greenberg AS, Roberts SB. Effects of a cereal rich in soluble fiber on body composition and dietary compliance during consumption of a hypocaloric diet. J Am Coll Nutr 2001;20:50–57. Singh B, Chauhan N. Modification of psyllium polysaccharides for use in oral insulin delivery. Food Hydrocolloids 2009;23:928–935. Slavin J. Dietary fiber and body weight. Nutrition 2005;21:411–418. Slavin J, Green H. Dietary fibre and satiety. Nutr Bull 2007;32:32–42. Smeets A, Gelencser A, Salgo AM, Westerperp-Plantenga M. The acute effects of a lunch containing resistant starch on energy and substrate utilization, ghrelin, GLP-1, PYY concentrations, and satiety. Appetite 2008;51:400.

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Stevens J, Levitsky DA, VanSoest PJ, Robertson JB, Kalkwarf HJ, Roe DA. Effect of psyllium gum and wheat bran on spontaneous energy intake. Am J Clin Nutr 1987;46:812–817. Stubbs RJ. Peripheral signals affecting food intake. Nutrition 1999;15:614–625. Stubbs RJ, Ritz P, Coward WA, Prentice AM. Covert manipulation of the ratio of dietary fat to carbohydrate and energy density: effect on food intake and energy balance in free-living men eating ad libitum. Am J Clin Nutr 1995;62:330–337. Surgeon General’s report on Nutrition and Health. U.S. Department of Health and Human Services. Government Printing Office, Washington, DC, 1988. Turnbull WH, Thomas HG. The effect of a Plantago ovata seed containing preparation on appetite variables, nutrient and energy intake. Int J Obes Relat Metab Disord 1995;19:338–342. Ueno H, Yamaguchi H, Mizuta M, Nakazato M. The role of PYY in feeding regulation. Regul Pept 2008;145:12–16. USDA. Dietary Guidelines for Americans. 2005. Available online at http://www.usda.gov/cnpp/DietGd.pdf. van Amelsvoort JM, Weststrate JA. Amylose–amylopectin ratio in a meal affects postprandial variables in male volunteers. Am J Clin Nutr 1992;55:712–718. van Nieuwenhoven MA, Kovacs EM, Brummer RJ, Westerterp-Plantenga MS, Brouns F. The effect of different dosages of guar gum on gastric emptying and small intestinal transit of a consumed semisolid meal. J Am Coll Nutr 2001;20:87–91. Weickert MO, Mohlig M, Koebnick C, Holst JJ, Namsolleck P, Ristow M, Osterhoff M, Rochlitz H, Rudovich N, Spranger J, Pfeiffer AFH. Impact of cereal fibre on glucose-relating factors. Diabetologia 2005;48:2343–2353. Weickert MO, M¨ohlig M, Sch¨ofl C, Arafat AM, Otto B, Viehoff H, Koebnick C, Kohl A, Spranger J, Pfeiffer AF. Cereal fiber improves whole-body insulin sensitivity in overweight and obese women. Diabetes Care 2006a;29(4):775–780.

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Weickert MO, Spranger J, Holst JJ, Otto B, Koebnick C, M¨ohlig M, Pfeiffer AF. Wheat-fibre-induced changes of postprandial peptide YY and ghrelin responses are not associated with acute alterations of satiety. Br J Nutr 2006b;96:795–798. Weststrate JA, van Amelsvoort JM. Effects of the amylose content of breakfast and lunch on postprandial variables in male volunteers. Am J Clin Nutr 1993;58:180–186. Whelan K, Efthymiou L, Judd PA, Preedy VR, Taylor MA. Appetite during consumption of enteral formula as a sole source of nutrition: the effect of supplementing pea-fibre and fructo-oligosaccharides. Br J Nutr 2006;96(2):350–356. Willis HJ, Eldridge AL, Beiseigel J, Thomas W, Slavin JL. Greater satiety response with resistant starch and corn bran in human subjects. Nutr Res 2009;29:100–105. Wood PJ. Relationships between solution properties of cereal beta glucans and physiological effects—a review. Trends Food Sci Technol 2004;15:313–320. Zarling EJ, Edison T, Berger S, Leya J, DeMeo M. Effect of dietary oat and soy fiber on bowel function and clinical tolerance in a tube feeding dependent population. J Am Coll Nutr 1994;13:565–568.

