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Bae J, Kim YE, Jung KJ, Jee SH, Lee BW. Association between serum beta-hydroxybutyrate levels and risk of type 2 diabetes mellitus in patients with impaired fasting glucose. Nutr Diabetes 2025; 15:16. [PMID: 40240753 PMCID: PMC12003790 DOI: 10.1038/s41387-025-00364-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/20/2025] [Accepted: 02/11/2025] [Indexed: 04/18/2025] Open
Abstract
OBJECTIVES Ketogenic conditions have gained attention due to their favorable metabolic prognoses. We aimed to investigate the association between blood levels of beta-hydroxybutyrate (βHB), the most abundant form of ketone body, and type 2 diabetes (T2D) incidence in patients with impaired fasting glucose (IFG). METHODS We randomly selected 500 patients with IFG from the prospective Korean Cancer Prevention Study II biobank. Blood levels of βHB were measured from the stored samples, and the diagnostic data from the Korean National Health Insurance Service were used to determine the probability of T2D-free survival. A multivariable Cox regression analysis was performed to assess the association between blood βHB levels and the incidence of new-onset T2D. RESULTS A total of 453 patients with IFG were included, and 105 (23%) developed T2D during a mean follow-up period of 10.9 years. Higher blood βHB levels in patients with IFG were associated with improved T2D-free survival, although it was not statistically significant (log-rank test, p = 0.058). In multivariable Cox regression models, βHB levels showed a tendency toward a lower risk of T2D, but it was not statistically significant (HR 0.70; 95% CI 0.47-1.04; p = 0.07). CONCLUSIONS In patients with IFG, the blood βHB level showed a tendency to be associated with the risk of new-onset T2D; however, this tendency was not statistically significant.
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Affiliation(s)
- Jaehyun Bae
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
| | - Young-Eun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Keum Ji Jung
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
| | - Sun Ha Jee
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
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2
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Emanuele F, Biondo M, Tomasello L, Arnaldi G, Guarnotta V. Ketogenic Diet in Steatotic Liver Disease: A Metabolic Approach to Hepatic Health. Nutrients 2025; 17:1269. [PMID: 40219026 PMCID: PMC11990071 DOI: 10.3390/nu17071269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 03/28/2025] [Accepted: 03/31/2025] [Indexed: 04/14/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver dysfunction worldwide, characterized by hepatic steatosis that may progress to nonalcoholic steatohepatitis and cirrhosis. Owing to its strong association with metabolic disorders, current management focuses on weight reduction via lifestyle modifications. Recently, the very-low-calorie ketogenic diet (VLCKD) has emerged as a promising intervention due to its potential for rapid weight loss and reduction in liver fat. This review aims to evaluate the clinical evidence regarding the impact of ketogenic diets on hepatic steatosis. We conducted an extensive MEDLINE literature search in databases including PubMed, Scopus, and Web of Science up to December 2024. Studies assessing the effects of ketogenic or low-carbohydrate high-fat diets on liver fat, evaluated by imaging, histology, or biochemical markers, were included. The analysis indicates that ketogenic diets significantly reduce hepatic fat content and improve metabolic parameters, including insulin sensitivity and liver enzyme levels. Evidence further suggests that substituting saturated fats with unsaturated fats or replacing carbohydrates with proteins may enhance these benefits. However, considerable variability exists among studies and long-term data remain limited. Although short-term outcomes are encouraging, potential adverse effects such as dyslipidaemia, gastrointestinal disturbances, and transient 'keto flu' symptoms require careful clinical monitoring. Future research should focus on elucidating underlying mechanisms, optimizing dietary composition, and assessing long-term safety to establish ketogenic diets as a robust strategy for managing MASLD.
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Affiliation(s)
- Fabrizio Emanuele
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties “G. D’Alessandro” (PROMISE), Section of Endocrinology, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (F.E.); (L.T.); (G.A.); (V.G.)
| | - Mattia Biondo
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze Ed. 16, 90128 Palermo, Italy;
| | - Laura Tomasello
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties “G. D’Alessandro” (PROMISE), Section of Endocrinology, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (F.E.); (L.T.); (G.A.); (V.G.)
| | - Giorgio Arnaldi
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties “G. D’Alessandro” (PROMISE), Section of Endocrinology, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (F.E.); (L.T.); (G.A.); (V.G.)
| | - Valentina Guarnotta
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties “G. D’Alessandro” (PROMISE), Section of Endocrinology, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy; (F.E.); (L.T.); (G.A.); (V.G.)
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3
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Paskaleva IN, Kaleva NN, Dimcheva TD, Markova PP, Ivanov IS. Low-Carbohydrate (Ketogenic) Diet in Children with Obesity: Part 1-Diet Impact on Anthropometric Indicators and Indicators of Metabolic Syndrome and Insulin Resistance. Diseases 2025; 13:94. [PMID: 40277805 PMCID: PMC12026416 DOI: 10.3390/diseases13040094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 03/17/2025] [Accepted: 03/21/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND The ketogenic diet has been successfully used in the last 100 years in the treatment of epilepsy and other neurological disorders. In recent decades, it gained wider application in the treatment of obesity, metabolic syndrome, and type 2 diabetes. However, there have been only a few studies on its use in children with obesity and associated metabolic disorders. OBJECTIVES To determine the clinical and metabolic effects of a well-formulated low-carbohydrate (ketogenic) diet in children with obesity. METHODS One hundred children with obesity and metabolic disorders underwent initial anthropometric, laboratory, and ultrasound examinations. They were placed on a well-formulated ketogenic diet and monitored for 4 months. The 58 patients who completed the study underwent follow-up examinations to assess the effects of the diet on anthropometric, clinical, and laboratory markers of metabolic syndrome and insulin resistance, cardiovascular risk factors, and certain hormone levels. Compliance with the diet, common difficulties in adhering to it, side effects, and positive changes in the patients' health were analyzed. RESULTS At the end of the study, the average weight loss for the entire group was 6.45 kg, with a reduction in BMI of 3.12 kg/m2. Significant improvements were also observed in insulin resistance indicators, including fasting insulin levels, HOMA-IR index, QUICKI (p < 0.0001), and adiponectin (p = 0.04). The cases of hepatosteatosis decreased twofold, the number of patients with arterial hypertension was significantly reduced, as well as the number of children receiving antihypertensive therapy. Additionally, the number of patients meeting the criteria for metabolic syndrome decreased threefold. CONCLUSIONS A well-formulated short-term ketogenic diet is effective in treating obesity, metabolic syndrome, and related comorbidities, and can be part of a comprehensive approach for these patients.
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Affiliation(s)
- Ivanka N. Paskaleva
- Department of Pediatrics “Prof. Dr. Ivan Andreev”, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria; (N.N.K.); (P.P.M.); (I.S.I.)
| | - Nartsis N. Kaleva
- Department of Pediatrics “Prof. Dr. Ivan Andreev”, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria; (N.N.K.); (P.P.M.); (I.S.I.)
| | - Teodora D. Dimcheva
- Department of Medical Informatics, Biostatistics and e-Learning, Faculty of Public Health, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria;
| | - Petya P. Markova
- Department of Pediatrics “Prof. Dr. Ivan Andreev”, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria; (N.N.K.); (P.P.M.); (I.S.I.)
| | - Ivan S. Ivanov
- Department of Pediatrics “Prof. Dr. Ivan Andreev”, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria; (N.N.K.); (P.P.M.); (I.S.I.)
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4
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Ruskin DN, Martinez LA, Masino SA. Ketogenic diet, adenosine, and dopamine in addiction and psychiatry. Front Nutr 2025; 12:1492306. [PMID: 40129664 PMCID: PMC11932665 DOI: 10.3389/fnut.2025.1492306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 02/11/2025] [Indexed: 03/26/2025] Open
Abstract
Adhering to the ketogenic diet can reduce or stop seizures, even when other treatments fail, via mechanism(s) distinct from other available therapies. These results have led to interest in the diet for treating conditions such as Alzheimer's disease, depression and schizophrenia. Evidence points to the neuromodulator adenosine as a key mechanism underlying therapeutic benefits of a ketogenic diet. Adenosine represents a unique and direct link among cell energy, neuronal activity, and gene expression, and adenosine receptors form functional heteromers with dopamine receptors. The importance of the dopaminergic system is established in addiction, as are the challenges of modulating the dopamine system directly. A mediator that could antagonize dopamine's effects would be useful, and adenosine is such a mediator due to its function and location. Studies report that the ketogenic diet improves cognition, sociability, and perseverative behaviors, and might improve depression. Many of the translational opportunities based on the ketogenic diet/adenosine link have come to the fore, including addiction, autism spectrum disorder, painful conditions, and a range of hyperdopaminergic disorders.
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Mullin SM, Kelly AJ, Ní Chathail MB, Norris S, Shannon CE, Roche HM. Macronutrient Modulation in Metabolic Dysfunction-Associated Steatotic Liver Disease-the Molecular Role of Fatty Acids compared with Sugars in Human Metabolism and Disease Progression. Adv Nutr 2025; 16:100375. [PMID: 39842721 PMCID: PMC11849631 DOI: 10.1016/j.advnut.2025.100375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/23/2024] [Accepted: 01/13/2025] [Indexed: 01/24/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant public health concern, with its progression to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis leading to severe outcomes including cirrhosis, hepatocellular carcinoma, and liver failure. Whereas obesity and excess energy intake are well-established contributors to the development and progression of MASLD, the distinct role of specific macronutrients is less clear. This review examines the mechanistic pathways through which dietary fatty acids and sugars contribute to the development of hepatic inflammation and fibrosis, offering a nuanced understanding of their respective roles in MASLD progression. In terms of addressing potential therapeutic options, human intervention studies that investigate whether modifying the intake of dietary fats and carbohydrates affects MASLD progression are reviewed. By integrating this evidence, this review seeks to bridge the gap in the understanding between the mechanisms of macronutrient-driven MASLD progression and the effect of altering the intake of these nutrients in the clinical setting and presents a foundation for future research into targeted dietary strategies for the treatment of the disease.
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Affiliation(s)
- Sinéad M Mullin
- School of Public Health, Physiotherapy and Sport Science, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland; Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland
| | - Aidan J Kelly
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Méabh B Ní Chathail
- School of Public Health, Physiotherapy and Sport Science, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland; Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland
| | - Suzanne Norris
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Christopher E Shannon
- Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland; School of Medicine, University College Dublin, Belfield, Dublin, Ireland
| | - Helen M Roche
- School of Public Health, Physiotherapy and Sport Science, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland; Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland; Institute for Global Food Security, Queen's University Belfast, Northern Ireland.
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6
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Guo M, Jiang X, Ouyang H, Zhang X, Zhang S, Wang P, Bi G, Wu T, Zhou W, Liang F, Yang X, Fan S, Fang JH, Chen P, Bi H. Parabacteroides distasonis promotes liver regeneration by increasing β-hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals. Acta Pharm Sin B 2025; 15:1430-1446. [PMID: 40370533 PMCID: PMC12069244 DOI: 10.1016/j.apsb.2025.01.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 12/04/2024] [Accepted: 12/20/2024] [Indexed: 05/16/2025] Open
Abstract
The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.
