GHB: Powerful Growth Hormone Secretagogue

Growth hormone is one of the many hormones that declines dramatically with age (Fig.1). Growth hormone has multiple functions in the body, including maintaining lean body mass, mobilizing fat, counteracting insulin, enhancing immunity, lowering blood pressure and improving cholesterol levels, increasing energy, and even improving vision. Many physicians now routinely prescribe growth hormone shots for middle-aged and older men and women for their health-enhancing, anti-aging effects. Bodybuilders and athletes have been taking growth hormone for years as an anabolic and performance-enhancing agent.

A claim about GHB that is frequently made by its supporters (and which is just as roundly denied or ignored by GHB's detractors) is that GHB is a powerful stimulant of growth hormone release by the pituitary.

If GHB could truly increase growth hormone levels, it would lend credence to the claims of many of its supporters that GHB has profound fat-burning and other anti-aging effects. Let's examine the basis for this belief that GHB may increase growth hormone release.

GHB increases Growth Hormone in Humans and Experimental Animals

One of the earliest indications of GHB's potential as a growth hormone stimulator was the study by Oyama and Takiguchi (1970), of the department of anesthesiology, Hirosaki University in Japan. They evaluated the effects of GHB--when used as a general anesthetic--on 10 patients (ranging in age from 14 to 48) undergoing surgery. The scientists found that after infusion of an average of 6 gm GHB, growth hormone levels rose significantly (6 times higher than controls!) and remained elevated for approximately two hours. They also noted no change in insulin or glucose levels. This is very significant, as exogenously administered Growth Hormone (i.e., administered by injections) tends to be diabetogenic, and tends to counteract the glucose-lowering effects of insulin.

Seven years later Takahara and his colleagues (1977[a]) evaluated the effects of GHB on growth hormone in six males, aged 25-40. Each subject was given 2.5 gm GHB intravenously. Not surprisingly, five of the subjects fell asleep within 20 minutes of the infusion, and slept for 30-150 minutes. Growth hormone levels began to climb after the infusion, reached a peak at 60 minutes, and then gradually declined (Fig. 2). Takahara and his team continued to performed studies on humans regarding growth hormone and GHB, with similar results (1977[b]; 1980)

In 1980, scientists at the National Institute of Health and Medical Research in France evaluated the GH-stimulating effects of GHB in 20 rats. After intrapertoneal administration of 100 mg/100 gm body weight, GH levels rose significantly (Figure 3) (Bluet-Pajot, et al, 1980). Other studies which confirmed GHB's GH-stimulating effects in humans included those of Yunoki (1982), and Gerra and colleagues (1994).

In 1997, yet another study was conducted with the specific purpose of determining whether GHB would enhance sleep and increase GH secretion in normal subjects. In this study, eight healthy subjects ranging in age from 24-28 participated. GHB dosages of 2.5 gm, 3.5 gm, and 4.5 gm were administered at bedtime once per week to at least 7 of the 8 subjects. The only "adverse effect" noted by any of the subjects was a feeling of inebriation by five of the subjects. Consistent with previous studies, the duration's of stages III and IV sleep were increased. These are thought to be the most restful and restorative sleep stages, and are also the stages in which growth hormone is maximally released. Figure 4 shows the effect of the low, medium and high doses of GHB on growth hormone, compared with placebo (Van Cauter, et al, 1997) (Fig. 4). Interestingly, Dr. Martin Scharf, one of the co-authors of the study, is one of the most eminent researchers in the world on the beneficial effects of GHB on narcolepsy, (a severe sleep disorder).

In fact, Van Cauter and Scharf have even applied for a U.S. Patent--"Use of gamma-hydroxybutyrate for the stimulation of sleep-related growth hormone secretion." This patent describes the use of GHB to reestablish normal nighttime growth hormone secretion in adults, by administering GHB just before retiring.

Long-Term Studies

Until recently, all of the studies on the growth hormone-releasing effects of GHB had been one-time studies. No one had studied the ability of GHB to stimulate growth hormone after long-term use. Michael Farley, a Florida-based naturopathic physician, has conducted a unique study that will allow us to make some inferences with regard to the long term growth hormone stimulating properties of GHB. Dr. Farley used a dietary supplement (RenewTrient ®) that contained a precursor of GHB-gamma butyrolactone (GBL). For all practical purposes, GHB and GBL have identical biochemical and physiological effects.