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APPENDIX

Global Suppliers of Ingredients for Weight Control Fiber and Carbohydrate-Based Ingredients National Starch for Hi Maize 5 in 1 fiber and Novelose www.foodinoovation.com Headquarters National Starch and Chemical Company 10, Finderne Ave Bridgewater, NJ 08807, USA Phone: 1-800 743-6343 UK, Ireland, Nordic Europe Dagmar Krappe Gruener Deich 110 20097 Hamburg, Germany Phone: +49 (0) 40-23915-0 Australia 7–9 Stanton Road Seven Hills, Sydney NSW 2147, Australia Phone: +61 2-9624-6022 277

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Roquette for NUTRIOSE: resistant dextrins www.roquette.com Headquarters ROQUETTE FRERES La Haute Loge 62080 Lestrem cedex, France Phone: + 33 3 21 63 36 00 Fax: + 33 3 21 63 38 50 Roquette America, Inc. 1417 Exchange Street Keokuk, IA 52632 Phone: 319-524-5757 Fax: 319-526-2345 FMC for hydrocolloids including alginate www.fmc.com Headquarters 1735 Market Street Philadelphia, PA 19103, USA Phone: 1-215-299-6000 Fax: 1-215-299-5998 TIC gums for hydrocolloids including alginate www.ticgums.com Headquarters 4609 Richlynn Dr. Belcamp, MD 21017, USA Phone: 1-410-273-7300

Lipid-Based Ingredients Cognis Nutrition and Health for conjugated linolenic acid http://www.cognis.com

Appendix

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Appendix

Head Office: Cognis GmbH Postfach 13 01 64 40551 D¨usseldorf, Germany Phone: +49 211 7940 0 Cognis North America Headquarters 5051 Estecreek Drive Cincinnati, OH 45232-1446, USA North America Phone: 1-800-254-1029 International Phone: +1-513-482-3000 Cognis Australia Pty. Ltd. 4 Saligna Drive Tullamarine VIC, 3043, Australia Phone: +61 3 9933 3500 Fax: +61 3 9933 3582 Cognis Japan Ltd. 20F Sphere Tower Tennoz 2-2-8 Higashi-Shinagawa Shinagawa-ku Tokyo 140-0002, Japan Phone: +81 (0)3 5769 6440 Fax: +81 (0)3 5769 6439 DSM Nutritional Products, Inc. for novel fat emulsion (Fabuless) www.dsm.com Headquarters: 45 Waterview Blvd Parsippany, New Jersey 07054, USA Phone: 1-908- 475-7412 Lipid Nutrition B.V. for PinnothinTM (Korean pine nut oil) www.lipidnutrition.com Head Office: Hogeweg 1 1520 AA Wormerveer, The Netherlands

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Direct Phone: +31 (0)75 629 22 11; +31 (0)75 629 2911 Fax: +31 (0)75 629 28 17 [email protected] Lipid Nutrition B.V. North America W. Durkee Road 24708 Channahon, IL 60410, USA Phone: +815 730 5244 [email protected] Lipid Nutrition B.V. Asia Pacific Level 10, Two IOI Square Putrajaya, Malaysia 62502 Phone: +603 8947 8888 The Procter & Gamble Company for sucrose polyester (Olestra) www.pgfoodingredients.com www.olean.com Customer Service P&G Food Ingredients 11530 Reed Hartman Hwy Cincinnati, OH 45241, USA Phone: 1-800-477-8899

Protein-Based Ingredients GELITA Group AG for Gelatine (GELITA) www.gelita.com Headquarters: Gammelsbacherstr. 2 69412 Eberbach, Germany Phone: +49 (0) 62 71 / 84 - 01 Fax: +49 (0) 62 71 / 84 - 27 00 GELITA USA Inc. 2445 Port Neal Industrial Rd. Sergeant Bluff, IA 51054, USA Phone: +1 712 943 5516 Fax: +1 712 943 3372

