High red and processed meat consumption is associated with non-alcoholic fatty liver disease and insulin resistance. Isocaloric Diets High in Animal or Plant Protein Reduce Liver Fat and Inflammation in Individuals With Type 2 Diabetes. Decrease of aminotransferase levels in obese women is related to body weight reduction, irrespective of type of diet. Effect of two different hypocaloric diets in transaminases and insulin resistance in nonalcoholic fatty liver disease and obese patients. Reduction in Obesity and Related Comorbid Conditions after Diet-Induced Weight Loss or Exercise-Induced Weight Loss in Men Effect of Mediterranean Diet and Antioxidant Formulation in Non-Alcoholic Fatty Liver Disease: A Randomized Study Short-Term Hypocaloric High-Fiber and High-Protein Diet Improves Hepatic Steatosis Assessed by Controlled Attenuation Parameter Ad Libitum Mediterranean and Low‐Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Effect of a low glycemic index Mediterranean diet on non-alcoholic fatty liver disease. A randomized controlled clinici trial Improvements in clinical characteristics of patients with non-alcoholic fatty liver disease, after an intervention based on the Mediterranean lifestyle: a randomised controlled clinical trial. A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease Diet associations with nonalcoholic fatty liver disease in an ethnically diverse population: the Multiethnic Cohort. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis.
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 aim ed 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 question naire ( FFQ ) and a detailed meat question naire . 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 question naire . 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 prospect i ve 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 BACKGROUND & AIMS Nonalcoholic fatty liver disease ( NAFLD ) is associated with increased risk of hepatic , cardiovascular , and metabolic diseases . High-protein diets , rich in methionine and branched chain amino acids ( BCAAs ) , apparently reduce liver fat , but can induce insulin resistance . We investigated the effects of diets high in animal protein ( AP ) vs plant protein ( PP ) , which differ in levels of methionine and BCAAs , in patients with type 2 diabetes and NAFLD . We examined levels of liver fat , lipogenic indices , markers of inflammation , serum levels of fibroblast growth factor 21 ( FGF21 ) , and activation of signaling pathways in adipose tissue . METHODS We performed a prospect i ve study of individuals with type 2 diabetes and NAFLD at a tertiary medical center in Germany from June 2013 through March 2015 . We analyzed data from 37 subjects placed on a diet high in AP ( rich in meat and dairy foods ; n = 18 ) or PP ( mainly legume protein ; n = 19 ) without calorie restriction for 6 weeks . The diets were isocaloric with the same macronutrient composition ( 30 % protein , 40 % carbohydrates , and 30 % fat ) . Participants were examined at the start of the study and after the 6-week diet period for body mass index , body composition , hip circumference , resting energy expenditure , and respiratory quotient . Body fat and intrahepatic fat were detected by magnetic resonance imaging and spectroscopy , respectively . Levels of glucose , insulin , liver enzymes , and inflammation markers , as well as individual free fatty acids and free amino acids , were measured in collected blood sample s. Hyperinsulinemic euglycemic clamps were performed to determine whole-body insulin sensitivity . Subcutaneous adipose tissue sample s were collected and analyzed for gene expression patterns and phosphorylation of signaling proteins . RESULTS Postpr and ial levels of BCAAs and methionine were significantly higher in subjects on the AP vs the PP diet . The AP and PP diets each reduced liver fat by 36%-48 % within 6 weeks ( for AP diet P = .0002 ; for PP diet P = .001 ) . These reductions were unrelated to change in body weight , but correlated with down-regulation of lipolysis and lipogenic indices . Serum level of FGF21 decreased by 50 % in each group ( for AP diet P < .0002 ; for PP diet P < .0002 ) ; decrease in FGF21 correlated with loss of hepatic fat . In gene expression analyses of adipose tissue , expression of the FGF21 receptor cofactor β-klotho was associated with reduced expression of genes encoding lipolytic and lipogenic proteins . In patients on each diet , levels of hepatic enzymes and markers of inflammation decreased , insulin sensitivity increased , and serum level of keratin 18 decreased . CONCLUSIONS In a prospect i ve study of patients with type 2 diabetes , we found diets high in protein ( either animal or plant ) significantly reduced liver fat independently of body weight , and reduced markers of insulin resistance and hepatic necroinflammation . The diets appear to mediate these changes via lipolytic and lipogenic pathways in adipose tissue . Negative effects of BCAA or methionine were not detectable . FGF21 level appears to be a marker of metabolic improvement . Clinical Trials.gov ID NCT02402985 OBJECTIVE To evaluate the efficacy of low carbohydrate diet ( LCD ) as compared with low fat diet ( LFD ) to decrease aminotransferase levels in obese women with nonalcoholic fatty liver disease . MATERIAL AND METHODS A total of 59 women were r and omly enrolled in a non-controlled clinical intervention study to receive either LCD or LFD during six months . Apparently healthy non-pregnant obese women aged 20 to 65 years were eligible to participate . Previous diagnosis of hepatic disease , serum creatinine level ≥ 1.5 mg/dL , severe life-limiting medical illness , pregnancy , active participation in other dietary program , use of weight loss drugs , or alcohol consumption ≥ 30 g per day were exclusion criteria . RESULTS A total of 31 obese women who received LCD were compared with 28 women allocated in the LFD group . There were 3 ( LCD group ) and 2 ( LFD group ) women with lost of follow-up . No differences in the proportion of type 2 diabetes , hypertension and hyperlipidemia were noted between women in the LCD and LFD groups . At end of follow-up , there were not significant statistical differences in the anthropometric and biochemical characteristics between women in both groups . The weight loss was 5.7 and 5.5 % for women in the LCD LFD groups . Although the decrease of AST ( 31.7 and 22.4 % ) and ALT ( 41 and 33.3 % ) levels was more elevated in the women of LCD group , as compared with the LFD group , there were not significant statistical differences . CONCLUSIONS Our results show that weight loss , irrespective of the type of diet , reduces aminotransferase levels in obese women with NAFLD OBJECTIVE The aim of our study was to examine the changes in hypertransaminasemia after weight reduction in obese patients with and without NAFLD and the relation with insulin resistance . RESEARCH METHODS A population of 162 obese patients was r and omly allocated to two groups : a ) diet I ( low fat ) and b ) diet II ( low carbohydrate ) , dieting along 3 months .  Patients were classified as group I ( n=112 ) when serum ALT activity was normal or group II ( NAFLD , n=30 ) when serum ALT activity was ( > or=43 UI/L ) . RESULTS In control group with diet I , BMI , weight , fat mass , waist to hip ratio , waist circumference , systolic pressure , total cholesterol , LDL cholesterol , HOMA and insulin levels decreased . In NAFLD group with diet I improved the same parameters and glucose , triglycerides , ALT , AST , gamaglutamine transferase levels , too . In control group with diet II , BMI , weight , fat mass , waist to hip ratio , waist circumference , systolic pressure , total cholesterol , LDL cholesterol , HOMA and insulin levels decreased . In NAFLD group with diet II improved the same parameters and glucose , triglycerides , ALT and gamaglutamine transferase levels , without statistical changes in AST . CONCLUSION We showed that weight reduction secondary to two hypocaloric diets was associated with improvement in hipertransaminasemia and insulin resistance in NAFLD patients In 1997 , the World Health Organization published a l and mark document recognizing obesity as a worldwide disease that poses a serious threat to public health ( 1 ) . Persons who are overweight or obese have substantially increased risk for morbidity from numerous chronic disorders , such as diabetes ( 2 , 3 ) , hypertension ( 4 , 5 ) , and cardiovascular disease ( 6 , 7 ) . Obesity-related health risk is greater when excess fat is deposited in the abdomen region because this phenotype is a stronger predictor of cardiovascular disease and type 2 diabetes mellitus than general obesity is ( 8 - 11 ) . This may be partially explained by excess accumulation of visceral fat , an independent correlate of insulin resistance ( 9 - 11 ) and dyslipidemia ( 8 , 9 ) . These observations highlight the need to identify appropriate treatment strategies to prevent and reduce obesity and suggest that the effectiveness