Sport supplements

[orto]

Sports supplements
Can dietary additives boost athletic performance and potential?
Mark L. Rubinstein, MD; Daniel G. Federman, MD

VOL 108 / NO 4 / SEPTEMBER 15, 2000 / POSTGRADUATE MEDICINE



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CME learning objectives

To understand the proposed benefits of the sports supplements most commonly used by amateur and professional athletes
To learn about the possible side effects of each supplement
To understand that no long-term safety data on these supplements have been published
The authors disclose no financial interests in this article.



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Preview: Nutritional sports supplements, many of which are endorsed by professional athletes, are increasing in popularity among casual and adolescent sports enthusiasts, bodybuilders, and weight lifters. Because many people consider nutritional additives to be "natural" and therefore "safe," patients may not consider the possible effects of those substances when taken in high doses or in combination with medications. Drs Rubinstein and Federman present an interesting overview of several sports supplements and examine the consequences and caveats of their use, as well as the reasons for their popularity.
Rubinstein ML, Federman DG. Sports supplements: can dietary additives boost athletic performance and potential? Postgrad Med 2000;108(4):103-12



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The combination of diet and resistance training usually promotes a gain of up to 1 kg per month in fat-free muscle mass (1). The lengthy course and variable outcomes produced by traditional methods of bodybuilding have increased popular interest in nutritional supplements that might enhance the process.

Athletes have used performance-enhancing drugs since the early fifth century; early athletes may have ingested substances made from deer liver to impart speed or lion heart to increase strength (2). The endorsement of popular athletes like home-run record holders Mark McGwire and Sammy Sosa, who use creatine, increases public interest in the use of nutritional sports supplements, the manufacture of which is unregulated. Mark McGwire has also admitted to using androstenedione, an over-the-counter precursor of testosterone .

There are few epidemiologic data on creatine, androstenedione, and other nutritional supplements used by adolescents and adults. According to a recent article (3), the lifetime use of anabolic steroids is 4.9% in men and 2.4% in women. The use of legal, over-the-counter supplements is probably even more common. A recent study conducted by the National Collegiate Athletic Association (4) described supplement use among 13,914 college athletes. Thirteen percent of those studied used creatine, and 1% used dehydroepiandrosterone (DHEA). There are no data on the prevalence of androstenedione use.

This article discusses the effects and side effects produced by the sports supplements used most often by athletes and nonathletes to lose weight, build lean muscle mass, and increase strength. The purported benefits of taking each of those supplements--and the concomitant hazards--are summarized for quick reference in table 1.

Table 1. Uses, effects, and side effects of common nutritional sports supplements
Supplement Purpose Effects Side effects

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Androstenedione To increase muscle mass May increase serum testosterone levels Decreased HDL cholesterol level, ?testicular atrophy, behavioral changes, acne, premature closure of epiphysial plates

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Creatine To increase strength, endurance, lean body weight Involved in phosphorylation of ADP to ATP; may improve performance of short-duration, high-intensity activities such as weight lifting Water retention, gastric distress, muscle cramping, ?renal insufficiency

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DHEA To increase muscle mass, weight loss Mildly androgenic precursor of testosterone and estrogen Not known

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Chromium To increase muscle mass, fat loss Assists in the binding of insulin to its receptor Anemia

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HDL, high-density lipoprotein; ADP, adenosine diphosphate; ATP, adenosine triphosphate; DHEA, dehydroepiandrosterone.


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Androstenedione
Androstenedione is marketed as a "natural alternative" to anabolic steroids . It is used to increase serum testosterone levels and promote muscle growth during training. In its natural form, androstenedione is an androgen produced by the adrenal glands and gonads. The androstenedione marketed for oral consumption is derived from plants and is supplied in tablets in recommended doses of 100 to 300 mg per day. A precursor of estrone and testosterone, androstenedione, which has only weak anabolic activity, is usually converted to testosterone by 17 beta-hydroxysteroid dehydrogenase.

