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.

Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1α, PPAR-γ, CEBP-α and CEBP-ß genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD). METHODS: Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: At the endpoint, mRNA expression levels of SIRT1(p = 0.001), PGC-1α (p = 0.011) and AMPK (p = 0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-γ, CEBP-α and CEBP-ß between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p = 0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1α as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in triglyceride was inversely correlated with percent of changes in the expression levels of SIRT1. CONCLUSION: OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "REGISTERED UNDER IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER NO: IRCT20090609002017N32".

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.

The effect of propolis supplementation in improving antioxidant status: A systematic review and meta-analysis of controlled clinical trials.

The present study aimed to assess the effect of propolis supplementation on oxidative status, a key contributor to the etiology of many chronic diseases. A systematic search of multiple databases, including Web of Science, SCOPUS, Embase, PubMed, and Google Scholar, was conducted from inception to October 2022 to identify articles examining the effect of propolis on glutathione (GSH), glutathione peroxidase (GPX), total antioxidant capacity (TAC), superoxide dismutase (SOD), and malondialdehyde (MDA) levels. The quality of the included studies was evaluated using the Cochrane Collaboration tool. A total of nine studies were included in the final analysis, and a random-effects model was used to pool the estimated effects. Results showed that propolis supplementation significantly increased the levels of GSH (SMD = 3.16; 95% CI: 1.15, 5.18; I2 = 97.2%), GPX (SMD = 0.56; 95% CI: 0.07, 1.05; p = 0.025; I2 = 62.3%), and TAC (SMD = 3.26; 95% CI: 0.89, 5.62; I2 = 97.8%, p < 0.001). However, the effect of propolis on SOD was not significant (SMD = 0.05; 95% CI: -0.25, 0.34; I2 = 0.0%). Although the MDA concentration was not significantly decreased overall (SMD = -0.85, 95% CI: -1.70, 0.09; I2 = 93.3%), a significant decrease in MDA levels was observed at doses ≥1000 mg/day (SMD = -1.90; 95% CI: -2.97, -0.82; I2 = 86.4) and supplementation durations of less than 11 weeks (SMD = -1.56; 95% CI: -2.60, -0.51; I2 = 90.4). These results suggest that propolis is a safe supplement with a beneficial effect on GSH, GPX, and TAC levels and may be an effective adjunctive therapy for diseases where oxidative stress is a key factor in the etiology. However, further high-quality studies are necessary to make more precise and comprehensive recommendations given the limited number of studies, clinical diversity, and other limitations.

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".

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.

Effects of Probiotics Supplementation on CRP, IL-6, and Length of ICU Stay in Traumatic Brain Injuries and Multiple Trauma Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Method: This meta-analysis aims to evaluate the effectiveness of probiotics in reducing inflammatory biomarkers and the length of intensive care unit (ICU) stays. PubMed-Medline, SCOPUS, Embase, and Google Scholar databases up to July 2021 were searched. The meta-analysis was carried out using random-effect analysis. To determine the sources of heterogeneity, subgroup analyses were performed. In case of the presence of publication bias, trim and fill analysis was carried out. The Cochrane Collaboration tool was used for checking the quality assessment. We hypothesized that probiotics would improve inflammatory markers (CRP and IL-6) and the length of ICU stay in traumatic brain injury and multiple trauma patients. Results: The present meta-analysis, which includes a total of seven studies, showed that there were no significant effects of probiotics supplementation on interleukin (IL)-6 (Hedges's g = -2.46 pg/ml; 95% CI: -12.16, 7.25; P=0.39), C-reactive protein (CRP) (Hedges's g = -1.10 mg/L; 95% CI: -2.27, 0.06; P=0.06), and the length of staying in ICU. The overall number of RCTs included in the analysis and the total sample size were insufficient to make firm conclusions. Conclusion: As a result, more carefully designed RCTs are needed to investigate the effect of probiotics on inflammatory biomarkers and the length of ICU stay in traumatic brain injuries and multiple trauma patients in greater detail.

Propolis supplementation in obese patients with non-alcoholic fatty liver disease: effects on glucose homeostasis, lipid profile, liver function, anthropometric indices and meta-inflammation.

