Effects of Hydroxycitric Acid Supplementation on Body Composition, Obesity Indices, Appetite, Leptin, and Adiponectin of Women with NAFLD on a Calorie-Restricted Diet.

Background: This trial assessed the effects of a calorie-restricted diet (CRD) with hydroxycitric acid (HCA) supplementation on appetite-regulating hormones, obesity indices, body composition, and appetite in women with nonalcoholic fatty liver disease (NAFLD). Methods: This study was carried out on 44 overweight/obese women with NAFLD. The patients were randomly assigned into two groups, namely, "Intervention group" (receiving individual CRD plus HCA tablets per day) and "Control group" (receiving only CRD) for eight weeks. Obesity indices, body composition, appetite status, and serum levels of leptin and adiponectin were assessed before and after the intervention. Results: Forty patients completed the trial. At the end of the trial, although significant reductions were found in most of the studied obesity indices in the intervention group, there was only a significant decrease in waist circumference and waist-to-height ratio in the control group. Fat mass and muscle mass significantly decreased in the intervention group (p=0.044 and p=0.024, respectively), and the reduction in visceral fat in the intervention group was significantly greater than that in the control group (-0.49 kg vs -0.37 kg, p=0.024). Intra- and intergroup differences in serum leptin and adiponectin levels and their ratios before and after the trial were not significant. We found a negative and marginally significant correlation between percent of changes in serum adiponectin level and percent of changes in visceral adipose tissue (VAT) (r = -0.429, p=0.067) and BMI (r = -0.440, p=0.059) as well as an inverse relationship between percent of changes in leptin/adiponectin with VAT (r = -0.724, p < 0.001) in the intervention group. Conclusion: HCA plus weight loss diet could significantly reduce visceral adipose tissue without any significant changes in serum leptin and adiponectin levels.

Association of systemic inflammatory indices with anthropometric measures, metabolic factors, and liver function in non-alcoholic fatty liver disease.

The present cross-sectional study aimed to explore the relationship between systemic inflammatory indices (SIIs) and anthropometric measures, metabolic, and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). This study was carried out on 238 NAFLD patients with overweight or obesity, aged 18-55 years. Anthropometric measurements were done and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were estimated. Metabolic factors including serum glucose, lipid profile, liver function biomarkers, and complete blood cell count were assessed after a 24-h fasting state. SIIs including the ratios of neutrophil to lymphocyte (NLR), monocytes to lymphocyte (MLR), platelet to lymphocyte (PLR), and monocytes to high-density lipoprotein cholesterol (MHR) were calculated. Results indicate that apart from PLR, all of the SIIs significantly changed by increasing steatosis severity (all p < 0.05). Moreover, changes in NLR showed a significant association with anthropometric indices including waist circumference (p = 0.032), BMI (p = 0.047), and WHtR (p = 0.002), as well as levels of fasting blood sugar (p = 0.045), triglycerides, (p = 0.025) and low-density lipoprotein cholesterol (p = 0.006). The findings also indicate the relations between lipid profile and all studied SIIs, notably MHR and MLR. All of the SIIs exhibited associations with some liver function indices as well. MHR was positively correlated with the metabolic risk factors of NAFLD while, oppositely, PLR was considered as a preventive marker of NAFLD.

Does myo-inositol supplementation influence oxidative stress biomarkers in patients with non-alcoholic fatty liver disease?

