title: Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium.
abstract: BACKGROUND
  Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality.
  
  
  METHODS
  In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488.
  
  
  RESULTS
  We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and <30 nmol/L were 1.15 (1.00-1.29), 1.33 (1.16-1.51), and 1.67 (1.44-1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L.
  
  
  CONCLUSIONS
  In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
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authors.lastname: Gaksch
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
authors.forename: Rolf
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authors.lastname: Jorde
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
authors.forename: Guri
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authors.lastname: Grimnes
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
authors.forename: Ragnar
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authors.affiliation: Tromsø Cardiovascular Research Group UNN, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Henrik
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authors.lastname: Schirmer
authors.affiliation: Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Tom
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authors.lastname: Wilsgaard
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
authors.forename: Ellisiv B
authors.initials: EB
authors.lastname: Mathiesen
authors.affiliation: Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
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authors.affiliation: Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Maja-Lisa
authors.initials: ML
authors.lastname: Løchen
authors.affiliation: Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.|Synlab Academy, Mannheim, Germany.|Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Winfried
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authors.lastname: März
authors.affiliation: Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.|Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany.
authors.forename: Marcus E
authors.initials: ME
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authors.affiliation: Department of Cardiology, Medical University of Graz, Graz, Austria.|Specialist Clinic for Rehabilitation Bad Aussee, Bad Aussee, Austria.|Department of Internal Medicine - Cardiology, Charité University Hospital Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Andreas
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authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.|Department of Cardiology, Medical University of Graz, Graz, Austria.|Swiss Cardiovascular Center Bern, Department of Cardiology, Bern University Hospital, Bern, Switzerland.
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authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.
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authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.|Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Thor
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authors.lastname: Aspelund
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland.|Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
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authors.affiliation: Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Femke
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authors.lastname: Rutters
authors.affiliation: Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Joline W J
authors.initials: JW
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authors.affiliation: Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
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authors.initials: E
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authors.affiliation: Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
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authors.affiliation: Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Jacqueline M
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authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Diana
authors.initials: D
authors.lastname: Grove-Laugesen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Rejnmark
authors.affiliation: Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany.
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authors.initials: MA
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authors.affiliation: Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany.
authors.forename: Gert B M
authors.initials: GB
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authors.affiliation: Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany.
authors.forename: Christa
authors.initials: C
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authors.affiliation: Department of Epidemiology and Health Monitoring, Robert Koch Institute, Berlin, Germany.
authors.forename: Michael
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authors.affiliation: Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Karin M A
authors.initials: KM
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authors.affiliation: Department of Health Sciences and the EMGO Institute for Health and Care Research, Faculty of Earth and Life Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ingeborg A
authors.initials: IA
authors.lastname: Brouwer
authors.affiliation: Department of Internal Medicine, Endocrine Section, VU University medical center, Amsterdam, the Netherlands.
authors.forename: Paul
authors.initials: P
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authors.affiliation: Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Natasja M
authors.initials: NM
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authors.affiliation: National Institute of Health Office of Dietary Supplements, Bethesda, Maryland, United States of America.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Sempos
authors.affiliation: Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, Illinois, United States of America.
authors.forename: Ramón A
authors.initials: RA
authors.lastname: Durazo-Arvizu
authors.affiliation: Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
authors.forename: Zuzana
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authors.lastname: Škrabáková
authors.affiliation: Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
authors.forename: Kirsten G
authors.initials: KG
authors.lastname: Dowling
authors.affiliation: Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.|Department of Medicine, University College Cork, Cork, Ireland.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Cashman
authors.affiliation: Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.|Irish Centre for Fetal and Neonatal Translational Research [INFANT], University College Cork, Cork, Ireland.
authors.forename: Mairead
authors.initials: M
authors.lastname: Kiely
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.|Department of Epidemiology and Biostatistics and EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Stefan
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authors.lastname: Pilz
mesh_terms: D000368:Aged; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012015:Reference Standards; D015996:Survival Rate; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000592:standards; D014808:Vitamin D Deficiency / Q000401:mortality* / Q000517:prevention & control
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D