Glycine vs L-Glutamine

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

L-Glutamine is the most abundant amino acid in plasma and skeletal muscle. It is the primary fuel source for enterocytes (intestinal epithelial cells) and rapidly dividing immune cells (lymphocytes, neutrophils). Glutamine maintains intestinal tight junction integrity by modulating tight junction proteins (occludin, claudin-1, ZO-1), preventing intestinal hyperpermeability ('leaky gut'). It serves as a nitrogen shuttle between tissues, is a precursor for nucleotide synthesis (purines and pyrimidines), contributes to gluconeogenesis, and buffers ammonia via glutamine synthetase. During catabolic stress (illness, surgery, intense exercise), glutamine becomes conditionally essential.

Standard Dosing

5-10g daily

Timing

On empty stomach for gut healing. Post-workout for muscle recovery. Dissolves easily in water.

Cycle Duration

8-12 weeks for gut healing; ongoing for maintenance

Side Effects

• Generally well-tolerated
• Bloating at high doses
• Constipation
• Headache
• Theoretical excess glutamate conversion in sensitive individuals (excitotoxicity concern)

Contraindications

• Hepatic encephalopathy (glutamine to glutamate to ammonia conversion)
• Reye's syndrome
• Severe renal failure
• Some cancers are glutamine-dependent (discuss with oncologist)

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