Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States
BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g3656 (Published 17 June 2014)
Ben Schöttker, postdoctoral scientist1, Rolf Jorde, professor23, Anne Peasey, postdoctoral scientist4, Barbara Thorand, senior researcher in epidemiology5, Eugène H J M Jansen, postdoctoral scientist6, Lisette de Groot, professor of nutrition and ageing7, Martinette Streppel, postdoctoral scientist7, Julian Gardiner, research associate4, José Manuèl Ordóñez-Mena, PhD candidate18, Laura Perna, postdoctoral scientist1, Tom Wilsgaard, professor9, Wolfgang Rathmann, senior researcher in epidemiology10, Edith Feskens, professor7, Ellen Kampman, professor7, Galatios Siganos, research associate9, Inger Njølstad, professor9, Ellisiv Bøgeberg Mathiesen, professor11, Růžena Kubínová, senior researcher12, Andrzej Pająk, professor13, Roman Topor-Madry, senior researcher13, Abdonas Tamosiunas, professor14, Maria Hughes, postdoctoral scientist15, Frank Kee, professor15, Martin Bobak, professor4, Antonia Trichopoulou, professor1617, Paolo Boffetta, professor1618, Hermann Brenner, professor1 on behalf of the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES)
1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
2Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø (UiT) the Arctic University of Norway, 9037 Tromsø, Norway
3Division of Internal Medicine, University Hospital of North Norway, 9038 Tromsø, Norway
4Department Epidemiology and Public Health, University College London, London WC1E 6BT, UK
5Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
6Laboratory for Health Protection Research, National Institute for Public Health and the Environment, 3720 BA Bilthoven, Netherlands
7Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands
8Network Aging Research (NAR), University of Heidelberg, Heidelberg, Germany
9Epidemiology of Chronic Diseases Research Group, Department of community medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway
10German Diabetes Center, Institute for Biometrics and Epidemiology, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
11Brain and Circulation Research Group, Department of clinical medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway
12National Institute of Public Health, Prague, Czech Republic
13Jagiellonian University Medical College, Faculty of Health Sciences, Krakow, Poland
14Institute of Cardiology of Lithuanian University of Health Sciences, Kaunas, Lithuania
15UKCRC Centre of Excellence for Public Health, Queens University Belfast, Northern Ireland, UK
16Hellenic Health Foundation, Kaisareias 13 & Alexandroupoleos, Athens 11527, Greece
17University of Athens, Medical School, Department of Hygiene, Epidemiology and Medical Statistics, Mikras Asias 75 st, Athens 11527, Greece
18Institute for Translational Epidemiology and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Correspondence to: B Schöttker b.schoettker at dkfz.de
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.
Design Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.
Setting General population.
Participants 26 018 men and women aged 50-79 years
Main outcome measures 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.
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