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TOPICS
Preface, Prof. Asker Jeukendrup
This is the third Sport Nutrition conference of this format, organized and hosted by the University of Birmingham. The rst one was organized in Birmingham (UK) and coincided with the Tour de France start in London in 2007. In 2008, the successful Birmingham conference was followed up by a one day conference the day before the start of the annual American College of Sports Medicine meeting in Indianapolis (USA) and the third conference was back in Birmingham. This time the conference was be hosted at Villa Park, Aston Villas football ground with a rich history, and the School of Sport and Exercise Sciences at the University of Birmingham. The Schools building is brand new and one of the largest purpose built Sport and Exercise Science facilities in the world. The main goal of the conferences is to bridge the gap between the science on the one side and practice on the other side. There often appears to be a division between the science and practice. Scientists and practitioners do not always seem to speak the same language, communication is often far from optimal and as a results the new ndings of scientists get misinterpreted or are not used at all and the practitioners keep looking for the answers to their practical questions. This series of conferences were set up to bridge the gap and establish links between the science and practice and between scientists and practitioners. Researchers with a strong background in sports and with an ability to communicate and translate the science into a practical message were selected and talked about areas of sports nutrition that are rapidly developing. In this conference the topics of weight loss through high protein diets, supplements to increase fat oxidation, train lowcompete high!, and many other current topics in sports nutrition were discussed. This booklet summarises the presentations and should give you a quick update on the areas as well as some practical information, so that you can take the information and make changes to your, or your athletes nutrition plans! PowerBar and Nestle Nutrition have supported these conferences which demonstrates their dedication to provide the athletes with current and accurate information. I want to thank them for making this possible and the authors for their contributions and their effort to translate often complicated science into a compact and user friendly message. I hope that you will nd the content of this booklet useful and that it will help to make positive changes to your nutrition. Asker Jeukendrup

Content
Preface ............................................................................................................................................................................................................................... 2 Asker E. Jeukendrup 1 - Protein and weight loss ........................................................................................................................................................................................ 3 Kevin D. Tipton 2 - Train low - compete high! ................................................................................................................................................................................... 7 Keith Baar 3 - Hydration: what is new? ....................................................................................................................................................................................10 Asker E. Jeukendrup 4 - Nutrition and the immune system: what works and what does't ................................................................................................. 14 Mike Gleeson 5 - Nutrition and Genetics ....................................................................................................................................................................................... 19 Mark Tarnopolsky 6 - Are Men and Women the Same? ...................................................................................................................................................................25 Brent C. Ruby 7 - Fat burning: how and why? ............................................................................................................................................................................. 29 Asker E. Jeukendrup 2

Protein and weight loss

Kevin D. Tipton School of Sport and Exercise Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom Weight control is a signicant issue for many people, including athletes. Obesity is prevalent and increasing in our society and is associated with many chronic diseases. Athletes may want to lose weight for aesthetic reasons or to attain a better force to mass ratio to improve performance. In general, weight loss is accomplished by creating a negative energy balance for a sufcient period of time. Thus, decreased energy intake through dietary energy restriction and/or increased energy output through increased activity are necessary. For sedentary individuals, the best strategy is likely to decrease energy intake and increase exercise and habitual activity to lose weight over a relatively prolonged time period. However, many athletes may desire rapid weight loss for competitive reasons and often can not increase activity levels to any signicant degree. Thus, control of dietary energy intake is crucial. Recently, it has become evident that weight loss may be inuenced, not only by the total energy intake, but also by the composition of the diet. In particular, protein intake has received a great deal of attention in regard to weight loss. A role for protein in weight loss? Many athletes and others restrict energy intake in order to achieve loss of body mass. Generally, for both health and competitive reasons, it is more desirable for the loss of body mass to come as loss of fat, rather than muscle. However, negative energy balance may result in a signicant loss of lean body mass (3), perhaps leading to compromised performance (2) or health (7). Thus, a dietary strategy that allows weight loss while maintaining muscle would be very important for many exercisers. Recently, many studies have demonstrated that increased protein content of the diet, particularly in combination with exercise training, may improve weight loss and reduce the loss of lean body mass in overweight and obese individuals during low energy dieting (3). Furthermore, weight regain after the low calorie period ends is less when protein intake is high compared to more normal dietary compositions (5). Thus, high protein intake seems to be quite advisable during weight loss, at least in obese and overweight individuals. What is a high protein diet? One important factor to consider is the denition of a high protein diet. There are several ways to consider protein content of a diet. Table 1 presents dietary composition of a weight maintenance and low energy diet for an 80 kg athlete, intended to result in weight loss in two ways regular (normal) dietary composition and high protein. Note that the composition of the diet can be determined as the absolute amount of the protein (or other nutrient of interest), the % of total energy (calories) as protein and the amount of protein ingested per kg of body weight. In this example, the carbohydrate intake has been kept constant, from a % energy standpoint, in consideration of the importance of carbohydrate for exercise capacity. However, in order to reduce total energy intake, carbohydrate has to go down on a g/kg body weight basis. In this example, fat intake is reduced to make room for protein. Note that as the energy intake drops, the fat intake must be dramatically reduced to accommodate the increased protein. In practice, this issue may be problematic and design of the diet must be carefully considered. In the scientic literature, the denition of a high protein diet varies from ~27 up to ~70% of total energy intake or from an absolute amount of ~ 90g up to almost 300g of protein per day. Another way to consider the protein content is relative to carbohydrate intake. In fact, many of the studies that examined the impact of high protein dietary composition on changes in body composition exchanged the carbohydrate content of the diet for protein a practice that would likely be problematic for athletes. These studies often manipulated the diet as a ratio of carbohydrate/ protein. In the normal diets the ratio was ~3.5 and in high protein the it was less than 1.5, e.g. ~60% carbohydrates and 18% protein compared to ~40% carbohydrate compared to 30-35% protein. Some examples of a normal and a high protein diet are provided in Table 1.

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Table 1. Examples of a dietary composition for normal and high protein diets for a weight maintenance and low calorie diet intended to result in weight loss for a representative 80 kg male. Dietary composition is given as absolute amount (total), per kg body weight and as a % of energy.
Diet Total Energy [kcal] Carbohydrates [g] Fat [g] Protein [g] Weight maintenance Low calorie Weight maintenance Low calorie Weight maintenance Low calorie Weight maintenance Low calorie 3500 kcal 2100 kcal 440 g 265 g 135 g 80 g 132 g 80 g Normal Per kg body wt. 44 kcal/kg 26 kcal/kg 5.50 g/kg 3.31 g/kg 1.69 g/kg 1.00 g/kg 1.65 g/kg 1.00 g/kg 50 % 50 % 35 % 35 % 15 % 15 % % energy Total 3500 kcal 2100 kcal 440 g 262 g 135 g 35 g 132 g 184 g High Protein Per kg body wt. 44 kcal/kg 26 kcal/kg 5.50 g/kg 3.28 g/kg 1.69 g/kg 0.44 g/kg 1.65 g/kg 2.25 g/kg 50 % 50 % 35 % 15 % 15 % 35 % % energy

How does a high protein diet work? At this point, it is uncertain how the protein content of the diet preserves muscle during weight loss. Several possible mechanisms have been suggested. Protein and satiety Protein has a high satiety value. That is, feelings of hunger are less with a high protein diet (5). So, if someone is to eat a high proportion of their calories as protein, that person will eat less total calories leading to the potential for weight loss. This effect is seen both with one meal and over weeks of eating higher protein. Interestingly, the level of satiety may be related, not only to the total amount of protein in the diet, but also to the type of protein. There is now good evidence that satiety is greater with animal protein sources, rather than plant protein sources. For example, one study demonstrated that ingestion of pork protein resulted in greater feelings of satiety than did soy protein (5). Even the specic protein ingested may have different effects on satiety casein ingestion seems to have less of an impact on satiety than whey protein. All of these studies have been performed in untrained and non exercising subjects, therefore the satiation effect of different meals, foods and proteins in athletes and exercisers remains to be determined. Another important consideration when examining the impact of proteins on satiety is that, in practice, it is rare that a particular food, let alone a particular protein, is eaten in isolation. The concurrent consumption of other foods will impact the overall effect of the protein on satiety. Very few people do or even will eat only one food source at a time. Therefore, care should be taken when applying the results of these studies in practice, especially in athletes and other regular exercisers. It is probably more important to maintain a relatively high amount of protein in the diet over time so that the overall feelings of satiety are greater resulting in less total food intake. Protein and diet induced thermogenesis The level of satiety associated with higher protein intake may be related to the level of diet-induced thermogenesis, i.e. heat production or inefcient utilization of the protein. It takes more energy to process the protein than it does carbohydrates or fats (5). Whereas the energy available from protein is the same as carbohydrates, it takes about 25% of that energy to process the protein reducing the net energy gained from eating the protein. The thermogenic effect of the protein may be at least partially determined by the stimulation of protein synthesis following protein ingestion. Protein synthesis is an energetically expensive process, thus stimulation of the synthesis of proteins, especially in muscle, will result in an overall increase in energy expenditure. Interestingly, the increased energy expenditure associated with higher protein intake is thought by some scientists to contribute to the feeling of satiety. Satiety seems to be associated with low oxygen availability, such as mountaineers experience at high altitude. It has been proposed that the increased oxygen consumption and higher body temperature that follows high protein feeding contributes to a feeling of oxygen deprivation and thus increases satiety. However, more research needs to be conducted to determine the details of the relationship between satiety and thermogenesis. Essential amino acids may preserve muscle mass The preservation of lean mass during weight loss has been attributed to the increased essential amino acid levels provided by the extra protein. It is the essential amino acids, in particular, that stimulate muscle protein synthesis. The amino acid leucine especially is thought to be important. Leucine stimulates initiation of translation and increases protein synthesis (1) which may help to reduce the net loss of muscle protein. Some examples of good sources of protein and BCAA are provided in Table 2. 4

Table 2. Food items high in protein (animal and plant protein sources) and branched-chain amino acids.
Protein Animal Food Skim Milk (dairy) Beef Chicken Plant Soy protein Legumes (beans and peas) Whole grains Dairy Beef Chicken BCAA

Protein may increase fat oxidation Furthermore, there is evidence that increased protein content may lead to increased fat oxidation, perhaps due to the leucine. Finally, it seems that dairy protein, in particular, may be the best protein source for weight loss. Again, the importance of dairy is often attributed to its leucine content. How it all might work Figure 1 illustrates a hypothetical scenario by which increased protein results in maintenance of lean mass during low calorie weight loss diets. Protein and exercise stimulate muscle protein synthesis, possibly due to the leucine content in the protein. Protein synthesis is energetically expensive. Increased synthesis increases the amount of muscle protein. Muscle tissue is also more energetic than fat tissue, so it increases the metabolic rate. Since the body is in negative energy balance, the energy must come from stored sources, i.e. body fat. So, oxidation of fat for energy to run protein synthesis and muscle tissue is increased. Thus, lean mass is preserved while fat mass is lost. There is still much work to be done to determine if this pathway is, in fact, the way in which protein and exercise result in preservation of lean body mass. Figure 1. Hypothetical schematic diagram of the mechanism by which increased protein results in greater loss of fat as compared to muscle during low calorie dieting.

