Current popular ergogenic aids used in sports: a critical review. (Review Paper).

Abstract

Many athletes make extensive use of ergogenic aids in the hope that they can favourably affect athletic performance and increase lean body mass. Supplementation with creatine, glutamine, camitine, leucine and its metabolite hydroxymethylbutyrate (HMB), and branched chain amino acids (BCAA) has been hypothesised to assist in the achievement of optimal sports performance. Despite an increasing amount of scientific evidence and popularity, uncertainty about the effectiveness and safety of these supplements still exists.

A survey was undertaken of the supplements being promoted in the most popular sports magazines in Australia. Approximately one quarter of the advertisements for supplements in the magazines surveyed were for creatine (54%), glutamine (24%), HMB (20%), and BCAA (2%). A critical literature review of trials of the effect of these ergogenic aids on exercise performance trials was conducted. Creatine supplementation appears to have substantial scientific support as a safe and effective nutritional strategy to enhance exercise performance and improve training adaptations in high-intensity, short-term ([less than or equal to] 30 seconds) exercise tasks, with limited recovery time between repetitions. Carnitine supplementation has been reported to increase exercise capacity in disease states. However, in healthy athletes carnitine was not shown to have an ergogenic effect. There was limited evidence that the use of HMB supplementation resulted in gains in strength and body mass. There was an abundance of clinical evi dence supporting the requirement for exogenous glutamine in critically ill patients and in the over-training syndrome. However, for healthy subjects, the few scientific studies available suggested that glutamine is only of benefit for athletes with true deficiency. Research findings regarding the effects of BCAA supplementation are somewhat equivocal. Most reviews evaluating the central fatigue hypothesis suggest that BCAA is not an effective ergogenic supplement, nor is it ergolytic. Further research is needed for better evaluation of the safety and efficacy of many of these supplements, especially focussing on their use in specific sporting situations.

Key words: ergogenic aids, hydroxymethylbutyrate, branched chain amino acids, creatine, carnitine, glutamine, sport nutrition, exercise

Introduction

The provision of sports supplements has become a multimillion dollar business and in popular sports magazines (such as Muscular Development, Iron Man, Muscles Magazine Flex, Muscle and Fitness, Muscle Media), creatine, glutamine, hydroxymethylbutyrate (HMB) and branched chain amino acids (BCAA) are among the most promoted supplements.

The process of substantiating the performance benefits or outcomes from nutrient supplementation is difficult. Under specific conditions ergogenic aids can have some positive effects on performance, lean body mass, strength and changes in body composition. Unfortunately there is often inadequate experimental evidence of efficacy or what exists is of poor quality. For some supplements there are sound trials demonstrating efficacy in the laboratory setting but not in the sports setting (1).

The following considerations are relevant when studying the effectiveness of specific sports ergogenic aids:

(1) In appropriate subject population; subjects should be highly trained in the specific sport performance factors that theoretically are enhanced by use of the sports ergogenic. If the sports ergogenic is effective, it should improve performance beyond the effects of training. Highly trained aerobic athletes, such as marathon runners or road cyclists, should serve as subjects, so that the variability in performance measures can be minimised;

(2) the performance tests used should be valid and reliable. Both laboratory (well-controlled) and field (real-world conditions) tests provide valuable information. Subjects should undertake a learning trial or trials to become proficient in the tests; the treatment should be based on sound theoretical rationale;

(3) an appropriate placebo should be used. The best design involves repeated-measures, crossover approach in which each subject randomly takes both the treatment and placebo, with an appropriate washout period between, and a double-blind protocol;

(4) investigators attempt to control extraneous factors and control the test environment that might influence test performance. During the conduct of the study, the athletes should maintain normal dietary and exercise training habits. Factors such as the exact composition and amount of an amino acid, the amount per serving and timing of ingestion in relation to the exercise may all influence study outcome (2);

(5) appropriate statistical techniques should be used to minimise the chance of statistical error (1) and how best to examine the data genreated by the studies (3). It must be considered whether statistical tests will detect the very small differences that can enhance performance.

Methods

A comprehensive literature review was conducted to find studies that examined the relationship between sports or ergogenic supplementation and changes in performance, strength and any other physiological metabolic response. The following databases were searched: MEDLINE (1996 to Week 3 September 2001, whole file), ProQuest 5000, American Physiological Society, Sprunger, SwetsNet Navigator and High Wire Press. Information about study design, method, sample size, subject characteristics, dose-effect and study outcomes published in peer-reviewed journals were summarised. Given the limited number of studies found and the heterogeneity of study design and characteristics, discussion of each supplement was conducted using the most credible evidence available to build a critical review of the state of the science at the current time. Assessment of quality and content was undertaken by the author. Information about study design, method, sample size, subject characteristics, dose-effect and study outcomes were conside red.

Results and discussion

Creatine

Creatine is a naturally occurring amino acid derived from the amino acids glycine, arginine, and methionine. Most creatine is stored in skeletal muscle, primarily as phosphocreatine; the remainder is found in the heart, brain, and testes (4,5). The daily creatine requirement is approximately two to three grams; half is obtained from diet, primarily from meat (500 g of uncooked steak contains about two grams of creatine) (6) and fish, while the remainder is synthesised (7). The amount of phosphocreatme in the skeletal muscle partially determines the length of time that maximum muscle work can be done (8). In theory, an increased store of creatine or phosphocreatine could improve the ability to produce energy during high-intensity exercise as well as improve the speed of recovery from high-intensity exercise (9). Creatine may also independently result in increased body mass (10), although in the first few weeks much of this increase may be due to increased water retention (8). Its use as a supplement to enhance sport performance has not been prohibited by the International Olympic Committee (8). Nevertheless, the US Food and Drug Administration recently warned consumers to consult a health professional before using creatine, and bodies such as the American College of Sports Medicine have taken a cautious view on the benefits and side effects of nutritional ergogenics aids (14). The safety of prolonged creatine supplementation has not been established, however, short-term supplementation (up to eight weeks) has not been associated with major health risks (3,6). Whether there are side effects from long-term use of creatine, particularly with high doses associated with rapid loading, remains to be determined. Some undocumented anecdotal reports indicate creatine supplementation may lead to muscle cramps, nausea, gastrointestinal upset, headache and possible muscle strains (3,6).

Table 1 shows the results of 35 studies on creatine supplementation. Most studies were undertaken using an experimental design, using a placebo control with the subjects supplemented with creatine at 0 to 25 g per day. In only one study subjects were administered 40 g of creatine per day (12). The creatine trials were from three days to 11 weeks in duration and included both healthy males and females, elite and untrained subjects (in the specific sport performance factors), active and sedentary participants. Of 35 studies ten did not find any significant effect of creatine supplementation on metabolism, performance or strength, nor any ergogenic effects or changes in body composition (13-22).

High-intensity ergometer protocols

In six studies using exercise tests ranging in duration from six to 30 seconds, the creatine group experienced a significantly lower decrease in performance compared to the placebo group (23-29). However, in four studies the investigators reported that creatine supplements produced no significant differences in peak or maximum power, time to exhaustion, performance or any other work measure (13,14,18,19). These more recent studies support the review by Williams (1) of 17 earlier studies, using cycle ergometer performance in a laboratory setting, 11 of which reported an ergogenic effect of creatine. Four of the 11 studies using cycle ergometer test summarised in Table 1 did not find improvements in the groups supplemented with creatine. In three of these studies the reason for the lack of effect may be that subjects were untrained (13,18,19) and in the other study a possible explanation for the negative result could be the cycle ergometry test, because the maximal performance was evaluated in a single test (a single ten-second test), one prior to and the other following, the supplementation period (14). Creatine is not usually considered ergogenic for single-bout or first-bout of exercise, because the likely benefit is too small to be detected (3).

Isokinetic protocols

Recent trials investigating the influence of creatine on isokinetic torque (elbow flexion) did not find significant effects (16,21), but earlier studies in the laboratory setting have shown that supplementation with 20 to 40 g per day for four to seven days may improve isokinetic torque force production and attenuate the decline in power during repetitive isokinetic exercise (6).

Isometric and resistance exercise protocols

Studies of the effect of creatine supplementation on isometric (knee extension, handgrip, elbow flexion) and resistance exercise tests (bench press, squat strength/jump, peak force and peak power) indicate changes in muscle ATP cost of contraction for isometric exercise (12,22). Only two of nine studies (12,22) failed to find this. Both studies used small sample sizes (nine subjects), and in one study the subjects differed in gender (six females and three males) and were not randomised (22). Also, because the sample size was small, it was possible that the study groups had different proportions of non-responders to creatine. Across studies there is evidence that the creatine-loading response varies between individuals, with approximately 30 % of individuals being 'non-responders' or failing to significantly increase muscle creatine stores (3,30). Ideally, studies employing large sample sizes and co-variant analysis should be used. This approach allows real changes to be detected and may also identify the char acteristics of individuals that predict 'response' and 'non-response' (3). Measurement of creatine stores in muscle (e.g. using magnetic resonance spectroscopy, a non-invasive method) is another way to determine if a person has responded with increases in muscle creatine after supplementation (31,32).

Sport performance protocols

Five studies have investigated the effect of creatine supplementation on actual sport performance (sprint running and swimming in a field setting), using high-intensity, short-duration repetitive activities (14,15,20,33,34). The outcomes were unanimous--finding no effect of creatine supplementation on performance. In one study, an increase in body mass occurred but there were no significant performance changes (33). More investigations are needed concerning the use of creatine in sports events involving multiple high-intensity, intermittent exercise tasks, such as soccer. In two studies of running performance creatine supplementation failed to improve run time (15,17). However, Harris et al. (35) also tested creatine supplementation and running performance, and it was found that the group that received supplementation (30 g of creatine for six days), showed enhanced performance in the final run and best time over 300 M. The authors suggested the increased use of phosphocreatine during exercise may contribute to the buffering of hydrogen ions (35). As has been found in laboratory studies, creatine supplementation does not appear to enhance performance in field studies involving more prolonged high-intensity tasks. Four of five field studies involving swimming and running performance, all using a double-blind placebo design, reported negative findings concerning the efficacy of creatine supplementation (1).

Factors influencing creatine supplementation

Dietary background may have a significant effect in creatine supplementation studies. Co-ingestion of substantial amounts of carbohydrate (57 to 100 g) with creatine doses has been shown to enhance creatine accumulation (36,37). The amount of carbohydrate that induces alterations on creatine loading is still under investigation but researchers should ensure adequate carbohydrate when studying the effects of supplementary creatine. Vegetarians do not consume a source of creatine and may demonstrate reduced body creatine stores, suggesting they do not totally compensate for the lack of dietary intake (38). It has been hypothesised that a high dosage of caffeine (5 mg per kg per day) counteracts the ergogenic effect of creatine supplementation (12,39) but there is some evidence that caffeine (in the quantities commonly found in food and beverages) does not interfere with creatine loading (40). Supplementation with caffeine (5 mg per kg per day) does not alter creatine-induced improvements in repeated high-intens ity exercise (41), maximal torque and contraction time in humans (42). A range of exercise activities may benefit from caffeine supplementation (3).

