M A L L O R C A SUPPORTED BY

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1 SUPPORTED BY M A L L O R C A

2 Preface The booklet in front of you is the summary of the 11th Sport Nutrition conference. For this conference we have returned to the beautiful island of Mallorca. With Mallorca being one of the most popular locations for off-season training by many road cyclists and triathletes we had come up with the theme nutritional coaching strategies to modulate training efficiency for this meeting. Again several leading scientists shared their insights with a select group of sports nutritionists, sports dietitians, physiologists, coaches, and athletes. The format of these conferences has been highly successful and this is due to the unique formula that we use. In short, we bring together a relatively small audience consisting of leading sports nutrition professionals, a small number of elite speakers, journalists, and a few elite athletes and coaches. The carefully selected speakers are not only academically well established but also have a background in sport and do not only deliver excellent scientific presentations but can translate the science to something of practical use. By combining this with a number of hot topics in sports nutrition, and sufficient time to interact, we create some great discussions. Therefore, we have introduced workshops to further bridge the gap between science and practice. The main theme of this and all previous conferences: translating the often complicated science into a practical message that is of immediate use to an athlete or coach. This aim of this booklet is to provide a short overview of the science and a number of practical guidelines illustrated with figures and tables. These conferences, the summary booklet you have in front of you, the DVDs and a web site with information are an important step in closing the existing gap between biomedical science and sports practice. We hope the information provided will be of use. I want to thank Zibi Szlufcik, Jessica Marsch and Daniel Albrecht for all the hard work in putting this together and making it all possible. Also, I would like to express my sincere gratitude to PowerBar and the Nestlè Nutrition Institute. Without their help and support in staging this conference we would not have been able to produce these and other materials. Luc van Loon Maastricht University Content Preface Luc van Loon Nutrition to manipulate adaptation to endurance type exercise training John A. Hawley Is nitrate the new magic bullit? Andrew M Jones Dietary strategies to attenuate muscle loss during recovery from injury Kevin Tipton Nutritional strategies to support adaptation to high intensity interval training in team sports Martin J. Gibala Practical limitations of ingesting large amounts of carbohydrate during exercise Asker Jeukendrup Use of oral ph-buffers to improve performance during high intensity exercise Louise M Burke Protein intake to allow post-exercise muscle reconditioning Luc J.C. van Loon Nutritional support to maintain proper immune status during intense training Michael Gleeson Notes

3 1 Nutrition to manipulate adaptation to endurance type exercise training John A. Hawley RMIT University Melbourne, Australia The influence of a short-term (<10 days) reduction in carbohydrate availability on exercise capacity was first studied almost a century ago, but the first modern-day investigation to systematically examine the effects of this intervention on training adaptation and performance was undertaken relatively recently by Scandinavian researchers (2). Using a clever experimental model, these workers studied seven previously untrained male subjects who completed a training program of leg knee extensor exercise 5 days/week for 10 weeks in which both of the subject s legs were trained according to a different schedule (with the total amount of work undertaken by each leg being the same). As such, one leg was trained twice a day, every second day in which the second training session was commenced with low glycogen content (LOW), whereas the contra-lateral leg trained daily under conditions of high glycogen availability (HIGH) every session. Muscle biopsies were taken from both legs before and after and 10 weeks of training and sub-maximal and maximal exercise testing was performed pre- and post-training. Resting muscle glycogen content was only increased in LOW after the training intervention (P<0.05), and while there was a training-induced increase in the maximal activity of citrate synthase in both legs (P<0.05), the magnitude of increase was significantly greater in LOW than HIGH (P<0.05). The magnitude of increase in post-training exercise time to exhaustion (measured as the time to exhaustion at 90% of post-training maximal power output) was twice as great for LOW as HIGH (~20 vs. 12 min; P<0.05). These results clearly demonstrate that adaptation and endurance performance is augmented by lack of substrate (i.e., muscle glycogen) availability, at least for previously untrained subjects undergoing a short-term training intervention (3). The term train-low, compete-high was promulgated to describe this novel training approach (2). Subsequently Yeo et al. (7) investigated the train-low paradigm during a 3 week intervention in well-trained individuals. These workers reasoned that athletes would have maximized their training adaptation and that further gains would be negligible, irrespective of whether they trained with low or normal levels of muscle glycogen. Training frequency and intensity was manipulated so that intense interval training sessions were commenced at a time when glycogen stores were lowered by ~50% through prior exercise, or were replete (7). Maximal self-selected power output during selected training sessions was worse when athletes commenced intervals with low compared to normal glycogen availability. Yet despite this lower training impulse resting muscle glycogen concentration, the maximal activities of citrate synthase and β-h ydroxyacyl-coa-dehydrogenase (β-had) and the total protein content of cytochrome C oxidase subunit IV were higher (compared to pre-training values) only in subjects who commenced interval training with low muscle glycogen content. Hulston et al. (5) also reported that self-selected power output was compromised when trained cyclists started high-intensity interval training sessions with low glycogen stores, and that tracer-derived measures of fat oxidation during submaximal cycling were increased after train-low. In addition to altering endogenous carbohydrate stores, other exercise-diet protocols have been utilized to manipulate exogenous glucose availability including training after an overnight fast, prolonged training with or without an overnight fast and withholding carbohydrate intake during the session, and/or withholding carbohydrate during the first hours of recovery (reviewed in 1, 3 and 4). In contrast to the robust effects of commencing endurance training sessions with low muscle glycogen stores, the results of studies that have manipulated glucose availability before, during, and/or after endurance exercise on selected muscle adaptations are equivocal. Several investigations report that after 6-10 week intervention periods, a range of training-responsive metabolic markers (including succinate dehydrogenase [SDH] activity, GLUT-4 and hexokinase II content) are increased by a similar extent with or without carbohydrate supplementation. Other studies, however, have reported subtle differences in muscle adaptation after reducing carbohydrate availability during training (1,3,4,). To date, only one study has examined the interactive effects of endogenous muscle glycogen and exogenous glucose availability on training adaptation. Morton et al. (6) employed a variety of training protocols (twice per day, two days/week or once per day, four days/week) and dietary manipulations (with or without carbohydrate support before and during exercise) in recreational subjects for six weeks. All protocols were associated with an increase in the protein concentrations of COX-IV and the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1-α), with no differences in the magnitude of change between groups who trained with low versus high carbohydrate availability. Only the maximal activity of SDH was greater in subjects who commenced training with lowered muscle glycogen stores and who did not receive carbohydrate support during/after training. Taken collectively, the results of these studies demonstrate that independent of prior training status, short-term (3-10 week) training programs in which a portion of workouts are commenced with either low muscle glycogen and/or low exogenous glucose availability augment training 3

4 adaptation (i.e., increase the maximal activities of selected enzymes involved in carbohydrate and/or lipid metabolism and promote mitochondrial biogenesis) to a greater extent than when all workouts are undertaken with normal or elevated glycogen stores (1,3,4). However, carbohydrate availability is not the only variable manipulated in these investigations. The studies employed different modes of training, a range in the number of training sessions (both in total number and those undertaken under conditions of low carbohydrate availability) along with variable intervention periods. It is quite possible that some of the results are not directly attributable to differences in carbohydrate availability per se but rather to the effects of the exercise training protocol itself (i.e., differences in recovery time between workouts, training once-a-day versus twice every second day). Notwithstanding this possibility, there is no evidence of impaired adaptation (or a decrement to performance outcomes) after short-term training with low carbohydrate availability. Practical recommendations for coach, athlete and sports practioner There is often a mismatch between the changes in cellular mechanistic variables and whole body functional outcomes (changes in training capacity or measures of performance). This makes it difficult to make firm practical recommendations to athletes, coaches and sport nutritionists working in the field about the utility of train-low diettraining strategies. Skeletal muscle metabolism is only one factor in determining performance, which involves the integration of whole body systems including the role of the central nervous system in determining pacing strategies and perceptions of fatigue or effort. We currently lack the appropriate tools to accurately measure exercise/sports performance, in particularly the ability to detect small changes that are worthwhile to a competitive athlete in order to change the outcomes of real world events. Some train low strategies may have negative effects on parameters related to an athlete s health or performance that either acutely, or over the long-term, counte-ract the positive effects achieved on isolated muscle characteristics. An indirect outcome of dietary periodization may be changes in the training stimulus; a common finding when training sessions are undertaken with low carbohydrate availability is that subjects frequently chose a lower workload or intensity because they perceive the effort to be higher, at least in their initial exposure to training low This outcome would seem counter-intuitive for the preparation of competitive athletes, where high intensity workouts and the generation of high power outputs are a critical component of a periodised training program. It may simply be the case that current studies have not been sophisticated enough to integrate various combinations and permutations of train low strategies into the periodized training programs of highly-trained athletes. The preparation of elite athletes involves a range of training activities with various goals. It may be that training low needs to be carefully integrated into parts of this complex system to allow a performance benefit to be achieved in concert with the measurable cellular changes. 4

