L-Citrulline and L-Arginine Supplementation in Cardiovascular and Exercise Physiology - A Comprehensive Review on Endothelial Function, Blood Pressure, and Physical Performance

Introduction and Purpose: L-citrulline and L-arginine are amino acids involved in nitric oxide (NO) synthesis, which plays a vital role in regulating vascular tone, arterial pressure, and exercise-induced physiological responses. This review aims to assess the effectiveness of L-citrulline and L-arginine supplementation in improving endothelial function, lowering blood pressure, and enhancing physical performance in both healthy and clinical populations. Brief Description of the State of Knowledge: Forty-three studies were included, ranging from randomized controlled trials to mechanistic investigations involving athletes, hypertensive patients, older adults, and postmenopausal women. L-citrulline demonstrated superior bioavailability compared to L-arginine and more effectively increased plasma arginine concentrations. Both supplements were associated with improved endothelial-dependent vasodilation and moderate blood pressure reductions, especially at daily doses ≥6 g. Some studies also reported benefits in VO₂ kinetics, reduced perceived exertion, and enhanced exercise tolerance. However, the results concerning measurable performance improvements remain inconsistent and context-specific. Conclusions: Supplementation with L-citrulline and L-arginine may offer non-pharmacological support for vascular health and exercise efficiency, particularly in individuals with endothelial dysfunction. Further studies are warranted to determine optimal dosing strategies and identify the populations most likely to benefit.