High red meat consumption among PNPLA3 polymorphism carriers is associated with NAFLD in a multi-center cross-sectional study.

BACKGROUND & AIM: Patatin-like phospholipase domain-containing 3 gene (PNPLA3) polymorphism has been implicated in susceptibility to non-alcoholic fatty liver disease (NAFLD), with evidence for potential interaction with nutrition. However, the combination of meat consumption with genetic polymorphism has not been tested. Therefore, this study aims to test the association between the joint presence of PNPLA3 rs738409 G-allele with high meat consumption and NAFLD in populations with diverse meat consumption. METHODS: A cross-sectional study among Israeli screening and Brazilian primary healthcare populations. Food consumption was assessed by a food-frequency questionnaire. PNPLA3 polymorphism was defined as homozygous (GG) or heterozygous (GC). Inconclusive/probable NAFLD was defined as a fatty liver index (FLI) ≥ 30 and probable NAFLD as FLI ≥ 60. RESULTS: The sample included 511 subjects from the screening and primary healthcare populations (n = 213 and n = 298, respectively). Genetic polymorphism (homozygous GG or heterozygous GC) combined with high consumption of total meat, red and/or processed meat, unprocessed red meat, and processed meat was associated with the highest odds for inconclusive/probable NAFLD (OR = 2.75, 95%CI 1.27-5.97, p = 0.011; OR = 3.24, 1.43-7.34, p = 0.005; OR = 2.92, 1.32-6.47, p = 0.008; OR = 3.16, 1.46-6.83, p = 0.003, respectively), adjusting for age, gender, BMI, alcohol consumption, carbohydrate, and saturated fat intake. In addition, genetic polymorphism combined with high processed meat consumption was associated with the highest odds for probable NAFLD (OR = 2.40, 95%CI 1.04-5.56, p = 0.040). CONCLUSIONS: High red meat intake may confer a greater risk for NAFLD among PNPLA3 polymorphism carriers. Prospective studies are needed to confirm these findings and consider minimizing red and processed meat consumption among PNPLA3 polymorphism carriers.

Ultra-processed food consumption and non-alcoholic fatty liver disease, metabolic syndrome and insulin resistance: A systematic review.

Background: High ultra-processed food (UPF) consumption is associated with the development of various diet-related non-communicable diseases, especially obesity and type 2 diabetes. The present study aimed to systematically review the association between UPF consumption and non-alcoholic fatty liver disease (NAFLD) and its leading risk factors; metabolic syndrome (MetS) and insulin resistance (IR). Methods: A comprehensive search was conducted in PubMed, Scopus, Embase, Web of Science, CINAHL, and Cochrane (March 2023), and references of the identified articles were checked. The search keywords were defined through an exploratory investigation in addition to MeSH and similarly controlled vocabulary thesauruses. Observational and interventional studies were included. Studies that focused only on specific groups of processed foods or overlapping dietary patterns were excluded. The quality assessment was conducted using the Joanna Briggs Institute's critical appraisal tools for observational studies and Cochrane's risk of bias 2 tool for randomized-control trials. A narrative synthesis was employed to report the results. Results: Fifteen studies were included, with a total of 52,885 participants, one randomized-controlled trial, and fourteen observational studies (nine cross-sectional and five prospective). The review has shown a significant association between UPF consumption and NAFLD in three studies out of six, MetS in five out of eight, and IR in one out of three. All large-scale prospective cohorts that studied NAFLD or MetS outcomes demonstrated a positive association. In contrast, studies that did not demonstrate significant associations were mostly cross-sectional and small. The evidence for an association with IR was insufficient and conflicting. Conclusion: The included studies are few, observational, and based upon self-reported dietary assessment tools. However, current evidence indicates that UPF is not only associated with obesity and type 2 diabetes but may also be a risk factor for NAFLD and MetS. UPF is a worldwide concern deserving further longitudinal research. Impact and implications: Overconsumption of ultra-processed food (UPF) may lead to the development of obesity and type 2 diabetes, but the association with non-alcoholic fatty liver disease (NAFLD) is not well established. The present systematic review shows that UPF may be associated with NAFLD, although more large prospective studies are needed. These findings emphasize the importance of minimizing the consumption of UPF to prevent NAFLD and other metabolic diseases among the general adult population. This systematic review and further prospective studies, epidemiological or interventional, can help physicians provide patients with evidence-based nutritional recommendations and will support policymakers in restricting the marketing of UPF as well as promoting affordable, healthy, and minimally processed foods.

