Vitamin D3 (cholecalciferol) is more efficacious than Vitamin D2 (ergocalciferol) at regulating calcium absorption and bone quality in rats.

Differential efficacy of vitamin D2 (D2) versus vitamin D3 (D3) in improving classical functions in target organs remain incompletely understood. Previous studies show contradictory results, with limited comprehensive assessment of functional and molecular outcomes across classical target organs namely intestine, bone and kidney. This study investigated the comparative effects of D2 and D3, administered independently or in combination at different dosages, on these organs using a rat model. Weanling male Sprague-Dawley rats were subjected to a depletion-repletion study design with diets containing D2, D3, combination (D2 +D3), or vitamin D deficient (VDD) diet. Our results demonstrated that vitamin D3 supplementation elevated serum 25(OH)D levels more efficiently compared to vitamin D2, while concurrent D2 administration reduced the potential of D3 to increase 25(OH)D3 levels. Both D2 and D3 maintained serum Ca and PTH in the normal range. Intestinal 45Ca absorption was higher in groups receiving D3-based diets in a dose-dependent manner. Furthermore, D3 supplementation had superior effects on bone length, width and strength compared to D2. Vitamin D3 more effectively reduced trabecular bone area in the rehabilitation phase. Additionally, the expression of genes involved in renal calcium reabsorption (Trpv5, Calbindin-D28k, Pmca1b) and vitamin D metabolism/function (Cubilin, Vdr) were significantly altered in VDD group and better corrected with D3 than D2 during rehabilitation. These findings suggest that vitamin D3 is more efficacious than vitamin D2 in improving blood levels of 25(OH)D and majority of the classical functions. Hence vitamin D3 appears to be the superior choice for both prevention and rehabilitation purposes.