Search Results (41)

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly attracting growing concern around the world. While there has been progress in the development of pharmacologic treatments, lifestyle and dietary interventions remain as the first-line approach for management. This scoping review aimed to identify dietary strategies for managing MASLD and to highlight current research gaps and challenges. Methods: A systematic search of PubMed and Science Direct was conducted up to 10 July 2025, for relevant studies on dietary modifications and MASLD. Data extracted included types of interventions, outcomes related to liver health, and research limitations. Results: Dietary interventions were shown to consistently improve hepatic and metabolic outcomes. In a randomized controlled trial of 12 weeks (n = 259), a Mediterranean diet reduced hepatic steatosis by 39% and improved insulin sensitivity. A calorie-restricted lifestyle program in adults with MASLD (n = 196) reduced liver fat by 25% over 52 weeks. Resistant starch supplementation (n = 200) lowered intrahepatic triglyceride content by 8% through gut microbiome modulation. A pilot RCT of medically tailored meals in cirrhosis (n = 40) reduced ascites symptoms and improved quality of life. Finally, prebiotic supplementation in MASLD (n = 200) lowered systemic inflammation and increased immune-regulating microbes. In contrast, Western dietary patterns and ultra-processed foods were consistently linked to lipotoxicity and inflammation. Conclusions: Dietary interventions remain critical for the management of chronic liver disease and continue to play a vital role even as pharmacotherapy options emerge. Further research should explore precision nutrition and microbiome-based therapies while also addressing the methodological limitations like the underutilization of causal inference frameworks. Finally, it is also important to consider culturally tailored interventions to account for barriers in access and equity in underserved populations. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and climate change are major global health challenges. Aim: Our aim was to assess the relationship between intrahepatic fat content (IFC) and diet-related environmental impact in a Mediterranean diet (MD)-based intervention. Design: The design included a six-month longitudinal analysis within the frame of a FLIPAN randomized controlled trial, including 60 participants aged 40–60 years with MASLD, metabolic syndrome and obesity. Methods: IFC expressed as a percentage (%IFC) was measured by magnetic resonance imaging, and dietary intake was assessed via a validated food frequency questionnaire (FFQ). Environmental impacts of diets were estimated using life cycle assessment data from the Agribalyse^® database, focusing on greenhouse gas (GHG) emissions, water use, energy use and land use. A composite sustainability score was also calculated. Changes in liver fat and environmental footprints were analyzed using a general linear model (GLM) adjusted for within-subject variability and partial correlation analysis adjusted for energy intake, MD adherence and body weight. Results: The participants with the highest %IFC reduction group in the GLM showed the highest decreases in GHG emissions and land use. Water use increased in this same group. Energy use and the composite sustainability score did not differ significantly between groups. Higher %IFC reductions were also associated with higher MD adherence and lower visceral fat. When the adjusted partial correlation analysis for the environmental parameters was performed, only water use remained significant. Conclusions: Higher reductions in %IFC were linked to dietary patterns with lower GHG emissions and land use and higher water use. However, when adjusted by energy intake, MD adherence and body weight in continuous modeling, only higher water use was related to lower %IFC. These findings highlight the complexity of achieving environmentally sustainable and health-promoting diets. Full article

