EAAs (Essential Amino Acids) vs L-Citrulline

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

L-Citrulline is converted to L-arginine in the kidneys via argininosuccinate synthase and argininosuccinate lyase (bypassing hepatic first-pass metabolism that degrades oral L-arginine). L-arginine is then the substrate for endothelial nitric oxide synthase (eNOS), producing nitric oxide (NO). NO activates soluble guanylyl cyclase (sGC), increasing cGMP, causing vascular smooth muscle relaxation and vasodilation. Citrulline also participates in the urea cycle (ammonia detoxification), and supplementation increases plasma arginine more effectively than arginine supplementation itself due to bypass of intestinal and hepatic arginase.

Standard Dosing

3-6g L-citrulline daily or 6-8g citrulline malate

Timing

30-60 minutes pre-workout for exercise performance. For blood pressure: split AM/PM doses. Powder form in water.

Cycle Duration

ongoing

Side Effects

• Mild GI discomfort
• Bloating
• Headache (vasodilation)
• Generally very well-tolerated even at high doses

Contraindications

• Concurrent nitroglycerin/nitrate therapy
• Severe hypotension
• Urea cycle disorders (citrullinemia)

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