It has been suspected for years that administration of supraphysiologic doses of testosterone enhances the gains in muscle mass and strength produced by resistance training (5). It was thus thought that orally administered androstenedione would produce the effect of parenterally administered anabolic steroids.

Early reports suggested that androstenedione could increase serum testosterone levels. The initial German patent application reported increases in serum testosterone of 40% to 83% when 50-mg doses of androstenedione were administered and increases of 111% to 237% when 100-mg doses were given. Mahesh and Greenblatt (6) reported a sixfold to sevenfold increase in serum testosterone levels 60 minutes after 100-mg doses of androstenedione were administered to healthy women. Little is known about the effects of androstenedione supplementation on muscle gain and weight loss. In an 8-week randomized, controlled study of 30 healthy men who ingested either 300 mg of androstenedione per day or placebo, King and associates (7) found no evidence that the use of androstenedione increased serum testosterone levels. They did find elevated levels of serum estrone, which suggests that most of the androstenedione underwent aromatization to estrogen. The investigators also failed to demonstrate noticeable ergogenic effects of androstenedione on the results of resistance training. When the study groups (androstenedione versus placebo) were compared, the investigators noted no difference in lean body mass, no appreciable decrease in fat mass, and no difference in mean cross-sectional areas of type II muscle fiber. However, there was a significant decrease in serum high-density lipoprotein (HDL) cholesterol levels (from 42 to 37 mg/dL, P<.05) that persisted after the study period in the androstenedione group. The daily dose of androstenedione used in this study was 300 mg, whereas many athletes ingest 500 to 1,200 mg/day (3).

Safety
Few data are available on the safety of androstenedione use, but whether taking the supplement increases serum testosterone levels is a matter of concern. Exogenously administered testosterone decreases endogenous testosterone levels and causes testicular atrophy, behavioral changes, acne, and possibly an increase in the risk of prostate cancer. In addition, supraphysiologic levels of testosterone in adolescents can cause premature closing of the epiphysial plates, which leads to decreased height (8). Increased levels of serum testosterone have also been associated with an increased risk of cardiovascular disease, which may result from a decreased level of serum HDL cholesterol (7).

Efficacy
There are no conclusive data on the muscle-building potential of androstenedione. Although early studies indicated an increase in serum testosterone levels as a result of androstenedione use, those findings have not been reproduced. The study by King and associates (7) included only men, and the study by Mahesh and Greenblatt (6) included only women. The differences in sex of the subjects in those two studies might have contributed to the contradictory findings, although no physiologic explanation is apparent. It is also difficult to explain the massive elevations in testosterone noted in the German patent application with ingestion of 100 mg of androstenedione daily, when King and associates (7) reported no elevations with ingestion of 300 mg per day.

If androstenedione does promote supraphysiologic levels of testosterone and subsequent gains in muscle strength and performance, it may produce the same deleterious effects as exogenously administered testosterone.

Creatine
The manufacturers of creatine claim that it increases strength, endurance, and lean body weight. Naturally formed by the liver and kidneys, creatine is also found in meat and fish. The typical American diet provides about 1 to 2 g of creatine per day (9). Because 1 to 2 g of creatine is synthesized by the body daily, an additional 1 to 2 g per day is required exogenously from dietary consumption.

Ninety-five percent of creatine in the body is found in muscle (one third as free creatine and two thirds as phosphocreatine), where it is involved with the phosphorylation of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) (10). Cells with high energy requirements use phosphocreatine as a phosphate donor for the generation of ATP. Skeletal-muscle cells store enough creatine as phosphocreatine to enable about 10 seconds of high-intensity activity. Creatine is eliminated in the kidney by irreversible conversion to creatinine.

