Science

GEORGE F.CAHILL,JR., RICHARD L.VEECH

D-13-hydroxybutyrate, the principal “ketone” body in starving man, displaces glucose as the predominating fuel for brain, decreasing the need for glucose synthesis in liver(and kidney)and according lyspares its precursor, muscle-derived amino acids. Thus normal 70 kg. man survives 2-3 months of starvation instead of several weeks, and obese man many months to over a year. Without this metabolic adaptation, H. sapiens could not have evolved such a large brain. Recent studies have shown that D-f3-hydroxybutyrate, the principal “ketone”, is not just a fuel, but a “superfuel” more efficiently producing ATP energy than glucose or fatty acid. In a perfused rat heart preparation, it increased contractility and decreased oxygen consumption. It has also protected neuronal cells in tissue culture against exposure to toxins associated with Alzheimer’s or Parkinson’s. In a rodent model it decreased the death of lung cells induced by hemorrhagic shock. Also, mice exposed to hypoxia survived longer. These and other data suggest a potential use of f-hydroxybutyrate in a number of medical and non-medical conditions where oxygen supply or substrate utilization may be limited. Efforts are underway to prepare esters of f-hydroxybutyrate which can be taken orally or parenterally to study its potential therapeutic applications.