Correspondence

Oral Sucrose and Exercise Tolerance in McArdle's Disease

N Engl J Med 2004; 350:1575-1576April 8, 2004

Article

To the Editor:

Vissing and Haller (Dec. 25 issue)1 show that sucrose ingestion before exercise can markedly improve aerobic exercise tolerance in patients with McArdle's disease. However, as the authors note, this strategy may lead to increased insulin secretion that could potentially inhibit the use of fatty acids and is not useful in situations involving unexpected aerobic activity or prolonged physical activity. The authors may wish to consider uncooked cornstarch as a carbohydrate source for patients with McArdle's disease, as previously reported by Chen et al. in patients with type I glycogen storage disease.2 Bolus uncooked-cornstarch ingestion provides for a sustained increase in serum glucose concentrations (lasting up to five or six hours) that is similar to the increase with a continuous isocaloric intragastric infusion of glucose, without a pronounced rise in serum insulin.3 Uncooked cornstarch alone or in conjunction with sucrose would probably overcome many of the limitations of the current strategy and might increase the availability of oxidative substrate and lead to a sustained increase in oxidative capacity, as the authors have reported with a continuous intravenous glucose infusion.4

Jason L. Gaglia, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215
jgaglia@bidmc.harvard.edu

Joseph I. Wolfsdorf, M.B., B.Ch.
Children's Hospital, Boston, MA 02115

4 References

1. 1

   Vissing J, Haller RG. The effect of oral sucrose on exercise tolerance in patients with McArdle's disease. N Engl J Med 2003;349:2503-2509
   Full Text | Web of Science | Medline

2. 2

   Chen YT, Cornblath M, Sidbury JB. Cornstarch therapy in type I glycogen storage disease. N Engl J Med 1984;310:171-175
   Full Text | Web of Science | Medline

3. 3

   Wolfsdorf JI, Plotkin RA, Laffel LM, Crigler JF Jr. Continuous glucose for treatment of patients with type 1 glycogen-storage disease: comparison of the effects of dextrose and uncooked cornstarch on biochemical variables. Am J Clin Nutr 1990;52:1043-1050
   Web of Science | Medline

4. 4

   Haller RG, Vissing J. Spontaneous “second wind“ and glucose-induced second “second wind“ in McArdle disease: oxidative mechanisms. Arch Neurol 2002;59:1395-1402
   CrossRef | Web of Science | Medline

Author/Editor Response

As Drs. Gaglia and Wolfsdorf note, hypoglycemia due to blocked conversion of hepatic glucose-6-phosphate to glucose in glycogen storage disease type I can be ameliorated with the use of uncooked cornstarch.1 Blood glucose is normal in glycogen storage disease type V (McArdle's disease); hepatic glycogenolysis during exercise is actually exaggerated,2,3 thus fueling the characteristic spontaneous “second wind” after 8 to 10 minutes of exercise.4 The dose–response effects of oral sucrose indicate that a large increase in plasma glucose (>2 mmol per liter) is needed to rescue muscle metabolism from the oxidative fuel crisis that prevails during the first minutes of exercise in patients with McArdle's disease.5 Oral polysaccharides marginally increase plasma glucose when hepatic glycogenolysis is normal and are therefore unlikely to correct this early fuel limitation.

Eleven of our patients with McArdle's disease used oral sucrose 2 to 14 times per week for one to two years, without weight gain. Furthermore, exercise after oral sucrose ingestion counteracts the neurohormonal effects of rapid increases in plasma glucose. Although cornstarch is unlikely to improve exercise performance in the critical period before the second wind, the question of whether such supplements could improve oxidative capacity during prolonged exercise in patients with McArdle's disease should be investigated.

John Vissing, M.D., Ph.D.
National University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark
vissing@rh.dk

Ronald G. Haller, M.D.
Presbyterian Hospital, Dallas, TX 75231

5 References

1. 1

   Chen YT, Cornblath M, Sidbury JB. Cornstarch therapy in type I glycogen storage disease. N Engl J Med 1984;310:171-175
   Full Text | Web of Science | Medline

2. 2

   Vissing J, Lewis SF, Galbo H, Haller RG. Effect of deficient muscular glycogenolysis on extramuscular fuel production in exercise. J Appl Physiol 1992;72:1773-1779
   Web of Science | Medline

3. 3

   Nielsen JN, Wojtaszewski JFP, Haller RG, et al. Role of 5'AMP-activated protein kinase in glycogen synthase activity and glucose utilization: insights from patients with McArdle's disease. J Physiol 2002;541:979-989
   CrossRef | Web of Science | Medline

4. 4

   Haller RG, Vissing J. Spontaneous “second wind“ and glucose-induced second “second wind“ in McArdle disease: oxidative mechanisms. Arch Neurol 2002;59:1395-1402
   CrossRef | Web of Science | Medline

5. 5

   Vissing J, Haller RG. The effect of oral sucrose on exercise tolerance in patients with McArdle's disease. N Engl J Med 2003;349:2503-2509
   Full Text | Web of Science | Medline