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Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature

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TLDR
Clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions involved in the ketogenic diet and nonalcoholic fatty liver disease are focused on, to provide an accurate revision of current literature on KDs and NAFLD.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, characterized by hepatic fat accumulation and possible development of inflammation, fibrosis, and cancer. The ketogenic diet (KD), with its drastic carbohydrate reduction, is a now popular weight loss intervention, despite safety concerns on a possible association with fatty liver. However, KDs were also reported to be beneficial on hepatic pathology, with ketone bodies recently proposed as effective modulators of inflammation and fibrosis. If the beneficial impact of weight loss on NAFLD is established, less is known on the effect of macronutrient distribution on such outcome. In a hypocaloric regimen, the latter seems not to be crucial, whereas at higher calorie intake, macronutrient ratio and, theoretically, ketosis, may become important. KDs could positively impact NAFLD for their very low carbohydrate content, and whether ketosis plays an additional role is unknown. Indeed, several mechanisms may directly link ketosis and NAFLD improvement, and elucidating these aspects would pave the way for new therapeutic strategies. We herein aimed at providing an accurate revision of current literature on KDs and NAFLD, focusing on clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions.

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Journal ArticleDOI

Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations

TL;DR: In this paper , the authors summarized the experimental and/or clinical evidence of the efficacy and safety of the ketogenic diet in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels.
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Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study.

TL;DR: VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins, and are more effective in maintaining muscle performance.
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Overview of Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Sugary Food Consumption and Other Dietary Components in Its Development.

TL;DR: In this article, the authors discuss the role of specific nutrients and the effects of different dietary interventions on non-alcoholic steatohepatitis (NASH), an inflammatory subtype that can lead to liver fibrosis and cirrhosis.
Journal ArticleDOI

Scientific evidence underlying contraindications to the ketogenic diet: An update.

TL;DR: A critical revision of the literature behind each safety alert is provided, in order to guide through the treatment options in the case of subjects with an indication to the KD and a borderline safe situation.
References
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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance

TL;DR: It is established that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity, and that the NlrP3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
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The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease

TL;DR: In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases such as Muckle–Wells syndrome, familial cold autoinflammatory syndrome and urate crystal–induced peritonitis and the findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of theNLRP3 inflammasome.
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Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor

TL;DR: It is reported that the ketone body d-β-hydroxybutyrate (βOHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs), and treatment of mice with βOHB conferred substantial protection against oxidative stress.
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A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial.

TL;DR: Body weight, body composition, serum lipid levels, and adverse effects over 24 weeks in hyperlipidemic persons who were randomly assigned to follow a low-carbohydrate, ketogenic, or low-fat, low-cholesterol, reduced-calorie diet are examined.
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Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome

TL;DR: NAFLD might be a more direct predictor of type 2 diabetes, cardiovascular disease, non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma than metabolic syndrome because it is associated with high liver fat content.
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