Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium
Gaksch M, Jorde R, Grimnes G, Joakimsen R, Schirmer H, Wilsgaard T, Mathiesen EB, Njølstad I, Løchen ML, März W, Kleber ME, Tomaschitz A, Grübler M, Eiriksdottir G, Gudmundsson EF, Harris TB, Cotch MF, Aspelund T, Gudnason V, Rutters F, Beulens JW, van 't Riet E, Nijpels G, Dekker JM, Grove-Laugesen D, Rejnmark L, Busch MA, Mensink GB, Scheidt-Nave C, Thamm M, Swart KM, Brouwer IA, Lips P, van Schoor NM, Sempos CT, Durazo-Arvizu RA, Škrabáková Z, Dowling KG, Cashman KD, Kiely M, Pilz S
PloS one · 225 citations
How it was studied
- Design
- Meta-analysis (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- University or hospital
- Karl-Franzens-Universität Graz
- University or hospital
- Medizinische Universität Graz
- Government
- National Institutes of Health
- Government
- Seventh Framework Programme
- Government
- Intramural NIH HHS
- Grants
- National Institutes of Health (Z99 EY999999); Seventh Framework Programme (613977); National Institutes of Health (Z01 EY000401); National Institutes of Health (ZIA EY000401)
Based on 5 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2017-02-16 · PLoS One · vol. 12 · issue 2 · p. e0170791
- Publisher
- Public Library of Science
- Cited
- 355 citations · more than 100% of similar papers · 9.1× the field average
- Impact
- Top 10% most cited in its field
- References
- 46 works
- Access
- Open access (journal) · PUBLIC-DOMAIN
- Research areas
- Vitamin D Research Studies · Vitamin C and Antioxidants Research · Digestive system and related health
- Keywords
- Vitamin D and neurology, Meta-analysis, Medicine, MEDLINE, vitamin D deficiency, Gerontology, Internal medicine, Biology, Biochemistry
- MeSH
- humans, vitamin d deficiency, vitamin d, survival rate, prospective studies, reference standards, aged, middle aged, europe, female, male
41 authors
From AT, NO, DE, CH, IS, US, NL, DK, IE
- Martin GakschMedical University of Graz
- Rolf JordeUiT The Arctic University of Norway
- Guri GrimnesUiT The Arctic University of Norway
- Ragnar Martin JoakimsenUiT The Arctic University of Norway
- Henrik SchirmerUiT The Arctic University of Norway
- Tom WilsgaardUiT The Arctic University of Norway
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC0).
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