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Affiliation(s)
- Manlan Guo
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xiaowen Jiang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Hui Ouyang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xianglong Zhang
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Shuaishuai Zhang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Peng Wang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Guofang Bi
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Ting Wu
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Wenhong Zhou
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Fengting Liang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xiao Yang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
- The State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China
| | - Shicheng Fan
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jian-hong Fang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Peng Chen
- Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Huichang Bi
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong–Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
- The State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China
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Paoli A. The Influence of Physical Exercise, Ketogenic Diet, and Time-Restricted Eating on De Novo Lipogenesis: A Narrative Review. Nutrients 2025; 17:663. [PMID: 40004991 PMCID: PMC11858292 DOI: 10.3390/nu17040663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/04/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
De novo lipogenesis (DNL) is a metabolic pathway that converts carbohydrates into fatty acids, primarily occurring in the liver and, to a lesser extent, in adipose tissue. While hepatic DNL is highly responsive to dietary carbohydrate intake and regulated by insulin via transcription factors like SREBP-1c, adipose DNL is more modest and less sensitive to dietary overfeeding. Dysregulated DNL contributes to metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Lifestyle interventions, such as physical exercise, ketogenic diets, and time-restricted eating (TRE) offer promising strategies to regulate DNL and improve metabolic health. Physical exercise enhances glucose uptake in muscles, reduces insulin levels, and promotes lipid oxidation, thereby suppressing hepatic DNL. Endurance and resistance training also improve mitochondrial function, further mitigating hepatic triglyceride accumulation. Ketogenic diets shift energy metabolism toward fatty acid oxidation and ketogenesis, lower insulin, and directly downregulate lipogenic enzyme activity in the liver. TRE aligns feeding with circadian rhythms by optimizing AMP-activated protein kinase (AMPK) activation during fasting periods, which suppresses DNL and enhances lipid metabolism. The combined effects of these interventions demonstrate significant potential for improving lipid profiles, reducing hepatic triglycerides, and preventing lipotoxicity. By addressing the distinct roles of the liver and adipose DNL, these strategies target systemic and localized lipid metabolism dysregulation. Although further research is needed to fully understand their long-term impact, these findings highlight the transformative potential of integrating these approaches into clinical practice to manage metabolic disorders and their associated complications.
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Affiliation(s)
- Antonio Paoli
- Department of Biomedical Sciences, University of Padua, 35100 Padua, Italy;
- Research Center for High Performance Sport, UCAM Catholic University of Murcia, 30107 Murcia, Spain
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Saslow LR, Krinock J, O'Brien A, Raymond K, Bayandorian H, Moskowitz JT, Daubenmier J, Oliveri A, Marriott DJ, Griauzde DH, Speliotes EK. A Very Low-Carbohydrate Program in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease and Phospholipase Domain-Containing Protein 3 Risk Genotype: Pre-Post Intervention Study. JMIR Form Res 2025; 9:e60051. [PMID: 39801107 PMCID: PMC11740387 DOI: 10.2196/60051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 09/24/2024] [Accepted: 10/10/2024] [Indexed: 01/30/2025] Open
Abstract
Background Insulin resistance and the G allele of rs738409 interact to create a greater risk of metabolic dysfunction-associated steatotic liver disease. Objective This study aims to confirm that one promising way to reduce insulin resistance is by following a very low-carbohydrate (VLC) dietary pattern. Methods Adults with rs738409-GG or -CG with liver steatosis and elevated liver function tests, were taught an ad libitum VLC diet, positive affect and mindful eating skills, goal setting, and self-monitoring and given feedback and coaching for 4 months. We measured liver steatosis, anthropometric, serum metabolic diet adherence, and quality of life measures. Results In this small pilot trial, of the 11 participants enrolled, 9 (82%) participants completed outcomes. All 11 participants viewed at least 1 session of the intervention, and 8 (73%) participants viewed at least half of the sessions. Among the 9 participants who provided 4-month self-report information, intervention satisfaction was high (mean 6.22, 95% CI 5.58-6.85), with 5 (56%) participants rating the intervention the top score, and 4 (44%) participants reporting they did not plan to stop following the VLC diet. Across participants with a 4-month hepatic liver fat percent measurement, the percent change in liver fat was -33.17% (95% CI -86.48 to 20.14), and in only the participants who were adherent to the eating pattern, the percent change in liver fat was -53.12% (95% CI -71.25 to -34.99). Amongst participants with a 4-month hepatic liver fat percent measurement, 6 out of 8 (75%) participants were considered responders, with a relative decline in liver fat ≥30%, and of the 9 participants with a 4-month body weight, 9 (100%) participants lost ≥5% of their body weight. There were no serious adverse events. Conclusions Results suggest the feasibility, acceptability, and preliminary efficacy of the VLC intervention in adults with higher genetic risk for metabolic dysfunction-associated steatotic liver disease, although there is a need for further studies given the small sample size and the high risk of substantial biases in this small pilot study.
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Affiliation(s)
- Laura R Saslow
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Jamie Krinock
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Alison O'Brien
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Kaitlyn Raymond
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Hovig Bayandorian
- Department of Health Behavior and Biological Sciences, School of Nursing, University of Michigan, Ann Arbor, MI, United States
- Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
- Institute of Holistic Health Studies, San Francisco State University, San Francisco, CA, United States
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Medical Sciences Building II, Room 4741, Ann Arbor, MI, 48109, United States, 1 734-647-2964
- Department of Systems, Populations and Leadership, School of Nursing, University of Michigan, Ann Arbor, MI, United States
- VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
- Gilbert S Omenn Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Judith T Moskowitz
- Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Jennifer Daubenmier
- Institute of Holistic Health Studies, San Francisco State University, San Francisco, CA, United States
| | - Antonino Oliveri
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Medical Sciences Building II, Room 4741, Ann Arbor, MI, 48109, United States, 1 734-647-2964
| | - Deanna J Marriott
- Department of Systems, Populations and Leadership, School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Dina H Griauzde
- VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Elizabeth K Speliotes
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Medical Sciences Building II, Room 4741, Ann Arbor, MI, 48109, United States, 1 734-647-2964
- Gilbert S Omenn Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, United States
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9
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Cannataro R, Petro JL, Abrego-Guandique DM, Cione E, Caroleo MC, Kreider RB, Bonilla DA. Ketogenic Diet Plus Resistance Training Applied to Physio-Pathological Conditions: A Brief Review. APPLIED SCIENCES 2024; 14:5445. [DOI: 10.3390/app14135445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2024]
Abstract
The ketogenic diet (KD) is a nutritional strategy characterized by a reduced intake of carbohydrates (between 30 and 45 g per day or ≈5% of one’s total calories from this macronutrient). The regimen induces physiological ketosis in which serum levels of ketone bodies increase from 0.5 to 3.0 mM, becoming an essential contributor to energy production. The popularity of using the KD to lose weight and its application in specific physio-pathological conditions, such as epilepsy, lipedema, and polycystic ovary syndrome, which is maintained over extended periods, gave us the impulse to write this brief review. In these types of physio-pathological conditions, subjects can achieve favorable training outcomes even if adhering to a KD. Therefore, performing resistance training under the KD to enhance muscle status and quality of life could be possible. It is important to note that, while some statements here suggest potential future directions, they are hypotheses that require experimental validation, even if they are supported by the independent benefits reported from the KD and resistance training and represent a promising area for future research.
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Affiliation(s)
- Roberto Cannataro
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy
- Galascreen Laboratories, University of Calabria, 87036 Rende, CS, Italy
- Research Division, Dynamical Business & Science Society, DBSS International SAS, Bogotá 110861, Colombia
| | - Jorge Luis Petro
- Research Division, Dynamical Business & Science Society, DBSS International SAS, Bogotá 110861, Colombia
- Research Group in Physical Activity, Sports and Health Sciences (GICAFS), Universidad de Córdoba, Montería 230002, Colombia
| | | | - Erika Cione
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy
- Galascreen Laboratories, University of Calabria, 87036 Rende, CS, Italy
| | - Maria Cristina Caroleo
- Department of Health Sciences, University of Magna Graecia Catanzaro, 88100 Catanzaro, CZ, Italy
| | - Richard B. Kreider
- Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Texas A&M University, College Station, TX 77843, USA
| | - Diego A. Bonilla
- Research Division, Dynamical Business & Science Society, DBSS International SAS, Bogotá 110861, Colombia
- Research Group in Physical Activity, Sports and Health Sciences (GICAFS), Universidad de Córdoba, Montería 230002, Colombia
- Hologenomiks Research Group, Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
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10
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Vidal-Cevallos P, Sorroza-Martínez AP, Chávez-Tapia NC, Uribe M, Montalvo-Javé EE, Nuño-Lámbarri N. The Relationship between Pathogenesis and Possible Treatments for the MASLD-Cirrhosis Spectrum. Int J Mol Sci 2024; 25:4397. [PMID: 38673981 PMCID: PMC11050641 DOI: 10.3390/ijms25084397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/04/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a term that entails a broad spectrum of conditions that vary in severity. Its development is influenced by multiple factors such as environment, microbiome, comorbidities, and genetic factors. MASLD is closely related to metabolic syndrome as it is caused by an alteration in the metabolism of fatty acids due to the accumulation of lipids because of an imbalance between its absorption and elimination in the liver. Its progression to fibrosis is due to a constant flow of fatty acids through the mitochondria and the inability of the liver to slow down this metabolic load, which generates oxidative stress and lipid peroxidation, triggering cell death. The development and progression of MASLD are closely related to unhealthy lifestyle habits, and nutritional epigenetic and genetic mechanisms have also been implicated. Currently, lifestyle modification is the first-line treatment for MASLD and nonalcoholic steatohepatitis; weight loss of ≥10% produces resolution of steatohepatitis and fibrosis regression. In many patients, body weight reduction cannot be achieved; therefore, pharmacological treatment should be offered in particular populations.
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Affiliation(s)
- Paulina Vidal-Cevallos
- Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico; (P.V.-C.); (N.C.C.-T.); (M.U.); (E.E.M.-J.)
| | | | - Norberto C. Chávez-Tapia
- Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico; (P.V.-C.); (N.C.C.-T.); (M.U.); (E.E.M.-J.)
- Translational Research Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico;
| | - Misael Uribe
- Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico; (P.V.-C.); (N.C.C.-T.); (M.U.); (E.E.M.-J.)
| | - Eduardo E. Montalvo-Javé
- Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico; (P.V.-C.); (N.C.C.-T.); (M.U.); (E.E.M.-J.)
- Department of Surgery, Faculty of Medicine, Universidad Nacional Autónoma de Mexico, Mexico City 04360, Mexico
- Hepatopancreatobiliary Clinic, Department of Surgery, Hospital General de Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico
| | - Natalia Nuño-Lámbarri
- Translational Research Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico;
- Department of Surgery, Faculty of Medicine, Universidad Nacional Autónoma de Mexico, Mexico City 04360, Mexico
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11
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Zuo Q, Park NH, Lee JK, Santaliz-Casiano A, Madak-Erdogan Z. Navigating nonalcoholic fatty liver disease (NAFLD): Exploring the roles of estrogens, pharmacological and medical interventions, and life style. Steroids 2024; 203:109330. [PMID: 37923152 DOI: 10.1016/j.steroids.2023.109330] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/28/2023] [Accepted: 10/31/2023] [Indexed: 11/07/2023]
Abstract
The pursuit of studying this subject is driven by the urgency to address the increasing global prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) and its profound health implications. NAFLD represents a significant public health concern due to its association with metabolic disorders, cardiovascular complications, and the potential progression to more severe conditions like non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Liver estrogen signaling is important for maintaining liver function, and loss of estrogens increases the likelihood of NAFLD in postmenopausal women. Understanding the multifaceted mechanisms underlying NAFLD pathogenesis, its varied treatment strategies, and their effectiveness is crucial for devising comprehensive and targeted interventions. By unraveling the intricate interplay between genetics, lifestyle, hormonal regulation, and gut microbiota, we can unlock insights into risk stratification, early detection, and personalized therapeutic approaches. Furthermore, investigating the emerging pharmaceutical interventions and dietary modifications offers the potential to revolutionize disease management. This review reinforces the role of collaboration in refining NAFLD comprehension, unveiling novel therapeutic pathways, and ultimately improving patient outcomes for this intricate hepatic condition.
