Statin myopathy and vitamin D deficiency

A recent editorial provided reasonably convincing evidence that there is a relationship between low vitamin D levels and statin associated muscle symptoms, SAMS (see statin myopathy and vitamin d def athero2017 in dropbox, or  Glueck CJ. Atherosclerosis. 2017; 256: 125). See article for the references.

Details/summary of data:

-- one study showed an inverse relationship between CK levels and vitamin D levels in patients on simvastatin, independent of symptoms

-- a non-blinded study with high-dose vitamin D to normalize serum levels found that up to 95% of 134 patients with SAMS were free of muscle symptoms on reinstating statins, and this continued for up to 24 months later (the last time point measured)

-- another trial of 150 patients with SAMS with a median vitamin D of 21ng/ml and given vitamin D supplements found that 87% were successfully able to restart their statins and remain symptom-free for 24 months

-- a meta-analysis of 2420 patients documented that vitamin D levels tend to be lower in patients with SAMS; several other studies have confirmed that in patients with SAMS and low vitamin D levels, repleting the vitamin D levels leads to about 90% being able to tolerate rechallenge with statins

Commentary:

-- SAMS is quite frequent, varies somewhat depending on the statin use/dose, but is reported in about 10% of patients.

-- Myopathy is also a reasonably common symptom of vitamin D deficiency

-- there are studies which suggest that even those with intolerable muscle symptoms from 3 or more statins, only 43% had muscle symptoms on rechallenge (and 27% had muscle symptoms only on placebo, 17% had symptoms to neither drug). ie, there is likely a pretty big placebo effect. See http://gmodestmedblogs.blogspot.com/2016/04/nonstatin-lipid-lowering-drugs-and.html/ . Though the 90+% success rates with vitamin D noted above are a bit eye-popping.

-- so, a provocative editorial. Clearly, especially in light of the potentially large placebo effect, and in light of the importance of statins in preventing clinical cardiovascular outcomes, there should be a well-designed randomized control trial to assess the true benefit of vitamin D repletion in those with SAMS who are vitamin D deficient. It is notable in several of the uncontrolled studies, increasing vitamin D even in patients with levels in the low 20 ng/ml range was effective, which is actually above what the Endocrine Society defines as deficient, <20 ng/ml. so, it makes sense in future RCTs to look at those patients who have SAMS and with 25-OH vitamin D levels <30 ng/ml or so to see if vitamin D supplementation helps, or perhaps in all-comers to see if there is a 25-OH vitamin D threshold.  The meta-analysis mentioned above found that the difference in vitamin D levels in those with and without SAMS was 28 vs 35 ng/ml.

Bottom line: statins are important for many patients, SAMS is common as is vitamin D deficiency, there are likely other benefits from vitamin D sufficiency anyway, vitamin D supplementation is pretty benign and inexpensive, so to me it seems reasonable at this point to try vitamin D supplementation in patients who are intolerant of statins because of SAMS, even if there baseline levels seem pretty good. 

see http://gmodestmedblogs.blogspot.com/search/label/vitamin%20d for an arry of blogs on vitamin d.