Related Experiment Video
Updated: Jun 22, 2026
A Chronic High-Intensity Interval Training and Diet-Induced Obesity Model to Maximize Exercise Effort and Induce Physiologic Changes in Rats
Published on: April 28, 2023
Effect of changes in fat availability on exercise capacity in McArdle disease
Susanne T Andersen1, Tina D Jeppesen, Tanja Taivassalo
1Neuromuscular Research Unit, Department of Neurology, and Copenhagen Muscle Research Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Background:
The major fuel for exercising muscle at low exercise intensities is fat.
Objective:
To investigate the role of fat metabolism in McArdle disease (also known as glycogen storage disease type V), an inborn error of muscle glycogenolysis, by manipulating free fatty acid availability for oxidation during exercise.
Design:
Randomized, placebo-controlled, crossover trial.
Setting:
Hospitalized care.
Patients:
Ten patients (8 men and 2 women) with McArdle disease.
Interventions:
Patients cycled at a constant workload corresponding to 70% of their maximum oxygen consumption. In random order and on separate days, patients received nicotinic acid (a known blocker of lipolysis) to decrease the availability of free fatty acids or 20% Intralipid infusion to increase free fatty acid availability during exercise. Results were compared with placebo (isotonic sodium chloride solution infusion) and glucose infusion trials.
Main Outcome Measures:
Exercise tolerance was assessed by heart rate response to exercise during different infusions.
Results:
Free fatty acid levels more than tripled by Intralipid infusion and were halved by nicotinic acid administration. Heart rate was significantly higher during exercise in the Intralipid infusion and nicotinic acid trials compared with the placebo and glucose infusion trials, an effect that was observed before and after the patients had experienced the second wind phenomenon.
Conclusions:
Lipids are an important source of fuel for exercising muscle in McArdle disease, but maximal rates of fat oxidation seem limited and cannot be increased above physiologically normal rates during exercise. This limitation is probably caused by a metabolic bottleneck in the tricarboxylic acid cycle due to impaired glycolytic flux in McArdle disease. Therapies aimed at enhancing fat use in McArdle disease should be combined with interventions targeting expansion of the tricarboxylic acid cycle.
Related Concept Videos
01:24Muscle Recovery and Fatigue
01:20Exercise and Cardiovascular Response
Light to moderate physical activity initiates a series of interconnected responses in the body. The heart rate modestly increases in anticipation of the workout, followed by widespread vasodilation as oxygen consumption by skeletal muscles increases. This results in decreased peripheral resistance, increased capillary blood flow, and accelerated...
01:17Exercise and Cardiac Output
Sustained exercise increases the muscles' oxygen demand, which can be met...
01:26Imbalances in Cardiac Output
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send blood...