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The Role of Diet in Fatty Liver Disease

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (20 September 2020) | Viewed by 70218

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Dr. Francesco Angelico

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Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro, 00185 Rome, Italy
Interests: atherosclerosis; risk factors; metabolic diseases; fatty liver disease; dyslipidaemia
Special Issues, Collections and Topics in MDPI journals

Dr. Domenico Ferro

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Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Interests: lipoproteins; atherosclerosis; platelet activity; liver disease; non-alcoholic fatty liver diseases (NAFLD)

Dr. Francesco Baratta

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Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy
Interests: liver diseases; dyslipidemia; risk factors; atherosclerosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alcoholic (AFLD) and non-alcoholic fatty liver disease (NAFLD) represent the most common liver diseases worldwide. Most consumers of more than two drinks per day suffer from hepatomegaly due to steatosis—a benign state that may further progress to steatohepatitis and cirrhosis. The spread of NAFLD is strongly associated with the increasing prevalence of obesity and type 2 diabetes due to changing lifestyles and dietary habits. However, most people with fatty liver in the absence of significant hepatic fibrosis do not develop serious liver problems. Conversely, they have an increased chance of developing cardiovascular diseases, which represent the major causes of death in this setting. Dietary cancelling may play a major role in the management of fatty liver disease. The aim of this Special Issue, “The Role of Diet in Fatty Liver Disease”, is to provide an update on the different nutritional approaches to AFLD/NAFLD and its related pathophysiological mechanisms and metabolic comorbidities. Contributions may include original articles, systematic reviews, and meta-analyses on the role of diet on the prevention and treatment of fatty liver disease.

Dr. Francesco Angelico
Dr. Domenico Ferro
Dr. Francesco Baratta
Guest Editors

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Keywords

non-alcoholic fatty liver
alcoholic fatty liver
non-alcoholic steatohepatitis
Mediterranean Diet
lipopolysaccharides

Published Papers (12 papers)

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Editorial

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6 pages, 221 KiB

Open AccessEditorial

Is the Mediterranean Diet the Best Approach to NAFLD Treatment Today?

by Francesco Angelico, Domenico Ferro and Francesco Baratta

Nutrients 2021, 13(3), 739; https://doi.org/10.3390/nu13030739 - 26 Feb 2021

Cited by 7 | Viewed by 2785

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent diseases worldwide, involving about 20–30% of the general population [...] Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

Research

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16 pages, 3018 KiB

Open AccessArticle

Bilberry Anthocyanins Ameliorate NAFLD by Improving Dyslipidemia and Gut Microbiome Dysbiosis

by Hironobu Nakano, Shusong Wu, Kozue Sakao, Taichi Hara, Jianhua He, Santos Garcia, Kalidas Shetty and De-Xing Hou

Nutrients 2020, 12(11), 3252; https://doi.org/10.3390/nu12113252 - 23 Oct 2020

Cited by 40 | Viewed by 5110

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome closely linked to dyslipidemia and gut microbiome dysbiosis. Bilberry anthocyanins (BA) have been reported to have preventive effects against metabolic syndrome. This study aimed to investigate the protective effects and mechanisms of BA in a Western diet (WD)-induced mouse model. The results revealed that supplementation with BA attenuated the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-c), fat content in liver, 2-thiobarbituric acid reactive substances (TBARS) and α-smooth muscle actin (α-SMA) caused by WD. Furthermore, gut microbiota characterized by 16S rRNA sequencing revealed that BA reduced remarkably the ratio of Firmicutes/Bacteroidetes (F/B) and modified gut microbiome. In particular, BA increased the relative abundance of g_Akkermansia and g_Parabacteroides. Taken together, our data demonstrated that BA might ameliorate WD-induced NAFLD by attenuating dyslipidemia and gut microbiome dysbiosis. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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14 pages, 1518 KiB

Open AccessArticle

Very Low-Carbohydrate Ketogenic Diet for the Treatment of Severe Obesity and Associated Non-Alcoholic Fatty Liver Disease: The Role of Sex Differences

by Marco D’Abbondanza, Stefano Ministrini, Giacomo Pucci, Elisa Nulli Migliola, Eva-Edvige Martorelli, Vito Gandolfo, Donatella Siepi, Graziana Lupattelli and Gaetano Vaudo

