{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T22:14:18Z","timestamp":1791670458256,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008055","name":"Fundaci\u00f3n Eugenio Rodr\u00edguez Pascual","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008061","name":"Fundaci\u00f3n Mutua Madrile\u00f1a","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Mitochondrial encephalomyopathy, lactic acidosis and stroke\u2010like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA mutations. There are no disease\u2010modifying therapies, and treatment remains mainly supportive. It has been shown previously that patients with MELAS syndrome have significantly increased cerebrospinal fluid (CSF) glutamate and significantly decreased CSF glutamine levels compared to controls. Glutamine has many metabolic fates in neurons and astrocytes, and the glutamate\u2013glutamine cycle couples with many metabolic pathways depending on cellular requirements. The aim was to compare CSF glutamate and glutamine levels before and after dietary glutamine supplementation. It is postulated that high\u2010dose oral glutamine supplementation could reduce the increase in glutamate levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This open\u2010label, single\u2010cohort study determined the safety and changes in glutamate and glutamine levels in CSF after 12\u2009weeks of oral glutamine supplementation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine adult patients with MELAS syndrome (66.7% females, mean age 35.8\u2009\u00b1\u20093.2\u2009years) were included. After glutamine supplementation, CSF glutamate levels were significantly reduced (9.77\u2009\u00b1\u20091.21 vs. 18.48\u2009\u00b1\u20091.34\u2009\u03bcmol\/l, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and CSF glutamine levels were significantly increased (433.66\u2009\u00b1\u200915.31 vs. 336.31\u2009\u00b1\u200912.92\u2009\u03bcmol\/l, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.002). A side effect observed in four of nine patients was a mild sensation of satiety. One patient developed mild and transient elevation of transaminases, and another patient was admitted for an epileptic status without stroke\u2010like episode.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study demonstrates that high\u2010dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration Information<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> Identifier: NCT04948138. Initial release 24 June 2021, first patient enrolled 1 July 2021. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04948138\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04948138<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15626","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T12:54:18Z","timestamp":1667652858000},"page":"538-547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["High\u2010dose oral glutamine supplementation reduces elevated glutamate levels in cerebrospinal fluid in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke\u2010like episodes syndrome"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5114-5689","authenticated-orcid":false,"given":"Mar\u00eda 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