The calorie deficiency hypothesis of ketogenesis tested in man

Abstract

According to the calorie deficiency hypothesis of ketogenesis, ketosis is due to calorie deficiency per se rather than to a specific lack of carbohydrates at the cellular level. The demonstration of adequate supplies of Krebs cycle intermediates in ketosis and the alleviation of ketosis by ketogenic fat diets in calorically adequate amounts in rats have been considered to support the calorie deficiency hypothesis. In this study, acetone concentrations in alveolar air were determined by means of gas chromatography in four non-obese fasting human subjects. The concentrations of acetone during the first 2–3 days of fasting rose from 0.3 μg. to approximately 3 μ g. 100 mg. of alveolar air. During the subsequent 2 days the acetone concentrations increased sharply in a linear pattern until they reached a plateau at approximately 30 μ g. 100 ml. alveolar air. It was demonstrated that a “ketogenic” diet furnishing over 92 per cent of its calories in the form of fat delayed the development of ketosis when administered from the beginning of the experimental period. Once maximal starvation ketosis has developed, 2000 calories of this diet per day no longer had an “antiketotic” effect. In contrast, only 1000 calories of pure carbohydrates taken in one meal resulted in the complete alleviation of ketosis during the sebsequent 2 days, in spite of continued calorie deficiency. These observations are suggestive of a ketosisretarding effect of “ketogenic” diets when compared with complete fasting. The results obtained during maximal starvation ketosis however, are incompatible with the calorie deficiency hypothesis of ketogenesis in man, and support an antiketotic effect specific for carbohydrates.