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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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.
I: Journal of Inherited Metabolic Disease, Bind 45, Nr. 3, 2022, s. 502-516.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 - Publisher Copyright: © 2022 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.
PY - 2022
Y1 - 2022
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 - exercise capacity
KW - exogenous ketone bodies
KW - glycogen storage disease type V
KW - ketone ester
KW - McArdle disease
U2 - 10.1002/jimd.12484
DO - 10.1002/jimd.12484
M3 - Journal article
C2 - 35150142
AN - SCOPUS:85124821229
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: 307817252