Hyperhomocysteinaemia: a critical review of old and new aspects.

Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular (CVD) and neurodegenerative diseases, osteoporotic fractures and pregnancy complications. HHCY is common and is mostly related to B-vitamin deficiency. Retrospective and prospective studies emphasise the causal relationship between HHCY and CVD risk. Some reported vitamin intervention trials, however, did not demonstrate lower risk of CVD after treatment. Confounding factors on the one hand and low subject numbers on the other hand reduced the statistical power of the results. Re-analysis of the VISP study (after excluding renal failure and vitamin B12 status tampering factors), detected a 21% decrease in the risk of stroke. This number has been confirmed by results from the HOPE 2 vitamin intervention trial. A significant decline of stroke-mortality (8 to 16%) has been observed in the USA and Canada after fortification of grain products with folate. Despite negative results from secondary prevention trials regarding the CVD risk reduction there is convincing evidence about the effectiveness of B-vitamin supplementation in lowering the risk of stroke (approximately 20%). Additionally, HHCY was recently linked to the occurrence and severity of chronic heart insufficiency. HHCY is also a risk factor for osteoporotic fractures and vitamin treatment can lower the fracture risk. HHCY predicts the decline in cognitive function with age. Hypomethylation is among the central mechanisms through which HHCY may damage the brain. HHCY and low folate are causal factors for pregnancy complications. In addition to the recommended folate supplementation, vitamin B12 supplementation may also decrease pregnancy complications.