Possible mechanisms of interaction between statins and vitamin D

Myalgia, the most common statin-related complaint, may affect 10–15% of patients on statins1 and affect patient compliance. There have been several reports regarding the relationship between vitamin D deficiencies and statin-induced myalgia.2–6 In addition, vitamin D levels have been reported to affect the lipid lowering actions of some statins.8,9 The mechanism of these interactions is poorly understood and is believed to contradict the expected action of vitamin D on statin metabolism.7 In a published review,7 authors speculate that vitamin D, by activating CYP3A4, should decrease atorvastatin levels and the efficacy of atorvastatin in reducing total and LDL cholesterol, but the opposite has been observed.8 In this article, we have tried to connect the missing links between the statin metabolism and the actions of vitamin D in inducing statin metabolism. We researched the chemistry and metabolism of the statins especially in terms of the role of Cytochrome P-450 (CYP). Since not all the statins are metabolized similarly, the effect of vitamin D on their metabolism is not universal. ### Vitamin D levels and statin effectiveness Some research data suggest that there is a relationship between vitamin D levels and statin effectiveness. One research has suggested that adequate vitamin D levels >30 nmol/l may be required for atorvastatin to reduce lipid levels8 because 63 vitamin D-deficient patients did not respond to low- or high dose of atorvastatin in terms of total cholesterol or LDL at 12 months while patients with insufficient and normal levels of vitamin D showed expected reduction in cholesterol. In one additional study,9 supplemental vitamin D (800 IU/day) enhanced the effect of atorvastatin therapy on total and LDL cholesterol ( P  < 0.005). ### Vitamin D deficiency and statin myopathy There is also evidence for the relationship of vitamin D deficiency to statin myopathy.2–6 One study3 reported resolution of myalgia (92%) …