United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)

Abstract

Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for 4 days and in longer studies at intakes of 120 mg/d for 12 weeks. Some studies showed that GABA was associated with a transient and moderate drop in blood pressure (<10% change). No studies were available on effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA were found. Chronic administration of GABA to rats and dogs at doses up to 1 g/kg/day showed no signs of toxicity. Because some studies showed that GABA was associated with decreases in blood pressure, it is conceivable that concurrent use of GABA with anti-hypertensive medications could increase risk of hypotension. Caution is advised for pregnant and lactating women since GABA can affect neurotransmitters and the endocrine system, i.e., increases in growth hormone and prolactin levels.

Keywords: 4-aminobutanoic acid; GABA; adverse effects; adverse events; dietary supplements; gamma-amino butyric acid; hypotension; interactions; safety review; γ-amino butyric acid.

Figure 1

Literature search strategy showing the combination of search terms used and the number of articles included in the manuscript and the total number of articles retrieved by each search for each outcome. Most publications were concerning GABA as a neurotransmitter, its metabolism, and its derivatives and prodrugs such as pregabalin, gabapentin, and articles describing GABA function as an innate metabolite in the human body. T, total articles retrieved; N, articles included in the review.

Figure 2

Gamma-aminobutyric acid (GABA, 4-aminobutyric acid).

Figure 3

In the GABA shunt, GABA is synthesized from glutamate in a process catalyzed by GAD. GABA is metabolized by GABA-T into succinate semi-aldehyde, which is then reduced to gamma-hydroxybutyrate or oxidized to succinate and eventually converted to CO₂ and water via the TCA cycle. GAD, glutamatic acid decarboxylase; GABA-T, GABA transaminase; SSA, succinic semialdehyde; SSA-DH, succinic semialdehyde dehydrogenase; TCA cycle, tricarboxylic acid cycle. Green, enzymes; Orange, cofactor.