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

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Jan. 17, 2022

The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate regimen that mimics the metabolism of fasting state to induce production ketone bodies. KD has long been established as remarkably successful dietary approach for treatment intractable epilepsy increasingly garnered research attention rapidly in past decade, subject emerging evidence promising therapeutic potential various diseases, besides epilepsy, from obesity malignancies. In this review, we summarize experimental and/or clinical efficacy safety different discuss possible mechanisms action based on recent advances understanding influence at cellular molecular levels. We emphasize may function through multiple mechanisms, which remain be further elucidated. challenges future directions implementation spectrum diseases have discussed. suggest that, with encouraging effects increasing insights into action, randomized controlled trials should conducted elucidate foundation use KD.

Language: Английский

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

Obesity Reviews, Journal Year: 2020, Volume and Issue: 21(8)

Published: March 24, 2020

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

Language: Английский

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Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD)

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is a series of diseases, involving excessive lipid deposition in the and often accompanied by obesity, diabetes, dyslipidemia, abnormal blood pressure, other metabolic disorders. In order to more accurately reflect its pathogenesis, an international consensus renamed NAFLD 2020 as (dysfunction) associated with (MAFLD). The changes diet lifestyle are recognized non-drug treatment strategies; however, due complex pathogenesis NAFLD, current drug therapies mainly focused on pathogenic factors, key links related disorders targets. There still lack specific drugs. clinical studies, common treatments include regulation glucose metabolism protect anti-inflammation. based enterohepatic axis, targeting gut microbiota, gradually emerging, various new metabolism-regulating drugs also under development. Therefore, this review article has comprehensively discussed research advancements recent years.

Language: Английский

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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

Nutrients, Journal Year: 2021, Volume and Issue: 13(5), P. 1442 - 1442

Published: April 24, 2021

NAFLD is the world's most common chronic liver disease, and its increasing prevalence parallels global rise in diabetes obesity. It characterised by fat accumulation evolving to non-alcoholic steatohepatitis (NASH), an inflammatory subtype that can lead fibrosis cirrhosis. Currently, there no effective pharmacotherapeutic treatment for NAFLD. Treatment therefore based on lifestyle modifications including changes diet exercise, although it unclear what form of intervention is. The aim this review, then, discuss role specific nutrients effects different dietary interventions well established unhealthy rich calories, sugars, saturated fats low polyunsaturated fatty acids, fibre, micronutrients plays a critical development progression disease. However, few clinical trials have evaluated nutrition We, therefore, summarise currently known about macronutrients, foods, patterns prevention treatment. Most current guidelines recommend low-calorie, plant-based diets, such as Mediterranean diet, pattern treat More are required, however, identify best evidence-based approach.

Language: Английский

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Diet and exercise in NAFLD/NASH: Beyond the obvious

Liver International, Journal Year: 2021, Volume and Issue: 41(10), P. 2249 - 2268

Published: July 30, 2021

Lifestyle represents the most relevant factor for non-alcoholic fatty liver disease (NAFLD) as hepatic manifestation of metabolic syndrome. Although a tremendous body clinical and preclinical data on effectiveness dietary lifestyle interventions exist, complexity this topic makes firm evidence-based recommendations nutrition exercise in NAFLD difficult. The aim review is to guide readers through labyrinth recent scientific findings diet steatohepatitis (NASH), summarizing "obvious" holistic manner simultaneously highlighting stimulating aspects translational research "beyond obvious". Specifically, importance calorie restriction regardless composition evidence from low-carbohydrate diets target incidence severity are discussed. aspect ketogenesis-potentially achieved via intermittent restriction-seems be central these warranting further investigation. Interactions with gut microbiota individual genetic background need comprehensively understood order develop personalized concepts strategies patients NAFLD/NASH.

Language: Английский

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Inflammation and Nutrition: Friend or Foe?