Creatine, which is now the most popular supplement among football players (4), is available as creatine monohydrate in a powder or capsule. Recommended regimens involve a 5-day loading period of 20 g per day, after which the maintenance dose is 10 g per day. Adherence to that protocol can increase total creatine stores by 17% to 22% (11). However, skeletal muscle has a saturation limit that cannot be increased by additional supplementation. This has important implications for persons who ingest more than the recommended dose of creatine, because excess creatine is converted to creatinine, which can be nephrotoxic in high concentrations. Recent data (12) have shown that high doses of creatine may not be required, because ingesting 3 g per day may effectively increase tissue levels of creatine. Muscle levels of creatine return to baseline about 28 days after the discontinuation of supplementation.

Several studies support the claim that creatine may improve the performance of short-duration, high-intensity activities such as weight lifting. Most of these studies included small numbers of subjects in whom only modest gains were reported. For example, Earnest and associates (13) studied eight men who were randomly assigned to receive either creatine (20 g/day for 14 days) or placebo. The investigators reported a 6% increase in the maximum weight lifted on the bench press by the subjects who ingested creatine supplements.

Volek and colleagues (10) studied the effect of creatine supplementation (25 g/day for 7 days) on 14 men in a randomized, double-blind study. They found a significant increase in the number of bench press repetitions completed by those who ingested supplementary creatine.

In a randomized, double-blind study, Hamilton-Ward and associates (14) evaluated the effect of creatine use on the muscle strength of 20 women athletes, 10 of whom ingested 25 g a day for 7 days. The group who ingested creatine completed more elbow flexion repetitions, which was not statistically significant.

Although these three studies demonstrated improved weight lifting performance in subjects who ingested creatine supplements, several studies have not shown improved sprint speed, swimming performance, or cycling performance with supplemental creatine (9).

Research has shown that weight gain occurs during supplementation with creatine (1). Much of that weight gain may be due to increased water retention by muscle cells through an increased osmotic gradient produced by increased intramuscular salt (phosphocreatine) and decreased urine output.

Hultman and coworkers (12) reported that a significant decrease in urine output occurred on the first day of creatine supplementation; by day 5, urine output was normal. This finding suggests that gains in mass during that 5-day period were primarily due to water retention. However, some of that weight gain might have resulted from an increase in lean muscle mass produced by more vigorous efforts from subjects who had ingested creatine.

Safety
No serious side effects have been documented in persons who follow the manufacturer's recommended dosing guidelines for creatine supplementation. In a placebo-controlled study of 34 subjects who ingested 20 g of creatine daily for 5 days and then 10 g daily for 51 days (9), no significant change in serum urea nitrogen and creatinine levels before and after supplementation was detected.

Because creatine is excreted as creatinine, some experts feel that high doses could potentiate renal failure, as demonstrated in a case report of a previously healthy 20-year-old man in whom interstitial nephritis developed after he began taking creatine supplements (15). However, that report is controversial because the patient described may have had preexisting renal disease.

Side effects from creatine supplementation have been primarily anecdotal and related to gastric distress and muscle cramping (possibly caused by increased water retention in muscle fibers). No long-term studies on creatine supplementation in humans have been conducted. Long-term creatine supplementation in rats causes a down-regulation of the creatine transporter in skeletal muscle (16). Although this finding has not been replicated in humans, the possibility of down-regulation could be important in the long-term use of creatine.

Efficacy
Many studies (9-11,13) indicate that creatine supplementation produces slight gains in the performance of short-duration, high-intensity activities. Unfortunately, the sample sizes of those studies were small, and the methods used to measure strength and endurance (eg, the maximum number of repetitions performed on the bench press) were not standardized or validated. In addition, different measurements of strength and endurance were used in each study.

Dehydroepiandrosterone
The manufacturers of DHEA claim that both weight loss and increased muscle mass result from the use of this supplement (4). Produced by the adrenal glands, DHEA is a mildly androgenic precursor of testosterone and estrogen. A synthetic form is sold in capsule, tablet, and liquid preparations in recommended doses of 30 to 90 mg per day.

