The importance of hyperhomocysteinemia as a risk factor for diseases: An overview

Hyperhomocysteinemia is the result of a disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological studies hav e proven, that hyperhomocysteinemia is a risk factor for atherosclerotic ca rdiovascular diseases, stroke, peripheral arterial occlusive disease and ve nous thrombosis. Conflicting results come from prospective studies. Trials which are now in progress may clarify the "causality" of high homocysteine concentrations and will assess the value of homocysteine-lowering therapy. The induction of the atherogenic process by hyperhomocysteinemia seems to b e associated with an alteration of endothelial and smooth muscle cell funct ion leading to an accelerated formation of reactive oxygen species. An incr eased endothelial expression of adhesion molecules will then lead to an enh anced deposition of oxidized LDL in the vessel wall with the formation of f oam cells. Additionally, hyperhomocysteinemia interferes with the coagulati on system and thus also has prothrombotic effects. There is a high prevalence of hyperhomocysteinemia as a sign of a vitamin d eficiency in elderly subjects which strongly increases with age. Elderly pe ople have a high frequency of vitamin B-12 deficiency which can be diagnose d more reliably by the measurement of serum methylmalonic acid (MMA) level than by serum vitamin B-12. Subjects following a strict vegetarian diet als o have a high prevalence of hyperhomocysteinemia caused by functional vitam in B-12 deficiency (increased MMA level). Last but not least, hyperhomocyst einemia is a factor in the pathogenesis of neural tube defects and pre-ecla mpsia. An early diagnosis of vitamin B-12 deficiency is important for the p revention of neurological damages. Homocysteine should be measured in patients with a history of atherothrombo tic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in obese subjects, in elderly people, in postmenopausal women, an d in early pregnancy. A specific diagnosis of an underlying vitamin deficie ncy is important for adequate treatment. Individuals with homocysteine leve l >12 mu mol/l should increase and/or supplement their dietary intake of vi tamins.