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GELITA Mexico S. de R.L. de C.V. Emiliano Zapata S/N Col. Emiliano Zapata Lerma, Mex. C.P. 52000, Mexico Phone: +52 7 28 / 285 0101 Fax: +52 7 28 / 285 1856 GELITA Nederland B.V. Handelsweg 24 9563 TR Ter Apelkanaal, The Netherlands Phone: +31 (0) 5 99 / 34 57 00 Fax: +31 (0) 5 99 / 47 05 08 GELITA Australia Pty. Ltd. (P.O. Box 276, Botany NSW 1455) Unit L2, Level 2, 2 A Lord Street Botany NSW 2019, Australia Phone: +61 (2) 95 78 - 70 00 Fax: +61 (2) 95 78 - 70 50 National Dairy Council for dairy products including whey protein and casein www.nationaldairycouncil.com 10255 West Higgins Rd, Suite 900 Rosemont, IL, USA [email protected] Phone: 1-312-240-2880; 1-847-803-2000 Agri-Mark for whey protein www.agrimarkwheyprotiens.com Phone: 1-608-783-9755 Fax: 1-608-783-9778 American Casein Company for casein www.americancasein.com Phone: 1-609-387-3130 Fax: 1-609-387-7204

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Davisco Foods for whey protein www.daviscofoods.com Phone: 1-800-757-7611 or 952-914-0400 Fax: 952-914-0887 Meiji for dairy products www.meiji-milk.com Tokyo, Japan Phone: +81-3-5653-0305 Fax: +81-3-5653-0290 Solae for soy protein www.solae.com 4300 Duncan Avenue St. Louis, MO 63110, USA Phone: 1-800-325-7108

Other Ingredients Pharma Foods International for green tea extracts www.pharmafoods.co.jp Phone: +81-75-394-8600 Fax: +81-75-394-0099 Lonza for l-carnitine and derivatives www.carnitine.com Phone: 800-955-7426 Fax: 201-794-2695 [email protected] Orcas International for l-carnitine www.orcas-intl.com Phone: 973-252-7100 Fax: 973-252-7104 [email protected] InterHealth for hydroxycitric acid www.interhealthusa.com Phone: 707-751-2800 Fax: 707-751-2802

Appendix

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Index ACO. See Acyl-CoA oxidase (ACO) Activated protein kinase (AMPK), 143 regulation of ROS and, 183–184 Acyl-CoA oxidase (ACO), 169 Adipocyte marker proteins, antiadipogenic effect of green tea and, 186–187 Adipocytes, and obesity, 177–178 Adipocyte-specific secretory factor (ADSF), 182 Adipogenesis, soy peptides reduces adiposity by inhibition of, 144–147 Adipose tissue, role in obesity, 97–98 Adiposity reduction, by soy peptides inhibiting lipid absorption and regulation of lipid metabolism, 141–143 inhibition of adipogenesis, 144–147 Ad libitum, 12 ADSF. See Adipocyte-specific secretory factor (ADSF) Air displacement pletismography (Bod Pod), 9 α-lactalbumin, 113–115 Alginate, 243 studies reporting positive effects of, 244 Amino acids arginine (ARG), 129 AMPK. See Activated protein kinase (AMPK) Animal models, to study effects of calcium and dairy intake, 80–81 Anthropometry–skinfold measurements, for measuring body fat, 9

Antiadipogenic effect of EGCG CDK 2 dependent signaling pathway, 182–183 via activation of AMPK, 183 via ERK dependent signaling pathway, 180–182 via regulation of ROS, 183–184 via resistin, 182 of green tea via downregulation of adipocyte marker proteins and its target genes, 186–187 via inhibition of lipogenic enzymes, 184–186 Appetite, 26 CCK release and effects on, 27 Satiety hormones effects on, 27 serotonin in regulation of, 110 ARG. See Amino acids arginine (ARG) Barley, 246 studies reporting no significant effects of, 249 studies reporting positive effects of, 247–248 β-conglycinin hydrolysates, 145, 147 BIA. See Bioelectrical impedance (BIA) Bioactive peptides, 136 Bioelectrical impedance (BIA), 9 Black soy peptide (BSP), 140–141 BMI. See Body mass index (BMI)

