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.

Selenium and zinc supplementation in HIV-infected patients.

Background: The Human Immunodeficiency Virus (HIV) epidemic is still a public health concern. Micronutrient deficiencies can fasten the progression of this syndrome. Selenium and zinc are essential trace elements, which exert antioxidant and anti-inflammatory activities in HIV infection. The present overview aimed to evaluate the current knowledge from systematic reviews (SRs) of the effects of selenium and zinc supplementation in HIV patients to show the most updated and comprehensive summary of previous SRs. Methods: The current study was performed according to the guidelines of the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statements. To assess the quality of articles we used the Measurement Tool to Checklist Assess Systematic Reviews (AMSTAR). PubMed/Medline, Web of Science, Scopus, and EMBASE databases and Google Scholar web search engine were searched up until March 2022, using relevant keywords. Results: Among 3731 articles assessed, five and four studies met the inclusion criteria for selenium and zinc supplementation, respectively. Four studies found that selenium supplementation can be effective in delaying CD4 decline in HIV-infected patients. In four SRs, the dosage of selenium supplementation was 200 µg/day. Three studies, however, reported no significant effect of zinc supplementation on CD4 cell counts, and HIV viral load. The dosage of zinc supplementation ranged from 12 to 100 mg/day. The intervention duration ranged from 2 weeks to 18 months. Conclusion: In the present study, we identified some clinical evidence of a potential beneficial effect of selenium supplementation in HIV-infected patients.

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 boron citrate supplementation on cardiometabolic factors, inflammatory biomarkers and anthropometric measures in obese patients: study protocol for a randomised, double-blind clinical trial.

INTRODUCTION: Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. The efficacy and safety of boron citrate (BC), a novel therapeutic approach, in patients with obesity are not known. The current trial will take place to determine the effects of BC supplementation on cardiometabolic factors, inflammatory biomarkers, anthropometric measures and body composition in obese patients. METHODS AND ANALYSIS: This double-blind, placebo-controlled, randomised clinical trial will involve 60 eligible obese participants aged 18-60 years. Participants will randomly be allocated to receive either BC capsules (containing 10 mg of boron) in the intervention group or placebo capsules (containing 10 mg of maltodextrin) in the placebo group for 12 weeks. Moreover, physical activity and dietary recommendations will be provided for both groups. To assess the dietary intakes of participants, a 3-day food record (2 days of the week and 1 day of the weekend) will be filled. Cardiometabolic factors, inflammatory biomarkers including tumour necrosis factor α, C reactive protein, interleukin-6 and interleukin-10 levels, anthropometric measures and body composition will be assessed at the baseline and end of the intervention. The findings of this study will provide evidence for the effectiveness of BC in the management of obesity. ETHICS AND DISSEMINATION: There are so far no reported adverse effects associated with the use of boron. This trial was approved by the Ethics Committee of Tabriz University of Medical Sciences (approval number: IR.TBZMED.REC.1401.350). Positive as well as negative findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: IRCT20220806055624N1.

Nutrition interventions to address nutritional problems in HIV-positive patients: translating knowledge into practice.

BACKGROUND: Human immunodeficiency virus (HIV) infection and malnutrition negatively reinforce each other. Malnutrition leads to further immune deficiency and accelerates disease progression. The present overview aimed to investigate the current knowledge from review articles on the role of nutrition interventions as well as food and nutrition policies on HIV-related outcomes in adults to present future strategies for strengthening food and nutrition response to HIV. METHODS: We searched PubMed/Medline, Scopus, Embase, ProQuest, and Ovid databases using the relevant keywords. The search was limited to studies published in English until April 2022. All types of reviews studies (systematic review, narrative review, and other types of review studies) which evaluated the impact of nutritional program/interventions on HIV progression were included. RESULTS: Although nutrition programs in HIV care have resulted in improvements in nutritional symptoms and increase the quality life of HIV patients, these programs should evaluate the nutritional health of HIV-infected patients in a way that can be sustainable in the long term. In additions, demographic, clinical, and nutritional, social characteristics influence nutritional outcomes, which provide potential opportunities for future research. CONCLUSION: Nutrition assessment, education and counseling, and food supplements where necessary should be an integral part of HIV treatment programs.

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.

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".

