Sports Med 2009; 39 (12): 977-979 0112-1642/09/0012-0977/$49.95/0
ACKNOWLEDGEMENT
ª 2009 Adis Data Information BV. All rights reserved.
Dear Reader As we reach the final issue of the year for Sports Medicine, we hope that you have found the articles published throughout 2009 to be both interesting and informative. The editor and publishing staff have appreciated the high quality of content contributed to the journal this year and the forward programme for 2010 looks set to build on these standards as we continue to provide you with the very best of drug safety research and opinion. We were delighted this year to launch our new interactive online platform, AdisOnline, which we hope will help you navigate our content. The platform includes many new features including access to featured articles and collections, ability to see the most viewed and e-mailed articles across all titles and provides many personalization features. The platform also allows exporting of figures to PowerPoint. The high quality of a number of our journal titles was further recognized in the new ISI impact factors for 2008. The impact factor of Clinical Drug Investigation increased to 1.3 (an increase of over 100%), Molecular Diagnosis and Therapy increased to 2.14 (an increase of 54%), Drugs increased to 4.13 and PharmacoEconomics increased to 2.8. Clinical Pharmacokinetics also registered an increase in its impact factor. The impact factor of Drug Safety held steady for another year a 3.537, compared to 3.536 last year, illustrating the consistent importance to the literature of the articles the journal publishes. Adis has been providing quality content to healthcare professionals for nearly 40 years. This year saw several of our titles celebrate major milestones: Sports Medicine (25 years), Clinical Drug Investigation (20 years), CNS Drugs and BioDrugs (15 years), and Pediatric Drugs (10 years). In 2010, the American Journal of Clinical Dermatology will celebrate its 10-year anniversary. In 2011, many more of our titles have major anniversaries. Last, but not the least, we would like to say a big thank you to all the authors who have contributed articles to Sports Medicine in the last 12 months. Without their hard work and diligence we would not have been able to publish the journal. The quality of published articles reflects also the significant time and effort dedicated by the peer reviewers who ensure that we continue to publish content of the highest possible standard. In addition to the members of our Honorary Editorial Board, we would like to thank the following individuals who acted as referees for articles published in Sports Medicine in 2009: Chris R. Abbiss, Australia Nidhal B. Abdelkrim, Tunisia Edmund O. Acevedo, USA Lucia Alejandro, Spain R. McNeill Alexander, UK J.B. Allen, USA
Fernanda Amicarelli, Italy Duarte Araujo, Portugal Chris I. Ardern, Canada Elizabeth A. Arendt, USA Per Aspenberg, Sweden Robert J. Aughey, Australia
978
Stephen P. Bailey, USA James C. Baldi, New Zealand Carla Bann, USA Adrian G. Barnett, Australia Thomas J. Barstow, USA Peter P. Bartsch, Germany Fabien A. Basset, Canada David G. Behm, Canada Ralph Beneke, UK David Bentley, Australia Catherine S. Berkey, USA Alfred Bernard, Belgium Tomasz M. Bielecki, Poland Veronique L. Billat, France Alexander Boldyrev, Russian Federation Marc Bonnefoy, France Katarina T. Borer, USA Heather Bowles, USA Helen Brown, Australia Lee E. Brown, USA Marybeth Brown, USA Nick Brown, Australia Wendy Brown, Australia Johannes Brug, the Netherlands Jonathan D. Buckley, Australia Louise M. Burke, Australia Dale J. Butterwick, Canada Chris Button, New Zealand Jeffrey Bytomski, USA Jose A.L. Calbet, Spain Robert C. Cantu, USA Michael R. Carmont, UK James B. Carter, Canada Alison Carver, Australia Douglas Casa, USA Carmen Castaneda-Sceppa, USA George D. Chloros, USA Sally A. Clark, Australia Vernon G. Coffey, Australia Damian Coleman, UK David O. Conant-Norville, USA Kirsten Corder, UK Aaron J. Coutts, Australia Kay L. Cox, Australia Lynette L. Craft, USA Elizabeth V. Cyarto, Australia Brian Dawson, Australia Laura C. Decoster, USA J. Scott Delaney, Canada Michaela C. Devries, Canada Gurpreet Dhaliwal, USA P.E. di Prampero, Italy Mary K. Dinger, USA David D. Docherty, Canada Scott Drawer, UK Barry B. Drust, UK Jose A. Duarte, Portugal G. Duncan, USA James S. Duncan, New Zealand Andrea L. Dunn, USA Conrad P. Earnest, USA Tammie R. Ebert, Australia Eric Eils, Germany Mahmoud S. El-Sayed, UK
ª 2009 Adis Data Information BV. All rights reserved.
Carolyn A. Emery, Canada Luigi Fattorini, Italy Bo Fernhall, USA Caroline F. Finch, Australia Marie T. Flores, Chile Brian C. Focht, USA Daniel T.-P. Fong, China Carl C. Foster, USA Jonathon Fowles, Canada Belinda J. Gabbe, Australia Olivier Galy, New Caledonia Theodore T. Ganley, USA H. Gaulrapp, Germany J. Parry Gerber, USA Nathan N. Gibbs, Australia Carmen Gomez-Cabrera, Spain Christopher J. Gore, Australia Eric D.B. Goulet, Canada Michael T. Gross, USA Bernard B. Gutin, USA Joseph Hamill, USA Karyn L. Hamilton, USA Per M. Haram, Norway Marcus H. Heitger, New Zealand Jay Hertel, USA Timothy Hewett, USA William R. Hiatt, USA Lisa Hodgson, UK Jan Hoff, Norway Peter Hofmann, Austria Wildor Hollmann, Germany Tricia J. Hubbard, USA Clare Hume, Australia Veronica K. Jamnik, Canada Tero A. Jarvinen, Finland Lisa B. Johnston, USA Fawzi Kadi, Sweden Stavros K. Kakkos, Greece Jyotsna N. Kalavar, USA James D. Kang, USA Simon Kemp, UK Robert W. Kenefick, USA John P. Kirwan, USA William J. Kraemer, USA Jesper Krogh, Denmark David E. Laaksonen, Finland Ylva T. Lagerros, Sweden Paul B. Laursen, Australia Peter le Rossignol, Australia Tzai-Li Li, Taiwan Martin Lindstrom, Sweden Marius Locke, Canada Jim Macintyre, USA Clare MacMahon, Australia Nicola N. Maffulli, UK Peter Magyari, USA Nele Mahieu, Belgium Andrew A. Maiorana, Australia Gerald A. Malanga, USA Frank E. Marino, Australia Derek Marks, USA Joseph C. Maroon, USA Robert N. Marshall, New Zealand Lester Mayers, USA
Sports Med 2009; 39 (12)
Acknowledgement
979
Brendon McDermott, USA Michael R. McGuigan, Australia Terry McMorris, UK Robert G. McMurray, USA Lars R. McNaughton, UK Christa Meisinger, Germany Antti A. Mero, Finland Michael C. Meyers, USA Adrian W. Midgley, UK Edward Miech, USA A. Lynn Millar, USA Allan Mishra, USA Michael Molloy, Ireland Stefan P. Mortensen, Denmark Richard Hugh Morton, New Zealand Christian Munthe, Sweden Nanette Mutrie, UK Andrew T. Nathanson, USA Karl M. Newell, USA Jeanne F. Nichols, USA Tim D. Noakes, South Africa E.G. Noble, Canada Maria Nordlund, Sweden Lars Norgren, Sweden Kevin I. Norton, Australia John J. Orchard, Australia Francesco F. Orio, Italy Sergej M. Ostojic, Yugoslavia Nicole M. Panhuyzen-Goedkoop, the Netherlands Gaynor Parfitt, UK Brian B. Parr, USA Timothy E. Paterick, USA Helene Pavlov, USA Stephane Perrey, France Danny M. Pincivero, USA Jennifer A. Pintar, USA Kenneth H. Pitetti, USA David C. Poole, USA Ermanno Rampinini, Italy Dan K. Ramsey, USA Dennis N. Ranalli, USA Christopher Randolph, USA Thomas Reilly, UK Caroline R. Richardson, USA James H. Rimmer, USA Kai Roecker, Germany Christer G. Rolf, UK Dori E. Rosenberg, USA Thomas W. Rowland, USA
Kristin L. Sainani, USA Philo U. Saunders, Australia Timothy Scheett, USA Ernest Schilders, UK Jean-Paul Schmid, Switzerland E. Todd Schroeder, USA Andrew L. Sherman, USA Richard Shuttleworth, Australia Arthur J. Siegel, USA Ronald J. Sigal, Canada Holly J. Silvers, USA Indrani Sinha-Hikim, USA Sarianna Sipila, Finland Evelyne P. Soriano, Brazil Tim Spalding, UK Alan St Clair Gibson, UK Joseph W. Starnes, USA Darren J. Stefanyshyn, Canada David J. Stensel, UK Emma Stevenson, UK Jeffrey R. Stout, USA Eric J. Strauss, USA James Stray-Gundersen, USA Alasdair G. Sutherland, UK Jeroen Swart, South Africa Janet L. Taylor, Australia Richard D. Telford, Australia Gershon Tenenbaum, USA Peter M. Tiidus, Canada Ian R. Tofler, USA Tarkan Tuli, Germany Maria L. Urso, USA Jaci Van Heest, USA Geoffrey M. Verrall, Australia Niels B.J. Vollaard, UK Serge P. von Duvillard, USA Darren E.R. Warburton, Canada Gordon L. Warren, USA Wendy Watson, Australia Jon P. Wehrlin, Switzerland Joseph P. Weir, USA Randall L. Wilber, USA Mark Williams, UK Jonathan E. Wingo, USA Kate Woolf-May, UK Maurice R. Yeadon, UK Warren B. Young, Australia Bohdanna T. Zazulak, USA Rebecca A. Zifchock, USA
We look forward to your continued support in 2010 and to bringing you first-class content from around the globe. With best wishes from the staff of Sports Medicine and all at Adis, a Wolters Kluwer business.
ª 2009 Adis Data Information BV. All rights reserved.
Sports Med 2009; 39 (12)
Sports Med 2009; 39 (12): 981-993 0112-1642/09/0012-0981/$49.95/0
CURRENT OPINION
ª 2009 Adis Data Information BV. All rights reserved.
Why Do Pedometers Work? A Reflection upon the Factors Related to Successfully Increasing Physical Activity Catrine Tudor-Locke1 and Lesley Lutes2 1 Walking Behaviour Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA 2 Department of Psychology, East Carolina University, Greenville, North Carolina, USA
Abstract
The results of two recent independent meta-analyses focused on pedometerbased programmes conclude that they work; that is, they are effective. Specifically, physical activity increases while blood pressure and weight decrease as a result of participating in a pedometer-based intervention. An improved understanding of the unique measurement and motivational properties of pedometers as behaviour-change tools will assist researchers and practitioners to maximize benefits. In an effort to begin to outline why pedometers work, for whom, and under what conditions, the purpose of this current opinion article is to explore the published literature (drawing heavily from those studies previously identified in published meta-analyses and our own work in this area) to identify factors related to using pedometers to increase physical activity. In particular it is important to: (i) gain a better understanding of the activitypromoting characteristics of pedometers; (ii) determine effective elements of pedometer-based programming; and (iii) identify participants who engage in, and benefit most from, such programming. Pedometers are most sensitive to walking behaviours, which is consistent with public health and clinical approaches to increasing physical activity. Specifically, they offer an affordable and accessible technology that is simplistic in output, low-literacy friendly, and immediately understandable to end-users. Support materials are becoming readily available for researchers and practitioners in terms of expected (normative or benchmark) values, patterns of change, indices to aid screening and interpretation, and measurement protocols. Pedometer-based programme theory is now being articulated and tested, and the critical elements necessary to shape a successful programme are becoming more clearly defined. More research is needed, however, to compare the effectiveness of self-selected individualized goals with tailored goals (based on a specified baseline characteristic, for example), standardized goals (e.g. percentage-based increments) and pre-set uniformly administered goals (i.e. a volume total of 10 000 steps/ day or an incremental total of 2000 extra steps/day for everyone). Since most studies of pedometer-based programmes have been of relatively short duration, it is unknown to what extent observed changes are sustainable or whether it is possible to continue to accrue benefits over long-term adherence. Peer delivery of treatment has the potential for enabling wider and less costly dissemination, although this has not been directly evaluated. In addition, the majority of pedometer-based programme participants to date have been women,
Tudor-Locke & Lutes
982
suggesting that more research is needed on men and how they react to this form of physical activity intervention. Increases in steps/day have been negatively correlated with baseline values, indicating that those with lower baseline steps/day stand to make the greatest relative incremental increases in physical activity behaviour. A clearly articulated programme theory is lacking in most interventions. A clearer understanding is needed of what programme features, including the nature of goal-setting, are necessary for optimal participant success. Additionally, we need a better profile of the participant who benefits most, and/or requires additional or alternative strategies to succeed in their personal behaviour-change attempts. Continued efforts to refine answers regarding what works well for whom under what conditions will foster evidencebased applications of pedometer-based programmes.
Physical activity assessment has benefited from the rapid expansion of body-worn technologies, including accelerometers and pedometers, which have greatly advanced researchers’, practitioners’ and lay people’s interest in quantifying, and ability to quantify, physical activity patterns and volumes. Of the two instruments, however, the pedometer has been used more frequently as a motivational tool imbedded in an intervention programme. As testament to the growing interest in pedometer-based programming, two recent metaanalyses examined such programmes’ efficacy in terms of increasing walking behaviours.[1,2] Specifically, Richardson et al.[1] summarized findings from nine randomized and controlled pedometerbased programmes and found that participants increased their activity by 1800–4500 steps/day and lost a modest amount of weight (on the order of approximately 0.05 kg/week) over the course of interventions lasting from 4 weeks to 1 year (median duration 16 weeks). Bravata et al.[2] considered both randomized, controlled studies and observational studies, and reported similar changes: pedometer users increased their physical activity by approximately 2100–2500 steps/day and decreased their body mass index (BMI) by 0.38 kg/m2. The pedometer-based interventions described in the published meta-analyses[1,2] offer inspiration, but few alone can serve as useful programme templates due to a lack of a clearly articulated detailed programme or intervention theory.[3] Theorybased health behaviour-change programmes are believed to be more effective than those that do not ª 2009 Adis Data Information BV. All rights reserved.
use theory; unfortunately, a recent review of theorybased programming indicated only 35.7% of health behaviour-change programmes published between 2000 and 2005 even mentioned theory.[4] A detailed programme theory is necessary to organize and explain what happens in a programme and why. It is initially informed by the existing programmerelated literature and clinical experience.[3] Therefore, in an effort to begin to outline why pedometers work, for whom, and under what conditions, the purpose of this current opinion article is to reflect upon characteristics of pedometers, pedometer-based programming, and the participants who engage in such programming. Such a discourse is necessary to better understand theoretical mechanisms in an effort to refine and replicate optimal programming templates. 1. Characteristics of Pedometers 1.1 Measurement Mechanism
Pedometers are generally designed to be most sensitive to detecting ambulatory activity, and this is a ‘good thing’ in terms of measuring and motivating walking behaviours. Of all types of physical activity, walking is most commonly encouraged.[5] It is the most commonly reported form of leisuretime physical activity,[6] and it is also a functional component of shopping, transportation and walking the dog, to name but a few examples of other forms of walking behaviours.[7] Pedometers offer a simple estimate of physical activity volume Sports Med 2009; 39 (12)
Why Do Pedometers Work?
in terms of steps taken. This uncomplicated and straightforward output is a direct indicator of movement as a result of behavioural choices. Traditional pedometers detect steps by using a horizontal, spring-suspended lever arm which moves up and down as a result of vertical accelerations of the hip. A step is recorded when a vertical acceleration above the manufacturer-designed force sensitivity threshold of the pedometer (e.g. 0.35 g for the Yamax pedometer [Yamax Corp., Tokyo, Japan]) deflects the lever arm sufficiently to complete an electronic circuit. The electronic circuitry within a pedometer is designed to accumulate steps and continually display this updated information on a digital screen. A force sensitivity threshold is an important pedometer characteristic, regardless of its underlying measurement mechanism, since it is necessary to censor out ‘non-steps’ (e.g. inevitable jostling during car driving[8]). The sensitivity/specificity trade-off, however, results in a loss of recorded low acceleration steps, typical of slower paces (e.g. steps taken while standing in line at the grocery store). Since health promotion efforts have focused on the benefits of brisk walking, or that of at least moderate intensity, this censoring feature should not be problematic in most populations, and in fact can be interpreted as an attribute as it conveniently pushes the participant to focus more on detectable walking behaviours. Unfortunately, specific pedometer force sensitivity thresholds for detecting steps can vary widely between available instruments[9] and are only as consistent between instruments of the same brand as factory quality control efforts impose. This unfortunate circumstance undermines the consistency of operationally defining a step, and impairs our ability to compare step outputs across populations and studies. At this time there is no conversion factor available to ‘correct’ step outputs from different instruments. However, a number of pedometer brand-to-brand comparisons have been conducted,[10-12] which have identified researchquality pedometers. It is important to clearly declare here that the effectiveness of pedometerbased programming is prefaced on the use of valid and reliable instruments, like the Yamax brand pedometers, for example. The effectiveness of ª 2009 Adis Data Information BV. All rights reserved.
983
lesser instruments is questionable and potentially detrimental to behaviour-change efforts.[13] Since pedometers are typically designed to be most sensitive to vertical accelerations at the hip, it almost goes without saying that pedometers (and waist-worn accelerometers) do not detect nonambulatory activities, including swimming, cycling and weight training. The prevalence of participation in these activities is quite low. Only 5.8% of adults report swimming, 11% report cycling and 8.6% report weight-training when asked about activities performed over the past 30 days.[14] Fortunately, these types of activities are salient and therefore more easily recalled, so a combination of pedometer and self-report should suffice to capture them.[15] Adding ‘bonus steps’ to daily pedometerdetermined steps for performance of these types of non-ambulatory activities (e.g. 200 extra steps for every 10 minutes of active time) is a strategy that may work well on the individual level for interventions, but appears not to be necessary for population level analyses.[16] Traditional pedometers are also not designed to detect intensity of activity. Furthermore, pedometer attachments that rotate the instrument off the vertical plane will impair measurement function. For example, in obese individuals it is possible that a pedometer will be tilted off the vertical axis in manufacturer-recommended attachment sites (i.e. typically at the waist, centered over the right knee), resulting in compromised detection of lower force steps.[17,18] To solve this problem, there are instruments that offer improved precision in obese individuals[17] (see below), with the caveat that these might result in the sensitivity/specificity trade-off mentioned above. However, some researchers have reported that pedometers can be moved about on the waist band (e.g. placed on the mid-axillary line or in line with the posterior thigh where it is less likely to be tilted) without compromising measurement properties.[18,19] Specifically, we have had success with teaching participants how to attach the pedometer so that it is not tilted, and to monitor the accuracy of their pedometers on a daily basis with a simple 20-step test, adjusting placement as necessary.[19] Emerging technologies include a piezoelectric accelerometer mechanism that generates a sine Sports Med 2009; 39 (12)
Tudor-Locke & Lutes
984
wave corresponding to vertical accelerations at the hip during walking and running. A count of the sine waves is interpreted as steps taken. Some of these instruments can also provide outputs related to the intensity of these steps. An added feature is an on-board memory function that recalls previous days’ data. The NL-1000 (New-Lifestyles Inc., Lees Summit, MO, USA), NL-2000(New-Lifestyles Inc.), Kenz Lifecorder EX (Suzenken Co., Ltd, Nagoya, Japan) and the Omron HJ 720ITC (Omron Corp., Kyoto, Japan) are examples. The latter two instruments can also transfer data directly to a computer by way of a USB cable, facilitating data management requirements. Although these added features are useful to researchers, the evaluation of their impact on individual behaviour is limited. For example, although the measurement mechanism of the piezoelectric pedometers does provide a more precise estimate of steps taken in obese individuals,[17] the published meta-analysis demonstrated pedometer effectiveness (even in obese individuals) without necessarily using this technology. 1.2 Acceptability to End-Users
Although a wide variety of commercial pedometers are available, most are small, unobtrusive in their attachment on the body (typically clipping directly to a waist band), and inexpensive (approximately $US20–$US50; year of costing 2009). As such, pedometers offer an accessible technology that is simplistic in output, low-literacy friendly and immediately understandable to end-users. Their output is personalized, since each individual can be equipped with their own pedometer. Furthermore, with consistent wear, pedometers are plausibly effective for longer term monitoring and behaviour change, much like a wristwatch can be used for self-monitoring behaviours that are timedependent throughout the day. Focus groups conducted following completion of a pedometerbased programme revealed that pedometers are well accepted and are considered to be highly useful goal-setting tools, capable of immediately increasing personal awareness of physical activity levels, and providing sources of readily available visual feedback.[19-21] Although pedometer manuª 2009 Adis Data Information BV. All rights reserved.
facturers offer an array of value-added features (delayed reset buttons, multiple day memories, ‘talking’ pedometers, etc.) and outputs (estimates of distance walked, energy expended, time in activity of at least moderate intensity, etc.), it has been our observed experience of the participants with whom we have worked that most are comfortable with a simple output of steps taken and a single reset button. Furthermore, mathematical manipulations (accomplished by an on-board pedometer microprocessing feature or resulting from post-data processing) of the simple step output to extrapolate distance walked (based on inputted stride length or height) and/or energy expended (based on sex, age, mass or a selection of these) result in diminishing accuracy.[22] The cumulative and readily available visual feedback is a pedometer characteristic that warrants further discussion. The cumulative nature of the counted steps provides a constant and changing barometer reflecting personal behaviour choices as they occur in real-time. Unlike instruments that may require downloading and/or other types of processing prior to personal access, traditional pedometers offer instantaneous awareness to the end-user that can then be directly acted upon. That being said, emerging technologies are capable of providing both immediate feedback and more complex data analysis after download. Used for baseline behavioural assessment, the immediate feedback provides the user with a readily digestible estimate of personal physical activity level, which can inform decisions about behaviour change. Used as part of a guided and repetitive self-monitoring, feedback and goalsetting process, the pedometer provides up-tothe-minute information that can spur and hone behaviour choices. 1.3 Availability of Related ‘Software’ Facilitating Use
We have previously likened pedometers to computer hardware (e.g. keyboards, monitors, disks, etc.).[23] However, without the accompanying software (e.g. expected values, standardized protocols, indices to interpret change, data management rules, reporting procedures, etc.) their use is limited. We are now benefiting from the Sports Med 2009; 39 (12)
Why Do Pedometers Work?
independent and collective efforts of a growing number of researchers and practitioners who continue to publish quality work related to the impact of pedometer-based programmes on activity. Cases in point are the two meta-analyses previously mentioned[1,2] and a third,[24] all of which provide vital expected (normative or benchmark) values, necessary for interpreting change and comparison purposes, and variance estimates required for determining sample size. Similar data are now available for young populations.[25] Patterns of change[26,27] have also been published, which are useful for facilitating local implementation and evaluation. Efforts have also been made to identify practical indices reflective of public health guidelines,[28] to classify hierarchical levels of physical activity,[29,30] and to link threshold values with outcomes of interest including BMI[31,32] and body fat percentage.[33] Practical guidance for measurement protocols and procedures has been published[34] and recently expanded to young populations.[35] These rich and growing publicly available resources are invaluable to facilitate optimal use of pedometers in physical activity interventions. 2. Characteristics of Pedometer-Based Physical Activity Interventions 2.1 Nothing Quite Like a Good Theory
It is important to reiterate that pedometers are simple tools and that successful interventions are ultimately based on empirically validated treatments that are informed by good theory.[3] This includes identifying and clearly articulating key components or activities that must be present in a programme; this in turn is informed by existing behavioural theories, models and accepted techniques. Behavioural and social scientists interested in physical activity have employed a number of theories and models originally developed for other behavioural applications (e.g. addiction and smoking cessation), often in combination, to better understand this unique behaviour and to design successful interventions. These theories and models generally include: (i) classical learning theory; (ii) the health belief model; (iii) the transtheoretical model; (iv) relapse prevention; (v) social ª 2009 Adis Data Information BV. All rights reserved.
985
cognitive theory; (vi) theory of reasoned action and planned behaviour; (vii) social support; (viii) selfregulation theory; and (ix) ecological approaches.[36] Table I catalogues the theoretically based models/ techniques and intervention goal algorithms of pedometer-based interventions identified in the recent meta-analyses.[1,2] At present only a handful of these interventions[26,58,61,63] have explicitly acknowledged using a recognized health behaviourchange theory to guide programme design and delivery. We know of only one that has presented its programme theory in a logic model (i.e. an accepted tool used to illustrate programme components, outcomes and linkages between them).[3] For example, drawing primarily from social cognitive theory and the transtheoretical model, we previously identified the critical inputs underlying the First Step Program – a pedometer-based daily physical activity intervention originally developed for individuals with type 2 diabetes mellitus.[3] These critical inputs included: (i) individualized programming (e.g. self-selected incremental goals); (ii) flexibility in structure of regimen; (iii) activity that is of moderate intensity and focused specifically on walking behaviours; (iv) acceptable self-monitoring and feedback tools; and (v) follow-up contact. In addition, a facilitated programme was selected to guide participants through decision balance techniques early in the behaviour-change process, and self-contracts were imbedded as a regular part of an incremental and individualized goal-setting process. Relapse prevention and planning was incorporated during the behaviour-change period.[64] Social cognitive theory[65] dictates that the constructs of self-efficacy and social support are important mediating variables in programmes designed to increase physical activity behaviours. Since the most influential source of self-efficacy is performance accomplishment or mastery, it follows that opportunities to directly experience physical activity (i.e. go for a walk) are integral to good programme design. Brief group walks incorporated into the First Step Program were useful for increasing personal awareness of steps taken in a specific time frame (necessary for selecting informed incremental goals) and also provided opportunity for socialization.[21] Social Sports Med 2009; 39 (12)
986
ª 2009 Adis Data Information BV. All rights reserved.
Table I. Theoretical models/techniques and intervention goal algorithms of pedometer-based interventions identified in recent meta-analyses[1,2] Target population
Explicitly identified theoretical model (in bold type) or technique
Intervention goal algorithm
Araiza et al.,[37] 2006
Adults with type II diabetes mellitus
None identified
Achieve 10 000 steps/day
de Block et al.,[38] 2006
Adults with COPD
Motivational interviewing
To › lifestyle PA
Butler and Dwyer,[39] 2004
Sedentary adults
None identified
To › PA 30 min (~3000 steps) daily during wk 1 and 2, › to 40 min (~4000 steps) during wk 3 and 4
Chan et al.,[26] 2004
Sedentary adult employees
Social cognitive theory and transtheoretical model
To › PA weekly
Croteau,[40] 2004
Adult employees
Goal setting based on baseline step counts
If <8000 steps/day at baseline, then › 10% every 2 wk until >10 000; if 8000–10 000, then increased 5% every 2 wk until >10 000; if >10 000 at baseline, then maintain
Eastep et al.,[41] 2004
Healthy adults
Feedback
Centre-based exercise class and recommendations to increase daily PA through walking
Engel and Lindner,[42] 2006
Adults with type II diabetes
Coaching (including problemsolving, education, self-efficacy, goal-setting, and social support
If healthy older adult step goals = 6000–8500, if older adult with disabilities and chronic illness, step goals = 3500–5500
Hultquist et al.,[43] 2005
Sedentary non-smoking adult women
Self-monitoring
Achieve 10 000 steps/day
Izawa et al.,[44] 2005
Adults with a history of myocardial infarction
Self-efficacy theory and transtheoretical model
Centre-based cardiac rehabilitation programme – no goals specified
Jensen et al.,[45] 2004
Obese older adult women
Goal-setting and self-monitoring
› daily steps by 5000 and additional goals if warranted
Kilmer et al.,[46] 2005
Adults with neuromuscular diseases
Self-monitoring
› daily steps by 25% compared with baseline
Koulouri et al.,[47] 2006
Healthy adults
None identified
› daily steps by 2000 compared with baseline
Lindberg,[48] 2000
Sedentary healthy adults
Self-monitoring and motivational messages
Achieve 10 000 steps/day
Moreau et al.,[49] 2001
Adult postmenopausal women
Self-monitoring and goal setting
› distance by 1.4 km above their baseline wk 1, › 0.5 each time until the desired walking of › to 3.0 km/day by wk 3
Ransdell et al.,[50] 2004
Multi-generational women in families
Self-monitoring
› duration and volume of activity by 10% every 2 weeks and to › lifestyle-oriented PA
Schneider et al.,[51] 2006
Overweight and obese adults
Self-monitoring
Achieve 7000 steps/day for wk 1, 8000 steps/day for wk 2, 9000 steps/day for week 3, and 10 000 steps/day thereafter
Sidman et al.,[52] 2004
Adult sedentary women
Goal-setting
Achieve 10 000 steps/day or to › daily steps by 1000–3000
Stovitz et al.,[53] 2005
Healthy adults
Goal-setting
› daily steps by 400 each week
Sugiura et al.,[54] 2002
Adult menopausal women
Goal-setting and centre-based exercise
› daily steps by 2000–3000 in addition to the exercise class
Swartz et al.,[55] 2003
Overweight inactive women
Self-monitoring
Achieve 10 000 steps/day Continued next page
Tudor-Locke & Lutes
Sports Med 2009; 39 (12)
Source, year
› daily steps by 2000 compared with baseline Adults from a single state Wyatt et al.,[62] 2004
Self-monitoring
African American breast cancer survivors Wilson et al.,[61] 2005
ª 2009 Adis Data Information BV. All rights reserved.
support can take many forms beyond professional follow-up contact and includes personal support networks encompassing peers, family and friends. Activating personal support networks offers a prospect of establishing ongoing support that extends well beyond formal programme structures, and provides a natural opportunity to foster sustainability of behaviour change.[3,19]
2.2 The Importance and Nature of a Goal
COPD = chronic obstructive pulmonary disease; PA = physical activity; › indicates increase.
Progressive step goals (not described
Postmenopausal African American women Williams et al.,[60] 2005
Health belief model
› daily step goals compared with baseline by taking into consideration the 10 000 steps/day general recommendation and the participant’s self-selected targeted value
Older male and female adults with coronary artery disease VanWormer et al.,[59] 2004
Behavioural contracting and selfmonitoring
None described
Adults with type II diabetes Tudor-Locke et al.,[58] 2004
None identified
› daily steps by 3000 compared with baseline
Adult employees Thomas and Williams,[57] 2006
Social cognitive theory and transtheoretical model
› daily steps each week with an ultimate goal of 10 000 steps/day
Older adults with knee osteoarthritis Talbot et al.,[56] 2003
Goal-setting and self-monitoring
› 10% compared with baseline every 4 wks for an overall goal of 30% above baseline steps/day
Target population
Goal-setting, self-monitoring and feedback
987
Source, year
Table I. Contd
Explicitly identified theoretical model (in bold type) or technique
Intervention goal algorithm
Why Do Pedometers Work?
Since pedometers are ‘personal wear’ items, which reflect individual behaviours, they fit very well into a programme of self-monitoring, personalized feedback, and self-selected incremental goal-setting. Programmes that have encouraged increased physical activity in the absence of a goal have shown no significant improvements in steps/day compared with those with increases of ‡2000 steps/day in programmes that have promoted the use of the 10 000 steps/day goal or other goals (although few studies have evaluated alternative goals, which limits conclusions specifically about the ultimate magnitude of the goal and its efficacy).[2] Although it is tempting to adopt an ‘across the board’ prescription of a specified total or incremental number of steps/day, individualized programming is more personally relevant, easily adjusted as needed, and is likely to be well endured by typically sedentary individuals (the most likely target of a pedometer-based physical activity intervention). Individualized programming that uniquely engages and responds to an individual and encourages self-selection of a personal goal (e.g. the First Step Program) is not quite the same thing as a tailored intervention, which may include automatic responses and messaging created to address the needs of a group of individuals defined, for example, on baseline steps/ day. However, such an approach may be both efficient and effective. For example, in three recent studies,[66-68] participants uploaded or manually entered their daily step counts over the Internet and received pre-set tailored feedback regarding goal-setting based on automatic algorithms. All Sports Med 2009; 39 (12)
Tudor-Locke & Lutes
988
studies showed significant improvements in steps/ day over the course of the intervention. An alternative approach has been to promote percentage-based goals.[46,50] The concern with strictly implementing this approach is that the absolute incremental number of steps will be higher with higher baselines, presenting greater and possibly insurmountable challenges (and perhaps under-challenging those with lower baselines). Since there is little research that has studied alternative goals or goal-setting strategies, more is needed comparing the effectiveness of: (i) self-selected goals; (ii) goals tailored to individuals defined by a baseline characteristic; (iii) standardized goals (e.g. percentage-based increments); and (iv) pre-set uniformly administered goals (i.e. a volume total like 10 000 steps/day or an incremental total like 2000 steps/day for everyone). It may very well be that setting and working towards any goal that represents an increase over baseline values is of much greater importance than the manner in which it is set. 2.3 Self-Monitoring
As discussed above (sections 1.2 and 2.2), the pedometer is an acceptable self-monitoring and feedback tool. However, its power is enhanced if it is coupled with some formal process of recording daily values (e.g. on a simple calendar) as a strategy to help reinforce activity behaviours.[19,21] Metaanalysis results[2] have indicated that participants in pedometer-based programmes who recorded their daily step count increased their activity by approximately 2000–3200 steps/day over baseline. This is significantly greater than those who were not required to record their data (mean change 832 steps/day). Participants have reported that the act of recording (i.e. writing down)[19,20,40] pedometer data over the course of days on a simple paper calendar provides additional visual feedback of progress, illuminates personal behaviour patterns of interest (e.g. weekend vs weekday steps), and produces a tangible record of personal success. Requiring participants to submit their data (e.g. in person, by mail or by electronic means) also provides a sense of accountability.[20] Follow-up contact is a form of social support and is considered ª 2009 Adis Data Information BV. All rights reserved.
important to continued motivation. It has taken the form of telephone calls,[21] postcards,[58] emails[20,40] and face-to-face interactions[26] – to name a few examples. The future brings the promise of increased availability of commercially interactive websites and purchasable software to be used in tandem with objectively monitored physical activity entered either manually[69] or by instrument download.[66,67] 2.4 Strategies
Since pedometers capture a cumulative count of steps taken throughout the day, ultimate flexibility in structure of a personalized regimen is assured; almost limitless options are available to accrue daily steps. Croteau[70] catalogued strategies reported by participants engaged in a pedometer-based programme: 64.7% walked to a meeting or workrelated errand, 50% walked after work, 35.5% walked before work, 47.1% walked at lunch, 32.4% walked on the weekend, 32.4% walked while travelling, 32.4% walked with the dog, and 29.4% walked to a destination (e.g. work/store). In addition, 50% of participants reported parking further away, 23.5% preferentially used the stairs rather than an elevator, and 52.9% performed other cardiovascular activity. Participation in sports and exercise has been shown to produce consistently higher steps/day over 1 continuous year of monitoring.[71] Programme participants have reported adopting personal strategies of taking a ‘day off’ without guilt (secure in the knowledge that they could alter their behaviour on subsequent days), and ‘banking steps’ in anticipation of a sedentary day.[19] 2.5 Delivery Options
Little research has been conducted on the possible role that interventionists’ characteristics might play in moderating participants’ attempts at behaviour-change in pedometer-based programmes. Interventionists’ characteristics include such aspects as the programme deliverer’s similarity to programme recipients, personal attitudes and physical activity behaviours, comfort with the intervention, and training.[3] We have recently demonstrated that a pedometer-based programme delivered either by a peer leader (e.g. an individual with type 2 diabetes who had previously completed Sports Med 2009; 39 (12)
Why Do Pedometers Work?
the same programme) or a professional (e.g. a nurse or dietician)[72] elicited similarly favourable changes in steps/day, weight, waist girth, resting heart rate, and blood pressure. Peer delivery has the potential for enabling wider and less costly dissemination, although this has not been directly evaluated. Another delivery option that is rapidly gaining popularity is by computer. Initial reviews of physical activity interventions[73,74] delivered in this manner have shown variable success of tailored interventions delivered by computer. However, more recent studies of computer-delivered, theorybased interventions that have also incorporated a pedometer have shown clear and consistent success (i.e. an increase of 1300–2000 steps/day over baseline values).[66-68] Since most studies of pedometer-based programmes have been of relatively short duration, it is unknown to what extent observed changes are sustainable or whether it is possible to continue to accrue benefits over long-term adherence. Clearly, the optimal length of an intervention is unknown. As stated above, Richardson et al.[1] catalogued pedometer-based interventions lasting from 4 weeks to 1 year. They reported a strong negative relationship between study duration and resulting weight loss, indicating that benefits are potentiated with prolonged adherence. Chan and Tudor-Locke[75] reported that participants who completed the First Step Program (i.e. wore the pedometer for at least 9 weeks and completed a survey at 12 weeks) reported higher steps/day at 12 weeks (approximately 12 000 steps/day) and at the 1-year follow-up (approximately 11 000 steps/day) compared with baseline values (approximately 7800 steps/day). The First Step Program documented an immediate increase in steps/day that peaked at the end of formal contact, and although it deteriorated somewhat over time, still remained elevated compared with baseline values.[27,58] It is possible that by implementing ‘booster sessions’ (extended but infrequent contact), researchers and practitioners might be able to facilitate prolonged behaviour change. However, we do not yet know the optimal pattern of contact necessary to sustain adherence. ª 2009 Adis Data Information BV. All rights reserved.
989
3. Characteristics of Participants The study of the characteristics of pedometerbased programme participants has been primarily limited to a descriptive nature. The majority of pedometer-based programme participants to date have been women (73% of programme participants from studies included in the Richardson metaanalysis were women[1]), who took between 4700 to 7000 steps/day (i.e. sedentary or low active[29,30]) and were overweight at baseline. However, these characteristics may also reflect recruitment strategies to some extent. There is some evidence to suggest that pedometers may be appealing only for short-term behaviour monitoring in men.[76] An exploratory analysis of factors related to pedometer-based programme adherence and completion revealed that those most likely to complete the programme were overweight or obese class I (i.e. with a BMI between 30 and 35 kg/m2).[77] The authors speculated that the higher attrition in normal weight individuals potentially suggests a personal sense of programme irrelevance. For those with greater levels of obesity (i.e. class II and class III), higher attrition might have indicated a more overwhelming sense of challenge. The authors also observed that attrition was characterized by lower initial incremental changes in steps/day and subsequent regression towards baseline values. Increases in steps/day have been negatively correlated (r = -0.368) with baseline values, indicating that those with lower baseline steps/day stand to make the greatest relative incremental increases in physical activity behaviour.[26] However, there was no noted correlation between increases in steps/day and baseline BMI values. The meta-analysis conducted by Bravata et al.[2] of both randomized controlled trials and observational studies of pedometer-based programmes indicated that sex, BMI and race/ethnicity were not significant predictors of increased activity. In terms of anticipated changes in health outcomes as a result of increased steps/day, we recently reported that individual responses vary widely.[72] Specifically, we noted that although First Step Program participants’ waist girth decreased by 1.5–1.7 cm on average, the range of change was widely variable (-16 cm to +10 cm). Sports Med 2009; 39 (12)
Tudor-Locke & Lutes
990
Table II. Factors related to successfully increasing physical activity in pedometer-based programmes Characteristics of pedometers
Characteristics of the programme
Characteristics of participants
Most sensitive to ambulatory activity Simple estimate of physical activity volume expressed as steps/day Displays accumulated steps taken Able to censor out ‘non-steps’ Acceptable to end-users Affordable, valid and reliable instruments available Small and unobtrusive, typically attached to the waist band Accessible technology, low-literacy friendly, immediately understandable Offers readily available and personalized visual feedback Useful self-monitoring, goal-setting, and feedback tools Immediately increases awareness of physical activity levels Increasingly available resource materials to support measurement and motivation efforts
Need to clearly articulate underlying programme theory Minimally, a programme of selfmonitoring, incremental goal-setting, and personalized feedback Fundamental importance of a goal, possibly 10 000 steps/day, possibly selfselected, but little alternative research has been conducted Flexibility in structure of a personalized regimen Need to record and submit daily values Follow-up contact as one form of social support Opportunities to build self-efficacy Activating personal support networks Peer delivery is effective and may enable dissemination Optimal programme duration and pattern of contact unknown to support sustainability
Majority of participants have been women; may reflect recruitment strategies to some extent May be only appealing for short-term behaviour monitoring in men Those most likely to complete are overweight and obese class I Attrition indicated by lower initial incremental changes in steps/day, regression to baseline values Individual responses vary Little is known about who benefits most
More research is necessary to identify who benefits most from pedometer-based programming in order to target such interventions more appropriately.
evidence-based applications of pedometer-based programmes. Acknowledgements
4. Conclusions The results of the two recent meta-analyses[1,2] focused on pedometer-based programmes conclude that they work. An improved understanding of the unique properties of pedometers as behaviour-change tools will assist researchers and practitioners to maximize these attributes. A clearer understanding is also needed of what programme features, including the nature of goal-setting, are necessary for optimal participant success. Finally, we need a better profile of the participant who benefits most, and/or requires additional or alternative strategies to succeed in their personal behaviour-change attempts. It is premature to offer an optimal programme template; however, we have compiled a summary of the factors related to successfully increasing physical activity in pedometer-based programmes in table II. Continued efforts to refine answers to what works well for whom and under what conditions will foster ª 2009 Adis Data Information BV. All rights reserved.
