Nutrition Supplements: Science vs Hype

Thomas D. Armsey Jr, MD; Gary A. Green, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 25 - NO. 6 - JUNE 97

In Brief: Aggressive marketing has led millions of recreational and elite athletes to use nutrition supplements in hopes of improving performance. Unfortunately, these aids can be costly and potentially harmful, and the advertised ergogenic gains are often based on little or no scientific evidence. No benefits have been convincingly demonstrated for amino acids, L-carnitine, L-tryptophan, or chromium picolinate. Creatine, beta-hydroxy-beta-methylbutyrate, and dehydroepiandrosterone (DHEA) may confer ergogenic or anabolic effects. Chromium picolinate and DHEA have adverse side effects, and the safety of the other products remains in question.

Nutrition supplements are a lucrative business in the United States. According to the Council for Responsible Nutrition (1), the retail sale of dietary supplements generated $3.3 billion in 1990, and revenues increase each year. This enormous expenditure is largely the result of aggressive advertising aimed at high school, college, and recreational athletes, all eager for anabolic-steroid-like gains through dietary aids. Riding the crest of the fitness wave, nutrition supplements appeal to millions of consumers willing to pay billions of dollars for alleged benefits that are too good to be true.

Unfortunately, these supplements are subject to little regulation by the US Food and Drug Administration (FDA). Advertised claims to the contrary, many supplements have not been subjected to the scientific scrutiny required of prescription drugs. Furthermore, given the size and continued growth of the supplement industry, the FDA will probably never be able to monitor its products effectively. The resulting lack of regulation can lead to unscrupulous advertising, impurities in manufacturing, and potentially dangerous reactions among supplement users.

Such potential outcomes obligate physicians to learn about current nutrition supplements so they can educate patients about the effects and risks of supplement use. Team physicians in particular can advise athletes, coaches, and administrators in these matters. Competing with slick advertisements and exaggerated claims can be difficult, but by using recent scientific research on commonly used supplements, their mechanisms of action, and possible adverse reactions, physicians can offer sound recommendations to patients who are either users or interested in trying these aids.

Creatine Monohydrate

Creatine, or methylguanidine-acetic acid, is an amino acid that was first identified in 1835 by Chevreul. It is synthesized from arginine and glycine in the liver, pancreas, and kidneys and is also available in meats and fish (2). Creatine was first introduced as a potential ergogenic aid in 1993 as creatine monohydrate and is currently being used extensively by athletes throughout the United States. A National Collegiate Athletic Association (NCAA) study, publication pending, revealed that 13% of intercollegiate athletes have used creatine monohydrate in the past 12 months (Frank Uryasz, personal communication, February 1997).

According to current theory, creatine supplementation increases the bioavailability of phosphocreatine (PCr) in skeletal muscle cells. This increase is thought to enhance muscle performance in two ways. First, more available PCr allows faster resynthesis of adenosine triphosphate (ATP) to provide energy for brief, high-intensity exercise, like sprinting, jumping, or weight lifting. Second, PCr buffers the intracellular hydrogen ions associated with lactate production and muscle fatigue during exercise. Therefore, creatine supplementation may provide an ergogenic effect by increasing the force of muscular contraction and prolonging anaerobic exercise (3).

Numerous well-designed studies have demonstrated that creatine supplementation has an ergogenic potential. Greenhaff et al (4) showed that 5-day oral dosages of 20 g/day increased muscle creatine availability by 20% and significantly accelerated PCr regeneration after intense muscle contraction. Birch et al (5) and Harris et al (6), in laboratory and field studies, demonstrated significant performance enhancement in male athletes, in both brief, high-intensity work and total time to exhaustion, using creatine supplementation of 20 to 30 g/day.

Recent data reveal that the mean creatine concentration in human skeletal muscle is 125 mmole/kg-dm (dry muscle), with a normal range between 90 and 160 mmole/kg-dm (7). This wide spectrum of creatine concentration may explain why some of the published studies have not demonstrated significant ergogenic effects. In a study by Greenhaff (7), approximately half of the tested athletic subjects exhibited concentrations lower than 125 mmole/kg-dm, with strict vegetarians substantially lower. These individuals exhibited the most significant increases in muscle creatine concentration, PCr regeneration, and performance enhancement with the use of creatine. On the other hand, athletes with elevated baseline levels of creatine showed little or no ergogenic effect when tested after ingesting creatine.

