2008 birmingham low res

7/27/2019 2008 Birmingham Low Res

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This is the third Sport Nutrition conference of this format, organized and hosted by the University of Birmingham.

The first 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 Exer-

cise Science facilities in the world.

The main goal of the conferences is to bridge the gap between the science on the one side and practiceon 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 findings 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 bet-

ween 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 low-

compete high!, and many other current topics in sports nutrition were discussed. This booklet summarises the presen-

tations 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 find the content of this booklet useful and that it will help to make positive changes to your nutriti-

on.

Asker Jeukendrup

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?...................................................................................................................................................................25Brent C. Ruby

7 - Fat burning: how and why? ............................................................................................................................................................................. 29

Asker E. Jeukendrup

Preface, Prof. Asker Jeukendrup

Content


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Kevin D. Tipton

School of Sport and Exercise Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom

Weight control is a significant issue for many people, including athletes. Obesity is prevalent and increasing in our so-

ciety 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 sufficient period of time. Thus, decreased energy intake through dietary en-

ergy 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 signifi-

cant degree. Thus, control of dietary energy intake is crucial. Recently, it has become evident that

weight loss may be influenced, 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 significant 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 withexercise 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 definition 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 carbo-

hydrate 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

scientific literature, the definition 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 com-

position 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.

1 Protein and weight loss


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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

Normal

Per kg body wt. % energy Total

High Protein

Per kg body wt. % energy

Energy

[kcal]

Weight maintenance

Low calorie

3500 kcal

2100 kcal

44 kcal/kg

26 kcal/kg

3500 kcal

2100 kcal

44 kcal/kg

26 kcal/kg

Carbohydrates [g] Weight maintenance

Low calorie

440 g

265 g

5.50 g/kg

3.31 g/kg

50 %

50 %

440 g

262 g

5.50 g/kg

3.28 g/kg

50 %

50 %

Fat

[g]

Weight maintenance

Low calorie

135 g

80 g

1.69 g/kg

1.00 g/kg

35 %

35 %

135 g

35 g

1.69 g/kg

0.44 g/kg

35 %

15 %

Protein

[g]

Weight maintenance

Low calorie

132 g

80 g

1.65 g/kg

1.00 g/kg

15 %

15 %

132 g

184 g

1.65 g/kg

2.25 g/kg

15 %

35 %

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 demonstra-

ted that ingestion of pork protein resulted in greater feelings of satiety than did soy protein (5). Even the specific 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 inefficient utilization of the protein. It takes more energy to process the protein than it does carbo-hydrates 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 provi-

ded 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.


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Table 2. Food items high in protein (animal and plant protein sources) and branched-chain amino acids.

Protein BCAA

Animal Plant

Food Skim Milk (dairy) Soy protein Dairy

Beef Legumes (beans and peas) Beef

Chicken Whole grains Chicken

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 im-

portance 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 preli-

minary 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 influ-

ence the response to these diets which may not be similar for already well-trained athletes.

There seem to be some conflicting 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).


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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 mu-

scle 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 specific 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 theappropriate 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. The specific goals of the individual should be carefully considered.

2. 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, fish 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 ofprotein 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 onnutrition 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 Sport s 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 d isease. Am J Clin Nutr 84 : 475-482, 2006


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2 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 conditio-

ning and performance. However, the validity of this philosophy is now being challenged. It is becoming clear that there

are benefits to training in a glycogen-depleted state. The potential benefits 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 benefits 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 exercisecould greatly vary the glycogen content in skeletal muscle (Bergstrom et al., 1967). This final observa-

tion, 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 first time

that a high muscle glycogen was beneficial 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 arterio-

venous 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 beneficial 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. The-

se results have now been confirmed 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 ex-

pected to have a glycogen sparing effect during competition leading to improved performance. While this might be true

at low 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 po-

sitive effect on performance. However, in shorter, higher intensity events (10K run, time trial cycling, rowing), training in


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a glycogen-depleted state will have less of a performance benefit. One caveat is that for competitions

such as world championships and Olympics, where heats are run prior to the finals, low glycogen

training, and the resulting increase in the capacity to use fat as a fuel, may improve recovery and

therefore have beneficial 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 beneficial 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 beneficial?