Evidence in athletes is limited Whereas there is ample evidence for preservation of lean body mass loss during weight loss from low calorie dieting in overweight and obese populations consuming high protein diets (3; 5), there is little information available on athletic populations. Clearly, the metabolic and training status of athletic individuals differs from that of obese and overweight, particularly sedentary, individuals. Athletes are usually healthy and unlikely to suffer from metabolic diseases, or preliminary states of diseases, which are often apparent in inactive, obese subjects. Thus, the metabolic situation is different and may impact the response to high protein, low calorie diets. Furthermore, initiation of a training program may inuence the response to these diets which may not be similar for already well-trained athletes. There seem to be some conicting data on the impact of increased protein intake during weight loss in athletes. One study using a technique called N balance supports the idea that increased protein intake preserves muscle during low calorie dieting in body builders (6). However, a more recent study found no effect of increased protein or branched chain amino acid (BCAA) intake on lean body mass loss during weight loss in athletes (4). 5

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We recently decided to examine the impact of increased protein intake during low calorie dieting in weight lifters. Two groups of athletes consumed 60% of their normal calorie intake for two weeks. The composition of the diet varied between groups. One group consumed a diet that resembled their normal dietary pattern. The other group consumed a high protein diet. Both groups lost the same amount of fat, but the group consuming more protein lost little if any muscle while the other group lost muscle mass. Thus, the group with the normal diet lost more total weight. Interestingly, there was no difference in satiety between the two groups. It is likely that this lack of impact on satiety was due to our study design. In this study we controlled dietary intake. Thus, the subjects did not get to choose their level of energy intake. In the studies in which satiety is impacted, the level of dietary intake is not controlled. However, the lack of effect of protein intake on satiety could also be due to the fact that we studied athletes rather than obese and otherwise untrained individuals. More specic studies should be performed to examine this possibility. Summary The results of this study suggest that the goals of the athlete should be carefully considered before deciding on the appropriate nutritional strategy for weight loss. If total weight lost without consideration of what kind of tissue is lost is important, then a high protein dietary composition may not be desirable. However, if maintaining muscle is crucial, then perhaps a high protein diet would be best. Guidelines for Use of Protein for Weight Loss 1. 2. The specic goals of the individual should be carefully considered. For overweight and obese sedentary individuals, protein may be increased in the diet at the expense of carbohy drates. 3. For gradual weight loss and preservation of muscle mass, obese and overweight individuals should consume a carbohydrate to protein ratio of ~1.5 while consuming calories that correspond to ~80% of energy requirements and increase activity, preferably with resistance exercise as a major component. 4. The recommendation of athletes should be made based on their goals. 5. For most athletes careful consideration of the carbohydrate intake should be made, i.e. carbohydrate intake should not be lowered to increase the protein intake. 6. If the absolute amount of weight lost is the primary goal, a high protein diet may not be the best choice for an athlete. 7. If it is more important to maintain muscle than to lose large amounts of total mass, a high protein diet is recom mended. 8. Protein intake may best be increased by increasing the amount of low-fat dairy, e.g. yoghurt, skim milk, lean meats, e.g. chicken breast, sirloin steak, sh and other seafood, e.g. tuna in water, shrimp, grouper, oats and whole grains and, if necessary, protein supplements. Reference List

1. Anthony JC, Anthony TG, Kimball SR and Jefferson LS. Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr 131: 856S-860S, 2001. 2. Fogelholm GM, Koskinen R, Laakso J, Rankinen T and Ruokonen I. Gradual and rapid weight loss: effects on nutrition and performance in male athletes. Med Sci Sports Exerc 25: 371-377, 1993. 3. Layman DK and Walker DA. Potential importance of leucine in treatment of obesity and the metabolic syndrome. J Nutr 136: 319S-323S, 2006. 4. Mourier A, Bigard AX, de KE, Roger B, Legrand H and Guezennec CY. Combined effects of caloric restriction and branched-chain amino acid supplementation on body composition and exercise performance in elite wrestlers. Int J Sports Med 18: 47-55, 1997. 5. Paddon-Jones D, Westman E, Mattes RD, Wolfe RR, Astrup A and Westerterp-Plantenga M. Protein, weight management, and satiety. Am J Clin Nutr 87: 1558S-1561S, 2008. 6. Walberg JL, Leidy MK, Sturgill DJ, Hinkle DE, Ritchey SJ and Sebolt DR. Macronutrient content of a hypoenergy diet affects nitrogen retention and muscle function in weight lifters. Int J Sports Med 9: 261-266, 1988. 7. Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr 84: 475-482, 2006

Train low - compete high!

Keith Baar Division of Molecular Physiology, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom Introduction Glycogen loading has been known to increase endurance performance for many years (Bergstrom & Hultman, 1967a). As a result, most athletes and coaches believe that training in a glycogen-loaded state is essential to optimal conditioning and performance. However, the validity of this philosophy is now being challenged. It is becoming clear that there are benets to training in a glycogen-depleted state. The potential benets of training in the glycogen-depleted state have recently led many coaches and scientists to espouse a new training philosophy: Train low-compete high. Here we will discuss the evidence in support of this philosophy as well as the potential mechanism underlying the benets of training in a low glycogen state. Importance of glycogen as a fuel for endurance exercise Glycogen is the principal storage form of carbohydrate in mammals. In 1858 (Bernard, 1858) Claude Bernard isolated carbohydrate from liver and muscle (Young, 1957). Bernards landmark discovery provided direct evidence that muscle and liver had an accessible form of energy for meeting energy demands during exercise. Almost a century later, Bergstrom and Hultman began to investigate the role of glycogen in exercise (Bergstrom & Hultman, 1966); discovering a relationship between glycogen and exercise performance (Bergstrom et al., 1967). These early studies demonstrated that the glycogen content of a muscle is a major determinant of the capacity to sustain endurance exercise (Bergstrom & Hultman, 1967a). Importantly, they also demonstrated that diet and exercise could greatly vary the glycogen content in skeletal muscle (Bergstrom et al., 1967). This nal observation, that eating a high carbohydrate diet following exercise increased the recovery of muscle glycogen stores compared to a fat or protein diet, provided direct evidence that dietary glucose was the precursor for muscle glycogen (Bergstrom & Hultman, 1967b; Hultman & Bergstrom, 1967) and suggested for the rst time that a high muscle glycogen was benecial for endurance performance. Glycogen and whole body substrate utilization In the low glycogen state, whole body metabolism shifts drastically. In humans, glycogen depletion results in increased systemic release of amino acids from muscle protein breakdown, increased fat metabolism (calculated from arteriovenous differences), reduced pyruvate oxidation, and increased stress hormones such as cortisol and epinephrine (Blomstrand & Saltin, 1999; Steensberg et al., 2002). As a result of these changes, it is not surprising that performance is negatively affected by low muscle glycogen. However, some have postulated that lower glycogen during training alters whole body substrate metabolism in a manner that stimulates the activation of cellular signaling pathways that might be involved in the muscular adaptation to training (Steensberg et al., 2002). Glycogen depletion training and endurance training adaptation In support of the benecial effects of training in a glycogen-depleted state, Hansen et al. (Hansen et al., 2005) have shown that 10 weeks of training in a glycogen-depleted state resulted in an 85% greater increase in time to exhaustion compared with training with high glycogen. The reason for this greater increase in endurance was a larger increase in citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD) and other important enzymes of fat metabolism. These results have now been conrmed in highly trained cyclists suggesting that, regardless of the athletes training state, training in a glycogen-depleted state results in an increased capacity to use fat as a fuel during exercise. Glycogen depletion training and endurance performance Since training in the glycogen-depleted state improves the capacity for fat oxidation, this type of training might be expected to have a glycogen sparing effect during competition leading to improved performance. While this might be true at low intensities (<70% whole body VO2max) exercise, it does not appear to have a positive effect on performance at higher intensities (>70% whole body VO2max) where CHO are the primary fuel source. What this means is that in long duration endurance competition (triathlon, marathon, road cycling), training in a glycogen-depleted state will have a positive effect on performance. However, in shorter, higher intensity events (10K run, time trial cycling, rowing), training in 7

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a glycogen-depleted state will have less of a performance benet. One caveat is that for competitions such as world championships and Olympics, where heats are run prior to the nals, low glycogen training, and the resulting increase in the capacity to use fat as a fuel, may improve recovery and therefore have benecial effects on subsequent performances. Resistance training it a glycogen-depleted state Unlike endurance training, resistance training in a glycogen-depleted state does not seem to have any benecial effects. If anything, weight training in a glycogen-depleted state may decrease training adaptations. It is already clear that the transcriptional changes following resistance exercise are no different in a glycogen-depleted state and the greater metabolic stress of training with low glycogen will negatively affect the primary pathway leading to increased muscle protein synthesis. Therefore, for strength events, training in a glycogen-depleted state should be avoided. Why is endurance training in a glycogen-depleted state benecial? Endurance training in a glycogen-depleted state results in an improved capacity to use fat to fuel exercise. One important question is why? Some recent work has given clues as to how training in a glycogen-depleted state results in this benecial effect. Narkar et al (Narkar et al., 2008) recently showed that training rats on a treadmill while at the same time giving them a drug that activated a transcription factor called PPAR resulted in the same changes that occur when training in the glycogen-depleted state: increased capacity to use fat as a fuel. Increasing the enzymes that are required for oxidizing fatty acids is what PPAR does. The result in this study was the rats that both got the drug and trained on the treadmill increased their ability to run at ~50% VO2max by 70% over those that just ran on the treadmill. These data suggest that exercising in the glycogen-depleted state activates PPAR to a greater extent than training in the glycogen-loaded state. PPAR seems to be activated by a byproduct of the breakdown of fat in muscle. As discussed above, exercising in the glycogen-depleted state increases circulating fatty acids and the oxidation of fat during exercise resulting in more of the byproduct and more PPAR activation. Figure 1 The potential effects of training in low muscle glycogen states on the PPAR transcription factor. A. In the low muscle glycogen state, more fatty acids are available resulting in the activation of PPAR; B. In the high muscle glycogen state, a greater proportion of carbohydrates are used resulting in lower PPAR activation and less adaptation of the fatty acid oxidation enzymes.

How to train in a glycogen-depleted state If you compete in long duration endurance events, or train athletes who do, a natural question is how do I implement these techniques in my own training? The positive effects of training with low glycogen require glycogen levels to be decreased by about one third that of the normal. This can be accomplished by performing steady state exercise at ~70% of 8

max for 30 minutes to 1 hour without consuming a CHO supplement. Following the depletion stage, a second session is performed. This session can be performed immediately, or following a fast of 1-3 hours. Ideally, the second session should include high intensity work as this type of training maximally activates the molecular targets that improve endurance performance (Table 1). As with all training techniques, each athlete will have to determine whether training with low glycogen affects their recovery and therefore the overall intensity of their training. Table 1: Examples of glycogen-depletion training sessions for different sports Sport Marathon Depletion Session 1h @ 75% HRmax Adaptive Session 6 x 800m at 1 mile pace with 1.5min recovery, or 4 x 1200m at 3K race pace with 3min recovery, or 2 x 2 miles at 10K pace with 10min recovery 1h at 75% HRmax 6 x 5min at 95% HRmax with 2min recovery 2 x 20min hills @ 80% Wmax 15 x 50m with 10sec recovery, or 10 x 200m with 20sec recovery, or 4 x 400m with 40sec recovery All with increasing intensity (1st med last race pace) Morning - 3h ride with 3 x 10min @ 90% Wmax, or Morning 1h run with 2 x 1 mile at 10K pace Regular training with team, skills sessions, repeated sprints, ball skills, etc.

Road Cycling Swimming

1h @ 70% HRmax 20x 150m @ medium-high effort 15 sec rest 30 x 100m @ medium-high effort 15 sec rest

Triathlon Football/Soccer Rugby/US Football, Sprinting, Rowing, Time trial cycling

4h bike with no supplementation Low CHO dinner 30min run @75% HRmax

This type of training is not recommended

Conclusions Training in a muscle glycogen-depleted state increases an athletes ability to oxidize fat. In long duration endurance competition this increase in fat oxidation may spare muscle glycogen and improve performance. However, in strength events and endurance events lasting less than 1 hour, where stored ATP, phosphocreatine, and CHO are the primary sources of fuel, there is no performance benet to training in a muscle glycogen-depleted state.

References
Bergstrom J, Hermansen L, Hultman E & Saltin B. (1967). Diet, muscle glycogen and physical performance. Acta Physiol Scand 71, 140-150. Bergstrom J & Hultman E. (1966). The effect of exercise on muscle glycogen and electrolytes in normals. Scand J Clin Lab Invest 18, 16-20. Bergstrom J & Hultman E. (1967a). A study of the glycogen metabolism during exercise in man. Scand J Clin Lab Invest 19, 218-228. Bergstrom J & Hultman E. (1967b). Synthesis of muscle glycogen in man after glucose and fructose infusion. Acta Med Scand 182, 93-107. Bernard C. (1858). Nouvelles recherches exprimentales sur les phnomnes glycogeniques du foie. . Comptes rendus de la Socit de biologie 2, 1-7. Blomstrand E & Saltin B. (1999). Effect of muscle glycogen on glucose, lactate and amino acid metabolism during exercise and recovery in human subjects. J Physiol 514 ( Pt 1), 293-302. Hansen AK, Fischer CP, Plomgaard P, Andersen JL, Saltin B & Pedersen BK. (2005). Skeletal muscle adaptation: training twice every second day vs. training once daily. J Appl Physiol 98, 93-99. Hultman E & Bergstrom J. (1967). Muscle glycogen synthesis in relation to diet studied in normal subjects. Acta Med Scand 182, 109-117. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ & Evans RM. (2008). AMPK and PPARdelta agonists are exercise mimetics. Cell 134, 405-415. Steensberg A, van Hall G, Keller C, Osada T, Schjerling P, Pedersen BK, Saltin B & Febbraio MA. (2002). Muscle glycogen content and glucose uptake during exercise in humans: inuence of prior exercise and dietary manipulation. J Physiol 541, 273-281. Young FG. (1957). Claude Bernard and the discovery of glycogen; a century of retrospect. Br Med J 1, 1431-1437.

