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Investigating the Link between Ketogenic Diet, NAFLD, Mitochondria, and Oxidative Stress: A Narrative Review

Published: 8 May 2023
(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)

Abstract

Together with the global rise in obesity and metabolic syndrome, the prevalence of individuals who suffer from nonalcoholic fatty liver disease (NAFLD) has risen dramatically. NAFLD is currently the most common chronic liver disease and includes a continuum of liver disorders from initial fat accumulation to nonalcoholic steatohepatitis (NASH), considered the more severe forms, which can evolve in, cirrhosis, and hepatocellular carcinoma. Common features of NAFLD includes altered lipid metabolism mainly linked to mitochondrial dysfunction, which, as a vicious cycle, aggravates oxidative stress and promotes inflammation and, as a consequence, the progressive death of hepatocytes and the severe form of NAFLD. A ketogenic diet (KD), i.e., a diet very low in carbohydrates (<30 g/die) that induces “physiological ketosis”, has been demonstrated to alleviate oxidative stress and restore mitochondrial function. Based on this, the aim of the present review is to analyze the body of evidence regarding the potential therapeutic role of KD in NAFLD, focusing on the interplay between mitochondria and the liver, the effects of ketosis on oxidative stress pathways, and the impact of KD on liver and mitochondrial function.

9. Conclusions

KD seems to improve mitochondrial dysfunction by stimulating mitochondriogenesis, mitochondrial dynamics, and bioenergetic pathways, as observed especially in vitro and in vivo studies. Ketosis itself plays a pivotal role in stimulating the activation of several key factors involved in liver-protective activities that alleviate oxidative damage, the inflammatory response, and, globally, liver function. However, despite the promising results reported in NAFLD patients, more high-quality, randomized clinical trials are needed.