A global action agenda for turning the tide on fatty liver disease.

BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

Consumption of Ultra-Processed Food and Cognitive Decline among Older Adults With Type-2 Diabetes.

BACKGROUND: Ultra-processed food (UPF) consumption is related to increased morbidity and mortality. However, knowledge on its association with cognitive function is lacking. In this longitudinal study, we examined the associations between UPF intake and cognitive decline in older adults with type-2 diabetes (T2D). METHODS: The sample included initially nondemented T2D older adults (≥65 years), from the Israel Diabetes and Cognitive Decline study, who had complete information on nutrition at baseline and at least 3 cognitive assessments (mean follow-up 5.3 ± 1.5 years). Nutritional intake was evaluated by a validated Food-Frequency Questionnaire, and foods were categorized as UPF based on NOVA classification. Percent of calories from UPF were calculated from total caloric consumption in total and specific food groups. Mixed effect models were used to examine the link between UPF intake (top vs bottom quartiles) and change in cognitive function overall and in specific domains, adjusting for potential confounders. RESULTS: Of the total sample (N = 568; mean age 71.3 ± 4.5 years, 60% men), 141 consumed >31% kcal from UPF (top quartile). Greater intake of ultra-processed meat was associated with a faster decline in executive functions and global cognition (ß = -0.041 ± 0.013; p = .002 and ß = -0.026 ± 0.010; p = .011, respectively). Additionally, consumption of ultra-processed oils/spreads was associated with faster decline in executive functions and global cognition (ß = -0.037 ± 0.014; p = .006 and ß = -0.028 ± 0.010; p = .009, respectively). Total UPF consumption and UPF-derived from dairy products and bread/pastries/starch were not associated with cognitive change. CONCLUSION: This study suggests that a high intake of ultra-processed meat and oils/spreads may be associated with accelerated cognitive decline in older individuals with T2D.

Efficacy of Wholistic Turmeric Supplement on Adenomatous Polyps in Patients with Familial Adenomatous Polyposis-A Randomized, Double-Blinded, Placebo-Controlled Study.

Several studies have demonstrated that curcumin can cause the regression of polyps in familial adenomatous polyposis (FAP), while others have shown negative results. Wholistic turmeric (WT) containing curcumin and additional bioactive compounds may contribute to this effect. We performed a double-blinded, randomized, controlled trial to assess the efficacy of WT in FAP patients. Ten FAP patients were randomly assigned to receive either WT or placebo for 6 months. Colonoscopies were performed at baseline and after 6 months. The polyp number and size, as well as the cumulative polyp burden, were assessed. No differences were noted between the groups in terms of changes from the baseline's polyp number, size, or burden. However, stratifying the data according to the right vs. left colon indicated a decrease in the median polyp number (from 5.5 to 1.5, p = 0.06) and polyp burden (from 24.25 mm to 11.5 mm, p = 0.028) in the left colon of the patients in the WT group. The adjusted left polyp number and burden in the WT arm were lower by 5.39 (p = 0.034) and 14.68 mm (p = 0.059), respectively. Whether WT can be used to reduce the polyp burden of patients with predominantly left-sided polyps remains to be seen; thus, further larger prospective trials are required.

High Meat Consumption Is Prospectively Associated with the Risk of Non-Alcoholic Fatty Liver Disease and Presumed Significant Fibrosis.

