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Vitamin B12 deficiency and cardiovascular diseases

Over 50,000 subjects worldwide are currently included in intervention trials (secondary prevention) in order to answer the question whether B-vitamins supplementation improves the cardiovascular risk. Several published randomized trials and a meta-analysis indicating that lowering tHcy levels with B-vitamins did not result in cardiovascular benefit (1-3). In general, the clinical validity of secondary prevention trials has significant limitations because all study subjects receive basis medications that interfere with the tHcy lowering by B-vitamins, which makes it difficult to figure out an additional effect by B-vitamins regarding cardiovascular endpoints. The clinical power of large meta-analysis is required to get valid information.

The latest meta-analysis by Wald et al. (4) includes data from 75 studies with 22,068 patients and 23,618 controls and 14 intervention trials with tHcy lowering by B-vitamins that included 39,597 patients who were effected by cardiovascular events. A significant and independent association between plasma tHcy level and the risk for heart and circulatory diseases had been confirmed. Carriers of the TT-genotype of MTHFR gene had compared with carriers of the CC-genotype (wild type) a 16% higher cardiovascular risk whereby the difference in plasma tHcy concentration between TT- and CC-genotype was 1.9 µmol/L in average. Despite tHcy was lowered in the intervention studies of the meta-analysis by 3.3 µmol/L, a decline in the cardiovascular risk was not found. However, in B-vitamin supplementation studies where the use of aspirin was low, the tHcy lowering was associated with a decline of CVD risk by 7%. But in studies with a high rate of aspirin intake a lowering of the cardiovascular risk has not been observed. FA supplementation seems to lower the risk of CVD in primary prevention studies in population not using antiplatelet therapy like aspirin. In secondary prevention, FA supplementation does not seem to provide an additional effect regarding lowering of CVD risk.


1.     Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578-88.
2.     Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-77.
3.     Spence JD, Stampfer MJ. Understanding the complexity of homocysteine lowering with vitamins: the potential role of subgroup analyses. JAMA 2011;306:2610-1.
4.     Wald DS, Morris JK, Wald NJ. Reconciling the evidence on serum homocysteine and ischaemic heart disease: a meta-analysis. PLoS ONE 2011;6:e16473.