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

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 are dose dependent.

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

Graphical abstract

Fig. 1

(A) Blood glucose and (B) lactate levels in response to exercise without previous carbohydrate ingestion (placebo condition) in patients with McArdle disease and healthy controls. Data are presented as mean ± SD. *** p < 0.001, Significant differences between groups.

Fig. 2

Electromyographic activity (normalized RMS) of the VL and RF muscles in patients with McArdle disease and healthy controls during (A and B) the constant load bout and (C and D) the maximal ramp test. Data are presented as mean ± SD. * p < 0.05, significant differences between groups. RF = rectus femoris; RMS = root main square; VL = vastus lateralis.

Fig. 3

(A) VT and (B) PPO following the ingestion of different doses of CHO or a placebo supplement in patients with McArdle disease. Both individual (lines) and mean ± SD are shown. CHO = carbohydrate; PPO = peak power output; VT = ventilatory threshold; W = watt.

Fig. 4

(A) Blood glucose and (B) lactate levels following the ingestion of different doses of CHO or a placebo supplement in patients with McArdle disease. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01, significant differences between placebo and 75 g CHO. ^##p < 0.01, ^###p < 0.001, significant differences between placebo and 150 g CHO. CHO = carbohydrate.

Fig. 5

Electromyographic activity (normalized RMS) of the VL and RF muscles in McArdle patients during (A and B) the constant load bout and (C and D) the maximal ramp test following the ingestion of a placebo supplement or different doses of CHO. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01, significant differences between placebo and 75 g CHO. ^#p < 0.05, significant differences between placebo and 150 g CHO. CHO = carbohydrate; RF = rectus femoris; RMS = root main square; VL = vastus lateralis.

Fig. 6

(A and B) Glucose uptake and (C and D) lactate production in wild-type and McArdle mouse myotubes cultured under different glucose concentrations. * p < 0.05, ** p < 0.01, *** p < 0.001, significant differences between doses.