Acute ketone supplementation in the absence of muscle glycogen utilization: Insights from McArdle disease.

Tomàs Pinós, Lidia B Alejo, Laureano M Ozcoidi, David Barranco-Gil, María Morán, Alfredo Santalla, Pedro L Valenzuela, Alejandro Lucia, Asunción Bustos, Laura Castellote-Bellés, Roser Ferrer-Costa, Mónica Villarreal-Salazar

Journal: Clinical nutrition (Edinburgh, Scotland) 2024;43(3):692-700

PMID: 38320460

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND & AIMS

Ketone supplementation is gaining popularity. Yet, its effects on exercise performance when muscle glycogen cannot be used remain to be determined. McArdle disease can provide insight into this question, as these patients are unable to obtain energy from muscle glycogen, presenting a severely impaired physical capacity. We therefore aimed to assess the effects of acute ketone supplementation in the absence of muscle glycogen utilization (McArdle disease).

METHODS

In a randomized cross-over design, patients with an inherited block in muscle glycogen breakdown (i.e., McArdle disease, n = 8) and healthy controls (n = 7) underwent a submaximal (constant-load) test that was followed by a maximal ramp test, after the ingestion of a placebo or an exogenous ketone ester supplement (30 g of D-beta hydroxybutyrate/D 1,3 butanediol monoester). Patients were also assessed after carbohydrate (75 g) ingestion, which is currently considered best clinical practice in McArdle disease.

RESULTS

Ketone supplementation induced ketosis in all participants (blood [ketones] = 3.7 ± 0.9 mM) and modified some gas-exchange responses (notably increasing respiratory exchange ratio, especially in patients). Patients showed an impaired exercise capacity (-65 % peak power output (PPO) compared to controls, p < 0.001) and ketone supplementation resulted in a further impairment (-11.6 % vs. placebo, p = 0.001), with no effects in controls (p = 0.268). In patients, carbohydrate supplementation resulted in a higher PPO compared to ketones (+21.5 %, p = 0.001) and a similar response was observed vs. placebo (+12.6 %, p = 0.057).

CONCLUSIONS

In individuals who cannot utilize muscle glycogen but have a preserved ability to oxidize blood-borne glucose and fat (McArdle disease), acute ketone supplementation impairs exercise capacity, whereas carbohydrate ingestion exerts the opposite, beneficial effect.

Address: Physical Activity and Health Research Group ('PaHerg'), Research Institute of Hospital '12 de Octubre' ('imas12'), Madrid, Spain; Department of Systems Biology, University of Alcalá, Madrid, Spain. Electronic address: [email protected].; Department of Sport and Computer Science, Section of Physical Education and Sports, Faculty of Sport, Universidad Pablo de Olavide, Sevilla, Spain; EVOPRED Research Group, Universidad Europea de Canarias, Tenerife, Spain.; Physical Activity and Health Research Group ('PaHerg'), Research Institute of Hospital '12 de Octubre' ('imas12'), Madrid, Spain; Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain.; Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain.; Hospital Reina Sofía de Tudela, Servicio Navarro de Salud, Navarra, Spain.; Department of Clinical Biochemistry, Laboratoris Clínics, Hospital Universitari Vall d'Hebron, Barcelona, Spain.; Mitochondrial and Neuromuscular Disorders Unit, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Madrid, Spain.; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Madrid, Spain; Mitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital 12 de Octubre (imas12), Madrid, Spain.; Mitochondrial and Neuromuscular Disorders Unit, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Madrid, Spain. Electronic address: [email protected].

DOI: 10.1016/j.clnu.2024.01.026

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MeSH Terms: Humans, Blood Glucose, Dietary Supplements, Glycogen, Glycogen Storage Disease Type V, Ketones, Muscles, Cross-Over Studies