TY - JOUR

T1 - 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

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

N1 - Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

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

UR - http://www.scopus.com/inward/record.url?scp=85174013060&partnerID=8YFLogxK

U2 - 10.1016/j.clnu.2023.09.006

DO - 10.1016/j.clnu.2023.09.006

M3 - Journal article

C2 - 37769369

AN - SCOPUS:85174013060

VL - 42

SP - 2124

EP - 2137

JO - Clinical Nutrition

JF - Clinical Nutrition

SN - 0261-5614

IS - 11

ER -