of these treatments would be enhanced if abdominal obesity , particularly visceral fat , was substantially reduced . Diet restriction remains the most common method of obesity reduction ( 12 ) . Despite the observation that low levels of physical activity are a major cause of obesity ( 13 ) , increased physical activity alone is not thought to be a useful strategy for obesity reduction . Some reports have suggested that physical activity in obese adults results in only modest weight loss ( approximately 1 to 2 kg ) independent of the effects of diet restriction ( 14 ) . However , these conclusions are drawn from studies in which individual energy intake and expenditure were not rigorously controlled or accurately measured ( 15 - 17 ) . Moreover , in most studies , the negative energy balance induced by exercise was modest enough that substantial weight loss was not expected ( 15 - 17 ) . Currently , no compelling evidence supports the observation that exercise alone is not a useful method for reducing total or abdominal obesity . It is well known that a single exercise session is associated with a significant improvement in insulin-stimulated glucose uptake ( 18 , 19 ) . It is also clear that weight loss is associated with an improvement in insulin action ( 20 - 24 ) . It is unclear , however , whether regular exercise improves glucose metabolism after the short-term effects of exercise and changes in body fat distribution are considered . Segal and colleagues ( 25 ) controlled for the confounding effect of the last exercise session and body composition changes and found that exercise had no independent effect on insulin sensitivity ( 25 ) . Given the established importance of insulin resistance as an antecedent to both cardiovascular disease and type 2 diabetes mellitus ( 26 ) , it is important to clarify whether exercise improves insulin action independent of fat loss . We performed a r and omized , controlled trial to determine the independent effect of diet-induced or exercise-induced weight loss on obesity and insulin resistance in moderately obese men . We also evaluated whether exercise without weight loss was associated with reductions in abdominal obesity and insulin resistance . Methods Participants Participants were recruited from Kingston , Ontario , Canada , a typical suburban region , through the general media . We selected men with a body mass index greater than 27 kg/m2 and a waist circumference greater than 100 cm whose weight had been stable ( 2 kg ) for 6 months before study entry . Participants were nonsmokers who consumed an average of fewer than two alcoholic beverages per day , had a sedentary lifestyle , and took no medications known to affect the principal outcome measures . All participants had a preparticipation medical examination that included screening for normal glucose tolerance and plasma lipid profile . A computer program was used to r and omly assign eligible men to one of the following four groups : control , diet-induced weight loss , exercise-induced weight loss , and exercise without weight loss ( Figure 1 ) . Of the 101 participants who were r and omly assigned to groups , 34 chose not to participate because they were dissatisfied with their assigned group , 5 were diabetic or dyslipidemic , and 3 were relocated because of job transfers . Those who chose not to participate and those who completed the trial were similar with regard to anthropometric variables . In addition , those who completed the trial were similar to those who did not in each group ( P > 0.10 ) . Baseline characteristics among groups were similar for all participants ( Table 1 ) . All participants gave fully informed written consent . The study was conducted in accordance with the ethical guidelines of Queen 's University . The participants did not receive monetary compensation . Figure 1 . Flow of participants through the study . Table 1 . Selected Anthropometric , Magnetic Resonance Imaging , and Metabolic Variables before Treatment and 3 Months after Treatment Diet and Exercise Regimen During the baseline period , daily energy requirements for all participants were determined by estimating resting energy expenditure and multiplying the obtained value by a factor of 1.5 ( 27 ) . All participants followed a weight maintenance diet ( 55 % to 60 % carbohydrate , 15 % to 20 % protein , and 20 % to 25 % fat ) for a 4- to 5-week baseline period . During this period , body weight was monitored to determine the accuracy of the prescribed energy requirement , which