Farley evaluated the effect of GBL on growth hormone, IGF-1, and glucose (glucose can be considered an indirect indicator of GH levels). The test subjects included ten males (aged 28-53). Three had used GBL every night for over one year, while seven had not previously used it.

Farley noted elevations of growth hormone and IGF1, and reductions in blood sugar in all subjects. However, those who had not previously used GBL had higher levels of growth hormone and IGF1, and greater reductions in blood sugar than the "experienced" GBL users. For example, the average increase from baseline to a peak at 60 minutes ranged from 0.56 to 7.1 NG/ML for the seven GBL "non-users." The four subjects who used GBL for over one year had average values of 0.5 to 2.4 NG/ML, respectively.

HGH Assay of Normal Test Subjects
BASELINE 30 min. 60 min, 90 min. 120.min
SN1 0.5 0.5 2.2 0.7 0.5
SN2 0.8 0.5 4.5 1.4 0.5
SN3 0.5 1.6 5 4 1.2
SN4 0.5 0.5 4.2 3.9 1.5
SN5 0.6 0.6 20 18 9.7
SN6 0.5 1.5 5.9 2.7 0.6
SN7 0.5 0.7 7.9 303 1
Average 0.557143 0.842857 7.1 4.857143 2.142857
HGH Assay of One Year Renewtrient Users
SRU8 0.5 0.8 2.2
SRU9 0.5 1.2 2.5 4.1 2
SRU10 0.5 2 1.7
SRU11 0.5 0.5 0.5 0.7 1.2
Average 0.5 0.85 1,45 2.4 1.775

Farley found that test subjects who had the lowest blood glucose levels had the greatest increases in growth hormone. Consequently, he recommends taking GBL on an empty stomach --i.e., about three hours after eating--in order to maximize the release of growth hormone.

Farley's study, while interesting, leaves us with a few questions, and some suggestions for further study. First, the test was performed in the morning, using a fairly small dose of GBL (0.25 mg/kg). This dose is about half that normally required to induce sleep - confirmed by the fact that none of the subjects fell asleep.

All of the previous studies on GHB and growth hormone used sleep-inducing doses of GHB. Since GH is released in greatest quantity during Stage III and IV of normal sleep, and since GHB enhances these sleep stages, researchers hypothesized that this was the cause of GHB-stimulated GH release. However, Farley's study showed that GBL enhances GH release even when sleep is not induced. Would the GH release have been even more significant if higher doses had been used?

Farley's study affirms the long term safety of GBL, as the three long term users suffered no adverse side effects, and maintained a significant growth hormone releasing response. However, since long term daily use did result in a reduction of the growth hormone stimulating effects of GHB, we (Farley and Dean) recommend against chronic daily use of GHB and its precursors (GBL and BD). We believe that consumers of GHB should take a break periodically, and avoid using GHB two or three days each week. This should prevent receptor down-regulation, and optimize the benefits.

Conclusions

GHB and its precursors (GBL and BD) are clearly powerful growth hormone secretagogues. A patent has been issued for GHB's use as a growth hormone stimulant - held by one of the leading GHB researchers in the world. A prescription version of GHB is pending imminent approval by the FDA (sic) named Xyrem ® and manufactured by Orphan Medical. These two facts lend credence to the safety and efficacy of GHB in elevating growth hormone, as reported in this review. GHB's growth hormone stimulating effect is just one more of the numerous reasons this miracle nutrient has such a beneficial effect on our health and well-being.