5 Figure 1. Training intensity (expressed as a percentage of peak sustained power output [PPO]) sustained during highintensity interval training sessions (HIT) undertaken on three occasions per week during a three week intervention period. Each HIT session consisted of eight repetitions of five min work bouts separated by one minute of active recovery (100 W). See text for further details of nutrient-exercise manipulation. Values are reported as mean ± standard error. * Significantly different between train-high (HIGH) and train-low (LOW). Reprinted from reference 7. References 1. Burke LM, Fuelling strategies to optimise performance training high or training low? Scand J Sports Med Science 20 (Suppl 2): 48-58, Hansen AK, Fischer CP, Plomgaard P, Andersen JL, Saltin B, Pedersen BK. Skeletal muscle adaptation: training twice every second day vs. training once daily. J App Physiol 98:93-99, Hawley JA, Burke LM. Carbohydrate availability and training adaptation: effects on cell metabolism. Exerc Sport Sci Rev 38: , Hawley JA, Burke LM, Phillips SM, Spriet LL. Nutritional modulation of training-induced skeletal muscle adaptations. J Appl Physiol 110: , Hulston CJ, Venables MC, Mann CH, Martin C, Philp A, Baar K, Jeukendrup AE. Training with Low Muscle Glycogen Enhances Fat Metabolism in Well-Trained Cyclists. Med Sci Sports Exerc 42: , Morton JP, Croft L, Bartlett JD, Maclaren DP, Reilly T, Evans L, McArdle A, Drust B. Reduced carbohydrate availability does not modulate training-induced heat shock protein adaptations but does upregulate oxidative enzyme activity in human skeletal muscle. J Appl Physiol 106: , Yeo WK, Paton CD, Garnham AP, Burke LM, Carey AL, Hawley JA. Skeletal muscle adaptation and performance responses to once a day versus twice-every-second-day endurance training regimens. J Appl Physiol 105: ,

6 2 Is nitrate the new magic bullit? Andrew M Jones University of Exeter, United Kingdom Introduction Nitric oxide (NO) is an important physiological signalling molecule that can modulate skeletal muscle function through its role in the regulation of blood flow, muscle contractility, glucose and calcium homeostasis, and mitochondrial respiration and biogenesis (1). Until quite recently, it was considered that NO was generated solely through the oxidation of the amino acid l-arginine in a reaction catalysed by nitric oxide synthase (NOS; 2). It is now appreciated, however, that NO may also be produced by the reduction of nitrate to nitrite and subsequently of nitrite to NO (3). This pathway may be particularly important in conditions of low oxygen availability, such as in skeletal muscle during exercise. Nitrate and nitrite are present in the body as the products of NO production through NOS but are also modulated through the diet. Nitrate in foods, particularly green leafy vegetables (Table 1), can be reduced to nitrite by oral bacteria, leading to an increased plasma nitrite concentration which serves as a circulating reservoir for NO production (4). Nitrate and Exercise Several recent studies have addressed the extent to which dietary nitrate supplementation might affect the physiological responses to exercise. Larsen et al. (5) first showed that three days of sodium nitrate supplementation (0.1 mmol/kg/ day) reduced resting blood pressure and the O2 cost of sub-maximal cycle exercise. Subsequently, our research group reported that enhancing NO bioavailability through supplementation of the diet with a natural foodstuff (nitrate-rich beetroot juice) reduces resting blood pressure and the O2 cost of exercise and improves exercise performance (6-10). In our first study on this topic (6), we found that 4-6 days of dietary nitrate supplementation (0.5 L of beetroot juice per day containing ~ 6 mmol nitrate) reduced the steady-state O2 cost of sub-maximal cycle exercise by 5% and extended the time-to-exhaustion during high-intensity cycling by 16%. These effects were highly surprising given that the O2 cost of sub-maximal exercise has been considered to be essentially fixed. We and others have subsequently confirmed these findings in other populations and with different exercise modalities. Mechanisms We used 31P- magnetic resonance spectroscopy to investigate the mechanistic bases for the lower O2 cost of exercise observed following nitrate supplementation (7). We found that nitrate supplementation resulted in both a reduced pulmonary O2 uptake and a reduced muscle metabolic perturbation, enabling high-intensity knee-extension exercise to be tolerated for a greater period of time. These data imply that the reduced O2 cost of exercise following dietary nitrate supplementation is related to a reduced ATP cost of muscle force production, perhaps consequent to reduced crossbridge cycling or sarcoplasmic reticulum Ca2+-ATPase activity (11). It is also possible, however, that nitrate supplementation enhances mitochondrial efficiency: Larsen et al. (12) have recently reported that sodium nitrate supplementation reduced proton leakage and increased the mitochondrial P/O ratio. It is possible that greater NO bioavailability alters both muscle contractile efficiency and the efficiency of oxidative metabolism. Applications The positive effects of nitrate supplementation on the O2 cost of sub-maximal exercise can be manifest acutely (i.e. 2.5 hours following a 6 mmol nitrate bolus ) and this effect can be maintained for at least 15 days if supplementation at the same daily dose is continued (8). Because beetroot juice contains compounds other than nitrate that might also be bioactive, we have developed a nitrate-depleted beetroot juice as a placebo. We found that nitrate-depleted beetroot juice had no physiological effects relative to a control condition whereas nitrate-rich beetroot juice reduced the O2 cost of both walking and running and extended the time-to-exhaustion by 15% (9). These results confirm that nitrate is the key bioactive component of beetroot juice, though it cannot be discounted that other components (such as antioxidants and polyphenols) act synergistically and facilitate the bioconversion of nitrate to NO. Most recently, we have investigated the influence of acute dietary nitrate supplementation on 4 km and 16.1 km time trial (TT) performance in competitive cyclists (10). We found that cyclists were able to produce a greater power output for the same rate of pulmonary O2 uptake, resulting in a 2.7% reduction in the time to complete both TT distances. 6

7 Practical Recommendations The available evidence indicates that dietary supplementation with 5-7 mmol nitrate (approximately 0.1 mmol/kg body mass) results in a significant increase in plasma [nitrite] and associated physiological effects including a lower resting blood pressure, reduced pulmonary O2 uptake during sub-maximal exercise and enhanced exercise tolerance or performance (5-10, 13). This dose of nitrate can readily be achieved through the consumption of 0.5 L of beetroot juice (or an equivalent high-nitrate foodstuff). Following a 5-6 mmol bolus of nitrate, plasma [nitrite] typically peaks within 2-3 hours and remains elevated for a further 6-9 hours before declining towards baseline (14). Therefore, it is recommended that nitrate is consumed approximately 3 hours prior to competition or training. A daily dose of a high-nitrate supplement is required if plasma [nitrite] is to remain elevated. It is presently unclear if, and in what ways, sustained dietary nitrate supplementation might impact upon adaptations to training: on the one hand, increased NO bioavailability might simulate mitochondrial biogenesis; on the other hand, nitrate has anti-oxidant properties that might blunt cellular adaptations. There is the possibility that uncontrolled high doses of nitrate salts might be harmful to health. In contrast, natural sources of nitrate are likely to promote health (15). For this reason, it is recommended that athletes wishing to explore possible ergogenic effects of nitrate supplementation employ a natural, rather than pharmacological, approach (16) Future Directions Although nitrate supplementation appears to hold promise as an ergogenic aid, it is important to recognise that there is still much that we do not know. For example, all of the published studies to date have involved recreational or moderately-trained subjects and it is not known if nitrate supplementation is effective in elite athletes. Also, while the ingestion of 5-6 mmol nitrate appears to be effective, the dose-response relationship between nitrate supplementation and performance remains to be established. The influence of nitrate supplementation on short-term high-intensity exercise, intermittent exercise, and long-term endurance exercise has not been investigated. Finally, it is possible that clinical populations and the elderly may benefit from dietary nitrate supplementation if it can be shown to reduce the O2 cost of the activities of daily living. Nitrate content (mg/100 g fresh weight) Very high (>250) High ( ) Medium (50-100) Low (20-50) Very low (<20) Table 1: Nitrate Content of Selected Vegetables Vegetable Beetroot, spinach, lettuce, rocket, celery, cress, chervil Celeriac, fennel, leek, endive, parsley Cabbage, savoy cabbage, turnip, dill Broccoli, carrot, cauliflower, cucumber, pumpkin Asparagus, aubergine, onion, mushroom, pea, pepper, potato, sweet potato, tomato References 1. Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev 2001;81: Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329: Duncan C, Dougall H, Johnston P, Green S, Brogan R, Smith L, Golden M, Benjamin N. Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat Med 1995;1: Lundberg JO, Govoni M. Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med 2004;37: Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007;191: Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol. 2009;107: Bailey SJ Fulford J, Vanhatalo A, Winyard PG, Blackwell JR, DiMenna FJ, Wilkerson DP, Benjamin N, Jones AM. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol. 2010;109: Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Pavey TG, Wilkerson DP, Benjamin N, Winyard PG, Jones AM. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am J Physiol Regul Integr Comp Physiol. 2010;299:R Lansley KE, Winyard PG, Fulford J, Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Gilchrist M, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study. J Appl Physiol. 2011;110: Lansley KE, Winyard PG, Bailey SJ, Vanhatalo A, Wilkerson DP, Blackwell JR, Gilchrist M, Benjamin N, Jones AM. Acute dietary nitrate supplementation improves cycling time trial performance. Med Sci Sports Exerc. 2011;43: Ferreira LF, Behnke BJ. A toast to health and performance! Beetroot juice lowers blood pressure and the O2 cost of exercise. J Appl Physiol. 2011;110: Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B, Lundberg JO, Weitzberg E. Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab. 2011;13: Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol. 2011;110: Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia A. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 2008;51: Gilchrist M, Winyard PG, Benjamin N. Dietary nitrate--good or bad? Nitric Oxide 2010;22: Lundberg JO, Larsen FJ, Weitzberg E. Supplementation with nitrate and nitrite salts in exercise: a word of caution. J Appl Physiol. 2011;111:

