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

Abstract

Endurance; Glycogen storage disease; Supplement

Resistencia; Enfermedad por almacenamiento de glucógeno; Suplemento

Resistència; Malaltia per emmagatzematge de glucogen; Suplement

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 are dose dependent.

Research by PLV is supported by a Sara Borrell postdoctoral contract granted by Instituto de Salud Carlos III (CD21/00138). PLV, DB-G and AL are funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder (Alejandro Lucia, Grant No. PI18/00139). TP is funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder (Tomàs Pinós, Grant No. PI22/00201). Funders had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.