The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have higher intestinal mucosal permeability, leading to the lipopolysaccharide (LPS) leakage and endotoxemia. This, in turn, leads to oxidative stress (OS) and neuro-inflammation caused by the gut-brain axis, affecting the neurotrophic factors levels such as brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100 B) levels. In this study, it was hypothesized that the thylakoid membranes of spinach supplementation along with a hypocaloric diet may have improved the LPS levels, neurotrophic factors, and OS in PCOS patients. METHODS: In this double-blind, randomized, placebo-controlled, and clinical trial, 48 women with obesity and diagnosed with PCOS based on Rotterdam criteria were randomly assigned to thylakoid (N = 21) and placebo groups (N = 23). A personalized hypocaloric diet with 500 calories less than the total energy expenditure was prescribed to all patients. The participants were daily supplemented with either a 5 g/day thylakoid-rich spinach extract or a placebo (5 g cornstarch) for 12 weeks along with a prescribed low-calorie diet. Anthropometric measurements and biochemical parameters were assessed at baseline and after the 12-week intervention. RESULTS: A statistically significant decrease in the LPS levels (P < 0.001) and an increase in the BDNF levels (P < 0.001) were recorded for the participants receiving the oral thylakoid supplements and a low-calorie diet. Furthermore, significant decreases were observed in fasting blood glucose, insulin, homeostatic model of assessment for insulin resistance, free testosterone index, and follicle-stimulating hormone / luteinizing hormone ratio in both groups (P < 0.05). No significant differences were detected between the two groups regarding the changes in malondialdehyde, catalase, total antioxidant capacity, and S100B levels (P > 0.05). CONCLUSIONS: In sum, the thylakoid membranes of spinach supplemented with a hypocaloric diet reduced the LPS levels, increased the BDNF levels, and improved the glycemic profile and sex-hormone levels; however, they had no effects on the OS markers levels after 12 weeks of intervention.

Alpha-lipoic acid supplementation affects serum lipids in a dose and duration-dependent manner in different health status.

Background: Many studies have investigated the effect of alpha-lipoic acid (ALA) supplementation on lipid profile, and different results have been obtained from these studies. The current systematic review and dose-response meta-analysis was conducted to achive a strong conclusion about the effect of ALA supplementation on lipid profile including total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL, HDL) and triglycerides (TG). Methods: A systematic search was performed in PubMed, SCOPUS, ProQuest and Embase for randomized placebo-controlled human trials that examined the effect of ALA supplementation on lipid profile up to November 2020. The dose and duration of ALA supplementation for included studies were ranged between 300-1200 mg/d and 2-16 weeks respectively. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were used to evaluate the effect size. Cochran's Q and I2 tests were also used to assess between-study's heterogeneity. In addition, subgroup analysis was performed to investigate potential sources of heterogeneity. Dose-response relationship was done using fractional polynomial modeling. Results: Among all eligible studies, 12 studies with a total number of 548 participants were selected. ALA caused a significant reduction on TC (WMD): -10.78 mg/dl, 95% CI: -20.81, -0.74, P=0.002), LDL (WMD: -10.88 mg/dl, 95% CI: -19.52, -2.24, P=0.014) and TG (WMD: -31.02 mg/dl, 95% CI: -49.63, -12.42, P<0.001). There was also a non-significant increaes in HDL concentrations. In addition, dose-response analysis showed a positive association between LDL (Pnon-linearity=0.026), TG (Pnon-linearity<0.001) and duration of intervention in a non-linear model. Conclusion: The present meta-analysis revealed the beneficial effects of ALA supplementation on TC, LDL and TG levels. Moreover, the beneficial effects of ALA supplementation on LDL and TG levels was duration-dependent.

An updated systematic review and dose-response meta-analysis of the randomized controlled trials on the effects of alpha-lipoic acid supplementation on inflammatory biomarkers.

Data about the effects of alpha-lipoic acid (ALA) supplementation on inflammatory markers are inconsistent. This systematic review and dose-response meta-analysis of randomized controlled trials was performed to summarize the effects of ALA supplementation on inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase, and SCOPUS from inception to February 2020. Among all of the eligible studies, 20 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran's Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eligible studies with a total sample size of 947 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced CRP (WMD: -0.69 mg/L, 95% CI: -1.13, -0.26, P=0.002), IL-6 (WMD: -1.83 pg/ml, 95% CI: -2.90, -0.76, P=0.001), and TNF-α concentrations (WMD: -0.45 pg/ml, 95% CI: -0.85, -0.04, P=0.032). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on serum CRP, IL-6 and TNF-α concentration. In subgroup analysis, ALA dosage, baseline concentrations of the parameter, sample size, and gender were considered as possible sources of heterogeneity. In summary, ALA supplementation improves inflammatory markers without any evidence of non-linear association to dose or duration of the trial.

