Powerful Growth Hormone Secretagog
By Ward Dean, M.D.
Most scientific or popular articles that attempt to demonize GHB (gamma hydroxy butyric acid) or its precursors GBL (gamma butyrolactone) or 1, 4 BD (butanediol), include an “obligatory” list of purported benefits attributed to GHB by its supporters. Among these claimed (and usually summarily discounted or dismissed) benefits is that GHB is a powerful secretagog of growth hormone (GH). Growth hormone is one of the many hormones that declines dramatically with age (Fig. 1). Growth hormone has multiple functions in the body, including maintenance of lean body mass, mobilization of fat, counter-acting insulin, enhancing immunity, lowering blood pressure and improving cholesterol levels, increasing energy, and even improved vision. Many physicians are now regularly prescribing growth hormone shots for middle-aged and older men and women for its health enhancing, anti-aging effects; and younger bodybuilders and athletes have been taking growth hormone for years as an anabolic and performance enhancing agent. Consequently, if GHB could truly increase growth hormone release by the pituitary, it would lend credence to the claims of many GHB supporters that it has profound fat-burning and other antiaging effects. Let’s examine the basis for this belief that GHB may increase growth hormone levels.
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 GH (i.e., by injections) tends to be diabetogenic, and tends to act as an insulin antagonist. Seven years later Takahara and his colleagues (1977a) 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. GH 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 (1977b; 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 intraperitoneal administration of 100 mg/100 gm bodyweight, GH levels rose significantly (Fig. 3) (Bluet-Pajot, et al, 1980). Other studies which confirmed GHB’s GHstimulating 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, 3.5, 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 durations 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 is one of the most eminent researchers in the world on the beneficial effects of GHB on narcolepsy, a severe sleep disorder. Van Cauter and Scharf have applied for a U.S. Patent, “Use of gamma-hydroxybutyrate for the stimulation of sleeprelated 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.
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 (1997a) 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, 1997b). 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.
Until recently, no one had studied the long-term efficacy of GHB’s growth hormone stimulating effects. Michael Farley, a Florida-based naturopathic physician, has conducted a unique study that will allow us to make some inferences. Dr. Farley evaluated the growth hormone stimulating effects of a dietary supplement (RenewTrient) — gamma butyrolactone (GBL). GBL converts rapidly in the body into GHB, resulting in clinical effects virtually identical to those caused by GHB. Farley’s study was designed to evaluate the effect of GBL on GH, IGF-1, and glucose (an indirect indicator of GH levels). The test subjects included 10 males (aged 28-53). Three had used GBL nightly 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. The GH response of the five test subjects with the highest initial glucose levels was compared with the GH response of those with the lowest initial glucose levels. The average GH level in those with the lowest initial glucose levels increased from 0.52 NG/ML at baseline to 7.42 NG/ML at the 60 minute peak. In contrast, those with the highest blood glucose levels started with an average GH level of .5 NG/ML at baseline and rose to only 3.66 NG/ML at the 60 minute peak.
Farley found that test subjects who had the lowest blood glucose levels had the greatest increases in GH. Consequently, he recommends taking GBL on an empty stomach—i.e, about three hours after eating—in order to maximize the release of GH. His findings also seem to indicate that the pituitary responds less vigorously to GBL in those who consume GBL on a daily basis. Again, Farley recommends against long-term daily use, and suggests avoiding GHB and its precursors (GBL and BD) two or three days a week, in order to avoid receptor down-regulation, and to optimize the benefits.
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. 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, 1997a, 32: 1, 85-90.
11. Vescovi, P.P., and Di Gennaro, C. Di. Failure of gammahydroxybutyric acid to stimulate growth hormone secretion in cocaine addicts. Neurpoeptides, 1997b, 31: 5, 459-462.
12. 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