Serum folate concentrations and all-cause, cardiovascular disease and cancer mortality: A cohort study based on 1999–2010 National Health and Nutrition Examination Survey (NHANES)

Background: The relationships between serum folate levels and all-cause, cardiovascular disease (CVD), and cancer mortality are controversial.

Methods: Utilizing 1999–2010 National Health and Nutrition Examination Survey (NHANES) and linked mortality data, we performed a cohort study with 28,845 participants and used Cox proportional hazards models and restricted cubic spline plots to elucidate the dose–response relationships between serum folate status and all-cause, CVD and cancer mortality.

Results: During an average follow-up for 6.2 years, 2821, 545 and 628 deaths were attributed to all-causes, CVD and cancer, respectively. Lower folate levels were associated with increased mortality, with hazards ratios of 1.30 (95% confidence interval [CI]: 1.16–1.47) for all-cause mortality, 1.33 (95% CI: 1.01–1.76) for CVD mortality, and 1.47 (95% CI: 1.16–1.87) for cancer mortality (first quartiles versus second quartiles). A reversed J-shaped pattern was apparently observed in males and younger participants when analyzing all-cause mortality and in younger participants when it comes to CVD and cancer mortality.

Conclusions: Lower folate levels, but not restricted to folate deficiency, are linked with higher rates of all-cause, CVD and cancer mortality. Adverse effects of excess folate as well as age and gender differences on mortality need further investigation.