Endurance training in a glycogen-depleted state results in an improved capacity to use fat to fuel exercise. One impor-

tant question is why? Some recent work has given clues as to how training in a glycogen-depleted state results in this

beneficial 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 1The 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 stateIf 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 de-

creased by about one third that of the normal. This can be accomplished by performing steady state exercise at ~70% of


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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 Depletion Session Adaptive Session

Marathon 1h @ 75% HRmax 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% HRmaxRoad Cycling 1h @ 70% HRmax 6 x 5min at 95% HRmax with 2min recovery

2 x 20min hills @ 80% Wmax

Swimming 20x 150m @ medium-high effort 15

sec rest

30 x 100m @ medium-high

15 x 50m with 10sec recovery, or

10 x 200m with 20sec recovery, or

4 x 400m with 40sec recovery

effort 15 sec rest All with increasing intensity (1st med last race

pace)

Triathlon 4h bike with no supplementation

Low CHO dinner

Morning - 3h ride with 3 x 10min @ 90% Wmax, or

Morning 1h run with 2 x 1 mile at 10K pace

Football/Soccer 30min run @75% HRmax Regular training with team, skills sessions, repeated

sprints, ball skills, etc.

Rugby/US Football,Sprinting,

Rowing,

Time trial cycling

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 sour-

ces of fuel, there is no performance benefit 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 biologie2, 1-7.Blomstrand E & Saltin B. (1999). Effect of muscle glycogen on glucose, lactate and amino acid metabolism during exerciseand 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: trainingtwice every second d ay 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 contentand glucose uptake during exercise in humans: influence 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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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 fluid 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 ofheat 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 fluid 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 com-

plex. Fatigue may be influenced 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 ex-

cess 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

fluid losses equivalent to 3% of body mass or more. In hot conditions, similar water deficits 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 deficit. 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 fluid 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

sufficient to impair athletic performance) can occur before the desire for fluid intake is evident. This is where the debate

is hotting up (7).

The debate

Although there is a significant body of evidence that dehydration can impair exercise performance, Prof Noakes has war-

ned, 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 acomplex 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 per-

formance. Rather, exercise performance is modified (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 beneficial 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

fluids. 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?

3 Hydration: what is new?


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The guidelines

Until the early 1970s, the guidelines for fluid 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 fluid was ingested

(compared with no fluid ingestion). The guidelines evolved accordingly. By 1996, guidelines stated, individuals should

be encouraged to consume the maximal amount of fluids during exercise that can be tolerated without gastrointesti-

nal 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 deficit) and excessive changes

in electrolyte balance to avert compromised exercise performance. The amount and rate of fluid 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 fluid. The combinations highlighted in orange are either ingesting too little fluid resulting in weight loss of >3%

or ingesting too much fluid (weight gain).

