The
arginine metabolite
asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of
endothelial nitric oxide synthase (eNOS), an
enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular
hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular
arginine levels with supplemental
citrulline. Although the long-term impact of supplemental
citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of
citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with
heart failure. Supplemental
citrulline could be a practical option for primary or
secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3-6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate
citrulline's potential for aiding cardiovascular health.