This study assessed the effects of propolis supplementation on glucose homeostasis, lipid profile, liver function, anthropometric indices and meta-inflammation in patients with non-alcoholic fatty liver disease (NAFLD). In this double-blind placebo-controlled randomized clinical trial, 44 patients with NAFLD confirmed by ultrasonography findings were randomly allocated into either the "propolis" (n = 23) or "placebo" (n = 21) group along with a calorie-restricted diet (-500 kcal d-1) for 8 weeks. Fasting serum levels of metabolic factors, liver enzymes, and inflammatory factors, as well as anthropometric indices, dietary intake and appetite status were assessed pre-and post-intervention. The liver fibrosis score, homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were also calculated. The weight, body mass index (BMI), waist and hip circumferences, and waist to height ratio significantly decreased in both groups (p < 0.001), while the waist to hip ratio (p = 0.006) and serum level of total cholesterol (p = 0.038) decreased only in the propolis arm. However, no significant changes in anthropometric measurements and lipid profile were found between the groups at the end of the intervention. Fasting blood sugar (p = 0.037), the serum insulin level (p = 0.040), HOMA-IR (p = 007), desire to eat sweet foods (p = 0.005) and the NAFLD fibrosis score (p = 0.013) decreased significantly in the propolis group compared to the placebo group, post-intervention after adjusting for baseline values and potential confounders. However, QUICKI showed a significant increase (p = 0.015) in the propolis arm compared to the placebo at the study endpoint. Although there were significant reductions in the serum levels of inflammatory factors including tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4) and monocyte chemoattractant protein-1 (MCP-1), as well as liver enzymes and severity of fatty liver, between-group differences were not statistically significant after adjusting for the potential confounding factors. The estimated number needed to treat (NNT) due to 8-week propolis supplementation (510 mg per day) for at least 1-point improvement in NAFLD severity was found to be approximately 3. In conclusion, propolis supplementation along with a calorie-restricted diet for 8 weeks could significantly improve the glucose homeostasis, hepatic fibrosis score and liver function in patients with NAFLD. Further clinical trials are encouraged to study the effects of propolis supplementation in patients with long-term NAFLD.

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.

The impact of L-citrulline supplementation on glucose homeostasis, lipid profile, and some inflammatory factors in overweight and obese patients with type 2 diabetes: A double-blind randomized placebo-controlled trial.

This study investigated the impact of L-citrulline on glucose homeostasis, lipid profile, and inflammatory factors in overweight and obese patients with type 2 diabetes (T2D). In total, 54 participants with T2D were assigned to L-citrulline (3 g/day L-citrulline) or placebo groups and tested for 8 weeks. Serum levels of insulin, fasting glucose, hemoglobin A1c (HbA1c), lipid profile, tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and L-citrulline were measured pre- and post-intervention. Totally, 45 patients were enrolled in the research. L-citrulline supplementation decreased serum levels of insulin (p = .025), glucose (p = .032), HbA1c (p = .001), HOMA-IR (p = .037), TNF-α (p = .036), and hs-CRP (p = .027) significantly. At the end of the study, despite the significant decrease in serum levels of triglyceride (p = .027) and the increase in high-density lipoprotein cholesterol levels (p < .001) in the L-citrulline group, no significant differences were found for these parameters between the groups. Moreover, no significant inter- and intra-group changes were observed for dietary intakes, anthropometric indices, total and low-density lipoprotein cholesterol levels (p > .05). In conclusion, L-citrulline supplementation might improve glucose homeostasis, some lipid factors and inflammatory markers in overweight and obese patients with T2D.

Effect of high-dose vitamin D supplementation in combination with weight loss diet on glucose homeostasis, insulin resistance, and matrix metalloproteinases in obese subjects with vitamin D deficiency: a double-blind, placebo-controlled, randomized clinical trial.

