Abstract
BACKGROUND: Vitamin D deficiency is prevailing worldwide and linked to multiple diseases; however, its association with premature mortality remains unknown in the US. METHODS: To investigate the association between serum 25-hydroxyvitamin D or 25(OH)D concentrations and premature mortality and life expectancy in a nationally representative cohort of US adults. We analyzed data of adults aged ≥ 18 years included in the National Health and Nutrition Examination Survey from the Third National Health and Nutrition Examination (NHANES III) (1988 - 1994) and NAHANES (2001 - 2018) with linkage to the National Death Index through December 31, 2019 were investigated. Data were analyzed between July and November in 2024. Serum 25(OH)D was computed as the sum of 25(OH)D3 and 25(OH)D2 concentrations measured by standardized liquid chromatography-tandem mass spectrometry. RESULTS: Totally 62,704 adults (weighted mean [SE] age: 46.0 [0.19] years; 51.2% women; 26,971 non-Hispanic White adults, 14,228 non-Hispanic Black adults, and 12,436 Mexican American adults) were followed up over a median (IQR) of 12.2 (12.0 to 12.5) years, with 6,323 documented premature deaths. Compared to adults with sufficient 25(OH)D (≥ 75.0 nmol/L), multi-adjusted hazard ratio (HR) was 1.18 (95% confidence interval [CI], 1.07 to 1.30), 1.60 (1.42 to 1.79), and 2.29 (1.92 to 2.72) in those with insufficient (50.0 - 74.9 nmol/L), moderately deficient (25.0 - 49.9 nmol/L), and severely deficient 25(OH)D (< 25.0 nmol/L), respectively (P(trend) < 0.001). Corresponding life expectancy at age 50 in each group was 31.3 (31.0 to 31.6), 30.6 (30.3 to 30.9), 29.2 (28.9 to 29.4), and 26.9 (26.7 to 27.2) years, respectively. Equivalently, adults in insufficiency, moderate deficiency, and severe deficiency groups lived on average 0.7 (95% CI: 0.1 to 1.3), 2.1 (1.6 to 2.4), and 4.4 (3.8 to 4.9) fewer years, respectively, at age 50 compared to those in sufficiency group. The association was stronger in women than in man (HRs comparing severely deficient to sufficient 25(OH)D concentrations, 2.67 [2.14 to 3.34] in women and 1.92 [1.42 to 2.58] in men), and in White adults than in Black adults (2.64 [1.95 to 3.56] in White adults and 1.55 [1.20 to 2.01] in Black adults) or in Mexican American adults (2.30 [1.53 to 3.46]) (all P(interaction) < 0.001). CONCLUSIONS: In this national cohort, our findings indicated that compared to sufficiency, deficiency, even moderate, in serum 25(OH)D concentrations could correlate with a significantly increased risk of premature mortality and shortened life expectancy, especially among women and White individuals.