The effect of soy isoflavones supplementation on metabolic status in patients with non-alcoholic fatty liver disease: a randomized placebo controlled clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) accounts as a crucial health concern with a huge burden on health and economic systems. The aim of this study is to evaluate the effect of soy isoflavones supplementation on metabolic status in patients with NAFLD. METHODS: In this randomized clinical trial, 50 patients with NAFLD were randomly allocated to either soy isoflavone or placebo groups for 12 weeks. The soy isoflavone group took 100 mg/d soy isoflavone and the placebo group took the similar tablets containing starch. Anthropometric indices, blood lipids, glycemic parameters and blood pressure were measured at the beginning and at the end of the study. RESULTS: At the end of week 12 the level of serum triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TC) was significantly decreased only in soy isoflavone group compared to baseline (P < 0.05). Although waist circumference (WC) decreased significantly in both groups after 12 weeks of intervention (P < 0.05), hip circumference (HC) decreased significantly only in soy isoflavone group (P = 0.001). No significant changes observed regarding high density lipoprotein (HDL) and blood pressure in both groups. At the end of the study, serum glucose level was significantly decreased in the placebo group compared to baseline (P = 0.047). No significant changes demonstrated in the soy isoflavone group in regard to glycemic parameters (P > 0.05). CONCLUSIONS: This study revealed that soy isoflavones could significantly reduce TG, LDL TC, WC and HC in NAFLD patients. TRIAL REGISTRATION: The Ethics committee of Ahvaz Jundishapur University of Medical Sciences approved the protocol of the present clinical research (IR.AJUMS.REC.1401.155). The study was in accordance with the Declaration of Helsinki. This study's registered number and date are IRCT20220801055597N1 and 20.09.2022, respectively at https://fa.irct.ir .

The Protective Effects of Syringic Acid on Bisphenol A-Induced Neurotoxicity Possibly Through AMPK/PGC-1α/Fndc5 and CREB/BDNF Signaling Pathways.

Bisphenol A (BPA), an endocrine disruptor, is commonly used to produce epoxy resins and polycarbonate plastics. Continuous exposure to BPA may contribute to the development of diseases in humans and seriously affect their health. Previous research suggests a significant relationship between the increased incidence of neurological diseases and the level of BPA in the living environment. Syringic acid (SA), a natural derivative of gallic acid, has recently considered much attention due to neuromodulator activity and its anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Therefore, in this study, we aimed to investigate the effects of SA on oxidative stress, apoptosis, memory and locomotor disorders, and mitochondrial function, and to identify the mechanisms related to Alzheimer's disease (AD) in the brain of rats receiving high doses of BPA. For this purpose, male Wistar rats received BPA (50, 100, and 200 mg/kg) and SA (50 mg/kg) for 21 days. The results showed that BPA exposure significantly altered the rats' neurobehavioral responses. Additionally, BPA, by increasing the level of ROS, and MDA level, increased the level of oxidative stress while reducing the level of antioxidant enzymes, such as SOD, CAT, GPx, and mitochondrial GSH. The administration of BPA at 200 mg/kg significantly decreased the expression of ERRα, TFAM, irisin, PGC-1α, Bcl-2, and FNDC5, while it increased the expression of TrkB, cytochrome C, caspase 3, and Bax. Moreover, the Western blotting results showed that BPA increased the levels of P-AMPK, GSK3b, p-tau, and Aß, while it decreased the levels of PKA, P-PKA, Akt, BDNF, CREB, P-CREB, and PI3K. Meanwhile, SA at 50 mg/kg reversed the behavioral, biochemical, and molecular changes induced by high doses of BPA. Overall, BPA could lead to the development of AD by affecting the mitochondria-dependent apoptosis pathway, as well as AMPK/PGC-1α/FNDC5 and CREB/BDNF/TrkB signaling pathways, and finally, by increasing the expression of tau and Aß proteins. In conclusion, SA, as an antioxidant, significantly reduced the toxicity of BPA.

The effect of soy isoflavones on non-alcoholic fatty liver disease and the level of fibroblast growth factor-21 and fetuin A.

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Subjects were randomized to either receive two tablets of soy isoflavone (100 mg/day) or placebo. At week 12, the serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and controlled attenuation parameter (CAP) score were significantly decreased only in the soy isoflavone group (P < 0.05). A significant decline in the gamma glutamyl transferase (GGT) level was observed only in the placebo group (P = 0.017). A significant increase in the serum level of fetuin A was shown in both groups at the end of the trial with a significantly greater increment in the soy isoflavone group compared to the placebo group (P < 0.05). The changes in the serum level of FGF-21 were not significant in any of the two groups. Steatosis grade significantly improved only in the soy isoflavone group (P = 0.045). There was no significant change in the fibrosis grade in the groups. Soy isoflavone intake led to a decrease in ALT, AST, CAP score, steatosis grade and an increase in the level of fetuin A. However, no significant changes were observed in the fibrosis grade and serum levels of GGT and FGF-21.

A hypocaloric high-protein diet supplemented with ß-cryptoxanthin improves non-alcoholic fatty liver disease: a randomized controlled trial.

