Meta-Analysis

.2023 Apr 7;15(8):1810.

doi: 10.3390/nu15081810.

Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials

Antonio Ruiz-García^{1 2}, Vicente Pallarés-Carratalá^{3 4}, Miguel Turégano-Yedro⁵, Ferran Torres⁶, Víctor Sapena⁶, Alejandro Martin-Gorgojo⁷, Jose M Martin-Moreno^{8 9}

Affiliations

¹ Lipids and Cardiovascular Prevention Unit, Pinto University Health Center, 28320 Madrid, Spain.
² Department of Medicine, European University of Madrid, 28670 Madrid, Spain.
³ Health Surveillance Unit, Castellón Mutual Insurance Union, 12003 Castellón, Spain.
⁴ Department of Medicine, Universitat Jaume I, 12006 Castellón, Spain.
⁵ Aldea Moret Health Center, 10195 Cáceres, Spain.
⁶ Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona Bellaterra, 08193 Barcelona, Spain.
⁷ STI/Dermatology Department, Madrid City Council, 28014 Madrid, Spain.
⁸ Department of Preventive Medicine and Public Health, University of Valencia, 46010 Valencia, Spain.
⁹ Biomedical Research Institute INCLIVA, Clinic University Hospital, 46010 Valencia, Spain.

PMID:37111028
PMCID: PMC10146299
DOI: 10.3390/nu15081810

Meta-Analysis

Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials

Antonio Ruiz-García et al. Nutrients.2023.

.2023 Apr 7;15(8):1810.

doi: 10.3390/nu15081810.

Authors

Antonio Ruiz-García^{1 2}, Vicente Pallarés-Carratalá^{3 4}, Miguel Turégano-Yedro⁵, Ferran Torres⁶, Víctor Sapena⁶, Alejandro Martin-Gorgojo⁷, Jose M Martin-Moreno^{8 9}

Affiliations

¹ Lipids and Cardiovascular Prevention Unit, Pinto University Health Center, 28320 Madrid, Spain.
² Department of Medicine, European University of Madrid, 28670 Madrid, Spain.
³ Health Surveillance Unit, Castellón Mutual Insurance Union, 12003 Castellón, Spain.
⁴ Department of Medicine, Universitat Jaume I, 12006 Castellón, Spain.
⁵ Aldea Moret Health Center, 10195 Cáceres, Spain.
⁶ Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona Bellaterra, 08193 Barcelona, Spain.
⁷ STI/Dermatology Department, Madrid City Council, 28014 Madrid, Spain.
⁸ Department of Preventive Medicine and Public Health, University of Valencia, 46010 Valencia, Spain.
⁹ Biomedical Research Institute INCLIVA, Clinic University Hospital, 46010 Valencia, Spain.

PMID:37111028
PMCID: PMC10146299
DOI: 10.3390/nu15081810

Abstract

Background: The impact of vitamin D supplementation on cardiovascular outcomes and mortality risk reduction remains unclear due to conflicting study findings.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), published between 1983 and 2022, that reported the effect of vitamin D supplementation in adults versus placebo or no treatment on all-cause mortality (ACM), cardiovascular mortality (CVM), non-cardiovascular mortality (non-CVM), and cardiovascular morbidities. Only studies with a follow-up period longer than one year were included. The primary outcomes were ACM and CVM. Secondary outcomes were non-CVM, myocardial infarction, stroke, heart failure, and major or extended adverse cardiovascular events. Subgroup analyses were performed according to low-, fair- and good-quality RCTs.

Results: Eighty RCTs were assessed, including 82,210 participants receiving vitamin D supplementation and 80,921 receiving placebo or no treatment. The participants' mean (SD) age was 66.1 (11.2) years, and 68.6% were female. Vitamin D supplementation was associated with a lower risk of ACM (OR: 0.95 [95%CI 0.91-0.99]p = 0.013), was close to statistical significance for a lower risk of non-CVM (OR: 0.94 [95%CI 0.87-1.00]p = 0.055), and was not statistically associated with a lower risk of any cardiovascular morbi-mortality outcome. Meta-analysis of low-quality RCTs showed no association with cardiovascular or non-cardiovascular morbi-mortality outcomes.

Conclusions: The emerging results of our meta-analysis present evidence that vitamin D supplementation appears to decrease the risk of ACM (especially convincing in the fair- and good-quality RCTs), while not showing a decrease in the specific cardiovascular morbidity and mortality risk. Thus, we conclude that further research is warranted in this area, with well-planned and executed studies as the basis for more robust recommendations.

Keywords: all-cause mortality; cardiovascular mortality; heart failure; major adverse cardiovascular events; meta-analysis; myocardial infarction; stroke; systematic review; vitamin D.

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Conflict of interest statement

The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Figure 1**
PRISMA flowchart of search and selection of RCTs.

**Figure 2**
Forest plot of the effect of vitamin D supplementation on all-cause mortality.

**Figure 3**
Effect of vitamin D supplementation on cardiovascular and non-cardiovascular mortality. (A) Forest plot of cardiovascular mortality. (B) Forest plot of non-cardiovascular mortality.

**Figure 4**
Forest plots of the effect of vitamin D supplementation on cardiovascular outcomes. (A) Effect of vitamin D supplementation on nonfatal myocardial infarction. (B) Effect of vitamin D supplementation on nonfatal stroke (haemorrhagic or ischemic). (C) Effect of vitamin D supplementation on heart failure. (D) Effect of vitamin D supplementation on the composite endpoint of major adverse cardiovascular events (MACE), including cardiovascular mortality, along with fatal and nonfatal myocardial infarction. (E) Effect of vitamin D supplementation on extended MACE, composite endpoint including MACE or coronary revascularization procedures (percutaneous coronary intervention or coronary artery bypass grafting).

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Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials

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Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials

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Conflict of interest statement

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