The effects of probiotics on VCAM-1 and ICAM-1: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: We performed the present systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of probiotics on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels in adults. METHODS: A systematic search current to April 2022 was performed in MEDLINE, EMBASE, and Cochrane Database using relevant keywords to detect eligible articles. A random-effects model was used to estimate the standardized mean difference (SMD) and 95% confidence interval (95% CI). RESULTS: Six eligible trials were included in the final analysis. The pooled analysis revealed that there was a significant reduction in VCAM-1 from baseline to post-probiotic course with standardized mean difference [SMD: -0.66 ng/ml; 95% CI: -1.09, -0.23 ng/ml; P = 0.003]. The effects of probiotic intake on VCAM-1 were more pronounced when it was received via supplements [SMD: -0.61 ng/ml; 95% CI: -1.08, -0.14 ng/ml; P = 0.010], for 12 weeks [SMD: -0.60 ng/ml; 95% CI: -1.09, -0.12 ng/ml; P = 0.014] and when it was prescribed for individuals with metabolic syndrome [SMD: -0.79 ng/ml; 95% CI: -1.40, -0.19 ng/ml; P = 0.010]. Moreover, VCAM-1 levels were decreased in the subgroup of multispecies probiotic regiments [SMD: -0.71 ng/ml; 95% CI: -1.38, -0.04 ng/ml; P = 0.039]. CONCLUSION: Our study demonstrates potential beneficial effects of probiotics on VCAM-1 in adults. However, more larger-scale, long-time RCTs are needed to confirm the accurate effect of probiotics on endothelial dysfunction biomarkers.

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.

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.

Probiotic therapy, a novel and efficient adjuvant approach to improve glycemic status: An umbrella meta-analysis.

BACKGROUND: Probiotics exert several promoting effects on the glycemic status, however, the results of meta-analyses are inconsistent. we conducted an umbrella meta-analysis, across existing systematic reviews and meta-analyses of clinical trials to determine the definite effects of supplementation with probiotics on glycemic indices. METHODS: A comprehensive systematic search of PubMed/Medline, Scopus, EMBASE, and Web of Science was carried out till August 2021. The random-effects model was employed to conduct meta-analysis. Meta-analysis studies of randomized clinical trials examining the impacts of probiotics supplementation on glycemic indices were qualified in the current umbrella meta-analysis. RESULTS: 48 articles out of 693 in the literature search qualified for inclusion in the umbrella meta-analysis. Pooled effects of probiotics on fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), and insulin levels were reported in articles 45, 21, 35, and 33, respectively. The analysis indicated a significant decrease of FPG (ES= -0.51 mg/dL; 95% CI: -0.63, -0.38, p < 0.001), HbA1c (ES = -0.32 mg/dL; 95% CI: -0.44, -0.20, p < 0.001), HOMA-IR (ES= -0.56; 95% CI: -0.66, -0.47, p < 0.001), and insulin levels (ES= -1.09 IU/mL; 95% CI: -1.37, -0.81, p = 0.006) by probiotics supplementation. CONCLUSION: Probiotics have amending effects on FPG, HbA1c, HOMA-IR, and insulin levels. A < 8-week period of probiotic supplementation in the moderate dosages (108 or 109 CFU) is an efficacious approach in improving glycemic parameters. Overall, probiotics could be recommended as an adjuvant anti-hyperglycemic agent.

Nano-curcumin supplementation in critically ill patients with sepsis: a randomized clinical trial investigating the inflammatory biomarkers, oxidative stress indices, endothelial function, clinical outcomes and nutritional status.

Sepsis is a severe reaction and excessive immune response to infection, which can lead to organ dysfunction, and death. This study aimed to investigate the protective effect of nano-curcumin (NC) on inflammatory biomarkers, endothelial function, oxidative stress indices, biochemical factors, nutritional status, and clinical outcomes in patients with sepsis. In the present double-blind placebo-controlled randomized clinical trial, 40 ICU-admitted patients were randomly allocated into either NC or placebo group for 10 days. Both nano-curcumin (160 mg) and placebo were administered via a nasogastric tube twice a day. The mRNA expression of nuclear-related factor 2 (Nrf-2), BCL2 associated X (BAX), B-cell lymphoma 2 (BCL-2), and toll-like receptor 4 (TLR-4) genes in the peripheral blood mononuclear cells (PBMCs), and the serum levels of primary, secondary, tertiary, and exploratory outcomes were assessed before the baseline and on days 5 and 10. There were significant improvements in the primary outcomes, including inflammatory markers (IL-6, IL-18, IL-1ß, IL-10, TLR-4, BCL-2 and BAX), markers of endothelial function (ICAM-1 and VCAM-1), and oxidative stress indices (malondialdehyde (MDA), nuclear-related factor 2 (Nrf-2), catalase, superoxide dismutase (SOD), and TAC) (p < 0.005) in the NC group compared to the placebo group after 10 days, while no significant increase was observed in the glutathione peroxidase (GPx) level between the two groups. However, no significant decrease was observed in the levels of secondary outcomes, including biochemical factors (creatinine, fasting blood sugar (FBS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, triglycerides (TG) and total cholesterol (TC)) (P > 0.05). Our results showed that in the tertiary outcome (nutritional status), there was no significant increase (P > 0.05) except for TLC (P = 0.003). NC supplementation also resulted in a significant decrease in the exploratory outcomes including the SOFA score and the duration of mechanical ventilation (P < 0.05). Supplementation with NC may be a promising treatment strategy for critically ill patients with sepsis. However, further experiments are suggested to investigate the effects of nano-curcumin on biochemical pathways involved in sepsis.

