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

Randomized placebo-controlled trial in adults with histologically confirmed colorectal adenoma recruited from colonoscopy patients in London, United Kingdom. The active folic acid group included 15 participants.

Folic acid was given as 400 mg/day for 10 weeks. The route of administration was not stated; the active arm was compared with placebo.

Folic acid supplementation improved folate status, lowered homocysteine, and was associated with increased DNA methylation markers in leukocytes and colorectal mucosa. In the folic acid group, serum folate increased from 7.4 to 13.4, erythrocyte folate increased from 282 to 443, and plasma homocysteine decreased from 12.2 to 10.7. [3 H] methyl incorporation fell in leucocyte DNA from 748 to 515 Bq/mg DNA (p = 0.05) and in colonic DNA from 602 to 451 Bq/mg DNA (p = 0.09). These findings suggest that folate-related DNA hypomethylation can be reversed by physiological folic acid intake, although larger studies are needed to confirm effects on clinically important cancer outcomes.

The active intervention arm was very small (n = 15) and treatment lasted only 10 weeks, limiting precision and long-term inference. Cancer-related endpoints were not assessed, and the colonic DNA methylation result was borderline and not conventionally significant (p = 0.09). Generalizability is limited to patients with colorectal adenoma, and the source packet reports the folic acid dose in a way that may reflect a unit/reporting issue.