Marathon time (h) Fluid intake (L/h) 05:00 04:30 04:00 03:30 03:00

Pace (min/mile) 11:30 10:20 09:12 08:00 06:55

Pace (km/h) 8.4 9.4 10.6 12.1 14.1

Sweat rate (L/h) 0.4 0.5 0.6 0.8 1

Person 50 kg 0.0 -4.0 % -4.5 % -4.8 % -5.6 % -6.0 %

0.2 -2.0 % -2.7 % -3.2 % -4.2 % -4.8 %

0.4 0.0 % -0.9 % -1.6 % -2.8 % -3.6 %

0.6 2.0 % 0.9 % 0.0 % -1.4 % -2.4 %

0.8 4.0 % 2.7 % 1.6 % 0.0 % -1.2 %

1.0 6.0 % 4.5 % 3.2 % 1.4 % 0.0 %

Person 65 kg 0.0 -3.1 % -3.5 % -3.7 % -4.3 % -4.6 %

0.2 -1.5 % -2.1 % -2.5 % -3.2 % -3.7 %

0.4 0.0 % 0.7 % -1.2 % -2.2 % -2.8 %

0.6 1.5 % 0.7 % 0.0 % -1.1 % -1.8 %

0.8 3.1 % 2.1 % 1.2 % 0.0 % -0.9 %

1.0 4.6 % 3.5 % 2.5 % 1.1 % 0.0 %

Person 80 kg 0.0 -2.5 % -2.8 % -3.0 % -3.5 % -3.8 %

0.2 -1.3 % -1.7 % -2.0 % -2.6 % -3.0 %0.4 0.0 % -0.6 % -1.0 % -1.8 % -2.3 %

0.6 1.3 % 0.6 % 0.0 % -0.9 % -1.5 %

0.8 2.5 % 1.7 % 1.0 % 0.0 % -0.8 %

1.0 3.8 % 2.8 % 2.0 % 0.9 % 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 condi-


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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 benefits. 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 Claim Evidence

Caffeine Caffeine is a diuretic and should be avoided

before and during exercise

Caffeine ingested in moderate doses (up to

300mg) is not a diuretic and there is no reasonto restrict caffeine intake at levels below 300 mg.

Creatine Creatine increases water storage, removes

water from the vascular space and increases

heat stress

There is no evidence that creatine increases

heat stress or decreases performance in hot

conditions.

Glycerol Glycerol is a hyperhydrating agent which in-

creases water storage, reduces heat stress and

improvces exercise performance in the heat

Glycerol can result in increased water storage,

reduced heat stress in extreme conditions and

there are some reports of improved perfor-

mance. Its use however, is impractical and can

cause side effects.

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 contrac-tions. 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 confirmed 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 difficult to estimate

sodium losses and therefore difficult 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 difficult to investigate, sodium

deficits seem to play an important role in the development of cramps.

Combining energy and fluid

Especially during prolonged exercise when carbohydrates reserves become depleted, carbohydrate intake in addition

to fluid intake is important. However, it is known that with increasing carbohydrate intake (increasing carbohydrate

concentration), the absorption of fluid may be impaired. Hence sports drinks are always a compromise between delive-

ring energy and delivering fluid. Most sports drinks are in the 4-8% carbohydrate range where the impairment in fluid

absorption is still acceptable. However, in the >10% range it is generally thought that both gastric emptying and absorp-tion of fluid are hampered even though it may result in a greater delivery of carbohydrate. Interestingly we recently advi-

sed 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 fluid 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 fluid delivery. In studies where stable isotopes were used to label water and

study fluid delivery it was demonstrated however that mixtures of glucose and fructose result in a faster rate of gastric

emptying and a superior fluid delivery compared with a single carbohydrate (Figure 1). Therefore in situations where

both carbohydrate and fluid delivery are important and the exercise duration is >2h it would be advised to take solutionswith 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 fluid and carbohydrate delivery compared with a single carbohydrate (Glucose: GLU).

Figure redrawn from (2, 3).

1. Currell K, and Jeukendrup AE.Superior endurance performance with ingestion of multiple transportable carbohydrates. Med Sci Sports Exerc 40: 275-281, 2008.

2. Jeukendrup AE, and Moseley L.Multiple transportable carbohydrates enhance gastric emptying and fluid delivery Scand J Med Sci Sports In press: 2008.

3. 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.

4. Noakes TD.Drinking guidelines for exercise: what evidence is there that athletes should dr ink as much as tolerable,to replace the weight lost during exercise or ad libitum? J Sports Sci 25: 781-796, 2007.

5. Noakes TD.Hydration in the marathon : using thirst to gauge safe fluid replacement. Sports Med 37: 463-466, 2007.

6. Sawka MN, Burke LM, Eichner ER, Maughan RJ, Montain SJ, and Stachenfeld NS. American College of Sports Medicine position stand.Exercise and fluid replacement. Med Sci Sports Exerc 39 : 377-390, 2007.