The effects of butyrate supplementation on glycemic control, lipid profile, blood pressure, nitric oxide level and glutathione peroxidase activity in type 2 diabetic patients: A randomized triple -blind, placebo-controlled trial.

BACKGROUND: This study aimed to investigate the effects of oral NaBut on metabolic parameters, blood pressure, and oxidative stress indices including glutathione peroxidase (GPx) and nitric oxide (NO) status in type 2 diabetic patients. METHODS: In the current interventional trial, 42 patients with type 2 diabetes mellitus (T2DM) were randomly allocated into either NaBut (n = 21) or placebo (n = 21) group for six weeks. Serum concentrations of metabolic parameters, GPx, NO as well as blood pressure were assessed before and after the intervention. RESULTS: Within-group findings demonstrated that NaBut administration significantly reduced systolic and diastolic blood pressure (p = 0.016 and p = 0.002, respectively). Blood sugar 2-hr postprandial (BS2hpp) was also significantly decreased in the intervention and placebo groups (p = 0.016 and p = 0.019, respectively), but the between-group differences were not statistically significant. Differences in homeostatic model assessment of insulin resistance (HOMA-IR) were not significant between groups after adjustment for potential confounders (p = 0.061). NaBut supplementation was also found to significantly increase total cholesterol (p = 0.001), low-density lipoprotein cholesterol (p = 0.005), and insulin levels (p = 0.047) compared to the baseline, while decreased NO levels (p = 0.040). However, there were no significant between-group differences in these parameters. No significant differences were also found in other parameters. CONCLUSIONS: We observed significant within-group decreases in systolic and diastolic blood pressure as well as BS2hpp following oral butyrate treatment. While no or even adverse changes in other biochemical parameters were found. Further investigations with longer durations are warranted to more vividly elucidate the effects of NaBut supplementation on patients with T2DM. Registered under Iranian Registry of Clinical Trials website (http://www.irct.ir), Identifier no. IRC T20090609002017N33.

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.

Possible therapeutic effects of boron citrate and oleoylethanolamide supplementation in patients with COVID-19: A pilot randomized, double-blind, clinical trial.

BACKGROUND: The present study aimed to assess the therapeutic effects of boron citrate and oleoylethanolamide supplementation in patients with COVID-19. METHODS: Forty adult patients with a diagnosis of COVID-19 were recruited in the present study. Patients were randomized in a 1:1:1:1 allocation ratio to 1of 4 treatment groups: (A) 5 mg of boron citrate twice a day, (B) 200 mg of oleoylethanolamide twice a day, (C) both therapies, or (D) routine treatments without any study medications. At pre-and post-intervention phase, some clinical and biochemical parameters were assessed. RESULTS: Supplementation with boron citrate alone or in combination with oleoylethanolamide significantly improved O2 saturation and respiratory rate (p < 0.01). At the end of the study, significant increases in white blood cell and lymphocyte count were observed in the boron citrate and combined groups (p < 0.001). Boron citrate supplementation led to a significant decrease in serum lactate dehydrogenase (p = 0.026) and erythrocyte sedimentation rate (p = 0.014), compared with other groups. Furthermore, boron citrate in combination with oleoylethanolamide resulted in a significant reduction in the high-sensitivity C-reactive protein and interleukin-1ß concentrations (p = 0.031 and p = 0.027, respectively). No significant differences were found among four groups post-intervention, in terms of hemoglobin concentrations, platelet count, and serum interleukin-6 levels. At the end of the study, common symptoms of COVID-19 including cough, fatigue, shortness of breath, and myalgia significantly improved in the supplemented groups, compared to the placebo (p < 0.05). CONCLUSION: Supplementation with boron citrate alone or in combination with oleoylethanolamide could improve some clinical and biochemical parameters in COVID-19 patients.