No sources of funding were used to assist in the preparation of this article. Dr Tudor-Locke receives royalties from the sale of a self-help book focused on using pedometers to increase physical activity. The authors have no other conflicts of interest that are directly relevant to the content of this article.
References 1. Richardson CR, Newton TL, Abraham JJ, et al. A metaanalysis of pedometer-based walking interventions and weight loss. Ann Fam Med 2008 Jan-Feb; 6 (1): 69-77 2. Bravata DM, Smith-Spangler C, Sundaram V, et al. Using pedometers to increase physical activity and improve health: a systematic review. JAMA 2007 Nov 21; 298 (19): 2296-304 3. Tudor-Locke C, Myers AM, Rodger NW. Development of a theory-based daily activity intervention for individuals with type 2 diabetes. Diabetes Educ 2001 Jan-Feb; 27 (1): 85-93 4. Painter JE, Borba CP, Hynes M, et al. The use of theory in health behavior research from 2000 to 2005: a systematic review. Ann Behav Med 2008 Jun; 35 (3): 358-62 5. Siegel PZ, Brackbill RM, Heath GW. The epidemiology of walking for exercise: implications for promoting activity among sedentary groups. Am J Public Health 1995 May; 85 (5): 706-10
Sports Med 2009; 39 (12)
Why Do Pedometers Work?
6. Rafferty AP, Reeves MJ, McGee HB, et al. Physical activity patterns among walkers and compliance with public health recommendations. Med Sci Sports Exerc 2002 Aug; 34 (8): 1255-61 7. Tudor-Locke C, Ham SA. Walking behaviors reported in the American Time Use Survey 2003-2005. J Phys Act Health 2008 Sep; 5 (5): 633-47 8. Le Masurier GC, Tudor-Locke C. Comparison of pedometer and accelerometer accuracy under controlled conditions. Med Sci Sports Exerc 2003 May; 35 (5): 867-71 9. Schneider PL, Crouter SE, Lukajic O, et al. Accuracy and reliability of 10 pedometers for measuring steps over a s400-m walk. Med Sci Sports Exerc 2003 Oct; 35 (10): 1779-84 10. Le Masurier GC, Lee SM, Tudor-Locke C. Motion sensor accuracy under controlled and free-living conditions. Med Sci Sports Exerc 2004 May; 36 (5): 905-10 11. Melanson EL, Knoll JR, Bell ML, et al. Commercially available pedometers: considerations for accurate step counting. Prev Med 2004 Aug; 39 (2): 361-8 12. Schneider PL, Crouter SE, Bassett DR. Pedometer measures of free-living physical activity: comparison of 13 models. Med Sci Sports Exerc 2004 Feb; 36 (2): 331-5 13. Tudor-Locke C, Sisson SB, Lee SM, et al. Evaluation of quality of commercial pedometers. Can J Public Health 2006 Mar-Apr; 97 Suppl. 1: S10-5, S10-6 14. Ham SA, Kruger J, Tudor-Locke C. Participation by US adults in sports, exercise, and recreational physical activities. J Phys Act Health 2009; 6: 1-10 15. Kriska A. Ethnic and cultural issues in assessing physical activity. Res Q Exerc Sport 2000 Jun; 71 (2 Suppl.): S47-53 16. Miller R, Brown W, Tudor-Locke C. But what about swimming and cycling? How to ‘count’ non-ambulatory activity when using pedometers to assess physical activity. J Phys Act Health 2006; 3 (3): 257-66 17. Crouter SE, Schneider PL, Bassett Jr DR. Spring-levered versus piezo-electric pedometer accuracy in overweight and obese adults. Med Sci Sports Exerc 2005 Oct; 37 (10): 1673-9 18. Swartz AM, Bassett Jr DR, Moore JB, et al. Effects of body mass index on the accuracy of an electronic pedometer. Int J Sports Med 2003 Nov; 24 (8): 588-92 19. Lauzon N, Chan CB, Myers AM, et al. Participant experiences in a workplace pedometer-based physical activity program. J Phys Act Health 2008; 5 (5): 675-87 20. Heesch KC, Dinger MK, McClary KR, et al. Experiences of women in a minimal contact pedometer-based intervention: a qualitative study. Women Health 2005; 41 (2): 97-116 21. Tudor-Locke C, Myers AM, Rodger NW. Formative evaluation of the First Step Program: a practical intervention to increase daily physical activity. Can J Diab Care 2000; 47 (1): 23-8 22. Crouter SE, Schneider PL, Karabulut M, et al. Validity of 10 electronic pedometers for measuring steps, distance, and energy cost. Med Sci Sports Exerc 2003 Aug; 35 (8): 1455-60 23. Tudor-Locke C. Taking steps toward increased physical activity: using pedometers to measure and motivate. Res Digest 2002; 3 (17): 1-8
ª 2009 Adis Data Information BV. All rights reserved.
991
24. Bohannon RW. Number of pedometer-assessed steps taken per day by adults: a descriptive meta-analysis. Phys Ther 2007 Dec; 87 (12): 1642-50 25. Tudor-Locke C, McClain JJ, Hart TL, et al. Expected values for pedometer-determined physical activity in youth. Res Q Exerc Sport 2009 Jun: 80 (2): 164-74 26. Chan CB, Ryan DA, Tudor-Locke C. Health benefits of a pedometer-based physical activity intervention in sedentary workers. Prev Med 2004 Dec; 39 (6): 1215-22 27. Tudor-Locke C, Myers AM, Bell RC, et al. Preliminary outcome evaluation of the First Step Program: a daily physical activity intervention for individuals with type 2 diabetes. Patient Educ Couns 2002 May; 47 (1): 23-8 28. Tudor-Locke C, Sisson SB, Collova T, et al. Pedometerdetermined step count guidelines for classifying walking intensity in a young ostensibly healthy population. Can J Appl Physiol 2005 Dec; 30 (6): 666-76 29. Tudor-Locke C, Bassett Jr DR. How many steps/day are enough? Preliminary pedometer indices for public health. Sports Med 2004; 34 (1): 1-8 30. Tudor-Locke C, Hatano Y, Pangrazi RP, et al. Revisiting how many steps are enough? Med Sci Sports Exerc 2008 Jul; 40 (7 Suppl.): S537-43 31. Tudor-Locke C, Bassett Jr DR, Rutherford WJ, et al. BMIreferenced cut points for pedometer-determined steps per day in adults. J Phys Act Health 2008; 5 Suppl. 1: S126-39 32. Tudor-Locke C, Pangrazi RP, Corbin CB, et al. BMIreferenced standards for recommended pedometerdetermined steps/day in children. Prev Med 2004 Jun; 38 (6): 857-64 33. Duncan JS, Schofield G, Duncan EK. Pedometerdetermined physical activity and body composition in New Zealand children. Med Sci Sports Exerc 2006 Aug; 38 (8): 1402-9 34. Tudor-Locke C, Myers AM. Methodological considerations for researchers and practitioners using pedometers to measure physical (ambulatory) activity. Res Q Exerc Sport 2001 Mar; 72 (1): 1-12 35. Tudor-Locke C, McClain JJ, Hart TL, et al. Pedometry methods for assessing free-living youth. Res Q Exerc Sport 2009 Jun; 80 (2): 175-84 36. US Department of Health and Human Services. Physical activity and health: a report of the Surgeon General. Atlanta (GA): US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, 1996 37. Araiza P, Hewes H, Gashetewa C, et al. Efficacy of a pedometer-based physical activity program on parameters of diabetes control in type 2 diabetes mellitus. Metabolism 2006 Oct; 55 (10): 1382-7 38. de Blok BM, de Greef MH, ten Hacken NH, et al. The effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation in patients with COPD: a pilot study. Patient Educ Couns 2006 Apr; 61 (1): 48-55 39. Butler L, Dwyer D. Pedometers may not provide a positive effect on walking activity. Health Promot J Austr 2004; 15: 134-6
Sports Med 2009; 39 (12)
992
40. Croteau KA. A preliminary study on the impact of a pedometer-based intervention on daily steps. Am J Health Promot 2004 Jan-Feb; 18 (3): 217-20 41. Eastep E, Beveridge S, Eisenman P, et al. Does augmented feedback from pedometers increase adults’ walking behavior? Percept Mot Skills 2004 Oct; 99 (2): 392-402 42. Engel L, Lindner H. Impact of using a pedometer on time spent walking in older adults with type 2 diabetes. Diabetes Educ 2006 Jan-Feb; 32 (1): 98-107 43. Hultquist CN, Albright C, Thompson DL. Comparison of walking recommendations in previously inactive women. Med Sci Sports Exerc 2005 Apr; 37 (4): 676-83 44. Izawa KP, Watanabe S, Omiya K, et al. Effect of the selfmonitoring approach on exercise maintenance during cardiac rehabilitation: a randomized, controlled trial. Am J Phys Med Rehabil 2005 May; 84 (5): 313-21 45. Jensen GL, Roy MA, Buchanan AE, et al. Weight loss intervention for obese older women: improvements in performance and function. Obes Res 2004 Nov; 12 (11): 1814-20 46. Kilmer DD, Wright NC, Aitkens S. Impact of a home-based activity and dietary intervention in people with slowly progressive neuromuscular diseases. Arch Phys Med Rehabil 2005 Nov; 86 (11): 2150-6 47. Koulouri AA, Tigbe WW, Lean ME. The effect of advice to walk 2000 extra steps daily on food intake. J Hum Nutr Diet 2006 Aug; 19 (4): 263-6 48. Lindberg R. Active living: on the road with the 10,000 Steps program. J Am Diet Assoc 2000 Aug; 100 (8): 878-9 49. Moreau KL, Degarmo R, Langley J, et al. Increasing daily walking lowers blood pressure in postmenopausal women. Med Sci Sports Exerc 2001 Nov; 33 (11): 1825-31 50. Ransdell LB, Robertson L, Ornes L, et al. Generations Exercising Together to Improve Fitness (GET FIT): a pilot study designed to increase physical activity and improve health-related fitness in three generations of women. Women Health 2004; 40 (3): 77-94 51. Schneider PL, Bassett Jr DR, Thompson DL, et al. Effects of a 10,000 steps per day goal in overweight adults. Am J Health Promot 2006 Nov-Dec; 21 (2): 85-9 52. Sidman CL, Corbin CB, Le Masurier G. Promoting physical activity among sedentary women using pedometers. Res Q Exerc Sport 2004 Jun; 75 (2): 122-9 53. Stovitz SD, VanWormer JJ, Center BA, et al. Pedometers as a means to increase ambulatory activity for patients seen at a family medicine clinic. J Am Board Fam Pract 2005 SepOct; 18 (5): 335-43 54. Sugiura H, Kajima K, Mirbod SM, et al. Effects of longterm moderate exercise and increase in number of daily steps on serum lipids in women: randomised controlled trial [ISRCTN21921919]. BMC Womens Health 2002; 2 (1): 3 55. Swartz AM, Strath SJ, Bassett DR, et al. Increasing daily walking improves glucose tolerance in overweight women. Prev Med 2003 Oct; 37 (4): 356-62 56. Talbot LA, Gaines JM, Huynh TN, et al. A home-based pedometer-driven walking program to increase physical activity in older adults with osteoarthritis of the knee: a preliminary study. J Am Geriatr Soc 2003 Mar; 51 (3): 387-92
ª 2009 Adis Data Information BV. All rights reserved.
Tudor-Locke & Lutes
57. Thomas L, Williams M. Promoting physical activity in the workplace: using pedometers to increase daily activity levels. Health Promot J Austr 2006 Aug; 17 (2): 97-102 58. Tudor-Locke C, Bell RC, Myers AM, et al. Controlled outcome evaluation of the First Step Program: a daily physical activity intervention for individuals with type II diabetes. Int J Obes Relat Metab Disord 2004 Jan; 28 (1): 113-9 59. VanWormer JJ, Boucher JL, Pronk NP, et al. Lifestyle behavior change and coronary artery disease: effectiveness of a telephone-based counseling program. J Nutr Educ Behav 2004 Nov-Dec; 36 (6): 333-4 60. Williams BR, Bezner J, Chesbro SB, et al. The effect of a behavioral contract on adherence to a walking program in postmenopausal African American women. Top Geriatr Rehabil 2005; 21 (4): 332-4 61. Wilson DB, Porter JS, Parker G, et al. Anthropometric changes using a walking intervention in African American breast cancer survivors: a pilot study. Prev Chronic Dis 2005 Apr; 2 (2): A16 62. Wyatt HR, Peters JC, Reed GW, et al. Using electronic step counters to increase lifestyle physical activity: Colorado on the move. J Phys Act Health 2004; 1: 181-90 63. Izawa KP, Yamada S, Oka K, et al. Long-term exercise maintenance, physical activity, and health-related quality of life after cardiac rehabilitation. Am J Phys Med Rehabil 2004 Dec; 83 (12): 884-92 64. Marlatt GA, Gordon JR. Relapse prevention: maintenance strategies in the treatment of addictive behaviors. New York (NY): Guilford Press, 1985 65. Bandura A. Social foundations of thought and action: a social-cognitive theory. Englewood Cliffs (NJ): PrenticeHall, 1986 66. Richardson CR, Mehari KS, McIntyre LG, et al. A randomized trial comparing structured and lifestyle goals in an internet-mediated walking program for people with type 2 diabetes. Int J Behav Nutr Phys Act 2007; 4: 59 67. Richardson CR, Brown BB, Foley S, et al. Feasibility of adding enhanced pedometer feedback to nutritional counseling for weight loss. J Med Internet Res 2005; 7 (5): e56 68. Carr LJ, Bartee RT, Dorozynski C, et al. Internet-delivered behavior change program increases physical activity and improves cardiometabolic disease risk factors in sedentary adults: results of a randomized controlled trial. Prev Med 2008 May; 46 (5): 431-8 69. Craig CL, Tudor-Locke C, Bauman A. Twelve-month effects of Canada on the Move: a population-wide campaign to promote pedometer use and walking. Health Educ Res 2007 Jun; 22 (3): 406-13 70. Croteau KA. Strategies used to increase lifestyle physical activity in a pedometer-based intervention. J Allied Health 2004 Winter; 33 (4): 278-81 71. Tudor-Locke C, Bassett DR, Swartz AM, et al. A preliminary study of one year of pedometer self-monitoring. Ann Behav Med 2004 Dec; 28 (3): 158-62 72. Tudor-Locke C, Lauzon N, Myers AM, et al. Effectiveness of the First Step Program delivered by professionals versus peers. J Phys Act Health 2009; 6: 456-62 73. Kroeze W, Werkman A, Brug J. A systematic review of randomized trials on the effectiveness of computer-tailored
Sports Med 2009; 39 (12)
Why Do Pedometers Work?
education on physical activity and dietary behaviors. Ann Behav Med 2006 Jun; 31 (3): 205-23 74. van den Berg MH, Schoones JW, Vliet Vlieland TP. Internetbased physical activity interventions: a systematic review of the literature. J Med Internet Res 2007; 9 (3): e26 75. Chan CB, Tudor-Locke C. Real-world evaluation of a community-based pedometerintervention. J Phys Act Health 2008 Sep; 5 (5): 648-64 76. Burton NW, Walsh A, Brown WJ. It just doesn’t speak to me: mid-aged men’s reactions to ‘10,000 Steps a Day’. Health Promot J Austr 2008 Apr; 19 (1): 52-9
ª 2009 Adis Data Information BV. All rights reserved.
993
77. Tudor-Locke C, Chan CB. An exploratory analysis of adherence patterns and program completion of a pedometerbased physical activity intervention. J Phys Act Health 2006; 3 (2): 210-20
Correspondence: Dr Catrine Tudor-Locke, Director, Walking Behaviour Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. E-mail:
[email protected]
Sports Med 2009; 39 (12)
Sports Med 2009; 39 (12): 995-1009 0112-1642/09/0012-0995/$49.95/0
REVIEW ARTICLE
ª 2009 Adis Data Information BV. All rights reserved.
Encouraging Walking for Transport and Physical Activity in Children and Adolescents How Important is the Built Environment? Billie Giles-Corti,1 Sally F. Kelty,1 Stephen R. Zubrick2 and Karen P. Villanueva1 1 Centre for the Built Environment and Health, School of Population Health, University of Western Australia, Crawley, Western Australia, Australia 2 Centre for Developmental Health, Curtin University of Technology and Telethon Institute for Child Health Research, West Perth, Western Australia, Australia
Contents Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 995 1. Built Environment (BE) Influences on the Physical Activity (PA) of Children and Young People. . . . . . 997 2. BE Factors that Influence Walking in Children and Young People. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 997 2.1 Destinations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 997 2.2 Neighbourhood Walkability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 998 2.3 Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 998 3. BE Factors Associated with PA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1000 3.1 Destinations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1000 3.2 Neighbourhood Walkability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1001 3.3 Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1001 3.4 Neighbourhood Aesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1001 4. Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1002 4.1 What are the Implications? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1003 4.2 Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1005 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1005
Abstract
In the post-World War II era, there have been dramatic changes to the environment that appear to be having a detrimental impact on the lifestyles and incidental physical activities of young people. These changes are not trivial and have the potential to influence not only physical health, but also mental health and child development. However, the evidence of the impact of the built environment on physical activity to date is inconsistent. This review examines the evidence on the association between the built environment and walking for transport as well as physical activity generally, with a focus on methodological issues that may explain inconsistencies in the literature to date. It appears that many studies fail to measure behaviour-specific environmental correlates, and insufficient attention is being given to differences according to the age of study participants. Higher levels of out-of-school-hours physical activity and walking appear to be significantly associated with higher levels of urban density and
Giles-Corti et al.
996
neighbourhoods with mixed-use planning, especially for older children and adolescents. Proximate recreational facilities also appear to predict young people’s level of physical activity. However, there are inconsistencies in the literature involving studies with younger children. Independent mobility increases with age. For younger children, the impact of the built environment is influenced by the decision-making of parents as the gatekeepers of their behaviour. Cross-cultural differences may also be present and are worthy of greater exploration. As children develop and are given more independent mobility, it appears that the way neighbourhoods are designed – particularly in terms of proximity and connectivity to local destinations, including schools and shopping centres, and the presence of footpaths – becomes a determinant of whether children are able, and are permitted by their parents, to walk and use destinations locally. If older children and adolescents are to enjoy health and developmental benefits of independent mobility, a key priority must be in reducing exposure to traffic and in increasing surveillance on streets (i.e. ‘eyes-onthe-street’) through neighbourhood and building design, by encouraging others to walk locally, and by discouraging motor vehicle use in favour of walking and cycling. Parents need to be assured that the rights and safety of pedestrians (and cyclists) – particularly child pedestrians and cyclists – are paramount if we are to turn around our ‘child-free streets’, now so prevalent in contemporary Australian and US cities. There remains a need for more age- and sex-specific research using behaviour- and context-specific measures, with a view to building a more consistent evidence base to inform future environmental interventions.
Increasing physical activity is one key strategy in curbing the alarming increases witnessed over the past 30 years in childhood and adolescent obesity and preventable chronic diseases in this young population.[1,2] Physically active children are at reduced risk of developing chronic diseases[3,4] and have enhanced psychological and emotional wellbeing.[5,6] Even children with chronic diseases function better if they are physically active.[7] Although youth-specific physical activity (PA) guidelines recommend at least 60 minutes of daily moderate- to vigorous-intensity physical activities (MVPA),[4,8] a sizeable number of young people do not engage in sufficient MVPA on a regular daily basis.[9] Given the evidence, focusing attention on children and young people is justified.[10] It is now generally well accepted that changes in the environment are contributing to the obesity epidemic by impacting upon three key behaviours: sedentariness, PA and overeating.[11-13] As Kelty et al.[14] observe, before World War II, habitual active travel, active play, incidental activity, physically demanding work and household chores were ª 2009 Adis Data Information BV. All rights reserved.
integral to daily life, work and play. However, technological advances have dramatically reduced incidental PA. For example, driving is now the preferred and most prevalent mode of transport in most developed countries.[15] Numerous laboursaving devices are readily available in households and workplaces.[14] In many Western nations, especially in Australia, workers now work longer hours than their parents and grandparents and are increasingly employed in more sedentary jobs.[16] Popular leisure-time activities, especially for children and adolescents, have also become more sedentary, e.g. electronic gaming.[9,17] In contemporary society a sedentary lifestyle has become the norm, hence the need to actively encourage more PA, especially active play, incidental PA and transport-related walking or cycling.[5] The idea of optimizing environments to provide healthful choices and to facilitate behaviour change is not new.[18] Yet in a recent systematic review of PA interventions targeting youth, Van Sluijs and colleagues[19] found that most well-designed intervention studies undertaken to date were Sports Med 2009; 39 (12)
Encouraging Walking in Children and Adolescents
knowledge-based interventions, with little evidence that they were effective. Rather their review confirmed lessons from tobacco control,[20] that effective interventions targeting youth need to be comprehensive and multifaceted: (i) educating about and promoting PA; (ii) targeting gatekeepers of healthful behaviours (i.e. parents, teachers); and (iii) providing opportunities to be active in the various settings regularly frequented by youth, i.e. school, home and neighbourhoods.[21] Until recently, PA research has focused on understanding individual and social environmental correlates of behaviour. Studies on the impact of the built environment (BE) on the PA of youth are relatively new, although a growing body of evidence is now emerging.[22-25] In this invited review we examine the evidence on the association between the BE and walking for transport as well as PA. The BE is defined as ‘‘the neighborhoods, roads, buildings, food sources, and recreational facilities in which people live, work, are educated, eat and play’’.[26] This review does not seek to replicate previous reviews of the literature, but rather focuses on methodological issues that may explain inconsistencies in the literature to date. Where there does appear to be consistent evidence, we go on to consider actions that could be taken by practitioners and policy-makers to create a supportive BE that encourages more PA in youth. Finally, we consider areas for future research. The presentation of the literature is structured around Pikora and colleagues’ Systematic Pedestrian and Cycling Environmental Scan (SPACES) framework of environmental determinants of walking in adults.[27] However, no evidence was available for some features of the framework, which are therefore not considered in the text. 1. Built Environment (BE) Influences on the Physical Activity (PA) of Children and Young People There is now a growing body of evidence showing that the BE has a significant influence on the active lifestyle choices of adults, particularly walking for transport.[12,28] Although our knowledge about children and adolescents is more limited, a body of evidence is developing.[14,22,24-26] ª 2009 Adis Data Information BV. All rights reserved.
997
While positive associations have been identified,[14,22,24] there are conflicting evidence and conclusions being drawn about the potential impact of the BE on young people’s behaviour,[14,22,24-26] depending on age and sex.[29] In an earlier paper, we argued that this relationship was behaviour- and context-specific.[30] Many previous studies and some reviews have failed to consider behaviourspecific correlates. Thus, in this review, we consider behaviour-specific evidence of environmental correlates and seek to highlight age and sex differences that may explain inconsistencies in research findings to date. 2. BE Factors that Influence Walking in Children and Young People Active transport (AT) includes travel by foot, bicycle and other non-motorized vehicles.[31] Increasing AT has been identified as one strategy that could increase community PA levels[31-33] as well as producing environmental[34,35] and social benefits.[36] Evidence from both Australia and the UK estimates that approximately 20% of car trips made during weekday morning rush-hour periods are short journeys made by parents dropping children at school.[37,38] Increasing daily activities such as walking to school and doing errands with or for parents have been identified as realistic strategies for increasing PA.[33,39] Yet there is consistent evidence that AT among children and adolescents has declined in the last two decades.[40-44] A reduction in active trips to school appears to be the major contributor to this decline. A number of factors are implicated in why children and adolescents are engaging in lower levels of AT,[23] including a range of demographic[43,45-48] and parental factors.[23] However, as argued by Andersen[49] and others,[50] unquestionably the BE plays a critical role by influencing opportunities for, and the safety of, AT. These BE factors are considered below. 2.1 Destinations
Destinations refer to the commercial and recreational land uses found in neighbourhoods, e.g. the parks, sports centres, shops, cinemas or public Sports Med 2009; 39 (12)
Giles-Corti et al.
998
services contained in a geographical area. In adults, there is considerable evidence that both walking for transport and recreation is more likely if destinations are present,[12] and recent evidence suggests that the variety and mix of destinations nearby is important.[51] Research on young people mirrors these findings, with proximity to relevant destinations also being critical, as outlined below. Time and distance are key factors that influence whether children or adolescents walk or cycle for transport to school or other destinations.[25,38,41,52-55] Nevertheless, few studies have defined a ‘walkable distance’ for children.[56] Timperio et al.[54] showed that, after adjustment, children living within 800 m of their school were 5–10 times more likely to commute actively to school. This was consistent with parents of these children reporting that 1.6 km (roundtrip) was a walkable distance for their children.[57] Similarly, in the US, McMillan[58] found that children were more likely to engage in AT to school if the school was within 1 km of their home. Although there is increasing evidence that distance to school and other destinations influences levels of walking or cycling,[50] many of the childhood AT studies failed to control for distance to destinations.[45,59] A US study by Falb and colleagues[60] estimated that only 1–51% of children lived within a ‘safe and reasonable’ walking distance from school, which in this study was defined as at least 1 mile (1.6 km) from the school along the street network along streets with a posted traffic speed of <25 miles/hour (40 km/h). Thus, a range of other urban design features may determine destination proximity, thereby influencing the potential for children to walk to school and other destinations. These are discussed below in terms of neighbourhood walkability. 2.2 Neighbourhood Walkability
A key factor that determines the proximity of destinations is neighbourhood walkability. Walkable neighbourhoods combine a range of neighbourhood features known to enhance walking, and are specifically designed for ease of pedestrian travel. As shown in figure 1, walkable neighbourhoods are characterized by: (i) street networks based on the traditional grid system that provides ª 2009 Adis Data Information BV. All rights reserved.
enhanced street connectivity and a variety of direct routes to local destinations; (ii) moderate to high urban density, which means more people have access to local destinations, which in turn increases the viability of local businesses and transit; and (iii) mixed land uses incorporating residential dwellings, shops, utilities, services and parks.[26] In contrast, low walkable neighbourhoods (see figure 2) have low density, poor access to shops and services, and disconnected street networks based on cul-de-sacs that feed into high-speed arterial roads, providing hazardous barriers for walkers and cyclists.[26] It is well established that neighbourhood walkability influences walking for transport in adults,[12,32,61-63] although fewer studies have explored how it influences walking in children and adolescents. The available studies suggest that young people who live in pedestrian-friendly or high-walkable neighbourhoods are more likely to walk to school,[64] particularly in high-income areas.[65] However, most studies of youth to date have examined specific aspects of the neighbourhood rather than an overall walkability index per se. For example, a number of studies involving children and adolescents (aged 9–15 years) have found that, irrespective of sex, AT to and from school was significantly more likely in neighbourhoods with better street connectivity, mixed land use and/or higher population densities.[25,58,59,66] Nevertheless, there appear to be inconsistencies in the evidence depending upon the age,[54,67] ethnicity and socioeconomic status of the study participants.[65] Inconsistencies in the evidence are potentially influenced by different ways of measuring environmental characteristics (e.g. connectivity) and definitions of neighbourhoods[56] and may also be due to varying levels of adjustment in models. For example, Timperio and colleagues[54] found that living in steeper neighbourhoods decreased walking in younger children, but not older children. However, most studies do not adjust for topography. 2.3 Safety
Children’s AT and independent mobility are influenced by traffic congestion and real and Sports Med 2009; 39 (12)
Encouraging Walking in Children and Adolescents
Fig. 1. Traditional grid system of a high walkable traditional neighbourhood in Perth, WA, Australia. Suburb is mixed residential (detached houses, semi-detached cottages, modern blocks of flats) with mixed retail (shops, pubs, cafes, cinema, hardware, supermarkets) within walking distance. Road and cadastre/lot parcel data provided by Department of Planning and Infrastructure, Perth, WA, Australia, 2006.
perceived parental concerns about personal and traffic safety.[14,22,23,25,33,55,68] Parental concerns for children’s safety on the roads are somewhat justified.[26] In Australia and the US, pedestrian motor vehicle collisions are a leading cause of paediatric mortality.[26,69,70] The risk of childpedestrian injury is related to overall exposure to traffic, and the number and/or type of streets crossed is often used as the proxy for traffic exposure.[47,71] The peak time for child pedestrian injuries is between 2pm and 4pm[72] and during school term time.[73] Moreover, there is an inverse relationship between pedestrian injury rates and the proportion of children driven home.[72] In elementary school children, parental concerns significantly influence whether children are allowed to walk or cycle in their local communities or to and from school.[68] These concerns range from traffic danger,[40] lack of safe roadcrossing infrastructure and exposure to traffic (especially on busy roads with fast travelling vehicles),[58,74] the presence of visual obstructions (such as parked cars creating unsafe places to cross roads),[75] concerns for personal safety or ‘stranger danger’,[14,48,76] as well as bullying.[68] ª 2009 Adis Data Information BV. All rights reserved.
999
There is some evidence that parents who allow their child to walk to school remain concerned that their child may be injured in an accident.[25] In the US, perceived traffic danger is estimated to inhibit approximately 40% of children (some 20 million) from walking or cycling to school.[76] Nevertheless, the more parents who drive their children to school (e.g. because of concerns about safety), the less safe the roads are for children who wish to walk or who have no choice but to use AT modes.[77] In older primary-school children, the presence of crossings[57,64] and having no busy roads to cross[54] increases the likelihood of children, particularly boys, walking to school. Thus, the need to control traffic and create safer routes to school is critical if children are to be safe, and parents are to be willing to permit their child to walk.[38] Although there are few published interventions, cross-sectional evidence suggests that the creation of safer routes to school increases children actively commuting to school.[64] Moreover, several studies have found that higher levels of walking for both children and adolescents are associated with the presence of sidewalks
Fig. 2. Low walkable conventional neighbourhood located south of the Perth central business district, WA, Australia. The suburb is primarily detached dwellings with few retail services and no shops within walking distance of most homes. Road and cadastre/lot parcel data provided by Department of Planning and Infrastructure, Perth, WA, Australia, 2006.
Sports Med 2009; 39 (12)
Giles-Corti et al.
1000
(footpaths) en route to and from home, school and recreational venues.[58,64,78] Some studies have examined whether specific sidewalk features are associated with increased levels of walking. In a US sample of male adolescents, for example, higher levels of brisk walking were recorded when sidewalks were free of physical obstructions.[79] In contrast, other studies from a variety of countries with different age groups and urban settings have found no relationship between walking levels and sidewalk condition[80,81] or whether walkways were sheltered.[81] Other prominent safety concerns relate to the presence of surveillance and street lighting. Evenson et al.[78] found that, compared with inactive and overweight/obese adolescent girls, physically active girls with a healthy weight were more likely to believe their neighbourhoods are safe places in which to be active. These teenagers perceived that there was good surveillance because other walkers and joggers were visible in the area. They were also less concerned than their inactive peers with antisocial behaviour and more likely to judge their neighbourhood as having a low crime rate. Their study also observed that adolescent girls were more physically active in neighbourhoods where the streets were well lit and when traffic volume was higher on the routes they walked. In another US study it was confirmed that surveillance was an important neighbourhood feature and that younger children were more likely to walk to school if at least 50% of the homes they passed en route had windows facing the street.[58] The positive association between PA and traffic volume appears to be counter-intuitive given parental and child concerns about traffic, and the increased risk of pedestrian injury associated with traffic exposure. However, it is possible that the presence of traffic along popular walking routes increases perceived and actual surveillance, thereby increasing feelings of personal safety. Moreover, popular routes may be used by both pedestrians and drivers travelling to the same destinations. Thus, in locations where there are more destinations to walk to, there also may be more traffic. Qualitative research that probes motives for walking and perceptions of the environment, and the interaction between the ª 2009 Adis Data Information BV. All rights reserved.
two, may help elucidate this seemingly counterintuitive finding.[14] 3. BE Factors Associated with PA Although it has been suggested that the predictive capacity of studies on the BE might be enhanced if behaviour-specific measures of the environment were used to predict context-specific behaviours,[30] many studies of youth examine the impact of the BE on PA, irrespective of its specific type. In these studies, a variety of methods have been used to measure behaviour, including various self-report measures[55,66,82,83] and objectively with pedometers or accelerometers.[84-86] 3.1 Destinations
The presence of public spaces, especially parks with sports pitches, and sports centres (i.e. recreation centres) appears to be significantly associated with higher MVPA in young people. Research findings from Australia, Europe and the US concur that irrespective of age (4–17 years) or sex, the proximity of parks and sports centres to young people’s homes is associated with higher use and higher weekly PA. These results have been observed regardless of whether PA is measured through self-report, such as an exercise or PA journal,[82,83,87-90] or objectively, using pedometers or accelerometers.[78,85,91] When parks and sports centres are within 800 m of the homes of both children and adolescents (aged 8–16 years) it appears that young people are more likely to use the facility and are more likely to walk or cycle to get there from their homes.[85,91] Epstein and colleagues[85] found that when facilities were within 800 m from participants’ homes, objectively measured weekly MVPA differed by 17.2–38.9 min/wk. In the same way that proximity and mix of venues is important for adults,[51] it also appears to be important in youth. Evenson et al.[78] found that when adolescent girls had a choice of 9–14 different PA venues close to home, on average their MVPA was 84.9 min/wk higher compared with girls who only had four venues near their home. Nevertheless, as long as children had access to transportation, even having one sports centre or Sports Med 2009; 39 (12)
Encouraging Walking in Children and Adolescents
dance club within 8 km from their homes was associated with a 5% reduction in risk of being overweight or obese.[90] In this respect, if venues are not nearby or self-transportation is not an option, parental transportation is a key determinant of a child’s participation in sport and activity sessions.[92] 3.2 Neighbourhood Walkability
Some studies have examined the impact of walkability specifically on out-of-school PA and found a positive age-dependent association. A large US study of children and young people aged 5–20 years by Frank and colleagues[83] found no association between out-of-school PA and neighbourhood walkability in children aged 5–8 years, who typically have little independent mobility. However, for children aged ‡9 years, various neighbourhood features predicted their out-ofschool activities. For example, living in a higher density area was associated with higher levels of PA in those aged 9 through 20 years, and in areas with enhanced street connectivity in those aged 12 through 20 years. A Dutch study of children as young as 6 years found similar results,[89] with higher levels of weekly PA associated with residential density (but only up to a limit of six stories per building), better street connectivity and more manned zebra (pedestrian) crossings. Conversely, a study of US children (aged £12 years) found higher levels of out-of-school PA were associated with low-density single-zoned land use (urban sprawl).[93] These results suggest that the impact of urban planning on children and young people may be age dependent and related to the age at which children gain some independent mobility. In this regard, it appears there may be cross-cultural differences in the age children are permitted to be independently mobile. 3.3 Safety
Parental concerns about safety are a major factor influencing children’s independent mobility, and in turn their PA.[68] Nevertheless, many studies of adults[94] and children[22,88] examining the association between subjective assessment of neighbourhood safety and PA have reported null ª 2009 Adis Data Information BV. All rights reserved.
1001
or inconsistent findings. A number of factors may be responsible for these findings, including the way perceived safety is assessed, study location, the age of the children, whether studies are stratified by sex, and possibly because studies have failed to differentiate between indoor and outdoor physical activities.[94] However, in studies of inner city or urban adolescents that include objective measures of violent crime[88] or neighbourhood disorder,[95] negative associations have been found with out-of-school PA and recreational PA, respectively. Moreover, studies of older children and adolescents examining perceived safety of parks have shown a negative association between low safety and PA in girls.[96] Carver and colleagues[68] suggest that parents’ concern about safety in parks (e.g. ‘stranger danger’ and bullying) deters them from allowing their children to visit parks alone. Thus, it is possible that in neighbourhoods where crime, violence or bullying is prevalent, where parks are not perceived to be safe or where a park is on a busy road, independently mobile adolescents constrain their outdoor physical activities, and the level of constraint may vary by sex. 3.4 Neighbourhood Aesthetics
Although proximity is important, there are additional complexities over and above physical access that determine use of destinations and the impact on PA levels. The aesthetic aspects of the natural environment or BE have the potential to make being physically active more pleasurable and interesting.[14] For example, one study of adolescent females found that simply having a proximate sports centre was insufficient to increase PA levels.[97] Rather, the aesthetic qualities of the sports centre appeared to influence its use by these young girls. Similarly, certain park attributes have also been found to be associated with increasing weekly PA in young people. For example, parks with higher quality sporting pitches and better overall amenities like fresh drinking water were preferred by both boys and girls and were significantly associated with higher levels of PA.[84] These researchers also found that parks with skateboard ramps were positively Sports Med 2009; 39 (12)
1002
associated with higher weekly PA for boys, although negatively associated with girls’ PA.[84] More qualitative research is required to better understand why the presence of a facility such as a skateboard ramp might negatively influence PA in girls and whether this is associated with perceived levels of safety.[14] For example, Veitch and colleagues[98] found that teenage boys often took over skateboard parks and this deterred other users. Thus, further investigation is warranted to explore aspects of public spaces that encourage multiple users and, in particular, space that provides both boys and girls with a supportive environment that encourages their PA. A Dutch study found that higher levels of childhood PA were also associated with certain aesthetic features, i.e. higher ratings of overall local neighbourhood attractiveness, more green space (parks and gardens), less visible litter, less urban decay, and less concrete-covered playgrounds.[66] These findings were supported in a study of adolescent girls in Scotland[97] and adolescent girls in Portugal.[99] As yet, limited research has been undertaken on the importance of neighbourhood aesthetics on youth and whether aesthetic qualities of the BE impact directly through the child or young person, and/or indirectly through their impacts on parents or guardians as the gatekeepers of their children’s behaviour.[14] 4. Discussion Encouraging children to be physically active is not only important for improving their physical and mental health, but also important in terms of maximizing their enjoyment and contributing to healthy child development.[5] Children who participate in fun and enjoyable physical activities that involve social interactions are likely to be more active than others, thereby improving longterm physical and mental health outcomes and contributing to healthy child development.[5] In the last decade, research on the environmental factors associated with PA has escalated; however, until relatively recently the focus has been on adults rather than children or young people. Although there have already been a number of reviews of the evidence,[22,24] the conclusions being ª 2009 Adis Data Information BV. All rights reserved.