While creatine use has skyrocketed, no serious side effects have been scientifically verified in subjects using relatively brief (less than 4 weeks) creatine regimens. However, there are anecdotal reports of a dramatic increase in muscle cramping associated with the use of creatine monohydrate (J. Kinderknecht, MD, personal communication, June 1996). Future research will, we hope, clarify whether these adverse reactions are caused by creatine supplementation.

Chromium Picolinate

Chromium is an essential trace mineral present in various foods, such as mushrooms, prunes, nuts, whole grain breads, and cereals (8). A normal American diet contains 50% to 60% of the recommended daily allowance (RDA) of chromium. It has an extremely low gastrointestinal absorption rate, so supplement manufacturers have bound chromium with picolinate (CrPic) to increase the absorption and bioavailability.

Chromium supplementation became popular after it was found that exercise increases chromium loss, raising the concern that chromium deficiency may be common among athletes (9). Chromium seems to function as a co-factor that enhances the action of insulin, especially in carbohydrate, fat, and protein metabolism. Promoters of CrPic claim it increases glycogen synthesis, improves glucose tolerance and lipid profiles, and increases amino acid incorporation in muscle.

CrPic supplementation gained scientific credence in the early 1980s when researchers demonstrated anabolic-steroid-like effects with dosages of 200 micrograms/day. Evans (10,11) and Hasten et al (12) demonstrated a decreased percentage of body fat and increased lean mass among college athletes and students who took CrPic supplements and performed resistance exercise training. However, critical analysis of these studies reveals that imprecise measurement techniques, rather than CrPic supplementation, may account for these "ergogenic" results. More recent studies by Clancy et al (13) and Hallmark et al (14), using more precise measurement techniques, failed to demonstrate any significant improvement in percent body fat, lean body mass, or strength.

Most studies of CrPic supplementation reveal no side effects except gastrointestinal intolerance with dosages of 50 to 200 micrograms/day for less than 1 month. However, anecdotal reports of serious adverse effects, including anemia (15), cognitive impairment (16), chromosome damage (17), and interstitial nephritis (18) have been reported with CrPic ingestion in increased dosages and/or durations. Therefore, the use of chromium picolinate supplementation as an ergogenic aid should be strongly discouraged and considered potentially dangerous.

Amino Acids

Amino acids are the basic structural units of proteins, and one might expect that the more amino acids ingested, the greater the potential for building skeletal muscle. According to the 1989 RDA, an average adult must ingest 0.8 g/kg lean body mass/day of protein in order to fulfill the body's protein requirements. Athletes, however, have traditionally been assumed to need significantly more protein than the average individual, so they commonly use various protein supplements.

Theories suggest that increasing the bioavailability of amino acids promotes protein synthesis and attenuates the muscle loss that occurs during both strength and endurance exercise. These theories have gained support through scientific experimentation in protein metabolism. Fern et al (19) and Lemon et al (20) demonstrated that strength trainers increased protein synthesis with substantially increased protein ingestion during 4 weeks of resistance training. By tracking the nitrogen balance of these athletes, a new daily protein requirement (1.4 to 1.8 g/kg lean mass/day) was developed for strength athletes.

Amino acid supplementation also plays a role in endurance athletes. Lemon (21) and Gontzen et al (22) demonstrated that endurance athletes who train at moderate intensity (55% to 65% of VO2 max) and high intensity (80% of VO2 max) for more than 100 minutes significantly increase protein breakdown unless their protein intake equals 1.2 to 1.4 g/kg lean mass/day.

Several factors make the amount of amino acids that athletes need less clear. Although all of the cited studies demonstrate the advisability of protein intakes higher than the current RDA, no well-designed study has yet shown that amino acid supplementation enhances performance. In addition, no scientific evidence supports protein supplementation in dosages greater than 2 g/kg lean mass/day. Finally, the improved conditioning that occurs over a 4- to 8-week training period may decrease protein breakdown, which may result in a maintenance protein requirement much closer to the current RDA.

L-Carnitine

Carnitine is a quaternary amine whose physiologically active form is beta-hydroxy-gamma-trimethylammonium butyrate. This is found in meats and dairy products and is synthesized in the human liver and kidneys from two essential amino acids, lysine and methionine. L-carnitine is thought to be ergogenic in two ways. First, by increasing free fatty acid transport across mitochondrial membranes, carnitine may increase fatty acid oxidation and utilization for energy, thus sparing muscle glycogen. Second, by buffering pyruvate, and thus reducing muscle lactate accumulation associated with fatigue, carnitine may prolong exercise.