8 3 Dietary strategies to attenuate muscle loss during recovery from injury Kevin Tipton University of Stirling, United Kingdom Injuries are an unfortunate, but unavoidable part of sport. Injuries resulting from physical activity may lead to impairments in muscle size, strength and function, thus preventing optimal training and competitive success for an athlete. Injuries resulting in reduced training and immobilization of the injured limb will lead to loss of muscle mass. Muscle function often follows muscle loss. One aspect of recovery that is often overlooked is nutrition. There has been much written about nutrition for injury, but surprisingly little is directly based on actual research. The focus of the discussion primarily will be on acute, traumatic injuries and the problems associated with limb immobility and muscle loss. Inflammation Immediately following a severe injury, an inflammatory response is initiated. The type and severity of the injury will determine how long this lasts. Given that inflammation may be crucial for healing, elimination of the inflammation is unlikely to be ideal for healing. Thus, excessive supplementation to decrease inflammation may be harmful to healing. Perhaps a first do no harm or risk/benefit concept is the best recommendation. Thus, a well-balanced diet with ample fruits and vegetables likely will not go amiss. Loss of muscle mass during immobility If immobility is required following injury, the most obvious result is loss of muscle function resulting from changes in tendon and loss of muscle mass. The primary metabolic factor leading to muscle loss is a decrease in the rate of muscle protein, particularly myofibrillar protein, synthesis (Glover et al., 2008). Interestingly - perhaps unexpectedly to many - protein breakdown also decreases, at least in humans.thus, nutritional interventions should focus on alleviating, as much as possible, the decrease in rates of muscle protein synthesis so that both the magnitude and duration of periods of negative muscle protein balance will be minimized. Anabolic resistance Another detrimental response to immobilization is that the response of muscle to anabolic stimuli is reduced. A recent investigation from Canada demonstrated that immobility decreases the ability of myofibrillar proteins to respond to increased availability of amino acids (Glover et al., 2008). That study suggests that higher levels of blood amino acids, such as following greater protein intake, do have a greater impact on the rate of muscle protein synthesis than lower levels. Thus, higher doses of protein intake may be important at any given meal, even if the overall protein intake is not necessarily increased. Despite the inability of increased protein intake to alleviate muscle loss during immobility due to anabolic resistance, perhaps there are other nutritional interventions that could - at least potentially - decrease this resistance. Leucine and omega-3 fatty acids (n3fa) may help overcome the resistance of muscle protein synthesis to anabolic stimuli. However, to date, no study has specifically examined the impact of ingesting extra leucine or n3fa with or without protein on muscle protein synthesis and muscle loss in immobilized human muscle. However, it is intriguing to consider and should be studied. Energy intake Another important consideration during injury-induced immobilisation is the appropriate energy intake. The first impulse of most injured athletes likely would be to reduce energy intake quite substantially. By necessity, the total energy expenditure likely will decrease during immobility. Depending on which limb is immobilized, a substantial decrease in total energy expenditure may develop voluntarily, because exercise is more difficult or less convenient, or by necessity as options are limited. However, there are factors to consider that should impact the magnitude of the necessary reduction. First, it is quite clear that during the healing process, energy expenditure is increased - particularly early on and if the injury is severe by up to as much as 20%. So, whereas energy expenditure may still be less than during training, the total may not be as low as many would at first assume. Another factor related to energy intake that may need to be considered by many injured athletes is the energy cost of getting around. If an injury results in the necessity to use crutches, the energy cost is dramatically increased. Ambulation with crutches results in energy expenditures in the range of from 2-3X than that of regular walking (Waters et al., 1987). Thus, depending on how much crutching is done, energy intake may not need to go down by much at all. 8

9 The energy intake during immobilization also may have an impact on muscle protein synthesis. Care should be taken to ensure that any decrease in energy intake is not so much that optimal muscle protein synthesis is unsupported. It is clear that negative energy balance decreases muscle protein synthesis. Decreased synthesis is the major contributor to muscle loss. Clearly, the proper balance should be sought, but perhaps a wee bit of weight gain may be preferable to lack of energy to support proper muscle healing. That decision must be made after careful assessment and consultation between the nutritionist, athlete and coach. Bone, tendons and ligaments Muscle loss is the obvious focus during disuse stemming from injury. However, bone, tendons and ligaments are important for exercise performance and also are impacted negatively by immobilisation. The connective tissue protein, collagen, is the primary component of tendons and ligaments. Decreased tendon collagen synthesis from immobilisation results in changes in tendon mechanical properties. Collagen synthesis rates in tendon and muscle do not respond to increased amino acid levels (Babraj et al., 2005), suggesting that protein feeding would have little impact on tendon healing. Bone collagen synthesis, an important aspect of bone healing, on the other hand, does respond to increased amino acid level. Certainly, sufficient intake of calcium and vitamin D is important for optimal healing. However, other aspects of tendon, bone and ligament healing in relation to collagen remain to be determined. Conclusions and Recommendations Limb immobilisation from injuries has profound implications for muscle and tendon metabolism leading to loss of muscle size, strength and function. During immobilisation, ample energy and protein should be consumed. Potentially, increased leucine intake may be helpful to diminish the anabolic resistance. An overly restrictive energy intake may actually be detrimental. Supplementation of n3fa may help diminish the loss of muscle with immobilization. Phase 1 Immobilization Avoid deficiencies, including energy Protein + Leucine? Sufficient mictonutrient intake (avoid megadoses) Limit alcohol intake Omega-3 FA? Phase 2 Recovery Ample energy Ample Protein Timed protein intake may be advisable Omega-3 FA? Creatine? Avoid chronic drug administration References 1. Babraj JA, Cuthbertson DJ, Smith K, Langberg H, Miller B, Krogsgaard MR, Kjaer M & Rennie MJ (2005a) Collagen synthesis in human musculoskeletal tissues and skin. Am J Physiol Endocrinol Metab 289, E Glover EI, Phillips SM, Oates BR, Tang JE, Tarnopolsky MA, Selby A, Smith K & Rennie MJ (2008) Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion. Journal of Physiology-London 586, Waters RL, Campbell J & Perry J (1987) Energy cost of three-point crutch ambulation in fracture patients. J Orthop Trauma 1,

10 4 Nutritional strategies to support adaptation to high-intensity interval training in team sports Martin J. Gibala McMaster University, Canada Introduction Team sports are characterized by intermittent high-intensity activity patterns. For a given player the metabolic demands will vary depending on many factors including position, playing style and game strategy. Typically however, play consists of short periods of very intense or all out efforts interspersed with longer periods of low-intensity activity, and training programs are at least partly designed to simulate this activity pattern. Much of our knowledge regarding the metabolic demands of training and competition in team sport comes from studies conducted on soccer players (2). Top players can perform brief intense sprints over m while covering a total of km during the course of a match. The intermittent nature of this type of activity requires a high capacity for both aerobic (oxidative) and anaerobic (non-oxidative) energy provision, with skeletal muscle glycogen being a predominant fuel source (11). Metabolic Factors Limiting Performance During Intense Intermittent Exercise Fatigue is a complex, multi-factorial process, but intense intermittent exercise performance can potentially be limited by reduced muscle glycogen availability and/or metabolic by-products associated with the breakdown of this critical fuel source. Almost half the individual muscle fibres examined after a standard soccer match were either completely or nearly completely emptied of glycogen, suggesting that fibre-specific depletion may have impaired force-generating capacity and contributed to the reduced sprint performance observed after the second half of play (11). Another potential mechanism related to glycogen metabolism is the metabolic acidosis that can occur during intense muscle contraction, owing to increased hydrogen ion [H+] accumulation in conjunction with lactate [La-] production. Intense intermittent exercise can cause significant decreases in muscle ph that are associated with impaired metabolic and contractile processes (15), although the acute change in muscle ph reported after a soccer game was modest and unrelated to the decline in sprint performance observed (11). Nonetheless, a high buffering capacity has been associated with enhanced high-intensity exercise performance (15). Skeletal Muscle Adaptation to High-Intensity Interval Training High-intensity interval training (HIT) is infinitely variable and the specific physiological adaptations induced by this form of training are determined by numerous factors including the precise nature of the exercise stimulus, i.e., the intensity, duration and number of intervals performed as well as the nature and duration of the recovery periods (12). Interval intensity is a critical variable that can be quantified in various ways, but HIT generally refers repeated efforts that correspond to 90% of maximal heart rate or 85% of peak oxygen uptake. Numerous short-term HIT protocols mainly cycling or running models have been shown to induce adaptations in skeletal muscle that enhance the capacity for both oxidative and non-oxidative metabolism (6,10). As little as six sessions of HIT over two weeks can increase the content of mitochondrial enzymes, alter substrate metabolism (such that muscle glycogen is used more efficiently during exercise), and improve buffering capacity. Much of this work has been conducted on recreational athletes, and while short-term HIT can also improve performance in high-trained subjects, the precise mechanisms responsible are less clear. It has been suggested that training-induced changes in Na+/K+ pump activity may help to preserve cell excitability and force production, thereby delay fatigue development during intense exercise (10). Potential Nutritional Strategies to Alter HIT Adaptation Guidelines are available regarding the appropriate selection of food and fluids, timing of intake, and supplement choices (1), including recommendations by sports nutrition experts specifically tailored to team sport players (3,14). The general consensus is that athletes should consume a high carbohydrate diet (6-12 g/kg/d) in order to maximize muscle glycogen availability and meet the energy demands of training and competition. However, there is also evidence to suggest that periodic training with reduced carbohydrate availability may augment HIT-induced adaptations in skeletal muscle (7), including one study that applied the train low theory to a team sport model. Morton et al. (13) studied three groups of recreationally active men who performed 6 wk of high-intensity intermittent running. Two groups of subjects trained twice per day, two days per week, such that half of their training was performed in a glycogen-reduced state, whereas the third group trained once per day, four days per week, under conditions of high carbohydrate availability. One of the low groups received a carbohydrate drink prior to the second training session whereas the other group received a non-energetic placebo. The most intriguing finding was that training under conditions of reduced carbohydrate availability (i.e., the low group without the carbohydrate drink) provided an enhanced stimulus for skeletal muscle adaptation, such that 10

