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L-Citrulline is produced as a byproduct of nitric oxide synthesis (arginine → NO + citrulline) and recycled back to arginine in the kidneys via the arginine-citrulline cycle. Supplemental citrulline effectively raises plasma arginine levels by 30-50% — more than oral arginine itself, which is extensively metabolized by arginase in the gut and liver.
Higher arginine availability means more substrate for nitric oxide synthase (eNOS), producing more NO. Nitric oxide is a potent vasodilator — it relaxes blood vessel walls, reducing blood pressure, improving blood flow to muscles (exercise performance) and erectile tissue.
Citrulline malate (citrulline bonded to malic acid) is the most common exercise form. The malate may contribute to aerobic energy production via the TCA cycle, though this is secondary to the NO mechanism.
Both increase NO/vasodilation — additive hypotension risk
Additive NO/vasodilation — severe hypotension risk
Additive BP lowering — monitor
NO has mild antiplatelet effects — theoretical additive
Not Prohibited
Allerton TD et al. L-Citrulline supplementation: impact on cardiometabolic health.
Cormio L et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction.
Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic performance.
Moinard C et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns.
Independently graded against 173,636 indexed supplements with 177 published clinical interactions, sourced from PubMed, FDA CAERS, openFDA, and NIH DSLD | Last updated: April 2026
Not medical advice. Based on published clinical research and systematic reviews.