Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial

Abstract

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean AE standard deviation change = 9.7 AE 6.7 and 5.1 AE 3.5 ng/ml in patients treated withThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

A Randomized, Open-Label Study to Assess Efficacy of Weekly Assumption of Cholecalciferol versus Calcifediol in Older Patients with Hypovitaminosis D

“…In conclusion, the present study confirms previous findings from Ruggiero et al, but includes a larger cohort [19] and provides additional evidence regarding the oldest-old population, which is usually underrepresented in clinical trials. Compared to previous findings [16,19], 25OH-vitamin D3 levels in our cohorts are higher at baseline as well as at the three-month follow-up; a possible explanation could be that we excluded all patients with malabsorption and those taking medications that could reduce vitamin D absorption.…”

“…These findings can be explained by the different intestinal absorption kinetics in older patients. Indeed, cholecalciferol is transported by chylomicrons and reaches the bloodstream via lymphatic circulation [ 44 , 45 ], while calcifediol is absorbed more effectively (almost 100%) [ 16 ], as it is transported directly into the bloodstream via the portal vein [ 46 ]. Furthermore, since calcifediol does not require hepatic conversion, it shows a linear relationship between the dose administered and the achieved serum levels [ 18 ].…”

“…Few studies have evaluated differences in the efficacy of the two compounds in correcting vitamin D deficiency among different age groups—mainly young adults and post-menopausal women [ 14 , 15 , 16 , 17 , 18 ]; however, data in the older and oldest-old population are very scarce, and only Ruggiero et al considered a population with a mean age >80 years [ 19 ]. Given the paucity of data for individuals in this specific age range, who are often hospitalized for fragility fractures and would benefit most from vitamin D supplementation, we conducted a prospective, randomized study to evaluate which vitamin D formulation—between cholecalciferol and calcifediol—is the most effective in treating hypovitaminosis D in older adults.…”

Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients

“…Few studies have compared the efficacy of calcifediol and cholecalciferol in increasing serum 25(OH)D levels and have reported similar findings. However, none of them compared monthly doses of both metabolites 33 .…”

“…In fact, calcifediol may have some advantages over native vitamin D3. Thus, the former has a more reliable intestinal absorption (close to 100%) and can more rapidly restore serum concentrations of 25OHD as it does not require hepatic 25-hydroxylation 33 , 51 . In fact, calcifediol is three times more potent than oral cholecalciferol in raising serum 25OHD levels 52 .…”