11 the increase in oxidative enzymes was superior compared to the two carbohydrate-supplemented conditions. However, the training-induced improvements in a high-intensity intermittent running test were similar among all three groups of subjects. Thus, while periodic training with reduced glycogen availability stimulated greater muscle adaptations, this did not translate into improved performance. Several nutritional supplements have been reported to enhance acute intermittent high-intensity exercise performance (2,14). In contrast, relatively little is known regarding the effect of chronic interventions, and whether supplementation over a period of weeks or months augments HIT-induced physiological remodeling. Limited evidence suggests that two supplements sodium bicarbonate and ß-alanine could potentially augment training adaptations by altering muscle buffering capacity. Edge et al. (5) reported that subjects who ingested sodium bicarbonate over an eight-week highintensity intermittent cycle training program, matched for total volume, experienced greater improvements in time-trial performance compared to a placebo group. Biopsies revealed no differences in several measured metabolites, but the authors posited the sodium bicarbonate group may have experienced greater gains in muscle oxidative capacity. ß-alanine supplementation increases muscle carnosine content and one group has reported greater strength gains after 10 weeks of resistance training (9). However, this is not a universal finding and no studies have directly investigated the potential for chronic ß-alanine supplementation to alter skeletal muscle adaptations to HIT (4). Figure 1. Theoretical model by which nutritional manipulation could augment adaptation to high-intensity interval training (HIT) by optimizing the effect of successive training bouts. While nutrient availability is a potent modulator of many acute responses to exercise (8) at present there is little direct evidence to support the model (i.e., in terms of specific physiological adaptations to HIT that are altered by chronic nutritional manipulation). References 1. American Dietetic Association; Dietitians of Canada; American College of Sports Medicine. Nutrition and athletic performance. Med Sci Sports Exerc. 41: , Bangsbo J, Mohr M, Krustrup P. Physical and metabolic demands of training and match-play in the elite football player. J Sports Sci. 24: , Bishop D. Dietary supplements and team-sport performance. Sports Med. 40: , Derave W, Everaert I, Beeckman S, Baguet A. Muscle carnosine metabolism and beta-alanine supplementation in relation to exercise and training. Sports Med. 40:247-63, Edge J, Bishop D, Goodman C. Effects of chronic NaHCO3 ingestion during interval training on changes to muscle buffer capacity, metabolism, and short-term endurance performance. J Appl Physiol. 101: , Gibala MJ, McGee SL. Metabolic adaptations to short-term high-intensity interval training: a little pain for a lot of gain? Exerc Sport Sci Rev. 36:58-63, Hawley JA, Burke LM. Carbohydrate availability and training adaptation: effects on cell metabolism. Exerc Sport Sci Rev. 38: , Hawley JA, Burke LM, Phillips SM, Spriet LL. Nutritional modulation of training-induced skeletal muscle adaptations. J Appl Physiol. 110: , Hoffman J, Ratamess N, Kang J, Mangine G, Faigenbaum A, Stout J. Effect of creatine and beta-alanine supplementation on performance and endocrine responses in strength/power athletes. Int J Sport Nutr Exerc Metab. 16: , Iaia FM, Bangsbo J. Speed endurance training is a powerful stimulus for physiological adaptations and performance improvements of athletes. Scand J Med Sci Sports. 20 Suppl 2:11-23, Krustrup P, Mohr M, Steensberg A, Bencke J, Kjaer M, Bangsbo J. Muscle and blood metabolites during a soccer game: implications for sprint performance. Med Sci Sports Exerc. 38: , Laursen PB. Training for intense exercise performance: high-intensity or high-volume training? Scand J Med Sci Sports. 20 Suppl 2:1-10, Morton JP, Croft L, Bartlett JD, Maclaren DP, Reilly T, Evans L, McArdle A, Drust B. Reduced carbohydrate availability does not modulate traininginduced heat shock protein adaptations but does upregulate oxidative enzyme activity in human skeletal muscle. J Appl Physiol. 106: , Mujika I, Burke LM. Nutrition in team sports. Ann Nutr Metab. 57 Suppl 2:26-35, Sahlin K. Metabolic factors in fatigue. Sports Med. 13:99-107,

12 5 Practical limitations of ingesting large amounts of carbohydrate during exercise Asker Jeukendrup University of Birmingham, United Kingdom Introduction It is known for a long time that carbohydrate ingestion during prolonged exercise (>2h) can enhance performance. More recently it has been demonstrated that carbohydrate can also improve exercise performance of high intensity and 1 hour duration. The underlying mechanisms may be completely different and therefore these two scenarios will be discussed separately. Carbohydrate feeding and high intensity exercise In 1997 we reported that carbohydrate feeding can also improve performance during shorter duration exercise of higher intensity (5). We studied cyclists who performed a 40 km time trial with or without carbohydrate and they were 1 min faster with carbohydrate. This was a large and unexpected effect for which we did not have an explanation at the time. During exercise of 1 hour duration, hypoglycaemia does not develop and blood glucose concentrations may even rise. Also, it takes time before carbohydrate is absorbed, and transported to and used by the muscle,we calculated that only a small percentage of the carbohydrate ingested during these time trials was actually used as a fuel. This amount was thought to be too small to provide additional fuel and result in a beneficial effect. When we infused glucose directly into the blood, we saw that this glucose was taken up by the muscle and utilised but there was no effect on performance (3). This taught us that providing fuel during this type of exercise is not that important and carbohydrate must somehow influences the brain. In the next study we asked cyclists to repeat the 40km time trial but only rinse their mouth with a carbohydrate solution without swallowing any of it. The carbohydrate used in this study was a non-sweet maltodextrin solution, containing carbohydrate but tasteless. The rinsing protocol was standardized. Subjects would rinse their mouth for 5 seconds with the drink and then spit the drink out into a bowl. They were not allowed to swallow any of the drink. The results were remarkable: performance was improved with the carbohydrate mouth rinse compared with placebo and the magnitude of the effect was the same as the effect we had seen in the early study with carbohydrate ingestion (2)! They were about 1 minute faster, even though none of the carbohydrate had actually Rinsing your mouth with carbohydrate during exercise can improve exercise performance in events lasting 30-60min, even when that carbohydrate is not ingested. entered the body (no carbohydrate is absorbed in the mouth). Perhaps the carbohydrate in the mouth rinse had connected with a receptor in the mouth that subsequently sent a signal to the brain. This signal probably informed the brain that food was on its way and this reduced the perception of effort, making the exercise task easier. These results were reproduced in several other studies (see Table 1). Brain imaging In follow up studies conducted at the University of Birmingham brain scans (fmri) were used to see if there was increased activity in certain areas of the brain with a carbohydrate mouth rinse that was not present with a placebo mouth rinse (4). Indeed the study revealed that with a carbohydrate mouth rinse certain areas of the brain such as the reward centre and areas involved in motor control were activated. The areas investigated included the insula/frontal operculum, orbitofrontal cortex and striatum (Figure 1). During strenuous exercise many afferent signals arising from muscle, joints, lungs, skin and core temperature receptors are sent to the brain. Over time these signals will be perceived as unpleasant and consciously or unconsciously this will lead to an inhibition of motor output. This is often called central fatigue. Athletes tend to regulate their physical activity to keep their levels of discomfort within acceptable limits. It is not clear exactly which pathways are involved in this inhibitory activity but it seems plausible that the signals arising from the carbohydrate receptors in the mouth are counteracting some of these negative signals. Perhaps the sensors are telling the brain that you have nothing to worry about, because energy is on its way. The exact nature of the communication is unknown but the studies clearly show that there is a huge amount of communication between mouth and brain, even before any carbohydrate is delivered! 12

13 Figure 1: A simplified model of the actions of a carbohydrate mouth rinse. Carbohydrate receptors in the mouth send positive signals to three main areas in the brain (insula/frontal operculum, the orbitofrontal cortex and the striatum). These signals are integrated with negative signals from the periphery and an appropriate motor output is generated. Authors Exercise Effect (+ is enhancing) Performance effect Carter et al (2) ~1h cycling +2.9% Improved Pottier et al (8) ~1h cycling +3.7% Improved Rollo et al (10) 30 min running +2.0% Improved Rollo et al (9) 1h running +2.0% Improved Chambers et al (4) ~1h cycling +1.9% Improved Beelen et al (1) ~1 h cycling +0.5% (ns) No effect Witham et al (11) ~1h running -0.3% No Effect Table 1: Summary of studies currently in the literature that investigated the effects of a carbohydrate mouth rinse on performance So what does all this mean in terms of practical advice? Well, it appears that it is not necessary to take on board large amounts of carbohydrate during exercise lasting approximately 30 min to 1 hour. Simple rinsing your mouth with carbohydrate may be sufficient. I have already seen athletes with lolly pops and little sweets in their mouth before and during competition. Maybe that is a practical solution? It must also be said that in most conditions the performance effects with the mouth rinse were similar to ingesting the drink, so there does not seem to be a disadvantage of taking the drink, although occasionally athletes may complain of gastro-intestinal distress when taking on board too much fluid. Of course when the exercise is more prolonged (2h or more), carbohydrate becomes a very important fuel and it is essential to take carbohydrate on board. For a more detailed review see (7). Carbohydrate feeding and prolonged exercise (>2h) During more prolonged exercise (>2h) carbohydrate work in a different way and they provide an alternative substrate thereby sparing the body s small carbohydrate stores. The ingested carbohydrate can prevent a drop in blood glucose concentration and can help to maintain high rates of carbohydrate oxidation which is necessary to maintain relatively high exercise intensity. Several factors have been suggested to influence the oxidation of carbohydrate from a drink including feeding schedule, type and amount of carbohydrate ingested and the exercise intensity. Some of these factors have only small effects (for example timing), whereas other factors have major effects on exogenous carbohydrate oxidation (amount, type). Some types of carbohydrate are oxidized more readily than others. Roughly they can be divided into two categories: carbohydrates that can be oxidized at rates up to 60 g/h and carbohydrates that can be oxidized at rates up to 30 g/h (see table 1). 13