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Affiliation(s)
- Qianying Zuo
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
| | - Nicole Hwajin Park
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
| | - Jenna Kathryn Lee
- Department of Neuroscience, Northwestern University, Evanston, IL 60208, USA
| | - Ashlie Santaliz-Casiano
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
| | - Zeynep Madak-Erdogan
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
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12
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Charlot A, Bringolf A, Debrut L, Mallard J, Charles AL, Crouchet E, Duteil D, Geny B, Zoll J. Changes in Macronutrients during Dieting Lead to Weight Cycling and Metabolic Complications in Mouse Model. Nutrients 2024; 16:646. [PMID: 38474774 DOI: 10.3390/nu16050646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 02/13/2024] [Accepted: 02/23/2024] [Indexed: 03/14/2024] Open
Abstract
Weight cycling is a major challenge in obesity management. Caloric restriction is known to promote this phenomenon, but the impact of macronutrient changes during dieting remains unclear. This study aimed to determine the role of macronutrient changes in weight maintenance without caloric restriction by alternating between two hypercaloric diets: a high-carbohydrate, high-fat Western diet (WD) and a low-carbohydrate, high-fat diet (LCHDF). Obesity was induced in 8-week-old C57BL/6 male mice by 10 weeks of WD feeding. Then, the mice were subjected to 12 weeks of LCHFD interspersed with WD (I-WD), 3 periods of 2-week LCHFD followed by 2 periods of 3-week WD, or 12 weeks of continuous WD (C-WD). C-WD and I-WD mice were compared to standard diet (SD) mice. In the I-WD group, each LCHFD period decreased weight gain, but mice regained weight after WD resumption. I-WD mice exhibited obesity, dyslipidemia, and glucose intolerance, similarly to the C-WD mice. I-WD mice also developed nonalcoholic steatohepatitis, associated with an increase in type-III collagen gene expression and a decrease in FGF21 protein levels, in comparison with SD. I-WD mice developed weight cycling despite maintaining a high caloric consumption, suggesting that changes in macronutrients during dieting are also a trigger of weight regain.
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Affiliation(s)
- Anouk Charlot
- Biomedicine Research Center of Strasbourg (CRBS), UR 3072, "Mitochondrie, Stress Oxydant et Plasticité Musculaire", University of Strasbourg, 67000 Strasbourg, France
- Faculty of Sport Sciences, University of Strasbourg, 67000 Strasbourg, France
| | - Anthony Bringolf
- Biomedicine Research Center of Strasbourg (CRBS), UR 3072, "Mitochondrie, Stress Oxydant et Plasticité Musculaire", University of Strasbourg, 67000 Strasbourg, France
| | - Léa Debrut
- CNRS, University of Strasbourg, Inserm, IGBMC UMR 7104-UMR-S 1258, 67400 Illkirch, France
| | - Joris Mallard
- Biomedicine Research Center of Strasbourg (CRBS), UR 3072, "Mitochondrie, Stress Oxydant et Plasticité Musculaire", University of Strasbourg, 67000 Strasbourg, France
- Faculty of Sport Sciences, University of Strasbourg, 67000 Strasbourg, France
- Institute of Cancerology Strasbourg Europe (ICANS), 67200 Strasbourg, France
| | - Anne-Laure Charles
- Biomedicine Research Center of Strasbourg (CRBS), UR 3072, "Mitochondrie, Stress Oxydant et Plasticité Musculaire", University of Strasbourg, 67000 Strasbourg, France
- Faculty of Medicine, University of Strasbourg, 67000 Strasbourg, France
| | - Emilie Crouchet
- Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, University of Strasbourg, Inserm, 67000 Strasbourg, France
| | - Delphine Duteil
- CNRS, University of Strasbourg, Inserm, IGBMC UMR 7104-UMR-S 1258, 67400 Illkirch, France
| | - Bernard Geny
- Biomedicine Research Center of Strasbourg (CRBS), UR 3072, "Mitochondrie, Stress Oxydant et Plasticité Musculaire", University of Strasbourg, 67000 Strasbourg, France
- Faculty of Medicine, University of Strasbourg, 67000 Strasbourg, France
- Service de Physiologie et Explorations Fonctionnelles, University Hospital of Strasbourg, 67091 Strasbourg, France
| | - Joffrey Zoll
- Biomedicine Research Center of Strasbourg (CRBS), UR 3072, "Mitochondrie, Stress Oxydant et Plasticité Musculaire", University of Strasbourg, 67000 Strasbourg, France
- Faculty of Medicine, University of Strasbourg, 67000 Strasbourg, France
- Service de Physiologie et Explorations Fonctionnelles, University Hospital of Strasbourg, 67091 Strasbourg, France
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13
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Field R, Field T, Pourkazemi F, Rooney K. Low-carbohydrate and ketogenic diets: a scoping review of neurological and inflammatory outcomes in human studies and their relevance to chronic pain. Nutr Res Rev 2023; 36:295-319. [PMID: 35438071 DOI: 10.1017/s0954422422000087] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Dietary restriction of carbohydrate has been demonstrated to be beneficial for nervous system dysfunction in animal models and may be beneficial for human chronic pain. The purpose of this review is to assess the impact of a low-carbohydrate/ketogenic diet on the adult nervous system function and inflammatory biomarkers to inform nutritional research for chronic pain. An electronic database search was carried out in May 2021. Publications were screened for prospective research with dietary carbohydrate intake <130 g per day and duration of ≥2 weeks. Studies were categorised into those reporting adult neurological outcomes to be extracted for analysis and those reporting other adult research outcomes. Both groups were screened again for reported inflammatory biomarkers. From 1548 studies, there were 847 studies included. Sixty-four reported neurological outcomes with 83% showing improvement. Five hundred and twenty-three studies had a different research focus (metabolic n = 394, sport/performance n = 51, cancer n = 33, general n = 30, neurological with non-neuro outcomes n = 12, or gastrointestinal n = 4). The second screen identified sixty-three studies reporting on inflammatory biomarkers, with 71% reporting a reduction in inflammation. The overall results suggest a favourable outcome on the nervous system and inflammatory biomarkers from a reduction in dietary carbohydrates. Both nervous system sensitisation and inflammation occur in chronic pain, and the results from this review indicate it may be improved by low-carbohydrate nutritional therapy. More clinical trials within this population are required to build on the few human trials that have been done.
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Affiliation(s)
- Rowena Field
- Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Tara Field
- The New South Wales Ministry of Health (NSW Health), Sydney, Australia
| | | | - Kieron Rooney
- Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
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14
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Paoli A, Cerullo G. Investigating the Link between Ketogenic Diet, NAFLD, Mitochondria, and Oxidative Stress: A Narrative Review. Antioxidants (Basel) 2023; 12:antiox12051065. [PMID: 37237931 DOI: 10.3390/antiox12051065] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/28/2023] [Accepted: 05/04/2023] [Indexed: 05/28/2023] Open
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.
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Affiliation(s)
- Antonio Paoli
- Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
- Research Center for High Performance Sport, UCAM Catholic University of Murcia, 30107 Murcia, Spain
| | - Giuseppe Cerullo
- Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
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15
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Rushing KA, Bolyard ML, Kelty T, Wieschhaus N, Pavela G, Rector RS, Plaisance EP. Dietary ketone ester attenuates the accretion of adiposity and liver steatosis in mice fed a high-fat, high-sugar diet. Front Physiol 2023; 14:1165224. [PMID: 37113697 PMCID: PMC10128912 DOI: 10.3389/fphys.2023.1165224] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 03/30/2023] [Indexed: 04/29/2023] Open
Abstract
Objective: The ketone diester, R,S-1,3-butanediol diacetoacetate (BD-AcAc2), attenuates the accretion of adiposity and reduces hepatic steatosis in high-fat diet-induced obese mice when carbohydrate energy is removed from the diet to accommodate energy from the ester. Reducing carbohydrate energy is a potential confounder due to the well-known effects of carbohydrate restriction on components of energy balance and metabolism. Therefore, the current investigation was designed to determine whether the addition of BD-AcAc2 to a high-fat, high-sugar diet (with no reduction in carbohydrate energy) would attenuate the accretion of adiposity and markers of hepatic steatosis and inflammation. Methods: Sixteen 11-week-old male C57BL/6J mice were randomized to one of two groups for 9 weeks (n = 8 per group): 1) Control (CON, HFHS diet) or 2) Ketone ester (KE, HFHS diet + BD-AcAc2, 25% by kcals). Results: Body weight increased by 56% in CON (27.8 ± 2.5 to 43.4 ± 3.7 g, p < 0.001) and by 13% in KE (28.0 ± 0.8 to 31.7 ± 3.1 g, p = 0.001). Non-alcoholic fatty liver disease activity scores (NAS) for hepatic steatosis, inflammation, and ballooning were lower in the KE group compared to CON (p < 0.001 for all). Markers of hepatic inflammation [Tnfα (p = 0.036); Mcp1 (p < 0.001)], macrophage content [(Cd68 (p = 0.012)], and collagen deposition and hepatic stellate cell activation [(αSma (p = 0.004); Col1A1 (p < 0.001)] were significantly lower in the KE group compared to CON. Conclusion: These findings extend those of our previous work and show that BD-AcAc2 attenuates the accretion of adiposity and reduces markers of liver steatosis, inflammation, ballooning, and fibrosis in lean mice placed on a HFHS diet where carbohydrate energy was not removed to accommodate energy from addition of the diester.
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Affiliation(s)
- Kelsey A. Rushing
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Mickey L. Bolyard
- Department of Human Studies, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Taylor Kelty
- Research Service, Harry S. Truman Memorial Veterans’ Hospital, Department of Nutrition and Exercise Physiology, Medicine—Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, United States
| | - Nicole Wieschhaus
- Research Service, Harry S. Truman Memorial Veterans’ Hospital, Department of Nutrition and Exercise Physiology, Medicine—Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, United States
| | - Gregory Pavela
- Department of Health Behavior, University of Alabama at Birmingham, Birmingham, AL, United States
| | - R. Scott Rector
- Research Service, Harry S. Truman Memorial Veterans’ Hospital, Department of Nutrition and Exercise Physiology, Medicine—Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, United States
| | - Eric P. Plaisance
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United States
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16
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Newberry C, Kumar S. Dietary and nutrition considerations in caring for patients with nonalcoholic fatty liver disease: Updates for the practicing clinician. Nutr Clin Pract 2023; 38:70-79. [PMID: 36183354 DOI: 10.1002/ncp.10917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 08/10/2022] [Accepted: 09/02/2022] [Indexed: 01/11/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide, affecting up to one-third of the global population. The disease is defined by excess fat deposition in the liver and has a strong correlation with metabolic syndrome, which, in turn, is also a risk factor for disease progression, including the development of steatohepatitis, advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Although a number of medications are being explored for disease mitigation, nothing is currently approved, and the mainstay of therapy remains dietary and lifestyle intervention that promotes weight loss as well as management of comorbid conditions. The landscape that guides care for patients with NAFLD continues to evolve. Clinicians caring for these patients need to consider underlying disease state and nutrition risk in addition to concurrent related diagnoses, such as insulin resistance and hyperlipidemia, when formulating treatment plans. The following is a comprehensive review of the current dietary and nutrition considerations in the management of patients with NAFLD, with a special emphasis on implications for the practicing clinician.