Like androstenedione, DHEA may be converted to testosterone in vivo and may thus impart the benefits of increased testosterone (eg, increased strength, muscle mass). Age-related decreases in serum levels of DHEA are associated with an increase in intraabdominal fat. Supplementation with DHEA may reduce fat deposition.

Results of animal studies support the finding that DHEA protects against obesity. Han and associates (17) found a marked reduction in the weight of male rats that were fed DHEA. The rats were divided into two groups, one of which was fed supplementary DHEA. After about 21 months, the rats were killed, and their body-fat composition was determined. Rats that received supplementary DHEA had a significantly lower total body weight and exhibited a reduction in the percent of body fat, despite a quantity of food intake similar to that of their control counterparts. Because of reports that DHEA-treated rats have an increased resting metabolic rate, the investigators speculated that supplementation with DHEA prevents the storage of energy as fat.

Nestler and associates (18) studied five men who received a large dose of supplementary DHEA (1,600 mg/day) for 28 days. In those subjects, hydrodensiometric measurement showed a significant increase in serum DHEA levels and a 31% reduction in body fat. There was no concomitant increase in serum testosterone levels.

In another small study in which lower doses of DHEA were administered to an obese adolescent population, Vogiatzi and associates (19) found no significant effect on body weight, body composition measured with dual energy x-ray absorptiometry (DEXA), or lipid levels. Study subjects were given 40 mg of DHEA sublingually twice daily for 8 weeks. The investigators did not find elevated levels of serum testosterone in the male study subjects who received supplementary DHEA, despite statistically significant increases in serum DHEA levels compared with those levels in subjects who received placebo.

Safety
No side effects were reported in either of the studies just described. However, if the ingestion of higher doses of supplementary DHEA would result in elevated serum testosterone levels, then perhaps side effects similar to those produced by anabolic steroids could result from DHEA supplementation.

Efficacy
The lack of benefit from supplementation in the study by Vogiatzi and associates (19) could be attributed to the small sample size and comparatively low dose of DHEA administered. The decrease in body fat without an associated increase in testosterone as described by Nestler and associates (18) is difficult to explain. Statistical analyses were conducted on all study variables except for the percent of change in body fat (the significance of which remains undetermined). In addition, the extremely small number of study subjects detracts from the investigators' conclusions.

The studies described here focus on the effects of DHEA on body composition; there are no published studies on the effect of DHEA on athletic performance. This is especially surprising because many athletes ingest DHEA to build muscle mass and enhance athletic performance.

Chromium
Chromium is marketed as a nutrient that promotes muscle growth and fat loss. A trace element found in nuts, asparagus, prunes, brewer's yeast, wine, and beer, chromium is stored in bone, the liver, and soft tissue (4). Chromium helps insulin bind to receptors and may thus enhance its actions, which include glucose uptake and amino acid metabolism. The mechanism by which chromium potentiates the effects of insulin is not fully understood. The rationale of chromium use is that by aiding the transport of glucose and protein into muscle cells through enhanced insulin action, muscle catabolism is decreased and muscle mass is increased.

Chromium deficiency is almost always accompanied by glucose intolerance. Anderson and associates (20) described a chromium-deficient population in whom glucose intolerance improved because of chromium supplementation. The investigators found no such improvement in hyperglycemic subjects who were not chromium-deficient. Unfortunately, several studies of athletes with diabetes are inconsistent in their reports of the benefits of chromium supplementation (21).

Because chromium is poorly absorbed in the gastrointestinal tract, it is combined with picolinate to increase absorption. Although there is no US recommended daily allowance for chromium, the Food and Nutrition Board has estimated safe, adequate daily dietary intake to be between 50 and 200 micrograms (4).

