Real-world evidence for the effectiveness of vitamin D supplementation in reduction of total and cause-specific mortality.

Abstract

Meta-analyses of randomized controlled trials (RCTs) have demonstrated the efficacy of vitamin D supplementation for reduced cancer mortality, all-cause mortality, and respiratory tract infections. However, whether and to what extent this translates into effectiveness in real-world practice is unknown. We assessed the association of vitamin D supplement use (as an over-the-counter drug or as part of a multivitamin product), vitamin D deficiency (25-hydroxyvitamin D, 25[OH]D <30 nmol/L), and insufficiency (25[OH]D 30 to <50 nmol/L) with all-cause and cause-specific mortality in 445,601 participants, aged 40-73 years, from the UK Biobank cohort. A total of 4.3% and a 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. A total of 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 supplement 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 supplement users had 11%, 11%, and 29% lower cancer, cardiovascular disease, and respiratory disease mortality than nonusers, respectively (not significant for cardiovascular disease mortality). This large study suggests that in the real world, the efficacy of vitamin D supplements in reducing mortality may be at least as good as observed in RCTs.