7. Sawka MN, and Noakes TD.Does dehydration impair exercise performance? Med Sci Sports Exerc 39 : 1209-1217, 2007.


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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 infec-

tions 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 ifperformed 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 fight opportunistic infections including colds and influenza. 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 increa-

sed 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 remem-

ber that any sustained deficiency of an essential vitamin or mineral will result in ill health and it is extremely unlikelythat 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 deficiencies of the nutrients that play an essential role in immune cell functions. Inadequate

protein-energy intake or deficiencies of certain micronutrients (e.g. iron, zinc and vitamins B6 and B12), decrease immu-

ne 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 thatcertain 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

4 Nutrition and the immune system:what works and what doesnt


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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 ofefficacy in animals, in vitro experiments, children, the elderly or clinical patients

in severe catabolic states and direct evidence for their efficacy for preventing exercise-induced immune depression or

improving immune system status in athletes is usually lacking.

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 immunefunction. 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 ofantioxidant 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 findings of a benefit 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 sufficient. Exces-

sive supplementation with other antioxidants cannot be recommended because there is little evidence of benefit, while

it is known that over-supplementation can actually diminish the 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 im-

pair 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 proliferati-

on, have failed to find any beneficial effect. Although provision of glutamine has been shown to

have a beneficial 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 exercise-

induced 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 flavonoids (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 flavonoid

quercetin decreased URTI incidence in the 2 weeks following a 3-day intensified 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 efficacy 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 beneficial bacteria increase and usuallynumbers of species considered harmful are decreased. This has been associated with a range of potential benefits 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 dai-

ly probiotic ingestion results in fewer days of respiratory illness and lower severity of URTI symptoms. In one study this


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was associated with a significant increase in whole blood culture interferon- production, which may be one mechanism

underpinning the positive clinical outcomes.

In conclusion, it is difficult to make firm 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 confidence that

individual amino acids, colostrum, echinacea, vitamin E and zinc are unlikely to be of benefit to athletes who are not

deficient 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 fight infection, particularly vitamin C, vitamin A and zinc. A good well-balanced 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 fluid,

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 benefit 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, flavonoids 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 scientific evidence that the supplement boosts immunity and/or reduces infection

incidence in humans

Nutrition supplement Evidence Immune boosting properties (claims)

Arginine Nonessential amino acid that is a precursor in the synthesis of

nitric oxide which is a cytotoxic molecule capable of destroy-

ing microorganisms and virus-infected cells. Claimed to en-

hance immune response and increase resistance to infection.

There is no evidence that arginine has any effect on immunity

in healthy humans.

Beta()-glucan 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 benefit for human athletes.

Bovine colostrum First milk of the cow that contains antibodies, growth factors

and cytokines. Claimed to boost mucosal immunity and

increase resistance to infection. One study suggests an effect

in elevating salivary IgA in human endurance runners but no

evidence that this modifies infection risk.

Carbohydrate Ingestion of carbohydrate (30-60 g/h) attenuates stress

hormone and (some) immune pertubations during exercise

but only very limited evidence that this modifies infection riskin human athletes.

Curcumin A component of the Indian spice, tumeric and has potent anti-

inflammatory activity. There is no evidence that curcumin has

any effect on immunity in healthy humans.

Echinacea Herbal extract that is a popular supplement among athletes.

Claimed to boost immunity via stimulatory effects on ma-

crophages. Early human studies indicated possible beneficial

effects but more recent, larger scale and better controlled

studies indicate no effect of Echinacea on infection incidence

or cold symptom severity.

Garlic 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 healthyhumans is lacking.

Ginseng 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.

Green tea Contains the amino acid, L-theanine and antioxidants such as

epigallocatechin gallate and other polyphenols. Claimed to

improve T lymphocyte functions. Evidence for immune modu-

lating effects in healthy humans is lacking.

