Hyperlipoproteinemia (a) and Phytoestrogen Therapy in Dialysis Patients: A Review.

PURPOSE: Hyperlipoproteinemia (a) is a prevalent complication in dialysis patients, with no valid treatment strategy. The aim of this narrative review was to investigate the clinical significance of hyperlipoproteinemia (a) and phytoestrogen therapy in dialysis patients. METHODS: A comprehensive literature search of the published data was performed regarding the effects of phytoestrogen therapy on hyperlipoproteinemia (a) in dialysis patients. FINDINGS: Hyperlipoproteinemia (a) occurs in dialysis patients due to decreased catabolism and increased synthesis of lipoprotein (a) [Lp(a)]. A few clinical trials have studied the effects of phytoestrogens on serum Lp(a). All studies of dialysis patients or nonuremic individuals with hyperlipoproteinemia (a), except one, showed that phytoestrogens could significantly reduce serum Lp(a) levels. However, all investigations of phytoestrogen therapy in individuals with normal serum Lp(a) levels showed that it had no effect on serum Lp(a). Phytoestrogens seem to have effects similar to those of estrogen in lowering Lp(a) concentrations. IMPLICATIONS: Considering the high prevalence of hyperlipoproteinemia (a) in dialysis patients, phytoestrogen therapy is a reasonable approach for reducing serum Lp(a) levels and its complications in these patients.

The effects of rice bran supplementation for management of blood lipids: A GRADE-assessed systematic review, dose-response meta-analysis, and meta-regression of randomized controlled trials.

BACKGROUND: We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of rice bran supplementation on serum lipid profile levels. METHODS: We searched PubMed/Medline, Scopus, ISI Web of Science, and Google Scholar using related keywords. Published RCTs exploring the effects of rice bran consumption on lipid profile were searched up to June 2022. Evidence certainty was assessed on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The data were pooled using a random-effects model and reported as weighted mean difference (WMD) and 95% confidence interval (CI) for each outcome. RESULTS: Meta-analysis of eight RCTs (with 11 effect sizes) showed no significant effect of rice bran supplementation on serum levels of triglyceride (WMD: -11.38 mg/dl; 95% CI: -27.73, 4.96; P = 0.17), total cholesterol (WMD: -0.68 mg/dl; 95% CI: -7.25, 5.88; P = 0.834), low-density lipoprotein cholesterol (WMD: -1.68 mg/dl; 95% CI: -8.46, 5.09; P = 0.627) and high-density lipoprotein cholesterol (WMD: 0.16 mg/dl; 95% CI: -1.52, 1.85; P = 0.848) compared to control group. CONCLUSION: Our meta-analysis suggests that rice bran supplementation has no significant effects on serum levels of lipid profile components. However, larger studies with longer durations and improved methodological quality are needed before firm conclusions can be reached.

Probiotics and synbiotics supplementation improve glycemic control parameters in subjects with prediabetes and type 2 diabetes mellitus: A GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.

Probiotics and synbiotics have been proposed to exhibit an important role in glucose homeostasis and maintain the balance of the gut microbiota. However, clinical trials have shown mixed findings. Therefore, we conducted a systematic review and meta-analysis of all eligible randomized controlled trials (RCTs) examining the effects of probiotics and synbiotics intake on glycemic outcomes among individuals with prediabetes and type 2 diabetes mellitus (T2DM). The PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library were searched up to March 2022 for published RCTs exploring the effectiveness of probiotics and synbiotics compared to control on glycemic outcomes. The random-effects model was applied in order to the estimation of 95 % confidence interval (CI) and the weighted mean difference (WMD) for each endpoint. Meta-analysis of forty-six RCTs (3067 participants) showed that probiotics and synbiotics supplementation significantly reduced fasting plasma glucose (FPG) (weighted mean difference (WMD): - 11.18 mg/dl, 95 % CI: - 13.60, - 8.75, p ˂0.001), fasting insulin serum level (WMD: -1.23 µIU/ml, 95 % CI: -1.76, -0.71, p ˂0.001), hemoglobin A1c (HbA1c) (WMD: -0.35 %, 95 % CI: -0.44, -0.26, p˂0.001), and homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: -0.87, 95 % CI: -1.09, -0.65, p˂0.001). Additionally, probiotics and synbiotics intake resulted in an increase in values of quantitative insulin-sensitivity check index (QUICKI) (WMD: 0.01, 95 % CI: 0.00, 0.01, p˂0.001). However, probiotics and synbiotics consumption did not change glucose values following oral glucose tolerance test (OGTT). Our findings suggest that probiotic and synbiotic intake has favorable effects on glycemic profile in patients with prediabetes and T2DM.

