{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:19:01Z","timestamp":1782544741632,"version":"3.54.5"},"reference-count":113,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2014the 25-alpha-hydroxylated metabolite\u2014in 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.<\/jats:p>","DOI":"10.3390\/nu11051016","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T08:19:59Z","timestamp":1557389999000},"page":"1016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?"],"prefix":"10.3390","volume":"11","author":[{"given":"Roberto","family":"Cesareo","sequence":"first","affiliation":[{"name":"Unit of Metabolic Diseases, Department of Internal Medicine, S. Maria Goretti Hospital, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6739-4417","authenticated-orcid":false,"given":"Alberto","family":"Falchetti","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Unit for Bone Metabolism Diseases and Diabetes &amp; Lab of Endocrine and Metabolic Research; University of Milan, and EndOsMet, Villa Donatello Private Hospital, 50100 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1417-287X","authenticated-orcid":false,"given":"Roberto","family":"Attanasio","sequence":"additional","affiliation":[{"name":"Endocrinology Service, IRCCS Orthopedic Institute Galeazzi, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-0700","authenticated-orcid":false,"given":"Gaia","family":"Tabacco","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Diabetes, University Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4576-3381","authenticated-orcid":false,"given":"Anda Mihaela","family":"Naciu","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Diabetes, University Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1143-4926","authenticated-orcid":false,"given":"Andrea","family":"Palermo","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Diabetes, University Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1210\/jc.2004-2364","article-title":"Prevalence of vitamin D inadequacy among postmenopausal north American women receiving osteoporosis therapy","volume":"90","author":"Holick","year":"2005","journal-title":"J. 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