Background: Statin therapy is a cornerstone of cardiovascular disease treatment and prevention. Unfortunately, 7%-29% of statin-treated patients complain of muscular fatigue, cramps, and/or pain (statin-associated muscle symptoms [SAMS]). In recent years, the important role of vitamin D in muscle health maintenance has been highlighted. In addition, hypovitaminosis D is very prevalent, and might be a reversible risk factor for SAMS occurrence. Methods: In our controlled intervention study, patients suffering from both SAMS and hypovitaminosis D underwent vitamin D replacement for 6 months. SAMS intensity and its impact on the quality of life were evaluated with a questionnaire during follow-up. A subgroup of patients who were not at the low-density lipoprotein cholesterol (LDL-C) target attempted a statin rechallenge after 3 months. Control subjects, with SAMS only, were not treated. Results: Blood vitamin D levels reached 261% of baseline values. Pain intensity was reduced by 63%, and all life quality indicators improved. At follow-up, percentage variations in SAMS intensity and in vitamin D levels were inversely related (r = 0.57, P = 0.002). In a multiple regression analysis, this association was found to be independent. Among the rechallenge subgroup, 75% successfully tolerated high-intensity statins during the follow-up. The parameters of interest were unchanged in control subjects. Conclusions: In our findings, the amount of increase in vitamin D concentrations is directly related to SAMS improvement. Although randomized studies are needed, 25(OH)D levels can be measured, and eventually supplemented, in all patients suffering from SAMS, and this can be done together with a statin rechallenge after 3 months for patients who are not at the LDL-C target. Register: The study protocol was registered with the EudraCT clinical trial register [ID: 2019-003250-83] in date April 8, 2020.
Keywords: SAMS; dyslipidemia; myalgia; statin; vitamin D.