β-Hydroxybutyrate Elicits Favorable Mitochondrial Changes in Skeletal Muscle

Abstract

The clinical benefit of ketosis has historically and almost exclusively centered on neurological conditions, lending insight into how ketones alter mitochondrial function in neurons. However, there is a gap in our understanding of how ketones influence mitochondria within skeletal muscle cells. The purpose of this study was to elucidate the specific effects of β-hydroxybutyrate (β-HB) on muscle cell mitochondrial physiology. In addition to increased cell viability, murine myotubes displayed beneficial mitochondrial changes evident in reduced H2O2 emission and less mitochondrial fission, which may be a result of a β-HB-induced reduction in ceramides. Furthermore, muscle from rats in sustained ketosis similarly produced less H2O2 despite an increase in mitochondrial respiration and no apparent change in mitochondrial quantity. In sum, these results indicate a general improvement in muscle cell mitochondrial function when β-HB is provided as a fuel.

Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats

“…Therefore, the relative muscle mass was higher in KD animals. This finding is consistent with earlier reports describing four-week ketogenic diet feeding [ 6 , 24 , 25 ]. Consequently, application of a ketogenic diet for four weeks is not harmful to muscle quantity.…”

“…However, these findings contradict those of studies that have shown lowered mitochondria function [ 5 , 21 ] and decreased CS activity [ 21 ] by a ketogenic diet. In this regard, Parker et al reported recently that a ketogenic diet followed for four weeks decreased CS activity in the red portion, but not in the white portion of gastrocnemius muscles in rats [ 25 ]. This finding suggests that mitochondrial enzyme adaptation to ketogenic diet depends on the muscle fiber type.…”

“…This finding suggests that mitochondrial enzyme adaptation to ketogenic diet depends on the muscle fiber type. In addition, EDL muscle has different proportions of muscle fiber types from those of gastrocnemius muscle [ 42 , 49 ] used in earlier studies [ 5 , 21 , 25 ]. Although our results indicate a positive role of ketogenic diet on mitochondria, a study examining muscle fiber types must be conducted to ascertain ketogenic diet effects on those enzymes in skeletal muscle.…”

COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm

“…An NADH, which fuels complex I of the ETC, is also generated during R-BHB oxidation to acetoacetate. R-BHB has also been shown to increase PGC-1 α levels [ 94 ] and mitochondrial fusion [ 95 , 96 ], which are known to increase mitochondrial energy generation. Therefore, ketone body catabolism is a substantial source of ATP when the cytokine storm leads to the block of the mitochondrial oxidation of carbohydrate catabolites.…”

Ketogenic diets: Opportunities and limitations in practical application (LITERATURE REVIEW)

“…Recent discoveries have revealed that ketones, such as acetoacetate (AcAc) and its precursor β-hydroxybutyrate (β-HB), are not only viable fuel sources for all cells with mitochondria, including the brain (14,15) but are also legitimate signalling molecules, eliciting advantageous changes in inflammation (16), cognition (17,18), oxidative stress (19) and more. Beyond pathology, ketones may also be a relevant metabolic fuel in the context of physical activity, improving athletic performance (20) and myocardial adenosine triphosphate (ATP) generation (21,22).…”