Association of serum vitamin C with all-cause and cause-specific death: Data from National Health and Nutrition Examination Survey (NHANES 2003-2006)

Objectives: The association between levels of circulating vitamin C and mortality remains controversial. The aim of this study was to explore the non-linear association between serum vitamin C levels and all-cause or cause-specific mortality.

Methods: We included 9902 US adults with their serum vitamin C levels from the National Health and Nutrition Examination Survey (NHANES 2003-2006). Their survival information was retrieved from baseline until 2015 using the national death index. Multivariable Cox proportional hazards models were used to show the risk for all-cause or cause-specific death according to baseline serum vitamin C levels. Smooth curve fitting and threshold effect analyses were used to clarify potential nonlinearity.

Results: During a median follow-up of 10.6 y, there were 1558 all-cause deaths, including 320 from cancer, 374 from cardiovascular disease (CVD), and 120 from respiratory diseases. Serum vitamin C levels had a U-shaped relationship with all-cause or CVD-associated mortality. Interestingly, serum vitamin C levels lower than the threshold value (1.06 mg/dL) were negatively associated with all-cause (fully adjusted hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.59-0.86) and CVD (fully adjusted HR, 0.70; 95% CI, 0.47-1.03) mortality. In contrast, serum vitamin C levels higher than the threshold value (1.06 mg/dL) were positively associated with all-cause (fully adjusted HR, 1.33; 95% CI, 1.15-1.54) and CVD (fully adjusted HR, 1.60, 95% CI, 1.23-2.10) mortality, respectively.

Conclusion: Serum vitamin C levels showed a U-shaped relationship with all-cause and CVD-associated deaths among US adults using the NHANES data.