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Fat metabolism during exercise in patients with McArdle disease

From the Neuromuscular Research Unit (M.C.Ø., T.D.J., S.T.A., S.H., N.P., J.V.), Department of Neurology, and Copenhagen Muscle Research Center (M.C.Ø., T.D.J., S.T.A., S.H., N.P., G.v.H., J.V.), Rigshospitalet, University of Copenhagen, Denmark; Neuromuscular Center (T.T., R.G.H.), Institute for Exercise and Environmental Medicine of Presbyterian Hospital, and Department of Neurology, University of Texas Southwestern Medical Center and VA Medical Center, Dallas, TX; and Department of Biomedical Sciences (G.v.H.), University of Copenhagen, Denmark.

Address correspondence and reprint requests to Dr. Mette Cathrine Ørngreen, Neuromuscular Research Unit 3342, University of Copenhagen, Rigshospitalet Blegdamsvej 9, DK-2100 Copenhagen, Denmark rh10679{at}rh.dk

Objective: It is known that muscle phosphorylase deficiency restricts carbohydrate utilization, but the implications for muscle fat metabolism have not been studied. We questioned whether patients with McArdle disease can compensate for the blocked muscle glycogen breakdown by enhancing fat oxidation during exercise.

Methods: We studied total fat oxidation by indirect calorimetry and palmitate turnover by stable isotope methodology in 11 patients with McArdle disease and 11 healthy controls. Cycle exercise at a constant workload of 50% to 60% of maximal oxygen uptake capacity was used to evaluate fatty acid oxidation (FAO) in the patients. Healthy controls were exercised at the same absolute workload.

Results: We found that palmitate oxidation and disposal, total fat oxidation, and plasma levels of palmitate and total free fatty acids (FFAs) were significantly higher, whereas total carbohydrate oxidation was lower, during exercise in patients with McArdle disease vs healthy controls. We found augmented fat oxidation with the onset of a second wind, but further increases in FFA availability, as exercise continued, did not result in further increases in FAO.

Conclusion: These results indicate that patients with McArdle disease have exaggerated fat oxidation during prolonged, low-intensity exercise and that increased fat oxidation may be an important mechanism of the spontaneous second wind. The fact that increasing availability of free fatty acids with more prolonged exercise did not increase fatty acid oxidation suggests that blocked glycogenolysis may limit the capacity of fat oxidation to compensate for the energy deficit in McArdle disease.

BMI = body mass index; bpm = beats per minute; CHO = carbohydrate oxidation; FAO = fatty acid oxidation; FFA = free fatty acid; Ra = rate of appearance; Rd = rate of disappearance; RER = respiratory exchange rate; Rox = rate of oxidation; TAG = triacylglycerol; TCA = tricarboxylic acid; VO₂= oxygen consumption; VO_2max = maximal oxygen uptake capacity.

Supported by grants from The Danish Medical Research Council, The Novo Nordisk Foundation, and The Copenhagen Hospital Community Foundation.

Disclosure: The authors report no disclosures.

Received July 16, 2008. Accepted in final form November 17, 2008.

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