The association between dietary intake of branched-chain amino acids and odds and severity of rheumatoid arthritis.

This case-control study investigated the link between dietary branched-chain amino acids (BCAAs) and the risk and severity of rheumatoid arthritis (RA). We assessed dietary BCAA intake in 95 RA patients and 190 matched controls using a food frequency questionnaire. We also assessed the disease severity using the disease activity score 28 (DAS-28), ESR, VAS, morning stiffness, and tender and swollen joints. Higher BCAA intake, expressed as a percentage of total protein, was significantly associated with increased risk of RA for total BCAAs (OR 2.14, 95% CI 1.53-3.00, P < 0.001), leucine (OR 2.40, 95% CI 1.70-3.38, P < 0.001), isoleucine (OR 2.04, 95% CI 1.46-2.85, P < 0.001), and valine (OR 1.87, 95% CI 1.35-2.59, P < 0.001). These associations remained significant even after adjusting for potential confounders (P < 0.001). However, BCAA intake did not show any significant association with RA severity in either crude or multivariate models (P > 0.05). Our findings suggest that higher dietary BCAA intake may contribute to the development of RA, but further research is needed to confirm these observations and explore the underlying mechanisms.

Effect of cardamom consumption on inflammation and blood pressure in adults: A systematic review and meta-analysis of randomized clinical trials.

Cardamom has the potential to offer anti-inflammatory and antihypertensive advantages, but the findings from clinical trials have been inconsistent. To address this knowledge gap, the present systematic review and meta-analysis were conducted to evaluate the anti-inflammatory and antihypertensive effects of cardamom in adults. We systematically searched databases including PubMed, Scopus, and ISI Web of Sciences, for papers published up to October 2022 to identify clinical studies. Eight eligible studies were included in the meta-analysis. A fixed model was used to estimate weighted mean difference (WMD), standardized mean difference (SMD), and 95% confidence interval (95% CI). The results showed that cardamom significantly reduced the levels of inflammatory factors, including hs-CRP (SMD: -0.60 mg/dL; 95% CI: -0.78 to 0.42), IL-6 (WMD: -1.25 mg/dL; 95% CI: -1.48 to -1.03), TNF-α (WMD: -2.10 kg; 95% CI: -2.36 to -1.84, p < .001), and measures of systolic (WMD: -0.54 mmHg, 95% CI: -0.88, -0.19, p = .002) and diastolic (WMD: -0.90 mmHg; 95% CI: -1.07 to -0.73) blood pressure. The current meta-analysis showed that cardamom can help reduce inflammation and improve blood pressure. However, due to the limited number of studies, caution must be exercised when interpreting the current results.

The association between dietary insulin index and dietary insulin load with rheumatoid arthritis.

This study was designed to assess the relationship between dietary insulin index (DII) and dietary insulin load (DIL) and rheumatoid arthritis (RA) risk in a case-control study. This study enrolled ninety-five newly diagnosed RA patients and 200 age- and sex-matched healthy controls. Dietary intakes were assessed using a validated 168-item semi-quantitative FFQ. DII and DIL were calculated using food insulin index values from previously published data. In the unadjusted model, individuals in the highest DIL tertile had the significantly higher odds of RA than those in the lowest tertile of the DIL scores (OR = 1·32, 95 % CI (1·15, 1·78), Pfor trend = 0·009). After adjusting for confounders, the risk of RA was 2·73 times higher for participants in the highest tertile of DIL than for those in the lowest tertile (OR = 2·73, 95 % CI (1·22, 3·95), Pfor trend < 0·001). In addition, patients in the highest DII tertile had higher risk of RA than those in the first tertile (OR = 2·22, 95 % CI (1·48, 3·95), Pfor trend = 0·008). This association persisted after adjusting for potential confounders (OR = 3·75, 95 % CI (3·18, 6·78), Pfor trend = 0·002). Our findings suggest that diets high in DII and DIL may increase the risk of developing RA, independent of other potential confounders. These findings can be verified by more research, particularly with a prospective design.