was adjusted accordingly to maintain body weight . Controls were asked to maintain body weight throughout the 12-week treatment period . Participants in the diet-induced weight loss group were asked to reduce the isocaloric diet by 700 kcal/d during the treatment period to achieve a weekly weight loss of approximately 0.6 kg . To lose the same amount of weight , participants in the exercise-induced weight loss group were asked to maintain the isocaloric diet for the duration of the treatment period and to perform exercise that expended 700 kcal/d . Participants assigned to exercise without weight loss were asked to maintain body weight . Therefore , they consumed enough calories to compensate for the energy expended during the daily exercise sessions ( approximately 700 kcal ) . At the end of the treatment period , isocaloric requirements were determined and prescribed for a 2-week weight stabilization period . All participants were free-living and consumed self-selected foods .  No vitamins or other nutritional supplements were prescribed . Each person participated in a series of weekly 1-hour seminars in which a dietitian taught proper food selection and preparation . Participants were told that the composition of the maintenance and energy-reduced diets should be approximately 55 % to 60 % carbohydrate , 15 % to 20 % protein , and 20 % to 25 % fat . Participants kept and analyzed daily , detailed food records for the duration of the study period ( approximately 20 weeks ) ; the study dietitian also review ed these records . For the 2-week period during which doubly labeled water measurements were acquired ( weeks 6 and 7 ) , the diet records were analyzed by using a computerized program ( Food Processor , Esha Research , Salem , Oregon ) . Participants in both exercise groups performed daily exercise ( brisk walking or light jogging ) on a motorized treadmill for the duration of the 12-week trial . The length of each exercise session was determined by the time required to expend 700 kcal . Participants were asked to exercise at an intensity not greater than 70 % of their peak oxygen uptake ( Vo 2 ) ( approximately 80 % of maximal heart rate ) . Energy expenditure was determined by using the heart rate and oxygen consumption data that were obtained from the pretreatment grade d exercise test and were adjusted according to the results of two subsequent tests performed at weeks 4 and 8 . During each session , heart rate was monitored every 5 minutes by using an automated heart rate monitor ( Polar Oy , Kempele , Finl and ) . All exercise sessions were by appointment and were supervised . Peak Vo 2 was determined by using a grade d treadmill test and st and ard open-circuit spirometry techniques ( SensorMedics , Yorba Linda , California ) . Energy Expenditure Total energy expenditure for 14 days was measured by using a two-point doubly labeled water method ( 28 ) . Deuterium enrichment was analyzed by using a 903 deuterium dual-inlet isotope ratio mass spectrometer ( VG Isogas , Cheshire , United Kingdom ) . Oxygen-18 was determined by using a SIRA 12 isotope ratio mass spectrometer ( VG Isogas ) . Total energy expenditure was calculated by using the DeWeir formula ( 29 ) . After an overnight stay in the hospital , resting metabolic rate was measured at 7:00 a.m. by using indirect calorimetry with a modified mask system ( Teem 100 , Aerosport , Inc. , Ann Arbor , Michigan ) . Values were obtained for 30 minutes , and the last 25 minutes were used to determine resting metabolic rate . Resting systolic and diastolic blood pressure were measured when the participant was supine . Magnetic Resonance Imaging and Anthropometric Measurements Whole-body data from magnetic resonance imaging ( approximately 45 equidistant images ) were obtained with a General Electric 1.5-Tesla magnet ( Milwaukee , Wisconsin ) by using an established protocol described in detail elsewhere ( 30 ) . Once acquired , the data were transferred to a st and -alone work station ( Silicon Graphics , Mountain View , California ) for analysis with specially design ed computer software ( Tomovision , Inc. , Montreal , Canada ) , the procedures for which are described elsewhere ( 31 ) . For adipose tissue ( fat ) and skeletal muscle , volume units ( L ) were converted to mass units ( kg ) by multiplying the volumes by the assumed constant density for fat ( 0.92 kg/L ) and fat-free skeletal muscle ( 1.04 kg/L ) ( 32 ) . All anthropometric circumference measurements were obtained by using st and ard procedures