Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: results of a randomized placebo-controlled trial

Background and Purpose— To determine the effect of B vitamin treatment on the incidence of cancer among patients with stroke or transient ischemic attack. Methods— A total of 8164 patients with recent stroke or transient ischemic attack were randomly allocated to double-blind treatment with 1 tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B 6 , 500 μg vitamin B 12 ) and followed for a median of 3.4 years for any cancer as an adverse event. Results— There was no significant difference in the incidence of any cancer among participants assigned B vitamins compared with placebo (4.04% versus 4.59%; risk ratio, 0.86; 95% CI, 0.70–1.07) and no difference in cancer mortality (2.35% versus 2.09%; risk ratio, 1.09; 0.81–1.46). Among 1899 patients with diabetes, the incidence of cancer was higher among participants assigned B vitamins compared with placebo (5.35% versus 3.28%; adjusted risk ratio, 2.21; 1.31–3.73), whereas among 6168 patients without diabetes, the incidence of cancer was lower among participants assigned B vitamins compared with placebo (3.66% versus 5.03%; adjusted risk ratio, 0.67; 0.51–0.87; P for interaction=0.0001). Conclusions— Daily administration of folic acid, vitamin B 6 , and vitamin B 12 to 8164 patients with recent stroke or transient ischemic attack for a median of 3.4 years had no significant effect, compared with placebo, on cancer incidence or mortality. However, a post hoc subgroup analysis raises the hypothesis that folic acid treatment may increase the incidence of cancer among diabetics and reduce the incidence of cancer among nondiabetics with a history of stroke or transient ischemic attack. Clinical Trial Registration— URL: www.clinicaltrials.gov . Unique identifier: NCT00097669. URL: www.controlled-trials.com . Unique identifier: ISRCTN74743444.