Bezafibrate in skeletal muscle fatty acid oxidation disorders: a randomized clinical trial
Mette Cathrine Ørngreen1, Karen Lindhardt Madsen, Nicolai Preisler
1From the Neuromuscular Clinic and Research Unit (M.C.Ø, K.L.M., N.P., G.A., J.V.), Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark; and Centre de Référence de pathologie neuromusculaire Paris-Est (P.L.), Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, France.
Objective:
To assess whether bezafibrate increases fatty acid oxidation (FAO) and lowers heart rate (HR) during exercise in patients with carnitine palmitoyltransferase (CPT) II and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies.
Methods:
This was a 3-month, randomized, double-blind, crossover study of bezafibrate in patients with CPT II (n = 5) and VLCAD (n = 5) deficiencies. Primary outcome measures were changes in FAO, measured with stable-isotope methodology and indirect calorimetry, and changes in HR during exercise.
Results:
Bezafibrate lowered low-density lipoprotein, triglyceride, and free fatty acid concentrations; however, there were no changes in palmitate oxidation, FAO, or HR during exercise.
Conclusion:
Bezafibrate does not improve clinical symptoms or FAO during exercise in patients with CPT II and VLCAD deficiencies. These findings indicate that previous in vitro studies suggesting a therapeutic potential for fibrates in disorders of FAO do not translate into clinically meaningful effects in vivo.
Classification Of Evidence:
This study provides Class I evidence that bezafibrate 200 mg 3 times daily is ineffective in improving changes in FAO and HR during exercise in adults with CPT II and VLCAD deficiencies.