described elsewhere ( 30 ) . Insulin Sensitivity and Glucose Tolerance Participants consumed a weight-maintenance diet consisting of at least 200 g of carbohydrate for a minimum of 4 days and were asked to avoid strenuous physical activity for 3 days before insulin Non-alcoholic fatty liver disease ( NAFLD ) is the most common liver disease worldwide , characterized by liver fatty acid accumulation and fibrosis , not due to excessive alcohol consumption . Notably , nutritional habits have been reported to be implicated in the onset and severity of the hepatic damage , while the Mediterranean diet has shown beneficial effects on NAFLD . Free radicals and oxidative stress were suggested to be involved in the pathogenesis and progression of NAFLD , and several data highlighted the efficacy of antioxidant supplementation in its treatment . The aim of this study was to compare the effects of the Mediterranean diet , with or without an antioxidant complex supplement , in overweight patients suffering from NAFLD . In this prospect i ve study , fifty Caucasian overweight patients were r and omized into three groups ( Groups A – C ) . A personalized moderately hypocaloric Mediterranean diet was prescribed to all patients included in the A and B groups . In addition to the diet , Group B was administered antioxidant supplementation daily and for the period of six months . Group C did not have any type of treatment . The study proved that the Mediterranean diet alone or in association with the antioxidant complex  improved anthropometric parameters , lipid profile and reduced hepatic fat accumulation and liver stiffness . However , Group B patients , in which the diet was associated with antioxidant intake , showed not only a significant improvement in insulin sensitivity , but also a more consistent reduction of anthropometric parameters when compared with Group A patients . Taken together , these results support the benefit of antioxidant supplementation in overweight patients with NAFLD OBJECTIVES : Non-alcoholic fatty liver disease is one of the most prevalent liver diseases and increases the risk of fibrosis and cirrhosis . Current st and ard treatment focuses on lifestyle interventions . The primary aim of this study was to assess the effects of a short-term low-calorie diet on hepatic steatosis , using the controlled attenuation parameter ( CAP ) as quantitative tool . METHODS : In this prospect i ve observational study , 60 patients with hepatic steatosis were monitored during a hypocaloric high-fiber , high-protein diet containing 1,000 kcal/day . At baseline and after 14 days , we measured hepatic fat contents using CAP during transient elastography , body composition with bioelectrical impedance analysis , and serum liver function tests and lipid profiles using st and ard clinical –chemical assays . RESULTS : The median age was 56 years ( 25–78 years ) ; 51.7 % were women and median body mass index was 31.9 kg/m2 ( 22.4–44.8 kg/m2 ) . After 14 days , a significant CAP reduction ( 14.0 % ; P<0.001 ) was observed from 295 dB/m ( 216–400 dB/m ) to 266 dB/m ( 100–353 dB/m ) . In parallel , body weight decreased by 4.6 % ( P<0.001 ) , of which 61.9 % was body fat . In addition , liver stiffness ( P=0.002 ) , γ-GT activities , and serum lipid concentrations decreased ( all P<0.001 ) . CONCLUSIONS : This study shows for the first time that non-invasive elastography can be used to monitor rapid effects of dietary treatment for hepatic steatosis . CAP improvements occur after only 14 days on short-term low-calorie diet , together with reductions of body composition parameters , serum lipids , and liver enzymes , pointing to the dynamics of hepatic lipid turnover Although diet-induced weight loss is first-line treatment for patients with nonalcoholic fatty liver disease ( NAFLD ) , long-term maintenance is difficult . The optimal diet for improvement in either NAFLD or associated cardiometabolic risk factors , regardless of weight loss , is unknown . We examined the effect of two ad libitum isocaloric diets ( Mediterranean [ MD ] or low fat [ LF ] ) on hepatic steatosis ( HS ) and cardiometabolic risk factors .  Subjects with NAFLD were r and omized to a 12-week blinded dietary intervention ( MD vs. LF ) . HS was determined by magnetic resonance spectroscopy ( MRS ) .  