Building superathletes through ergogenics

Competitive events may soon be won by athletes with the best molecular biologist.

Issue: April 2006

ByNathaniel Winer, MD

Performance-enhancing or ergogenic drugs have long been used by professional and elite athletes to gain a competitive advantage. The drive to succeed in sports is powerful and lucrative; a poll of Olympic-level athletes showed that most would opt to take an undetectable, banned substance that would ensure winning medals, even if the illicit drug ultimately proved to be fatal.

Commonly used ergogenics include anabolic and androgenic hormones, steroid precursors such as androstenedione and dehydroepiandrosterone, “designer” steroids such as tetrahydrogestrinone (THG), creatine, ephedra alkaloids, over-the-counter nutraceuticals, erythropoietin and growth hormone (hGH).

A competitive event may now be won not by the athlete who has the best physiologist, but rather the superior pharmacologist and, perhaps, molecular biologist. Most worrisome has been the use of these agents by young people, even those of middle-school age, who seek to emulate sports icons, improve body image, enhance social standing, or increase the likelihood of obtaining college athletic scholarships. While testing for drug use in athletes has reduced abuse, detection of naturally occurring substances such as growth hormone remains elusive and has fueled a resurgence of doping.

Biosynthetic hGH, which must be given by injection, may cost as much as $5,000 a month and is widely available for purchase on the Internet. Although epidemiological data on the extent of hGH abuse are lacking, reports of seizure of hGH supplies by police and customs officials suggest that hGH use is widespread. The hormone is banned by all major sports leagues.

Adverse effects of hGH use in young people include transmission of hepatitis and HIV by nonsterile needles, premature epiphyseal closure, jaw enlargement, hypertension and slipped capital femoral epiphysis.

Growth hormone provides a variety of beneficial effects in adult growth hormone deficiency, including improvement of exercise performance and strength, which probably results from increased total body protein turnover, enhanced muscle synthesis and lipolysis.

In contrast, under conditions of hGH excess, as in untreated acromegaly, muscular strength is diminished and longevity is reduced. The World Anti-Doping Agency considers doping as “any substance foreign to the body or any physiological substance taken in abnormal quantity … with the sole purpose of increasing in an artificial and unfair manner … performance in competition.”

images/et/200604/Nathaniel Winer, MD [photo]
Nathaniel Winer

The ban would preclude performing a clinical trial designed to demonstrate whether hGH supplementation has performance-enhancing effects. Nevertheless, it is possible that trained athletes receiving intermittent doses of hGH may perceive small improvements in performance sufficient to produce a “winning edge.”

Experiments in nature may provide insight into the role genes play in athletic prowess. A case report describes a 4½ year-old boy who was found to have a loss-of-function mutation of the gene for myostatin, an inhibitor of skeletal muscle growth.

The child was the offspring of a professional athlete mother whose family members possessed exceptional physical strength. With the muscle bulk and strength of a miniature body-builder, he was able to hold two 3 kg dumbbells with his arms extended horizontally.

Since myostatin is also expressed in the heart, it was of interest that the child had no evidence of cardiomyopathy or conduction disturbance. The role of myostatin in regulating skeletal muscle growth has recently been defined by studies in mice which show that targeted disruption of the myostatin gene doubles skeletal muscle mass, whereas overexpression of the gene leads to muscle wasting.

Although therapeutic inactivation of myostatin has the potential to help patients with muscle-wasting disorders, anti-doping officials shudder over the nightmarish scenario of athletes injecting a retroviral myostatin gene, given the risks of gene therapy and the difficulty of tracing an illicit source.

Emerging technologies may also allow manipulation of the hGH/IGF-1 axis. Mice engineered to carry an extra copy of the gene for IGF-1, first described in 2001 and dubbed “Schwarzenegger mice,” have increased muscle mass and strength, better recovery from injury, and prolonged longevity compared to their wild-type counterparts. IGF-1 may act to reduce muscle degeneration, alter the inflammatory process, limit fibrosis, and enhance the natural phenomenon of mobilization and reprogramming of bone marrow-derived myoblasts. Could the techniques that make supermice be used in the future to create human superathletes?

The problem of detection of hGH use has been addressed in a study of over 800 elite athletes by comparing indirect measures of growth hormone action, such as IGF-1, IGFBP (binding protein)-2, IGFBP-3, and bone and soft tissue markers within two hours of a competitive event with those of normal and athletic subjects. There were no significant differences in markers between groups except for the absence of an age-dependent fall in IGFBP-2 among elite athletes.

For more information:

Nathaniel Winer, MD, is a Professor of Medicine at SUNY Downstate Medical Center in Brooklyn, New York and a member of Endocrine Today’s Editorial Board.

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McHugh CM, Park RT, Sonksen PH, et al. Challenges in detecting the abuse of growth hormone in sport. Clin Chem. 2005;51:1587-93.

Schuelke M, Wagner KR, Stolz LE, et al. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004 Jun 24;350(26):2682-8.

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Healy ML, Dall R, Gibney J, et al. Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting. J Clin Endocrinol Metab. 2005;90(2):641-9.