Optimizing Nitric Oxide Production for Exercise Performance & Vascular Function: A Narrative Review on the Combination of Glutathione and Citrulline

Introduction: Citrulline has been thoroughly researched and well documented to increase plasma arginine levels, boosting nitric oxide (NO) synthesis via the nitric oxide synthase (NOS) pathway. While glutathione, a key antioxidant, protects NO from oxidative degradation and helps maintain vascular signaling integrity. When taken together, these nutrients may offer enhanced and/or sustained NO bioavailability, supporting vascular function, recovery, and exercise performance more effectively than citrulline alone. Methods: A literature review was conducted to explore the relationships between glutathione, citrulline, NO, and vascular health. Three databases, PubMed, ScienceDirect, and Google Scholar and eight search terms were used to find relevant articles. Results: Four double-blind placebo controlled human clinical trials found the combination of glutathione and l-citrulline to be more effective in enhancing and sustaining NO production levels and flow mediated dilation (vasodilation) better than citrulline alone (P<0.03). Conclusions: Collectively, these studies support the functional synergy between citrulline and glutathione in promoting NO-related health and performance outcomes offering a promising nutritional strategy for athletes, aging individuals, and those seeking cardiovascular support.