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Methods of sustaining dietary ketosis in Sprague‐Dawley rats (643.5)
Author(s) -
Kesl Shan,
Poff Angela,
Ward Nathan,
Fiorelli Tina,
Ari Csilla,
D'Agostino Dominic
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.643.5
Subject(s) - ketosis , medium chain triglyceride , ketogenic diet , ketone bodies , medicine , triglyceride , adverse effect , endocrinology , cholesterol , metabolism , epilepsy , diabetes mellitus , psychiatry
The ketogenic diet (KD) has been successfully used to treat pediatric refractory epilepsy since the 1920s and is currently being investigated as an adjunct treatment for cancer and neurological disorders. The therapeutic efficacy of the ketogenic diet results from an elevation of blood ketones. Concerns regarding this treatment include low compliance due to restrictive diet and adverse effects on blood lipids. We hypothesized ketone precursor supplementation would elevate blood ketone levels to therapeutic ranges (2‐5mM) without need for dietary restriction. We tested the effects of the following ketone precursors on blood glucose, ketones, and lipids with a 28‐day dose escalation study in male Sprague‐Dawley rats: R,S‐1,3‐Butandiol (BD), a mineral (Na+/K+) salt of β‐hydroxybutyrate (βHB) (SO), medium chain triglyceride (MCT) oil (MO), SO+MO 1:1 mixture (SM), acetoacetate ketone ester (KE), and control (H2O) (n 蠅8). Days 1‐14, rats received a daily 5g/kg intragastric gavage, and days 15‐28 rats received a 10g/kg dose of their respective test substances. BD and KE rats were not increased to 10g/kg based on previous toxicology studies and were administered a 5g/kg dose for the duration of the study. 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. At days 1, 7, 14, 21 and 28 substances significantly decreased blood glucose and elevated βHB without dietary restriction. There were no significant elevations in the lipid panel for any of the substances. Grant Funding Source : Funded by the Office of Naval Research