(AN) Real-World Evidence for The Effectiveness of Vitamin D Supplementation in The Reduction of Total and Cause-Specific Mortality. Results from Half a Million Participants of The UK Biobank Cohort Study

Publication Number: 330

Background: Meta-analyses of randomized controlled trials (RCTs) demonstrated the efficacy of vitamin D supplementation for reduced cancer mortality, all-cause mortality, and respiratory tract infections. However, whether and to which extent this translates into effectiveness in the real world is unknown.

Objectives: To investigate whether the intake of vitamin D supplements is associated with reduced all-cause and cause-specific mortality in real-world settings, and to validate the associations of 25(OH)D levels with mortality outcomes.

Methods: Setting: This prospective cohort study employed 445,601 UK Biobank population recruited between 2006 and 2010, after excluding those without available information on the use of vitamin D or multivitamin supplements, and those who had no measured 25(OH)D at baseline.
Exposure: Intake of vitamin D and/or multivitamin supplement, vitamin D status (categorized by measured 25(OH)D concentration).
Outcomes: All-cause mortality, cause-specific mortality (cardiovascular, cancer, and respiratory mortality).
Statistical analysis: Cox proportional hazard regression was used to assess the associations of vitamin D supplements and vitamin D status with the mortality outcomes, after stepwise adjusting for a range of covariates including sociodemographic, lifestyle, and health-related factors that were identified to be determinants of vitamin D deficiency.

Results: Overall, 4.3% and further 20.4% of the study participants reported regularly taking vitamin D or multivitamin supplements, respectively. Still, the majority had either vitamin D deficiency (21.0%) or insufficiency (34.3%). We detected 49 independent determinants of vitamin D deficiency and vitamin D supplement use, and used them to adjust Cox regression models for all mortality outcomes. 29,107 (6.5%) participants died during a median follow-up time of 11.8 years. Both vitamin D deficiency and insufficiency were strongly associated with all mortality outcomes. Self-reported vitamin D supplements use (83% over-the-counter/17% prescription drugs) and multivitamin intake were significantly associated with 10% and 5% lower all-cause mortality, respectively. Furthermore, regular vitamin D supplements users had 11%, 11% and 29% lower cancer, cardiovascular disease and respiratory disease mortality than non-users, respectively (not significant for cardiovascular disease mortality).

Conclusions: With data from the large, population-based UK Biobank, this study confirmed that the efficacy of vitamin D supplements for all-cause mortality shown in RCTs is similar to real-world data. Furthermore, our study shows that the RCT-based evidence for a protective effect from respiratory tract infections may translate into lower respiratory disease mortality.