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No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study

Patients with glycogen storage disease type V (GSDV), also known as McArdle disease, have blocked glycogen breakdown due to myophosphorylase deficiency, leading to exercise intolerance, muscle pain, and risk of muscle damage. Blood‐derived ketone bodies (KBs) constitute an alternative energy source...

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Autores principales: Løkken, Nicoline, Storgaard, Jesper H., Revsbech, Karoline L., Voermans, Nicol C., Van Hall, Gerrit, Vissing, John, Ørngreen, Mette C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304134/
https://www.ncbi.nlm.nih.gov/pubmed/35150142
http://dx.doi.org/10.1002/jimd.12484
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author Løkken, Nicoline
Storgaard, Jesper H.
Revsbech, Karoline L.
Voermans, Nicol C.
Van Hall, Gerrit
Vissing, John
Ørngreen, Mette C.
author_facet Løkken, Nicoline
Storgaard, Jesper H.
Revsbech, Karoline L.
Voermans, Nicol C.
Van Hall, Gerrit
Vissing, John
Ørngreen, Mette C.
author_sort Løkken, Nicoline
collection PubMed
description Patients with glycogen storage disease type V (GSDV), also known as McArdle disease, have blocked glycogen breakdown due to myophosphorylase deficiency, leading to exercise intolerance, muscle pain, and risk of muscle damage. Blood‐derived ketone bodies (KBs) constitute an alternative energy source that could fuel the muscle independent of glycogenolysis. However, except for long‐time fasting or ketogenic dieting, KBs are present in low quantities. This led us to explore the effects of a drink containing exogenously produced KBs in the form of D‐β‐hydroxybutyrate esters (KE) on exercise capacity and metabolism in patients with GSDV. Eight GSDV patients and four healthy controls (HC) were included in this placebo‐controlled, cross‐over study where subjects were randomized to receive a KE drink with 395 mgKE/kg or placebo drink on two separate days 25 min before a submaximal cycle exercise test. The primary outcome was exercise capacity as indicated by heart rate response (HR) to exercise. Secondary outcomes included perceived exertion (PE) and measures of KB, carbohydrate, and fat metabolism during exercise. In GSDV, the KE drink vs. placebo increased plasma KBs and KB oxidation (p ≤ 0.0001) but did not improve exercise capacity as judged from HR (p = 0.120) and PE (p = 0.109). In addition, the KE drink lowered plasma glucose, free fatty acids, and lowered lipolytic rate and glucose rate of appearance compared with placebo. Similar results were found in the HC group. The present study indicates that an increase in KB oxidation by oral KE supplementation does not improve exercise capacity in GSDV possibly because of KB‐induced inhibition of lipolysis and liver glucose output. Thus, oral KE supplementation alone cannot be recommended as a treatment option for patients with GSDV.
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spelling pubmed-93041342022-07-28 No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study Løkken, Nicoline Storgaard, Jesper H. Revsbech, Karoline L. Voermans, Nicol C. Van Hall, Gerrit Vissing, John Ørngreen, Mette C. J Inherit Metab Dis Original Articles Patients with glycogen storage disease type V (GSDV), also known as McArdle disease, have blocked glycogen breakdown due to myophosphorylase deficiency, leading to exercise intolerance, muscle pain, and risk of muscle damage. Blood‐derived ketone bodies (KBs) constitute an alternative energy source that could fuel the muscle independent of glycogenolysis. However, except for long‐time fasting or ketogenic dieting, KBs are present in low quantities. This led us to explore the effects of a drink containing exogenously produced KBs in the form of D‐β‐hydroxybutyrate esters (KE) on exercise capacity and metabolism in patients with GSDV. Eight GSDV patients and four healthy controls (HC) were included in this placebo‐controlled, cross‐over study where subjects were randomized to receive a KE drink with 395 mgKE/kg or placebo drink on two separate days 25 min before a submaximal cycle exercise test. The primary outcome was exercise capacity as indicated by heart rate response (HR) to exercise. Secondary outcomes included perceived exertion (PE) and measures of KB, carbohydrate, and fat metabolism during exercise. In GSDV, the KE drink vs. placebo increased plasma KBs and KB oxidation (p ≤ 0.0001) but did not improve exercise capacity as judged from HR (p = 0.120) and PE (p = 0.109). In addition, the KE drink lowered plasma glucose, free fatty acids, and lowered lipolytic rate and glucose rate of appearance compared with placebo. Similar results were found in the HC group. The present study indicates that an increase in KB oxidation by oral KE supplementation does not improve exercise capacity in GSDV possibly because of KB‐induced inhibition of lipolysis and liver glucose output. Thus, oral KE supplementation alone cannot be recommended as a treatment option for patients with GSDV. John Wiley & Sons, Inc. 2022-02-20 2022-05 /pmc/articles/PMC9304134/ /pubmed/35150142 http://dx.doi.org/10.1002/jimd.12484 Text en © 2022 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Løkken, Nicoline
Storgaard, Jesper H.
Revsbech, Karoline L.
Voermans, Nicol C.
Van Hall, Gerrit
Vissing, John
Ørngreen, Mette C.
No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study
title No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study
title_full No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study
title_fullStr No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study
title_full_unstemmed No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study
title_short No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo‐controlled cross‐over study
title_sort no effect of oral ketone ester supplementation on exercise capacity in patients with mcardle disease and healthy controls: a randomized placebo‐controlled cross‐over study
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304134/
https://www.ncbi.nlm.nih.gov/pubmed/35150142
http://dx.doi.org/10.1002/jimd.12484
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