Hypovitaminosis D is becoming a notable health problem worldwide. A consensus exists among several different medical societies as to the need for adequate levels of
vitamin D for bone and general health. The correct method by which to restore normal
vitamin D levels is still a matter of debate. Although
cholecalciferol remains the most commonly distributed form of
vitamin D supplementation worldwide, several drugs with
vitamin D activity are available for clinical use, and making the correct selection for the individual patient may be challenging. In this narrative review, we aim to contribute to the current knowledge base on the possible and appropriate use of
calcifediol-the 25-alpha-hydroxylated metabolite-in relation to its chemical characteristics, its biological properties, and its pathophysiological aspects. Furthermore, we examine the trials that have aimed to evaluate the effect of
calcifediol on the restoration of normal
vitamin D levels.
Calcifediol is more soluble than
cholecalciferol in organic
solvents, due to its high polarity. Good intestinal absorption and high affinity for the
vitamin-D-binding protein positively affect the bioavailability of
calcifediol compared with
cholecalciferol. In particular, orally administered
calcifediol shows a much shorter half-life than oral
cholecalciferol. Most findings suggest that oral
calcifediol is about three- to five-fold more powerful than oral
cholecalciferol, and that it has a higher rate of intestinal absorption. Accordingly,
calcifediol can be particularly useful in treating diseases associated with decreased intestinal absorption, as well as
obesity (given its lower trapping in the adipose tissue) and potentially neurological diseases treated with drugs that interfere with the hepatic
cytochrome P-450 enzyme system, resulting in decreased synthesis of
calcifediol. Up to now, there has not been enough clinical evidence for its use in the context of
osteoporosis treatment.