Overview of Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Sugary Food Consumption and Other Dietary Components in Its Development

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

Metabolic-Associated Fatty Liver Disease (MAFLD), Diabetes,and Cardiovascular Disease: Associations with Fructose Metabolism and Gut Microbiota

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition associated with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies NAFLD, the current nomenclature has been revised, and the term metabolic-associated fatty liver disease (MAFLD) has been proposed. The new definition emphasizes the bidirectional relationships and increases awareness in looking for fatty liver disease among patients with T2DM and CVD or its risk factors, as well as looking for these diseases among patients with NAFLD. The most recommended treatment method of NAFLD is lifestyle changes, including dietary fructose limitation, although other treatment methods of NAFLD have recently emerged and are being studied. Given the focus on the liver–gut axis targeting, bacteria may also be a future aim of NAFLD treatment given the microbiome signatures discriminating healthy individuals from those with NAFLD. In this review article, we will provide an overview of the associations of fructose consumption, gut microbiota, diabetes, and CVD in patients with NAFLD.     

Nonalcoholic Fatty liver disease and obesity.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized medical condition that may progress to hepatic cirrhosis with liver failure. The pathologic picture resembles that of alcohol-induced liver injury, but it occurs in patients who do not abuse alcohol. NAFLD is more common among patients with evidence of insulin resistance. NAFLD refers to a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. The clinical implications of NAFLD are derived mostly from its common occurrence in the general population, specifically in obese individuals, and its potential to progress to cirrhosis and liver failure. It is difficult to propose a treatment strategy for NAFLD because its pathogenesis is poorly understood; however, the most commonly associated clinical features of obesity, diabetes mellitus, lipid disorders, and hypertension deserve therapeutic interventions independent of NAFLD. It is also not known if and how treatment of these other conditions affects the natural history of NAFLD, particularly in the long term.     

Effects of trace components of dietary fat on cholesterol metabolism: phytosterols,oxysterols, and squalene

The effect of dietary fats on serum cholesterol is widely assumed to be due solely to the fatty acids and cholesterol they contain. Phytosterols, sterol oxidation products, and sterol precursors such as squalene, however, are often present in dietary fats. Little is known of the physiology of these substances in natural foods and most published diet studies do not consider them at all. Supplementation of the diet with high-dose phytosterols is now recommended for prevention of heart disease, but both recent and old data strongly suggest that the lower levels of phytosterols naturally present in vegetable fats may also reduce cholesterol absorption and serum cholesterol substantially. Moreover, unmeasured phytosterols may confound otherwise well-controlled diet studies because there is an inverse correlation between phytosterol and saturated fatty acid content of vegetable fats. Sterol oxidation products, many of which are found in foods, are potent regulators of lipoprotein and cholesterol transport pathways in vitro. Squalene is a phytosterol precursor abundant in olive oil that is at least partly absorbed and then quantitatively converted to cholesterol. The effects of dietary triglyceride-derived fatty acids have not been experimentally separated from the effects of trace fat components in most clinical studies. A better understanding of the activity of sterol-related dietary components is needed to reduce variability in diet studies, accurately assess the effects of dietary fatty acids and to maximize the effectiveness of dietary treatment for hypercholesterolemia.     

Nutritional Management of Insulin Resistance in Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) is an emerging global health concern. It is the most common form of chronic liver disease in Western countries, affecting both adults and children. NAFLD encompasses a broad spectrum of fatty liver disease, ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH), and is strongly associated with obesity, insulin resistance, and dyslipidemia. First-line therapy for NAFLD includes weight loss achieved through diet and physical activity. However, there is a lack of evidenced-based dietary recommendations. The American Diabetes Association’s (ADA) recommendations that aim to reduce the risk of diabetes and cardiovascular disease may also be applicable to the NAFLD population. The objectives of this review are to: (1) provide an overview of NAFLD in the context of insulin resistance, and (2) provide a rationale for applying relevant aspects of the ADA recommendations to the nutritional management of NAFLD.     

The role of diet and nutrient composition in nonalcoholic Fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world. NAFLD is tightly linked to insulin resistance and considered to be the hepatic manifestation of the metabolic syndrome. The cornerstone of any treatment regimen for patients with NAFLD is lifestyle modification focused on weight loss, exercise, and improving insulin sensitivity. Here we review the literature and discuss the role of diet and nutrient composition in the management of NAFLD. Because there are currently no specific dietary guidelines for NAFLD, this review proposes a dietary framework for patients with NAFLD based on the available evidence and extrapolates from dietary guidelines aimed at reducing insulin resistance and cardiovascular risk.     