14 Slowly Oxidized Carbohydrates (~30 g/h) (not recommended) Fructose (a sugar found in honey, fruits, etc.) Galactose (a sugar found in sugar beets) Isomaltulose (a sugar found in honey and sugarcane) Trehalose (a sugar found in microorganisms) Amylose (from starch breakdown) Rapidly Oxidized Carbohydrates (~60 g/h) Glucose (a sugar formed by the breakdown of starch) Sucrose (table sugar glucose plus fructose) Maltose (two glucose molecules) Maltodextrins (from starch breakdown) Amylopectin (from starch breakdown) Very rapidly oxidized carbohydrate mixes (90g/h) Glucose (60 g/h) + Fructose (30 g/h) Glucose (60 g/h) + Fructose (30 g/h) Glucose (60 g/h) + sucrose (15 g/h) + fructose (15 g/h) Table 2: Oxidation of different carbohydrates The optimal amount is likely to be the amount of carbohydrate that results in the highest carbohydrate oxidation rates without causing gastro-intestinal problems. However, ingesting more does not always result in higher oxidation. When carbohydrate intake is increased from very little to about g/h, there is generally an increase in the oxidation of the carbohydrate. However if the intake is increased further there is no additional oxidation of the carbohydrate. Therefore we have always concluded that there is no point taking more than grams of carbohydrate per hour. Multiple transportable carbohydrates The reason that exogenous carbohydrate oxidation is limited to approximately 60 grams per hour is most likely due to a limitation in intestinal absorption. To understand this we will have to study the process of absorption in a bit more detail. Absorption is basically the transport of nutrients from the inside of the intestine (the lumen) to the outside (the inside of your body where it will be carried away by the blood stream). Glucose is transported by a specific transport protein called SGLT1 (see Figure 2). Figure 2: Glucose and fructose absorption occurs through 2 different transporters in the intestine. Glucose use the sodium dependent transporter SGLT1 and fructose uses GLUT5. We believe that this transporter is working at full capacity when g of glucose is ingested per hour. So ingesting more will not result in more absorption because the transporter is saturated. So in order to get more carbohydrates into the blood stream, another transporter has to be used and it happens that fructose uses a different transporter called GLUT5. So if we give enough glucose to saturate the SGLT1 transporter and we give fructose in the same drink, we should be able to get more carbohydrates into the body by using GLUT5. We have since performed studies that have confirmed that oxidation of the mixtures of carbohydrate can be oxidized at much higher rates than single carbohydrates! In fact we have observed oxidation values as high as 105 g/h! This is 75% higher than what was previously thought to be the absolute maximum! Of course the intake of carbohydrate has to be very high as well 14

15 Multiple transportable carbohydrates (i.e. glucose and fructose) can increase exogenous carbohydrate oxidation, fluid delivery, reduce fatigue, improve performance and reduce gastro-intestinal discomfort and this may not always be practical. In most of the studies we have used blends that were glucose:fructose or maltodextrin:fructose in a 2:1 ratio. It is possible to make up these drinks yourself although some sports nutrition products with this composition are now starting to emerge on the market! In addition to better carbohydrate delivery with these carbohydrate blends, fluid delivery also seems to be improved. We have shown that with a glucose+fructose solution fluid delivery was significantly faster than with a glucose solution. In the lab, we have also consistently observed that the carbohydrate blends are better tolerated than the single carbohydrates. Finally, in hot conditions it is more difficult to absorb the carbohydrate but we have seen improvements with glucose+fructose drinks suggesting that these carbohydrate blends are particularly effective in hot conditions. As mentioned before, in order to achieve these high oxidation rates, large amounts of carbohydrate have to be ingested. Some of the laboratory studies used extreme amounts of carbohydrates which may not be possible in a competition situation. Therefore the advice for long races (>3h) would be to aim for an intake of 90 grams of carbohydrate per hour and this carbohydrate must be a mixture of glucose and fructose, maltodextrin and fructose or glucose, sucrose and fructose (Table 2). Most of those mixtures would be very sweet and the advantage of using maltodextrins is that it reduces this sweetness. It is important to remember that if a single carbohydrate is ingested at that rate, it will accumulate in the intestine and is likely to cause gastro-intestinal distress. For a more detailed review see (6). It is possible to ingest carbohydrate at that rate by selecting different carbohydrate sources. The appropriate intake can be achieved in various ways and recent studies have shown that glucose:fructiose from gels and energy bars is just as effective in increasing exogenous carbohydrate oxidation rates as ingesting a drink. This means that the athlete can mix and match to get the desired amount of carbohydrate. The exact choices will be down to personal preference and tolerance. Provide 90 g/h (up to 120 g/h) of a carbohydrate blend This blend could be glucose+fructose (or maltodextrin+fructose) If you use a normal sports drink (one carbohydrate) g/h A mixture of 2:1 glucose+fructose (or maltodextrin+fructose) seems to work and cause minimal GI distress The carbohydrate can come from drinks, gels or bars and the athlete can mix and match depending on personal preference and tolerance. Add sodium ( g sodium chloride (i.e. table salt) or 5-15 g sodium citrate Add water depending on conditions (try to replace sweat losses and avoid major weight loss) Never experiment in an important race! Always try new strategies in training first! Table 3: Guidelines for carbohydrate intake during exercise >3h All recommendations for carbohydrate intake are summarized in Table 4. From this table it becomes obvious that the optimal carbohydrate type and amount is dependent on the duration of the exercise bout. The gut is extremely adaptable. Practice your carbohydrate intake strategy in training! Do not experiment in competition. Table 4: Recommendations for carbohydrate intake during various durations of exercise 15

16 References 1. Beelen M, Berghuis J, Bonaparte B, Ballak SB, Jeukendrup AE, and van Loon LJ. Carbohydrate mouth rinsing in the fed state: lack of enhancement of time-trial performance. Int J Sport Nutr Exerc Metab 19: , Carter JM, Jeukendrup AE, and Jones DA. The effect of carbohydrate mouth rinse on 1-h cycle time trial performance. Med Sci Sports Exerc 36: , Carter JM, Jeukendrup AE, Mann CH, and Jones DA. The effect of glucose infusion on glucose kinetics during a 1-h time trial. Med Sci Sports Exerc 36: , Chambers ES, Bridge MW, and Jones DA. Carbohydrate sensing in the human mouth: effects on exercise performance and brain activity. J Physiol 587: , Jeukendrup A, Brouns F, Wagenmakers AJ, and Saris WH. Carbohydrate-electrolyte feedings improve 1 h time trial cycling performance. Int J Sports Med 18: , Jeukendrup AE. Carbohydrate and exercise performance: the role of multiple transportable carbohydrates. Curr Opin Clin Nutr Metab Care 13: , Jeukendrup AE and Chambers ES. Oral carbohydrate sensing and exercise performance. Curr Opin Clin Nutr Metab Care 13: , Pottier A, Bouckaert J, Gilis W, Roels T, and Derave W. Mouth rinse but not ingestion of a carbohydrate solution improves 1-h cycle time trial performance. Scand J Med Sci Sports, Rollo I, Cole M, Miller R, and Williams C. The Influence of Mouth-Rinsing A Carbohydrate Solution on 1 Hour Running Performance. Med Sci Sports Exerc, Rollo I, Williams C, Gant N, and Nute M. The influence of carbohydrate mouth rinse on self-selected speeds during a 30-min treadmill run. Int J Sport Nutr Exerc Metab 18: , Whitham M and McKinney J. Effect of a carbohydrate mouthwash on running time-trial performance. J Sports Sci 25: ,

17 6 Use of oral ph-buffers to improve performance during high intensity exercise Louise M Burke Australian Institute Of Sport, Canberra, Australia Bicarbonate is an extracellular anion with important roles in maintaining ph and electrolyte gradients between intra and extracellular environments. Consumption of large amounts of dietary bicarbonate ( bicarbonate loading ) can temporarily increase blood bicarbonate concentrations and ph, enhancing the buffering capacity of the extracellular space and, indirectly, the active muscle. High rates of anaerobic glycolysis in the muscle can produce hydrogen ions in excess of intracellular buffering capacity; however, the enhancement of the extracellular bicarbonate pool and ph increases the efflux of the accumulating H+ in the muscle into the extracellular space for disposal. Bicarbonate loading has been used as an ergogenic strategy for sporting events which are dependent on the generation of energy via anaerobic glycolysis. A simplistic view of these events is that they are limited by the body s capacity to manage the progressive increase in the acidity of the intracellular environment. What is the best way to bicarbonate load and what are the down sides? The most common way to bicarbonate load is to ingest an acute dose in the hours before the targeted exercise session. The typical protocol is a dose of 300 mg per kg of the athlete s body mass (i.e. ~ 20 g for a 70 kg athlete), taken 1-2 hours prior to exercise. The most widely available form of bicarbonate is the common household/cooking product, sodium bicarbonate. Many athletes find, however, that it is unpalatably salty. Alternative options include using pharmaceutical urinary alkaliser products used to treat urinary tract infections (e.g. flavoured powders such as Ural TM or capsules such as Sodibic TM). Citrate has also been used as a potential buffering agent; however, it appears to be less effective in enhancing performance and associated with greater side-effects (Carr et al. 2011a). The major disadvantage of bicarbonate supplementation is the possibility of gastro-intestinal (GI) upsets with symptoms such as nausea, stomach pain, diarrhoea and vomiting. This is a serious practical consideration for athletes in a competition setting. The previous advice to athletes to overcome this issue was to consume the bicarbonate dose with plenty of water or other fluids to reduce the risk of hyperosmotic diarrhea. We recently undertook a systematic study of various protocols of bicarbonate supplementation, varying the time taken to consume the load (spreading it over min), the form of the bicarbonate (flavoured powder or capsules) and the co-ingestion of various amounts of fluid or food with the bicarbonate (Carr et al. 2011b). Of the protocols we tested, the best strategy to optimise blood alkalosis and to reduce the occurrence of gastro-intestinal symptoms was to consume bicarbonate capsules in a spread-out protocol, commencing min before the start of exercise with a small meal composed of carbohydrate-rich foods and some fluid. Athletes should practise with strategies to fine-tune the protocols that work best for them. Athletes should also consider the potential for other side-effects. The use of sodium bicarbonate means that large quantities of sodium are ingested, which when taken with fluid can lead to a temporary fluid retention or hyper-hydration. Although useful in some sports in which high rates of sweat loss are otherwise likely to lead to a significant fluid deficit, the body mass gain may be unwelcome in weight-bearing sports (e.g. cycling or running uphill, clearing steeplechase barriers). Although bicarbonate loading is a legal strategy in competitive sport, it can produce urine with a ph that falls outside the range that is acceptable for laboratory testing. If this occurs, the athlete may need to wait several hours before they can produce a urine sample with ph levels that are acceptable to drug testing authorities. This may disrupt the athlete s post-event routine. Which sporting events can benefit? Theoretically, bicarbonate loading could assist sporting events which are limited by high rates of generation of energy via anaerobic glycolysis. The obvious candidates are events involving sustained high-intensity exercise lasting 1-7 min, such as middle distance swimming, middle distance running and rowing events. However, bicarbonate loading may also benefit the performance of longer events (e.g min) involving sustained exercise just below the so-called anaerobic threshold if it can support the athlete for periods in which the pace is increased (i.e. surges during the event, the final sprint to the end). Similarly, the repeated-sprint performance typical of team and racquet sports, and even combative sports, may also be enhanced by improved buffering. Over the past 40 years, this potential has been investigated in a large number of studies with various levels of application to real-life sport. Ideally, such research would involve highly-trained competitors, exercise protocols with high reliability and ecological validity, and implementation of nutrition strategies that simulate real-world practices (e.g. typical preevent meals, use of other nutritional supplements, weight-making tactics). Although few studies achieve all such charac- 17