As there is limited and inconsistent evidence in potential role of vitamin D on insulin resistance and matrix metalloproteinases, this study aimed to examine the effect of vitamin D supplementation on glucose homeostasis, insulin resistance, and matrix metalloproteinases in obese subjects with vitamin D deficiency. A total of 44 participants with serum 25-hydroxyvitamin D (25(OH)D) level ≤ 50 nmol/L and body mass index (BMI) 30-40 kg/m2 were randomly allocated into receiving weight reduction diet with either 50 000 IU vitamin D3 pearl (n = 22) or placebo (n = 22) once weekly for 12 weeks. Primary outcomes were changes in fasting serum glucose (FSG), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and matrix metalloproteinases (MMPs). Secondary outcomes were changes in weight, BMI, 25(OH)D, calcium, phosphorous and parathyroid hormone (PTH). Sun exposure and dietary intakes were also assessed. Serum levels of 25(OH)D3 increased significantly with a simultaneous decrease in serum concentration of PTH in the vitamin D group. Weight, BMI, FSG, and MMP-9 decreased significantly in both groups, and there were significant differences in changes in weight, serum 25(OH)D3, PTH, and MMP-9 levels between the groups. Within- and between-groups analysis revealed no significant differences in serum calcium, phosphorous, serum insulin, HOMA-IR, QUICKI, and MMP-2 after intervention. Our results indicated that improvement in vitamin D status resulted in greater reductions in weight and MMP-9 during weight loss. These preliminary results are sufficient to warrant a bigger study group.

Potential roles of Citrulline and watermelon extract on metabolic and inflammatory variables in diabetes mellitus, current evidence and future directions: A systematic review.

OBJECTIVE: Diabetes mellitus is a prevalent endocrine disorder worldwide. Citrulline is an α-amino acid, which is abundant in watermelon, and a precursor of arginine and nitric oxide. Decreased bioavailability of nitric oxide is associated with insulin resistance. The present systematic review focused on the existing evidence of citrulline and watermelon extract effects on metabolic and inflammatory parameters in diabetes mellitus. METHODS: A systematic search of the databases PubMed, Scopus, EMBASE, ProQuest and Google Scholar was conducted for relevant papers published from inception until October 2018. All clinical trials, animal and in vitro studies published in the English language that assessed the role of citrulline and watermelon extract on diabetes mellitus, were eligible. Studies providing inadequate information were excluded. RESULTS: Out of 1262 articles we found, only eight articles met the inclusion criteria for analysis. In three studies an increase in the synthesis of nitric oxide was reported with citrulline and watermelon extract supplementation. Four studies showed a significant reduction in blood glucose after supplementation with watermelon extract, and two studies reported a decrease in a number of inflammatory biomarkers following citrulline supplementation. Although citrulline intake caused a significant reduction in HOMA-IR in one study, inconsistent results were revealed on the effects of citrulline and watermelon extract on insulin levels and lipid profile. CONCLUSION: Citrulline and watermelon extract could improve nitric oxide synthesis, glycaemic status and inflammation in diabetes mellitus. However, further studies are required to shed light on the underlying mechanisms.

Effect of vitamin D supplementation in combination with weight loss diet on lipid profile and sirtuin 1 in obese subjects with vitamin D deficiency: a double blind randomized clinical trial.

Background: Due to inconsistent evidence regarding the potential role of vitamin D on lipid profile and sirtuin 1 (SIRT-1), this study was designed to investigate the effect of vitamin D supplementation in combination with weight loss diet on lipid profile and SIRT-1 in obese subjects with vitamin D deficiency. Methods: Forty-four obese subjects with vitamin D deficiency were randomly assigned in a randomized clinical trial to receive either a weight reduction diet supplemented with 50000IU vitamin D3 pearl (n = 22) or placebo (n = 22) once weekly for 12 weeks. Changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and low high density lipoprotein cholesterol (HDL-C) and SIRT-1 were the primary outcomes. Secondary outcomes were changes in body mass index (BMI), 25(OH) D and parathyroid hormone (PTH). Physical activity and dietary intakes were also assessed. Results: During the intervention, PTH (mean difference, -33.36; 95% CI: -49.15 to -17.57;P<0.001) and LDL-C (mean difference, -15.91; 95% CI: -21.76 to -10.07; P<0.001) decreased and 25(OH) D (mean difference, 36.44; 95% CI: 29.05 to 43.83; P<0.001) increased significantly in the vitamin D group. BMI (mean differences: -2.40; 95% CI: [-2.92 to-1.88] in vitamin D group and mean differences: -1.90; 95% CI [-6.58 to -3.01] in placebo group, P<0.05 for both groups), TC (mean difference,-21.31; 95% CI: -27.24 to -15.38; P<0.001 in vitamin D group and mean difference, -12.54; 95% CI: -19.02 to -6.06; P<0.001 in placebo group) and TG (mean difference,-21.31; 95% CI: -27.24 to -15.38; P<0.001in vitamin D group and mean difference, -12.54; 95% CI: -19.02 to -6.06; P<0.001 in placebo group) decreased and SIRT-1(mean difference, 3.95; 95% CI: 1.18 to 6.73; P=0.007in vitamin D group and mean difference,1.91; 95% CI: 0.31 to 3.63 in placebo group, P=0.022) increase significantly in both group. At end of the study, 25(OH) D and PTH showed significant differences in between-group analyses(P<0.05). No significant difference was detected for HDL-C in within and between groups. Conclusion: This study gives no support for any beneficial effect of vitamin D supplementation on lipid profile and SIRT-1 in obese subjects with vitamin D deficiency.

