The crucial question is whether the elevated blood homocysteine level causes cardiovascular disease or whether cardiovascular disease causes the elevated blood homocysteine level. A review of 43 studies found that most cross-sectional and case control studies were able to find an association between blood homocysteine levels and cardiovascular disease risk whereas most prospective studies were not (4). The authors noted that the few prospective studies showing an association included subjects with pre-existing cardiovascular disease.
They concluded that elevated homocysteine levels were a consequence of cardiovascular disease and not a cause of it. By contrast, a more recent meta-analysis of 72 studies of subjects with a genetically determined elevated homocysteine level and 20 prospective studies of normal subjects concluded that there was “strong evidence that the association between homocysteine and cardiovascular disease is causal” (5). The authors concluded that lowering homocysteine levels by 3 μmol/l would reduce the risk of heart disease by 16%.
It has been suggested that coffee consumption elevates homocysteine levels and that abstention from coffee lowers them. While seven cross-sectional studies (6, 7, 8, 9, 10, 11, 12) have shown that coffee consumption is positively associated with plasma total homocysteine concentrations in both men and women, three other cross-sectional studies (13, 14, 15) failed to show any association.
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