Discovered over 50 years ago, gamma-amino-beta-hydroxybutyric acid (abbreviated GABOB) is a natural substance found in the brain that possesses some useful pharmacological properties. Initially studied as an anti-epilepsy treatment, it has broader applications in the areas of anxiety and stress reduction, and growth hormone production. GABOB is marketed as the drug Gamibetal® in Mexico and Italy, but elsewhere is not widely available, despite its therapeutic potential and excellent safety profile. Let’s take a look at this natural stress-reliever with anti-aging benefits.
GABA-like Effects of GABOB
GABOB is a physiological metabolite of the neurotransmitter gamma-aminobutyric acid (GABA). Structurally, it is almost identical to GABA (except for the addition of a hydroxyl (-OH) group; see Figure) and exerts similar pharmacological effects. (1) GABA is the main inhibitory, or calming, neurotransmitter in the brain and regulates the excitability of neurons throughout the nervous system by binding to specific receptors. Low levels of this neurotransmitter are associated with restlessness, anxiety, and mood disorders, (2,3) and drugs that act on GABA receptors or pathways (such as GABOB, as we will see below) produce stress-relieving, anti-anxiety, and anti-convulsive effects. (2,4) Like GABA, GABOB is a neurodepressant, and inhibits stimulated activity of the brain in animals and humans. (1)
GABOB and Epilepsy Treatment
Dozens of studies on GABOB were performed in the 1960’s, especially in the area of epilepsy treatment. Epilepsy is a brain disorder that produces seizures due to abnormal or excessive neuronal activity in the brain. GABOB has been shown to block excitatory neural circuitry and inhibit or attenuate experimentally induced convulsions or seizures in animals. (5-7) One animal study of note from the 1960’s documented the complete cure of epilepsy in dogs after intravenous (IV) treatment with GABOB. (8) In clinical studies from that decade, GABOB was effective in preventing and alleviating epileptic seizures in humans. (5) Unfortunately, the abstracts of these studies are no longer available and in many cases, it is not clear whether the drug was administered orally or subcutaneously. As expected, GABOB is significantly more potent when delivered by IV rather than taken by mouth in tablet form. In more recent years, GABOB has been used as an adjunct oral therapy for the treatment of epilepsy, co-administered with another anti-convulsant drug. This application as an add-on therapy was evaluated in a 1997 study on adults with severe epilepsy. In addition to their standard antiepileptic medication, 25 patients were orally administered 250 mg GABOB twice daily for 26 weeks. A 50 percent reduction in seizure frequency was observed in 25 percent of these patients. No adverse effects were reported. (9) (Note: It would have been interesting to evaluate if a higher dose, i.e., 500 mg, twice, daily would have shown even greater efficacy in reducing seizures in these patients.)
GABOB is a Natural Tranquilizer
Besides epilepsy treatment, GABOB possesses a more universal application for the general population: due to its inhibitory and calming action, it may also be used for alleviating stress, anxiety, restlessness, hyperactivity, and sleep disturbances. A safe, effective, and natural anxiolytic, without the potential for addiction or troubling side effects typical of other tranquilizers (such as benzodiazepines like Valium®), is a boon to our 21st century fast-paced world.
GABOB and Growth Hormone Secretion
Equally, and perhaps even more importantly to anti-aging enthusiasts, is that GABOB has been shown to be a growth hormone secretagogue, promoting the release of this important peptide hormone from the pituitary gland. Growth hormone (GH) is a major regulator of body growth in youth, but plays crucial maintenance, regeneration and repair functions throughout life; it regulates carbohydrate and lipid metabolism, cardiovascular, immune, and brain function, bone density and skin integrity. As an anabolic hormone, GH influences the ratio of lean muscle mass to adipose tissue (body fat) mass. As with other hormones, levels of GH fall with advancing age, leading to declining lean muscle mass, increased body fat, thinning skin, decreased bone density, lowered immune and cardiovascular function, even brain aging. (10-13) Studies show that intravenous GH administration results in increased lean muscle mass, skin thickness, and bone density; decreased body fat, enhanced immune and cardiovascular function, and improvements in learning and memory. (11,13) In 1990, a ground-breaking study reported that in men aged 61 to 81, six months of intravenous GH therapy reversed physiological changes incurred during 10 to 20 years of aging. (11) GH administration can literally subtract years from one’s biological age and is among the most powerful anti-aging strategies available today.
