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Bodybuilding Pharmacology: Snooze, You Lose

The amino acid most often linked to growth hormone release is arginine, but the GH picture also includes more complex brain chemistry. Growth-hormone-releasing hormone, or GHRH, is released by the hypothalamus, and somatostatin, known as both SST and growth-hormone-inhibiting hormone, is released in the brain and elsewhere in the body. Scientists believe that amino acids stimulate the production of GH by inhibiting the release of SST.

Two recent studies highlight those effects in people engaged in weight training. In one, the focus was on melatonin.1 Thirty young men and 30 young women were randomly given either melatonin supplements in doses of one-half milligram or five milligrams or a one-milligram dose of a placebo. They then did leg presses, seven sets of seven reps, each with a weight equal to 85 percent of their one-rep maximums. Blood samples were taken at various intervals to determine hormone and blood responses.

The men who received five milligrams of melatonin experienced an increase of GH release, which was attributed to a blunting of SST. In fact, compared to the men who got the placebo, they had a 157 percent rise in GH prior to training and a 132 percent increase over resting levels after the workout. The response to melatonin was far lower in women, which was thought to be related to the higher concentration of estrogen in their bodies.

The interesting aspect of the study was that the melatonin increase in GH wasn’t entirely due to a blunting of SST. The melatonin-GH connection shows up on other pathways in the body as well.

Melatonin is available as an over-the-counter supplement, and its primary use is to treat insomnia and jet lag. First discovered in 1958, it’s produced in the pineal gland, located in the brain just behind the eyes. Ancients considered the pineal gland the third eye, and mystical qualities were attributed to it. Melatonin is known as the hormone of darkness because it’s secreted in darkness and inhibited by light. It plays a major role in the control of circadian body rhythms and is secreted under the influence of a bundle of nerve cells in the hypothalamus called the suprachiasmatic nucleus—the brain’s timekeeper organ.

The immediate precursor of melatonin synthesis is the amino acid L-tryptophan. Tryptophan was formerly sold over the counter as a sleep aid, but it was banned because of contaminated batches from Japan that caused serious health problems in some users. More recently, L-tryptophan supplements have quietly reemerged in the marketplace. Enzymes convert tryptophan into 5-HTP, which is then converted into the brain neurotransmitter serotonin. Serotonin is then converted into melatonin in a two-step process that occurs gradually throughout the day. The more you’re exposed to bright light at night, the less melatonin your brain secretes. Darkness prompts the suprachiasmatic nucleus to signal the pineal gland to release melatonin. The retina of the eye, bone marrow, gastrointestinal tract and lymphocytes, or white blood cells, also produce melatonin, albeit in smaller amounts. The bioavailability of melatonin supplements varies from 8 to 56 percent. As with most oral doses of hormones, melatonin is transported to the liver, where it breaks down considerably as it is metabolized—between 30 and 60 percent within an hour. For that reason many melatonin supplements are sold in timed-release form as a means of maintaining sleep throughout the night.

Natural melatonin production declines with age, which may explain why many older people have insomnia issues. Melatonin also decreases with various diseases, including cardiovascular disease, type 2 diabetes and Alzheimer’s.

In 1993 melatonin was identified as a potent antioxidant. One study of older women who took six milligrams experienced a decrease in the oxidation of low-density lipoprotein, the “bad” cholesterol. In vitro, or test-tube, studies showed that it has twice the antioxidant power of vitamin E and four times that of vitamin C. One study found that eating walnuts, a natural source of melatonin, improved the antioxidant capacity of the blood.2 Other food sources include rice, barley, corn and oats. Melatonin boosts the activity of the body’s built-in antioxidants, such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase,3 and it blunts the activity of pro-oxidant enzymes, including the ones related to nitric oxide metabolism.

Several emerging studies suggest that melatonin may help prevent various types of cancer by way of both antioxidant and immune-system mechanisms. It supports the function of several immune cells, such as killer T-cells and helper T-cells, which destroy incipient tumors. Many diseases linked to aging are related to a lowering of immune function, and melatonin is known to block that response.4 In addition, melatonin attacks hormones linked to the spread of cancer in the body, including insulinlike growth factor 1 and prolactin, which means it works against prostate and breast cancers.

Melatonin can readily permeate the blood-brain barrier, which is a mechanism in the blood vessels that blocks toxins and other substances in the blood from entering the brain. The point is, melatonin can operate (for example) as an antioxidant against beta-amyloid, a protein linked to Alzheimer’s disease.

