In middle-aged and older adults with type 2 diabetes, 4 weeks of citrulline supplementation at 6 g/day increases forearm muscle microvascular reactivity, as measured by elevated TOI range, hyperemic response, and 2-minute area under the curve during reactive hyperemia, indicating enhanced capillary perfusion in skeletal muscle.

Citrulline is absorbed and turned into arginine in the kidneys, which gives more arginine to blood vessel cells. These cells use arginine to make nitric oxide, a molecule that tells small blood vessels to open wider. In people with type 2 diabetes, an enzyme called arginase normally steals arginine and stops nitric oxide production, but citrulline blocks arginase, letting more nitric oxide be made. This opens up tiny blood vessels in muscle, allowing more blood to flow through when the muscle needs oxygen.