Non-alcoholic fatty liver disease (NAFLD) has been associated with meat consumption in cross-sectional studies. However, only a few prospective studies have been conducted, and they did not test for liver fibrosis. We aimed to assess the association between meat consumption changes and the incidence and remission of NAFLD and significant liver fibrosis. We used a prospective cohort study design, including 316 subjects aged 40-70 years, participating in baseline and follow-up evaluations at Tel-Aviv Medical Center. NAFLD was determined by liver ultrasound or controlled attenuation parameter (CAP), and liver fibrosis was determined by FibroScan. Meat consumption (g/day) was assessed by a food frequency questionnaire (FFQ). In multivariable-adjusted analyses, high consumption of red and/or processed meat (≥gender-specific median) was associated with a higher risk of NAFLD with elevated alanine aminotransferase (ALT) (OR = 3.75, 1.21-11.62, p = 0.022). Consistently high (in both baseline and follow-up evaluations) total meat consumption was associated with 2.55-fold (95% CI 1.27-5.12, p = 0.009) greater odds for new onset and/or persistence of NAFLD compared to consistently low meat consumption. A similar association was shown for consistently high consumption of red and/or processed meat (OR = 2.12, 95% CI 1.11-4.05, p = 0.022). Consistently high red and/or processed meat consumption was associated with 4.77-fold (95% CI 1.36-16.69, p = 0.014) greater odds for significant fibrosis compared to consistently low consumption. Minimizing the consumption of red and/or processed meat may help prevent NAFLD and significant fibrosis.

One size does not fit all; practical, personal tailoring of the diet to NAFLD patients.

Different dietary regimens for weight loss have developed over the years. Since the most evidenced treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction, it is not surprising that more diets targeting obesity are also utilized for NAFLD treatment. However, beyond the desired weight loss effects, one should not ignore the dietary composition of each diet, which may not necessarily be healthy or safe over the long term for hepatic and extrahepatic outcomes, especially cardiometabolic outcomes. Some of these diets are rich in saturated fat and red meat, are very strict, and require close medical supervision. Some may also be very difficult to adhere to for long periods, thus reducing the patient's motivation. The evidence for a direct benefit to NAFLD by restrictive diets such as very-low-carb, ketogenic, very-low-calorie diets, and intermittent fasting is scarce, and the long-term safety has not been tested. Nowadays, the approach is that the diet should be tailored to the patient's cultural and personal preferences. There is strong evidence for the independent protective association of NAFLD with a diet based on healthy eating patterns of minimally-processed foods, low in sugar and saturated fat, high in polyphenols, and healthy types of fats. This leads to the conclusion that a Mediterranean diet should serve as a basis that can be restructured into other kinds of diets. This review will elaborate on the different diets and their role in NAFLD. It will provide a practical guide to tailor the diet to the patients without compromising its composition and safety.

Liver Fibrosis Marker and Postoperative Mortality in Patients Without Overt Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) can progress to advanced fibrosis, which, in the nonsurgical population, is associated with poor hepatic and extrahepatic outcomes. Despite its high prevalence, NAFLD and related liver fibrosis may be overlooked during the preoperative evaluation, and the role of liver fibrosis as an independent risk factor for surgical-related mortality has yet to be tested. The aim of this study was to assess whether fibrosis-4 (FIB-4), which consists of age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelets, a validated marker of liver fibrosis, is associated with postoperative mortality in the general surgical population. METHODS: A historical cohort of patients undergoing general anesthesia at an academic medical center between 2014 and 2018 was analyzed. Exclusion criteria included known liver disease, acute liver disease or hepatic failure, and alcohol use disorder. FIB-4 score was categorized into 3 validated predefined categories: FIB-4 ≤1.3, ruling out advanced fibrosis; >1.3 and <2.67, inconclusive; and ≥2.67, suggesting advanced fibrosis. The primary analytic method was propensity score matching (FIB-4 was dichotomized to indicate advanced fibrosis), and a secondary analysis included a multivariable logistic regression. RESULTS: Of 19,861 included subjects, 1995 (10%) had advanced fibrosis per FIB-4 criteria. Mortality occurred intraoperatively in 15 patients (0.1%), during hospitalization in 272 patients (1.4%), and within 30 days of surgery in 417 patients (2.1%). FIB-4 ≥2.67 was associated with increased intraoperative mortality (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.25-10.58), mortality during hospitalization (OR, 3.14; 95% CI, 2.37-4.16), and within 30 days from surgery (OR, 2.46; 95% CI, 1.95-3.10), after adjusting for other risk factors. FIB-4 was related to increased mortality in a dose-dependent manner for the 3 FIB-4 categories ≤1.3 (reference), >1.3 and <2.67, and ≥2.67, respectively; during hospitalization (OR, 1.89; 95% CI, 1.34-2.65 and OR, 4.70; 95% CI, 3.27-6.76) and within 30 days from surgery (OR, 1.77; 95% CI, 1.36-2.31 and OR, 3.55; 95% CI, 2.65-4.77). In a 1:1 propensity-matched sample (N = 1994 per group), the differences in mortality remained. Comparing the FIB-4 ≥2.67 versus the FIB-4 <2.67 groups, respectively, mortality during hospitalization was 5.1% vs 2.2% (OR, 2.70; 95% CI, 1.81-4.02), and 30-day mortality was 6.6% vs 3.4% (OR, 2.26; 95% CI, 1.62-3.14). CONCLUSIONS: A simple liver fibrosis marker is strongly associated with perioperative mortality in a population without apparent liver disease, and may aid in future surgical risk stratification and preoperative optimization.

