Effect of changes in fat availability on exercise capacity in McArdle disease.
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.


METHODS
Randomized, placebo-controlled, crossover trial.


METHODS
Hospitalized care.


METHODS
Ten patients (8 men and 2 women) with McArdle disease.


METHODS
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.


METHODS
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.
Andersen
Susanne T
ST
Neuromuscular Research Unit, Department of Neurology, and Copenhagen Muscle Research Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Jeppesen
Tina D
TD
Taivassalo
Tanja
T
Sveen
Marie-Louise
ML
Heinicke
Katja
K
Haller
Ronald G
RG
Vissing
John
J
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D002952:Citric Acid Cycle / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D017079:Exercise Tolerance / Q000187:drug effects* / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006012:Glycogen Storage Disease Type V / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D008053:Lipid Mobilization / Q000187:drug effects* / Q000502:physiology; D008297:Male; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009525:Niacin / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010809:Physical Fitness / Q000502:physiology; D010919:Placebos; D016896:Treatment Outcome; D055815:Young Adult
D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D010919:Placebos; D009525:Niacin