Evidence for a U-shaped relationship between prehospital vitamin D status and mortality: a cohort study

J Clin Endocrinol Metab. 2014 Apr;99(4):1461-9. doi: 10.1210/jc.2013-3481. Epub 2014 Jan 13.


Objective: 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.

Design: We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011.

Setting: The study was conducted at two Boston teaching hospitals.

Patients: A total of 24,094 adult inpatients participated in the study.

Intervention: There was no intervention.

Measurements: 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.

Results: 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].

Limitations: A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Diagnostic Tests, Routine
  • Female
  • Hospital Mortality*
  • Hospitalization / statistics & numerical data*
  • Humans
  • Inpatients / statistics & numerical data
  • Male
  • Middle Aged
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / mortality


  • Vitamin D
  • 25-hydroxyvitamin D