FP.18 Modified ketogenic diet in patients with McArdle disease: A double-blind, placebo-controlled, cross-over study

Abstract

McArdle disease is caused by myophosphorylase deficiency leading to blocked glycogen breakdown in skeletal muscle. Patients present with exercise intolerance and muscle pain, which can progress to muscle damage. To date there is no cure for McArdle disease. A modified ketogenic diet regime as treatment option has shown promising early results in a previously published pilot-study. The positive effects were partly caused by provision of alternative fuels in the form of ketone bodies and by improvement of fat metabolism. The present study investigates if the modified ketogenic diet regimes investigated in the pilot study are effective in improving exercise capacity in a larger cohort of patients with McArdle disease in a controlled set up. Patients are randomized in this ongoing double-blind, placebo-controlled, cross-over study to receive a modified ketogenic diet or placebo diet first for 3 weeks followed by a wash-out period of a minimum of 2 weeks followed by the opposite diet. The primary outcome is changes in heart rate during constant load cycling. Secondary outcomes include changes in plasma metabolites including ketone bodies, reduction in perceived exertion and changes in indirect calorimetry measures. So far, 18 patients with verified McArdle disease from Denmark and the United Kingdom have been included. Half of the patients (10) received placebo and a ketogenic diet regime containing 75%/15%/10% (fat/protein/carbohydrate) of which 8 completed and 2 dropped out. The other half (8) received a ketogenic diet containing 80%/15%/5% (fat/protein/carbohydrate) or placebo. In this part, 2 have completed, 5 are ongoing and 1 dropped out. The goal is to include a total of 20 patients. The study remains blinded and the results will be analyzed when the last participant has completed the study. The results will be presented at the conference.