GABA

GABA (gamma-aminobutyric acid) is a mediator of nervous inhibition whose heightened liberation occurs during sleep and near-sleep states, functioning as a core component of the body's protective anti-stress system. 2 Peat argued that GABA is synthesized from glutamic acid by the enzyme glutamic acid decarboxylase (GAD), a process requiring vitamin B6 as a coenzyme. 2 He noted that GAD is a peculiar enzyme inactivated by cold, suggesting it is relatively inactive in the resting state but becomes more active during brain activation or exhaustion, producing more GABA to promote rest and restoration. 2

Peat situated GABA within a broad, holistic inhibitory network that opposes excitatory and catabolic processes. He observed that the protective steroids progesterone and pregnenolone act on the GABA receptor to reinforce its inhibitory effects, while estrogen has the opposite action, inhibiting GABA's function. 9 This system extends structurally to other amino acids; Peat wrote that the similarity between the structures and actions of glycine and GABA suggests their receptors are similar, if not identical, and that both are opposed by the excitatory amino acid system activated by glutamic and aspartic acid. 9 Dinkov has extended this by noting that many medium and short-chain saturated fatty acids are direct agonists of the GABA receptor, which explains the anti-epileptic mechanism of ketogenic diets. 10

The GABA system is central to tissue renewal and stress resistance without stimulating cell multiplication. Peat explained that GABA and progesterone improve regeneration by preventing premature cell death and promoting normal differentiation and maturation, countering the excitotoxic and mitochondrial-damaging effects of polyunsaturated fatty acids released during cellular excitation. 2 He described GABA analogs as one of the most actively studied classes of adaptogens, with a wide range of stress-blocking actions including neural inhibition, progesterone promotion, and blood sugar regulation. 3 Dinkov has argued that GABA agonists suppress the cortisol and estrogen pathways, leaving a hormonal profile of pregnenolone, progesterone, and DHEA that characterizes a youthful, anti-stress state. 10

Regarding practical application, Peat acknowledged that oral GABA supplementation normally does not cross the blood-brain barrier, but he cited research showing that stress can eliminate this barrier, allowing GABA to enter an exhausted brain and exert a beneficial inhibitory action. 2 He recommended supporting the GABA system with magnesium, glucose, carbon dioxide, and anti-inflammatory pro-GABA steroids rather than relying solely on direct supplementation. 7 Dinkov has cited human studies showing that even 100 milligrams of oral GABA significantly lowers anxiety and depression scores, and that its effect synergizes with L-theanine. 8 Peat also noted that the tropical fruit passionfruit contains compounds made along with GABA that help eliminate stressful over-excitation, and that even the sedative effects of cannabis can be protective against toxic over-stimulation by acting on this system. 5