Folic Acid + B12 Lowers Homocysteine

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Semin Thromb Hemost. 2000;26(3):341-8.

Vitamin supplements and cardiovascular risk: review of the

randomized trials of homocysteine-lowering vitamin supplements.

e R, Armitage J.

Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, England.

robert.clarke@...

Epidemiological studies have shown that higher blood homocysteine

levels appear to be associated with higher risks of coronary,

cerebral, and peripheral vascular disease and are inversely related to

blood levels of folate and of vitamin B12 and vitamin B6. However,

observational studies cannot exclude the possibility that elevated

homocysteine levels may be associated with some other factor, rather

than being causally related to vascular disease. Large-scale clinical

trials of sufficient dose and duration of treatment are required to

test this hypothesis, but there was substantial uncertainty about the

optimal vitamin regimen to test in such trials. A meta-analysis of 12

randomized trials of vitamin supplements to lower homocysteine levels

was carried out to determine the optimal dose of folic acid required

to lower homocysteine levels and to assess whether vitamin B12 or

vitamin B6 had additive effects. This meta-analysis demonstrated that

reductions in blood homocysteine levels were greater at higher

pretreatment blood homocysteine levels and at lower pretreatment

folate concentrations. After standardization for a pretreatment

homocysteine concentration of 12 micromol/L and folate concentration

of 12 nmol/L (approximate average concentrations for western

populations), dietary folic acid reduced homocysteine levels by 25%

(95% confidence interval [CI]: 23 to 28%) with similar effects in a

daily dosage range of 0.5 to 5 mg. Vitamin B12 (mean 0.5 mg) produced

an additional reduction in blood homocysteine of 7%, whereas vitamin

B6 (mean 16.5 mg) did not have any significant effect. Hence, in

typical populations, daily supplementation with both 0.5 to 5 mg folic

acid and about 0.5 mg vitamin B12 would be expected to reduce

homocysteine levels by one quarter to one third (from about 12

micromol/L to about 8 to 9 micromol/L). Large-scale randomized trials

of such regimens are now required to determine whether lowering

homocysteine levels by folic acid and vitamin B12, with or without

added vitamin B6, reduces the risk of vascular disease.