The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias

Myalgias are the most common side effect of statin use and the commonest cause for discontinuing therapy. Vitamin D has known physiologic functions in muscle and vitamin D deficiency is known to cause myalgias, with its correction leading to disappearance of muscle symptoms. The 521T>C SLCO1B1*5 gene polymorphism decreasing function in the gene coding for a liver anion transporter that is responsible for statin uptake has been found to explain the majority of statin-associated muscle symptoms. Patients with statin-associated myalgias have been reported to improve with vitamin D supplementation. We therefore investigated (i) whether repletion of vitamin D in deficient patients with myalgias could lead to tolerance for subsequent statin therapy and (ii) whether vitamin D status modifies the effect of the SLCO1B1*5 genotype on myalgia risk. Using a retrospective cohort of 64 patients in whom 25-hydroxyvitamin D [25(OH) D] had been measured for any reason while on statin therapy, including 46 patients who consented to be genotyped, we found strong evidence showing that repletion of vitamin D in vitamin D deficient patients improved myalgias. Of 21 vitamin D deficient patients with intolerable statin-associated myalgias, 14 of 15 rechallenged with statins were subsequently symptomfree, with one patient experiencing mild and tolerable symptoms, far exceeding expected rates of acquired tolerability with no therapy (p = 0.01). In addition, while the SLCO1B1*5 genotype was associated with a three-fold increased risk of myalgias (p = 0.07), this risk was not found to differ by vitamin D status (p = 0.60).