Non-alcoholic fatty liver disease in children now: lifestyle changes and pharmacologic treatments

Over the past decade, non-alcoholic fatty liver disease (NAFLD) has become one of most common chronic liver diseases in children. A greater understanding about the risk factors and molecular pathogenesis of NAFLD suggests that lifestyle interventions aiming to decrease obesity/body mass index and metabolic derangement are the first line of treatments adopted in children affected by this disease. However, because these therapeutic options are often at the beginning misjudged by the patients and their parents, the use of pharmacologic agents may help to protect the liver and other organs from further irreversible tissue damage. Pharmacologic therapies against one or more specific factors and/or molecules involved in the development of NAFLD (i.e., insulin resistance, free fatty acid lipid toxicity, and oxidative stress) also might slow the progression of this increasingly prevalent pediatric disorder. On this basis, insulin sensitizers, antioxidants, cytoprotective agents, and dietary supplementations have been evaluated in pediatric clinical trials. In this review, we discuss the efficacy of the dietary approaches, possibly coupled with regular exercise, on decreasing the metabolic and histologic damage in pediatric NAFLD. We also emphasize several advantages of the pharmacologic treatments adopted or adoptable in combination with lifestyle interventions in children with NAFLD.     

Nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis not associated with a significant intake of ethanol. Insulin resistance is central to the pathogenesis of NAFLD; thus obesity, diabetes, and the metabolic syndrome are frequently associated with the disease. Consequently, as these metabolic conditions emerge as major health problems in Western society, it is now recognized that NAFLD is the most common chronic liver condition in the Western world. NAFLD is generally asymptomatic, although a minority of patients may present with evidence of progressive liver injury with complications of cirrhosis, liver failure, and hepatocellular carcinoma. Despite being common and potentially serious, relatively little is known about the natural history or prognostic significance of NAFLD. Although diabetes, obesity, and age are recognized risk factors for advanced liver disease, other significant factors leading to progressive liver injury remain to be identified. The treatment of NAFLD focuses upon modifying metabolic risk factors. Insulin-sensitizing and hepatoprotective drugs have been subjected to study trials, but as yet, no agent has conclusively been demonstrated to prevent disease progression. Management is further complicated by the inability to predict which patients will develop liver-related morbidity and thus benefit from treatment.     

Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.     

Phytosterols, phytostanols and their esters: from natural to functional foods

Phytosterols, phytostanols and their esters are a group of steroid alcohols that occur naturally in plants. As natural constituents of plant structures, phytosterols contribute to the regulation of the fluidity and permeability of cell membranes. They are found mostly in vegetable oils, fruits, nuts, cereals and legumes. The most abundant phytosterols are β-sitosterol, campesterol and stigmasterol. During the last 15 years the market for phytosterols, as dietary supplements, has lead to a rapidly growing worldwide market for functional foods containing phytosterols and stanols. Even though many different clinical trials have clearly demonstrated that phytosterols reduce LDL-cholesterol, it is unclear whether phytosterols have a positive effect on cardiovascular disease. Until now, there are no data related to the effect of phytosterol consumption on the development of cardiovascular diseases. This review focuses on the biochemistry of phytosterols, their metabolism and role in health and in pathological conditions.     

The Influence of Dietary Fat on Liver Fat Accumulation

Obesity is a known risk factor for the development of non-alcoholic fatty liver disease (NAFLD); however, it has been suggested that dietary fat, both amount and composition, may play a pivotal role in its development, independent of body fatness. Studies that have investigated the role of dietary fat on liver fat accumulation are reasonably sparse. We review here the available work that has investigated the impact of dietary fat: amount, composition and frequency, on liver fat accumulation in human observational and intervention studies. Overall, it would seem that total calorie consumption, rather than dietary fat composition, is an important factor in the development of fatty liver disease in humans.     

Hepatoprotective Effect of Herb Formula KIOM2012H against Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a hepatic ailment with a rapidly increasing incidence due to dietary hypernutrition and subsequent obesity. Fatty liver disease can lead to steatohepatitis, fibrosis, cirrhosis, and even cancer, which is associated with various complications. Discovering effective natural materials and herbs can provide alternative and complementary medical treatments to current chemical pharmaceuticals. To develop an effective natural agent for NAFLD, we formulated a combination of four herb mixtures (KIOM2012H) and observed lipid-lowering efficacy. The inhibitory effects of KIOM2012H on free fatty acid-induced lipid accumulation, triglyceride contents, and gene expressions were analyzed in HepG2 cells. Using high fat diet-fed mice, body weight changes, gross liver appearances, hepatic triglyceride contents, and gene expressions were evaluated. KIOM2012H dose-dependently inhibited lipid accumulation and gene expressions involved in lipogenesis and related regulators. Experimental animals also showed a decrease in body weight changes and lipid-associated physiological parameters. This study shows that KIOM2012H has an alleviating effect on fatty acid and lipid accumulation, and therefore can be applied for development of new therapeutic pharmaceuticals for treatment of NAFLD using natural products and herbs.     

