Effect of resveratrol administration on ovarian morphology, determined by transvaginal ultrasound for the women with polycystic ovary syndrome (PCOS).

Intake of resveratrol has been associated with improved ovarian morphology under in vitro and in the animal models; however, this finding has not been confirmed in trials. The aim of our study was, therefore, to use a placebo-controlled approach with the detailed assessment of the ovarian morphology by applying transvaginal ultrasound to examine the effectiveness of this therapeutic approach in this group of women. The mean age of all participants was 28·61 (sd 4·99) years, with the mean BMI of 28·26 (sd 5·62) kg/m2. Resveratrol therapy, as compared with placebo, was associated with a significantly higher rate of improvement in the ovarian morphology (P = 0·02). Women who received resveratrol had a more dominant follicle than those getting placebo, with a significant reduction in the ovarian volume (P < 0·05). However, the number of follicle count per ovary (FNPO), stromal area (SA), ovarian echogenicity and distribution of follicles were not significantly altered (P > 0·05). Forty-one women with polycystic ovary syndrome (PCOS) were randomly assigned (1:1) to 3 months of daily 1000 mg resveratrol or placebo. Random assignment was done by blocked randomisation. Our primary endpoints were the change in the ovarian volume, SA and antral FNPO from the baseline to 3 months. Secondary endpoints were improvement in the distribution of follicles and ovarian echogenicity. Differences between the resveratrol and control groups were evaluated by Chi-square, Fisher's exact test and repeated-measures ANOVA. Treatment with resveratrol significantly reduced the ovarian volume and polycystic ovarian morphology, thus suggesting a disease-modifying effect in PCOS.

Effects of supplementation with main coffee components including caffeine and/or chlorogenic acid on hepatic, metabolic, and inflammatory indices in patients with non-alcoholic fatty liver disease and type 2 diabetes: a randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is much more frequent and more severe, including cirrhosis, hepatocellular carcinoma in patients with type 2 diabetes. Coffee is a complex beverage with hundreds of compounds whereas caffeine and chlorogenic acid are the most abundant bioactive compounds. The published epidemiological data demonstrating beneficial associations between all categories of coffee exposure and ranges of liver outcomes are rapidly growing; however, the main contributors and cause-effect relationships have not yet been elucidated. To address existing knowledge gaps, we sought to determine the efficacy and safety of 6 months chlorogenic acid and/or caffeine supplementation in patients with type 2 diabetes affected by NAFLD. METHODS: This trial was carried out at two Diabetes Centers to assess the effects of supplementation with daily doses of 200 mg chlorogenic acid, 200 mg caffeine, 200 mg chlorogenic acid plus 200 mg caffeine or placebo (starch) in patients with type 2 diabetes and NAFLD. The primary endpoint was reduction of hepatic fat and stiffness measured by FibroScan, and changes in serum hepatic enzymes and cytokeratin - 18 (CK-18) levels. Secondary endpoints were improvements in metabolic (including fasting glucose, homeostasis model assessment-estimated insulin resistance (HOMA-IR), hemoglobin A1c (HBA1C), C-peptide, insulin and lipid profiles) and inflammatory (including nuclear factor k-B (NF-KB), tumor necrosis factor (TNF-α), high sensitive- C reactive protein(hs-CRP)) parameters from baseline to the end of treatment. RESULTS: Neither chlorogenic acid nor caffeine was superior to placebo in attenuation of the hepatic fat and stiffness and other hepatic outcomes in patients with diabetes and NAFLD. Except for the lower level of total cholesterol in caffeine group (p = 0.04), and higher level of insulin in chlorogenic acid plus caffeine group (p = 0.01) compared with placebo, there were no significant differences among the treatment groups. CONCLUSION: These findings do not recommend caffeine and/or chlorogenic acid to treat NAFLD in type 2 diabetes patients. TRIAL REGISTRATION: IRCT201707024010N21 . Registered 14 September 2017.

Effect of resveratrol on menstrual cyclicity, hyperandrogenism and metabolic profile in women with PCOS.