Nutrients 2020, 12(9), 2748; https://doi.org/10.3390/nu12092748 - 9 Sep 2020

Cited by 38 | Viewed by 8828

Abstract

Very low-carbohydrate ketogenic diets (VLCKDs) are an emerging nutritional treatment for severe obesity and are associated with a significant improvement in non-alcoholic fatty liver disease (NAFLD). Little is known about the effect of sex differences on weight loss induced by following a VLCKD. The aim of this study was to investigate the effects of sex differences on weight loss and NAFLD improvement in patients with severe obesity undergoing a VLCKD. Forty-two females and 28 males with severe obesity underwent a 25-day VLCKD. Anthropometric parameters, bioimpedentiometry, degree of liver steatosis measured by ultrasonography, liver function tests, and glucose homeostasis were measured before and after the VLCKD. Males experienced a significantly larger excess body weight loss (EBWL) and a greater reduction in γ-glutamyl transferase (γGT) than females. Dividing the female group by menopausal status, a significant difference between males and pre-menopausal females was found for both EBWL and γGT. No significant difference between groups was observed for improvement in the Edmonton stage or in the degree of steatosis. We conclude that the efficacy of following a VLCKD in severe obesity is affected by sex differences and, for females, by menopausal status. Males seem to experience larger benefits than females in terms of EBWL and NAFLD improvement. These differences are attenuated after menopause, probably because of changes in hormonal profile and body composition. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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11 pages, 915 KiB

Open AccessArticle

Poor Adherence to Mediterranean Diet and Serum Lipopolysaccharide Are Associated with Oxidative Stress in Patients with Non-Alcoholic Fatty Liver Disease

by Francesco Baratta, Daniele Pastori, Simona Bartimoccia, Vittoria Cammisotto, Nicholas Cocomello, Alessandra Colantoni, Cristina Nocella, Roberto Carnevale, Domenico Ferro, Francesco Angelico, Francesco Violi and Maria Del Ben

Nutrients 2020, 12(6), 1732; https://doi.org/10.3390/nu12061732 - 10 Jun 2020

Cited by 32 | Viewed by 3125

Abstract

Oxidative stress plays a pivotal role in non-alcoholic fatty liver disease (NAFLD). Factors inducing oxidative stress in NAFLD may be several; however, a relationship with the adherence to Mediterranean Diet (Med-diet) and with serum lipopolysaccharide (LPS) has been poorly investigated in this setting. The aim was to investigate factors associated with impaired oxidative stress in NAFLD, focusing on the potential role of LPS and Med-diet. We enrolled 238 consecutive outpatients from the PLINIO study, in whom we measured the soluble Nox2-derived peptide (sNox2-dp), a marker of systemic oxidative stress, and serum LPS. Adherence to Med-diet was investigated by a nine-item validated dietary questionnaire. Serum sNox2-dp and LPS were higher in patients with NAFLD compared to those without (25.0 vs. 9.0 pg/mL, p < 0.001 and 62.0 vs. 44.9 pg/mL, p < 0.001, respectively). In patients with NAFLD, the highest sNox2-dp tertile was associated with the top serum LPS tertile (Odds Ratio (OR): 4.71; p < 0.001), APRI > 0.7 (OR: 6.96; p = 0.005) and Med-diet-score > 6 (OR: 0.14; p = 0.026). Analyzing individual foods, the daily consumption of wine (OR: 0.29, p = 0.046) and the adequate weekly consumption of fish (OR: 0.32, p = 0.030) inversely correlated with the top sNox2-dp tertile. In conclusion, patients with NAFLD showed impaired oxidative stress. Levels of sNox2 correlated with serum LPS and with low adherence to Med-Diet. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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13 pages, 513 KiB