Early studies by Gorostiaga et al (23), Wyss et al (24), and Natalie et al (25) indirectly demonstrated an ergogenic effect of this compound. These studies showed a decreased respiratory exchange ratio (RER) with L-carnitine supplementation (2 to 6 g/day) during exercise, suggesting that fatty acids rather than carbohydrates were used for energy. However, these studies had several problems in methodology, including the use of the RER as the sole measure of enhanced fatty acid oxidation. The RER is an indirect measure of lipid utilization that is influenced by many factors, such as preexercise diet, fitness level, and exercise intensity and duration (26). These confounders were not controlled and may have influenced the results.

A more controlled study by Vuchovich et al (27) avoided these problems by directly measuring muscle glycogen and lactate levels through biopsy and serum analysis. This study failed to demonstrate any glycogen-sparing effect or reductions in lactate levels while supplementing with 6 g/day of L-carnitine. Furthermore, no study to date has confirmed performance enhancement with carnitine supplementation. Finally, many currently available supplements actually contain D-carnitine, which is physiologically inactive in humans but may cause significant muscle weakness through mechanisms that deplete L-carnitine in tissues. Therefore, carnitine should not be advocated as an ergogenic supplement.

L-Tryptophan

L-tryptophan, an essential amino acid, is not commercially available in its pure form but is found in many combination supplement products and reportedly remedies insomnia, depression, anxiety, and premenstrual tension (28). Athletes in the past decade have taken L-tryptophan because of its advertised ergogenic effects. The theoretical mechanism for these effects is an increase in serotonin levels in the brain; these increases produce analgesia and reduce the discomfort of prolonged muscular effort, thereby delaying fatigue. This theoretical model gained scientific credence in 1988 when Segura and Ventura (29) demonstrated a 49% increase in total exercise time to exhaustion when subjects ingested a total of 1.2 g of L-tryptophan (four 300-mg doses within 24 hours of exercise) vs placebo. Such a profound improvement in performance is difficult to imagine, and these results have never been replicated. Two larger, well-designed studies by Seltzer et al (30) and Stensrud et al (31) failed to demonstrate any improvement in subjective or objective outcome measures when supplementing with 1.2 g of L-tryptophan vs placebo. The results of these two studies are more consistent with current research data on exercise.

Physicians should be aware of two other developments that argue against supplementing with L-tryptophan. Its use has declined among elite athletes, possibly suggesting that they are recognizing its minimal ergogenic effects. More important, L-tryptophan ingestion was linked to multiple cases of eosinophilia myalgia syndrome and 32 deaths (28). Though these cases were probably due to contamination of L-tryptophan produced by one Japanese manufacturer, and not to the amino acid itself, they illustrate the quality and purity questions regarding unregulated supplements.

Beta-Hydroxy-Beta-Methylbutyrate

One of the most recent additions to the nutrition supplement market is beta-hydroxy-beta-methylbutyrate (HMB). It is a metabolite of the essential branched-chain amino acid leucine and is produced in small amounts endogenously. HMB is also found in catfish, citrus fruits, and breast milk. In the early 1980s, researchers at Iowa State University hypothesized that HMB was the bioactive component in leucine metabolism that regulates protein metabolism. The exact mechanism of this process is unknown, but promoters hypothesize that HMB regulates the enzymes responsible for protein breakdown. They propose that high HMB levels decrease protein catabolism, thereby creating a net anabolic effect.

Research in livestock (32-36) and humans seems to suggest that supplementation with HMB may increase muscle mass and strength. Nissen conducted two randomized, double-blind, placebo-controlled studies (37,38) to evaluate the ergogenic potential of HMB in exercising men. In the first study, 41 untrained subjects participated in a 4-week resistance training program. The subjects, whose diets were controlled, were given either HMB supplements of 1.5 or 3 g/day or a placebo. Those receiving HMB supplements showed significant improvements in muscle mass and strength as well as significant decreases in muscle breakdown products (3-methylhistidine and creatine phosphokinase) when compared with placebo subjects. The second study evaluated trained and untrained male subjects in a similarly designed weight training program. Relative to a placebo group, the subjects supplementing with 3 g/day demonstrated significant increases in muscle mass and one-repetition maximum bench press as well as decreases in percent body fat.

Further studies of HMB may continue to support the supplement's anabolic effects and elucidate its role in protein metabolism. No side effects of HMB supplementation have been reported, but the safety of this agent is still unknown. Therefore, it is premature to recommend its use as a safe and effective ergogenic aid.

Dehydroepiandrosterone

Attention focused on dehydroepiandrosterone (DHEA) in 1996 when the FDA banned its sale and distribution for therapeutic uses until its safety and value could be reviewed. The ensuing media attention popularized this supplement, and manufacturers began selling it as a nutritional aid rather than a therapeutic drug.

