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 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.

Dietary protein intake and mortality among survivors of liver cirrhosis: a prospective cohort study.

BACKGROUND: Liver cirrhosis is a worldwide burden and is associated with poor clinical outcomes, including increased mortality. The beneficial effects of dietary modifications in reducing morbidity and mortality are inevitable. AIM: The current study aimed to evaluate the potential association of dietary protein intake with the cirrhosis-related mortality. METHODS: In this cohort study, 121 ambulatory cirrhotic patients with at least 6 months of cirrhosis diagnosis were followed-up for 48 months. A 168-item validated food frequency questionnaire was used for dietary intake assessment. Total dietary protein was classified as dairy, vegetable and animal protein. We estimated crude and multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), applying Cox proportional hazard analyses. RESULTS: After full adjustment for confounders, analyses showed that total (HR = 0.38, 95% CI = 0.2-1.1, p trend = 0.045) and dairy (HR = 0.38, 95% CI = 0.13-1.1, p trend = 0.046) protein intake was associated with a 62% lower risk of cirrhosis-related mortality. While a higher intake of animal protein was associated with a 3.8-fold increase in the risk of mortality in patients (HR = 3.8, 95% CI = 1.7-8.2, p trend = 0.035). Higher intake of vegetable protein was inversely but not significantly associated with mortality risk. CONCLUSION: A comprehensive evaluation of the associations of dietary protein intake with cirrhosis-related mortality indicated that a higher intakes of total and dairy protein and a lower intakes of animal protein are associated with a reduced risk of mortality in cirrhotic patients.

Dietary fiber intake and risk of gallstone: a case-control study.

BACKGROUND: Gallstone disease (GSD) and its complications are major public health issues globally. Although many community-based studies had addressed the risk factors for GSD, little is known about the associations between dietary factors and risk of disease. The present study aimed to investigate the potential associations between dietary fibers with the risk of gallstone disease. METHODS: In this case-control study, 189 GSD patients with less than one month of diagnosis and 342 age­matched controls were enrolled. Dietary intakes were assessed using a 168-item semi-quantitative validated food frequency questionnaire. Crude and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through cox proportional hazards regression models. RESULTS: Comparing the highest versus the lowest tertile, significant reverse associations were observed between odds of GSD and each category of dietary fiber intake including total (OR T3 vs. T1 = 0.44, 95% CI: 0.37-0.7, P for trend = 0.015), soluble (OR T3 vs. T1 = 0.51, 95% CI: 0.3-0.8, P for trend = 0.048) and insoluble (OR T3 vs. T1 = 0.56, 95% CI: 0.3-0.9, P for trend < 0.001). The relationship between dietary fiber intake and the risk of gallstones was more prominent in overweight and obese subjects than in subjects with a normal body mass index. CONCLUSION: Comprehensive assessment of the associations of dietary fiber intake with GSD showed that higher intakes of dietary fiber were significantly associated with reduced GSD risk.

Molecular mechanisms of vitamin D plus Bisphenol A effects on adipogenesis in human adipose-derived mesenchymal stem cells.

BACKGROUND: Obesity is considered a major health concern and mounting evidence suggests that the exposure to environmental endocrine disruptors, including Bisphenol-A (BPA), may enhance the risk to develop the disease. Moreover, growing documents propose that the vitamin D may contribute to adipogenic signaling and lipid accumulation during adipocyte differentiation. We focused on the molecular mechanism of vitamin D and BPA in human adipose-derived mesenchymal stem cells (hADMSCs) which vitamin D and BPA may influence adipose tissue development and function. METHODS: Human adipose-derived mesenchymal stem cells were cultured for 14 days in lipogenic differentiation media containing continuous concentrations of vitamin D plus BPA (0.1 nM or 10 nM). The expression of adipogenic markers including the peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBP α) CCAAT-enhancer-binding protein ß (C/EBP ß), fatty acid synthase (FASN), lipoprotein lipase (LPL), sterol regulatory element-binding protein-1c (SREBP1c), insulin-induced gene-2 (INSIG2), vitamin D receptor (VDR), estrogen receptor-beta (ER-ß), fatty acid-binding protein-4 (FABP4), and glucose transporter-4 (GLUT4) was measured using Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Lipid accumulation was visualized with staining with Oil Red O. RESULTS: In the morphological assessment of mesenchymal stem cells treated with a concentration of 10 nM vitamin D plus BPA, more lipid accumulations were observed in comparison with the group with 0.1 nM concentration. Treatment of hADMSCs with vitamin D plus BPA (0.1 nM) significantly inhibited the induction of PPARγ, C/EBP ß, C/EBP α, and FASN related to adipocyte differentiation and development. However, the exposure of cells to the concentration of 10 nM vitamin D plus BPA induced the expression of these genes associated to the adipogenesis. The remarkable increase in the level of SREBP1c was associated to the suppression of INSIG2 in treated preadipocytes with 10 nM vitamin D plus BPA. Our findings showed that the expression of VDR, ERß, GLUT4, and FABP4 were upregulated through differentiation with the highest concentrations in 0.1 nM vitamin D plus BPA group for VDR, ERß, and GLUT4. CONCLUSIONS: Vitamin D plus BPA at concentration of 10 nM boosted the adipogenesis during the critical stages of adipocytes development, whereas it seems to inhibit this process at concentration of 0.1 nM.

