{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:20:10Z","timestamp":1783938010217,"version":"3.55.0"},"reference-count":15,"publisher":"BMJ","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ Case Reports"],"abstract":"<jats:p>The majority of the patients with multiple sclerosis (MS) experience fatigue. Some observations indicate that fatigue and related manifestations concomitant with MS could be associated with an intracellular mild thiamine deficiency. We recruited 15 patients with MS who also experience fatigue and assessed the severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine and thiamine pyrophosphate levels were within normal limit in all the patients, high-dose thiamine therapy administered orally or parenterally led to an appreciable improvement of the fatigue. The absence of apparent decrease in blood thiamine despite the presence of symptoms referable to a mild thiamine deficiency suggests that these patients may have a dysfunction of the mechanisms of intracellular transport or structural enzymatic abnormalities. The administration of large quantities of thiamine was effective in reversing the fatigue in MS, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations.<\/jats:p>","DOI":"10.1136\/bcr-2013-009144","type":"journal-article","created":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T08:34:11Z","timestamp":1373963651000},"page":"bcr2013009144","source":"Crossref","is-referenced-by-count":15,"title":["High dose thiamine improves fatigue in multiple sclerosis"],"prefix":"10.1136","volume":"2013","author":[{"given":"Antonio","family":"Costantini","sequence":"first","affiliation":[{"name":"Department of Neurological Rehabilitation, Villa Immacolata, Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agostino","family":"Nappo","sequence":"additional","affiliation":[{"name":"Department of Neurological Rehabilitation, Villa Immacolata, Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Immacolata","family":"Pala","sequence":"additional","affiliation":[{"name":"Department of Neurological Rehabilitation, Villa Immacolata, Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Zappone","sequence":"additional","affiliation":[{"name":"Department of Neurological Rehabilitation, Villa Immacolata, Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2013,7,16]]},"reference":[{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.1","doi-asserted-by":"crossref","unstructured":"Costantini A Pala MI . Thiamine and fatigue in inflammatory bowel diseases: an open-label pilot study. J Altern Complement Med. Published Online First: 4 Feb 2013. doi:10.1089\/acm.2011.0840","DOI":"10.1089\/acm.2011.0840"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1093\/sleep\/33.8.1061","article-title":"Fatigue in multiple sclerosis: mechanisms, evaluation and treatment","volume":"2013","author":"Braley","year":"2010","journal-title":"Sleep"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.3","unstructured":"World Health Organization. \u00a0 Thiamine deficiency and its prevention and control in major emergencies . Geneva: Department of Nutrition for Heath and Development, WHO; 1999, Report no: WHO\/NHD\/99. 13."},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jns.2008.07.032","article-title":"Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression","volume":"2013","author":"Regenold","year":"2008","journal-title":"J Neurol Sci"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.5","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1365-2990.2008.00987.x","article-title":"Mitochondria and disease progression in multiple sclerosis. 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Application to patients with multiple sclerosis and systemic lupus erythematosus","volume":"2013","author":"Krupp","year":"1989","journal-title":"Arch Neurol"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0378-4347(91)80311-Y","article-title":"Determination of thiamine and its phosphate esters by gradient-elution high-performance liquid chromatography","volume":"2013","author":"Lee","year":"1991","journal-title":"J Chromatogr"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.8","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1472-6904-12-4","article-title":"Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects","volume":"2013","author":"Smithline","year":"2012","journal-title":"BMC Clin Pharmacol"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/ecam\/nek009","article-title":"A review of the biochemistry, metabolism and clinical benefits of thiamin(e) and its derivatives","volume":"2013","author":"Lonsdale","year":"2006","journal-title":"Evid Based Complement Alternat Med"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.10","unstructured":"Fauci S Braunwald E Kasper DL . Harrison \u2018s principles of internal medicine 17th edn., New York: McGraw-Hill, Inc., 1999."},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.11","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1056\/NEJMc0809100","article-title":"Mutation in a thiamine-transporter gene and Wernicke's-like encephalopathy","volume":"2013","author":"Kono","year":"2009","journal-title":"N Engl J Med"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2091-3-8","article-title":"[Mitochondria from cultured cells derived from normal and thiamine-responsive megaloblastic anemia individuals efficiently import thiamine diphosphate]","volume":"2013","author":"Song","year":"2002","journal-title":"BMC Biochem"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.13","first-page":"805","article-title":"[Results of the treatment of multiple sclerosis with cocarboxylase]","volume":"2013","author":"Krysztofiak","year":"1960","journal-title":"Neurol Neurochir Psychiatr Pol"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.14","doi-asserted-by":"crossref","first-page":"483","DOI":"10.5694\/j.1326-5377.2011.tb03068.x","article-title":"Wernicke's encephalopathy in a non-alcoholic patient with a normal blood thiamine level","volume":"2013","author":"Davies","year":"2011","journal-title":"Med J Aust"},{"key":"2025082704062724000_2013.jul16_1.bcr2013009144.15","doi-asserted-by":"crossref","unstructured":"Costantini A Pala MI Colangeli M . Thiamine and spinocerebellar ataxia type 2. BMJ Case Rep. Published Online: 10 Jan 2013. doi:10.1136\/bcr-2012-007302.","DOI":"10.1136\/bcr-2012-007302"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2013-009144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T11:06:33Z","timestamp":1756292793000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2013-009144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,16]]},"references-count":15,"alternative-id":["10.1136\/bcr-2013-009144"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2013-009144","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,16]]}}}