Methods of sustaining dietary ketosis and its effects on lipid profile

Abstract

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.

What is claimed is: 
     
         1 . A method of suppressing hunger in a patient by administering a composition comprising:
 a ketogenic agent, wherein the ketogenic agent is:
 R,S-1,3-Butandiol, R,S-1,3-butanediol acetoacetate diester, or a combination thereof; 
   wherein the composition suppresses hunger in the patient.   
     
     
         2 . The method of  claim 1 , wherein the ketogenic agent is R,S-1,3-butanediol acetoacetate diester. 
     
     
         3 . The method of  claim 1 , wherein the 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 1 , wherein each ketogenic agent is administered at between 5 g/kg and 10 g/kg. 
     
     
         6 . The method of  claim 5 , 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. 
     
     
         7 . The method of  claim 1 , wherein the ketogenic agent is administered at about 1 g/kg/day and about 10 g/kg/day. 
     
     
         8 . The method of  claim 7 , wherein each ketogenic agent is administered at about 1 g/kg/day and about 10 g/kg/day. 
     
     
         9 . The method of  claim 8 , wherein each ketogenic agent is administered at 1 g/kg/day, 1 g/kg/day, 1.25 g/kg/day, 1.5 g/kg/day, 2 g/kg/day, 2.5 g/kg/day, 3 g/kg/day, 3.5 g/kg/day, 4 g/kg/day, 4.5 g/kg/day, 5 g/kg/day, 5.5 g/kg/day, 6 g/kg/day, 7 g/kg/day, 8 g/kg/day, 8.5 g/kg/day, 9 g/kg/day, 9.5 g/kg/day, or 10 g/kg/day. 
     
     
         10 . A method of suppressing hunger in a patient by administering a composition comprising R,S-1,3-butanediol acetoacetate diester,
 wherein the composition suppresses hunger in the patient.   
     
     
         11 . The method of  claim 10 , further comprising R,S-1,3-butanediol. 
     
     
         12 . The method of  claim 10 , wherein R,S-1,3-butanediol acetoacetate diester is administered at between 5 g/kg and 10 g/kg. 
     
     
         13 . The method of  claim 12 , wherein R,S-1,3-butanediol acetoacetate diester is administered at 5 g/kg, 6 g/kg, 7 g/kg, 8 g/kg, 9 g/kg, or 10 g/kg. 
     
     
         14 . The method of  claim 11 , wherein R,S-1,3-butanediol and R,S-1,3-butanediol acetoacetate diester are independently administered at between 5 g/kg and 10 g/kg. 
     
     
         15 . The method of  claim 14 , wherein R,S-1,3-butanediol and R,S-1,3-butanediol acetoacetate diester are independently administered at 5 g/kg, 6 g/kg, 7 g/kg, 8 g/kg, 9 g/kg, or 10 g/kg. 
     
     
         16 . The method of  claim 10 , R,S-1,3-butanediol acetoacetate diester is administered at about 1 g/kg/day to about 10 g/kg/day. 
     
     
         17 . The method of  claim 16 , wherein R,S-1,3-butanediol acetoacetate diester is administered at 1 g/kg/day, 1 g/kg/day, 1.25 g/kg/day, 1.5 g/kg/day, 2 g/kg/day, 2.5 g/kg/day, 3 g/kg/day, 3.5 g/kg/day, 4 g/kg/day, 4.5 g/kg/day, 5 g/kg/day, 5.5 g/kg/day, 6 g/kg/day, 7 g/kg/day, 8 g/kg/day, 8.5 g/kg/day, 9 g/kg/day, 9.5 g/kg/day, or 10 g/kg/day. 
     
     
         18 . The method of  claim 11 , R,S-1,3-butanediol is administered at about 1 g/kg/day to about 10 g/kg/day. 
     
     
         19 . The method of  claim 18 , wherein R,S-1,3-butanediol is administered at 1 g/kg/day, 1 g/kg/day, 1.25 g/kg/day, 1.5 g/kg/day, 2 g/kg/day, 2.5 g/kg/day, 3 g/kg/day, 3.5 g/kg/day, 4 g/kg/day, 4.5 g/kg/day, 5 g/kg/day, 5.5 g/kg/day, 6 g/kg/day, 7 g/kg/day, 8 g/kg/day, 8.5 g/kg/day, 9 g/kg/day, 9.5 g/kg/day, or 10 g/kg/day.