Nitric oxide (NO) is one of the body’s most potent vasodilators and, as such, is a key player in increasing and maintaining blood flow to skeletal muscle. NO is produced by a few mechanisms in the body—one of which occurs when l-arginine and oxygen react with endothelial nitric oxide synthase (eNOS), another mechanism is occurs with reduction of inorganic nitrate. Increased NO production allows for greater blood flow to muscles and organs, which promotes increased muscle pumps and vascularity, increased flushing of muscle metabolites and replenished nutrients, removal of free radicals, and increased oxygen delivery. Taken together, increased NO production optimizes the skeletal muscle environment for anabolism.
NO boosters have been on the market for several years and are a main ingredient in many preworkout formulations. Over the years, science has shown that several “claimed” NO boosters work well, not so well, or no at all—this has led to ongoing research aimed at finding the ideal supplement or combination of supplements that undeniably promote increased NO production in humans.
A recent multi-phase study published in the Journal of the International Society for Sports Nutrition investigated the effectiveness of L-citrulline and/or glutathione (a potent antioxidant) on markers indicative of NO synthesis under in vivo conditions with rodents and humans and also in an in vitro condition. The most relevant findings came from the human phase of the study, which showed that stacking L-citrulline and glutathione significantly increased markers of NO production, which were most notable 30 minutes post-exercise. Notably, no other conditions boosted markers of NO and, if anything, post-exercise NO production diminished (from baseline levels) in the placebo condition.
ACTION POINT: Based on the findings from this study, stack 2g of L-citrulline with 200mg of glutathione 60 minutes before training. On non-training days take the same stack in the evening before bed.
McKinley-Barnard S, Andre T, Morita M, Willoughby DS Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis. J Int Soc Sports Nutr. 2015 Jun 10;12:27.