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The Rate of Ketogenesis in Human Subjects on High Fat Diets, as Influenced by Different Sugars

Department of Vital Economics, The University of Rochester

1. In connection with the determination of specific dynamic action of butter fat and of superimposed sugar reported in the preceding paper, the urines collected for nitrogen analysis and blood samples, appropriately spaced, were analyzed for the ketone substances and sugar in eight of the nine subjects. It thus was possible to compare ketogenesis on the high fat diet with the respiratory metabolism and changes induced in both by the administration of sugar (C.P. corn glucose, fructose and sucrose).

2. Analysis, like the calorimetric observations, began on the third day of the all-cream diet. The increase in ketonemia from the third to the fourth day was 8.8 mg.%, or 33% greater. The increase in ketonuria was 41%. A meal of fat containing from 240 to 450 gm. 4X cream given on the fourth day increased the ketonemia in an average period of 4.1 hours 22%; the average increased excretion in the same time was 29%.

3. Sugar was administered at two intervals after the fat, 3 to 5 hours, called ‘early’ and 11 to 15 hours, called ‘late.’ Doses varied from 25 to 100 gm. The average effect of the ‘early’ dose on blood ketones in 3 hours (average 3.3 hours) was a reduction of 8.3 mg.%—the range from + 4.9 mg.% to -21.6 mg.%. The average reduction with sucrose was 10.7 mg.% and with glucose 5.4 mg.%. There was no definite relation of the effect to the amount of sugar given. Excretion was sometimes reduced and sometimes increased.

4. Blood sugar increased in all cases but at the 3.3 hour sampling varied from -35 mg.% to + 105 mg.% from the level before sugar ingestion. No parallelism was shown between blood sugar level and change in ketonemia or in total ketosis (meaning mg.% in blood multiplied by blood volume, taken as 8.8% of body weight).

5. Change in rate of ketogenesis, calculated from the total ketosis and the ketonuria, in milligrams per hour varied from + 280 mg. to - 828 mg. Sucrose invariably caused a decrease, while glucose in smaller doses (25 and 50 gm.) caused an increase and in larger doses (100 gm.) a decrease. In two paired experiments (100 gm. of sugar following nearly equal feedings of cream, the two subjects in each comparison being nearly equal in weight) glucose caused a decrease twice as great as sucrose.

6. The increased combustion of carbohydrate in five experiments was more than sufficient to extinguish the ketogenesis according to Shaffer's theory, but in no case did so within 3 to 4 hours. In one experiment out of nine the actual change agreed with theory. In the remaining three there was a decrease in carbohydrate oxidized. The CO₂-combining power of the blood increased in two experiments with sucrose and one with fructose; it decreased in two with glucose and one with fructose. The R.Q. changes found apparently were not affected by changes in CO₂-combining power except in one instance with fructose.

7. In comparing the ‘late’ dose of sugar with the ‘early’ it was found that the change in rate of ketogenesis was negative following the ‘late’ dose in all of the six experiments, whereas the ‘early’ dose caused a positive change in three of the six. In all but one experiment there was a greater combustion of sugar following the ‘late’ dose than following the ‘early.’

Manuscript received 15 July 1936.