Summary

Creatine supplementation appears to be most effective in enhancing repetitive short-duration ([less than or equal to] 30 seconds), high-intensity tasks such as cycle ergometry; strength, torque and force production; and jump performance in a laboratory setting. In general, creatine supplementation has not been shown consistently to enhance performance in exercise tasks dependent on the lactic acid energy system (anaerobic glycolysis). Additionally, creatine supplementation has not been shown to enhance performance in aerobic endurance exercise tasks. More research is indicated, particularly on the effect of chronic supplementation as an aid to improving performance in competitive sport and of lower intensity activity, such as those performed by non-athletes in daily gym activities.

Hydroxymethylbutyrate (HMB)

The leucine metabolite hydroxymethylbutyrate (HMB) is found in some foods in small amounts (catfish and some citrus fruits), it is found in breast milk, and it is used and produced by body tissues (8). It has recently become a popular dietary supplement purported to promote gains in fat free mass and strength during resistance training (9). The rationale is that leucine and its metabolite [alpha]-ketoisocaproate appear to inhibit protein degradation (59,60) and this anti-proteolytic effect may be mediated by HMB. Although it seems that HMB has some influence on protein metabolism, the mechanisms behind any effects are unknown. It may regulate protein synthesis either through hormonal receptor effects (cortisol, testosterone, GH, IGF-1, insulin) or by modulating the enzymes responsible for muscle tissue breakdown. Hydroxymethylbutyrate may have effects on the metabolism of leucine and glutamine and perhaps other anabolic and anticatabolic amino acids, or may decrease gluconeogenesis and the subsequent oxidatio n of amino acids in the intracellular amino acid pool and catabolism of skeletal muscle cellular protein (8). It appears to be nontoxic (61,62).

Table 2 summarises data collected from eight studies (from 1996 to 2000) in which humans were fed 0 g, 3 g and/or 6 g HMB per day. The studies were from three to eight weeks' duration, included both males and females and healthy athletes or/and exercising subjects.

Of the eight studies only one found that HMB supplementation did not affect catabolism or induce changes in body composition and strength (63). This trial was not placebo-controlled and of short duration (28 days) and this may explain the lack of effect. Seven other studies on HMB supplementation have found significantly less exercise-induced proteolysis and muscle damage (64,65); increased strength and gains in fat free mass (64-66); or larger gains in muscle function and in resistance training (64,65). Only three studies (63,64) assessed exercise training in highly trained individuals and/or athletes. A recent study by S later et al. (68) reported HMB supplementation did not change strength or body composition in resistance-trained male athletes. It may be that further studies with highly trained individuals will find the impact of the supplements on exercise outcome are different to the earlier studies with less trained individuals (9).

All studies reported in Table 2 supplemented with 3 g of HMB per day. In two studies, 1.5 g of HMB per day was tested and compared with the results obtained with 3 g per day. Less effect was found for increase in strength and decrease of the exercise-induced proteolysis (64,65). Some other studies have compared 6 g HMB per day with 3 g per day, but doses of HMB higher than 3 g a day do not promote strength or gains in fat free mass (63-69). The popular use of supplemental HMB at 3 g per day for periods of up to one month (in a healthy population) as an ergogenic aid for exercise appears to be well-tolerated and safe in humans (62).

Summary

Given the generally good quality design of most of these studies, and the consistency of proven effects, it can be concluded that there is reasonable evidence that HMB supplementation results in gains in strength and body mass associated with resistance training, on enhancement of loss of body fat and on recovery from exercise (3). Although HMB supplementation during training may enhance training adaptations in untrained individuals initiating training, it is less clear whether HMB supplementation reduces markers of catabolism or promotes greater gains in fat free mass and strength during resistance training in well-trained athletes.

Glutamine

Glutamine provides nitrogen for the synthesis of nucleotides required in the formation of DNA and RNA during lymphocyte proliferation and macrophage activation (9). As glutamine is an important fuel for white blood cells, reductions in blood glutamine concentrations following intense exercise may contribute to immune suppression in overtrained athletes (70-73). Glutamine is utilised at a high rate by certain cells of the immune system (neutrophils, lymphocytes, and macrophages) and is essential for the viability and normal functioning of these cells (74,75). After prolonged intense exercise the number of lymphocytes in the blood is reduced, the function of natural killer cells is suppressed and secretory immunity is impaired (76). Glutamine has been demonstrated of benefit in trauma patients and individuals stressed by surgery (77,78). Although there are differences between exercising individuals and these patients, glutamine supplementation in athletes may be beneficial in increasing the anabolic drive (8). It has been theorised that a chronic glutamine debit may be responsible for the immunosuppression suffered by some athletes, and that supplementation may overcome the impaired immunity suffered by athletes undertaking repeated bouts of heavy training and overtraining (3). Regular runners are six times more likely to contract a cold virus in winter than nonparticipants (79). The few studies of increasing plasma glutamine concentrations with supplements have shown little or no effect on energy production or immune status (80,81). It is unclear whether long-term supplementation of glutamine affects protein synthesis, body composition, or the incidence of upper respiratory-tract infections during training (9).

The role of glutamine as an ergogenic aid has not been demonstrated in the scientific literature. Although there is evidence to support the requirement for exogenous glutamine in the maintenance of muscle protein mass and immune system function in the overtraining syndrome (77,78,82-84), little research has examined the use of glutamine for athletes (68). Blood glutamine concentrations may serve as a marker for determining whether athletes are overtraining (8,85). Studies have shown that decreased plasma glutamine concentrations are an objective, measurement of severe exercise stress and overtraining (86,87).

Summary

Few scientific data are available concerning potential benefits of glutamine supplementation for athletes. Further work is necessary to determine whether the benefits of exogenous glutamine supplementation shown in clinical situations apply in athletic populations. In those athletes demonstrating decreased plasma glutamine, supplements are indicated but this condition is uncommon.

Branched chain amino acids (BCAA)

The branched chain amino acids, valine, leucine and isoleucine, unlike most other amino acids, are oxidised by muscle cells, providing a source of cellular energy as ATP and phosphocreatine (7). There is a significant activation of BCAA metabolism with prolonged exercise, and studies indicate that this is more pronounced in endurance-trained subjects (88). Plasma concentrations of BCAAs are more affected by changes in energy, protein, fat, and carbohydrate intake in humans (89) than are the concentrations of other amino acids. Theoretically, BCAA supplementation (30% to 35% leucine) before and during endurance exercise may prevent or decrease the net rate of protein degradation, improve mental and physical performance and may have a sparing effect on muscle glycogen degradation and depletion of muscle glycogen stores (90). During intense training BCAA supplementation can help minimise protein degradation and thereby lead to greater gains in fat free mass (91-93), however, it can significantly increase plasma ammonia (toxic to the brain and muscle) (77) and lower physical performance in humans (94) and in rats (95). Reduced availability of BCAA has been theorised to contribute to central fatigue (79). During endurance exercise, BCAA are taken up by the muscles and the resultant decline in plasma BCAA can lead to an increase in the ratio of free tryptophan to BCAA, promoting the formation of the neurotransmitter 5-hydroxytryptamine (5-HT) in the brain. It has been shown to induce sleep, depress motor neuron excitability, influence autonomic and endocrine function, and suppress appetite in both humans and animals (93,96,97). An exercise-induced imbalance in the ratio of free tryptophan to BCAA has been implicated as a cause of acute physiological and psychological fatigue (the central fatigue) (93,96,97). The ingestion of carbohydrate during exercise minimises the unfavourable change in the ratio of plasma free tryptophan: BCAA (3,98).

Table 3 shows the results of nine studies on the effect of BCAA supplementation (from 1991 to 2001). The studies were undertaken using placebo-controlled designs and subjects were supplemented with up to 22 g of BCAA. The trials were short-term studies from a few hours to a day. Healthy males and females were used, including both trained and untrained subjects. Three of nine studies failed to find any significant effect of BCAA supplementation on metabolism and/or performance (99-101).

Performance-based endpoints (fatigue, work performed and mental performance)

Of four studies in which performance was considered the main and/or only outcome, three failed to show any benefit of BCAA supplementation (99-101). The one study that reported an increase in performance of a 'slower runners' group (85) has been criticised for its methodology (11). Mental performance was measured in three of the nine studies using the Stroop Colour Word Test, and in all three improvements were found (100,102,103).

Metabolic-based endpoints

Metabolic endpoints (ammonia accumulation and production, the tryptophan: BCAA ratio, amino acids and lactate production, protein breakdown) were tested in four studies (104-107) and improvements were found in all. However in the study of Blomstrand and Saltin (107) the anabolic effect on muscle protein metabolism may be significant only during recovery. The results observed during exercise were too variable to form any conclusion.

Carbohydrate is not only an energy source during exercise but may also have positive effects on amino acid metabolism (108) and nitrogen balance (109-112). The positive effects are likely due to an insulin-mediated stimulation of protein synthesis and an attenuation of protein breakdown (3). Supplementation with carbohydrate during exercise suppresses the rise in free fatty acids concentrations, thereby attenuating the increase in free tryptophan concentrations (98) that is an effective strategy against both peripheral and central mechanisms of fatigue (3). Thus, several investigators emphasise the importance of dietary carbohydrate before, during and between repeated bouts of prolonged exercise to minimise central fatigue (81,97,98,113,114).

Summary

Research findings regarding the effects of BCAA supplementation on endurance performance in humans do not offer substantial proof. Most other reviewers evaluating the central fatigue hypothesis have concluded overall there is not convincing evidence that supplementation with BCAA prevents or stimulates central fatigue (108,115-118). Studies comparing the intake of BCAA and carbohydrate with the supplementation of carbohydrate alone are necessary to determine if BCAA exert an independent effect.

Carnitine

Carnitine in humans is derived from both dietary sources and endogenous biosynthesis. Meat and dairy products are major dietary sources of this compound (119). According to Brass, a number of specific mechanisms have been postulated for an effect of carnitine on exercise performance including: enhanced muscle fatty acid oxidation; decreased rate of muscle glycogen depletion; shifts in substrate utilisation in muscle from fatty acid to glucose; activation of pyruvate dehydrogenase via lowering of acetyl-CoA; improved muscle fatigue resistance; and replacement of carnitine lost during training (120). If carnitine administration increases muscle fatty acid oxidation, this might also delay the use of muscle glycogen and thus delay fatigue development (121).

Table 4 shows the results of 11 studies on the effect of carnitine supplementation (1988 to 2000). Most studies involved oral supplementation with carnitine at 0 to 6 g per day but two studies used intravenous carnitine administration (122,123). The duration of trials ranged from one to 28 days, they included only healthy males, and used untrained, moderately-trained or highly-trained subjects. Three of the 11 studies found a significant effect of carnitine supplementation on performance plasma concentration of lactate and pyruvate, time to exhaustion or maximal oxygen consumption during exercise ([VO.sub.2max]) (124-126).

Performance-based protocols

Some studies in which exercise capacity was tested with use of [VO.sub.2max] and/or performance endpoints failed to show any benefit of carnitine supplementation (127,128). Similarly, studies searching for any ergogenic effect of carnitine supplementation during bouts of high-intensity anaerobic exercise in highly-trained subjects and during aerobic combined with anaerobic exercise failed to identify any improvement in metabolism, performance or lean body mass (122,129). However in one study, although no changes were found during exercise, an increase in fatty acid oxidation during recovery was observed (122).

