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Received Sep 21, 2017; Accepted Dec 27, 2017
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.
1. Introduction
All cells of the human body require ATP as the fundamental energy source to support life. Because mitochondria produce the majority of ATP, impaired mitochondrial function is implicated in the majority of today’s most concerning chronic and degenerative health conditions including obesity, cardiovascular disease, cancer, diabetes, sarcopenia, and neurodegenerative diseases [1]. Much of this association between mitochondrial function and disease can be attributed to excessive mitochondrial production of reactive oxygen species (ROS) [2].
Although mitochondrial ROS (mtROS) are generally considered harmful, which is certainly the case at high concentrations, modest levels stimulate necessary biological processes such as proliferation, differentiation, and immunity [3]. Adaptations that enhance resistance to oxidative stress are also induced by mtROS [3], possibly decreasing net ROS production during basal metabolism. This adaptive response is called mitohormesis [4–6] and is a promising mechanism through which lifestyle interventions that enhance mitochondrial function may, in turn, enhance resistance to chronic and degenerative diseases.
By dramatically shifting energy metabolism towards ketogenesis and fatty acid oxidation, ketogenic diets are likely to have a profound effect on mitochondrial function. However, despite the rapidly growing amount of research on ketogenic diets and their effects on various disease states, only a small amount of this research has focused on mitochondrial function or oxidative stress. The well-established increase in fat oxidation induced by a ketogenic diet [7, 8] clearly indicates prominent connection with mitochondrial function and, in turn, oxidative stress and mitohormesis [5, 6, 9]. Therefore, the purpose of this review is to describe the current, but limited, understanding of how ketogenic diets may affect mitochondrial function and resistance to oxidative stress, particularly within the context of extending human healthspan.
2. Nutritional Ketosis
The use of lifestyle interventions to treat and prevent chronic disease is attractive because of their potential to lower medical costs and produce more robust and holistic improvements in health. Ketogenic diets have been studied sporadically for more than 100 years, but over the last 15 years, a growing number of researchers have contributed to what is now...