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

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Янв. 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.

Язык: Английский

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Ketone bodies: from enemy to friend and guardian angel

BMC Medicine, Год журнала: 2021, Номер 19(1)

Опубликована: Дек. 9, 2021

Abstract During starvation, fasting, or a diet containing little digestible carbohydrates, the circulating insulin levels are decreased. This promotes lipolysis, and breakdown of fat becomes major source energy. The hepatic energy metabolism is regulated so that under these circumstances, ketone bodies generated from β-oxidation fatty acids secreted as ancillary fuel, in addition to gluconeogenesis. Increased plasma thus indicate dietary shortage carbohydrates. Ketone not only serve fuel but also promote resistance oxidative inflammatory stress, there decrease anabolic insulin-dependent expenditure. It has been suggested beneficial non-metabolic actions on organ functions mediated by them acting ligand specific cellular targets. We propose here role different pathway initiated induction stress mitochondria during increased ketolysis. Oxidative induced body long term because it initiates an adaptive (hormetic) response characterized activation master regulators cell-protective mechanism, nuclear factor erythroid 2-related 2 (Nrf2), sirtuins, AMP-activated kinase. results resolving upregulation anti-oxidative anti-inflammatory activities, improved mitochondrial function growth, DNA repair, autophagy. In heart, enhanced ketolysis improves damage after ischemic insults cardiotoxic doxorubicin. Sodium-dependent glucose co-transporter (SGLT2) inhibitors may exert their cardioprotective action via increasing conclude synthesis use periods deficient food supply low causes latter protective which allows cells cope with lower availability. Keywords Ketogenic diet, bodies, Beta hydroxybutyrate, Insulin, Obesity, Type diabetes, Inflammation, Cardiovascular disease, SGLT2, Hormesis

Язык: Английский

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Obesity Management in Adults

JAMA, Год журнала: 2023, Номер 330(20), С. 2000 - 2000

Опубликована: Ноя. 28, 2023

Importance Obesity affects approximately 42% of US adults and is associated with increased rates type 2 diabetes, hypertension, cardiovascular disease, sleep disorders, osteoarthritis, premature death. Observations A body mass index (BMI) 25 or greater commonly used to define overweight, a BMI 30 obesity, lower thresholds for Asian populations (BMI ≥25-27.5), although use alone not recommended determine individual risk. Individuals obesity have higher incident disease. In men 39, event are 20.21 per 1000 person-years compared 13.72 in normal BMI. women 39.9, 9.97 6.37 Among people 5% 10% weight loss improves systolic blood pressure by about 3 mm Hg those may decrease hemoglobin 1c 0.6% 1% diabetes. Evidence-based treatment includes interventions addressing 5 major categories: behavioral interventions, nutrition, physical activity, pharmacotherapy, metabolic/bariatric procedures. Comprehensive care plans combine appropriate patients. Multicomponent ideally consisting at least 14 sessions 6 months promote lifestyle changes, including components such as self-monitoring, dietary activity counseling, problem solving, often produce loss, regain occurs 25% more participants 2-year follow-up. Effective nutritional approaches focus on reducing total caloric intake strategies based patient preferences. Physical without calorie reduction typically causes less (2-3 kg) but important weight-loss maintenance. Commonly prescribed medications antidepressants (eg, mirtazapine, amitriptyline) antihyperglycemics glyburide insulin cause gain, clinicians should review consider alternatives. Antiobesity nonpregnant patients overweight weight-related comorbidities conjunction modifications. Six currently approved the Food Drug Administration long-term use: glucagon-like peptide receptor 1 (GLP-1) agonists (semaglutide liraglutide only), tirzepatide (a glucose-dependent insulinotropic polypeptide/GLP-1 agonist), phentermine-topiramate, naltrexone-bupropion, orlistat. Of these, has greatest effect, mean 21% 72 weeks. Endoscopic procedures (ie, intragastric balloon endoscopic sleeve gastroplasty) can attain 13% months. Weight from metabolic bariatric surgeries laparoscopic gastrectomy Roux-en-Y gastric bypass) ranges 30% 12 Maintaining difficult, clinical guidelines support antiobesity when maintenance inadequate alone. Conclusion Relevance US. Behavioral GLP-1 8% surgery loss. Comprehensive, evidence-based combines

Язык: Английский

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Implicating the effect of ketogenic diet as a preventive measure to obesity and diabetes mellitus

Life Sciences, Год журнала: 2020, Номер 264, С. 118661 - 118661

Опубликована: Окт. 26, 2020

Язык: 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, Год журнала: 2021, Номер 13(5), С. 1442 - 1442

Опубликована: Апрель 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.

