Vitamin C Intake is Inversely Associated with Cardiovascular Mortality in a Cohort of Spanish Graduates: The SUN Project

Observational studies have found a protective effect of vitamin C on cardiovascular health. However, results are inconsistent, and residual confounding by fiber might be present. The aim of this study was to assess the association of vitamin C with the incidence of cardiovascular disease (CVD) and cardiovascular mortality (CVM) while accounting for fiber intake and adherence to the Mediterranean dietary pattern. We followed up 13,421 participants in the Seguimiento Universidad de Navarra (University of Navarra follow-up) (SUN) cohort for a mean time of 11 years. Information was collected at baseline and every two years through mailed questionnaires. Diet was assessed with a validated semi-quantitative food frequency questionnaire. Incident CVD was defined as incident fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, or death due to any cardiovascular cause. CVM was defined as death due to cardiovascular causes. Events were confirmed by physicians in the study team after revision of medical records. Cox proportional hazard models were fitted to assess the associations of (a) energy-adjusted and (b) fiber-adjusted vitamin C intake with CVD and CVM. We found energy-adjusted vitamin C was inversely associated with CVD and CVM after adjusting for several confounding factors, including fiber from foods other than fruits and vegetables, and adherence to the Mediterranean dietary pattern. On the other hand, when vitamin C was adjusted for total fiber intake using the residuals method, we found a significant inverse association with CVM (HR (95% confidence interval (CI)) for the third tertile compared to the first tertile, 0.30 (0.12-0.72), but not with CVD in the fully adjusted model.