Ultra-processed food is associated with features of metabolic syndrome and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: High consumption of ultra-processed food (UPF) is associated with mortality and chronic morbidity but has not been studied concerning to non-alcoholic fatty liver disease (NAFLD). We aimed to test the association of UPF consumption with metabolic syndrome, NAFLD and related-liver damage. METHODS: A cross-sectional study among volunteers who underwent abdominal ultrasound (AUS), anthropometrics, blood pressure measurements, and fasting blood tests including FibroMax for non-invasive assessment of NASH and significant fibrosis. A food-frequency questionnaire was used to evaluate UPF consumption using the NOVA classification. RESULTS: A total of 789 subjects were included in the total sample (mean age 58.83 ± 6.58 years, 52.60% men), a reliable FibroMax test was obtained from 714 subjects, 305 subjects were diagnosed with NAFLD. High consumption of UPF was associated with higher odds for metabolic syndrome (OR = 1.88, 95% CI 1.31-2.71, P = .001) and its components; hypertension, hypertriglyceridemia, and low HDL, among the entire sample (OR = 1.53, 1.07-2.19, P = .026; OR = 1.51, 1.08-2.11, P = .017; OR = 1.55, 1.05-2.29, P = .028). In addition, it was associated with higher odds for NASH and hypertension (OR = 1.89, 1.07-3.38, P = .030; OR = 2.26, 1.20-4.26, P = .012 respectively) among subjects with NAFLD. Stratification by smoking status revealed an association between high UPF consumption and significant fibrosis among ever smokers in the entire sample and among subjects with NAFLD (OR = 1.89, 95% CI 1.03-3.45, P = .039; OR = 2.85, 1.14-7.14, P = .026 respectively). CONCLUSIONS: High UPF consumption is associated with metabolic syndrome in the general population, and among those with NAFLD it is associated with NASH marker. Ever-smoking may act synergistically with UPF to amplify the risk for fibrosis.

Nutritional Evaluation and Treatment of the Cirrhotic Patient.

Malnutrition and sarcopenia that lead to functional deterioration, frailty, and increased risk for complications and mortality are common in cirrhosis. Sarcopenic obesity, which is associated with worse outcomes than either condition alone, may be overlooked. Lifestyle intervention aiming for moderate weight reduction can be offered to obese compensated cirrhotic patients, with diet consisting of reduced caloric intake, achieved by reduction of carbohydrate and fat intake, while maintaining high protein intake. Dietary and moderate exercise interventions in patients with cirrhosis are beneficial. Cirrhotic patients with malnutrition should have nutritional counseling, and all patients should be encouraged to avoid a sedentary lifestyle.

Ultra-Processed Food Intake and Smoking Interact in Relation with Colorectal Adenomas.

