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

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 defi ciency 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 modifi es (and -more importantly -improves) the end points and the related outcomes. According to the current state of scientifi c knowledge, it seems thus reasonable to conclude that lowering homocysteine alone is probably insuffi cient 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 benefi t from a more aggressive treatment of other modifi able risk factors, as recently shown by result of the 5-year Fenofi brate Intervention and Event Lowering in Diabetes (FIELD) trial.

Homocysteine, cysteine, folate and vitamin B12 status in type 2 diabetic patients with chronic kidney disease

“…Perturbations of homocysteine metabolism, particularly intracellular, and subsequently circulating accumulation of homocysteine, i.e. hyperhomocysteinemia (hHcy), are associated with vascular disease risk as well as other pathologies, and the progression of chronic kidney disease (CKD) [1,2]. Moreover, in type 2 diabetes (T2D), hHcy is strongly associated with increased risk of cardiovascular disease (CVD) and mortality [3].…”

Relationship between metformin use, vitamin B12 deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes

“…The drug may interfere with the calcium-dependent absorption of B12 [6,7]. In general, B12 deficiency is a cause of hyperhomocysteinemia [8], which is a risk factor for micro-and macrovascular complications [9][10][11]. However, as far as we are aware, no systematic analysis of the status of B12, homocysteine (HC) and vascular complications in relation to metformin use has been performed in patients with T2DM.…”

Analytical performance and method comparison study of the total homocysteine immunoassay on the AIA 600II analyser

“…Hyperhomocysteinaemia (HHcy) is a well-established independent risk factor for cardiovascular diseases; the role of homocysteinaemia in risk stratification was largely supported by epidemiological studies [1].…”

“…Hyperhomocysteinaemia has recently also been associated with other pathological conditions such as peripheral neuropathy, renal failure, hypotiroidism, Alzheimer disease and other dementias, pregnancy complications and birth defects [1,2].…”