Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress.

Published

Journal Article

Elevated plasma homocysteine levels are associated with an increased risk of atherosclerosis and thrombosis, as well as a variety of other pathologies such as birth defects, Alzheimer's disease and other dementias, osteoporosis, diabetes and renal disease. Homocysteine metabolism is catalyzed by a number of enzymes that require B-vitamins as cofactors, and homocysteine levels are particularly responsive to folate status. The predictive power of plasma homocysteine level as a risk factor for atherothrombotic orders raised the appealing hypothesis that reduction of homocysteine levels by vitamin supplementation might result in a commensurate reduction is the risk of atherothrombotic events. Unfortunately, most clinical trials failed to show a significant benefit of vitamin supplementation on cardiovascular events, in spite of significant lowering of plasma homocysteine levels. Thus, it is not clear whether homocysteine actually plays a causal role in many pathologies with which it is associated, or whether it is instead a marker for some other underlying mechanism. A large body of data links hyperhomocysteinemia and folate status with oxidant stress. In this article I review data that suggests that homocysteine not only promotes cellular and protein injury via oxidant mechanisms, but is also a marker for the presence of pathological oxidant stress. Thus, it is possible that hyperhomocysteinemia is not a common primary cause of atherothrombotic disorders in the general population, but rather a marker of systemic or endothelial oxidant stress that is a major mediator of these disorders.

Full Text

Duke Authors

Cited Authors

  • Hoffman, M

Published Date

  • December 2011

Published In

Volume / Issue

  • 77 / 6

Start / End Page

  • 1088 - 1093

PubMed ID

  • 21963358

Pubmed Central ID

  • 21963358

Electronic International Standard Serial Number (EISSN)

  • 1532-2777

International Standard Serial Number (ISSN)

  • 0306-9877

Digital Object Identifier (DOI)

  • 10.1016/j.mehy.2011.09.009

Language

  • eng