Open AccessArticle

Association between Non-Alcoholic Fatty Liver Disease and Dietary Habits, Stress, and Health-Related Quality of Life in Korean Adults

by A Lum Han

Nutrients 2020, 12(6), 1555; https://doi.org/10.3390/nu12061555 - 27 May 2020

Cited by 15 | Viewed by 3448

Abstract

Considering the increasing prevalence of non-alcoholic fatty liver disease (NAFLD), this study aimed to evaluate the association between NAFLD and dietary habits, stress, and health-related quality of life (HRQoL) in Korean individuals by using data from the Korea National Health and Nutrition Examination Survey (KNHANES) VI 2013–2015. NAFLD was defined in individuals with a hepatic steatosis index (HSI) value ≥36. Eating habits were assessed based on the frequencies of eating and eating out; stress was assessed through the stress perception rate; and the EuroQol-5D (EQ-5D) questionnaire was used to assess the HRQoL. We performed a complex sample logistic regression analysis and estimated the odds ratios by adjusting for significant factors to evaluate associations between NAFLD and dietary habits, stress, and HRQoL. Occurrence of NAFLD was not significantly associated with meal frequencies over one week. With an increase in stress, based on the stress perception rate, the risk of NAFLD increased 1.316-fold (95% confidence interval (CI): 1.175–1.469, p < 0.05). Additionally, a decrease in the EQ-5D score by 1 increased the risk of NAFLD 3.38-fold (95% CI: 1.893–4.844, p < 0.05). Thus, NAFLD treatment should include stress management, and underlying HRQoL should be considered during treatment. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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13 pages, 1282 KiB

Open AccessArticle

The Protective Effect of Cynara Cardunculus Extract in Diet-Induced NAFLD: Involvement of OCTN1 and OCTN2 Transporter Subfamily

by Francesca Oppedisano, Carolina Muscoli, Vincenzo Musolino, Cristina Carresi, Roberta Macrì, Caterina Giancotta, Francesca Bosco, Jessica Maiuolo, Federica Scarano, Sara Paone, Saverio Nucera, Maria Caterina Zito, Miriam Scicchitano, Stefano Ruga, Monica Ragusa, Ernesto Palma, Annamaria Tavernese, Rocco Mollace, Ezio Bombardelli and Vincenzo Mollace

Nutrients 2020, 12(5), 1435; https://doi.org/10.3390/nu12051435 - 15 May 2020

Cited by 24 | Viewed by 3731

Abstract

Hyperlipidemia and insulin-resistance are often associated with Non-Alcoholic Fatty Liver Disease (NAFLD) thereby representing a true issue worldwide due to increased risk of developing cardiovascular and systemic disorders. Although clear evidence suggests that circulating fatty acids contribute to pathophysiological mechanisms underlying NAFLD and hyperlipidemia, further studies are required to better identify potential beneficial approaches for counteracting such a disease. Recently, several artichoke extracts have been used for both reducing hyperlipidemia, insulin-resistance and NAFLD, though the mechanism is unclear. Here we used a wild type of Cynara Cardunculus extract (CyC), rich in sesquiterpens and antioxidant active ingredients, in rats fed a High Fat Diet (HFD) compared to a Normal Fat Diet (NFD). In particular, in rats fed HFD for four consecutive weeks, we found a significant increase of serum cholesterol, triglyceride and serum glucose. This effect was accompanied by increased body weight and by histopathological features of liver steatosis. The alterations of metabolic parameters found in HFDs were antagonised dose-dependently by daily oral supplementation of rats with CyC 10 and 20 mg/kg over four weeks, an effect associated to significant improvement of liver steatosis. The effect of CyC (20 mg/kg) was also associated to enhanced expression of both OCTN1 and OCTN2 carnitine-linked transporters. Thus, present data suggest a contribution of carnitine system in the protective effect of CyC in diet-induced hyperlipidemia, insulin-resistance and NAFLD. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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Review

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15 pages, 343 KiB

Open AccessReview

A Comprehensive Review Evaluating the Impact of Protein Source (Vegetarian vs. Meat Based) in Hepatic Encephalopathy

by Umair Iqbal, Ravirajsinh N. Jadeja, Harshit S. Khara and Sandeep Khurana

Nutrients 2021, 13(2), 370; https://doi.org/10.3390/nu13020370 - 26 Jan 2021

Cited by 9 | Viewed by 5842

Abstract

Hepatic encephalopathy (HE) is a common neurological consequence in patients with cirrhosis and has a healthcare burden of USD 5370 to 50,120 per patient annually. HE significantly hampers the quality of life and is a major cause of morbidity and mortality. Patients with cirrhosis are at a high risk for protein-calorie malnutrition due to altered metabolism. Current evidence has changed the old belief of protein restriction in patients with cirrhosis and now 1.2 to 1.5 g/kg/day protein intake is recommended. Case series and studies with small numbers of participants showed that a vegetarian protein diet decreases the symptoms of HE when compared to a meat-based diet, but the evidence is limited and requires further larger randomized controlled trials. However, vegetable or milk-based protein diets are good substitutes for patients averse to meat intake. Branch chain amino acids (BCAA) (leucine, isoleucine and valine) have also been shown to be effective in alleviating symptoms of HE and are recommended as an alternative therapy in patients with cirrhosis for the treatment of HE. In this review, we provide an overview of current literature evaluating the role of protein intake in the management of HE in cirrhosis. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

