Methyl Donor Nutrient Intake and Incidence of Type 2 Diabetes: Results From Three Large U.S. Cohorts

OBJECTIVE We examined whether intake of methyl donor nutrients, including vitamins B2, B6, and B12 and folate, from foods and/or supplements is associated with type 2 diabetes risk. RESEARCH DESIGN AND METHODS We included 203,644 women and men from the Nurses’ Health Study (1984–2016), Nurses’ Health Study 2 (1991–2017), and Health Professionals Follow-Up Study (1986–2016). Dietary data were collected every 2–4 years with use of semiquantitative food-frequency questionnaires. Cox proportional hazards models with time-varying covariates were used to evaluate associations between each nutrient and type 2 diabetes risk. We combined cohort-specific hazard ratios (HRs) using inverse variance–weighted fixed-effects meta-analyses. RESULTS During 4,900,181 person-years of follow-up, we documented 19,475 incident type 2 diabetes cases. In multivariable-adjusted meta-analyses, participants in the highest quintiles of total vitamin B2 and B6 intakes had lower risk of diabetes compared with those in the lowest quintiles (HR 0.93 [95% CI 0.89, 0.98] for B2 and 0.93 [0.89, 0.97] for B6). With stratification by source, significant associations remained for B2 from food but not from supplements. Neither association for B6 from food nor association for B6 from supplements attained significance. No association was observed between total B12 intake and diabetes. However, B12 from food was marginally associated with higher diabetes risk (1.05 [1.00–1.11]) but not after additional adjustment for red meat intake (1.04 [0.99–1.10]). No evidence of association was observed between intakes of folate and diabetes. CONCLUSIONS The results of our study suggest that higher intake of vitamin B2 and B6, especially B2 from food sources, may be associated with a modestly lower type 2 diabetes risk.