Serum Folate and Chronic Disease Risk: Findings from a Cohort of United States Adults

Background: Previous studies have suggested that folate may provide protection against various chronic conditions.

Methods: We examined the effect of serum folate concentration on mortality and chronic disease incidence in a nationally representative sample of 3059 adults of the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study who were first examined from 1971 through 1975 and who were followed for about 19 years through 1992. Proportional hazards regression was used to estimate hazard ratios for the lowest quintile of serum folate compared with the highest quintile for selected causes of death and disease incidence.

Results: The hazards ratio for all-cause mortality was 1.18 (95% CI: 0.91-1.52); for mortality for diseases of the circulatory system, 1.31 (95% CI: 0.82-2.12); and for cancer mortality, 0.99 (95% CI: 0.46-2.11). The hazard ratio for incidence of diseases of the circulatory system was 1.04 (95% CI: 0.86-1.26); and for cancer incidence, 1.00 (95% CI: 0.61-1.66). The hazards ratio for all-cause mortality was 1.26 (95% CI: 1.01-1.57) for participants with a serum folate of <9.3 nmol/l compared with other participants.

Conclusions: Low levels of serum folate may be associated with mortality from all-causes and cardiovascular disease. However, the study lacked power to adequately examine the association between folate and disease-specific endpoints. Additional studies, using serum and other measures of folate nutritional status, are needed to examine the relationship between folate nutrition and other more specifically defined health outcomes.