13 pages, 944 KiB

Open AccessReview

Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation

by Arianna Pani, Riccardo Giossi, Danilo Menichelli, Veronica Andrea Fittipaldo, Francesca Agnelli, Elvira Inglese, Alessandra Romandini, Rossana Roncato, Basilio Pintaudi, Francesco Del Sole and Francesco Scaglione

Nutrients 2020, 12(11), 3379; https://doi.org/10.3390/nu12113379 - 3 Nov 2020

Cited by 31 | Viewed by 6369

Abstract

Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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15 pages, 4161 KiB

Open AccessReview

Nuts and Non-Alcoholic Fatty Liver Disease: Are Nuts Safe for Patients with Fatty Liver Disease?

by Maria Corina Plaz Torres, Giorgia Bodini, Manuele Furnari, Elisa Marabotto, Patrizia Zentilin and Edoardo G. Giannini

Nutrients 2020, 12(11), 3363; https://doi.org/10.3390/nu12113363 - 1 Nov 2020

Cited by 16 | Viewed by 4730

Abstract

Diet and lifestyle interventions are the recommended treatment for patients with non-alcoholic fatty liver disease (NAFLD), with the aim of achieving a 7–10% weight loss. Several dietary patterns have been suggested for this purpose, however, to date, the best one is represented by the Mediterranean diet (MD) as it is rich in macro- and micro- nutrients known for their effectiveness in health-promotion and cardio-vascular disease prevention. Moreover, MD is characterized by the inclusion of nuts. These foods have shown potential benefits in health-promotion as they are rich in fibers, which have lipid-lowering effects, rich in mono- and poly-unsaturated fatty acids, which help reduce insulin-resistance and serum cholesterol, and contain anti-oxidants which reduce oxidative stress and inflammation. Additionally, nuts are associated with a better control, or reduction, of Body Mass Index (BMI). All these effects are useful targets to achieve in NAFLD, so that nuts have been proposed as a suitable dietary treatment supplement for weight and metabolic control in these patients. In recent years, health authorities raised an alert on nuts consumption as these may be at high risk of aflatoxin (AF) contamination, for which controls and legislations are different among countries. AF is a well-known cancerogenic agent and a recognized risk factor for hepatocellular carcinoma. Patients with NAFLD have an overall, inherent sevenfold increased risk of developing hepatocellular carcinoma as compared with the general population. In this context, one could argue that recommending the inclusion of nuts in the diet of NAFLD patients has to be balanced with the risk of potential chronic exposure to AF, and every effort should be pursued to assure the safety of these nutrients. In this review, we aim to summarize the benefits of nuts consumption, the evidence for AF contamination of nuts and the consequent potential risks in patients with NAFLD. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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14 pages, 755 KiB

Open AccessReview

Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update

by Ilaria Barchetta, Flavia Agata Cimini and Maria Gisella Cavallo

Nutrients 2020, 12(11), 3302; https://doi.org/10.3390/nu12113302 - 28 Oct 2020

Cited by 93 | Viewed by 10558

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease worldwide; it ranges from simple steatosis to steatohepatitis (NASH) and, potentially, cirrhosis and hepatocarcinoma. NAFLD is also an independent risk factor for type 2 diabetes, cardiovascular diseases, and mortality. As it is largely associated with insulin resistance and related disorders, NAFLD has been recently re-named as Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD). At present, there are no approved pharmacological treatments for this condition. Vitamin D is a molecule with extensive anti-fibrotic, anti-inflammatory, and insulin-sensitizing properties, which have been proven also in hepatic cells and is involved in immune-metabolic pathways within the gut–adipose tissue–liver axis. Epidemiological data support a relationship hypovitaminosis D and the presence of NAFLD and steatohepatitis (NASH); however, results from vitamin D supplementation trials on liver outcomes are controversial. This narrative review provides an overview of the latest evidence on pathophysiological pathways connecting vitamin D to NAFLD, with emphasis on the effects of vitamin D treatment in MAFLD by a nonsystematic literature review of PubMed published clinical trials. This article conforms to the Scale for Assessment of Narrative Review Articles (SANRA) guidelines. Evidence so far available supports the hypothesis of potential benefits of vitamin D supplementation in selected populations of NAFLD patients, as those with shorter disease duration and mild to moderate liver damage. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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9 pages, 287 KiB