Giles-Corti et al.
drawn appear to be inconsistent. This paper has attempted to understand the conflicting evidence. As suggested by McMillan[23] and others,[56] the impact of the BE on the activity levels of children and adolescents may depend upon a range of factors, including the child’s age (including differences between older and younger children and adolescents), the level of independent mobility, social norms and parental factors. However, in addition, inconsistencies in the evidence base may also arise because studies have not included behaviour-specific measures of the environment and context-specific behavioural measures,[30,100] and varying environmental measures and neighbourhood definitions have been adopted.[56] Crosscultural differences may also exist, particularly for younger children.[77] Many of the environmental factors that influence adult PA – particularly walking for transport – are similar to those that influence independently mobile older children and adolescents. For example, there is consistent evidence that in older children and adolescents proximate destinations are important for increasing both PA and AT.[50] However, there is considerable inconsistency in the literature involving studies with younger children. Independent mobility increases with age. Thus, the impact of access to parks and sports centres on the PA of younger children’s activities or neighbourhood walkability on walking is likely to be influenced by parental decision making, as the gatekeepers of younger children’s behaviour.[23,101,102] Moreover, it is possible that cross-cultural differences exist for parents of younger children with more favourable societal attitudes (possibly because of more supportive neighbourhood environments) in parts of Europe and Scandinavia compared with other developed countries such as Australia and the US. Higher levels of out-of-school-hours PA and walking were significantly associated with higher levels of urban density and neighbourhoods with mixed-use planning, especially for older children and adolescents. Once again, it is likely that these results reflect the levels of independent mobility experienced by older children rather than differential impacts of density or land use mix on children of different age groups. Adolescence marks Sports Med 2009; 39 (12)
Encouraging Walking in Children and Adolescents
the time when many parents begin to permit their children greater independent mobility and freedom to explore their local environment.[103] Hence, as children get older, the walkability of the local neighbourhood becomes even more influential, either hindering or facilitating their level of independent mobility as well as their development.[104] The evidence suggests that proximate and accessible sport centres and parks are important places for young people, particularly adolescents. Thus, having these destinations close to young people’s homes may significantly increase weekly MVPA. In the last few years researchers have begun to explore aspects of park and sports centre design preferred by young people, and subtle differences are apparent.[80,97] However, this research is in its infancy and little is known about why young people choose to use certain facilities and not others. For example, there is little evidence on the impact of socially determined factors, such as the cost of entry, on patronage of facilities. If young people are to be encouraged to become more active, more research is required on what aspects of the BE increase their activity and on the range of specific facilitators and barriers to using public places (e.g. parks and sports centres). Importantly, more needs to be known about preferences of young people and the role played by financial impediments in determining their use of local destinations. Another layer of complexity is the influence of the developmental phases of children and young people and their impact on their physical activity, particularly if children are unable to participate. There is a dearth of research in this area,[105] which could be a fruitful future line of enquiry. As children get older, the real and perceived safety of a neighbourhood will determine the extent to which their outdoor physical activities and local walking are constrained or encouraged. Unsafe neighbourhoods constrain outdoor physical activities of local residents, including children and young people[68,94] – particularly girls and young women. When objective rather than subjective safety is measured, there is a consistent negative relationship between PA and crime or social disorder,[94] unlike in studies that measure perceptions ª 2009 Adis Data Information BV. All rights reserved.
1003
of neighbourhood safety, which often produce inconsistent results. This is not to say that perceptions of safety are not important. Rather, as suggested by Foster and Giles-Corti,[94] it is likely that the inconsistencies are due to the way perceptions of ‘neighbourhood safety’ are measured. For example, from a child’s perspective, aspects of safety could include traffic safety, at least three types of personal safety (i.e. ‘stranger danger’, attack and bullying), safety from crime or violence, as well as indicators of safety such as incivilities. Using more specific measures may not only assist in producing a more consistent evidence base, but would also assist in developing interventions. In terms of neighbourhood aesthetics, at this stage there is limited evidence on its impact on youth and whether its influence is mediated through their parents. However, based on the limited amount of literature available, it appears that young people are more likely to be physically active in neighbourhoods that offer a variety of places to visit, and the aesthetic appeal of neighbourhoods and destinations may be important.[5] 4.1 What are the Implications?
From a regional and neighbourhood planning perspective there is evidence that certain aspects of neighbourhoods make them walkable, i.e. compact neighbourhoods with connected street networks, higher densities and mixed-use planning as well as transit. However, importantly, there may be thresholds for these factors that may be relevant for children, and this warrants further research. For example, a European study[89] found that densities no higher than six stories were associated with higher levels of PA in children. As the field advances and recommendations are made to policy-makers and practitioners, being mindful of thresholds and any potential negative impacts of the BE on different target groups (children, adults and older adults) is critical to avoid the development of policy that is harmful to, rather than protective of, health. Nevertheless, as children develop and are given more independent mobility, the way neighbourhoods are designed – particularly in terms of proximity and connectivity to local destinations including schools and shopping centres, and the Sports Med 2009; 39 (12)
1004
presence of footpaths – becomes a major determinant of whether children are able, and are permitted by their parents, to walk locally. Irrespective of the provision of places to walk to, and walking infrastructure that facilitates local walking, a key point of parental decision-making for permitting a child to walk is their (and society’s) assessment of how safe the neighbourhood is in terms of both traffic and personal safety. If older children and adolescents are to experience the joys and child development benefits of independent mobility, a key priority must be in reducing motor vehicle use in favour of pedestrians, cyclists and transit users, thereby reducing exposure to traffic and increasing surveillance on streets (i.e. ‘eyes-on-the-street’ through neighbourhood and building design and encouraging others to walk locally). Parents need to be assured that the rights and safety of pedestrians (and cyclists) – particularly child pedestrians and cyclists – are paramount if we are to turn around our ‘child-free streets’, now so prevalent in contemporary Australian and US cities. Although the focus to date has been on providing safe routes to schools, greater attention could be given to creating safe routes to all local destinations such as shops and shopping centres, which would enhance the quality and walkability of local environments for all residents, including children, adolescents and older adults. Clearly, access to formal and informal recreational facilities is a prerequisite for children, young people and others in order for them to play sport and to participate in active recreation. From a child’s perspective, participation in sport and formal recreational activities is important, providing many benefits over and above the physical health benefits. From a developmental perspective, participation in physically active clubs (e.g. martial arts, dancing) or sporting teams is important for both physical and mental health. Firstly, physically active youth develop more muscle mass and stronger bones characterized by high mineral content and density. Stronger joints and bones help protect against the onset of debilitating diseases such as osteoporosis in middle and older age, especially for females.[106,107] Secondly, being in a club or a team provides a rich environment where ª 2009 Adis Data Information BV. All rights reserved.
Giles-Corti et al.
cultural norms of behaviour are learnt. Young people in clubs learn about cooperation, sharing resources, self-discipline, to accept loss and defeat, learn sportsmanship and conflict resolution.[103] Although these skills are not acquired through PA per se, they are learnt in specific environments. Within clubs young people are exposed to the times and places where certain behaviour is accepted (such as teamwork and gracious losing) while other behaviour is discouraged (e.g. bullying or vocal outbursts).[108] According to Petersen,[103] as these skills learnt in clubs and teams are often generic they are usually transferable to other settings such as in school. It is possible that such skills (such as gracious losing and cooperation) acquired through clubs accounts for why club and team members are popular with their peers. Moreover, young people’s use of community and youth facilities has been shown to be associated with their higher academic achievement.[104] For older children and adolescents, the presence of recreational facilities is also associated with higher levels of PA, and this is further enhanced when the mix and variety of recreational facilities increases. There is some evidence that young people will walk to parks and recreation/ sports centres if they are within approximately 800 m of their homes, and there is evidence that they will travel to clubs and specialized recreational activities several kilometres away, provided they have access to transportation. However, the presence of recreational facilities alone may be necessary but insufficient to encourage use. Attention also needs to be given to attractiveness of those facilities to young people (particularly girls) in terms of aesthetics and programming, and broader issues of accessibility, i.e. the ease and safety with which they can be accessed by transit or whether major roads need to be crossed, as well as the cost of accessing those facilities. The design,[109] location, programmes and cost of recreational facilities may facilitate or impede their use by young people, who have their own set of needs, preferences and desires about how they would like to use their leisure time. At the same time, young people and children often rely on their parents for transportation to access distant destinations if facilities are not proximate or easily Sports Med 2009; 39 (12)
Encouraging Walking in Children and Adolescents
accessed by transit, and for financial support if the use involves a cost. Being mindful of these other aspects of accessibility is critical. Finally, regarding future research, there are many gaps in the evidence to date. From a child and young person’s perspective, better conceptualization is required of variables such as definitions of neighbourhood, ‘neighbourhood safety’ and aesthetics, as well as a better understanding of aspects of the BE that influence children and young people’s behaviour (e.g. the design of parks). There is also a dearth of literature about cycling in children and adolescents. Given the potential for cycling to increase children’s mobility in adolescence, and the child and spatial development benefits likely to accrue from gaining this level of independence, more research in this area may be warranted. At this stage, few studies have considered the mechanisms through which the BE influences children and young people’s behaviour and the mediating effects of parental decision making. Moreover, to date, most of the evidence is crosssectional, and longitudinal evidence would assist in establishing causal relationships. There is also a need for theoretical studies that incorporate an ecological model,[110] with consideration being given to the relative influence of individual, social, environmental and BE factors. This would assist in advancing the field by providing guidance for future interventions. Thus, although good progress has been made, this area of research is in its infancy. 4.2 Limitations
This is a narrative review, rather than a systematic review, which is a limitation. Nevertheless, its aim was to examine inconsistencies in the evidence and hypothesize why these might be occurring. Moreover, it sought to examine specific behaviours rather than general physical activity. It is likely that systematic reviews that fail to differentiate between specific behaviours and age groups (younger children, older children and adolescents) will present a confusing picture of the state of evidence. In this sense, the narrative review was a suitable methodology and proved a useful tool for elucidating inconsistencies in the literature. ª 2009 Adis Data Information BV. All rights reserved.
1005
Another limitation is that this review has not explored the relationship between home environments and PA. Increasingly, the home environment is becoming important as a venue for young people’s PA as parents become more fearful about personal and traffic safety, and consequently young people become more housebound. A number of studies have identified that various aspects of the home environment (e.g. the number of televisions[111] and whether located in the child’s bedroom)[112] are associated with levels of PA and sedentariness in younger members of households. In addition, relatively recent trends in the way houses are being built may also be contributing to declining levels of PA in children. For example, in Australia, housing developers are now selling larger homes on smaller housing lot sizes. This has substantially increased the size of the housing footprint on lots while reducing the amount of outdoor space available for play by children (and dogs). Salmon and colleagues[113] have found a negative association between yard size and sedentariness, which in turn has been shown to be related to weight status. Thus, one might expect that in the future the old fashioned notion of ‘playing outside’ may vanish, with children retreating to televisions and computers in bedrooms or internal play areas. Potentially, this will further decrease children’s PA with a detrimental impact on their physical and mental health, not to mention aspects of child development derived from exploring local environments.[14] 5. Conclusions In the post-World War II era, there have been dramatic changes to the environment that appear to be having a detrimental impact on the lifestyles and incidental PAs of young people. These changes are not trivial and, as discussed in this review, have the potential to not only influence physical health, but also mental health and child development. However, the evidence on the impact of the BE to date is inconsistent. This is probably due to a number of reasons. Firstly, this area of research is in its infancy and the conceptualization and measurement of environments is still evolving. Secondly, the behaviours and environments are Sports Med 2009; 39 (12)
Giles-Corti et al.
1006
complex. Finally, it is only now becoming apparent that there are differential impacts on children and adolescents of different ages and sexes, as well as cross-cultural differences, suggesting that specific studies and/or stratified analyses are required. Despite the complexities involved, it is clear this is an important area of future research with enormous potential to inform policy and practice aimed at creating environmental conditions that encourage and facilitate PA in children and young people.
10.
11. 12.
13. 14.
Acknowledgements This manuscript was written for work undertaken as part of a Population Health Capacity Building Grant (#458668). BG-C is supported by an NHMRC Senior Research Fellow (#503712), SFK by a post-doctoral fellowship funded by the PHCBG (#458668) and KPV by an Australian Post-Graduate Award. The authors gratefully acknowledge the helpful comments provided by Dr Anna Timperio, Centre for Physical Activity and Nutrition, Deakin University, and also three anonymous reviewers.
15.
16.
17. 18.
References 1. WHO. Young people: need to move for health and wellbeing. Geneva: World Health Organization, 2004 2. ASSO. Obesity in Australian children. Australian Society for the Study of Obesity, 2004 [online]. Available from URL: http://www.asso.org.au/freestyler/gui/files//factsheet_ children_prevalence.pdf [Accessed 2009 Oct 1] 3. Boreham C, Riddoch C. The physical activity, fitness and health of children. J Sports Sci 2001; 19: 915-29 4. Daniels SR, Arnett DK, Eckel RH, et al. AHA scientific statement: overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation 2005; 111 (15): 1999-2012 5. Kelty SF, Zubrick SR, Giles-Corti B. Healthy body, healthy mind: why physically active children are healthier physically, psychologically and socially. In: Beaulieu N, editor. Physical activity and children: new research, Hauppauge (NY): Nova Science Publishers Inc., 2008 6. Biddle S, Gorely T, Stensel D. Health-enhancing physical activity and sedentary behaviour in children and adolescents. J Sports Sci 2004; 22 (8): 679-701 7. Goldberg B. Sports and exercise for children with chronic health conditions. Champaign (IL): Human Kinetics, 1995 8. Commonwealth Department of Health and Aging. Australia’s physical activity recommendations for children and young people, 2006 [online]. Available from URL: http:// www.health.gov.au/internet/main/publishing.nsf/content/ health-pubhlth-strateg-phys-act-guidelines#rec_5_12 [Accessed 2009 Oct 1] 9. Janssen I, Katzmarzyk P, Boyce WF, et al. Comparison of overweight and obesity prevalence in school-aged youth
ª 2009 Adis Data Information BV. All rights reserved.
19.
20.
21.
22.
23.
24.
25.
26.
27.
from 34 countries and their relationships with physical activity and dietary patterns. Obes Rev 2005; 6: 123-32 van Mechelen W, Twisk J, Post G, et al. Physical activity of young people: the Amsterdam Longitudinal Growth and Health Study. Med Sci Sports Exerc 2000; 32 (9): 1610-6 Hill J, Wyatt H, Reed G, et al. Obesity and the environment: where do we go from here? Science 2003; 299: 853-5 Transportation Research Board. Does the built environment influence physical activity? Examining the evidence. Washington, DC: TRB, 2005 Kopelman P. Health risks associated with overweight and obesity. Obes Rev 2007; 8 Suppl. 1: 13-7 Kelty SF, Giles-Corti B, Zubrick SR. Physical activity and young people: the impact of the built environment in encouraging play, fun and being active. In: Beaulieu NP, editor. Physical activity and children: new research. Hauppauge (NY): Nova Science Publishers Inc., 2008 Newman P, Kenworthy J. Sustainability and cities: overcoming automobile dependence: an international sourcebook. Aldershot: Gower, 1989 Campbell I. Long working hours in Australia: workingtime regulation and employer pressures. CASR Working Papers Number 2005-2: Centre for Applied Social Research, 2005 Booth M. What proportion of Australian children are sufficiently active? Med J Aust 2000; 173 Suppl. 7: S6-7 WHO. The Ottawa charter for health promotion. Health Prom Int 1986; 1: 3-5 Van Sluijs E, McMinn A, Griffin S. Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials. BMJ 2007 6 Oct; 335: 703-7 Green LW, Orleans CT, Ottoson JM, et al. Inferring strategies for disseminating physical activity policies, programs, and practices from the successes of tobacco control. Am J Prev Med 2006 Oct; 31 (4 Suppl.): S66-81 Giles-Corti B, Salmon J. Encouraging children and adolescents to be more active. BMJ 2007 Oct 6; 335 (7622): 677-8 Davison KK, Lawson CT. Do attributes in the physical environment influence children’s physical activity? A review of the literature. Int J Behav Nutr Phys Activity 2006; 3: 19 McMillan T. Urban form and a child’s trip to school: the current literature and a model for future research. J Planning Lit 2005; 19 (4): 440-56 Ferreira I, van der Horst K, Wendel-Vos W, et al. Environmental correlates of physical activity in youth: a review and update. Obes Rev 2007 Mar; 8 (2): 129-54 Salmon J, Salmon L, Crawford DA, et al. Associations among individual, social, and environmental barriers and children’s walking or cycling to school. Am J Health Prom 2007 Nov-Dec; 22 (2): 107-13 Sallis JF, Glanz K. The role of built environments in physical activity, eating, and obesity in childhood. Future Child 2006 Spring; 16 (1): 89-108 Pikora T, Giles-Corti B, Bull F, et al. Developing a framework for assessment of the environmental determinants of walking and cycling. Soc Sci Med 2003; 56: 1693-793
Sports Med 2009; 39 (12)
Encouraging Walking in Children and Adolescents
28. Owen N, Humpel N, Leslie E, et al. Understanding environmental influences on walking: review and research agenda. Am J Prev Med 2004; 27 (1): 67-76 29. Panter JR, Jones AP, van Sluijs EM. Environmental determinants of active travel in youth: a review and framework for future research. Int J Behav Nutr Phys Act 2008; 5: 34 30. Giles-Corti B, Timperio A, Bull F, et al. Understanding physical activity environmental correlates: increased specificity for ecological models. Exerc Sport Sci Rev 2005 Oct; 33 (4): 175-81 31. National Public Health Partnership. Promoting active transport: an intervention portfolio to increase physical activity as a means of transport. Melbourne (VIC): NPHP, 2001 32. Saelens B, Sallis J, Frank L. Environmental correlates of walking and cycling: findings from the transportation, urban design, and planning literatures. Ann Behav Med 2003; 25 (2): 80-91 33. Jago R, Baranowski T. Non-curricular approaches for increasing physical activity in youth: a review. Prev Med 2004; 39 (1): 157-63 34. Mason C. Transport and health: en route to a healthier Australia? Med J Aust 2000; 172: 230-2 35. DETR. Encouraging walking: advice to local authorities. London: Department of the Environment, Transport and the Regions, 2000 36. Leyden KM. Social capital and the built environment: the importance of walkable neighborhoods. Am J Pub Health 2003 Sep; 93 (9): 1546-51 37. Morris J, Wang F, Lilja L. School children’s travel patterns: a look back and a way forward. Transport Engineer Aust 2001; 7 (1-2): 15-25 38. Black C, Collins A, Snell M. Encouraging walking: the case of journey-to-school trips in compact urban areas. Urban Studies 2001 Jun; 38 (7): 1121-41 39. Dietz A, Gortmaker S. Preventing obesity in children and adolescents. Ann Rev Pub Health 2001; 22: 337-53 40. Harten N, Olds T. Patterns of active transport in 11-12 year old Australian children. Aust NZ J Pub Health 2004; 28: 167-72 41. French S, Story M, Jeffery R. Environmental influences on eating and physical activity. Ann Rev Pub Health 2001; 22: 309-35 42. Bradshaw R. School children’s travel: the journey to school. Geography 2001 Jan; 86: 77-8 43. Roberts I. Safely to school? Lancet 1996 Jun 15; 347 (9016): 1642 44. Salmon J, Timperio A, Cleland V, et al. Trends in children’s physical activity and weight status in high and low socioeconomic status areas of Melbourne, Victoria, 1985-2001. Aust NZ J Pub Health 2005 Aug; 29 (4): 337-42 45. Evenson K, Huston S, McMillen B, et al. Statewide prevalence and correlates of walking and bicycling to school. Arch Ped Adolesc Med [NLM-Medline] 2003 Sep; 157 (9): 887-92 46. Metcalf B, Voss L, Jeffrey A, et al. Physical activity cost of the school run: impact on schoolchildren being driven to school. BMJ 2004; 329: 832-3
ª 2009 Adis Data Information BV. All rights reserved.
1007
47. Carlin JB, Stevenson MR, Roberts I, et al. Walking to school and traffic exposure in Australian children. Aust NZ J Pub Health 1997 Jun; 21 (3): 286-92 48. DiGuiseppi C, Roberts I, Li L, et al. Determinants of car travel on daily journeys to school: cross sectional survey of primary school children. BMJ 1998 May 9; 316 (7142): 1426-8 49. Andersen L. Physical activity and health. BMJ 2007; 334: 1173 50. Tester JM. The built environment: designing communities to promote physical activity in children. Pediatrics 2009 Jun; 123 (6): 1591-8 51. McCormack GR, Giles-Corti B, Bulsara M. Correlates of using neighborhood recreational destinations in physically active respondents. J Phys Act Health 2007 Jan; 4 (1): 39-53 52. Anonymous. School transportation modes: Georgia, 2000. Morbid Mortal Weekly Rep 2002; 51 (32): 704-5 53. EPA. Travel and environmental implications of school siting. Washington, DC: United States Environmental Protection Agency, 2003: report no.: EPA-231-R-03-004 54. Timperio A, Ball K, Salmon J, et al. Personal, family, social, and environmental correlates of active commuting to school. Am J Prev Med 2006; 30 (1): 45-51 55. Carver A, Salmon J, Campbell K, et al. How do perceptions of local neighborhood relate to adolescents’ walking and cycling? Am J Health Prom 2005; 20 (2): 139-47 56. Dunton GF, Kaplan J, Wolch J, et al. Physical environmental correlates of childhood obesity: a systematic review. Obes Rev 2009 Jul; 10 (4): 393-402 57. Timperio A, Crawford D, Telford A, et al. Perceptions about the local neighborhood and walking and cycling among children. Prev Med 2004 Jan; 38 (1): 39-47 58. McMillan TE. The relative influence of urban form on a child’s travel mode to school. Transport Res (Part A: Policy and Practice) 2007; 1 (41): 69-79 59. Braza M, Shoemaker W, Seeley A. Neighborhood design and rates of walking and biking to elementary school in 34 California communities. Am J Health Prom 2004; 19 (2): 128-36 60. Falb M, Kanny D, Powell KE, et al. Estimating the proportion of children who can walk to school. Am J Prev Med 2007; 33 (4): 269-75 61. Frank LD, Saelens BE, Powell KE, et al. Stepping towards causation: do built environments or neighborhood and travel preferences explain physical activity, driving, and obesity? Soc Sci Med 2007 Jul 16; 65 (9): 1898-914 62. Frank L, Schmid T, Sallis J, et al. Linking objectively measured physical activity with objectively measured urban form: findings from SMARTRAQ. Am J Prev Med 2005; 28 (2 Suppl. 2): 117-25 63. Owen N, Cerin E, Leslie E, et al. Neighborhood walkability and the walking behavior of Australian adults. Am J Prev Med 2007 Nov; 33 (5): 387-95 64. Boarnet MG, Anderson CL, Day K, et al. Evaluation of the California Safe Routes to School legislation: urban form changes and children’s active transportation to school. Am J Prev Med 2005 Feb; 28 (2): 134-40
Sports Med 2009; 39 (12)
1008
65. Kerr J, Rosenberg D, Sallis JF, et al. Active commuting to school: associations with environment and parental concerns. Med Sci Sports Exerc 2006; 38 (4): 787-93 66. de Vries H. Comment on ‘‘modifiable family and school environmental factors associated with smoking status among adolescents in Guangzhou, China’’. Prev Med 2007 Aug-Sep; 45 (2-3): 119-20 67. Ewing R, Schroeer W, Green W. School location and student travel. Transport Res Rec 2004; 1895: 55-63 68. Carver A, Timperio A, Crawford D. Playing it safe: the influence of neighbourhood safety on children’s physical activity (a review). Health Place 2008; 14 (2): 217-27 69. Moon L, Meyer P, Grau J. Australia’s young people: their health and wellbeing. Canberra (ACT): AIHW, 1999: report no.: /AIHW, Cat No. PHE 19 70. Cross DS, Hall MR. Child pedestrian safety: the role of behavioural science. Med J Aust 2005; 182 (7): 318-9 71. Macpherson A, Roberts I, Pless I. Children’s exposure to traffic and pedestrian injuries. Am J Public Health 1998 Dec; 88 (12): 1840-3 72. Rao R, Hawkins M, Guyer B. Children’s exposure to traffic and risk of pedestrian injury in an urban setting. Bull NY Acad Med 1997; 74 (1): 65-80 73. LaScala EA, Gruenewald PJ, Johnson FW. An ecological study of the locations of schools and child pedestrian injury collisions. Accid Anal Prevent 2004; 36 (4): 569-76 74. Timperio A, Salmon J, Ball K. Evidence-based strategies to promote physical activity among children, adolescents and young adults: review and update. J Sci Med Sport 2004; (7): 20-9 75. Stevenson M, Jamrozik KD, Spittle J. A case-control study of traffic risk factors and child pedestrian injury. Int J Epidemiol 1995; 24 (5): 957-64 76. Anonymous. Barriers to children walking and biking to school: United States, 1999. Morbid Mortal Weekly Rep 2002; 51 (32): 701-4 77. Hillman M, Adams J, Whitelegg J. One false move: a study of children’s independent mobility. London: PSI Publishing, 1990 78. Evenson KR, Scott MM, Cohen DA, et al. Girls’ perception of neighborhood factors on physical activity, sedentary behavior, and BMI. Obesity 2007; 15 (2): 430-45 79. Jago R, Baranowski T, Zakeri I, et al. Observed environmental features and the physical activity of adolescent males. Am J Prev Med 2005 Aug; 29 (2): 98-104 80. Mota J, Almeida M, Santos P, et al. Perceived neighbourhood environments and physical activity in adolescents. Prev Med 2005; 41: 834-6 81. Ziviani J, Kopeshke R, Wadley D. Children walking to school: parent perceptions of environmental and psychosocial influences. Aust Occupation Ther J 2006; 53 (1): 27-34 82. Brodersen NH, Steptoe A, Williamson S, et al. Sociodemographic, developmental, environmental, and psychological correlates of physical activity and sedentary behavior at age 11 to 12. Ann Behav Med 2005; 29 (1): 2-11 83. Frank LD, Kerr J, Chapman J, et al. Urban form relationships with walk trip frequency and distance among youth. Am J Health Prom 2007; 21 (4): 305-11
ª 2009 Adis Data Information BV. All rights reserved.
Giles-Corti et al.
84. Cohen DA, Ashwood JS, Scott MM, et al. Public parks and physical activity among adolescent girls. Pediatrics 2006; 118 (5): 1381-9 85. Epstein LH, Raja S, Gold SS, et al. Reducing sedentary behavior: the relationship between park area and the physical activity of youth. Psychol Sci 2006; 17 (8): 654-9 86. Norman GJ, Nutter SK, Ryan S, et al. Community design and access to recreational facilities as correlates of adolescent physical activity and body-mass index. J Phys Activity Health 2006; 3 Suppl. 1: 118-28 87. Roemmich JN, Epstein LH, Raja S, et al. Association of access to parks and recreational facilities with the physical activity of young children. Prev Med 2006; 43: 437-41 88. Gomez JE, Johnson BA, Selva M, et al. Violent crime and outdoor physical activity among inner-city youth. Prev Med 2004; 39 (5): 876-81 89. de Vries SI, Bakker I, van Mechelen W, et al. Determinants of activity-friendly neighbourhoods for children: results from the SPACE study. Am J Health Prom 2007; 21 (4): 312-659 90. Gordon-Larsen P, Nelson MC, Page P, et al. Inequality in the built environment underlies key health disparities in physical activity and obesity. Pediatrics 2006; 117 (2): 417-24 91. Cohen DA, Ashwood S, Scott M, et al. Proximity to school and physical activity among middle school girls: the Trial of Activity for Adolescent Girls study. J Phys Activity Health 2006; 3 Suppl. 1: S129-38 92. Hoefer WR, McKenzie TL, Sallis JF, et al. Parental provision of transportation for adolescent physical activity. Am J Prev Med 2001; 21 (1): 48-51 93. Copperman RB, Bhat CR. An analysis of the determinants of children’s weekend physical activity participation. Transportation 2007; 34: 67-87 94. Foster S, Giles-Corti B. The built environment, neighborhood crime and constrained physical activity: an exploration of inconsistent findings. Prev Med 2008; 47 (3): 241-51 95. Molnar BE, Gortmaker SL, Bull FC, et al. Unsafe to play? Neighborhood disorder and lack of safety predict reduced physical activity among urban children and adolescents. Am J Health Prom 2004 May-Jun; 18 (5): 378-86 96. Sallis JF, Taylor WC, Dowda M, et al. Correlates of vigorous physical activity for children in grades 1 through 12: comparing parent-reported and objectively measured physical activity. Ped Exerc Sci 2002 Feb; 14 (1): 30-44 97. Whitehead SH, Biddle SJH, O’Donovan TM, et al. Social, psychological and physical environmental factors in groups differing by levels of physical activity: a study of Scottish adolescent girls. Ped Exerc Sci 2006; 18 (2): 226-39 98. Veitch J, Bagley S, Ball k, et al. Where do children usually play? A qualitative study of parents’ perceptions of influences on children’s active free-play. Health Place 2006; 12 (4): 383-93 99. Mota J, Delgado N, Almeida M, et al. Physical activity, overweight, and perceptions of neighborhood environments among Portuguese girls. J Phys Activity Health 2006; 3 (3): 314-22
Sports Med 2009; 39 (12)
Encouraging Walking in Children and Adolescents
100. Salmon J, Timperio A. Prevalence, trends and environmental influences on child and youth physical activity. Med Sport Sci 2007; 50: 183-99 101. Adkins S, Sherwood NE, Story M, et al. Physical activity among African-American girls: the role of parents and the home environment. Obes Res 2004; 12 Suppl.: 38S-45S 102. Kligerman M, Sallis JF, Ryan S, et al. Association of neighbourhood design and recreation environment variables with physical activity and body mass index in adolescents. Am J Health Prom 2007; 21 (4): 274-7 103. Peterson C. Looking forward through the lifespan: developmental psychology. 4th ed. Sydney (NSW): Prentice Hall, 2004 104. Hin L. Built environment and children’s academic performance: a Hong Kong perspective. Habitat Int 2009; 33: 45-51 105. Holt NL, Spence JC, Sehn ZL, et al. Neighborhood and developmental differences in children’s perceptions of opportunities for play and physical activity. Health Place 2008 Mar; 14 (1): 2-14 106. Bass S, Pearce G, Bradney M, et al. Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts. J Bone Mineral Res 1998; 13 (3): 500-7 107. Matthews BL, Bennell KL, McKay HA, et al. Dancing for bone health: a 3-year longitudinal study of bone mineral accrual across puberty in female non-elite dancers and controls. Osteoporosis Int 2006; 17 (7): 1043-54
ª 2009 Adis Data Information BV. All rights reserved.
1009
108. Akers RL. Criminological theories: introduction and evaluation. 2nd ed. Los Angeles (CA): Roxbury Publishing, 1997 109. Tester J, Baker R. Making the playfields even: evaluating the impact of an environmental intervention on park use and physical activity [online]. Available from URL: http://www. ncbi.nlm.nih.gov/pubmed/19463491 [Accessed 2009 Oct 1] 110. Sallis JF, Cervero RB, Ascher W, et al. An ecological approach to creating active living communities. Annu Rev Public Health 2006; 27: 297-322 111. Roemmich JN, Epstein LH, Raja S, et al. The neighborhood and home environments: disparate relationships with physical activity and sedentary behaviors in youth. Ann Behav Med 2007; 33 (1): 29-38 112. Adachi-Meija A, Longacre M, Gibson J, et al. Children with a TV in their bedroom at higher risk for being overweight. Int J Obes 2007; 31: 644-51 113. Salmon J, Telford A, Crawford D. The Children’s Leisure Activities Study: summary report. Melbourne (VIC): Centre for Physical Activity and Nutrition Research, 2004
Correspondence: Prof. Billie Giles-Corti, Centre for the Built Environment and Health, School of Population Health, M707, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. E-mail:
[email protected]
Sports Med 2009; 39 (12)
Sports Med 2009; 39 (12): 1011-1032 0112-1642/09/0012-1011/$49.95/0
REVIEW ARTICLE
ª 2009 Adis Data Information BV. All rights reserved.
Does Antioxidant Vitamin Supplementation Protect against Muscle Damage? Cian McGinley, Amir Shafat and Alan E. Donnelly Department of Physical Education and Sport Sciences, University of Limerick, Limerick, Ireland
Contents Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Exercise-Induced Muscle Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Vitamin C (Ascorbic Acid). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Vitamin E (Tocopherol). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Animal Supplementation Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Human Supplementation Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Vitamin C Supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.1 Acute Supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.2 Post-Exercise Supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.3 Pre-Exercise Supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.4 Combined Supplementation Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Vitamin E Supplementation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.1 Pre-Exercise Supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.2 Combined Supplementation Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Vitamin C and Vitamin E Comparative Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3.1 Post-Exercise Supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3.2 Pre-Exercise Supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3.3 Combined Supplementation Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. Summary of Antioxidant Supplementation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Abstract
1011 1012 1014 1015 1015 1016 1017 1018 1018 1018 1018 1021 1022 1022 1024 1025 1025 1025 1027 1028 1028
The high forces undergone during repetitive eccentric, or lengthening, contractions place skeletal muscle under considerable stress, in particular if unaccustomed. Although muscle is highly adaptive, the responses to stress may not be optimally regulated by the body. Reactive oxygen species (ROS) are one component of the stress response that may contribute to muscle damage after eccentric exercise. Antioxidants may in turn scavenge ROS, thereby preventing or attenuating muscle damage. The antioxidant vitamins C (ascorbic acid) and E (tocopherol) are among the most commonly used sport supplements, and are often taken in large doses by athletes and other sportspersons because of their potential protective effect against muscle damage. This review assesses studies that have investigated the effects of these two antioxidants, alone or in combination, on muscle damage and oxidative
McGinley et al.
1012
stress. Studies have used a variety of supplementation strategies, with variations in dosage, timing and duration of supplementation. Although there is some evidence to show that both antioxidants can reduce indices of oxidative stress, there is little evidence to support a role for vitamin C and/or vitamin E in protecting against muscle damage. Indeed, antioxidant supplementation may actually interfere with the cellular signalling functions of ROS, thereby adversely affecting muscle performance. Furthermore, recent studies have cast doubt on the benign effects of long-term, high-dosage antioxidant supplementation. High doses of vitamin E, in particular, may increase all-cause mortality. Although some equivocation remains in the extant literature regarding the beneficial effects of antioxidant vitamin supplementation on muscle damage, there is little evidence to support such a role. Since the potential for long-term harm does exist, the casual use of high doses of antioxidants by athletes and others should perhaps be curtailed.
1. Exercise-Induced Muscle Damage Physical exercise places particular systems in the body under varying degrees of stress. One of the main benefits of exercise is that the body then adapts to the stresses it has been placed under. Skeletal muscle, in particular, adapts to the high or repetitive forces it undergoes during resistance or endurance type exercise. However, the response to stress, and the subsequent adaptation, might not be optimally regulated by the body. Physiological mechanisms that regulate the response to exercise-induced stress in skeletal muscle are of great interest, as it may be possible to manipulate specific components of the stress response in order to minimize unnecessary functional deficits such as pain and loss of force production. One such component that may contribute to exerciseinduced muscle damage (EIMD) is the oxygencentred free radicals: reactive oxygen species (ROS). It is widely accepted that unaccustomed highintensity exercise can result in damage to active muscle fibres, outwardly manifesting as soreness, stiffness (e.g. reduced range of motion) and a reduction in the force-producing capability of the muscle.[1-5] This is particularly the case with exercise that involves muscle contractions whereby the muscle lengthens as it produces forces, commonly referred to as eccentric contractions (although it has been argued that this nomenclature is inappropriate for describing this type of muscle ª 2009 Adis Data Information BV. All rights reserved.
action[6]). Soreness following eccentric exercise initially appears within the first 24–48 hours after exercise, and lasts for several days depending on the extent of the damage,[7] while force loss after eccentric exercise is evident immediately upon finishing exercise, also persisting for several days depending on the severity of damage.[3] Moreover, a shift in the length-tension curve towards longer muscle lengths is thought to evince a failure of actin and myosin filaments of the weakest sarcomeres to reinterdigitate, commonly known as the popping-sarcomere hypothesis.[5] Further evidence for EIMD comes from a failure of excitation-contraction coupling[8] – most likely due to damage to the ryanodine receptors of the sarcoplasmic reticulum leading to increased intracellular calcium ([Ca2+]i)[9,10] – and is indirectly measurable by the preferential and prolonged loss of force at low frequencies of electrical stimulation (low frequency fatigue [LFF]). Additionally, an increase in the blood levels of myoproteins such as creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin, myosin heavy chain fragments and troponin is indicative of disruption to the sarcolemma.[11,12] A likely inflammatory response to EIMD – referred to as the phagocytic stage of EIMD[2] because of the migration of neutrophils to the site of injury, followed by monocytes and macrophages – that can contribute to secondary damage may be indicated by the presence of such phagocytic cells, which in turn may be identified indirectly by the secretion Sports Med 2009; 39 (12)
Antioxidant Vitamins and Muscle Damage
of cytokines (intracellular signalling molecules that coordinate the inflammatory response,[13] e.g. interleukins) at the site of muscle damage.[14] The inflammatory response is also characterized by oedema, with an infiltration of fluid and plasma proteins into affected tissue.[15] Direct evidence of EIMD can be found in histological and immunohistochemical analysis of disruption to cytoskeletal and myofibrillar proteins,[16] or by using imaging techniques such as MRI.[17] The potential contribution of ROS to EIMD has been addressed in several recent reviews.[18-23] Briefly, potential sources for ROS production in skeletal muscle can be separated into primary and secondary sources of ROS. The primary sources are endogenous sites within muscle, whereas the secondary sites are exogenous to muscle but directly influence reduction-oxidation (redox) status.[24] The main source of ROS is reputedly through electron leakage in the mitochondrial electron transport chain, i.e. during mitochondrial phosphorylation,[25] although this has recently been called into question.[24] Another potential primary source is via xanthine oxidase metabolism in capillary endothelium.[26] The main secondary sources of ROS are generated during the inflammatory process by phagocytic cells such as neutrophils, and possibly by increased accumulation of [Ca2+]i in the muscle, and disruption of iron-containing proteins.[27] Although skeletal muscle is said to be the major source of ROS during exercise,[28] it is important to note that there is a great potential for ROS production with aerobic exercise from other tissues, such as the heart, lungs or liver.[27] In order to minimize damage to tissues and cells, a balance must be maintained between oxidants (i.e. ROS) and antioxidants (reductants). Although cells have evolved a sophisticated antioxidant defence system against ROS, damage may occur when oxidants overwhelm antioxidants, changing the normal redox balance, a state commonly known as oxidative stress.[29] Under conditions of oxidative stress, ROS can damage lipids, proteins and DNA.[30] It is important to note, though, that ROS are not singularly damaging, and some recent studies have focused on the importance of ROS as signalling ª 2009 Adis Data Information BV. All rights reserved.
1013
molecules.[21,22,31-34] In fact, at low levels, ROS are said to be essential for optimal force production in unfatigued skeletal muscle.[35] Endogenously produced ROS have been found to play an important role in contraction-mediated glucose transport in fast-twitch muscle.[36] Furthermore, ROS are said to be important redox signalling molecules, activating several transcription factors such as heat shock factor 1 and nuclear factor (NF)-kB.[22,37] Suppression of NF-kB binding (by inhibiting xanthine oxidase) has been found to reduce the gene expression of key antioxidant enzymes.[34] Therefore, an alternative definition of oxidative stress is as a disruption of redox signalling and control.[37] This leads to the possibility that supplementation with antioxidants may retard cellular signalling, potentially interfering with crucial adaptive processes.[21,34] Numerous studies have investigated the effects of supplementation with vitamin C (ascorbic acid) and vitamin E (tocopherol), individually or in combination, on protecting the muscle from ROSinduced damage. The results to date are equivocal, with findings difficult to compare because of disparate supplementation strategies in terms of dosage and timing, as well as the use of different subject populations and exercise protocols. Most studies have used a selection of biomarkers of oxidative stress, but have failed to measure indices of EIMD. Therefore, while they may have found a protective effect for vitamin C and/or vitamin E on oxidative stress, a role for ROS in muscle damage was not investigated, and subsequently a protective effect for these antioxidants was not established or refuted. This review discusses only those supplementation studies that have measured direct or indirect indices of EIMD. Soreness and force loss are not unique to EIMD, and therefore it can be argued that these are not specific indices of muscle damage. Nevertheless, both soreness and force loss follow specific timecourses as a result of EIMD rather than, for example, fatigue.[4] Indeed, force loss has been described as being the best marker of EIMD due to its accuracy and reliability, and also because a reduction in force persists until the muscle returns to an undamaged state.[17,38] Soreness is the most commonly measured marker of EIMD;[17] Sports Med 2009; 39 (12)
McGinley et al.