Beyond cholesterol-lowering effects of plant sterols: clinical and experimental evidence of anti-inflammatory properties

Inflammation is a strong risk factor for cardiovascular disease. Dietary plant sterols are known to reduce plasma cholesterol levels and thereby reduce cardiovascular risk. Recent observations from animal and human studies have demonstrated anti-inflammatory effects of phytosterols. For example, several animal and human studies report reductions in the levels of proinflammatory cytokines, including C-reactive protein, after consumption of dietary plant sterols. Although the cholesterol-lowering effects of phytosterols in humans are well documented, studies on the effects of phytosterols on inflammatory markers have produced inconsistent results. This review summarizes and discusses findings from recent animal and human studies with regard to the potential anti-inflammatory effects of dietary phytosterols. Findings on the effects of plant sterols on inflammation remain limited and confounding. Future research using better-designed and well-controlled laboratory studies and clinical trials are needed to fully understand the mechanisms through which phytosterols influence inflammation. Additional well-designed placebo-controlled studies are needed to better understand how and to what extent dietary plant sterols may modify the immune system and the production of inflammatory markers.     

Comparison of Dietary Control and Atorvastatin on High Fat Diet Induced Hepatic Steatosis and Hyperlipidemia in Rats

Background  

Treatment with atorvastatin (ATO) or dietary control has been demonstrated to benefit patients with non-alcoholic fatty liver disease (NAFLD) and hyperlipidemia. However, little is known on whether combination of dietary control and ATO treatment could enhance the therapeutic effect.     

Effect of Different Types of Intermittent Fasting on Biochemical and Anthropometric Parameters among Patients with Metabolic-Associated Fatty Liver Disease (MAFLD)—A Systematic Review

Metabolic-associated fatty liver disease (MAFLD), previously called non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease worldwide. It is characterised by excessive fat accumulation in hepatocytes. Currently, no pharmacological therapy is effective for this disease, so non-pharmacological alternatives such as diet, supplementation or physical activity are being sought. For this reason, we reviewed the available databases to analyse the studies conducted to date using different modifications of intermittent fasting among patients with MAFLD. Eight studies using this dietary strategy were included in this review. The results obtained in the different trials are varied and do not allow a clear determination of the effect of the different types of intermittent fasting on anthropometric and biochemical parameters among patients with MAFLD. However, this type of diet seems to show some therapeutic potential, but further studies are needed.     

Update on non-alcoholic fatty liver disease in children

Non-alcoholic fatty liver disease (NAFLD) is probably the most common cause of liver disease in the pediatric community. It is closely associated with obesity and insulin resistance. NAFLD may lead to non-alcoholic steatohepatitis (NASH). Although NASH is a prerequisite for the definition of NAFLD in adults and children, distinct differences are often apparent in the extent or location of fat, inflammation and fibrosis. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to summarize what is known about pediatric NAFLD in terms of prevalence, pathogenesis, diagnosis, histology and treatment.     

Relation of Dietary Patterns and Nutritional Profile to Hepatic Fibrosis in a Sample of Lebanese Non-Alcoholic Fatty Liver Disease Patients

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver injury worldwide. NAFLD can evolve into non-alcoholic steatohepatitis (NASH) with or without fibrosis. The objectives of this study were to determine the nutritional profile and dietary patterns of NAFLD Lebanese patients and to report the type of diet-related to the presence of hepatic fibrosis. We hypothesized that the traditional pattern was related to a low risk of fibrosis. This cross-sectional study included 320 eligible Lebanese NAFLD patients. Three dietary patterns were identified: the Traditional diet, the High Fruit diet, and the Westernized diet. Multivariate analysis showed a significant relationship between high adherence to the traditional diet and absence of hepatic fibrosis with a decreased risk of 82%, p = 0.031 after adjusting for its covariables. Fruits were absent from this dietary pattern. Although our results pointed to a possible relationship between fibrosis in NAFLD patients and fruit intake, experimental studies are needed to show whether this is a causal relationship. However, the results obtained in this study may contribute to the planning of dietary interventions and recommendations and enable a better follow-up for NAFLD patients with fibrosis.     

Dietary Fructose Reduction Improves Markers of Cardiovascular Disease Risk in Hispanic-American Adolescents with NAFLD

Nonalcoholic fatty liver disease (NAFLD) is now thought to be the most common liver disease worldwide. Cardiovascular complications are a leading cause of mortality in NAFLD. Fructose, a common nutrient in the westernized diet, has been reported to be associated with increased cardiovascular risk, but its impact on adolescents with NAFLD is not well understood. We designed a 4-week randomized, controlled, double-blinded beverage intervention study. Twenty-four overweight Hispanic-American adolescents who had hepatic fat >8% on imaging and who were regular consumers of sweet beverages were enrolled and randomized to calorie-matched study-provided fructose only or glucose only beverages. After 4 weeks, there was no significant change in hepatic fat or body weight in either group. In the glucose beverage group there was significantly improved adipose insulin sensitivity, high sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) oxidation. These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis. Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials.     

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.