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Wang Y, Wu G, Wang Y, Rehman A, Yu L, Zhang H, Jin Q, Suleria HAR, Wang X. Recent developments, challenges, and prospects of dietary omega-3 PUFA-fortified foods: Focusing on their effects on cardiovascular diseases. Food Chem 2025; 470:142498. [PMID: 39736180 DOI: 10.1016/j.foodchem.2024.142498] [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: 06/06/2024] [Revised: 11/30/2024] [Accepted: 12/13/2024] [Indexed: 01/01/2025]
Abstract
Dietary omega-3 polyunsaturated fatty acids (Dω-3 PUFAs) have been extensively studied and have been proven to offer notable benefits for heart health. Scientific meta-analysis strongly endorses them as potent bioactive agents capable of preventing and managing cardiovascular diseases (CVDs). Fortification of foods with Dω-3 PUFAs is a potential strategy for enhancing Dω-3 PUFA intake in an effort to continue strengthening public health outcomes. This review analyzed recent trends in the fortification of foods with Dω-3 PUFAs in relation to technological developments, challenges linked to the method, and future scope. Additionally, recent clinical trials and research on the effect of Dω-3 PUFA-fortified food consumption on cardiovascular health are reviewed. Technological trends in fortification methods, namely microencapsulation- and nanoencapsulation, have made considerable progress to date, along with excellent stability in both processing and storage conditions and favorable bioaccessibility and sensory attributes of fortified foods. There is a tremendous deal of promise for cardiovascular health based on recent clinical trial findings that fortifying food with Dω-3 PUFAs decreased the incidence of heart disease, blood pressure, and lipid profiles. In summary, substantial progress has been made in addressing the challenges of Dω-3 PUFA fortification. However, further multidisciplinary research is needed to inculcate effectiveness toward achieving the maximum possible Dω-3 PUFAs to protect against the harmful effects of CVDs and continue global health progress.
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Affiliation(s)
- Yongjin Wang
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China
| | - Gangcheng Wu
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China
| | - Yandan Wang
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China
| | - Abdur Rehman
- School of Food and Biological Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China
| | - Le Yu
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China; National Center of Technology Innovation for Dairy, Hohhot 010000, China
| | - Hui Zhang
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China
| | - Qingzhe Jin
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China
| | - Hafiz Ansar Rasul Suleria
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, Australia
| | - Xingguo Wang
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China.
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Smith MR, Yu EL, Malki GJ, Newton KP, Goyal NP, Heskett KM, Schwimmer JB. Systematic review of exercise for the treatment of pediatric metabolic dysfunction-associated steatotic liver disease. PLoS One 2024; 19:e0314542. [PMID: 39656734 DOI: 10.1371/journal.pone.0314542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 11/12/2024] [Indexed: 12/17/2024] Open
Abstract
BACKGROUND & AIMS Steatotic liver disease affects approximately 1 in 10 children in the U.S. and increases the risk of cirrhosis, diabetes, and cardiovascular disease. Lifestyle modification centered on increased physical activity and dietary improvement is the primary management approach. However, significant gaps in the literature hinder the establishment of exercise as a targeted therapeutic strategy for pediatric metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of studies assessing the impact of exercise interventions on validated hepatic outcomes in children with NAFLD. METHODS We searched CENTRAL, PubMed, Embase, Web of Science, CINAHL, and Google Scholar on June 5 and 6, 2023, for studies in English involving children aged 0 to 19 years diagnosed with NAFLD or at increased risk for NAFLD due to overweight or obesity. We updated the search on August 8, 2024. Eligible studies were required to examine the impact of exercise interventions on hepatic steatosis or liver chemistry. The risk of bias was assessed with RoB2 and ROBINS-I. Data extraction was performed by two independent reviewers. RESULTS After screening 1578 unique records, 16 studies involving 998 children were included. This comprised seven studies comparing exercise intervention with non-exercising controls, three uncontrolled studies of exercise intervention, two studies comparing exercise plus lifestyle interventions with lifestyle interventions alone, and nine studies comparing different types of exercise interventions. Five of the 11 studies that evaluated hepatic steatosis reported an absolute decrease of 1% to 3%. In the nine studies that evaluated liver chemistry, no significant changes were observed. CONCLUSIONS Evidence supporting exercise intervention for the treatment of pediatric MASLD is limited. Existing studies were constrained by their methodological approaches; thus, there is a pressing need for high-quality future research. This will enable the development of precise, evidence-based exercise guidelines crucial for the effective clinical management of this condition.
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Affiliation(s)
- Martha R Smith
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California, United States of America
- Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, United States of America
| | - Elizabeth L Yu
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California, United States of America
- Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California, United States of America
| | - Ghattas J Malki
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California, United States of America
| | - Kimberly P Newton
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California, United States of America
- Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California, United States of America
| | - Nidhi P Goyal
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California, United States of America
- Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California, United States of America
| | - Karen M Heskett
- The Library, University of California San Diego, La Jolla, California, United States of America
| | - Jeffrey B Schwimmer
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California, United States of America
- Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California, United States of America
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Omaña-Guzmán I, Rosas-Diaz M, Martínez-López YE, Perez-Navarro LM, Diaz-Badillo A, Alanis A, Bustamante A, Castillo-Ruiz O, Del Toro-Cisneros N, Esquivel-Hernandez DA, Garcia-Villalobos G, Garibay-Nieto N, Garcia-Oropesa EM, Hernandez-Martinez JC, Lopez-Sosa EB, Maldonado C, Martinez D, Membreno J, Moctezuma-Chavez OO, Munguia-Cisneros CX, Nava-González EJ, Perales-Torres AL, Pérez-García A, Rivera-Marrero H, Valdez A, Vázquez-Chávez AA, Ramirez-Pfeiffer C, Carter KV, Tapia B, Vela L, Lopez-Alvarenga JC. Strategic interventions in clinical randomized trials for metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity in the pediatric population: a systematic review with meta-analysis and bibliometric analysis. BMC Med 2024; 22:548. [PMID: 39574069 PMCID: PMC11580631 DOI: 10.1186/s12916-024-03744-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 10/31/2024] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a prevalent hepatic condition linked to metabolic alterations. It gradually causes liver damage and potentially progresses to cirrhosis. Despite its significance, research, especially in the pediatric population, is limited, leading to contradictory findings in diagnosis and treatment. This meta-analysis aims to synthesize existing literature on therapeutic interventions for MASLD in children and adolescents. METHODS A comprehensive search of randomized controlled clinical trials yielded 634 entries from PubMed, Scopus, and Web of Science up to 2023. Interventions included medications, behavioral modifications, dietary changes, probiotics, supplements, surgical procedures, or combinations. The analysis focused on studies with treatment duration of at least 3 months, employing a random-effects REML meta-analysis model. Treatment effects on anthropometric measurements and biochemical components were examined and adjusted for heterogeneity factors analysis. A bibliometric analysis for insights into research contributors was performed. RESULTS The systematic review incorporated 31 clinical trials, with 24 meeting criteria for meta-analysis. These comprised 3 medication studies, 20 with supplements, 4 focusing on lifestyle, and 4 centered on diets. Significant overall treatment effects were observed for ALT, AST, BMI, and HOMA-IR mainly by supplements and lifestyle. Meta-regression identified age, BMI changes, and treatment duration as factors modifying ALT concentrations. Bibliometric analysis involving 31 linked studies highlighted contributions from 13 countries, with the USA, Spain, and Chile being the most influential. CONCLUSIONS We conclude that supplementation and lifestyle changes can effectively impact ALT and AST levels, which can help address liver issues in obese children. However, the evaluation of risk bias, the high heterogeneity, and the bibliometric analysis emphasize the need for more high-quality studies and broader inclusion of diverse child populations to provide better therapeutic recommendations. TRIAL REGISTRATION PROSPERO, CRD42023393952. Registered on January 25, 2023.
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Affiliation(s)
- Isabel Omaña-Guzmán
- Pediatric Obesity Clinic and Wellness Unit, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
| | - Marisol Rosas-Diaz
- Laboratorio de Biologia Molecular, Universidad Autónoma de Tamaulipas, Tamaulipas, Mexico
| | | | | | - Alvaro Diaz-Badillo
- Department of Health and Behavioral Sciences, Texas A&M University, San Antonio, TX, USA
| | - Anthony Alanis
- School of Medicine, The University of Texas Rio Grande Valley, Edinburg, TX, USA
| | | | | | - Noemi Del Toro-Cisneros
- Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de La Nutricion Salvador Zubiran, Mexico City, Mexico
| | | | | | - Nayely Garibay-Nieto
- Pediatric Obesity Clinic and Wellness Unit, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
| | | | | | - Elena Beatriz Lopez-Sosa
- Angiologia y Cirugía Vascular, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado de México (ISSTE), Hospital 20 de Noviembre, Mexico City, Mexico
| | - Carlos Maldonado
- Instituto Nacional de Enfermedaes Respiratorias, Mexico City, Mexico
| | - David Martinez
- Department of Biology, The University of Texas Rio Grande Valley, Edinburg, TX, USA
| | - Joshua Membreno
- School of Medicine, The University of Texas Rio Grande Valley, Edinburg, TX, USA
| | | | - Claudia X Munguia-Cisneros
- Centro Especializado de Metabolismo y Diabetes (CEDIAMET), Universidad México Americana del Norte, Tamaulipas, Mexico
| | - Edna J Nava-González
- Facultad de Salud Pública y Nutrición, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
| | | | - Adolfo Pérez-García
- Research Department, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | | | - Alisha Valdez
- School of Medicine, The University of Texas Rio Grande Valley, Edinburg, TX, USA
| | | | | | - Kathleen V Carter
- School of Medicine, The University of Texas Rio Grande Valley, Edinburg, TX, USA
| | - Beatriz Tapia
- Faculty Affairs, Asst Dean Faculty Development, The University of Texas Rio Grande Valley, Edinburg, TX, USA
- Division of Population Health & Biostatistics, School of Medicine, University of Texas Rio Grande Valley, 2102 Treasure Hills Boulevard, Edinburg, TX, 78550, USA
| | - Leonel Vela
- Division of Population Health & Biostatistics, School of Medicine, University of Texas Rio Grande Valley, 2102 Treasure Hills Boulevard, Edinburg, TX, 78550, USA
| | - Juan Carlos Lopez-Alvarenga
- Escuela de Medicina, Universidad México Americana del Norte, Reynosa, Tamaulipas, Mexico.
- Division of Population Health & Biostatistics, School of Medicine, University of Texas Rio Grande Valley, 2102 Treasure Hills Boulevard, Edinburg, TX, 78550, USA.
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McTavish PV, Mutch DM. Omega-3 fatty acid regulation of lipoprotein lipase and FAT/CD36 and its impact on white adipose tissue lipid uptake. Lipids Health Dis 2024; 23:386. [PMID: 39567971 PMCID: PMC11580630 DOI: 10.1186/s12944-024-02376-7] [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: 09/20/2024] [Accepted: 11/13/2024] [Indexed: 11/22/2024] Open
Abstract
Lipid uptake by white adipose tissue (WAT) is critically important for storage of excess energy and to protect peripheral tissues from ectopic lipid deposition. When WAT becomes dysfunctional (i.e., with obesity), it is characterized by impaired lipid uptake and increased lipolysis which, together, promote whole-body dyslipidemia. Omega-3 polyunsaturated fatty acids (N-3 PUFA) are widely studied for their triacylglycerol (TAG)-lowering properties and cardiometabolic health benefits. One potential mechanism underlying these benefits is the modification of WAT lipid uptake; however, there are gaps in our understanding regarding the specific mechanisms by which N-3 PUFA function. Evidence to date suggests that N-3 PUFA promote TAG clearance by increasing lipoprotein lipase (LPL) activity and the abundance of fatty acid transporters. Specifically, N-3 PUFA have been shown to increase LPL activity through increased gene transcription and modifications of endogenously produced LPL regulators such as apolipoprotein C-II/III and angiopoietin-like proteins. This review presents and discusses the available in vitro and in vivo research to provide a comprehensive overview of N-3 PUFA regulation of WAT lipid uptake in healthy and obese contexts. Additionally, we highlight areas where more research is necessary to better understand the contribution of increased WAT lipid uptake in relation to the TAG-lowering properties associated with N-3 PUFA.