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Affiliation(s)
- Carolyn Newberry
- Division of Gastroenterology, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Weill Cornell Medical Center, New York, New York, USA
| | - Sonal Kumar
- Division of Gastroenterology, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Weill Cornell Medical Center, New York, New York, USA
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17
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Oh S, Lee J, Chun S, Choi JE, Kim MN, Chon YE, Ha Y, Hwang SG, Choi SW, Hong KW. Interaction between the PNPLA3 Gene and Nutritional Factors on NAFLD Development: The Korean Genome and Epidemiology Study. Nutrients 2022; 15:152. [PMID: 36615809 PMCID: PMC9824262 DOI: 10.3390/nu15010152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 12/18/2022] [Accepted: 12/21/2022] [Indexed: 12/31/2022] Open
Abstract
Genetic and nutritional factors contribute to the development of non-alcoholic fatty liver disease (NAFLD); however, gene-diet interactions in NAFLD development are poorly understood. In this case-control study, a large dataset from the Korean Genome and Epidemiology Study cohort (n = 72,299) comprising genomic data, medical records, social history, and dietary data was used. We investigated the interactions between the PNPLA3 rs738409 genotype and nutritional factors and their possible effect on the risk of NAFLD development in 2950 patients with NAFLD and 12,907 controls. In the PNPLA3 risk allele group, high protein, fat, sodium, phosphorus, niacin, and vitamin B6 intakes were associated with a decreased risk of NAFLD. In the non-risk allele group, only high fat intake was associated with a decreased risk of NAFLD. Among these nutrients, high sodium intake had a significant protective interaction with the PNPLA3 genotype against NAFLD (p = 0.002). Among salty foods, only kimchi had a significant protective effect against the PNPLA3 genotype (p = 0.012). Thus, the PNPLA3 genotype is differentially associated with nutritional factors. In particular, it interacts with kimchi, a fermented vegetable dish. Therefore, fermented vegetables may serve as a tailored therapeutic food for people with the PNPLA3 risk allele.
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Affiliation(s)
- Sooyeon Oh
- Chaum Life Center, CHA University School of Medicine, Seoul 06062, Republic of Korea
| | - Jooho Lee
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of Korea
| | - Sukyung Chun
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of Korea
| | - Ja-Eun Choi
- Healthcare R&D Division, Theragen Bio Co., Ltd., Suwon 16229, Republic of Korea
| | - Mi Na Kim
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of Korea
| | - Young Eun Chon
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of Korea
| | - Yeonjung Ha
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of Korea
| | - Seong-Gyu Hwang
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of Korea
| | - Sang-Woon Choi
- Chaum Life Center, CHA University School of Medicine, Seoul 06062, Republic of Korea
| | - Kyung-Won Hong
- Healthcare R&D Division, Theragen Bio Co., Ltd., Suwon 16229, Republic of Korea
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18
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Yaghoubi F, Darand M, Vasmehjani AA, Darabi Z, Talenezhad N, Mirzavandi F, Hosseinzadeh M. Adherence to low carbohydrate diets and non-alcoholic fatty liver disease: a case control study. BMC Nutr 2022; 8:140. [PMID: 36447244 PMCID: PMC9706826 DOI: 10.1186/s40795-022-00625-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 10/26/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is defined as the excessive accumulation of fat in the liver cells of people who do not drink alcohol. The aim of study is investigated the association between low carbohydrate diets (LCDs) and NAFLD. METHODS This age and gender-matched case-control study was conducted on 120 patients newly diagnosed with NAFLD and 120 adults without NAFLD. Diagnosis of NAFLD based on laboratory tests and abdominal ultrasound. Low carbohydrate diets score calculated on the percentage of energy as carbohydrate, fat, and protein. Participants in the highest rank intake of fat and protein and lowest intake of carbohydrate received 10 points. Multivariable logistic odds ratio was used for examine the relation between LCDs and NAFLD. RESULTS This study showed subjects in the highest tertile of LCD has more intake of zinc and vitamin B12 compare to lowest. Also, intake of protein (p = 0.02) carbohydrate (p < 0.02) and cholesterol (p = 0.02) were significantly higher in patient with NAFLD compare to control subjects. There was no significant association between LCD and risk of NAFLD (OR: 1.36; 95% CI: 0.97-1.92; P-trend = 0.13) in crude and adjusted (OR: 1.31; 95% CI: 0.84-2.04; P-trend = 0.23) model. CONCLUSION However, we showed that intake of protein, carbohydrate and cholesterol are higher in NAFLD, but our results of study showed that LCDs with higher proportion intakes of protein and fat was not associated with NAFLD. Further prospective studies are required for confirm these associations.
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Affiliation(s)
- Fatemeh Yaghoubi
- grid.412505.70000 0004 0612 5912Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mina Darand
- grid.411036.10000 0001 1498 685XDepartment of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Aazam Ahmadi Vasmehjani
- grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,Department of Nutrition, School of Public Health, Shahid Sadughi University of Medical Sciences, Yazd, Iran
| | - Zahra Darabi
- grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,Department of Nutrition, School of Public Health, Shahid Sadughi University of Medical Sciences, Yazd, Iran
| | - Nasir Talenezhad
- grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,Department of Nutrition, School of Public Health, Shahid Sadughi University of Medical Sciences, Yazd, Iran
| | - Farhang Mirzavandi
- grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,Department of Nutrition, School of Public Health, Shahid Sadughi University of Medical Sciences, Yazd, Iran
| | - Mahdieh Hosseinzadeh
- grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,Department of Nutrition, School of Public Health, Shahid Sadughi University of Medical Sciences, Yazd, Iran
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19
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Bischoff SC, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2022; 41:2364-2405. [PMID: 35970666 DOI: 10.1016/j.clnu.2022.07.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France; Department of Clinical Nutrition, Paul-Brousse-Hospital, Villejuif, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim GGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Ivashkin VT, Maevskaya MV, Zharkova MS, Kotovskaya YV, Tkacheva ON, Troshina EA, Shestakova MV, Maev IV, Breder VV, Gheivandova NI, Doshchitsin VL, Dudinskaya EN, Ershova EV, Kodzoeva KB, Komshilova KA, Korochanskaya NV, Mayorov AY, Mishina EE, Nadinskaya MY, Nikitin IG, Pogosova NV, Tarzimanova AI, Shamkhalova MS. Clinical Practice Guidelines of the Russian Scientific Liver Society, Russian Gastroenterological Association, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians and National Society for Preventive Cardiology on Diagnosis and Treatment of Non-Alcoholic Liver Disease. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2022; 32:104-140. [DOI: 10.22416/1382-4376-2022-32-4-104-140] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Aim:present clinical guidelines, aimed at general practitioners, gastroenterologists, cardiologists, endocrinologists, comprise up-to-date methods of diagnosis and treatment of non-alcoholic fatty liver disease.Key points.Nonalcoholic fatty liver disease, the most wide-spread chronic liver disease, is characterized by accumulation of fat by more than 5 % of hepatocytes and presented by two histological forms: steatosis and nonalcoholic steatohepatitis. Clinical guidelines provide current views on pathogenesis of nonalcoholic fatty liver disease as a multisystem disease, methods of invasive and noninvasive diagnosis of steatosis and liver fibrosis, principles of nondrug treatment and pharmacotherapy of nonalcoholic fatty liver disease and associated conditions. Complications of nonalcoholic fatty liver disease include aggravation of cardiometabolic risks, development of hepatocellular cancer, progression of liver fibrosis to cirrhotic stage.Conclusion.Progression of liver disease can be avoided, cardiometabolic risks can be reduced and patients' prognosis — improved by the timely recognition of diagnosis of nonalcoholic fatty liver disease and associated comorbidities and competent multidisciplinary management of these patients.
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Affiliation(s)
| | | | | | - Yu. V. Kotovskaya
- Russian Gerontology Research and Clinical Centre, Pirogov Russian National Research Medical University
| | - O. N. Tkacheva
- Russian Gerontology Research and Clinical Centre, Pirogov Russian National Research Medical University
| | | | | | - I. V. Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - V. V. Breder
- Blokhin National Medical Research Center of Oncology
| | | | | | - E. N. Dudinskaya
- Russian Gerontology Research and Clinical Centre, Pirogov Russian National Research Medical University
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21
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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22
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Authors, Collaborators:. Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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Sripongpun P, Churuangsuk C, Bunchorntavakul C. Current Evidence Concerning Effects of Ketogenic Diet and Intermittent Fasting in Patients with Nonalcoholic Fatty Liver. J Clin Transl Hepatol 2022; 10:730-739. [PMID: 36062288 PMCID: PMC9396320 DOI: 10.14218/jcth.2021.00494] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 02/04/2022] [Accepted: 04/10/2022] [Indexed: 12/04/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is emerging globally, while no therapeutic medication has been approved as an effective treatment to date, lifestyle intervention through dietary modification and physical exercise plays a critical role in NAFLD management. In terms of dietary modification, Mediterranean diet is the most studied dietary pattern and is recommended in many guidelines, however, it may not be feasible and affordable for many patients. Recently, a ketogenic diet and intermittent fasting have gained public attention and have been studied in the role of weight management. This article reviews specifically whether these trendy dietary patterns have an effect on NAFLD outcomes regarding intrahepatic fat content, fibrosis, and liver enzymes, the scientific rationales behind these particular dietary patterns, as well as the safety concerns in some certain patient groups.
