{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T21:56:18Z","timestamp":1773093378809,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T00:00:00Z","timestamp":1568419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013220","name":"Ultragenyx Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To study if treatment with triheptanoin, a 7\u2010carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen\u2010dependent expansion of tricarboxylic acid cycle (TCA), which may restrict fat oxidation. We hypothesized that triheptanoin metabolism generates substrates for the TCA, which potentially boosts fat oxidation and improves exercise tolerance in McArdle disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Double\u2010blind, placebo\u2010controlled, crossover study in patients with McArdle disease completing two treatment periods of 14\u00a0days each with a triheptanoin or placebo diet (1\u00a0g\/kg\/day). Primary outcome was change in mean heart rate during 20\u00a0min submaximal exercise on a cycle ergometer. Secondary outcomes were change in peak workload and oxygen uptake along with changes in blood metabolites and respiratory quotients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nineteen of 22 patients completed the trial. Malate levels rose on triheptanoin treatment versus placebo (8.0\u00a0\u00b1\u00a0SD2.3 vs. 5.5\u00a0\u00b1\u00a0SD1.8\u00a0<jats:italic>\u00b5<\/jats:italic>mol\/L, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), but dropped from rest to exercise (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). There was no difference in exercise heart rates between triheptanoin (120\u00a0\u00b1\u00a0SD16\u00a0bpm) and placebo (121\u00a0\u00b1\u00a0SD16\u00a0bpm) treatments. Compared with placebo, triheptanoin did not change the submaximal respiratory quotient (0.82\u00a0\u00b1\u00a0SD0.05 vs. 0.84\u00a0\u00b1\u00a0SD0.03), peak workload (105\u00a0\u00b1\u00a0SD38 vs. 102\u00a0\u00b1\u00a0SD31\u00a0Watts), or peak oxygen uptake (1938\u00a0\u00b1\u00a0SD499 vs. 1977\u00a0\u00b1\u00a0SD380\u00a0mL\/min).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Despite increased resting plasma malate with triheptanoin, the increase was insufficient to generate a normal TCA turnover during exercise and the treatment has no effect on exercise capacity or oxidative metabolism in patients with McArdle disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50863","type":"journal-article","created":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T10:11:26Z","timestamp":1568455886000},"page":"1949-1960","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["No effect of triheptanoin on exercise performance in McArdle disease"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0145-1084","authenticated-orcid":false,"given":"Karen L.","family":"Madsen","sequence":"first","affiliation":[{"name":"Copenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Lafor\u00eat","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence des maladies neuromusculaires Nord\/Est\/Ile de France, Service de Neurologie H\u00f4pital Raymond\u2010Poincar\u00e9, AP\u2010HP Garches France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid E.","family":"Buch","sequence":"additional","affiliation":[{"name":"Copenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mads G.","family":"Stemmerik","sequence":"additional","affiliation":[{"name":"Copenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Ottolenghi","sequence":"additional","affiliation":[{"name":"Metabolomics Unit, Service des Explorations fonctionnelles Necker Hospital and Descartes University of Paris, AP\u2010HP Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane N.","family":"Hatem","sequence":"additional","affiliation":[{"name":"Institute of Cardiometabolism and Nutrition La Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, AP\u2010HP Paris France"},{"name":"Cardiology Institute La Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, AP\u2010HP Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel T.","family":"Raaschou\u2010Pedersen","sequence":"additional","affiliation":[{"name":"Copenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanna S.","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Copenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Atencio","sequence":"additional","affiliation":[{"name":"Inserm U 1127, CNRS UMR 7225, ICM F\u201075013 Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010Pierre","family":"Luton","sequence":"additional","affiliation":[{"name":"Inserm U 1127, CNRS UMR 7225, ICM F\u201075013 Paris 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