Beneficial effects of probiotic and synbiotic supplementation on some cardiovascular risk factors among individuals with prediabetes and type 2 diabetes mellitus: A grade-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.

Previous studies suggested that probiotics/synbiotics administration exerts some beneficial effects on cardiometabolic risk factors. However, the results from trials have been inconsistent. This study aimed to identify the impact of probiotic and synbiotic supplements on cardiovascular health factors in patients with type 2 diabetes mellitus (T2DM) and prediabetes We searched PubMed/MEDLINE, Web of Science, and Scopus up to February 2022 to identify eligible RCTs. Estimating 95 % confidence (CI) and the weighted mean difference (WMD) for weight, body mass index (BMI), waist circumferences (WC), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP), the random-effects model was used. In the current meta-analysis, 54 RCTs were included. With the probiotic/synbiotics intervention, several parameters changed significantly, including weight (WMD: -0.38, 95 % CI: -0.63 to -0.12 Kg), TG (WMD: -19.08, 95 % CI: -27.65 to -10.51 mg/dl), TC (WMD: -10.46, 95 % CI: -15.19 to -5.72 mg/dl), LDL-C (WMD: -4.87, 95 % CI: -7.65 to -2.09 mg/dl), HDL-C (WMD: -2.70, 95 % CI: 1.33-4.07 mg/dl), SBP (WMD: -3.81, 95 % CI: -6.24 to -1.38 mmHg), and DBP (WMD: -2.01, 95 % CI: -3.12 to -0.91 mmHg). In the subgroup analysis, probiotics/synbiotics supplementation resulted in a greater change in lipid profile components in T2DM patients. Weight and BMI reduced only after synbiotic supplementation. We found that the administration of probiotics and synbiotics had beneficial effects on lipid profiles, anthropometric indices, and blood pressure in individuals with T2DM.

Flaxseed supplementation improves anthropometric measurements, metabolic, and inflammatory biomarkers in overweight and obese adults.

Background: The aim of this study was to assess the effects of supplementation with flaxseed on anthropometric measurements, lipid profile, insulin resistance, and inflammatory biomarkers in overweight and obese adults. Methods: Fifty overweight and obese adults with body mass index (BMI) of 30.72 ± 3.31 kg/m2 participated in this study. Participants were randomly assigned to take lifestyle advice or lifestyle advice plus 30 g/day milled flaxseed for 12 weeks. The primary outcome was body weight; secondary outcomes included other anthropometric parameters, lipid profile and inflammatory biomarkers. Results: At the end of the study, the following significant mean differences were seen in flaxseed and control groups, respectively: weight [-9.36 vs. -3.09 kg; P < 0.001], BMI [-3.34 vs. -1.2 kg/m2; P < 0.001], triglycerides [-62.88 vs. -9.85 mg/dL; P < 0.001], total cholesterol [-32.2 vs. -14.95 mg/dL; P = 0.04], homeostatic model assessment (HOMA-IR) [1.25 vs. -0.32; P = 0.024], high sensitive- C reactive protein [-2.2 vs. -1.01 mmol/L; P < 0.001] and tumor necrosis factor-α [-1.34 vs. -0.14 pg/mL; P = 0.005]. Conclusion: These results suggest that flaxseed supplementation in addition to lifestyle modification is significantly superior to lifestyle modification alone for weight loss. More studies with different dosages of flaxseed are needed to find the optimal dosage. This trial was registered at clinicaltrials.gov as NCT02410668.

A review on differential effects of dietary fatty acids on weight, appetite and energy expenditure.

