Folic acid supplementation ups risk of sessile serrated adenomas/polyps

There are no delayed treatment effects with folic acid supplementation, but it appears to be associated with a higher risk of sessile serrated adenomas/polyps (SSA/Ps), a study has found.

A total of 1,021 participants diagnosed with colorectal adenomas were randomized to 1 mg/d of folic acid (n=516) or placebo (n=505), with or without aspirin. The original 3-year treatment period was extended into a subsequent colonoscopy interval but was stopped prematurely on 1 October 2004.

After the initial 3-year follow-up, 66 participants who extended treatment underwent a second colonoscopic surveillance interval with additional post-treatment follow-up. Information about a subsequent surveillance colonoscopy occurring before completion of follow-up on 31 May 2012 was provided by 490 participants, including 325 who extended treatment.

Conventional adenoma, SSA/P or colorectal cancer was the study endpoint. Risk ratios (RR) and 95 percent confidence intervals (CIs) were adjusted for baseline characteristics associated with availability of follow-up.

Of the participants who extended treatment, 118 (36 percent) in the placebo group and 146 (43 percent) in the folic acid group had any colorectal neoplasia during the second surveillance interval (RR, 1.21, 95 percent CI, 0.99–1.47; p=0.06).

Extended folic acid supplementation was statistically significantly associated with an increased risk of SSA/Ps during the second surveillance interval (RR, 1.94, 1.02–3.68; p=0.04).

No evidence of post-treatment effects were found for any colorectal neoplasia (RR, 1.01, 0.80–1.28; p=0.94). Additionally, there was no longer a statistically significant post-treatment effect for SSA/P (RR, 1.38, 0.59–3.19; p=0.46).

“The Aspirin/Folate Polyp Prevention Study previously found [that] folic acid increased [the] risk of advanced and multiple colorectal adenomas during a surveillance colonoscopy interval starting about 3 years after randomization,” the authors said.