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is one of the leading causes of chronic liver disease, affecting 30% of the global adult population and continuing to rise. Objective: We aimed to assess the effect of a two-year follow-up Mediterranean diet intervention on parameters of liver health in MASLD patients. Methods: Sixty-two people between 40 and 60 years of age, all diagnosed with MASLD, were enrolled in the two-year clinical trial, who were randomly assigned to one of three interventions following the Mediterranean diet pattern and the promotion of physical activity. After the intervention, the participants were categorized into two groups according to their progress in adhering to the Mediterranean diet (MedDiet), which was assessed at four follow-up time points, conducted at the start of this study and after 6, 12, and 24 months of intervention. A multivariate general linear model adjusted for age, sex, and intervention (diet and physical activity) was used. Bonferroni’s post hoc test identified differences between groups and sessions within the same group. Results: Participants in the highly adherent group showed significantly stronger improvement in anthropometric measures, lipid profile, and liver enzyme levels during the follow-up period, along with a reduction in the Dietary Inflammatory Index, intrahepatic fat content, the fatty liver index, and plasma cytokeratin-18 levels compared to baseline. The progress observed in several parameters at 12 months came to a standstill, likely because of the COVID-19 pandemic at that time. At 24 months, following the COVID-19 pandemic, these parameters improved as a result of better adherence to the Mediterranean diet. Conclusions: Greater adherence to the Mediterranean diet, along with increased physical activity, significantly enhances liver health markers in individuals with MASLD. These findings support the Mediterranean lifestyle as an effective non-pharmacological strategy to improve liver health and prevent liver-related complications in MASLD patients, potentially reducing the future public health burden. Full article

Background and Objectives: The pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remains incompletely understood. However, recent studies highlight the interactions between muscle, liver, and adipose tissue. This study aimed to explore the relationships between clinical indicators of MASLD and sarcopenia, cardiorespiratory fitness, fatigue, and mood. Materials and Methods: The study involved 60 participants, including 28 healthy controls and 32 with MASLD, categorized into two disease subgroups: 15 with MASL and 17 with metabolic dysfunction-associated steatohepatitis (MASH). Participants completed an incremental speed shuttle walk test to evaluate cardiorespiratory fitness, a hand-held dynamometer assessment for appendicular muscle strength, and the timed up and go test for physical performance. Physical activity level, fatigue, quality of life, and emotional state were assessed using questionnaires. The test results were compared between groups and with disease characteristics. Results: MASL and MASH groups showed reduced cardiorespiratory fitness (p < 0.001). The knee extensors were significantly weaker in both MASL and MASH groups (p < 0.001 and p = 0.001, respectively). The MASH group reported higher levels of depression and negative health perception (p = 0.006 and p = 0.03, respectively). Muscle strength in patients with MASLD showed a significant negative association with depression (OR = −0.384, 95% CI: −3.10 to −0.74, p = 0.003), intrahepatic triglyceride content (OR = −0.287, 95% CI: −1.31 to −0.11, p = 0.023), and LDL (OR = −0.286, 95% CI: −0.02 to −0.33, p = 0.03). In contrast, a positive association was observed between VO₂ and muscle strength (OR = 0.531, 95% CI 1.27 to 3.47, p < 0.001). Conclusions: This study suggests that muscle strength is linked to key metabolic parameters, such as hepatic fat, LDL levels, and aerobic capacity, that may contribute to the development and progression of MASLD. Interventions aimed at preserving or enhancing muscle strength in MASLD patients may be essential for preventing liver damage and improving metabolic health. Full article

Background: The rising prevalence of metabolic-dysfunction-associated steatotic liver disease (MASLD) is a significant health challenge, and the consumption of ultra-processed foods (UPFs) could play a key role. Aim: The aim is assess the impact of UPF consumption changes on the development and progression of MASLD in adults. Design: This is a longitudinal study to assess how changes in UPF consumption affect liver fat and MASLD parameters over 6 months in 70 participants. Methods: Dietary intake was assessed using a validated food frequency questionnaire, and foods were classified according to the NOVA system. Participants were divided into three groups based on UPF consumption changes: maximum (T1), medium (T2), and minimum reduction (T3). Fatty liver parameters were assessed with magnetic resonance imaging and ultrasonography. Mediterranean diet (Med-diet) adherence and sociodemographic parameters were also recorded. The General Linear Model was used to determine relationships between UPF consumption, fatty liver disease parameters, and diet. Results: Participants in T1 experienced a 7.7% reduction in intrahepatic fat content (IFC) compared to 2.6% in T3. T1 showed increased Med-diet adherence and decreased meat and sweets consumption. The energy intake decreased by 605.3 kcal/day in T1, while T3 showed an increase of 209.5 kcal/day. Conclusions: Reducing UPF consumption leads to a decrease in IFC, associated with high Med-diet adherence and low calorie intake. Adopting these dietary patterns aligns with global sustainability goals and could further benefit MASLD patients by addressing environmental challenges alongside improving liver health. Full article