Does nano-curcumin supplementation improve hematological indices in critically ill patients with sepsis? A randomized controlled clinical trial.

Sepsis is the final common pathway to death for severe infectious diseases worldwide. The present trial aimed to investigate the effects of nano-curcumin supplementation on hematological indices in critically ill patients with sepsis. Fourteen ICU-admitted patients were randomly allocated into either nano-curcumin or placebo group for 10 days. The blood indices, serum levels of inflammatory biomarker and presepsin as well as nutrition status, and clinical outcomes were assessed before the intervention and on days 5 and 10. White blood cells, neutrophils, platelets, erythrocyte sedimentation rate (ESR), and the levels of interleukin-8 significantly decreased in the nano-curcumin group compared to the placebo after 10 days of intervention (p = .024, p = .045, p = .017, p = .041, and p = .004, respectively). There was also a marginal meaningful decrease in serum presepsin levels in the intervention group compared to the placebo at the end of the study (p = .054). However, total lymphocyte count showed a significant increase in the nano-curcumin group compared to the placebo at the end-point (p = .04). No significant differences were found in the level of lymphocyte and the ratios of neutrophil/lymphocyte and platelet/lymphocyte between the study groups. Moreover, no significant between-group differences were observed for other study outcomes, post-intervention. Collectively, nano-curcumin may be a useful adjuvant therapy in critically ill patients with sepsis. However, further trials are suggested to examine the effects of nano-curcumin in the management of sepsis and its complications. PRACTICAL APPLICATIONS: Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5- dione) or diferuloylmethane is widely used in medicine due to its several biological properties. Recent evidence has shown that curcumin possesses multiple pharmacological activities including immune-modulatory, antioxidant, anti-inflammatory, anti-cancer, and anti-microbial effects. In this study, it was observed that nano-curcumin at a dose of 160 mg for 10 days, without side effects, reduced some inflammatory factors and regulated the immune responses in sepsis patients. For the first time, this trial was conducted to determine the effect of nano-curcumin on hematological indices and the serum levels of presepsin and IL-8.

Effects of naringenin supplementation on cardiovascular risk factors in overweight/obese patients with nonalcoholic fatty liver disease: a pilot double-blind, placebo-controlled, randomized clinical trial.

OBJECTIVE: Although several experimental models have suggested promising pharmacological effects of naringenin in the management of obesity and its related disorders, the effects of naringenin supplementation on cardiovascular disorders as one of the main complications of nonalcoholic fatty liver disease (NAFLD) are yet to be examined in humans. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, 44 overweight/obese patients with NAFLD were equally allocated into either naringenin or placebo group for 4 weeks. Cardiovascular risk factors including atherogenic factors, hematological indices, obesity-related parameters, blood pressure, and heart rate were assessed pre- and postintervention. RESULTS: The atherogenic index of plasma value, serum non-HDL-C levels as well as total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C, low-density lipoprotein cholesterol/HDL-C, and non-HDL-C/HDL-C ratios were significantly reduced in the intervention group, compared to the placebo group post intervention (P < 0.05). Moreover, there was a significant reduction in BMI and visceral fat level in the intervention group when compared with the placebo group (P = 0.001 and P = 0.039, respectively). Furthermore, naringenin supplementation could marginally reduce systolic blood pressure (P = 0.055). Mean corpuscular hemoglobin increased significantly in the naringenin group compared to the placebo group at the endpoint (P = 0.023). Supplementation with naringenin also resulted in a marginally significant increase in the mean corpuscular hemoglobin concentration when compared with the placebo group (P = 0.050). There were no significant between-group differences for other study outcomes post intervention. CONCLUSION: In conclusion, these data indicate that naringenin supplementation may be a promising treatment strategy for cardiovascular complications among NAFLD patients. However, further trials are warranted.