1,25-Dihydroxyvitamin D3 modulates adipogenesis of human adipose-derived mesenchymal stem cells dose-dependently.

PURPOSE: 1,25-dihydroxyvitamin D3 may regulate adipogenesis in adipocytes in-vitro, but little is known about possible molecular mechanisms related to the inhibitory effect of 1,25-dihydroxyvitamin D3 on adipogenesis in humans҆ adipose tissue. METHODOLOGY: In this study, human adipose-derived mesenchymal stem cells (hASCs) were cultured for 14 days in adipogenic differentiation media containing concentrations of 1,25-dihydroxyvitamin D3 (10-10-10-8 M). The extent of adipogenic differentiation in ASCs was assessed by Oil Red O staining and quantitative polymerase chain reaction (PCR) to determine expression levels of key adipogenic markers. RESULTS: Our results showed that vitamin D receptor (VDR), as a mediator of most actions of 1,25-dihydroxyvitamin D3, glucose trasporter-4 (GLUT4),and fatty acid binding protein-4 (FABP4) was expressed in vitamin D-treated hASCs. However, the protein level of these markers was lower than the control group. Treatment of human preadipocytes with 1,25-dihydroxyvitamin D3 significantly altered expression of adipogenic markers and triglyceride accumulation in a dose-dependent manner. 1,25-dihydroxyvitamin D3 at concentration of 10-8 M enhanced expression of sterol regulatory element-binding protein-1c (SREBP1c), CCAAT-enhancer-binding protein-ß (C/EBPß), a mitotic clonal expansion, peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FASN), a marker of de novo lipogenesis,and lipoprotein lipase (LPL). CONCLUSION: Our findings revealed that 1,25-dihydroxyvitamin D3 may provoke adipocyte development in critical periods of adipogenesis at concentration of 10-8 M, thereby leading to a greater risk of obesity in adulthood and an augmented risk of obesity-related diseases including diabetes, cardiovascular diseases, and some cancers.

Antioxidant vitamin intakes and risk of depression, anxiety and stress among female adolescents.

BACKGROUND AND AIM: The relation of some antioxidant nutrients with psychological disorders has been studied previously. The aim of this study was to examine the association between antioxidant vitamin intakes and the risk of depression, anxiety, and stress. METHODS: This cross-sectional study was conducted on 263 Tehranian female adolescents. Dietary intakes of vitamin E, C, and ß-Carotene were determined using a valid and reliable food-frequency questionnaire. Depression, anxiety, and stress scores were characterized by DASS-21 (Depression Anxiety Stress Score-21 items) questionnaire. The multivariable logistic regression models were used to determine the odds ratios (ORs) and 95% confidence intervals (95%CIs) of depression, anxiety, and stress across tertiles of antioxidant vitamin intakes. RESULTS: The mean ± SD age of participants was 16.20 ± 0.97 years. Also, the mean ± SD depression, anxiety and stress scores of participants were 9.89 ± 4.15, 8.43 ± 4.39 and 14.00 ± 6.45, respectively. In the fully adjusted model, subjects in the highest tertile of ß-Carotene had a lower prevalence of depression (OR:0.46, 95%CI:0.23-0.95), anxiety (OR:0.40, 95%CI:0.20-0.81), and stress (OR:0.35, 95%CI:0.17-0.73) compared to the lowest tertile (P for trend<0.05). Moreover, individuals in the top tertile of vitamin E had a lower prevalence of stress, in comparison to the bottom tertile (OR:0.34, 95% CI:0.13-0.89), (P for trend<0.05). However, no significant associations were found between the intakes of vitamin E and C and other psychological disorders. CONCLUSION: In this study, higher intake of ß-Carotene was associated with lower prevalence of depression, anxiety and stress. Also, we found an inverse relationship between vitamin E intake and the risk of stress.

Bisphenol A enhances adipogenic signaling pathways in human mesenchymal stem cells.

