Association Between Vitamin D Supplementation and Statin-Associated Muscle Symptoms: A Systematic Review

Although low vitamin D levels are associated with statin-associated muscle symptoms (SAMS), it remains unclear if vitamin D supplementation leads to symptom improvement.We performed a systematic review to evaluate the association of vitamin D supplementation with resolution of SAMS.We searched Medline (PubMed), Embase and Cochrane Library till 12 December 2021. Full length articles that reported on the association between vitamin D supplementation in adult patients with SAMS were included.We identified 8 interventional studies comprising 669 participants. Majority of the participants were of Caucasian ethnicity and the mean age of participants ranged from 59.5 to 64.8 years old. The studies recruited patients with initial mean pre-treatment vitamin D levels ranging from 17.8 to 22.0ng/mL. Follow up duration ranged from 2 to 24 months and mean post-treatment vitamin D levels ranged from 34.3 to 56.0ng/mL. We found that vitamin D supplementation was associated with improved statin tolerance in 509 out of 606 (83.9%) patients across the 7 studies which reported patient numbers after supplementation (95% CI = 0.81-0.87, I2 = 72% n = 7). None of the studies were randomized controlled trials (RCTs) and hence placebo effect of vitamin D could not be ruled out. Nocebo effect of statin was also not assessed by any of the studies.Vitamin D supplementation in patients with mild-moderate vitamin D insufficiency was associated with improvement of SAMS. However, quantitative efficacy analysis was not possible and this observed association is likely confounded by nocebo and placebo effects. RCTs are required to conclusively assess the utility of vitamin D supplementation in improving SAMS.