Glycine vs NAC (N-Acetyl Cysteine)

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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Mechanism

NAC is a precursor to L-cysteine, the rate-limiting substrate for glutathione (GSH) synthesis via glutamate-cysteine ligase. It directly replenishes intracellular GSH, the master endogenous antioxidant. NAC also modulates glutamatergic neurotransmission by stimulating the cystine-glutamate antiporter (system Xc-), influencing extrasynaptic glutamate levels. Additionally, it acts as a mucolytic by cleaving disulfide bonds in mucus glycoproteins.

Standard Dosing

600-1200mg daily

Timing

On empty stomach for best absorption, 30 min before meals. Split doses if >600mg.

Cycle Duration

Cycle 8 weeks on, 2 weeks off (to avoid potential downregulation of endogenous GSH production)

Side Effects

• Nausea
• GI upset
• Sulfurous odor/taste
• Rare: skin rash
• Potential zinc/copper chelation at very high doses

Contraindications

• Active gastric ulcers (may increase gastric acid)
• Asthma (rare bronchospasm with inhaled form)
• Concurrent chemotherapy (discuss with oncologist)

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