Open AccessReview

Microbiota, Fiber, and NAFLD: Is There Any Connection?

by Alejandra Pérez-Montes de Oca, María Teresa Julián, Analía Ramos, Manel Puig-Domingo and Nuria Alonso

Nutrients 2020, 12(10), 3100; https://doi.org/10.3390/nu12103100 - 12 Oct 2020

Cited by 33 | Viewed by 5438

Abstract

Gut microbiota can contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD). In fact, some specific changes of gut microbiota are observed in patients in what is called dysbiota. There has been a lot of investigation by using a variety of interventions, including diet, showing the possibility to modify components of gastrointestinal dysbiota towards healthy and multivariate microbiota to restore physiologic status. One of the main focuses has been dietary fiber (DF), in which most of its variants are prebiotics. The highest effective treatment for NAFLD is, so far, weight loss achieved by caloric restriction. DF supplementation with oligofructose facilitates weight loss, enhances the production of beneficial metabolites, decreases some pathogenic bacteria population by increasing Bifidobacteria, and has effects on intestinal barrier permeability. DF use has been associated with improvement in diverse metabolic diseases, including NAFLD, by modifying gut microbiota. Additionally, it has been shown that a higher insoluble fiber consumption (≥7.5 g/day) revealed improvements in 3 different scores of liver fibrosis. Further research is needed, but given the evidence available, it is reasonable to prescribe its consumption in early stages of NAFLD in order to prevent disease progression. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

14 pages, 855 KiB

Open AccessReview

New Insights into the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Gut-Derived Lipopolysaccharides and Oxidative Stress

by Domenico Ferro, Francesco Baratta, Daniele Pastori, Nicholas Cocomello, Alessandra Colantoni, Francesco Angelico and Maria Del Ben

Nutrients 2020, 12(9), 2762; https://doi.org/10.3390/nu12092762 - 10 Sep 2020

Cited by 94 | Viewed by 9148

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The intricate NAFLD pathogenesis is summarized by the multiple-hits hypothesis, which combines all the environmental and genetic factors that promote the development of NAFLD into a single scenario. Among these, bacterial lipopolysaccharides (LPS) are derived from the overgrowth of Gram-negative bacteria and translocated mainly as a consequence of enhanced intestinal permeability. Furthermore, oxidative stress is increased in NAFLD as a consequence of reactive oxygen species (ROS) overproduction and a shortage of endogenous antioxidant molecules, and it is promoted by the interaction between LPS and the Toll-like receptor 4 system. Interestingly, oxidative stress, which has previously been described as being overexpressed in cardiovascular disease, could represent the link between LPS and the increased cardiovascular risk in NAFLD subjects. To date, the only effective strategy for the treatment of NAFLD and non-alcoholic steatohepatitis (NASH) is the loss of at least 5% body weight in overweight and/or obese subjects. However, the dose-dependent effects of multispecies probiotic supplementation on the serum LPS level and cardiometabolic profile in obese postmenopausal women were demonstrated. In addition, many antibiotics have regulatory effects on intestinal microbiota and were able to reduce serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor alpha (TNF-α) in NASH animal models. Regarding the oxidant status, a Mediterranean diet has been reported to reduce oxidant stress, while vitamin E at high daily dosages induced the resolution of NASH in 36% of treated patients. Silymarin had the positive effect of reducing transaminase levels in NAFLD patients and long-term treatment may also decrease fibrosis and slow liver disease progression in NASH. Finally, the influence of nutraceuticals on gut microbiota and oxidant stress in NAFLD patients has not yet been well elucidated and there are insufficient data either to support or refuse their use in these subjects. Full article

(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)

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