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3
Hydration: what is new?
Asker Jeukendrup University of Birmingham, UK The topic of hydration has received considerable attention in the last few years and there has been debate about the recommendations that should be given to athletes. Reports of overdrinking and resulting hyponatremia have raised questions about current uid intake practices and the guidelines have been challenged. The recommendations given to athletes have recently been adjusted, so they are clearer and easier to interpret. Also, the ingestion of substances like creatine, caffeine and glycerol have been questioned in regards to safety and hydration status. Then there is the issue of heat cramps, a problem for many athletes, but are there solutions? Finally whilst hydration may be important, it is also important to provide fuel during prolonged exercise. So what are the best ways to provide fuel and uid at the same time. Dehydration impairs performance: the evidence Fatigue toward the end of a prolonged sporting event is typically multifaceted and the underlying mechanisms are complex. Fatigue may be inuenced by dehydration as well as by fuel substrate depletion. It has been demonstrated that exercise performance can be impaired when an individual is dehydrated by as little as 2% of body weight. Losses in excess of 5% of body weight can decrease the capacity for work by about 30%. Even high intensity exercise may be affected by dehydration. In cool laboratory conditions, maximal aerobic power decreases by about 5% when persons experience uid losses equivalent to 3% of body mass or more. In hot conditions, similar water decits can cause a larger decrease in VO2max. Endurance capacity is impaired much more in hot environments than in cool conditions, which suggests that impaired thermoregulation is an important causal factor in the reduced exercise performance associated with a body-water decit. Severe dehydration also poses a health risk in that it increases the risk of cramps, heat exhaustion, and life-threatening heat stroke. Studies have also shown that uid ingestion during exercise help to restore plasma volume to near pre-exercise levels and prevents the adverse effects of dehydration on muscle strength, endurance, and coordination. It was argued that relying on feeling thirsty as the signal to drink is unreliable because a considerable degree of dehydration (certainly sufcient to impair athletic performance) can occur before the desire for uid intake is evident. This is where the debate is hotting up (7). The debate Although there is a signicant body of evidence that dehydration can impair exercise performance, Prof Noakes has warned, that the extrapolation of these mostly laboratory studies to a real life situation can be problematic (4, 5). Instead of advising to drink to avoid dehydration, Noakes advocates drinking according to thirst (4, 5). Dr Noakes argues that thirst and not dehydration is the factor that determines performance as thirst is part of a complex mechanism, regulated centrally in the brain, the goal of which is to ensure that athletes do not damage their health by continuing to exercise while drinking too little during exercise. Thirst is driven by the level of dehydration which is detected by the brain as a change in plasma osmolality (thickness of the plasma). Osmolality will be one of the key homeostatic variables that a complex system will actively regulate during exercise. According to Noakes interpretation, dehydration is not the direct cause of an impaired exercise performance. Rather, exercise performance is modied (impaired) under certain stressful conditions in order to ensure that the osmolality of the brain remains within the homeostatic range. Dr Noakes also argues that the common advice of drinking before you get thirsty and drinking to prevent dehydration may sometimes result in overdrinking and hyponatremia may be the consequence. Finally he makes the point that dehydration may sometimes be benecial to performance as the fastest runners in a marathon are the ones who are dehydrated the most. Thirst is a basic physiological instinct that the body uses to maintain normal thickness of body uids. Part of Dr Noakes reasoning is that humans evolved the thirst mechanism over millennia and it is the only system used by all other creatures on this earth. Why should it not also be ideal for humans?

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The guidelines Until the early 1970s, the guidelines for uid ingestion during exercise were not to drink. In the years to follow studies demonstrated that performance was reduced by dehydration and performance was enhanced when uid was ingested (compared with no uid ingestion). The guidelines evolved accordingly. By 1996, guidelines stated, individuals should be encouraged to consume the maximal amount of uids during exercise that can be tolerated without gastrointestinal discomfort up to a rate equal to that lost from sweating, which may have been interpreted by some as to drink as much as tolerable. Since then the American College of Sports Medicine has reworded the advice to The goal of drinking during exercise is to prevent excessive dehydration (>2% BW loss from water decit) and excessive changes in electrolyte balance to avert compromised exercise performance. The amount and rate of uid replacement depends upon the individual sweating rate, exercise duration, and opportunities to drink (6). Regular measurements of body weight can help to determine the sweat losses. Table 1 gives an overview of estimates sweat rates for persons with different body weights and sweat rates. Table 1: Estimated weight losses (as % body weight) whilst running a marathon at different paces and ingesting different amounts of uid. The combinations highlighted in orange are either ingesting too little uid resulting in weight loss of >3% or ingesting too much uid (weight gain). Marathon time (h) Pace (min/mile) Pace (km/h) Sweat rate (L/h) Person 50 kg 0.0 0.2 0.4 0.6 0.8 1.0 Person 65 kg 0.0 0.2 0.4 0.6 0.8 1.0 Person 80 kg 0.0 0.2 0.4 0.6 0.8 1.0 Fluid intake (L/h) 05:00 11:30 8.4 0.4 -4.0 % -2.0 % 0.0 % 2.0 % 4.0 % 6.0 % -3.1 % -1.5 % 0.0 % 1.5 % 3.1 % 4.6 % -2.5 % -1.3 % 0.0 % 1.3 % 2.5 % 3.8 % 04:30 10:20 9.4 0.5 -4.5 % -2.7 % -0.9 % 0.9 % 2.7 % 4.5 % -3.5 % -2.1 % 0.7 % 0.7 % 2.1 % 3.5 % -2.8 % -1.7 % -0.6 % 0.6 % 1.7 % 2.8 % 04:00 09:12 10.6 0.6 -4.8 % -3.2 % -1.6 % 0.0 % 1.6 % 3.2 % -3.7 % -2.5 % -1.2 % 0.0 % 1.2 % 2.5 % -3.0 % -2.0 % -1.0 % 0.0 % 1.0 % 2.0 % 03:30 08:00 12.1 0.8 -5.6 % -4.2 % -2.8 % -1.4 % 0.0 % 1.4 % -4.3 % -3.2 % -2.2 % -1.1 % 0.0 % 1.1 % -3.5 % -2.6 % -1.8 % -0.9 % 0.0 % 0.9 % 03:00 06:55 14.1 1 -6.0 % -4.8 % -3.6 % -2.4 % -1.2 % 0.0 % -4.6 % -3.7 % -2.8 % -1.8 % -0.9 % 0.0 % -3.8 % -3.0 % -2.3 % -1.5 % -0.8 % 0.0 %

Creatine, caffeine and glycerol Caffeine has long been recognized as a diuretic. Therefore it has often been advised to avoid caffeine especially before and during exercise. However, the early studies used relatively large doses of caffeine (>300mg) and in more recent studies, in which smaller doses were used, caffeine did not promote dehydration at rest or during exercise. Based on the current evidence there is no reason to restrict caffeine intake at levels below 300 mg (Table 2). Creatine is a supplement used by many strength athletes. The intake of creatine usually increases body mass because water is stored in the intracellular space. It has been argued that water is drawn from the vascular space and that creatine intake should be restricted. However, there is no evidence that creatine ingested in normal doses increases heat stress or decreases performance in hot condi11

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tions so based on the current evidence an advice to restrict creatine intake has no foundation (Table 2). Glycerol is a hyperhydrating agent that is sometimes used to hyperhydrate before competition. Glycerol increases the water storage and can, in some conditions, protect against heat stress. There are also a few studies that demonstrate performance benets. However, taking glycerol is not very practical and can cause side effects. Relatively large amounts of glycerol would have to be ingested with very large amounts of water. Headaches are very common. For these reasons glycerol hyperhydration is not a very user friendly strategy (table 2). Table 2: Supplements and their impact on hydration Supplement Caffeine Claim Caffeine is a diuretic and should be avoided before and during exercise Creatine increases water storage, removes water from the vascular space and increases heat stress Glycerol is a hyperhydrating agent which increases water storage, reduces heat stress and improvces exercise performance in the heat Evidence Caffeine ingested in moderate doses (up to 300mg) is not a diuretic and there is no reason to restrict caffeine intake at levels below 300 mg. There is no evidence that creatine increases heat stress or decreases performance in hot conditions. Glycerol can result in increased water storage, reduced heat stress in extreme conditions and there are some reports of improved performance. Its use however, is impractical and can cause side effects. Creatine Glycerol Heat cramps Cramps are common in athletes and seem to occur more, when the exercise is more prolonged, more intense and in hot conditions. Cramps are basically a form of motor unit hyperactivity and result in painful involuntary muscle contractions. Heat cramps are associated with large sweat (salt and water) losses. The difference between heat cramps and exercise associated cramps are subtle but can be conrmed when sodium replacement resolves the cramps. It seems to be possible to treat heat cramps quite effectively with sodium intake. Unfortunately at present it is difcult to estimate sodium losses and therefore difcult to predict how much sodium athletes should take in extreme conditions. Sodium intake does not only have to take place during exercise but some of the replacement could simply be with meals and the day before competition. Although the exact etiology of heat cramps is unknown and difcult to investigate, sodium decits seem to play an important role in the development of cramps. Combining energy and uid Especially during prolonged exercise when carbohydrates reserves become depleted, carbohydrate intake in addition to uid intake is important. However, it is known that with increasing carbohydrate intake (increasing carbohydrate concentration), the absorption of uid may be impaired. Hence sports drinks are always a compromise between delivering energy and delivering uid. Most sports drinks are in the 4-8% carbohydrate range where the impairment in uid absorption is still acceptable. However, in the >10% range it is generally thought that both gastric emptying and absorption of uid are hampered even though it may result in a greater delivery of carbohydrate. Interestingly we recently advised very high carbohydrate intakes for prolonged exercise in the region of 90 g/h (1.5 g/min). When such large amounts of carbohydrate were ingested in the form of glucose+fructose the delivery of carbohydrate to the working muscle was improved (Figure 1) (3) and performance was increased 8% more than with a traditional sports drink containing one type of carbohydrate (1). Such large amounts of carbohydrate can only be delivered in concentrated carbohydrate solutions unless very large volumes of uid would be consumed. For example, to ingest 90 g of carbohydrate per hour, one would have to drink 750 ml of a 12% carbohydrate solution or 1.5L of a 6% carbohydrate solution. Ingesting 1.5L/h is not always practical or even possible and therefore one would have to resort to drinking a more concentrated solution. However according to existing information this would reduce uid delivery. In studies where stable isotopes were used to label water and study uid delivery it was demonstrated however that mixtures of glucose and fructose result in a faster rate of gastric emptying and a superior uid delivery compared with a single carbohydrate (Figure 1). Therefore in situations where both carbohydrate and uid delivery are important and the exercise duration is >2h it would be advised to take solutions with multiple transportable carbohydrates and ensure an intake of 60-90g/h.

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Figure 1: Multiple transportable carbohydrates such as fructose and glucose (GLU+FRU) appear to have faster gastric emptying, and result in greater uid and carbohydrate delivery compared with a single carbohydrate (Glucose: GLU). Figure redrawn from (2, 3).

1. 2. 3. 4. 5. 6. 7.

Currell K, and Jeukendrup AE. Superior endurance performance with ingestion of multiple transportable carbohydrates. Med Sci Sports Exerc 40: 275-281, 2008. Jeukendrup AE, and Moseley L. Multiple transportable carbohydrates enhance gastric emptying and uid delivery Scand J Med Sci Sports In press: 2008. Jeukendrup AE, Moseley L, Mainwaring GI, Samuels S, Perry S, and Mann CH. Exogenous carbohydrate oxidation during ultraendurance exercise. J Appl Physiol 100: 1134-1141, 2006. Noakes TD. Drinking guidelines for exercise: what evidence is there that athletes should drink as much as tolerable, to replace the weight lost during exercise or ad libitum? J Sports Sci 25: 781-796, 2007. Noakes TD. Hydration in the marathon : using thirst to gauge safe uid replacement. Sports Med 37: 463-466, 2007. Sawka MN, Burke LM, Eichner ER, Maughan RJ, Montain SJ, and Stachenfeld NS. American College of Sports Medicine position stand. Exercise and uid replacement. Med Sci Sports Exerc 39: 377-390, 2007. Sawka MN, and Noakes TD. Does dehydration impair exercise performance? Med Sci Sports Exerc 39: 1209-1217, 2007.

