Serum Antioxidant Status and Cause-Specific Mortality in US Adults: Results from the National Health and Nutrition Examination Survey (NHANES) 1999–2002

Abstract

Abstract Objectives Oxidative stress is one of the most important risk factors of non-communicable diseases. Studies on the association of serum antioxidants with mortality in a representative sample of US adults are still limited with inconsistent results. The objective of this study was to examine associations between serum concentrations of antioxidants (vitamins A and E, γ-tocopherol, total carotenoids, and β-carotene) and mortality among US adults. Methods The study cohort included adults aged ≥20 years who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2002, with measured serum antioxidants and mortality follow-up through December 31st, 2015 (N = 10,291). Outcomes were all-cause, cancer, and cardiovascular (CVD) mortality. Cox Proportional Hazards modelling was used to estimate adjusted hazards ratios (aHR) and 95% confidence intervals (CIs) for associations between serum antioxidant levels and mortality. Results Median follow-up was 14.2 years, with 2708 deaths, 556 from CVD, and 471 from cancer. Overall, a high level of vitamin E (>1529.5 ug/dL) was associated with increased risk of all-cause mortality (aHR: 1.3; 95% CI: 1.10, 1.54), while a low carotenoid level (<46.73 ug/dL) was associated with increased risk of all-cause mortality (aHR: 1.25; 95% CI: 0.88, 1.43). Vitamin A, γ-tocopherol, and β-carotene were not associated with mortality. The positive association between vitamin E and all-cause mortality was stronger among non-Hispanic whites (aHR: 1.37; 95% CI: 1.15, 1.65). Among Hispanics, compared to participants with vitamin A levels between 48.41–58.93 (ug/dL), participants in the highest vitamin A quartile (>70.54 ug/dL) had increased risk of all-cause and CVD mortality, while the third quartile (58.94–70.54 ug/dL) had reduced risk of cancer mortality. Among non-Hispanic blacks, total carotenoid levels between 63.60–87.24 (ug/dL) were negatively associated with all-cause mortality and vitamin E levels between 1154.57–1529.54 (ug/dL) were associated with decreased risk of cancer mortality, while high vitamin A levels were associated with increased CVD mortality. Conclusions Findings suggest that optimal levels of serum antioxidants may protect against mortality, with differences between race/ethnicity. Further studies in minority populations are warranted to confirm the findings. Funding Sources N/A.