Evidence for a U-Shaped Relationship Between Prehospital Vitamin D Status and Mortality: A Cohort Study

Abstract

The objective of the study was to examine the association between prehospital serum 25-hydroxyvitamin D [25(OH)D]and the risk of mortality after hospital admission. We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011. The study was conducted at two Boston teaching hospitals. A total of 24 094 adult inpatients participated in the study. There was no intervention. All patients had serum 25(OH)D measured before hospitalization. The exposure of interest was 25(OH)D categorized as less than 10 ng/mL, 10–19.9 ng/mL, 20–29.9 ng/mL, 30–49.9 ng/mL, 50–59.9 ng/mL, 60–69.9 ng/mL, and 70 ng/mL or greater. The main outcome measure was 90-day mortality. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression with inclusion of potential confounders. After adjustment for age, gender, race (white vs nonwhite), patient type (surgical vs medical), season of 25(OH)D draw, and the Deyo-Charlson index, patients with 25(OH)D levels less than 30 ng/mL or 60 ng/mL or greater had higher odds of 90-day mortality compared with patients with levels of 30–49.9 ng/mL [adjusted OR (95% confidence interval) for 25(OH)D <10 ng/mL, 10–19.9 ng/mL, 20–29.9 ng/mL, 50–59.9 ng/mL, 60–69.9 ng/mL, and ≥70 ng/mL was 2.01 (1.68–2.40), 1.89 (1.64–2.18), 1.34 (1.16–1.56), 0.94 (0.69–1.26), 1.52 (1.03–2.25), and 1.69 (1.09–2.61), respectively, compared with patients with 25(OH)D levels 30–49.9 ng/mL]. A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study. Analysis of 24 094 adult patients showed that 25(OH)D levels less than 20 ng/mL and 60 ng/mL or greater before hospitalization were associated with an increased odds of 90-day mortality. Although previous reports have suggested an association between low vitamin D status and mortality, these data raise the issue of potential harm from high serum 25(OH)D levels, provide a rationale for an upper limit to supplementation, and emphasize the need for caution in the use of extremely high doses of vitamin D among patients.