1014
however, there are weak correlations between soreness and functional or biochemical measures of eccentric damage.[39] While soreness may cooccur with EIMD, it does not specifically indicate damage. Nevertheless, it has been used by several authors as a functional index of EIMD, and for the purposes of inclusivity in the current review with regard to supplementation studies these papers are included. For this review, English-language literature searches of the PubMed and ISI Web of Science databases were performed up to August 2008. Combinations of the following keywords were used as search terms: ‘muscle damage’, ‘muscle injury’, ‘eccentric’, ‘lengthening contractions’, ‘reactive oxygen species’, ‘oxidative stress’, ‘free radicals’, ‘antioxidants’, ‘vitamins’. In addition, references of retrieved articles were screened for potentially relevant articles. Importantly, recent studies have cast doubt on the benign effect of supplementing with different antioxidants. In a study of 77 721 men and women aged 50–76 years that investigated the association between vitamin use and cancer, long-term supplementation with high doses of vitamin E was associated with a small increased risk of lung cancer, being most prominent in smokers.[40] A meta-analysis of 135 967 men or non-pregnant women in 19 clinical trials (mean age ranged from 47 to 84 years) that assessed the dose-response relationship between vitamin E and total mortality recommended that doses ‡400 IU/day should be avoided because of the apparent increase in all-cause mortality.[41] Most of the trials in this review are reported as including subjects at high risk of chronic disease. Similarly, a meta-analysis and Cochrane Review of antioxidant supplementation studies from the same group found that vitamin E, as well as vitamin A and b-carotene, but not vitamin C, appeared to increase mortality when taken alone or in combination.[42,43] The latter paper included 232 550 men and non-pregnant women aged 62 (18–103) years [mean (range)], with 164 439 healthy subjects (21 trials), and the remainder (46 trials) having a variety of diseases. These papers noted no adverse effects of vitamin C supplementation where investigated; however, an upper limit of 2000 mg/day of vitamin C has ª 2009 Adis Data Information BV. All rights reserved.
previously been recommended because of the potential for osmotic diarrhoea.[44] Moreover, in the presence of transition metal ions such as iron or copper, high concentrations of ascorbic acid can act as a pro-oxidant, although this has not been definitively established in vivo in humans.[45] It seems that prolonged supplementation with some antioxidant vitamins may have long-term negative consequences for health. Perhaps of more relevance to athletes and sportspersons is the possibility that antioxidant supplementation may interfere with the cellular signalling function of ROS, thereby retarding the adaptive response of muscle to the stress of exercise. Given the potential harmful effect of antioxidant supplementation, is there evidence in the literature that short-term supplementation may be of benefit to exercise performance and recovery? If so, which antioxidant vitamins and which dosing regimens could be effective? This review seeks to address these questions. 2. Antioxidants Antioxidants can be classified as enzymatic or non-enzymatic. Essentially, enzymatic antioxidants represent the body’s own evolved defence against oxidants such as ROS, while non-enzymatic antioxidants can be ingested from food or other dietary sources. Enzymatic antioxidants such as the superoxide dismutases (SODs), glutathione peroxidase (GPx), and catalase deal with oxidants in a very specific manner, whereas nonenzymatic antioxidants such as the lipid-soluble vitamin E, b-carotene, co-enzyme Q10 (CoQ), and the water-soluble vitamin C, glutathione, and uric acid are less specific.[37] Antioxidants work in complex synergy in protecting against ROS-induced damage, with intracellular and extracellular sites of action for both types of antioxidants – although the enzymatic antioxidants are primarily intracellular.[46] The mitochondria, in particular, are normally well protected against oxidative stress.[47] Typically, antioxidants protect against ROS by either converting ROS into less reactive molecules (known as scavenging) or by preventing the transformation of less reactive ROS into the more highly reactive forms.[48] Sports Med 2009; 39 (12)
Antioxidant Vitamins and Muscle Damage
2.1 Vitamin C (Ascorbic Acid)
Vitamin C exists in two forms: as L-ascorbic acid (C6H8O6), or in its oxidized form L-dehydroascorbic acid.[49] Ascorbic acid is the most important water-soluble antioxidant vitamin, readily donating electrons.[50] It has two functions as an antioxidant: (i) directly scavenging specific ROS, as well as lipid hydroperoxides; and (ii) helping recycle vitamin E from its radical form.[45,48] Packer et al.[51] provided the first direct evidence of an interaction between the two antioxidant vitamins, using pulse radiolysis. Vitamin E (a-tocopherol) was shown to act as the primary antioxidant, with the resultant a-tocopheroxyl radical reacting with ascorbic acid to recycle vitamin E. The vitamin C radical (ascorbyl) produced by regeneration of vitamin E is a less reactive radical,[52] and can be reduced back to ascorbic acid by thiols such as glutathione, as well as by NADH (reduced nicontinamide adenine dinucleotide) semiascorbyl reductase.[48] Vitamin C also recycles uric acid, glutathione and b-carotene from their radical forms.[52] Being water-soluble, ascorbic acid is readily absorbed but is not stored in the body.[53] It is primarily transported in plasma in its free form, with the remainder transported as L-dehydroascorbic acid (5%) or bound to the protein albumin.[49] Ascorbic acid is located in the cytosolic compartment of cells,[54] and while found throughout the body, in skeletal muscle it is found only in small amounts, i.e. <15 mg/100 g of wet tissue.[49] It is located in the cytosol in lymphocytes only in the free form of ascorbic acid. In a vitamin C depletion-repletion study in men, supplementing with 100 mg ascorbic acid per day resulted in saturation of neutrophils, monocytes and lymphocytes.[55] On the other hand, plasma concentrations continued to increase at dosages up to 2500 mg/day, albeit nearing saturation at 400 mg/day. However, doses >500 mg/day resulted in greater excretion of ascorbic acid in the urine. 2.2 Vitamin E (Tocopherol)
Vitamin E is the most important lipid-soluble antioxidant vitamin.[56] It is absorbed in the small ª 2009 Adis Data Information BV. All rights reserved.
1015
intestine and exists in eight different natural forms: a-, b-, g- and d-tocopherol and a-, b-, gand d-tocotrienol.[49] The most biologically active form is a-tocopherol, which in its natural form is called RRR-a-tocopherol or d-a-tocopherol.[57] Vitamin E is transported in plasma lipoproteins and is thought to be delivered to the tissue through lipoprotein lipase-mediated triglyceriderich lipoprotein catabolism, through the lowdensity lipoprotein receptor, as well via the exchange between vitamin E-rich lipoproteins and vitamin E-poor membranes.[57] It has been suggested that tissues with high lipoprotein lipase activity such as skeletal muscle might transfer vitamin E via this mechanism.[58] Vitamin E is found in most tissues, stored in lipid-rich membranes such as mitochondria, the sarcoplasmic reticulum and the plasma membrane, but the majority is stored in adipose tissue in the adipocytes.[48,49,59] During intensive exercise, plasma a-tocopherol levels have been found to increase, suggesting a-tocopherol is mobilized from other tissues in response to exercise.[60] Vitamin E is known as a chain-breaking antioxidant, stopping progression of the lipid peroxidation chain reaction. Furthermore, it acts as an important scavenger of the superoxide, hydroxyl and lipid peroxyl radicals.[48] This interaction with radicals results in the formation of the vitamin E radical a-tocopheroxyl. Therefore, under conditions of oxidative stress, tissue levels of vitamin E can be depleted. Vitamin E can be recycled from its radical form by vitamin C: 1. a-tocopherol + ROO - ROOH + a-tocopheroxyl. 2. a-tocopheroxyl + ascorbic acid - a-tocopherol + ascorbyl radical. Other antioxidants such as glutathione, CoQ, cysteine and a-lipoic acid also recycle vitamin E, but at a slower rate than vitamin C.[61] Importantly, a-tocopherol may act as a pro-oxidant in the absence of these antioxidants.[62] Providing vitamin E (800 IU/day) to men for 48 days has been previously found to increase the plasma concentration of a-tocopherol but to reduce the concentration of g-tocopherol.[63] It has been suggested that this occurs because the liver preferentially secretes a-tocopherol into the Sports Med 2009; 39 (12)
McGinley et al.
1016
plasma while concurrently excreting g-tocopherol into bile.[58] Similar findings have been found in skeletal muscle content of both isoforms of vitamin E after 30 days’ supplementation with the same dose of a-tocopherol.[64] Interestingly, in a study in rats, g-tocopherol but not a-tocopherol was found to suppress pro-inflammatory cytokines and attenuate inflammation-induced damage.[65] This may have implications for vitamin E supplementation in muscle damage studies in humans. 3. Animal Supplementation Studies A number of studies have provided antioxidant vitamins to animals in order to assess any potential effects on indices of EIMD. However, what relevance do animal studies have in attempting to educe a possible effect of antioxidants on
muscle damage in humans? One obvious species difference is that animal muscles (typically rodents) have different fibre type populations and different architectures. Consequently, animal muscle may not necessarily respond in a similar way to human muscle during damaging contractions. The contraction protocols in animal studies have induced severe damage that is simply not possible to induce voluntarily in humans. Moreover, many animals can in fact synthesize vitamin C, unlike humans, who require it in their diet.[66] Consequently, studies using animals frequently investigate the effects on muscle damage of vitamin E supplementation but do not normally provide vitamin C to animals. A notable feature of the animal studies in the current review (table I) is that investigators invariably provided supplementation for a period
Table I. Rodent studies investigating the effect of vitamin E (tocopherol) [VE] supplementation on markers of exercise-induced muscle damage and oxidative stress after exercise Study
Supplementation
Exercise model
daily dosage
duration
Gohil et al.[67]
40 IU VE per kg food or diet deficient in VE or a diet deficient in VE but with 3 g VC per kg food
8–10 wk pre
You et al.[68]
2 g VC and 1 g VE per kg food
2 wk pre
Damage marker
Oxidative stress marker
test
effect
test
Treadmill test to exhaustion
Time to exhaustion
›
None
90 min downhill running
Time to exhaustion
–
GSSG: TGSHa,b MDAa,b PCa,c
effect
– – fl /–
Warren et al.[69]
10 000 IU VE per kg food
5 wk pre
150 min downhill walking
Po Histology G-6-PDHa CKb
– – – –
Sensitivity to pro-oxidants
fl
Coombes et al.[70]
10 000 IU VE per kg food and 1.65 g a-LA per kg food
8 wk pre
Electrical stimulation
Po Pt
– fld
MDA-TBARSa LOOHa
fl fl
Van Der Meulen et al.[71]
200 mL of 70% w/v VE/ethanol
5–8 d pre
225 ECC
Po Cellular Infiltration CKe PKe
– – fl fl
None
a
Measured in muscle.
b
Measured in plasma.
c
Measured in whole blood.
d
Maximal twitch force was reduced pre-exercise indicating a potential negative effect of VE on muscle function.
e
Measured in serum.
a-LA = a-lipoic acid; CK = creatine kinase; ECC = eccentric contractions; G-6-PDH = glucose-6-phosphate-dehydrogenase; GSSG = oxidized glutathione; LOOH = lipid hydroperoxides; MDA-TBARS = malondialdehyde-thiobarbituric acid reactive substances; PC = protein carbonyls; PK = pyruvate kinase; Po = maximal tetanic force; pre = pre-exercise; Pt = maximal twitch force; TGSH = total glutathione; VC = vitamin C; › indicates significantly higher than a control group; fl indicates significantly lower than a control group; – indicates not significantly different than a control group.
ª 2009 Adis Data Information BV. All rights reserved.
Sports Med 2009; 39 (12)
Antioxidant Vitamins and Muscle Damage
prior to an exercise bout, rather than providing either a single acute dose or supplementing animals post-exercise. In one such study in rats, time to exhaustion in a treadmill running test was found to be significantly reduced in vitamin E-deficient rats compared with rats receiving vitamin E for 8–10 weeks.[67] However, no measurements were made of oxidative stress biomarkers, so it is not possible to infer that the performance decrement was as a result of increased ROS production. Interestingly, one of the vitamin E-deficient groups received 3 g of vitamin C per kilogram of food. While it could be interpreted that the lack of vitamin E resulted in a performance decrement, such high doses of vitamin C may in fact have had a pro-oxidant effect. In a more recent study, no difference was seen in treadmill run time between rats receiving both vitamin C and vitamin E and a control group.[68] Several indices of oxidative stress were measured, with a reduction in vastus intermedius and soleus (but not vastus lateralis) protein carbonyl (formed when amino acids are oxidized[72]) content the only difference between treatment and control. In a separate study, rats receiving vitamin E for 5 weeks prior to 150 minutes of downhill walking showed no attenuation of muscle damage measured by either histology or by plasma CK compared with a control group.[69] Muscle vitamin E content was greatly increased by the supplementation regimen. The authors interpreted these findings as indicating that lipid peroxidation does not contribute to muscle membrane damage, although this was speculative, as no direct or indirect measurements of oxidative stress were made. Again in rats, a combination of vitamin E and a-lipoic acid for 8 weeks before exercise was found to reduce exercise-induced lipid peroxidation, but not to reduce fatigue as measured by force decrement.[70] Interestingly, the high dose of vitamin E used (10 000 IU/kg food) was thought to have negatively affected muscle function, with a non-exercise treatment group showing a reduction in force compared with a control group. Long durations of supplementation with vitamin E have not proven to be effective in protecting against damage, although it is clear that direct ª 2009 Adis Data Information BV. All rights reserved.
1017
assessment of damage across several timepoints is lacking in these studies. In a study that utilized a shorter duration of supplementation, infusing vitamin E for 5–8 days before exercise was found to be sufficient in raising muscle content of vitamin E ~3-fold in rats.[71] Following 225 lengthening contractions, muscle damage was indicated by ~70% force reduction 30 minutes post-exercise and cellular infiltration in muscle sections 3 days (but not 1 hour) after exercise. A reduced serum CK response in the treatment group suggests that vitamin E might have protected against membrane damage, but again there was no effect on other indices of muscle damage. While there is some evidence to suggest vitamin E may protect against exercise-induced oxidative stress, there is no convincing evidence to suggest a beneficial effect of vitamin C or vitamin E in protecting against muscle damage in rodents. Of course, interpreting findings from animal studies and relating them to humans should be done cautiously. 4. Human Supplementation Studies Species differences aside, it is important to question how human studies vary from those using rodents. Although the subject populations are less homogeneous, particularly in terms of prior training status, the most notable difference is that supplementation strategies in human research have been more varied. Human studies have used pre-exercise supplementation, postexercise supplementation, acute (single-dose) supplementation, or indeed a combination of these strategies. The disparate strategies reflect the equivocation regarding the effects of antioxidant supplementation on muscle damage. Furthermore, research has been conducted into the effects of vitamin C or vitamin E individually, or in combination. The two antioxidants work synergistically, and importantly they function in aqueous and lipid compartments, respectively. Hence, a combination of the two might be expected to offer more comprehensive protection against ROS than individual supplementation would.[73] The following sections detail studies of vitamin C and vitamin E individually, and Sports Med 2009; 39 (12)
McGinley et al.
1018
comparative studies of the two antioxidants alone or in combination. In an attempt to ascertain whether timing of supplementation is an important factor, studies are categorized as preexercise, post-exercise or acute dose supplementation. Of course, the variety of strategies used inevitably results in overlap of these categories, and these studies are covered under combined supplementation strategies. 4.1 Vitamin C Supplementation 4.1.1 Acute Supplementation
Ascorbic acid is not stored in the body in great amounts due to its water-soluble nature, the majority being transported in the plasma. It is therefore plausible that if vitamin C was efficacious in protecting against muscle damage, then a single dose provided at the appropriate time may, in boosting plasma levels, offer protection. There is no evidence, however, to support this contention (table II). The effects of an acute dose of ascorbic acid 2 hours before 90 minutes of intermittent shuttle running were investigated using a placebo-controlled, crossover design.[74] Supplementation did not affect the moderate increases in serum CK, serum aspartate aminotransferase or delayed onset muscle soreness (DOMS). The noticeable difference between groups was that plasma and lymphocyte vitamin C concentration was elevated significantly in response to exercise in the treatment group compared with placebo, suggesting that vitamin C may have been mobilized in the treatment group in response to exercise-induced oxidative stress. The authors suggested that the failure of vitamin C to attenuate indices of oxidative stress might have been because of ineffective timing of supplementation. However, an earlier study demonstrated a protective effect against ROS production using an identical dosing strategy.[85] The latter study did not measure any indices of muscle damage. 4.1.2 Post-Exercise Supplementation
What is the rationale behind supplementing subjects with vitamin C after an exercise bout? Because vitamin C is primarily located in the plasma and not stored in the active tissue to any great extent, raising plasma levels of the antiª 2009 Adis Data Information BV. All rights reserved.
oxidant to coincide with increased ROS production, such as during the inflammatory phase of muscle damage, may potentially offer increased antioxidant protection at the time of peak oxidant production. Supplementing with vitamin C for 3 days after an intermittent shuttle running bout failed to attenuate the increase in interleukin (IL)-6 response.[75] Post-exercise supplementation with vitamin C did not affect any indices of muscle damage or lipid peroxidation. Interestingly, a study that provided vitamin C in combination with N-acetylcysteine (NAC; an antioxidant drug with pro-glutathione effects) or a placebo to subjects immediately after 30 eccentric contractions, and for the subsequent 7 days, found evidence of a pro-oxidant effect.[76] Several biomarkers of oxidative stress were measured (see table II), and a typically larger increase in the treatment group provided a convincing argument for a pro-oxidant effect of combined vitamin C and NAC. Muscle damage was indicated by delayed increase in blood levels of the muscle proteins CK, LDH and myoglobin, with peak levels measured either 2 or 3 days after exercise. A between-group comparison found a significantly higher LDH concentration 3 days post-exercise in the antioxidants group. Soreness and reduced range of motion (ROM) followed patterns typical of EIMD, with no difference seen between groups. The supplements were not tested individually, so the contribution of each could not be gauged. It is important to note that no direct measurements of either muscle damage or ROS production were taken. Moreover, this was not a crossover design, thus baseline differences in damage susceptibility between groups cannot be discounted. 4.1.3 Pre-Exercise Supplementation
The majority of vitamin C studies have used a pre-supplementation strategy, either alone or combined with post-supplementation. Contracting skeletal muscle results in increased ROS production, although the magnitude of ROS produced, for example due to electron leakage along the mitochondrial transport chain, is disputed.[24] Nevertheless, a pre-exercise supplementation Sports Med 2009; 39 (12)
Study
Subjects
Supplementation
Exercise model
daily dosage
duration
Damage marker
Oxidative stress marker
test
treatment effect
test
treatment effect
9 active men
1 g VC
Single dose 2 h pre
90 min LIST
CKa AAa DOMS Force loss
– – – –b
MDAc Uric acida
– –
Thompson et al.[75]
16 active men
400 mg VC
3 d post
90 min LIST
DOMS Force loss IL-6c CKa Myoglobina
– – – – –
MDAc Uric acida
– –
Childs et al.[76]
14 healthy untrained men
12.5 mg VC and 10 mg NAC per kg bodyweight
7 d post
30 ECC of elbow flexors at 80% eccentric 1RM
CKc – LDHc › a Myoglobin – DOMS – ROM – c IL-6 – c MPO fl
PGFc GPxc LOOHc SODc TAOCa
›d ›e › › ›
Thompson et al.[77]
16 active men
400 mg VC
2 wk pref
90 min LIST
CKa – Myoglobina – –g DOMS Force loss –b IL-6a fl CRPa –
MDAc Uric acidc
fl –
Davison and Gleeson[78]
9 endurance trained men
1 g VC
2 wk pre
2.5 h cycling at 60% . VO2max
IL-6c N-OBA WBC
– – fl
MDAc TAOCc
N/C ›
Tauler et al.[79]
16 endurance trained men
18.3 – 0.9 mg VC per kg bodyweight
Not statedh
Duathlon (10 km run, 40 km cycle, 5 km run)
LDHa
fl
Catalasei GPxi GPeri SODi Uric acida
›j – fl N/C fl
Kaminski and Boal[80]
19 healthy men and women
3 g VC
3 d pre and 4 d post
15 min ECC of calf
DOMS
flk
None
Continued next page
1019
Sports Med 2009; 39 (12)
Thompson et al.[74]
Antioxidant Vitamins and Muscle Damage
ª 2009 Adis Data Information BV. All rights reserved.
Table II. Human studies investigating the effect of vitamin C (ascorbic acid) [VC] supplementation on markers of exercise-induced muscle damage and oxidative stress after exercise
Study
Subjects
Supplementation
Exercise model
daily dosage
duration
Damage marker
Oxidative stress marker
test
treatment effect
test
treatment effect
Bryer and Goldfarb[81]
18 healthy untrained men
3 g VC
2 wk pre and 4 d post
70 ECC of elbow flexors
CKc DOMS Force loss ROM
– fl – –
GSSG:TGSHl
fl
Close et al.[82]
20 untrained men
1 g VC
Acute dose 2 h pre and 14 d post
30 min downhill running
DOMS Force loss
– ›
MDAa TGSH
fl N/C
Connolly et al.[83]
24 healthy untrained men and women
3 g VC
3 d pre and 5 d post
40 ECC of elbow flexors
Force loss DOMS ROM
– – –
None
Thompson et al.[84]
14 healthy untrained men
400 mg VC
2 wk pre and 3 d post
30 min downhill running
CKa Myoglobina DOMS Force loss IL-6c
– – – – –
None
a
1020
ª 2009 Adis Data Information BV. All rights reserved.
Table II. Contd
Measured in serum.
b
Twelve measures of force were made with a difference between treatment and placebo for only one measure and at one timepoint.
c
Measured in plasma.
d
p = 0.07.
e
There was no significant increase post-exercise but there was a significant difference between treatment and placebo on day 2 post-exercise.
f
Supplementation was provided for 12 d but stopped 36 h before exercise.
g
There was no difference in soreness between groups apart from mild upper body soreness that was evident in the placebo group only post-exercise.
h
The supplemented group consisted of subjects with an habitually higher dietary VC intake than subjects in the control group.
i
Measured in erythrocytes.
j
Increased post-exercise in the supplemented group only, but catalase activity was higher in the control group overall.
k
Soreness was lower with treatment for some measures and at some timepoints. See text for description of study limitations.
l
Measured in whole blood.
McGinley et al.
Sports Med 2009; 39 (12)
1RM = one-repetition maximum; AA = aspartate aminotransferase; CK = creatine kinase; CRP = C-reactive protein; DOMS = delayed-onset muscle soreness; ECC = eccentric contractions; GPer = glutathione peroxidase using cumene hydroperoxide as substrate; GPx = glutathione peroxidase using hydrogen peroxide as substrate; GSSG = oxidized glutathione; IL-6 = interleukin-6; LDH = lactate dehydrogenase; LIST = Loughborough Intermittent Shuttle Test; LOOH = lipid hydroperoxides; MDA = malondialdehyde; MPO = myeloperoxidase; NAC = N-acetylcysteine; N/C = no change after exercise; N-OBA = neutrophil oxidative burst activity (whole blood); PGF = 8-epi-prostaglandin F2a; post = post. exercise; pre = pre-exercise; ROM = range of motion; SOD = superoxide dismutase; TAOC = total antioxidant capacity; TGSH = total blood glutathione; VO2max = maximal oxygen uptake; WBC = white blood cells (circulating leukocytes and neutrophils); › indicates significantly higher than a control group; fl indicates significantly lower than a control group; – indicates not significantly different than a control group.
Antioxidant Vitamins and Muscle Damage
strategy seeks to increase levels of vitamin C in the plasma, as well as in water-soluble compartments such as the cytosol, mitochondrial matrix and extracellular fluids, thereby increasing bioavailability to the active tissue, so that the antioxidant is readily mobilized to counteract the increase in ROS during exercise. Several studies have provided vitamin C for 2 weeks prior to different modes of exercise. In one such study, plasma malondialdehyde (MDA; a secondary marker of lipid peroxidation[86]) was found to increase after an intermittent shuttle running test, but was lower 2 and 24 hours after exercise in the vitamin C-supplemented group.[77] Inflammation was demonstrated by an ~8-fold increase in serum IL-6, with a return to baseline levels occurring more rapidly with vitamin C supplementation, but there was no effect of treatment seen on C-reactive protein (CRP) increase. Indices of muscle damage suggest that damage was quite mild, with no notable effects of treatment. Disparate findings were provided in a separate study that found that vitamin C did not prevent the exercise-induced increase in IL-6 after 2.5 hours’ cycling exercise.[78] The reason for the differences is unclear, although the use of exercise protocols with differing levels of metabolic demand, and thus different levels of ROS production, is one possible factor. Indeed, the latter study reported no post-exercise increase in plasma MDA. It is possible that vitamin C supplementation increases the baseline response of enzymatic antioxidants.[87] Following 8 weeks’ supplementation with vitamin C prior to a bout of one-legged cycling exercise, baseline activity of both SOD and catalase in lymphocytes was found to be elevated in a treatment group compared with placebo. However, conflicting evidence for upregulation of protective enzymes after vitamin C supplementation was provided in a separate study.[79] The contrast could in part be explained by the use of untrained versus trained subjects, and different exercise protocols and vitamin C levels. 4.1.4 Combined Supplementation Strategy
In one of the first studies to examine the effect of vitamin C supplementation on DOMS, ascorª 2009 Adis Data Information BV. All rights reserved.
1021
bic acid was provided to subjects for 3 days before and 4 days after eccentric exercise of the plantar flexors.[80] The study was a placebocontrolled crossover design, and although the authors reported less DOMS in the vitamin C-supplemented group, several subjects demonstrated no difference in soreness between treatment and placebo. Furthermore, training status of subjects was not established. Conclusions as to a positive effect of vitamin C in protecting from DOMS are therefore quite weak in this study. Additionally, the dose of vitamin C was greater than recommended upper tolerable levels,[44] and a pro-oxidant effect at such high levels cannot be discounted. A more recent single-trial study that used a similar large daily dose of vitamin C for 2 weeks before and 4 days after eccentric contractions of the elbow extensors also reported lower DOMS in the vitamin C-supplemented group.[81] There was, however, no difference between treatment and placebo groups in ROM, force loss or plasma CK response after exercise. There was no evidence of a pro-oxidant effect of vitamin C in this study, with a reduction in the ratio of oxidized glutathione to total glutathione (GSSG : TGSH) evident in the blood at 4 and 24 hours post-exercise in the treatment group. In another study, the effects of supplementing with ascorbic acid for 2 hours before and 14 days after 30 minutes of downhill running was investigated.[82] There was no effect of treatment on DOMS, whilst torque loss was actually more prolonged with vitamin C supplementation. Serum MDA was elevated at 72 and 96 hours postexercise, and the increase was reduced by vitamin C supplementation. Similarly, there was no effect of treatment on DOMS in subjects receiving either vitamin C or placebo for 3 days prior to and 5 days after a bout of eccentric contractions of the elbow flexors.[83] In this study, force loss and reduced ROM after exercise followed patterns typical of EIMD, but there was no effect of treatment. A separate study found no effect of providing vitamin C to subjects for 14 days before and 3 days after eccentric downhill running on any indices of muscle damage.[84] In apparent contradiction to previous findings from the same Sports Med 2009; 39 (12)
1022
group,[77] vitamin C did not affect the time-course or extent of IL-6 response to exercise. This supports similar findings after 90 minutes’ downhill running,[88] but it is in contrast to the findings from other authors.[76,89] The reason for the differences is unclear, although it may have been due to the use of exercise protocols with differing levels of metabolic demand. In a letter to the editor of the European Journal of Applied Physiology, a pro-oxidant effect of vitamin C was proposed as being a reason for the difference between these studies;[90] however, there is no evidence from the studies to support this. The findings detailed above are equivocal with regard to a protective effect of vitamin C supplementation on exercise-induced oxidative stress. It is difficult to compare studies that have utilized a variety of supplementation strategies, exercise protocols or subject cohorts. Additionally, there has been little direct measurement of muscle damage, thus it is unclear to what extent muscle damage was induced in many of these studies. On balance, evidence for a potential protective effect of vitamin C supplementation against EIMD is not convincing. 4.2 Vitamin E Supplementation 4.2.1 Pre-Exercise Supplementation
Unlike vitamin C, and because of its lipidsoluble nature, vitamin E is stored in the body. It is perhaps logical to assume, therefore, that in order to optimize the potential protective effects of vitamin E, it is necessary to build up tissue stores of the antioxidant. In fact, studies have invariably utilized a pre-exercise supplementation strategy, alone or in combination with post-exercise supplementation, when investigating whether vitamin E offers protection against EIMD (table III). The effects of 48 days of vitamin E supplementation on eccentric muscle damage were investigated using a double-blind, crossover design.[91,92] Subjects received either a-tocopherol or a placebo until the day before 45 minutes of downhill running. Supplementation was recommenced 3 days after exercise. Additionally, subjects were either considered young (<30 years old) or old (>55 years old). Interestingly the older ª 2009 Adis Data Information BV. All rights reserved.
McGinley et al.
subjects had higher plasma levels of vitamin E after supplementation, despite receiving the same dose. Plasma CK levels peaked in all subjects 1 day after exercise, never reaching more than 400 IU/L/g creatinine. Although the authors found that vitamin E resulted in reduced CK in the younger group and greater CK in the older group, concentrations were not greatly elevated above baseline, suggesting that damage, if present, was minimal. Vitamin E attenuated the increase at 24 hours post-exercise in IL-1b but not tumour necrosis factor-a. IL-6 release was not affected by exercise, but was found to be lower in the vitamin E group compared with placebo throughout the measurement period. Collectively, these data indicate that vitamin E supplementation had no effect on markers of muscle damage, but did moderate exercise-induced inflammation. However, muscle damage was not strongly in evidence, as indicated by the mild increase in CK. Without further data, the extent of oxidative stress is unknown. In a study by Beaton et al.[93] of muscle damage, subjects received either vitamin E or placebo for 30 days prior to eccentric contractions of the quadriceps. Muscle damage in both treatment and placebo groups was indicated by Z-band streaming visible in biopsies taken 24 hours postexercise, but there was no evidence of disruption to the structural proteins desmin and dystrophin. Infiltration of neutrophils and macrophages was seen in muscle 24 hours after exercise, with no effect of treatment. No biopsies were taken later than 24 hours after exercise, therefore evidence for secondary inflammation and damage may have been missed. There was no effect of vitamin E on serum CK, torque loss or DOMS. Despite the volume of contractions, the subjects did not appear to be severely damaged, which is further supported by the absence of oedema post-exercise. The effects of 2 weeks’ prior vitamin E supplementation on EIMD after a heavy resistance exercise bout was investigated using resistancetrained subjects.[94] Vitamin E significantly reduced the post-exercise increase in CK, but had no effect on DOMS or the increase in plasma MDA post-exercise. The CK response in this Sports Med 2009; 39 (12)
Study
Subjects
Supplementation
Exercise model
Damage marker
Oxidative stress marker
test
treatment effect
test
treatment effect
Y–; O › Y–; O › fl/fl fl –/–
LPa iPF2b SODc
– – –
fl – – N/C – N/C N/C N/C
None
daily dosage
duration
800 IU a-toc
48 d pre
45 min downhill running CKa Neutrophilsa IL-1ba/b IL-6b TNFaa/b
21 inactive men Y (<30 y) or O (>55 y)
Beaton et al.[93]
16 healthy untrained 1200 IU a-toc men
30 d pre
240 maximal ECC of the quadriceps
McBride et al.[94]
12 resistance trained men
1200 IU a-toc
2 wk pre
Whole-body resistance CKa exercisef DOMS
fl –
MDATBARSa
–
Avery et al.[95]
18 healthy untrained 1200 IU a-toc men
21 d pre and 10 d postg
Whole-body resistance CKd › DOMS exerciseh – i Performance –
MDATBARSa
–
Sacheck et al.[96]
32 active men Y (26 – 3 y) or O (71 – 4 y)
12 wkj
45 min downhill running CKd
Yfl; O›k
iPF2a MDAa TAOCd 8-oxodGl
Y–; O › Yfl; O› – –
Phillips et al.[97]
40 healthy untrained 300 mg mixed tocopherols, men 300 mg flavanoids, 800 mg DHX
– – – – fl fl
None
1000 IU a-toc
CKd DOMS Force loss Oedema Z-bande Desmin Dystrophin Cellular infiltration
7 d pre and 30 ECC of elbow flexors CKd 7 d post at 80% eccentric 1RM LDHd DOMS ROM CRPd IL-6d
Continued next page
1023
Sports Med 2009; 39 (12)
Cannon et al.[91,92]
Antioxidant Vitamins and Muscle Damage
ª 2009 Adis Data Information BV. All rights reserved.
Table III. Human studies investigating the effect of vitamin E (tocopherol) [VE] supplementation on markers of exercise-induced muscle damage and oxidative stress after exercise
McGinley et al.
Measured in leukocytes.
k
l
ª 2009 Adis Data Information BV. All rights reserved.
1RM = one-repetition maximum; 8-oxodG = 8-oxo-7,8-dihydro-20 -deoxyguanosine; a-toc = a-tocopherol; CK = creatine kinase; CRP = C-reactive protein; DHX = docosahexaenoate (o-3 fatty acid); DOMS = delayed-onset muscle soreness; ECC = eccentric contractions; IL-1b = interleukin-1b; IL-6 = interleukin-6; iPF2 = F2-isoprostanes; LDH = lactate dehydrogenase; LP = lipid peroxides; MDA-TBARS = malondialdehyde-thiobarbituric acid reactive substances; N/C = no change after exercise; O = old; post = post-exercise; pre = pre-exercise; ROM = range of motion; SOD = superoxide dismutase; TAOC = total antioxidant capacity; TNFa = tumour necrosis factor-a; Y = young; › indicates significantly higher than a control group; fl indicates significantly lower than a control group; – indicates not significantly different than a control group.
Supplementation was provided for 12 weeks, with an exercise bout performed both before and after supplementation.
CK was reduced 24 hours post-exercise (second bout) in the young treatment group but increased in the older treatment group. Baseline CK was significantly greater in both young and old VE groups.
j
Four sets of 10 repetitions of four upper and lower body exercises at variety of % repetition maximum. Three such bouts were performed over 7 d.
A series of performance tests of maximal strength, power and muscular endurance were performed.
h
i
A circuit format consisting of three sets of 8–10 repetitions of eight upper and lower body exercises performed at 10-repetition maximum.
There were three exercise bouts over 7 days. Supplementation was provided during this period and for 3 further days.
Z-band streaming. e
g
Measured in serum. d
f
F2-Isoprostane secretion from mononuclear cells.
Released from neutrophils. c
Measured in plasma.
b
a
Table III. Contd
1024
study was quite modest, implying minimal damage. Other studies detailed in this review have typically found no protective effects of vitamin E on greater CK responses. Indeed, a separate study found a greater increase in CK with the same dose of vitamin E supplementation after resistance exercise, albeit in untrained men.[95] The oxidative stress response to downhill running in subjects receiving a-tocopherol for 12 weeks before exercise was assessed in young (26 – 3 years) and old (71 – 4 years) volunteers.[96] Plasma lipid peroxidation was evidenced by an increase in MDA immediately post-exercise, and a peak increase in F2-isoprostanes (iPF2; prostaglandin-like substances produced by ROSinduced oxidation of arachidonic acid[86]) 72 hours post-exercise. There were some mild effects of treatment, with the MDA response reduced at 72 hours in the younger vitamin E group but elevated post-exercise in the older group, whilst plasma iPF2 concentration was lower in the older vitamin E subjects. Moderate increases in serum CK were the only indicator of muscle damage, with a peak (maximum of ~500 U/L) measured at 24 hours post-exercise in all groups. Mixed results of treatment were seen, with elevated baseline values in both treatment groups, but reduced CK and increased CK in young and older subjects, respectively, at 24 hours post-exercise. Overall, there appeared to be a moderate protective effect of vitamin E against oxidative stress, but an interesting point is that, similar to the studies by Cannon and co-authors,[91,92] there were some contrasting responses between the young and old subjects. An important caveat with this study is the possibility of a repeated bout effect due to the performance of an eccentric exercise bout immediately pre-supplementation followed by a post-supplementation bout 12 weeks later. 4.2.2 Combined Supplementation Strategy
Using a shorter pre-exercise supplementation protocol (7 days) than the studies above, as well as supplementing post-exercise (7 days), the effects of mixed tocopherols, flavanoids and docosahexaenoate (o-3 fatty acid) were studied prior to eccentric contractions of the elbow flexors. Compared with a parallel placebo group, serum Sports Med 2009; 39 (12)
Antioxidant Vitamins and Muscle Damage
IL-6 and CRP increased less after exercise in the treatment group.[97] There was no effect of treatment on the moderate increases in CK and LDH, or on the increased DOMS or reduced ROM evident after exercise. As with the vitamin C supplementation studies detailed earlier, there is a lack of direct measurement of both muscle damage and ROS production in vitamin E supplementation studies. Evidence for a protective effect of vitamin E against exercise-induced oxidative stress is equivocal, although this may in part be compounded by the use of different assays or biomarkers. There is some, albeit weak and indirect, evidence that vitamin E may protect against membrane damage and exercise-induced inflammation. However, confirmation of this by measuring damage directly in the muscle is lacking. 4.3 Vitamin C and Vitamin E Comparative Studies
There is no convincing evidence that vitamin C or vitamin E individually protects against EIMD. However, would a combination of the watersoluble and lipid-soluble antioxidants offer more comprehensive protection against ROS production in different compartments of active muscle tissue? Several studies have sought to answer exactly this question (table IV). The studies discussed in the following sections examined the effects of vitamin C and vitamin E, and occasionally other antioxidants, in combination on indices of oxidative stress and/or muscle damage, or contrasted the effects of vitamin C and vitamin E individually. 4.3.1 Post-Exercise Supplementation
Supplementation with ascorbic acid and atocopherol for 28 days before two-legged knee extensor exercise was found to attenuate the exercise-induced IL-6 response.[89] Plasma IL-6 increased immediately post-exercise, peaking at 4 hours post-exercise, but the net leg release of IL-6 was ~6-fold greater in the placebo group. Muscle IL-6 protein and IL-6 gene expression increased after exercise, with no effect seen with treatment. Plasma IL-1ra (receptor antagonist) increased ª 2009 Adis Data Information BV. All rights reserved.
1025
with placebo but not treatment after 3 and 6 hours, and CRP increased at 23 hours post-exercise with placebo only. While antioxidant supplementation appeared to reduce indices of exercise-induced inflammation, there was no evidence of muscle damage in this study, with no change in plasma CK levels after exercise. Lipid peroxidation was indicated by a ~2.4-fold increase in 8-epiprostaglandin F2a (the most commonly measured F2-isoprostane[105]) at 3 hours after exercise in the placebo group, but treatment prevented this response. 4.3.2 Pre-Exercise Supplementation
A complex mixture of antioxidants that included vitamin C and a-tocopherol was given to subjects for 7 days prior to a treadmill run to exhaustion.[98] Compared with placebo, treatment did not affect DNA damage measured in peripheral blood mononuclear cells using the comet assay (also known as single-cell gel electrophoresis, a technique for determining oxidative DNA damage in individual cells by measuring strand breaks, incomplete excision repair sites and alkali-labile sites[106]), the post-exercise increase in plasma total antioxidant capacity (TAOC), or the increase in blood concentration of LDH. The results suggest not only was there no protective effect of antioxidant treatment on oxidative damage, but the elevated levels of lipid hydroperoxides hint that a pro-oxidant effect may have been seen with the combination of antioxidants used here. Although further evidence would be required to justify this, the supplement contained 800 mg of NAC. As was noted earlier, evidence of a pro-oxidant effect was found with a similar dose of NAC combined with vitamin C, albeit with post-exercise rather than pre-exercise supplementation.[76] A series of papers resulting from the one study found no protective effects of vitamin C and vitamin E supplementation from EIMD.[99-101] Trained runners received a-tocopherol and vitamin C daily for 6 weeks prior to a 50 km run. Numerous measurements were taken between the three studies (see table IV), but the main findings were that supplementation prevented an increase in lipid peroxidation as measured by plasma iPF2, whilst supplementation attenuated the exercise-induced Sports Med 2009; 39 (12)
Study
Subjects
Supplementation
Exercise model
dosage
duration
Damage marker
Oxidative stress marker
test
treatment effect
test
treatment effect
Petersen et al.[88]
20 healthy untrained men
500 mg VC and 400 mg VE
2 wk pre and 1 wk post
90 min downhill running
CKa IL-6a IL-1raa Lymphocytes NK cells
– – – – –
None
Fischer et al.[89]
14 healthy men
500 mg VC and 400 IU a-toc
28 d pre and 1 d post
3 h concentric twolegged knee extensor exercise
CKa CRPa IL-6a IL-1raa IL-6b mRNA IL-6b protein
N/C fl flc fl – –
PGFa
Davison et al.[98]
14 healthy men
600 mg VC, 400 IU a-toc, 400 mg a-LA, 200 mg Co-Q, 12 mg Mn, 800 mg NAC, 400 mg selenium
7 d pre
Treadmill run to . exhaustion (VO2max)
LDHa
–
Comet – assaye LOOHf › g TAOCa –
Mastaloudis et al.[99-101]
300 mg a-toc and 1 g VC 22 trained runners men and women
6 wk pre
50 km ultramarathon
Run time Torque loss CKa LDHa CRPa IL-1ba IL-6a TNFaa
– – – – – N/C – –
iPF2a fl Comet –men, fl women e assay Uric – acid
Jakeman and Maxwell;[102] Maxwell et al.[103]
24 healthy men and women
21 d pre and 7 d post
60 min box-stepping
Force loss LFF (20 : 50 Hz) CKa
VC fl , VE– VC fl , VE–
MDAa N/C TAOCa – – Uric acida
12 healthy untrained men
500 mg VC and 1200 IU a-toc
30 d pre and 7 d post
300 maximal ECC of the Force loss knee extensors LFF (20 : 50 Hz) DOMS Oedema
– fl fl
fld
None
– – Continued next page
McGinley et al.