A study by Evans (22) supports the "fat-burning" effects of chromium in humans. Sixteen of 31 male football players involved in resistance training were given 200 micrograms of chromium a day for 6 weeks, and 15 were given placebo. When the two groups were compared, the group who ingested the chromium supplement had a greater gain in lean body weight (2.6 versus 1.8 kg). In addition, the investigators reported a 3.4-kg loss of fat in the chromium-supplemented group compared with a loss of only 1 kg in the placebo group. This study has been criticized for its poor statistical analysis and for the use of skin-fold measurements instead of more accurate methods to determine body composition.

Subsequent studies using more precise measurements of body composition, such as DEXA or hydrodensiometry, have not indicated that chromium supplementation produces a loss of fat (4). Kreider (1) used DEXA for body composition analysis and determined that athletes who ingested 800 micrograms of supplementary chromium daily for 28 days had no significant difference in muscle mass compared with that in a control group given a carbohydrate placebo.

The lack of support for chromium as an ergonomic health aid may result from the relatively short duration of studies. In one study, Bulbulian and associates (23) monitored subjects for considerably longer than in prior studies. Hydrodensiometry was used to determine that 20 male or female college swimmers who received 400 micrograms of supplementary chromium a day for 24 weeks experienced a significant (6.4%) decrease in body fat when compared with the group who received placebo.

Clancy and colleagues (24) reported on 36 college football players who ingested supplementary chromium picolinate (200 g/day) for 9 weeks. Using isometric elbow and knee flexion-extension measurements, the investigators found no difference in strength between study subjects and controls. When body fat was measured by underwater weighing, they found no difference in the percent of body fat in the two groups.

In an 8-week study of chromium supplementation, Lukaski and coworkers (25) measured serum and urinary chromium levels in subjects. Despite finding increased serum levels of chromium in men who ingested supplementary chromium, the investigators reported no difference in body mass, composition, or muscle strength in the groups studied.

Safety
Chromium doses of 600 micrograms for 6 weeks have been associated with renal failure (26). Chromium may also cause anemia, perhaps because chromium binds transferrin and may thus impair iron transport (25).

Efficacy
Evidence indicates that chromium supplementation does not increase lean body mass, decrease fat mass, or increase muscle strength (21). Only two studies (22,23) have reported decreases in body fat, and both had serious flaws, such as poor statistical analysis and imprecise measurements of body fat.

Conclusion
More research is required to determine the merits and toxicities of sports supplements, which are increasing in popularity among collegiate and casual athletes. Current studies that pertain to sports supplements are few, and those that have been published include only small numbers of subjects. In addition, a more rigorous scientific approach must be used for the evaluation of these supplements.

Because of the dearth of scientific support, it is unwise to recommend any of these supplements to patients, although no serious side effects are attributed to having taken the manufacturers' recommended doses. With the exception of creatine, sports supplements do not appear to provide any of the effects claimed by their manufacturers. Creatine may modestly enhance the performance of activities requiring short bursts of energy and thus may enable more rigorous weight lifting. Over time, increased muscle mass could result, although this has yet to be proved.

Physicians should also be aware that many patients take more than the recommended doses of these supplements, either because of the perception that the supplements are natural and therefore safe or because of the "more is better" philosophy. Additional research is needed to establish the safety and efficacy of higher doses as well as the recommended doses for each supplement available to the general public.