Metabolic indices protocols

Most of the studies measuring metabolic indices of exercise (muscle fuel, muscle carnitine content, time to exhaustion, substrate utilisation, i.e. lipid or carbohydrate oxidation) failed to find any effect of carnitine administration (123,126,130-133). However Vecchiet et al. (128) found a decrease in lactate accumulation and/or production and Siliprandi et al. (125) reported a reduction in lactate and pyruvate. The latter study involved supplementation 60 or 90 minutes before exercise and it is difficult to discern if sufficient time elapsed for absorption and muscle uptake (125).

Although most studies demonstrate an increase in plasma carnitine concentrations following supplementation of I to 6 g carnitine per day, the effect on muscle carnitine content is less clear. The consensus is that there is no compelling evidence that the muscle content of carnitine is enhanced by supplementation (3,134,135). The few studies that report favourable metabolic outcomes, or an increase in exercise performance, are hard to explain. Hultman et al. (136) consider that it is unlikely that carnitine supplementation over a period of days to weeks will change total muscle carnitine content in humans. Available data confirm that muscle carnitine content is not increased by supplementation protocols similar to those described above (123,132,133), despite increases in plasma carnitine concentrations (120,122,123,129,132,133). Thus, although it is possible that camitine affects exercise physiology without modifying muscle carnitine poois, such a mechanism would clearly be distinct from the rationale usually made for supplementation. It is still possible that increases in muscle carnitine content might result from longer duration of therapy or/and muscle camitine homeostasis (120).

Only three studies provide evidence for a distinct effect of carnitine, the studies by Arenas et al. (126,137) and Huertas et al. (138). They examined only athletes engaged in training programs for periods of one to six months. Under these conditions, carnitine supplementation prevented a training-associated decrease in muscle carnitine content and also increased muscle activity of key oxidative enzymes, including pyruvate dehydrogenase and electron transport chain enzymes. The physiological effect of these changes is unknown and further corroboration of these findings is needed.

Summary

The data available to date do not allow a definitive conclusion concerning the effect of carnitine on exercise metabolism and performance. Most studies have design limitations and further research using placebo-controlled trials, with bigger sample sizes, and examining other relevant endpoints is indicated.

Conclusions

Table 5 summarises the supplementation studies reviewed, evaluating the strength of the ergogenic effect and the conditions under which each supplement is ergogenic.

Creatine is the most studied of the amino acid supplements. Creatine supplementation appears to be an effective nutritional strategy to enhance high-intensity exercise performance and improve training adaptations in high-intensity, short-term ([less than or equal to]30 seconds) exercise tasks, with limited recovery time between repetitions. No significant improvement in aerobic endurance exercise tasks is demonstrated. Further research in field settings is needed to study effects on intermittent activity. The safety of long-term supplementation requires further study, particularly with regard to large doses that are associated with rapid loading and unconfirmed side effects such as cramps, muscle tears and pulls.

A small number of recent well-designed studies of supplementation with HMB indicate that it results in gains in strength and body mass associated with resistance training, as well as enhanced loss of body fat and recovery from exercise in the healthy population. Whether the same outcomes would be found for highly-trained individuals is not clear and more research is needed.

There is an abundance of clinical evidence supporting the need for exogenous glutamine in critically ill patients for the maintenance of muscle protein mass and immune system function. However, for healthy subjects the few scientific results available suggest that glutamine is only of benefit for athletes who show a true deficiency. The overtrained may have lower glutamine plasma concentrations but it remains unclear whether supplementation improves their condition.

Research findings regarding the effects of BCAA supplementation are equivocal. Most reviews evaluating the central fatigue hypothesis suggest that BCAA is not an effective ergogenic supplement. The few data available do not allow a conclusive position regarding the effect of BCAA supplementation on exercise metabolism and performance and more studies are needed.

Carnitine supplementation has been reported to increase exercise capacity in disease states. However, in healthy athletes carnitine fails to provide a significant ergogenic effect. Moreover, the few study trials that reported favourable outcomes or an increase in exercise performance suffer from design limitations.

Further research is still needed for better evaluation of the safety and efficacy of many of these supplements, especially focussing on their use in specific sporting situations. The marketing of sport supplements is an international, multimillion dollar business that preys upon the desires of athletes to be the best. The most appropriate advice to athletes may be to avoid using a specific sport supplement until the product has been evaluated for safety, efficacy, potency and legality. Athletes should discuss the use of any supplement with a qualified sports nutritionist, dietitian, or health professional. All users and creators of supplement information should consult the sport policy of the Australian Institute of Sport (www.ais.org.au/nutrition)--under supplements.

Table 1

Summary of research studies on creatine supplementation in exercising,
trained or untrained individual, published 1996-2000 (n=35)

Study                               Subjects

High intensity ergometer protocols

Barnett et al. 1996 (13)            17M (active males)

Burke et al. 1996 (14)              32M/F (elite swimmers)

Casey et al. 1996 (23)              9M (healthy males)

Cooke & Barnes, 1997 (18)           80M

Kirksey et al. 1997 (25)            36M/F (track/field athletes)

Odland et al. 1997 (19)             9M (active but untrained

Prevost et al. 1997 (26)            18M/F (college students)

Schneider et al. 1997 (24)          9M (untrained males)

Smith et al. 1998 (27)              15M/F (untrained)

Vandenbuerie et al. 1998 (28)       12M (amateur cyclists)

Kamber et al. 1999 (29)             10M (trained sport students)


Isokinetic protocols

Vandenberghe et al. 1996a (16)      20F
Hamilton-Ward et al. 1997 (21)      20F (athletes)
Van Leemputte et al. 1999 (43)      16M (untrained)


Isometric, isotonic and resistance
 exercise protocols

Vandenberghe et al. 1996b (12)      9M (healthy males)

Becque et al. 1997 (44)             23M (weight-lifters)

Kurosawa et al. 1997 (45)           5M/F (healthy)

Vandenberghe et al. 1997a (46)      19F (healthy sedentary)

Volek et al. 1997 (47)              14M (healthy active)


Isometric, isotonic and resistance
 exercise protocols

Maganaris & Maughan, 1998 (48)      10M (weight-trained)


Smith et al. 1999 (32)              9M/F (active-untrained)

Stone et al. 1999 (49)              42M (college football players)



Urbanski et al. 1999 (50)           10M (active-untrained)
                                    untrained)


Volek et al. 1999 (51)              19M (resistance-trained)



Burke et al. 2000 (52)              41M (university athletes





Sport performance protocols

Mujika et al. 1996 (33)             20M/F (elite swimmers)
                                    swimmers)
Redondo et al. 1996 (15)            18M/F (trained athletes)

Bosco et al. 1997 (53)              14M (sprinters & jumpers


Goldberg & Bechtel, 1997 (20)       34M (football/track athletes)
Grindstaff et al. 1997 (54)         18M/F (junior swimmers)

Terrillion et al. 1997 (17)         12M (competitive runners)

McNaughton et al. 1998 (55)         16 M (elite surf-ski/kayak)

Peyrebrune et al. 1998 (56)         14M (elite swimmers)

Leenders et al. 1999 (57)           32M/F (college swimmers)

Theodorou et al. 1999 (58)          22 M/F (clite swimmers)



Study                               Study type (a)

High intensity ergometer protocols

Barnett et al. 1996 (13)            RDBPC

Burke et al. 1996 (14)              RDBPC

Casey et al. 1996 (23)              SGRM

Cooke & Barnes, 1997 (18)           RPC

Kirksey et al. 1997 (25)            RDBPC

Odland et al. 1997 (19)             SGRM

Prevost et al. 1997 (26)            RPC

Schneider et al. 1997 (24)          RSBPC

Smith et al. 1998 (27)              RDBPC

Vandenbuerie et al. 1998 (28)       RDBPC

Kamber et al. 1999 (29)             DBPCX


Isokinetic protocols

Vandenberghe et al. 1996a (16)      RDBPC
Hamilton-Ward et al. 1997 (21)      RDBPC
Van Leemputte et al. 1999 (43)      DBPC


Isometric, isotonic and resistance
 exercise protocols

Vandenberghe et al. 1996b (12)      RDBPCX

Becque et al. 1997 (44)             DBPC

Kurosawa et al. 1997 (45)           SGRM

Vandenberghe et al. 1997a (46)      DBPC

Volek et al. 1997 (47)              RDBPC


Isometric, isotonic and resistance
 exercise protocols

Maganaris & Maughan, 1998 (48)      RDBPCX


Smith et al. 1999 (32)              SBPC

Stone et al. 1999 (49)              RDBPC



Urbanski et al. 1999 (50)           RDBPCX



Volek et al. 1999 (51)              RDBPC



Burke et al. 2000 (52)              RDBPC





Sport performance protocols

Mujika et al. 1996 (33)             RDBPC

Redondo et al. 1996 (15)            RDBPC

Bosco et al. 1997 (53)              RBDPC


Goldberg & Bechtel, 1997 (20)       RDBPC
Grindstaff et al. 1997 (54)         RDBPC

Terrillion et al. 1997 (17)         RDBPC

McNaughton et al. 1998 (55)         RDBPCX

Peyrebrune et al. 1998 (56)         RDBPC

Leenders et al. 1999 (57)           RDBPC

Theodorou et al. 1999 (58)          RPC



Study                               Creatine dose-trial

High intensity ergometer protocols

Barnett et al. 1996 (13)            20 g/day-4 days

Burke et al. 1996 (14)              20 g/day-5 days

Casey et al. 1996 (23)              20 g/day-5days

Cooke & Barnes, 1997 (18)           20 g/day-5days

Kirksey et al. 1997 (25)            0.3 g/kg/day-42 days

Odland et al. 1997 (19)             20 g/day-3 days

Prevost et al. 1997 (26)            18.75 g/day-5 days
                                    2.25 g/day-7days
Schneider et al. 1997 (24)          25 g/day-7 days

Smith et al. 1998 (27)              20 g/day-5 days

Vandenbuerie et al. 1998 (28)       25 g/day-4 days

Kamber et al. 1999 (29)             20 g/day-5 d (28 days trial)


Isokinetic protocols

Vandenberghe et al. 1996a (16)      20 g/day-4 days
Hamilton-Ward et al. 1997 (21)      25 g/day-7 days
Van Leemputte et al. 1999 (43)      20 g/day-5 days


Isometric, isotonic and resistance
 exercise protocols

Vandenberghe et al. 1996b (12)      40 g/day-6 days

Becque et al. 1997 (44)             20 g/day-7 days

Kurosawa et al. 1997 (45)           5 g/day-14 days

Vandenberghe et al. 1997a (46)      20 g and 5 g/day-10 weeks

Volek et al. 1997 (47)              25 g/day-7 days


Isometric, isotonic and resistance
 exercise protocols

Maganaris & Maughan, 1998 (48)      10 g/day-5days


Smith et al. 1999 (32)              0.3 g/kg/day-5 days

Stone et al. 1999 (49)              0.22 g/kg/day-7 weeks



Urbanski et al. 1999 (50)           20 g/day-5 days



Volek et al. 1999 (51)              25 g/day-1 week &
                                    5 g/day-11 weeks


Burke et al. 2000 (52)              7.7 g/day-21 days





Sport performance protocols

Mujika et al. 1996 (33)             20 g/day-5 days

Redondo et al. 1996 (15)            25 g/day-7 days

Bosco et al. 1997 (53)              20 g/day-5 days


Goldberg & Bechtel, 1997 (20)       3 g/day-14 days
Grindstaff et al. 1997 (54)         21 g/day-9 days

