Citrulline

Citrulline is one of the three dietary amino acids in the urea cycle (the other two are L-arginine and L-ornithine). Taking citrulline increases plasma levels of arginine and improves the ammonia recycling process and nitric oxide metabolism. Consequently, citrulline may be useful in situations in which nitric oxide is relevant, such as athletic performance, vascular health, and erectile dysfunction. There are very few foods that have useful amounts of citrulline, but watermelon is a notable exception. The two most common forms of citrulline are L-citrulline and citrulline malate.

There is limited evidence that citrulline supplementation can reduce ratings of perceived exertion, decrease muscle soreness, and increase power output and total repetitions performed in resistance training.^[76][77][78] More research is needed to determine whether different supplement dosages, different formulations, or longer periods of ingestion can further improve exercise performance.

A considerable amount of research suggests that supplementation with citrulline mildly reduces blood pressure.^[79] More research is needed on citrulline’s potential effects for erectile dysfunction, but a small amount of research suggests a beneficial effect.^[68]

Although the safety of long-term supplementation with high doses of citrulline warrants further investigation, research to date suggests that it is well tolerated in most individuals. Unlike arginine and ornithine, high doses of citrulline don't seem to result in gastrointestinal distress.^[77]

Citrulline supplementation increases the body’s arginine levels. Because arginine is the main substrate for the synthesis of nitric oxide, citrulline ingestion can indirectly increase nitric oxide production. In turn, given the role of nitric oxide in vasodilation, mitochondrial respiration, calcium handling, and glucose uptake, greater amounts of nitric oxide can theoretically improve circulatory health and muscle function and reduce fatigue.