{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T23:07:44Z","timestamp":1770160064067,"version":"3.49.0"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU next generation","award":["PRIN 2022 2022M9JL3T"],"award-info":[{"award-number":["PRIN 2022 2022M9JL3T"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Vitamin D insufficiency remains common in adults, and supplementation with cholecalciferol (vitamin D3) is widely used to improve circulating 25-hydroxyvitamin D [25(OH)D]. At the same time, circular-economy strategies are increasingly applied to nutraceutical production, including the valorization of fish processing by-products as sources of lipid-soluble bioactives. However, clinical evidence directly comparing fish processing by-product-derived vitamin D3 with conventional synthetic vitamin D3 at commonly used nutritional doses remains limited. D-FISH is a single-center, randomized, double-blind, parallel-group, non-inferiority trial enrolling adults aged 18\u201360 years with a baseline plasma of 25(OH)D 20\u201340 ng\/mL. Participants will be randomized (1:1) to receive either fish processing by-product-derived or synthetic vitamin D3 at the same nutritional dose (600 IU once daily with the evening meal) for 12 weeks. The primary endpoint is the between-group difference in the change in plasma 25(OH)D from day 0 to day 84, assessed against a pre-specified non-inferiority margin of 5 ng\/mL, with analyses conducted in full analysis and per-protocol populations. Secondary endpoints include markers of mineral metabolism (calcium, phosphorus, PTH), fasting lipid profile, anthropometrics, and tolerability\/safety outcomes; early 25(OH)D kinetics will be explored at 72 h, day 7, and day 28. The study will inform biochemical non-inferiority and short-term tolerability but is not powered to evaluate clinical outcomes (NCT07127796).<\/jats:p>","DOI":"10.3390\/jcm15031186","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:48:01Z","timestamp":1770115681000},"page":"1186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The D-FISH Trial: A Randomized, Double-Blind, Non-Inferiority Trial Comparing Fish Processing By-Product-Derived Versus Synthetic Vitamin D3 Supplementation in Adults with Suboptimal 25-Hydroxyvitamin D"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7853-0042","authenticated-orcid":false,"given":"Federica","family":"Fogacci","sequence":"first","affiliation":[{"name":"Hypertension and Cardiovascular Risk Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40100 Bologna, Italy"},{"name":"Italian Society of Nutraceuticals (SINut), 40100 Bologna, Italy"},{"name":"Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum 25240, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2830-3006","authenticated-orcid":false,"given":"Serra \u0130layda","family":"Yerlita\u015f Ta\u015ftan","sequence":"additional","affiliation":[{"name":"Hypertension and Cardiovascular Risk Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40100 Bologna, Italy"},{"name":"Department of Biostatistics, Erciyes University School of Medicine, Kayseri 38039, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7984-7614","authenticated-orcid":false,"given":"Cristina","family":"Scollo","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Unit, IRCCS AOU BO, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Lago","sequence":"additional","affiliation":[{"name":"Hypertension and Cardiovascular Risk Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40100 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Bertini","sequence":"additional","affiliation":[{"name":"Hypertension and Cardiovascular Risk Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40100 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6231-8709","authenticated-orcid":false,"given":"Gianni","family":"Sagratini","sequence":"additional","affiliation":[{"name":"Italian Society of Nutraceuticals (SINut), 40100 Bologna, Italy"},{"name":"Chemistry Interdisciplinary Project (ChIP), School of Pharmacy, University of Camerino, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-3884","authenticated-orcid":false,"given":"Arrigo F. G.","family":"Cicero","sequence":"additional","affiliation":[{"name":"Hypertension and Cardiovascular Risk Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40100 Bologna, Italy"},{"name":"Cardiovascular Medicine Unit, IRCCS AOU BO, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the VITADWASTE Working Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","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. 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