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

Published online by Cambridge University Press:  09 March 2007

Kirsten B. Holven ,
Tor S. Haugstad ,
Torbjørn Holm ,
Pål Aukrust ,
Leiv Ose  and
Marit S. Nenseter
Kirsten B. Holven*
Affiliation:
Research Institute for Internal Medicine University Hospital Rikshospitalet, Oslo, Norway The Lipid Clinic, University Hospital Rikshospitalet, Oslo, Norway
Tor S. Haugstad
Affiliation:
Pediatric Research Institute, University Hospital Rikshospitalet, Oslo, Norway
Torbjørn Holm
Affiliation:
Research Institute for Internal Medicine University Hospital Rikshospitalet, Oslo, Norway Department of Cardiology, University Hospital Rikshospitalet, Oslo, Norway
Pål Aukrust
Affiliation:
Research Institute for Internal Medicine University Hospital Rikshospitalet, Oslo, Norway Section of Clinical Immunology and Infection Diseases, Medical Department, University Hospital Rikshospitalet, Oslo, Norway
Leiv Ose
Affiliation:
The Lipid Clinic, University Hospital Rikshospitalet, Oslo, Norway
Marit S. Nenseter
Affiliation:
Research Institute for Internal Medicine University Hospital Rikshospitalet, Oslo, Norway The Lipid Clinic, University Hospital Rikshospitalet, Oslo, Norway Section of Clinical Immunology and Infection Diseases, Medical Department, University Hospital Rikshospitalet, Oslo, Norway
*
*Corresponding author: Dr Kirsten B. Holven, fax +47 2307 3630, email kirsten.holven@basalmed.uio.no
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Abstract

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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.

Keywords

HomocysteineFolic acidAsymmetric dimethylarginineNitric-oxide-derived endproducts
Type
Research Article
Information
British Journal of Nutrition , Volume 89 , Issue 3 , March 2003 , pp. 359 - 363
Copyright
Copyright © The Nutrition Society 2003

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