Amino Acids
Evidence: strong_human
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: 3-6g L-citrulline daily or 6-8g citrulline malate
Maintenance: 3-6g/day
Administration: oral
Timing: 30-60 minutes pre-workout for exercise performance. For blood pressure: split AM/PM doses. Powder form in water.
Duration: ongoing
L-citrulline is SUPERIOR to L-arginine supplementation for NO production — this is a critical point that contradicts much of the arginine marketing. Oral arginine is extensively degraded by intestinal arginase and hepatic first-pass metabolism, while citrulline bypasses both. Citrulline malate provides the additional benefit of malate (Krebs cycle intermediate, supports ATP regeneration). The PDE5 inhibitor interaction should be flagged for any client using erectile dysfunction medications. Pre-workout timing is well-established for exercise performance (reduced fatigue, improved blood flow, enhanced endurance).
Pure L-citrulline or citrulline malate (2:1 citrulline:malic acid ratio). L-citrulline is preferred over L-arginine for raising plasma arginine and NO levels due to bypassing first-pass metabolism. Powder form is most practical at these doses. Brands: NOW L-Citrulline Powder, Nutricost, BulkSupplements.
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