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Affiliation(s)
- Patrick V McTavish
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - David M Mutch
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, N1G 2W1, Canada.
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Scarpellini E, Scarcella M, Tack JF, Scarlata GGM, Zanetti M, Abenavoli L. Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease. Antioxidants (Basel) 2024; 13:1386. [PMID: 39594528 PMCID: PMC11591341 DOI: 10.3390/antiox13111386] [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: 09/02/2024] [Revised: 10/24/2024] [Accepted: 10/30/2024] [Indexed: 11/28/2024] Open
Abstract
Background: The gut microbiota constitutes a complex microorganism community that harbors bacteria, viruses, fungi, protozoa, and archaea. The human gut bacterial microbiota has been extensively proven to participate in human metabolism, immunity, and nutrient absorption. Its imbalance, namely "dysbiosis", has been linked to disordered metabolism. Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the features of deranged human metabolism and is the leading cause of liver cirrhosis and hepatocellular carcinoma. Thus, there is a pathophysiological link between gut dysbiosis and MASLD. Aims and Methods: We aimed to review the literature data on the composition of the human bacterial gut microbiota and its dysbiosis in MASLD and describe the concept of the "gut-liver axis". Moreover, we reviewed the approaches for gut microbiota modulation in MASLD treatment. Results: There is consolidated evidence of particular gut dysbiosis associated with MASLD and its stages. The model explaining the relationship between gut microbiota and the liver has a bidirectional organization, explaining the physiopathology of MASLD. Oxidative stress is one of the keystones in the pathophysiology of MASLD and fibrosis generation. There is promising and consolidated evidence for the efficacy of pre- and probiotics in reversing gut dysbiosis in MASLD patients, with therapeutic effects. Few yet encouraging data on fecal microbiota transplantation (FMT) in MASLD are available in the literature. Conclusions: The gut dysbiosis characteristic of MASLD is a key target in its reversal and treatment via diet, pre/probiotics, and FMT treatment. Oxidative stress modulation remains a promising target for MASLD treatment, prevention, and reversal.
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Affiliation(s)
- Emidio Scarpellini
- Translational Research in Gastroeintestinal Disorders, Gasthuisberg University Hospital, KULeuven, Herestraat 49, 3000 Lueven, Belgium;
| | - Marialaura Scarcella
- Anesthesia, Intensive Care and Nutritional Science-Azienda Ospedaliera “Santa Maria”, Via Tristano di Joannuccio, 05100 Terni, Italy;
| | - Jan F. Tack
- Translational Research in Gastroeintestinal Disorders, Gasthuisberg University Hospital, KULeuven, Herestraat 49, 3000 Lueven, Belgium;
| | | | - Michela Zanetti
- Geriatrics Department, Nutrition and Malnutrition Unit, Azienda Sanitario-Universitaria Giuliano Isontina, Ospedale Maggiore, piazza dell’Ospitale 1, 34100 Triste, Italy;
| | - Ludovico Abenavoli
- Department of Health Sciences, University “Magna Graecia”, 88100 Catanzaro, Italy; (G.G.M.S.); (L.A.)
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Amangurbanova M, Daher R, Asbeutah AA, Vemuri B, Mirza H, Waseem S, Malik A, Welty FK. Higher epicardial adipose tissue volume is associated with higher coronary fatty plaque volume and is regulated by waist circumference but not EPA+DHA supplementation. J Clin Lipidol 2024; 18:e773-e786. [PMID: 39289125 DOI: 10.1016/j.jacl.2024.06.006] [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: 02/04/2024] [Revised: 05/13/2024] [Accepted: 06/26/2024] [Indexed: 09/19/2024]
Abstract
BACKGROUND Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation lower triglyceride levels. The impact on epicardial adipose tissue volume (EATV), which is associated with cardiovascular events, is unclear. OBJECTIVE To determine if triglyceride reduction with EPA+DHA supplementation decreases EATV and whether EATV affects coronary plaque. METHODS 139 subjects with coronary artery disease (CAD) on statins were randomized to 3.36 g EPA+DHA daily or none (control) for 30 months. EATV, coronary plaque volumes and coronary artery calcium score were measured with coronary computed tomographic angiography. RESULTS Change in triglyceride level correlated with change in EATV (r=0.236; p=0.006). Despite a 6.7% triglyceride reduction (p=0.021) with EPA+DHA supplementation compared to no change in control (between group p=0.034); both groups had similar reductions in EATV possibly due to statin treatment. EATV above the median (>115.6 cm3) was the only determinant of baseline coronary fatty plaque volume (β=2.4, p=0.010). After multivariate adjustment, waist circumference, a surrogate of abdominal visceral adiposity, was the only determinant of baseline EATV (odds ratio {OR]:1.093; 95% confidence interval [CI]:1.003-1.192, p=0.042). Moreover, increase in waist circumference was the only predictor of an increase in EATV at 30 months (β=0.320, p=0.018). CONCLUSIONS EATV is associated with higher coronary fatty plaque volume and is regulated by waist circumference but not EPA+DHA supplementation at 30-month follow-up in CAD patients on statin treatment. The direct correlation between waist circumference and EATV suggests that maintaining a healthy weight may limit EATV and coronary fatty plaque volume, potentially leading to a decrease in cardiovascular events.
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Affiliation(s)
- Maral Amangurbanova
- Division of Cardiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, United States (Drs Amangurbanova, Asbeutah, Vemuri, Mirza, Waseem, Malik, Welty)
| | - Ralph Daher
- Cooper University Healthcare, Camden, NJ, United States (Dr Daher)
| | - Abdul Aziz Asbeutah
- Division of Cardiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, United States (Drs Amangurbanova, Asbeutah, Vemuri, Mirza, Waseem, Malik, Welty)
| | - Bhavya Vemuri
- Division of Cardiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, United States (Drs Amangurbanova, Asbeutah, Vemuri, Mirza, Waseem, Malik, Welty)
| | - Hasan Mirza
- Division of Cardiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, United States (Drs Amangurbanova, Asbeutah, Vemuri, Mirza, Waseem, Malik, Welty)
| | - Smaha Waseem
- Division of Cardiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, United States (Drs Amangurbanova, Asbeutah, Vemuri, Mirza, Waseem, Malik, Welty)
| | - Abdulaziz Malik
- Division of Cardiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, United States (Drs Amangurbanova, Asbeutah, Vemuri, Mirza, Waseem, Malik, Welty)
| | - Francine K Welty
- Division of Cardiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, United States (Drs Amangurbanova, Asbeutah, Vemuri, Mirza, Waseem, Malik, Welty).
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Guo C, Liu Z, Fan H, Wang H, Zhang X, Zhao S, Li Y, Wang T, Dai L, Huang J, Chen X, Zhang T. Nonlinear relationships of circulating polyunsaturated fatty acids with the complications of liver cirrhosis: A prospective, longitudinal cohort study. Clin Nutr 2024; 43:2083-2091. [PMID: 39094473 DOI: 10.1016/j.clnu.2024.07.027] [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: 05/15/2024] [Revised: 07/24/2024] [Accepted: 07/24/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND & AIMS The role of circulating polyunsaturated fatty acids (PUFAs) in preventing liver cirrhosis complications remains unclear. METHODS Between 2006 and 2010, 273,834 UK Biobank participants with plasma PUFA quantification data were enrolled and followed up until October 31, 2022. Plasma PUFAs were quantified using a high-throughput nuclear magnetic resonance-based metabolic profiling platform. Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma. RESULTS During a median follow-up of 13.9 years, 2026 participants developed liver cirrhosis complications. Total plasma PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA) were inversely associated with the risk of liver cirrhosis complications, whereas the plasma omega-6/omega-3 ratio was positively associated. Nonparametrically restricted cubic spline regression showed nonlinear associations of plasma PUFAs with liver cirrhosis complications. The inflection points were 4.78 mmol/L for total PUFAs, 0.73 mmol/L for omega-3 PUFAs, 0.25 mmol/L for DHA, 4.07 mmol/L for omega-6 PUFAs, and 2.99 mmol/L for LA. Plasma omega-3 PUFAs were negatively associated with the risk of liver cirrhosis complications when omega-3 PUFAs were <0.73 mmol/L (adjusted hazard ratio [HR], 0.11 [0.08-0.16]), whereas the association was inverted when omega-3 PUFAs were ≥0.73 mmol/L (adjusted HR, 1.87 [1.20-2.92]). CONCLUSIONS The protective effect of plasma omega-3 PUFAs on liver cirrhosis complications is reversed after passing the corresponding inflection point, suggesting an optimal dietary omega-3 PUFA supplementation dose.
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Affiliation(s)
- Chengnan Guo
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China; Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Zhenqiu Liu
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Hong Fan
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Haili Wang
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Xin Zhang
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Shuzhen Zhao
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Yi Li
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Tianye Wang
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Luojia Dai
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Jiayi Huang
- Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
| | - Tiejun Zhang
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China; Department of Epidemiology, School of Public Health, Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
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Serbis A, Polyzos SA, Paschou SA, Siomou E, Kiortsis DN. Diet, exercise, and supplements: what is their role in the management of the metabolic dysfunction-associated steatotic liver disease in children? Endocrine 2024; 85:988-1006. [PMID: 38519764 DOI: 10.1007/s12020-024-03783-7] [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: 02/15/2024] [Accepted: 03/13/2024] [Indexed: 03/25/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the main cause of chronic liver disease in children and adolescents. Indeed, epidemiological studies have shown that MASLD affects up to 40% of children with obesity. Despite the recent approval of medications that target weight loss in adolescents that could have benefits on pediatric MASLD, lifestyle interventions, such as diet and exercise, remain the mainstay of our therapeutic approach. More specifically, studies on diet alone have focused on the possible role of carbohydrate or fat restriction, albeit without a definite answer on the best approach. Weight loss after dietary intervention in children with obesity and MASLD has a beneficial effect, regardless of the diet used. In relation to the role of exercise in MASLD reversal, indirect evidence comes from studies showing that a sedentary lifestyle leading to poor fitness, and low muscle mass is associated with MASLD. However, research on the direct effect of exercise on MASLD in children is scarce. A combination of diet and exercise seems to be beneficial with several studies showing improvement in surrogate markers of MASLD, such as serum alanine aminotransferase and hepatic fat fraction, the latter evaluated with imaging studies. Several dietary supplements, such as vitamin E, probiotics, and omega-3 fatty acid supplements have also been studied in children and adolescents with MASLD, but with equivocal results. This review aims to critically present available data on the effects of lifestyle interventions, including diet, exercise, and dietary supplements, on pediatric MASLD, thus suggesting a frame for future research that could enhance our knowledge on pediatric MASLD management and optimize clinicians' approach to this vexing medical condition.
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Affiliation(s)
- Anastasios Serbis
- Department of Pediatrics, School of Medicine, University of Ioannina, Ioannina, Greece.
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stavroula A Paschou
- Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Ekaterini Siomou
- Department of Pediatrics, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios N Kiortsis
- Laboratory of Physiology, Medical School, University of Ioannina, Ioannina, Greece
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9
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Sohouli MH, Bagheri SE, Fatahi S, Rohani P. The effects of weight loss interventions on children and adolescents with non-alcoholic fatty liver disease: A systematic review and meta-analysis. Obes Sci Pract 2024; 10:e758. [PMID: 38682153 PMCID: PMC11047132 DOI: 10.1002/osp4.758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 03/26/2024] [Accepted: 04/12/2024] [Indexed: 05/01/2024] Open
Abstract
Background Overall, there is conflicting evidence regarding the beneficial effects of optimal lifestyle modification, particularly weight loss interventions, with nonalcoholic fatty liver disease (non-alcoholic fatty liver disease (NAFLD)). Therefore, this study investigated the effects of weight loss interventions on laboratory and clinical parameters in children and adolescents with NAFLD. Methods Original databases (PubMed/MEDLINE, Web of Science, SCOPUS, and Embase) were searched using standard keywords to identify all controlled trials investigating the effects of weight loss interventions among NAFLD children and adolescents. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis. Results Eighteen eligible clinical trials were included in this systematic review and meta-analysis. The pooled findings showed that especially more intense weight loss interventions significantly reduced the glucose (p = 0.007), insulin (p = 0.002), homeostatic model assessment-insulin resistance (HOMA-IR) (p = 0.003), weight (p = 0.025), body mass index (BMI) (p = 0.003), BMI z-score (p < 0.001), waist circumference (WC) (p = 0.013), triglyceride (TG) (p = 0.001), and aspartate transaminase (AST) (p = 0.027). However, no significant changes were found in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine transaminase (ALT), and hepatic steatosis grades (all p > 0.05) following weight loss interventions. Conclusions Weight loss interventions had significant effects on NAFLD-related parameters including glucose, insulin, HOMA-IR, weight, BMI, BMI z-score, WC, TG, and AST.
