EAAs (Essential Amino Acids) vs HMB (Beta-Hydroxy Beta-Methylbutyrate)

Mechanism

The 9 essential amino acids (leucine, isoleucine, valine, lysine, methionine, phenylalanine, threonine, tryptophan, histidine) cannot be synthesized endogenously and must be consumed. Leucine is the primary mTORC1 activator (via Sestrin2 and CASTOR1 sensors), triggering p70S6K and 4E-BP1 phosphorylation to initiate muscle protein synthesis (MPS). The remaining EAAs are required as substrates for the actual protein synthesis — leucine signals the process, but all 9 EAAs must be present to complete it. EAA supplementation achieves comparable MPS stimulation to whey protein with fewer total calories.

Standard Dosing

6-12g per serving

Timing

Intra-workout (sipped during training) or immediately post-workout. Can also be used between meals to maintain elevated MPS throughout the day.

Cycle Duration

ongoing during training periods

Side Effects

• Mild GI discomfort
• Nausea (if concentrated)
• Bloating
• Generally very well tolerated

Contraindications

• Maple syrup urine disease (branched-chain amino acid metabolism disorder)
• Phenylketonuria (phenylalanine content)
• 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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