Smoking and ultra-processed foods (UPFs), a substantial part of the western diet, have been suggested to have a potential carcinogenic effect, though epidemiologic data are lacking. We aimed to examine the association between high UPF intake and colorectal adenomas, and to test the interaction with smoking. In a case-control study among consecutive subjects undergoing colonoscopy in a tertiary center during 2010-2015, UPF intake and smoking were compared between cases with colorectal adenomas and controls. Within 652 participants (cases, n = 294 and controls, n = 358), high UPF intake (defined as percent of kcal from UPF above the study sample upper tertile) was positively associated with adenomas (Odds ratio (OR) = 1.75, 95% Confidence interval (CI) 1.14-2.68), advanced and proximal adenomas (OR = 2.17, 1.29-3.65 and OR = 2.38, 1.37-4.11) among the whole study sample; and with adenomas (OR = 3.54, 1.90-6.61), non-advanced adenomas (OR = 2.60, 1.20-5.63), advanced adenomas (OR = 4.76, 2.20-10.30), proximal adenomas (OR = 6.23, 2.67-14.52), and distal adenomas (OR = 2.49, 1.21-5.13) among smokers. Additionally, a dose-dependent association was observed between tertiles of UPF intake and adenomas only among smokers (p for trend < 0.001). A significant interaction between smoking and high UPF intake was detected (p for interaction = 0.004). High intake of UPFs is strongly and independently associated with colorectal adenomas, especially advanced and proximal adenoma, and interacts with smoking. Results highlight smokers as more susceptible to the negative health effects of UPF consumption on colorectal neoplasia.

Serum Malondialdehyde is Associated with Non-Alcoholic Fatty Liver and Related Liver Damage Differentially in Men and Women.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are associated with increased oxidative stress and lipid peroxidation, but large studies are lacking. The aim was to test the association of malondialdehyde (MDA), as a marker of oxidative damage of lipids, with NAFLD and liver damage markers, and to test the association between dietary vitamins E and C intake and MDA levels. METHODS: A cross-sectional study was carried out among subjects who underwent blood tests including FibroMax for non-invasive assessment of NASH and fibrosis. MDA was evaluated by reaction with Thiobarbituric acid and HPLC-fluorescence detection method. NAFLD was diagnosed by abdominal ultrasound. FINDINGS: MDA measurements were available for 394 subjects. In multivariate analysis, the odds for NAFLD were higher with the rise of MDA levels in a dose-response manner, adjusting for age, gender, BMI, and lifestyle factors. Only among men, higher serum MDA was associated of higher odds for NAFLD and NASH and/or fibrosis (OR = 2.59, 95% CI 1.33-5.07, P = 0.005; OR = 2.04, 1.02-4.06, P = 0.043, respectively). Higher vitamin E intake was associated with lower odds of high serum MDA level (OR = 0.28 95% CI 0.13-0.62, P = 0.002). In conclusion, serum MDA is associated with NAFLD and markers of NASH or fibrosis among men. Dietary vitamin E may be protective among women.

Higher phenolic acid intake independently associates with lower prevalence of insulin resistance and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: The inverse association between non-alcoholic fatty liver disease (NAFLD) and diets rich in fruit and vegetables has been demonstrated, but the specific compounds that may be responsible for this association need to be elucidated. The aim of this study was to test the association between phenolic acid consumption, NAFLD, and insulin resistance (IR). METHODS: A cross-sectional cohort of individuals included in a metabolic screening program was studied. Liver steatosis was evaluated by ultrasonography and quantified by the hepatorenal index (HRI); fibrosis was assessed by FibroTest; IR by the sample upper quartile of the homeostatic model assessment score. Dietary intake was measured by a food frequency questionnaire. The phenolic acid content of food was calculated according to Phenol-Explorer. RESULTS: A total of 789 individuals were included (52.6% men, age 58.83 ± 6.58 years). Higher (above the upper median) phenolic acid intake was inversely associated with the presence of NAFLD (odds ratio [OR] 0.69; 95% CI 0.49-0.98; p = 0.036), higher HRI (OR 0.64; 95% CI 0.45-0.91; p = 0.013) and higher IR (OR 0.61; 95% CI 0.42-0.87; p = 0.007), when adjusted for age, gender, body mass index, and lifestyle factors. Considering specific classes of phenolic acids, higher hydroxybenzoic acid intake was independently associated with lower odds of NAFLD, higher HRI and fibrosis. Higher hydroxycinnamic acid intake was independently associated with lower odds of IR. CONCLUSION: A higher intake of phenolic acids is associated with a lower prevalence of liver steatosis and IR in a cross-sectional study, suggesting a possible protective effect that requires confirmation in prospective studies. LAY SUMMARY: High dietary intake of total phenolic acids is associated with a lower prevalence of non-alcoholic fatty liver disease and insulin resistance. A high intake of hydroxybenzoic acids, a class of phenolic acids, is associated with a lower prevalence of steatosis and clinically significant fibrosis, while a high intake of hydroxycinnamic acids, another class of phenolic acids, is associated with a lower prevalence of insulin resistance.