The association between weight and chronic diseases is well defined. The quality and quantity of dietary fatty acids is an important external factor and appetite and energy expenditure, are important internal factors in determining body weight. On the other hand, dietary fatty acids composition can modulate appetite and energy metabolism, but not all fats are equal in producing metabolic responses.Given the accumulating evidence for differential effects of various dietary fatty acids, one important area of investigation is to scrutinize their roles in weight, appetite and energy expenditure modulation. There is substantial evidence to suggest that saturated fatty acids have a greater effect on appetite control, although in the long run may result in more weight gain than unsaturated fatty acids due to a weaker stimulation of energy expenditure. In contrast, mono-unsaturated fats do not have much effects on appetite control, but they can be beneficial in weight control over the long term due to stimulatory effects on energy expenditure. Interestingly, in case of poly unsaturated fats, including n-3 and n-6, their effect on increasing energy expenditure is aligned, but they act differently in controlling weight and appetite.

Flaxseed and/or hesperidin supplementation in metabolic syndrome: an open-labeled randomized controlled trial.

PURPOSE: The aim of the present study was to compare the clinical effect of flaxseed and hesperidin alone and with combination in patients with metabolic syndrome. Number of participants with treated metabolic syndrome was assessed as a primary end point. METHODS: In this 12-week randomized controlled trial, ninety-eight patients with metabolic syndrome randomly assigned to receive either whole flaxseed powder (30 g/day), or hesperidin (1 g/day), or combination of 30 g flaxseed and 1 g hesperidin or no supplement while adhering a lifestyle modification program. RESULTS: In comparison to control group, systolic blood pressure (- 5.68 vs. - 2.91 mmHg, P = 0.041) and serum concentrations of triglyceride (- 50.06 vs. 3.87 mg/dL, P = 0.033) in hesperidin group showed a significant reduction over 12 weeks of intervention. Comparison of the results of flaxseed group with the control group showed a significant improvement in serum concentrations of triglyceride (- 66 vs. 3.87 mg/dL, P = 0.028), insulin (- 4.27 vs. - 2.51 mU/L, P = 0.003) and accordingly insulin resistance (- 1.19 vs. - 0.76, P = 0.005) and sensitivity (0.03 vs. 0.01, P = 0.022) indices in flaxseed group. Combination of flaxseed and hesperidin improved three of five metabolic syndrome components including serum concentrations of triglyceride, glucose and systolic blood pressure as compared to placebo. Interestingly, co-administration of flaxseed and hesperidin with 77.3% reduction in the prevalence of defined metabolic syndrome was revealed to be most effective in controlling the metabolic syndrome, after which the group of flaxseed with 76% reduction and hesperidin group with 54.5% reduction were ranked second and third, respectively. CONCLUSIONS: It can be concluded that co-administration of flaxseed and hesperidin appears to be superior to either supplementation alone on metabolic syndrome treatment, while the effects of flaxseed are stronger than hesperidin supplementation.

The efficacy of flaxseed and hesperidin on non-alcoholic fatty liver disease: an open-labeled randomized controlled trial.

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is growing in prevalence globally and no definitive evidence for any approved pharmacological approaches for patients with NAFLD has been found yet. This study was aimed to assess the clinical effects of flaxseed and hesperidin in patients with NAFLD. SUBJECTS/METHODS: In this randomized, controlled, clinical trial, one hundred eligible patients with NAFLD were enrolled and randomly assigned to four dietary intervention groups including lifestyle modification program (control), lifestyle modification program with 30 g whole flaxseed powder, lifestyle modification program with 1 g hesperidin supplementation, and lifestyle modification program with combination of 30 g flaxseed and 1 g hesperidin (flax-hes) for 12 weeks. The changes in anthropometric parameters, metabolic profiles of glucose and lipids, inflammatory biomarkers and hepatic steatosis and fibrosis were evaluated. RESULTS: After the 12-week dietary interventions, significant reductions in body mass index, glucose hemostasis parameters and hepatic steatosis were observed in all groups. Repeated measures analysis of variance revealed a significant effect for time relative to almost all paraclinical parameters. Post hoc analysis with Bonferroni correction revealed that the three intervention groups experienced significant decreases in plasma levels of alanine aminotransferase, indices of insulin resistance and insulin sensitivity, fasting glucose and fatty liver index compared to control (p < 0.008). CONCLUSIONS: In conclusion, our study confirmed that hesperidin and flaxseed supplementation improved glucose and lipid metabolism, while reduced inflammation and hepatic steatosis (controlled attenuation parameter) in NAFLD patients. The synergistic effects of their combination were observed on plasma glucose concentration and HOMA-IR.