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Affiliation(s)
- Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Chaitong Churuangsuk
- Nutrition and Obesity Management Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, Rangsit University, Bangkok, Thailand
- Correspondence to: Chalermrat Bunchorntavakul, Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Phayathai Road, Ratchathewi District, Bangkok 10400, Thailand. ORCID: https://orcid.org/0000-0002-8842-032X. Tel.: +66-2-354-8108-9, Fax: +66-2-3548179, E-mail:
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24
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Liu TT, Qiu H, Liu SY, Chien C, Wang JH, Wong MW, Yi CH, Lin L, Lei WY, Liang SW, Hung JS, Huang JF, Chen CL, Han MAT. Modifications decrease hepatic steatosis in Taiwanese with metabolic-associated fatty liver disease. Kaohsiung J Med Sci 2022; 38:1012-1019. [PMID: 35993503 DOI: 10.1002/kjm2.12580] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 06/14/2022] [Accepted: 07/12/2022] [Indexed: 11/09/2022] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a growing global problem associated with increasing obesity prevalence. Lifestyle modifications are currently recommended, including weight reduction, exercise, and diet control. This study evaluated the short-term effect of lifestyle modifications on transient elastography (TE) values in an obese population with MAFLD. Thirty-two MAFLD patients were recruited for this prospective study and all subjects participated in a 3-month program of lifestyle modification. Sequential demographic parameters and biochemical tests were compared before and after program completion. Liver fat and fibrosis changes were measured using TE with controlled attenuated parameter (CAP) and liver stiffness measurements (LSM). The mean age was 38.7 years old (10 males). The body weight (88.09 kg vs. 80.35 kg), body mass index (32.24 kg/m2 vs. 29.4 kg/m2 ), waist (103.19 cm vs. 95.75 cm), and hip circumference (111.67 cm vs. 104.75 cm), and blood pressure (128/78 mmHg vs. 119/71 mmHg) significantly improved before and after the intervention, respectively. Aspartate aminotransaminase (24.06 U/L vs. 18.91 U/L), alanine aminotransaminase (33 U/L vs. 23.72 U/L), creatinine (0.75 mg/dl vs. 0.70 mg/dl), cholesterol (176.41 mg/dl vs. 166.22 m/dl), gamma-glutamyl transferase (26.59 IU/L vs. 19.81 IU/L), and low-density lipoprotein cholesterol (115.63 mg/dl vs. 103.19 mg/dl) also improved after the 3-month intervention. The average CAP significantly decreased after intervention (297.5 dB/m vs. 255.0 dB/m), however, no significant difference in LSM was observed (5.24 kPa vs. 4.82 kPa). The current study suggests that short-term lifestyle modification can effectively improve hepatic steatosis, and TE may serve as a monitoring tool for therapeutic intervention.
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Affiliation(s)
- Tso-Tsai Liu
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - He Qiu
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Shi-Yu Liu
- Department of Nutrition, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Chieh Chien
- Department of Rehabilitation Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Jen-Hung Wang
- Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Ming-Wun Wong
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.,School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Hsun Yi
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Lin Lin
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Shu-Wei Liang
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Jui-Sheng Hung
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.,Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
| | - Ma Ai Thanda Han
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.,Division of Gastroenterology and Hepatology, Department of Medicine, Banner University Medical Center, University of Arizona, Phoenix, Arizona, USA
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25
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Zelber-Sagi S, Grinshpan LS, Ivancovsky-Wajcman D, Goldenshluger A, Gepner Y. One size does not fit all; practical, personal tailoring of the diet to NAFLD patients. Liver Int 2022; 42:1731-1750. [PMID: 35675167 DOI: 10.1111/liv.15335] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 06/03/2022] [Accepted: 06/06/2022] [Indexed: 02/13/2023]
Abstract
Different dietary regimens for weight loss have developed over the years. Since the most evidenced treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction, it is not surprising that more diets targeting obesity are also utilized for NAFLD treatment. However, beyond the desired weight loss effects, one should not ignore the dietary composition of each diet, which may not necessarily be healthy or safe over the long term for hepatic and extrahepatic outcomes, especially cardiometabolic outcomes. Some of these diets are rich in saturated fat and red meat, are very strict, and require close medical supervision. Some may also be very difficult to adhere to for long periods, thus reducing the patient's motivation. The evidence for a direct benefit to NAFLD by restrictive diets such as very-low-carb, ketogenic, very-low-calorie diets, and intermittent fasting is scarce, and the long-term safety has not been tested. Nowadays, the approach is that the diet should be tailored to the patient's cultural and personal preferences. There is strong evidence for the independent protective association of NAFLD with a diet based on healthy eating patterns of minimally-processed foods, low in sugar and saturated fat, high in polyphenols, and healthy types of fats. This leads to the conclusion that a Mediterranean diet should serve as a basis that can be restructured into other kinds of diets. This review will elaborate on the different diets and their role in NAFLD. It will provide a practical guide to tailor the diet to the patients without compromising its composition and safety.
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Affiliation(s)
- Shira Zelber-Sagi
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.,Department of Gastroenterology Tel Aviv Medical Center, Tel Aviv, Israel
| | - Laura Sol Grinshpan
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.,Department of Gastroenterology Tel Aviv Medical Center, Tel Aviv, Israel
| | - Dana Ivancovsky-Wajcman
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.,Department of Gastroenterology Tel Aviv Medical Center, Tel Aviv, Israel
| | - Ariela Goldenshluger
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, and Sylvan Adams Sports Institute, Tel-Aviv University, Tel-Aviv, Israel
| | - Yftach Gepner
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, and Sylvan Adams Sports Institute, Tel-Aviv University, Tel-Aviv, Israel
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Mooli RGR, Ramakrishnan SK. Emerging Role of Hepatic Ketogenesis in Fatty Liver Disease. Front Physiol 2022; 13:946474. [PMID: 35860662 PMCID: PMC9289363 DOI: 10.3389/fphys.2022.946474] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/08/2022] [Indexed: 11/18/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver diseases, arise from non-alcoholic fatty liver (NAFL) characterized by excessive fat accumulation as triglycerides. Although NAFL is benign, it could progress to non-alcoholic steatohepatitis (NASH) manifested with inflammation, hepatocyte damage and fibrosis. A subset of NASH patients develops end-stage liver diseases such as cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is highly complex and strongly associated with perturbations in lipid and glucose metabolism. Lipid disposal pathways, in particular, impairment in condensation of acetyl-CoA derived from β-oxidation into ketogenic pathway strongly influence the hepatic lipid loads and glucose metabolism. Current evidence suggests that ketogenesis dispose up to two-thirds of the lipids entering the liver, and its dysregulation significantly contribute to the NAFLD pathogenesis. Moreover, ketone body administration in mice and humans shows a significant improvement in NAFLD. This review focuses on hepatic ketogenesis and its role in NAFLD pathogenesis. We review the possible mechanisms through which impaired hepatic ketogenesis may promote NAFLD progression. Finally, the review sheds light on the therapeutic implications of a ketogenic diet in NAFLD.
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Shrestha A, Pradhananga S. Holistic Approach in the Management of Nonalcoholic Fatty Liver Disease. Euroasian J Hepatogastroenterol 2022; 12:S51-S58. [PMID: 36466101 PMCID: PMC9681569 DOI: 10.5005/jp-journals-10018-1359] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/08/2025] Open
Abstract
UNLABELLED Nonalcoholic fatty liver disease (NAFLD), in a few decades, is expected to be the commonest cause of end-stage liver disease and liver cancer surpassing all other etiologies. Urbanization and modern lifestyle have led to global epidemic of NAFLD with alarming prevalence rates across the globe. Its multisystemic involvement manifests as metabolic syndrome, diabetes, cardiovascular disease, end-stage liver disease, and hepatic and extrahepatic malignancies. The absence of promising therapy for halting disease progression in NAFLD is a challenge that is not only limited to liver disease but also other organs involved. It is unrealistic to expect any significant impact of pharmacotherapies in overall survival of NAFLD patients, given that the morbidity and mortality in these patients are contributed by conditions other than that of liver. Liver-centric approach in managing NAFLD will be futile unless the problem is dealt in a holistic manner. Lifestyle modifications have been repeatedly appraised in prevention and treatment of various diseases linked to metabolic syndrome including NAFLD. Despite being inexpensive and highly efficacious in prevention and treatment of different manifestations of NAFLD, lifestyle intervention often fails to gather sufficient interest among patients and physicians alike. This review intends to highlight pleiotropic nature of this disease, limitations of currently available pharmacotherapies and evidence that emphasizing lifestyle intervention is the only way to holistically deal in patients with NAFLD. HOW TO CITE THIS ARTICLE Shrestha A, Pradhananga S. Holistic Approach in the Management of Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S51-S58.
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Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals. Atherosclerosis 2022; 348:1-7. [DOI: 10.1016/j.atherosclerosis.2022.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 02/25/2022] [Accepted: 03/15/2022] [Indexed: 11/18/2022]
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Charlot A, Zoll J. Beneficial Effects of the Ketogenic Diet in Metabolic Syndrome: A Systematic Review. DIABETOLOGY 2022; 3:292-309. [DOI: 10.3390/diabetology3020020] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Metabolic syndrome (MetS) is a major societal concern due to its increasing prevalence and its high risk of cardiovascular complications. The ketogenic diet (KD), a high fat, low carbohydrate, and non-caloric restrictive diet, is a new popular weight loss intervention but its beneficial effects are controversial. This study aims to gather all of the relevant studies using KD for metabolic disease treatment to determine its beneficial effects and evaluate its safety and efficacy for patients. Following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 20 articles in the final review. Overall, most of the studies showed a significant effect of KD on weight loss (17/19 articles), BMI (7/7), glucose levels (9/13), insulin levels (7/9), HOMA-IR (4/5), HbA1c (7/7), total cholesterol (6/9), TG (13/15), AST (3/4), and ALT (3/5), and no major side effects. The results heterogeneity seems to be explained by a difference of diet composition and duration. In conclusion, KD is a safety diet which seems to be a promising approach for obesity and MetS treatment, even if the optimal carbohydrate proportion and diet duration must be explored to enhance the beneficial effects of KD.
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Affiliation(s)
- Anouk Charlot
- Centre de Recherche de Biomédecine de Strasbourg, UR 3072 Mitochondrie, Stress Oxydant et Protection Musculaire, Université de Strasbourg, 67000 Strasbourg, France
| | - Joffrey Zoll
- Centre de Recherche de Biomédecine de Strasbourg, UR 3072 Mitochondrie, Stress Oxydant et Protection Musculaire, Université de Strasbourg, 67000 Strasbourg, France
- Service de Physiologie et d’Explorations Fonctionnelles Respiratoires, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France
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Asif S, Kim RY, Fatica T, Sim J, Zhao X, Oh Y, Denoncourt A, Cheung A, Downey M, Mulvihill EE, Kim KH. Hmgcs2-mediated ketogenesis modulates high-fat diet-induced hepatosteatosis. Mol Metab 2022; 61:101494. [PMID: 35421611 PMCID: PMC9039870 DOI: 10.1016/j.molmet.2022.101494] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE Aberrant ketogenesis is correlated with the degree of steatosis in NAFLD patients, and an inborn error of ketogenesis (mitochondrial HMG-CoA synthase deficiency) is commonly associated with the development of the fatty liver. Here we aimed to determine the impact of Hmgcs2-mediated ketogenesis and its modulations on the development and treatment of fatty liver disease. METHODS Loss- and gain-of-ketogenic function through in vivo and in vitro models, achieved by Hmgcs2 knockout and overexpression, respectively, were examined to investigate the role of ketogenesis in the hepatic lipid accumulation during neonatal development and the diet-induced NAFLD mouse model. RESULTS Ketogenic function was decreased in NAFLD mice with a reduction in Hmgcs2 expression. Mice lacking Hmgcs2 developed spontaneous fatty liver phenotype during postnatal development, which was rescued by a shift to a low-fat dietary composition via early weaning. Hmgcs2 heterozygous mice, which exhibited reduced ketogenic activity, were more susceptible to diet-induced NAFLD development, whereas HMGCS2 overexpression in NAFLD mice improved hepatosteatosis and glucose homeostasis. CONCLUSIONS Our study adds new knowledge to the field of ketone body metabolism and shows that Hmgcs2-mediated ketogenesis modulates hepatic lipid regulation under a fat-enriched nutritional environment. The regulation of hepatic ketogenesis may be a viable therapeutic strategy in the prevention and treatment of hepatosteatosis.
