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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 Jun 17; 348:g3656.BMJ

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.

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.

Links

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Authors+Show Affiliations

Schöttker B
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany b.schoettker@dkfz.de.
Jorde R
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.
Peasey A
Department Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
Thorand B
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Jansen EH
Laboratory for Health Protection Research, National Institute for Public Health and the Environment, 3720 BA Bilthoven, Netherlands.
Groot Ld
Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
Streppel M
Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
Gardiner J
Department Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
Ordóñez-Mena JM
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.
Perna L
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Wilsgaard T
Epidemiology of Chronic Diseases Research Group, Department of community medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway.
Rathmann W
German Diabetes Center, Institute for Biometrics and Epidemiology, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Feskens E
Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
Kampman E
Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
Siganos G
Epidemiology of Chronic Diseases Research Group, Department of community medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway.
Njølstad I
Epidemiology of Chronic Diseases Research Group, Department of community medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway.
Mathiesen EB
Brain and Circulation Research Group, Department of clinical medicine, UiT the Arctic University of Norway, 9037 Tromsø, Norway.
Kubínová R
National Institute of Public Health, Prague, Czech Republic.
Pająk A
Jagiellonian University Medical College, Faculty of Health Sciences, Krakow, Poland.
Topor-Madry R
Jagiellonian University Medical College, Faculty of Health Sciences, Krakow, Poland.
Tamosiunas A
Institute of Cardiology of Lithuanian University of Health Sciences, Kaunas, Lithuania.
Hughes M
UKCRC Centre of Excellence for Public Health, Queens University Belfast, Northern Ireland, UK.
Kee F
UKCRC Centre of Excellence for Public Health, Queens University Belfast, Northern Ireland, UK.
Bobak M
Department Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
Trichopoulou A
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.
Boffetta P
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.
Brenner H
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Consortium on Health and Ageing: Network of Cohorts in Europe and the United States
No affiliation info available

MeSH

Age FactorsAgedCardiovascular DiseasesCohort StudiesEuropeFemaleHumansMaleMiddle AgedNeoplasmsSeasonsSex FactorsUnited StatesVitamin DVitamin D Deficiency

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24938302

Citation

Schöttker, Ben, et al. "Vitamin D and Mortality: Meta-analysis of Individual Participant Data From a Large Consortium of Cohort Studies From Europe and the United States." BMJ (Clinical Research Ed.), vol. 348, 2014, pp. g3656.
Schöttker B, Jorde R, Peasey A, et al. 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:g3656.
Schöttker, B., Jorde, R., Peasey, A., Thorand, B., Jansen, E. H., Groot, L. d., Streppel, M., Gardiner, J., Ordóñez-Mena, J. M., Perna, L., Wilsgaard, T., Rathmann, W., Feskens, E., Kampman, E., Siganos, G., Njølstad, I., Mathiesen, E. B., Kubínová, R., Pająk, A., ... Brenner, H. (2014). Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ (Clinical Research Ed.), 348, g3656. https://doi.org/10.1136/bmj.g3656
Schöttker B, et al. 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 Jun 17;348:g3656. PubMed PMID: 24938302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. AU - Schöttker,Ben, AU - Jorde,Rolf, AU - Peasey,Anne, AU - Thorand,Barbara, AU - Jansen,Eugène H J M, AU - Groot,Lisette de, AU - Streppel,Martinette, AU - Gardiner,Julian, AU - Ordóñez-Mena,José Manuèl, AU - Perna,Laura, AU - Wilsgaard,Tom, AU - Rathmann,Wolfgang, AU - Feskens,Edith, AU - Kampman,Ellen, AU - Siganos,Galatios, AU - Njølstad,Inger, AU - Mathiesen,Ellisiv Bøgeberg, AU - Kubínová,Růžena, AU - Pająk,Andrzej, AU - Topor-Madry,Roman, AU - Tamosiunas,Abdonas, AU - Hughes,Maria, AU - Kee,Frank, AU - Bobak,Martin, AU - Trichopoulou,Antonia, AU - Boffetta,Paolo, AU - Brenner,Hermann, AU - ,, Y1 - 2014/06/17/ PY - 2014/6/19/entrez PY - 2014/6/19/pubmed PY - 2014/8/30/medline SP - g3656 EP - g3656 JF - BMJ (Clinical research ed.) JO - BMJ VL - 348 N2 - 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. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/24938302/Vitamin_D_and_mortality:_meta_analysis_of_individual_participant_data_from_a_large_consortium_of_cohort_studies_from_Europe_and_the_United_States_ DB - PRIME DP - Unbound Medicine ER -