title: Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES.
abstract: BACKGROUND
  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.
  
  
  METHODS
  The study included 15 099 participants aged ≥ 20 years with 3784 deaths.
  
  
  METHODS
  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.
authors.affiliation: Office of Dietary Supplements, National Institutes of Health, Bethesda, Maryland 20816-7517, USA. semposch@mail.nih.gov
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Sempos
authors.forename: Ramón A
authors.initials: RA
authors.lastname: Durazo-Arvizu
authors.forename: Bess
authors.initials: B
authors.lastname: Dawson-Hughes
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Yetley
authors.forename: Anne C
authors.initials: AC
authors.lastname: Looker
authors.forename: Rosemary L
authors.initials: RL
authors.lastname: Schleicher
authors.forename: Guichan
authors.initials: G
authors.lastname: Cao
authors.forename: Vicki
authors.initials: V
authors.lastname: Burt
authors.forename: Holly
authors.initials: H
authors.lastname: Kramer
authors.forename: Regan L
authors.initials: RL
authors.lastname: Bailey
authors.forename: Johanna T
authors.initials: JT
authors.lastname: Dwyer
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.forename: Jaime
authors.initials: J
authors.lastname: Gahche
authors.forename: Paul M
authors.initials: PM
authors.lastname: Coates
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: Picciano
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002112:Calcifediol / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006306:Health Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009752:Nutritional Status; D016012:Poisson Distribution; D012727:Sex Characteristics; D014481:United States / Q000453:epidemiology; D014808:Vitamin D Deficiency / Q000097:blood / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015652:25-Hydroxyvitamin D 2; D002112:Calcifediol