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Nutrients 2017, 9(9), 1019; doi:10.3390/nu9091019

The 1-Week and 8-Month Effects of a Ketogenic Diet or Ketone Salt Supplementation on Multi-Organ Markers of Oxidative Stress and Mitochondrial Function in Rats

School of Kinesiology, Auburn University, Auburn, AL 36849, USA
Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA
Department of Human Health Performance, University of Montana, Missoula, MT 59812, USA
Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine—Auburn Campus, Auburn, AL 36849, USA
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, USA
Applied Sports Performance Institute, Tampa, FL 33607, USA
Authors to whom correspondence should be addressed.
Received: 28 August 2017 / Revised: 11 September 2017 / Accepted: 13 September 2017 / Published: 15 September 2017
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
View Full-Text   |   Download PDF [3269 KB, uploaded 15 September 2017]   |  


We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow (SC) (n = 10) or SC + KS (~1.2 g/day, n = 10). For long-term feedings, 4 month-old male rats were provided KD (n = 8), SC (n = 7) or SC + KS (n = 7) for 8 months and rotarod tested every 2 months. Blood, brain (whole cortex), liver and gastrocnemius muscle were harvested from all rats for biochemical analyses. Additionally, mitochondria from the brain, muscle and liver tissue of long-term-fed rats were analyzed for mitochondrial quantity (maximal citrate synthase activity), quality (state 3 and 4 respiration) and reactive oxygen species (ROS) assays. Liver antioxidant capacity trended higher in short-term KD- and SC + KS-fed versus SC-fed rats, and short-term KD-fed rats exhibited significantly greater serum ketones compared to SC + KS-fed rats indicating that the diet (not KS supplementation) induced ketonemia. In long term-fed rats: (a) serum ketones were significantly greater in KD- versus SC- and SC + KS-fed rats; (b) liver antioxidant capacity and glutathione peroxidase protein was significantly greater in KD- versus SC-fed rats, respectively, while liver protein carbonyls were lowest in KD-fed rats; and (c) gastrocnemius mitochondrial ROS production was significantly greater in KD-fed rats versus other groups, and this paralleled lower mitochondrial glutathione levels. Additionally, the gastrocnemius pyruvate-malate mitochondrial respiratory control ratio was significantly impaired in long-term KD-fed rats, and gastrocnemius mitochondrial quantity was lowest in these animals. Rotarod performance was greatest in KD-fed rats versus all other groups at 2, 4 and 8 months, although there was a significant age-related decline in performance existed in KD-fed rats which was not evident in the other two groups. In conclusion, short- and long-term KD improves select markers of liver oxidative stress compared to SC feeding, although long-term KD feeding may negatively affect skeletal muscle mitochondrial physiology. View Full-Text
Keywords: ketogenic dieting; ketone salts; skeletal muscle; brain; liver; oxidative stress; mitochondria ketogenic dieting; ketone salts; skeletal muscle; brain; liver; oxidative stress; mitochondria

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Kephart, W.C.; Mumford, P.W.; Mao, X.; Romero, M.A.; Hyatt, H.W.; Zhang, Y.; Mobley, C.B.; Quindry, J.C.; Young, K.C.; Beck, D.T.; Martin, J.S.; McCullough, D.J.; D’Agostino, D.P.; Lowery, R.P.; Wilson, J.M.; Kavazis, A.N.; Roberts, M.D. The 1-Week and 8-Month Effects of a Ketogenic Diet or Ketone Salt Supplementation on Multi-Organ Markers of Oxidative Stress and Mitochondrial Function in Rats. Nutrients 2017, 9, 1019.

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