References
Kreider RB. Dietary supplements and the promotion of muscle growth with resistance exercise. Sports Med 1999;27(2):97-110
Applegate EA, Grivetti LE. Search for the competitive edge: a history of dietary fads and supplements. J Nutr 1997;127(5 Suppl):869S-73
Yesalis CE 3d. Medical, legal, and societal implications of androstenedione use. JAMA 1999;281(21):2043-4
Johnson WA, Landry GL. Nutritional supplements: fact vs fiction. Adolesc Med 1998;9(3):501-13
Bhasin S, Storer TW, Berman N, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 1996;335(1):1-7
King DS, Sharp RL, Vukovich MD, et al. Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial. JAMA 1999;281(21):2020-8
Creatine and androstenedione--two "dietary supplements." Med Lett Drugs Ther 1998;40(1039):105-6
Williams MH, Branch JD. Creatine supplementation and exercise performance: an update. J Am Coll Nutr 1998;17(3):216-34
Juhn MS, Tarnopolsky M. Oral creatine supplementation and athletic performance: a critical review. Clin J Sport Med 1998;8(4):286-97
Hultman E, Söderlund K, Timmons JA, et al. Muscle creatine loading in men. J Appl Physiol 1996;81(1):232-7
Earnest CP, Snell PG, Rodriguez R, et al. The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 1995;153(2):207-9
Hamilton-Ward K, Meyers M, Skelly WA, et al. The effect of creatine supplementation on upper extremity anaerobic response in females. (Abstr) Med Sci Sports Exerc 1997;29:S146
Koshy KM, Griswold E, Schneeberger EE. Interstitial nephritis in a patient taking creatine. N Engl J Med 1999;340(10):814-5
Guerrero-Ontiveros ML, Wallimann T. Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle. Mol Cell Biochem 1998;184:427-37
Han DH, Hansen PA, Chen MM, et al. DHEA treatment reduces fat accumulation and protects against insulin resistance in male rats. J Gerontol A Biol Sci Med Sci 1998;53(1):B19-24
Nestler JE, Barlascini CO, Clore JN, et al. Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab 1998;66(1):57-61
Vogiatzi MG, Boeck MA, Vlachopapadopoulou E, et al. Dehydroepiandrosterone in morbidly obese adolescents: effects on weight, body composition, lipids, and insulin resistance. Metabolism 1996;45(8):1011-5
Anderson RA, Polansky MM, Bryden NA, et al. Supplemental-chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets. Am J Clin Nutr 1991;54(5):909-16
Clarkson PM. Effects of exercise on chromium levels: is supplementation required? Sports Med 1997;23(6):341-9
Evans GW. The effect of chromium picolinate on insulin controlled parameters in humans. Int J Biosoc Med Res 1989;11:163-80
Bulbulian R, Pringle DD, Liddy MS. Chromium picolinate supplementation in male and female swimmers. (Abstr) Med Sci Sports Exerc 1996;28:S111
Clancy SP, Clarkson PM, DeCheke ME, et al. Effects of chromium picolinate supplementation on body composition, strength, and urinary chromium loss in college football players. Int J Sport Nutr 1994;4(2):142-53
Lukaski HC, Bolonchuk WW, Siders WA, et al. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr 1996;63(6):954-65
Wasser WG, Feldman NS, D'Agati VD. Chronic renal failure after ingestion of over-the-counter chromium picolinate. (Letter) Ann Intern Med 1997;126(5):410
Drs Rubinstein and Federman are members of the department of medicine, Yale University School of Medicine, New Haven, Connecticut. Dr Federman is also a staff member of the Veterans Administration Connecticut Health Care System, West Haven. Correspondence: Daniel G. Federman, MD, VA Connecticut HCS (11ACSL), 950 Campbell Ave, West Haven, CT 06516. E-mail: [email protected].

[painintheazz]

Some interesting things, only skimmed it but still interesting.

Pain

[BIG TEXAN]

I'll have to read more when I have some time today.

[sean ross]

ID LIKE TO KNOW ABOUT TESTOSTERONE FREE STEROIDS .I AM 18 YEARS OLD AND I HAVENT BEEN ON ANY STEROIDS BEFORE.

[Vibrantred94gt]

Very interesting about the dhea. I recently tried lena systme 7 which is 7 keto dhea. (whats the 7keto part?) Anyways, stopped taking it..don't know why, just like the eca stack better. I can FEEL that working.

I might try getting some straigt dhea though, and try taking it in large amounts. A 31 % reduction in fat is a lot. That was at 1600mg a day.

Interesting stuff though, good post.