Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?

Abstract

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.

Rapid improvement in vitamin D status with dietary 25-hydroxycholecalciferol in vitamin D insufficient dogs

“…Our results indicate that the potency of 25(OH)D 3 in the HyD ® supplement was more than five times that of D3 for the dietary matrix studied. A greater potency of 25(OH)D 3 relative to D3 for raising plasma 25(OH)D 3 concentration is consistent with prior work in dogs and dosage trials in other species ( 17 , 32 , 43 , 45 , 46 ) .…”

“…Comparatively, alimentary uptake of 25(OH)D 3 is more rapid than that of D3 because it has greater water solubility and intestinal protein-binding capabilities ( 30 , 31 ) . Alimentary 25(OH)D 3 enters circulation more directly relative to D3, first in portal blood then systemic circulation bound to plasma proteins ( 32 ) .…”

Pathophysiological Implication of Vitamin D in Diabetic Kidney Disease

“…Several factors affect vitamin D status, such as sun exposure, skin pigmentation (less pigment allowing to synthesize more previtamin D), time of day, season, area of skin exposed to sunlight, body weight (only 1% of body fat increase was associated with 0.46 ± 0.22 ng/mL reduction in circulating 25(OH)D [51]), latitude, food-related vitamin D intake, and age (older people synthesizing less previtamin D) [48, 52]. Recommended daily intake and tolerable upper intake of vitamin D for adults are 600 IU/day and 4,000 IU/day, respectively [53].…”

Proton Pump Inhibitors and Fractures in Adults: A Critical Appraisal and Review of the Literature

“…PPIs, enhancing gastric pH, could interfere with calcium absorption. It can lead to a negative calcium balance with consequent secondary hyperparathyroidism and increased bone loss [ 5 , 16 , 17 ]. Chonan et al in an animal in vivo evaluation showed that rats on omeprazole therapy presented calcium malabsorption, and the reduction of intestinal pH with dietary lactate prevented the calcium absorption in rats fed with omeprazole [ 18 ].…”