Sports Med 2009; 39 (12)
Shafat et al.[104]
(VE) 400 mg a-toc or (VC) 400 mg VC
1026
ª 2009 Adis Data Information BV. All rights reserved.
Table IV. Human studies investigating the effect of vitamin C (ascorbic acid) [VC] and/or vitamin E (tocopherol) [VE] supplementation on markers of exercise-induced muscle damage and oxidative stress after exercise
uptake; › indicates significantly higher than a control group; fl indicates significantly lower than a control group; – indicates not significantly different than a control group.
Lipid hydroperoxide concentration was greater overall in the treatment group. g
LOOH = lipid hydroperoxides; MDA = malondialdehyde; Mn = manganese; mRNA = messenger RNA; NAC = N-acetylcysteine; N/C = no change after exercise; NK = natural killer . cells; PGF = 8-epi-prostaglandin F2a; post = post-exercise; pre = pre-exercise; TAOC = total antioxidant capacity; TNFa = tumour necrosis factor-a; VO2max = maximal oxygen
Measured in serum. f
ª 2009 Adis Data Information BV. All rights reserved.
1027
contractions; IL-1b = interleukin-1b; IL-1ra = interleukin-1 receptor agonist; IL-6 = interleukin-6; iPF2 = F2-isoprostanes; LDH = lactate dehydrogenase; LFF = low frequency fatigue;
Measured in peripheral blood mononuclear cells. e
a-LA = a-lipoic acid; a-toc = a-tocopherol; CK = creatine kinase; CoQ = co-enzyme Q10; CRP = C-reactive protein; DOMS = delayed-onset muscle soreness; EEC = eccentric
There was a significant increase post-exercise in the control group only.
Arterial plasma IL-6 increased similarly post-exercise in both groups, but there was a lower increase in systemic plasma IL-6 with treatment. Similarly, net release of IL-6 from the c
d
Measured in muscle. b
contracting leg was lower with treatment.
Measured in plasma. a
Table IV. Contd
Antioxidant Vitamins and Muscle Damage
increase in DNA damage in women but not in men. Treatment did not affect the post-exercise reduction in torque. These data provide no evidence for a protective effect of vitamin C and E against muscle damage. Antioxidants did not reduce exercise-induced inflammation. As has already been noted (see section 4.2.1), there is considerable equivocation regarding the interaction between antioxidants and inflammation. 4.3.3 Combined Supplementation Strategy
In two eccentric damage papers from the same group, the comparative effects of vitamin C or vitamin E supplementation on several markers of oxidative stress and muscle damage were investigated.[102,103] Subjects received either atocopherol, ascorbic acid or a placebo daily for 21 days prior to and 7 days after a bout of eccentric box-stepping. Treatment did not affect the increase in TAOC, whilst there was no parallel increase in plasma MDA. Muscle damage was measured by CK, maximal voluntary contraction and LFF (measured as 20 : 50 Hz ratio). Plasma CK peaked on day 1 post-exercise with a moderate increase of ~70–80% of baseline concentration, with no significant difference between groups. There was no difference between groups in maximal voluntary contraction response immediately post-exercise, with a reduction of 23% overall. The vitamin C group recovered more quickly than either the placebo or vitamin E groups, with less force loss found 1 day after exercise. Interestingly, LFF was evident in all groups, but was less severe in the vitamin C-supplemented group. LFF is an indirect marker of excitation-contraction coupling failure, reflecting impaired function of the sarcoplasmic reticulum. Because the sarcoplasmic reticulum is a lipid membrane, it might be expected that a protective effect would be provided by the lipid-soluble vitamin E rather than the watersoluble vitamin C, as appeared to have been the case in a later study in rats.[71] This was not the case here, and in fact the authors attributed the protection provided by vitamin C to its regenerating effect on vitamin E. In a separate study, there was no evidence for a protective effect of vitamin C and vitamin E on muscle damage after downhill running.[88] Sports Med 2009; 39 (12)
McGinley et al.
1028
Treatment provided for 2 weeks before and 1 week after exercise had no effect on plasma CK, plasma IL-6, plasma IL-1ra or on a variety of inflammatory cells. Muscle damage was not measured directly, but levels of plasma CK suggest that membrane damage was not severe. Whilst antioxidant treatment was not found to prevent exercise-induced inflammation, there were no ROS or muscle damage data with which to educe a potential effect of vitamin C and vitamin E. The difference between the lack of a treatment effect on cytokines here and those of a later study from the same group[89] was attributed by the authors to the shorter supplementation duration used here. Alternatively, the conflicting findings may have been due to the different exercise protocols used, i.e. eccentric downhill running in the former study and concentric leg exercise in the latter study. The effects of vitamin C and vitamin E supplementation on functional measures of muscle damage after an eccentric exercise bout were investigated by Shafat et al.[104] using a single-blind, single-trial design. Subjects received either vitamin C plus a-tocopherol or placebo for 30 days before and 7 days after eccentric contractions of the knee extensors. Treatment attenuated the reduction in maximal voluntary contraction postexercise, as well as moderating the extent of LFF (20 : 50 Hz ratio), but there was no effect of treatment on muscle soreness. No indices of oxidative stress were measured in this study, nor were there blood or muscle markers of muscle damage. A limitation of this study was the failure to use a crossover design, so it is possible group differences may have affected results. An earlier study produced similar findings with vitamin C but not vitamin E supplementation,[102] whereas the majority of studies investigating a mixture of the two antioxidants have measured oxidative stress or inflammation as opposed to muscle damage. 5. Summary of Antioxidant Supplementation There are clearly several conflicting pieces of information from the research in this field. Studies have separately identified a role for vitamin ª 2009 Adis Data Information BV. All rights reserved.
C and vitamin E alone or in combination in protecting against oxidative stress, muscle damage or inflammation. However, for each study providing evidence for a positive effect there are other studies providing equally convincing evidence for either no effect or, on occasion, a negative effect of antioxidant supplementation. Definitive conclusions are complicated by the timing and dosage variations with antioxidants, and by the use of contrasting subject populations. Varying degrees of muscle damage have been induced by contrasting exercise protocols. Metabolic demands of exercise protocols have varied from low with single limb eccentric contractions to high with exhausting endurance exercise. This alone affects ROS production greatly, with the more aerobic exercise increasing oxygen turnover, and likely increasing mitochondrial ROS production. Importantly, the validity and specificity of several techniques used to measure both muscle damage[17] and, in particular, oxidative stress[86,106-119] have been subject to criticism, and there is a need for more robust data. There is a gap in the literature for research into the potential protective effects of vitamin C and vitamin E that provides direct evidence of muscle damage with concurrent evidence of oxidative stress in humans. 6. Conclusions The majority of studies investigating oxidative stress with exercise have failed to provide direct evidence for muscle damage. Therefore, studies showing a protective effect of antioxidants may in fact be showing that antioxidants protect against, for example, force loss as a result of fatigue, and not damage to the muscle structure or membrane. There is some limited evidence from studies that have shown a protective effect on indirect indices of muscle damage for vitamin C but not vitamin E,[102] vitamin E alone,[94,96] or a combination of the two.[104] Despite this, the majority of studies have failed to demonstrate a protective effect of various supplementation strategies on indices of muscle damage (tables II–IV). It is unclear why disparate findings were found in the former studies. One common feature was that the studies did not use a crossover design, thus it is Sports Med 2009; 39 (12)
Antioxidant Vitamins and Muscle Damage
possible that effects of treatment were actually due to group differences. Furthermore, direct indices of muscle damage were not measured in any of the studies, thus differences may not have reflected actual differences in muscle damage. It is possible that supplementing with vitamin C and vitamin E does not provide specific protection from the species of ROS formed during exercise. It has been stated that one of the principal problems with antioxidant supplementation is that ROS cannot be easily targeted and scavenged in biological systems.[120] Therefore, ROS may contribute to muscle damage but non-enzymatic antioxidants may not scavenge the relevant ROS. Zerba et al.[121] provided some indirect support for this, whereby supplementing with the enzymatic antioxidant SOD – a specific scavenger of superoxide radicals – reduced indices of muscle damage in mice, notably attenuating infiltration of inflammatory cells. Recent research has found that long-term antioxidant supplementation, in particular with vitamin E, and at high doses, may increase mortality.[40-43] This is an important caveat to consider before conducting further research into these supplements. From the extant literature, there is no strong evidence for recommending antioxidant supplementation to athletes or individuals habitually involved in potentially damaging exercise. Given that antioxidants do not appear to be beneficial in protecting against muscle damage, and that vitamin E in particular may in fact be potentially harmful, the casual use of large doses of antioxidants should be curtailed. Of greater relevance to athletes and other sportspersons, antioxidant supplementation may not only fail to protect against EIMD, but could in fact interfere with the cellular signalling functions of ROS.[21,22,31-34] Therefore, in ingesting antioxidant vitamins in an attempt to enhance muscle performance, these individuals may actually be retarding the adaptive processes to exercise. Acknowledgements No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.
ª 2009 Adis Data Information BV. All rights reserved.
1029
References 1. Allen DG. Eccentric muscle damage: mechanisms of early reduction of force. Acta Physiol Scand 2001 Mar; 171 (3): 311-9 2. Armstrong RB. Initial events in exercise-induced muscular injury. Med Sci Sports Exerc 1990 Aug; 22 (4): 429-35 3. Clarkson PM, Hubal MJ. Exercise-induced muscle damage in humans. Am J Phys Med Rehabil 2002 Nov; 81 (11 Suppl.): S52-69 4. Dop Ba¨r PR, Reijneveld JC, Wokke JHJ, et al. Muscle damage induced by exercise: nature, prevention and repair. In: Salmons S, editor. Muscle damage. Oxford: Oxford University Press, 1997: 1-27 5. Proske U, Morgan DL. Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications. J Physiol 2001 Dec 1; 537 (Pt 2): 333-45 6. Faulkner JA. Terminology for contractions of muscles during shortening, while isometric, and during lengthening. J Appl Physiol 2003 Aug; 95 (2): 455-9 7. Ebbeling CB, Clarkson PM. Exercise-induced muscle damage and adaptation. Sports Med 1989 Apr; 7 (4): 207-34 8. Warren GL, Ingalls CP, Lowe DA, et al. Excitation-contraction uncoupling: major role in contraction-induced muscle injury. Exerc Sport Sci Rev 2001 Apr; 29 (2): 82-7 9. Jones DA. High-and low-frequency fatigue revisited. Acta Physiol Scand 1996 Mar; 156 (3): 265-70 10. Westerblad H, Bruton JD, Allen DG, et al. Functional significance of Ca2+ in long-lasting fatigue of skeletal muscle. Eur J Appl Physiol 2000 Oct; 83 (2-3): 166-74 11. Lovering RM, De Deyne PG. Contractile function, sarcolemma integrity, and the loss of dystrophin after skeletal muscle eccentric contraction-induced injury. Am J Physiol Cell Physiol 2004 Feb; 286 (2): C230-8 12. Sorichter S, Puschendorf B, Mair J. Skeletal muscle injury induced by eccentric muscle action: muscle proteins as markers of muscle fiber injury. Exerc Immunol Rev 1999; 5: 5-21 13. Reid MB, Li YP. Cytokines and oxidative signalling in skeletal muscle. Acta Physiol Scand 2001 Mar; 171 (3): 225-32 14. Tidball JG. Inflammatory cell response to acute muscle injury. Med Sci Sports Exerc 1995 Jul; 27 (7): 1022-32 15. Smith LL. Acute inflammation: the underlying mechanism in delayed onset muscle soreness? Med Sci Sports Exerc 1991 May; 23 (5): 542-51 16. Hoppeler H. Exercise-induced ultrastructural changes in skeletal muscle. Int J Sports Med 1986 Aug; 7 (4): 187-204 17. Warren GL, Lowe DA, Armstrong RB. Measurement tools used in the study of eccentric contraction-induced injury. Sports Med 1999 Jan; 27 (1): 43-59 18. Close GL, Kayani A, Vasilaki A, et al. Skeletal muscle damage with exercise and aging. Sports Med 2005; 35 (5): 413-27 19. Finaud J, Lac G, Filaire E. Oxidative stress: relationship with exercise and training. Sports Med 2006; 36 (4): 327-58 20. Urso ML, Clarkson PM. Oxidative stress, exercise, and antioxidant supplementation. Toxicology 2003 Jul 15; 189 (1-2): 41-54 21. Jackson MJ. Free radicals generated by contracting muscle: by-products of metabolism or key regulators of mus-
Sports Med 2009; 39 (12)
McGinley et al.
1030
22.
23.
24.
25. 26.
27.
28.
29. 30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
cle function? Free Radic Biol Med 2008 Jan 15; 44 (2): 132-41 Close GL, Ashton T, McArdle A, et al. The emerging role of free radicals in delayed onset muscle soreness and contraction-induced muscle injury. Comp Biochem Physiol A Mol Integr Physiol 2005 Nov; 142 (3): 257-66 Vollaard NB, Shearman JP, Cooper CE. Exercise-induced oxidative stress: myths, realities and physiological relevance. Sports Med 2005; 35 (12): 1045-62 Jackson MJ, Pye D, Palomero J. The production of reactive oxygen and nitrogen species by skeletal muscle. J Appl Physiol 2007 Apr; 102 (4): 1664-70 Jackson MJ, O’Farrell S. Free radicals and muscle damage. Br Med Bull 1993 Jul; 49 (3): 630-41 White CR, Shelton JE, Moellering D, et al. Exercise and xanthine oxidase in the vasculature: superoxide and nitric oxide interactions. In: Sen CK, Packer L, Ha¨nninen O, editors. Handbook of oxidants and antioxidants in exercise. Amsterdam: Elsevier, 2000: 69-86 Jackson MJ. Exercise and oxygen radical production by muscle. In: Sen CK, Packer L, Ha¨nninen O, editors. Handbook of oxidants and antioxidants in exercise. Amsterdam: Elsevier, 2000: 57-68 McArdle A, Pattwell D, Vasilaki A, et al. Contractile activity-induced oxidative stress: cellular origin and adaptive responses. Am J Physiol Cell Physiol 2001 Mar; 280 (3): C621-7 Packer L. Highlight: oxidative stress. Biol Chem 2002 MarApr; 383 (3-4): 345 Jackson MJ, Khassaf M, Vasilaki A, et al. Vitamin E and the oxidative stress of exercise. Ann N Y Acad Sci 2004 Dec; 1031: 158-68 Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 2000 Dec; 279 (6): L1005-28 Gomez-Cabrera MC, Domenech E, Vin˜a J. Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med 2008 Jan 15; 44 (2): 126-31 Jackson MJ. Free radicals in skin and muscle: damaging agents or signals for adaptation? Proc Nutr Soc 1999 Aug; 58 (3): 673-6 Ji LL, Gomez-Cabrera MC, Vin˜a J. Exercise and hormesis: activation of cellular antioxidant signaling pathway. Ann N Y Acad Sci 2006 May; 1067: 425-35 Reid MB. Redox modulation of skeletal muscle contraction: what we know and what we don’t. J Appl Physiol 2001 Feb; 90 (2): 724-31 Sandstrom ME, Zhang SJ, Bruton J, et al. Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle. J Physiol 2006 Aug 15; 575 (Pt 1): 251-62 Packer L, Cadenas E. Oxidants and antioxidants revisited: new concepts of oxidative stress. Free Radic Res 2007 Sep; 41 (9): 951-2 Brooks SV, Zerba E, Faulkner JA. Injury to muscle fibres after single stretches of passive and maximally stimulated muscles in mice. J Physiol 1995 Oct 15; 488 (Pt 2): 459-69 Rodenburg JB, Bar PR, De Boer RW. Relations between muscle soreness and biochemical and functional outcomes
ª 2009 Adis Data Information BV. All rights reserved.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53. 54. 55.
56.
of eccentric exercise. J Appl Physiol 1993 Jun; 74 (6): 2976-83 Slatore CG, Littman AJ, Au DH, et al. Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer. Am J Respir Crit Care Med 2008 Mar 1; 177 (5): 524-30 Miller III ER, Pastor-Barriuso R, Dalal D, et al. Metaanalysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005 Jan 4; 142 (1): 37-46 Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and metaanalysis. JAMA 2007 Feb 28; 297 (8): 842-57 Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2008; (2): CD007176 Hathcock JN, Azzi A, Blumberg J, et al. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr 2005 Apr; 81 (4): 736-45 Carr A, Frei B. Does vitamin C act as a pro-oxidant under physiological conditions? Faseb J 1999 Jun; 13 (9): 1007-24 Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. Faseb J 1987 Dec; 1 (6): 441-5 Sjodin B, Hellsten Westing Y, Apple FS. Biochemical mechanisms for oxygen free radical formation during exercise. Sports Med 1990 Oct; 10 (4): 236-54 Powers SK, Sen CK. Physiological antioxidants and exercise training. In: Sen CK, Packer L, Ha¨nninen O, editors. Handbook of oxidants and antioxidants in exercise. Amsterdam: Elsevier, 2000: 221-42 Decker EA, Clarkson PM. Dietary sources and bioavailability of essential and nonessential antioxidants. In: Sen CK, Packer L, Ha¨nninen O, editors. Handbook of oxidants and antioxidants in exercise. Amsterdam: Elsevier, 2000: 323-58 Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A 1989 Aug; 86 (16): 6377-81 Packer JE, Slater TF, Willson RL. Direct observation of a free radical interaction between vitamin E and vitamin C. Nature 1979 Apr 19; 278 (5706): 737-8 Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr 1999 Jun; 69 (6): 1086107 Naidu KA. Vitamin C in human health and disease is still a mystery? An overview. Nutr J 2003 Aug 21; 2: 7 Evans WJ. Vitamin E, vitamin C, and exercise. Am J Clin Nutr 2000 Aug; 72 (2 Suppl.): 647S-52S Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A 1996 Apr 16; 93 (8): 3704-9 Packer L. Oxidants, antioxidant nutrients and the athlete. J Sports Sci 1997 Jun; 15 (3): 353-63
Sports Med 2009; 39 (12)
Antioxidant Vitamins and Muscle Damage
57. Traber MG. Vitamin E. In: Sen CK, Packer L, Ha¨nninen O, editors. Handbook of oxidants and antioxidants in exercise. Amsterdam: Elsevier, 2000: 359-71 58. Burton GW, Traber MG. Vitamin E: antioxidant activity, biokinetics, and bioavailability. Annu Rev Nutr 1990; 10: 357-82 59. Traber MG, Kayden HJ. Tocopherol distribution and intracellular localization in human adipose tissue. Am J Clin Nutr 1987 Sep; 46 (3): 488-95 60. Pincemail J, Deby C, Camus G, et al. Tocopherol mobilization during intensive exercise. Eur J Appl Physiol Occup Physiol 1988; 57 (2): 189-91 61. Niki E. Interaction of ascorbate and a-tocopherol. Ann N Y Acad Sci 1987; 498: 186-99 62. Bowry VW, Mohr D, Cleary J, et al. Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free human low density lipoprotein. J Biol Chem 1995 Mar 17; 270 (11): 5756-63 63. Meydani M, Evans WJ, Handelman G, et al. Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults. Am J Physiol 1993 May; 264 (5 Pt 2): R992-8 64. Meydani M, Fielding RA, Cannon JG, et al. Muscle uptake of vitamin E and its association with muscle fiber type. J Nutr Biochem 1997 Feb; 8 (2): 74-8 65. Jiang Q, Ames BN. g-Tocopherol, but not a-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J 2003 May; 17 (8): 816-22 66. Sen CK, Goldfarb AH. Antioxidants and physical exercise. In: Sen CK, Packer L, Ha¨nninen O, editors. Handbook of oxidants and antioxidants in exercise. Amsterdam: Elsevier, 2000: 297-20 67. Gohil K, Packer L, de Lumen B, et al. Vitamin E deficiency and vitamin C supplements: exercise and mitochondrial oxidation. J Appl Physiol 1986 Jun; 60 (6): 1986-91 68. You T, Goldfarb AH, Bloomer RJ, et al. Oxidative stress response in normal and antioxidant supplemented rats to a downhill run: changes in blood and skeletal muscles. Can J Appl Physiol 2005 Dec; 30 (6): 677-89 69. Warren JA, Jenkins RR, Packer L, et al. Elevated muscle vitamin E does not attenuate eccentric exercise-induced muscle injury. J Appl Physiol 1992 Jun; 72 (6): 2168-75 70. Coombes JS, Powers SK, Rowell B, et al. Effects of vitamin E and a-lipoic acid on skeletal muscle contractile properties. J Appl Physiol 2001 Apr; 90 (4): 1424-30 71. Van Der Meulen JH, McArdle A, Jackson MJ, et al. Contraction-induced injury to the extensor digitorum longus muscles of rats: the role of vitamin E. J Appl Physiol 1997 Sep; 83 (3): 817-23 72. Dalle-Donne I, Rossi R, Giustarini D, et al. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 2003 Mar; 329 (1-2): 23-38 73. Sen CK. Oxidants and antioxidants in exercise. J Appl Physiol 1995 Sep; 79 (3): 675-86 74. Thompson D, Williams C, Kingsley M, et al. Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation. Int J Sports Med 2001 Jan; 22 (1): 68-75 75. Thompson D, Williams C, Garcia-Roves P, et al. Postexercise vitamin C supplementation and recovery from de-
ª 2009 Adis Data Information BV. All rights reserved.
1031
76.
77.
78.
79.
80. 81.
82.
83.
84.
85.
86.
87.
88.
89.
90.
manding exercise. Eur J Appl Physiol 2003 May; 89 (3-4): 393-400 Childs A, Jacobs C, Kaminski T, et al. Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free Radic Biol Med 2001 Sep 15; 31 (6): 745-53 Thompson D, Williams C, McGregor SJ, et al. Prolonged vitamin C supplementation and recovery from demanding exercise. Int J Sport Nutr Exerc Metab 2001 Dec; 11 (4): 466-81 Davison G, Gleeson M. The effect of 2 weeks vitamin C supplementation on immunoendocrine responses to 2.5 h cycling exercise in man. Eur J Appl Physiol 2006 Jul; 97 (4): 454-61 Tauler P, Aguilo´ A, Gimeno I, et al. Influence of vitamin C diet supplementation on endogenous antioxidant defences during exhaustive exercise. Pflugers Arch 2003 Sep; 446 (6): 658-64 Kaminski M, Boal R. An effect of ascorbic acid on delayedonset muscle soreness. Pain 1992 Sep; 50 (3): 317-21 Bryer SC, Goldfarb AH. Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stress to eccentric exercise. Int J Sport Nutr Exerc Metab 2006 Jun; 16 (3): 270-80 Close GL, Ashton T, Cable T, et al. Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process. Br J Nutr 2006 May; 95 (5): 976-81 Connolly DAJ, Lauzon C, Agnew J, et al. The effects of vitamin C supplementation on symptoms of delayed onset muscle soreness. J Sports Med Phys Fitness 2006 Sep; 46 (3): 462-7 Thompson D, Bailey DM, Hill J, et al. Prolonged vitamin C supplementation and recovery from eccentric exercise. Eur J Appl Physiol 2004 Jun; 92 (1-2): 133-8 Ashton T, Young IS, Peters JR, et al. Electron spin resonance spectroscopy, exercise, and oxidative stress: an ascorbic acid intervention study. J Appl Physiol 1999 Dec; 87 (6): 2032-6 Han D, Loukianoff S, McLaughlin L. Oxidative stress indices: analytical aspects and significance. In: Sen CK, Packer L, Ha¨nninen O, editors. Handbook of oxidants and antioxidants in exercise. Amsterdam: Elsevier, 2000: 433-83 Khassaf M, McArdle A, Esanu C, et al. Effect of vitamin C supplements on antioxidant defence and stress proteins in human lymphocytes and skeletal muscle. J Physiol 2003 Jun 1; 549 (Pt 2): 645-52 Petersen EW, Ostrowski K, Ibfelt T, et al. Effect of vitamin supplementation on cytokine response and on muscle damage after strenuous exercise. Am J Physiol Cell Physiol 2001 Jun; 280 (6): C1570-5 Fischer CP, Hiscock NJ, Penkowa M, et al. Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle. J Physiol 2004 Jul 15; 558 (Pt 2): 633-45 Bailey DM. Supplemental ascorbate and exercise-induced IL-6 metabolism: focus on Fenton chemistry and redox-
Sports Med 2009; 39 (12)
McGinley et al.
1032
91.
92.
93.
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105.
regulation of vascular homeostasis. Eur J Appl Physiol 2005 Jul; 94 (4): 487-9 Cannon JG, Orencole SF, Fielding RA, et al. Acute phase response in exercise: interaction of age and vitamin E on neutrophils and muscle enzyme release. Am J Physiol 1990 Dec; 259 (6 Pt 2): R1214-9 Cannon JG, Meydani SN, Fielding RA, et al. Acute phase response in exercise: II, associations between vitamin E, cytokines, and muscle proteolysis. Am J Physiol 1991 Jun; 260 (6 Pt 2): R1235-40 Beaton LJ, Allan DA, Tarnopolsky MA, et al. Contraction-induced muscle damage is unaffected by vitamin E supplementation. Med Sci Sports Exerc 2002 May; 34 (5): 798-805 McBride JM, Kraemer WJ, Triplett-McBride T, et al. Effect of resistance exercise on free radical production. Med Sci Sports Exerc 1998 Jan; 30 (1): 67-72 Avery NG, Kaiser JL, Sharman MJ, et al. Effects of vitamin E supplementation on recovery from repeated bouts of resistance exercise. J Strength Cond Res 2003 Nov; 17 (4): 801-9 Sacheck JM, Milbury PE, Cannon JG, et al. Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men. Free Radic Biol Med 2003 Jun 15; 34 (12): 1575-88 Phillips T, Childs AC, Dreon DM, et al. A dietary supplement attenuates IL-6 and CRP after eccentric exercise in untrained males. Med Sci Sports Exerc 2003 Dec; 35 (12): 2032-37 Davison GW, Hughes CM, Bell RA. Exercise and mononuclear cell DNA damage: the effects of antioxidant supplementation. Int J Sport Nutr Exerc Metab 2005 Oct; 15 (5): 480-92 Mastaloudis A, Morrow JD, Hopkins DW, et al. Antioxidant supplementation prevents exercise-induced lipid peroxidation, but not inflammation, in ultramarathon runners. Free Radic Biol Med 2004 May 15; 36 (10): 1329-41 Mastaloudis A, Traber MG, Carstensen K, et al. Antioxidants did not prevent muscle damage in response to an ultramarathon run. Med Sci Sports Exerc 2006 Jan; 38 (1): 72-80 Mastaloudis A, Yu TW, O’Donnell RP, et al. Endurance exercise results in DNA damage as detected by the comet assay. Free Radic Biol Med 2004 Apr 15; 36 (8): 966-75 Jakeman P, Maxwell S. Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise. Eur J Appl Physiol Occup Physiol 1993; 67 (5): 426-30 Maxwell SRJ, Jakeman P, Thomason H, et al. Changes in plasma antioxidant status during eccentric exercise and the effect of vitamin supplementation. Free Radic Res Commun 1993; 19 (3): 191-202 Shafat A, Butler P, Jensen RL, et al. Effects of dietary supplementation with vitamins C and E on muscle function during and after eccentric contractions in humans. Eur J Appl Physiol 2004 Oct; 93 (1-2): 196-202 McCall MR, Frei B. Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med 1999 Apr; 26 (7-8): 1034-53
ª 2009 Adis Data Information BV. All rights reserved.
106. Griffiths HR, Moller L, Bartosz G, et al. Biomarkers. Mol Aspects Med 2002 Feb-Jun; 23 (1-3): 101-208 107. Asensi M, Sastre J, Pallardo FV, et al. A high-performance liquid chromatography method for measurement of oxidized glutathione in biological samples. Anal Biochem 1994 Mar; 217 (2): 323-8 108. Burcham PC, Kuhan YT. Introduction of carbonyl groups into proteins by the lipid peroxidation product, malondialdehyde. Biochem Biophys Res Commun 1996 Mar 27; 220 (3): 996-1001 109. Cao G, Prior RL. Comparison of different analytical methods for assessing total antioxidant capacity of human serum. Clin Chem 1998 Jun; 44 (6 Pt 1): 1309-15 110. de Zwart LL, Meerman JHN, Commandeur JNM, et al. Biomarkers of free radical damage applications in experimental animals and in humans. Free Radic Biol Med 1999 Jan; 26 (1-2): 202-26 111. Ghiselli A, Serafini M, Natella F, et al. Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med 2000 Dec; 29 (11): 1106-14 112. Jackson MJ. An overview of methods for assessment of free radical activity in biology. Proc Nutr Soc 1999 Nov; 58 (4): 1001-6 113. Jenkins RR. Exercise and oxidative stress methodology: a critique. Am J Clin Nutr 2000 Aug; 72 (2 Suppl.): 670S-4S 114. Kadiiska MB, Gladen BC, Baird DD, et al. Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radic Biol Med 2005 Mar 15; 38 (6): 698-710 115. Møller P, Loft S. Oxidative DNA damage in human white blood cells in dietary antioxidant intervention studies. Am J Clin Nutr 2002 Aug; 76 (2): 303-30 116. Morrow JD, Roberts 2nd LJ. Mass spectrometric quantification of F2-isoprostanes in biological fluids and tissues as measure of oxidant stress. Methods Enzymol 1999; 300: 3-12 117. Springfield JR, Levitt MD. Pitfalls in the use of breath pentane measurements to assess lipid peroxidation. J Lipid Res 1994 Aug; 35 (8): 1497-504 118. Stadtman ER. Protein oxidation and aging. Science 1992 Aug 28; 257 (5074): 1220-4 119. Waring WS, Mishra V, Maxwell SRJ. Comparison of spectrophotometric and enhanced chemiluminescent assays of serum antioxidant capacity. Clin Chim Acta 2003 Dec; 338 (1-2): 67-71 120. Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull 1993 Jul; 49 (3): 481-93 121. Zerba E, Komorowski TE, Faulkner JA. Free radical injury to skeletal muscles of young, adult, and old mice. Am J Physiol 1990 Mar; 258 (3 Pt 1): C429-35
Correspondence: Prof. Alan E. Donnelly, Department of Physical Education and Sport Sciences, University of Limerick, Castletroy, Limerick, Ireland. E-mail:
[email protected]
Sports Med 2009; 39 (12)
Sports Med 2009; 39 (12): 1033-1054 0112-1642/09/0012-1033/$49.95/0
REVIEW ARTICLE
ª 2009 Adis Data Information BV. All rights reserved.
Bovine Colostrum Supplementation and Exercise Performance Potential Mechanisms Cecilia M. Shing,1 Denise C. Hunter2 * and Lesley M. Stevenson2 * 1 School of Human Life Sciences, University of Tasmania, Launceston, Tasmania, Australia 2 Centre for Phytochemistry and Pharmacology, Southern Cross University, Lismore, New South Wales, Australia
Contents Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Bovine Colostrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Gastrointestinal Health and Integrity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Immune System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Influence on the Neuroendocrine System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Additional Pathways of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Supplementation for Improved Exercise Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Body Composition, Strength and Power . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Endurance Performance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Anaerobic Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Immune Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Gastrointestinal Health and Integrity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Kinetics and Safety. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Combined Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Abstract
1033 1034 1035 1036 1037 1037 1038 1038 1044 1045 1046 1047 1048 1050 1050
Bovine colostrum (BC) is rich in immune, growth and antimicrobial factors, which promote tissue growth and the development of the digestive tract and immune function in neonatal calves. Although the value of BC to human adults is not well understood, supplementation with BC is becoming increasingly popular in trained athletes to promote exercise performance. The combined presence of insulin-like growth factors (IGF), transforming growth factors, immunoglobulins, cytokines, lactoferrin and lysozyme, in addition to hormones such as growth hormone, gonadotrophin-releasing hormone, luteinizing hormone-releasing hormone and glucocorticoids, would suggest that BC might improve immune function, gastrointestinal integrity and the neuroendocrine system, parameters that may be compromised as a result of intensive training. A review of studies investigating the influence of BC supplementation on
* DCH and LMS are currently with the Health and Food Group, the Horticulture and Food Research Institute of New Zealand, Auckland, New Zealand.
Shing et al.
1034
exercise performance suggests that BC supplementation is most effective during periods of high-intensity training and recovery from high-intensity training, possibly as a result of increased plasma IGF-1, improved intramuscular buffering capacity, increases in lean body mass and increases in salivary IgA. However, there are contradicting data for most parameters that have been considered to date, suggesting that small improvements across a range of parameters might contribute to improved performance and recovery, although this cannot be concluded with certainty because the various doses and length of supplementation with BC in different studies prevent direct comparison of results. Future research on the influence of BC on sports performance will only be of value if the dose and length of supplementation of a well-defined BC product is standardized across studies, and the bioavailability of the active constituents in BC is determined.
1. Bovine Colostrum Bovine colostrum (BC) is the milk produced by cows in the first days after parturition. BC is rich in immune, growth and antimicrobial factors that are homologous to those found in human colostrum but expressed in greater concentrations.[1] The concentrations of bioactive components are greatest in the first milkings with concentrations decreasing over the subsequent 3 days.[2-5] For this reason, colostrum produced on the first day of calving is considered superior in quality to that produced in the later days of lactation. BC provides passive transfer of immunity to the newborn calf whose immune system is not fully developed at birth, and a source of growth factors to contribute to the development of the digestive tract.[6] Immune factors such as immunoglobulins, cytokines, lactoferrin and lysozyme are found in colostrum while the predominant growth factors are insulin-like growth factors (IGFs) and transforming growth factors (TGFs). Immunoglobulins make a significant contribution to the protein content of colostrum and the concentration of IgG is up to 100 times greater than the concentration found in normal milk.[7] IgG is able to bind complement, a complex group of immune proteins, to directly lyse infected cells. It can also enhance cytotoxic activity of natural killer cells and phagocytosis by binding to macrophages and neutrophils.[8] BC also contains a number of cytokines that are important in stimulating the calf immune ª 2009 Adis Data Information BV. All rights reserved.
system and are also important messengers within the human immune system.[9] Of the growth factors contained in BC, the most prevalent is IGF-1 (reported at concentrations of 50–2000 mg/mL),[10] which has an amino acid sequence homologous to human IGF-1.[11] IGF-1 mediates the effects of growth hormone on muscle protein synthesis[12] and plays an important role in the regulation of metabolism.[13] Other growth factors in colostrum include TGF-b, epidermal growth factor and fibroblast growth factor, which all play a role in cell proliferation and repair.[14] Colostrum also contains a number of hormones that are known to influence the hypothalamus, pituitary and adrenal glands and gonadal function.[15] Specific hormones include growth hormone, gonadotrophin-releasing hormone, luteinizing hormone-releasing hormone, glucocorticoids and possibly testosterone.[15] The function of these hormones in colostrum is not clear; however, it is postulated that they play a role in gastrointestinal development and immune system maturation of the neonate. Oligosaccharides and glycoproteins contained in BC may provide an energy source for the calf[16] while a-1 acid glycoprotein may be an important modulator of inflammation.[17] For an extensive review of the components of BC the reader is referred to van Hooijdonk et al.,[18] Korhonen et al.[2] and Gopal and Gill.[16] The importance of colostrum for the development of the neonate is well recognized. The homologous composition of BC to human Sports Med 2009; 39 (12)
Colostrum and Performance
colostrum, and the fact that growth and immune factors are expressed in much greater concentrations in BC, has led to the use of BC by humans to ‘boost’ immune function and promote tissue growth. Supplementation in humans has been associated with the successful treatment of enteric pathogens,[19] inhibition of gastrointestinal damage associated with non-steroidal antiinflammatory drug (NSAID) administration[20-22] and reduction of upper respiratory illness symptoms.[23,24] In more recent years, BC has been used by some athletes as a nutritional supplement to enhance immune function, improve exercise performance and recovery, and increase lean muscle mass. While all BC contains antibodies specific to a variety of antigens, a distinction should be made between BC and hyperimmune BC that is the result of immunization against specific microorganisms. Studies investigating the effects of colostrum on exercise performance have used non-hyperimmune, standard BC preparations which are more readily available and cost effective than hyperimmune BC. As the focus of this review is on the effects of BC supplementation on exercise performance and potential mechanisms, we have confined the review of literature to research that has used non-hyperimmune, standard BC preparations. 1.1 Gastrointestinal Health and Integrity
Gastrointestinal differentiation and maturation observed in newborn calves following colostrum ingestion reinforces the importance of BC for their survival,[25,26] particularly as the absence of parenteral nutrition is associated with an increased risk of disease and mortality.[27] Growth factors in colostrum include IGF-1, TGF-b, epidermal growth factor and fibroblast growth factor, which play a role in gastrointestinal growth, cell proliferation and repair.[14] In vivo human studies have demonstrated a significant increase in gastrointestinal villus height and depth following epidermal growth factor administration in neonates with congenital microvillus atrophy.[28] In vivo animal studies have also provided evidence for the positive effects of epiª 2009 Adis Data Information BV. All rights reserved.
1035
dermal growth factor and IGF-1 on enhanced recovery following bowel resections.[29] The potential for BC to improve gastrointestinal health and integrity has led to human supplementation trials, one of which has shown BC supplementation to be successful in the treatment of distal colitis. Colostrum, self-administered twice daily via an enema, significantly improved the histology score of muscle biopsies taken from the affected area, as well as symptom severity and duration when compared with a placebo.[30] A mechanism proposed for the improvements associated with colostral enema administration was an increase in cell growth and proliferation of the epithelium, and a possible cytoprotective effect to prevent gastric damage.[30] Reductions in gastric damage and improved epithelial integrity may dampen inflammation. In healthy humans, colostrum supplementation may prove beneficial to gut health. BC coadministered with NSAIDs reduced the increase in intestinal permeability otherwise observed when NSAIDs were administered with a whey protein placebo.[22] A similar reduction in gastrointestinal damage following BC administration in rats has been observed following TGF-b administration.[21] When administered alone, TGF-b is susceptible to digestion with fasting gastric juices, but in the presence of casein, enzyme inhibitors and other peptides contained in BC, the breakdown of growth factors can be prevented, maintaining their activity following ingestion.[31] Growth factors within colostrum may be responsible for the observed reduction in intestinal damage associated with NSAID administration and increases in cell proliferation in both rats and humans.[21,22] BC containing 2 mg/L of IGF-1 and 25 mg/L of TGF-b was administered to rats and associated with reduced gastric damage in a dose-dependent manner when compared with a standard milk preparation.[21] Recent investigations by Kim and colleagues[32] also support the benefit of coadministration of colostrum with NSAIDs, showing that colostrum supplementation in combination with diclofenac administration prevents mucosal damage of the small intestine and reduces intestinal permeability.[20] Sports Med 2009; 39 (12)
1036
Research suggests that BC has no influence on intestinal absorption in healthy humans.[33] Potential changes in nutrient uptake were investigated by Brinkworth and Buckley[33] following an 8-week period of BC supplementation at 60 g/day. Subjects completed an oral L-alanine tolerance test and an oral glucose tolerance test pre- and post-supplementation. No differences were observed in glucose and insulin levels or alanine uptake in the plasma. Although plasma concentrations of nutrients reflect the balance of their addition to and removal from the circulation, Brinkworth and Buckley[33] concluded that it was unlikely that BC affected intestinal absorption, because in animals, improved intestinal absorption is associated with an increase in plasma nutrient concentrations. Changes in intestinal permeability following colostrum supplementation require further research. The potential of colostrum in improving gastrointestinal health may also explain improved exercise performance following BC supplementation. BC supplementation in humans may only be beneficial to the gastrointestinal system during inflammation and disruption of the gastric mucosa. Supplementation (12 weeks at 3 g/day) has recently been associated with a significant decrease in recurrent diarrhoea in children,[23] which suggests BC may reduce gastrointestinal disturbance during periods of inflammation and stress. While direct application of BC to the colon is associated with enhanced cell growth and proliferation,[30] the influence of oral BC supplementation on the morphology of the gastrointestinal tract requires further research. 1.2 Immune System
Colostrum provides the newborn with immunoglobulins, maternal lymphocytes and cytokines that contribute to mucosal immunity.[34] Unlike humans, where IgG transfer takes place in utero, bovine calves are dependent on the transfer of IgG and other immunoglobulins via colostrum from the mammary glands.[35] Attainment of passive immunity is essential within the first hours of life as the ability of neonatal calves to absorb macromolecules is reduced due to the ª 2009 Adis Data Information BV. All rights reserved.