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Affiliation(s)
- Shaza Asif
- University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Ri Youn Kim
- University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada
| | - Thet Fatica
- University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada
| | - Jordan Sim
- Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON, K1H 8M5, Canada
| | - Xiaoling Zhao
- University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada
| | - Yena Oh
- University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Alix Denoncourt
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, Ottawa, ON, K1H 8M5, Canada
| | - Angela Cheung
- Gastroenterology and Hepatology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, K1H 8M5, Canada; The Ottawa Hospital Research Institute, Chronic Disease Program, Ottawa, ON, K1Y 4E9, Canada
| | - Michael Downey
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada; Ottawa Institute of Systems Biology, Ottawa, ON, K1H 8M5, Canada
| | - Erin E Mulvihill
- University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Kyoung-Han Kim
- University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
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Barrea L, Caprio M, Watanabe M, Cammarata G, Feraco A, Muscogiuri G, Verde L, Colao A, Savastano S. Could very low-calorie ketogenic diets turn off low grade inflammation in obesity? Emerging evidence. Crit Rev Food Sci Nutr 2022; 63:8320-8336. [PMID: 35373658 DOI: 10.1080/10408398.2022.2054935] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Obesity is an emerging non-communicable disease associated with chronic low-grade inflammation and oxidative stress, compounded by the development of many obesity-related diseases, such as cardiovascular disease, type 2 diabetes mellitus, and a range of cancers. Originally developed for the treatment of epilepsy in drug non-responder children, the ketogenic diet (KD) is being increasingly used in the treatment of many diseases, including obesity and obesity-related conditions. The KD is a dietary pattern characterized by high fat intake, moderate to low protein consumption, and very low carbohydrate intake (<50 g) that has proved to be an effective and weight-loss tool. In addition, it also appears to be a dietary intervention capable of improving the inflammatory state and oxidative stress in individuals with obesity by means of several mechanisms. The main activity of the KD has been linked to improving mitochondrial function and decreasing oxidative stress. β-hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species, improving mitochondrial respiration. In addition, KDs exert anti-inflammatory activity through several mechanisms, e.g., by inhibiting activation of the nuclear factor kappa-light-chain-enhancer of activated B cells, and the inflammatory nucleotide-binding, leucine-rich-containing family, pyrin domain-containing-3, and inhibiting histone deacetylases. Given the rising interest in the topic, this review looks at the underlying anti-inflammatory and antioxidant mechanisms of KDs and their possible recruitment in the treatment of obesity and obesity-related disorders.
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Affiliation(s)
- Luigi Barrea
- Dipartimento di Scienze Umanistiche, Università Telematica Pegaso, Napoli, Italy
- Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Department of Clinical Medicine and Surgery, Endocrinology Unit, University Medical School of Naples, Naples, Italy
| | - Massimiliano Caprio
- Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, Rome, Italy
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome, Italy
| | - Mikiko Watanabe
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy
| | - Giuseppe Cammarata
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI) and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
| | - Alessandra Feraco
- Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, Rome, Italy
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome, Italy
| | - Giovanna Muscogiuri
- Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Department of Clinical Medicine and Surgery, Endocrinology Unit, University Medical School of Naples, Naples, Italy
- Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Naples, Italy
- Cattedra Unesco "Educazione alla salute e allo sviluppo sostenibile", University Federico II, Naples, Italy
| | - Ludovica Verde
- Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Department of Clinical Medicine and Surgery, Endocrinology Unit, University Medical School of Naples, Naples, Italy
- Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Naples, Italy
| | - Annamaria Colao
- Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Department of Clinical Medicine and Surgery, Endocrinology Unit, University Medical School of Naples, Naples, Italy
- Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Naples, Italy
- Cattedra Unesco "Educazione alla salute e allo sviluppo sostenibile", University Federico II, Naples, Italy
| | - Silvia Savastano
- Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Department of Clinical Medicine and Surgery, Endocrinology Unit, University Medical School of Naples, Naples, Italy
- Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Naples, Italy
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Maevskaya M, Kotovskaya Y, Ivashkin V, Tkacheva O, Troshina E, Shestakova M, Breder V, Geyvandova N, Doschitsin V, Dudinskaya E, Ershova E, Kodzoeva K, Komshilova K, Korochanskaya N, Mayorov A, Mishina E, Nadinskaya M, Nikitin I, Pogosova N, Tarzimanova A, Shamkhalova M. The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities. TERAPEVT ARKH 2022; 94:216-253. [PMID: 36286746 DOI: 10.26442/00403660.2022.02.201363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Indexed: 12/15/2022]
Abstract
The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM.
The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described.
The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, etc.), chronic kidney disease (CKD) and the risk of developing hepatocellular cancer (HCC) were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented.
The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid (UDCA) molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered.
The ability of UDCA to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.
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Ilyas Z, Perna S, A. Alalwan T, Zahid MN, Spadaccini D, Gasparri C, Peroni G, Faragli A, Alogna A, La Porta E, Ali Redha A, Negro M, Cerullo G, D’Antona G, Rondanelli M. The Ketogenic Diet: Is It an Answer for Sarcopenic Obesity? Nutrients 2022; 14:620. [PMID: 35276979 PMCID: PMC8838342 DOI: 10.3390/nu14030620] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 01/02/2022] [Accepted: 01/10/2022] [Indexed: 12/18/2022] Open
Abstract
This review aims to define the effectiveness of the ketogenic diet (KD) for the management of sarcopenic obesity. As the combination of sarcopenia and obesity appears to have multiple negative metabolic effects, this narrative review discusses the effects of the ketogenic diet as a possible synergic intervention to decrease visceral adipose tissue (VAT) and fatty infiltration of the liver as well as modulate and improve the gut microbiota, inflammation and body composition. The results of this review support the evidence that the KD improves metabolic health and expands adipose tissue γδ T cells that are important for glycaemia control during obesity. The KD is also a therapeutic option for individuals with sarcopenic obesity due to its positive effect on VAT, adipose tissue, cytokines such as blood biochemistry, gut microbiota, and body composition. However, the long-term effect of a KD on these outcomes requires further investigations before general recommendations can be made.
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Affiliation(s)
- Zahra Ilyas
- Department of Laboratory, Bahrain Specialist Hospital, Juffair P.O. Box 10588, Bahrain
- Department of Biology, College of Science, Sakhir Campus, University of Bahrain, Zallaq P.O. Box 32038, Bahrain; (S.P.); (T.A.A.); (M.N.Z.)
| | - Simone Perna
- Department of Biology, College of Science, Sakhir Campus, University of Bahrain, Zallaq P.O. Box 32038, Bahrain; (S.P.); (T.A.A.); (M.N.Z.)
| | - Tariq A. Alalwan
- Department of Biology, College of Science, Sakhir Campus, University of Bahrain, Zallaq P.O. Box 32038, Bahrain; (S.P.); (T.A.A.); (M.N.Z.)
| | - Muhammad Nauman Zahid
- Department of Biology, College of Science, Sakhir Campus, University of Bahrain, Zallaq P.O. Box 32038, Bahrain; (S.P.); (T.A.A.); (M.N.Z.)
| | - Daniele Spadaccini
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (D.S.); (C.G.); (G.P.)
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (D.S.); (C.G.); (G.P.)
| | - Gabriella Peroni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (D.S.); (C.G.); (G.P.)
| | - Alessandro Faragli
- Department of Internal Medicine/Cardiology, Deutsches Herzzentrum Berlin, 13353 Berlin, Germany;
- Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany;
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany
- Berlin Institute of Health (BIH), 10178 Berlin, Germany
| | - Alessio Alogna
- Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany;
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany
- Berlin Institute of Health (BIH), 10178 Berlin, Germany
| | - Edoardo La Porta
- Department of Cardionephrology, Istituto Clinico Ligure Di Alta Specialità (ICLAS), GVM Care and Research, 16035 Rapallo, Italy;
- Department of Internal Medicine (DiMi), University of Genova, 16121 Genova, Italy
| | - Ali Ali Redha
- Department of Chemistry, College of Science, Sakhir Campus, University of Bahrain, Zallaq P.O. Box 32038, Bahrain;
- Chemistry Department, School of Science, Loughborough University, Loughborough LE11 3TU, UK
| | - Massimo Negro
- CRIAMS-Sport Medicine Centre, 27058 Voghera, Italy; (M.N.); (G.D.)
| | - Giuseppe Cerullo
- Department of Movement and Wellbeing Sciences, University of Naples “Parthenope”, 80133 Napoli, Italy;
| | - Giuseppe D’Antona
- CRIAMS-Sport Medicine Centre, 27058 Voghera, Italy; (M.N.); (G.D.)
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy;
| | - Mariangela Rondanelli
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy;
- IRCCS Mondino Foundation, 27100 Pavia, Italy
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A Al-Samhari G, M Al-Mushiki G, Tamrakar R, Abdullahi G, Lin YD, Tang XY. Fasting, Nutrition and Weight Loss: An Approach to Refine Non-Alcoholic Fatty Liver Disease. J Nutr Sci Vitaminol (Tokyo) 2022; 67:366-374. [PMID: 34980714 DOI: 10.3177/jnsv.67.366] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered as one of the most common causes of chronic liver disease. It includes a group of conditions associated with fat deposition in liver cells. Also, NAFLD is strongly associated with obesity and insulin resistance (IR). Until now, there is no pharmacological treatment validated for this disease. Fasting, nutritional intervention, and weight loss can be considered the first line in treating hepatic steatosis. This review is based on the scientific evidence showing the results of these interventions in the past years. The results include fasting and nutritional support for NAFLD treatment in humans. In clinical trials and cohort studies, an increase in hepatic fat content was correlated with a weight loss of at least 7% and a diet resembling the Mediterranean diet (MD) improving hepatic biomarkers and histological regression of NAFLD. Fasting is a dietary approach known to improve the lipid profile in healthy and obese populations by decreasing overall cholesterol, triglycerides, LDL, and increasing HDL. Bariatric surgery helps improve liver fat content in patients with serious health problems due to overweight.
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Affiliation(s)
| | | | - Rashi Tamrakar
- Internal Medicine, The First Affiliated Hospital of Guangxi Medical University
| | - Gibirima Abdullahi
- Internal Medicine, The First Affiliated Hospital of Guangxi Medical University
| | - Yue-Dong Lin
- School of Public Health, Guangxi Medical University
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Gunaseelan L, Khan US, Khalid F, Hamid MA. Non-alcoholic Fatty Liver Disease and Carbohydrate Restricted Diets: A Case Report and Literature Review. Cureus 2021; 13:e18641. [PMID: 34786236 PMCID: PMC8577499 DOI: 10.7759/cureus.18641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2021] [Indexed: 11/24/2022] Open
Abstract
Non-alcoholic fatty liver disease is the accumulation of excessive fat in the liver. Various treatment options are available to manage the condition, among which carbohydrate restriction has been shown to reduce liver fat accumulation, liver inflammation, serum liver enzyme levels, and hepatic de-novo lipogenesis in people with non-alcoholic fatty liver disease. Here, we present a case report of a 25-year-old South Asian patient presenting with right upper quadrant pain, fatigue, and headaches. After confirmation of non-Alcoholic fatty liver disease (NAFLD) diagnosis by biopsy, the patient initiated a low-carbohydrate diet. Four months after which significant improvement was noticed in clinical and laboratory parameters. Peer-reviewed publications were then sourced from online databases to explore the efficacy of low-carbohydrate diets for NAFLD. Our results were compared with the existing data. However, limited literature existed for such an intervention in the South Asian population therefore, the case report is novel. Combined with findings from the literature, our results from the case report supported our hypothesis that carbohydrate restriction might promote a reduction in hepatic fat accumulation and inflammation in patients with NAFLD and diabetes in various ethnicities including South Asians.