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is prevalent among obese individuals and can progress to non-alcoholic steatohepatitis (NASH). Bariatric surgery is known to induce significant weight loss and may improve NAFLD. This systematic review uniquely synthesizes current evidence on the effects of bariatric surgery on intrahepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF), and assesses study quality using the Newcastle–Ottawa Scale (NOS). Materials and Methods: The literature search was conducted across the PubMed, Scopus, and Web of Science databases up to October 2024, identifying 12 prospective cohort studies involving 613 patients who underwent bariatric surgery. Inclusion criteria included adult patients with NAFLD undergoing bariatric surgery, assessment of liver fat changes using MRI-PDFF before and after surgery, and studies reporting quantitative data on liver fat fraction and relevant clinical parameters. Data extraction focused on patient demographics, surgical procedures, specific weight loss outcomes (delta BMI), changes in intrahepatic fat content (delta MRI-PDFF), and quality assessment scores based on the NOS. Results: Significant reductions in intrahepatic fat content were observed across all studies, with delta MRI-PDFF reductions ranging from 6.9% to 14%. Weight loss outcomes varied, with excess weight loss percentages up to 81.3% and BMI reductions up to 12 kg/m². The quality assessment scores ranged from six to nine out of nine, indicating generally high-quality studies. Correlations were noted between the degree of weight loss and reduction in liver fat content. Several studies reported high rates of resolution of steatosis and NASH post-operatively. Conclusions: Bariatric surgery leads to significant reductions in intrahepatic fat content and improvements in NAFLD among obese patients. The degree of weight loss correlates with the reduction in liver fat. These findings underscore the clinical utility of bariatric surgery as a strategic intervention for managing NAFLD in obese individuals, potentially influencing clinical practice guidelines by integrating bariatric surgery as a viable treatment option for NAFLD-related hepatic conditions. Full article

Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease observed in clinical practice worldwide. This disorder has been independently associated with an increased risk of developing chronic kidney disease (CKD). The aim of this study was to evaluate whether a 2-year intervention based on a Mediterranean diet (MedDiet) and physical activity focussed on reducing intrahepatic fat contents (IFC) was associated with a decreased risk of CKD. Forty adults (50% women) residing in Mallorca, aged 48 to 60 years, diagnosed with MAFLD were recruited. Participants were divided into two groups based on whether they improved IFC measured by nuclear magnetic resonance. Anthropometric and clinical parameters improved in responders, including reduced weight, body mass index (BMI), and waist circumference. Only responders showed improvements in lipid profile and liver enzymes. Haematological parameters showed favourable changes in both groups. Oxidative stress and inflammatory biomarkers differed between groups. Responders had lower plasma interleukine-18 (IL-18) levels, but higher erythrocyte malonaldehyde (MDA) levels. Non-responders showed increased erythrocyte catalase and superoxide dismutase activity. After 2 years, non-responders had higher serum creatinine, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) levels, while responders showed reductions in these parameters together with uric acid and urine albumin-to-creatinine ratio (UACR). Positive correlations were found between changes in IFC and kidney injury biomarkers, including MDRD and serum creatinine levels. In conclusion, a healthy diet based on the Mediterranean dietary pattern and lifestyle promotes significant improvements in parameters related to cardiovascular, hepatic, and renal health. Full article