Vitamin C An essential water-soluble antioxidant vitamin taken in me-

gadoses by many athletes. Some evidence from some (but not

all) human studies that high dose vitamin C (>200 mg/day)

can be effective in reducing infection risk in stress situations

and following ultramarathon races. May work by reducing

stress hormone and anti-inflammatory cytokine responses to

exercise.


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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 benefit for younger healthy

humans or athletes..

Whey protein Whey protein from cows milk contains various amino acids,

peptides and proteins including lactoferrin and immunoglo-

bulins. 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.Zinc An essential mineral that is claimed to reduce incidence and

duration of colds. No evidence for reduced infection incidence

with zinc supplementation in humans. Some (but not all)

human studies suggest a reduction in duration of cold sym-

ptoms if zinc gluconate lozenges are administered within 24

h of cold symptom onset. Unlikely to be of any real benefit to

athletes unless they are zinc deficient.

The scientific evidence is indicated with meaning very strong evidence

and 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 responsesto 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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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 gene-

tics evaluates how sequence variants influence physical and physiological characteristics (pheno-

type). 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 sequen-

cing 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 dys-

trophy, an understanding of genetics and gene expression has been extremely helpful from a diagnostic and therapeu-

tic 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 defining 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 non-

coding DNA can actually encode for modifying forms of RNA called micro RNAs which can influence mRNA abundance

and other changes in non-coding region (i.e. tri- and tetra-nucleotide expansions) can influence gene expression in

surrounding regions.

DNA is transcribed into RNA in a gene specific 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 specific or

clustered pattern of gene transcription, the primary transcript undergoes a series of modifications 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 tran-

script is read by a transfer RNA (tRNA) in the presence of ribosomes free in the cytoplasm or on the rough endoplasmic

reticulum. The process oftranslation 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 specific codon. Following translation, a

number of proteins undergo post-translational modifications ranging from phosphorylation to assembly into multi-meric complexes. Technically speaking, even the process of protein degradation can be considered a post-translational

modification that can alter protein abundance. (Figure 1)

5 Nutrition and Genetics


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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 influence 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 pertainingto 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 influence the response to nutrients and exercise.

Gene expression and transcriptome profiling 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 tran-

scription as well as the rate of mRNA degradation; however, to measure these in vivo is difficult, 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 expressi-

on to indicate mRNA abundance unless otherwise specified. I will focus this section on two main areas 1. Does carbohy-

drate 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 mitochondrialvolume. A large number of variables change during endurance exercise that can influence mitochondrial biogenesis

including; calcium, AMP (via AMPK), hypoxia, and stretch activation. After the discovery that peroxisome proliferator-ac-

tivated 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 influence 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 specific over-expression studies.

Given that PGC-1 responds to both energy and nutrient status of the cell (9), one of the first

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, shouldan 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?


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The likely nutrient candidates for influencing gene expression in skeletal muscle are the glycogen concen-

tration 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 andPGC-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 influence on the mRNA abundance for some genes involved in substrate metabolism, one study found that post-

exercise 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 influence 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 par-

ticipated 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 break-

down 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 influence 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 benefit to training athletes in a state of high vs low CHO availability. It is likely that any poten-tial gain induced by training in a energy/CHO depleted state would be offset by a negative influence on the day to day

ability to train at a sufficient 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 phos-

phocreatine (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 myofibrillar protein synthesis. Although we (7), and others, have not found an increase in

myofibrillar 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 crea-

tine loading is likely related to transient water retention, and the water retention may be the mechanism behind theattenuation in protein degradation and leucine oxidation. In addition to the acute effects of creatine monohydrate con-

sumption, 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

influence cellular molecular signaling and that leads to enhanced training gains.


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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 re-

cruitment 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 significantly 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 develop-

ment 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 influence 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 genein the human body. Most gene arrays use either bead (Illumina) or silicon chip (Affymetrix) technology to affix 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 fluorescent tag and incubated on the chip or bead. The fluorescent

intensity is proportional to the abundance of each specific 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 specific 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 influence 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 sequencevariants can influence 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 influ-

ence 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 befor

2008 birmingham low res

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