Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma

Interventional study in adults with histologically confirmed colorectal adenoma, conducted at King’s College Hospital in London, United Kingdom, with measurements taken at baseline and after 10 weeks. Dietary folate and alcohol intake were assessed with a food frequency questionnaire, and participants using folic acid or vitamin B12 supplements before study entry were excluded.

Folic acid was given daily for 10 weeks at 400 mg/day. The route of administration was not stated; a placebo comparator was used.

Folic acid supplementation increased DNA methylation and improved folate status in patients with colorectal adenoma. Serum folate increased from 7.4 to 13.4 mg/l (change +6.0, p<0.001), erythrocyte folate from 282 to 443 mg/l (change +161, p<0.001), and plasma homocysteine decreased from 12.2 to 10.7 mmol/l (change -1.5, p=0.04). Leucocyte DNA methylation increased by 31% (95% CI 16-47%; p=0.001) and colonic mucosa DNA methylation increased by 25% (95% CI 11-39%; p=0.02); placebo showed no significant changes. These findings support the conclusion that physiological folic acid intake can reverse DNA hypomethylation.

The intervention was short at 10 weeks and was conducted in a single center among adults with colorectal adenoma, which limits generalizability. Route of administration was not stated, and the colonic [3H] methyl incorporation change did not reach conventional significance (p=0.09).