By helping to reset body rhythms, melatonin can help reduce the fatigue associated with jet lag. Many people find that doses of 0.3 to 0.5 milligrams are effective for sleep; doses of one to three milligrams are about 10 to 30 times higher than the body ever produces. As you might expect, the primary side effects of melatonin are drowsiness, fatigue and depression. In fact, those who suffer from depression are advised to avoid it because it magnifies depressive episodes. It can also bring on an asthma attack because it fosters the production of cytokines, which are implicated in respiratory inflammation.

One way that melatonin may encourage sleep is through an interaction with gamma aminobutyric acid. GABA was discovered in 1883, but its effect in the brain wasn’t discerned until 1950. It’s the brain’s primary inhibitory neurotransmitter, meaning that it provides a calming and slowing activity in the brain’s neurons. Most pharmaceutical insomnia drugs interact with GABA brain receptors, although a new drug, ramelton (Rozerem), interacts with melatonin.

By-products of GABA made in the brain can bring on sleep, the most notorious being the “date rape” drug GHB. Rapidly inducing a comalike condition for short periods, it is metabolized to carbon dioxide and water in four hours. ALL GHB wasn’t always considered dangerous. At one time, it was aggressively marketed to bodybuilders as an aid to GH release. Structurally, it looks a lot like beta-hydroxybutarate, a ketone body produced in greater amounts during low-carb dieting. When used properly—that is, without any other depressant, such as alcohol or sleeping pills—GHB was a safe and effective sleeping aid. Soon enough, however, it became a popular substance of abuse. Several teens who combined it with large amounts of beer found themselves in 48-hour comas that left no lingering side effects.

Because of its unsavory, though largely undeserved, reputation, GHB was banned in 1990, although it is available in prescription form as a drug called Xyrem, used to treat narcolepsy, or sudden episodes of deep sleep. In France, GHB is used to treat alcohol withdrawal. Not long after the initial ban, several analogues of it appeared on the market, such as GBL and BD, all touted as precursors of GH. They, too, were eventually banned, even though one of them was recently discovered in a popular children’s toy imported from Australia. Lost in all the hoopla about the dangers of GHB was the fact that it had been previously used for some 30 years in Europe as a safe and effective presurgical relaxant.

So GHB is gone, but what about its “parent,” GABA, which does stimulate GH release? It’s still readily available over the counter. A recent study featured 11 weight-trained young men, who took either three grams of GABA or a placebo, followed by either rest or a weight workout.5 The combination of exercise and GABA led to a 200 percent increase in active GH. The effect was thought to be attributable to a blunting of SST or a rise in growth-hormone-releasing-hormone secretion or both.

Like melatonin, GABA is made in the brain from an amino acid, this time glutamic acid. It’s an excitatory neurotransmitter, or brain stimulant. When exposed to specific enzymes and the active form of vitamin B6, however, it converts into the inhibitory form of GABA. You wouldn’t want to supplement with straight glutamic acid, which studies associate with a lowering of GH when taken before exercise and the production of cortisol and prolactin—not good.

Most studies show that unlike melatonin, GABA cannot get past the blood-brain barrier. Most active GABA is directly synthesized within the brain itself. Several supplements contain a form of GABA that is designed for greater uptake into the brain. On the other hand, studies also show that it can support GH release, although exactly how isn’t clear.

So should you go out and purchase a bundle of melatonin and GABA and await delivery of GH? Great idea—if you wanted to fall asleep before training. They both bring on drowsiness and sleep, the last thing you want before working out. Many bodybuilders either drink coffee or take caffeine pills before workouts to increase alertness and decrease fatigue. Some even take amphetamines—also not good.

Melatonin and GABA may be useful for sleep, but taking them before working out would seem self-defeating. While interesting, the new studies offer little practical value to those engaged in bodybuilding training.


1 Nassar, E., et al. (2007). Effects of a single dose of N-acetyl-5-methoxytryptamine (melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females. J Inter Soc Sports Nutr. In press.

2 Reiter, R.J., et al.(2005). Melatonin in walnuts: Influence on levels of melatonin and total antioxidant capacity of blood. Nutrition. 21:920-924.

3 Reiter, R.J., et al. (2003). Melatonin as an antioxidant: Biochemical mechanisms and pathophysiological implications in humans. Acta Biochem Pol. 50:1129-1146. 4 Zhang, Z., et al. (2005). Melatonin, immune function and aging. Immun Ageing. 2:17.

5 Powers, M.B., et al. (2007). Growth hormone isoform responses to GABA ingestion at rest and after exercise. Med Sci Sports Exer. 40:104-110. IM

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