Hesperidin reduces depressive symptoms in post-coronary artery bypass graft patients with mild depression.

Previous studies have shown that hesperidin may have beneficial effects on depression; however, to the best of our knowledge, no clinical trial has yet been conducted in this area. The aim of the present study was, therefore, to determine the effects of hesperidin on depression, serum brain-derived neurotrophic factor (BDNF), and serum cortisol levels in post-coronary artery bypass graft (CABG) patients. Toward this goal, 73 post-CABG patients with depression symptoms were enrolled. The participants were randomly divided into two groups to receive either 200 mg/day hesperidin (n = 38) or placebo (n = 35) for 12 weeks. Depressive symptoms, serum BDNF, and cortisol levels were then assessed at the baseline and after intervention. Beck Depression Inventory-II (BDI-II) was also used to determine the severity of depression. Sixty-six patients completed the trial. Hesperidin decreased depression severity after 12 weeks, as compared to placebo (p = .004), but serum BDNF and cortisol were not statistically significantly different in the two groups after the intervention. Subgroup analyses also showed that, while in the patients with mild depression, the score of BDI-II was significantly different in the hesperidin and placebo groups after intervention; there was no difference in the severity of depression between the two groups in patients with moderate-to-severe depression. To conclude, a dose of 200 mg/day hesperidin may reduce depressive symptoms after 12 weeks in post-CABG patients with mild depression.

Hesperidin reduces serum levels of triglyceride after coronary artery bypass graft surgery.

Hesperidin, as an antioxidant and anti-inflammatory agent, has beneficial effects on cardiovascular diseases. This study aimed to determine the effects of hesperidin supplementation on inflammation, oxidative stress, and lipid profile in depressed coronary artery bypass graft surgery (CABG) patients. Eighty patients after coronary artery bypass graft surgery participated in this clinical trial and were randomly divided into two groups. The intervention group received 200 mg/d pure hesperidin supplement and the second group received placebo for 12 weeks. Both groups continued their usual diet. Serum concentrations of inflammatory and stress oxidative markers (hs-CRP, P-selectin, and ox-LDL) were measured and compared at baseline and the end of the intervention. The changes in serum levels of triglyceride were significantly different between the two groups (p < .05). HDL-c significantly increased in groups but the differences between the two groups were not statistically significant (p > .05). Hesperidin did not affect FBS, other lipid parameters, hs-CRP, P-selectin, and OX-LDL (p > .05). SBP and DBP differences were not statistically significant (p > .05). After 12 weeks of intervention, hesperidin reduced serum levels of triglyceride in depressed post-CABG patients.

Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: a multicentral-triple blind randomized clinical trial.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines. Methods: The present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-ß), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method. Findings: Ellagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (-24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; -5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; -18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-ß in any of the study groups (p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores (p < 0.05), and no significant changes observed in PRI score (p > 0.05). Conclusion: Ellagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression.Clinical trial registration: (https://en.irct.ir/trial/53020), IRCT20120415009472N22.

The effects of Ellagic acid supplementation on neurotrophic, inflammation, and oxidative stress factors, and indoleamine 2, 3-dioxygenase gene expression in multiple sclerosis patients with mild to moderate depressive symptoms: A randomized, triple-blind, placebo-controlled trial.