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Affiliation(s)
| | - Umna S Khan
- Medicine and Surgery, Dow International Medical College, Karachi, PAK
| | - Fatima Khalid
- Medicine and Surgery, University College of Medicine and Dentistry, Lahore, PAK
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36
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Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease With and Without Liver Fibrosis in Nondiabetic Adults. Am J Gastroenterol 2021; 116:2270-2278. [PMID: 34114568 DOI: 10.14309/ajg.0000000000001344] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 05/14/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Dietary carbohydrate restriction or ketogenic diets are known to be beneficial in preventing liver fat accumulation. However, the effect of ketonemia on the risk of nonalcoholic fatty liver disease (NAFLD) in nondiabetic population is largely unknown. We investigated the association between fasting ketonuria and the risk of incident NAFLD in healthy adults. METHODS A cohort of 153,076 nondiabetic Koreans with no hepatic steatosis and low probability of fibrosis at baseline was followed for a median of 4.1 years. The outcome was incident hepatic steatosis with or without liver fibrosis, and it was assessed by liver ultrasound and noninvasive fibrosis indices, including fibrosis-4 and the NAFLD fibrosis score (NFS). Parametric proportional hazard models were used to estimate hazard ratios (HRs) for outcome according to ketonuria status. RESULTS Within 677,702.1 person-years of follow-up, 31,079 subjects developed hepatic steatosis. Compared with no ketonuria (reference), fasting ketonuria was significantly associated with a decreased risk of incident hepatic steatosis, with multivariable-adjusted HRs (95% confidence interval) of 0.81 (0.78-0.84). The corresponding HRs for incident hepatic steatosis with intermediate-to-high NFS were 0.79 (0.69-0.90). Similar associations were observed replacing NFS with fibrosis-4. In addition, the presence of persistent ketonuria at both baseline and subsequent visit was associated with the greatest decrease in the adjusted HR for incident NAFLD. DISCUSSION Ketonuria was associated with a reduced risk of developing incident hepatic steatosis with and without intermediate-to-high probability of advanced fibrosis in a large cohort of nondiabetic healthy individuals. The role of hyperketonemia in the prevention of NAFLD requires further exploration.
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Abstract
PURPOSE OF REVIEW This review outlines recent research in the application of low carbohydrate diets (LCD) for insulin resistance (IR) and metabolic syndrome (MetS). RECENT FINDINGS Studies included in this review explore how a LCD can be used in the management of patients with IR and MetS. LCDs have been shown to result in Type 2 Diabetes Mellitus (T2DM) remission, improve lipid profiles and dramatically reduce intrahepatic fat. SUMMARY The field of nutritional science is notoriously complex. The LCD has a simple narrative, which can easily and safely be applied in clinical practice. Current guidelines recognise and encourage the use of LCD as a valid option for patients with T2DM and obesity. Structured, evidence-based education should be available for all clinicians to increase confidence and ensure consistency and quality control. Further real-world evidence into the application and scalability of a LCD are required. The use of digital health solutions and improved health technology should see significant advances in this field, with dietary habit being driven by patient-derived health data in response to food, and not population-based food guidelines. The narrative around MetS and IR needs to change from progression to remission, with a LCD being a valid option for this.
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Westman EC. Type 2 Diabetes Mellitus: A Pathophysiologic Perspective. Front Nutr 2021; 8:707371. [PMID: 34447776 PMCID: PMC8384107 DOI: 10.3389/fnut.2021.707371] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 07/20/2021] [Indexed: 12/12/2022] Open
Abstract
Type 2 Diabetes Mellitus (T2DM) is characterized by chronically elevated blood glucose (hyperglycemia) and elevated blood insulin (hyperinsulinemia). When the blood glucose concentration is 100 milligrams/deciliter the bloodstream of an average adult contains about 5–10 grams of glucose. Carbohydrate-restricted diets have been used effectively to treat obesity and T2DM for over 100 years, and their effectiveness may simply be due to lowering the dietary contribution to glucose and insulin levels, which then leads to improvements in hyperglycemia and hyperinsulinemia. Treatments for T2DM that lead to improvements in glycemic control and reductions in blood insulin levels are sensible based on this pathophysiologic perspective. In this article, a pathophysiological argument for using carbohydrate restriction to treat T2DM will be made.
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Affiliation(s)
- Eric C Westman
- Department of Medicine, Duke University, Durham, NC, United States
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39
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Obesity and aging: Molecular mechanisms and therapeutic approaches. Ageing Res Rev 2021; 67:101268. [PMID: 33556548 DOI: 10.1016/j.arr.2021.101268] [Citation(s) in RCA: 122] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 01/19/2021] [Accepted: 02/02/2021] [Indexed: 02/08/2023]
Abstract
The epidemic of obesity is a major challenge for health policymakers due to its far-reaching effects on population health and potentially overwhelming financial burden on healthcare systems. Obesity is associated with an increased risk of developing acute and chronic diseases, including hypertension, stroke, myocardial infarction, cardiovascular disease, diabetes, and cancer. Interestingly, the metabolic dysregulation associated with obesity is similar to that observed in normal aging, and substantial evidence suggests the potential of obesity to accelerate aging. Therefore, understanding the mechanism of fat tissue dysfunction in obesity could provide insights into the processes that contribute to the metabolic dysfunction associated with the aging process. Here, we review the molecular and cellular mechanisms underlying both obesity and aging, and how obesity and aging can predispose individuals to chronic health complications. The potential of lifestyle and pharmacological interventions to counter obesity and obesity-related pathologies, as well as aging, is also addressed.
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40
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Crabtree CD, Kackley ML, Buga A, Fell B, LaFountain RA, Hyde PN, Sapper TN, Kraemer WJ, Scandling D, Simonetti OP, Volek JS. Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults. Nutrients 2021; 13:966. [PMID: 33802651 PMCID: PMC8002465 DOI: 10.3390/nu13030966] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/13/2021] [Accepted: 03/15/2021] [Indexed: 12/15/2022] Open
Abstract
Ketogenic diets (KDs) often contain high levels of saturated fat, which may increase liver fat, but the lower carbohydrate intake may have the opposite effect. Using a controlled feeding design, we compared liver fat responses to a hypocaloric KD with a placebo (PL) versus an energy-matched low-fat diet (LFD) in overweight adults. We also examined the added effect of a ketone supplement (KS). Overweight adults were randomized to a 6-week KD (KD + PL) or a KD with KS (KD + KS); an LFD group was recruited separately. All diets were estimated to provide 75% of energy expenditure. Weight loss was similar between groups (p > 0.05). Liver fat assessed by magnetic resonance imaging decreased after 6 week (p = 0.004) with no group differences (p > 0.05). A subset with nonalcoholic fatty liver disease (NAFLD) (liver fat > 5%, n = 12) showed a greater reduction in liver fat, but no group differences. In KD participants with NAFLD, 92% of the variability in change in liver fat was explained by baseline liver fat (p < 0.001). A short-term hypocaloric KD high in saturated fat does not adversely impact liver health and is not impacted by exogenous ketones. Hypocaloric low-fat and KDs can both be used in the short-term to significantly reduce liver fat in individuals with NAFLD.
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Affiliation(s)
- Christopher D. Crabtree
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
| | - Madison L. Kackley
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
| | - Alexandru Buga
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
| | - Brandon Fell
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
| | - Richard A. LaFountain
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
| | - Parker N. Hyde
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
| | - Teryn N. Sapper
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
| | - William J. Kraemer
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
| | - Debbie Scandling
- Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA; (D.S.); (O.P.S.)
| | - Orlando P. Simonetti
- Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA; (D.S.); (O.P.S.)
- Departments of Radiology and Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Jeff S. Volek
- Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA; (C.D.C.); (M.L.K.); (A.B.); (B.F.); (R.A.L.); (P.N.H.); (T.N.S.); (W.J.K.)
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Kim A, Krishnan A, Hamilton JP, Woreta TA. The Impact of Dietary Patterns and Nutrition in Nonalcoholic Fatty Liver Disease. Gastroenterol Clin North Am 2021; 50:217-241. [PMID: 33518166 DOI: 10.1016/j.gtc.2020.10.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes of chronic liver disease worldwide. The prevalence of NAFLD has grown proportionally with the rise in obesity, sedentary lifestyle, unhealthy dietary patterns, and metabolic syndrome. Currently, in the absence of approved pharmacologic treatment, the keystone of treatment is lifestyle modification focused on achieving a weight loss of 7%-10%, cardiovascular exercise, and improving insulin sensitivity. The primary aim of this review is to outline the effect of different dietetic approaches against NAFLD and highlight the important micronutrient components in the management of NAFLD.
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Affiliation(s)
- Ahyoung Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - James P Hamilton
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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42
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Moszak M, Szulińska M, Walczak-Gałęzewska M, Bogdański P. Nutritional Approach Targeting Gut Microbiota in NAFLD-To Date. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:1616. [PMID: 33567710 PMCID: PMC7916007 DOI: 10.3390/ijerph18041616] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/05/2021] [Accepted: 01/25/2021] [Indexed: 12/18/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a significant clinical and epidemiological problem that affects around 25% of the adult global population. A large body of clinical evidence highlights that NAFLD is associated with increased liver-related morbidity and mortality and an increased risk of cardiovascular disease, extrahepatic cancers, type 2 diabetes, and chronic kidney disease. Recently, a series of studies revealed the pivotal role of gut microbiota (GM) dysbiosis in NAFLD's pathogenesis. The GM plays an essential role in different metabolic pathways, including the fermentation of diet polysaccharides, energy harvest, choline regulation, and bile acid metabolism. One of the most critical factors in GM stabilization is the diet; therefore, nutritional therapyappearsto be a promising tool in NAFLD therapy. This paper aims to review the current knowledge regardingthe nutritional approach and its implications with GM and NAFLD treatment. We discuss the positive impact of probiotics, prebiotics, and symbiotics in a reverse dysbiosis state in NAFLD and show the potential beneficial effects of bioactive substances from the diet. The full description of the mechanism of action and comprehensive examination of the impact of nutritional interventions on GM modulation may, in the future, be a simple but essential tool supporting NAFLD therapy.
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Affiliation(s)
- Małgorzata Moszak
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| | - Monika Szulińska
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| | - Marta Walczak-Gałęzewska
- Department of Internal Medicine, Metabolic Disorders, and Hypertension, Poznań University of Medical Sciences, 61-701 Poznań, Poland;
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
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43
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Rives C, Fougerat A, Ellero-Simatos S, Loiseau N, Guillou H, Gamet-Payrastre L, Wahli W. Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants. Biomolecules 2020; 10:E1702. [PMID: 33371482 PMCID: PMC7767499 DOI: 10.3390/biom10121702] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/14/2020] [Accepted: 12/15/2020] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is often the hepatic expression of metabolic syndrome and its comorbidities that comprise, among others, obesity and insulin-resistance. NAFLD involves a large spectrum of clinical conditions. These range from steatosis, a benign liver disorder characterized by the accumulation of fat in hepatocytes, to non-alcoholic steatohepatitis (NASH), which is characterized by inflammation, hepatocyte damage, and liver fibrosis. NASH can further progress to cirrhosis and hepatocellular carcinoma. The etiology of NAFLD involves both genetic and environmental factors, including an unhealthy lifestyle. Of note, unhealthy eating is clearly associated with NAFLD development and progression to NASH. Both macronutrients (sugars, lipids, proteins) and micronutrients (vitamins, phytoingredients, antioxidants) affect NAFLD pathogenesis. Furthermore, some evidence indicates disruption of metabolic homeostasis by food contaminants, some of which are risk factor candidates in NAFLD. At the molecular level, several models have been proposed for the pathogenesis of NAFLD. Most importantly, oxidative stress and mitochondrial damage have been reported to be causative in NAFLD initiation and progression. The aim of this review is to provide an overview of the contribution of nutrients and food contaminants, especially pesticides, to oxidative stress and how they may influence NAFLD pathogenesis.