From a total of 56 subjects enrolled , 49 completed the intervention and 48 were included for analysis . During the intervention , subjects on the MD had significantly higher total and monounsaturated fat , but lower carbohydrate and sodium , intakes compared to LF subjects ( P < 0.01 ) . At week 12 , HS had reduced significantly in both groups ( P < 0.01 ) , and there was no difference in liver fat reduction between groups ( P = 0.32 ) , with mean ( SD ) relative reductions of 25.0 % ( ±25.3 % ) in LF and 32.4 % ( ±25.5 % ) in MD . Liver enzymes also improved significantly in both groups . Weight loss was minimal and not different between groups ( -1.6 [ ±2.1 ] kg in LF vs -2.1 [ ±2.5 ] kg in MD ; P = 0.52 ) . Within-group improvements in Framingham Risk Score ( FRS ) , total cholesterol , serum triglyceride ( TG ) , and glycated hemoglobin ( HbA1c ) were observed in the MD ( all P < 0.05 ) , but not with the LF diet . Adherence was higher for the MD compared to LF ( 88 % vs. 64 % ; P = 0.048 ) . Conclusion : Ad libitum low-fat and Mediterranean diets both improve HS to a similar degree OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity UNLABELLED Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease . Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids . We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard . A total of 170 overweight and obese , otherwise healthy subjects were r and omized to either reduced carbohydrate ( n = 84 ) or reduced fat ( n = 86 ) , total energy restricted diet ( -30 % of energy intake before diet ) for 6 months . Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography . Subjects were also su bmi tted to fat spectroscopy of liver and oral glucose tolerance testing . In all , 102 subjects completed the diet intervention with measurements of intrahepatic lipid content . Both hypocaloric diets decreased body weight , total body fat , visceral fat , and intrahepatic lipid content . Subjects with high baseline intrahepatic lipids ( > 5.56 % ) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values ( < 5.56 % ) irrespective of diet composition . In contrast , changes in visceral fat mass and insulin sensitivity were similar between subgroups , with low and high baseline intrahepatic lipids . CONCLUSION A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet . The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet Introduction Non-Alcoholic Fatty Liver Disease ( NAFLD ) is currently the most common form of liver disease worldwide affecting all ages and ethnic groups and it has become a consistent threat even in young people . Our aim was to estimate the effect of a Low Glycemic Index Mediterranean Diet ( LGIMD ) on the NAFLD score as measured by a Liver Ultrasonography ( LUS ) . Design NUTRIzione in EPAtologia ( NUTRIEPA ) is a population -based Double-Blind RCT . Data were collected in 2011 and analyzed in 2013 - 14 . Setting / participants 98 men and women coming from Putignano ( Puglia , Southern Italy ) were drawn from a previous r and omly sample d population -based study and identified as having moderate or severe NAFLD.InterventionThe intervention strategy was the assignment of a LGIMD or a control diet . Outcome measures The main outcome measure was NAFLD score , defined by LUS . Results After r and omization , 50 subjects were assigned to a LGIMD and 48 to a control diet . The study lasted six months and all participants were subject to monthly controls/checks . Adherence to the LGIMD as measured by Mediterranean Adequacy Index ( MAI ) showed a median of 10.1 . A negative interaction between time and LGIMD on the NAFLD score ( -4.14 , 95 % CI -6.78,-1.49 ) was observed , and became more evident at the sixth month ( -4.43 , 95%CI -7.15 , -1.71 ) . A positive effect of the interaction among LGIMD , time and age ( Third month : 0.07 , 95 % CI 0.02 , 0.12 ; Sixth month : 0.08 , 95 % CI 0.03,0.13 ) was also observed . Conclusions LGIMD was found to decrease the NAFLD score in a relatively short time . Encouraging those subjects who do not seek medical attention but still have NAFLD to follow a LGIMD and other life-style interventions , may reduce the degree of severity of the disease .  