BACKGROUND: Depression is one of the most common psychological disorders among multiple sclerosis (MS) patients that characterized as the first symptoms. Ellagic acid is a natural polyphenol that may have neuroprotective properties through antioxidant, anti-inflammatory, and immunomodulatory effects. PURPOSE: The aim of the present study was to investigate the effects of Ellagic acid on circulating levels of brain derived neurotrophic factor (BDNF), interferon-γ (IFN-Æ´), nitric oxide (NO), nuclear factor erythroid-2-related factor 2 (Nrf2), cortisol, serotonergic system, and indoleamine 2, 3-dioxygenase (IDO) gene expression in MS patients with mild to moderate depressive symptoms. STUDY DESIGN: A randomized triple-blind clinical trial. METHODS: The eligible patients according to the inclusion criteria were randomly divided into two groups: either 180 mg Ellagic acid (Axenic company) (n = 25) or 180 mg maltodextrin (n = 25) group for 12 weeks. The Ellagic acid supplement were identical to placebo in shape, color and odor. Serum BDNF, NO, Nrf2, cortisol, serotonin, and IFN-Æ´ were measured by ELISA kit in the baseline and end of the study. Also, demographic characteristics, anthropometric measurements, physical activity, food intake, Beck Depression Inventory-II (BDI-II) and expanding disability status scale (EDSS) questionnaires, as well as IDO gene expression were assessed. SPSS software version 24 was used for statistical analysis. RESULTS: Fifty patients were evaluated, and a significant decrease in BDI-II (p = 0.001), IFN-Æ´ (p = 0.001), NO (p = 0.004), cortisol (p = 0.015), IDO gene expression (p = 0.001) and as well as increased the level of BDNF (p = 0.006) and serotonin (p = 0.019) was observed among those who received 90 mg Ellagic acid twice a day for 12 weeks versus control group. However, there were no significant differences between groups for Nrf2 levels (p>0.05) at the end of study. CONCLUSION: The current study indicates that Ellagic acid intervention has a favorable effect on depression in MS patients. This is achieved by reducing BDI-II scores, as well as levels of NO, cortisol, IFN-Æ´, and IDO gene expression. Furthermore, we found a significant elevation in circulating levels of BDNF and serotonin.

The effect of coenzyme Q10 supplementation on liver enzymes: A systematic review and meta-analysis of randomized clinical trials.

Coenzyme Q10 is a potent antioxidant and is necessary for energy production in mitochondria. Clinical data have suggested that coenzyme Q10 (CoQ10) has some beneficial effects on liver function. However, these results are equivocal. This systematic review and meta-analysis aimed to clarify the effect of coenzyme Q10 supplementation on the serum concentration of liver function enzymes. We searched the online databases using relevant keywords up to April 2022. Randomized clinical trials (RCTs) investigating the effect of CoQ10, compared with a control group, on serum concentrations of liver enzymes were included. We found a significant reduction following supplementation with CoQ10 on serum concentrations of alanine aminotransferase (ALT) based on 15 effect sizes from 13 RCTs (weighted mean difference [WMD] = -5.33 IU/L; 95% CI: -10.63, -0.03; p = .04), aspartate aminotransferase (AST) based on 15 effect sizes from 13 RCTs (WMD = -4.91 IU/L; 95% CI: -9.35, -0.47; p = .03) and gamma-glutamyl transferase (GGT) based on eight effect sizes from six RCTs (WMD = -8.07 IU/L; 95% CI: -12.82, -3.32; p = .001; I 2 = 91.6%). However, we found no significant effects of CoQ10 supplementation on alkaline phosphatase concentration (WMD = 1.10 IU/L; 95% CI: -5.98, 8.18; p = .76). CoQ10 supplementation significantly improves circulating ALT, AST, and GGT levels; therefore, it might positively affect liver function. Further high-quality RCTs with more extended intervention periods and larger sample sizes are recommended to confirm our results.

Senescence of bone marrow mesenchymal stem cells in Wistar male rats receiving normal chow/high-calorie diets with/without vitamin D.

