AbstractBackgroundLow vitamin D serum levels have been associated with unfavourable lipid profile and poorer response to atorvastatin. Aims of this study were to test the effects of 25‐hydroxyvitamin D3 (calcifediol) compared to parental vitamin D3 (cholecalciferol) supplementation on modifications of plasma 25(OH)D levels and lipid profile.Materials and methodsFifty‐seven postmenopausal women (aged 59·03 ± 6·73 years) who were at low risk of fracture and with basal plasma 25(OH)D < 30 ng/mL were included if they were on atorvastatin treatment prescribed as appropriate. Recruited women were randomized to receive oral calcifediol or cholecalciferol, both at a dose of 140 μg according to a weekly regimen.ResultsAt baseline, 25(OH)D was negatively associated with BMI (r = −0·37; P = 0·004), total cholesterol (r = −0·31; P = 0·01) and LDL‐C (r = −0·32; P = 0·02). After 24 weeks, 25(OH)D increased significantly in both groups (P < 0·001), although higher levels were obtained with calcifediol as compared with cholecalciferol (P < 0·001). Only in the calcifediol group, a significant reduction of LDL‐C (P = 0·01) and an increase of HDL‐C (P = 0·02) were obtained, even after adjustment for age, and baseline BMI, 25(OH)D and lipid levels (P < 0·05). The percentage changes in 25(OH)D levels were associated with the variations of LDL‐C (r = −0·44; P = 0·01) and HDL‐C levels (r = 0·30; P = 0·10).ConclusionCalcifediol administration in osteopenic and dyslipidemic postmenopausal women with low 25(OH)D improves lipid profile when added to an ongoing atorvastatin treatment.