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Affiliation(s)
- Mohammad Hassan Sohouli
- Student Research CommitteeDepartment of Clinical Nutrition and DieteticsFaculty of Nutrition and Food TechnologyShahid Beheshti University of Medical SciencesTehranIran
- Pediatric Gastroenterology and Hepatology Research CenterPediatrics Centre of ExcellenceChildren's Medical CenterTehran University of Medical SciencesTehranIran
| | | | - Somaye Fatahi
- Pediatric Gastroenterology, Hepatology, and Nutrition Research CenterResearch Institute for Children's HealthShahid Beheshti University of Medical SciencesTehranIran
| | - Pejman Rohani
- Pediatric Gastroenterology and Hepatology Research CenterPediatrics Centre of ExcellenceChildren's Medical CenterTehran University of Medical SciencesTehranIran
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10
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Calcaterra V, Cena H, Garella V, Loperfido F, Chillemi C, Manuelli M, Mannarino S, Zuccotti G. Assessment of Epicardial Fat in Children: Its Role as a Cardiovascular Risk Factor and How It Is Influenced by Lifestyle Habits. Nutrients 2024; 16:420. [PMID: 38337703 PMCID: PMC10857556 DOI: 10.3390/nu16030420] [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: 01/13/2024] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024] Open
Abstract
Epicardial adipose tissue (EAT) stands out as a distinctive repository of visceral fat, positioned in close anatomical and functional proximity to the heart. EAT has emerged as a distinctive reservoir of visceral fat, intricately interlinked with cardiovascular health, particularly within the domain of cardiovascular diseases (CVDs). The aim of our overview is to highlight the role of EAT as a marker for cardiovascular risk in children. We also explore the influence of unhealthy lifestyle habits as predisposing factors for the deposition of EAT. The literature data accentuate the consequential impact of lifestyle choices on EAT dynamics, with sedentary behavior and unwholesome dietary practices being contributory to a heightened cardiovascular risk. Lifestyle interventions with a multidisciplinary approach are therefore pivotal, involving a nutritionally balanced diet rich in polyunsaturated and monounsaturated fatty acids, regular engagement in aerobic exercise, and psychosocial support to effectively mitigate cardiovascular risks in children. Specific interventions, such as high-intensity intermittent training and circuit training, reveal favorable outcomes in diminishing the EAT volume and enhancing cardiometabolic health. Future clinical studies focusing on EAT in children are crucial for advancing our understanding and developing targeted strategies for cardiovascular risk management in this population.
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Affiliation(s)
- Valeria Calcaterra
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy;
| | - Hellas Cena
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (F.L.)
- Clinical Nutrition and Dietetics Service, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy;
| | - Vittoria Garella
- Pediatric Cardiology Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.G.); (C.C.); (S.M.)
| | - Federica Loperfido
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (H.C.); (F.L.)
| | - Claudia Chillemi
- Pediatric Cardiology Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.G.); (C.C.); (S.M.)
| | - Matteo Manuelli
- Clinical Nutrition and Dietetics Service, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy;
| | - Savina Mannarino
- Pediatric Cardiology Unit, “V. Buzzi” Children’s Hospital, 20154 Milan, Italy; (V.G.); (C.C.); (S.M.)
| | - Gianvincenzo Zuccotti
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy;
- Department of Biomedical and Clinical Science “L. Sacco”, University of Milan, 20157 Milan, Italy
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11
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Moore E, Patanwala I, Jafari A, Davies IG, Kirwan RP, Newson L, Mazidi M, Lane KE. A systematic review and meta-analysis of randomized controlled trials to evaluate plant-based omega-3 polyunsaturated fatty acids in nonalcoholic fatty liver disease patient biomarkers and parameters. Nutr Rev 2024; 82:143-165. [PMID: 37290426 PMCID: PMC10777680 DOI: 10.1093/nutrit/nuad054] [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] [Indexed: 06/10/2023] Open
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is prevalent in 25-30% of British and European populations, representing a potential global public health crisis. Marine omega-3 (n-3) polyunsaturated fatty acids offer well-evidenced benefits to NAFLD biomarkers; however, the effect of plant-based n-3 has not been evaluated with a systematic review and meta-analysis. OBJECTIVE The review aimed to systematically evaluate the effect of plant-based n-3 supplementation on NAFLD surrogate biomarkers and parameters. DATA SOURCES Medline (EBSCO), PubMed, CINAHL (EBSCO), Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and Google Scholar databases were searched to identify randomized controlled trials published between January 1970 and March 2022 evaluating the impact of plant-based n-3 interventions on diagnosed NAFLD. The review followed the PRISMA checklist and is PROSPERO registered (CRD42021251980). DATA EXTRACTION A random-effects model and generic inverse variance methods synthesized quantitative data, followed by a leave-one-out method for sensitivity analysis. We identified 986 articles; after the application of selection criteria, six studies remained with 362 patients with NAFLD. RESULTS The meta-analysis showed that plant-based n-3 fatty acid supplementation significantly reduced alanine aminotransferase (ALT) (mean difference: 8.04 IU/L; 95% confidence interval: 14.70, 1.38; I2 = 48.61%) and plasma/serum triglycerides (44.51 mg/dL; 95% confidence interval: -76.93, -12.08; I2 = 69.93%), alongside body-composition markers in patients with NAFLD (P < 0.05). CONCLUSION Plant-based n-3 fatty acid supplementation improves ALT enzyme biomarkers, triglycerides, body mass index, waist circumference, and weight loss when combined with lifestyle interventions to increase physical activity and a calorie-controlled diet. Further research is needed to identify the most effective plant-based n-3 sources in larger numbers of patients with NAFLD over longer study durations. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42021251980.
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Affiliation(s)
- Ella Moore
- Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | | | - Alireza Jafari
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Ian G Davies
- Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Richard P Kirwan
- Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Lisa Newson
- School of Psychology, Liverpool John Moores University, Liverpool, United Kingdom
| | - Mohsen Mazidi
- Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
| | - Katie E Lane
- Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom
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12
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Sandel P, Ma L, Wang H, Pasman EA. You Are What You Eat: A Review on Dietary Interventions for Treating Pediatric Nonalcoholic Fatty Liver Disease. Nutrients 2023; 15:3350. [PMID: 37571287 PMCID: PMC10421125 DOI: 10.3390/nu15153350] [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: 06/26/2023] [Revised: 07/20/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
As the obesity pandemic worsens, cases of pediatric nonalcoholic fatty liver disease (NAFLD) and complications of this disease, such as progressive liver failure, in young adults will continue to rise. Lifestyle changes in the form of dietary modifications and exercise are currently first-line treatments. Large pediatric-specific randomized controlled trials to support specific interventions are currently lacking. A variety of dietary modifications in children with NAFLD have been suggested and studied with mixed results, including low-sugar and high-protein diets, the Mediterranean diet, and the Dietary Approach to Stop Hypertension (DASH). The roles of dietary supplements such as Vitamin E, polyunsaturated fatty acids (PUFAs), ginger, and probiotics have also been investigated. A further understanding of specific dietary interventions and supplements is needed to provide both generalizable and sustainable dietary recommendations to reverse the progression of NAFLD in the pediatric population.
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Affiliation(s)
- Piper Sandel
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Lawrence Ma
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Helen Wang
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Eric A. Pasman
- Division of Pediatric Gastroenterology, Department of Pediatrics, Naval Medical Center San Diego, San Diego, CA 92134, USA;
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
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13
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Vell MS, Creasy KT, Scorletti E, Seeling KS, Hehl L, Rendel MD, Schneider KM, Schneider CV. Omega-3 intake is associated with liver disease protection. Front Public Health 2023; 11:1192099. [PMID: 37538264 PMCID: PMC10394692 DOI: 10.3389/fpubh.2023.1192099] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 07/04/2023] [Indexed: 08/05/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease are among the most common liver diseases worldwide, and there are currently no Food and Drug Administration (FDA)-approved treatments. Recent studies have focused on lifestyle changes to prevent and treat NAFLD. Omega-3 supplementation is associated with improved outcomes in patients with chronic liver disease. However, it is unclear whether Omega-3 supplementation can prevent the development of liver disease, particularly in individuals at an increased (genetic) risk. Methods In this UK Biobank cohort study, we established a multivariate cox proportional hazards model for the risk of incident liver disease during an 11 year follow up time. We adjusted the model for diabetes, prevalent cardiovascular disorders, socioeconomic status, diet, alcohol consumption, physical activity, medication intake (insulin, biguanides, statins and aspirin), and baseline characteristics. Results Omega-3 supplementation reduced the risk of incident liver disease (HR = 0.716; 95% CI: 0.639, 0.802; p = 7.6 × 10-9). This protective association was particularly evident for alcoholic liver disease (HR = 0.559; 95% CI: 0.347, 0.833; p = 4.3 × 10-3), liver failure (HR = 0.548; 95% CI: 0.343, 0.875; p = 1.2 × 10-2), and non-alcoholic liver disease (HR = 0.784; 95% CI: 0.650, 0.944; p = 1.0 × 10-2). Interestingly, we were able to replicate the association with reduced risk of NAFLD in a subset with liver MRIs (HR = 0.846; 95% CI: 0.777, 0.921; p = 1.1 × 10-4). In particular, women benefited from Omega-3 supplementation as well as heterozygous allele carriers of the liver-damaging variant PNPLA3 rs738409. Conclusions Omega-3 supplementation may reduce the incidence of liver disease. Our study highlights the potential of personalized treatment strategies for individuals at risk of metabolic liver disease. Further evaluation in clinical trials is warranted before Omega-3 can be recommended for the prevention of liver disease.
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Affiliation(s)
- Mara Sophie Vell
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Kate Townsend Creasy
- Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, United States
| | - Eleonora Scorletti
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Katharina Sophie Seeling
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Leonida Hehl
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Miriam Daphne Rendel
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Kai Markus Schneider
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
| | - Carolin Victoria Schneider
- Department of Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- The Institute for Translational Medicine and Therapeutics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
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14
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Spiezia C, Di Rosa C, Fintini D, Ferrara P, De Gara L, Khazrai YM. Nutritional Approaches in Children with Overweight or Obesity and Hepatic Steatosis. Nutrients 2023; 15:nu15112435. [PMID: 37299398 DOI: 10.3390/nu15112435] [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: 04/17/2023] [Revised: 05/11/2023] [Accepted: 05/19/2023] [Indexed: 06/12/2023] Open
Abstract
Childhood obesity is a global public health problem. Worldwide, 41 million children under 5 years and 340 million children and adolescents between 5 and 19 years are overweight. In addition, the recent COVID-19 epidemic has further amplified this social phenomenon. Obesity is a condition associated with various comorbidities, such as nonalcoholic fatty liver disease (NAFLD). The pathophysiology of NAFLD in obesity is intricate and involves the interaction and dysregulation of several mechanisms, such as insulin resistance, cytokine signaling, and alteration of the gut microbiota. NAFLD is defined as the presence of hepatic steatosis in more than 5% of hepatocytes, evaluated by histological analysis. It can evolve from hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver failure. Body weight reduction through lifestyle modification remains the first-line intervention for the management of pediatric NAFLD. Indeed, studies suggest that diets low in fat and sugar and conversely rich in dietary fibers promote the improvement of metabolic parameters. This review aims to evaluate the existing relationship between obesity and NAFLD in the pediatric population and to assess the dietary patterns and nutritional supplementations that can be recommended to prevent and manage obesity and its comorbidities.