Terrillion et al. 1997 (17)         20 g/day-5 days

McNaughton et al. 1998 (55)         20 g/day-5 days

Peyrebrune et al. 1998 (56)         9 g/day-5 days

Leenders et al. 1999 (57)           20 g/day-6 days

Theodorou et al. 1999 (58)          25 g/day-4 days



Study                               Event/Exercise test

High intensity ergometer protocols

Barnett et al. 1996 (13)            Cycling (7 x 10 sec sprints)

Burke et al. 1996 (14)              Leg ergometry (2 x 10 sec sprints)

Casey et al. 1996 (23)              Cycling (2 x 30 sec sprints)

Cooke & Barnes, 1997 (18)           Cycling (30, 60, 90, 120 sec of
                                    recovery)
Kirksey et al. 1997 (25)            Cycling (Wingate test)

Odland et al. 1997 (19)             Cycling (30 sec Wingate test)

Prevost et al. 1997 (26)            Cycling (time exhaustion at 150%
                                    [VO.sub.2 max])
Schneider et al. 1997 (24)          Cycling (5 x 15sec)

Smith et al. 1998 (27)              Cycling (4 maximal bouts-
                                    ergonometer)
Vandenbuerie et al. 1998 (28)       Cycling (progressive to exhaustion)

Kamber et al. 1999 (29)             Cycling (10 x 6 sec, 30 sec rest)


Isokinetic protocols

Vandenberghe et al. 1996a (16)      Isokinetic (5 x 30 max arm)
Hamilton-Ward et al. 1997 (21)      Isokinetic (elbow flexion torque)
Van Leemputte et al. 1999 (43)      Maximal isometric elbow-flexions on
                                    isokinetic dymometer

Isometric, isotonic and resistance
 exercise protocols

Vandenberghe et al. 1996b (12)      Isometric and isokinetic (3 x max)

Becque et al. 1997 (44)             Isotonic (bicep curl 1-repetition
                                    max)
Kurosawa et al. 1997 (45)           Isometric (high intensity)

Vandenberghe et al. 1997a (46)      Resistance training (3 hrs/week)

Volek et al. 1997 (47)              Isotonic (jump squad 5 x 10
                                    repetition max)

Isometric, isotonic and resistance
 exercise protocols

Maganaris & Maughan, 1998 (48)      Knee extension (maximal and
                                     exhaustion)

Smith et al. 1999 (32)              Leg knee extension to exhaustion

Stone et al. 1999 (49)              Resistance exercise



Urbanski et al. 1999 (50)           Maximal & submaximal isometric knee
                                    estension and handgrip exercise


Volek et al. 1999 (51)              Resistance exercise (bench press,
                                     squat, strength/jump and
                                     muscular endurance)

Burke et al. 2000 (52)              Bench press until exhaustion, peak
                                     force and peak power




Sport performance protocols

Mujika et al. 1996 (33)             Swimming (25 m, 50 m and 100 m)

Redondo et al. 1996 (15)            Running (3 x 60 m sprint)

Bosco et al. 1997 (53)              Jumping and running and treadmill
                                     run

Goldberg & Bechtel, 1997 (20)       Isotonic (1 repetition max bench)
Grindstaff et al. 1997 (54)         Swimming (3 x 100 m freestyle
                                     sprint)
Terrillion et al. 1997 (17)         Running (2 x maximal 700 m run)

McNaughton et al. 1998 (55)         Kayaking (kayak ergonometer test)

Peyrebrune et al. 1998 (56)         Swimming (maximal swims)

Leenders et al. 1999 (57)           Swimming

Theodorou et al. 1999 (58)          Swimming



Study                               Effect

High intensity ergometer protocols

Barnett et al. 1996 (13)            No

Burke et al. 1996 (14)              No

Casey et al. 1996 (23)              Yes

Cooke & Barnes, 1997 (18)           No

Kirksey et al. 1997 (25)            Yes

Odland et al. 1997 (19)             No

Prevost et al. 1997 (26)            Yes

Schneider et al. 1997 (24)          Yes

Smith et al. 1998 (27)              Yes

Vandenbuerie et al. 1998 (28)       Yes

Kamber et al. 1999 (29)             Yes


Isokinetic protocols

Vandenberghe et al. 1996a (16)      No
Hamilton-Ward et al. 1997 (21)      No
Van Leemputte et al. 1999 (43)      Yes


Isometric, isotonic and resistance
 exercise protocols

Vandenberghe et al. 1996b (12)      Yes

Becque et al. 1997 (44)             Yes

Kurosawa et al. 1997 (45)           Yes

Vandenberghe et al. 1997a (46)      Yes

Volek et al. 1997 (47)              Yes


Isometric, isotonic and resistance
 exercise protocols

Maganaris & Maughan, 1998 (48)      Yes


Smith et al. 1999 (32)              No

Stone et al. 1999 (49)              Yes



Urbanski et al. 1999 (50)           Yes



Volek et al. 1999 (51)              Yes



Burke et al. 2000 (52)              Yes





Sport performance protocols

Mujika et al. 1996 (33)             Yes

Redondo et al. 1996 (15)            No

Bosco et al. 1997 (53)              Yes


Goldberg & Bechtel, 1997 (20)       No
Grindstaff et al. 1997 (54)         Yes

Terrillion et al. 1997 (17)         No

McNaughton et al. 1998 (55)         Yes

Peyrebrune et al. 1998 (56)         Yes

Leenders et al. 1999 (57)           Yes

Theodorou et al. 1999 (58)          Yes



Study                               Comments

High intensity ergometer protocols

Barnett et al. 1996 (13)            No effect on multiple cycle perform

Burke et al. 1996 (14)              No significant effect on leg
                                    ergometry performance
Casey et al. 1996 (23)              Increase in total work (1%) and
                                    peak power (4%)
Cooke & Barnes, 1997 (18)           No effect on maximum power or peak
                                    power output
Kirksey et al. 1997 (25)            Increase in mean peak power (13%)

Odland et al. 1997 (19)             No effect on any recorded exercise
                                    measures
Prevost et al. 1997 (26)            Significant increase was found for
                                    all work measures
Schneider et al. 1997 (24)          Improved total work (6.5%) during
                                    bout of maximal cycling
Smith et al. 1998 (27)              Improved time to exhaustion at
                                    shorter, higher-intensity exercise
Vandenbuerie et al. 1998 (28)       Improved power output for the
                                    maximal sprints
Kamber et al. 1999 (29)             Supplementation improved short-term
                                    performance, increased body mass

Isokinetic protocols

Vandenberghe et al. 1996a (16)      No ergogenic effect
Hamilton-Ward et al. 1997 (21)      No ergogenic effect was found
Van Leemputte et al. 1999 (43)      Relaxation time reduced following
                                    creatine

Isometric, isotonic and resistance
 exercise protocols

Vandenberghe et al. 1996b (12)      Increase in torque production, but
                                    no effect for isometric
Becque et al. 1997 (44)             Increase in bicep curl (28%)

Kurosawa et al. 1997 (45)           Ergogenic effect (20% untrained
                                    arm, 35% trained arm)
Vandenberghe et al. 1997a (46)      Long-term supplementation enhances
                                    progress of muscle strength
Volek et al. 1997 (47)              Significant increase in repetitions
                                    to exhaustion and peak power for
                                    squats. Increase in body mass
Isometric, isotonic and resistance
 exercise protocols

Maganaris & Maughan, 1998 (48)      Increased maximum voluntary
                                     contraction, endurance capacity
                                     and body mass
Smith et al. 1999 (32)              Muscle ATP cost of contraction
                                     not affected
Stone et al. 1999 (49)              Increased squat and bench press,
                                     static vertical jump power output.
                                     Increase in body mass and lean
                                     body mass
Urbanski et al. 1999 (50)           Increased maximal and submaximal
                                     knee-extension torque, handgrip
                                     exercise and time to fatigue. No
                                     significant increase in body mass
Volek et al. 1999 (51)              Improved bench press and squat,
                                     increased muscle fibre cross-
                                     sectional areas. Increase in body
                                     mass and lean body mass
Burke et al. 2000 (52)              Increased total work and great
                                     improvements in force and power
                                     peak. Improved factors associated
                                     with short-duration, high-
                                     intensity activity

Sport performance protocols

Mujika et al. 1996 (33)             Increase in body mass but no
                                     significant performance changes
Redondo et al. 1996 (15)            No significant difference between
                                     groups
Bosco et al. 1997 (53)              Improved jumping performance of the
                                     jumping test and improved
                                     intensive running time exhaustion
Goldberg & Bechtel, 1997 (20)       No ergogenic effect was found
Grindstaff et al. 1997 (54)         Improved swim time

Terrillion et al. 1997 (17)         No significant differences between
                                     placebo or supplemented
McNaughton et al. 1998 (55)         Significant increase in work in all
                                     tests, increase in body mass
Peyrebrune et al. 1998 (56)         Increased performance as there was
                                     a reduction in total sprint time
Leenders et al. 1999 (57)           Mean overall swimming velocity
                                     improved. No change in body mass
Theodorou et al. 1999 (58)          Improvement (1.5%) in mean swim and
                                     interval set. Increase in body
                                     mass

(a)RDBPC: randomised double-blind placebo control, RPC: randomised
placebo control, RSBPC: randomised single-blind placebo control, SGRM:
single group repeated measures; RDBPCX: randomised double-blind placebo
control crossover.

Table 2

Summary of the research studies on [beta]-hydroxy-[beta]-methylbutyrate
(HMB) supplementation in exercising (trained or untrained individuals),
conducted from 1996-2000 (n = 8)

          Study                  Subjects

Nissen et al. 1996a (65)         n = 41M)
(Endurance-exercise)        (healthy subjects


Nissen et al. 1996a (65)          n = 28
(Resistance-training)       (trained subjects)



Nissen et al. 1996b (64)         n = 40M
(Resistance-training)



Kreider et al. 1999 (63)    n = 40M (athletes)
(Resistance-training)



Kreider et al. 1999 (63)    n = 41M (athletes)
(Resistance-training)



Knitter et al. 2000 (66)          n = 13
(Resistance-training)            (5M 8F)

Gallagher et al. 2000 (69)       n = 37M
(Strength-training)





Panton et al. 2000 (67)           n = 75
(Resistance-training)           (39M 36F)




          Study                       Study type

Nissen et al. 1996a (65)    Placebo-controlled, Randomised
(Endurance-exercise)


Nissen et al. 1996a (65)    Placebo-controlled,
(Resistance-training)       Single-blind, Randomised



Nissen et al. 1996b (64)    Placebo-controlled, Randomised
(Resistance-training)



Kreider et al. 1999 (63)    Double-blind, Randomised
(Resistance-training)



Kreider et al. 1999 (63)    Double-blind,
(Resistance-training)       Placebo-controlled, Randomised



Knitter et al. 2000 (66)    Double-blind,
(Resistance-training)       Placebo-controlled, Randomised

Gallagher et al. 2000 (69)  Double-blind,
(Strength-training)         Placebo-controlled, Randomised





Panton et al. 2000 (67)     Double-blind,
(Resistance-training)       Placebo-controlled, Randomised




          Study             HMB dose-duration trial         Effect

Nissen et al. 1996a (65)    1.5 g or 3 g/day - 3 wk trial    Yes
(Endurance-exercise)


Nissen et al. 1996a (65)    3 g/day - 7 wk trial             Yes
(Resistance-training)



Nissen et al. 1996b (64)    3 g/day - 4 wk trail             Yes
(Resistance-training)



Kreider et al. 1999 (63)    3 g or 6 g/day - 28 days trial    No
(Resistance-training)



Kreider et al. 1999 (63)    3 g or 6 g/day - 4 wk trial      Yes
(Resistance-training)



Knitter et al. 2000 (66)    3 g/day - 8 wk trial             Yes
(Resistance-training)

Gallagher et al. 2000 (69)  3 g or 6 g/day - 7 wk trial      Yes
(Strength-training)





Panton et al. 2000 (67)     3 g/day - 4 wk trial             Yes
(Resistance-training)




          Study                        Comments

Nissen et al. 1996a (65)    HMB significantly decreased
(Endurance-exercise)        the exercise-induced
                            proteolysis and increase
                            strength.
Nissen et al. 1996a (65)    HMB prevented proteolysis and
(Resistance-training)       muscle damage and results in
                            larger gains in muscle
                            function and in
                            resistance-training.
Nissen et al. 1996b (64)    HMB supplementation increased
(Resistance-training)       bench press strength, fat
                            free mass gain, but no effect
                            on fat mass.