Язык: Английский

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The Role of Ketogenic Diet in the Treatment of Neurological Diseases

Nutrients, Год журнала: 2022, Номер 14(23), С. 5003 - 5003

Опубликована: Ноя. 24, 2022

Over a hundred years of study on the favourable effect ketogenic diets in treatment epilepsy have contributed to long-lasting discussion its potential influence other neurological diseases. A significant increase number scientific studies that field has been currently observed. The aim this paper is widespread, thorough analysis available evidence respect role diet therapy diseases such as: epilepsy, Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS) and migraine. wide range mechanisms action demonstrated diseases, including, among effects, reduction inflammatory conditions amount reactive oxygen species (ROS), restoration myelin sheath neurons, formation regeneration mitochondria, neuronal metabolism, provision an alternative source energy for neurons (ketone bodies), glucose insulin concentrations, amyloid plaques, induction autophagy, alleviation microglia activation, excessive modulation intestinal microbiota, expression genes, dopamine production glutamine conversion into GABA. discussed (including randomised controlled studies), conducted patients, stressed effectiveness promising therapeutic frequent advantage was over non-ketogenic (in control groups) with simultaneous safety feasibility when conducting nutritional model.

Язык: Английский

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Developing dietary interventions as therapy for cancer

Nature reviews. Cancer, Год журнала: 2022, Номер 22(8), С. 452 - 466

Опубликована: Май 25, 2022

Язык: Английский

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A Heart-Healthy Diet for Cardiovascular Disease Prevention: Where Are We Now?

Vascular Health and Risk Management, Год журнала: 2023, Номер Volume 19, С. 237 - 253

Опубликована: Апрель 1, 2023

Purpose of Review: The relationship between cardiovascular health and diet is evolving. Lifestyle modifications including changes are the primary approach in managing cardiometabolic risk factors. Thus, understanding different diets their impact on important guiding secondary prevention disease (CVD). Yet, there many barriers limitations to adopting a heart healthy diet. Recent Findings: Diets rich fruits, vegetables, legumes, whole grains, lean protein sources, with minimization/avoidance processed foods, trans-fats, sugar sweetened beverages, recommended by guidelines. Mediterranean, DASH, plant-based have all proven cardioprotective varying degrees endorsed professional healthcare societies, while other emerging such as ketogenic intermittent fasting require more long-term study. effects gut microbiome opened new path for precision medicine improve certain dietary metabolites, trimethylamine N-oxide, factors, along diversity gene pathways relation CVD management, being explored. Summary: In this review, we provide comprehensive up-to-date overview established health. We discuss effectiveness various most importantly approaches nutritional counseling where traditional non-traditional practiced, helping patients adopt diets. address regarding food insecurity, poor access, socioeconomic burden. Lastly, need multidisciplinary team-based approach, role nutrition specialist, implementing culturally-tailored recommendations. Understanding finding ways overcome heart-healthy will take us miles management. Keywords: disease, diet, guidelines, nutrition, disparities,

Язык: Английский

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Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial

Psychiatry Research, Год журнала: 2024, Номер 335, С. 115866 - 115866

Опубликована: Март 20, 2024

The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this shown promise psychiatric illness. We conducted a 4–month pilot study to investigate effects KD on individuals with schizophrenia or bipolar disorder existing abnormalities. Twenty–three participants were enrolled single–arm trial. Results showcased improvements health, no meeting syndrome criteria by conclusion. Adherent experienced significant reduction weight (12%), BMI waist circumference (13%), visceral adipose tissue (36%). Observed biomarker enhancements population include 27% decrease HOMA–IR, 25% drop triglyceride levels. In measurements, showed 32% Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved an average 31%, proportion that started elevated symptomatology at least 1–point CGI (79%). outcomes across cohort encompassed increased life satisfaction (17%) enhanced sleep quality (19%). This trial underscores potential advantages adjunctive dietary grappling serious mental

Язык: Английский

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Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials

BMC Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Май 25, 2023

Abstract Background Systematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits ketogenic diets (KD) in various participants such as patients with epilepsy adults overweight or obesity . Nevertheless, there has been little synthesis strength quality this evidence aggregate. Methods To grade from published RCTs that assessed association KD, low-carbohydrate high-fat diet (K-LCHF), very low-calorie KD (VLCKD) health outcomes, PubMed, EMBASE, Epistemonikos, Cochrane database systematic were searched up to February 15, 2023. Meta-analyses included. re-performed using a random-effects model. The per provided was rated by GRADE (Grading Recommendations, Assessment, Development, Evaluations) criteria high, moderate, low, low. Results We included 17 comprising 68 (median [interquartile range, IQR] sample size 42 [20–104] follow-up period 13 [8–36] weeks) 115 unique associations. There 51 statistically significant associations (44%) which four supported high-quality (reduced triglyceride ( n = 2), seizure frequency 1) increased low-density lipoprotein cholesterol (LDL-C) 1)) moderate-quality (decrease body weight, respiratory exchange ratio (RER), hemoglobin A 1c , total cholesterol). remaining low (26 associations) (17 evidence. In obese adults, VLCKD significantly associated improvement anthropometric cardiometabolic outcomes without worsening muscle mass, LDL-C, cholesterol. K-LCHF reduced weight fat percentage, but also mass healthy participants. Conclusions This umbrella review found beneficial moderate on several parameters. However, clinically meaningful increase LDL-C. Clinical long-term are warranted investigate whether short-term effects will translate cardiovascular events mortality.

Язык: Английский

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