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Affiliation(s)
- Chiara Spiezia
- Research Unit of Food Science and Human Nutrition, Department of Science and Technology for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21-00128 Roma, Italy
| | - Claudia Di Rosa
- Research Unit of Food Science and Human Nutrition, Department of Science and Technology for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21-00128 Roma, Italy
| | - Danilo Fintini
- Endocrinology and Diabetology Unit, Bambino Gesù Children's Hospital, IRCCS L.go S.Onofrio, 4-00165 Roma, Italy
| | - Pietro Ferrara
- Operative Research Unit of Pediatrics, Department of Medicine and Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200-00128 Roma, Italy
| | - Laura De Gara
- Research Unit of Food Science and Human Nutrition, Department of Science and Technology for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21-00128 Roma, Italy
| | - Yeganeh Manon Khazrai
- Research Unit of Food Science and Human Nutrition, Department of Science and Technology for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21-00128 Roma, Italy
- Operative Research Unit of Nutrition and Prevention, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200-00128 Roma, Italy
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15
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Capra ME, Stanyevic B, Giudice A, Monopoli D, Decarolis NM, Esposito S, Biasucci G. Long-Chain Polyunsaturated Fatty Acids Effects on Cardiovascular Risk in Childhood: A Narrative Review. Nutrients 2023; 15:nu15071661. [PMID: 37049503 PMCID: PMC10096679 DOI: 10.3390/nu15071661] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 03/24/2023] [Accepted: 03/28/2023] [Indexed: 04/14/2023] Open
Abstract
Long-chain polyunsaturated fatty acids (LCPUFAs) are semi-essential fatty acids widely studied in adult subjects for their healthy-heart effects, especially on secondary prevention in patients who already experienced a cardiac event. LCPUFAs consumption is safe, without adverse effects, and they are usually well-tolerated; they can be taken either in foods or as nutritional supplements. LCPUFAs' positive effect on global health has been worldwide recognized also for pediatric patients. In childhood and adolescence, research has mainly focused on LCPUFAs' effects on neurodevelopment, brain and visual functions and on maternal-fetal medicine, yet their cardiovascular effects in childhood are still understudied. Atherosclerosis is a multifactorial process that starts even before birth and progresses throughout life; thus, cardiovascular prevention is advisable and effective from the very first years of life. Nutritional and lifestyle interventions are the main factors that can interfere with atherosclerosis in childhood, and the consumption of specific nutrients, such as LCPUFAs, can enhance positive nutritional effects. The aim of our narrative review is to analyze the effect of LCPUFAs on cardiovascular risk factors and on cardiovascular risk prevention in developmental age, focusing on specific conditions such as weight excess and dyslipidemia.
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Affiliation(s)
- Maria Elena Capra
- Pediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy
- Società Italiana di Nutrizione Pediatrica, 20126 Milan, Italy
| | - Brigida Stanyevic
- Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy
| | - Antonella Giudice
- Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy
| | - Delia Monopoli
- Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy
| | - Nicola Mattia Decarolis
- Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy
| | - Susanna Esposito
- Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126 Parma, Italy
| | - Giacomo Biasucci
- Pediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy
- Società Italiana di Nutrizione Pediatrica, 20126 Milan, Italy
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
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16
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Fiore G, Pascuzzi MC, Di Profio E, Corsello A, Agostinelli M, La Mendola A, Milanta C, Campoy C, Calcaterra V, Zuccotti G, Verduci E. Bioactive compounds in childhood obesity and associated metabolic complications: Current evidence, controversies and perspectives. Pharmacol Res 2023; 187:106599. [PMID: 36503001 DOI: 10.1016/j.phrs.2022.106599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/30/2022] [Accepted: 12/01/2022] [Indexed: 12/13/2022]
Abstract
Obesity represents the most frequent chronic disease among children worldwide, with a significant global burden on society. Metabolically unhealthy obesity (MUO) can affect children since their first years of life, and novel therapeutic strategies to tackle metabolic complications are under investigation. This review focuses on bioactive compounds and their possible beneficial effects on obesity, particularly omega-3, docosahexaenoic acid, vitamin D, biotics, polysaccharide macromolecules, polyphenols, inositols, alpha lipoic acid, and bromelaine. Our aim is to summarize current evidence about bioactive compounds in the treatment of obesity, highlighting recent findings on their use in children and adolescents. Most studied molecules are omega-3 and vitamin D, despite the heterogeneity between the studies. Moreover, given the emerging interest in the gut-brain axis in the link between metabolic health and microbiota, various studies on prebiotics, probiotics, synbiotics, postbiotics and polysaccharide macromolecules have been considered. Some preclinical studies seem to highlight a possible role of the polyphenols, even if their clinical evidence is still discussed. Lastly, we describe possible effects of inositols and alpha-lipoic acid. Despite some dietary supplements seem to be promising in overweight subjects, only in a few of them a dose/response efficacy has been found in the pediatric age. Innovative, well-designed and targeted clinical trials are then needed to prove the beneficial effects of these compounds that could support the standard behavioral therapy for obesity.
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Affiliation(s)
- Giulia Fiore
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy.
| | | | - Elisabetta Di Profio
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy.
| | - Antonio Corsello
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy.
| | - Marta Agostinelli
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy.
| | - Alice La Mendola
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy.
| | - Chiara Milanta
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy.
| | - Cristina Campoy
- Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain; EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, Granada, Spain; Spanish Network of Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada's node, Institute of Health Carlos III, 28029 Madrid, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), San Cecilio University Hospital. Health Sciences Technological Park, 18016 Granada, Spain.
| | - Valeria Calcaterra
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy; Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy.
| | - Gianvincenzo Zuccotti
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy; Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, 20144 Milan, Italy; Pediatric Clinical Research Center, Fondazione Romeo ed Enrica Invernizzi, University of Milan, Milan, Italy.
| | - Elvira Verduci
- Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Italy; Department of Health Sciences, University of Milan, Milan, Italy.
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17
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Theodoridis X, Kalopitas G, Vadarlis A, Bakaloudi DR, Gkiourtzis Ν, Dionysopoulos G, Karanika E, Tsekitsidi E, Chourdakis M. Comparative efficacy of different treatment modalities in the management of pediatric non-alcoholic fatty liver disease: A systematic review and network meta-analysis. Pharmacol Ther 2022; 240:108294. [PMID: 36183848 DOI: 10.1016/j.pharmthera.2022.108294] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 09/09/2022] [Accepted: 09/26/2022] [Indexed: 12/15/2022]
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) in children is constantly rising. Lifestyle modification is the cornerstone of the management of pediatric NAFLD. Even though several clinical trials have been conducted, there are barely any approved medications or supplements that can be used in the management of pediatric NAFLD. The aim of our study was to systematically review the current literature and perform a network meta-analysis to compare the different treatment interventions in pediatric NAFLD. Pubmed/Medline, Embase and Scopus were searched from inception to 2 December 2021. The primary outcomes were changes in alanine transaminase (`concentrations. Secondary outcomes were changes in aspartate aminotransferase (AST), lipidemic and other biochemical parameters concentrations and body mass index (BMI) values. The evaluation of transitivity was performed by comparing the distribution of potential effect modifiers across the difference comparisons. Our study included 1241 participants from 18 studies. Different interventions such as omega 3 fatty acids and probiotics seem to exert possible beneficial effects in the management of pediatric NAFLD. Vitamin D and vitamin E supplementation alone or in combination with other interventions also seem to be beneficial in specific patient groups. Several interventions such as omega-3 fatty acids, probiotics and vitamin D and E can be combined with lifestyle modification to manage pediatric NAFLD. Decisions should be individualized based on the patient's profile. Future studies with optimal methodology are needed to draw safe and applicable conclusions.
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Affiliation(s)
- Xenophon Theodoridis
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Georgios Kalopitas
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; Division of Gastroenterology and Hepatology, 1(st) Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Andreas Vadarlis
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; Department of Gastroenterology and Hepatology, General Hospital of Thessaloniki "G. Papanikolaou", Thessaloniki, Greece.
| | - Dimitra Rafailia Bakaloudi
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Νikolaos Gkiourtzis
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; 4(th) Department of Pediatrics, Papageorgiou University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Georgios Dionysopoulos
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Evangelia Karanika
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Eirini Tsekitsidi
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social- Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
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Effects of Omega-3-Rich Pork Lard on Serum Lipid Profile and Gut Microbiome in C57BL/6NJ Mice. INTERNATIONAL JOURNAL OF FOOD SCIENCE 2022; 2022:9269968. [DOI: 10.1155/2022/9269968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 10/24/2022] [Accepted: 10/29/2022] [Indexed: 11/23/2022]
Abstract
Background and Aims. Hyperlipidemia is a risk factor for cardiovascular diseases. This study is aimed at investigating the effects of consuming omega-3-rich pork lard on the serum lipid profile and gut microbiome of the mice model. Methods and Results. We divided 23 C57BL/6NJ males (16-week-old) into 3 groups, and each group received either a control diet, a high-fat diet of coconut oil (coconut oil), or a high-fat diet of omega-3-rich pork lard (omega lard) for 28 days. Thereafter, fasting serum lipids and fecal microbiomes were analyzed. The serum cholesterol, triglyceride, and LDL levels of the omega lard-treated group were significantly reduced compared to the coconut oil-treated group (
). However, the microbiome analysis revealed a significant increase in the abundance of Lachnospiraceae in the omega lard-treated group compared to the coconut oil-treated group (
). Furthermore, Spearman’s correlation analysis revealed that the increased serum lipid content was positively correlated with the abundance of Bacteroidaceae (
) and negatively correlated with the abundance of Lachnospiraceae (
). Conclusions. These findings suggested that omega-3-rich pork lard altered the serum lipid profile and gut microbiome in the mice model. Practical Application. The excellent protection offered by omega-3-rich pork lard against hyperlipidemia indicated that pork lard could be used as alternative cooking oil for health-conscious individuals. It could also be introduced as a functional ingredient for patients with hyperlipidemia.
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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: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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20
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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. Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025. 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] [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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21
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Epicardial Adipose Tissue: A Novel Potential Imaging Marker of Comorbidities Caused by Chronic Inflammation. Nutrients 2022; 14:nu14142926. [PMID: 35889883 PMCID: PMC9316118 DOI: 10.3390/nu14142926] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 07/09/2022] [Indexed: 12/11/2022] Open
Abstract
The observation of correlations between obesity and chronic metabolic and cardiovascular diseases has led to the emergence of strong interests in “adipocyte biology”, in particular in relation to a specific visceral adipose tissue that is the epicardial adipose tissue (EAT) and its pro-inflammatory role. In recent years, different imaging techniques frequently used in daily clinical practice have tried to obtain an EAT quantification. We provide a useful update on comorbidities related to chronic inflammation typical of cardiac adiposity, analyzing how the EAT assessment could impact and provide data on the patient prognosis. We assessed for eligibility 50 papers, with a total of 10,458 patients focusing the review on the evaluation of EAT in two main contexts: cardiovascular and metabolic diseases. Given its peculiar properties and rapid responsiveness, EAT could act as a marker to investigate the basal risk factor and follow-up conditions. In the future, EAT could represent a therapeutic target for new medications. The assessment of EAT should become part of clinical practice to help clinicians to identify patients at greater risk of developing cardiovascular and/or metabolic diseases and to provide information on their clinical and therapeutic outcomes.
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22
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Quek SXZ, Tan EXX, Ren YP, Muthiah M, Loo EXL, Tham EH, Siah KTH. Factors early in life associated with hepatic steatosis. World J Hepatol 2022; 14:1235-1247. [PMID: 35978672 PMCID: PMC9258263 DOI: 10.4254/wjh.v14.i6.1235] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/01/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) mirrors the obesity epidemic. NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis, fibrosis and cirrhosis and/or hepatocellular carcinoma. Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity.