18 teristics, a summary of relevant investigations of bicarbonate supplementation and sports performance shows reasonable but not unanimous support for the benefits of bicarbonate loading for the sporting scenarios previously mentioned ( However, this literature does not address some practical issues. For example, studies may investigate the execution of a single exercise task without including a warm-up (which usually involves high-intensity efforts) or the requirement to repeat this task (as occurs in sports in which heats, semi-finals and finals decide the overall outcome). There are few studies of the combined use of supplements - for example, bicarbonate supplementation with acute use of caffeine and nitrate or the chronic use of creatine and beta-alanine. It is important to know if the effects are additive, counteractive or synergistic. Reviews of the larger body of literature have concluded that bicarbonate loading can be of benefit to some athletes, particularly the so-called power events which last 1-7 min and operate at very high power outputs supported by high rates of anaerobic glycolysis. An early meta-analysis (Matson & Tran 1993) concluded that the ingestion of sodium bicarbonate has a moderate positive effect on exercise of 30 s to 7 min, with the mean performance of the bicarbonate trial being 0.44 standard deviations better than the placebo trial. Ergogenic effects were related to the level of metabolic acidosis achieved during the exercise, showing the importance of attaining a threshold ph gradient across the cell membrane from the combination of the accumulation of intracellular H+ and the extracellular alkalosis. Another narrative review (Requena et al. 2005) concluded that athletes competing in high intensity sports involving fast motor unit activity and large muscle mass recruitment (athletics events, cycling, rowing, swimming and many team sports) could benefit from bicarbonate loading. Finally, a recent comprehensive meta-analysis involved 38 studies and 137 estimates of the effect of sodium bicarbonate supplementation on exercise. It found a possibly moderate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 0.3 g/kg/bm) in a single 1-min sprint in male athletes (Carr et al. 2011b). Study and subject characteristics had the following modifying small effects: an increase of 0.5% (±0.6%) with a 0.1 mg/kg/bm increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g min); reductions of 1.1% (±1.1%) with non-athletes and 0.7% (±1.4%) with females. There was a small correlation between performance and pre-exercise increase in blood bicarbonate. Alternative ways to use bicarbonate in sport A variation of the acute loading regime is to load bicarbonate in small doses over consecutive days prior to a competitive event or race. An advantage of this method is that the muscle extracellular buffering capacity is enhanced with a potentially reduced risk of gastrointestinal distress. Typically, a slightly larger dose (500 mg/kg/d) is divided into 3 or 4 smaller doses over the day for 3-5 days prior to the exercise bout. Initial studies showed that several days of such dosing builds up blood buffer levels that persist for at least 24 hours after the last dose (McNaughton & Thompson 2001). Therefore, this protocol could be used to achieve a loading preparation for multiple events over the same or successive days. Furthermore, since the bicarbonate doses are spread over the day, they may be timed to avoid high-risk periods for gut upsets (i.e. before exercise). It may also be possible to finish loading a day before an important race and further reduce the potential for GI problems. Unfortunately, there are few studies of the effectiveness of this serial loading on sports performance. Another line of investigation is the chronic use of bicarbonate to support the training process. Edge and co-workers`(2006) studied the effects of chronically loading with bicarbonate (400 mg/kg BM) prior to interval training sessions (3/week) over an 8 week training block in moderately trained female athletes. The bicarbonate supplemented group showed substantially greater improvements in both lactate threshold (26% vs. 15%) and time to exhaustion (164% vs. 123%) than a placebo group. The authors speculated that training intensity rather than accumulation of hydrogen ions is important in increasing endogenous muscle buffering capacity, and that buffering protocols may reduce damage to muscle proteins. Summary Bicarbonate loading is an evidence based supplementation practice that has the potential to enhance the performance of various sports. While this potential has been realised and practised by many athletes, it is likely that there are still many ways in which further benefits can be developed and individualised for specific athletes or specific events. 18

19 References 1. Carr AJ, Hopkins WG, Gore CJ. HYPERLINK Effects of acute alkalosis and acidosis on performance: a meta-analysis. Sports Med. 2011a; 41(10): Carr AJ, Slater GJ, Gore CJ, Dawson B, Burke LM. HYPERLINK Effect of sodium bicarbonate on [HCO3-], ph, and gastrointestinal symptoms. Int J Sport Nutr Exerc Metab. 2011b 21(3): Edge, J, Bishop D, Goodman C. Effects of chronic NaHCO3 ingestion during interval training on changes to muscle buffer capacity, metabolism and short-term endurance performance. J Appl Physiol. 2006;101: Matson LG, Tran ZT. Effects of sodium bicarbonate ingestion on anaerobic performance: a meta-analytic review. Int J Sport Nutr 1993;3: McNaughton L, Thompson D. Acute versus chronic sodium bicarbonate ingestion and anaerobic work and power output. J Sports Med Phys Fitness 2001;41: Requena, B, Zabala M, Padial P, Feriche B. Sodium bicarbonate and sodium citrate: ergogenic aids? J Strength Cond Res. 2005;19:

20 7 Dietary protein intake to allow post-exercise muscle reconditioning Luc J.C. van Loon University Of Maastricht, Netherlands Introduction With athletes approaching their limits with respect to training volume and intensity, good nutritional practice becomes even more important. This has renewed the interest among athletes, coaches, and exercise physiologists in the role of nutrition on the skeletal muscle adaptive response to exercise training. A single bout of exercise stimulates both muscle protein synthesis and, to a lesser extent, muscle protein breakdown. However, post-exercise protein balance will remain negative in the absence of food intake. Dietary protein ingestion stimulates skeletal muscle protein synthesis, inhibits protein breakdown and, as such, stimulates muscle protein accretion following both resistance (4, 7, 11, 16, 17) as well as endurance (6, 12) type exercise. This will lead to a greater skeletal muscle adaptive response to each successive exercise bout, resulting in more effective muscle reconditioning. Despite limited evidence, some basic guidelines can be defined regarding the preferred amount, source, and timing of dietary protein that should be ingested to allow proper post-exercise muscle reconditioning. Amount of dietary protein Though it has been well established that dietary protein ingestion effectively stimulates muscle protein synthesis rates both at rest and following exercise, there is much less information on the amount of dietary protein that should be ingested to maximize post-exercise muscle protein synthesis rates. Moore et al. (13) reported that post-exercise muscle protein synthesis rates increased with the ingestion of greater amounts of protein, reaching maximal stimulation after ingesting 20 g of (egg) protein. The authors speculated that athletes should ingest this amount of dietary protein 5-6 times daily to maximize skeletal muscle protein accretion. Source of dietary protein Various studies have reported improvements in post-exercise protein balance and/or greater muscle protein synthesis rates following the ingestion of whey protein (15), casein protein (15), soy protein (18), casein protein hydrolysate (10, 11), egg protein (13), and whole-milk and/or fat-free milk (5, 18). To date few studies have tried to assess differences in the post-exercise muscle protein synthetic response to different types of protein. Milk protein and its main isolated constituents, whey and casein, offer an anabolic advantage over soy protein (14, 18). Furthermore, whey protein seems to induce a greater muscle protein synthetic response when compared with casein (14). The different muscle protein synthetic response is likely attributed to differences in protein digestion and absorption kinetics (8, 15) as well as amino acid composition (14). Carbohydrate co-ingestion In the endurance athlete, rapid restoration of depleted muscle glycogen stores is often a priority after completing a single bout of exercise. As a consequence, endurance trained athletes generally focus on carbohydrate ingestion to accelerate post-exercise recovery. Co-ingestion of small amounts of protein can accelerate muscle glycogen repletion when less than optimum amounts of carbohydrate (<1.0 g/kg bodyweight/h) are ingested during post-exercise recovery (1). Ingestion of carbohydrate during post-exercise recovery inhibits exercise stimulated muscle protein breakdown. Therefore, resistance athletes often ingest a combination of protein plus carbohydrate during recovery from exercise. However, co-ingesting carbohydrate does not further increase post-exercise muscle protein synthesis rates when ample protein is already ingested (7). Though carbohydrate co-ingestion is not required to maximize post-exercise muscle protein synthesis rates, it is likely that a little carbohydrate will attenuate the post-exercise rise in muscle protein breakdown rate, thereby improving protein balance (4). Timing of dietary protein ingestion The timing of protein ingestion represents another important factor stimulating post-exercise muscle anabolism. A more direct provision of dietary protein following cessation of exercise has been shown to result in a more positive protein balance, when compared to protein provides several hours after exercise. Furthermore, recent studies suggest that carbohydrate and protein co-ingestion prior to and/or during exercise may further augment post-exercise muscle protein accretion (2, 17). The latter has been attributed to a more rapid supply of amino acids to the muscle during the acute stages of post-exercise recovery. However, protein ingestion prior to and/or during exercise already stimulates muscle protein synthesis during exercise, thereby creating a larger timeframe for muscle protein synthesis to be elevated (2, 3, 9). 20