A healthy lifestyle pattern has a protective association with colorectal polyps.

BACKGROUND: Colorectal cancer is associated with lifestyle characteristics such as diet, physical inactivity, obesity, and smoking, but these are not incorporated in screening recommendations. Moreover, the joint association of these factors with various colorectal polyps is not established. METHODS: A case-control study, among consecutive subjects aged 40-70 years, undergoing colonoscopy. Cases with colorectal polyps were compared with controls. Detailed information was gathered regarding polyp histology and anatomic location, demographics, medical history, anthropometrics, and lifestyle. The healthy lifestyle index was estimated as the sum of: non-smoking, maintaining a healthy weight, healthy diet, and physical activity. RESULTS: A total of 788 participants were included (cases n = 403, controls n = 385). The healthy lifestyle index had a negative association with colorectal polyps (OR = 0.72, 95% CI 0.62-0.85, P < 0.001), both adenomas and serrated polyps (OR = 0.75, 0.64-0.89, and OR = 0.59, 0.44-0.79, respectively), and both proximal and distal adenomas (OR = 0.77, 0.62-0.95, and OR = 0.73, 0.59-0.90, respectively). Adherence to ≥ 2 healthy lifestyle components was strongly related with colorectal polyps (OR = 0.50, 0.34-0.75, P = 0.001). Abstinence from smoking, and a healthy diet were the factors most strongly associated with lower odds of colorectal polyps (OR = 0.58, 0.42-0.79, and OR = 0.61, 0.44-0.85, respectively). CONCLUSIONS: Adherence to a healthy lifestyle (≥2 healthy lifestyle components) is inversely associated with colorectal polyps, especially serrated and distal polyps, with no dose-response association. Components most strongly associated with lower odds of colorectal polyps were maintaining a healthy diet and abstinence from smoking. Lifestyle-related characteristics may assist in risk stratification and are potential goals for colorectal neoplasia prevention.

Dietary vitamin E and C intake is inversely associated with the severity of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Although antioxidants have a protective potential in nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), there is limited evidence regarding the role of dietary intake of antioxidants. The aim was to test the association between dietary vitamins E and C intake and NAFLD, NASH and fibrosis markers. METHODS: Cross-sectional study of a large cohort of subjects undergoing colonoscopy. The presence of NAFLD was evaluated by ultrasonography. The level of steatosis was defined using SteatoTest, moderate-severe NASH using new quantitative NashTest and borderline-significant fibrosis ≥ F1-F2 using FibroTest. Nutritional intake was measured by food frequency questionnaire (FFQ). RESULTS: Overall, 789 subjects were included (52.6% men, age 58.83 ±â€¯6.58 years), 714 had reliable FibroMax. Adjusting for BMI, dietary and lifestyle factors, the upper tertile of vitamin E intake/1000 Kcal was associated with lower odds of NASH (OR = 0.64, 0.43-0.94, P = 0.024). There was an inverse association between reaching the recommended vitamin E intake and NASH (OR = 0.48, 0.30-0.77, P = 0.002). The upper tertile of vitamin C intake/1000 Kcal was associated with lower odds of NAFLD and NASH (OR = 0.68, 0.47-0.99, P = 0.045; OR = 0.57, 0.38-0.84, P = 0.004, respectively). Both vitamins were related with the level of steatosis according to SteatoTest. CONCLUSION: Vitamin E and C intake may be protective from NAFLD-related liver damage.

