Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins?

OBJECTIVES: Low levels of 25-hydroxyvitamin D are associated with higher risk of cardiovascular morbidity and mortality. Large trials demonstrated that statins significantly decrease cardiovascular morbidity and mortality. 7-dehydrocholesterol is the precursor of both cholesterol and vitamin D. The aim of this study was to investigate the possible effect of rosuvastatin on vitamin D metabolism. METHODS: The study was performed in a prospective cohort design. The study group consisted of 91 hyperlipidemic patients who had not been treated with lipid lowering medications. Lipid parameters, 25 hydroxyvitamin-D, 1,25-dihydroxyvitamin D, and bone alkaline phosphatase were obtained at baseline and after 8 weeks of rosuvastatin treatment. RESULTS: None of the subjects withdrew from the study because of the adverse effects. The mean age was 59.9 +/- 12.5 years. The majority of the patients were male (55, 60%). Seventeen patients were diabetic, and 43 patients had systemic hypertension. There was a significant increase in 25-hydroxyvitamin D, from mean 14.0 (range 3.7- 67) to mean 36.3 (range 3.8 -117) ng/ml (p < 0.001), and also an increase of 1,25-dihydroxyvitamin D from mean 22.9 +/- 11.2 to 26.6 +/- 9.3 pg/dl (p = 0.023). Bone alkaline phosphatase decreased after 8 weeks of rosuvastatin treatment, mean 17.7 (range 2.6-214) to mean 9.5 (range 2.3-19.1) u/l (p < 0.001) rosuvastatin treatment. CONCLUSION: This study has shown an effect of rosuvastatin on vitamin D metabolism, with an increase in both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. This may be an important pleiotropic effect whereby rosuvastatin reduces mortality in patients with coronary artery disease. Further studies are needed to clarify the relationship between statins and vitamin D metabolism.

STATIN-D study: comparison of the influences of rosuvastatin and fluvastatin treatment on the levels of 25 hydroxyvitamin D.

Several studies have shown that low 25-hydroxyvitamin D levels are associated with higher risk of cardiovascular disease and an increase in 25-hydroxyvitamin D levels protects against cardiovascular disease. In this study, we aimed to compare the effects of rosuvastatin and fluvastatin on vitamin D metabolism. The study population consisted of 134 hyperlipidemic patients who had not previously been treated with lipid lowering medications. Patients were randomized in a 1:1 ratio to rosuvastatin 10 mg or fluvastatin 80 mg XL during the study. Lipid parameters, 25 hydroxyvitamin-D, and bone alkaline phosphatase (BALP) were obtained at baseline and after 8 weeks of rosuvastatin and fluvastatin treatment. Sixty-nine patients were administered rosuvastatin, and 65 patients fluvastatin. Total Cholesterol and LDL cholesterol decreased after 8 weeks of both rosuvastatin and fluvastatin treatments. Rosuvastatin was significantly more effective than fluvastatin on lowering total (P < 0.001) and LDL cholesterol (P < 0.001). There was a significant increase in 25-hydroxyvitamin D with rosuvastatin treatment (P < 0.001), whereas no significant change in 25-hydroxyvitamin D was observed with fluvastatin treatment. Mean BALP fell from 18.5 to 9.6 u/I (P < 0.001) with rosuvastatin and from 17.0 to 12.8 with fluvastatin (P= 0.004). There was no significant difference in BALP levels between rosuvastatin and fluvastatin treatment (P= 0.368). The present study demonstrated that 25-hydroxyvitamin D levels increased with rosuvastatin treatment; whereas fluvastatin treatment had no effect on 25-hydroxyvitamin D. This disparity could be related to the potency or the bioavailability of these two statins. Further studies are needed to clarify the relationship between statins and the vitamin D physiology.