Oral α-lipoic acid supplementation in patients with non-alcoholic fatty liver disease: effects on adipokines and liver histology features.

Considering the importance of adipokines in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and due to the possible beneficial effects of α-lipoic acid (α-LA) on these adipose-derived hormones, this study aimed to investigate the effect of α-LA supplementation on adipokines and liver steatosis in obese patients with NAFLD. In a double-blind, placebo-controlled randomized clinical trial with two parallel groups, fifty patients with NAFLD were randomized to receive daily supplementation with either two capsules of α-LA (each capsule containing 600 mg α-LA) or two placebo capsules, daily for 12 weeks. At the baseline, all participants received consultation on how to implement a healthy diet into their daily lives. Anthropometric measures, dietary intakes, liver enzymes and adipokines were assessed at the baseline and after 12 weeks of intervention. A significant reduction was observed in the serum levels of insulin (P = 0.024) and leptin (P = 0.019) in the α-LA group compared to the placebo group, but changes in anthropometric and body composition measures, serum glucose (FSG), resistin, irisin and liver enzymes did not differ between the groups. α-LA supplementation resulted in a statistically significant elevation in the quantitative insulin sensitivity check index (QUICKI) (P = 0.033), serum levels of adiponectin (P = 0.008) and adiponectin-to-leptin ratio (P = 0.007) compared to the placebo. The liver steatosis intensity improved significantly. Nonetheless, no significant differences were observed between the study groups in the liver steatosis intensity, at the end of the study. According to the results, α-LA supplementation for 12 weeks improved insulin resistance, serum levels of insulin, adiponectin and leptin without changing anthropometric measures, serum liver enzymes, resistin and irisin.

Effect of vitamin D supplementation along with weight loss diet on meta-inflammation and fat mass in obese subjects with vitamin D deficiency: A double-blind placebo-controlled randomized clinical trial.

BACKGROUND & AIMS: Low serum 25-hydroxyvitamin D (25OHD) is common in obese people. Obesity is associated with a state of low-grade inflammation (meta-inflammation). There is an increasing evidence indicating that vitamin D has anti-adipogenic activity and immunoregulatory effect. This study aimed to assess the effect of vitamin D supplementation on meta-inflammation and fat mass in obese subjects with vitamin D deficiency. MATERIALS AND METHODS: In this double-blind placebo-controlled randomized clinical trial, 44 obese subjects with vitamin D deficiency (25OHD < 50 nmol/L) were assigned into vitamin D (a weight reduction diet + bolus weekly dose of 50 000 IU vitamin D) or placebo group (weight reduction diet + edible paraffin weekly) for 12 weeks. Weight, fat mass and serum levels of 25OHD, calcium, parathyroid hormone (PTH), monocyte chemoattractant protein-1 (MCP-1), interleukin-1ß (IL-1ß) and Toll-like receptor 4 (TLR4) were assessed before and after the intervention. RESULTS: Vitamin D supplementation resulted in significant increase of serum 25OHD level (P < 0.001), and significant decrease in PTH (P < 0.001), MCP-1 (P < 0.05), IL-1ß (P < 0.05) and TLR-4 (P < 0.05); compared to the baseline values in vitamin D group. Weight, BMI and fat mass decreased in both groups (P < 0.05). Between the groups, there were significant decrease in weight, fat mass, serum MCP-1 and PTH concentrations and significant increase in serum 25OHD concentrations after intervention with vitamin D supplementation compared to placebo (P < 0.05). CONCLUSIONS: Improvement in vitamin D status in obese subjects with vitamin D deficiency in combination with weight loss diet resulted in weight, fat mass and MCP-1 decrease. Weight loss and vitamin D supplementation may act synergistically to reduce levels of meta-inflammation.