The effect of melatonin on treatment of patients with non-alcoholic fatty liver disease: a randomized double blind clinical trial.

OBJECTIVES: Many factors implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) are including oxidative stress, insulin resistance and abnormal production of adipokines. The aim of this clinical trial was to evaluate the effect of melatonin supplement on some important biochemical markers and signs related to NAFLD. DESIGN: A randomized double-blind, placebo-controlled, clinical trial. SETTING: Twenty-four participants in the melatonin group and 21 participants in the placebo group completed the study. INTERVENTION: Participants received 6 mg melatonin or placebo daily, 1 h before bedtime. The intervention period was 12 weeks. MAIN OUTCOME MEASURES: Anthropometric measurements, systolic and diastolic blood pressure, liver enzymes, high sensitive C­reactive protein (hs-CRP), fatty liver grade, also leptin and adiponectin serum levels, were measured at the baseline and the end of intervention. RESULTS: A significant improvement was observed in weight (p = 0.043), waist circumference (p = 0.027), abdominal circumference (p = 0.043), systolic (p = 0.039), and diastolic (p = 0.015) blood pressure, leptin serum levels (p = 0.032), hs-CRP (p = 0.024), alanine aminotransferase (p = 0.011), aspartate aminotransferase (p = 0.034), also the grade of fatty liver (p = 0.020) in melatonin treated group compared with the placebo. CONCLUSIONS: Administration of 6 mg/day melatonin had improvement effect on many factors related to NAFLD such as liver enzymes, hs-CRP, anthropometric measurements, blood pressure, leptin serum levels and the grade of fatty liver.

Effects of soy isoflavones on serum lipids and lipoprotein (a) in peritoneal dialysis patients.

BACKGROUND AND AIM: Lipid abnormalities are common in peritoneal dialysis (PD) patients and no effective treatment to decrease serum lipoprotein (a) [Lp(a)] in dialysis patients is known so far. Therefore, this research was designed to investigate the effects of soy isoflavone supplement on serum lipids and Lp(a) in PD patients. METHODS & RESULTS: In this randomized, double-blind, placebo-controlled trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The patients in the isoflavone group received 100 mg soy isoflavone daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient and serum triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and Lp(a) were measured. Serum Lp(a) reduced significantly up to 10% in the isoflavone group at the end of week 8 compared to baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). Serum HDL-C increased significantly up to 11.5% in the isoflavone group at the end of week 8 compared to baseline (P = 0.05), and the increment was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum triglycerides, total cholesterol, and LDL-C. CONCLUSIONS: This study indicates that daily administration of 100 mg soy isoflavones reduces serum Lp(a) and increases HDL-C concentration which are two determinants of cardiovascular disease in PD patients. CLINICALTRIALS.GOV: NCT03773029. REGISTRATION NUMBER AND DATE: NCT03773029 - 2018.

Effects of soy isoflavones on serum systemic and vascular inflammation markers and oxidative stress in peritoneal dialysis patients: A randomized controlled trial.

Cardiovascular disease (CVD) is common in peritoneal dialysis (PD) patients. This study was designed to investigate the effects of isoflavones on systemic and vascular inflammation markers and oxidative stress in PD patients. In this randomized clinical trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The isoflavone group received 100 mg soy isoflavones daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of eighth week, serum high sensitive C-reactive protein (hs-CRP), intercellular adhesion molecule type 1 (ICAM-1), vascular cell adhesion molecule type 1 (VCAM-1), E-selectin, and malondialdehyde were measured. Serum VCAM-1 decreased significantly in the isoflavone group at the end of Week 8 compared to baseline (p = .01), whereas no significant change was observed in the placebo group. Serum ICAM-1 decreased significantly in the isoflavone (p = .01) and placebo (p = .01) group compared to baseline. However, the reduction of ICAM-1 was significantly higher in the isoflavone group than in the placebo group (p = .02). There were no significant differences between the two groups in mean changes of serum E-selectin, malondialdehyde, and hs-CRP. This study indicates that isoflavones reduce serum VCAM-1 and ICAM-1, which are two CVD risk factors, in PD patients.