283

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284 Body composition. See also Body weight calcium and dairy products effects on, 70–73 changes after consumption of control/high-catechin, 190–191 CLA effects on, 8–9 clinical studies of CLA on, 10–15 exercise subjects with BMI less then 25, 12 long-term studies, 10–11 in subjects with BMI greater then 25, 12–13 methods for measuring, 9–10 satiety of high-protein diet and change in, 128–129 Body fat control, in animals by RD, 222 Body fat mass, CLA mechanism for decreasing, 5–6 Body fat reduction. See also Adiposity reduction by CLA, 6–15 effect on body shape, 13 effects on body composition and body weight, 8–10 meta-analysis study, 14–15 overview, 6–7 quality of material used for, 7–8 effects of high-calcium and high-dairy diets on, 71 Body mass index (BMI) body weight and, 9 CLA and exercise subjects with less then 25, 12 CLA and subjects with greater then 25, 12–13 Body shape, and CLA, 13 Body weight. See also Body composition calcium and dairy products effects on, 70–73 CLA effects on, 8–9 green tea effects on, 164–166 methods for measuring, 9–10 reduction by soy peptides, 143–144 role of calcium consumption on, 79 β-pancreatic cells, 97 BSP. See Black soy peptide (BSP)

Printer Name: Yet to Come

Index Caffeine. See also Capsaicin efficacy of long-term experiments for, 166–167 short-term experiments for, 163–164 food/supplement applications of, 170–171 global suppliers of, 171 mechanisms of action of, 167–169 patent of, 171 safety of, 169–170 Calcium. See Dietary calcium Calcium modulation, of adiposity, 81 Calipers, for measuring body fat, 9 Caloric intake. See also Food intake in adults during 1971-2000, 44 efficacy of Olibra
r and, 56–58 PinnoThinTM FFA effects on, 35 Caloric value, of RD, 219–220 cAMP. See Cyclic amino mono phosphate (cAMP) Capsaicin, 201–208. See also Caffeine effects on feeding behaviors, 203–205 efficacy of, 202–206 food/supplement applications of, 207 weight control and, 208 mechanism of actions, 206 overview, 201–202 patents on, 207 role in weight control, 207–208 safety of, 206–207 suppliers of, 208 thermogenic effect of, 203 Capsicum, 202 CARDIA. See Cumulative incidence observational population-based prospective study (CARDIA) Carnitine palmitoyltransferase (CPT) activity, 6 Casein, 123 effects on satiety long-term, 126–127 short-term, 123–126 food supplement applications of, 130 global suppliers of, 130 patents on, 130

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Index Catechins and caffeine, 168–169 effect on gene expression of UCP, 169 green tea, 167 Catechol-O-methyltransferase (COMT), 167 CCK. See Cholecystokinin (CCK) CCK1 R. See CCK1 receptor (CCK1R) CCK1 receptor (CCK1 R), 140 CCK receptors, 140 CDK 2. See Cyclin-dependent kinase 2 (CDK 2) Central nervous system, regulation of satiety and FI by, 229–233 Cheese, 83 r , 105 Cheese product versus GELITA
Chocolate dessert, ingredients of, 106 Cholecystokinin (CCK), 26 effects on appetite, 27 PinnoThinTM effects on releasing, 29–30, 31–32 regulation of FI, 232 released in proximal small intestine, 26 c-Jun-N-terminal kinases (JNK), 180 CLA. See Conjugated linoleic acids (CLA) Claims, on CLA, 16–17 CLA products GC–MS profile of unpatented and patented, 8 CognisGmbH, 5 Collagen, 102–105 characteristics of, 102 development of calorie-reduced products and, 103 used for fat reduction, 103 used in meat-producing industry, 102–103 water-binding capacity of, 103 COMT. See Catechol-O-methyltransferase (COMT) COMTL allele, 167–168 Conjugated linoleic acids (CLA) absorption and metabolism of, 5 application in functional foods, 17 body fat reduction by, 6–15 effect on body shape, 13

