Folic acid, vitamin B12 supplementation may increase colorectal cancer risk
Supplementation with folic acid and vitamin B12 potentially contributes to an increased risk of colorectal cancer (CRC), according to data from the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial.
B-PROOF included 2,524 individuals (mean age 74 years) randomized to receive 2–3 years daily supplementation with folic acid 400 μg plus vitamin B12 500 μg (n=1,257) vs placebo (control; n=1,267) on fracture incidence. Researchers obtained data on cancer incidence from the Netherlands cancer registry.
A total of 314 individuals were diagnosed with any cancer (13.6 percent in the intervention group vs 11.3 percent in the control group), while 68 developed CRC (3.4 percent in the intervention group vs 2.0 percent in the control group) during a median follow up of 78 months.
Multivariable Cox proportional hazards models showed that compared with placebo, folic acid plus vitamin B12 supplementation was associated with a tendency toward a higher risk of any cancer (hazard ratio [HR], 1.25; 95 percent CI, 1.00–1.57) and a significantly elevated risk of CRC (HR, 1.77; 1.08–2.90).
Exploratory analysis stratified by duration of the treatment (2 vs 3 years) revealed that the risk estimate for CRC was slightly weaker, although still significant, in participants with 2 years of folic acid plus vitamin B12 supplementation (HR, 1.72; 1.03–2.88).
The present data indicate that older adults receiving supplementation with combined folic acid and vitamin B12 have a slight excess risk of developing any cancer but a significantly elevated risk of developing CRC, researchers said, adding that the effect on CRC risk is even more pronounced in compliant individuals.
However, additional investigation is needed to ascertain whether the increased cancer risk is due to an individual effect of folic acid or vitamin-B12, or an interactive effect of both supplements combined, they said.