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4
Nutrition and the immune system: what works and what doesnt
Michael Gleeson School of Sport and Exercise Sciences, Loughborough University, Loughborough LE11 3TU, United Kingdom Introduction There is some evidence that athletes who are training hard or who have recently competed in endurance race events are at increased risk of picking up minor illnesses and infections. The most common illnesses in athletes are viral infections of the upper respiratory tract. In themselves, these are generally trivial, but they can interrupt training or cause an athlete to miss (or under-perform in) important competitions. Prolonged bouts of strenuous exercise, particularly if performed without carbohydrate intake, and periods of hard training with limited recovery and/or inadequate energy intake may compromise the bodys immune system, and high levels of stress hormones brought on by chronic physical and/or psychological stress reduce its ability to ght opportunistic infections including colds and inuenza. Acute bouts of strenuous aerobic exercise lasting 90 minutes or more have been shown to result in transient depression of several aspects of both innate and acquired immunity including decreased functional responses of monocytes, neutrophils, natural killer cells and T and B lymphocytes 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. Other factors such as psychological stress, lack of sleep and malnutrition can also depress immunity and lead to increased risk of infection (Figure 1). Maintaining an effective immune system Adequate nutrition and in particular appropriate intakes of energy, protein, vitamins and minerals are essential to maintain the bodys natural defences against disease causing micro-organisms (pathogens). It is important to remember that any sustained deciency of an essential vitamin or mineral will result in ill health and it is extremely unlikely that an unhealthy athlete will perform to the best of his or her potential. Therefore, the key to maintaining an effective immune system is to avoid deciencies of the nutrients that play an essential role in immune cell functions. Inadequate protein-energy intake or deciencies of certain micronutrients (e.g. iron, zinc and vitamins B6 and B12), decrease immune defences against invading pathogens and make the individual more susceptible to infection. Thus, athletes are best advised to consume a sound diet that meets their energy needs and contains a variety of foods. Dietary surveys show that most athletes are well able to meet the recommended intakes for vitamins and minerals by eating everyday foods. Those at risk of sub-optimal intakes of these micronutrients include athletes who restrict their energy intake, especially over long periods, usually in an attempt to lose weight (fat) and athletes who follow eating patterns with restricted food variety and reliance on foods with a poor micronutrient density. 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. However, nutrition is just one of a number of strategies that can help to reduce infection risk in athletes (see Table 1). It is also worth remembering that certain infections can also affect nutritional status by causing appetite suppression, malabsorption, increased losses of endogenous nutrients and increased nutrient requirements. Figure 1: Causes of increased infection risk in athletes

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Nutrition supplements to limit exercise-induced immune depression Certain supplements may boost immune function and reduce infection risk in immunocompromised individuals. While there are many nutritional supplements including arginine, glutamine, bovine colostrum and whey protein, vitamin C, probiotics, zinc and herbals such as echinacea on the market that are claimed to boost immunity (Table 2), such claims are often based on selective evidence of efcacy in animals, in vitro experiments, children, the elderly or clinical patients in severe catabolic states and direct evidence for their efcacy for preventing exercise-induced immune depression or improving immune system status in athletes is usually lacking. 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 30-60 grams per hour) during prolonged workouts, which lowers circulating adrenaline and cortisol levels and delays the appearance of symptoms of overreaching during intensive training periods. Several placebo-controlled studies in runners and cyclists have shown that carbohydrate ingestion (usually in the form of a beverage) during prolonged exercise is effective in attenuating changes in immune function. However, evidence is currently lacking to demonstrate that this translates to a reduced incidence of upper respiratory tract infection (URTI) following competitive events. 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 cortisol response to prolonged exercise. These studies have used combinations of vitamin C and E, or vitamin C alone, and provide a possible mechanism to explain earlier ndings of a benet of vitamin C supplementation in reducing the incidence of URTI symptoms in individuals who took part in ultramarathon races. The bodys tissue stores become saturated with regular vitamin C intakes of 200 mg/day, so this amount, should in theory, be sufcient. Excessive supplementation with other antioxidants cannot be recommended because there is little evidence of benet, while it is known that over-supplementation can actually diminish the bodys natural antioxidant defence system. Ensuring that the diet contains plenty of fresh fruits and vegetables is probably the wisest option. Glutamine is the most abundant free amino acid in human muscle and plasma and is utilised at very high rates by leukocytes, particularly lymphocytes and monocytes. Reduced levels of plasma glutamine have been observed following prolonged exercise and it has been suggested that such a decrease could impair immune function. In the 1990s a reduction in URTI incidence after marathon events was reported for runners who ingested a glutamine supplement after the race but several more recent studies that have investigated the effect of large amounts of glutamine supplementation during and after exercise on the exercise-induced falls in immune cell functions, including lymphocyte proliferation, have failed to nd any benecial effect. Although provision of glutamine has been shown to have a benecial effect on gut function, morbidity and mortality and on some aspects of immune cell function in clinical studies of diseased or traumatised patients, it would appear that exerciseinduced falls in glutamine availability are not large enough to diminish immune function. Hence, supplementation with glutamine cannot be recommended. There are numerous other nutritional components that could potentially offer immune protection to athletes. Several including beta-glucan (a polysaccharide derived from yeast, fungi and oats), curcumin (a component of the tumeric spice) and various plant avonoids (polyphenols with potent antioxidant properties) have been shown to possess immunostimulatory effects in animal and in vitro models and studies are ongoing to test their effectiveness in human athletes. One recent placebo-controlled study in cyclists indicated that daily supplementation with the avonoid quercetin decreased URTI incidence in the 2 weeks following a 3-day intensied training period, although none of the measured exercise-induced changes in immune function were altered. Using a similar study design, an 18-day period of oat beta-glucan supplementation did not alter chronic resting or exercise-induced changes in immune function or URTI incidence compared with placebo. In recent years a few studies have examined the efcacy of oral probiotics in athletes and some of these have shown some promise. Often called the friendly bacteria, probiotics are live microorganisms which when administered in adequate amounts, modify the intestinal microbiota such that the numbers of benecial bacteria increase and usually numbers of species considered harmful are decreased. This has been associated with a range of potential benets to gut health, as well as modulation of immune function by their interaction with the gut-associated lymphoid tissue, leading to positive effects on the systemic immune system. Some placebo-controlled studies in athletes have indicated that daily probiotic ingestion results in fewer days of respiratory illness and lower severity of URTI symptoms. In one study this 15

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was associated with a signicant increase in whole blood culture interferon- production, which may be one mechanism underpinning the positive clinical outcomes. In conclusion, it is difcult to make rm judgments about which nutritional supplements are, and which are not, effective in boosting immunity or reducing infection risk in athletes. It is safe to say with reasonable condence that individual amino acids, colostrum, echinacea, vitamin E and zinc are unlikely to be of benet to athletes who are not decient in protein or micronutrients. Judgment on others, alone or in combination, must await further large-scale, well-controlled studies in athletic humans. Table 1: Strategies to counter illness risk in athletes Diet is important for immune function and many vitamins and minerals are associated with the ability to ght infection, particularly vitamin C, vitamin A and zinc. A good wellbalanced diet should provide all the necessary vitamins and minerals, but if fresh fruit and vegetables are not readily available multivitamin supplements should be considered. Nutritional considerations should emphasize the need for adequate intakes of uid, carbohydrate, protein and micronutrients. Ensuring the recovery of glycogen stores on a day-to-day basis and consuming carbohydrate during exercise (about 30-60 g of carbo hydrate per hour during exercise seems to be effective) appear to be ways of minimizing the temporary immunodepression associated with an acute bout of prolonged exercise and reduces chances of developing overreaching symptoms. The evidence for the benet of so-called immune-boosting supplements (e.g. glutamine, echinacea, colo strum) is weak, though there is some evidence that probiotics and several antioxidant compounds (e.g. vita min C, avonoids such as quercetin) may be effective in reducing infection risk. Avoid getting a dry mouth, both during competition and at rest; this can be done by drinking at regular inter vals and maintaining hydration status. Never share drink bottles, cutlery or towels and use properly treated water for consumption. Other behavioural, lifestyle changes such as good hygiene practice (washing hands and brushing teeth regularly; using an antibacterial mouth rinse), may limit transmission of contagious illnesses by reducing exposure to common sources of infection. Avoid putting the hands to the eyes and nose (a major route of viral self-innoculation). Keep other life/social/psychological stresses to a minimum and get regular and adequate sleep. Avoid rapid weight loss. Before important competitive events, avoid sick people and large crowds in enclosed spaces when possible Medical support including regular check ups, appropriate immunization and prophylaxis may be particularly important for athletes who are at high risk of succumbing to recurrent infection. Vaccinate athletes and all support staff who are in regular contact with athletes. Be aware of particular vulnerability to infection after training or competition, especially in the winter months. Training should be stopped if the athlete has a fever and/or systemic symptoms including aching joints and muscles. It is probably OK to continue training (though at a reduced load) if the symptoms are all above the neck. Iron supplements should not be taken during periods of infection. Team members with infection should be isolated as much as possible from the rest of the team.

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Table 2: Nutrition supplements and the scientic evidence that the supplement boosts immunity and/or reduces infection incidence in humans Nutrition supplement Arginine Evidence 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 -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 benet 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 modies 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 modies infection risk in human athletes. A component of the Indian spice, tumeric and has potent antiinammatory 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 benecial effects but more recent, larger scale and better controlled studies indicate no effect of Echinacea on infection incidence or cold symptom severity. Ancient herbal remedy that is claimed to have antibacterial actions and to boost immunity, especially natural killer cell activity. Evidence for immune modulating effects in healthy humans is lacking. Asian (Panex) ginseng 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 healthy humans is lacking. Contains the amino acid, L-theanine and antioxidants such as epigallocatechin gallate and other polyphenols. Claimed to improve T lymphocyte functions. Evidence for immune modulating effects in healthy humans is lacking. 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-inammatory cytokine responses to exercise. 17

Beta()-glucan

Bovine colostrum

Carbohydrate

Curcumin

Echinacea

Garlic

Ginseng

Green tea

Vitamin C

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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 benet for younger healthy humans or athletes.. Whey protein from cows 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 enhanced lymphocyte function observed in studies in animals and AIDs patients. There is no evidence that whey protein has any effect on immunity in healthy humans. 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 benet to athletes unless they are zinc decient. Whey protein Zinc The scientic evidence is indicated with meaning very strong evidence and Limited to no evidence. Suggested additional resources
Calder PC, Field CJ, and Gill HS. Nutrition and Immune Function. CABI Publishing, Oxford, 2002. Davison G, and Gleeson M. The effect of 2 weeks vitamin C supplementation on immunoendocrine responses to 2.5 h cycling exercise in man. European Journal of Applied Physiology 97(4): 454-461, 2006. Gleeson M. Immune Function in Sport and Exercise. Elsevier, Edinburgh, 2005. Gleeson M. Can nutrition limit exercise-induced immunodepression? Nutrition Reviews 64(3): 1-13, 2006. Gleeson M, Nieman DC, and Pedersen BK. Exercise, nutrition and immune function. Journal of Sports Sciences 22(1): 115-125, 2004. Nieman DC, and Pedersen BK. Nutrition and Exercise Immunology. CRC Press, Boca Raton, 2000.

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Nutrition and Genetics

Mark Tarnopolsky Department of Pediatrics and Medicine, McMaster University Medical Center, Hamilton, Ontario, Canada.