Shing et al.
process of intestinal closure that begins after birth and is complete around 24 hours post partum.[36] Insufficient or inadequate colostrum intake, and therefore IgG supply, has been related to increased morbidity and mortality in calves.[25,26] Conversely, high colostrum feedings have been associated with enhanced intestinal development.[37] BC contains a number of cytokines that are important messengers within the human immune system. These are also important in stimulating the calf immune system (i.e. interleukin [IL]-1b, IL-6, tumour necrosis factor [TNF]-a, interferon [IFN]-g and IL-1 receptor antagonist).[9] Proinflammatory BC cytokines have been found to regulate the blastogenic activity of peripheral blood mononuclear cells from calves, although adult cow cells were less active when treated with the same cytokines.[38] While there has been research to show that the integrity of bovine immunoglobulins and growth factors are maintained following the processing of colostrum to powder,[39] little is known of the cytokine content of commercially processed BC. While the cytokine content of commercial BC preparations is yet to be determined, other factors in BC may influence the human immune system following supplementation through the stimulation of cytokine production. BC has been shown to increase cytokine messenger RNA in cells of intestinal Peyer’s patches in weaned piglets receiving 1–5 g/day of BC for 3 weeks,[40] and recently our group has investigated the ability of a commercially available BC supplement to stimulate cytokine secretion from peripheral blood mononuclear cells under resting and inflammatory conditions.[41] IFN-g, IL-10 and IL-2 secretion significantly increased with increasing concentrations of BC under resting conditions in vitro. The addition of BC to cells co-cultured with lipopolysaccharide significantly reduced the secretion of TNF, IL-6 and IL-4,[41] suggesting that supplementation may reduce proinflammatory cytokine production following strenuous exercise, which is associated with elevated lipopolysaccharide concentrations.[42] A depressed immune system is associated with an increased risk of upper respiratory tract Sports Med 2009; 39 (12)
Colostrum and Performance
infection (URTI). The potentially beneficial effects of BC on immune function may be related to the observed reduction in URTI symptoms following a period of supplementation. Children experiencing recurrent URTIs experienced a significant reduction in the incidence of URTIs with 12 weeks of BC supplementation at 3 g/day.[23] Although this study was not placebocontrolled, other studies support a reduction in URTI symptoms in athletes following a period of BC supplementation.[24] It is thought that an increase in salivary IgA affords greater protection against URTI,[43] and the authors speculated that this may have been the primary mechanism responsible for the decreased incidence of URTI associated with BC supplementation.[24] A recent study by our group showed no change in salivary IgA concentration or secretion rate over 8 weeks of supplementation at a dose of 10 g/day, but reported a trend (p = 0.05) for a reduction in URTI symptoms.[44] The relationship between BC, salivary IgA concentration and URTI requires further investigation using similar doses and supplementation periods. 1.3 Influence on the Neuroendocrine System
Colostrum has been shown to enhance maturation of the hypothalamic-pituitary-somatotropic axis and influence neuroendocrine function of calves[34] via the direct transport of colostral proteins into cerebral spinal fluid.[45,46] Homeostasis is maintained by the hypothalamic-pituitary-adrenal (HPA) axis and interactions between autonomic and immune tissues are well established. A blunted HPA axis, which may be modulated by cytokines, is associated with increased mood disturbance, fatigue and other sickness behaviour.[47] BC contains hormones that influence the HPA axis and gonadal hormone production.[28] Specific hormones include growth hormone, gonadotrophin-releasing hormone, luteinizing hormone-releasing hormone, glucocorticoids and possibly testosterone.[15] While the specific function of these hormones in colostrum is not clear, it is postulated that they play a role in gastrointestinal development, immune system maturation of the neonate and modulation of the neuroendocrine system. It is yet to be ª 2009 Adis Data Information BV. All rights reserved.
1037
determined whether components of BC cross the blood-brain barrier in humans and hormone concentrations in processed BC are yet to be quantified. Negative perturbations in mood state, that may be influenced by hypothalamic neuropeptides and releasing factors, are associated with periods of intense training.[48] BC protein concentrate (bovine CPC) supplementation has been associated with a decrease in fatigue and increase in vigour (determined by profile of mood states) in healthy males following 8 weeks of BC supplementation at 20 g/day.[49] BC supplementation appears to positively influence mood state, which may reflect maintenance of homeostasis of neuroendocrine function;[50] however, further research is required to confirm previous findings and determine mechanistic pathways via which BC may influence mood state. 1.4 Additional Pathways of Action
In combination with the influence of BC on immune, gastrointestinal and neuroendocrine properties, colostrum may also act as an antioxidant and promote tissue growth outside the gut.[51] The addition of BC to rat tumour cell lines in vitro has been shown to reduce levels of lipid hydroperoxides in culture supernatants.[51] The antioxidant properties of BC may be attributed to lactoferrin, an iron chelator that reduces neutrophil oxidant production associated with inflammation. BC also contains the antioxidants vitamin E, vitamin C and selenium;[52] however, lactoferrin is present in greater concentrations (reported to range from 1.5 to 5 mg/mL).[53] The implications of exercise-associated oxidative damage remains unclear, as does the role of BC in preventing lipid peroxidation in humans. The ability of a commercial BC powder to promote tissue growth was recently investigated by Torre and colleagues.[54] Canine skin fibroblasts were cultured in the presence of colostrum at concentrations of 0.1–1.0 mg/mL for 24 and 48 hours. Skin cells proliferated in a dosedependent manner with increasing concentrations of colostrum. While the authors did not investigate a specific mechanism responsible for Sports Med 2009; 39 (12)
1038
cell proliferation, Sporn and colleagues[55] demonstrated that bovine TGF, isolated from salivary gland and kidney tissue, promoted wound healing in rats where increased protein, collagen and DNA at the wound site were reported. The ability of BC to promote human skeletal muscle tissue growth in vitro has yet to be investigated. 2. Supplementation for Improved Exercise Performance BC supplementation has increased among athletes as a means of enhancing immune function, increasing lean body mass and/or improving exercise performance. Mero and colleagues[56] were the first to investigate the effect of BC on serum immunoglobulins, IGF-1 and explosive power performance in an athletic population in 1997. Since then, research has investigated the ability of BC supplementation to improve endurance performance, increase strength and improve anaerobic performance, and determine mechanisms responsible for improvements in exercise performance associated with BC. There is evidence to suggest that BC supplementation may improve anaerobic and power performance; improvements in repeat sprint performance,[57] peak vertical jump power[58,59] and peak cycle power[58] have been reported. Improvements in cycling time-trial performance following prolonged endurance performance,[60] improved repeat running performance following a short recovery period,[61] and maintenance of ventilatory threshold following a high-intensity training period[44] suggest that colostrum may also enhance recovery, and in turn improve repeat endurance performance. Strength improvements following BC supplementation are less clear, with some investigations reporting an increase in one-repetition maximum (1RM) following 12 weeks of supplementation[62] and others reporting no change in upper or lower body strength following 8 weeks of supplementation.[63,64] One study has reported increases in lean body mass;[63] however, this occurred independent of strength gains. Studies investigating the effects of BC supplementation on exercise performance, body composition and biochemical ª 2009 Adis Data Information BV. All rights reserved.
Shing et al.
variables in healthy adult humans are presented in table I. 2.1 Body Composition, Strength and Power
As well as providing calves with a concentrated source of protein, non-nutrient factors in BC contribute greatly to their growth and development. Calves fed BC have increased amounts of protein and improved growth performance compared with calves fed a milk replacer.[76] BC has been shown to increase the hypothalamic-pituitary-somatotropic axis in calves, significantly increasing IGF-1 concentration,[77] which is associated with stimulation of muscle growth.[78] Several studies conducted since the work of Mero and colleagues[56] have considered the influence of colostrum supplementation on possible changes in body composition, strength and power. While colostrum in combination with other components such as creatine may significantly enhance muscle strength,[64,65] the potential for colostrum alone to stimulate these changes remains unclear. The first investigation to examine whether colostrum supplementation would elicit changes in body composition was conducted by Antonio and colleagues.[63] Resistance-trained males (n = 14) and females (n = 8) were randomly assigned to either a colostrum (20 g/day) or a placebo group prior to participating in an 8-week resistance and aerobic programme that involved three training sessions per week. Body composition was assessed prior to and on completion of the study using dual energy x-ay absorptiometry. Exercise performance was also assessed pre- and post-supplementation with 1RM strength tests, running time to fatigue and total repetitions to fatigue at 50% and 100% of bodyweight (females and males, respectively). Bodyweight significantly increased for the placebo group (2.44 kg, p < 0.05), primarily due to an increase in fat mass, while the colostrum group showed a significant increase in lean body mass (1.49 kg, p < 0.05) without recording any significant change in bodyweight (due to a decrease in fat mass). There were no significant differences between groups in time to fatigue, maximum strength or muscular endurance. Unfortunately, as IGF-1 was not measured, it is not clear whether the Sports Med 2009; 39 (12)
Subjects
Dose (per day) and period of supplementation
Study design
Training protocol
Variables measured
Findings* (compared with placebo)
Mero et al.,[56] 1997
M sprinters and jumpers (n = 9)
Group 1: 25 mL Group 2: 125 mL for 8 days
db, pc, r, co
6 days of training that included speed, strength and aerobic components
4.32 nmol/L › IGF-1 for 125 mL BC
Leppa¨luoto et al.,[59] 2000a
M and F athletes (n = 10)
400 mL for 12 days
db, pc, co
Not reported although testing was carried out day 11 of supplementation and repeated on day 12
IGF-1 IgA IgG Amino acid Hormones Countermovement jump . VO2max Countermovement jump Squat jump IGF-1 GH Testosterone
Antonio et al.,[63] 2001
M and F active (n = 22)
20 g for 8 weeks
db, pc
Aerobic and heavy resistance training minimum three times per week
1RM bench press Submaximal bench press Running time to fatigue Lean body mass
2.4% › in lean body mass
Kreider et al.,[65] 2001a
M and F resistance trained (n = 49)
Group 1: 60 g BC Group 2: 60 g creatine Group 3: 60 g BC + creatine for 12 weeks
db, pc, r
Periodized resistance training programme 4 days per week
Total mass Fat-free mass Fat mass
› total mass (groups 1 to 3: 2.0 kg, 1.7 kg, 3.0 kg) › fatfree mass (groups 1 to 3: 1.3 kg, 1.9 kg, 2.6 kg)
Kerksick et al.,[62] 2001a
M and F resistance trained (n = 49)
Group 1: 60 g BC Group 2: 60 g creatine Group 3: 60 g BC + creatine for 12 weeks
db, pc, r
Periodized resistance training programme 4 days per week
1RM bench press 1RM leg press 30s Wingate test 80% 1RM
› in bench press 1RM (groups 1 to 3: 62 kg, 70 kg, 121 kg)
Buckley et al.,[61] 2002
M untrained (n = 39)
60 g for 8 weeks
db, pc, r
45 min running training at threshold three times per week
2 x treadmill TTF separated by 20 min IGF-1
4.6% › in peak running speed during second treadmill run
Maintenance of O2 uptake from day 11 to day 12 ( fl 7% in placebo group) › flight times from day 11 to day 12
Continued next page
1039
Sports Med 2009; 39 (12)
Study, year
Colostrum and Performance
ª 2009 Adis Data Information BV. All rights reserved.
Table I. Summary of studies that have examined the influence of bovine colostrum (BC) supplementation on exercise performance, body composition and blood and saliva variables in healthy, adult humans
Subjects
Dose (per day) and period of supplementation
Study design
Training protocol
Variables measured
Findings* (compared with placebo)
Hoffman et al.,[66] 2005
M and F elite hockey players (n = 35)
60 g for 8 weeks
db, pc, r
Normal training
5 · 10 m sprints Vertical jump Shuttle-run test Body composition
4.8% › in 5 · 10 m sprint performance
Brinkworth et al.,[67] 2002
F elite rowers (n = 13)
60 g for 9 weeks
db, pc, r
Rowing training and strength-plyometric training
2 x rowing ergo tests separated by 15 min passive recovery Blood buffer capacity
22% › in blood buffering capacity
Mero et al.,[68] 2002
M and F active adults (n = 35)
20 g for 2 weeks
db, pc, r
2 weeks of specific event training (75%) and strength training (25%)
IGF-1 Serum IgA Serum IgG Salivary IgA
17% › in IGF-1 33% › in salivary IgA
Coombes et al.,[60] 2002
M trained cyclists (n = 42)
Group 1: 20 g Group 2: 60 g for 8 weeks
db, pc, r
Normal training
Buckley et al.,[58] 2003
M active (n = 51)
60 g for 8 weeks
db, pc, r
Alternate resistance and plyometric training 6 days per week
Vertical jump power Peak anaerobic cycle power Anaerobic capacity 1RM IGF-1
7.2% › in peak vertical jump 13.8% › in peak cycle power
Fry et al.,[64] 2003
M and F recreationally weight trained (n = 19)
Group 1: 60 g Myovive + BC Group 2: 60 g Myovive + protein Group 3: 60 g BC + protein for 12 weeks
db, pc, r
Heavy resistance training 4 days per week
Body composition 1RM Fibre type distribution Fibre type area Myosin heavy chain content
No significant differences
O’Leary,[69] 2003a
M active (n = 16)
20 g for 8 weeks
Not stated
Not stated
30s Wingate test Creatine kinase Lactate
No significant differences
. VO2max test Work-based time-trial IGF-1
20 g: 19% improvement in time-trial performance 60g: 16% improvement in time-trial performance
Continued next page
Shing et al.
Sports Med 2009; 39 (12)
Study, year
1040
ª 2009 Adis Data Information BV. All rights reserved.
Table I. Contd
Study, year
Subjects
Dose (per day) and period of supplementation
Study design
Training protocol
Variables measured
Findings* (compared with placebo)
Brinkworth et al.,[70] 2004
M active (n = 34)
20 g for 8 weeks
db, pc, r
Resistance training of non-dominant arm elbow flexors
4.2% › in CSA 2.3% › in circumference
Brinkworth and Buckley,[71] 2004
F elite rowers (n = 13)
60 g for 9 weeks
db, pc, r
Sample et al.,[72] 2004 a
Active healthy elderly aged 59–74 years (n = 16)
20 g for 8 weeks
db, pc, r
Rowing training and strength-plyometric training Maintained normal physical activity levels
Mero et al.,[73] 2005
M physically active (n = 12)
20 g for 14 days
db, pc, co
Strength training session
Crooks et al.,[74] 2006
M and F marathon runners (n = 35) M trained cyclists (n = 29)
26 g for 12 weeks
db, pc, r
10 g for 8 weeks
db, pc, r
Marathon training, culminating in a marathon race Normal cycle training including 5 days of HIT
1RM Maximal voluntary contraction of flexors Upper arm CSA Upper arm circumference Haemoglobin Plasma buffer capacity 1RM leg press Hand grip strength . VO2 Capillary density Fibre type Muscle protein (biopsy of vastus lateralis) Serum amino acids (femoral arterial and venous blood sampling) Maximal voluntary contraction URTI symptoms Salivary IgA
10 g for 8 weeks
db, pc, r
Shing et al.,[75] 2006
Shing et al.,[44] 2007
Normal cycle training including 5 days of HIT
No significant differences
No significant differences
13% › serum concentrations of essential amino acids › muscle protein synthesis and breakdown
79% › in IgA
BC maintained ventilatory threshold following HIT (4.6% drop in placebo group) 89% › pre-exercise serum soluble TNF receptor 1 and suppressed the postexercise decrease in cytotoxic/ suppressor T cells during HIT period (BC: -1.0%, placebo: -9.2%)
Abstract only.
co = crossover; CSA = cross-sectional area; db = double blind; F = female; GH = growth hormone; HIT = high-intensity training; Igs = immunoglobulins; IGF-1 = insulin-like growth factor-1; M = male; min = minutes; Myovive = supplement containing creatine; pc = placebo controlled; r = randomized; RM = repetition maximum; TNF = tumour necrosis factor; . TTF = time to fatigue; URTI = upper respiratory tract infection; VO2max = maximum oxygen uptake/consumption; › indicates increase; fl indicates decrease; * p < 0.05.
1041
Sports Med 2009; 39 (12)
a
M trained cyclists (n = 29)
40 km time-trial Ventilatory threshold TTF Lymphocyte and neutrophil surface markers Serum Igs Serum cytokines URTI symptoms Salivary IgA
Colostrum and Performance
ª 2009 Adis Data Information BV. All rights reserved.
Table I. Contd
1042
observed increase in lean body mass following BC supplementation was related to an increase in serum IGF-1 concentration.[63] In contrast to the findings of Antonio and colleagues, Kerksick et al.[62] reported an increase in maximal strength following 12 weeks of BC supplementation. Forty-nine resistance-trained male and female subjects participated in a 12-week training programme in which participants were assigned to a placebo group, a colostrum group (60 g), a creatine group or a colostrum-creatine combined group. Maximal strength was determined by 1RM bench press and leg press followed by a strength endurance bench and leg press at 80% 1RM. Potential changes in anaerobic performance were examined using a 30-second Wingate test and body composition was monitored during the study using dual energy x-ray absorptiometry. 1RM bench press for the colostrum, creatine and combined creatine and colostrum groups increased significantly when compared with the placebo group (p < 0.05). No significant differences were observed for sprint performance between the four groups. There was a significant interaction of group and fat-free mass, with greatest gains experienced by the combined BC and creatine group (placebo = 0.8 kg, colostrum = 1.3 kg, creatine = 1.9 kg, colostrumcreatine combined = 2.6 kg).[65] While colostrum supplementation in combination with 12 weeks of resistance training has been shown to improve maximal strength,[62] supplementation at the same dose (60 g/day) during 8 weeks of strength and plyometric training was not associated with changes in maximal strength.[58] Fifty-one physically active (but not specifically resistance-trained) males participated in six exercise sessions per week, alternating between resistance and plyometric training. Resistance training was performed at high and low intensities and the plyometric training was performed with maximal effort three times a week. There were significant improvements from baseline in 1RM, training volumes completed and anaerobic work capacity for both groups across the experimental period (p < 0.01). BC supplementation significantly improved peak cycle power and vertical jump height, suggesting that colostrum was ª 2009 Adis Data Information BV. All rights reserved.
Shing et al.
beneficial to explosive power activities. Adaptations to plyometric training include increased type IIa fibres and increased fibre diameter.[79] Fry and colleagues[64] investigated changes in fibre type and diameter following 12 weeks of BC supplementation and resistance training and reported a nonsignificant increase in type IIa fibre average crosssectional area (BC [n = 6]: before = 5428 – 802 mm2, after = 6588 – 529 mm2; placebo [n = 5]: before = 7908 – 1042 mm2, after = 7688 – 789 mm2). Because of small subject numbers, the power to detect a difference in fibre type area was <0.8. Greater subject numbers would be required to determine if BC influences fibre type area. Improvements in explosive activities following colostrum supplementation are supported by the work of Leppa¨luoto and colleagues.[59] In a double-blind, crossover design, ten athletes performed maximal oxygen uptake testing and two jump tests on days 11 and 12 of supplementation.[59] Colostrum significantly improved jump flight times and maintained maximal oxygen uptake from day 11 to day 12 of supplementation when compared with the placebo group (p < 0.05). There were no differences between groups for IGF-1, growth hormone, creatine kinase, testosterone or IL-6. While the authors concluded that BC supplementation was beneficial during heavy training periods, limited conclusions can be drawn from the study, as neither the dose administered nor details of training and diet control were reported by the authors and the investigation is yet to be published in a peer-reviewed journal. Previous work by Mero and colleagues[56] showed that 8 days of BC supplementation was not sufficient to influence vertical jump performance. Brinkworth and colleagues[70] again investigated the influence of colostrum on potential changes in body composition over 8 weeks using the same dose (60 g) that was used in their previous work. Physically active males strengthtrained the elbow flexors of their non-dominant arm 4 days a week. One RM bicep curl, magnetic resonance imaging and maximal voluntary isometric contraction of the upper arm were measured at baseline and following 4 and 8 weeks of supplementation. When compared with both Sports Med 2009; 39 (12)
Colostrum and Performance
their untrained arm and with the placebo group, upper limb circumference and total crosssectional area were increased in the trained arm of subjects supplementing with colostrum. There were no significant differences between groups for upper limb muscle cross-sectional area. The authors attributed the increase in cross-sectional area following colostrum supplementation to an increase in skin cross-sectional area, and indeed previous research has shown that canine skin cells proliferate in a dose-dependent manner with increasing concentrations of colostrum.[54] However, the MRI did not allow for differentiation between skin and subcutaneous fat so an increase in subcutaneous fat of the trained arm cannot be excluded.[70] Strength improvements were not significantly different between trained and untrained limbs. Mero and colleagues have been the only group to date to report increases in serum IGF-1 concentration following BC supplementation for 8[56] and 14 days.[68,80] Typically degraded in the gastrointestinal tract, it has been suggested that factors contained in BC may aid the absorption of IGF-1 by preventing its breakdown and digestion.[31] Previous research involving rats has shown that 9% of IGF-1 ingested alone appears in the bloodstream, while 67% of IGF-1 survives digestion when administered with casein.[81] Absorption of IGF-1 contained in BC may therefore be assisted by proteins that aid its uptake and prevent gastric breakdown. Normal serum IGF-1 values for 20- to 30-year-olds range from 14 to 48 nmol/L. The average increase in IGF-1 reported by Mero and colleagues[80] was 5.32 nmol/L (from 20 to 25.32 nmol/L). The amount of IGF-1 contained in the dose was approximately 74 mg/day. At this dose, if approximately 65% of IGF-1 was absorbed, the concentration of IGF-1 would only be expected to rise by approximately 1.05 nmol/L. This suggests that the increase in serum IGF-1 reported by Mero and colleagues[80] was probably due to an increase in endogenous production. To confirm that the source of additional IGF-1 was endogenous, Mero et al.[56,80] investigated the origin of increased serum IGF-1 following colostrum supplementation. Twelve recreationally active males and females ingested labelled human ª 2009 Adis Data Information BV. All rights reserved.
1043
recombinant IGF.[80] Total, free and bound IGF-1 were subsequently measured in serum; the ingested labelled IGF-1 appeared fragmented in circulation. Only 4% of ingested 123I-rhIGF-1 eluted at 40-90 kDa, whereas previous research has shown 123 I-rhIGF-1 to elute at 150 and 43 kDa. IGF-1 has also been shown to have a rapid in vivo breakdown. The authors did not give the total yield of 123I-rhIGF-1, and it is not therefore clear whether there was significant digestion of the 123I tracer. Their findings led the authors to conclude that IGF-1 is unlikely to be absorbed from BC and that the increase in IGF-1 observed in their earlier work was due to an increase in endogenous production.[80] This conclusion cannot be supported as labelled IGF-1 was administered alone and it is unlikely that these results would directly reflect the absorption of IGF-1 in a BC preparation where components of BC would prevent the breakdown and digestion of IGF-1 in the gastrointestinal tract.[31] While Mero and colleagues reported significant increases in serum IGF-1 concentrations following BC supplementation for 8 and 14 days,[56,68] other researchers using similar doses but longer supplementation periods have reported no change.[58,60] Kuipers et al.,[82] Buckley et al.[58] and Coombes et al.[60] analysed IGF-1 following 4–8 weeks of BC supplementation and showed no significant changes. Buckley et al.[58] suggested that an increase in IGF-1 may be transient as negative feedback mechanisms may act to return circulating IGF-1 concentrations to baseline during longer supplementation periods. An increase in IGF-1 concentration even following a short supplementation period remains equivocal, however, as IGF-1 levels following 12 days of BC supplementation remained unchanged, as reported by Leppa¨luoto et al.[59] Circulating IGF concentrations are sensitive to energy intake and levels of physical activity,[83] and it is therefore necessary to ensure that energy balance is monitored in future when investigating changes in IGF-1 following BC supplementation. BC supplementation has been associated with an increase in lean body mass,[63,65] increases in strength,[62] increases in vertical jump height and flight times[58,59] and improved peak power Sports Med 2009; 39 (12)
1044
output.[58] However, these findings remain inconsistent across studies, possibly due to differences in training protocols, the training status of subjects, supplementation duration and measures used to assess performance. While there is a significant stimulatory effect of colostrum on bovine epithelial cell lines cultured in vitro, smooth muscle cells do not grow when cultured with colostrum.[84] Increases in lean body mass following BC supplementation that have not been associated with increases in strength may be attributable to an increase in the non-contractile portion of muscle. Fibroblast growth is stimulated by BC[54] and it is possible that increases in lean body mass are the result of increases in collagen; however, this remains speculative. The influence of colostrum supplementation on skeletal muscle growth requires further investigation. 2.2 Endurance Performance
BC supplementation has been shown to improve recovery from repeat bouts of exercise,[61] improve time-trial performance following prolonged submaximal exercise,[60] and maintain exercise performance following a period of highintensity training.[75] The reported increase in circulating IGF-1 following BC supplementation by Mero and colleagues[56] led Buckley and co-workers[61] to investigate the potential benefit of BC on endurance performance. If colostrum supplementation leads to an increase in serum IGF-1 concentration, it is possible that exercise capacity may be enhanced as a result of alterations in substrate utilization and/or cardiac output. IGF-1 has been shown to increase stroke volume and cardiac output in healthy males[85] and elicit a decrease in insulin concentration and an increase in the concentration of free fatty acids, increasing lipolysis.[85,86] To examine this possibility, Buckley and colleagues[61] supplemented 39 male subjects with either colostrum (60 g/day) or a placebo for 8 weeks. Training over the experimental period included three 45-minute running sessions per week. Participants performed two incremental treadmill tests, separated by 20 minutes’ passive recovery, at baseline and following 4 and 8 weeks of supª 2009 Adis Data Information BV. All rights reserved.
Shing et al.
plementation. No significant changes in running performance were observed following 4 weeks of supplementation. However, at 8 weeks, subjects in the colostrum group covered a significantly greater distance and completed more work in the second treadmill test than the placebo group (4.6% increase; p < 0.04). The mechanism for the significant improvement in running performance could not be explained by alterations in respiratory exchange ratio, lactate threshold or IGF-1 concentration and, to date, there has been no reported increase in . maximum oxygen uptake/consumption (VO2max) following BC supplementation despite increases in endurance performance.[60,61] The first study to investigate a dose response of BC on endurance performance was conducted by Coombes and colleagues.[60] Cyclists (n = 42) completed a work-based cycle time-trial (2.8 kJ/kg), following a 2-hour endurance ride, both before and after 8 weeks of supplementation. The study was a double-blind, placebo-controlled trial in which cyclists were assigned to ingest 20 or 60 g/day of BC or a placebo (whey protein powder). Time-trial performance significantly improved in cyclists who were supplemented with colostrum when compared with the placebo group (20 g = decrease of 158 seconds, 60 g = decrease of 134 seconds; both p < 0.05). The similar improvements in performance observed for the two colostrum groups suggest that there may be a limit beyond which a higher BC dose does not provide any added performance benefit.[60] As with the findings of Buckley et al.,[87] performance improvements could not be explained by an increase in IGF-1 concentration. The authors speculated that improved endurance performance may have been the result of enhanced nutrient uptake from the small intestine, mediated by other growth factors found in colostrum. Increases in nutrient uptake and improved gastrointestinal absorption have been associated with colostrum administration in calf studies.[6] BC supplementation in humans has not been associated with increased plasma nutrient concentrations;[33] however, to date the influence of BC on gastrointestinal changes in humans has not been directly measured, possibly because of the invasive nature of the techniques required (i.e. an endoscopy). Sports Med 2009; 39 (12)
Colostrum and Performance
While increases in endurance performance following a period of BC supplementation cannot be explained by an increase in circulating IGF-1, a study has shown maintenance of ventilatory threshold and improved economy during periods of high-intensity training.[75] A 10 g/day dose of BC improved 40 km time-trial performance at the end of a 5-day high-intensity training period but not during normal training when compared with a whey protein placebo.[75] Research has previously found that colostrum feeding in newborn calves increases plasma glucose concentrations and is associated with enhanced activity of the gluconeogenesis rate-limiting enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase.[88] While increased muscle glycogen levels during normal training do not improve 1-hour cycling performance[89] or 45-minute cycling performance (at an average intensity of . 82% VO2max),[90] during repeated days of highintensity exercise enhanced muscle glycogen content may prevent and/or delay fatigue.[91,92] Whether BC improves muscle glycogen resynthesis during periods of intense training warrants investigation. The disparate findings of improved endurance cycling performance by Coombes et al.[60] and an unclear influence of BC supplementation on 40 km time-trial performance during normal training in our recent investigation[75] may be explained by differences in the time-trial protocol used (2.8 kJ/kg [approximately 13 minutes] following a 2-hour submaximal ride and a 40 km time-trial) and fasting state. It is also possible that the smaller dose (10 g) of bovine CPC used in the study by Shing et al.[75] may not have been sufficient to elicit the same improvements in performance during normal training periods.[60] It remains to be determined if a 10 g dose of colostrum improves short duration (approximately 13 minutes) cycle time-trial performance following 2 hours of submaximal endurance performance. BC appears to be beneficial to endurance performance, particularly during periods of intense training or overload that may be associated with fatigue and a reduction in ventilatory threshold. Although Mero and colleagues have reported an increase in serum IGF-1 concentration following ª 2009 Adis Data Information BV. All rights reserved.
1045
BC supplementation,[56,68,80] changes in endurance performance and repeat exercise performance appear to be independent of increases in IGF-1, although to date only two studies have investigated IGF-1 and endurance performance.[60,61] While IGF-1 may increase in response to strength training with BC supplementation,[56,80] increases in serum IGF-1 are yet to be reported in combination with improvements in endurance performance. 2.3 Anaerobic Performance
BC ingestion increases circulating proteins and stimulates skeletal muscle growth in the neonatal calf.[76,93] If colostrum is able to increase muscle fibre size and systemic protein concentrations it may prove beneficial for anaerobic performance. Limited evidence suggesting that colostrum may elicit increases in muscle protein content in humans[63,65] led Brinkworth and colleagues[67] to examine whether colostrum supplementation could enhance the buffering of H+. The main buffers of H+ come from skeletal muscle and include protein, inorganic phosphate and phosphocreatine, while components of blood including haemoglobin, bicarbonate and plasma proteins also buffer H+. Brinkworth and colleagues[67] suggested that the rate of intramuscular acidosis during intense work could potentially be reduced following colostrum supplementation. They examined the influence of BC supplementation on blood buffering capacity in response to a 9-week training programme with 13 elite female rowers; subjects consumed either 60 g of colostrum per day or 60 g of whey protein powder.[67] Two incremental rowing tests (consisting of 4 · 3-minute stages) each separated by 15 minutes were used to assess performance prior to and on completion of the supplementation period; buffering capacity was estimated from differences in blood lactate and blood pH measures taken at the end of each workload during the tests. Analysis found that blood buffering capacity was significantly increased following 9 weeks of BC supplementation (BC = 40.8 – 5.9 slykes [unit of buffer capacity] vs placebo = 33.4 – 5.3 slykes; p < 0.05). Whilst the Sports Med 2009; 39 (12)
Shing et al.
1046
buffer capacity of blood was increased, there were no significant differences in exercise performance between the two groups. Brinkworth and Buckley[71] conducted a further investigation using data collected from the previous study of Brinkworth and colleagues[67] to determine the component of blood buffering capacity that was enhanced following BC supplementation. Results from this study revealed no significant differences in resting haemoglobin concentrations, plasma bicarbonate levels or plasma buffering capacity (all systemic buffers) between colostrum-supplemented and placebo groups. Interestingly, the authors concluded that the observed increase in buffering capacity from their previous work[67] was the result of enhanced muscle buffering capacity. Muscle buffering capacity was unable to be determined as no biopsy samples were collected. As blood buffering capacity was improved in the original investigation, some component of systemic circulation must have changed as a result of BC supplementation as systemic markers were used to calculate blood buffering capacity. It is possible that the increase in blood buffer capacity observed by Brinkworth and colleagues[67] was due to an increase in the ability of haemoglobin to buffer H+ (deoxyhaemoglobin is superior to oxygenated haemoglobin) or an increase in intracellular phosphate. An increase in muscle buffer capacity following BC supplementation is yet to be determined and will require direct measurement of muscle pH and muscle lactate concentrations. In light of the data reported by Brinkworth and colleagues,[67] it is possible that improved buffering capacity may have been responsible for the changes in sprint performance reported by Hofman and colleagues[57] following colostrum supplementation. Elite male (n = 18) and female (n = 17) hockey players were supplemented with either colostrum (at 60 g/day) or placebo for 8 weeks. Repeated sprint running performance (5 · 10 m) significantly improved in the colostrum supplemented group (p < 0.05) compared with the placebo group. Unfortunately, only performance measures were reported in this study so the mechanism behind the improvement in sprint performance remains unclear. ª 2009 Adis Data Information BV. All rights reserved.
In contrast, other authors have shown no improvements in the anaerobic measures of a 30-second Wingate test[69] or a time-to-fatigue test at 110% of ventilatory threshold.[75] At present, data are too limited to support the use of BC supplementation for improvements in anaerobic performance; however, BC may influence recovery suggesting the potential for supplementation to benefit repeat anaerobic performance. 2.4 Immune Function
The importance of BC for the development of the calf immune system has led to the use of BC as a supplement in humans that is purported to enhance immunity. Intense exercise is known to suppress immunity for up to several hours post-exercise[94] and due to the large volumes of high-intensity training that endurance athletes undertake, they are often at a relatively high risk of symptoms of overreaching[95-97] and URTIs.[98] Brinkworth and Buckley[24] recently investigated the relationship between BC supplementation and URTI incidence. Retrospective self-reported data from daily illness log books were collected from studies involving resistance training or endurance training interventions in which subjects ingested BC 60 g/day (n = 93) or a placebo (n = 81) over an 8-week period. Although data from individual studies were not presented, the combined results suggest that the percentage of subjects experiencing URTIs was greater in the placebo group than in the BCsupplemented group (48% and 32%, respectively; p = 0.03), although the duration was not significantly different between groups. While the benefits of BC on reduced URTI symptoms are recognized, to date only four investigations have examined the influence of BC supplementation on immune markers in trained populations.[44,56,74,80] Early work by Mero and colleagues[56] reported that 8 days of supplementation with a BC liquid (25 mL and 125 mL) during normal training did not increase salivary IgA concentration. Subsequent work by the same authors showed that athletes ingesting BC powder for 2 weeks at a dose of 20 g/day experienced a 33% increase in resting salivary IgA concentrations (p < 0.01).[80] While the duration of supplementation was Sports Med 2009; 39 (12)
Colostrum and Performance
longer in the later study, the disparate results could also be explained by the lower concentrations of active growth and immune factors in the BC liquid used in the initial investigation. The liquid BC (125 mL) contained 8.45 mg of IGF-1, 0.048 g of IgG and an undetectable amount of IgA,[56] while the BC powder contained 74 mg of IGF-1, 4.5 g of IgG and 0.3 g of IgA per dose. A significant increase in resting salivary IgA concentration has been shown following 12 weeks of BC supplementation (at 26 g/day) in marathon runners (colostrum group = 101.5 mg/L and placebo group = 58.2 mg/L, p < 0.05).[74] Interestingly, this increase in salivary IgA was not associated with a significant difference in the reported incidence of URTIs between groups. A recent investigation by our group showed no change in salivary IgA concentrations following 8 weeks of supplementation.[44] Differences in colostrum dosage and supplementation duration may be responsible for the disparate findings. Crooks and colleagues[74] supplemented runners with BC at 26 g/day for 12 weeks while Mero and colleagues[80] reported an increase in salivary IgA following only 2 weeks of colostrum supplementation with a 20 g/day dose. Eight weeks of BC supplementation at 10 g/day had no effect on salivary IgA concentration.[44] The potential of colostrum to allow athletes to tolerate higher volumes of (or more intense) training, without the same degree of post-exercise immune suppression was recently investigated by our group. As there is no ideal single marker to measure immune modulation following a nutrition intervention,[99] a number of immune variables and activation markers were chosen to provide an overview of immune function. A 10 g/day dose of BC had no effect on natural killer cell cytotoxicity, lymphocyte or neutrophil surface markers; however, BC supplementation did increase circulating concentrations of the anti-inflammatory cytokine serum soluble TNF receptor 1. While other circulating cytokines did not significantly change, it is possible that local cytokine production was influenced by BC supplementation. The potential for BC to influence cytokine profile is supported by an increase in cytokine production (IFN-g and IL-2) from peripheral blood mononuclear cells in vitro ª 2009 Adis Data Information BV. All rights reserved.
1047
following co-culture with colostrum.[41] BC supplementation also prevented a decrease in postexercise IgG2 and cytotoxic/suppressor T cells following high-intensity training. Reductions in IgG2 and cytotoxic/suppressor T cells have been associated with strenuous exercise.[100-102] While the clinical significance of maintained concentrations remains to be determined, they may offer protection during the ‘open window’ period and contribute to the trend for reduced upper respiratory illness.[41] Cytotoxic/suppressor T cells have been reported to secrete a T helper-1 cytokine profile,[103] which has been associated with the down-regulation of the binding site for rhinovirus.[104] Symptoms that present as URTIs may also actually be associated with an elevation of proinflammatory cytokines,[105] so it is possible that a reduction in URTI symptoms may be independent of increases in salivary IgA concentration. Direct in vitro stimulation of peripheral blood mononuclear cells is associated with the secretion of cytokines associated with cell-mediated immunity. Alterations in cytokine production, in particular the proinflammatory cytokine IL-1b, which is associated with exercise-related fatigue,[106] could potentially influence exercise performance. Lakier Smith[107] proposed a cytokine hypothesis of overtraining in which repeated training without adequate recovery leads to fatigue, decreased mood state, activation of sympathetic nervous system and suppression of HPA-gonadal axis. Changes in cytokine concentrations that may result from BC supplementation have the potential to influence exercise performance and aspects of recovery. 2.5 Gastrointestinal Health and Integrity
Evidence indicates that BC positively influences gastrointestinal integrity,[55] permeability[37,38,60] and inflammation,[55] particularly when taken with NSAIDs. An increase in intestinal permeability may impair exercise performance as a result of translocation of bacterial endotoxin, nausea and diarrhoea.[108] BC may be beneficial during intense exercise that could increase intestinal permeability, particularly in the heat.[42] Gastrointestinal hyperpermeability and endotoxin concentration in Sports Med 2009; 39 (12)
1048
rats following heat stress is reduced with colostrum supplementation.[109] Mechanisms contributing to heat stress include increases in plasma lipopolysaccharide and inflammatory cytokines.[110] To date, only one investigation has reported on the influence of BC on intestinal permeability during exercise. Buckley and colleagues[111] investigated the potential of BC supplementation to reduce exercise-associated increases in intestinal permeability. Subjects ingested colostrum, whey protein (placebo) or nil (control) over an 8-week period of running training; intestinal permeability determined by urinary excretion of lactulose and rhamnose was measured pre-supplementation and on completion of the training period. In contrast to the findings of previous rat studies,[22] the BC and whey protein groups showed a significant increase in intestinal permeability when compared with the control group. Buckley and colleagues[111] speculated that the increase in intestinal permeability resulting from colostrum and whey protein supplementation may stimulate macromolecular transport and uptake of colostrum components. Increased intestinal permeability has been associated with adverse gastrointestinal symptoms and enhanced endotoxin translocation across the gut into circulation.[112] If BC and whey protein do increase intestinal permeability, supplementation may not be advisable for athletes prone to ‘leaky gut’ syndrome. Whether the reported increase in intestinal permeability was associated with increased endotoxin translocation across the gut remains to be determined. It is important to note that this research is only published as an abstract and no performance measures were reported by the authors,[111] limiting the conclusions that may be drawn for this investigation. Nevertheless, BC may be beneficial during exercise in the heat and endotoxaemia-related heat stroke, and to date there is no published research investigating the effect of colostrum on gastrointestinal permeability in humans exercising in the heat. This would be an interesting area of future research. 3. Kinetics and Safety BC ingestion in newborn calves increases plasma IgG, lactoferrin and total protein.[46] While an increase in serum essential amino acids ª 2009 Adis Data Information BV. All rights reserved.
