B vitamins intake and cancer risk: a structured narrative review of evidence on riboflavin, pyridoxine, cobalamin and folate.

Abstract

B vitamins play key roles in one-carbon metabolism, DNA synthesis and methylation, and redox regulation. Their potential association with cancer risk remains debated due to heterogeneous findings and methodological limitations across studies. This structured narrative review aimed to summarize and clinically contextualize the available evidence on the relationship between the intake of vitamins B2 (riboflavin), B6 (pyridoxine), B12 (cobalamin) and folate (vitamin B9) and the risk of selected cancers. A structured literature search was performed in PubMed up to 2 September 2025. Evidence was synthesized narratively, prioritizing meta-analyses (including dose-response meta-analyses) of observational studies, and including randomized controlled trials on B-vitamin supplementation when clinically relevant. Methodological quality and risk of bias were appraised narratively focusing on key domains such as exposure assessment, confounding, selection bias, and outcome assessment. Most evidence derives from observational studies assessing dietary intake and circulating biomarkers. Riboflavin and vitamin B6 intake were generally associated with a reduced risk of colorectal cancer in several meta-analyses, including dose-response analyses. Vitamin B12 showed inconsistent associations across cancer sites, with concerns regarding confounding by diet and baseline nutritional status. Folate intake and folic acid supplementation showed mixed findings, with some evidence suggesting protective effects in specific populations, while randomized trials raised concerns about potential adverse effects in selected contexts and dosages. Overall, heterogeneity across studies was substantial, partly explained by differences in exposure definitions, baseline folate fortification policies, and co-interventions. Available evidence suggests potentially protective associations for riboflavin and vitamin B6-particularly for colorectal cancer-whereas findings for vitamin B12 and folate remain inconsistent and context-dependent. Given relevant methodological limitations and potential biases, further well-designed prospective studies and targeted trials are needed to clarify dose, timing and population-specific effects of B vitamins on cancer risk.