Homocysteine: cholesterol of the 90s?

Homocysteine is a sulfur-containing amino acid generated through the demeth ylation of methionine. It is largely catabolized by trans-sulfuration to cy steine but it may also be remethylated to methionine. Dubbed 'the cholester ol of the 90s' by the-lay press, homocysteine is thought to be thrombophili c and to damage the vascular endothelium. Total plasma homocysteine (tHcy) is now established as a clinical risk factor for coronary artery;disease, a s well as other arterial and venous occlusive disease in adult populations. Regulation of homocysteine is dependent on nutrient intake, especially fol ate, vitamins B-6 and B-12. It is also controlled by common genetic variati ons (polymorphisms) in how vitamins are utilized as cofactors in the reacti ons 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 mu st be taken in assaying tHcy. plasma should be separated shortly after coll ection, to avoid artifactual increases due to synthesis by blood cells in v itro. Reference methods have not been validated and criteria for establishi ng reference ranges should take into account the variable prevalence of phy siological hyperhomocysteinemia. Determination of tHcy should probably be l imited 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 a nd reliability of molecular diagnosis will speed its introduction into clin ical laboratory practice - particularly in relation to diagnosis of thrombo philic disorders. Clinical research initiatives are being driven by the ben efit that should be achieved by correction with vitamin supplements, partic ularly folate and B vitamins, but it must be recognized that prospective co ntrolled studies to validate clinical benefit are only now being initiated. At the moment, it is safe to say that hyperhomocysteinemia is one of the f ew prevalent biochemical risk factors for thromboembolic disease that might be corrected by vitamin supplements. Such a possibility lies behind the gr owing momentum to recommend increased supplements of folate and B vitamins to at-risk population and patient groups today. (C) 1999 Elsevier Science B .V. All rights reserved.