Methods of sustaining dietary ketosis and its effects on lipid profile
The ketogenic diet (KD) has therapeutic implications in many disease states. It was hypothesized ketone precursor supplementation would elevate blood ketone levels to therapeutic ranges (2-7 mM) without need for dietary restriction. The effects of ketogenic agents were tested on blood glucose, ketones, and lipids with a 28-day dose escalation study in male Sprague-Dawley rats: R,S-1,3-Butandiol (BD), acetoacetate ketone ester (KE), and control (H 2 O) (n≥8). Days 1-28, rats received a daily 5 g/kg intragastric gavage, based on previous toxicology studies. Once weekly, whole blood samples (10 μl) were acquired for analysis of glucose and βHB at 0, 0.5, 1, 4, 8, and 12 hours after test substance administration, or until βHB returned to baseline. At day 1 and 28, 10 μL of whole blood were collected to measure triglycerides, total cholesterol, and HDL concentration. Significant elevation of blood ketone was observed with a significant inverse relationship with blood glucose for the duration of the experiment. There were no significant changes in the lipid panel for any of the substances. There were significant reductions in body weight when animals were treated with either BD or KE as compared to control.
1. A method of suppressing hunger in a human patient in need thereof comprising: administering a therapeutically effective amount of a composition comprising a ketogenic agent to elevate one or more ketone bodies for at least four (4) hours and suppress hunger in the human patient;
wherein the ketogenic agent is R,S-1,3-butanediol acetoacetate monoester; R,S-1,3-butanediol diacetoacetate ester; or a combination thereof;
wherein administration of the composition induces ketosis in the human patient, and
wherein the human patient consumes an average of greater than 50 g of carbohydrate per day.
2. The method of claim 1 , wherein the ketogenic agent is R,S-1,3-butanediol diacetoacetate ester.
3. The method of claim 1 , wherein the ketogenic agent is administered at between 5 g/kg and 10 g/kg, or wherein each ketogenic agent is administered at between 5 g/kg and 10 g/kg.
4. The method of claim 3 , wherein the ketogenic agent is administered at 5 g/kg, 6 g/kg, 7 g/kg, 8 g/kg, 9 g/kg, or 10 g/kg.
5. The method of claim 3 , wherein each ketogenic agent is administered at 5 g/kg, 6 g/kg, 7 g/kg, 8 g/kg, 9 g/kg, or 10 g/kg.
6. The method of claim 1 , wherein the ketogenic agent is administered between about 2 g/day and about 50 g/day, or wherein each ketogenic agent is administered between about 2 g/day and about 50 g/day.
7. The method of claim 1 , wherein the one or more ketone bodies in the human patient is present in a concentration of 1.1 mM/L or greater.
8. The method of claim 1 , wherein the ketone supplement is administered chronically.
9. The method of claim 1 , wherein the ketogenic agent is administered between about 2 g/day and about 15 g/day.