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 ornithine and 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.
A considerable amount of research suggests that chronic supplementation with citrulline mildly reduces blood pressure and mildly improves blood flow, particularly in individuals with hypertension or other cardiovascular problems. Limited research suggests that supplementation with citrulline, both short-term and long-term, can reduce fatigue, increase power output, and improve endurance in both aerobic and anaerobic exercise. More research is needed for citrulline’s potential effects on erectile dysfunction, but a small amount of research suggests a beneficial effect.
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.
Most studies that examined the effect of citrulline on circulatory health have used daily doses of 6 grams. For improving sports performance, the daily dose used in most studies was 6 grams of citrulline or 8–12 grams of citrulline malate, which is a combination of citrulline and malate (an ionized form of malic acid).
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 improve circulatory health and muscle function and reduce fatigue.