285 effects on body composition and body weight, 8–10 meta-analysis study, 14–15 overview, 6–7 quality of material used for, 7–8 carnitine palmitoyltransferase activity and, 6 chemical structure of isomers, 4 claims on, 15–16 and clinical studies on body composition, 10–15 exercise subjects with BMI less then 25, 12 long-term studies, 10–11 in subjects with BMI greater then 25, 12–13 in dairy products and ruminant meat, 4–5 efficacy in foods, 13–14 labeling of, 16 and lipoprotein lipase activity, 5–6 mechanism for decreasing body fat mass, 5–6 mixed isomers and safety evaluation, 15–16 overview, 3–5 regulatory status of, 16–17 sensory impact of, 19 stability of, 18–19 CPT activity. See Carnitine palmitoyltransferase (CPT) activity Critical Reviews in Food Science and Nutrition, 49 Cumulative incidence observational population-based prospective study (CARDIA), 77 Cyclic amino mono phosphate (cAMP), 168 Cyclin-dependent kinase 2 (CDK 2), 182–183 Dairy products cheese, 83 food application of, 82–84 nonfat dry milk, 83 overview, 68–69

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286 Dairy products (Cont.) patent of, 84 scientific evidence on efficacy and mechanism of action of, 69–82 animal models and in vitro studies, 80–81 observational studies and secondary analyses of clinical trials, 75–80 randomized clinical trials, 69–75 summary of, 82 yogurt, 83 DEXA. See Dual energy X-ray absorptiometry (DEXA) d-fenfluramine, 110 Diet and Health: Implications for Reducing Chronic Disease Risk, 44 Dietary calcium effect on energy and substrate metabolism, 74 effects on body weight, 70–73 energy expenditure and consumption of, 73–75 food application of, 82–84 overview, 68–69 patent of, 84 scientific evidence on efficacy and mechanism of action of, 69–82 animal models and in vitro studies, 80–81 observational studies and secondary analyses of clinical trials, 75–80 randomized clinical trials, 69–75 summary of, 82 Dietary fiber alginate, 243 authoritative statements related to, 234–235 barley, 246 guar gum, 235–243 inulin, oligofructose, and polydextrose, 254–259 mechanism of actions, 233–234 oat β-glucan, 243–245 psyllium, 235 resistant starches, 259–265 soy fiber, oat hull fiber, and sugar beet fiber, 246–254 wheat and wheat bran, 246

Printer Name: Yet to Come

Index Dietary proteins, satiating properties of, 113 Dieting versus lifestyle, 49–50 Digestibility, of RD, 218–219 Dual energy X-ray absorptiometry (DEXA), 9 EC. See Epicatechin (EC) ECG. See Epicatechin-3-gallate (ECG) EGC. See Epigallocatechin (EGC) EGCG. See Epigallocatechin-3-gallate (EGCG) EMS. See Eosinophilia-myalgia syndrome (EMS) Energy expenditure calcium and dairy foods consumption, 73–75 catechins and caffeine increase, 168–169 satiety of high-protein diet and increase in, 128 soy peptides reduces body weight by increasing, 143–144 Energy intake. See Caloric intake Eosinophilia-myalgia syndrome (EMS), 112 Epicatechin (EC), 179 Epicatechin-3-gallate (ECG), 179 Epigallocatechin (EGC), 179 Epigallocatechin-3-gallate (EGCG), 177 antiadipogenic effect of CDK 2 dependent signaling pathway, 182–183 via activation of AMPK, 183 via ERK dependent signaling pathway, 180–182 via regulation of ROS, 183–184 via resistin, 182 antiobesity mechanisms of, 180–187 inhibition of lipid-related enzymes in cell-free systems, 185 structures of, 179 ERK. See Extracellular signal-regulated kinase (ERK) Extracellular signal-regulated kinase (ERK), 180–182

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Index FabulessTM . See Olibra
r Fat-free mass (FFM), 60 influence of protein, ARG and LYS on, 129 Fat/oil replacement formulation matrix, of olestra, 51 Fecal excretion, calcium and dairy foods consumption, 73–75 Fermentation, of RD, 219 FFA. See Free fatty acids (FFA) FFM. See Fat-free mass (FFM) FI. See Food intake (FI) Food consumption, regulated by hypothalamus, 100 Food intake (FI). See also Caloric intake mechanism of action of soy peptides regulates, 137–141 olive oil placebo effects on, 33 PinnoThinTM effects on, 28–29, 33 ad libitum, 33–36 regulation by central nervous system, 229–233 long-term, 232–233 short-term, 229–232 serotonin in regulation of, 110 Four-compartment model, 9 Free fatty acids (FFA), 27 enzymatic hydrolysis of triglycerides into, 28 role in release of satiety hormones, 27–28 Functional foods, CLA application in, 17 Garcinia cambogia, 141 Gastric emptying, 230 GDH. See Glutamate dehydrogenase (GDH) Gelatin, 95–107 characteristics of, 102 collagenous peptides and, 102 dessert created by using, 104 raw material for, 101 technological properties of, 101–106 gelling properties, 105 used in meat-producing industry, 102–103

