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

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.

Cardiovascular disease risk score derivation and validation in Abu Dhabi, United Arab Emirates. Retrospective Cohort Study

“…This is similar to the results of our study, as the significant association was only with cardiac events but not overall SCVD or mortality. By contrast, in a Mendelian randomization analysis from the UK Biobank, a large-scale, prospective cohort from England, Scotland, and Wales, all-cause mortality increased by 25% for participants with a screening and management could be highly recommended to decrease CAD events attributed to it (26,27). Additionally, debate remains on the best tests for measuring vitamin D and recommended levels of vitamin D intake (28).…”

“…Although this study has a limitation of the lack of information on vitamin D supplementation, a recent Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials found that vitamin D supplementation could reduce CVD events but not CVD or overall mortality. With vitamin D supplementation being recommended for more therapeutic and preventive justification and the high prevalence of vitamin D deficiency in the UAE and the region, its screening and management could be highly recommended to decrease CAD events attributed to it (26,27). Additionally, debate remains on the best tests for measuring vitamin D and recommended levels of vitamin D intake (28).…”

Is Dietary (Food) Supplement Intake Reported in European National Nutrition Surveys?

“…In the VITAL study, supplementation with omega-3 fatty acids and vitamin D did not lessen the risk for cardiovascular events or cancer [13]. On the other hand, there are studies that have shown promising results, such as a possible link to decreased cancer incidence with MVM supplements [74] or supplementation with vitamin D linked with a lower risk of all-cause mortality [75]. Nevertheless, data are inadequate to recommend the use of DSs for the diminution of non-communicable diseases such as CVD events and cancer and all-cause mortality [12,76,77].…”

Evaluating low and high vitamin D levels in Ecuadorian cities from 2018 to 2022: interrupted time series and a cross-sectional study

“…25(OH)D deficiency has been linked to acute and chronic diseases that affect not only the skeletal system but also other physiological systems. Timely treatment for individuals with 25(OH)D deficiency can potentially improve their quality of life and reduce associated health risks 8…”

“…Timely treatment for individuals with 25(OH)D deficiency can potentially improve their quality of life and reduce associated health risks. 8 …”