References:

  1. Bluet-Pajot, Schaub, C., and Nassiet, J. Growth hormone response to hypoglycemia under gamma hydroxybutyrate narco-analgesia in the rat. Neuroendocrinology, 1978, 26: 141-149.
  2. Bluet-Pajot, M.T., Schaub, C., Mounier, F., Segalen, A., Duhault, J., and Kordon, C. Monoaminergic regulation of growth hormone in the rat. J Endocr, 1980, 86: 387-396.
  3. Gerra, G., Marcato, A., Fertonani, A., Avanzini, P., et al. Gamma hydroxybutyric acid (GHB) and neuroendocrine function in humans. Neuroendocrinol Lett, 1994, 16: 1, 55-63.
  4. Oyama, T., and Takiguchi, M. Effects of gamma hydroxybutyrate and surgery on plasma human growth hormone and insulin levels. Agressologie, 1970, 11: 3, 289-298.
  5. Takahara, Jiro, Yunoki, Sho, Yakushiji, Wataru, et al. Stimulatory effects of gamma hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinol Metab, 1977, 44: 1014-1017.
  6. Takahara, Jiro, Yunoki, Sho, Yakushiji, Wataru, Yamauchi, J., Ofuji, N., et al. Effects of gamma hydroxybutyric acid and gamma amino beta hydroxybutyric acid on growth hormone, prolactin, LH, FSH, TSH and cortisol secretion in man. Program of the 59th Annual Meeting of the Endocrine Society, Chicago, IL, 1977, 254.
  7. Takahara, Jiro, Yunoki, Sho, Hosogi, Hidemi, Yakushiji, Wataru, et al. Concomitant increases in serum growth hormone and hypothalamic somatostatin in rats after injection of gamma aminobutyric acid, aminooxyacetic acid, or gamma hydroxybutyric acid. Endocrinology, 1980, 106: 343-347.
  8. Van Cauter, Eve, Plat, Laurence, Scharf, Martin B., Leproult, Rachel, Cespedes, Sonya, L'Hermite-Baleriaux, Mireille, and Copinschi, Georges. Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young men. J Clin Invest, 1997, 100: 3, 745-753.
  9. Van Cauter, Eve, and Scharf, Martin B. Use of gamma hydroxybutyrate for the stimulation of sleep-related growth hormone secretion. U.S. Patent application 485,059, 7 June 1995, 42 pp.
  10. Yunoki, Sho. Studies of gamma-aminobutyric acid (GAGA) and its metabolite on the control mechanism of secretion of anterior pituitary hormones. Part II. Effects of gamma-hydroxybutyric acid (GHB) on secretion of anterior pituitary hormones in human subjects. Okayama Igakkai Zasshi, 1982, 94: 899-913.

FOOTNOTE

Effects of GHB on Growth Hormone in recovering Alcoholics and Cocaine Addicts

Alcoholics are known to have impaired growth hormone secretion and low levels of IGF-1. Since GHB has been demonstrated to predictably stimulate growth hormone in animals and humans, Vescovi and Coiro (1997[a]) evaluated the effects of GHB in 22 male chronic alcoholics, aged 38-52, all of whom had been abstinent from alcohol for at least one year. These scientists evaluated the ability of the pituitary to respond to 30 gm of intravenous arginine - a standard test of the pituitary's growth hormone-releasing capability. In each subject, the arginine induced significant growth hormone increase. However, GHB surprisingly failed to stimulate growth hormone (Fig. 5). The authors concluded that even long-term abstinence from alcohol is unable to restore 5-HT1D receptors and GHB-mediated neurotransmission that regulate GH secretion. These same authors did a similar study with cocaine addicts, who had discontinued cocaine use one month prior to the test. They found that GHB did not increase growth hormone in cocaine addicts, similar to the response of alcoholics (Vescovi and Di Gennaro, 1997[b]).

They concluded that alcoholism and cocaine use are related to disorders of the serotonergic and GABAergic controls of GH secretion, and that the neurological damage produced by many years of alcohol or cocaine consumption may unfortunately be irreversible.

References

  1. Vescovi, P.P., and Coiro, V. Persistence of defective serotonergic and GABAergic controls of growth hormone secretion in long-term abstinent alcoholics. Alcohol and Alcoholism, 1997[a], 32: 1, 85-90.
  2. Vescovi, P.P., and Di Gennaro, C. Di. Failure of gammahydroxybutyric acid to stimulate growth hormone secretion in cocaine addicts. Neurpoeptides, 1997[b], 31: 5, 459-462.

 

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