Nutrients, Journal Year: 2023, Volume and Issue: 15(5), P. 1159 - 1159

Published: Feb. 25, 2023

The importance of the interplay between inflammation and nutrition has generated much interest in recent times. Inflammation been identified as a key driver for disease-related malnutrition, leading to anorexia, reduced food intake, muscle catabolism, insulin resistance, which are stimulating catabolic state. Interesting data suggest that also modulates response nutritional treatment. Studies have demonstrated patients with high show no interventions, while lower levels do. This may explain contradictory results trials date. Several studies heterogeneous patient populations, or critically ill advanced cancer patients, not found significant benefits on clinical outcome. Vice versa, several dietary patterns nutrients pro- anti-inflammatory properties identified, demonstrating influences inflammation. Within this review, we summarize discuss advances both role malnutrition effect

Language: Английский

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Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 11, 2024

Abstract Diet, serving as a vital source of nutrients, exerts profound influence on human health and disease progression. Recently, dietary interventions have emerged promising adjunctive treatment strategies not only for cancer but also neurodegenerative diseases, autoimmune cardiovascular metabolic disorders. These demonstrated substantial potential in modulating metabolism, trajectory, therapeutic responses. Metabolic reprogramming is hallmark malignant progression, deeper understanding this phenomenon tumors its effects immune regulation significant challenge that impedes eradication. Dietary intake, key environmental factor, can tumor metabolism. Emerging evidence indicates might affect the nutrient availability tumors, thereby increasing efficacy treatments. However, intricate interplay between pathogenesis other diseases complex. Despite encouraging results, mechanisms underlying diet-based remain largely unexplored, often resulting underutilization management. In review, we aim to illuminate various interventions, including calorie restriction, fasting-mimicking diet, ketogenic protein restriction high-salt high-fat high-fiber aforementioned diseases. We explore multifaceted impacts these encompassing their immunomodulatory effects, biological impacts, molecular mechanisms. This review offers valuable insights into application therapies

Language: Английский

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Updated mechanisms of MASLD pathogenesis

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 22, 2024

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) has garnered considerable attention globally. Changing lifestyles, over-nutrition, and physical inactivity have promoted its development. MASLD is typically accompanied by obesity strongly linked to metabolic syndromes. Given that prevalence on the rise, there an urgent need elucidate pathogenesis. Hepatic lipid accumulation generally triggers lipotoxicity induces or progress steatohepatitis (MASH) mediating endoplasmic reticulum stress, oxidative organelle dysfunction, ferroptosis. Recently, significant been directed towards exploring role of gut microbial dysbiosis in development MASLD, offering a novel therapeutic target for MASLD. Considering are no recognized pharmacological therapies due diversity mechanisms involved difficulty associated with undertaking clinical trials, potential targets remain elusive. Thus, this article aimed summarize evaluate prominent roles lipotoxicity, ferroptosis, microbes underlying their effects. Furthermore, existing advances challenges treatment were outlined.

Language: Английский

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Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1638 - 1638

Published: July 8, 2020

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis the initial stage of disease, which characterized by lipid accumulation in hepatocytes, can progress to non-alcoholic steatohepatitis (NASH) inflammation various levels fibrosis that further increase risk developing cirrhosis hepatocellular carcinoma. The pathogenesis NAFLD influenced interactions between genetic environmental factors involves several biological processes multiple organs. No effective therapy currently available for treatment NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear regulate many functions disturbed NAFLD, including glucose metabolism, as well inflammation. Thus, they represent relevant clinical targets In this review, we describe determinants mechanisms underlying its progression complications, current therapeutic strategies employed. We also focus on complementary distinct roles PPAR isotypes effects first-generation agonists. Finally, review novel safe agonists improved efficacy their potential use

Language: Английский

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Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study

The Journal of Clinical Endocrinology & Metabolism, Journal Year: 2020, Volume and Issue: 105(9), P. 2939 - 2949

Published: June 2, 2020

Abstract Context We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on microbiota in patients with obesity insulin resistance to test hypothesis that source may modulate response VLCKD interventions. Subjects Methods Forty-eight (19 males 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass [BMI] 35.9 4.1 kg/m2) were randomly assigned three regimens (≤800 kcal/day) containing plant, protein. Anthropometric indexes; blood urine chemistry, including parameters kidney, liver, glucose, lipid metabolism; composition; muscle strength; taxonomic composition gut microbiome assessed. Adverse events also recorded. Results Body weight, BMI, pressure, waist circumference, HOMA index, insulin, total low-density lipoprotein cholesterol decreased all patients. Patients who consumed whey had a more pronounced improvement strength. The markers renal function worsened slightly group. A decrease relative abundance Firmicutes an increase Bacteroidetes observed after consumption VLCKDs. This pattern was less consuming Conclusions VLCKDs led significant weight loss striking metabolic over period. based vegetable have safer profile result healthier than those proteins. are effective maintaining performance.

Language: Английский

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