Inflammatory biomarkers response to two dosages of vitamin D supplementation in patients with ulcerative colitis: A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: This study was designed to determine the effects of two dosages of vitamin D supplementation on inflammatory biomarkers in patients with ulcerative colitis (UC). METHODS: Fifty mild to moderate active UC patients were randomly assigned to consume either 2000 or 1000 IU/day vitamin D for 12 weeks. Inflammatory biomarkers, disease activity, quality of life, anthropometric indices, dietary intakes, and physical activity were measured at the beginning and the end of the study. RESULTS: Serum level of hs-CRP decreased in both groups at the end of study, but the changes were not significantly different within and between groups. Serum level of TNF-α in the high dose group was reduced at the end of the study non-significantly (P-value = 0.289). In the low dose group, a significant increase in serum TNF-α concentration was observed (p ≤ 0.001). The changes in serum TNF-α were significantly different between two groups (p = 0.005); however, after adjusting for the effect of confounders, the significance effect was disappeared (p = 0.162). Activity of NF-κB increased in both groups while this increase was significant in the low dose group compared to the baseline (p ≤ 0.001), and to high dose group (p = 0.006). After adjustment for confounders, the difference between groups remained statistically significant (p = 0.002). CONCLUSION: Our results indicate that 12 weeks supplementation with 2000 IU/day vitamin D prevents from systematic inflammation, while decreasing disease activity in patients with mild to moderate active UC. Further studies are needed to find the optimum dosage and duration of supplementation. This Trial was registered at IRCT.ir with number of IRCT 20100524004010N22.

The effect of hesperidin supplementation on metabolic profiles in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: Hesperidin as an antioxidant flavonoid exerts anti-adipogenic, anti-inflammatory, anti-oxidant and anti-hypercholesterolemic effects. Besides, the increasing prevalence of metabolic syndrome (MetS) and its allied complications, on the one hand, and the willingness of individuals to use natural products for curing their diseases, on the other hand, led to the design of this study to evaluate the efficacy of hesperidin in normalizing the metabolic abnormalities in patients with MetS. METHODS: In this clinical trial with a parallel-group design, 49 patients with MetS received either 500-mg hesperidin or placebo, twice daily, for 12 weeks. Number of participants with treated MetS was considered as a primary end point. Anthropometric parameters, dietary intake, physical activity, lipid profile, glucose homeostasis parameter, tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP) were assessed at the beginning and at the end of the study. This trial is registered at clinicaltrials.gov as NCT03734874. RESULTS: Compared with the placebo group, hesperidin decreased fasting glucose level (- 6.07 vs. - 13.32 mg/dL, P = 0.043), triglyceride (- 8.83 vs. - 49.09 mg/dL, P = 0.049), systolic blood pressure (- 0.58 vs. - 2.68 mmHg, P = 0.048) and TNF-α (- 1.29 vs. - 4.44 pg/mL, P = 0.009). Based on the within-group analysis, hesperidin led to significant decrease in serum levels of glucose, insulin, triglyceride, total cholesterol, low density lipoprotein cholesterol, TNF-α and hs-CRP, while in control group only glucose and insulin significantly decreased. CONCLUSIONS: The results indicate that hesperidin supplementation can improve metabolic abnormalities and inflammatory status in patients with MetS.

The effects of black seed supplementation on cardiovascular risk factors in patients with nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is highly related to cardiovascular disorders risk factors. This study aimed to evaluate the effects of black seed (Nigella sativa) supplementation on cardiovascular disorders risk factors in patients with NAFLD. This randomized, double-blind, placebo-controlled clinical trial was conducted on 50 patients with NAFLD. Participants were assigned to receive a lifestyle modification plus 2 g/day of either N. sativa or placebo for 12 weeks. Compared with the placebo, N. sativa supplementation led to significant reductions in serum glucose (-7.95 vs. -1.22; p = .041), serum insulin (-3.87 vs. -1.07; p = .027), homeostatic model of assessment for insulin resistance (-1.02 vs. -0.28; p = .021), and a significant increase in quantitative insulin sensitivity check index (0.03 vs. 0.006; p = .002). All of these changes were remained significant after adjusting for known confounding variables; however, there was no significant difference in lipid profile changes between the two groups (p = .05). N. sativa supplementation significantly decreased hepatic steatosis percentage compared with the placebo after adjustment for confounding variables (p = .005). In conclusion, our results indicate that daily intake of 2-g N. sativa plus lifestyle modification is superior to lifestyle modification alone in amelioration of insulin resistance and hepatic steatosis in patients with NAFLD.