Introduction. The term genetics traditionally refers to the study of the arrangement of the genetic code within the DNA for a given gene or set of genes by characterizing how the organization of the DNA bases (adenine (A), cytosine (C), guanine (G), and thymidine (T)), are arranged into three base sequences (codons) to encode for amino acids that make proteins. The traditional discipline of medical genetics evaluates how sequence variants inuence physical and physiological characteristics (phenotype). In the past few years, there has been a blurring of the borders of traditional genetics and molecular biology where theses terms have been interchangeably used to refer to the evaluation of differences in DNA, mRNA and, in some cases, even signaling within a cell. With large scale sequencing efforts and microarray (gene chip) technology, a new generation of genomics (the study of the global properties of the genome) has emerged. The subsequent omics explosion now encompasses over two dozen various disciplines (RNA = transcriptome; protein = proteome; metabolites = metabolome, etc.). An interest in genetics and its application to nutrition and exercise physiology has been embryonic and still is in the earliest stages of development. In other disciplines such as oncology, cardiovascular disease and muscular dystrophy, an understanding of genetics and gene expression has been extremely helpful from a diagnostic and therapeutic perspective. The purpose of this brief review will be to cover some of the basics of genetics and gene expression and explore the potential for genetics and molecular biology to advance the understanding of exercise and sport nutrition. (Table 1). The human genome consists of approximately 3 billion DNA letters (A, C, G, T) that are arranged on a series of 23-paired chromosomes. The DNA is arranged into a series of genes (a region of the DNA encoding for a protein) with a start and stop code on dening the boundaries of each of the approximately 35,000 genes in the human body. The exact number of genes in the human body is still a bit unclear but the estimate of ~ 35,000 emerged when the human genome sequence was cracked as published in simultaneous papers in Nature (Human Genome Project) and Science (Celera Genomics). Prior to these publications, it was felt that there might be as many as 100,000 genes in the human body and this relatively small number came as a surprise to many scientists. These genes are organized in relatively small clusters throughout the entire DNA with extremely large tracks of non-coding DNA intervening between each gene. It was initially thought that much of the intervening sequences were junk however it is now known that areas of noncoding DNA can actually encode for modifying forms of RNA called micro RNAs which can inuence mRNA abundance and other changes in non-coding region (i.e. tri- and tetra-nucleotide expansions) can inuence gene expression in surrounding regions. DNA is transcribed into RNA in a gene specic manner in response to a variety of signals that ultimately converge on transcription factors which bind to promoter regions in the 5 region upstream of a given gene. In addition to the promoter regions, which are very close to the start sequence for a gene, there are enhancers which can be many thousands of base pairs upstream and interact with a promoter region due to the fact that DNA is often coiled and wrapped around histone proteins. After a cellular signal (nutrient, stretch, exercise, hormone, etc.) triggers a specic or clustered pattern of gene transcription, the primary transcript undergoes a series of modications including capping, poly adenylation, and splicing out of the introns to make a mature mRNA that is exported out of the nucleus. The mRNA signal abundance can be further regulated after transcription by RNA degradation and microRNAs. The mRNA transcript is read by a transfer RNA (tRNA) in the presence of ribosomes free in the cytoplasm or on the rough endoplasmic reticulum. The process of translation requires ribosomal RNA, charged amino acids and tRNA (i.e., leucyl-tRNA), and initiation, elongation and termination factors. The original DNA code is read from the complimentary mRNA through the anticodon on the tRNA to insert the correct amino acid corresponding to the specic codon. Following translation, a number of proteins undergo post-translational modications ranging from phosphorylation to assembly into multimeric complexes. Technically speaking, even the process of protein degradation can be considered a post-translational modication that can alter protein abundance. (Figure 1)

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Figure 1 Overview of nutrient interactions with transciption and translation Most of the molecular literature in exercise and sport nutrition has focused on the inuence of exercise and nutrition on translational and post-translational processes. For example, it is well known that a number of signaling molecules respond with changes in abundance and phosporylation in response to exercise and nutrient abundance. Probably the best explored area is the use of amino acids and carbohydrate consumption in the post-resistance exercise period to alter the phosphorylation status of mTOR and downstream kinases (i.e., p70S6K1 and rpS6). Some have referred to proteins such as the SIRTs, PPARs and mTOR as nutrient sensors. This paper will explore two main themes pertaining to genetics and sport nutrition; namely, the use of mRNA content and transcriptome signatures to evaluate nutritional interventions, and the evaluation of how gene polymorphisms could inuence the response to nutrients and exercise. Gene expression and transcriptome proling to evaluate exercise/sport nutrition. Many of the studies in exercise physiology and sport nutrition use the term gene expression, when in reality they are measuring steady state mRNA abundance in skeletal muscle. The mRNA abundance is a function of the rate of transcription as well as the rate of mRNA degradation; however, to measure these in vivo is difcult, if not impossible from small muscle biopsy samples in humans. Consequently, most studies use methods such as RT-PCR to measure mRNA abundance following an exercise and/or a nutritional intervention. For purposes of this review, I will use gene expression to indicate mRNA abundance unless otherwise specied. I will focus this section on two main areas 1. Does carbohydrate availability alter mitochondrial biogenesis?, and 2. Does creatine monohydrate have pre-translational effects? I. Does carbohydrate availability alter mitochondrial biogenesis and training adaptations? One of the main adaptations in human skeletal muscle to endurance exercise training is the increase in mitochondrial volume. A large number of variables change during endurance exercise that can inuence mitochondrial biogenesis including; calcium, AMP (via AMPK), hypoxia, and stretch activation. After the discovery that peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1) was a key regulator of mitochondrial biogenesis, there was a large interest in evaluating how training and nutritional interventions could inuence PGC-1 expression and protein abundance. Although PGC-1 may not be essential for mitochondrial biogenesis, it remains an important regulator of adaptation under normal physiological circumstances as evidenced by the enhanced mitochondrial adaptation observed with muscle specic over-expression studies. Given that PGC-1 responds to both energy and nutrient status of the cell (9), one of the rst hypotheses put forth was that exercise training in a fasted state may lead to higher induction of the signals that lead to an increase in PGC-1 content, and or fat oxidation in skeletal muscle. In addition to PGC-1 mRNA abundance, there are a large number of other genes that are expressed in the few hours after endurance exercise (i.e., PDK4, FOX01, IL-6 receptor, etc.) (5). Put simply, should an athlete train in the fasted (low or empty) as opposed to a fed (high or full) state in order to augment gene expression for molecular species involved in mitochondrial biogenesis and fat oxidation in order to enhance the classical phenotypic outcomes of endurance exercise training? 20

The likely nutrient candidates for inuencing gene expression in skeletal muscle are the glycogen concentration and free fatty acid (FFA) availability (these are usually reciprocal). The acute consumption of carbohydrate during endurance exercise has been shown to attenuate the induction of PDK4 mRNA and attenuate the induction of several genes related to lipid metabolism (FAT/CD36, CPT1, and UCP-3). One study evaluated the mRNA response of several molecular species to 2 h of cycling in the fed and fasted state and with and without carbohydrate feedings and found that exercise per se increased PGC-1 and PRC mRNA abundance immediately post-exercise, while PPAR and FKHR increased 1 3 h post-exercise, and these increases were independent of the above interventions, designed to alter FFA availability (10). Another study used the lipolysis inhibitor, acipimox, and found that the acute exercise induction of mRNA for PDK4 and PGC-1 and reduction of CPT1 were not altered by the drug after acute endurance exercise (12). A recent study looked at PGC-1 mRNA and protein abundance following an acute endurance exercise bout after subjects were in a high- (HC) and a low- (LC) glycogen state (6). Although there was a negative relationship between muscle glycogen content and PGC-1 protein abundance (- 0.62), there was no difference between the HC and LC condition for either PGC-1 protein or mRNA abundance (6). The correlation in the latter study was mildly suggestive that PGC-1 protein was higher with low glycogen (higher nutrient/metabolic stress). In addition to acute pre-and during-exercise carbohydrate having an inuence on the mRNA abundance for some genes involved in substrate metabolism, one study found that postexercise consumption of a high (10 g/kg) or low (0.9 g/kg) carbohydrate diet for 48 h after exercise had a more robust effect on muscle mRNA abundance (1). The high CHO diet induced glycogenin and GLUT4, and repressed PDK-4, mRNA abundance while the low CHO diet induced genes involved in fat metabolism (FAT/CD36, UCP-3) (1). Another study evaluated the inuence of a high vs low CHO diet consumed for 24 h after endurance exercise in mRNA abundance (8). The latter study found that the high CHO diet reversed the exercise induced activation of PDK-4, CPT-1 and UCP-3 by 5 8 h post-exercise; yet, the low CHO diet showed a persistence of the exercise induced induction of these genes until 24 h of recovery (8). In summary, the acute consumption of CHO generally leads to an induction of the mRNA abundance for genes involved in glucose uptake (GLUT4) and glycogen synthesis (glycogenin) with lower PDK-4; whereas, fasting and other conditions that increase FFA abundance lead to an induction of some, but not all, genes involved in FFA uptake (FAT/CD36) and metabolism (CPT-1, UCP-3). Irrespective of nutritional alterations in the exercise induced mRNA abundance, the ultimate proof in the pudding comes from training studies that evaluate the ultimate phenotypic outcome. In one study moderately trained men participated in a 6 week intensive endurance exercise program while training in the fasted (N = 10) or fed (N = 10) state and evaluated changes in VO2peak, glycogen depletion and the changes in several proteins (2). Although glycogen breakdown was attenuated and fatty acid binding protein was higher in the fasted-trained group, there were no differences in the change in VO2peak (2). Furthermore, endurance training for seven weeks while consuming a high fat vs high CHO diet led to lesser improvements in endurance capacity, even when carbohydrate was given immediately prior to- and during- and acute exercise bout. Overall, it appears that although dietary manipulation can inuence the acute exercise induced induction of some mRNA species that could theoretically lead to enhanced mitochondrial biogenesis and/or fat oxidation, there does not appear to be a practical benet to training athletes in a state of high vs low CHO availability. It is likely that any potential gain induced by training in a energy/CHO depleted state would be offset by a negative inuence on the day to day ability to train at a sufcient intensity and/or duration. II. Does creatine monohydrate have pre-translational effects? Creatine (Cr) monohydrate consumption of 3 g/d for a month or 20 g/d for 3 5 days can increase muscle Cr and phosphocreatine (PCr) by 15 30 %, especially in those with low endogenous Cr stores. The increase in muscle PCr stores is the likely mechanism behind the ergogenic effect of creatine monohydrate consumption in high intensity sprint and repetitive sprint activities. In addition to the temporal energy buffering described above, several lines of reasoning suggest that creatine may have effects at the cellular level. For example, early studies in cell culture have suggested that creatine can increase myobrillar protein synthesis. Although we (7), and others, have not found an increase in myobrillar or mixed muscle protein synthesis following creatine supplementation, our group has found a reduction in leucine oxidation and lower whole body protein breakdown. The acute increase in body mass seen with acute creatine loading is likely related to transient water retention, and the water retention may be the mechanism behind the attenuation in protein degradation and leucine oxidation. In addition to the acute effects of creatine monohydrate consumption, several studies have found that longer term consumption during a period of resistance exercise training led to a potentiation of strength and fat-free mass gains. Consequently, some have suggested that creatine loading could inuence cellular molecular signaling and that leads to enhanced training gains. 21

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One study found that the mRNA for myosin heavy chain (MHC) I and IIx were higher in men who completed a resistance exercise training program while consuming creatine monohydrate as compared with placebo (13), and related this to changes they found in a similar study where the creatine group showed higher myogenin and MRF-4 mRNA and protein expression following training (14). Another group found that there was also a greater increase in the basal mRNA abundance for collagen 1, GLUT-4, and MHCI, and MHC immediately following an acute bout of resistance exercise (3). Another study found that resting muscle showed an ~ 35 % increase in basal mRNA abundance for both IGF-I and IGF-II following creatine supplementation (4). Given that creatine monohydrate has been shown to enhance satellite cell recruitment in response to muscle contraction, it is unclear whether the gene expression changes in the aforementioned studies are in the mature skeletal muscle or the satellite cells. We have used gene array technology to evaluate the effect of acute creatine monohydrate supplementation on basal mRNA abundance in human skeletal muscle. We found that CrM supplementation signicantly up-regulated (1.3- to 5.0-fold) the mRNA content for genes involved in signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We also found that there was a higher abundance of several protein kinases that are involved in sensing cell volume and hypothesized that creatine may function indirectly by increasing cell volume and the effects on mRNA abundance are secondary to this effect. Nutragenomics: Interaction of nutrients with gene expression. In essence, there are two main areas in which there are likely to be many new advances in the near future where gene expression will allow us a much deeper insight into exercise physiology and sport nutrition. One area is the development of characteristic mRNA signatures to evaluate how different training methods and nutrition can be evaluated rapidly following an intervention. A second area will be the evaluation of how inter-individual sequence variants (gene polymorphisms) can inuence the responsivity of individuals to an exercise and/or nutritional stimulus. I. The potential use of molecular signatures in the evaluation of nutrition/exercise interactions. With the introduction of gene array technology it is now possible to evaluate the abundance of essentially every gene in the human body. Most gene arrays use either bead (Illumina) or silicon chip (Affymetrix) technology to afx many thousands of oligonucleotides to a solid support. The mRNA is extracted from the tissue samples (pre vs post, disease vs control, fasted vs fed, etc.) and labeled with a uorescent tag and incubated on the chip or bead. The uorescent intensity is proportional to the abundance of each specic mRNA. Consequently, one can obtain a gene signature for a given intervention and use that signature to evaluate whether an intervention enhances or attenuates the signature of interest. To my knowledge, this strategy has not yet been employed in exercise nutrition; however, the technology is there and it is only a matter of time before different training strategies and nutritional interventions are evaluated in such a fashion. The advantage of such and approach is that an investigator could in essence rapidly screen new dietary and/or training interventions using the technology and then choose the one that enhances the specic gene signature. II. Do gene polymorphisms explain responders and non-responders? The term polymorphism refers to heritable traits that are passed on through generations that inuence the phenotype of an individual. Some of the best known examples of polymorphisms are sexual dimorphism (discussed by Dr. Brent Ruby in this monograph) and blood types. Exercise scientists have traditionally been interested in how DNA sequence variants can inuence the responsivity of an individual to a given type of exercise training. The intuitive excitement and logic of using mitochondrial DNA polymorphisms (haplotypes) to explain endurance exercise performance was however met with minimal success. More recently, scientists have looked at a number of targeted DNA sequence variants (a single nucleotide difference at one locus is called a single nucleotide polymorphism or SNP) and how they inuence the inherent ability to perform sport or the magnitude of the responsiveness to an exercise training program. The largest study to date that has looked at SNPs and other sequence variants (deletions, duplications and insertions) is the HERITAGE family study (HEalth, RIsk factors, exercise Training And GEnetics). This study evaluated parents and three or more biological offspring from 90 Caucasian and 40 African-American families with blood and exercise testing completed before and after a 20 wk exercise program. This study has produced over 100 papers describing SNPs and quantitative trait loci (QTL, specic regions in the chromosome associate with a given trait but the exact SNP or other sequence variant is unknown) partially explaining traits such as C-reactive protein, changes in heart rate, and other phenotypic outcomes of exercise training. Another study called the Functional single nucleotide polymorphisms (SNP) Associated with Muscle Size and Strength (FAMuSS) will be evaluating the response of 1000 men and women to unilateral resistance exercise and evaluating the association 22