The antioxidant activity of artichoke (Cynara scolymus): A systematic review and meta-analysis of animal studies.

Current evidence has shown antioxidant activity of artichoke as a potent source of antioxidant compounds. However, it seems that the antioxidant activity of artichoke has not yet been reviewed. Therefore, the present study was designed to perform a systematic review of human studies, animal models, and in vitro systems and to conduct a meta-analysis of animal studies on the antioxidant effects of artichoke. We searched four electronic databases till April 2018 using relevant keywords. All English language articles were assessed. For animal studies, standardized mean difference was pooled using a random effects model. The included studies were evaluated for eligibility and risk of bias. Thirty-nine articles (two human, 23 animal, and 14 in vitro studies) were reviewed. The results of in vitro systems supported the antioxidant effect of artichoke, whereas limited clinical trials indicated no change or a slight improvement of antioxidant status. Finding of animal studies indicated that artichoke extract supplementation increased superoxide dismutase, catalase, glutathione, and glutathione peroxidase level in liver, as well as, decreased malondialdehyde level in liver and plasma of animals with induced disease significantly compared with comparison group. This meta-analysis provided convincing evidence for antioxidant activity of artichoke in animals.

The effect of alpha-lipoic acid on inflammatory markers and body composition in obese patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Some animal studies suggest that alpha-lipoic acid (ALA) can improve disease outcome. The aim of this study was to investigate the effects of ALA supplementation on liver enzymes and inflammatory markers in obese patients with NAFLD. METHODS: In the current randomized, double-blind, placebo-controlled clinical trial, 50 obese patients with NAFLD were randomly allocated to either "ALA"(received 1200 mg ALA as two capsules per day plus 400 mg vitamin E) or "placebo"(received placebo containing starch, as two capsules per day plus 400 mg vitamin E) groups for 12 weeks. Body composition and anthropometric measures, serum levels of liver enzymes, adiponectin, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and ferritin were measured at baseline and the end of the study. RESULTS AND DISCUSSION: A total number of 45 patients completed the study (ALA group = 23; placebo group = 22). The serum concentration of IL-6 decreased significantly in ALA group in comparison with the placebo group, at end of the study (P = 0.049). Furthermore, ALA intake resulted in a significant increase in serum adiponectin levels compared to placebo (P = 0.008). A significant improvement was observed in liver steatosis grade of the patients in both groups, compared to baseline (P < 0.05). However, there was no difference between the two groups for the changes in liver steatosis, by the end of the study. Body composition and anthropometric measures, liver enzymes, MCP-1 and ferritin serum levels were not significantly different between the study groups, neither at the baseline nor at the end of the study. WHAT IS NEW AND CONCLUSION: Collectively, ALA supplementation improved serum adiponectin and IL-6 levels, without changing serum liver enzymes and liver steatosis in obese patients with NAFLD.

Effects of artichoke leaf extract supplementation on metabolic parameters in women with metabolic syndrome: Influence of TCF7L2-rs7903146 and FTO-rs9939609 polymorphisms.

The metabolic syndrome (MetS) is a multicomponent condition with a complex etiology involving genetic and environmental factors. Artichoke leaf extract (ALE) has shown favorable effects on lipid and glucose metabolism. The present study aimed to investigate the effects of ALE supplementation on metabolic parameters in women with MetS, using a nutrigenetics approach. In this double-blind randomized clinical trial, 50 women (aged 20-50 years) with MetS were randomly allocated into the two groups: "ALE group" (received 1,800 mg hydroalcoholic extract of artichoke as four tablets per day) and "placebo group" (received placebo consisted of corn starch, lactose, and avicel as four tablets per day) for 12 weeks. The biochemical and anthropometric parameters were determined before and after the intervention. The FTO-rs9939609 and the TCF7L2-rs7903146 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism. In carriers of A allele of the FTO-rs9939609, ALE supplementation resulted in a statistically significant decrease in serum triglyceride level compared with placebo (-19.11% vs. 10.83%; p < .05), with no other significant differences between the two groups. The TCF7L2-rs7903146 polymorphism showed no interaction with response to ALE (p > .05). These findings suggest that ALE supplementation may improve serum triglyceride level in A allele genotype of FTO-rs9939609 polymorphism in women with MetS.

