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The most concerning findings come from two trials using folic acid combined with 400500 g/day of B12: Ebbing (2009) found a statistically significant increase in overall cancer incidence (RR 1.21, CI 1.031.41) B-PROOF found an increased risk of colon cancer (HR 2.17, CI 1.263.75) in the per-protocol analysis (Oliai Araghi, 2019)