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Affiliation(s)
- Clémence Rives
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Anne Fougerat
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Sandrine Ellero-Simatos
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Nicolas Loiseau
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Hervé Guillou
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Laurence Gamet-Payrastre
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
| | - Walter Wahli
- Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, EVT, INP-Purpan, UPS, 31300 Toulouse, France; (C.R.); (A.F.); (S.E.-S.); (N.L.); (H.G.)
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, 11 Mandalay Road, Singapore 308232, Singapore
- Center for Integrative Genomics, Université de Lausanne, Le Génopode, CH-1015 Lausanne, Switzerland
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44
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Parra-Vargas M, Rodriguez-Echevarria R, Jimenez-Chillaron JC. Nutritional Approaches for the Management of Nonalcoholic Fatty Liver Disease: An Evidence-Based Review. Nutrients 2020; 12:E3860. [PMID: 33348700 PMCID: PMC7766941 DOI: 10.3390/nu12123860] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/09/2020] [Accepted: 12/11/2020] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is on the rise worldwide representing a public health issue. Its coexistence with obesity and other metabolic alterations is highly frequent. Therefore, current therapy interventions for NAFLD are mainly focused on progressive weight loss through modulation of overall calorie intake with or without specific macronutrient adjustments. Furthermore, other relevant nutritional interventions are built on food selection and time-restricted eating. Since every strategy might bring different results, choosing the optimal diet therapy for a patient is a complicated task, because NAFLD is a multifactorial complex disease. Importantly, some factors need to be considered, such as nutrition-based evidence in terms of hepatic morphophysiological improvements as well as adherence of the patient to the meal plan and adaptability in their cultural context. Thus, the purpose of this review is to explore and compare the subtleties and nuances of the most relevant clinical practice guidelines and the nutritional approaches for the management of NAFLD with a special attention to tangible outcomes and long-term adherence.
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Affiliation(s)
- Marcela Parra-Vargas
- Endocrinology Division, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain;
- Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
| | - Roberto Rodriguez-Echevarria
- Institute of Translational Nutrigenetics and Nutrigenomics, Department of Molecular Biology and Genomics, CUCS, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico;
| | - Josep C. Jimenez-Chillaron
- Endocrinology Division, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain;
- Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
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Keith L, Seo CA, Rowsemitt C, Pfeffer M, Wahi M, Staggs M, Dudek J, Gower B, Carmody M. Ketogenic diet as a potential intervention for lipedema. Med Hypotheses 2020; 146:110435. [PMID: 33303304 DOI: 10.1016/j.mehy.2020.110435] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 11/06/2020] [Accepted: 11/24/2020] [Indexed: 02/06/2023]
Abstract
Lipedema (LI) is a common yet misdiagnosed condition, often misconstrued with obesity. LI affects women almost exclusively, and its painful and life-changing symptoms have long been thought to be resistant to the lifestyle interventions such as diet and exercise. In this paper, we discuss possible mechanisms by which patients adopting a ketogenic diet (KD) can alleviate many of the unwanted clinical features of LI. This paper is also an effort to provide evidence for the hypothesis of the potency of this dietary intervention for addressing the symptoms of LI. Specifically, we examine the scientific evidence of effectiveness of adopting a KD by patients to alleviate clinical features associated with LI, including excessive and disproportionate lower body adipose tissue (AT) deposition, pain, and reduction in quality of life (QoL). We also explore several clinical features of LI currently under debate, including the potential existence and nature of edema, metabolic and hormonal dysfunction, inflammation, and fibrosis. The effectiveness of a KD on addressing clinical features of LI has been demonstrated in human studies, and shows promise as an intervention for LI. We hope this paper leads to an improved understanding of optimal nutritional management for patients with LI and stimulates future research in this area of study.
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Affiliation(s)
- L Keith
- The Lipedema Project, Boston, MA, USA; Lipedema Simplified, Boston, MA, USA.
| | - C A Seo
- The Lipedema Project, Boston, MA, USA; Lipedema Simplified, Boston, MA, USA
| | - C Rowsemitt
- Lipedema Simplified, Boston, MA, USA; Comprehensive Weight Management, Templeton, CA and Providence, RI, USA; The Lipedema Project: Medical Advisory Board, Boston, MA, USA
| | - M Pfeffer
- Lipedema Simplified, Boston, MA, USA; The Lipedema Project: Medical Advisory Board, Boston, MA, USA; I Choose Health, Metung, Australia
| | - M Wahi
- DethWench Professional Services, Boston, MA, USA
| | - M Staggs
- Lipedema Simplified, Boston, MA, USA
| | - J Dudek
- The Lipedema Project: Medical Advisory Board, Boston, MA, USA; SWPS University of Social Sciences and Humanities, Warsaw, Poland
| | - B Gower
- University of Alabama at Birmingham, Department of Nutrition Sciences, Birmingham, AL, USA
| | - M Carmody
- Harvard Medical School, Boston, MA, USA
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46
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Bischoff SC, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Plauth M. ESPEN practical guideline: Clinical nutrition in liver disease. Clin Nutr 2020; 39:3533-3562. [PMID: 33213977 DOI: 10.1016/j.clnu.2020.09.001] [Citation(s) in RCA: 188] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The Practical guideline is based on the current scientific ESPEN guideline on Clinical Nutrition in Liver Disease. METHODS It has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. RESULTS A total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in liver patients and on liver complications associated with medical nutrition. CONCLUSION This practical guideline gives guidance to health care providers involved in the management of liver disease to offer optimal nutritional care.
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Affiliation(s)
- Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany
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Campos-Murguía A, Ruiz-Margáin A, González-Regueiro JA, Macías-Rodríguez RU. Clinical assessment and management of liver fibrosis in non-alcoholic fatty liver disease. World J Gastroenterol 2020; 26:5919-5943. [PMID: 33132645 PMCID: PMC7584064 DOI: 10.3748/wjg.v26.i39.5919] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 05/24/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression. To properly detect fibrosis, it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores, followed by a complementary imaging study (transient elastography, magnetic resonance elastography or acoustic radiation force impulse) and finally a liver biopsy, when needed. To help with the selection of the most appropriate method a Fagan's nomogram analysis is provided in this review, describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis. Finally, treatment should always include diet and exercise, as well as controlling the components of the metabolic syndrome, +/- vitamin E, considering the presence of sleep apnea, and when available, allocate those patients with advanced fibrosis or high risk of progression into clinical trials. The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD, aiming to decrease/stop its progression and improve their prognosis.
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Affiliation(s)
- Alejandro Campos-Murguía
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Astrid Ruiz-Margáin
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - José A González-Regueiro
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Ricardo U Macías-Rodríguez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
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48
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Westman EC, Yancy WS. Using a low-carbohydrate diet to treat obesity and type 2 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 2020; 27:255-260. [PMID: 32740047 DOI: 10.1097/med.0000000000000565] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE OF REVIEW This study will provide a narrative review of the history of the clinical use of low-carbohydrate diets and give a practical example of how to implement a low-carbohydrate diet, with an emphasis on deprescribing medications. RECENT FINDINGS Low-carbohydrate diets have been used since the late 19th century to treat obesity and type 2 diabetes mellitus (T2DM). Recently, clinical research has validated the use of low-carbohydrate diets for individuals affected by obesity and T2DM, and these diets are included in several national clinical guidelines. Because medications are commonly used to treat hypertension and T2DM, special consideration must be made to monitor and reduce these medications to avoid overmedication. Clinic visits and home monitoring of blood pressure and glucose levels are important tools to alert clinicians that a reduction in medication levels may be indicated. SUMMARY Low-carbohydrate diets have been utilized clinically for many years to treat obesity and T2DM and can be used alongside effective monitoring to safely deprescribe dispensable medications for these diseases.
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Affiliation(s)
- Eric C Westman
- Division of General Internal Medicine, Department of Medicine, Duke University Medical Center
| | - William S Yancy
- Division of General Internal Medicine, Department of Medicine, Duke University Medical Center
- Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center
- Duke Diet and Fitness Center, Duke University Health System, Durham, North Carolina, USA
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49
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Moore MP, Cunningham RP, Dashek RJ, Mucinski JM, Rector RS. A Fad too Far? Dietary Strategies for the Prevention and Treatment of NAFLD. Obesity (Silver Spring) 2020; 28:1843-1852. [PMID: 32893456 PMCID: PMC7511422 DOI: 10.1002/oby.22964] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 06/04/2020] [Accepted: 06/06/2020] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years, concurrent with rising rates of obesity and other metabolic diseases. Currently, there are no FDA-approved pharmacological therapies for NAFLD, and lifestyle interventions, including weight loss and exercise, remain the cornerstones for treatment. Manipulating diet composition and eating patterns may be a sustainable approach to NAFLD treatment. Dietary strategies including Paleolithic, ketogenic, Mediterranean, high-protein, plant-based, low-carbohydrate, and intermittent fasting diets have become increasingly popular because of their purported benefits on metabolic disease. This review highlights what is currently known about these popular dietary approaches in the management of NAFLD in clinical populations with mechanistic insight from animal studies. It also identifies key knowledge gaps to better inform future preclinical and clinical studies aimed at the treatment of NAFLD.
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Affiliation(s)
- Mary P. Moore
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - Rory P. Cunningham
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - Ryan J. Dashek
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Comparative Medicine Program, University of Missouri, Columbia, MO 65211
| | - Justine M. Mucinski
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - R. Scott Rector
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
- Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65211
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50
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Watanabe M, Tozzi R, Risi R, Tuccinardi D, Mariani S, Basciani S, Spera G, Lubrano C, Gnessi L. Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature. Obes Rev 2020; 21:e13024. [PMID: 32207237 PMCID: PMC7379247 DOI: 10.1111/obr.13024] [Citation(s) in RCA: 150] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 03/02/2020] [Accepted: 03/08/2020] [Indexed: 12/14/2022]
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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Affiliation(s)
- Mikiko Watanabe
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza University of RomeRomeItaly
| | - Rossella Tozzi
- Department of Molecular MedicineSapienza University of RomeRomeItaly
| | - Renata Risi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza University of RomeRomeItaly
| | - Dario Tuccinardi
- Department of Endocrinology and DiabetesUniversity Campus Bio‐Medico of RomeRomeItaly
| | - Stefania Mariani
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza University of RomeRomeItaly
| | - Sabrina Basciani
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza University of RomeRomeItaly
| | - Giovanni Spera
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza University of RomeRomeItaly
| | - Carla Lubrano
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza University of RomeRomeItaly
| | - Lucio Gnessi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza University of RomeRomeItaly
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