Kreider et al. 1999 (63)    28 d of HMB supplementation in
(Resistance-training)       athletes does not reduce
                            catabolism or induce changes
                            in body composition and
                            strength.
Kreider et al. 1999 (63)    HMB supplementation promotes
(Resistance-training)       no gains in body mass, fat
                            free mass or fat mass, but
                            trend for increase work output
                            on sprint test.
Knitter et al. 2000 (66)    HMB helps prevent
(Resistance-training)       exercise-induced muscle
                            damage.
Gallagher et al. 2000 (69)  Higher doses of HMB (>3 g/d)
(Strength-training)         do not promote strength or
                            fat free mass gains, however 3
                            g appears to increase peak of
                            isometric and isokinetic
                            torque values and fat free
                            mass gains.
Panton et al. 2000 (67)     HMB supplementation may
(Resistance-training)       increase upper body strength
                            and decrease muscle damage,
                            regardless of gender and
                            training status.

Table 3

Summary of research studies on branched chain amino acid (BCAA)
supplementation in exercising, trained or untrained individuals, from
1991-2001 (n = 9)

Study                            Subjects           Study type (a)

Soccer player protocols

Blomstrand et al. 1991 (103)     6F (national       DBPCX
                                 standard soccer-
                                 field-players)

Davis et al. 1999 (101)          8M and F (active)  PCX






Runner protocols

Blomstrand & Newsholme,          26M (cross-        RPC
1992 (102)                       country)
                                 32M (marathon
                                 runners)






Davis et al. 1999 (101)          8M and F (active)  PCX





Krogh ergonseter protocols

MacLean et al. 1994 (104)        5M (healthy        RPC (own
                                 subjects)          control)




MacLean et al. 1996 (105)        5M (healthy        RPC (own
                                 subjects)          control)






Cyclist protocols

Madsen et al. 1996 (99)          9M (well-trained   DBPCX
                                 cyclists)

Blomstrand et al. 1997 (100)     7M (trained        RDBPCX
                                 cyclists)



Mittleman et al. 1998 (106)      7M and 6F (13      DBPCX
                                 subjects)
                                 (moderately
                                 trained)

Blomstrand & Saltin, 2001 (107)  7M (recreational   PC
                                 cyclists)







Study                            Carnitine dose-trial (b)

Soccer player protocols

Blomstrand et al. 1991 (103)     6%CHO+7.5 g BCAA or
                                 6%CHO
                                 40%val+35%leu+25%ile

Davis et al. 1999 (101)          CHO+7 g BCAA or CHO or placebo
                                 (before/during/after)





Runner protocols

Blomstrand & Newsholme,          7.5 g BCAA (cross-country) or
1992 (102)                       12 g BCAA (marathon)
                                 50%val+35%leu+15%ile or
                                 5%CHO+BCAA (cross-country)
                                 40%val+35%leu+25%ile or
                                 6%CHO+BCAA (marathon)




Davis et al. 1999 (101)          CHO+7 g BCAA or CHO or
                                 placebo (before/during/after)




Krogh ergonseter protocols

MacLean et al. 1994 (104)        77 mg/kg (~5.5 g, 2 x 38.5 mg/kg
                                 45 min and 20 min before test)
                                 30%val+44%leu+26%ile



MacLean et al. 1996 (105)        308 mg/kg (154, 77 mg/kg- 45 &
                                 20 min prior to test and
                                 77 mg/kg-5 min after starting the
                                 test ~22 g)
                                 30%val+44%leu+26%ile



Cyclist protocols

Madsen et al. 1996 (99)          3.5 L @ 5% glucose or 5%
                                 glucose + 18 g BCAA:
                                 50%val+35%leu+15% ile
Blomstrand et al. 1997 (100)     90 mg/kg (~6.5 g), 40% val+35%
                                 leu+25% ile



Mittleman et al. 1998 (106)      9.4 g F and 15.8 g M 54%
                                 leu+19% ile+ 27% val



Blomstrand & Saltin, 2001 (107)  100 mg/kg (~7 g) in 1.5 L 150 ml
                                 before and immediately before
                                 test, during and after test
                                 30%val+45%leu+25%ile





Study                            Event/Exercise test (c)

Soccer player protocols

Blomstrand et al. 1991 (103)     Soccer match (2 games
                                 separated by one week) CWT
                                 given before (~2 h) and
                                 within the game
Davis et al. 1999 (101)          Running--intermittent shuttle
                                 run until exhaustion





Runner protocols

Blomstrand & Newsholme,          Run - 30 km cross-country race or
1992 (102)                       marathon
                                 Run time + CWT after cross-
                                 country run






Davis et al. 1999 (101)          Running--intermittent shuttle run
                                 until exhaustion




Krogh ergonseter protocols

MacLean et al. 1994 (104)        Krogh ergonseter modified for one-
                                 legged knee extensor. 60 min of
                                 dynamic knee extensor exercise
                                 ~71% of maximum work capacity


MacLean et al. 1996 (105)        Krogh ergometer modified for one-
                                 legged knee extensor. 90 min of
                                 dynamic knee exercise ~64% of
                                 maximum workload




Cyclist protocols

Madsen et al. 1996 (99)          Cycling 100 km time trial as fast
                                 as possible (own bikes) connected
                                 to a magnetic brake
Blomstrand et al. 1997 (100)     Cycling 60 min @ ~70%[VO.sub.2max]
                                 + 20 min time trial. Stroop Colour
                                 Word Test after ride


Mittleman et al. 1998 (106)      Cycling (ergometry) in the heat
                                 (34[degrees]C), time to exhaustion
                                 @ 40%[VO.sub.2max]


Blomstrand & Saltin, 2001 (107)  Cycling 1 hour of ergometer cycle
                                 exercise and 2 hours of recovery
                                 period. Work rate ~164W ~75%
                                 [VO.sub.2max]





Study                            Effect

Soccer player protocols

Blomstrand et al. 1991 (103)     Yes



Davis et al. 1999 (101)          No






Runner protocols

Blomstrand & Newsholme,          Yes
1992 (102)








Davis et al. 1999 (101)          No





Krogh ergonseter protocols

MacLean et al. 1994 (104)        Yes





MacLean et al. 1996 (105)        Yes







Cyclist protocols

Madsen et al. 1996 (99)          No


Blomstrand et al. 1997 (100)     No




Mittleman et al. 1998 (106)      Yes




Blomstrand & Saltin, 2001 (107)  Yes








Study                            Comments

Soccer player protocols

Blomstrand et al. 1991 (103)     Improvement in CWT after game
                                 with CHO+BCAA. No such effect
                                 was found when subjects took
                                 the placebo drink (CHO).
Davis et al. 1999 (101)          No performance differences
                                 between (CHO or CHO+BCAA)
                                 trials. CHO and CHO+BCAA
                                 increased time to fatigue
                                 compared to placebo. No
                                 further enhancement with BCAA.

Runner protocols

Blomstrand & Newsholme,          CWT performance improved in BCAA
1992 (102)                       trial after cross-country run.
                                 'Slower runners' in BCAA group
                                 (marathon) ran faster but no
                                 significant effect on performance
                                 in the 'faster runners' group.
                                 BCAA ingested during exercise might
                                 decrease the net rate of protein
                                 degradation in human skeletal
                                 muscle during exercise.
Davis et al. 1999 (101)          No performance differences between
                                 (CHO or CHO+BCAA) trials. CHO
                                 and CHO+BCAA increased time to
                                 fatigue compared to placebo. No
                                 further enhancement with BCAA.

Krogh ergonseter protocols

MacLean et al. 1994 (104)        BCC supplementation results in
                                 significantly greater muscle
                                 ammonia production during
                                 exercise. Increased results in
                                 decrease of muscle protein
                                 breakdown during exercise.
MacLean et al. 1996 (105)        Long-term exercise+BCAA
                                 administration significantly
                                 increase muscle ammonia, alanine &
                                 glutamine production, as well as
                                 lower lactate production, than is
                                 observed without BCAA
                                 supplementation.

Cyclist protocols

Madsen et al. 1996 (99)          No performance differences between
                                 trials. Plasma BCAA and ammonia
                                 levels higher with BCAA trial.
Blomstrand et al. 1997 (100)     No difference in physical
                                 performance between 2 trials (work
                                 done at the last 20 min maximal
                                 exercise), CWT improved after
                                 exercise-BCAA trial.
Mittleman et al. 1998 (106)      Increased time to exhaustion with
                                 BCAA, increase in plasma BCAA and
                                 decrease tryptophan:BCAA. Trend to
                                 higher plasma ammonia. No
                                 difference between genders.
Blomstrand & Saltin, 2001 (107)  BCAA have an anablic effect on
                                 muscle protein metabolism during
                                 recovery. Protein synthesis
                                 stimulated and/or protein
                                 degradation decreased as an effect
                                 of BCAA ingestion. However during
                                 exercise the data is too variable
                                 to make any conclusion.

(a)RDBPCX: randomised double-blind placebo control crossover, RPC:
randomised placebo control, DBPCX: double-blind placebo control,
crossover, PC: placebo control, PCX: placebo control crossover.

(b)CHO: carbohydrate, BCAA: branched chain amino acids, Val: valine,
Leu: leucine, Ile: isoleucine.

(c)[VO.sub.2max]: maximal Oxygen consumption during exercise, CWT:
Stroop Colour Word Test.

