No effect of triheptanoin on exercise performance in McArdle disease
Abstract Objective To study if treatment with triheptanoin, a 7‐carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen‐dependent expansion of tricarboxylic acid cycle (TCA), which may restrict fat oxida...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-10-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.50863 |
| _version_ | 1818675305136521216 |
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| author | Karen L. Madsen Pascal Laforêt Astrid E. Buch Mads G. Stemmerik Chris Ottolenghi Stéphane N. Hatem Daniel T. Raaschou‐Pedersen Nanna S. Poulsen Maria Atencio Marie‐Pierre Luton Alexandre Ceccaldi Ronald G. Haller Ros Quinlivan Fanny Mochel John Vissing |
| author_facet | Karen L. Madsen Pascal Laforêt Astrid E. Buch Mads G. Stemmerik Chris Ottolenghi Stéphane N. Hatem Daniel T. Raaschou‐Pedersen Nanna S. Poulsen Maria Atencio Marie‐Pierre Luton Alexandre Ceccaldi Ronald G. Haller Ros Quinlivan Fanny Mochel John Vissing |
| author_sort | Karen L. Madsen |
| collection | DOAJ |
| description | Abstract Objective To study if treatment with triheptanoin, a 7‐carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen‐dependent 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. Methods Double‐blind, placebo‐controlled, crossover study in patients with McArdle disease completing two treatment periods of 14 days each with a triheptanoin or placebo diet (1 g/kg/day). Primary outcome was change in mean heart rate during 20 min 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. Results Nineteen of 22 patients completed the trial. Malate levels rose on triheptanoin treatment versus placebo (8.0 ± SD2.3 vs. 5.5 ± SD1.8 µmol/L, P < 0.001), but dropped from rest to exercise (P < 0.001). There was no difference in exercise heart rates between triheptanoin (120 ± SD16 bpm) and placebo (121 ± SD16 bpm) treatments. Compared with placebo, triheptanoin did not change the submaximal respiratory quotient (0.82 ± SD0.05 vs. 0.84 ± SD0.03), peak workload (105 ± SD38 vs. 102 ± SD31 Watts), or peak oxygen uptake (1938 ± SD499 vs. 1977 ± SD380 mL/min). Interpretation 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. |
| first_indexed | 2024-12-17T08:25:28Z |
| format | Article |
| id | doaj.art-32794b790c334ac29be88d845d7d8d09 |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-12-17T08:25:28Z |
| publishDate | 2019-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-32794b790c334ac29be88d845d7d8d092022-12-21T21:56:47ZengWileyAnnals of Clinical and Translational Neurology2328-95032019-10-016101949196010.1002/acn3.50863No effect of triheptanoin on exercise performance in McArdle diseaseKaren L. Madsen0Pascal Laforêt1Astrid E. Buch2Mads G. Stemmerik3Chris Ottolenghi4Stéphane N. Hatem5Daniel T. Raaschou‐Pedersen6Nanna S. Poulsen7Maria Atencio8Marie‐Pierre Luton9Alexandre Ceccaldi10Ronald G. Haller11Ros Quinlivan12Fanny Mochel13John Vissing14Copenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen DenmarkCentre de référence des maladies neuromusculaires Nord/Est/Ile de France, Service de Neurologie Hôpital Raymond‐Poincaré, AP‐HP Garches FranceCopenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen DenmarkCopenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen DenmarkMetabolomics Unit, Service des Explorations fonctionnelles Necker Hospital and Descartes University of Paris, AP‐HP Paris FranceInstitute of Cardiometabolism and Nutrition La Pitié‐Salpêtrière Hospital, AP‐HP Paris FranceCopenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen DenmarkCopenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen DenmarkInserm U 1127, CNRS UMR 7225, ICM F‐75013Paris FranceInserm U 1127, CNRS UMR 7225, ICM F‐75013Paris FranceInstitute of Cardiometabolism and Nutrition La Pitié‐Salpêtrière Hospital, AP‐HP Paris FranceNeuromuscular Center Institute for Exercise and Environmental Medicine of Texas Health Presbyterian Hospital Dallas TexasMRC Centre for Neuromuscular Diseases National Hospital for Neurology and Neurosurgery, Queen Square London EnglandInserm U 1127, CNRS UMR 7225, ICM F‐75013Paris FranceCopenhagen Neuromuscular Center, Department of Neurology Rigshospitalet and University of Copenhagen Copenhagen DenmarkAbstract Objective To study if treatment with triheptanoin, a 7‐carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen‐dependent 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. Methods Double‐blind, placebo‐controlled, crossover study in patients with McArdle disease completing two treatment periods of 14 days each with a triheptanoin or placebo diet (1 g/kg/day). Primary outcome was change in mean heart rate during 20 min 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. Results Nineteen of 22 patients completed the trial. Malate levels rose on triheptanoin treatment versus placebo (8.0 ± SD2.3 vs. 5.5 ± SD1.8 µmol/L, P < 0.001), but dropped from rest to exercise (P < 0.001). There was no difference in exercise heart rates between triheptanoin (120 ± SD16 bpm) and placebo (121 ± SD16 bpm) treatments. Compared with placebo, triheptanoin did not change the submaximal respiratory quotient (0.82 ± SD0.05 vs. 0.84 ± SD0.03), peak workload (105 ± SD38 vs. 102 ± SD31 Watts), or peak oxygen uptake (1938 ± SD499 vs. 1977 ± SD380 mL/min). Interpretation 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.https://doi.org/10.1002/acn3.50863 |
| spellingShingle | Karen L. Madsen Pascal Laforêt Astrid E. Buch Mads G. Stemmerik Chris Ottolenghi Stéphane N. Hatem Daniel T. Raaschou‐Pedersen Nanna S. Poulsen Maria Atencio Marie‐Pierre Luton Alexandre Ceccaldi Ronald G. Haller Ros Quinlivan Fanny Mochel John Vissing No effect of triheptanoin on exercise performance in McArdle disease Annals of Clinical and Translational Neurology |
| title | No effect of triheptanoin on exercise performance in McArdle disease |
| title_full | No effect of triheptanoin on exercise performance in McArdle disease |
| title_fullStr | No effect of triheptanoin on exercise performance in McArdle disease |
| title_full_unstemmed | No effect of triheptanoin on exercise performance in McArdle disease |
| title_short | No effect of triheptanoin on exercise performance in McArdle disease |
| title_sort | no effect of triheptanoin on exercise performance in mcardle disease |
| url | https://doi.org/10.1002/acn3.50863 |
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