Calcifediol: a review of its pharmacological characteristics and clinical use in correcting vitamin D deficiency

Abstract

Background In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D 3 (cholecalciferol) or vitamin D 2 (ergocalciferol). Calcifediol (25-hydroxyvitamin D 3 ) has recently become available more widely. Methods By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D 3 , and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions. Results For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3−10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D 3 in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D 3 , calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D 3 , it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D 3 and thus is less prone to sequestration in adipose tissue. Conclusion Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D 3 for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations.

The role and impact of abnormal vitamin levels in autism spectrum disorders

“…As a steroid hormone, VD, obtained from food, supplements, and sunlight exposure without the biological activity of vitamins D2 or D3, is rapidly hydroxylated by 25-hydroxylase in the liver to form 25-hydroxyvitamin D (25(OH)2D calcitriol), 152 which is synthesized and bound to allow the VD-binding protein to circulate, where it is hydroxylated by the kidneys to produce active 1α,25 dihydroxy VD (calcitriol). 153 The classical biological role of estriol as the active form of VD in controlling calcium and phosphate metabolism in bone health, 154 and previous studies have revealed that VD also regulates cell differentiation, strengthens the immune system, reduces oxidative stress and inflammation, and has neurotrophic effects in addition to its role in bone development.…”

Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis

“…Previous research has highlighted the involvement of VD in various body systems, regulating cell differentiation, enhancing the immune system, reducing oxidative stress and inflammation, and exerting neurotrophic effects. [75][76][77] Organisms in low VD states are more susceptible to oxidative stress and altered neurotransmitter signaling of dopamine and serotonin, leading to abnormal immune responses. 45 These immune responses have been shown to be metabolically abnormal in ASD.…”

Clinical Practice Guidelines of the Latin American Federation of Endocrinology for the use of vitamin D in the maintenance of bone health: recommendations for the Latin American context

“…Comparative clinical trials have shown that calcifediol at doses comparable to those of vitamin D3 induces a more rapid and larger increase in serum 25(OH)D concentrations. In terms of potency, calcifediol is between three and six times more potent than vitamin D3, a factor that may be beneficial when a rapid increase in vitamin D is needed [ 48 ].…”