Effects of naringenin supplementation in overweight/obese patients with non-alcoholic fatty liver disease: study protocol for a randomized double-blind clinical trial.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease worldwide. Flavonoids, a group of natural compounds, have garnered a great deal of attention in the management of NAFLD because of their profitable effects on glucose and lipid metabolism, inflammation, and oxidative stress which are the pivotal pathophysiological pathways in NAFLD. Naringenin is a citrus-derived flavonoid with a broad spectrum of potential biological effects including anti-inflammatory and antioxidant properties, which may exert protective effects against NAFLD. The present clinical trial aims to examine the efficacy of naringenin supplementation on plasma adiponectin and neurogulin-4 (NRG-4) concentrations, metabolic parameters, and liver function indices in overweight/obese patients with NAFLD. METHODS AND ANALYSIS: This is a double-blind, randomized, placebo-controlled clinical study that will investigate the impacts of naringenin supplementation in overweight/obese patients with NAFLD. Liver ultrasonography will be applied to diagnose NAFLD. Forty-four eligible overweight/obese subjects with NAFLD will be selected and randomly assigned to receive naringenin capsules or identical placebo (each capsule contains 100 mg of naringenin or cellulose), twice daily for 4 weeks. Participants will be asked to remain on their usual diet and physical activity. Safety of naringenin supplementation was confirmed by the study pharmacist. The primary outcome of this study is changes in adiponectin circulating levels. The secondary outcomes include changes in NRG-4 levels, liver function indices, metabolic parameters, body weight, body mass index (BMI), waist circumference (WC), blood pressure, and hematological parameters. Statistical analysis will be conducted using the SPSS software (version 25), and P value less than 0.05 will be regarded as statistically significant. DISCUSSION: We hypothesize that naringenin administration may be useful for treating NAFLD by modulating energy balance, glucose and lipid metabolism, oxidative stress, and inflammation through different mechanisms. The current trial will exhibit the effects of naringenin, whether negative or positive, on NAFLD status. ETHICAL ASPECTS: The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1399.439). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT201311250155336N12 . Registered on 6 June 2020.

A comprehensive mechanistic and therapeutic insight into the effect of chicory (Cichorium intybus) supplementation in diabetes mellitus: A systematic review of literature.

BACKGROUND: Cichorium intybus is a rich source of terpenoids and phenolic compounds, one of the effective methods in managing and reducing the complications of chronic diseases such as diabetes mellitus. The purpose of this systematic review was to evaluate the evidence obtained from animal and human studies on the effects of chicory on metabolic indicators (such as inflammation, oxidative stress, blood sugar and dyslipidaemia) of diabetes mellitus. MATERIALS AND METHODS: This systematic search was performed in ProQuest, PubMed, Google Scholar, Scopus, Cochrane Central Register of Controlled Trials, Embase and Science Direct databases and on articles published until August 2021. All of the animal studies and clinical trials included in this systematic review that assessed the effect of chicory on metabolic risk markers in diabetes were published in English language journals. RESULTS: Finally, amongst 686 articles, only 23 articles met the needed criteria for further analysis. Out of 23 articles, 3 studies on humans and 20 studies on animals have been carried out. Fifteen of the 19 studies that evaluated the effect of chicory on the glycaemic index showed that Cichorium intybus improved blood glucose index (it had no effect in two human studies and three animal studies). Ten of the 13 studies evaluating the effect of Cichorium intybus on lipid profiles showed that it improved dyslipidaemia. Also, all 12 studies showed that chicory significantly reduces oxidative stress and inflammation. CONCLUSION: According to the available evidence, Cichorium intybus might improve the glycaemic status, dyslipidaemia, oxidative stress and inflammation. However, further studies are recommended for a comprehensive conclusion about the exact mechanism of chicory in diabetic patients.

Spirulina supplementation as an adjuvant therapy in enhancement of antioxidant capacity: A systematic review and meta-analysis of controlled clinical trials.

BACKGROUND: Spirulina, a type of blue-green algae, is used as an adjuvant treatment of metabolic and inflammatory diseases. Evidence about the effects of spirulina on antioxidant system are conflicting. Thus, this quantitative review aimed to summarise the effects of spirulina administration on antioxidant status biomarkers. METHODS: Systematic searches were conducted using the PubMed/Medline, Scopus, Web of Science and EMBASE, up to May 2021. Random effect analysis was applied to perform meta-analysis. Subgroup analyses and multivariate meta-regression were performed to find heterogeneity sources. Quality assessment was conducted using Cochrane Collaboration's tool. Trim and fill analysis were also carried out in case of the presence of publication bias. RESULTS: A total of nine articles that enrolled 415 subjects were included in the present meta-analysis. Obtained findings exhibited that spirulina supplementation had marginal significant effect on total antioxidant capacity (TAC) (SMD = 0.49; 95% CI: -0.001, 0.98; P = .05) and superoxide dismutase (SOD) activity (SMD = 0.72; 95% CI: -0.03, 1.46; P = .06), while did not affect glutathione peroxidase (GPx) activity (SMD=0.27; 95% CI: -0.23, 0.77; P = .29). CONCLUSIONS: Spirulina consumption may exert beneficial effects on enhancement of antioxidant system. A marginal significant increasing effect on TAC and SOD activity were found by spirulina administration. However, it did not affect GPx activity.