Shing et al.
following BC supplementation has been reported in humans,[73] the pharmacokinetics of BC following ingestion in humans is yet to be determined. The tight junctions in the adult human gut reduce passive absorption and, for many years, it was unclear if and how ingested immunoglobulins could be absorbed in humans or if BC would be degraded in the stomach. Recently, however, the major histocompatability complex class I-related Fc-receptor has been shown to mediate in vitro IgG epithelial transport by trancytosis.[113] This may be a possible mechanism for transport of colostral IgG to mucosal surfaces in humans and there is recent evidence to suggest absorption in humans and animals despite gut closure.[40] Following BC ingestion, immunoglobulins have been shown to withstand digestion in the gut and to be able to exert their effects on the small and large intestine.[114] The integrity of BC after digestion in humans is yet to be extensively researched. It has been suggested that factors contained in BC may aid the absorption of active components by preventing their breakdown and digestion in the gastrointestinal tract.[31] Research is required to determine the absorption of active components into the circulation and to further explore the influence of BC on the gastrointestinal environment, where BC has previously been shown to stimulate gastrointestinalassociated lymphoid tissue.[40] The ingestion of BC is well tolerated and to date there is only one peer-reviewed investigation that has reported slight stomach discomfort associated with BC supplementation.[74] While reports of adverse effects of BC supplementation in humans are limited, those intolerant to cow’s milk proteins, such as casein and whey or lactose (which are present in small concentrations), should avoid BC. No reported toxicological or histopathological abnormalities have been found in rats supplemented with BC at 3% and 10% of total food intake for a period of 3 months,[115] and similarly no adverse reactions have been reported in humans ingesting 26 g/day for 3 months.[74] The long-term (>12 weeks) safety of supplementation in humans is yet to be determined so caution should be taken when ingesting colostrum for prolonged, continuous Sports Med 2009; 39 (12)
Colostrum and Performance
1049
periods. Colostrum sold in Australia and New Zealand must be from local herds or herds from countries considered bovine spongiform encephalopathy-free and must conform to the Therapeutic Goods Administration guidelines. BC is not considered a banned substance despite containing IGF-1, which is banned by the International Olympic Committee under the category of peptide hormones, mimetics and analogues. As BC may have the potential to increase serum IGF-1 following supplementation,[56] athletes taking colostrum run the risk of testing positive for banned substances. To date, only one published investigation has examined the likelihood of this occurring. Kuipers and colleagues[82] supplemented athletes with 60 g/day of colostrum and collected blood prior to and following 4 weeks of supplementation for the analysis of IGF-1 and associated binding protein,
Direct absorption of BC?
IGF binding protein-3. Urine was also collected for routine analysis of banned substances (e.g. peptide hormones, anabolic agents, stimulants) by an accredited International Olympic Committee Laboratory; urine was collected both after an overnight fast and 2 hours following BC ingestion. Analysis of blood samples revealed no significant increase in IGF-1 or its associated binding protein and there were no positive doping tests returned for the athletes (i.e. no banned substances detected) from the International Olympic Committee Laboratory. Whether this finding reflects the lack of bioavailability of IGF1 or whether BC ingestion over an extended period (>4 weeks) would result in a positive doping test is yet to be determined, particularly as improvements in performance are often reported after 8 weeks of supplementation but not after 4 weeks.[58,61]
In vivo
Central nervous system
Blood-brain barrier GHRH
Autonomic nervous system
Hypothalamus
Pituitary
↑ GH
Neuroendocrine system
↑ Sympathetic activity
Liver
MAPK pathway
↓ URTI[24]
Proteasome inhibition Trend towards an ↑ type IIA fibre area[64]
↑ Fat free mass[63,65]
↑ TNFr1 cleaved by TACE ↑ sTNFr1[44]
↑ Explosive power[57,58,59]
↑ Circulating amino acid concentration[73]
Ex vivo BC + PBMC
↑ Salivary IgA[68,74]
↑ Vigour ↓ Fatigue[49] ↑ Endogenous IGF-1[56,68,80]
↑ Parasympathetic activity
↑ IFN-γ, IL-10 and IL-2[41] MAPK pathway Jun NH2− terminal kinase inhibition
Prevents LPSinduced IL-6 release[41]
↑ Strength[62] Fig. 1. Potential pathways of action for reported changes associated with bovine colostrum (BC) supplementation. Dashed circles denote significant changes observed in previous literature. Dashed arrows represent possible interactions. GH = growth hormone; GHRH = gonadotrophin hormone-releasing hormone; IFN = interferon; IGF = insulin-like growth factor; IL = interleukin; LPS = lipopolysaccharide; MAPK = mitogenactivated protein kinase; PBMC = peripheral blood mononuclear cells; sTNFr1 = soluble tumour necrosis factor receptor 1; TACE = tumour necrosis a-converting enzyme; URTI = upper respiratory tract infection; › indicates increase; fl indicates decrease.
ª 2009 Adis Data Information BV. All rights reserved.
Sports Med 2009; 39 (12)
Shing et al.
1050
4. Combined Effects It is more than likely that BC supplementation influences numerous pathways within the human body given the varied components of colostrum. Figure 1 presents significant findings reported in humans following a period of BC supplementation and potential pathways that may be influenced by BC. It is important to note that the influence of BC on these pathways remains speculative; however, the intention is to present potential mechanisms for observed changes following BC supplementation and possible pathways of action to investigate in future work. 5. Conclusions BC contains a range of proteins, immune factors and hormones, which are homologous to the contents of human colostrum. The influence of BC on the growth and development of calves is well understood, but the influence of BC on adult human health is not. Whilst supplementation with BC may be increasing among athletes, in many instances conclusions from studies showing the effect of BC on exercise performance and recovery are equivocal. Data that show improvements in exercise performance and recovery, and changes in immune function during and following supplementation are limited. BC supplementation does not appear to influence body composition during a period of endurance training; however, the data suggest that supplementation is beneficial to exercise performance following consecutive days of high-intensity training (HIT) and to recovery in the days following HIT. Potential mechanisms that researchers have speculated may be responsible for observed improvements in exercise performance and immune surveillance following colostrum supplementation include increases in plasma concentrations of IGF-1,[56] improved intramuscular buffering capacity,[67] increases in lean body mass[63] and increases in salivary IgA concentrations.[74,80] Given that there are contradictory reports regarding the influence of BC on each of these parameters, the changes may be considered modest, but the cumulative effect on a ª 2009 Adis Data Information BV. All rights reserved.
range of parameters may result in improved performance and recovery. Repeated trials, using a well-defined BC product at a standard dosage and length of supplementation, and measuring a wide range of performance and immune parameters, are required to confirm this hypothesis. However, the interpretation of data from such trials will only be relevant once the metabolism and uptake of BC constituents from the gut has been elucidated and researchers are confident of the possible bioactive constituents that may contribute to improved exercise performance. Acknowledgements Cecilia Shing has previously received funding from Numico Research Australia to investigate the influence of colostrum supplementation on exercise performance. Lesley Stevenson was formerly employed by Numico Research Australia. Denise Hunter has no conflicts of interest that are directly relevant to the content of this review. No funding support was received for the preparation of this manuscript. The authors would like to thank Sonya Marshall of Bond University for input into early stage drafts of this manuscript.
References 1. Uruakpa FO, Ismond MAH, Akobundu ENT. Colostrum and its benefits: a review. Nutr Res 2002; 22: 755-67 2. Korhonen H, Marnila P, Gill HS. Milk immunoglobulins and complement factors. Br J Nutr 2000; 84 Suppl. 1: S75-80 3. Hagiwara K, Kataoka S, Yamanaka H, et al. Detection of cytokines in bovine colostrum. Vet Immunol Immunopathol 2000; 76: 183-90 4. Mandalapu P, Pabst HF, Paetkau V. A novel immunosuppressive factor in human colostrum. Cell Immunol 1995; 162: 178-84 5. Ginjala V, Pakkanen R. Determination of transforming growth factor-beta 1 (TGF-beta 1) and insulin-like growth factor (IGF-1) in bovine colostrum samples. J Immunoassay 1998; 19: 195-207 6. Blattler U, Hammon HM, Morel C, et al. Feeding colostrum, its composition and feeding duration variably modify proliferation and morphology of the intestine and digestive enzyme activities of neonatal calves. J Nutr 2001; 131: 1256-63 7. Mach JP, Pahud JJ. Secretory IgA: a major immunoglobulin in most bovine external secretions. J Immunol 1971; 106: 552-63 8. Suga M, Ando M, Tanaka F, et al. Triggering effects of opsonized-IgG antibody on the superoxide release in the phagosome and phagosome-lysosome fusion by pulmonary alveolar macrophages in rabbits. J Clin Lab Immunol 1990; 33: 55-9 9. Togo S, Shimokawa T, Fukuchi Y, et al. Alternative splicing of myeloid IgA Fc receptor (Fc alpha R, CD89)
Sports Med 2009; 39 (12)
Colostrum and Performance
10. 11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
transcripts in inflammatory responses. FEBS Lett 2003; 535: 205-9 Pakkanen R, Aalto J. Growth factors and antimicrobial factors of bovine colostrum. Int Dairy J 1997; 7: 285-97 Francis GL, Upton FM, Ballard FJ, et al. Insulin-like growth factors 1 and 2 in bovine colostrums: sequences and biological activities compared with those of a potent truncated form. Biochem J 1988; 251: 95-103 Fryburg DA, Jahn LA, Hill SA, et al. Insulin and insulinlike growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms. J Clin Invest 1995; 96: 1722-9 Froesch ER, Hussain MA, Schmid C, et al. Insulin-like growth factor I: physiology, metabolic effects and clinical uses. Diabetes Metab Rev 1996; 12: 195-215 Wong WM, Wright NA. Epidermal growth factor, epidermal growth factor receptors, intestinal growth, and adaptation. J Parenter Enteral Nutr 1999; 23 (5 Suppl.): S83-8 Amarant T, Fridkin M, Koch Y. Luteinizing hormonereleasing hormone and thyrotropin-releasing hormone in human and bovine milk. Eur J Biochem 1982; 127: 647-50 Gopal PK, Gill HS. Oligosaccharides and glycoconjugates in bovine milk and colostrum. Br J Nutr 2000; 84 Suppl. 1: S69-74 Ceciliani F, Pocacqua V, Provasi E, et al. Identification of the bovine alpha1-acid glycoprotein in colostrum and milk. Vet Res 2005; 36: 735-46 van Hooijdonk AC, Kussendrager KD, Steijns JM. In vivo antimicrobial and antiviral activity of components in bovine milk and colostrum involved in non-specific defence. Br J Nutr 2000; 84 Suppl. 1: S127-34 Floren CH, Chinenye S, Elfstrand L, et al. ColoPlus, a new product based on bovine colostrum, alleviates HIVassociated diarrhoea. Scand J Gastroenterol 2006; 41: 682-6 Kim JW, Jeon WK, Yun JW, et al. Protective effects of bovine colostrum on non-steroidal anti-inflammatory drug induced intestinal damage in rats. Asia Pac J Clin Nutr 2005; 14: 103-7 Playford RJ, Floyd DN, Macdonald CE, et al. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut 1999; 44: 653-8 Playford RJ, MacDonald CE, Calnan DP, et al. Coadministration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability. Clin Sci (Lond) 2001; 100: 627-33 Patel K, Rana R. Pedimune in recurrent respiratory infection and diarrhea: the Indian experience. The PRIDE study. Indian J Pediatr 2006; 73: 585-91 Brinkworth GD, Buckley JD. Concentrated bovine colostrum protein supplementation reduces the incidence of self-reported symptoms of upper respiratory tract infection in adult males. Eur J Nutr 2003; 42: 228-32 McGuire TC, Pfeiffer NE, Weikel JM, et al. Failure of colostral immunoglobulin transfer in calves dying from infectious disease. J Am Vet Med Assoc 1976; 169: 713-8 Rea DE, Tyler JW, Hancock DD, et al. Prediction of calf mortality by use of tests for passive transfer of colostral immunoglobulin. J Am Vet Med Assoc 1996; 208: 2047-9
ª 2009 Adis Data Information BV. All rights reserved.
1051
27. Brignole TJ, Stott GH. Effect of suckling followed by bottle feeding colostrum on immunoglobulin absorption and calf survival. J Dairy Sci 1980; 63: 451-6 28. Walker-Smith JA, Phillips AD, Walford N, et al. Intravenous epidermal growth factor/urogastrone increases small-intestinal cell proliferation in congenital microvillous atrophy. Lancet 1985; 2: 1239-40 29. Steeb CB, Shoubridge CA, Tivey DR, et al. Systemic infusion of IGF-I or LR(3)IGF-I stimulates visceral organ growth and proliferation of gut tissues in suckling rats. Am J Physiol 1997; 272: G522-33 30. Khan Z, Macdonald C, Wicks AC, et al. Use of the ‘nutriceutical’, bovine colostrum, for the treatment of distal colitis: results from an initial study. Aliment Pharmacol Ther 2002; 16: 1917-22 31. Playford RJ, Woodman AC, Clark P, et al. Effect of luminal growth factor preservation on intestinal growth. Lancet 1993; 341: 843-8 32. Kim JW, Jeon WK, Kim EJ. Combined effects of bovine colostrum and glutamine in diclofenac-induced bacterial translocation in rat. Clin Nutr 2005; 24: 785-93 33. Brinkworth GD, Buckley JD. Bovine colostrum supplementation does not affect nutrient absorptive capacity in healthy young men. Nutr Res 2003; 23: 1619-29 34. Salmon H. The mammary gland and neonate mucosal immunity. Vet Immunol Immunopathol 1999; 72: 143-55 35. Quigley JD, Strohbehn RE, Kost CJ, et al. Formulation of colostrum supplements, colostrum replacers and acquisition of passive immunity in neonatal calves. J Dairy Sci 2001; 84: 2059-65 36. Stott GH, Marx DB, Menefee BE, et al. Colostral immunoglobulin transfer in calves: I. Period of absorption. J Dairy Sci 1979; 62: 1632-8 37. Ontsouka CE, Sauter SN, Blum JW, et al. Effects of colostrum feeding and dexamethasone treatment on mRNA levels of insulin-like growth factors (IGF)-I and -II, IGF binding proteins-2 and -3, and on receptors for growth hormone, IGF-I, IGF-II, and insulin in the gastrointestinal tract of neonatal calves. Domest Anim Endocrinol 2004; 26: 155-75 38. Yamanaka H, Hagiwara K, Kirisawa R, et al. Proinflammatory cytokines in bovine colostrum potentiate the mitogenic response of peripheral blood mononuclear cells from newborn calves through IL-2 and CD25 expression. Microbiol Immunol 2003; 47: 461-8 39. Elfstrand L, Lindmark-Mansson H, Oaulsson M, et al. Immunoglobulins, growth factors and growth hormone in bovine colostrum and the effects of processing. Int Dairy J 2002; 12: 879-87 40. Boudry C, Buldgena A, Portetelleb D, et al. Effect of bovine colostrum supplementation on cytokine mRNA expression in weaned piglets. Livestock Sci 2007; 108: 295-8 41. Shing CM, Peake J, Suzuki K, et al. Bovine colostrum modulates cytokine production in human peripheral blood mononuclear cells stimulated with lipopolysaccharide and phytohemagglutinin. J Int Cyt Res 2007; 27: 835-9 42. Jeukendrup AE, Vet-Joop K, Sturk A, et al. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and
Sports Med 2009; 39 (12)
Shing et al.
1052
43.
44.
45.
46.
47.
48.
49.
50.
51.
52. 53. 54.
55.
56.
57.
58.
59.
after a long-distance triathlon in highly trained men. Clin Sci (Lond) 2000; 98: 47-55 Gleeson M. Mucosal immune responses and risk of respiratory illness in elite athletes. Exerc Immunol Rev 2000; 6: 5-42 Shing CM, Peake J, Suzuki K, et al. Effects of bovine colostrum supplementation on immune variables in highly trained cyclists. J Appl Physiol 2007; 102: 1113-22 Talukder MJ, Takeuchi T, Harada E. Receptor-mediated transport of lactoferrin into the cerebrospinal fluid via plasma in young calves. J Vet Med Sci 2003; 65: 957-64 Talukder MJ, Takeuchi T, Harada E. Transport of colostral macromolecules into the cerebrospinal fluid via plasma in newborn calves. J Dairy Sci 2002; 85: 514-24 Watkins LR, Maier SF. The pain of being sick: implications of immune-to-brain communication for understanding pain. Annu Rev Psychol 2000; 51: 29-57 Maso F, Lac G, Filaire E, et al. Salivary testosterone and cortisol in rugby players: correlation with psychological overtraining items. Br J Sports Med 2004; 38: 260-3 Marshall-Gradisnik SM, Sample R, O’Leary L, et al. Improvements in health and psychological indicators in healthy males after eight-week bovine colostrum powder supplementation [abstract]. Aust J Dairy Technol 2003; 58: 197 Filaire E, Legrand B, Lac G, et al. Training of elite cyclists: effects on mood state and selected hormonal responses. J Sports Sci 2004; 22: 1025-33 Odland L, Wallin S, Walum E. Lipid peroxidation and activities of tyrosine aminotransferase and glutamine synthetase in hepatoma and glioma cells grown in bovine colostrum-supplemented medium. In Vitro Cell Dev Biol 1986; 22: 259-62 Przybylska J, Albera E, Kankofer M. Antioxidants in bovine colostrum. Reprod Domest Anim 2007; 42: 402-9 Korhonen BH. Antimicrobial factors in bovine colsotrum. J Sci Agric Soc Finland 1977; 49: 434-47 Torre C, Jeusette I, Serra M, et al. Bovine colostrum increases proliferation of canine skin fibroblasts. J Nutr 2006; 136: 2058S-60 Sporn MB, Roberts AB, Shull JH, et al. Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science 1983; 219: 1329-31 Mero A, Miikkulainen H, Riski J, et al. Effects of bovine colostrum supplementation on serum IGF-I, IgG, hormone, and saliva IgA during training. J Appl Physiol 1997; 83: 1144-51 Hofman Z, Smeets R, Verlaan G, et al. The effect of bovine colostrum supplementation on exercise performance in elite field hockey players. Int J Sport Nutr Exerc Metab 2002; 12: 461-9 Buckley JD, Brinkworth GD, Abbott MJ. Effect of bovine colostrum on anaerobic exercise performance and plasma insulin-like growth factor I. J Sports Sci 2003; 21: 577-88 Leppa¨luoto J, Rasi S, Martikkala V, et al. Bovine colostrum supplementation enhances physical performance on maximal exercise tests. 2000 Pre-Olympic Congress Sports Medicine and Physical Education International Congress on Sport Science; 2000 Sep 7-13: Brisbane (QLD)
ª 2009 Adis Data Information BV. All rights reserved.
60. Coombes JS, Conacher M, Austen SK, et al. Dose effects of oral bovine colostrum on physical work capacity in cyclists. Med Sci Sports Exerc 2002; 34: 1184-8 61. Buckley JD, Abbott MJ, Brinkworth GD, et al. Bovine colostrum supplementation during endurance running training improves recovery, but not performance. J Sci Med Sport 2002; 5: 65-79 62. Kerksick C, Kreider R, Rasmussen C, et al. Effects of bovine colostrum supplementation on training adaptations II: performance [abstract]. FASEB J 2001; 15: LB315 63. Antonio J, Sanders MS, Van Gammeren D. The effects of bovine colostrum supplementation on body composition and exercise performance in active men and women. Nutrition 2001; 17: 243-7 64. Fry A, Schilling B, Chiu L, et al. Muscle fibre and performance adaptations to resistance exercise with MyoVive, colostrum or casein and whey supplementation. Res Sports Med 2003; 11: 109-27 65. Kreider R, Rasmussen C, Kerksick C, et al. Effects of bovine colostrum supplementation on training adaptations: I. Body composition [abstract]. FASEB J 2001; 15: LB316 66. Hoffman JR, Kang J, Ratamess NA, et al. Biochemical and hormonal responses during an intercollegiate football season. Med Sci Sports Exerc 2005; 37: 1237-41 67. Brinkworth GD, Buckley JD, Bourdon PC, et al. Oral bovine colostrum supplementation enhances buffer capacity but not rowing performance in elite female rowers. Int J Sport Nutr Exerc Metab 2002; 12: 349-65 68. Mero A, Nyka¨nen T, Rasi S, et al. IGF-1, IGFBP-3, growth hormone and testosterone in male and female athletes during bovine colostrum supplementation [abstract]. Med Sci Sports Exerc 2002; 35: s299 69. O’Leary L. Assessment of anaerobic performance in healthy males after an eight week concentrated bovine colostrum supplementation. Australian Conference of Science and Medicine in Sport; 2003 Oct 25-28: Canberra (ACT) 70. Brinkworth GD, Buckley JD, Slavotinek JP, et al. Effect of bovine colostrum supplementation on the composition of resistance trained and untrained limbs in healthy young men. Eur J Appl Physiol 2004; 91 (1): 53-60 71. Brinkworth GD, Buckley JD. Bovine colostrum supplementation does not affect plasma buffer capacity or haemoglobin content in elite female rowers. Eur J Appl Physiol 2004; 91: 353-6 72. Sample R, O’Leary L, Myers S, et al. Bovine colostrum supplementation and its effect on muscle histology, strength, performance and body composition in the elderly [abstract]. J Sci Med Sport 2004; 7: S16 73. Mero A, Nykanen T, Keinanen O, et al. Protein metabolism and strength performance after bovine colostrum supplementation. Amino Acids 2005; 28: 327-35 74. Crooks C, Wall C, Cross M, et al. The effect of bovine colostrum supplementation on salivary IgA in distance runners. Int J Sport Nutr Exerc Metab 2006; 16: 47-64 75. Shing CM, Jenkins DG, Stevenson L, et al. The influence of bovine colostrum supplementation on exercise performance in highly-trained cyclists. Br J Sports Med 2006; 40: 797-801 76. Kuhne S, Hammon HM, Bruckmaier RM, et al. Growth performance, metabolic and endocrine traits, and absorptive
Sports Med 2009; 39 (12)
Colostrum and Performance
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
90.
91.
92.
capacity in neonatal calves fed either colostrum or milk replacer at two levels. J Anim Sci 2000; 78: 609-20 Hammon H, Blum JW. The somatotropic axis in neonatal calves can be modulated by nutrition, growth hormone, and Long-R3-IGF-I. Am J Physiol 1997; 273: E130-8 Sacheck JM, Ohtsuka A, McLary SC, et al. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab 2004; 287: E591-601 Malisoux L, Francaux M, Nielens H, et al. Calcium sensitivity of human single muscle fibers following plyometric training. Med Sci Sports Exerc 2006; 38: 1901-8 Mero A, Kahkonen J, Nykanen T, et al. IGF-I, IgA, and IgG responses to bovine colostrum supplementation during training. J Appl Physiol 2002; 93: 732-9 Kimura T, Murakawa Y, Ohno M, et al. Gastrointestinal absorption of recombinant human insulin-like growth factor-1 in rats. J Pharmacol Exp Ther 1997; 283: 611-8 Kuipers H, van Breda E, Verlaan G, et al. Effects of oral bovine colostrum supplementation on serum insulin-like growth factor-I levels. Nutrition 2002; 18: 566-7 Nemet D, Pontello AM, Rose-Gottron C, et al. Cytokines and growth factors during and after a wrestling season in adolescent boys. Med Sci Sports Exerc 2004; 36: 794-800 Steimer KS, Packard R, Holden D, et al. The serum-free growth of cultured cells in bovine colostrum and in milk obtained later in the lactation period. J Cell Physiol 1981; 109: 223-34 Donath MY, Jenni R, Brunner HP, et al. Cardiovascular and metabolic effects of insulin-like growth factor I at rest and during exercise in humans. J Clin Endocrinol Metab 1996; 81: 4089-94 Hussain MA, Schmitz O, Mengel A, et al. Comparison of the effects of growth hormone and insulin-like growth factor I on substrate oxidation and on insulin sensitivity in growth hormone-deficient humans. J Clin Invest 1994; 94: 1126-33 Buckley J, Abbott M, Martin S, et al. Effects of an oral bovine colostrum supplement (intact TM) on running performance. Australian Conference of Science and Medicine in Sport; 1998 Oct 13-16; Adelaide (SA) Hammon HM, Sauter SN, Reist M, et al. Dexamethasone and colostrum feeding affect hepatic gluconeogenic enzymes differently in neonatal calves. J Anim Sci 2003; 81: 3095-106 Hawley JA, Palmer GS, Noakes TD. Effects of 3 days of carbohydrate supplementation on muscle glycogen content and utilisation during a 1-h cycling performance. Eur J Appl Physiol Occup Physiol 1997; 75: 407-12 Kavouras SA, Troup JP, Berning JR. The influence of low versus high carbohydrate diet on a 45-min strenuous cycling exercise. Int J Sport Nutr Exerc Metab 2004; 14: 62-72 McInerney P, Lessard SJ, Burke LM, et al. Failure to repeatedly supercompensate muscle glycogen stores in highly trained men. Med Sci Sports Exerc 2005; 37: 404-11 Karlsson J, Saltin B. Diet, muscle glycogen, and endurance performance. J Appl Physiol 1971; 31: 203-6
ª 2009 Adis Data Information BV. All rights reserved.
1053
93. Rauprich AB, Hammon HM, Blum JW. Influence of feeding different amounts of first colostrum on metabolic, endocrine, and health status and on growth performance in neonatal calves. J Anim Sci 2000; 78: 896-908 94. Nieman DC. Is infection risk linked to exercise workload? Med Sci Sports Exerc 2000; 32: S406-11 95. Atlaoui D, Duclos M, Gouarne C, et al. The 24-h urinary cortisol/cortisone ratio for monitoring training in elite swimmers. Med Sci Sports Exerc 2004; 36: 218-24 96. Halson SL, Bridge MW, Meeusen R, et al. Time course of performance changes and fatigue markers during intensified training in trained cyclists. J Appl Physiol 2002; 93: 947-56 97. Halson SL, Lancaster GI, Jeukendrup AE, et al. Immunological responses to overreaching in cyclists. Med Sci Sports Exerc 2003; 35: 854-61 98. Fitzgerald L. Overtraining increases the susceptibility to infection. Int J Sports Med 1991; 12 Suppl. 1: S5-8 99. Gleeson M. Assessing immune function changes in exercise and diet intervention studies. Curr Opin Clin Nutr Metab Care 2005; 8: 511-5 100. McKune AJ, Smith LL, Semple SJ, et al. Immunoglobulin responses to a repeated bout of downhill running. Br J Sports Med 2006 Oct; 40: 844-9 101. McKune AJ, Smith LL, Semple SJ, et al. Influence of ultraendurance exercise on immunoglobulin isotypes and subclasses. Br J Sports Med 2005; 39: 665-70 102. McKune AJ, Smith LL, Semple SJ, et al. Changes in mucosal and humoral atopic-related markers and immunoglobulins in elite cyclists participating in the Vuelta a Espana. Int J Sports Med 2006; 27: 560-6 103. Biron CA. Cytokines in the generation of immune responses to, and resolution of, virus infection. Curr Opin Immunol 1994; 6: 530-8 104. Sethi SK, Bianco A, Allen JT, et al. Interferon-gamma (IFN-gamma) down-regulates the rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) on human airway epithelial cells. Clin Exp Immunol 1997; 110: 362-9 105. Bachert C, van Kempen MJ, Hopken K, et al. Elevated levels of myeloperoxidase, pro-inflammatory cytokines and chemokines in naturally acquired upper respiratory tract infections. Eur Arch Otorhinolaryngol 2001; 258: 406-12 106. Carmichael MD, Davis JM, Murphy EA, et al. Role of brain IL-beta on fatigue following exercise-induced muscle damage. Am J Physiol Regul Integr Comp Physiol 2006; 291 (5): R1344-8 107. Lakier Smith L. Overtraining, excessive exercise, and altered immunity: is this a T helper-1 versus T helper-2 lymphocyte response? Sports Med 2003; 33: 347-64 108. Lambert GP, Broussard LJ, Mason BL, et al. Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages. J Appl Physiol 2001; 90: 2075-80 109. Prosser C, Stelwagen K, Cummins R, et al. Reduction in heat-induced gastrointestinal hyperpermeability in rats by bovine colostrum and goat milk powders. J Appl Physiol 2004; 96: 650-4 110. Lim CL, Wilson G, Brown L, et al. Pre-existing inflammatory state compromises heat tolerance in rats exposed
Sports Med 2009; 39 (12)
1054
to heat stress. Am J Physiol Regul Integr Comp Physiol 2007; 292: R186-94 111. Buckley JD, Brinkworth GD, Southcott E, et al. Bovine colostrum and whey protein supplementation during running training increase intestinal permeability [abstract]. Asia Pac J Clin Nutr 2004; 13: S81 112. Caradonna L, Amati L, Magrone T, et al. Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J Endotoxin Res 2000; 6: 205-14 113. Spiekermann GM, Finn PW, Ward ES, et al. Receptormediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung. J Exp Med 2002; 196: 303-10
ª 2009 Adis Data Information BV. All rights reserved.
Shing et al.
114. Roos N, Mahe S, Benamouzig R, et al. 15N-labeled immunoglobulins from bovine colostrum are partially resistant to digestion in human intestine. J Nutr 1995; 125: 1238-44 115. Davis PF, Greenhill NS, Rowan AM, et al. The safety of New Zealand bovine colostrum: nutritional and physiological evaluation in rats. Food Chem Toxicol 2007; 45: 229-36
Correspondence: Dr Cecilia M. Shing, School of Human Life Sciences, Locked Bag 1320, University of Tasmania, Launceston, TAS 7250, Australia. E-mail:
[email protected]
Sports Med 2009; 39 (12)
RESEARCH REVIEW
Sports Med 2009; 39 (12): 1055-1069 0112-1642/09/0012-1055/$49.95/0
ª 2009 Adis Data Information BV. All rights reserved.
Oligomenorrhoea in Exercising Women A Polycystic Ovarian Syndrome Phenotype or Distinct Entity? Susan Awdishu,1 Nancy I. Williams,2 Sheila E. Laredo3 and Mary Jane De Souza2 1 Women’s Exercise and Bone Health Laboratory, Graduate Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada 2 Women’s Health and Exercise Laboratory, Department of Kinesiology, Penn State University, University Park, Pennsylvania, USA 3 Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada
Abstract
To date, the predominant mechanism underlying menstrual disturbances in exercising women supports an underlying energy deficiency-related aetiology, in which a failure to compensate dietary intake for the energy cost of exercise suppresses reproductive function. Increasing evidence demonstrates that energy deficiency plays a causal role in the induction of amenorrhoea in exercising women, and consistent with this mechanism are findings of glucoregulatory perturbations such as low triiodothyronine, reduced insulin secretion and elevated cortisol, growth hormone and ghrelin levels. The menstrual disturbance that may differ in its energetic characteristics and, perhaps in its androgenic and ovarian steroid environment, is oligomenorrhoea. We conducted a systematic review of the literature to begin to understand whether oligomenorrhoea in exercising women is a mild subclinical phenotype of polycystic ovarian syndrome (PCOS) in which exercise is conferring beneficial effects in protecting women from the classic PCOS phenotype, or whether oligomenorrhoea is part of the spectrum of menstrual disturbances caused by an energy deficiency that is often reported in exercising women with menstrual disturbances. We included observational, randomized controlled trials and cross-sectional studies that reported clinical, hormonal and metabolic profiles in exercising women with amenorrhoea or oligomenorrhoea and in women with PCOS. Previous studies examining the underlying mechanisms and consequences of exercise-associated menstrual disturbances have grouped exercising amenorrhoeic and oligomenorrhoeic women into a single group, and have relied primarily on self-reported menstrual history. Although scarce, the data available to date suggest that hyperandrogenism, such as that observed in PCOS, may likely be associated with oligomenorrhoea in exercising women, and may not always represent hypothalamic inhibition secondary to an energy deficiency. It is critical to closely examine the metabolic and endocrine status of women with menstrual disturbances because the treatment strategies for energy deficiency-related menstrual disturbances differ from that of disturbances traceable to hyperandrogenaemia. Further investigation is necessary to explore whether different endocrine aetiologies underly menstrual disturbances, particularly oligomenorrhoea, in physically active women.
1056
Ovulatory cyclic reproductive function involves the successful recruitment and development of ovarian follicles, oocyte maturation and ovulation, and formation of a corpus luteum, which contributes to the necessary secretory changes of the endometrium should fertilization occur.[1-3] Precise signals that inhibit or stimulate the hypothalamus regulate these repetitive cycles.[1-3] Classic experiments by Knobil[1-3] demonstrate the key components of this neuroendocrine system, specifically the modulating effects of ovarian steroids on gonadotropin hormones and the requirement for pulsatile secretion of gonadotropin-releasing hormone into the pituitary portal system. A disruption of the hypothalamic-pituitary-gonadal axis can lead to a spectrum of menstrual cycle perturbations ranging from subtle (i.e. luteal phase defects) to more severe menstrual disturbances (i.e. amenorrhoea).[4] The spectrum of menstrual disturbances observed in exercising women is depicted in figure 1. In exercising women, the prevalence of menstrual disturbances is high, with anovulatory and luteal phase defects being the most common abnormality associated with physical activity and exercise.[5] A higher prevalence of menstrual disturbances has been observed in specific sports in which thinness offers a competitive advantage, such as gymnastics and cross-country running.[6,7] At the extreme end of the spectrum is amenorrhoea, defined as no menses for 3 or more consecutive months, which is associated with chronic estrogen deficiency and clinical sequelae such as decreased bone mineral density.[4] Reports of the prevalence of amenorrhoea in athletes range from 1% to 66%.[8-11] Oligomenorrhoea is defined by irregular and inconsistent menstrual cycles of 36–90 days in length,[4,11] and to date there are no definitive prevalence data available for oligomenorrhoea in exercising women. However, as we suggest in this review, the prevalence of oligomenorrhoea in exercising women may be confounded by the presentation of various phenotypes of polycystic ovarian syndrome (PCOS) in athletic women. Moreover, since oligomenorrhoea is difficult to study owing to the inherent irregularity of the cycles, investigators have often grouped this menstrual disturbance with ameª 2009 Adis Data Information BV. All rights reserved.
Awdishu et al.
norrhoea, presuming that these two conditions in the exercise environment are similar. A large body of evidence suggests that the mechanism responsible for menstrual disturbances in exercising women is consistent with an underlying energy deficiency.[12-17] Indeed, it is well documented that in exercising women, the failure to compensate dietary intake for the energy cost of exercise can have a profound suppressive effect on the reproductive axis.[12,14] Reproduction is a physiologically costly process that requires significant energy. When energy is scarce, metabolic fuel is repartitioned away from long-term processes such as growth, immune function and reproduction to processes necessary for immediate survival. The availability of oxidizable metabolic fuel (i.e. glucose, free fatty acids, ketones) has been shown in animal models to represent an important modulator of reproductive function.[18] Thus far, the specific mechanism whereby the energy status of the body is transmitted to the hypothalamus is unknown, although experiments in rodents, non-human primates and in humans have yielded results supporting the importance of numerous metabolic signals.[18,19] Increasing evidence demonstrates that energy deficiency plays a causal role in the induction of exercise-associated menstrual disturbances.[13,14] Consistent with an energy deficiency-related aetiology, metabolic alterations such as low triiodothyronine (TT3), insulin and leptin, and elevated cortisol, growth hormone and ghrelin levels have been observed in amenorrhoeic exercising women.[4,17,20,21] Of interest, many of the metabolic adjustments to energy deficiency reportedly vary in magnitude with the severity of menstrual perturbation observed.[15,22] Although irregular cycles of extended length, i.e. oligomenorrhoea, is a condition commonly included in the spectrum of perturbations of the menstrual cycle associated with exercise, some investigators have suggested that the reproductive and metabolic hormonal profiles of women displaying oligomenorrhoea is not consistent with that of other exercise-related menstrual abnormalities.[23] Specifically, it is proposed that essential hyperandrogenism is, more often than not, the primary mechanism underlying oligomenorrhoea in exercising women.[23] Sports Med 2009; 39 (12)
25
30
0
5
0
5
E1G (ng/mL)
0.35 0.30 0.25 0.20 0.15 0.10 0.05 0
10 15 20 25 30 35 Day of cycle
200 180 160 140 120 100 80 60 40 20 0
20 18 16 14 12 10 8 6 4 2 0 0
5
10 15 20 Day of cycle
LPD Ovulatory
25
PdG (ug/mL)
30
E1G ng/mL PdG ug/mL
LH (m/u/mL)
20 18 16 14 12 10 8 6 4 2 0
200 180 160 140 120 100 80 60 40 20 0
PdG (ng/mL)
E1G (ng/mL)
R003-1 Day vs R003-1 E1G ng/mL R003-1 Day vs R003-1 PdG ug/mL R003-1 Day vs R003-1 LH m/u/mL
10 15 20 Day of cycle
25
E1G ng/mL PdG ug/mL 200 180 160 140 120 100 80 60 40 20 0
30
20 18 16 14 12 10 8 6 4 2 0 0
5
10 15 20 Day of cycle
25
PdG (ng/mL)
10 15 20 Day of cycle
E1G (ng/mL)
5
20 18 16 14 12 10 8 6 4 2 0
200 180 160 140 120 100 80 60 40 20 0
PdG (ng/mL)
0
PdG (ug/mL)
20 18 16 14 12 10 8 6 4 2 0
Day vs E1G ng/mL Day vs PdG ug/mL
E1G (ng/mL)
E1G (ng/mL)
200 180 160 140 120 100 80 60 40 20 0
Oligomenorrhoea in Exercising Women
ª 2009 Adis Data Information BV. All rights reserved.
E1G ng/mL PdG ug/mL
30
Oligomenorrhoiec
Anovulatory
Amenorrhoiec
Fig. 1. Spectrum of reproductive disturbances, ranging from ovulatory cycles, subtle presentations of luteal phase deficiency (LPD) and anovulatory cycles to the most severe menstrual disturbance, amenorrhoea. Data shown are depicted by daily estrone glucuronide (E1G), pregnanediol glucuronide (PdG) and luteinizing hormone (LH) concentrations.
1057
Sports Med 2009; 39 (12)
1058
Hyperandrogenism, defined as elevated serum androgen levels and/or the clinical expression of the biological action of hyperandrogenism (i.e. hirsutism), is the most widely accepted principal feature of PCOS.[24,25] Affecting nearly 6–8% of the population,[26] PCOS is the most common endocrine disorder among women of reproductive age.[26,27] Currently, two primary sets of criteria for PCOS are in widespread use,[25,28] and are shown in table I. The first definition of PCOS was established by an expert panel convened by the National Institutes of Health (NIH) in 1990. The following major criteria were established for the NIH definition of PCOS in this order of importance: (i) hyperandrogenaemia or clinical evidence of hyperandrogenism; (ii) oligo-ovulation and (iii) exclusion of other commonly related disorders.[25] The second definition arose from an expert conference in Rotterdam sponsored by the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine in 2003 referred to as the Rotterdam Criteria.[28] These criteria established that PCOS was apparent when at least two of the following features were present: (i) oligo- or anovulation, (ii) clinical and/or biochemical hyperandrogenaemia and (iii) polycystic ovaries on ultrasound with the exclusion of other commonly related disorders.[28] In a recent systematic review of literature to identify different phenotypes of Table I. Current definitions of polycystic ovarian syndrome arising from two expert conference proceedings sponsored by the National Institute of Child Health and Human Disease of the US National Institutes of Health (NIH) and the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) Criteria NIH Hyperandrogenism and/or hyperandrogenaemia Oligo-anovulation Exclusion of other known disorders ESHRE/ASRM Oligo- and/or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries Exclusion of other known disorders
ª 2009 Adis Data Information BV. All rights reserved.
Awdishu et al.
