Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease?: Results from a randomized, single-blind, placebo-controlled, cross-over study

Nicoline Løkken; Maja Risager Nielsen; Mads Godtfeldt Stemmerik; Charlotte Ellerton; Karoline Lolk Revsbech; Margaret Macrae; Anna Slipsager; Bjørg Krett; Gry Hatting Beha; Frida Emanuelsson; Gerrit van Hall; Rosaline Quinlivan; John Vissing

doi:10.1016/j.clnu.2023.09.006

Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study

Nicoline Løkken^*, Maja Risager Nielsen, Mads Godtfeldt Stemmerik, Charlotte Ellerton, Karoline Lolk Revsbech, Margaret Macrae, Anna Slipsager, Bjørg Krett, Gry Hatting Beha, Frida Emanuelsson, Gerrit van Hall, Rosaline Quinlivan, John Vissing

^*Corresponding author for this work

3 Citations (Scopus)

Abstract

BACKGROUND: McArdle disease is caused by myophosphorylase deficiency leading to blocked glycogenolysis in skeletal muscle. Consequently, individuals with McArdle disease have intolerance to physical activity, muscle fatigue, and pain. These symptoms vary according to the availability of alternative fuels for muscle contraction. In theory, a modified ketogenic diet (mKD) can provide alternative fuels in the form of ketone bodies and potentially boost fat oxidation.

METHODS: This randomized, single-blind, placebo-controlled, cross-over study aimed to investigate if a mKD improves exercise capacity in individuals with McArdle disease. Participants were randomized to follow a mKD (75-80% fat, 15% protein, 5-10% carbohydrates) or placebo diet (PD) first for three weeks, followed by a wash-out period, and then the opposite diet. The primary outcome was change in heart rate during constant-load cycling. Secondary outcomes included change in plasma metabolites, perceived exertion, indirect calorimetry measures, maximal exercise capacity, and patient-reported outcomes.

RESULTS: Fifteen out of 20 patients with genetically verified McArdle disease completed all study visits, and 14 were included in the data analyses. We found that the mKD induced a metabolic shift towards increased fat oxidation (∼60% increase), and a 19-fold increase in plasma β-hydroxybutyrate (p < 0.05). The mKD did not improve heart rate responses during constant-load cycling but did improve patient-reported outcomes and maximal exercise capacity (∼20% increase) compared to the PD.

CONCLUSION: The mKD did not alleviate all McArdle disease-related symptoms but did induce some positive changes. To date, no satisfactory treatment options exist other than exercise training. To that end, a mKD can be a possible nutritional strategy for some individuals with McArdle disease who are motivated to undertake a restrictive diet.

CLINICAL TRIAL REGISTRATION: clinical trials.gov: NCT04044508.

Original language	English
Journal	Clinical nutrition (Edinburgh, Scotland)
Volume	42
Issue number	11
Pages (from-to)	2124-2137
Number of pages	14
ISSN	0261-5614
DOIs	https://doi.org/10.1016/j.clnu.2023.09.006
Publication status	Published - Nov 2023

Keywords

Glycogen storage disease type V
McArdle disease
Modified ketogenic diet
Randomized clinical trial

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10.1016/j.clnu.2023.09.006

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Løkken, N., Nielsen, M. R., Stemmerik, M. G., Ellerton, C., Revsbech, K. L., Macrae, M., Slipsager, A., Krett, B., Beha, G. H., Emanuelsson, F., van Hall, G., Quinlivan, R., & Vissing, J. (2023). Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study. Clinical nutrition (Edinburgh, Scotland), 42(11), 2124-2137. https://doi.org/10.1016/j.clnu.2023.09.006

Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study. / Løkken, Nicoline; Nielsen, Maja Risager; Stemmerik, Mads Godtfeldt et al.
In: Clinical nutrition (Edinburgh, Scotland), Vol. 42, No. 11, 11.2023, p. 2124-2137.