Bone marrow mesenchymal stem cells (BM-MSCs) have a momentous function in the composition of the bone marrow microenvironment because of their many valuable properties and abilities, such as immunomodulation and hematopoiesis. The features and actions of MSCs are influenced by senescence, which may be affected by various factors such as nutritional/micronutrients status, e.g., vitamin D. This study aimed to examine the effects of a high-calorie diet (HCD) with/without vitamin D on BM-MSCs senescence. In the first phase, 48 middle-aged rats were fed a normal chow diet (NCD, n = 24) and an HCD (n = 24) for 26 weeks. Afterward, the rats in each group were randomly divided into three equal subgroups. Immediately, eight-rat from each diet group were sacrificed to assess the HCD effects on the first phase measurements. In the second phase, the remaining 4 groups of rats were fed either NCD or HCD with (6 IU/g) or without vitamin D (standard intake: 1 IU/g); in other words, in this phase, the animals were fed (a) NCD, (b) NCD plus vitamin D, (c) HCD, and (d) HCD plus vitamin D for 4 months. BM-MSCs were isolated and evaluated for P16INK4a, P38 MAPK, and Bmi-1 gene expression, reactive oxygen species (ROS) levels, SA-ß-gal activity, and cell cycle profile at the end of both phases. After 26 weeks (first phase), the ROS level, SA-ß-gal-positive cells, and cells in the G1 phase were significantly higher in HCD-fed rats than in NCD-fed ones (P < 0.05). HCD prescription did not significantly affect cells in the S and G2 phases (p > 0.05). Compared with the NCD-fed animals, P16INK4a and P38 MAPK gene expression were up-regulated in the HCD-fed animals; also, Bmi-1 gene expression was down-regulated (P < 0.05). BM-MSCs from vitamin D-treated rats (second phase) exhibited reduced mRNA levels of P16INK4a and P38 MAPK genes and increased Bmi-1 mRNA levels (all P < 0.05). Vitamin D prescription also declined the percentage of SA-ß-gal-positive cells, ROS levels, and the cells in the G1 phase and increased the cells in the S phase in both NCD and HCD-fed animals (P < 0.05). The reduction of the cells in the G2 phase in rats fed with an NCD plus vitamin D was statistically non-significant (P = 0.128) and significant in HCD plus vitamin D rats (P = 0.002). HCD accelerates BM-MSCs senescence, and vitamin D reduces BM-MSCs senescence biomarkers.

Protective Effect of Vitamin D Supplementation on Some Hemogram Derived Inflammatory Indices in Normal and High-Fat Diet Fed Male Wistar Rats.

Background: Hematological inflammatory indices are currently suggested to assess systemic inflammation. This study aims to investigate a vitamin D supplementation effect on hematological indices of inflammation in rats. Method: Forty-eight middle-aged male rats were allocated into a normal diet (ND) group (10% fat) and a high-fat diet (HFD) group (60% fat). The animals were fed for 26 weeks. After this period, each group was randomly divided into three subgroups, each of 8 rats: Group (1): animals were fed the ND and HFD containing 1 IU/g vitamin D for 4 months, group (2): animals were fed the ND and HFD containing 6 IU/g vitamin D for 4 months and group (3): animals were euthanized to evaluate the HFD effect. Serum 25-hydroxyvitamin D level, white blood cell count (WBCs), platelet count, platelet crit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) were measured. Results: The HFD, significantly increased body weight, PCT, PDW, PLR, NLR, and MLR and significantly reduced serum vitamin D levels compared to the ND (P < 0.05). There was a significant decrease in food intake, MPV, PDW, and NLR after vitamin D supplementation in the ND-fed group (P < 0.05). A significant reduction in platelet count, PCT, and MLR was observed after vitamin D supplementation in HFD-fed rats (P < 0.05). Conclusions: In our study, some hemogram-derived inflammatory indices were higher in the HFD-fed group, and vitamin D supplementation lowering effects on some hematological indices were seen in both ND and HFD groups.

The effects of melissa officinalis on depression and anxiety in type 2 diabetes patients with depression: a randomized double-blinded placebo-controlled clinical trial.

