Folic Acid Prevents the Initial Occurrence of Sporadic Colorectal Adenoma in Chinese Older than 50 Years of Age: A Randomized Clinical Trial

This was a multicenter randomized clinical trial in Chinese adults aged 50 to 80 years who had no colorectal adenoma on at least two prior colonoscopies and whose last colonoscopy was within 1 year before recruitment. The active folic acid arm had a mean age of 60.79 years, 50.92% male participants, and baseline plasma folate of 5.04 ng/mL.

Folic acid was given orally as 1 mg/day tablets for 3 years. The active regimen was compared with treatment without folic acid (multivitamin tablets containing no folate).

Folic acid 1 mg/day reduced the first occurrence of sporadic colorectal adenoma over 3 years. Any colorectal adenoma occurred in 64 participants (14.88%) in the folic acid group versus 132 (30.70%) in control, RR 0.49, 95% CI 0.37-0.63, P < 0.01. Benefits were also seen for left-sided adenoma, 42 vs 78 (9.77% vs 18.14%), RR 0.54, 95% CI 0.38-0.76, P = 0.001, and advanced adenoma, 8 vs 22 (1.86% vs 5.17%), RR 0.36, 95% CI 0.16-0.81, P = 0.01. Right-sided adenoma was not statistically significant, 16 vs 29 (3.72% vs 6.74%), RR 0.55, 95% CI 0.30-1.00, P = 0.07, and colorectal cancer was unchanged, 2 vs 2, RR 1.00, 95% CI 0.14-7.07, P = 1.00.

The follow-up was limited to 3 years, and the main endpoint was adenoma detection rather than colorectal cancer incidence. The study population was restricted to Chinese adults over 50 with repeated negative colonoscopies, which limits generalizability. Some safety reporting was brief, and several subgroup outcomes were not statistically significant.