GABA (Gamma-Aminobutyric Acid) vs Glycine

Mechanism

GABA is the primary inhibitory neurotransmitter in the CNS, activating GABA-A receptors (ligand-gated chloride ion channels, causing rapid inhibition) and GABA-B receptors (G-protein coupled, causing slow, sustained inhibition). Supplemental GABA's ability to cross the blood-brain barrier is debated — it likely acts primarily through the enteric nervous system (gut-brain axis), peripheral GABA receptors, and potentially via limited BBB penetration at the circumventricular organs. GABA promotes alpha brain waves (relaxation), increases growth hormone secretion (via GHRH modulation), and reduces sympathetic nervous system overactivation.

Standard Dosing

250-750mg daily

Timing

Evening before bed for sleep, or as needed for acute anxiety/stress. Sublingual onset: 15-20 minutes.

Cycle Duration

As needed or cycle 4-8 weeks on, 2 weeks off

Side Effects

• Drowsiness
• Tingling/flushing sensation (especially at higher doses — likely peripheral vasodilation)
• Mild shortness of breath sensation (transient)
• GI upset

Contraindications

• Severe respiratory depression
• Concurrent high-dose benzodiazepine use

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Mechanism

Glycine is the simplest amino acid with profound neurological and metabolic roles. It is an inhibitory neurotransmitter acting at glycine receptors (strychnine-sensitive) in the brainstem and spinal cord, inducing a drop in core body temperature that facilitates sleep onset. It is also an obligatory co-agonist at the NMDA receptor glycine binding site, modulating excitatory neurotransmission. Metabolically, glycine is the rate-limiting amino acid for glutathione synthesis (glutathione = glycine + cysteine + glutamate), a key substrate for collagen synthesis (every 3rd amino acid), essential for creatine synthesis, bile acid conjugation, heme synthesis, and one-carbon metabolism.

Standard Dosing

3-5g daily

Timing

3g before bed for sleep (core body temperature reduction). Divided doses during day for glutathione support. Powder in water has a mildly sweet taste.

Cycle Duration

ongoing

Side Effects

• Mild drowsiness
• Soft stools at high doses
• Nausea (rare)
• Generally extremely well-tolerated

Contraindications

• Very few absolute contraindications. Caution in severe renal disease.

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