METABOLIC MYOPATHIES I: P.272No effect of triheptanoin on exercise performance in patients with McArdle disease - a double blind placebo-controlled crossover study

Abstract

Patients with McArdle disease have blocked muscle glycogen breakdown due to an inherited defect myophosphorylase. This causes exercise intolerance with muscle pain, contractures and rhabdomyolysis. McArdle patients cannot increase fat oxidation to fully compensate for the energy deficiency due to a slow turnover in the tricarboxylic acid cycle (TCA). Metabolism of the 7-carbon fatty acid, triheptanoin, generates acetyl-CoA and propionyl-CoA, which enter the TCA and can therefore potentially boost fat oxidation in McArdle patients. In this double blind, placebo-controlled, crossover study we included 22 patients. Participants completed two 2-week treatment periods with a diet on triheptanoin or placebo oil (1g × kg-1 × day-1) separated by 1-2 weeks of washout. At baseline and at the end of the treatment periods, patients performed 20 minutes of submaximal exercise on a cycle ergometer followed by increments until exhaustion. Blood metabolites were measured every 10 minutes and exchange of O2. and CO2 was measured breath-by-breath. Nineteen patients completed the trial and qualified for data analysis. The patients had similar mean heart rates during submaximal exercise with triheptanoin (120±SD16 bpm) and with placebo treatment (121±SD16 bpm). Submaximal respiratory quotients were the same with triheptanoin (0.82±SD0.05) and placebo (0.84±SD0.03). They reached the same maximal workloads with treatment vs. placebo (105±SD38 vs. 102±SD31 Watts) and maximal oxygen uptake (1938±SD499 vs. 1977±SD380 mL × kg-1 × day-1). Blood glucose dropped with exercise to 4.6±SD0.8 vs. 4.4±SD1.0 mM and there was no difference in the production of ammonia with exercise (167±SD88 vs. 202±SD111 µM). Biochemical analyses of plasma TCA intermediates and fatty acids are ongoing. These preliminary data show no effect of triheptanoin treatment on exercise capacity and tolerance or muscle energy metabolism in McArdle patients.