287 r mayonnaise, composition of, GELITA
104 r versus cheese product, 105 GELITA
Ghrelin, 26 regulation of, 232 GLP-1. See Glucagon-like peptide-1 (GLP-1) Glucagon, 144 Glucagon-like peptide-1 (GLP-1), 26 effects on appetite, 27 Olibra
r effects on, 59 regulation of FI and, 231 Glutamate dehydrogenase (GDH), 188 Glycemic response, of RD, 222–223 Glycomacropeptide (GMP), 123, 125 GMP. See Glycomacropeptide (GMP) Green tea, 178–179 antiadipogenic effect via downregulation of adipocyte marker proteins and its target genes, 186–187 via inhibition of lipogenic enzymes, 184–186 clinical studies of, 189–192 efficacy of long-term experiments for, 164–166 short-term experiments for, 162–163 epidemiological observation of, 189–192 food/supplement applications of, 170–171 global suppliers of, 171 insulin-potentiating activity by, 187–189 mechanisms of action of, 167–169 patent of, 171 safety of, 169–170 Guar gum, 235–243 studies reporting no significant effects of, 242 studies reporting positive effects of, 239–241 Gut hormones, related to satiety, 231

HDF. See Human diploid fibroblasts (HDF) HDL. See High-density lipoproteins (HDL)

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288 High-density lipoproteins (HDL), 97 High-protein diet adverse effects of, 129–130 mechanisms to increase satiety of, 127–129 change in body composition, 128–129 changes in concentration of hormones/metabolites, 127–128 increase in energy expenditure, 128 during weight loss/maintenance, 122 Hormone-sensitive lipase (HSL), 168 HSL. See Hormone-sensitive lipase (HSL) 5-HTP. See 5-hydroxytryptophan (5-HTP) Human diploid fibroblasts (HDF), 184 Hunger. See also Satiety defined, 26 ratings after ingestion of α-lactalbumin, 114 Hydrodensitometry weighing, for body fat, 9 5-hydroxytryptamine. See Serotonin 5-hydroxytryptophan (5-HTP), 110, 112–113 Hypothalamus arcuate nucleus of, 229 food consumption regulated by, 100 serotonin role in regulation of appetite and food intake, 110 IGF-1. See Insulin-like growth factor-1 (IGF-1) Ileal brake, 230 Insulin-like growth factor-1 (IGF-1), 128 Insulin-potentiating activity, by green tea, 187–189 Insulin release, obesity and, 97–98 Insulin resistance syndrome (IRS), 76–77 Inulin, 254–259 studies reporting no significant effects of, 259 studies reporting positive effects of, 258 IRS. See Insulin resistance syndrome (IRS)

Printer Name: Yet to Come

Index JNK. See c-Jun-N-terminal kinases (JNK) Labeling, of CLA, 16 Large neutral amino acids (LNAA), 111, 113 LDL. See Low-density lipoproteins (LDL) LDL-R transcription, by soybean, 142–143 Lifestyl versus dieting, 49–50 Lipid absorption, soy peptides reduces adiposity by inhibiting, 141–143 Lipid metabolism, soy peptides reduces adiposity by regulating, 141–143 Lipogenic enzymes, antiadipogenic effect of green tea, 184–186 Lipoprotein lipase (LPL) activity, 5–6 LNAA. See Large neutral amino acids (LNAA) Low-density lipoproteins (LDL), 97 LPL activity. See Lipoprotein lipase (LPL) activity l-tryptophan, 111–113 serotonin synthesized by, 110–111 LYS. See Lysine (LYS) Lysine (LYS), 129 MAPK. See Mitogen-activated protein kinases (MAPK) MCAD. See Medium-chain acyl-CoA dehydrogenase (MCAD) Medium-chain acyl-CoA dehydrogenase (MCAD), 169 Metabolic syndrome. See also Obesity defined, 98 therapeutic options for, 98–101 Metabolizable energy versus net metabolizable energy, 99–100 Mitogen-activated protein kinases (MAPK), 180 Monoglyceride, 28 Monounsaturated fatty acids (MUFA), 28 MUFA. See Monounsaturated fatty acids (MUFA) National Weight Control Registry, 49 Near-infrared interactance (NIR), 9 Net energy value (NEV), of RD, 219–220

