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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

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@article{35f16683c2f847c89e4875b80b572872,
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",
abstract = "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.",
keywords = "Cross-Over Studies, Dietary Supplements, Esters, Exercise Tolerance/physiology, Glucose/metabolism, Glycogen Storage Disease Type V/metabolism, Humans, Ketone Bodies/metabolism, Ketones, Muscle, Skeletal/metabolism",
author = "Nicoline L{\o}kken and Storgaard, {Jesper H} and Revsbech, {Karoline L} and Voermans, {Nicol C} and {Van Hall}, Gerrit and John Vissing and {\O}rngreen, {Mette C}",
note = "{\textcopyright} 2022 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.",
year = "2022",
month = may,
doi = "10.1002/jimd.12484",
language = "English",
volume = "45",
pages = "502--516",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "3",

}

RIS

TY - JOUR

T1 - No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls

T2 - A randomized placebo-controlled cross-over study

AU - Løkken, Nicoline

AU - Storgaard, Jesper H

AU - Revsbech, Karoline L

AU - Voermans, Nicol C

AU - Van Hall, Gerrit

AU - Vissing, John

AU - Ørngreen, Mette C

N1 - © 2022 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

KW - Cross-Over Studies

KW - Dietary Supplements

KW - Esters

KW - Exercise Tolerance/physiology

KW - Glucose/metabolism

KW - Glycogen Storage Disease Type V/metabolism

KW - Humans

KW - Ketone Bodies/metabolism

KW - Ketones

KW - Muscle, Skeletal/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85124821229&partnerID=8YFLogxK

U2 - 10.1002/jimd.12484

DO - 10.1002/jimd.12484

M3 - Journal article

C2 - 35150142

VL - 45

SP - 502

EP - 516

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 3

ER -

ID: 78307231