Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2017 Feb 16;12(2):e0170791.
doi: 10.1371/journal.pone.0170791. eCollection 2017.

Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Martin Gaksch  1 , Rolf Jorde  2 , Guri Grimnes  2 , Ragnar Joakimsen  2 , Henrik Schirmer  3 , Tom Wilsgaard  4 , Ellisiv B Mathiesen  2 , Inger Njølstad  4 , Maja-Lisa Løchen  4 , Winfried März  5   6   7 , Marcus E Kleber  5   8 , Andreas Tomaschitz  9   10   11 , Martin Grübler  1   9   12 , Gudny Eiriksdottir  13 , Elias F Gudmundsson  13 , Tamara B Harris  14 , Mary F Cotch  15 , Thor Aspelund  13   16 , Vilmundur Gudnason  13   16 , Femke Rutters  17 , Joline W J Beulens  17   18 , Esther van 't Riet  17 , Giel Nijpels  17 , Jacqueline M Dekker  17 , Diana Grove-Laugesen  19 , Lars Rejnmark  19 , Markus A Busch  20 , Gert B M Mensink  20 , Christa Scheidt-Nave  20 , Michael Thamm  20 , Karin M A Swart  17 , Ingeborg A Brouwer  21 , Paul Lips  22 , Natasja M van Schoor  17 , Christopher T Sempos  23 , Ramón A Durazo-Arvizu  24 , Zuzana Škrabáková  25 , Kirsten G Dowling  25 , Kevin D Cashman  25   26 , Mairead Kiely  25   27 , Stefan Pilz  1   17
Affiliations
Meta-Analysis

Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Martin Gaksch et al. PLoS One. .

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.

Findings: 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.

Interpretation: 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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Dose-response trend of hazard ratios of death from all causes by standardized 25-hydroxyvitamin D.
Dose-response trend of hazard ratios of all-cause mortality by standardized 25-hydroxyvitamin D were adjusted for age, sex, body mass index and season of blood drawing concentrations. Hazard ratios [blue line with 95% confidence interval as the dotted blue lines] are referring to the 25-hydroxyvitamin D concentration of 83.4 nmol/L (i.e. the median 25-hydroxyvitamin D concentration for the group with 25-hydroxyvitamin D concentrations from 75 to 99.99 nmol/L).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8. 10.1210/jc.2010-2704 - DOI - PMC - PubMed
    1. Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB,et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev. 2013. August;12(10):976–89. 10.1016/j.autrev.2013.02.004 - DOI - PubMed
    1. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. 10.1210/jc.2011-0385 - DOI - PubMed
    1. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014;2(1):76–89. 10.1016/S2213-8587(13)70165-7 - DOI - PubMed
    1. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035 10.1136/bmj.g2035 - DOI - PMC - PubMed

Publication types

Associated data