Myo-inositol (MI) is a carbocyclic sugar polyalcohol. MI has known to exert anti-inflammatory, anti-oxidant, and anti-diabetic activities. This study aimed to investigate the effects of MI supplementation on oxidative stress biomarkers in obese patients with non-alcoholic fatty liver disease (NAFLD). In this double-blinded placebo-controlled randomized clinical trial, 51 newly diagnosed obese patients with NAFLD were randomly assigned to receive either MI (4 g/day) or placebo supplements accompanied by dietary recommendations for 8 weeks. Oxidative stress biomarkers, nutritional status, as well as liver enzymes and obesity indices were assessed pre- and post-intervention. A total of 48 patients completed the trial. Although anthropometric measures and obesity indices decreased significantly in both groups, the between-group differences adjusted for confounders were non-significant for these parameters, except for weight (p = .049); greater decrease was observed in the MI group. Iron and zinc intakes decreased significantly in both groups; however, between-group differences were non-significant at the end of the study. No significant between-group differences were revealed for other antioxidant micronutrients at the study endpoint. Sense of hunger, feeling to eat, desire to eat sweet and fatty foods reduced significantly in both groups (p < .05), while the feeling of satiety increased significantly in the placebo group (p = .002). No significant between-group differences were observed for these parameters, except for desire to eat fatty foods; a greater decrease was observed in the MI group (p = .034). Serum levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) significantly increased in both study groups (p < .05); however, the between-group differences were non-significant at the end of the study. Furthermore, the between-group differences were non-significant for other oxidative stress biomarkers, except for serum nitric oxide (NO) level; a greater decrease was observed in the MI group. MI supplementation could significantly improve weight, desire to eat fatty foods, serum levels of NO, as well as the aspartate aminotransferase (AST)/ALT ratio.

Clinical effectiveness of α-lipoic acid, myo-inositol and propolis supplementation on metabolic profiles and liver function in obese patients with NAFLD: A randomized controlled clinical trial.

BACKGROUND: To compare the effects of α-lipoic acid (ALA), myo-inositol (MI) and propolis supplementation on metabolic parameters and liver function in obese patients with non-alcoholic fatty liver disease (NAFLD) METHODS: Ninety-two obese patients with NAFLD were randomly allocated into one of the four groups (ALA, MI, propolis, and control groups) for 8 weeks. At pre-and post-intervention, anthropometric measures, metabolic parameters and liver function were assessed. Clinical effectiveness was assessed using Absolute Risk Reduction (ARR) and Number Needed to Treat (NNT). RESULTS: After 8 weeks, apart from waist-to-hip ratio, all studied anthropometric measures decreased significantly in each of the groups over the trial. Although the greatest improvements in glycemic indices were observed in MI group (p < 0.05), the differences among the groups were not significant. Control group showed the greatest reduction in serum triglyceride level (p = 0.026) while the greatest improvements in serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were observed in MI group (p = 0.043, p = 0.019 and p = 0.041, respectively). Alanine aminotransferase (ALT) levels reduced significantly in all groups, particularly in propolis group (p = 0.012). The greatest reduction in serum aspartate transaminase (AST) level was observed in control group (p < 0.001), however, the difference among the groups was statistically marginal (p = 0.058). The estimated NNTs for one grade reduction in liver steatosis for MI, ALA and propolis supplementation compared with control group were 1.5, 2.2 and 3, respectively. CONCLUSION: Dietary recommendation for weight loss accompanied by MI and then ALA supplementation improved metabolic parameters and liver steatosis. "Registered under ClinicalTrials.gov Identifier no: IRCT20100209003320N22".

Association of neck circumference-related indices with metabolic, atherogenic and liver function biomarkers in patients with non-alcoholic fatty liver disease: a cross-sectional study.

