Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats

Abstract

BackgroundNutritional ketosis induced by the ketogenic diet (KD) has therapeutic applications for many disease states. We hypothesized that oral administration of exogenous ketone supplements could produce sustained nutritional ketosis (>0.5 mM) without carbohydrate restriction.MethodsWe tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured.ResultsExogenous ketone supplementation caused a rapid and sustained elevation of βHB, reduction of glucose, and little change to lipid biomarkers compared to control animals.ConclusionsThis study demonstrates the efficacy and tolerability of oral exogenous ketone supplementation in inducing nutritional ketosis independent of dietary restriction.

Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats

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“…For the sub-chronic gavage administration the gavage dose was used that induced desired elevation of blood ketone based on our previous studies (Kesl et al, 2016). …”

An Evolutionary and Mechanistic Perspective on Dietary Carbohydrate Restriction in Cancer Prevention

“…For instance, a reciprocal association between blood glucose and KB levels has been shown in both mice [136] and human cancer patients [135]. The significance of high KBs lies in their ability to retard tumor growth [137][138][139][140].…”

Diazoxide for Lowering Insulin Levels in Breast Cancer Patients

“…While hyperglycemia correlates with poor outcomes in cancer patients [2], this side effect could be overcome by combining the drug with (a) acarbose, which completely inhibited mammary carcinogenesis in rats [5]; (b) carbohydrate restriction, which by itself could retard tumor growth [6]; and (c) medium chain triglycerides and exogenous ketone bodies, which rapidly elevate ketone body levels while decreasing blood glucose concentration [7]. Such combinations could have the potential to prolong tamoxifen‐induced remissions markedly.…”