Hyperhomocysteinemia in health and disease: where we are now, and where do we go from here?

Abstract

Abstract Homocysteine is a sulfur-containing amino acid, which is synthesized from the precursor methionine through a multi-step process, and then reconverted to methionine or catabolyzed into cysteine. The presence of vitamin B9 (folic acid), vitamin B6 (pyridoxine) and vitamin B12 (cobalamin) is essential in homocysteine metabolism, wherein deficiency of one or more of these nutrients is associated with various degree of hyperhomocysteinemia. There is little doubt that hyperhomocysteinemia is associated with several human disorders, such as cardiovascular disease, neurodegenerative disorders, pregnancy complications and fractures, so that its measurement might be useful for risk assessment. Nevertheless, several randomized homocysteine-lowering therapy trials have failed to show that supplementation with vitamins B substantially modifies (and – more importantly – improves) the end points and the related outcomes. According to the current state of scientific knowledge, it seems thus reasonable to conclude that lowering homocysteine alone is probably insufficient to mitigate the risk of thromboembolic, cardiovascular and neurodegenerative disorders inasmuch as this bizarre amino acid acts in strict synergy with other probably more powerful risk factors. Several lines of evidence suggest, however, that its measurement may be helpful for identifying subjects at greater risk of disease, who may thus benefit from a more aggressive treatment of other modifiable risk factors, as recently shown by result of the 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.