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Citrulline & Nitric Oxide

By Karyn Maier

Citrulline is an amino acid produced by the body as a byproduct of synthesizing another amino acid, arginine. This event is made possible by nitric oxide synthases, or NOS, a class of enzymes that synthesize nitric oxide from L-arginine, a form of arginine. The relationship between citrulline and nitric oxide impact the body in a variety of ways. In fact, both influence heart health and male sexual function.

Biological Effects

Citrulline is essential to make arginine, which helps to protect heart health by relaxing blood vessels and improving circulation. In turn, arginine is needed to produce nitric oxide, which also acts as a natural vasodilator. Nitric oxide is also involved in molecule signaling in cells. Too much nitric oxide, however, can cause vascular and neural damage. In fact, chronically high levels of nitric oxide are associated with an increased risk of neurodegenerative disease, such as Alzheimer's, Parkinson's and Huntington's diseases.

Diagnostic Value

Although citrulline is not normally present in proteins, it may infiltrate some proteins as the result of citrullination, a process precipitated by a different group of enzymes that become active when cells die or become inflamed. In response, the body produces antibodies to these proteins. This means that an elevated level of anti-citrullinated protein antibodies can signal the presence of disease even before symptoms appear. This is significant in terms of diagnostic value since people with rheumatoid arthritis, for example, have higher than normal ACPA levels because the proteins fibrin and vimentin are vulnerable to citrullination. Similarly, low levels of nitric oxide suggest there is limited citrulline and arginine available. On the other hand, elevated levels of citrulline indicate a deficiency of argininosuccinate synthase, which causes a hereditary disease called citrullinemia. According to Michael Xuehai Ye, Ph.D., and fellow researchers at the Children's Research Institute in Washington, D.C., citrullinemia often leads to coma and death in newborns within days unless gene therapy is administered within hours of birth.

Therapeutic Applications

Increasing citrulline intake will boost nitric oxide levels through arginine conversion, which may benefit people with high blood pressure and other cardiovascular conditions. Increasing nitric oxide levels may also help to prevent and treat erectile dysfunction in men since it improves blood flow, the same effect produced by the drug Viagra. In the January 2009 issue of the “American Journal of Clinical Nutrition,” researchers from the University of Arkansas for Medical Sciences reported that patients with sepsis or septic shock have severely low levels of citrulline and, therefore, low levels of arginine and nitric oxide. The scientists speculate that nutritional therapy with citrulline to restore arginine and nitric oxide metabolism might be beneficial in such cases.

Dietary Sources

Watermelon is a natural source of citrulline. Unfortunately, more of this substance resides in the rind than the flesh. New varieties of watermelon are being developed that will contain more citrulline in the fruit.

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