{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:47:36Z","timestamp":1792799256706,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"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>Background: The aim of this study was to investigate the pharmacokinetic (PK) and safety profile of high-dose vitamin D supplementation, comparing different schedules (daily, weekly, or bi-weekly) in an otherwise healthy vitamin D-deficient population. Methods: Single-center, open-label study on healthy subjects deficient in vitamin D (25 (OH)D &lt; 20 ng\/mL), randomized to receive cholecalciferol (DIBASE\u00ae, Abiogen Pharma, Italy) using three different schedules: Group A: 10,000 IU\/day for eight weeks followed by 1000 IU\/day for four weeks; Group B: 50,000 IU\/week for 12 weeks, Group C: 100,000 IU\/every other week for 12 weeks. Total cumulative doses were: 588,000 IU, 600,000 IU, 600,000 IU. The treatment regimens corresponded to the highest doses allowed for cholecalciferol for the correction of vitamin D deficiency in adults in Italy. Results: mean 25 (OH)D plasma levels significantly increased from baseline 13.5 \u00b1 3.7 ng\/mL to peak values of 81.0 \u00b1 15.0 ng\/mL in Group A, 63.6 \u00b1 7.9 ng\/mL in Group B and 59.4 \u00b1 12 ng\/mL in Group C. On day 28, all subjects showed 25 (OH)D levels \u226520 ng\/mL and 93.1% had 25 (OH)D levels \u226530 ng\/mL. On day 56 and 84, all subjects had 25 (OH)D levels \u226530 ng\/mL. No serious adverse events occurred during the study. Conclusions: normalization of 25 (OH)D serum levels was quickly attained with all the studied regimens. A more refracted schedule provided a higher systemic 25 (OH)D exposure.<\/jats:p>","DOI":"10.3390\/nu12061553","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T10:02:45Z","timestamp":1590660165000},"page":"1553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Pharmacokinetics of Oral Cholecalciferol in Healthy Subjects with Vitamin D Deficiency: A Randomized Open-Label Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-232X","authenticated-orcid":false,"given":"Angelo","family":"Fassio","sequence":"first","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8915-0755","authenticated-orcid":false,"given":"Giovanni","family":"Adami","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9692-2293","authenticated-orcid":false,"given":"Maurizio","family":"Rossini","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Giollo","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-8959","authenticated-orcid":false,"given":"Cristian","family":"Caimmi","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9335-3371","authenticated-orcid":false,"given":"Riccardo","family":"Bixio","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Viapiana","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Milleri","sequence":"additional","affiliation":[{"name":"Centro Ricerche Cliniche di Verona SRL, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Gatti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-3076","authenticated-orcid":false,"given":"Davide","family":"Gatti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Verona, 37131 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1159\/000343104","article-title":"The history of the discovery of vitamin D and its daughter steroid hormone","volume":"61","author":"Norman","year":"2012","journal-title":"Ann. Nutr. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nrendo.2017.31","article-title":"Comparative analysis of nutritional guidelines for vitamin D","volume":"13","author":"Bouillon","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1172\/JCI112134","article-title":"Aging decreases the capacity of human skin to produce vitamin D3","volume":"76","author":"MacLaughlin","year":"1985","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"353","DOI":"10.4065\/81.3.353","article-title":"High prevalence of vitamin D inadequacy and implications for health","volume":"81","author":"Holick","year":"2006","journal-title":"Mayo Clin. Proc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.beem.2018.09.014","article-title":"Vitamin D insufficiency: Definition, diagnosis and management","volume":"32","author":"Bouillon","year":"2018","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.3945\/ajcn.115.120873","article-title":"Vitamin D deficiency in Europe: Pandemic?","volume":"103","author":"Cashman","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1007\/s00394-017-1564-2","article-title":"A systematic review of vitamin D status in southern European countries","volume":"57","author":"Manios","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions","volume":"40","author":"Bouillon","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/09513590.2020.1731452","article-title":"Vitamin D supplementation: Much ado about nothing","volume":"36","author":"Gatti","year":"2020","journal-title":"Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wylon, K., Drozdenko, G., Krannich, A., Heine, G., D\u00f6lle, S., and Worm, M. (2017). Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169620"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/ejcn.2013.278","article-title":"Pharmacokinetics of daily versus monthly vitamin D3 supplementation in non-lactating women","volume":"68","author":"Meekins","year":"2014","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/jbmr.3122","article-title":"Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial","volume":"32","author":"Rahme","year":"2017","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.bone.2018.02.024","article-title":"Comparison of the effect of daily versus bolus dose maternal vitamin D3 supplementation on the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio","volume":"110","author":"Ketha","year":"2018","journal-title":"Bone"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00198-007-0465-2","article-title":"Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents","volume":"19","author":"Chel","year":"2008","journal-title":"Osteoporos. Int. J. Establ. Result Coop. Eur. Found. Osteoporos. Natl. Osteoporos. Found. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1917789","DOI":"10.1001\/jamanetworkopen.2019.17789","article-title":"Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis","volume":"2","author":"Yao","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"i6583","DOI":"10.1136\/bmj.i6583","article-title":"Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data","volume":"356","author":"Martineau","year":"2017","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1093\/annonc\/mdz059","article-title":"Vitamin D supplementation and total cancer incidence and mortality: A meta-analysis of randomized controlled trials","volume":"30","author":"Keum","year":"2019","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_19","unstructured":"(2020, May 20). DIBASE, Summary of Product 2017, Available online: https:\/\/farmaci.agenziafarmaco.gov.it\/aifa\/servlet\/PdfDownloadServlet?pdfFileName=footer_000972_036635_RCP.pdf&retry=0&sys=m0b1l3."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Galior, K., Grebe, S., and Singh, R. (2018). Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports. Nutrients, 10.","DOI":"10.3390\/nu10080953"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/labmed\/lmx077","article-title":"Vitamin D Toxicity: A 16-Year Retrospective Study at an Academic Medical Center","volume":"49","author":"Lee","year":"2018","journal-title":"Lab. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/bcp.13573","article-title":"A review of the growing risk of vitamin D toxicity from inappropriate practice","volume":"84","author":"Taylor","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Endocrine Society Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1210\/jc.2018-01414","article-title":"Controversies in Vitamin D: Summary Statement From an International Conference","volume":"104","author":"Giustina","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/ajcn\/87.6.1738","article-title":"25-Hydroxylation of vitamin D3: Relation to circulating vitamin D3 under various input conditions","volume":"87","author":"Heaney","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"De Niet, S., Coffiner, M., Da Silva, S., Jandrain, B., Souberbielle, J.-C., and Cavalier, E. (2018). A Randomized Study to Compare a Monthly to a Daily Administration of Vitamin D3; Supplementation. Nutrients, 10.","DOI":"10.3390\/nu10060659"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1152\/physrev.00014.2015","article-title":"Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects","volume":"96","author":"Christakos","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1093\/ajcn\/69.5.842","article-title":"Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety","volume":"69","author":"Vieth","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jsbmb.2017.01.021","article-title":"Vitamin D supplementation guidelines","volume":"175","author":"Pludowski","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1053\/ajkd.2000.8984","article-title":"Vitamin D deficiency is implicated in reduced serum albumin concentrations in patients with end-stage renal disease","volume":"36","author":"Yonemura","year":"2000","journal-title":"Am. J. Kidney Dis. Off. J. Natl. Kidney Found."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s40519-016-0312-6","article-title":"Vitamin D: Not just the bone. Evidence for beneficial pleiotropic extraskeletal effects","volume":"22","author":"Caprio","year":"2017","journal-title":"Eat. Weight Disord. EWD"},{"key":"ref_32","first-page":"452","article-title":"Vitamin D: Not just bone, but also immunity","volume":"107","author":"Gatti","year":"2016","journal-title":"Minerva Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.clinbiochem.2017.08.015","article-title":"The investigation of interferences in immunoassay","volume":"50","author":"Ward","year":"2017","journal-title":"Clin. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1258\/acb.2011.011073","article-title":"Analytical error and interference in immunoassay: Minimizing risk","volume":"48","author":"Sturgeon","year":"2011","journal-title":"Ann. Clin. Biochem."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/6\/1553\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:33:02Z","timestamp":1760175182000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/6\/1553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,27]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["nu12061553"],"URL":"https:\/\/doi.org\/10.3390\/nu12061553","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,27]]}}}