Dietary intervention of this kind , could also form the cornerstone of primary prevention of Type 2 Diabetes Mellitus ( T2DM ) and cardiovascular disease Lifestyle interventions remain the cornerstone therapy for non-alcoholic fatty liver disease ( NAFLD ) . This r and omised controlled single-blind clinical trial investigated the effect of Mediterranean diet ( MD ) or Mediterranean lifestyle , along with weight loss , in NAFLD patients . In all , sixty-three overweight/obese patients ( 50 ( sd 11 ) years , BMI = 31·8 ( sd 4·5 ) kg/m2 , 68 % men ) with ultrasonography-proven NAFLD ( and elevated alanine aminotransferase ( ALT ) and /or γ-glutamyl transpeptidase ( GGT ) levels ) were r and omised to the following groups : ( A ) control group ( CG ) , ( B ) Mediterranean diet group ( MDG ) or ( C ) Mediterranean lifestyle group ( MLG ) . Participants of MDG and MLG attended seven 60-min group sessions for 6 months , aim ing at weight loss and increasing adherence to MD . In the MLG , additional guidance for increasing physical activity and improving sleep habits were given . Patients in CG received only written information for a healthy lifestyle . At the end of 6 months , 88·8 % of participants completed the study . On the basis of intention-to-treat analysis , both MDG and MLG  showed greater weight reduction and higher adherence to MD compared with the CG ( all P<0·05 ) at the end of intervention . In addition , MLG increased vigorous exercise compared with the other two study groups ( P<0·001 ) and mid-day rest/naps compared with CG ( P=0·04 ) . MLG  showed significant improvements in ALT levels ( i.e. ALT<40 U/l ( P=0·03 ) and 50 % reduction of ALT levels ( P=0·009 ) ) and liver stiffness ( P=0·004 ) compared with CG after adjusting for % weight loss and baseline  values . MDG improved only liver stiffness compared with CG ( P<0·001 ) after adjusting for the aforementioned variables . Small changes towards the Mediterranean lifestyle , along with weight loss , can be a treatment option for patients with NAFLD Currently , there is no effective therapy for non-alcoholic fatty liver disease ( NAFLD ) , and although calorie restriction is recommended in guidelines , but adherence is an issue . The current study aim ed to determine the effectiveness of eight weeks intermittent fasting ( IF ) strategy in the control of NAFLD activity and the adherence rate of such strategy . This was a r and omized controlled trial with modified alternate-day calorie restriction ( MACR ) , a form of IF , as the active intervention and usual habitual diet as control . The outcome measures included changes in body mass index ( BMI ) , blood lipids ( cholesterol , LDL , HDL and triglyceride ) , fasting blood sugar ( FBS ) , liver enzymes ( ALT and AST ) , and ultrasound measurements of liver steatosis and 2-dimensional shear wave elastography ( SWE ) . Per- protocol ( PP ) analysis was performed with comparison within ( post vs. pre-intervention ) and between ( MACR vs. control ) groups and P < 0.05 as significant . Of 115 individuals with NAFLD , 43 satisfied the study entry criteria , and 33 were r and omised to MACR and 10 to control group , and after 8 weeks , 30 from MACR and 9 from control group completed PP .  Significant reduction in weight and BMI ( P = 0.001 and 0.02 respectively ) was observed in MACR vs. control . Likewise , ALT was reduced with MACR but not control ( P = 0.02 ) . No reductions in lipid parameters and FBS were found in between-group analyses ( all P > 0.22 ) . Both liver steatosis and fibrosis ( SWE ) scores were significantly reduced in MACR vs. controls ( both P < 0.01 ) . Adherence level for MACR remained between 75 - 83 % throughout the study . As a conclusion , eight weeks of IF ( MACR ) strategy appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate Epidemiological data on dietary risk factors for NAFLD from population -based studies , particularly in an ethnically diverse population , are scarce . We examined  dietary factors  in relation to NAFLD risk in African Americans , Japanese Americans , Latinos , Native Hawaiians , and whites in the Multiethnic Cohort ( MEC ) . A nested case-control analysis was conducted within the MEC , a large prospect i ve study with > 215,000 older-adult participants in Hawaii and California . NAFLD was identified using Medicare cl aims data , and controls were selected among participants without liver disease and individually matched to cases by birth year , sex , ethnicity , and length of Medicare enrollment .  Diet was assessed at baseline via a vali date d quantitative food frequency question naire .  Diet-NAFLD associations were quantified by odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) using multivariable conditional logistic regression . The study consisted of 2,974 NAFLD cases ( 518 with cirrhosis ; 2,456 without cirrhosis ) and 29,474 matched controls .  