Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability: Insights from McArdle disease

Pedro L Valenzuela; Alfredo Santalla; Lidia B Alejo; Andrea Merlo; Asunción Bustos; Laura Castellote-Bellés; Roser Ferrer-Costa; Nicola A Maffiuletti; David Barranco-Gil; Tomás Pinós; Alejandro Lucia

doi:10.1016/j.jshs.2023.11.006

Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability: Insights from McArdle disease

J Sport Health Sci. 2023 Nov 27:S2095-2546(23)00115-1. doi: 10.1016/j.jshs.2023.11.006. Online ahead of print.

Affiliations

¹ Physical Activity and Health Research Group ("PaHerg"), Research Institute of Hospital "12 de Octubre" ("imas12"), Madrid 28041, Spain; Department of Systems Biology, University of Alcalá, Madrid 28871, Spain. Electronic address: pedro.valenzuela92@gmail.com.
² Department of Sport and Computer Science, Section of Physical Education and Sports, Faculty of Sport, Universidad Pablo de Olavide, Sevilla 41013, Spain; EVOPRED Research Group, Universidad Europea de Canarias, Tenerife 38300, Spain.
³ Physical Activity and Health Research Group ("PaHerg"), Research Institute of Hospital "12 de Octubre" ("imas12"), Madrid 28041, Spain; Universidad Europea de Madrid, Faculty of Sport Sciences, Madrid 28670, Spain.
⁴ Gait & Motion Analysis Laboratory, Sol et Salus Hospital, Torre Pedrera di Rimini (RN) 47922, Italy.
⁵ Universidad Europea de Madrid, Faculty of Sport Sciences, Madrid 28670, Spain.
⁶ Department of Clinical Biochemistry, Laboratoris Clínics, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain.
⁷ Human Performance Lab, Schulthess Clinic, Zurich 8008, Switzerland.
⁸ Biomedical Research Networking Center on Rare Disorders (CIBERER), Barcelona 08035, Spain; Mitochondrial and Neuromuscular Disorders Unit, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona 08035, Spain. Electronic address: tomas.pinos@vhir.org.

PMID: 38030066
DOI: 10.1016/j.jshs.2023.11.006

Abstract

Background: This study aimed to determine the effect of different carbohydrate (CHO) doses on exercise capacity in patients with McArdle disease-the paradigm of "exercise intolerance", characterized by complete muscle glycogen unavailability-and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell (in vitro) level.

Methods: Patients with McArdle disease (n = 8) and healthy controls (n = 9) underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo. In a randomized, double-blinded, cross-over design, patients repeated the tests after consuming either 75 g or 150 g of CHO (glucose:fructose = 2:1). Cardiorespiratory, biochemical, perceptual, and electromyographic (EMG) variables were assessed. Additionally, glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations (0.35, 1.00, 4.50, and 10.00 g/L).

Results: Compared with controls, patients showed the "classical" second-wind phenomenon (after prior disproportionate tachycardia, myalgia, and excess electromyographic activity during submaximal exercise, all p < 0.05) and an impaired endurance exercise capacity (-51% ventilatory threshold and -55% peak power output, both p < 0.001). Regardless of the CHO dose (p < 0.05 for both doses compared with the placebo), CHO intake increased blood glucose and lactate levels, decreased fat oxidation rates, and attenuated the second wind in the patients. However, only the higher dose increased ventilatory threshold (+27%, p = 0.010) and peak power output (+18%, p = 0.007). In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes, whereas a dose-response effect was observed in McArdle myotubes.

Conclusion: CHO intake exerts beneficial effects on exercise capacity in McArdle disease, a condition associated with total muscle glycogen unavailability. Some of these benefits were dose dependent.

Keywords: Endurance; Glycogen storage disease; Glycogenosis; Nutrition; Supplement.