with various SNPs (11). The presence of the insertion (I), deletion (D) or I/D allele in the angiotensin converting enzyme gene has also received a lot of attention in the literature, especially in relation to a role in exercise adaptation. Most of the studies to date have used either a targeted approach or QTL approaches to dene loci or gene regions associated with a phenotype or phenotypic response to an intervention. More recently, a number of different SNP chips have been designed that can evaluate tens of thousands of SNPs simultaneously and this will likely lead to the identication of single SNPs and combinations of SNPs that will inuence a wide variety of phenotypes relevant to exercise nutrition. Although caffeine is technically a drug, its widespread use and benecial effects on sport performance, often place it in the category of sport nutrition. One area that is ripe for study would be how SNPs in the cytochrome P450 system alters caffeine metabolism, and how these SNPs could explain differences in the ergogenic effects of caffeine upon exercise performance. The potential for the new SNP chip technology to explain the phenomena of responders and nonresponders in a variety of areas of relevance to sport nutrition is huge and it is likely that many studies will be coming out in the next few years on the topic. Summary. The rapid explosion of the newer DNA technologies including gene chips and SNP chips has resulted in a reduction in cost that will place the methods in the hands of more sport nutrition scientists and hopefully uncover new information regarding the adaptability of the human body to exercise and how nutrition can inuence the phenotypic adaptations and to maximize performance. An exciting new area to consider is that the provision of anti-oxidant vitamins (vitamin C) can attenuate the acute increase in the mRNA for several molecular species involved in mitochondrial biogenesis in mice, and may attenuate training adaptations in humans.

References
1.

Arkinstall MJ, Tunstall RJ, Cameron-Smith D, and Hawley JA. Regulation of Metabolic Genes in Human Skeletal Muscle by Short-Term Exercise and Diet Manipulation. Am J Physiol Endocrinol Metab 2004. 2. De Bock K, Derave W, Eijnde BO, Hesselink MK, Koninckx E, Rose AJ, Schrauwen P, Bonen A, Richter EA, and Hespel P. Effect of training in the fasted state on metabolic responses during exercise with carbohydrate intake. J Appl Physiol 104: 1045-1055, 2008. 3. Deldicque L, Atherton P, Patel R, Theisen D, Nielens H, Rennie MJ, and Francaux M. Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. J Appl Physiol 104: 371-378, 2008. 4. Deldicque L, Louis M, Theisen D, Nielens H, Dehoux M, Thissen JP, Rennie MJ, and Francaux M. Increased IGF mRNA in human skeletal muscle after creatine supplementation. Med Sci Sports Exerc 37: 731-736, 2005. 5. Mahoney DJ, Parise G, Melov S, Safdar A, and Tarnopolsky MA. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. Faseb J 2005. 6. Mathai AS, Bonen A, Benton CR, Robinson DL, and Graham TE. Rapid exercise-induced changes in PGC-1{alpha} mRNA and protein in human skeletal muscle. J Appl Physiol 2008. 7. Parise G, Mihic S, MacLennan D, Yarasheski KE, and Tarnopolsky MA. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol 91: 1041-1047, 2001. 8. Pilegaard H, Osada T, Andersen LT, Helge JW, Saltin B, and Neufer PD. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise. Metabolism 54: 1048-1055, 2005. 9. Puigserver P, and Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24: 78-90, 2003. 10. Russell AP, Hesselink MK, Lo SK, and Schrauwen P. Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise. Faseb J 19: 986-988, 2005. 11. Thompson PD, Moyna N, Seip R, Price T, Clarkson P, Angelopoulos T, Gordon P, Pescatello L, Visich P, Zoeller R, Devaney JM, Gordish H, Bilbie S, and Hoffman EP. Functional polymorphisms associated with human muscle size and strength. Med Sci Sports Exerc 36: 1132-1139, 2004. 12. Tunstall RJ, McAinch AJ, Hargreaves M, van Loon LJ, and Cameron-Smith D. Reduced plasma free fatty acid availability during exercise: effect on gene expression. Eur J Appl Physiol 99: 485-493, 2007. 13. Willoughby DS, and Rosene J. Effects of oral creatine and resistance training on myosin heavy chain expression. Med Sci Sports Exerc 33: 1674-1681, 2001. 14. Willoughby DS, and Rosene JM. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc 35: 923-929, 2003.

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Table 1. Coming to term with terms AMP codon CPT DNA exon FAT/CD36 gene chip genome intron mRNA microRNA microarray PDK PCR proteome RNA RT-PCR SNP transcriptome transcription translation UCP adenosine monophosphate 3 base pair sequence encoding for a specic amino acid carnitine palmitoyl transferase deoxyribonucleic acid coding DNA sequence fatty acid translocase Microarray technology to study RNA or DNA the entire genetic sequence non-coding DNA sequence messenger RNA small 19-23 bp RNA species that regulate mRNA abundance method to study thousands of genes or mRNA species simultaneously on a glass/silica chip or beads pyruvate dehydrogenase kinase polymerase chain reaction (to amplify DNA or cDNA) global protein abundance ribonucleic acid reverse transcriptase PCR (to measure RNA abundance) single nucleotide polymorphism global mRNA abundance making mRNA from DNA template making protein from mRNA template uncoupling protein

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Are Men and Women the Same?

Brent C. Ruby University of Montana, Montana Center for Work Physiology and Exercise Metabolism, Missoula, MT, 59812

Introduction Are men different from women? A quick search command from the pivotal world of Google generates 319 million results. How the sexes may differ in fuel metabolism captures only about 1/2 of a percent of Googles attention. The primary discussions on how the sexes are similar and inherently different mingle in cyberspace and hover between psychology, workplace politics, learning patterns, social concerns, and the list continues to grow. In her 2005 book entitled, Why Men Never Remember and Women Never Forget, Marianne Legato recognizes some of the key ingredients that underline the differences between the sexes. In other words, our genes set us up for the sex well be, and our hormones salt the stew. The complex interaction between these two factorsespecially during specic windows when their levels drop or surge as they do during puberty and menopausemake the two sexes different and each of us different from one another as well. The primary focus of this discussion will include characteristics of fuel metabolism that can be altered by the salt of the stew and how these differences may be more prominent or suppressed at different stages of the life cycle. Additional attention will be directed to some of the methodology surrounding the measurement of muscle fuel use, the biological signicance of sex specic metabolic patterns, food fuels during muscle work and recovery, and how this transitions to the world outside of the laboratory. Should the advice for women be different than the advice we give to men? Anatomy, Physiology, and Research Design? Basic anatomy reveals unique sex characteristics rooted in biological signicance and function. However, the impact of sex on the underlying physiology offers more subtle differences at the cellular level during the selection, mobilization, and subsequent oxidation of muscle fuels during exercise. Although the data presented in Figure 1 represents a relatively small sample size (n=5 males, n=8 females), it shows the relative contribution of the dominant endogenous substrates available to the skeletal muscles of both sexes during moderate intensity exercise (65% if VO2peak). Both sexes rely heavily on fuels within the muscle as well as plasma FFA. These data suggest that the mechanisms by which unique sex characteristics exert control over the use of muscle substrates are less inuential compared to the dominant effects of training status and dietary state. The combination and relative contribution of these fuels to the working muscle during varying intensities and durations of exercise offers a near limitless series of metabolic choices. This combination is further inuenced and altered by the introduction of exogenous fuel sources, which may provide a large portion of muscle substrate during extended work and exercise settings.

Figure 1. Estimated relative contribution of endogenous muscle substrates oxidized at 65% of VO2peak. Data adapted from Romijn et al., 1993, 2000. Relative contribution data generated from indirect calorimetry and stable isotope infusion ([6,6 2H2] glucose and [2H2] palmitate. 25

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The majority of recent sex comparison studies evaluate similarly trained or tightly matched subjects (based on a series of criteria associated with current tness levels and training/competition histories) in a fasted state. In a recent review article, Tarnopolsky compares the data from 25 studies using meta-analyses and demonstrates a lower RER (higher relative contribution of fat to total energy expenditure) for females compared to males (0.87 and 0.90 for females and males, respectively). These data pool a variety of exercise protocols (with an exercise duration >60 min.) and approaches to subject selection. From these data, it appears that females demonstrate a higher fat oxidation compared to males during moderate intensity exercise. However, the underlying signicance from a biological and/or exercise performance/work perspective remains somewhat unclear. Additional insight can be gained from the literature investigating metabolic differences in children and adolescents. Timmons et al. (2007) has demonstrated that younger girls (aged 12 yr) show a higher rates of fat oxidation compared to older girls (aged 14 yr), an apparent inuence of the stages of puberty. How this may help explain sex differences in young adults (aged 18 yr) versus more mature endurance athletes (aged 25-35 yr) remains unclear. However, in response to the rigors of regular exercise training, the reproductive hormones that strongly inuence female sex characteristics ebb and ow as a function of energy intake and balance. From a biological standpoint, preservation of select endogenous substrates and shifting substrate use proles provide advantages to fetal development should pregnancy occur. In addition to the multiple factors that can inuence the availability, mobilization, and subsequent oxidation of these substrates are the numerous measurement techniques available. These have included the measurement of expired gas concentrations, the infusion and/or the ingestion of multiple stable isotopic tracers, in addition and/or in combination with the sampling of blood and muscle tissue. While all of these techniques provide a diverse series of variables to consider during the design of experimental procedures, additional concerns regarding the selection of research subjects and the exercise testing protocols should also be considered. This becomes a unique struggle in an attempt to adequately quantify an apples to oranges comparison using stringent laboratory control. To eat or not to eat during exercise? It has been suggested that because females have demonstrated a lower dependence on muscle glycogen during 90 minutes of moderate intensity exercise (Tarnopolsky, 1990), that they may excel in endurance and ultra-endurance events. However, to perform at a high level during these events, careful approaches to exogenous intake behavior are imperative. Therefore, it is unclear whether a slightly higher fat oxidation would provide clear benets during extended work settings where exogenous intake becomes mandatory to maintain work output. Wallis et al. (2006) evaluated the metabolic responses in similarly trained men and women during 2 hours of continuous cycling exercise (67% VO2peak) with and without exogenous carbohydrate (CHO). During the trials, subjects consumed equal volumes of CHO or water at regular intervals. Carbohydrate was consumed at a rate of 90 grams/ hour throughout the exercise. Exogenous CHO increased total CHO oxidation for both males and females and reached similar peak rates of oxidation (approximately 0.6 g.min-1). Overall, these data indicate that although exogenous carbohydrate intake suppresses the use of endogenous fuels (liver glycogen and whole body fat), the responses between the sexes are similar (Figure 2). Moreover, these data are similar to those reported by MKaouar et al. (2004) and Riddell et al. (2003) and suggest that both males and females may benet equally from similar exogenous feeding schedules during extended exercise/work settings. Although the idea of suggesting similar intake patterns for males and females simplies the calculations, the need for individual trial and error should not be understated. For a 72 kg male, an intake of 60g.hr-1 would amount to 0.8 g.kg-1. hr-1 compared to a 55 kg female (1.1 g.kg-1.hr-1), a difference that may result in signicant stomach discomfort in the smaller female. However, the trainability of the GI system to tolerate and accept exogenous CHO should also not be discounted. This requires further attention as it relates to maximizing the rate of exogenous CHO oxidation. This is especially true during extended bouts of muscle work during which the exogenous intake may assume nearly 100% of the total CHO oxidation.