BACKGROUND: The endocrine disruptor Bisphenol-A (BPA), has been involved in dysregulating adipose tissue development and increasing the risk of obesity. The objective of this experiment was to investigate whether treatment of human mesenchymal stem cells with BPA could modulate adipogenesis and adipocyte differentiation. METHODS: In this experimental study, the human adipose-derived mesenchymal stem cells (hASCs) were cultured for 2 weeks with continuous exposure to 10- 10 M or 10- 8 M concentrations of BPA. The extent of triglyceride accumulation was visualized by Oil Red O staining. To evaluate BPA effect on the expression levels of key adipogenic trascripotion factors and proteins, we used Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and ELISA. RESULTS: The results presented a dose-dependent triglyceride accumulation in treated cells with BPA. Additionally, we observed that BPA induced transcription of the Peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT-enhancer-binding protein-alpha (C/EBPα), CCAAT-enhancer-binding protein-beta (C/EBPß), sterol regulatory element-binding protein-1c (SREBP1c), Fatty acid synthase (FASN), and lipoprotein lipase (LPL); BPA suppressed the expression of Fatty acid binding protein-4 (FABP4) and Estrogen receptor-beta (ERß). CONCLUSIONS: Our findings supported the hypothesis that BPA enhances adipogenic differentiation thereby may play a role in development of obesity and dysregulation of metabolic homoeostasis.

The association between nutrition knowledge and adherence to a Mediterranean dietary pattern in Iranian female adolescents.

BACKGROUND: Adherence to a Mediterranean dietary pattern (MDP) has been reported to decrease chronic diseases. OBJECTIVE: The aim of the present study was to determine the association between nutrition knowledge (NK) and adherence to MDP in Iranian female adolescents. SUBJECTS: This cross-sectional study was conducted on 297 female adolescents aged 15-18 years. METHODS: The participants were interviewed using a valid and structured questionnaire to collect information on socio-demographic, lifestyle and anthropometric variables. Dietary intakes were assessed using a validated 168-item Food Frequency Questionnaire (FFQ). Adherence to MDP was measured by the Mediterranean-Style Dietary Pattern Score (MSDPS). Each participant's NK was determined using a 20-item NK questionnaire. RESULTS: The mean ± standard deviation (SD) age and body mass index (BMI) of participants were 16.1 ± 0.9 years and 22.3 ± 4.6 kg/m2, respectively. The median [interquartile range (IQR)] of the NK score and the MSDPS were 80.0 (68.0-87.0) and 15.2 (11.9-19.5), respectively. The odds ratio (OR) of higher adherence to MDP in the highest tertile of the NK score was 2.19 [95% confidence interval (CI): 1.22-3.95; p for trend = 0.009], compared to the lowest tertile after adjusting for age and energy intake. In a multivariable-adjusted model, after further adjustment for BMI, mother's/father's education level, mother's/father's employment status, parent's marital status and physical activity, the subjects in the highest tertile of the NK score had higher adherence to MDP compared with those in the lowest tertile (OR = 2.05; 95% CI, 1.09-3.83; p for trend = 0.013). CONCLUSION: Our findings support the hypothesis that a higher NK score is significantly associated with a higher MDP adherence score in Iranian female adolescents.

Evaluating fear of hypoglycemia, pediatric parenting stress, and self-efficacy among parents of children with type 1 diabetes and their correlation with glycemic control.

Background: This study was designed to determine the level of fear of hypoglycemia (FoH), pediatric parenting stress and selfefficacy in parents of children with type 1 diabetes (T1D). Methods: In this cross-sectional study, 61 families of children with T1D who had been diagnosed for at least 6 months recruited from "Gabric Diabetes Education Association" in Tehran. Sixty mothers and 41 fathers of 61 children (26 girls, age: 6.0-12.7 years) were assessed using the Hypoglycemia Fear Survey-Parent (HFS-P), Pediatric Inventory for Parents (PIP) and Self-Efficacy for Diabetes Scale-Parent (SED-P) questionnaires. Pearson correlation analysis was used to compute the correlation between HFS-P, PIP and SEDP scores separately for mother and fathers. Results: Only 8.3% of children had controlled diabetes. Internal reliability of the Persian version of all questionnaires was good. FoH were higher for mothers. Mothers whose children had diabetes for less than two years had significantly lower mean HFS-Behavior subscale (HFS-B) scores than mothers whose children had diabetes for more than two years. There was a positive correlation between fathers' mean HFS-B score and children's total insulin dose per day. Parents' FoH score was positively correlated with increased pediatric parenting stress. Findings also showed considerable emotional distress in 51% of mothers and 29.7% of fathers. Frequency of selfmonitoring blood glucose tests (SMBG) correlated negatively with HbA1c. Conclusion: We concluded that parents with high levels of FoH and stress may benefit from diabetes education. Important implications for education are considering psychological adjustment, recognizing diabetes-related fear and stress in parents, encouraging fathers to become actively involved in the child's diabetes management and emphasizing the importance of SMBG.

A 12-week double-blind randomized clinical trial of vitamin D3 supplementation on body fat mass in healthy overweight and obese women.

