Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES

J Clin Endocrinol Metab. 2013 Jul;98(7):3001-9. doi: 10.1210/jc.2013-1333. Epub 2013 May 10.


Context: A reverse J-shaped association between serum 25-hydroxyvitamin D (25[OH]D) concentration and all-cause mortality was suggested in a 9-year follow-up (1991-2000) analysis of the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994).

Objective: Our objective was to repeat the analyses with 6 years additional follow-up to evaluate whether the association persists through 15 years of follow-up.

Participants: The study included 15 099 participants aged ≥ 20 years with 3784 deaths.

Main outcome measure: Relative risk (RR) of death from all causes was adjusted for age, sex, race/ethnicity, and season using 2 Poisson regression approaches: traditional categorical and cubic splines. Results were given for 9 25(OH)D levels: <20, 20 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 74, 75 to 99 (reference), 100 to 119, and ≥ 120 nmol/L.

Results: The reverse J-shaped association became stronger with longer follow-up and was not affected by excluding deaths within the first 3 years of follow-up. Similar results were found from both statistical approaches for levels <20 through 119 nmol/L. Adjusted RR (95% confidence interval [CI]) estimates for all levels <60 nmol/L were significantly >1 compared with the reference group. The nadir of risk was 81 nmol/L (95% CI, 73-90 nmol/L). For 25(OH)D ≥ 120 nmol/L, results (RR, 95% CI) were slightly different using traditional categorical (1.5, 1.02-2.3) and cubic splines approaches (1.2, 0.9-1.4). The association appeared in men, women, adults ages 20 to 64 years, and non-Hispanic whites but was weaker in older adults. The study was too small to evaluate the association in non-Hispanic black and Mexican-American adults.

Conclusions: A reverse J-shaped association between serum 25(OH)D and all-cause mortality appears to be real. It is uncertain whether the association is causal.

Publication types

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

MeSH terms

  • 25-Hydroxyvitamin D 2 / blood*
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Calcifediol / blood*
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Health Surveys
  • Humans
  • Male
  • Middle Aged
  • Mortality*
  • Nutritional Status
  • Poisson Distribution
  • Sex Characteristics
  • United States / epidemiology
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / epidemiology
  • Young Adult


  • 25-Hydroxyvitamin D 2
  • Calcifediol