OBJECTIVE: The present study aimed to establish the association of neck circumference (NC)-related indices with metabolic, atherogenic and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). DESIGN: Cross-sectional study. SETTING: Outpatient clinics of Tabriz University of Medical Sciences. PARTICIPANTS: A total of 175 adult patients with NAFLD diagnosed by abdominal ultrasonography were included in this study. Sociodemographic characteristics, anthropometric measures and metabolic, atherogenic and liver function biomarkers were assessed. RESULTS: Results on 107 women and 68 men with NAFLD showed that 52%, 45.1% and 2.9% of patients had mild, moderate and severe NAFLD, respectively. There were significant differences in most of the anthropometric indices, serum levels of ferritin, creatinine and uric acid as well as liver enzymes, and Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI) between the genders (p<0.01). However, no significant differences were found in the glycaemic, lipid profile and atherogenic biomarkers. Both NC and neck-to-height ratio (NHtR) were significantly associated with body mass index (BMI) (p=0.018, p<0.001, respectively), waist circumference (WC) (p<0.001, p=0.044, respectively) and waist-to-hip ratio (WHR) (p<0.001, p=0.026, respectively) while results showed only a significant relationship between neck-to-waist ratio (NWR) with BMI (p<0.001) and WC (p<0.001). Among metabolic factors, there were significant and positive correlations between NC and serum haemoglobin A1c (r=0.198, p<0.001), AST (r=0.300, p<0.001), alanine aminotransferase (ALT) (r=0.348, p<0.001), ferritin (r=0.403, p<0.001) and uric acid (r=0.347, p=0.003) while AST/ALT ratio was inversely related to NC (r=-0.226, p=0.003). APRI, Lipid Accumulation Product Index and also Hepatic Steatosis Index were significantly correlated with NC, NHtR and NWR (p<0.01). CONCLUSIONS AND RELEVANCE: NC-related indices, particularly NC and NHtR, were correlated with some metabolic and liver function biomarkers (apart from lipid profile and atherogenic factors) in patients with NAFLD.

The effect of DASH diet on atherogenic indices, pro-oxidant-antioxidant balance, and liver steatosis in obese adults with non-alcoholic fatty liver disease: A double-blind controlled randomized clinical trial.

Background: The present clinical trial aimed to examine whether adherence to Dietary Approaches to Stop Hypertension (DASH) diet could improve lipid profile, the Pro-oxidant-antioxidant balance (PAB) as well as liver function in obese adults with non-alcoholic fatty liver disease (NAFLD). Methods: Sixty two patients with NAFLD were equally allocated into either DASH or low-calorie diet (LCD) group for 8 weeks. The primary and secondary outcomes were determined before and after the trial. Results: Forty patients completed the trial. Significant within group differences were found in dietary saturated fat, selenium, vitamins A and E as well as body weight and body mass index (BMI) and waist circumference (WC) after the intervention (P<0.05). DASH diet showed greater significant change in systolic and diastolic blood pressure without significant differences between the groups after 8 weeks. Apart from serum high-density lipoprotein cholesterol (HDL-C) and triglyceride/HDL-C, greater reductions were found not only in serum lipids and atherogenic indices (P<0.05) but also in serum aspartate aminotransferase (AST), AST to platelet ratio index (APRI) and lipid accumulation product (LAP) in DASH group in comparison to control group (P=0.008, P=0.019 and P=0.003, respectively). Nevertheless, there was not any difference in PAB level between the groups. Furthermore, adherence to DASH diet was more effective in alleviating liver steatosis compared with usual LCD (P=0.012). Conclusion: Adherence to DASH diet appears to be more effective in improving obesity, atherogenic and liver steatosis biomarkers but not oxidative stress (OS) than usual LCD.

Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of metabolic syndrome is closely associated with type 2 diabetes mellitus. Myo-inositol (MI)-a 6-C sugar alcohol-with insulin-mimetic, anti-diabetic, lipid-lowering, and anti-inflammatory properties has exerted favorable effects on insulin resistance-related disorders and metabolic disease, while recent animal studies revealed its positive effects on liver function. This study aimed to investigate the effects of MI supplementation on cardiometabolic factors, anthropometric measures, and liver function in obese patients with NAFLD. Methods: This double-blinded placebo-controlled randomized clinical trial was carried out on 48 obese patients with NAFLD who were randomly assigned to either MI (4g/day) or placebo (maltodextrin 4g/day) along with dietary recommendations for 8 weeks. Glycemic indices, lipid profile, liver enzymes anthropometric measures, and blood pressure were evaluated pre- and post-intervention. Dietary intakes were assessed using a 3-day 24 h recall and analyzed by Nutritionist IV software. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and beta-cell function (HOMA-B) was also estimated. Results: Anthropometric measures decreased significantly in both groups, while the reduction in weight (p = 0.049) and systolic blood pressure (p = 0.006) in the MI group was significantly greater than in the placebo group after adjusting for baseline values and energy intake. Although energy and macronutrient intakes decreased significantly in both groups, between-group differences were not significant after adjusting for the potential confounders. MI supplementation led to a significant reduction in serum fasting insulin (p = 0.008) and HOMA-IR (p = 0.046). There were significant improvements in lipid profile, liver enzymes, and aspartate aminotransferase/alanine aminotransferase ratio as well as serum ferritin level in the MI group, compared to the placebo group at the endpoint. By MI supplementation for eight weeks, 1 in 3 patients reduced one- grade in the severity of NAFLD. Conclusion: MI supplementation could significantly improve IR, lipid profile, and liver function in patients with NAFLD. Further clinical trials with larger sample sizes, longer duration, different MI doses, and other inositol derivatives are recommended.