BACKGROUND: Despite promising animal data, there is no randomized controlled trial (RCT) on the effects of high protein (HP)-diet and/or ß-cryptoxanthin in non-alcoholic fatty liver disease (NAFLD). AIMS: Safety and efficacy assessment of a hypocaloric HP-diet supplemented with ß-cryptoxanthin in NAFLD. METHODS: Ninety-two Iranian NAFLD outpatients were recruited for this 12-week, single-center, parallel-group, double-blind RCT and randomized into 4 arms (n = 23): HP-diet and ß-cryptoxanthin (hypocaloric HP-diet + ß-cryptoxanthin), HP-diet (hypocaloric HP-diet + placebo), ß-cryptoxanthin (standard hypocaloric diet + ß-cryptoxanthin), and control (standard hypocaloric diet + placebo). Serum levels of liver enzymes and grade of hepatic steatosis were assessed at baseline and study endpoint as outcome measures. RESULTS: In the intention-to-treat population (N = 92), HP-diet and ß-cryptoxanthin group experienced greater 12-week reductions in serum levels of liver enzymes than control group (mean difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase: - 27.2, - 7.2, - 39.2, and - 16.3 IU/L, respectively; all p < 0.010). Clinical remission rate (achieving grade 0 hepatic steatosis) in HP-diet and ß-cryptoxanthin group (82.6%) was also higher than other groups (13.0%, 17.4%, and 0.0% in HP-diet, ß-cryptoxanthin, and control groups, respectively; p < 0.001). Sixteen patients reported minor adverse events. CONCLUSION: A hypocaloric HP-diet supplemented with ß-cryptoxanthin safely and efficaciously improves NAFLD. TRIAL REGISTRATION NUMBER: This trial was registered at https://www.irct.ir as IRCT2017060210181N10.

An energy-restricted high-protein diet supplemented with ß-cryptoxanthin alleviated oxidative stress and inflammation in nonalcoholic fatty liver disease: a randomized controlled trial.

The efficacy of ß-cryptoxanthin (BCX), a high-protein diet (HPD), or both in reducing oxidative stress and inflammation in nonalcoholic fatty liver disease (NAFLD) has never been examined within a randomized controlled trial (RCT). Thus, we aimed to assess the efficacy of an energy-restricted HPD supplemented with BCX in alleviating these conditions in NAFLD in an RCT design. We hypothesized that this combination may improve oxidative stress and inflammation in NAFLD as compared to a standard energy-restricted diet. Ninety-two ultrasonographically confirmed overweight/obese adult NAFLD patients attending an outpatient clinic in Ahvaz, Iran, were recruited for this 12-week, single-center, parallel-group, double-blind RCT from 2017 to 2018. Subjects were randomized into 4 equal groups (n = 23): HPD-BCX (energy-restricted HPD + BCX), HPD (energy-restricted HPD + placebo), BCX (standard energy-restricted diet + BCX), and control (standard energy-restricted diet + placebo). Serum levels of oxidative stress- and inflammation-related markers, as primary outcome measures, were determined at baseline and at the study end point. The 1-way analysis of covariance models in the intention-to-treat population (N = 92) showed that the HPD-BCX group achieved greater 12-week reductions in malondialdehyde, high-sensitivity C-reactive protein, interleukin-6, and total cytokeratin-18 (CK18-M65) but higher increases in total antioxidant capacity and adiponectin compared to the control group (mean differences for malondialdehyde, high-sensitivity C-reactive protein, interleukin-6, total cytokeratin-18, total antioxidant capacity, and adiponectin were -1.9 nmol/mL, -1.0 mg/L, -2.0 ng/L, -270.9 ng/L, 2.5 U/mL, and 1.9 mg/L, respectively; all P < .001). These results show that an energy-restricted HPD supplemented with BCX more efficaciously alleviates oxidative stress and inflammation in NAFLD as compared to a standard energy-restricted diet.

A randomized, triple-blind, placebo-controlled clinical trial, evaluating the sesamin supplement effects on proteolytic enzymes, inflammatory markers, and clinical indices in women with rheumatoid arthritis.

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200-mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases-3) and inflammatory biomarkers (hs-CRP, IL-1ß, IL-6, TNF-α, and cyclooxygenase-2) were measured with enzyme-linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases-3 decreased significantly in sesamin group. Also, serum levels of hs-CRP, TNF-α, and cyclooxygenase-2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.

Effect of a high-protein diet with ß-cryptoxanthin supplementation on metabolic risk factors, oxidative and inflammatory biomarkers in non-alcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled clinical trial.

BACKGROUND: Excessive hepatic fat is associated with increased metabolic risk factors, production of inflammatory factors, and oxidative stress. High protein intake might trigger an increased hepatic lipid oxidation through an increase in hepatic energy expenditure. Furthermore, the majority of randomized controlled trials (RCT) in humans have failed to show whether carotenoids can be used to prevent and treat non-alcoholic fatty liver disease (NAFLD). However, it is notable and contradictory that NAFLD is rapidly escalating in Iran and other countries with lower intakes of fruit and vegetables (as sources of ß-cryptoxanthin [ß-CX] and carbohydrates) and higher intake of carbohydrates (as an agent of NAFLD); and the effects of ß-CX and a high protein diet (HPD) on NAFLD need to be investigated further. METHODS/DESIGN: This study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for 12 weeks to receive daily ß-CX 6 mg supplementation combined with a HPD on levels of metabolic factors, ß-CX, glycemic and lipid profiles, inflammatory factors, adipocytokines, and body composition. Ninety-two eligible patients, aged 18-60 years, of both genders, who are obese and overweight (body mass index [BMI] 25-40 kg/m2) will be randomly assigned to four groups as follow: HPD + placebo; normal protein diet + ß-CX (NPD + ß-CX); HPD + ß-CX; and NPD + placebo (control group). Two populations will be analyzed in this work. The intention-to-treat (ITT) population includes all patients who will be randomized, while the per-protocol (PP) population includes all individuals who complete the 12- week intervention (i.e. study completers). DISCUSSION: Our findings from this trial will contribute to the knowledge of the relationship between ß-CX supplementation and a HPD on NAFLD patients and determination of optimal macronutrient ratios without energy restriction. TRIAL REGISTRATION: Iran clinical trials registry, IRCT2017060210181N10 . Registered on 20 June 2017.