title: Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States.
abstract: OBJECTIVE
  To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.
  
  
  METHODS
  Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.
  
  
  METHODS
  General population.
  
  
  METHODS
  26,018 men and women aged 50-79 years.
  
  
  METHODS
  All-cause, cardiovascular, and cancer mortality.
  
  
  RESULTS
  25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.
  
  
  CONCLUSIONS
  Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany b.schoettker@dkfz.de.
authors.forename: Ben
authors.initials: B
authors.lastname: Schöttker
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø (UiT) the Arctic University of Norway, 9037 Tromsø, Norway Division of Internal Medicine, University Hospital of North Norway, 9038 Tromsø, Norway.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jorde
authors.affiliation: Department Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Peasey
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.affiliation: Laboratory for Health Protection Research, National Institute for Public Health and the Environment, 3720 BA Bilthoven, Netherlands.
authors.forename: Eugène H J M
authors.initials: EH
authors.lastname: Jansen
authors.affiliation: Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
authors.forename: Lisette de
authors.initials: Ld
authors.lastname: Groot
authors.affiliation: Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
authors.forename: Martinette
authors.initials: M
authors.lastname: Streppel
authors.affiliation: Department Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Gardiner
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany Network Aging Research (NAR), University of Heidelberg, Heidelberg, Germany.
authors.forename: José Manuèl
authors.initials: JM
authors.lastname: Ordóñez-Mena
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Perna
authors.affiliation: Epidemiology of Chronic Diseases Research Group, Department of community medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Wilsgaard
authors.affiliation: German Diabetes Center, Institute for Biometrics and Epidemiology, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.affiliation: Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
authors.forename: Edith
authors.initials: E
authors.lastname: Feskens
authors.affiliation: Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kampman
authors.affiliation: Epidemiology of Chronic Diseases Research Group, Department of community medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway.
authors.forename: Galatios
authors.initials: G
authors.lastname: Siganos
authors.affiliation: Epidemiology of Chronic Diseases Research Group, Department of community medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway.
authors.forename: Inger
authors.initials: I
authors.lastname: Njølstad
authors.affiliation: Brain and Circulation Research Group, Department of clinical medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway.
authors.forename: Ellisiv Bøgeberg
authors.initials: EB
authors.lastname: Mathiesen
authors.affiliation: National Institute of Public Health, Prague, Czech Republic.
authors.forename: Růžena
authors.initials: R
authors.lastname: Kubínová
authors.affiliation: Jagiellonian University Medical College, Faculty of Health Sciences, Krakow, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pająk
authors.affiliation: Jagiellonian University Medical College, Faculty of Health Sciences, Krakow, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Topor-Madry
authors.affiliation: Institute of Cardiology of Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Abdonas
authors.initials: A
authors.lastname: Tamosiunas
authors.affiliation: UKCRC Centre of Excellence for Public Health, Queens University Belfast, Northern Ireland, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Hughes
authors.affiliation: UKCRC Centre of Excellence for Public Health, Queens University Belfast, Northern Ireland, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Kee
authors.affiliation: Department Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Bobak
authors.affiliation: Hellenic Health Foundation, Kaisareias 13 & Alexandroupoleos, Athens 11527, Greece University of Athens, Medical School, Department of Hygiene, Epidemiology and Medical Statistics, Mikras Asias 75 st, Athens 11527, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Hellenic Health Foundation, Kaisareias 13 & Alexandroupoleos, Athens 11527, Greece Institute for Translational Epidemiology and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000401:mortality*; D012621:Seasons; D012737:Sex Factors; D014481:United States; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications / Q000401:mortality*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D