AIM To review the early developmental factors associated with NAFLD.
METHODS Databases MEDLINE via PubMed, and EMBASE and Reference Citation Analysis were searched and relevant publications up to April 30, 2021 were assessed. Original research studies that included risk factors associated with early development of NAFLD in human subjects were included. These factors include: Maternal factors, intrauterine and prenatal factors, post-natal factors, genetic and ethnic predisposition, childhood and adolescence environmental factors. Studies were excluded if they were review articles or animal studies, case reports or conference abstracts, or if NAFLD was not clearly defined and assessed radiologically.
RESULTS Of 1530 citations identified by electronic search, 420 duplicates were removed. Of the 1110 citations screened from title and abstract, 80 articles were included in the final analysis. Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) were associated with increased risk of NAFLD. Familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD. Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD. Studies relating to socioeconomic factors and its association with NAFLD reported confounding results.
CONCLUSION Maternal metabolic dysfunction during pregnancy, being exclusively breastfed for a longer time postnatally, diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.
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Affiliation(s)
- Sabrina Xin Zi Quek
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Eunice Xiang-Xuan Tan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Yi Ping Ren
- Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Evelyn Xiu Ling Loo
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore
| | - Elizabeth Huiwen Tham
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
| | - Kewin Tien Ho Siah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
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23
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Videla LA, Hernandez-Rodas MC, Metherel AH, Valenzuela R. Influence of the nutritional status and oxidative stress in the desaturation and elongation of n-3 and n-6 polyunsaturated fatty acids: Impact on non-alcoholic fatty liver disease. Prostaglandins Leukot Essent Fatty Acids 2022; 181:102441. [PMID: 35537354 DOI: 10.1016/j.plefa.2022.102441] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 04/19/2022] [Accepted: 04/20/2022] [Indexed: 12/25/2022]
Abstract
Polyunsaturated fatty acids (PUFA) play essential roles in cell membrane structure and physiological processes including signal transduction, cellular metabolism and tissue homeostasis to combat diseases. PUFA are either consumed from food or synthesized by enzymatic desaturation, elongation and peroxisomal β-oxidation. The nutritionally essential precursors α-linolenic acid (C18:3n-3; ALA) and linoleic acid (C18:2n-6; LA) are subjected to desaturation by Δ6D/Δ5D desaturases and elongation by elongases 2/5, enzymes that are induced by insulin and repressed by PUFA. Maintaining an optimally low n-6/n-3 PUFA ratio is linked to prevention of the development of several diseases, including nonalcoholic fatty liver disease (NAFLD) that is characterized by depletion of PUFA promoting hepatic steatosis and inflammation. In this context, supplementation with n-3 PUFA revealed significant lowering of hepatic steatosis in obese patients, whereas prevention of fatty liver by high-fat diet in mice is observed in n-3 PUFA and hydroxytyrosol co-administration. The aim of this work is to review the role of nutritional status and nutrient availability on markers of PUFA biosynthesis. In addition, the impact of oxidative stress developed as a result of NAFLD, a redox imbalance that may alter the expression and activity of the enzymes involved, and diminished n-3 PUFA levels by free-radical dependent peroxidation processes will be discussed.
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Affiliation(s)
- Luis A Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
| | | | - Adam H Metherel
- Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Rodrigo Valenzuela
- Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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24
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Ren X, Larsen SC, Lauritzen L, Olsen NJ, Rohde JF, Specht IO, Heitmann BL. Association between intake of marine fat and adiposity development among 2-6 year old children: Substitution analyses from the Healthy Start intervention study. Nutrition 2022; 103-104:111775. [DOI: 10.1016/j.nut.2022.111775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 06/03/2022] [Accepted: 06/06/2022] [Indexed: 10/31/2022]
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Dionysopoulos G, Kalopitas G, Vadarlis A, Bakaloudi DR, Gkiourtzis N, Karanika E, Tsekitsidi E, Chourdakis M. Can omega-3 fatty acids be beneficial in pediatric NAFLD? A systematic review and meta-analysis. Crit Rev Food Sci Nutr 2022; 63:8545-8553. [PMID: 35400251 DOI: 10.1080/10408398.2022.2062589] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children and no medications or supplements are currently recommended. The role of omega-3 (n-3) fatty acids has been investigated in clinical trials with promising results. The aim of this study is to provide a detailed summary of the evidence about the efficacy of n-3 in the treatment of pediatric NAFLD. A systematic literature search was performed through major electronic databases up to September 20, 2021 for randomized placebo-controlled trials, investigating the efficacy of n-3 fatty acids in children with NAFLD. The primary outcomes were changes in serum transaminases concentration, Body Mass Index (BMI) and improvement of ultrasonographic liver steatosis. The secondary outcomes were changes in the patients' serum lipid profile, γ-glutamyl transferase (GGT), fasting blood glucose (FBG), homeostatic model assessment of insulin resistance (ΗΟΜΑ-ΙR) and waist circumference (WC). Results were expressed as mean differences for continuous outcomes and odds ratios for dichotomous outcomes with 95% confidence intervals. Six RCTs (n = 378 patients) were included. Treatment with n-3, compared to placebo, resulted in a statistically significant reduction in transaminases concentration. In addition, a significant improvement in liver steatosis assessed by ultrasonography and a decrease in BMI were observed. N-3 fatty acids supplementation seems to be an effective alternative treatment in pediatric NAFLD by improving liver biochemistry, ultrasonographic steatosis and BMI. Further research is required concerning the effect of n-3 fatty acids in liver histology.
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Affiliation(s)
- Georgios Dionysopoulos
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgios Kalopitas
- Division of Gastroenterology and Hepatology, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Andreas Vadarlis
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Department of Gastroenterology and Hepatology, General Hospital of Thessaloniki "G. Papanikolaou,"Thessaloniki, Greece
| | - Dimitra Rafailia Bakaloudi
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Nikolaos Gkiourtzis
- 4th Department of Paediatrics, Papageorgiou University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Evangelia Karanika
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eirini Tsekitsidi
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Effect of Vitamin D and Docosahexaenoic Acid Co-Supplementation on Vitamin D Status, Body Composition, and Metabolic Markers in Obese Children: A Randomized, Double Blind, Controlled Study. Nutrients 2022; 14:nu14071397. [PMID: 35406010 PMCID: PMC9003047 DOI: 10.3390/nu14071397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/21/2022] [Accepted: 03/24/2022] [Indexed: 12/10/2022] Open
Abstract
Obese children are at high risk of developing vitamin D deficiency. Omega-3 polyunsaturated fatty acids and their derivatives might have a beneficial effect on vitamin D status of obese children, due to their anti-inflammatory action, and increasing its absorption. This multicenter, randomized, double-blind controlled study aims to investigate the effect of vitamin D and docosahexaenoic acid (DHA) co-supplementation for six months on vitamin D status, body composition, and metabolic markers of obese children with vitamin D deficiency. A total of 108 children were enrolled and 73 children completed the study: 33 were supplemented with an oral dose of 500 mg of DHA and 1200 IU/day of vitamin D3 and 41 were supplemented with 1200 IU/day of vitamin D3 + wheat germ oil. At the end of the study, more than 50% of the subjects improved their vitamin D status. However, co-supplementation was not more effective than vitamin D plus wheat germ oil. Fat mass percentage was significantly reduced, and body mass index improved in both groups, even if all the subjects were still obese at the end of the study. Children receiving both vitamin D and DHA presented a higher increase of DHA levels that could be relevant to prevent inflammatory-associated complications of obesity, but they had no effect on vitamin D levels.
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Maresin-1 and Inflammatory Disease. Int J Mol Sci 2022; 23:ijms23031367. [PMID: 35163291 PMCID: PMC8835953 DOI: 10.3390/ijms23031367] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 01/24/2022] [Accepted: 01/24/2022] [Indexed: 11/17/2022] Open
Abstract
Inflammation is an essential action to protect the host human body from external, harmful antigens and microorganisms. However, an excessive inflammation reaction sometimes exceeds tissue damage and can disrupt organ functions. Therefore, anti-inflammatory action and resolution mechanisms need to be clarified. Dietary foods are an essential daily lifestyle that influences various human physiological processes and pathological conditions. Especially, omega-3 fatty acids in the diet ameliorate chronic inflammatory skin diseases. Recent studies have identified that omega-3 fatty acid derivatives, such as the resolvin series, showed strong anti-inflammatory actions in various inflammatory diseases. Maresin-1 is a derivative of one of the representative omega-3 fatty acids, i.e., docosahexaenoic acid (DHA), and has shown beneficial action in inflammatory disease models. In this review, we summarize the detailed actions of maresin-1 in immune cells and inflammatory diseases.
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Low-salted salmon: Effects of salt reduction on physicochemical, lipidomic, and sensory characteristics. Lebensm Wiss Technol 2021. [DOI: 10.1016/j.lwt.2021.112311] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Jeyakumar SM, Vajreswari A. Pharmaconutrition strategy to resolve SARS-CoV-2-induced inflammatory cytokine storm in non-alcoholic fatty liver disease: Omega-3 long-chain polyunsaturated fatty acids. World J Clin Cases 2021; 9:9333-9349. [PMID: 34877270 PMCID: PMC8610854 DOI: 10.12998/wjcc.v9.i31.9333] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/18/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammation is one of the primary factors associated with the causation and/or progression of several lifestyle disorders, including obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). NAFLD is a spectrum of disorders, and starts with simple steatosis, progresses to non-alcoholic steatohepatitis, and then advances to fibrosis, cirrhosis and finally, hepatocellular carcinoma, due to perpetual cycles of insults caused by inflammation and other cellular stress. Emerging evidence has documented that patients with NAFLD have severe coronavirus disease 2019 (COVID-19), and patients with COVID-19 have a higher liver injury and mortality. Although the exact cause or mechanism is not known, inflammatory cytokine storm is a characteristic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is known to be associated with higher mortality among COVID-19 patients. Therefore, the COVID-19 pandemic seems to be a major concern in NAFLD patients, who have contracted SARS-CoV-2 infection and develop COVID-19. This is evident in patients at any stage of the NAFLD spectrum, as the inflammatory cytokine storm may cause and/or aggravate the progression or severity of NAFLD. Thus, there is a need for resolution of the inflammatory cytokine storm in these patients. A large body of evidence has demonstrated the efficacy of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) in NAFLD conditions, due to their anti-inflammatory, immunomodulatory and anti-viral properties. Therefore, intervention with ω-3 LCPUFA, an effective pharmaconutrient along with the standard treatment for COVID-19 may be useful in the management of the NAFLD spectrum in COVID-19 patients with pre-existing NAFLD conditions by resolving the inflammatory cytokine storm and thereby attenuating its progression. Although there are challenges in implementation, optimistically they can be circumvented and the pharmaconutrition strategy may be potentially helpful in tackling both the pandemics; NAFLD and COVID-19 at least in this subset of patients.
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Affiliation(s)
- Shanmugam M Jeyakumar
- Department of Clinical Pharmacology, ICMR-National Institute for Research in Tuberculosis, Chennai 600031, Tamil Nadu, India
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Herrera Vielma F, Valenzuela R, Videla LA, Zúñiga-Hernández J. N-3 Polyunsaturated Fatty Acids and Their Lipid Mediators as A Potential Immune-Nutritional Intervention: A Molecular and Clinical View in Hepatic Disease and Other Non-Communicable Illnesses. Nutrients 2021; 13:3384. [PMID: 34684386 PMCID: PMC8539469 DOI: 10.3390/nu13103384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/11/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
In recent years, the beneficial effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) intake on human health has been widely accepted in the field of immunonutrition. Today, we find a diversity of supplements based on n-3 PUFAs and/or minerals, vitamins and other substances. The main objective of this review is to discuss the importance of n-3 PUFAs and their derivatives on immunity and inflammatory status related to liver disease and other non-communicable illnesses. Based on the burden of liver diseases in 2019, more than two million people die from liver pathologies per year worldwide, because it is the organ most exposed to agents such as viruses, toxins and medications. Consequently, research conducted on n-3 PUFAs for liver disease has been gaining prominence with encouraging results, given that these fatty acids have anti-inflammatory and cytoprotective effects. In addition, it has been described that n-3 PUFAs are converted into a novel species of lipid intermediaries, specialized pro-resolving mediators (SPMs). At specific levels, SPMs improve the termination of inflammation as well as the repairing and regeneration of tissues, but they are deregulated in liver disease. Since evidence is still insufficient to carry out pharmacological trials to benefit the resolution of acute inflammation in non-communicable diseases, there remains a call for continuing preclinical and clinical research to better understand SPM actions and outcomes.