BACKGROUND: Depression is more common in diabetic patients, with a 1.5-fold increased risk of death.Melissa officinalis (M. officinalis) have anti-diabetic and anti-depression activities. The study aimed to determine the efficacy of M. officinalis extract on depression, anxiety, and sleep quality in patients with type 2 diabetes with depressive symptoms. METHODS: In this double-blind clinical trial, 60 volunteer patients (age range 20-65 years) with type 2 diabetes mellitus with symptoms of depression were randomized into the intervention (received 700 mg/day hydroalcoholic extract; n = 30) or control group (received 700 mg/day toasted flour; n = 30). Dietary intake, physical activity, anthropometric indices, FBS (Fasting blood sugar), hs-CRP(High-sensitivity C-reactiveprotein), depression, anxiety, and sleep quality were determined at the beginning and end of the study. Depression and anxiety were assessed by Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively; sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Sixty participants received M. officinalis extract or placebo, of which 44 patients completed the 12-week double-blind clinical trial. After 12-week the mean change of depression and anxiety scores were statistically significant between the two groups (p < 0.001 and p = 0.04, respectively), but no significant differences were observed in FBS, hs-CRP, anthropometric indices, sleep quality, and blood pressure.In the intervention group, there was a significant decrease in depression and anxiety severity(p < 0.001 and p = 0.01, respectively) at the end of the study compared to the baseline. TRIAL REGISTRATION: All protocols in this study were followed in accordance with the Helsinki Declaration (1989 revision). Ethical approval for this study was obtained from the Iran University of Medical Sciences Ethics committee (IR.IUMS.FMD.REC 1396.9413468004; research.iums.ac.ir). The study was registered at the Iranian Registry of Clinical Trials (IRCT201709239472N16); Registration date: 09/10/2017.

The Effect of the Saffron Intervention on NAFLD Status and Related Gene Expression in a Rat Model.

Background: According to the worldwide increasing prevalence of non-alcoholic fatty liver disease (NAFLD), the present study aimed to investigate the mechanism effects of saffron consumption on preventing NAFLD in a rat model. Methods: In an experimental study, 12 rats were randomly divided into 2 groups to be evaluated in the prevention phase for 7 weeks. In the prevention phase, the animals were randomly assigned to either fed HFHS + 250 mg/kg saffron (S) or fed with HFHS. Afterward, parts of the liver were excised for histopathologic examination. Plasma concentrations of ALT, AST, GGT, ALP, serum lipids, insulin concentrations, plasma glucose, hs-CRP, and TAC were measured. Moreover, Also, the gene expression of 6 target genes was evaluated, including FAS, ACC1, CPT1 ،PPARα ،DGAT2, and SREBP 1-c at the beginning and end of the study. Also, the differences among groups were evaluated by the Mann-Whitney test for non-normal data and the independent t test for normal data. Results: The prevention phase groups have a significant elevation in body weight ( P = 0.034) and food intake (P = 0.001) of the HFHS group versus HFHS + 250 mg/kg S group. Also, there was a significant difference between groups 1 and 2 for ALT (P = 0.011) and AST (P = 0.010), and TG (P = 0.040). The HFHS group had higher plasma levels of FBS (P = 0.001), insulin (P = 0.035), HOMA-IR (P = 0.032), and lower TAC (P = 0.041) versus the HFHS+ S group. Also, the difference between HFHS + 250 mg/kg S and HFHS for PPARα gene expression was significant (P = 0.030). Conclusion: The present study showed that consumption of saffron could prevent developing NAFLD in rats at least partially through modulation in gene expression of PPARα.

Effect of sumac powder on clinical symptoms, hyperandrogenism, inflammation, blood glucose, lipid profiles in women with polycystic ovary syndrome: A double-blind randomized clinical trial.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders associated with a high risk of diabetes, atherosclerosis, and cardiovascular disease. The purpose of this study was to determine the effect of sumac powder on clinical symptoms and laboratory parameters in women with PCOS. The double-blind randomized controlled clinical trial was conducted on 88 women with PCOS randomly assigned to the intervention and control groups. The intervention group received three capsules each containing 1 g of sumac powder for 12 weeks. All data and serum levels of sex hormone, hs-CRP, glucose, and lipid profiles were measured at the baseline and at the end of the study. Data were analyzed using SPSS version 25 software. The ANCOVA test results showed that hs-CRP level was significantly reduced in the intervention group (p = .008). Blood glucose and lipid profiles in the intervention group were significantly reduced compared to the placebo group (p < .05). Insulin sensitivity and HDL levels were increased significantly in the Sumac group after the intervention (p < .05). Sumac powder can reduce the inflammatory effects, and glycemic status and lipid profile of polycystic ovaries in affected women, but has no significant effect on anthropometric parameters and sex hormones.