BACKGROUND: Vitamin D concentrations are linked to body composition indices, particularly body fat mass. Relationships between hypovitaminosis D and obesity, described by both BMI and waist circumference, have been mentioned. We have investigated the effect of a 12-week vitamin D3 supplementation on anthropometric indices in healthy overweight and obese women. METHODS: In a double-blind, randomized, placebo-controlled, parallel-group trial, seventy-seven participants (age 38 ± 8.1 years, BMI 29.8 ± 4.1 kg/m²) were randomly allocated into two groups: vitamin D (25 µg per day as cholecalciferol) and placebo (25 µg per day as lactose) for 12 weeks. Body weight, height, waist, hip, fat mass, 25(OH) D, iPTH, and dietary intakes were measured before and after the intervention. RESULTS: Serum 25(OH)D significantly increased in the vitamin D group compared to the placebo group (38.2 ± 32.7 nmol/L vs. 4.6 ± 14.8 nmol/L; P<0.001) and serum iPTH concentrations were decreased by vitamin D3 supplementation (-0.26 ± 0.57 pmol/L vs. 0.27 ± 0.56 pmol/L; P<0.001). Supplementation with vitamin D3 caused a statistically significant decrease in body fat mass in the vitamin D group compared to the placebo group (-2.7 ± 2.1 kg vs. -0.47 ± 2.1 kg; P<0.001). However, body weight and waist circumference did not change significantly in both groups. A significant reverse correlation between changes in serum 25(OH) D concentrations and body fat mass was observed (r = -0.319, P = 0.005). CONCLUSION: Among healthy overweight and obese women, increasing 25(OH) D concentrations by vitamin D3 supplementation led to body fat mass reduction.

Lycopene an adjunctive therapy for Helicobacter pylori eradication: a quasi-control trial.

Although some herbal remedies in association with vitamin therapy have been investigated in eradicating HP, no research has been done to investigate the effects of lycopene it. Our aim was to understand if lycopene could be effective in eradication of HP. In this parallel group quasi-control trial, a total of 54 patients whose diagnosis of HP had been confirmed by rapid urease test (RUT) were enrolled. Group 1 received the standard 4-drug therapy to eradicate HP (Metronidazole 500 mg/BD, Amoxicillin 1g/BD, Omeprazole 20mg/BD, and Bismuth 240 mg/BD) and group 2 received the same regimen in association with Lycopene (30 mg/daily). One month after the initiation of the treatment, the patients were evaluated for HP eradication by RUT. Although eradication rate was higher in the second group, bivariate analysis showed no significant statistical difference between the two groups. In contrast with other nutrients, it seems that Lycopene does not have any significant effects on eradicating HP in comparison with the standard antibiotic therapy. The prevalence of HP is in association with socioeconomic situation, so the patients in different studies should be paid more attention about their own life style. We recommend that more studies can be designed by considering control group and placebo administration.

Vitamin D3 and the risk of CVD in overweight and obese women: a randomised controlled trial.

Evidence indicates that vitamin D deficiency contributes to CVD. We investigated the effect of vitamin D3 supplementation on cardiovascular risk factors in women. Healthy premenopausal overweight and obese women (n 77; mean age 38 (sd 8·1) years) were randomly allocated to the vitamin D (25 µg/d as cholecalciferol) or the placebo group in a double-blind manner for 12 weeks. Blood pressure, serum lipoproteins, apolipoproteins and anthropometric parameters were recorded. Dietary intake was recorded using 24 h food recall and FFQ. Physical activity was assessed by the International Physical Activity Questionnaire. Mean total cholesterol concentrations increased in the vitamin D group (0·08 (sd 0·56) mmol/l) but declined in the placebo group (0·47 (sd 0·58) mmol/l), and a significant effect was observed (P ≤ 0·001). In the vitamin D group, mean HDL-cholesterol concentration increased, whereas it decreased in the placebo group (0·07 (sd 0·2) v. - 0·03 (sd 0·2) mmol/l; P = 0·037). Mean apoA-I concentration increased in the vitamin D group, although it decreased in the placebo group (0·04 (sd 0·39) v. - 0·25 (sd 0·2) g/l; P ≤ 0·001). Mean LDL-cholesterol:apoB-100 ratio augmented in the vitamin D group, while this ratio declined in the placebo group (0·11 (sd 0·6) v. - 0·19 (sd 0·3); P = 0·014). Body fat mass was significantly decreased in the vitamin D group more than the placebo group ( - 2·7 (sd 2) v. - 0·4 (sd 2) kg; P ≤ 0·001). The findings showed that supplementation with vitamin D3 can significantly improve HDL-cholesterol, apoA-I concentrations and LDL-cholesterol:apoB-100 ratio, which remained significant in the multivariate model including anthropometric, dietary and physical activity measures.