Myositis-myalgia is the most common cause of statin intolerance, leading to 
cessation of statin use, with consequent failure to lower LDL cholesterol to 
target levels for primary and secondary prevention of cardiovascular disease 
(CVD). We hypothesize that symptomatic myositis-myalgia in hypercholesterolemic 
statin-treated patients with concurrent 25 (OH) vitamin D deficiency and statin 
intolerance may reflect a reversible interaction between vitamin D deficiency 
and statins on skeletal muscle. In hypercholesterolemic, vitamin D deficient 
patients, intolerant to statins because of myositis-myalgia, three non-blinded 
clinical case series have uniformly demonstrated that after supplementation with 
oral vitamin D2 which normalizes serum 25 (OH) vitamin D levels, statins can be 
successfully re-instituted in >90% of patients, without recurrent 
myositis-myalgia, with reduction of LDL cholesterol to target levels. 
Empirically, in 68 hypercholesterolemic patients, unable to tolerate≥1 statin 
because of myositis-myalgia, selected by low (<32 ng/ml) serum 25 (OH) vitamin 
D, we have prospectively assessed whether resolution of vitamin D deficiency 
would result in statin tolerance, free of myositis-myalgia. On no statins, 
50,000 units of vitamin D2 was given twice/week for 3 weeks, and was then 
continued once/week. After 3 weeks on vitamin D supplementation, statins were 
restarted, and patients were re-assessed after 3 months on statins while 
continuing vitamin D supplementation. At 3 months follow-up, on vitamin D 
supplementation and re-instituted statins, 62 of 68 (91%) previously 
statin-intolerant patients now tolerated statins well and were asymptomatic 
without myositis-myalgia. In these 68 patients, on vitamin D supplementation and 
statins, mean±SD vitamin D rose from 22±7 to 43±13 ng/ml (p<0.0001), and LDL 
cholesterol fell from 162±55 to 101±35 mg/dl (p<0.0001). Despite published and 
new empirical evidence, the medical establishment has refused to accept the 
hypothesis, requiring placebo-controlled, double-blind studies, none having been 
reported to date. A placebo-controlled, double-blind study is needed to document 
that normalization of serum 25 (OH) vitamin D levels in vitamin D deficient, 
statin intolerant patients would facilitate re-introduction of statins with 
concurrent freedom from myositis-myalgia. The ability to reverse 
myositis-myalgia in vitamin D deficient, statin intolerant, hypercholesterolemic 
patients by vitamin D supplementation would be extraordinarily valuable, 
facilitating reinstitution of statins to lower LDL cholesterol to reduce risk of 
CVD events. We hypothesize that symptomatic myositis-myalgia in 
hypercholesterolemic statin-treated patients with concurrent vitamin D 
deficiency producing statin intolerance may reflect a reversible interaction 
between vitamin D deficiency and statins on skeletal muscle.