title: Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress.
abstract: 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.
authors.affiliation: Pathology & Laboratory Medicine Service, Durham VA Medical Center, Durham, NC 27705, USA.
authors.forename: Maureane
authors.initials: M
authors.lastname: Hoffman
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism / Q000503:physiopathology*; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D008954:Models, Biological; D015394:Molecular Structure; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D015415:Biomarkers; D005492:Folic Acid