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Meta-Analysis
. 2014 Jun 17:348:g3656.
doi: 10.1136/bmj.g3656.

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Ben Schöttker  1 , Rolf Jorde  2 , Anne Peasey  3 , Barbara Thorand  4 , Eugène H J M Jansen  5 , Lisette de Groot  6 , Martinette Streppel  6 , Julian Gardiner  3 , José Manuèl Ordóñez-Mena  7 , Laura Perna  8 , Tom Wilsgaard  9 , Wolfgang Rathmann  10 , Edith Feskens  6 , Ellen Kampman  6 , Galatios Siganos  9 , Inger Njølstad  9 , Ellisiv Bøgeberg Mathiesen  11 , Růžena Kubínová  12 , Andrzej Pająk  13 , Roman Topor-Madry  13 , Abdonas Tamosiunas  14 , Maria Hughes  15 , Frank Kee  15 , Martin Bobak  3 , Antonia Trichopoulou  16 , Paolo Boffetta  17 , Hermann Brenner  8 ; Consortium on Health and Ageing: Network of Cohorts in Europe and the United States
Affiliations
Meta-Analysis

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Ben Schöttker et al. 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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Risk ratios of all-cause mortality for bottom versus top quintiles of 25-hydroxyvitamin D concentration in eight cohorts (meta-analysis of individual participant data)
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Fig 2 Risk ratios of cardiovascular mortality in subjects with and without a history of cardiovascular disease (top panel) and of cancer mortality in subjects with and without a history of cancer (bottom panel) for bottom versus top quintiles of 25-hydroxyvitamin D concentration in eight cohorts (meta-analysis of individual participant data)
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Fig 3 Dose-response trend of pooled effect estimates for the comparison of 25-hydroxyvitamin D quintiles (top quintile as reference) with respect to mortality outcomes
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Fig 4 Sex-, age-, and season-specific pooled effect estimates for bottom versus top quintiles of 25-hydroxyvitamin D concentration with respect to all-cause mortality, cardiovascular mortality in subjects without a history of cardiovascular disease (CVD), and cancer mortality in subjects without a history of cancer
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