21 More work is needed to address the relevance of the potential to stimulate muscle protein synthesis during exercise. Furthermore, the benefits of post-exercise nutrition on muscle protein synthesis during overnight recovery remain to be explored (1). Conclusion Protein ingestion following resistance and endurance type exercise activities will allow a more efficient adaptive response to each successive exercise bout, resulting in improved muscle tissue reconditioning. Whey protein seems most effective in stimulating acute post-exercise muscle protein synthesis. About 20 g protein should be provided during and/ or immediately after each exercise bout to allow maximal post-exercise muscle protein synthesis rates. Co-ingestion of large amounts of carbohydrate is not needed to further augment post-exercise muscle protein synthesis rates. Nutritional recommendations for the athlete Provide sufficient protein (20-25 g) with each main meal Ingest g dietary protein during or immediately after an exercise session Whey forms an excellent source of dietary protein to promote post-exercise recovery Co-ingest carbohydrate based on the need to replete liver and muscle glycogen stores Co-ingest some protein during more prolonged exercise activities (~0.15 g/kg bodyweight/h) Figure 1 Dose reponse relationship between the amount of protein ingested and post-exercise muscle protein synthesis (muscle FSR). Values represent means±sem. Means with different letters are significantly different from each other. Figure drawn based on the work by Moore et al., Figure 2 Practical recommendations for the athlete regarding dietary protein consumption during and/or after an exercise session. References 1. Beelen M, Burke LM, Gibala MJ, and van Loon LJ. Nutritional strategies to promote postexercise recovery. Int J Sport Nutr Exerc Metab 20: , Beelen M, Koopman R, Gijsen AP, Vandereyt H, Kies AK, Kuipers H, Saris WH, and van Loon LJ. Protein coingestion stimulates muscle protein synthesis during resistance-type exercise. Am J Physiol Endocrinol Metab 295: E70-77, Beelen M, Zorenc A, Pennings B, Senden JM, Kuipers H, and van Loon LJ. The impact of protein co-ingestion on muscle protein synthesis during continuous endurance type exercise. Am J Physiol Endocrinol Metab E945-E954, Borsheim E, Cree MG, Tipton KD, Elliott TA, Aarsland A, and Wolfe RR. Effect of carbohydrate intake on net muscle protein synthesis during recovery from resistance exercise. J Appl Physiol 96: , Elliot TA, Cree MG, Sanford AP, Wolfe RR, and Tipton KD. Milk ingestion stimulates net muscle protein synthesis following resistance exercise. Med Sci Sports Exerc 38: , Howarth KR, Moreau NA, Phillips SM, and Gibala MJ. Coingestion of protein with carbohydrate during recovery from endurance exercise stimulates skeletal muscle protein synthesis in humans. J Appl Physiol 106: , Koopman R, Beelen M, Stellingwerff T, Pennings B, Saris WH, Kies AK, Kuipers H, and van Loon LJ. Coingestion of carbohydrate with protein does not further augment postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab 293: E , Koopman R, Crombach N, Gijsen AP, Walrand S, Fauquant J, Kies AK, Lemosquet S, Saris WH, Boirie Y, and van Loon LJ. Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein. Am J Clin Nutr 90: , Koopman R, Pannemans DL, Jeukendrup AE, Gijsen AP, Senden JM, Halliday D, Saris WH, van Loon LJ, and Wagenmakers AJ. Combined ingestion of protein and carbohydrate improves protein balance during ultra-endurance exercise. Am J Physiol Endocrinol Metab 287: E , Koopman R, Verdijk L, Manders RJ, Gijsen AP, Gorselink M, Pijpers E, Wagenmakers AJ, and van Loon LJ. Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men. Am J Clin Nutr 84: , Koopman R, Wagenmakers AJ, Manders RJ, Zorenc AH, Senden JM, Gorselink M, Keizer HA, and van Loon LJ. Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects. Am J Physiol Endocrinol Metab 288: E , Levenhagen DK, Gresham JD, Carlson MG, Maron DJ, Borel MJ, and Flakoll PJ. Postexercise nutrient intake timing in humans is critical to recovery of leg glucose and protein homeostasis. Am J Physiol Endocrinol Metab 280: E , Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, and Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr 89: , Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, and Phillips SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol 107: , Tipton KD, Elliott TA, Cree MG, Wolf SE, Sanford AP, and Wolfe RR. Ingestion of casein and whey proteins result in muscle anabolism after resistance exercise. Med Sci Sports Exerc 36: , Tipton KD, Ferrando AA, Phillips SM, Doyle D, Jr., and Wolfe RR. Postexercise net protein synthesis in human muscle from orally administered amino acids. Am J Physiol 276: E , Tipton KD, Rasmussen BB, Miller SL, Wolf SE, Owens-Stovall SK, Petrini BE, and Wolfe RR. Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. Am J Physiol Endocrinol Metab 281: E , Wilkinson SB, Tarnopolsky MA, Macdonald MJ, Macdonald JR, Armstrong D, and Phillips SM. Consumption of fluid skim milk promotes greater muscle protein accretion after resistance exercise than does consumption of an isonitrogenous and isoenergetic soy-protein beverage. Am J Clin Nutr 85: ,

22 8 Nutritional support to maintain proper immune status during intense training Michael Gleeson Loughborough University, United Kingdom Introduction Athletes who engage in intense training or who have recently competed in endurance race events appear to be at increased risk of developing symptoms of minor respiratory illness (1). The most common illnesses in athletes are viral infections of the upper respiratory tract (i.e. the common cold) but athletes can also develop similar symptoms (e.g. sore throat) due to allergy or inflammation caused by inhalation of cold, dry or polluted air (2). In themselves, these symptoms are generally trivial, but no matter whether the cause is infectious or allergic inflammation, they can cause an athlete to interrupt training, under-perform or even miss an important competition. Prolonged bouts of strenuous exercise have been shown to result in transient depression of white blood cell functions and it is suggested that such changes create an open window of decreased host protection, during which viruses and bacteria can gain a foothold, increasing the risk of developing an infection (3). Other factors such as psychological stress, lack of sleep and malnutrition can also depress immunity and lead to increased risk of infection (Figure 1). There are also some situations in which an athlete s exposure to infectious agents may be increased, which is the other important determinant of infection risk. Figure 1: Causes of increased infection risk in athletes Maintaining an effective immune system Adequate nutrition and in particular appropriate intakes of energy, protein, vitamins and minerals are essential to maintain the body s natural defences against disease causing viruses and bacteria. Thus, athletes are best advised to consume a sound diet that meets their energy needs and contains a variety of foods and the key to maintaining an effective immune system is to avoid deficiencies of the nutrients that play an essential role in immune cell functions. Inadequate protein-energy intake or deficiencies of certain micronutrients (e.g. iron, zinc, magnesium, manganese, selenium, copper and vitamins A, C, D, E, B6, B12 and folic acid), decrease immune defences against invading pathogens and make the individual more susceptible to infection (4). Even short-term dieting in athletes who continue to train hard and results in a loss of a few kilograms body mass over the course of a few weeks can result in significant falls in several aspects of immune function. Thus, care should be taken to ensure adequate protein (and micronutrient) intakes during periods of intentional weight loss and it should be recognised that athletes undergoing weight reduction are likely to be more prone to infection. In general, a broad-range multivitamin/mineral supplement is the best choice to support a restricted food intake, and this may also be suitable for the travelling athlete in situations where food choices and quality may be limited. It has only recently been recognised that Vitamin D plays an important role in up-regulating immunity and this is a concern as Vitamin D insufficiency is common in athletes (5) especially if exposure to natural sunlight is limited. 22