DHEA was identified in 1934 as an androgen produced in the adrenal glands. It is a precursor to the endogenous production of both androgens and estrogens in primates (39). It is also available in wild yams, which are sold in many health food stores as a source of DHEA. As a precursor to androgenic steroids, DHEA may increase the production of testosterone and provide an anabolic steroid effect. Promoters claim that this compound slows the aging process and accordingly advertise it as the "fountain of youth."

Only a few randomized, double-blind, placebo-controlled studies on the effects of DHEA supplementation have been published. Two have demonstrated significant increases in androgenic steroid plasma levels, along with subjective improvements in physical and psychological well-being, while supplementing with 50 mg/day for 6 months (40) or 100 mg/day for up to 12 months (41). Whether DHEA has any effect on body composition or fat distribution is still unclear. Its effect on healthy individuals younger than 40 years old is also virtually unstudied.

DHEA users have reported few adverse effects from the supplement, but one is irreversible virilization in women, including hair loss, hirsutism, and voice deepening (42). In addition, men have reported irreversible gynecomastia, which may result from an elevation in estrogen levels. Because this supplement is so new, long-term adverse effects are unknown. Unlike most other nutrition supplements, DHEA may substantially increase the risk of uterine and prostate cancer that accompanies prolonged elevation in the levels of unopposed estrogen and testosterone. Therefore, the safety of this supplement must be questioned.

Of particular interest to competitive athletes is the effect that DHEA supplementation may have on the test used by the International Olympic Committee and NCAA in their screening for exogenous testosterone use. Using DHEA could alter the testosterone-epitestosterone ratio so it exceeds the 6:1 limit set by both groups (personal communication, Don Catlin, MD, 1997); thus DHEA users could risk disqualification from international competition.

Given the lack of evidence that DHEA enhances athletic performance and its potentially devastating adverse effects, DHEA supplementation is not recommended.

Purity, Cost, and Final Thoughts

Although some of the supplements discussed here may have benefits, physicians should remain skeptical about the use of any supplement. The purity of agents available to consumers is in doubt, as we have seen with L-tryptophan. The Medical Letter, for example, analyzed several commercial preparations of melatonin and found unidentifiable impurities in four of six samples (43). The supplements used for the research reported in this review were pure, but consumers in the largely unregulated marketplace cannot be assured of that same purity in the products they buy.

Table 1. Daily Dose Costs of Various Nutrition Supplements Used by Athletes.

Creatine

20-30 g/day (loading dose): $7.20/day for one week
10-15 g/day (maintenance dose): $3.60/day

Chromium
200 mg/day: $0.43/day
L-Carnitine
2.0 g/day: $2.67/day
Beta-Hydroxy-Beta-Methylbutrate

13 g/day: $3.48/day
11.5 g/day: $1.74/day

Dehydroepiandrosterone

150 mg/day: $0.67/day
1100 mg/day: $1.34/day

L-Tryptophan
Currently unavailable in pure form due to federal regulation

Sources: National Supplement Association and General Nutrition Centers

There is also the issue of cost (tables 1 and 2). At current rates, doses of the supplements discussed range as high as $7.20/day, the cost of a loading dose of creatine (20 to 30 g/day). It makes little sense to invest in supplements that offer minimal or no benefit, especially for athletic departments in this era of shrinking budgets.

Table 2. Protein Supplements Cost Comparison: Daily Cost of 2 g Protein/kg for a 70-kg Individual

Brand name protein powder: $9.80/day
($0.07/g protein)
Generic Protein Powder: $2.80/day ($0.02/g protein)
Tuna: $2.80/day ($0.02/g protein)

Source: National Supplement Association

The key word in nutrition supplements is nutrition. NCAA guidelines state that "there are no shortcuts to sound nutrition, and the use of suspected or advertised ergogenic aids may be detrimental and will, in most instances, provide no competitive advantage (44)." Physicians need to educate athletes, parents, coaches, trainers, and athletic administrators in sound dietary practices or see to it that a nutrition professional does so. Then nutrition supplements can be put in proper perspective, and decisions regarding their use can be based on proper scientific study and proven benefit to the individual.

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Dr Armsey is a clinical instructor and sports medicine fellow, and Dr Green is a clinical associate professor in the Department of Family Medicine at the University of California, Los Angeles, Medical Center. Address correspondence to Gary A. Green, MD, University of California, Los Angeles, Medical Center, Box 951683, Los Angeles, CA 90095-1683; e-mail to ggreen@fammed.medsch.ucla.edu.