Glycine vs HMB (Beta-Hydroxy Beta-Methylbutyrate)

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

HMB is a metabolite of leucine (produced endogenously at ~0.3g/day from typical leucine intake). It reduces proteolysis by inhibiting the ubiquitin-proteasome proteolytic pathway and attenuating caspase-mediated apoptosis in muscle cells. HMB also stimulates muscle protein synthesis via mTOR/p70S6K pathway activation (though less potently than leucine itself) and enhances sarcolemmal membrane integrity by serving as a precursor for de novo cholesterol synthesis in muscle cells (via HMG-CoA). The net effect is anti-catabolic rather than primarily anabolic — it prevents muscle breakdown more than it builds new muscle.

Standard Dosing

3g daily (1g 3x/day)

Timing

Split into 1g doses with meals (HMB-Ca) or 1-2g 30-60 min pre-exercise (HMB-FA for rapid absorption). Timing matters more for HMB-FA (free acid) than HMB-Ca (calcium salt).

Cycle Duration

ongoing during training periods

Side Effects

• Generally very well tolerated
• Mild GI discomfort
• Bloating

Contraindications

• Few known. Renal impairment (monitor at high doses).

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