Excessive lipid deposition affects hepatic homeostasis and contributes to the development of insulin resistance as a crucial factor for the deterioration of simple steatosis to steatohepatitis. So, it is essential to search for an effective agent for a new therapy for hepatic steatosis development before it progresses to the more advanced stages. Our study aimed to evaluate the potential protective effect of α-lipoic acid (α-LA) administration on the intrahepatic metabolism of sphingolipid and insulin signaling transduction in rats with metabolic dysfunction-associated steatotic liver disease (MASLD). The experiment was conducted on male Wistar rats subjected to a standard diet or a high-fat diet (HFD) and an intragastrically α-LA administration for eight weeks. High-performance liquid chromatography (HPLC) was used to determine sphingolipid content. Immunoblotting was used to measure the expression of selected proteins from sphingolipid and insulin signaling pathways. Multiplex assay kit was used to assess the level of the phosphorylated form of proteins from PI3K/Akt/mTOR transduction. The results revealed that α-LA decreased sphinganine, dihydroceramide, and sphingosine levels and increased ceramide level. We also observed an increased the concentration of phosphorylated forms of sphingosine and sphinganine. Changes in the expression of proteins from sphingolipid metabolism were consistent with changes in sphingolipid pools. Treatment with α-LA activated the PI3K/Akt/mTOR pathway, which enhanced the hepatic phosphorylation of Akt and mTOR. Based on these data, we concluded that α-lipoic acid may alleviate glucose intolerance and may have a protective influence on the sphingolipid metabolism under HFD; thus, this antioxidant appears to protect from MASLD development and steatosis deterioration. Full article

Background: The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. Objectives: To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) of NAFLD patients following a 24-month lifestyle intervention based on the MedDiet. Adult patients (n = 40; aged 40–60 years) diagnosed with NAFLD by magnetic resonance imaging were divided into two groups based on their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Anthropometrics, biochemistry parameters, intrahepatic fat contents (IFC), antioxidants, and inflammatory biomarkers were measured in plasma and erythrocytes before and after the intervention. Results: After the intervention, body mass index (BMI) and plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-chol), triglycerides, malondialdehyde (MDA), and cytokeratin-18 (CK18) decreased, and high-density lipoprotein cholesterol (HDL-chol) increased. Participants with high adherence to MedDiet showed lower IFC, hepatic enzyme (AST, ALT, and GGT), glycemia, oxidase LDL (oxLDL) plasma levels, and erythrocyte MDA levels. Higher antioxidant activity (erythrocyte catalase-CAT, superoxide dismutase-SOD, glutathione peroxidase-GPx, glutathione reductase-GRd, and total glutathione-GSH as well as PBMCs-CAT gene expression) was observed in these patients, along with a reduction of PBMCs reactive oxygen species production and Toll-like receptor 4 (TLR4) expression. Inverse associations were observed between adherence to the MedDiet and BMI, glycemia, AST, IFC, and CK18 plasma levels and oxLDL, CAT, SOD, and GRd activities in erythrocytes. A significant linear regression was observed between adherence to the MedDiet and antioxidant score. Conclusions: Adherence to the MedDiet is associated with improved plasma and PBMC antioxidant and inflammatory biomarker profiles and high antioxidant defences in erythrocytes. Full article

Introduction: Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) is a common cause of chronic liver disease. This review assessed the efficacy of a Low-Calorie Diet (LCD) on liver health and body weight in people living with MASLD and obesity. Methods: The study was registered with PROSPERO (CRD42021296501), and a literature search was conducted using multiple databases. The key inclusion criteria were randomised controlled trials or cohort studies, obesity/overweight and MASLD. Two authors screened abstracts, reviewed full texts and performed data extraction and quality assessment. The primary outcome was the change in the serum ALT, and secondary outcomes included the changes in the serum AST, intrahepatic lipid content (IHL), quantified non-invasively via MRI/MRS, and body weight. Results: Fifteen studies were included. The LCD reduced body weight by 9.1 kg versus the control (95%CI: −12.4, −5.8) but not serum ALT (−5.9 IU/L, −13.9, 2.0). Total Dietary Replacement (TDR) reduced IHL by −9.1% vs. the control (−15.6%, −2.6%). The Mediterranean-LCD for ≥12 months reduced ALT (−4.1 IU/L, −7.6, −0.5) and for 24 months reduced liver stiffness versus other LCDs. The Green-Mediterranean-LCD reduced IHL, independent of body weight. Limited studies assessed those of Black or Asian ethnicity, and there was heterogeneity in the methods assessing the liver fat content and fibrosis. Conclusions: In people with MASLD and obesity, an LCD intervention reduces IHL and body weight. Trials should focus on the recruitment of Black and Asian ethnicity participants. Full article