The effect of DASH diet on glycemic response, meta-inflammation and serum LPS in obese patients with NAFLD: a double-blind controlled randomized clinical trial.

BACKGROUND: As dietary approaches to stop hypertension (DASH) dietary pattern has been shown to be effective in hypertension and obesity, the present study investigated the effects of following DASH diet on glycemic, meta-inflammation, lipopolysaccharides (LPS) and liver function in obese patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In this double-blind controlled randomized clinical trial, 40 obese patients with NAFLD were randomly allocated into either "DASH diet" (n = 20) or calorie-restricted diet as "Control" (n = 20) group for 8 weeks. Anthropometric measures, blood pressure, glycemic response, liver enzymes, toll-like reseptor-4 (TLR-4) and monocyte chemoattractant protein (MCP-1) and LPS as well as Dixon's DASH diet index were assessed at baseline and after 8 weeks. RESULTS: After 8 weeks, although all obesity indices decreased significantly in both groups, the reduction in all anthropometric measures were significantly greater in DASH vs control group, after adjusting for baseline values and weight change. Fasting glucose level decreased in both group, however, no inter-group significant difference was found at the end of study. Nevertheless, serum levels of hemoglobin A1c (HbA1c), TLR-4, MCP-1 and LPS as well as aspartate aminotransferase (AST) decreased significantly in DASH group, after adjusting for baseline values and weight change (p < 0.001, p = 0.004, p = 0.027, p = 0.011, and p = 0.008, respectively). The estimated number needed to treats (NNTs) for one and two grade reductions in NAFLD severity following DASH diet were 2.5 and 6.67, respectively. CONCLUSION: Adherence to DASH diet could significantly improve weight, glycemia, inflammation and liver function in obese patients with NAFLD.

Non-alcoholic fatty liver disease across endocrinopathies: Interaction with sex hormones.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent chronic liver disease globally. NAFLD is strongly associated with metabolic syndrome and it has been recently suggested that to rename NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). NAFLD has been studied in different endocrine axes and accumulating body of clinical and experimental studies have suggested that NAFLD is associated with polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency (GHD), hypogonadism and other endocrine disorders. In fact, endocrine dysfunction may be considered as the major contributor for the development, progression, and severity of NAFLD. In the present comprehensive review, we discussed the epidemiological and clinical evidence on the epidemiology, pathophysiology, and management of NAFLD in endocrine disorders, with an emphasis on the effects of sex-specific hormones/conditions as well as molecular basis of NAFLD development in these endocrine diseases.

Serum copper, ceruloplasmin, and their relations to metabolic factors in nonalcoholic fatty liver disease: a cross-sectional study.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) characterized by excessive intrahepatic fat accumulation is increasing worldwide. This study aimed to investigate serum copper (Cu) and ceruloplasmin (Cer) levels and their relations to metabolic factors in NAFLD. METHODS: This cross-sectional study was conducted on 141 subjects with NAFLD diagnosed using abdominal ultrasonography. Personal information, anthropometric measures, glucose and lipid profile, and serum levels of liver enzymes were assessed. Fasting serum levels of Cu and Cer were determined using colorimetry and nephelometry assay, respectively. Odds ratios (ORs) were used to examine the associations of serum Cu and Cer levels with NAFLD risk. RESULTS: The results on 85 patients with NAFLD and 56 apparently healthy participants showed that all NAFLD cases and 53.6% of the healthy subjects were overweight or obese. More than half of the patients (58.8%) showed mild NAFLD. Age, weight, BMI, lipid profile, uric acid, and ferritin were significantly higher in NAFLD patients than the healthy cases. No significant differences were found in the concentrations of Cu and Cer between the groups. Only 7.4% of the healthy subjects and 2.4% of the patients were Cu deficient (<70 µg/dl). No association was found between the risk of NAFLD and serum Cu [OR: 0.994; 95% confidence interval (CI): 0.981-1.006] and Cer levels (OR: 0.414; 95% CI: 0.001-123.604) after adjusting for the confounders. CONCLUSION: Our findings revealed no association between Cu deficiency and NAFLD risk. Further human studies with larger sample sizes are required to investigate how Cu and Cer status may affect NAFLD.