Table 4

Summary of research studies on carnitine supplementation in exercising,
trained or untrained individuals, from 1988-2000 (n = 11)

Study                     Subjects                 Study type (a)

Soop et al. 1988 (130)    7M (moderately           CX (own controls)
                          trained)

Vecchiet et al.           10M (moderately          RDBPCX
1990 (124)                trained)

Siliprandi et al.         10M (moderately          RDBPCX
1990 (125)                trained)


Decombaz et al.           9M (untrained)           DBPCX
1993 (131)


Natali et al. 1993 (122)  12M (healthy active)     RPCX


Arenas et al.             16M (well-trained long-  RDBPC
1994 (126)                distance runners)


Barnett et al.            8M (healthy males)       EP-2 controls
1994 (132)

Brass et al. 1994 (123)   14M (healthy males)      RDBPCX



Trappe et al.             20M (highly-trained      RDBPC
1994 (129)                swimmers)


Vukovich et al.           SM (healthy males)       R, C (1st trial) 3
1994 (133)                                         trials

Colombani et al.          7M (endurance-trained    RDBPCX
1996 (127)                athletes)



Study                     Carnitine dose trial

Soop et al. 1988 (130)    5 g/d (orally)-5 days


Vecchiet et al.           2 g (orally) @ 1 h
1990 (124)                before exercise (acute
                          administration)
Siliprandi et al.         2 g (orally) @ 1 h
1990 (125)                before exercise (acute
                          administration)

Decombaz et al.           3 g/d (orally)-7 days
1993 (131)


Natali et al. 1993 (122)  3 g(intravenously)-1
                          dose 40 min before

Arenas et al.             2 g/day (orally)-28
1994 (126)                days


Barnett et al.            4 g/day (orally)-14
1994 (132)                days

Brass et al. 1994 (123)   92.5 mol/kg or
                          18.5 mol/kg
                          (intravenously)
                          administration-1 dose
Trappe et al.             4 g/day (orally)-7
1994 (129)                days 2 g twice daily


Vukovich et al.           6 g/day (orally) 7-14
1994 (133)                days

Colombani et al.          4 g (orally) 2 g @ 2 h
1996 (127)                before run and 2 g @
                          20 km mark


Study                     Event/Exercise test (b)              Effect

Soop et al. 1988 (130)    Cycling 120 min @ 50% [VO.sub.2max]  No


Vecchiet et al.           Cycling ergometer until exhaustion,  Yes
1990 (124)                72 hours rest and repeated exercise
                          test
Siliprandi et al.         Cycle to exhaustion (2 bouts of      Yes
1990 (125)                maximal ergometer) separated by a
                          3-day interval

Decombaz et al.           Cycling 20 min at 60% [VO.sub.2max]  No
1993 (131)                + CHO depletion regime


Natali et al. 1993 (122)  Cycling 40 min @60 w + 2 min         No
                          anaerobic exercise (250W) + 50 min
                          for recovery
Arenas et al.             Running 40-50% [VO.sub.2max] 90      Yes
1994 (126)                min/d for 5 days and 70-80%
                          [VO.sub.2max] 60 min/d for 2 days

Barnett et al.            Sprint cycling 90% [VO.sub.2max]/4   No
1994 (132)                min, rest 20 min and 5 x 1 min ride
                          at 115% [VO.sub.2max]
Brass et al. 1994 (123)   Bicycle ergometer test (RQ, FFA      No
                          glucose utilisation, [VO.sub.2] at
                          fixed workload)

Trappe et al.             Swimming bouts 5 x 91.4 m (100 yd)   No
1994 (129)                at supra-maximal intensity, 2 min
                          rest each

Vukovich et al.           Submaximal exercise (cycled 60 min   No
1994 (133)                at 70% [VO.sub.2max] - RQ, FFA
                          glucose utilisation, [VO.sub.2])
Colombani et al.          Marathon run + submaximal            No
1996 (127)                performance test day after marathon
                          + post-race lactate


Study                     Comments

Soop et al. 1988 (130)    No effect on muscle substrate
                          utilisation during exercise and at
                          rest.
Vecchiet et al.           Increased time and work until
1990 (124)                exhaustion, decrease in lactate
                          production and oxygen uptake.
Siliprandi et al.         Increased time to exhaustion.
1990 (125)                Post-exercise increase in plasma
                          lactate and pyruvate was after
                          maximal progressive work.
Decombaz et al.           No metabolic enhancement, substrate
1993 (131)                metabolism not affected during
                          submaximal exercise. Performance
                          was not measured.
Natali et al. 1993 (122)  No changes during exercise, but
                          increased fatty acid oxidation
                          during recovery.
Arenas et al.             Improvement in [VO.sub.2max] based
1994 (126)                on biochemical findings and
                          significant increase in the
                          pyruvate dehydrogenase.
Barnett et al.            No significant effect on muscle
1994 (132)                carnitine content and thus could
                          not alter lactate accumulation.
Brass et al. 1994 (123)   No effect on fuel metabolism during
                          exercise in humans.


Trappe et al.             No ergogenic benefit during
1994 (129)                repeated bouts of high-intensity
                          anaerobic exercise in highly
                          trained swimmers.
Vukovich et al.           No effect on lipid or carbohydrate
1994 (133)                oxidation during exercise.

Colombani et al.          No changes in exercise metabolism
1996 (127)                or marathon running time, no change
                          in recovery and submaximal test
                          performance post race.

(a)RDBPC: randomised double-blind placebo control, RDBPCX: randomised
double-blind placebo control crossover, RPCX: randomised placebo control
crossover, CX: crossover, DBPCX: double-blind placebo control crossover,
RC: randomised and control, EP: experimental protocol.

(b)[VO.sub.2max]: maximal Oxygen consumption during exercise,
[VO.sub.2]: oxygen consumption, RQ: respiratory quotient, FFA: free
fatty acids.

Table 5

Summary of recent studies on supplementation with popular ergogenic aids
and physical performance


Supplement   Evidence of    Condition for an ergogenic effect
  type         efficacy

 Creatine   Clear evidence  High-intensity, short-term exercise
            of efficacy     tasks ([less than or equal to]30
                            seconds, repeated exercise bouts
                            and limited recovery time between
                            repetitions.
 HMB (a)    Evidence of     Gains in strength and body mass
            efficacy is     associated with resistance
            limited         training, and recovery from exercis
            population.     healthy population
Glutamine                   No ergogenic effect



 BCAA (b)                   No ergogenic effect

Carnitine                   No ergogenic effect


                                                N[degrees] of
Supplement  Comments                              examined
  type                                             trials

 Creatine   No significant effect in aerobic         35
            endurance exercise tasks. Further
            research is needed (long-term
            studies, safety, side effects).

 HMB (a)    Studies mainly positive for novice        8
            rather than well-trained athletes.
            Limited number of studies.

Glutamine   Clinical evidence in the                  8
            maintenance of muscle mass and
            immune system function in
            critically ill patients.
 BCAA (b)   No ergogenic effect, further study        9
            is needed.
Carnitine   Study design limitations, further        11
            research is needed.

(a)HMB: hydroxymethylbutyrate.

(b)BCAA: branched chain amino acids.

Acknowledgment 

Acknowledgment is given to Dr Peter Williams who gave valuable assistance and helpful comments as a supervisor.

References

(1.) Williams MH. The ergogenic edge. Pushing the limits of sport performance. Champaign, II: Human Kinetics; 1998.

(2.) Wolfe RR. Protein supplements and exercise. Am J Clin Nutr 2000;72:551S-7S.

(3.) Burke L, Deakin M. Clinical sports nutrition, 2nd ed. Sydney: McGraw-Hill; 2000.

(4.) Balsom PD, Soderlund K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Med 1994;18:268-80.

(5.) Kreider RB. Creatine supplementation, analysis of ergogenic value, medical safety, and concerns. J Exerc Physiol Online 1998;1:7-19, www.css.edu/users/tboone2/asep/jan3.htm Accessed 16 March 2001.

(6.) Williams MH, Branch JD. Creatine supplementation and exercise performance: An update. J Am Coll Nutr 1998;17:216-34.

(7.) Williams MH, Kreider RB, Branch JD. Creatine: The power supplement. Champaign, II: Human Kinetics; 1999.

(8.) Di Pasquale MG. Amino acids and proteins for athletes. The anabolic edge. New York: CRC Press; 1997.

(9.) Kreider R. Effects of protein and amino acid supplementation on athletic performance. Sportscience 1999;3(1), www.sportsci.org/jour/9901/rbk.html Accessed 4 April 2001.

(10.) Balsom PD, Harridge SD, Soderlund K, Sjodin B, Ekblom B. Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 1993;149:521-3.

(11.) Position of the American Dietetic Association, Dieticians of Canada, and the American College of Sports Medicine: Nutrition and athletic performance. J Am Diet Assoc 2000;100:1543.

(12.) Vandenberghe K, Gillis N, Van Leemputte M, van Hecke Om Vans-tapel FM, Hespel P. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996;80:452-7.

(13.) Barnett C, Hinds M, Jenkins DG. Effects of oral creatine supplementation on multiple sprint cycle performance. Aust J Sci Med Sport 1996;28:35-9.

(14.) Burke LM, Pyne BD, Telford RD. Effect of oral creatine supplementation on single-effort sprint performance in elite swimmers. lot J Sport Nutr 1996;6:222-33.

(15.) Redondo D, Dowling EA, Graham BL, Almada AL, Williams MH. The affect of oral creatine monohydrate supplementation on running velocity. Jot J Sport Nutr 1996;6:213-21.

(16.) Vandenberghe K, Goris M, Van Hecke P, van Leemputte M, Vangerven L, Hespel P. Prolonged creatine intake facilitates the effects of strength training on intermittent exercise capacity. Insider 1996;4(3):1-2.

(17.) Terrillion KA, Kolkhorst FW, Dolgener FA, Joslyn SJ. The effect of creatine supplementation on two 700m maximal running bouts. Int J Sport Nutr 1997;7:138-43.

(18.) Cooke WH, Bames WS. The influence of recovery duration on high-intensity exercise performance after oral creatine supplementation. Can J Appl Physiol 1997;22:454-67.

(19.) Odland LM, MacDougall JD, Tarnopolsky MA, Elorriaga A, Burgman A. Effects of oral creatine supplementation on muscle [PCr] and short-term maximum power output. Med Sci Sports Exerc 1997;29:216-9.

(20.) Goldberg PG, Bechtel PJ. Effects of low dose creatine supplementation on strength, speed and power events by male athletes. Med Sci Sports Exerc 1997;29:251S.

(21.) Hamilton-Ward K, Meyers M, Skelly WA, Marley RI, Saunders SJ. Effect of creatine supplementation on upper extremity anaerobic response in females. Med Sci Sports Exerc 1997;29:146S.

(22.) Smith SA, Montain SJ, Matott RP, Zientara GP, Jolesz FA, Fielding RA. Effects of creatine supplementation on the energy cost of muscle contraction: a [P-MRS.sup.31] study. J Appl Physiol 1999;87:116-23.

(23.) Casey A, Constantin-Teodosiu D, Howell S, Hultman E, Greenhaff P. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 1996;271:31E-7E.

(24.) Schneider DA, Mcdonough PJ, Fadel PJ, Berwick JP. Creatine supplementation and total work performance during 15-s and 1-min bouts of maximal cycling. Aust J Sci Med Sports 1997;29:65-8.

(25.) Kirksey K, Warren BJ, Stone MH, Stone MR, Johnson RL. The effects of six weeks of creatine monohydrate supplementation in male and female track athletes. Med Sci Sports Exerc 1997;29:145S.

(26.) Prevost MC, Nelson AG, Morris GS. Creatine supplementation enhances intermittent work performance. Res Q Exerc Sport 1997;68:233-40.

(27.) Smith JC, Stephens DP, Hall EL, Jackson AW, Earnest CP. Effect of oral creatine ingestion on parameters of the work rate-time relationship and time to exhaustion in high-intensity cycling. Euro J Appl Physiol 1998;77:360-5.

