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Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality—Should Patients with Elevated Levels Be Supplemented with Citrulline?

Catalytic Longevity, 7831 Rush Rose Dr., Apt. 316, Carlsbad, CA 92009, USA
Academic Editor: Sampath Parthasarathy
Healthcare 2016, 4(3), 40; https://doi.org/10.3390/healthcare4030040
Received: 3 June 2016 / Revised: 21 June 2016 / Accepted: 27 June 2016 / Published: 8 July 2016
(This article belongs to the Special Issue Nutrition and Cardiovascular Disease)
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. View Full-Text
Keywords: cardiovascular; asymmetric dimethylarginine; nitric oxide synthase; citrulline; tetrahydrobiopterin; folic acid; statins; spirulina; NADPH oxidase; Alzheimer’s disease cardiovascular; asymmetric dimethylarginine; nitric oxide synthase; citrulline; tetrahydrobiopterin; folic acid; statins; spirulina; NADPH oxidase; Alzheimer’s disease
MDPI and ACS Style

McCarty, M.F. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality—Should Patients with Elevated Levels Be Supplemented with Citrulline? Healthcare 2016, 4, 40.

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