Folic Acid Supplementation in Postpolypectomy Patients in a Randomized Controlled Trial Increases Tissue Folate Concentrations and Reduces Aberrant DNA Biomarkers in Colonic Tissues Adjacent to the Former Polyp Site.

Randomized controlled trial conducted at a single Dublin hospital in adults with adenomatous colorectal polyps after polypectomy. The active folic acid arm included 12 participants, with baseline and 6-month repeat colonoscopy and tissue biomarker assessment.

Folic acid 600 mg/d was given for 6 months in the active treatment arm; the route and exact dosing frequency were not stated. The comparison group received placebo.

Folic acid supplementation improved colonocyte folate status and favorable folate-related DNA biomarkers in tissue adjacent to the former polyp site. In the active arm, adjacent-site colonocyte folate increased by 2.5 pg/10^5 cells versus 0.4 pg/10^5 cells with placebo (P = 0.045), global DNA hypomethylation fell from 1.7 ± 0.1 to 1.0 ± 0.1 (P < 0.001), and uracil misincorporation decreased by 0.5 ± 0.1 over time (P = 0.05), with a greater adjacent-site change than placebo (P = 0.05). Distal-site global DNA hypomethylation also improved with folic acid (P = 0.017), and no adverse events were recorded. Overall, the findings support a tissue-level beneficial effect of folic acid consistent with the field cancerization concept.

The trial was small, with only 12 participants in the folic acid arm and 8 in placebo, limiting precision and generalizability. Follow-up was short at 6 months, and several findings were exploratory and biomarker-based rather than clinical recurrence outcomes. Conduct at a single hospital also limits external validity.