{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:10:27Z","timestamp":1785859827535,"version":"3.56.0"},"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011306","name":"American Society for Investigative Pathology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008269","name":"Michigan Institute for Clinical and Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Michigan Pandemic Research Recovery"},{"name":"University of Michigan discretionary funds"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The long-term goal of our ongoing studies is to determine if, and to what extent, a multi-mineral product (Aquamin) could benefit individuals with ulcerative colitis (UC). As a step toward achieving that goal, we carried out a pilot 180-day biomarker trial (clinicaltrials.gov ID: NCT03869905) in patients with UC in remission or with mild disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Approach<\/jats:title>\n                    <jats:p>A total of 28 subjects participated in the study. Each subject was randomly assigned to receive either Aquamin for 180 days or placebo for 90 days. At Day-90, placebo subjects crossed over to Aquamin for the final 90 days. At Day-0, -90 and -180, serum samples were analyzed for C-reactive protein (CRP), alkaline phosphatase (ALP), intestine-specific ALP (ALPI), and for biomarkers of bone turnover (osteocalcin, TRAP5b and bone-specific ALP [BALP]). Stool specimens were assessed for fecal calprotectin (fCAL) and colon biopsies were examined histologically by Geboes scoring at the same time points. Each subject underwent DEXA scanning (at Day-0 and Day-180 only). In addition, mass spectrometry-based proteomic assessment was performed using colon biopsies obtained at each time point.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Subjects who received Aquamin for the complete 180-day period (a total of 12) demonstrated improvements in all biomarkers (CRP, fCAL, ALP, ALPI, and Geboes scoring); this was not observed in the placebo group (16 subjects). When cumulative pre-post differences were compared between the Aquamin and placebo groups, Aquamin treatment significantly decreased these differences (a 24% decrease as compared to a 38% increase with placebo, p\u2009=\u20090.0284). Subjects who received Aquamin for 90-days showed intermediary responses. Subjects receiving Aquamin for 180 days also demonstrated increases in bone mineral density (BMD) and bone mineral content (BMC), resulting in a statistically significant increase (7.3%, p\u2009=\u20090.0324) in the hip strength index over the treatment period. This was accompanied by increases in osteocalcin and TRAP5b and a decrease in BALP. The proteomic screen demonstrated upregulation of multiple gut barrier proteins, cell surface transporter molecules and certain proteins with anti-inflammatory potential in response to Aquamin. Aquamin treatment also led to downregulation of several proteins associated with the pro-inflammatory state.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results presented here suggest that the use of a multi-mineral intervention improves disease-related biomarkers in patients with UC. These studies suggest the potential value of the mineral intervention as a low-cost, non-toxic adjuvant therapy for mild UC or for individuals with UC in remission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0337408","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T18:32:07Z","timestamp":1765218727000},"page":"e0337408","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["A multi-mineral intervention to improve disease-related and mechanistic biomarkers in ulcerative colitis patients: Results from a randomized trial"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1361-5357","authenticated-orcid":true,"given":"Muhammad N.","family":"Aslam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle Kim","family":"Turgeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry D.","family":"Appelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Stidham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"McClintock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Moraga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0273-0165","authenticated-orcid":true,"given":"Isabelle","family":"Harber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara J.","family":"Jencks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly M.","family":"McNeely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananda","family":"Sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl J.","family":"Jepsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Varani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"issue":"18","key":"pone.0337408.ref001","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMra1102942","article-title":"Ulcerative colitis","volume":"365","author":"S Danese","year":"2011","journal-title":"N Engl J Med"},{"issue":"10401","key":"pone.0337408.ref002","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"C Le Berre","year":"2023","journal-title":"Lancet"},{"issue":"3","key":"pone.0337408.ref003","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1053\/j.gastro.2013.06.052","article-title":"Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management","volume":"145","author":"JE Eaton","year":"2013","journal-title":"Gastroenterology"},{"issue":"9","key":"pone.0337408.ref004","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1097\/MIB.0000000000000065","article-title":"Hepatobiliary manifestations of inflammatory bowel disease","volume":"20","author":"AJ Yarur","year":"2014","journal-title":"Inflamm Bowel Dis"},{"issue":"1","key":"pone.0337408.ref005","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40169-020-00270-0","article-title":"Bone mineral density is negatively correlated with ulcerative colitis: a systematic review and meta-analysis","volume":"9","author":"T Zhou","year":"2020","journal-title":"Clin Transl Med"},{"issue":"8","key":"pone.0337408.ref006","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1215734","article-title":"Vedolizumab as induction and maintenance therapy for ulcerative colitis","volume":"369","author":"BG Feagan","year":"2013","journal-title":"N Engl J Med"},{"issue":"8","key":"pone.0337408.ref007","first-page":"1188","article-title":"Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. 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