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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 (H₂O) (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.

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