Therapeutic Strategies for Protein Wasting States

Abstract

The ketoanalogue of leucine, αketoisocaproate (ketoleucine) has significant protein sparing effects in fasting man. Studies designed to test its therapeutic potential in the post operative period and in patients with Duchenne muscular dystrophy were performed. Post operative patients were randomised to receive either glucose, leucine, ketoleucine in equivalent amounts. Leucine infusions had no effect on nitrogen balance, 3methylhistidine excretion or the plasma levels of prealbumin and retinol binding protein compared with glucose. On the other hand, ketoleucine resulted in a less negative nitrogen balance, and reduced 3methylhistidine excretion. Plasma prealbumin and retinol binding protein concentrations at the end of the study were significantly higher in the ketoleucine group compared with the glucose group. Thus ketoleucine reduces nitrogen loss, myofibrillar breakdown and hepatic protein synthesis in postoperative patients. Leucine is without effect. In Duchenne muscular dystrophy, administration of the ornithine salt of ketoleucine along with the ornithine salt of the ketoanalogue of isoleucine and valine brought about a small (14%) but highly significant fall in net protein degradation as measured by 3methylhistidine excretion.