Hesperidin improves hepatic steatosis, hepatic enzymes, and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled, double-blind clinical trial.

This study aimed to evaluate the effects of hesperidin on nonalcoholic fatty liver disease (NAFLD) characteristics. In this randomized, double-blind, controlled clinical trial, 50 NAFLD patients were supplemented with either 1-g hesperidin capsule or identical placebo capsule for 12 weeks. During the intervention, both groups were advised to follow healthy lifestyle habits including dietary and physical activity recommendations. At the end of the study, hesperidin supplementation, compared with placebo, was associated with a significant reduction in alanine aminotransferase (p = .005), γ-glutamyltransferase (p = .004), total cholesterol (p = .016), triglyceride (p = .049), hepatic steatosis (p = .041), high-sensitivity C-reactive protein (p = .029), tumor necrosis factor-α, and nuclear factor-κB (NF-κB). In conclusion, our results indicate that hesperidin supplementation accompanied with lifestyle modification is superior to lifestyle modification alone in management of NAFLD at least partially through inhibiting NF-κB activation and improving lipid profile. Further studies with higher dose of hesperidin are required to find the optimal dose.

Nigella sativa and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: Results from a randomized, double-blind, placebo-controlled, clinical trial.

OBJECTIVE: The aim of this study was to assess the effects of Nigella sativa consumption on inflammatory biomarkers in patients with Non-alcoholic fatty liver disease (NAFLD). METHODS: This is a randomized, double-blind, placebo-controlled clinical trial. Fifty NAFLD patients were assigned to receive either two gram/day Nigella sativa seed as Nigella sativa group (NSG), or two gram/day starch as placebo group (PG) for 12 weeks. RESULTS: At the end of the study, the serum levels of tumor necrosis factor-α (TNF-α) decreased significantly compared with the beginning of the study in both groups, while the levels of high sensitive C reactive protein (hs-CRP) and nuclear factor kappa-B (NF-κB) only decreased significantly in the NSG (P 0 < 0.05). Only reduction in the serum levels of TNF-α was significantly more in NSG compared to the PG (P = 0.001). After adjusting the effects of confounding factors, the results remained unchanged. According to Fibroscan exam, hepatic steatosis and its percentage decreased significantly only in the NSG (P 0 < 0.005); however, the changes were not significantly different between two groups. After adjusting for confounding factors, only steatosis percentage reduction was significantly more in the NSG compared to PG (P = 0.005). CONCLUSION: Our results have shown that two gram/day consumption of Nigella sativa can reduce inflammatory biomarkers in patients with NAFLD. Further studies with different doses are highly recommended to find the optimal dosage.

The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status.

BACKGROUND: The optimum dosage for vitamin D supplementation has not yet been elucidated in patients with Ulcerative colitis (UC). The aim of this study was to investigate the effects of two vitamin D regimens in UC patients with vitamin D deficiency. METHODS: In this double blind randomized clinical trial, 50 patients with mild to moderate UC, who met inclusion criteria, received either 1000 or 2000 IU/day of vitamin D (as low dose or high dose group, respectively) for 12 weeks. Serum 25-hydroxy vitamin D (25-OHD) level, total antioxidant capacity (TAC), and Total Oxidant Status (TOS), the inflammatory bowel disease questionnaire - 9 (IBDQ-9) score and the Simple Clinical Colitis Activity Index Questionnaire (SCCAI) score were assessed before and after intervention. RESULTS: At the end of study, serum 25-OHD levels significantly increased in the high dose group (P < 0.001) and the increase was significantly more than low dose group (6.7 ± 3.8 ng/mL in the high dose group versus 0.2 ± 0.5 ng/mL in the low dose group) (P < 0.001). Serum TOS concentration decreased significantly (- 0.37 ± 0.26) only in the high dose group (P value = 0.023). There was no statistically significant change in serum TAC between two groups during the study. IBDQ-9 mean score significantly increased in high dose group compared to the low dose group (P value = 0.001) and SCCAI score in both groups reduced (- 2.58 ± 2.16 and - 0.9 ± 0.3 in high dose and low dose respectively), while this reduction was significant only in the high dose group (P value ≥0.001). CONCLUSION: Our results indicate that 2000 IU daily dose of vitamin D can increase serum 25-OHD concentration, and quality of life, while it reduces disease activity in UC patients with vitamin D deficiency. We recommend assessment of the vitamin D status in all patients with UC because they may benefit from vitamin D therapy.

