Volume 89, Issue 3, March (2003), pp. 359-363 © The Author 2003
doi:10.1079/BJN2002779

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Folic acid treatment reduces elevated plasma levels of asymmetric dimethylarginine in hyperhomocysteinaemic subjects

Kirsten B. Holven^1,2,CA, Tor S. Haugstad³, Torbjørn Holm^1,4, Pål Aukrust^1,5, Leiv Ose² and Marit S. Nenseter^1,2,6
1Research Institute for Internal Medicine University Hospital Rikshospitalet, Oslo, Norway
²The Lipid Clinic, University Hospital Rikshospitalet, Oslo, Norway
³Pediatric Research Institute, University Hospital Rikshospitalet, Oslo, Norway
⁴Department of Cardiology, University Hospital Rikshospitalet, Oslo, Norway
⁵Section of Clinical Immunology and Infection Diseases, Medical Department, University Hospital Rikshospitalet, Oslo, Norway
⁶MSD Cardiovascular Research Centre, University Hospital Rikshospitalet, Oslo, Norway

 (Received 22 March 2002–Revised 13 September 2002–Accepted 3 October 2002)

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been suggested to be a novel risk factor for endothelial dysfunction. It has previously been reported that hyperhomocysteinaemia may be associated with impaired endothelium-dependent vasodilation and reduced plasma level of NO-derived endproducts (NOx). In the present study, plasma levels of arginine and ADMA were measured in twenty-one healthy control subjects, and in twenty-one hyperhomocysteinaemic subjects before and after 6 weeks and 12 months of folic acid supplementation, and compared with previously measured plasma NOx values in the hyperhomocysteinaemic subjects. Compared with control subjects, hyperhomocysteinaemic subjects had higher plasma levels of arginine and ADMA. More importantly, folic acid therapy significantly reduced plasma levels of arginine and ADMA. Furthermore, plasma levels of arginine and ADMA were positively correlated with plasma homocysteine levels and negatively correlated with plasma folate, as well as negatively correlated with plasma NOx. Our results suggest that ADMA may be a mediator of the atherogenic effects of homocysteine.

Abbreviations: ADMA; asymmetric dimethylarginine; NOS; nitric-oxide synthase; NOx; nitric-oxide-derived endproduct

Keywords:
Homocysteine, Folic acid, Asymmetric dimethylarginine, Nitric-oxide-derived endproducts