Eligible for inclusion were randomised controlled trials (RCTs) that compared folic acid or folate (with or without other agents) with placebo (or agents other than folic acid) in adults with familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, a history of colorectal adenomas, or with no increased baseline risk of colorectal cancer. Outcomes had to include the recurrence of adenomas or advanced adenomas or the occurrence of colorectal cancer.
For populations with a history of adenomas, included trials compared: folic acid (0.5mg/day) with aspirin (300mg/day); folic acid (1mg/day) with aspirin (81mg/day or 325mg/day); and folic acid (5mg/day) with placebo. The mean age of participants ranged from 57 to 62 years. The duration of treatment in all trials was three years. Trials were conducted in the UK and USA.
For average-risk or general population studies (at no increased risk of colorectal cancer), the included populations had various conditions, including cardiovascular disease, diabetes and atrophic gastritis; no patients had a history of colorectal cancer nor were they at any greater risk of colorectal cancer than the general population. All trials compared folic acid with placebo: folic acid (2.5mg/day) plus vitamin B6 (50mg/day) plus vitamin B12 (1mg/day) against placebo; folic acid (20mg/day for one year, then 20mg twice weekly for one year) plus vitamin B12 against placebo. The mean age of participants ranged from 55 to 69 years. The duration of treatment ranged from two to seven years. Trials were conducted in China and the USA.
Three reviewers selected studies for inclusion in the review; a fourth reviewer double checked a random subsample of studies. Disagreements were resolved by discussion and consensus.