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Index Net metabolizable energy versus metabolizable energy, 99–100 NIR. See Near-infrared interactance (NIR) Nondialyzed soy protein hydrolysate (NSPH), 141–142 Nonfat dry milk, 83 No-observable adverse effect levels (NOAEL), of RD, 217 Norepinephrine (NE), 167 NSPH. See Nondialyzed soy protein hydrolysate (NSPH) r . See Resistant dextrin NUTRIOSE
(RD) r FB, 216, 217 NUTRIOSE
Nutrition, 96–97 Oat β-glucan, 243 studies reporting no significant effects of, 245 Oat fiber studies reporting no significant effects of, 255 Oat hull fiber, 246–254 Obesity. See also Metabolic syndrome adipocytes role in, 177–178 adipose tissue and, 97–98 analysis of, medical perspective, 97–98 olestra and, 47 weight maintenance for, 122 Obesity Reviews, 49 Olestra dieting versus lifestyle, 49–50 evolution of, 45–47 fat/oil replacement formulation matrix, 51 molecule, 46 potential food applications of, 50 role in cardiovascular and metabolic risk factors, 50–52 role in reducing fat-soluble environmental contaminants in body, 52 role in weight prevention, loss, and maintenance, 47–48 r Olibra
constituents of, 56 efficacy of, 56–60

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289 long-term experiments for, 58–60 short-term experiments for, 56–58 food/supplement applications of, 61–62 global suppliers of, 62 mechanisms of action, 61 patent, 62 safety aspect of, 61 Oligofructose (OF), 254–259 Olive oil placebo effects on CCK and GLP-1 release, 31 effects on food intake, 33 Oolong tea, insulin activity ratios in, 188 Peptide tyrosine tyrosine (PYY), 26 effects on appetite, 27 regulation of, 231–232 P&G. See Procter & Gamble Company (P&G) Phosphodiesterase, 168 Pine nut consumption, history of, 37 PinnoThinTM , 28 effects on in vitro CCK release, 29–30 effects on satiety and food intake, 28–29 food applications of, 36–37 and history of pine nut consumption, 37 unsaturated fatty acids found in, 29 in vivo effects on satiety hormones, 30–33 PinnoThinTM FFA effects on caloric intake, 35 effects on CCK and GLP-1 release, 31 effects on food intake, 33, 35 PinnoThinTM TG effects on CCK and GLP-1 release, 31 effects on food intake, 33 Pinus Koraiensis, 28 Polydextrose, 254–259 studies reporting effects of, 260 Polyunsaturated fatty acids (PUFA), 28 Preadipocyte factor-1 (pref-1), 145 increase by SPP and alcalase soy hydrolysates, 146 Preadipocytes, 145–146 Pref-1. See Preadipocyte factor-1 (pref-1) Procter & Gamble Company (P&G), 43, 45

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290 Protein-based diet exerts, effects on weight loss, 99–100 Psyllium, 235 studies reporting no significant effects of, 238 studies reporting positive effects of, 236–237 PUFA. See Polyunsaturated fatty acids (PUFA) Pyruvate, 168 PYY. See Peptide tyrosine tyrosine (PYY) RD. See Resistant dextrin (RD) Reactive oxygen species (ROS), 183–184 REE. See Resting energy expenditure (REE) Regulatory status, of CLA, 16–17 Resistant dextrin (RD) body fat control in animals by, 222 caloric value, 219–220 digestibility of, 218–219 effects on satiety, 221–222 glycemic response and, 222–223 fermentation of, 219 overview, 215–216 safety of, 216–217 in humans, 217–218 Resistant starches (RS), 259–265 studies reporting no significant effects of, 263–264 studies reporting positive effects of, 261–262 Resistin (RSTN), 182 Resting energy expenditure (REE), 59–60 FFM and, 60 Resting metabolic rate (RMR), 12 RMR. See Resting metabolic rate (RMR) ROS. See Reactive oxygen species (ROS) RSTN. See Resistin (RSTN) Satiety. See also Hunger authoritative statements related to, 234–235 clinical methods for measuring, 228–229 definition of, 26, 227–228 gut hormones related to, 231