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Figure 2. The relative contribution of endogenous and exogenous substrate oxidation during exercise. Adapted from Wallis et al. 2006). During a 10-hour intermittent exercise trial in our laboratory (Harger-Domitrovich et al. (2007)), males (n=7) and females (n=6) were provided with exogenous CHO or placebo. Net muscle glycogen use was 52% higher during the placebo trial. However, there were no differences between the sexes (Figure 3). Under these conditions (extended exercise), exogenous CHO accounts for a large percentage of the total CHO oxidation and reduces the demand placed on endogenous CHO sources (liver and muscle glycogen) regardless of sex.

Figure 3. Muscle glycogen breakdown for the two exercise trials. e=p<0.05 vs. CHO trial for males and females. Main effect for trial. Adapted from Harger-Domitrovich, 2007.

Loading and Recovery Although past data suggests that males and female derive similar benets from exogenous CHO consumed at similar rates, the ability to better prepare for endurance competitions through CHO loading may be somewhat limited to males. Tarnopolsky et al. (1995) showed that females were not able to increase muscle glycogen via traditional approaches to CHO loading. In contrast, if CHO intake can be increased to >8.0 g.kg-1.day-1, glycogen can be pre-loaded into the female muscle. However, this approach may be less practical for females due to the high % of CHO required to achieve super compensation (usually >70% of total energy intake). These data place further importance on maximizing the systems ability to tolerate higher rates of exogenous CHO sources during the period of exercise/work. In response to glycogen depleting exercise, Tarnopolsky et al. (1997) showed that a CHO or a CHO-protein source enhanced glycogen recovery similarly in males and females. This early approach to recovery may be recommended for both sexes if additional training periods/competitions are scheduled for later that day or the next. Sex comparisons outside of the typical laboratory Collectively, the literature suggests that there are testing situations in the laboratory where males and females differ in the selection and oxidation of muscle substrates. These observations are essential in understanding the basic biological signicance the sex hormones provide to development and reproduction. However, when transitioned outside of the laboratory, the subtle sex differences in the fasted state and the unique control exerted by the sex specic hormones become less inuential than the required dietary and environmental adjustments necessary to sustain muscle work in the eld. In these settings, sex is put aside and the hostilities of the environment dictate the required response. 27

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During the 2005/2006 Ironman World Championships in Kona, HI and during the 2007 Western States 100 ultramarathon, our laboratory quantied total energy expenditure (TEE) of competitors (doubly labeled water). In Kona, TEE was 9,253 and 9,920 kcals for the two male subjects and 8,238 kcals for the female. Relative to total body weight TEE for the female (135 kcals.kg-1) was slightly higher compared to the males (119 and 122 kcals.kg-1, respectively). For a 10-hour race, considering an average intake of 60 g.hr-1, exogenous CHO and total energy intake may account for approximately 2530% of the TEE. Similarly, during the Western States 100, males and females were evaluated for measures of TEE and water turnover (rH2O). Although males were signicantly heavier (78.48.0 kg) compared to females (61.57.7 kg), there were no differences in nish times (26.42.9 and 27.13.7 hours) or total energy expenditure (22123 and 22823 kcals.kg-1.race-1 for males and females, respectively). Calculated rates of water turnover were also similar for both sexes (25437 and 25949 ml.kg-1.race-1 for males and females, respectively). Conclusions Laboratory data demonstrates a tendency for females to oxidize more whole body fat in comparison to similarly trained males. The majority of these differences appear to be the result of 17- estradiol and the inuence it exerts on the mRNA of human skeletal muscle. These subtle alterations can inuence fat, CHO and protein metabolism to ensure a sex specic metabolism that asserts biological signicance to ensure an ideal in vivo environment for reproductive health. The extent to which these subtle variations may inuence extended muscle work or endurance competition is uncertain. However, it appears that the effects of exogenous CHO on substrate oxidation are similar for both males and females. Moreover, when compared under extended eld exercise conditions, subtle differences in metabolism are diminished and there are limited differences between males and females. Therefore there is no reason to believe that the nutrition advice given to females should be different than the advice given to males. Table 1. Nutritional intervention None Exogenous CHO during Rate --1-1.5* g.min-1 1 g.kg-1CHO @0, 60min post Physiological Response females > fat oxidation maximize CHO availability preserve endogenous CHO (liver, muscle?) > glycogen resynthesis Benet ? > power output > output longer >recovery for next session/comp

CHO during recovery

*1.5 g.min -1 only recommended when a mixture of carbohydrates is ingested i.e. glucose+fructose

References
Harger-Domitrovich SG, McClaughry AE, Gaskill SE, Ruby BC. Exogenous carbohydrate spares muscle glycogen in men and women during 10 h of exercise. Med Sci Sports Exerc. 2007 Dec;39(12):2171-9. MKaouar H, Pronnet F, Massicotte D, Lavoie C. Gender difference in the metabolic response to prolonged exercise with [13C]glucose ingestion. Eur J Appl Physiol. 2004 Aug;92(4-5):462-9. Epub 2004 May 8. Riddell MC, Partington SL, Stupka N, Armstrong D, Rennie C, Tarnopolsky MA. Substrate utilization during exercise performed with and without glucose ingestion in female and male endurance trained athletes. Int J Sport Nutr Exerc Metab. 2003 Dec;13(4):407-21. Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E, Wolfe RR. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol. 1993 Sep;265(3 Pt 1):E380-91. Romijn JA, Coyle EF, Sidossis LS, Rosenblatt J, Wolfe RR. Substrate metabolism during different exercise intensities in endurance-trained women. J Appl Physiol. 2000 May;88(5):1707-14. Tarnopolsky LJ, MacDougall JD, Atkinson SA, Tarnopolsky MA, Sutton JR. Gender differences in substrate for endurance exercise. J Appl Physiol. 1990 Jan;68(1):302-8. Tarnopolsky MA, Atkinson SA, Phillips SM, MacDougall JD. Carbohydrate loading and metabolism during exercise in men and women. J Appl Physiol. 1995 Apr;78(4):1360-8. Tarnopolsky MA, Bosman M, Macdonald JR, Vandeputte D, Martin J, Roy BD. Postexercise protein-carbohydrate and carbohydrate supplements increase muscle glycogen in men and women. J Appl Physiol. 1997 Dec;83(6):1877-83. Tarnopolsky MA. Sex differences in exercise metabolism and the role of 17-beta estradiol. Med Sci Sports Exerc. 2008 Apr;40(4):648-54. Timmons BW, Bar-Or O, Riddell MC. Energy substrate utilization during prolonged exercise with and without carbohydrate intake in preadolescent and adolescent girls. J Appl Physiol. 2007 Sep;103(3):995-1000. Epub 2007 Jul 5. Wallis GA, Dawson R, Achten J, Webber J, Jeukendrup AE. Metabolic response to carbohydrate ingestion during exercise in males and females. Am J Physiol Endocrinol Metab. 2006 Apr;290(4):E708-15. Epub 2005 Nov 8.

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Fat burning: how and why?

Asker E. Jeukendrup School of Sport and Exercise Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom Introduction Fat burning is a very popular and often used term amongst endurance athletes. There are fat burning workouts, fat burning nutrition supplements (fat burners), exercise machines in the gym have fat burning options and heart rate monitors tell you when you are in the fat burning zone. The term fat burning refers to the ability to oxidise (or burn) fat and use fat as a fuel instead of carbohydrate. Often fat burning is associated with weight loss, decreases in body fat and increases in lean body mass. However, it must be noted that such changes in body weight and body composition can only be achieved with a negative energy balance: you have to eat less calories than you expend, independent of the fuels you use! It is important to realise that increasing fat oxidation does not mean losing body fat or body weight! Here we will discuss the importance of fat burning and the most important factors that inuence fat burning as well as nutrition supplements that claim to increase fat burning. The importance of fat metabolism It is becoming increasingly clear that the ability to oxidise fat is important for both performance and health. It is also well established that well-trained endurance athletes have an increased capacity to oxidise fatty acids. This enables them to use fat as a fuel when carbohydrate stores become limited. In contrast, patients with obesity, insulin resistance and type II diabetes may have an impaired capacity to oxidise fat. As a result fatty acids may be stored in the muscle and in other tissues. This accumulation of lipid in the muscle and its metabolites may interfere with the regulation of metabolism. Although evidence for this is not available it is also attractive to think that an increased capacity to oxidise fat may aid those who want to loose weight and in particular body fat if used in combination with a negative energy balance. Factors that affect fat oxidation Exercise intensity One of the most important factors that determine the rate of fat oxidation during exercise is the intensity. Although several studies have described the relationship between exercise intensity and fat oxidation, only recently this relationship was studied over a wide range of intensities (2) (Figure 1). In absolute terms, carbohydrate oxidation will increase proportionally with exercise intensity, whereas the rate of fat oxidation will initially increase but will decrease again at higher exercise intensities (Figure 1). So although it is often claimed that you have to exercise at low intensities to oxidise fat, this is not necessarily true. In a series of recent studies we have dened the exercise intensity at which maximal fat oxidation is observed as Fatmax. In a group of trained individuals it was found that exercise at moderate intensity (62-63%VO2max or 7075%HRmax; Figure 1) was the optimal intensity for fat oxidation, whereas it was around 50%VO2max for less trained individuals (2, 8)). However, it must be noted that the inter-individual variation is very large. A trained person may have his maximal fat oxidation at 70%VO2max or 45%VO2max and the only way to really nd out is to perform one of these Fatmax tests in the laboratory. However, in reality the exact intensity at which fat oxidation peaks may not be that important because within 5-10% of this intensity (or 10-15 beats per minute), fat oxidation will be similarly high, and only when the intensity is 20% higher or so, fat oxidation will drop rapidly (Figure 1). This exercise intensity (Fatmax) or zone may have importance for weight loss programs, health-related exercise programs, and endurance training. However, very little research has been done.

