GABAvsGlycine

GABA binds to GABA-A receptors (ligand-gated Cl- channels with alpha1-6, beta1-3, gamma1-3 subunits) and GABA-B receptors (G-protein coupled, Gi/o mediated), reducing neuronal excitability through hyperpolarization. However, supplemental GABA has limited blood-brain barrier penetration due to absence of a dedicated transporter and rapid metabolism by GABA-transaminase and succinate semialdehyde dehydrogenase in periphery. The calming effects may be mediated through: (1) GABA-A and GABA-B receptors in the enteric nervous system (gut-brain axis) — vagal afferents project to the nucleus tractus solitarius and influence limbic regions; (2) small amounts crossing the BBB via paracellular leakage or in individuals with compromised barrier integrity; (3) peripheral effects reducing systemic stress markers (cortisol, heart rate variability). PharmaGABA (Lactobacillus fermentation product) may have better absorption via peptide-like transport or different pharmacokinetics.

Glycine acts as an inhibitory neurotransmitter by binding to strychnine-sensitive glycine receptors (GlyR) in the brainstem, spinal cord, and retina, hyperpolarizing neurons via chloride influx. It also serves as a mandatory co-agonist at the glycine-binding site (NR1 subunit) of NMDA glutamate receptors — without glycine binding, NMDA receptors cannot open their ion channel even when glutamate is present. This dual role means glycine both calms neural activity (sleep, anti-anxiety via GlyR) and supports excitatory learning processes (NMDA-dependent LTP and memory consolidation). Glycine lowers core body temperature at night by promoting peripheral vasodilation through nitric oxide, which improves sleep onset. It is a precursor for glutathione synthesis and modulates the glycinergic system in the suprachiasmatic nucleus.