Glycine

Mechanism of Action

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.

Dosing Protocol

Notes

The GlyNAC (Glycine + NAC) protocol from Baylor/Dr. Rajagopal Sekhar's research is arguably the most exciting development in accessible longevity supplementation — reversing hallmarks of aging in elderly humans by restoring glutathione synthesis. Typical GlyNAC protocol: 100mg/kg/day each of glycine and NAC. Glycine as a sleep aid (3g before bed) is well-studied and works via a different mechanism than GABA (thermoregulation). The sweet taste makes it an excellent powder supplement. Collagen is ~33% glycine but supplemental glycine provides a more direct and dose-controlled approach for GSH synthesis.

Stacking

• NAC (for glutathione synthesis — GlyNAC protocol)
• Magnesium (for sleep)
• Collagen
• L-Theanine

Interactions

• Clozapine [MEDIUM] — Glycine may reduce clozapine efficacy
• Antipsychotics [LOW] — Glycine as NMDA co-agonist is being studied as adjunctive therapy — discuss with psychiatrist

Contraindications

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

Side Effects

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

Key Papers

• 10.1016/j.sleep.2006.06.008
• 10.1007/s11357-021-00369-7
• 10.1016/j.freeradbiomed.2019.11.007

Source Quality

Pharmaceutical-grade glycine powder is inexpensive and widely available. Has a pleasant, slightly sweet taste — easily mixed into water. Brands: NOW Glycine Powder, BulkSupplements, Thorne Glycine.

Should Glycine Be in Your Stack?

Take the free assessment and get personalized recommendations based on your biology and goals.