(28.) Vandenburie F, Vanden Eyode B, Vandenberghe K. Effects of creatine loading on endurance capacity and sprint power in cyclists. Int J Sports Med 1998;19:490-5.

(29.) Kamber M, Koster M, Kreis R, Walker G, Boesch C, Hoppeler H. Creatine supplementation--Part I: performance, clinical chemistry, and muscle volume. Med Sci Sports Exerc 1999;31:1763-9.

(30.) Spriet LL. Ergogenic aids: recent advances and retreats. In: Lamb DR, Murray R, editors. Perspectives in exercise science and sports medicine. Vol. 10: Optimizing sports performance. Carmel, Indiana: Cooper Publishing Company; 1997. p.185-238.

(31.) Rico-Sanz J, Thomas EL, Jenkinson G, Mierisova S, lIes R, Bell JD. Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by H-MRS. J Appl Physiol 1999;87:2068-72.

(32.) Smith SA, Montain SJ, Matott RP, Zientara GP, Jolesz FA, Fielding RA. Effects of creatine supplementation on the energy cost of muscle contraction: a P-MRS study. J Appl Physiol 1999;87:116-23.

(33.) Mujika I, Chatard JC, Lacoste L, Barale F, Geyssant A. Creatine supplementation does not improve sprint performance in competitive swimmers. Med Sci Sports Exerc 1996;28:1435-41.

(34.) Stout JR, Echerson J, Noonan D, Moore G, Cullen D. The effects of a supplement designed to augment creatine uptake on exercise performance and fat free mass in football players. Med Sci Sports Exerc 1997;29:251S.

(35.) Harris RC, Viru M, Greenhaff E. The effect of oral creatine supplementation on running performance during maximal short term exercise in man. J Physiol 1993;467:74P.

(36.) Green AL, Hultman E, Macdonald IA, Sewell DA, Greenhaff FL. Carbohydrate ingestion augments skeletal muscle creatine accumulation during supplementation in man. Am J Physiol 1996;271:E812-E26.

(37.) Green AL, Simpson EJ, Littlewood JJ, Macdonald IA, Greenhaff PL. Carbohydrate ingestion augments creatine retention during creatine feeding in man. Acta Physiol Scand 1996;158:195-202.

(38.) Green AL, Macdonald IA, Greenhaff PL. The effects of creatine and carbohydrate on whole body creatine retention in vegetarians. Proc Nutr Soc 1997;56:81A.

(39.) Vandenberghe K, Van Hecke F, Van Leemputte M, Vanstapel FM, Hespel P. Inhibition of muscle phosphocreatine resynthesis by caffeine after creatine loading. Med Sci Sports Exerc 1997;29:249S.

(40.) Greenwalt D. Creatine and Caffeine. The Power Store 2001; http://www.thepowerstore.com. Accessed 24 Decenber 2002.

(41.) Gill ND, de Hedervary DG, Weatherby RF. Does caffeine counter-act the ergogenic effect of creatine supplementation? Brisbane, Australia: 2000 Pre-Olympic Sports Medicine and Physical Education International Congress on Sport Science; 2000. http://www.ausport.gov.au/fulltext/2000/preoly/abs275b.htm. Accessed 24 December 2002.

(42.) Hespel P, Op 't E, Van Leemputte M. Opposite actions of caffeine and creatine on muscle relaxation time in humans. J Appl Physiol 2002;92:513-8.

(43.) Van Leemputte M, Vandenberghe K, Hespel P. Shortening of muscle relaxation time after creatine loading. J Appl Physiol 1999;8:840-4.

(44.) Becque M, Lochmann JD, Melrose D. Effect of creatine supplementation during strength training on 1-RM and body composition. Med Sci Sports Exerc 1997;29:146S.

(45.) Kurosava Y, Iwane H, Hamaoka T, et al. Effects of oral creatine supplementation on high- and low-intensity grip exercise performance. Med Sci Sports Exerc 1997;29:251S.

(46.) Vandenberghe K, Goris M, Van Hecke F, van Leemputte M, Vangerven L, Hespel P. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997;83:2055-63.

(47.) Volek JS, Kraemer WJ, Bush JA, Boetes M, Incledon T, Clark KL et al. Creatine supplementation enhances muscular performance during high-intensity resistance exercise. J Am Diet Assoc 1997;97:765-70.

(48.) Maganaris CN, Maughan RJ. Creatine supplementation enhances maximum voluntary isometric force and endurance capacity in resistance trained men. Acta Physiol Scand 1998;163:279-87.

(49.) Stone MH, Sanborn K, Smith LL, O'Bryant JS, Hoke T, Utter AC, et al. Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players. Int J Sport Nutr 1999;9:146-65.

(50.) Urbanski RL, Vincent WJ, Yaspelkis BB. Creatine supplementaiton differentially affects maximal isometric strength and time of fatigue in large and small muscle groups. Int J Sport Nutr 1999;9:136-45.

(51.) Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL, et al. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 1999;31:1147-56.

(52.) Burke DG, Silver S, Holt LE, Smith Palmer T, Culligan CJ, Chilibeck PD. The effect of continuous low dose creatine supplementation on force, power and total work. Int J Sport Nutr Exerc Metab 2000;l0:235-44.

(53.) Bosco C, Tihanyi J, Pucspk J, Kovacs I, Gabossy A, Colli R, et al. Effect of oral creatine supplementation on jumping and running performance. Int J Sports Med 1997;18:369-72.

(54.) Grindstaff PD, Kreider R, Bishop R, Wilson M, Wood L, Alexander C, et al. Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers. Int J Sport Nutr 1997;7:330-46.

(55.) McNaughton LR, Dalton B, Tarr J. The effects of creatine supplementation on high-intensity exercise performance in elite performers. Eur J Appl Physiol Occup Physiol 1998;78:236-40.

(56.) Peyrebrune MC, Nevill ME, Donaldson FJ, Cosford DJ. The effects of oral creatine supplementation on performance in single and repeated sprint swimming. J Sports Sci 1998;16:271-9.

(57.) Leenders NM, Lamb DR, Nelson TE. Creatine supplementation and swimming performance. Int J Sport Nutr 1999;9:251-62.

(58.) Theodorou AS, Cooke CB, King RF, Hood C, Denison T, Wainwright BG, et al. The effect of longer-term creatine supplementation on elite swimming performance after an acute creatine loading. J Sports Sci 1999;17:853-9.

(59.) Nair KS, Schwartz RG, Welle S. Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans. Am J Physiol 1992;263:E928-34.

(60.) Nissen S, Panton L, Fuller J. Effect of feeding [beta]-hydroxy-[beta]-methylbutyrate (HMB) on body composition and strength of women. FASEB J 1996;11:A150.

(61.) Nissen S, Fuller JC Jr, Sell J, Perket PR, Rives DV. The effect of beta-hydroxy-beta-methylbutyrate on growth, mortality, and carcass qualities of broiler chickens. Poult Sci 1994;73:137-55.

(62.) Nissen S, Sharp R, Panton L, Vukovich M, Trappe SW, Fuller JC. [beta]-hydroxy-[beta]-methy1butyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors. J Nutr 2000;130:1937-45.

(63.) Kreider R, Ferreira M, Wilson M, Almada AL. Effects of calcium [beta]-HMB supplementation during resistance-training on markers of catabolism, body composition and strength. Int J Sports Med 1999;20:503-9.

(64.) Nissen S, Panton L, Wilhem R, Fuller JC. Effect of [beta]-hydroxy-[beta]-methylbutyrate (HMB) supplementation on strength and body composition of trained and untrained males undergoing intense resistance training. FASEB J 1996;l0:A287.

(65.) Nissen S, Sharp R, Ray M, Rathmacher JA, Rice J, Fuller JC et al. Effect of leucine [beta]-hydroxy-[beta]-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol 1996;81:2095-104.

(66.) Knitter AE, Panton L, Rathmacher JA, Peterson A, Sharp R. Effects of [beta]-hydroxy-[beta]-methylbutyrate on muscle damage after a prolonged run. J Appl Physiol 2000;89:1340-4.

(67.) Panton LB, Rathmacher JA, Baier S, Nissen S. Nutritional supplementation of the leucine metabolite [beta]-hydroxy-[beta]-methylbutyrate (HMB) during resistance training. Nutrition 2000;16:734-9.

(68.) Slater G, Jenkins D, Logan P, Lee H, Vukovich M, Rathmacher JA, et al. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men. Int J Sport Nutr 2001;1l:384-6.

(69.) Gallagher PM, Carrithers JA, Godard MP, Schulze KE, Trappe SW. [beta]-hydroxy-[beta]-methylbutyrate ingestion, Part 1: effects on strength and fat free mass. Med Sci Sports Exerc 2000;32:2109-15.

(70.) Parry-Billings M, Blomstrand E, Leighton B, Dimitriadis GD, Newsholme EA. Does endurance exercise impair glutamine metabolism? [abstract] Can J Sport Sci 1990;13:13.

(71.) Parry-Billings M, Budggit R, Koutedakis Y, Blomstrand E, Brooks S, Williams C, et al. Plasma amino acid concentrations in overtraining syndrome: Possible effects on the immune system. Med Sci Sports Exerc 1992;24:1353-8.

(72.) Kargotich S, Rowbottom DG, Keast D, et al. Plasma glutamine changes after high intensity exercise in elite male swimmers [abstract]. Med Sci Sports Exerc 1996;28:133S.

(73.) Newsholme EA, Calder PC. The proposed role of glutamine in some cells of the immune system and speculative consequences for the whole animal. Nutrition 1997;13:728-30.

(74.) Yagoob P, Calder PC. Glutamine requirement of proliferating T lymphocytes. Biochem Soc Trans 1996;24:78S.

(75.) Ogle CK, Ogle JD, Mao JX, Simon J, Noel JG, Li BG, et al. Effect of glutamine on phagocytosis and bacterial killing by normal and pediatric burn patient neutrophils. J Parenteral Enteral Nutr 1994;18:128-33.

(76.) Taaffe DR, Jin IH, Vu TH, Hoffman AR, Marcus R. Lack of effect of recombinant human growth hormone (GH) on muscle morphology and GH-insulin-like growth factor expression in resistance-trained elderly men. J Clin Endocrinol Metab 1996;81:421-5.

(77.) Walsh NP, Andrew KB, Robson PJ, Gleeson M. Glutamine, exercise and immune function. Sports Med 1998;26:177-91.

(78.) Antonio J, Street C. Glutamine: a potential useful supplement for athletes. Can J Appl Physiol 1999;24:l-14.

(79.) Nieman DC, Johanssen LM, Lee JW, Arabatzis K. Risk of infectious episodes in runners before and after the Los Angeles Marathon. J Sports Med Phys Fitness 1990;30:316-28.

(80.) Bruce M, Constantin-Teodosiu D, Greenhaff PL, Boobis CH, Williams C, Bowtell JL. Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle. Am J Physiol Endocrinol Metab 200l;280:E669-E75.

(81.) Nieman DC, Pendersen BK. Exercise and immune function. Recent developments. Sports Med 1999;27:72-80.

(82.) Rowbottom DG, Keast D, Goodman C, Morton AR. The haematological, biochemical and immunological profile of athletes suffering from the overtraining syndrome. Eur J Appl Physiol 1995;70:502-9.

(83.) Mackinnon LT, Hooper SL. Plasma glutamine and upper respiratory tract infection during intensified training in swimmers. Med Sci Sports Exerc 1996;28:285-90.

