Low serum 25 (OH) vitamin D levels (,32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients

WAQAS AHMED, NASEER KHAN, CHARLES J. GLUECK, SUMAN PANDEY, PING WANG, NAILA GOLDENBERG, MUHAMMAD UPPAL, and SURAJ KHANAL
CINCINNATI, OHIO

(Translational Research 2009;153:11–16)

Overall Summary:

Many patients cannot tolerate statin medications because they develop muscle cramps, pain, and weakness, and sometimes the muscles are tender to touch. We have found that most of these patients are deficient in serum Vitamin D. It appears that Vitamin D deficiency can produce mild muscle injury, and when this is superimposed on mild muscle injury associated with statin medications, then there is a synergistic effect, and the muscles hurt enough (myositis) so that the patients stop life-protecting statin medications. In patients who had statin intolerance because of myositis, and who had concurrent low serum Vitamin D, we reversed the vitamin D deficiency with 50,000 units of Vitamin D once per week or 2000 units per day, and when we restarted the statins, the great majority of patients tolerated them well, without myositis.

Scientific Summary

Our specific aims were to determine whether low serum 25 (OH) vitamin D (D2 1 D3) (,32 ng/mL) was associated with myalgia in statin-treated patients and whether the myalgia could be reversed by vitamin D supplementation while continuing statins.

After excluding subjects who took corticosteroids or supplemental vitamin D, serum 25 (OH) D was measured in 621 statin-treated patients, which consisted of 128 patients with myalgia at entry and 493 asymptomatic patients. The 128 myalgic patients had lower mean 6 standard deviation (SD) serum vitamin D than the 493 asymptomatic patients (28.6 6 13.2 vs 34.2 6 13.8 ng/mL, P , 0.0001), but they did not differ (p . 0.05) by age, body mass index (BMI), type 2 diabetes, or creatine kinase levels.

By analysis of variance, which was adjusted for race, sex, and age, the least square mean (6 standard error [SE]) serum vitamin D was lower in the 128 patients with myalgia than in the 493 asymptomatic patients (28.7 6 1.2 vs 34.3 6 0.6 ng/mL, P , 0.0001). Serum 25 (OH) D was low in 82 of 128 (64%) patients with myalgia versus 214 of 493 (43%) asymptomatic patients (c2 5 17.4, P , 0.0001). Of the 82 vitamin-
D–deficient, myalgic patients, while continuing statins, 38 were given vitamin D (50,000 units/week for 12 weeks), with a resultant increase in serum vitamin D from 20.4 6 7.3 to 48.2 6 17.9 ng/mL (P , 0.0001) and resolution of myalgia in 35 (92%).

We speculate that symptomatic myalgia in statin-treated patients with concurrent vitamin D deficiency may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle.