Supplementation of γ-Aminobutyric Acid as a Functional Nutrient.

γ-Aminobutyric acid (GABA) is an endogenous metabolite and signaling molecule that is widely distributed across plants, microorganisms, and mammalian tissues. Although classically viewed as the principal inhibitory neurotransmitter in the central nervous system, GABA also functions in peripheral organs, where it participates in receptor-mediated signaling, intermediary metabolism, epithelial barrier regulation, endocrine control, immune modulation, and host-microbiota communication. These features have renewed interest in oral GABA supplementation and in dietary or microbial strategies designed to increase luminal or circulating GABA availability. Despite increasing interest in oral GABA supplementation and microbiota-derived GABA, evidence remains fragmented across multiple disciplines and the translational relevance of peripheral GABA biology remains incompletely defined. This review considers GABA within a functional nutrient framework: not as an essential nutrient required to prevent deficiency, but as a nonessential bioactive metabolite whose exogenous availability may modulate physiological regulation under specific conditions. The literature was identified through structured PubMed searches of studies published from 2000 onward. This review summarizes current knowledge regarding exogenous sources of GABA, intestinal absorption, hepatic uptake, and metabolic fate, receptor-mediated and metabolite-mediated signaling mechanisms in peripheral tissues, and findings from experimental, preclinical, and clinical studies examining GABA supplementation in immune-, endocrine-, and metabolic-related contexts. The findings support GABA as a biologically active functional nutrient with potential roles in immune, endocrine, epithelial, hepatic, and metabolic regulation. While experimental studies consistently report beneficial effects on inflammatory and metabolic outcomes, human studies remain limited and have not yet established definitive clinical efficacy. Future studies should prioritize well-powered randomized controlled trials, dose-response analyses, long-term safety assessments, and biomarkers of tissue-specific GABA exposure and target engagement.