Mechanistic insights into the pleiotropic effects of butyrate as a potential therapeutic agent on NAFLD management: A systematic review.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases worldwide. As a multifaceted disease, NAFLD's pathogenesis is not entirely understood, but recent evidence reveals that gut microbiota plays a significant role in its progression. Butyrate, a gut microbiota metabolite, has been reported to have hepato-protective effects in NAFLD animal models. The purpose of this systematic review is to determine how butyrate affects the risk factors for NAFLD. Searches were conducted using relevant keywords in electronic databases up to March 2022. According to the evidence presented in this study, butyrate contributes to a wide variety of biological processes in the gut-liver axis. Its beneficial properties include improving intestinal homeostasis and liver health as well as anti-inflammatory, metabolism regulatory and anti-oxidative effects. These effects may be attributed to butyrate's ability to regulate gene expression as an epigenetic modulator and trigger cellular responses as a signalling molecule. However, the exact underlying mechanisms remain unclear. Human trials have not been performed on the effect of butyrate on NAFLD, so there are concerns about whether the results of animal studies can be translated to humans. This review summarises the current knowledge about the properties of butyrate, particularly its potential effects and mechanisms on liver health and NAFLD management.

The effect of hydroxy citric acid supplementation with calorie-restricted diet on metabolic, atherogenic and inflammatory biomarkers in women with non-alcoholic fatty liver disease: a randomized controlled clinical trial.

The objective of the present study was to examine the effects of hydroxy citric acid (HCA) extracts from Garcinia cambogia on metabolic, atherogenic and inflammatory biomarkers in obese women with non-alcoholic fatty liver disease (NAFLD). The present clinical trial was carried out on 40 overweight/obese women with NAFLD. The patients were randomly allocated into either the "HCA group" (receiving calorie-restricted diet (-700 kcal d-1) accompanied by HCA tablets) and the "control group" (receiving only calorie-restricted diet) for eight weeks. Weight, height, body mass index (BMI), and waist circumference (WC) were measured. Fasting blood sugar (FBS), lipid profile, liver enzymes, as well as inflammatory biomarkers were determined at baseline and after the intervention. Dietary intake was assessed at baseline and at the end of the trial and food intake data were analyzed by the Nutritionist IV software. Results showed a decrease in energy and macronutrient intake in both groups (p < 0.05). Weight, BMI, WC, and hip circumference as well as FBS, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) decreased and high-density lipoprotein cholesterol (HDL-C) increased significantly in the HCA group (p < 0.05). There were also significant reductions in WC, FBS, TG, total cholesterol, LDL-C in the control group while inter-group changes in FBS, TG, LDL-C and HDL-C were statistically significant. Although atherogenic indices reduced significantly in both groups, inter-group comparison revealed that the HCA group showed greater decrease in the TG/HDL-C ratio than the control group (p = 0.004). Other atherogenic indices including TC/HDL-C and non-HDL-C/HDL-C ratio showed greater reduction in the control versus HCA group (p < 0.01). Some inflammatory factors were reduced in the HCA group; however, no significant within- or between-group differences were revealed post-intervention. Our results indicated that HCA supplementation plus calorie-restricted diet could improve some metabolic factors without any significant effect on inflammation in patients with NAFLD.