The effect of Cornus mas fruit extract on vasomotor symptoms and sex hormones in postmenopausal women: a randomized, double-blind, clinical trial.

OBJECTIVES: Cornus mas fruit has various antioxidants and anti-inflammatory properties, so this study aims at assessing its effect on menopausal symptoms and sex hormones in postmenopausal women. METHODS: In the current randomized, double-blind clinical trial, 84 individuals (42 per group) were participated. C mas hydroalcoholic extract was prepared, and participants received 300 mg C mas extract or placebo three times a day (900 g in total) for 8 weeks. The demographic, dietary intake, and physical activity information were gathered. Anthropometric indices were measured by standard methods. Furthermore, menopause symptoms were assessed by Greene Climacteric Scale. Also, sex hormones were measured by enzyme-linked immunosorbent assay. RESULTS: Based on the results, there was a significant difference in total Greene score reduction between the intervention and placebo groups (-3.19 ± 0.54, -0.76 ± 0.32, and P < 0.001). In addition, vasomotor symptoms had a remarkable decrease in the C mas extract group (P < 0.001). Also, the intervention group demonstrated a decreasing trend in the number and duration of hot flushes. Moreover, follicle-stimulating hormone remarkably decreased and estradiol increased in the intervention group (P = 0.016 and P = 0.018). CONCLUSIONS: It has been found that the extract of C mas fruit has a favorable effect on vasomotor symptoms, sex hormones, and related complications in women experiencing menopausal symptoms.

The Effect of Zinc Supplementation on Circulating Levels of Brain-Derived Neurotrophic Factor (BDNF): A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: There are randomized controlled trials (RCTs) about the zinc supplementation effect on circulating levels of brain-derived neurotrophic factor (BDNF). However, the findings of these studies are inconsistent. The purpose of this systematic review and meta-analysis was to determine the zinc supplementation effect on BDNF and zinc levels in published RCTs. Methods: We searched PubMed/Medline, Cochrane, Scopus, ISI Web of Science, EMBASE, "Clinicaltrials.gov", "Cochrane Register of Controlled Trials", "IRCT" and also key journals up to 2019. RCTs with two intervention (zinc) and control (placebo) groups that evaluated zinc supplementation efficacy on BDNF levels were included. Study heterogeneity was assessed, and then, meta-analysis was performed using the fixed-effects model. Results: Four studies were included in the present secondary analysis. Compared with placebo, zinc supplementation significantly enhanced circulating levels of BDNF [(SMD): 0.31, 95% confidence interval (CI): (0.22, 0.61)] and zinc [(SMD): 0.88, 95% CI: (0.54, 1.22)] with no considerable heterogeneity among the studies [(Q = 3.46; P = 0.32; I2% = 13.4); (Q = 2.01; P = 0, 37; I2% = 0.5), respectively]. Conclusions: Our results propose that zinc supplementation can increase the circulating levels of BDNF and zinc. This study was registered at PROSPERO as CRD42020149513.

Effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus: A randomized clinical trial.

