Homocysteine: cholesterol of the 90s?

Homocysteine is a sulfur-containing amino acid generated through the demethylation of methionine. It is largely catabolized by trans-sulfuration to cysteine but it may also be remethylated to methionine. Dubbed 'the cholesterol of the 90s' by the lay press, homocysteine is thought to be thrombophilic and to damage the vascular endothelium. Total plasma homocysteine (tHcy) is now established as a clinical risk factor for coronary artery disease, as well as other arterial and venous occlusive disease in adult populations. Regulation of homocysteine is dependent on nutrient intake, especially folate, vitamins B6 and B12. It is also controlled by common genetic variations (polymorphisms) in how vitamins are utilized as cofactors in the reactions controlling homocysteine metabolism. Moreover, concentrations are age- and sex-dependent and are altered by renal function, hormonal status, drug intake and a variety of other common clinical factors. Considerable care must be taken in assaying tHcy. Plasma should be separated shortly after collection, to avoid artifactual increases due to synthesis by blood cells in vitro. Reference methods have not been validated and criteria for establishing reference ranges should take into account the variable prevalence of physiological hyperhomocysteinemia. Determination of tHcy should probably be limited to centres with relevant expertise and ability to maintain the high degree of precision required for reliable interpretation. Molecular testing for the genetic polymorphisms is still in the research phase but the ease and reliability of molecular diagnosis will speed its introduction into clinical laboratory practice--particularly in relation to diagnosis of thrombophilic disorders. Clinical research initiatives are being driven by the benefit that should be achieved by correction with vitamin supplements, particularly folate and B vitamins, but it must be recognized that prospective controlled studies to validate clinical benefit are only now being initiated. At the moment, it is safe to say that hyperhomocysteinemia is one of the few prevalent biochemical risk factors for thromboembolic disease that might be corrected by vitamin supplements. Such a possibility lies behind the growing momentum to recommend increased supplements of folate and B vitamins to at-risk population and patient groups today.