Unfortunately, GH injections are prohibitively costly, not readily available, and not without some side effects. The good news is that use of the natural compound GABOB, clinically proven to spur endogenous GH release (i.e., from one’s own pituitary), is an alternative, not to mention affordable, method to raise circulating levels of this key hormone. The GH-stimulating effect of GABOB was first demonstrated in a 1977 animal experiment in which an injection of GABOB caused a significant increase in plasma GH in the rat. Interesting, and not unexpectedly, an injection of the neurotransmitter precursor GABA also produced a similar result. (14) The next year, a human study confirmed the stimulatory effect of GABOB on pituitary function and GH release. (1) Nine women received injections of either 50 or 100 mg GABOB. Although the lower dose did not induce GH release, significant increases in plasma GH levels were observed 15 to 30 minutes after injection of the 100 mg dose. During the course of the experiments, researchers noticed occasional “changes in alertness” (i.e., sedation) in the subjects after injection with GABOB, indicating the drug’s depressive effect on the central nervous system (as we saw earlier). Two additional participants were administered a higher 150-mg GABOB injection, which resulted in loss of consciousness; this portion of the study was discontinued. (1) Although this profound effect was observed when the drug was delivered subcutaneously, it should be noted that orally administered GABOB, while providing a calming effect, does not lead to unconsciousness and is virtually side-effect free. In a similar experiment, three groups of six women received infusions of three different doses of GABOB over a 20 minute period (100 mg/min., 20 mg/min. and 3.5 mg/min.). Results indicated dose-dependent increases in plasma GH levels, with the highest dose infusion (100 mg/min.) producing the largest GH secretion. (15) Another study on men demonstrated that an intrathecal injection (i.e., into the sheath surrounding the spinal cord) of 300 mg GABOB caused significant increases in plasma GH levels at 60 minutes after injection. (16)
Similarities between the Butyric Acid Analogs GABOB and GHB
GABOB shares structural similarities (see Figure) and certain pharmacological properties with another GABA metabolite, gamma-hydroxybutyric acid (GHB). GHB has been shown to exert a number of therapeutic effects. At low oral doses, it produces mild relaxation and decreased anxiety; a moderate dose can induce restful sleep and treat insomnia; and higher oral doses (used to treat narcolepsy) induce a profoundly deep sleep (from which it may be difficult to be awakened). Note that although both GABA analogs have tranquilizing properties, the powerful degree of sedation that can be achieved by oral administration of GHB cannot be attained with oral GABOB (even though we did see earlier that a high enough dose of GABOB delivered subcutaneously does produce unconsciousness). Besides its tranquilizing effect (at low doses), another similarity GHB shares with GABOB is its GH-promoting action. Studies show that GHB stimulates GH secretion when injected intravenously (17) or taken orally. (18) Unfortunately, the FDA and DEA removed this safe and effective substance, which was once commercially available, from the market in the 1990’s in response to misperceptions and unscientific bias. At present, GHB can only be obtained as a prescription drug in the US. Fortunately, its structurally close analog, GABOB, is available (from IAS), and, while it cannot be used orally to induce a profound level of deep sleep or sedation, GABOB shares the tranquilizing and GH-promoting properties of GHB.
GABOB is available as Gamibetal® tablets, 500mg. The typical dose recommended by the manufacturer for treating restlessness, anxiety, or sleep disturbances, or as an add-on medication for epilepsy, is one to three tablets daily. The oral dose of Gamibetal® to spur endogenous GH secretion has not been established; a good starting point is two tablets at bedtime. Another product carried by IAS, Gamalate B6®, is also formulated with GABOB, if a lower dosage is desired. As we have just seen, the natural substance GABOB combats anxiety and stress and is a safe alternative to conventional tranquilizers. In addition, its growth hormone-promoting effects put it in the category of an anti-aging drug. Not widely known by mainstream medicine, hopefully the therapeutic potential of this useful compound will someday be fully realized.
gamma-aminobutyric acid (GABA)
gamma-amino-beta-hydroxybutyric acid (GABOB)
gamma -hydroxybutyric acid (GHB)
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