Background: Vascular dysfunction is a major complication of diabetes mellitus that leads to cardiovascular disease (CVD). This study aimed to examine the effects of omega-3 consumption on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus (T1DM). Methods: In this randomized, double-blind, placebo-controlled clinical trial, 51 adolescents (10-18 years) with T1DM completed the study. Patients received 600 mg/day [containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA)] of omega-3 or placebo for 12 weeks. Flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, blood urea nitrogen (BUN), creatinine, fasting blood sugar (FBS), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), serum insulin (SI), urine albumin-creatinine ratio (uACR), blood pressure, and anthropometric indices were assessed at the baseline and after the intervention. Results: Following supplementation, omega-3 significantly increased FMD (3.1 ± 4.2 vs. -0.6 ± 4%, p = 0.006) and decreased TG (-7.4 ± 10.7 vs. -0.1 ± 13.1 mg/dl, p = 0.022) in comparison with the placebo group. However, no significant difference was observed regarding CIMT (-0.005 ± 0.036 vs. 0.003 ± 0.021 mm, p = 0.33). Although hs-CRP was significantly decreased within the omega-3 group (p = 0.031); however, no significant change was observed compared to placebo group (p = 0.221). Omega-3 supplementation had no significant effect on other variables. Conclusion: Given the elevation in FMD and reduction in TG, omega-3 supplementation can improve vascular function and may reduce the risk of cardiovascular disease in adolescents with T1DM patients.

Effect of rosemary leaf powder with weight loss diet on lipid profile, glycemic status, and liver enzymes in patients with nonalcoholic fatty liver disease: A randomized, double-blind clinical trial.

Experimental and some clinical studies have shown beneficial effects of rosemary leaf on liver function and biochemical parameters. The present study aimed to examine the impact of rosemary leaf powder with a weight loss diet in patients with nonalcoholic fatty liver disease. In a randomized double-blinded clinical trial, 110 patients were randomly assigned to receive either 4 g rosemary leaf or placebo (starch) powders for 8 weeks. In addition, all participants in the study were given weight loss diet and physical activity recommendations. Compared with baseline, alanine aminotransferase (p < .001), aspartate aminotransferase (p < .001), alkaline phosphatase (p < .001), gamma glutamyltransferase (p < .001), fasting blood glucose (p < .001), fasting insulin (p < .001), insulin resistance (p < .001), total cholesterol (p = .003), triglyceride (p < .001), low-density lipoprotein cholesterol (p < .001), and anthropometric indices (weight, body mass index, and waist circumferences) decreased significantly in the rosemary and placebo group with weight loss. However, after 8 weeks, no significant difference between the rosemary and placebo groups was detected in the variables as mentioned above except homeostasis model assessment of ß-cell dysfunction (p = .014). The findings of the current clinical trial study revealed that rosemary group did produce changes, but they were not statistically different from those produced by the diet/activity intervention alone.

Evaluation of cytotoxicity and anticancer activity of kombucha and doxorubicin combination therapy on colorectal cancer cell line HCT-116.

BACKGROUND: Colorectal cancer is the third leading to death type of cancer in the world. The therapeutic guideline varied between different methods. As the main therapeutic guideline is chemotherapy, recent studies had shown utilization of natural products in combination with conventional medication, elevate the efficiency of chemotherapeutic methods. Kombucha is a traditional beverage obtained from the fermentation of green tea as a rich source of flavonoid medicinal plant. This study aimed to evaluate the natural potential of combination therapy of this natural product with doxorubicin as a chemotherapeutic agent. MATERIALS AND METHODS: The study was performed as in vitro evaluation of biological activity of kombucha on HCT-116 cell line (human colon cancer cell line). The cytotoxic effect of different kombucha beverages (fermented green tea) in comparison with green tea extract was evaluated by dimethylthiazolyl tetrazolium bromide (MTT) assay. In the next step, anticancer activity of doxorubicin as a general guideline chemotherapeutic agent in combination with kombucha was evaluated by cell cycle analysis and apoptosis assay flow cytometry. Apoptotic genes expression pattern was determined using real-time polymerase chain reaction. The experiments were designed in three independent replications and statistically analyzed using SPSS software. RESULTS: The results show that kombucha compared with the green tea extract caused more (1.2 fold) early apoptosis induction and G0/G1 phase arrest. Moreover, kombucha increased the expression levels of p21, p53, and B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein genes (2, 2.5, and 1.5 fold, respectively) while it decreased Bcl-2 gene expression level (5-8 fold) compared with doxorubicin alone. Combination of kombucha with doxorubicin shows 2-fold increased G0/G1 phase compared with the doxorubicin treatment. CONCLUSION: This result indicated that kombucha caused boosted anticancer activity of doxorubicin agent. These findings suggest that kombucha may be has an assistor and useful role in colorectal cancer treatment align with chemotherapy.