Research output: Contribution to journal › Journal article › Research › peer-review

Løkken, N, Nielsen, MR, Stemmerik, MG, Ellerton, C, Revsbech, KL, Macrae, M, Slipsager, A, Krett, B, Beha, GH, Emanuelsson, F, van Hall, G, Quinlivan, R & Vissing, J 2023, 'Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study', Clinical nutrition (Edinburgh, Scotland), vol. 42, no. 11, pp. 2124-2137. https://doi.org/10.1016/j.clnu.2023.09.006

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title = "Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease?: Results from a randomized, single-blind, placebo-controlled, cross-over study",

abstract = "BACKGROUND: McArdle disease is caused by myophosphorylase deficiency leading to blocked glycogenolysis in skeletal muscle. Consequently, individuals with McArdle disease have intolerance to physical activity, muscle fatigue, and pain. These symptoms vary according to the availability of alternative fuels for muscle contraction. In theory, a modified ketogenic diet (mKD) can provide alternative fuels in the form of ketone bodies and potentially boost fat oxidation.METHODS: This randomized, single-blind, placebo-controlled, cross-over study aimed to investigate if a mKD improves exercise capacity in individuals with McArdle disease. Participants were randomized to follow a mKD (75-80% fat, 15% protein, 5-10% carbohydrates) or placebo diet (PD) first for three weeks, followed by a wash-out period, and then the opposite diet. The primary outcome was change in heart rate during constant-load cycling. Secondary outcomes included change in plasma metabolites, perceived exertion, indirect calorimetry measures, maximal exercise capacity, and patient-reported outcomes.RESULTS: Fifteen out of 20 patients with genetically verified McArdle disease completed all study visits, and 14 were included in the data analyses. We found that the mKD induced a metabolic shift towards increased fat oxidation (∼60% increase), and a 19-fold increase in plasma β-hydroxybutyrate (p < 0.05). The mKD did not improve heart rate responses during constant-load cycling but did improve patient-reported outcomes and maximal exercise capacity (∼20% increase) compared to the PD.CONCLUSION: The mKD did not alleviate all McArdle disease-related symptoms but did induce some positive changes. To date, no satisfactory treatment options exist other than exercise training. To that end, a mKD can be a possible nutritional strategy for some individuals with McArdle disease who are motivated to undertake a restrictive diet.CLINICAL TRIAL REGISTRATION: clinical trials.gov: NCT04044508.",

keywords = "Glycogen storage disease type V, McArdle disease, Modified ketogenic diet, Randomized clinical trial",

author = "Nicoline L{\o}kken and Nielsen, {Maja Risager} and Stemmerik, {Mads Godtfeldt} and Charlotte Ellerton and Revsbech, {Karoline Lolk} and Margaret Macrae and Anna Slipsager and Bj{\o}rg Krett and Beha, {Gry Hatting} and Frida Emanuelsson and {van Hall}, Gerrit and Rosaline Quinlivan and John Vissing",

year = "2023",

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doi = "10.1016/j.clnu.2023.09.006",

language = "English",

volume = "42",

pages = "2124--2137",

journal = "Clinical nutrition (Edinburgh, Scotland)",

issn = "0261-5614",

publisher = "Elsevier BV",

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T1 - Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease?

T2 - Results from a randomized, single-blind, placebo-controlled, cross-over study