Non-alcoholic fatty liver disease (NAFLD) shows liver fat depots without alcohol consumption. NAFLD does not have specific drug therapies, with a healthy lifestyle and weight loss being the main approaches to prevent and treat NAFLD. The aim was to assess the antioxidant and pro-inflammatory state in patients with NAFLD after 12-month-lifestyle intervention depending on the change in adherence to a Mediterranean diet (AMD). Antioxidant and inflammatory biomarkers were measured in 67 adults (aged 40–60 years old) diagnosed with NAFLD. Anthropometric parameters and dietary intake were measured by a validated semi-quantitative 143-item food frequency questionnaire. The nutritional intervention improved anthropometric and biochemical parameters after a 12-month follow-up. However, decreases in alanine aminotransferase (ALT) and C reactive protein (CRP) were higher in participants with high AMD, which also showed higher improvement in physical fitness (Chester step test) and intrahepatic fat contents. The intervention reduced plasma levels of malondialdehyde, myeloperoxidase, zonulin, and omentin, and increased resolvin D1 (RvD1), whereas the decrease in leptin, ectodysplasin-A (EDA), cytokeratin-18 (CK-18), interleukin-1ra (IL-1ra) and endotoxin was only significant in participants with higher AMD. The current study showed that a one-year nutritional intervention improved main NAFLD features such as body mass index, IFC, liver enzymes, and prooxidant and proinflammatory status. There was also a decrease in the concentration of plasmatic endotoxin, suggesting an improvement in intestinal permeability. These health benefits were more evident in participants that improved AMD to a greater extent. The trial was registered at ClinicalTrials.gov with registry number NCT04442620. Full article

Background: Current guidelines aim to limit the dietary glycemic index (GI) and intake of saturated fatty acids (SFA). Several studies have shown favorable effects of low-GI or low-SFA diets on intrahepatic lipid content (IHL), but these studies were performed under overfeeding conditions or extreme differences in GI or SFA to maximize the contrast between diets. By combining changes in GI and SFA, we can mimic how people can improve their diet in a realistic setting. Objectives: We investigated the effect on liver fat content and substrate metabolism of both reducing GI and replacing SFA with polyunsaturated fat in practically realistic amounts under isocaloric conditions. Design and Methods: In a randomized crossover study, thirteen overweight participants consumed two diets, one high in GI and SFA (high GI/SFA) and one low in GI and SFA (low GI/SFA) with identical macronutrient composition, for two weeks each. Diets were equal in caloric content, consisted of habitual food items, and had a macronutrient composition that can be easily achieved in daily life. At the end of each intervention, IHL content/composition and liver glycogen were measured by magnetic resonance spectroscopy. Additionally, fasted and postprandial hepatic de novo lipogenesis and glycemic and metabolic responses were investigated. Results: IHL was significantly lower (−28%) after the two-week low-GI/SFA diet (2.4 ± 0.5% 95% CI [1.4, 3.4]) than after the two-week high-GI/SFA diet (3.3 ± 0.6% 95% CI [1.9, 4.7], p < 0.05). Although hepatic glycogen content, hepatic de novo lipogenesis, hepatic lipid composition, and substrate oxidation during the night were similar between the two diets, the glycemic response to the low-GI/SFA diet was reduced (p < 0.05). Conclusions: Changes in macronutrient quality can already have drastic effects on liver fat content and postprandial glycemia after two weeks and even when energy content and the percentage of total fat and carbohydrate remains unchanged. Full article