Study protocol of a randomized controlled clinical trial investigating the effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes.

BACKGROUND: Type 1 diabetes is a main health burden with several related comorbidities. It has been shown that endothelial function, vascular structure, and metabolic parameters are considerably disrupted in patients with type 1 diabetes. Omega-3 as an adjuvant therapy may exert profitable effects on type 1 diabetes and its complications by improving inflammation, oxidative stress, immune responses, and metabolic status. Because no randomized clinical trial has examined the effects of omega-3 consumption in children and adolescents with type 1 diabetes; the present study aims to close this gap. METHODS: This investigation is a randomized clinical trial, in which sixty adolescents with type 1 diabetes will be randomly assigned to receive either omega-3 (600 mg/day) or placebo capsules for 12 weeks. Evaluation of anthropometric parameters, flow-mediated dilation (FMD) as an endothelial function marker, carotid intima-media thickness (CIMT) as a vascular structure marker, proteinuria, biochemical factors including glycemic and lipid profile, blood urea nitrogen (BUN), creatinine, high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR), as well as blood pressure will be done at the baseline and end of the trial. Also, dietary intake and physical activity will be assessed throughout the study. Statistical analysis will be performed using the SPSS software (Version 24), and P < 0.05 will be considered statistically meaningful. DISCUSSION: It is hypothesized that omega-3 supplementation may be beneficial for the management of type 1 diabetes and its complications by reducing inflammation and oxidative stress and also modulating immune responses and glucose and lipid metabolism through various mechanisms. The present study aims to investigate any effect of omega-3 on patients with type 1 diabetes. ETHICAL ASPECTS: This trial received approval from Medical Ethics Committee of Iran University of Medical Sciences, Tehran, Iran (IR.IUMS.REC.1400.070). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20210419051010N1 . Registered on 29 April 2021.

Effect of spirulina and chlorella alone and combined on the healing process of diabetic wounds: an experimental model of diabetic rats.

BACKGROUND: Using chemical agents to cure diabetes mellitus and its complications may be accompanied by complications. New natural agents, such as spirulina and chlorella, could be used as alternative choices in this case. METHODS: 65 male Wistar rats were allocated to 5 groups: A (healthy control), B (diabetic rats with a normal diet), C (diabetic rats supplemented with 50 g/kg/day spirulina), D (diabetic rats supplemented with 50 g/kg/day chlorella) and E (diabetic rats supplemented with 25 g/kg/day chlorella and 25 g/kg/day spirulina). After 21 days, wounds were inflicted on the back of rats. Assessment of blood sugar (BS), high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), granulation tissue formation, vascularization, epithelialization, and percentage of wound healing were determined along with macroscopic examinations. RESULTS: The microscopic changes at days 3, 7, 14, and 21 showed significant evidence of improved angiogenesis, epithelial proliferation, and granulation tissue formation in the spirulina and chlorella treated rats compared with the controls (p˂0.05). Both spirulina and chlorella treatments of diabetic rats resulted in a significant reduction in BS and weight (p˂0.05), but VEGF and hs-CRP levels did not significantly change (p > 0.05). Percentage of wound healing was 100% on day 21 in all groups, except the control group B (97.8 ± 1.15%). CONCLUSIONS: The results of this study showed that supplementation with spirulina and chlorella alone and combined could improve wound healing indices in diabetic rats and could therefore be recommended for the management of diabetic ulcer.