Serum Soluble Receptor for AGE (sRAGE) Levels Are Associated With Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) has been demonstrated to be positively associated with serum advanced glycation end products (AGEs) and negatively with soluble receptor for AGE (sRAGE) in a few small studies. We aimed to test the association between lifestyle and sRAGE levels and the association between sRAGE levels or AGEs intake and NAFLD, insulin resistance (IR), and elevated alanine aminotransferase (ALT). METHODS: Cross-sectional analysis among participants of a screening study. Fasting blood tests and serum sRAGE levels were obtained. NAFLD and insulin resistance were evaluated by ultrasonography and homeostasis model assessment, respectively. Nutritional intake was measured by food frequency questionnaire, and the intake of dietary AGEs was calculated. RESULTS: A total of 743 subjects were included (52.6% men, mean age 58.83 ± 6.58 years, 38.7% NAFLD). Exercise was independently protective from low sRAGE levels (odds ratio [OR] = 0.71, 95% confidence interval 0.52-0.97, P = 0.031). Pack-years, working time, and sedentary time (OR = 1.51, 1.03-2.22, P = 0.036; OR = 1.66, 1.18-2.35, P = 0.004; OR = 1.64, 1.18-2.29, P = 0.004, respectively), and intake of red and/or processed meat or processed meat alone (OR = 1.01, 1.04-2.21, P = 0.045; OR = 1.49, 1.00-2.21, P = 0.048, respectively) were associated with increased odds for low sRAGE levels. Low sRAGE levels were independently associated with elevated ALT (OR = 1.69, 1.11-2.57, P = 0.014) and NAFLD with elevated ALT (OR = 2.17, 1.23-3.83, P = 0.007). High intake of dietary AGEs was associated with IR (OR = 2.04, 1.25-3.34 P = 0.004). DISCUSSION: Lifestyle is associated with sRAGE levels and, in turn, low levels of sRAGE are associated with NAFLD and elevated ALT.

High red and processed meat consumption is associated with non-alcoholic fatty liver disease and insulin resistance.

BACKGROUND & AIMS: High red and processed meat consumption is related to type 2 diabetes. In addition, cooking meat at high temperatures for a long duration forms heterocyclic amines (HCAs), which are related to oxidative stress. However, the association between meat consumption and non-alcoholic fatty liver disease (NAFLD) is yet to be thoroughly tested. Therefore, we aimed to test the association of meat type and cooking method with NAFLD and insulin resistance (IR). METHODS: This was a cross-sectional study in individuals who were 40-70 years old and underwent screening colonoscopy between 2013 and 2015 in a single center in Israel. NAFLD and IR were evaluated by ultrasonography and homeostasis model assessment. Meat type and cooking method were measured by a food frequency questionnaire (FFQ) and a detailed meat questionnaire. Unhealthy cooking methods were considered as frying and grilling to a level of well done and very well done. Dietary HCA intake was calculated. RESULTS: A total of 789 individuals had a valid FFQ and 357 had a valid meat questionnaire. High consumption of total meat (portions/day above the median) (odds ratio [OR] 1.49; 95% CI 1.05-2.13; p = 0.028; OR 1.63; 1.12-2.37; p = 0.011), red and/or processed meat (OR1.47; 95% CI 1.04-2.09; p = 0.031; OR1.55; 1.07-2.23; p = 0.020) was independently associated with higher odds of NAFLD and IR, respectively, when adjusted for: body mass index, physical activity, smoking, alcohol, energy, saturated fat and cholesterol intake. High intake of meat cooked using unhealthy methods (OR1.92; 95% CI 1.12-3.30; p = 0.018) and HCAs (OR2.22; 95% CI 1.28-3.86; p = 0.005) were independently associated with higher odds of IR. CONCLUSION: High consumption of red and/or processed meat is associated with both NAFLD and IR. High HCA intake is associated with IR. If confirmed in prospective studies, limiting the consumption of unhealthy meat types and improving preparation methods may be considered as part of NAFLD lifestyle treatment. LAY SUMMARY: High red and processed meat consumption is related to several diseases. In addition, cooking meat at high temperatures for a long duration forms heterocyclic amines, which have harmful health effects. Non-alcoholic fatty liver disease is a significant public health burden and its formation is strongly related to insulin resistance. In this study, both were found to be more frequent in people who consume relatively high quantities of red and processed meat. In addition, a high intake of heterocyclic amines was associated with insulin resistance.