Red meat ( P trend=0.010 ) , processed red meat ( P trend= 0.004 ) , poultry ( P trend= 0.005 ) and  cholesterol  ( P trend= 0.005 ) intakes were positively associated with NAFLD , while  dietary fiber intake ( P trend=0.003 ) was inversely associated with risk . Stronger associations were observed between red meat and cholesterol and NAFLD with cirrhosis than without cirrhosis ( P heterogeneity ≤0.014 ) . Conclusion Dietary factors are independently associated with NAFLD and NAFLD-related cirrhosis in a multiethnic population . Decreasing the consumption of cholesterol , red and processed meat and poultry and increasing consumption of fiber may reduce the risk for NAFLD and related advanced liver disease BACKGROUND & AIMS Non-alcoholic fatty liver disease ( NAFLD ) affects up to 30 % of the population and signifies increased risk of liver fibrosis and cirrhosis , type 2 diabetes , and cardiovascular disease . Therapies are limited . Weight loss is of benefit but is difficult to maintain . We aim ed at examining the effect of the Mediterranean diet ( MD ) , a diet high in monounsaturated fatty acids , on steatosis and insulin sensitivity , using gold st and ard techniques . METHODS Twelve non-diabetic subjects ( 6 Females/6 Males ) with biopsy-proven NAFLD were recruited for a r and omised , cross-over 6-week dietary intervention study . All subjects undertook both the MD and a control diet , a low fat-high carbohydrate diet ( LF/HCD ) , in r and om order with a 6-week wash-out period in- between . Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ( (1)H-MRS ) . RESULTS At baseline , subjects were abdominally obese with elevated fasting concentrations of glucose , insulin , triglycerides , ALT , and GGT . Insulin sensitivity at baseline was low ( M=2.7 ± 1.0 mg/kg/min(-1 ) ) . Mean weight loss was not different between the two diets ( p=0.22 ) . There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD : 39 ± 4 % versus 7 ± 3 % , as measured by (1)H-MRS ( p=0.012 ) . Insulin sensitivity improved with the MD , whereas after the LF/HCD there was no change ( p=0.03 between diets ) . CONCLUSIONS Even without weight loss , MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD , compared to current dietary advice . This diet should be further investigated in subjects with NAFLD BACKGROUND & AIMS It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis ( NASH ) . We examined the association between the magnitude of weight loss through lifestyle modifications and changes in histologic features of NASH . METHODS We conducted a prospect i ve study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks , from June 2009 through May 2013 , at a tertiary medical center in Havana , Cuba . Liver biopsies were collected when the study began and at week 52 of the diet and were analyzed histologically . RESULTS Paired liver biopsies were available from 261 patients . Among 293 patients who underwent lifestyle changes  for 52 weeks , 72 ( 25 % ) achieved resolution of steatohepatitis , 138 ( 47 % ) had reductions in nonalcoholic fatty liver disease activity score ( NAS ) , and 56 ( 19 % ) had regression of fibrosis . At week fifty-two , 88 subjects ( 30 % ) had lost ≥5 % of their weight . Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters ( odds ratios = 1.1 - 2.0 ; P < .01 ) . A higher proportion of subjects with ≥5 % weight loss had NASH resolution ( 51 of 88 [ 58 % ] ) and a 2-point reduction in NAS ( 72 of 88 [ 82 % ] ) than subjects who lost < 5 % of their weight ( P < .001 ) . All patients who lost ≥10 % of their weight had reductions NAS , 90 % had resolution of NASH , and 45 % had regression of fibrosis . All patients who lost 7%-10 % of their weight and had few risk factors also had reduced NAS . In patients with baseline characteristics that included female sex , body mass index ≥35 , fasting glucose > 5.5 mmol/L , and many ballooned cells , NAS scores decreased significantly with weight reductions ≥10 % . CONCLUSIONS A greater extent of weight loss , induced by lifestyle changes , is associated with the level of improvement in histologic features of NASH . The highest rates of NAS reduction , NASH resolution , and fibrosis regression occurred in patients with weight losses ≥10 %
Lifestyle interventions , namely optimizing nutrition and increasing physical activity , remain the cornerstone of therapy for non-alcoholic fatty liver disease ( NAFLD ) , as this can lead to the significant improvement or resolution of disease .
The optimal nutritional approach to treat NAFLD remains unclear .
The aim of this systematic review is to evaluate the effectiveness of different nutritional patterns on hepatic , metabolic , and weight-loss endpoints .