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Figure 1: Exercise intensity (expressed as %HRmax and %VO2max) and fat oxidation. Fat oxidation increases from low to moderate exercise intensities, peaks at Fatmax and decreases as the exercise intensity increases further. The grey area represents the Fatzone: a range of exercise intensities where fat oxidation is high. Dietary effect The other important factor is diet. A diet high in carbohydrate will suppress fat oxidation and a diet low in carbohydrate will result in high fat oxidation rates. Ingesting carbohydrate in the hours before exercise will raise insulin and subsequently suppress fat oxidation by up to about 35% (1). This effect of insulin on fat oxidation may last as long as 6-8 hours after a meal and this means that the highest fat oxidation rates can be achieved after an overnight fast. Exercise without breakfast has often been used by endurance athletes as a way to increase the fat oxidative capacity of the muscle. Recently a study was performed at the University of Leuven in Belgium in which they investigated the effect of an endurance training program (6 wk, 3 day/wk, 12 h) (5). The participants trained in the fasted or carbohydrate fed state. The investigators observed a decrease in muscle glycogen use and the activity of various proteins involved in fat metabolism was increased after training in the fasted state. However, fat oxidation during exercise was the same in the two groups. It is possible though that there are small but signicant changes in fat metabolism after fasted training but in this study changes in fat oxidation might have been masked by the fact that these subjects received carbohydrate during their experimental trials. It must also be noted that training after an overnight fast may reduce the exercise capacity and may therefore only be suitable for low to moderate intensity exercise sessions. The efcacy of such training for weight reduction is also not known. Duration of exercise It has been established for a long time that fat oxidation becomes an increasingly important fuel as exercise progresses. During ultra-endurance exercise fat oxidation can reach peaks of 1 g/min although fat oxidation may be reduced if carbohydrate is ingested before or during exercise. In terms of weight loss the duration of exercise may be one of the key factors as it is also the most effective way to increase energy expenditure. The mode of exercise The exercise modality also has an effect on fat oxidation. Fat oxidation has been shown to be higher for a given oxygen uptake during walking and running compared with cycling (3). The reason for this is not known but it has been suggested that it is related to the greater power output per muscle bre in cycling compared to running. Gender differences Although some studies in the literature have found no gender differences in metabolism, the majority of studies now indicate higher rates of fat oxidation in women compared with men. In a study in which 150 men and 150 women were compared over a wide range of exercise intensities, it was demonstrated that the women had higher rates of fat oxidation over the entire range of intensities and fat oxidation peaked at a slightly higher intensity (9). The differences however are small and may not be of great physiological signicance. Environment Environmental conditions can also inuence substrate utilisation. It is known that exercise in a hot environment will increase glycogen use and reduce fat oxidation and something similar can be observed at high altitude. Similarly when it is extremely cold and especially when shivering, carbohydrate metabolism will be stimulated at the expense of fat metabolism. 30

Exercise training The only effective way to increase fat oxidation during exercise at present is to perform regular physical activity. Exercise training will upregulate the enzymes of the fat oxidation pathways, increase mitochondrial mass, increase blood ow etc. all of which will enable higher rates of fat oxidation. Research has shown that as little as 4 weeks of regular exercise (3 times per week 30-60 min) can increase fat oxidation rates and cause enzymatic changes (6). Too little information is available to draw any conclusions about the optimal training programme to achieve these effects. Exercise programmes to lose weight or body fat The optimal exercise type, intensity, and duration for weight loss are still unclear. Current recommendations are mostly focused on increasing energy expenditure and increasing participation in exercise. Finding the optimal intensity for fat oxidation might aid in losing weight (fat loss) and support weight maintenance but evidence for this is currently lacking. It is also important to realise that the amount of fat oxidised during exercise is only small. Fat oxidation rates are on average 0.5 g/min at the optimal exercise intensity. So in order to oxidise 1 kg of fat mass, more than 33 hours of exercise is required. Walking or running exercise around 50-65%VO2max seems to be an optimal intensity to oxidise fat. The duration of exercise however, plays a crucial role with an increasing importance of fat oxidation with longer exercise. Of course this also has the potential to increase daily energy expenditure. If exercise is the only intervention used the main goal is usually to increase energy expenditure and reduce body fat. When combined with a diet program, however, it is mainly used to counteract the decrease in fat oxidation often seen after weight loss (4). Nutrition supplements There are many nutrition supplements on the market that claim to increase fat oxidation. These supplements include caffeine, carnitine, hydroxycitric acid (HCA), chromium, conjugated linoleic acid (CLA), guarana, citrus aurantium, asian ginseng, cayenne pepper, coleus forskholii, glucomannan, green tea, psyllium and pyruvate (a selection of supplements is listed in Table 1). With few exceptions, there is limited to no evidence that these supplements marketed as fat burners actually increase fat oxidation during exercise (7). We will discuss three supplements below. The rest is summarised in the table. Carnitine Carnitine is one of the most popular fat burners. It has been around for a long time and became very popular in the 90s after the Italian football team won the world champion and revealed that they had used carnitine. Carnitine is a substance produced by the body but also obtained via daily food intake. It is found mostly in meat and plays a crucial role in fat metabolism. Carnitine is responsible for the transport of fats into the mitochondria (the powerplants in the cells that provide the muscle with the energy to contract). Patients who cannot synthesize carnitine are unable to use fat as a fuel and they rely solely on carbohydrate. The entire theory that carnitine supplementation helps fat metabolism, however, is badsed on the premise that when you ingest carnitine that this carnitine enters the muscle the concentration of carnitine in the muscle increases. Studies in the 90s showed however, that even with large dose of carnitine the muscle carnitine concentration is unaffected and therefore carnitine cannot expected to have an effect on fat metabolism. The interest in carnitine disappeared (at least amongst scientists because athletes were still buying carnitine!). Recently however, there is some renewed interest in carnitine. Professor Paul Greenhaff and his coworkers at the University of Nottingham showed that IF you can increase the muscle carnitine, this can increase fat metabolism. They increased muscle carnitine by simultaneously increasing the insulin concentration and providing carnitine. So possibly carnitine may have some effects, especially long term if it is used in combination with carbohydrate. However, it is probably too early to draw any conclusions and the fact remains that most studies have not observed any effects of carnitine. Green tea Green tea has many suggested medicinal properties and there is actually some evidence that is does protect against various diseases. More recently research has focused on its effects on fat metabolism and although 90% of the research is on animals and not in humans the results are promising. We recently showed that ingesting a green tea extract the night before and an hour before a 30 min cycling bout increased fat metabolism by 20% (10). The green tea extract contains mainly Epogalocatechin gallate or EGCG, the active ingredient in green tea. EGCG is one of most powerful polyphenols with anti-oxidant properties, increased the activity of the enzyme responsible for the breakdown of catecholamines (adrenaline and noradrenaline). This in turn may result in higher concentrations of catecholamines and stimulation of lipolysis making more fatty acids available for oxidation. There is also some evidence that EGCG increases metabolic rate suggesting that it could help with weight loss. The green tea extract contains the active ingredient in a concentrated form and the dose that we used to see the 20% improvement in fat metabolism was fairly large. It would equate to drinking a liter of green tea. Whether smaller doses of green tea will still have an effect we dont know but this is something we are studying at the moment. 31

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Caffeine Caffeine is often associated with increased fat metabolism. However, whether caffeine actually has this effect depends on the type of exercise and the dose of caffeine. Effects on fat metabolism are typically seen at lower intensities of exercise and with relatively low doses of caffeine. At high doses of caffeine and at higher intensities of exercise, carbohydrate metabolism may be stimulated and fat metabolism may even be suppressed. Several fat burners contain at least some caffeine. Does a cup of coffee with breakfast work? Probably not a lot! The reason for that is that a breakfast will at least contain some carbohydrate and this will cause the hormone insulin to be released and this in turn will suppress fat metabolism. So although caffeine might stimulate fat metabolism a little, this effect would be completely overruled by insulin. This is not only true for caffeine but in fact for all supplements. Increased fat metabolism can probably only be observed in the morning, after an overnight fast and before breakfast. Therefore in order to stimulate fat metabolism there probably is no easy option! You still have to exercise; you may have to do this without breakfast. Fat burning exercise sessions can have a place in a weekly training schedule but it is probably not a good idea to do too many of these sessions in one week. Summary Higher fat oxidation rates during exercise are generally reective of good training status whereas low fat oxidation rates might be related to obesity and insulin resistance. Fat oxidation peaks on average at moderate intensities 5065%VO2max depending on the training status of the individuals (2, 9), increases with increasing exercise duration but is suppressed by carbohydrate intake. Fat oxidation is slightly higher in women than in men. Also altitude and hot (or very cold) environmental conditions can increase carbohydrate and reduce fat oxidation. Many supplements are claimed to improve fat oxidation but most supplements are ineffective. The only highly effective way to increase fat oxidation is through exercise training, although it is still unclear what the best training regimen is to get the largest improvements. Finally, it is important to note that there is a very large inter-individual variation in fat oxidation that is only partly explained by the factors mentioned above. This means that although the factors mentioned above can inuence fat oxidation, they cannot predict fat oxidation rates in an individual.

Table 1: Nutrition supplements and the scientic evidence that the supplement increases fat metabolism Nutrition supplement Caffeine Evidence Fat burning properties (claims) Caffeine stimulates lipolysis and the mobilization of FAs. These actions might occur indirectly by increasing the circulating catecholamine levels or directly by antagonizing adenosine receptors that normally inhibit hormone-sensitive lipase and FA oxidation. In some but not all conditions this can result in increased fat oxidation. Carnitine is essential for fat oxidation as it is needed to transport fatty acids into the mitochondria. Studies have shown however, that carnitine supplementation may not result in increased muscle carnitine supplementation and therefore it is not surprising that no effects on fat oxidation have been found. Nevertheless it is one of the supplements that is aggressively marketed as a fat burner. New studies may provide new insights and it is possible that Cayenne pepper has been used as a medicine for centuries, and has recently gained attention as a possible fat burning supplement. Cayenne contains capsaicin, which may help increase metabolic rate and stimulate circulation.

Carnitine

Cayenne pepper (Capsaicin)

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Chromium

Chromium was a very popular supplement a few years ago and was associated with ninsulin sensitivity and fat burning. There is no evidence that chromium has any effect on fat metabolism. Citrus aurantium (from bitter orange) contains ve andrenergic amines including synephrine and tyramine, which stimulate the beta-3 cell receptors, stimulating lipolysis. Coleus forskholii is an ancient herb that has gained attention lately as a possible fat burner. An extract called Forskolin present in Coleus has been found to be benecial in its ability to burn fat. Forskolin activates adenylate cyclase, which in turn triggers an increase in cyclic adenosine monophosphate (cAMP). This increase in cAMP turns on the system responsible for the release of fat from its stores. Fatty acids that have been linked with special properties (especially antioxidant properties) but have also been linked to increases in fat metabolism. Evidence is weak. The active constituent of guarana, guaranine, is nearly identical to caffeine and is likely to have similar properties. There is far less research with guaranine compared with caffeine. Asian ginseng (Panax ginseng) has been a part of Chinese medicine for over 2,000 years and was traditionally used to improve mental and physical vitality. Evidence for fat burning properties is lacking. Glucomannan is a dietary ber derived from the Konjac plant of South East Asia. It is included in fat burning supplements probably because of its potential effect on food intake. However, the bre itself has no effects on fat metabolism. The active constituents in green tea are the polyphenols, particularly the catechin, epigallocatechin gallate (EGCG). However green tea also contains caffeine. A recent study showed that fat oxidation during exercise increased by about 20%. HCA is a derivative of citric acid that is found in a variety of tropical plants. There is no evidence that it has any effect on fat metabolism Pyruvate is an intermediate of carbohydrate metabolism and it is difcult to see how pyruvate intake could increase fat oxidation. Nevertheless, this is one of the claims often made. Psyllium is a soluble ber that comes from the small reddish black seeds of the Plantago Psyllium plant. Like glucomannan, psyllium is probably marketed as a fat burner because of its potential effect on food intake. However, the bre itself has no effects on fat metabolism. L-tyrosine is a nonessential amino acid that serves as a precursor to catecholamines. The assumption is that more tyrosine results in chronically elevated catecholamine concentrations and increased lipolysis. There is no evidence to support this.

Citrus aurantium

Coleus forskholii (Forskolin)

Conjugated linoleic acid (CLA)

Guarana

Ginseng (Asian or Panax)

Glucomannan

Green tea

Hydroxycitric acid (HCA)

Pyruvate

Psyllium

Tyrosine

The scientic evidence is indicated with meaning very strong evidence and Limited to no evidence.

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References
1. Achten J, and Jeukendrup AE. The effect of pre-exercise carbohydrate feedings on the intensity that elicits maximal fat oxidation. J Sports Sci 21: 1017-1024, 2003. 2. Achten J, and Jeukendrup AE. Maximal fat oxidation during exercise in trained men. Int J Sports Med 24: 603-608, 2003. 3. Achten J, Venables MC, and Jeukendrup AE. Fat oxidation rates are higher during running compared with cycling over a wide range of intensities. Metabolism 52: 747-752, 2003. 4. Astrup A. Dietary composition, substrate balances and body fat in subjects with a predisposition to obesity. Int J Obes Relat Metab Disord 17 Suppl 3: S32-36; discussion S41-32, 1993. 5. De Bock K, Derave W, Eijnde BO, Hesselink MK, Koninckx E, Rose AJ, Schrauwen P, Bonen A, Richter EA, and Hespel P. Effect of training in the fasted state on metabolic responses during exercise with carbohydrate intake. J Appl Physiol 104: 1045-1055, 2008. 6. Holloszy JO, and Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 56: 831-838, 1984. 7. Jeukendrup AE, and Aldred S. Fat supplementation, health, and endurance performance. Nutrition 20: 678-688, 2004. 8. Jeukendrup AE, and Wallis GA. Measurement of substrate oxidation during exercise by means of gas exchange measurements. Int J Sports Med 26 Suppl 1: S28-37, 2005. 9. Venables MC, Achten J, and Jeukendrup AE. Determinants of fat oxidation during exercise in healthy men and women: a cross-sectional study. J Appl Physiol 98: 160-167, 2005. 10. Venables MC, Hulston CJ, Cox HR, and Jeukendrup AE. Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans. Am J Clin Nutr 87: 778-784, 2008.

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