Hepatocyte nuclear factor 4 alpha (HNF4α) is a key master transcriptional factor for hepatic fat and bile acid metabolic pathways. We aimed to investigate the role of HNF4α in non-alcoholic fatty liver disease (NAFLD). The role of HNF4α was evaluated in free fatty acid–induced lipotoxicity and chenodeoxycholic acid (CDCA)-induced bile acid toxicity. Furthermore, the role of HNF4α was evaluated in a methionine choline deficiency (MCD)-diet-induced NAFLD model. The overexpression of HNF4α reduced intracellular lipid contents and attenuated palmitic acid (PA)-induced lipotoxicity. However, the protective effects of HNF4α were reversed when CDCA was used in a co-treatment with PA. HNF4α knockdown recovered cell death from bile acid toxicity. The inhibition of HNF4α decreased intrahepatic inflammation and the NAFLD activity score in the MCD model. Hepatic HNF4α inhibition can attenuate bile acid toxicity and be more effective as a therapeutic strategy in NAFLD patients; however, it is necessary to study the optimal timing of HNF4α inhibition. Full article

Obesity is a risk factor for NAFLD. However, not all people with obesity have an excessive intrahepatic fat content. Adherence to a high-quality dietary pattern may also promote liver health in obesity. A cross-sectional study of 2967 women with overweight and obesity was carried out to assess the association between a Mediterranean diet and fatty liver. All women underwent clinical examination, anthropometric measurements, blood sampling, ultrasound measurements of abdominal visceral and subcutaneous fat, and assessment of adherence to the Mediterranean diet using the 14-item MEDAS questionnaire. Fatty liver index (FLI), NAFLD fatty liver steatosis (NAFLD-FLS) and hepatic steatosis index (HSI) were calculated. In women with obesity, the MEDAS score was inversely associated with FLI (β = −0.60, 95% CI: −1.04, −0.16, p = 0.008), NAFLD-FLS (β = −0.092, 95% CI: −0.134, −0.049, p < 0.001) and HSI (β = −0.17, 95% CI: −0.30, −0.04, p = 0.011). Stronger associations were observed in premenopausal women with obesity. Mediterranean diet was inversely associated with NAFLD-FLS in women with overweight, independently of menopausal status. In conclusion, Mediterranean diet is associated with a better liver status in women with overweight and obesity. This may have a public health impact and be useful in drafting nutritional guidelines for NAFLD. Full article

Background: COVID-19 lockdowns had a significant impact on people’s health, triggering levels of anxiety, perceived stress, and changes in food and nutritional status. Objectives: To assess the changes in dietary habits, metabolic syndrome (MetS) and liver parameters before and after the COVID-19 lockdown according to changes in intrahepatic fat content in adults with non-alcoholic fatty liver disease (NAFLD) and MetS. Design: Pre- and post-lockdown observation of the COVID-19 lockdown on fifty-nine 40–60-year-old participants with MetS and NAFLD, in a parallel group, randomised experiment intended to treat NAFLD. Methods: Anthropometrics, liver and MetS biochemical parameters, intrahepatic fat content by abdominal magnetic resonance imaging, and dietary assessment using a validated 148-item Food Frequency Questionnaire were collected pre-COVID-19 lockdown and post-lockdown. Results: COVID-19 lockdown led to negative changes in the liver of patients with NAFLD and MetS, with weight gain and increases in glycemia, ALT and intrahepatic fat content post lockdown. Participants with worsened liver status had low consumption of fibre, cheese, nuts and coffee, and high consumption of sweets and pastries. Participants who improved liver status ameliorated ALT values, waist circumference, and intrahepatic fat content, assessed by magnetic resonance imaging post-lockdown. Conclusions: The maintenance of healthy lifestyle habits is vital, especially for populations with NAFLD and MetS, to reduce unhealthy lifestyle patterns displayed during lockdown. Full article