Printer Name: Yet to Come

Index mechanisms to increase high-protein diet, 127–129 PinnoThinTM effects on, 28–29, 32 regulation by central nervous system, 229–233 side effects of, 129–130 Satiety hormones activity of, 26–27 effects on appetite, 27 FFA role in release of, 27–28 physiological factors affecting, 232–233 PinnoThinTM in vivo effects on, 30–33 Saturated fatty acids (SFA), 28 SBF. See Sugar beet fiber (SBF) SCFA. See Short-chain fatty acids (SCFA) Serotonin defined, 110 dietary amino acid interventions to increase precursor, 111–115 α-lactalbumin, 113–115 5-HTP, 112–113 l-tryptophan, 111–113 role in regulation of appetite and food intake, 110 synthesized by l-tryptophan, 110–111 SFA. See Saturated fatty acids (SFA) Short-chain fatty acids (SCFA), 218, 219, 233 SNS. See Sympathetic nerve system (SNS) Soy, 123 effects on satiety long-term, 126–127 short-term, 123–126 food supplement applications of, 130 global suppliers of, 130 patents on, 130 Soy fiber, 246–254 studies reporting no significant effects of, 256 Soy hydrolysate products inhibitory effects on preadipocyte proliferation, 145 Soy peptides antiobesity effects of, 138–139 dietary, 142 efficacy and mechanisms of action in weight control, 137–147

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Printer Name: Yet to Come

Index by increasing energy expenditure and thermogenesis, 143–144 by suppressing food intake, 137–141 food applications of, 147–148 global suppliers of, 149 role in reducing adiposity by inhibiting lipid absorption and regulation of lipid metabolism, 141–143 by inhibition of adipogenesis, 144–147 safety of, 148–149 Soy products, 150–151 Soy-purified peptides (SPP), 145 pref-1 increased by, 146 SPP. See Soy-purified peptides (SPP) STAT3 phosphorylation, 141 Substrate oxidation, calcium and dairy foods consumption, 73–75 Sugar beet fiber (SBF), 246–254 studies reporting no significant effects of, 257 Sympathetic nerve system (SNS), 167 capsaicin effects on thermogenesis, 206 Thermogenesis capsaicin increases, 206 soy peptides reduces body weight by increasing, 143–144 r CLA, 7 Tonalin
Tonalin TG 80, chemical structure of CLA isomers of, 4 Total body electrical conductivity (TOBEC), 9 Transient receptor potential vanilloid receptor1 (TRPV1), 206 Triglycerides, enzymatic hydrolysis into FFA, 28 TRPV1. See Transient receptor potential vanilloid receptor1 (TRPV1) UCP. See Uncoupling proteins (UCP) Uncoupling proteins (UCP), 169 United States National Research Council, 44

291 Unsaturated fatty acids, found in PinnoThinTM , 29 VAS. See Visual analogue scales (VAS) Visual analogue scales (VAS), to evaluate appetite sensations, 31–33 Water-binding capacity, of collagen, 103 Weight control/maintenance capsaicin for, 207–208 high protein intake during, 122 for obesity, 122 olestra and, 47–48 Olibra
r role in, 59 soy peptides in, 137–147 by suppressing food intake, 137–141 Weight loss caffeine role in, 166–167 dieting versus lifestyle, 49–50 high protein intake during, 122 olestra role in, 47–48 Olibra
r role in, 60 protein-based diet exerts effects on, 99–100 Wheat, 246 studies reporting no significant effects of, 251 studies reporting positive effects of, 250 Wheat bran, 246 studies reporting no significant effects of, 253 studies reporting positive effects of, 252 Whey, 123 effects on satiety long-term, 126–127 short-term, 123–126 food supplement applications of, 130 global suppliers of, 130 patents on, 130 Yogurt, 83