Antioxidant response to artichoke leaf extract supplementation in metabolic syndrome: A double-blind placebo-controlled randomized clinical trial.

BACKGROUND: Oxidative stress is associated with most components and complications of Metabolic Syndrome (MetS). Artichoke Leaf Extract (ALE) has demonstrated anti-oxidant properties in both laboratory and animal studies. AIM: This study was designed to examine the effects of ALE on oxidative stress indices in patients with MetS. METHODS: In the current double-blind placebo-controlled randomized clinical trial, 80 patients with MetS were randomly allocated to either "ALE group" (received 1800 mg ALE as four tablets per day) or "Placebo group" (received placebo containing cornstarch, lactose and avicel as four tablets per day) for 12 weeks. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), oxidized-LDL (ox-LDL), red blood cell glutathione peroxidase (GPx) and superoxidase dismutase (SOD), as well as dietary intakes were assessed at baseline and at the end of the study. RESULTS: A total number of 68 patients completed the study (ALE group = 33; placebo group = 35). Dietary intakes of energy, macronutrients, and micronutrients were not significantly different between two groups throughout the trial, with the exception of zinc (p < 0.05). The concentration of ox-LDL decreased significantly in ALE group in comparison to the placebo group (-266.8 ± 615.9 vs -129.5 ± 591.2 ng/L; p < 0.05). However, no significant inter- and intra-group changes in MDA, SOD, GPx, and TAC concentrations were observed. CONCLUSION: ALE decreased serum ox-LDL level in patients with MetS, with no beneficial effects on other antioxidant indices. CLINICAL TRIAL REGISTRATION NUMBER: IRCT201409033320N9.

Glucose homeostasis, insulin resistance and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: Beneficial effects of supplementation with microalgae Chlorella vulgaris: A double-blind placebo-controlled randomized clinical trial.

BACKGROUND: Chlorella vulgaris (C. vulgaris) is reported to improve dyslipidemia and hypertension; however, its effect on inflammatory biomarkers and insulin resistance has not been noticed thus far. Non-alcoholic fatty liver disease (NAFLD) as a hepatic symptom of metabolic syndrome is strongly associated with insulin resistance and inflammation. AIM OF THE STUDY: In the current interventional trial, we aimed to study the effects of C. vulgaris supplementation on glucose homeostasis, insulin resistance and inflammatory biomarkers in patients with NAFLD. METHODS: Seventy NAFLD patients confirmed by ultra-sonographic findings were randomly assigned into intervention group (four 300 mg tablets of C. vulgaris) or placebo group (four 300 mg tablets of placebos) for 8 weeks. Anthropometric measurements, liver enzymes, fasting serum glucose (FSG), insulin, high sensitive C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-α) were assessed and homeostatic model assessment (HOMA) score for insulin resistance was estimated before and after the intervention. RESULTS: Anthropometric measurements decreased significantly in both group (p < 0.001). However, mean reduction in weight was significantly higher in C. vulgaris - treated group compared to placebo group. Serum concentrations of liver enzymes, FSG and hs-CRP also significantly decreased and serum insulin concentration and HOMA score increased significantly only in C. vulgaris-treated group (P < 0.001, P < 0.006 and P < 0.025, respectively). Mean change in serum glucose and TNF-α levels were significant between the groups even after adjusting for the serum insulin and baseline values of variables (P = 0.014, P = 0.005, P = 0.014, respectively); between-group differences were not significant for the other variables by the end of study. CONCLUSION: To our finding, C. vulgaris supplementation could be considered as an adjunctive therapy to decrease weight and improve glycemic status and reducing hs-CRP as well as improving liver function in patients with NAFLD. IRCT NUMBER: 201202233320N7.