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Affiliation(s)
- Francisca Herrera Vielma
- Department of Biomedical Basic Sciences, School of Health Sciences, University of Talca, Talca 3460000, Chile;
| | - Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Luis A. Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Jessica Zúñiga-Hernández
- Department of Biomedical Basic Sciences, School of Health Sciences, University of Talca, Talca 3460000, Chile;
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Komolafe O, Buzzetti E, Linden A, Best LM, Madden AM, Roberts D, Chase TJ, Fritche D, Freeman SC, Cooper NJ, Sutton AJ, Milne EJ, Wright K, Pavlov CS, Davidson BR, Tsochatzis E, Gurusamy KS. Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 7:CD013157. [PMID: 34280304 PMCID: PMC8406904 DOI: 10.1002/14651858.cd013157.pub2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. OBJECTIVES • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up. AUTHORS' CONCLUSIONS The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes).
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Affiliation(s)
| | - Elena Buzzetti
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Lawrence Mj Best
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Angela M Madden
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Thomas Jg Chase
- Department of General Surgery, Homerton University Hospital NHS Foundation Trust, London, UK
| | | | - Suzanne C Freeman
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Nicola J Cooper
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Alex J Sutton
- Department of Health Sciences, University of Leicester, Leicester, UK
| | | | - Kathy Wright
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Chavdar S Pavlov
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Kurinchi Selvan Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
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Wu S, Zhu C, Wang Z, Wang S, Yuan P, Song T, Hou X, Lei Z. Effects of Fish Oil Supplementation on Cardiometabolic Risk Factors in Overweight or Obese Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials. Front Pediatr 2021; 9:604469. [PMID: 33987149 PMCID: PMC8110710 DOI: 10.3389/fped.2021.604469] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 02/22/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Influences of fish oil supplementation on body weight and other cardiometabolic factors in overweight or obese children and adolescents remain not fully understood. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of fish oil for these children. Methods: Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model, which incorporates the potential heterogeneity of the included studies, was used to pool the results. Results: Twelve RCTs including 1,028 overweight or obese children and adolescents were included. Compared to control, fish oil supplementation significantly reduced body mass index [BMI, mean difference (MD): -0.96 kg/m2, 95% confidence interval (CI): -1.69 to -0.23, P = 0.01] but did not significantly reduce body weight or waist circumference (P = 0.68 and 0.76). Moreover, fish oil supplementation significantly reduced serum triglyceride (MD: -0.24 mmol/L, 95% CI: -0.40 to -0.08, P = 0.004) but did not significantly affect serum total cholesterol and high-density or low-density lipoprotein cholesterol (P = 0.83, 0.42, and 0.31, respectively). Additionally, fish oil supplementation significantly lowered systolic blood pressure (SBP, MD: -2.46 mmHg, 95% CI: -4.93 to -0.01, P = 0.04) but did not significantly change diastolic blood pressure (P = 0.22). Supplementation with fish oil did not significantly affect fasting plasma glucose (P = 0.33). Conclusions: In overweight or obese children and adolescents, supplementation with fish oil could reduce BMI, decrease serum triglyceride, and lower SBP, while serum cholesterol and fasting glucose may not be significantly affected.
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Affiliation(s)
- Shaojing Wu
- Department of Clinical Nutrition, Hainan Maternal and Children's Medical Center, Haikou, China
| | - Chunhong Zhu
- Department of Pediatrics, Zhongshan Hospital Affiliated to Dalian University, Dalian, China
| | - Zhen Wang
- Department of Pediatrics, Zhongshan Hospital Affiliated to Dalian University, Dalian, China
| | - Shumei Wang
- Department of Pediatrics, Zhongshan Hospital Affiliated to Dalian University, Dalian, China
| | - Pengfei Yuan
- Department of Pediatrics, Zhongshan Hospital Affiliated to Dalian University, Dalian, China
| | - Tao Song
- Department of Pediatrics, Zhongshan Hospital Affiliated to Dalian University, Dalian, China
| | - Xiaoli Hou
- Department of Pediatrics, Zhongshan Hospital Affiliated to Dalian University, Dalian, China
| | - Zhixian Lei
- Department of Critical Medicine, Hainan Maternal and Children's Medical Center, Haikou, China
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Scapaticci S, D’Adamo E, Mohn A, Chiarelli F, Giannini C. Non-Alcoholic Fatty Liver Disease in Obese Youth With Insulin Resistance and Type 2 Diabetes. Front Endocrinol (Lausanne) 2021; 12:639548. [PMID: 33889132 PMCID: PMC8056131 DOI: 10.3389/fendo.2021.639548] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 01/28/2021] [Indexed: 02/06/2023] Open
Abstract
Currently, Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in children and adolescents worldwide. Simultaneously to the epidemic spreading of childhood obesity, the rate of affected young has dramatically increased in the last decades with an estimated prevalence of NAFLD of 3%-10% in pediatric subjects in the world. The continuous improvement in NAFLD knowledge has significantly defined several risk factors associated to the natural history of this complex liver alteration. Among them, Insulin Resistance (IR) is certainly one of the main features. As well, not surprisingly, abnormal glucose tolerance (prediabetes and diabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. In addition, other factors such as genetic, ethnicity, gender, age, puberty and lifestyle might affect the development and progression of hepatic alterations. However, available data are still lacking to confirm whether IR is a risk factor or a consequence of hepatic steatosis. There is also evidence that NAFLD is the hepatic manifestation of Metabolic Syndrome (MetS). In fact, NAFLD often coexist with central obesity, impaired glucose tolerance, dyslipidemia, and hypertension, which represent the main features of MetS. In this Review, main aspects of the natural history and risk factors of the disease are summarized in children and adolescents. In addition, the most relevant scientific evidence about the association between NAFLD and metabolic dysregulation, focusing on clinical, pathogenetic, and histological implication will be provided with some focuses on the main treatment options.
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Affiliation(s)
| | | | | | | | - Cosimo Giannini
- Department of Pediatrics, University of Chieti, Chieti, Italy
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Steffen BT, Guan W, Ding J, Nomura SO, Weir NL, Tsai MY. Plasma omega-3 and saturated fatty acids are differentially related to pericardial adipose tissue volume across race/ethnicity: the Multi-ethnic Study of Atherosclerosis. Eur J Clin Nutr 2021; 75:1237-1244. [PMID: 33398103 PMCID: PMC8254815 DOI: 10.1038/s41430-020-00833-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 11/02/2020] [Accepted: 12/02/2020] [Indexed: 11/13/2022]
Abstract
BACKGROUND: Pericardial adipose tissue (PAT) is a cardiometabolic risk factor influenced by race/ethnicity, inflammation, and metabolic dysfunction. Omega-3 fatty acids (FAs) and saturated FAs (SFAs) are known to affect these latter phenomena and may influence PAT accumulation. We aimed to determine whether plasma levels of these FAs are related to PAT volume and its rate of change over a median 3-year follow-up. METHODS: Cardiac computed tomography assessed PAT in 6,785 Multi-Ethnic Study of Atherosclerosis participants. Gas chromatography flame-ionization estimated plasma phospholipid fatty acids. Regression analyses estimated associations of FAs with PAT volume and its rate of change with adjustments for other risk factors. Race-interactions were tested. RESULTS: In cross-section, top tertiles of omega-3 FAs and odd-chained SFAs were associated with 2.8 and 4.93 cm3 lower PAT volumes, respectively; race/ethnicity was a significant modifying variable (p<0.002). Even-chained SFAs were associated with 3.5 cm3 greater PAT volume. With stratification by race/ethnicity, Chinese Americans in the top tertile of omega-3 FAs showed 10.5 cm3 greater PAT volume than those in the referent tertile. Black individuals in the top tertile of odd-chained SFAs showed 5.0 cm3 lower PAT compared to referents. Black and Chinese Americans in top tertiles of even-chained SFAs showed respective 3.7 and 5.9 cm3 greater PAT volumes compared to referents. Two associations were observed in prospective analyses among Caucasians; race interactions were non-significant. CONCLUSIONS: Cross-sectional and prospective findings provide inconclusive evidence as to whether plasma FAs are related to PAT in healthy individuals. Cohort studies with longer follow-up periods are warranted.
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Affiliation(s)
- Brian T Steffen
- Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA
| | - Weihua Guan
- Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN, USA
| | - Jingzhong Ding
- Department of Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Sarah O Nomura
- Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA
| | - Natalie L Weir
- Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA
| | - Michael Y Tsai
- Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA.
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Schiano E, Annunziata G, Ciampaglia R, Iannuzzo F, Maisto M, Tenore GC, Novellino E. Bioactive Compounds for the Management of Hypertriglyceridemia: Evidence From Clinical Trials and Putative Action Targets. Front Nutr 2020; 7:586178. [PMID: 33330588 PMCID: PMC7734325 DOI: 10.3389/fnut.2020.586178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 10/26/2020] [Indexed: 01/22/2023] Open
Abstract
Hypertriglyceridemia refers to the presence of elevated concentrations of triglycerides (TG) in the bloodstream (TG >200 mg/dL). This lipid alteration is known to be associated with an increased risk of atherosclerosis, contributing overall to the onset of atherosclerotic cardiovascular disease (CVD). Guidelines for the management of hypertriglyceridemia are based on both lifestyle intervention and pharmacological treatment, but poor adherence, medication-related costs and side effects can limit the success of these interventions. For this reason, the search for natural alternative approaches to reduce plasma TG levels currently represents a hot research field. This review article summarizes the most relevant clinical trials reporting the TG-reducing effect of different food-derived bioactive compounds. Furthermore, based on the evidence obtained from in vitro studies, we provide a description and classification of putative targets of action through which several bioactive compounds can exert a TG-lowering effect. Future research may lead to investigations of the efficacy of novel nutraceutical formulations consisting in a combination of bioactive compounds which contribute to the management of plasma TG levels through different action targets.
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Affiliation(s)
| | | | | | - Fortuna Iannuzzo
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Maria Maisto
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Gian Carlo Tenore
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Ettore Novellino
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
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Hou M, Zhou W, Sun L, Wang B, Shen J, Cao L, Lv H. Effect of Fish Oil on Insulin Sensitivity in Children: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials. Can J Diabetes 2020; 45:531-538.e1. [PMID: 33388274 DOI: 10.1016/j.jcjd.2020.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 09/18/2020] [Accepted: 11/13/2020] [Indexed: 10/22/2022]
Abstract
OBJECTIVES Fish oil has been shown to reduce the risk of metabolic disorders. However, the effects of fish oil intervention on glucose metabolism and insulin sensitivity are still controversial, especially in children. The current meta-analysis aimed to evaluate the effects of fish oil intervention on insulin sensitivity in children. METHODS The Cochrane Library, PubMed, Embase, Web of Science, ClinicalTrials.gov and China National Knowledge Infrastructure databases were searched up to August 2020 for relevant studies evaluating fish oil intake compared with placebo on insulin sensitivity indications (Homeostatic Model for Insulin Resistance). A fixed-effects model was used to calculate the pooled effect. RESULTS A total of 13 studies with 1,132 participants (567 in placebo group and 565 in fish oil group) were included in the meta-analysis. Compared with the placebo group, fish oil intervention had beneficial effects on insulin sensitivity in the pooled analysis (weighted mean difference, -0.219; 95% confidence interval, -0.392 to -0.046; p=0.013). In subgroup analyses, when the fish oil intervention period was short-term (≤6 months), low dose (eicosapentaenoic acid + docosahexaenoic acid dose <1.5 g/day) and high ratio (eicosapentaenoic acid to docosahexaenoic acid ≥1), it could improve insulin sensitivity. No heterogeneity was found for the pooled and subgroup analyses. CONCLUSION Fish oil intervention has a beneficial effect on insulin sensitivity in children.