(84.) Castell LM, Poortmans JR. Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol 1996;73:488-90.

(85.) Newsholme EA. Biochemical mechanisms to explain immunosuppression in well-trained and overtrained athletes. Int j Sports Med 1994;15 Suppl 3:142S-7S.

(86.) Keast D, Arstein D, Harper W, Fry RW, Morton AR. Depression of plasma glutamine concentration after exercise stress and its possible influence on he immune system. Med J Aust 1995;162:15-8.

(87.) Rowbottom DG, Keast D, Morton AR. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sports Med 1996;21:80-91.

(88.) Henriksson J. Effect of exercise on amino acid concentration in skeletal muscle and plasma. J Exp Biol 1991;160:149-65.

(89.) Adibi SA. Metabolism of branched-chain amino acids in altered nutrition. Metab Clin Exp 1976;25:1287-302.

(90.) Mero A. Leucine supplementation and intensive training [Review]. Sports Med 1999;27:347-58.

(91.) Kreider RB, Miriel V, Bertun E. Amino acid supplementation and exercise performance: proposed ergogenic value. Sports Med 1993;16:190-209.

(92.) Mourier A, Bigard AX, de Kerviler E. Combined effects of caloric restriction and branched-chain amino acid supplementation on body composition and exercise performance in elite wrestlers. Int J Sports Med 1997;18:47-55.

(93.) Kreider RB. Central fatigue hypothesis and overtraining. In: Kreider RB, Fry AC, O'Toole M, editors, Overtraining in sport. Champaign, Il: Human Kinetics; 1998. p. 309-31.

(94.) Lemon PW. Do athletes need more protein and amino acids? Int J Sport Nutr 1995;5Suppl:39-61.

(95.) Verger P, Aymard P, Cynobert L, Anton G, Luibi R. Effects of administration of branched-chain amino acids vs glucose during acute exercise in the rat. Physiol Behav 1994;55:523-6.

(96.) Newsholme EA, Parry-Billings M, McAndrew M, et al. Biochemical mechanism to explain some characteristics of overtraining. In: Brouns F. editor. Medical sport science, 32. Basel: Karger; 1991. p.79-93.

(97.) Gastmann UA, Lehmann MJ. Overtraining and the BCAA hypothesis. Med Sci Sports Exerc 1998;30:1173-8.

(98.) Davis JM, Bailey SP, Woods JA, Galiano FJ, Hamilton M, Bartizi WP. Effects of carbohydrate feeding on plasma free tryptophan and branched-chain amino acids during prolonged cycling. Eur J Appl Physiol 1992;65:513-9.

(99.) Madsen K, MacLean DA, Kiens B, Christensen D. Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100 km. J Appl Physiol 1996;81:2644-50.

(100.) Blomstrand E, Hassmen P, Ek S, Ekblom B, Newsholme EA. Influence of ingesting a solution of branched-chain amino acids on perceived exertion during exercise. Acta Physiol Scand 1997;159:41-9.

(101.) Davis JM, Welsh RS, De Volve KL, Alderson NA. Effects of branched-chain amino acids and carbohydrate on fatigue during intermittent high-intensity running. Int J Sport Med 1999;20:309-14.

(102.) Blomstrand E, Newsholme EA. Effect of branched-chain amino acid supplementation on the exercise-induced change in aromatic amino acid concentration in human muscle. Acts Physiol Scand 1992;146:293-8.

(103.) Blomstrand E, Hassmen P, Ekbom B, Newsholme EA. Administration of branched-chain amino acids during sustained exercise-effects on performance and on plasma concentration of some amino acids. Eur J Appl Physiol 1991;63:83-8.

(104.) MacLean DA, Graham TE, Saltin B. Branched-chain amino acids augment ammonia metabolism while attenuating protein breakdown during exercise. AJP Endocrinol Metab 1994;267:El010-E22.

(105.) MacLean DA, Graham TE, Saltin B. Stimulation of muscle ammonia production during exercise following branched-chain amino acid supplementation in humans. J Physiol 1996;493:909-22.

(106.) Mittleman KD, Ricci MR, Bailey SP. Branched-chain amino acids prolong exercise during heat stress in men and women. Med Sci Sports Exerc 1998;30:83-91.

(107.) Blomstrand E, Saltin B. BCAA intake affects protein metabolism in muscle after but not during exercise in humans. AJP-Endocrinology Metababolism 2001;281 :E365-E74 http://ajpendo.physiology.org/cig/content/full/281/2/E365 Accessed 24 September 2001.

(108.) Williams MH. Facts and fallacies of purported ergogenic amino acids supplements. Clin Sports Med 1999;18:633-49.

(109.) Todd KS, Butterfield GE, Calloway DH. Nitrogen balance in men with adequate and deficient energy intake at three levels of work. J Nutr 1984;114:2107-l8.

(110.) Lemon PWR, Mullin JP. The effect of initial muscle glycogen levels on protein catabolism during exercise. J Appl Physiol 1980;48:624-9.

(111.) Welle S, Matthews DE, Campbell RG, Nair KS. Stimulation of protein turnover by carbohydrate overfeeding in men. Am J Physiol 1989;E413-E7.

(112.) Krempf M, Hoerr RA, Pelletier VA, Marks LM, Gleason R, Young VR. An isotopic study of the effect of dietary carbohydrate on the metabolic fate of the dietary leucine and phenylalanine. Am J Clin Nutr 1993;57:161-9.

(113.) Wagenmakers AM, Beckers EJ, Brouns F, Kuipers H, Soeters PB, van der Vosse GJ. Carbohydrate supplementation, glycogen depletion, and amino acid metabolism during exercise. Am J Physiol 1991;260:E883-E90.

(114.) Zanker CL, Swaine IL, Castell LM, Newsholme EA. Responses of plasma glutamine, free tryptophan and branched-chain amino acids to prolonged exercise after a regime designed to reduce muscle glycogen. Eur J Appl Physiol 1997;75:543-8.

(115.) Davis JM. Carbohydrates, branched-chain amino acids, and endurance: The central fatigue hypothesis. Int J Sport Nutr 1995;55:29-38.

(116.) Jakeman PM. Amino acid metabolism, branched-chain amino acid feeding and brain monoamine function. Proc Nutr Soc 1998;57:36-41.

(117.) Meeusen R, De Meirleir K. 1995. Exercise and brain neurotransmission. Sports Med 20:160-88.

(118.) Wagenmakers AJM. Branched-chain amino acids and endurance performance. In: Reilly T, Orme M, editors. The clinical pharmacology of sport and exercise. Amsterdam: Elsevier Science BV; 1997.

(119.) Rebouche CJ, Engel AG. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. J Clin Invest 1984;73:857-67.

(120.) Brass EP. Supplemental carnitine and exercise. Am J Clin Nutr 2000;725:618S-23S.

(121.) Marconi C, Sassi G, Carpinelli A, Cerretelli P. Effects of L-carnitine loading on the aerobic and anaerobic performance of endurance athletes. Eur J Appl Physiol 1985;54:131-5.

(122.) Natali A, Santoro D, Brandi LS, Farraggiana D, Ciociaro D, Pecorin N, et al. Effects of acute hypercarnitinemia during increased fatty substrate oxidation in man. Metabolism l993;42:594-600.

(123.) Brass EP, Hoppel CL, Hiatt WR. Effect of intravenous L-carnitine on carnitine homeostasis and fuel metabolism during exercise in humans. Clin Pharmacol Ther 1994;55:618-92.

(124.) Veechiet L, Di Lisa F, Pieralisi G, Ripari P, Menabo R, Giamberardino MA et al. Influence of L-carnitine administration on maximal physical exercise. Eur J Appi Physiol Occup Physiol 1990;61:486-90.

(125.) Siliprandi N, Di Lisa F, Pieralisi G, Ripari P, Maccan F, Menabo R, et al. Metabolic changes induced by maximal exercise in human subjects following L-camitine administration. Biochim Biophys Acta 1990;1034:17-21.

(126.) Arenas J, Huertas R, Campos Y, Diaz AE, Villalon JM, Vilas E. Effects of L-carnitine on the pyruvare dehydrogenase complex and carnitine palmitoyl transferase activities in muscle of endurance athletes. FEBS Lett 1994;341:91-3.

(127.) Colombani P, Wenk C, Kunz I, Krahenbuhl S, Kuhnt MA, Frey-Rindova P. et al. Effects of L-carnitine supplementation on physical performance and energy metabolism of endurance-trained athletes: a double-blind crossover field study. Eur J Appl Physiol 1996;73:434-9.

(128.) Greig C, Finch KM, Jones DA, Cooper M, Sargeant AJ, Forte CA. The effect of oral supplementation with L-carnitine on maximal and submaximal exercise capacity. Eur J Appl Physiol 1987;56:457-60.

(129.) Trappe SW, Costill DL, Goodpaster B, Fink WJ. The effects of L-carnitine supplementation on performance during interval swimming. In J Sports Med 1994;15:181-5.

(130.) Soop M, Bjorkman O, Cederblad G, Hagenfeldt L. Influence of carnitine supplementation on muscle substrate and carnitine metabolism during exercise. J Appl Physiol 1988;64:2394-9.

(131.) Decombaz J, Deriaz O, Acheson K, Omender B, Jequier E. Effect of L-carnitine on submaximal exercise metabolism after depletion of muscle glycogen. Med Sci Sports Exerc 1993;25:733-40.

(132.) Barnett C, Costill DL, Vukovich MD, Cole KJ, Goodpaster BH, Trappe SW, et al. Effect of L-carnitine supplementation on muscle and blood carnitine content and lactate accumulation during high-intensity sprint cycling. Int J Sports Nutr 1994;4:280-8.

(133.) Vukovich MD, Costill DL, Fink WJ. Carnitine supplementation: effect on muscle carnitine and glycogen content during exercise. Med Sci Sports Exerc 1994;26:1122-9.

(134.) Wagenmakers AJM. L-carnitine supplementation and performance in man. In: Brouns F, editor. Advances in nutrition and top sport: medicine and sport science. Basel: Karger; 1991. p. 110-27.

(135.) Heinonen OJ. Carnitine and physical exercise. Sports Med 1996;22:109-32.

(136.) Hultman E, Cederblad G, Harper P. Carnitine administration as a tool to modify energy metabolism during exercise. Eur J Appl Physiol 1991;6:450.

(137.) Arenas J, Ricoy JR, Enemas AR, Pola P, D'Iddio S, Zeviani M, et al. Carnitine in muscle, serum, and urine of nonprofessional athletes: effects of physical exercise, training, and L-carnitine administration. Muscle Nerve 1991;14:598-604.

(138.) Huertas R, Campos Y, Diaz E, Desteban J, Vechietti L, Montanari G, et al. Respiratory chain enzymes in muscle of endurance athletes: effect of L-carnitine. Biochem Biophys Res Commun 1992;188:102-7.

This paper derives from a project that was completed in partial fulfillment of the MSc (Nutrition) course, in the Department of Biomedical Science at University of Wollongong, NSW G. Beduschi, MSc, BNutrDiet, Lecturer, FEPAR University, Parana, Brazil

Correspondence: G. Beduschi, R: Augusto Stellfeld, 1387, Bigorrilho, Curitiba -- Parana, Brazil 80430-140. Email: [e-mail]