GABA (Gamma-Aminobutyric Acid) vs HMB (Beta-Hydroxy Beta-Methylbutyrate)

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

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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