23 Nutrition strategies to limit exercise-induced immune depression Certain supplements may boost immune function and reduce infection risk in individuals who are subjected to stress (6). While there are many nutritional supplements on the market that are claimed to boost immunity (Table 1), such claims are often based on selective evidence of efficacy in animals, in vitro experiments, children, the elderly or clinical patients in severe catabolic states and direct evidence for their efficacy for preventing exercise-induced immune depression or improving immune system status in athletes is usually lacking. Carbohydrate beverages The best evidence supports the implementation of appropriate rest periods within the training micro-cycle and the use of a high carbohydrate diet and carbohydrate ingestion (about g/hour) during prolonged workouts, which lowers circulating stress hormone levels and delays the appearance of symptoms of overreaching during intensive training periods (7). This reduces the impact of prolonged exercise on several though not all, aspects of immune function although evidence is currently lacking to demonstrate that this translates to a reduced incidence of illness symptoms following competitive events. Antioxidant vitamins Although it is not known whether hard training increases the need for dietary antioxidants as the body naturally develops an effective defence with a balanced diet and endogenous antioxidant defences actually improve with exercise training some recent evidence suggests that regular intake of relatively high doses of antioxidant vitamins can also reduce the stress response to prolonged exercise (5). These studies have used combinations of vitamin C and E, or vitamin C alone, and provide a possible mechanism to explain earlier findings of a benefit of vitamin C supplementation in reducing the incidence of respiratory illness symptoms in individuals who took part in ultramarathon races (8). Excessive supplementation with other antioxidants cannot be recommended because there is little evidence of benefit, while it is known that over-supplementation can actually diminish the body s natural antioxidant defence system and may even impair or diminish some adaptations to training a hotly debated topic at present. Ensuring that the diet contains plenty of fresh fruits and vegetables is probably the wisest option. Immunonutrition Support for Athletes Various other nutritional supplements have been tested for their capacity to reduce immune changes following prolonged strenuous exercise and thus lower infection risk. This strategy is similar to the immunonutrition support provided to patients recovering from trauma and surgery, and to the frail elderly. Supplements studied thus far in human athletes include zinc, omega-3 polyunsaturated fatty acids, herbal extracts (e.g. Echinacea), plant sterols and polysaccharides (e.g. β-glucan), glutamine, branched-chain amino acids, and bovine colostrum. Although some supplements (e.g. zinc and some herbals) may reduce severity or duration of illness if taken close to the onset of symptoms, thus far, results have been generally disappointing with regard to reducing infection incidence (see Table 1), and focus has shifted to examining the effects of probiotics and plant polyphenols (e.g. quercetin). Quercetin The physiologic effects of dietary flavonols such as quercetin are of great current interest due to their antioxidant, antiinflammatory, anti-pathogenic, cardioprotective, and anticarcinogenic activities. Animal studies indicate that 7 days of quercetin feeding improves survival from influenza virus innoculation. A recent human study (9) showed that 1,000 mg/day quercetin for 3 weeks significantly increased plasma quercetin levels and reduced respiratory illness during the 2-weeks following a 3-day period of exhaustive exercise in cyclists. Immune dysfunction, inflammation, and oxidative stress, however, were not altered suggesting that quercetin may have exerted direct anti-viral effects. Probiotics In recent years several studies have examined the efficacy of oral probiotics in athletes and some of these, particularly those containing Lactobacillus strains, have shown some promise. Often called the friendly bacteria, probiotics are live microorganisms which when administered in adequate amounts, modify the bacterial population that inhabits our gut and modulate immune function by their interaction with the gut-associated lymphoid tissue, leading to positive effects on the systemic immune system. Some well-controlled studies in athletes have indicated that daily probiotic ingestion results in fewer days of respiratory illness and lower severity of URTI symptoms (10-13). Thus, probiotic supplements may convey some benefit to immunity and reduce URTI incidence as well as reducing gastrointestinal problems (a common complaint of endurance runners). Further large-scale studies are needed to confirm that taking probiotics can reduce the number of training days lost to infection and to determine the most effective probiotics as their effects are strainspecific. 23

24 Summary In conclusion, it is difficult to make firm judgments about which nutritional supplements are really effective in boosting immunity or reducing infection risk in athletes. It is safe to say with reasonable confidence that individual amino acids, colostrum, echinacea, vitamin E and zinc are unlikely to be of benefit. The ingestion of adequate amounts of protein and micronutrients in the diet (Vitamin D status may be of particular concern), intake of carbohydrate during exercise and daily consumption of probiotic and quercetin supplements currently offer the best chance of success. This approach is likely to be most effective in those individuals who are particularly prone to illness. Factors other than nutrition that may lower infection risk in athletes include reducing other life stresses, maintaining good oral and skin hygiene, obtaining adequate rest and sleep, avoiding sick people, and spacing prolonged training sessions and competitions as far apart as possible. Table 1: Immune boosting supplements claims and the scientific evidence for efficacy in humans Nutrition supplement Evidence Arginine Beta(β)-glucan Bovine colostrum Carbohydrate Curcumin Echinacea Asian ginseng (Panax ginseng) Probiotics Quercetin Immune boosting properties (claims) Nonessential amino acid that is a precursor in the synthesis of nitric oxide which is a cytotoxic molecule capable of destroying microorganisms and virus-infected cells. Claimed to enhance immune response and increase resistance to infection. There is no evidence that arginine has any effect on immunity in healthy humans. A polysaccharide derived from the cell wall of yeast, fungi, algae, and oats that stimulates immunity. Oral feedings of oat β-glucan can offset exercise-induced immune suppression and decrease susceptibility to upper respiratory tract infection in mice exercising heavily for three days. No evidence yet of a similar benefit for human athletes. First milk of the cow that contains antibodies, growth factors and cytokines. Claimed to boost mucosal immunity and increase resistance to infection. One study suggests an effect in elevating salivary IgA in human endurance runners but no evidence that this modifies infection risk. Ingestion of carbohydrate (30-60 g/h) attenuates stress hormone and (some) immune pertubations during exercise but only very limited evidence that this modifies infection risk in human athletes. A component of the Indian spice, tumeric and has potent anti-inflammatory activity. There is no evidence that curcumin has any effect on immunity in healthy humans. Herbal extract that is a popular supplement among athletes. Claimed to boost immunity via stimulatory effects on macrophages. Early human studies indicated possible beneficial effects but more recent, larger scale and better controlled studies indicate no effect of Echinacea on infection incidence or cold symptom severity. Ginseng (Asian or Panax) has been a part of Chinese medicine for over 2,000 years and was traditionally used to improve mental and physical vitality. Evidence for immune modulating effects in humans is lacking. Probiotics are live microorganisms which when administered orally for several weeks, can increase the numbers of beneficial bacteria in the gut and modulate systemic immune function. Some placebo-controlled studies in athletes have indicated that daily probiotic ingestion results in fewer days of respiratory illness and lower severity of symptoms but larger scale studies are needed. A flavonol (polyphenol) compound found in onions, apples, red wine, broccoli, tea, and Ginkgo biloba. Has antioxidant activities, inhibits protein kinases and regulates gene expression. Some limited evidence of reduced infection risk in human athletes with quercetin but mechanism of action unclear. 24

25 An essential water-soluble antioxidant vitamin taken in megadoses by many athletes. Some evidence from some (but not all) human studies that high dose vitamin C (>200 mg/day) can be effective in reducing infection risk in stress situations and following ultramarathon races. May work by reducing stress hormone and anti-inflammatory cytokine responses to exercise. Vitamin E An essential fat-soluble antioxidant vitamin that is another popular supplement taken in megadoses by athletes. Good evidence for some immune boosting effects in the frail elderly but no evidence of similar benefit for younger healthy humans or athletes.. Whey protein Whey protein from cow s milk contains various amino acids, peptides and proteins including lactoferrin and immunoglobulins. High content of the amino acid cysteine a precursor of the important intracellular antioxidant, glutathione. May be responsible for the enhanced lymphocyte function observed in studies on animals and AIDs patients. There is no evidence that whey protein has any effect on immunity in healthy humans. Zinc An essential mineral that is claimed to reduce incidence and duration of colds. No evidence for reduced infection incidence with zinc supplementation in humans. Some (but not all) human studies suggest a reduction in duration of cold symptoms if zinc gluconate lozenges are administered within 24 h of cold symptom onset. Unlikely to be of any real benefit to athletes unless they are zinc deficient. The scientific evidence is indicated with meaning very strong evidence and meaning limited to no evidence. Vitamin C References 1. Gleeson M (ed). Immune Function in Sport and Exercise. Elsevier, Edinburgh, Bermon S. Airway inflammation and upper respiratory tract infection in athletes: is there a link? Exercise Immunology Review 13: 6-14, Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC, Fleshner M, Green C, Pedersen BK, Hoffman-Goetz L, Rogers CJ, Northoff H, Abbasi A, Simon P. Position Statement Part One: Immune function and exercise. Exercise Immunology Review 17: 6-63, Walsh NP, Gleeson M, Pyne DB, Nieman DC, Dhabhar FS, Shephard RJ, Oliver SJ, Bermon S, Kajėnienė A. Position Statement Part Two: Maintaining immune health. Exercise Immunology Review 17: , Gleeson M. Exercise, nutrition and immunity. In: Diet, Immunity and Inflammation (edited by Calder PC and Yaqoob P), Chapter 30. Cambridge: Woodhead Publishing, Larson-Meyer DE, Willis KS. Vitamin D and athletes. Current Sports Medicine Reports 9: , Halson SL, Lancaster GI, Achten J, Gleeson M, Jeukendrup AE. Effect of carbohydrate supplementation on performance and carbohydrate oxidation following intensified cycling training. Journal of Applied Physiology 97: , Peters EM. Vitamins, immunity, and Infection risk in athletes. In: Nieman DC, Pedersen BK (eds) Nutrition and Exercise Immunology, pp CRC Press, Boca Raton, Nieman DC, Henson DA, Gross SJ, Jenkins DP, Davis JM, Murphy EA, Carmichael MD, Dumke CL, Utter AC, McAnulty SR, McAnulty LS, Mayer EP. Quercetin reduces illness but not immune perturbations after intensive exercise. Medicine and Science in Sports and Exercise 39: , Gleeson M, Thomas L. Exercise and immune function. Is there any evidence for probiotic benefit for sports people? Complete Nutrition 8: 35-37, Cox AJ, Pyne DB, Saunders PU, Fricker PA. Oral administration of the probiotic Lactobacillus fermentum VRI-003 and mucosal immunity in endurance athletes. British Journal of Sports Medicine 44: , Gleeson M, Bishop NC, Oliveira M, Tauler PJ. Daily probiotic s (Lactobacillus casei Shirota) reduction of infection incidence in athletes. International Journal of Sport Nutrition and Exercise Metabolism 21: 55-64, West NP, Pyne DB, Cripps AW, Hopkins WG, Eskesen DC, Jairath A, Christophersen CT, Conlon MA, Fricker PA. Lactobacillus fermentum (PCC(R)) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes. Nutrition Journal 10: 30,

26 26 Notes

27 Notes 27

28 M A L L O R C A for more information: and