AU - Løkken, Nicoline

AU - Nielsen, Maja Risager

AU - Stemmerik, Mads Godtfeldt

AU - Ellerton, Charlotte

AU - Revsbech, Karoline Lolk

AU - Macrae, Margaret

AU - Slipsager, Anna

AU - Krett, Bjørg

AU - Beha, Gry Hatting

AU - Emanuelsson, Frida

AU - van Hall, Gerrit

AU - Quinlivan, Rosaline

AU - Vissing, John

PY - 2023/11

Y1 - 2023/11

N2 - BACKGROUND: McArdle disease is caused by myophosphorylase deficiency leading to blocked glycogenolysis in skeletal muscle. Consequently, individuals with McArdle disease have intolerance to physical activity, muscle fatigue, and pain. These symptoms vary according to the availability of alternative fuels for muscle contraction. In theory, a modified ketogenic diet (mKD) can provide alternative fuels in the form of ketone bodies and potentially boost fat oxidation.METHODS: This randomized, single-blind, placebo-controlled, cross-over study aimed to investigate if a mKD improves exercise capacity in individuals with McArdle disease. Participants were randomized to follow a mKD (75-80% fat, 15% protein, 5-10% carbohydrates) or placebo diet (PD) first for three weeks, followed by a wash-out period, and then the opposite diet. The primary outcome was change in heart rate during constant-load cycling. Secondary outcomes included change in plasma metabolites, perceived exertion, indirect calorimetry measures, maximal exercise capacity, and patient-reported outcomes.RESULTS: Fifteen out of 20 patients with genetically verified McArdle disease completed all study visits, and 14 were included in the data analyses. We found that the mKD induced a metabolic shift towards increased fat oxidation (∼60% increase), and a 19-fold increase in plasma β-hydroxybutyrate (p < 0.05). The mKD did not improve heart rate responses during constant-load cycling but did improve patient-reported outcomes and maximal exercise capacity (∼20% increase) compared to the PD.CONCLUSION: The mKD did not alleviate all McArdle disease-related symptoms but did induce some positive changes. To date, no satisfactory treatment options exist other than exercise training. To that end, a mKD can be a possible nutritional strategy for some individuals with McArdle disease who are motivated to undertake a restrictive diet.CLINICAL TRIAL REGISTRATION: clinical trials.gov: NCT04044508.

AB - BACKGROUND: McArdle disease is caused by myophosphorylase deficiency leading to blocked glycogenolysis in skeletal muscle. Consequently, individuals with McArdle disease have intolerance to physical activity, muscle fatigue, and pain. These symptoms vary according to the availability of alternative fuels for muscle contraction. In theory, a modified ketogenic diet (mKD) can provide alternative fuels in the form of ketone bodies and potentially boost fat oxidation.METHODS: This randomized, single-blind, placebo-controlled, cross-over study aimed to investigate if a mKD improves exercise capacity in individuals with McArdle disease. Participants were randomized to follow a mKD (75-80% fat, 15% protein, 5-10% carbohydrates) or placebo diet (PD) first for three weeks, followed by a wash-out period, and then the opposite diet. The primary outcome was change in heart rate during constant-load cycling. Secondary outcomes included change in plasma metabolites, perceived exertion, indirect calorimetry measures, maximal exercise capacity, and patient-reported outcomes.RESULTS: Fifteen out of 20 patients with genetically verified McArdle disease completed all study visits, and 14 were included in the data analyses. We found that the mKD induced a metabolic shift towards increased fat oxidation (∼60% increase), and a 19-fold increase in plasma β-hydroxybutyrate (p < 0.05). The mKD did not improve heart rate responses during constant-load cycling but did improve patient-reported outcomes and maximal exercise capacity (∼20% increase) compared to the PD.CONCLUSION: The mKD did not alleviate all McArdle disease-related symptoms but did induce some positive changes. To date, no satisfactory treatment options exist other than exercise training. To that end, a mKD can be a possible nutritional strategy for some individuals with McArdle disease who are motivated to undertake a restrictive diet.CLINICAL TRIAL REGISTRATION: clinical trials.gov: NCT04044508.

KW - Glycogen storage disease type V

KW - McArdle disease

KW - Modified ketogenic diet

KW - Randomized clinical trial

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U2 - 10.1016/j.clnu.2023.09.006

DO - 10.1016/j.clnu.2023.09.006

M3 - Journal article

C2 - 37769369

SN - 0261-5614

VL - 42

SP - 2124

EP - 2137

JO - Clinical nutrition (Edinburgh, Scotland)

JF - Clinical nutrition (Edinburgh, Scotland)

IS - 11

ER -

Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study

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Keywords

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