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Affiliation(s)
- Miao Hou
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Wanping Zhou
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Ling Sun
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Bo Wang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jie Shen
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Lei Cao
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Haitao Lv
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
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Alberti G, Gana JC, Santos JL. Fructose, Omega 3 Fatty Acids, and Vitamin E: Involvement in Pediatric Non-Alcoholic Fatty Liver Disease. Nutrients 2020; 12:nu12113531. [PMID: 33212947 PMCID: PMC7698421 DOI: 10.3390/nu12113531] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/30/2020] [Accepted: 11/09/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most common form of liver disease in both adults and children, becoming the leading cause for liver transplant in many countries. Its prevalence has increased considerably in recent years, mainly due to the explosive increase in pediatric obesity rates. NAFLD is strongly associated with central obesity, diabetes, dyslipidemia and insulin resistance, and it has been considered as the hepatic manifestation of the metabolic syndrome. Its complex pathophysiology involves a series of metabolic, inflammatory and oxidative stress processes, among others. Given the sharp increase in the prevalence of NAFLD and the lack of an appropriate pharmacological approach, it is crucial to consider the prevention/management of the disease based on lifestyle modifications such as the adoption of a healthy nutrition pattern. Herein, we review the literature and discuss the role of three key nutrients involved in pediatric NAFLD: fructose and its participation in metabolism, Omega-3 fatty acids and its anti-inflammatory effects and vitamin E and its action on oxidative stress.
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Affiliation(s)
- Gigliola Alberti
- Gastroenterology and Nutrition Department, Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 3580000, Chile; (G.A.); (J.C.G.)
| | - Juan Cristóbal Gana
- Gastroenterology and Nutrition Department, Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 3580000, Chile; (G.A.); (J.C.G.)
| | - José L. Santos
- Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 3580000, Chile
- Correspondence: ; Tel.: +56-2-2354-3868
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Cansanção K, Citelli M, Carvalho Leite N, López de las Hazas MC, Dávalos A, Tavares do Carmo MDG, Peres WAF. Impact of Long-Term Supplementation with Fish Oil in Individuals with Non-Alcoholic Fatty Liver Disease: A Double Blind Randomized Placebo Controlled Clinical Trial. Nutrients 2020; 12:nu12113372. [PMID: 33147705 PMCID: PMC7693661 DOI: 10.3390/nu12113372] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease affecting up to 25% of the population worldwide. n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) have been associated with improved clinical parameters of NAFLD. Our purpose was to conduct a pilot study to evaluate the effects of n-3 PUFA supplementation in a randomized, double-blind, placebo-controlled clinical study performed on NAFLD individuals diagnosed by ultrasound. Patients received n-3 PUFA (n = 13) or placebo (n = 11) supplementation for six months. Circulating miR-122 expression (determined by quantitative real time-polymerase chain reaction (qRT-PCR), liver fibrosis (FibroScan®), red blood cells (RBC) fatty acids (gas chromatography), and biochemical tests were performed at baseline and after intervention. After the intervention, in the n-3 PUFA group, docosahexaenoic acid (DHA) and omega index increased significantly in RBC (p = 0.022 and p = 0.012, respectively), in addition to a significant reduction in alkaline phosphatase (ALP) (p = 0.002) and liver fibrosis (p = 0.039). However, there was no change in the expression of circulating miR-122 in both groups. Our results showed that omega-3 PUFA were incorporated in erythrocytes after six months of fish oil supplementary intake, and that n-3 PUFA were effective in reducing ALP and liver fibrosis without altering the expression of circulating miR-122 in individuals with NAFLD.
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Affiliation(s)
- Kátia Cansanção
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
| | - Marta Citelli
- Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20559-900, Brazil;
| | - Nathalie Carvalho Leite
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine of UFRJ, Rio de Janeiro 21.941-902, Brazil;
| | - María-Carmen López de las Hazas
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain; (M-C.L.d.l.H.); (A.D.)
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain; (M-C.L.d.l.H.); (A.D.)
| | - Maria das Graças Tavares do Carmo
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
| | - Wilza Arantes Ferreira Peres
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
- Correspondence: ; Tel.: +55-21-393864-32
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Effect of omega-3 fatty acids supplementation on anthropometric indices in children and adolescents: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2020; 53:102487. [PMID: 33066870 DOI: 10.1016/j.ctim.2020.102487] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/02/2020] [Accepted: 06/15/2020] [Indexed: 12/17/2022] Open
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Lee CH, Fu Y, Yang SJ, Chi CC. Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Non-Alcoholic Fatty Liver: A Systematic Review and Meta-Analysis. Nutrients 2020; 12:nu12092769. [PMID: 32932796 PMCID: PMC7551292 DOI: 10.3390/nu12092769] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 09/06/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
(1) Aim: Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease worldwide. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) bear anti-inflammatory action and can ameliorate hyperlipidemia. We wish to appraise the effects of n-3 PUFAs supplement on NAFLD. (2) Methods: We searched CENTRAL, Embase, and MEDLINE on 29 March 2020 for randomized control trials (RCTs) on the effects of n-3 PUFAs supplementation in treating NAFLD. The Cochrane Collaboration's tool was used to assess the risk of bias of included RCTs. (3) Results: We included 22 RCTs with 1366 participants. The risk of bias of included RCTs was generally low or unclear. n-3 PUFAs supplementation significantly reduced liver fat compared with placebo (pooled risk ratio 1.52; 95% confidence interval (CI) 1.09 to 2.13). n-3 PUFAs supplementation also significantly improved the levels of triglyceride, total cholesterol, high-density lipoprotein, and body-mass index, with pooled mean difference and 95% CI being -28.57 (-40.81 to -16.33), -7.82 (-14.86 to -0.79), 3.55 (1.38 to 5.73), and -0.46 (-0.84 to -0.08), respectively. (4) Conclusions: The current evidence supports the effects of n-3 PUFAs supplementation in improving fatty liver. n-3 PUFAs supplementation may also improve blood lipid levels and obesity.
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Affiliation(s)
- Cheng-Han Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Yun Fu
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Shih-Jyun Yang
- Department of Dermatology, Chang Gung Memorial Hospital, Keelung 20401, Taiwan;
| | - Ching-Chi Chi
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
- Correspondence: ; Tel.: +886-3-328-1200 (ext. 3556)
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Rombeek M, De Jesus S, Prapavessis H, Dempsey AA, Fraser D, Welisch E, Altamirano-Diaz L, Norozi K. Improving remote lifestyle intervention studies in children: Participant and caregiver feedback of the smart heart study. PATIENT EDUCATION AND COUNSELING 2020; 103:1326-1334. [PMID: 32089389 DOI: 10.1016/j.pec.2020.02.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 02/11/2020] [Accepted: 02/12/2020] [Indexed: 06/10/2023]
Abstract
OBJECTIVES We sought to describe and analyze the quantitative and qualitative feedback obtained from participants and their caregivers of the Smart Heart study, a successful 12-month lifestyle intervention for children with overweight or obesity and congenital heart disease that provided remote lifestyle counseling, to improve future lifestyle interventions in children. METHODS Thirty-six participants and caregivers were polled using a standard program evaluation questionnaire at the end of the intervention. Feedback was compiled into themes, and facilitators and barriers to program success were identified. RESULTS There was a high level of satisfaction with the intervention and staff interactions as well as a low perceived burden of participation. There were also specific concerns, including mixed impressions regarding technology usage and a less impressive indication of actual impactful behavior change. CONCLUSIONS The study identified five themes, and corresponding facilitators and barriers to participant compliance, from the Smart Heart intervention feedback and offered suggestions for improving future lifestyle behavioral intervention study designs in children. PRACTICE IMPLICATIONS Remote smartphone counseling is effective and efficient. It is recommended that the counseling messages are specific, the counseling schedule is patient-centric, patient burden is limited, methods with immediate patient feedback are used and family is included when feasible.
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Affiliation(s)
- Meghan Rombeek
- Department of Paediatrics, Western University, London, Canada
| | - Stefanie De Jesus
- Department of Paediatrics, Western University, London, Canada; School of Kinesiology, Western University, London, Canada
| | | | - Adam A Dempsey
- Department of Paediatrics, Western University, London, Canada; Paediatric Cardiopulmonary Research Laboratory, London Health Science Centre, London, Canada
| | - Douglas Fraser
- Department of Paediatrics, Western University, London, Canada; Children's Health Research Institute, London, Canada; Translational Research Centre, London, Canada; Lawson Health Research Institute, London, Canada
| | - Eva Welisch
- Department of Paediatrics, Western University, London, Canada; Paediatric Cardiopulmonary Research Laboratory, London Health Science Centre, London, Canada; Children's Health Research Institute, London, Canada
| | - Luis Altamirano-Diaz
- Department of Paediatrics, Western University, London, Canada; Paediatric Cardiopulmonary Research Laboratory, London Health Science Centre, London, Canada; Children's Health Research Institute, London, Canada
| | - Kambiz Norozi
- Department of Paediatrics, Western University, London, Canada; Paediatric Cardiopulmonary Research Laboratory, London Health Science Centre, London, Canada; Children's Health Research Institute, London, Canada; Lawson Health Research Institute, London, Canada; Department of Paediatric Cardiology and Intensive Care Medicine, Medical School Hannover, Germany.
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Goldner D, Lavine JE. Nonalcoholic Fatty Liver Disease in Children: Unique Considerations and Challenges. Gastroenterology 2020; 158:1967-1983.e1. [PMID: 32201176 DOI: 10.1053/j.gastro.2020.01.048] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 12/30/2019] [Accepted: 01/05/2020] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence in concert with the global epidemic of obesity and is being diagnosed at increasingly younger ages. The unique histologic features and early presentation of disease in pediatrics suggest that children and adults may differ with regard to etiopathogenesis, with children displaying a greater vulnerability to genetic and environmental factors. Of significant relevance to pediatrics, in utero and perinatal stressors may alter the lifelong health trajectory of a child, increasing the risk of NAFLD and other cardiometabolic diseases. The development and progression of disease in childhood is likely to carry increased risk of long-term morbidity. Novel biomarkers and therapeutic agents are needed to avoid the otherwise inevitable health and societal consequences of this rapidly expanding pediatric population.
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Affiliation(s)
- Dana Goldner
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Columbia University Medical Center, New York, New York
| | - Joel E Lavine
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Columbia University Medical Center, New York, New York.
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Doulberis M, Polyzos SA, Papaefthymiou A, Katsinelos P, Kiosses C, Kountouras J. Treatment of nonalcoholic fatty liver disease: from adult trials to perspectives in the management of children and adolescents. Expert Opin Pharmacother 2020; 21:247-251. [PMID: 31893958 DOI: 10.1080/14656566.2019.1702967] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Michael Doulberis
- Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.,Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.,First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Apostolis Papaefthymiou
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.,Department of Gastroenterology, General Military Hospital of Athens, Athens, Greece
| | - Panagiotis Katsinelos
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Christos Kiosses
- Department Gastroenterology and Hepatology, General Hospital Thun, Thun, Switzerland
| | - Jannis Kountouras
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
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Abstract
Omega-3 polyunsaturated fatty acids (PUFAs) include α-linolenic acid (ALA; 18:3 ω-3), stearidonic acid (SDA; 18:4 ω-3), eicosapentaenoic acid (EPA; 20:5 ω-3), docosapentaenoic acid (DPA; 22:5 ω-3), and docosahexaenoic acid (DHA; 22:6 ω-3). In the past few decades, many epidemiological studies have been conducted on the myriad health benefits of omega-3 PUFAs. In this review, we summarized the structural features, properties, dietary sources, metabolism, and bioavailability of omega-3 PUFAs and their effects on cardiovascular disease, diabetes, cancer, Alzheimer's disease, dementia, depression, visual and neurological development, and maternal and child health. Even though many health benefits of omega-3 PUFAs have been reported in the literature, there are also some controversies about their efficacy and certain benefits to human health.