AIM: The aim of this randomized trial was to find whether resveratrol could improve menstrual dysfunction, clinical signs (i.e., acne and hair loss), and the biochemical evidence of hyperandrogenism in the women with PCOS. METHODS: Women, in the age range of 18-40 years, diagnosed with PCOS, as defined by the Rotterdam criteria, and no other known cause of abnormal menstruation, were recruited. Participants were randomized based on a 1:1 ratio, to either 1000 mg resveratrol or 1000 mg placebo daily groups, for a period of 3 months. RESULTS: Seventy-eight patients were randomized: 39 to the resveratrol group and 39 to placebo. Results were analyzed according to the intention-to-treat principle. At the end of study, it was found that women who received resveratrol had a statistically higher regular menstruation rate, as compared to those who got placebo (76.47% vs. 51.61%; p = 0.03), and lower hair loss (32.10% vs. 68.00%; p = 0.009). We also found no significant differences between the two groups in terms of ovarian and adrenal androgens, sex hormone binding globulin (SHBG) levels, free androgen index (FAI), glycoinsulinemic metabolism and lipid profile. Moreover, the resveratrol treatment did not interfere with the thyroid, liver and kidney functions. The negative effect of resveratrol on the body composition was also observed, though not influencing changes in the weight, relative to the placebo group. CONCLUSION: Resveratrol improved menstrual cyclicity and hair loss, even though levels of androgens, insulin and lipids remained unchanged.

The Effect of Oligopin Supplementation on Hormonal and Metabolic Profiles in the Polycystic Ovary Syndrome: A Randomized Controlled Trial.

Background: A double blind clinical trial was performed to evaluate whether the polycystic ovary syndrome (PCOS)-specific serum markers and metabolic parameters would change in the women with PCOS during the three-month administration of oligopin. Methods: In this double-blind multicenter trial, we randomly assigned 80 PCOS women, based on a 1:1 ratio, to receive oligopin (n= 40) or maltodextrin as placebo (n = 40) for up to 3 months. As PCOS-specific outcomes, we investigated the changes in testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Secondary end points were metabolic (fasting glycaemia, hemoglobin A1c (HbA1c), lipids, insulin resistance (HOMA-IR)), anthropometrics parameters and blood pressure from the baseline to the end of treatment. We investigated serum transaminase, alkaline phosphatase (ALP), creatinine (Cr) and blood urea nitrogen (BUN) levels as hepatic and kidney outcomes, respectively. Results: The first participant was enrolled on April 18, 2018, and the last study visit took place on May 14, 2019. PCOS-specific serum parameters did not change during the three-month administration of oligopin (p > 0.05), except for a small increase in the FSH levels (p=0.03). Oligopin neither changed the metabolic profile nor the anthropometric parameters or blood pressure. ALP levels was significantly increased in placebo group, as compared with oligopin (p=0.01). Conclusion: Oligopin supplementation does not seem to be exerting a beneficial effect on both hormonal and metabolic parameters in the women with PCOS. Clinical Trial Registration: www.irct.ir, identifier IRCT20140406017139N3.

Risk factors for non-alcoholic fatty liver disease-associated hepatic fibrosis in type 2 diabetes patients.

AIMS: In patients with type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and liver fibrosis is frequent and presumably associated with increased cardiovascular disease risk and mortality. The objective was to investigate risk factors associated with hepatic fibrosis in patients with type 2 diabetes and NAFLD to provide a basis for the prevention and treatment. METHODS: Liver stiffness measurements (LSM) expressed in kilopascals (kPa) and controlled attenuation parameter (CAP) expressed in dB/m were diagnosed by transient elastography. Hepatic steatosis and significant fibrosis were defined as having a CAP score ≥ 260 dB/m and an LSM score ≥ 8 kPa, respectively. Associations between fibrosis categories with anthropometric and metabolic variables were determined; then, variables with statistical significance in the univariate analysis were included in multivariate model. RESULTS: A total of 108 participant with type 2 diabetes and NAFLD (mean age: 44.69 ± 5.57 years; mean duration of diabetes 4.68 ± 4.24 years) were recruited. In these patients, body mass index, obesity, fat mass, waist circumferences, resting energy expenditure, CAP score, fasting insulin, C-peptide, HbA1C, hs-CRP as well as liver enzymes and systolic blood pressure and diastolic blood pressure were positively associated with fibrosis (all p < 0.05). Using multivariate logistic regression, serum aspartate aminotransferase (OR 1.12; 95% CI 1.06-1.19), waist circumferences (odds ratio [OR] 1.15; 95% CI 1.05-1.25) and C-peptide (OR 3.81; 95% CI 1.5-9.7) remained as independently associated with liver fibrosis. CONCLUSION: For participants with type 2 diabetes with coexisting NAFLD, stratification by independent risk factors for fibrosis could have important prognostic value.