{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:26:52Z","timestamp":1787851612077,"version":"build-2784847793"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005860","name":"Helsefonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005860","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background &amp; aims<\/jats:title><jats:p>Fatigue has high negative impact on many patients with primary biliary cholangitis (PBC) and treatment options are limited. Recently we showed favorable effects of four weeks of high-dose thiamine treatment on fatigue in patients with inflammatory bowel disease. We aimed to investigate the effect and safety of high-dose (600\u20131800 mg daily) oral thiamine treatment on chronic fatigue in patients with PBC.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>Randomized, double-blinded, placebo-controlled crossover trial including patients with severe PBC-related fatigue. Participants were allocated 1:1 to either group 1) 4 weeks of high-dose thiamine, 4 weeks of washout, and 4 weeks of placebo; or group 2) 4 weeks of placebo, washout, and high-dose thiamine, respectively. Fatigue severity was quantified using the fatigue subscale of the PBC-40 questionnaire. The primary outcome was a fatigue reduction of \u2265 5 points after 4 weeks of high-dose thiamine treatment.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>We enrolled 36 patients; 34 completed the study. The overall mean reduction in fatigue was 5.0 points (95% CI: 2.5 to 7.5; p &lt; 0.001) for the combined group 1 and group 2. Crossover analysis showed a mean increase in fatigue of 0.3 points (95% CI: -4.2 to 3.8) after high-dose thiamine treatment compared to a 1.4 points (95% CI: 6.2 to \u20133.4) mean reduction after placebo (p = 0.55). Only mild and transient adverse events were recorded.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>Four weeks of high-dose oral thiamine treatment in patients with PBC was well tolerated and safe. However, high-dose thiamine was not superior to placebo in reducing PBC-related fatigue.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Trial registration<\/jats:title><jats:p>The trial was registered in the ClinicalTrials.gov (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04893993\" xlink:type=\"simple\">NCT04893993<\/jats:ext-link>) and EudraCT (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/trial\/2020-004935-26\/results\" xlink:type=\"simple\">2020-004935-26<\/jats:ext-link>).<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0301354","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T17:30:42Z","timestamp":1711733442000},"page":"e0301354","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["High-dose oral thiamine versus placebo for chronic fatigue in patients with primary biliary cholangitis: A crossover randomized clinical trial"],"prefix":"10.1371","volume":"19","author":[{"given":"Palle","family":"Bager","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bossen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-6539","authenticated-orcid":true,"given":"Rasmus","family":"Gantzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Gr\u00f8nb\u00e6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"pone.0301354.ref001","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1111\/jgh.15329","article-title":"Regional variation and temporal trend of primary biliary cholangitis epidemiology: A systematic review and meta-analysis","volume":"36","author":"T 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