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Association between vitamin D supplementation and mortality: systematic review and meta-analysis

BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4673 (Published 12 August 2019) Cite this as: BMJ 2019;366:l4673
  1. Yu Zhang, doctoral student1,
  2. Fang Fang, professor2,
  3. Jingjing Tang, doctoral student3,
  4. Lu Jia, associate professor4,
  5. Yuning Feng, resident1,
  6. Ping Xu, associate professor5,
  7. Andrew Faramand, resident6
  1. 1Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
  2. 2West China Hospital, Sichuan University, No 37, Guo Xue Xiang, Chengdu, Sichuan 610041, China
  3. 3Chinese University of Hong Kong, Shenzhen, Guangdong, China
  4. 4Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China
  5. 5Sichuan University Library, Chengdu, Sichuan, China
  6. 6University of Pittsburgh Medical Centre, Pittsburgh, PA, USA
  1. Correspondence to: F Fang fangfang1057{at}outlook.com
  • Accepted 5 July 2019

Abstract

Objective To investigate whether vitamin D supplementation is associated with lower mortality in adults.

Design Systematic review and meta-analysis of randomised controlled trials.

Data sources Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.

Eligibility criteria for selecting studies Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.

Main outcome measures All cause mortality.

Results 52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality.

Conclusions Vitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality.

Study registration PROSPERO registration number CRD42018117823.

Footnotes

  • Contributors: FF and YZ conceived the study and designed the protocol. PX performed the literature search. YZ and LJ selected the studies and extracted the relevant information. JT, YF, and YZ synthesised the data. YZ wrote the first draft of the paper. All authors critically revised successive drafts of the paper and approved the final version. FF and YZ are the study guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This work is supported by the projects of the National Natural Science Foundation of China (No 81100925 and No 81472361) and by the National Key R&D Program of China (No 2018YFA010860004). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the National Natural Science Foundation of China and the National Key R&D Program of China; 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.

  • Ethical approval: Not required.

  • Data sharing: Additional data available from the corresponding author at fangfang1057{at}outlook.com.

  • The lead author (FF) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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