Nutritional ketosis improves exercise metabolism in patients with very long-chain acyl-CoA dehydrogenase deficiency

This investigator-initiated, randomized, blinded, placebo-controlled crossover study included 5 patients with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). Patients drank either a ketone ester plus carbohydrate mix or an isocaloric carbohydrate drink, then cycled at their individual maximal fat oxidation work rate while quadriceps metabolism was measured by 31P-MR spectroscopy. The ketone ester rapidly induced mild ketosis and increased muscle beta-hydroxybutyrate content. During exercise, VLCADD-specific plasma acylcarnitines, quadriceps glycolytic intermediates and the in vivo Pi/PCr ratio were all lower with the ketone ester mix than with carbohydrate alone.