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Affiliation(s)
- Fereidoon Shahidi
- Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada;
| | - Priyatharini Ambigaipalan
- Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada;
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Musa-Veloso K, Venditti C, Lee HY, Darch M, Floyd S, West S, Simon R. Systematic review and meta-analysis of controlled intervention studies on the effectiveness of long-chain omega-3 fatty acids in patients with nonalcoholic fatty liver disease. Nutr Rev 2019; 76:581-602. [PMID: 29917092 PMCID: PMC6367993 DOI: 10.1093/nutrit/nuy022] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Context Treatment options for nonalcoholic fatty liver disease (NAFLD) are needed. Objective The aim of this review was to systematically assess the effects of omega-3 long-chain
polyunsaturated fatty acids (n-3 LC-PUFAs), particularly eicosapentaenoic acid and
docosahexaenoic acid, on liver-related and metabolic outcomes in adult and pediatric
patients with NAFLD. Data Sources The online information service ProQuest Dialog was used to search 8 literature
databases. Study Selection Controlled intervention studies in which the independent effects of n-3 LC-PUFAs could
be isolated were eligible for inclusion. Data Extraction The 18 unique studies that met the criteria for inclusion were divided into 2 sets, and
data transcriptions and study quality assessments were conducted in duplicate. Each
effect size was expressed as the weighted mean difference and 95%CI, using a
random-effects model and the inverse of the variance as a weighting factor. Results Based on the meta-analyses, supplementation with n-3 LC-PUFAs resulted in statistically
significant improvements in 6 of 13 metabolic risk factors, in levels of 2 of 3 liver
enzymes, in liver fat content (assessed via magnetic resonance imaging/spectroscopy),
and in steatosis score (assessed via ultrasonography). Histological measures of disease
[which were assessed only in patients with nonalcoholic steatohepatitis (NASH)] were
unaffected by n-3 LC-PUFA supplementation. Conclusions Omega-3 LC-PUFAs are useful in the dietary management of patients with NAFLD.
Additional trials are needed to better understand the effects of n-3 LC-PUFAs on
histological outcomes in patients with NASH. Systematic Review Registration PROSPERO CRD42017055951.
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Affiliation(s)
- Kathy Musa-Veloso
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Carolina Venditti
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Han Youl Lee
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Maryse Darch
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Seth Floyd
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Spencer West
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Ryan Simon
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
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NAFLD in children: new genes, new diagnostic modalities and new drugs. Nat Rev Gastroenterol Hepatol 2019; 16:517-530. [PMID: 31278377 DOI: 10.1038/s41575-019-0169-z] [Citation(s) in RCA: 195] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/04/2019] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has rapidly become the most common form of chronic liver disease in children and adolescents. Over the past 5 years, developments have revolutionized our understanding of the genetic factors, natural history, diagnostic modalities and therapeutic targets for this disease. New polymorphisms, such as those in PNPLA3, TM6SF2, MBOAT7 and GCKR, have been identified and used to predict the development and severity of NAFLD in both adults and children, and their interaction with environmental factors has been elucidated. Studies have demonstrated the true burden of paediatric NAFLD and its progression to end-stage liver disease in adulthood. In particular, nonalcoholic steatohepatitis can progress to advanced fibrosis and cirrhosis, emphasizing the importance of early diagnosis. Non-invasive imaging tests, such as transient elastography, will probably replace liver biopsy for the diagnosis of nonalcoholic steatohepatitis and the assessment of fibrosis severity in the near future. The therapeutic landscape is also expanding rapidly with the development of drugs that can modify liver steatosis, inflammation and fibrosis, indicating that pharmacotherapy for NAFLD will become available in the future. In this Review, we summarize current knowledge and new advances related to the pathogenesis and management of paediatric NAFLD.
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Di Sessa A, Cirillo G, Guarino S, Marzuillo P, Miraglia Del Giudice E. Pediatric non-alcoholic fatty liver disease: current perspectives on diagnosis and management. PEDIATRIC HEALTH MEDICINE AND THERAPEUTICS 2019; 10:89-97. [PMID: 31692530 PMCID: PMC6711552 DOI: 10.2147/phmt.s188989] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 08/13/2019] [Indexed: 12/14/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease in childhood. To date, the “multiple-hit” hypothesis is largely recognized as an explanation of NAFLD pathogenesis and progression. Obesity and features of the metabolic syndrome have been closely linked to NAFLD development. Due to the increased prevalence of obesity worldwide, NAFLD has reached epidemic proportions over time. Given its unfavorable cardiometabolic burden (such as cardiovascular and metabolic consequences), it represents a worrying phenomenon needing a more comprehensive and successful management. Laboratory tests and classical imaging techniques play a pivotal role in NAFLD diagnosis, but novel noninvasive alternative methods to diagnose and monitor NAFLD have been investigated. Currently, lifestyle modifications remain the mainstay treatment, although its efficacy is poor because of the lack of compliance. Pediatric research is focusing on multiple alternative treatments targeting the main pathogenic factors such as insulin-resistance, dyslipidemia, gut-liver axis and microbiota, oxidative stress, and proinflammatory pathways. Results from these studies are promising but larger validation is needed. Innovative therapeutic approaches might add an important piece in the complex knowledge of pediatric NAFLD. We aimed to summarize recent insights into NAFLD diagnosis and treatment in children, with a focus on possible future perspectives in pediatric research.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania "Luigi Vanvitelli", Napoli 80138, Italy
| | - Grazia Cirillo
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania "Luigi Vanvitelli", Napoli 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania "Luigi Vanvitelli", Napoli 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania "Luigi Vanvitelli", Napoli 80138, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania "Luigi Vanvitelli", Napoli 80138, Italy
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48
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Mann JP, Tang GY, Nobili V, Armstrong MJ. Evaluations of Lifestyle, Dietary, and Pharmacologic Treatments for Pediatric Nonalcoholic Fatty Liver Disease: A Systematic Review. Clin Gastroenterol Hepatol 2019; 17:1457-1476.e7. [PMID: 29857146 DOI: 10.1016/j.cgh.2018.05.023] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 05/06/2018] [Accepted: 05/20/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There are no approved treatments for pediatric nonalcoholic fatty liver disease (NAFLD) and there is a lack of consensus on the best outcome measure for randomized controlled trials. We performed a systematic review of treatments tested for pediatric NAFLD, the degree of heterogeneity in trial design, and endpoints analyzed in these studies. METHODS We searched publication databases and clinical trial registries through January 7, 2018 for randomized controlled trials (published and underway) of children (<18 years) with NAFLD. We assessed improvements in histologic features, radiologic and biochemical markers of reduced fibrosis, metabolic syndrome parameters, and adverse events. The quality of the trials was assessed using a modified version of the Cochrane risk of bias tool. RESULTS Our final analysis included 21 randomized controlled trials, comprising 1307 participants (mean age, 12.6 years; 63% male; mean duration of intervention, 8 months). Most studies evaluated weight loss with lifestyle intervention (n=8), oral polyunsaturated fatty acid treatment (PUFAs, n=6), or oral antioxidant treatment (n=7). Biomarkers of NAFLD decreased with weight loss, but most studies did not include histologic data. Trials of antioxidants were heterogeneous; some reported reduced histologic features of steatohepatitis with no effect on triglycerides or insulin resistance. PUFAs and probiotics reduced radiologic markers of steatosis, insulin resistance, and levels of triglycerides. Only 38% of the trials had biopsy-proven NAFLD as an inclusion criterion. There was heterogeneity in trial primary endpoints; 10 studies (48%) used levels of aminotransferases or ultrasonography findings as a primary endpoint and only 3 trials (14%) used histologic features as the primary endpoint. We identified 13 randomized controlled trials that are underway in children with NAFLD. None of the protocols include collection of liver biopsies; 9 trials (69%) will use magnetic resonance imaging quantification of steatosis as a primary outcome. CONCLUSIONS In a systematic review of published and active randomized controlled trials of children with NAFLD, we found a large amount of heterogeneity in study endpoints and inclusion criteria. Few trials included histologic analyses. Antioxidants appear to reduce some features of steatohepatitis. Effects of treatment with lifestyle modification, PUFAs, or probiotics have not been validated with histologic analysis. Trials that are underway quantify steatosis magnetic resonance imaging-outcomes are anticipated.
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Affiliation(s)
- Jake Peter Mann
- Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom.
| | - George Yizhou Tang
- Clinical School of Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Valerio Nobili
- Department of Pediatrics, University "La Sapienza," Rome, Italy; Hepatology, Gastroenterology, and Nutrition, Bambino Gesù Hospital, Rome, Italy
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Yang J, Fernández-Galilea M, Martínez-Fernández L, González-Muniesa P, Pérez-Chávez A, Martínez JA, Moreno-Aliaga MJ. Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation. Nutrients 2019; 11:E872. [PMID: 31003450 PMCID: PMC6521137 DOI: 10.3390/nu11040872] [Citation(s) in RCA: 163] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 04/12/2019] [Accepted: 04/15/2019] [Indexed: 02/06/2023] Open
Abstract
Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.
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Affiliation(s)
- Jinchunzi Yang
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - Marta Fernández-Galilea
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
| | - Leyre Martínez-Fernández
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - Pedro González-Muniesa
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
| | - Adriana Pérez-Chávez
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - J Alfredo Martínez
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
| | - Maria J Moreno-Aliaga
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
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50
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Rates of and Factors Associated With Placebo Response in Trials of Pharmacotherapies for Nonalcoholic Steatohepatitis: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2019; 17:616-629.e26. [PMID: 29913275 DOI: 10.1016/j.cgh.2018.06.011] [Citation(s) in RCA: 97] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Revised: 06/06/2018] [Accepted: 06/09/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS It is important to know the extent of the placebo effect in designing randomized controlled trials for patients with nonalcoholic steatohepatitis (NASH), to accurately calculate sample size and define treatment endpoints. METHODS We performed a systematic review and meta-analysis of the placebo groups from randomized controlled trials of adults with NASH that provided histologic and/or magnetic resonance image-based assessments. We identified trials through a comprehensive search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus, from each database's inception through January 2, 2018. RESULTS We identified 39 randomized controlled trials, comprising 1463 patients who received placebo. Histologic assessment data (the nonalcoholic fatty liver disease activity scores, NAS) were available from 956 patients; magnetic resonance spectroscopy data were available from 295 patients and magnetic resonance proton density fat fraction measurements from 61 patients. Overall, 25% of patients given placebo had an improvement in NAS by 2 or more points (95% CI, 21%-29%) with a small amount of heterogeneity (I2 = 27%). There were improvements by at least 1 point in steatosis scores of 33% ± 3% of patients, in hepatocyte ballooning scores of 30% ± 3% of patients, in lobular inflammation scores of 32% ± 3% of patients, and in fibrosis scores of 21% ± 3% of patients, with a moderate amount of heterogeneity among trials (I2 range, 51%-63%). Patients given placebo had a statistically significant improvement in NAS (by 0.72 ± 0.19), with a large amount of heterogeneity (I2 = 96%). Univariate and multivariate meta-regression showed that trials with a higher baseline NAS, those conducted in South America, and those in which patients had a decrease in body mass index, were associated with greater improvements in NAS among patients given placebo. Patients given placebo had significant reductions in intrahepatic triglyceride, measured by magnetic resonance spectroscopy (by 1.45% ± 0.54%) with moderate heterogeneity (I2 = 40%), and in magnetic resonance proton density fat fraction (by 2.43 ± 0.89), without heterogeneity (I2 = 0). Mean serum levels of alanine and aspartate aminotransferases decreased significantly (by 11.7 ± 3.8 U/L and 5.9 ± 2.1 U/L, respectively; P < .01 for both). CONCLUSIONS In a meta-analysis of randomized controlled trials of NASH, patients given placebo have significant histologic, radiologic, and biochemical responses. The placebo response should be considered in designing trials of agents for treatment of NASH.
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