Inflammatory markers response to citrulline supplementation in patients with non-alcoholic fatty liver disease: a randomized, double blind, placebo-controlled, clinical trial.

OBJECTIVES: The aim of this study was to investigate the effects of citrulline (Cit) supplementation on inflammatory markers and liver histopathology in patients with non-alcoholic fatty liver disease (NAFLD). In this clinical trial, fifty NAFLD patients were assigned to receive 2 g/day Cit or placebo for 3 months. RESULTS: At the end of study, serum high sensitive C-reactive protein (hs-CRP) and activity of nuclear factor kappa B (NF-κB) were reduced in Cit group significantly more than placebo group (P-value = 0.02 and < 0.01 respectively). Serum concentrations of tumor necrosis factor-α (TNF-α) was reduced in Cit group significantly more than placebo after adjusting for levels of baseline (P-value < 0.001). Moreover, Cit supplementation decreased serum alanine aminotransferase (ALT) and hepatic steatosis significantly (P = 0.04). Anthropometric measurements and hepatic enzymes did not change significantly in any group (P ≥ 0.05). In conclusion, our results showed that 12 weeks supplementation with 2 g/day Cit improved inflammatory markers in patients with NAFLD. Further studies with longer period of supplementation and different dosages of Cit are needed to be able to conclude. Trial registration IRCT201703194010N18 on 2017-10-13.

The effects of curcumin supplementation on liver enzymes, lipid profile, glucose homeostasis, and hepatic steatosis and fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major global health problem. The most common cause of death in these patients is due to cardiovascular disorders. The aim of this study was to examine the effects of curcumin supplementation on cardiovascular risk factors in patients with NAFLD. METHODS AND MATERIALS: In this randomized, placebo-controlled, clinical trial, fifty two patients with NAFLD were randomly assigned to receive life style recommendations plus either 1500 mg curcumin or placebo for 12 weeks. Anthropometric indices, blood lipid profile, insulin resistance, as well as hepatic steatosis and fibrosis scores were measured at the beginning and the end of the study, and compared between and within groups. RESULTS: Hepatic fibrosis, serum cholesterol, glucose and alanin aminotransferase (ALT) reduced significantly only in curcumin group (p < 0.05). Anthropometric indices, blood lipid profile, insulin resistance, and hepatic steatosis decreased significantly in both groups (p < 0.05), without any significant difference between two groups. CONCLUSION: Our results showed that daily intake of 1500 mg curcumin plus weight loss is not superior to weight loss alone in amelioration of cardiovascular risk factors in patients with NAFLD. Further studies with different dosages of curcumin are needed to be able to conclude about the effects of this dietary supplement on cardiovascular risk factors and NAFLD characteristics.

Investigation of different concentrations of MS media effects on gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni.

Stevia rebaudiana Bertoni is one of two species that contains steviol glycosides. Among steviol glycosides that extracted from leaves, stevioside and rebaudioside A are the two major and the sweetest glycosides that are about 200-300 times sweeter than sucrose with zero calories. The best method for stevia propagation is tissue culture. So, for investigation of nutrients in medium, we studied the effect of different concentrations of MS media (MS, 0.5 MS, 0.25 MS, 0 MS) on morphological traits, UGT74G1 and UGT76G1 genes expression and accumulation of steviol glycosides in stevia leaves. The best growth rate (0.472 mm/d) has occurred in plants grown in MS media. Also, the highest gene expression of UGT74G1 gene (1.000 Total lab unit) was seen under MS treatment. However, the highest expression level of UGT76G1 gene (1.701 Total lab unit) was observed at plants grown in 0 MS. The highest amount of both Stevioside and Rebaudioside A (14.23 and 8.12, respectively) were accumulated in plants under MS treatment. Obviously, dilution of MS media associated with decreasing in both expression of the intended genes and accumulation of steviol glycosides.