PCOS,[24] the Androgen Excess Society (AES) Task Force concluded that PCOS is primarily a disorder of androgen excess. While it is recognized that there are subclinical phenotypes of PCOS without overt hyperandrogenism present, validation of these phenotypes is required. Considering the features of PCOS, including ovulatory dysfunction, hyperandrogenaemia, hirsutism and polycystic ovaries, the AES Task Force identified nine phenotypes that could be considered PCOS, and are shown in table II.[24] Whereas it has recently been proposed that PCOS is a disorder of androgen excess or hyperandrogenism,[24] oligomenorrhoea in exercising women has generally been considered a component of a spectrum of menstrual disturbances (see figure 1) in exercising women with characteristic metabolic perturbations secondary to an energy deficit.[29] Given the potential for oligomenorrhoea to be associated with hyperandrogenism, it may be that exercising women with oligomenorrhoea do not present with the typical energy deficiencyrelated aetiology of menstrual disturbances classically observed in exercising women. This misclassification has led to the acceptance that oligomenorrhoea in exercising women is due to an energy deficiency-related aetiology. Consequently, treatment has been aimed at correcting an energy deficiency by increasing energy intake and/or decreasing energy expenditure. Given the higher prevalence of oligomenorrhoea in certain sports where muscle mass offers a competitive advantage, it may be that elevated androgenic profiles observed in oligomenorrhoeic women are an inherited or PCOS-related trait rather than an exercise-induced trait. As such, it would be surmised that some women with PCOS may naturally self-select into the athletic environment.[7] This possibility warrants further research as the treatment for energy deficiency differs from that of PCOS in that it likely involves increased energy intake. This paper will review existing literature to address the similarities and differences between oligomenorrhoea induced in association with exercise and that associated with PCOS. Specifically, it will address whether oligomenorrhoea in exercising women may be more consistent with a clinical Sports Med 2009; 39 (12)
Oligomenorrhoea in Exercising Women
1059
Table II. Polycystic ovarian syndrome phenotypes based on the presence or absence of hyperandrogenism, hirsutism, oligo-anovulation and polycystic ovaries according to the Androgen Excess Society (AES) 2006 position statement Feature
Phenotype A
B
C
D
E
F
G
H
I
J
Hyperandrogenaemia
+
+
+
+
-
-
+
-
+
-
Hirsutism
+
+
-
-
+
+
+
+
-
-
Oligo-anovulation
+
+
+
+
+
+
-
-
-
+
Polycystic ovaries
+
-
+
-
+
-
+
+
+
+
AES 2006 criteria
+
+
+
+
+
+
+
+
+
+
- indicates absence; + indicates presence.
or subclinical phenotype of PCOS[30] or whether oligomenorrhoea is indeed part of the spectrum of energy deficiency-related menstrual disturbances classically observed in exercising women. 1. Methods An electronic search of the computerized database PubMed was performed for the period 1970–2008 using the search terms: oligomenorrhoea, functional hypothalamic amenorrhoea, athletic amenorrhoea, polycystic ovary syndrome, androgens, menstrual disturbance, hirsutism, energy deficiency and undernutrition. We included all published studies of randomized controlled trials, observational and prospective studies, and cross-sectional studies that assessed oligomenorrhoea in both exercising and non-exercising women. Because the definition of oligomenorrhoea, i.e. menstrual cycles that are irregular and lengthened (36–90 days), displays overlap with a definition of amenorrhoea that is used commonly, i.e. absence of menses for 90 days, we included amenorrhoea in our discussions of the hormonal characteristics of oligomenorrhoea. We excluded studies not published in English. 2. Results 2.1 Reproductive Profiles: Exercising Amenorrhoeic and Oligomenorrhoeic Women
Exercise-associated amenorrhoea has been classified as hypothalamic amenorrhoea as luteinizing hormone (LH) pulsatility is suppressed and a prepubertal pattern of release is typically ª 2009 Adis Data Information BV. All rights reserved.
exhibited.[4,16,22,31] Because many investigators have not incorporated sampling periods long enough to capture oligomenorrhoeic cycles, scarce data exist that examines or characterizes the reproductive hormonal profiles of this group. For the most part, investigators often group exercising amenorrhoeic and oligomenorrhoeic women into a single group, and have relied primarily on self-reported menstrual history.[32-35] More recently, Rickenlund and colleagues[36] confirmed that LH pulsatility was decreased in amenorrhoeic athletes, and identified that the suppression of LH pulsatility was not apparent in separately grouped oligomenorrhoeic athletes. The latter group of athletes displayed an average of five menstrual cycles in the last year. Participants were amenorrhoeic if they failed to menstruate for the last 3 months, oligomenorrhoeic if menses occurred at intervals exceeding 6 weeks and not more than nine times in the last year, and regular menstruating if menses occurred within an interval of 22–34 days. Thus, the oligomenorrhoeic athletes did not demonstrate a LH pulsatility pattern characteristic of functional hypothalamic amenorrhoea, as previously described in amenorrhoeic athletes.[20] Data also suggestive of a unique hypothalamic-pituitary status in oligomenorrhoeic athletes have been published by Constantini and Warren.[7] They observed a significantly increased serum LH and follicle-stimulating hormone (FSH), and an elevated LH : FSH ratio in swimmers with oligomenorrhoea, where oligomenorrhoea was defined as two consecutive menstrual cycles shorter than 21 days or longer than 45 days.[7] Taken together, these studies suggest that oligomenorrhoeic exercising women Sports Med 2009; 39 (12)
1060
do not demonstrate suppressed levels of gonadotropins, evidence that perhaps these athletes are distinct from amenorrhoeic athletes with hypothalamic dysfunction. Although studies in amenorrhoeic exercising women have confirmed that, in addition to suppression of LH and FSH, ovarian steroid secretion is compromised,[31,37] no data have been published that describe the ovarian steroid profiles of oligomenorrhoeic exercising women. To date, there are no profiles in the literature of the specific daily ovarian steroid excretion of oligomenorrhoeic cycles in exercising women. We have recently monitored the menstrual cycles of exercising women with oligomenorrhoeic cycles, where oligomenorrhoea was defined as menstrual intervals of 36–90 days. We examined the ovarian steroid profiles in nine oligomenorrhoeic women by assessing daily urinary concentrations of estrone-1-glucuronide and pregnanediol glucuronide over one or two entire cycles. We assessed the presence or absence of ovulation using previously published methods of analysing urinary hormone profiles,[38] and we calculated follicular and luteal phase lengths. We observed that approximately half of the cycles evaluated were ovulatory.[38] Herein, we present two characteristic examples of oligomenorrhoeic cycles in exercising women in figures 2a and 2b. 2.2 Reproductive Profiles: Women with Polycystic Ovarian Syndrome (PCOS)
Numerous investigators have reported that women with PCOS have elevated levels of LH with suppressed FSH levels and an elevated LH : FSH ratio (LH : FSH >2),[39-41] which is in sharp contrast to that observed in women with functional hypothalamic amenorrhoea (LH : FSH <2).[42] Inadequate FSH secretion results in impaired follicular development whereas elevated LH levels enhance ovarian androgen production.[43] In a study by Taylor and colleagues,[40] 75% of anovulatory PCOS women had elevated pooled serum LH levels and 94% had an elevated LH : FSH ratio. Women with PCOS also have increased LH pulse frequency, in the order of one pulse per ª 2009 Adis Data Information BV. All rights reserved.
Awdishu et al.
hour, without the normal cyclic pattern observed in ovulatory women.[44] Typically, cyclic increases in progesterone result in slowing of LH pulsatility in ovulatory women during the luteal phase.[45] As PCOS is characterized by chronic oligo-ovulation or anovulation, these women do not experience the post-ovulatory rise in progesterone typically observed in ovulatory women.[45] Progesterone acts to slow LH pulse frequency; however, in women with PCOS it is hypothesized that this progesterone-mediated slowing of LH pulsatility is absent, resulting in a persistently rapid LH pulse frequency pattern.[45] Approximately 75% of women with PCOS have clinically evident menstrual dysfunction, i.e. oligomenorrhoea.[24] Furthermore, the majority of PCOS women are anovulatory; however, some women may demonstrate regular or intermittent ovulation, i.e. oligo-ovulatory cycles, but there are limited data regarding the long-term maintenance of ovulation in women with ovulatory PCOS. 2.3 Energetic Status: Exercising Amenorrhoeic and Oligomenorrhoeic Women
The relationship between exercise and menstrual disturbances has been evaluated in both observational and experimental studies. Amenorrhoea in exercising women is described as functional hypothalamic amenorrhoea, denoting its origins to hypothalamic disruption.[46] Inadequate caloric intake combined with high exercise energy expenditure can lead to energy deficiency, consequently resulting in energy conservation and suppression of reproductive function.[12-14] Existing evidence clearly demonstrates a strong association between energy deficiency and menstrual disturbances in physically active women.[5,17,22] Causal evidence supporting the link between energy deficiency and reproductive function was provided by Williams and colleagues[13] in a monkey model of the induction and reversal of amenorrhoea. Interestingly, menstrual cycles in the latter studies were shown to progressively lengthen prior to the development of amenorrhoea, suggesting that ‘oligomenorrhoea’ can transiently occur in association with energy Sports Med 2009; 39 (12)
Oligomenorrhoea in Exercising Women
1061
E1G (ng/mL) PdG (ng/mL) LH (m/U/mL) a 20
250
18 16
200
12 10
100
8
PdG (ug/mL)
E1G (ng/mL)
14 150
6 50
4 2
0
0 1
4
7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64 67 Day of cycle
b 180
20
160
18 16 14
120
12 100 10 80 8 60
PdG (ug/mL)
E1G (ng/mL) LH (mlU/mL)
140
6
40
4
20
2
0
0 1
4
7
10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 Day of cycle
Fig. 2. (a) Participant is a 21-year-old physically active woman who achieved menarche at the age of 16 years (gynaecological age = 5 years). Participant reported oligomenorrhoea since menarche. At evaluation she weighed 60.1 kg and body mass index was 21.8 kg/m2. Maximal oxygen uptake was 38.5 mL/kg/min and percent body fat was 25.4% as assessed by dual x-ray absorptiometry. Her screening endocrine panel (thyrotropin, free thyroxine [T4], prolactin, dehydroepiandrosterone sulphate [DHEAS], human chorionic gonadotrophin [HCG]) did not reveal any significant endocrinopathy explaining oligomenorrhoea. Resting energy expenditure (REE) measured by indirect calorimetry (on days 2–6 of measurement period) was 1286 kcal/day and, when corrected for fat free mass (FFM) was 30.6 kcal/day kg FFM. Predicted REE using the Harris-Benedict equation was 1430 kcal/day and the ratio of measured to predicted (Harris-Benedict) REE was 0.90. Data shown in (a) are a characteristic example of an oligomenorrhoeic anovulatory menstrual cycle of 69 days depicted by daily estrone glucuronide (E1G), pregnanediol glucuronide (PdG) and luteinizing hormone (LH) concentrations. The E1G and PdG data are aligned by chronological day of daily urinary hormone collections. (b) Participant is a 23-year-old physically active woman who achieved menarche at the age of 13 years (gynaecological age = 10 years). At evaluation, she weighed 52.6 kg and body mass index was 20.0 kg/m2. Maximal oxygen uptake was 47.2 mL/kg/min and percent body fat was 22.8% measured by dual x-ray absorptiometry. Her screening endocrine panel (thyrotropin, free T4, prolactin, DHEAS, HCG) did not reveal any significant endocrinopathy explaining oligomenorrhoea. REE measured by indirect calorimetry (on days 2–6 of menstrual cycle) was 1253 kcal/day and corrected for FFM was 32.2 kcal/day kg FFM. Predicted REE using the Harris-Benedict equation was 1362 kcal/day and the ratio of measured to predicted (Harris-Benedict) REE was 0.92. Data shown in (b) are a characteristic example of an oligomenorrhoeic ovulatory menstrual cycle of 58 days depicted by daily E1G, PdG and LH concentrations. The E1G and PdG data are aligned by chronological day of daily urinary hormone collections.
ª 2009 Adis Data Information BV. All rights reserved.
Sports Med 2009; 39 (12)
1062
deficiency. The numerous instances of ‘delayed menses’ (cycles of increased length) observed in the prospective exercise training study of Bullen et al.[47] in previously sedentary, eumenorrhoeic women also demonstrate that the lengthening of the menstrual cycle can occur in association with exercise training that is accompanied by energy deficiency. Clearly, more research is needed to differentiate the development of long cycles associated with energy deficiency from the more chronic presentation of irregular cycles termed ‘oligomenorrhoea’ that is described in crosssectional studies of women who reported a persistence of these types of cycles. Numerous studies support the existence of metabolic and endocrine adaptations to conserve energy in the face of a chronic energy deficiency. Metabolic alterations such as a suppressed resting energy expenditure (REE)[48,49] and reduced levels of TT3,[20] leptin[21] and insulin,[17] and glucoregulatory alterations such as elevated cortisol, growth hormone and ghrelin levels have been consistently observed in exercising amenorrhoeic women.[4,17] Unlike exercising amenorrhoeic women, studies to date examining exercising oligomenorrhoeic women have not demonstrated endocrine changes consistent with an energy deficiency-related aetiology.[36] For example, levels of growth hormone and cortisol were similar in oligomenorrhoeic athletes when compared with regularly menstruating athletes and sedentary controls.[36] Furthermore, no investigators to date have characterized oligomenorrhoeic and amenorrhoeic exercising women in independent groups, and thus there are no data to date that demonstrate a reduced REE in oligomenorrhoeic exercising women. It is likely that oligomenorrhoeic exercising women have decreased central adiposity compared with non-exercising women with PCOS, presumably secondary to their exercise training. As this finding may well represent a benefit of exercising training, exercising oligomenorrhoeic women may not display advanced metabolic abnormalities, i.e. decreased insulin sensitivity, which is observed in women with frank PCOS, but rather a metabolic environment more comparable to that in regularly menstruating exercising women. If the relevant metabolic marker ª 2009 Adis Data Information BV. All rights reserved.
Awdishu et al.
of PCOS is hyperandrogenism, then perhaps oligomenorrhoea in exercising women is a marker of hyperandrogenism. If exercising oligomenorrhoeic women display evidence of hyperandrogenism, then they may present with metabolic profiles similar to women with PCOS, but perhaps without the high degree of central adiposity that is commonly observed in PCOS women. 2.4 Energetic Status: Women with PCOS
More than 50% of women with PCOS are overweight or obese, with most exhibiting excess weight in the abdominal region.[26,50] As such, many women with PCOS display adverse metabolic profiles such as lipid-related abnormalities, insulin resistance and glucose intolerance, which translates into significantly increased risk for the development of type 2 diabetes mellitus and cardiovascular disease, as well as metabolic syndrome.[51-55] Results of numerous studies indicate that there is marked clinical heterogeneity within PCOS phenotypes with respect to metabolic risk profiles such that women who have polycystic ovarian morphology but lack hyperandrogenism or oligomenorrhoea have less extreme metabolic disturbances.[56-60] Shroff and colleagues[61] suggest that non-hyperandrogenic phenotypes may represent a form of PCOS associated with a mild subclinical metabolic profile. An increase in central body fat distribution and/or obesity has been demonstrated to exacerbate reproductive and metabolic disorders in women with PCOS, potentially exposing the emergence of the full or classic PCOS phenotype.[62] Excess adipose tissue increases peripheral aromatization of androgens to estrogens and also acts via insulin to decrease sex-hormonebinding globulin (SHBG), thus lowering circulating androgens.[63] Overall, an accumulation of body fat may act to transform a mild androgenic phenotype into classic PCOS.[64] In turn, data suggest that treatment of obesity may reduce the severity of PCOS symptoms.[65] Leanness in women may act to suppress androgen levels in comparison to non-lean women.[66] Numerous investigators have demonstrated the important effects of weight loss in improving the classic Sports Med 2009; 39 (12)
Oligomenorrhoea in Exercising Women
phenotype of PCOS to include improvements in reproductive and metabolic abnormalities.[67] Specific hormonal changes produced by weight loss include decreased circulating androgens, area under the curve insulin and leptin levels, improved insulin sensitivity and increased SHBG.[67,68] As exercise is a useful addition to any weight-loss programme and as exercise training, even in the absence of weight loss, can improve insulin sensitivity, lifestyle alterations aimed at PCOS patients often include recommendations for both diet and exercise.[69] Recently, Palomba and colleagues[69] compared the efficacy of a structured exercise programme with a diet programme in obese PCOS patients. The exercise programme consisted of three 30-minute training sessions per week at 60–70% of maximal oxygen consumption. The diet intervention consisted of a 24-week hypocaloric, high protein diet. Both interventions induced favourable effects within 12 weeks, without further improvements at 24 weeks. Specifically, both interventions caused improvements in bodyweight, body mass index (BMI), waist to hip ratio, insulin resistance, free androgen index (FAI), serum testosterone and SHBG. In the diet intervention group, bodyweight and BMI were more significantly reduced than in the exercise intervention group, and this change in bodyweight may be the mechanism by which improved insulin sensitivity results in improved reproductive function.[69] In the exercise intervention group, it is suggested that the improved insulin sensitivity was likely a result of a large reduction in waist circumference and perhaps by cellular muscle metabolism enhancement.[69] Exercise may confer beneficial effects by protecting women with PCOS from displaying the full clinical phenotype of PCOS and its associated risk markers (insulin resistance, cardiovascular disease) because of realized beneficial effects of exercise training on the metabolic environment, i.e. central adiposity and insulin sensitivity. For example, Vigorito and colleagues[70] evaluated the effects of a 3-month exercise training programme in women with PCOS on cardiopulmonary functional capacity and observed a significant reduction in BMI and a significant improvement in insulin sensitivity. These findings were corroboª 2009 Adis Data Information BV. All rights reserved.
1063
rated by Orio et al.,[30] who conducted a 12-week exercise programme in women with PCOS and also reported significant improvements in BMI, fasting insulin and glucose levels. Interestingly, improvements that were significant at the 12-week follow-up were also significant at a 24-week follow-up in the PCOS women who continued exercising, while these parameters worsened in the 12-week trained PCOS women assigned to a 12-week detraining period.[30] Finally, Manni and colleagues[71] demonstrated that voluntary exercise normalized ovarian morphology and biochemical features in a rat model with steroidinduced polycystic ovaries. Taken together, the abovementioned findings of exercise training studies in women with PCOS suggest that regular exercise may prove to be an effective treatment and possibly prevent PCOS. 2.5 Androgen Profiles: Exercising Amenorrhoeic and Oligomenorrhoeic Women
Miller and colleagues[72] demonstrated reduced endogenous androgen and dehydroepiandrosterone sulphate (DHEAS) levels in women with anorexia nervosa and normal weight women with hypothalamic amenorrhoea. Data suggest that normal weight women with hypothalamic amenorrhoea had comparable mean levels of total testosterone (TT), free testosterone (freeT) and DHEAS when compared with healthy eumenorrhoeic controls. Similarly, Laughlin and Yen[17] assessed nutritional and endocrine metabolic features in amenorrhoeic athletes, eumenorrhoeic athletes and sedentary controls. Although this study was designed to gain insight into the interrelationship of energy balance, markers of metabolic fuel and reproductive function, the assessment of androgens, specifically androstenedione, TT, FAI and SHBG, were completed. Among groups, there were no significant differences observed in androstenedione, testosterone or FAI. However, SHBG was significantly reduced in amenorrhoeic athletes in comparison with sedentary controls. In a subsequent study, Laughlin and colleagues[73] demonstrated reduced androstenedione levels in women with functional hypothalamic Sports Med 2009; 39 (12)
1064
amenorrhoea in comparison with regularly cycling controls; however, no difference in levels of TT or FAI were demonstrated. Taken together, these studies suggest that amenorrhoeic athletes have similar or reduced androgen levels in comparison with their eumenorrhoeic counterparts. Constantini and Warren[7] evaluated the menstrual status and reproductive hormones of swimmers, in whom thinness is not essential to exercise performance, and reported a high prevalence of delayed menarche and approximately an 80% prevalence of oligo/amenorrhoea defined by menstrual intervals longer than 45 days. Furthermore, elevated DHEAS and androstenedione were observed in these athletes. Results of this study indicated that the hormonal profile of swimmers with oligomenorrhoea was unique from the typical profile observed in other exercising women with hypothalamic amenorrhoea. Mild hyperandrogenism was suggested to be the mechanism underlying menstrual irregularity in these female swimmers. More recently, Rickenlund and colleagues[23] identified a subgroup of female athletes with oligomenorrhoea, defined as menses at an interval exceeding 6 weeks, that demonstrated higher serum levels of TT, freeT and androstenedione and lower SHBG. Furthermore, these women had a pathologically increased (i.e. out of clinical range) FAI compared with other athletes with or without menstrual disturbances. It was therefore suggested that essential hyperandrogenism, like that consistent with PCOS, may be the mechanism underlying oligomenorrhoea in some female athletes that may be unrelated to energy availability. In a subsequent study, these investigators[36] observed that oligomenorrhoeic athletes, defined as menses at an interval exceeding 6 weeks and no more than nine menses in the last year, had a higher 24-hour secretion of TT than all other exercising groups of amenorrhoeic and regularly cyclic athletes. However, concentrations of other endocrine markers such as growth hormone and cortisol were comparable in oligomenorrhoeic athletes and regularly menstruating athletes, thus failing to support an energy deficiencyrelated aetiology of their menstrual disturbance,[36] and again supportive of an androgen-derived aetiology of oligomenorrhoea in these women. ª 2009 Adis Data Information BV. All rights reserved.
Awdishu et al.
2.6 Androgen Profiles: Women with PCOS
It is currently recognized that androgen excess is a uniform characteristic and hallmark of PCOS.[24,25,45,74] Recent guidelines published by the AES have concluded that PCOS is primarily a disorder of androgen excess and without evidence of such, a diagnosis of PCOS cannot be established.[24] Furthermore, it was agreed that the most reliable indices of hyperandrogenism include hirsutism and freeT levels.[24] Biochemical hyperandrogenism is defined as increased serum androgen levels. Elevated androgen levels are observed in approximately 60–80% of women with PCOS.[24] The typical androgen profile of women with PCOS can include increased levels of serum TT, freeT, DHEAS, bioavailable testosterone and decreased levels of SHBG. In patients with PCOS, although freeT is considered the preferred reference measurement, the assay is complex and difficult to accurately measure.[75] As such, FAI is also considered a reliable diagnostic marker to distinguish hyperandrogenism.[76] This index incorporates TT, SHBG and albumin to yield a numerical value that reflects hyperandrogenaemia. Calculated values have been found to correlate closely with values estimated from reference measurement procedures.[75,76] The FAI is often increased in severe acne, androgenic alopecia and hirsutism.[76] A number of studies in women with PCOS have demonstrated elevated FAI in the range of 5.90–30,[39,41,44,60,77] and a FAI of >6.5 has been utilized as a sensitive and specific indicator of hyperandrogenism.[78] Over time, these biochemical abnormalities may progress to clinical hyperandrogenism, i.e. hirsutism, acne, androgenic alopecia and chronic oligo-anovulation.[43] Increased serum levels of TT, freeT and DHEAS have been observed in all phenotypes of PCOS, with higher mean levels in women characterized by the classic PCOS phenotype, and intermediate levels in women with ovulatory PCOS.[57] It is well documented that the PCOS phenotypes that include hyperandrogenism are associated with more severe metabolic, endocrine and reproductive risks while the non-androgenic phenotype defined by the Rotterdam criteria Sports Med 2009; 39 (12)
Oligomenorrhoea in Exercising Women
1065
Table III. Studies reporting androgens among amenorrhoeic (functional hypothalamic and athletes) and oligomenorrhoeic (sedentary or athletes) women with polycystic ovarian syndrome (PCOS) Study, year
Measure
Amenorrhoeic
Laughlin et al.,[73] 1998
TT
ü
-
DHEAS
Laughlin and Yen,[17] 1996
TT
ü
-
Androstenedione
fl ü
-
FAI
Rickenlund et al.,[23] 2003
-
FAI TT Androstenedione
-
Sex-hormone-binding globulin
fl
TT: sex-hormone-binding globulin
ü
ü
›
TT
›
freeT
›
Androstenedione Rickenlund et al.,[36] 2004
Diurnal TT
Azziz et al.,[24] 2006
TT
PCOS
-
freeT Goodarzi and Azziz,[74] 2006
Oligomenorrhoeic
-
› ü
fl
ü
› ü
DHEAS
› ›
freeT
›
Wakat et al.,[35] 1982
FAI
ü
›
Chang et al.,[58] 2005
FAI
ü
›
Taponen et al.,[39] 2003
FAI
ü
›
Mathur et al.,[78] 1981
FAI
ü
›
freeT
›
Bioavailable testosterone
›
DHEAS = dehydroepiandrosterone sulphate; FAI = free androgen index; freeT = free testosterone; TT = total testosterone; ü indicates study group compared with regularly cycling controls; › indicates concentrations greater than regularly cycling controls; fl indicates concentrations less than regularly cycling controls; – indicates concentrations the same as regular cycling controls.
(oligo-anovulation + polycystic ovaries) is associated with neuroendocrine profiles similar to ovulatory controls. Women with polycystic ovaries, hyperandrogenism and oligomenorrhoea generally have the most adverse metabolic profiles in comparison with other PCOS phenotypes (i.e. polycystic ovaries and oligomenorrhoea, polycystic ovaries and hyperandrogenism or hyperandrogenism and oligomenorrhoea),[56,58-61,79] i.e. these women are the most insulin resistant, have the most abnormal lipid profiles and have the highest BMI.[56] Table III summarizes studies reporting androgens in amenorrhoeic and oligomenorrhoeic PCOS women. ª 2009 Adis Data Information BV. All rights reserved.
3. Conclusions For the most part, studies examining the underlying mechanisms and consequences of exercise-associated menstrual disturbances have grouped exercising amenorrhoeic and oligomenorrhoeic women together, with the majority of investigators’ studies establishing this based on self-reported menstrual history.[32-35] Investigators to date have not carefully examined the daily ovarian steroid profiles to accurately determine menstrual status and proceed with careful evaluation of hormonal and energetic factors in order to determine whether separate findings distinguish Sports Med 2009; 39 (12)
Awdishu et al.
1066
oligomenorrhoeic and amenorrhoeic exercising women. This lack of detailed assessment has led to the general acceptance that oligomenorrhoea in exercising women is likely due to an energy deficiency-related aetiology. Consequently, treatment has been aimed at correcting an energy deficiency by increasing energy intake and/or decreasing energy expenditure. Oligomenorrhoea in exercising women is a menstrual disturbance that is under-investigated in the literature, likely attributable to the difficult nature of studying these inconsistent and irregular cycles. The exact underlying mechanism of this disturbance in exercising women may not always be related to an energy-deficient aetiology, as previously has been assumed, and further research is certainly warranted. Thus, oligomenorrhoea may not always represent an intermediate state in hypothalamic inhibition resulting from an energy deficiency; an alternate and likely possible explanation may be linked to hyperandrogenism. It is also critical to distinguish between oligomenorrhoeic and amenorrhoeic exercising women because the treatment strategy for amenorrhoea (increasing energy intake) likely differs from oligomenorrhoea (increasing energy expenditure and decreasing energy intake) as these variants likely represent unique underlying aetiologies. Further investigation into the hormonal environment may be necessary as the finding of elevated androgens could indicate PCOS and this may mandate appropriate treatments. We propose that investigators who assess women who have irregular cycles should specifically assess women for clinical and biochemical evidence of hyperandrogenism. We propose that the well validated and semi-quantitative Ferriman-Gallwey score[64] be utilized as a measure of hirsutism as well as a measure of the free androgens, and perhaps SHBG. Evidence from women with PCOS, and from our study of exercising women with oligomenorrhoea, suggests that low SHBG, which has good assay reproducibility, may be a useful marker as it is commonly associated with hyperandrogenism, and as it is also associated with insulin resistance which we propose underlies the predisposition to oligomenorrhoea in women who exercise. Women who have evidence of androgen ª 2009 Adis Data Information BV. All rights reserved.
excess or low SHBG should be considered at risk for a disorder other than energy deficiency associated with amenorrhoea in athletes. Moreover, in studies related to the Female Athlete Triad, investigators need to rule out hyperandrogenism in oligomenorrhoeic women, as this aetiology is not a component of the Female Athlete Triad. When oligomenorrhoea is present, a detailed history of menstrual status, exercise and diet history including history of stress fractures followed by clinical/laboratory tests to rule out other causes of menstrual disturbance (i.e. PCOS) is warranted. More studies are required to validate the underlying mechanism involved in this oligomenorrhoea in exercising women. Acknowledgements No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.
Reference 1. Knobil E. The neuroendocrine control of ovulation. Hum Reprod 1988; 3 (4): 469-72 2. Knobil E. The wisdom of the body revisited. News Physiol Sci 1999; 14 (2): 1-11 3. Knobil E. The GnrH pulse generator. Am J Obstet Gynecol 1990; 163 (11): 1721-7 4. De Souza MJ, Williams NI. Physiological aspects and clinical sequelae of energy deficiency and hypoestrogenism in exercising women. Hum Reprod Update 2004; 10 (5): 433-48 5. De Souza MJ, Miller BE, Loucks AB, et al. High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition. J Clin Endocrinol Metab 1998; 83 (12): 4220-32 6. Sanborn CF, Martin BJ, Wagner Jr WW. Is athletic amenorrhea specific to runners? Am J Obstet Gynecol 1982; 143 (8): 859-61 7. Constantini NW, Warren MP. Menstrual dysfunction in swimmers: a distinct entity. J Clin Endocrinol Metab 1995; 80 (9): 2740-4 8. Feicht CB, Johnson TS, Martin BJ, et al. Secondary amenorrhoea in athletes. Lancet 1978; 2 (8100): 1145-6 9. Dale E, Gerlach DH, Wilhite AL. Menstrual dysfunction in distance runners. Obstet Gynecol 1979; 54 (1): 47-53 10. Schwartz B, Cumming DC, Riordan E, et al. Exerciseassociated amenorrhea: a distinct entity? Am J Obstet Gynecol 1981; 141 (6): 662-70 11. Loucks AB, Horvath SM. Athletic amenorrhea: a review. Med Sci Sports Exerc 1985; 17 (1): 56-72
Sports Med 2009; 39 (12)
Oligomenorrhoea in Exercising Women
12. Loucks AB, Verdun M, Heath EM. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol 1998; 84 (1): 37-46 13. Williams NI, Caston-Balderrama AL, Helmreich DL, et al. Longitudinal changes in reproductive hormones and menstrual cyclicity in cynomolgus monkeys during strenuous exercise training: abrupt transition to exercise-induced amenorrhea. Endocrinology 2001; 142 (6): 2381-9 14. Williams NI, Helmreich DL, Parfitt DB, et al. Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J Clin Endocrinol Metab 2001; 86 (11): 5184-93 15. De Souza MJ, Lee DK, VanHeest JL, et al. Severity of energy-related menstrual disturbances increases in proportion to indices of energy conservation in exercising women. Fertil Steril 2007; 88 (4): 971-5 16. De Souza MJ, Leidy HJ, O’Donnell E, et al. Fasting ghrelin levels in physically active women: relationship with menstrual disturbances and metabolic hormones. J Clin Endocrinol Metab 2004; 89 (7): 3536-42 17. Laughlin GA, Yen SS. Nutritional and endocrine-metabolic aberrations in amenorrheic athletes. J Clin Endocrinol Metab 1996; 81 (12): 4301-9 18. Wade GN, Schneider JE, Li HY. Control of fertility by metabolic cues. Am J Physiol 1996; 270 (1 Pt 1): E1-19 19. Welt CK, Chan JL, Bullen J, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351 (10): 987-97 20. Loucks AB, Laughlin GA, Mortola JF, et al. Hypothalamic-pituitary-thyroidal function in eumenorrheic and amenorrheic athletes. J Clin Endocrinol Metab 1992; 75 (2): 514-8 21. Laughlin GA, Yen SSC. Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea. J Clin Endocrinol Metab 1997; 82 (1): 318-21 22. De Souza MJ, Van Heest J, Demers LM, et al. Luteal phase deficiency in recreational runners: evidence for a hypometabolic state. J Clin Endocrinol Metab 2003; 88 (1): 337-46 23. Rickenlund A, Carlstro¨m K, Ekblom B, et al. Hyperandrogenicity is an alternative mechanism underlying oligomenorrhea or amenorrhea in female athletes and may improve physical performance. Fertil Steril 2003; 79 (4): 947-55 24. Azziz R, Carmina E, Dewailly D, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006; 91 (11): 4237-45 25. Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, et al., editors. Polycystic ovary syndrome. Boston (MA): Blackwell Scientific, 1992: 377-84 26. Azziz R, et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004; 89 (6): 2745-9 27. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999; 84 (11): 4006-11
ª 2009 Adis Data Information BV. All rights reserved.
1067
28. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19 (1): 41-7 29. Zanker CL, Swaine IL. The relationship between serum oestradiol concentration and energy balance in young women distance runners. Int J Sports Med 1998; 19 (2): 104-8 30. Orio F, Vuolo L, Palomba S, et al. Metabolic and cardiopulmonary effects of detraining after a structured exercise training programme in young PCOS women. Clin Endocrinol (Oxf) 2008; 68 (6): 976-81 31. Loucks AB, Mortola JF, Girton L, et al. Alterations in the hypothalamic-pituitary-ovarian and the hypothalamicpituitary-adrenal axes in athletic women. J Clin Endocrinol Metab 1989; 68 (2): 402-11 32. Carlberg KA, Buckman MT, Peake GT, et al. Body composition of oligo/amenorrheic athletes. Med Sci Sports Exerc 1983; 15 (3): 215-7 33. Cobb KL, Bachrach LK, Greendale G, et al. Disordered eating, menstrual irregularity, and bone mineral density in female runners. Med Sci Sports Exerc 2003; 35 (5): 711-9 34. Shangold MM. Causes, evaluation, and management of athletic oligo/amenorrhea. Med Clin North Am 1985; 69 (1): 83-95 35. Wakat DK, Sweeney KA, Rogol AD. Reproductive system function in women cross-country runners. Med Sci Sports Exerc 1982; 14 (4): 263-9 36. Rickenlund A, Thore´n M, Carlstro¨m K, et al. Diurnal profiles of testosterone and pituitary hormones suggest different mechanisms for menstrual disturbances in endurance athletes. J Clin Endocrinol Metab 2004; 89 (2): 702-7 37. De Souza MJ, Lee D, VanHeest JL, et al. Severity of energyrelated menstrual disturbances increases in proportion to indices of energy conservation in exercising women. Fertil Steril 2007; 88 (4): 971-5 38. De Souza MJ, Williams NI, unpublished data 39. Taponen S, Martikainen H, Ja¨rvelin MR, et al. Hormonal profile of women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland birth cohort 1966 study. J Clin Endocrinol Metab 2003; 88 (1): 141-7 40. Taylor AE, McCourt B, Martin KA, et al. Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997; 82 (7): 2248-56 41. Arroyo A, Laughlin GA, Morales AJ, et al. Inappropriate gonadotropin secretion in polycystic ovary syndrome: influence of adiposity. J Clin Endocrinol Metab 1997; 82 (11): 3728-33 42. Berga SL, Daniels TL, Giles DE. Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations. Fertil Steril 1997; 67 (6): 1024-30 43. Blank SK, McCartney CR, Helm KD, et al. Neuroendocrine effects of androgens in adult polycystic ovary syndrome and female puberty. Semin Reprod Med 2007; 25 (5): 352-9 44. Yoo RY, Dewan A, Basu R, et al. Increased luteinizing hormone pulse frequency in obese oligomenorrheic girls
Sports Med 2009; 39 (12)
Awdishu et al.
1068
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
with no evidence of hyperandrogenism. Fertil Steril 2006; 85 (4): 1049-56 Blank SK, McCartney CR, Marshall JC. The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. Hum Reprod Update 2006; 12 (4): 351-61 Williams NI. Lessons from experimental disruptions of the menstrual cycle in humans and monkeys. Med Sci Sports Exerc 2003; 35 (9): 1564-72 Bullen BA, Skrinar GS, Beitins IZ, et al. Induction of menstrual disorders by strenuous exercise in untrained women. N Engl J Med 1985; 312 (21): 1349-53 Myerson M, Gutin B, Warren MP, et al. Resting metabolic rate and energy balance in amenorrheic and eumenorrheic runners. Med Sci Sports Exerc 1991; 23 (1): 15-22 Lebenstedt M, Platte P, Pirke KM. Reduced resting metabolic rate in athletes with menstrual disorders. Med Sci Sports Exerc 1999; 31 (9): 1250-6 Carmina E, Bucchieri S, Esposito A, et al. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab 2007; 92 (7): 2500-5 Vrbikova J, et al. Prevalence of insulin resistance and prediction of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome. Clin Chem Lab Med 2007; 45 (5): 639-44 Legro RS, Gnatuk CL, Kunselman AR, et al. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab 2005; 90 (6): 3236-42 Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 2001; 111 (8): 607-13 Dokras A, Bochner M, Hollinrake E, et al. Screening women with polycystic ovary syndrome for metabolic syndrome. Obstet Gynecol 2005; 106 (1): 131-7 Solomon CG, Hu FB, Dunaif A, et al. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab 2002; 87 (5): 2013-7 Barber TM, Wass JA, McCarthy MI, et al. Metabolic characteristics of women with polycystic ovaries and oligoamenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2007; 66 (4): 513-7 Carmina E, Chu MC, Longo RA, et al. Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. J Clin Endocrinol Metab 2005; 90 (5): 2545-9 Chang WY, Knochenhauer ES, Bartolucci AA, et al. Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical characterization of the three major clinical subgroups. Fertil Steril 2005; 83 (6): 1717-23 Dewailly D, Catteau-Jonard S, Reyss AC, et al. Oligoanovulation with polycystic ovaries but not overt hyperandrogenism. J Clin Endocrinol Metab 2006; 91 (10): 3922-7 Pehlivanov B, Orbetzova M. Characteristics of different phenotypes of polycystic ovary syndrome in a Bulgarian population. Gynecol Endocrinol 2007; 23 (10): 604-9
ª 2009 Adis Data Information BV. All rights reserved.
61. Shroff R, Syrop CH, Davis W, et al. Risk of metabolic complications in the new PCOS phenotypes based on the Rotterdam criteria. Fertil Steril 2007; 88 (5): 1389-95 62. Gosman GG, Katcher HI, Legro RS. Obesity and the role of gut and adipose hormones in female reproduction. Hum Reprod Update 2006; 12 (5): 585-601 63. Pasquali R. Obesity and androgens: facts and perspectives. Fertil Steril 2006; 85 (5): 1319-40 64. Carmina E. The spectrum of androgen excess disorders. Fertil Steril 2006; 85 (6): 1582-5 65. Huber-Buchholz MM, Carey DG, Norman RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab 1999; 84 (4): 1470-4 66. Baghaei F, Rosmond R, Westberg L, et al. The lean woman. Obes Res 2002; 10 (2): 115-21 67. Stamets K, Taylor DS, Kunselman A, et al. A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. Fertil Steril 2004; 81 (3): 630-7 68. Pasquali R, Gambineri A. Role of changes in dietary habits in polycystic ovary syndrome. Reprod Biomed Online 2004; 8 (4): 431-9 69. Palomba S, Giallauria F, Falbo A, et al. Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study. Hum Reprod 2008; 23 (3): 642-50 70. Vigorito C, Giallauria F, Palomba S, et al. Beneficial effects of a three-month structured exercise training program on cardiopulmonary functional capacity in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92 (4): 1379-84 71. Manni L, Cajander S, Lundeberg T, et al. Effect of exercise on ovarian morphology and expression of nerve growth factor and alpha(1)- and beta(2)-adrenergic receptors in rats with steroid-induced polycystic ovaries. J Neuroendocrinol 2005; 17 (12): 846-58 72. Miller KK, Lawson EA, Mathur V, et al. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. J Clin Endocrinol Metab 2007; 92 (4): 1334-9 73. Laughlin GA, Dominguez CE, Yen SS. Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1998; 83 (1): 25-32 74. Goodarzi MO, Azziz R. Diagnosis, epidemiology, and genetics of the polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab 2006; 20 (2): 193-205 75. Mueller A, Dittrich R, Cupisti S, et al. Is it necessary to measure free testosterone to assess hyperandrogenemia in women? The role of calculated free and bioavailable testosterone. Exp Clin Endocrinol Diabetes 2006; 114 (4): 182-7 76. Cho LW, Kilpatrick ES, Jayagopal V, et al. Biological variation of total testosterone, free androgen index and bioavailable testosterone in polycystic ovarian syndrome:
Sports Med 2009; 39 (12)
Oligomenorrhoea in Exercising Women
implications for identifying hyperandrogenaemia. Clin Endocrinol (Oxf) 2007; 68 (3): 390-4 77. Hahn S, Kuehnel W, Tan S, et al. Diagnostic value of calculated testosterone indices in the assessment of polycystic ovary syndrome. Clin Chem Lab Med 2007; 45 (2): 202-7 78. Mathur RS, Moody LO, Landgrebe S, et al. Plasma androgens and sex hormone-binding globulin in the evaluation of hirsute females. Fertil Steril 1981; 35 (1): 29-35
ª 2009 Adis Data Information BV. All rights reserved.
1069
79. Carmina E. Mild androgen phenotypes. Best Pract Res Clin Endocrinol Metab 2006; 20 (2): 207-20
Correspondence: Dr Mary Jane De Souza, Department of Kinesiology, Penn State University, University Park, PA 16803 USA. E-mail:
[email protected]
Sports Med 2009; 39 (12)