Citrus peel derived poly-methoxylated flavones (PMF).

The prevalence of obesity has increased substantially over the last several decades and several environmental factors have accelerated this trend. Poly-methoxy flavones (PMFs) exist abundantly in the peels of citrus, and their biological activities have been broadly examined in recent years. Several studies have examined the effects of PMFs on obesity and its-related diseases. This systematic review conducted to focus on the effect of PMFs on obesity and its related conditions management. The PubMed, Google Scholar, Scopus, and Science Direct databases were searched for relevant studies published before November 2020. Out of 1,615 records screened, 16 studies met the study criteria. The range of dosage of PMFs was varied from 10 to 200 mg/kg (5-26 weeks) and 1-100 µmol (2h-8 days) across selected animal and in vitro studies, respectively. The literature reviewed shows that PMFs modulate several biological processes associated with obesity such as lipid and glucose metabolism, inflammation, energy balance, and oxidative stress by different mechanisms. All of the animal studies showed significant positive effects of PMFs on obesity by reducing body weight (e.g. reduced weight gain by 21.04%), insulin resistance, energy expenditure, inhibiting lipogenesis and reduced blood lipids (e.g. reduced total cholesterol by 23.10%, TG by 44.35% and LDL by 34.41%). The results of the reviewed in vitro studies have revealed that treatment with PMFs significantly inhibits lipid accumulation in adipocytes (e.g. reduced lipid accumulation by 55-60%) and 3T3-L1 pre-adipocyte differentiation as well by decreasing the expression of PPARγ and C/EBPα and also reduces the number and size of fat cells and reduced TG content in adipocytes by 45.67% and 23.10% and 16.08% for nobiletin, tangeretin and hesperetin, respectively. Although current evidence supports the use of PMFs as a complementary treatment in obesity, future research is needed to validate this promising treatment modality.

Vitamin D supplementation and cardiac tissue inflammation in obese rats.

OBJECTIVE: The current study was aimed to evaluate the effects of active form of vitamin D on TGF- ß, NF-κB and MCP-1 in heart tissue of obese rats. METHODS: Forty rats were allocated into groups of normal diet and high fat diet for sixteen weeks; then each group was divided into two groups that received either 500 IU/kg vitamin D or placebo for five weeks. Biochemical parameters were assessed by ELISA kits. RESULTS: Vitamin D reduced TGF-ß in obese rats supplemented with vitamin D compared with other groups (P = 0.03). Moreover, vitamin D reduced MCP-1 concentrations in the heart tissues of both vitamin D administered groups compared to placebo one (P = 0.002). NF-κB in the heart of HFD + vitamin D group was significantly lower (P = 0.03). Current study also showed that vitamin D improves glycemic status and reduce insulin resistance significantly in HFD group (P = 0.008). CONCLUSION: Vitamin D was a potential anti- inflammatory mediator of cardiovascular disease and markers of glycemic status in obese rats. Further investigations are needed to better identify the therapeutic role of this vitamin in CVD and to elucidate the underlying mechanisms.

Dietary total antioxidant capacity (TAC), general and central obesity indices and serum lipids among adults: An updated systematic review and meta-analysis.

Background: In the present meta-analysis, we aimed to summarize the relationship between dietary total antioxidant capacity (TAC), general and central obesity indices and lipid profile in adult population. Methods: The electronic databases of Web of Sciences, PubMed, Scopus and Cochrane library were searched for relevant studies from inception to October 2019. The effect size was indicated as weighted mean difference (WMD) and 95% confidence intervals (CI) by using random effects model. The I2 index and Cochran's Q-test were used for evaluating heterogeneity. Results: From 2,469 studies identified, thirty-four studies (nineteen cross-sectional studies, thirteen cohort studies, two case-control studies) were included in the meta-analysis. According to our results, higher categories of TAC were associated with significantly lower serum triglyceride concentartions (TG; WMD: -7.58; CI: -11.42, -3.75; P < 0.001) and waist circumference (WC; WMD: -1.17; 95% CI: -1.47, -0.87; P < 0.001); while no significant change in body mass index (BMI; WMD: -0.17; 95% CI: -0.35, 0.01; P = 0.12), high density lipoprotein cholesterol (HDL-C; WMD: 0.61; 95% CI: -0.16, 1.40; P = 0.12), low density lipoprotein cholesterol (LDL-C; WMD: 1.34; 95% CI: -0.61, 3.30; P = 0.17) and total cholesterol (TC; WMD: 1.19; 95% CI: -1.46, 3.855; P = 0.37) was reported. Conclusion: Higher dietary TAC was related to reduced prevalence of central obesity, reduced WC and TG concentrations in the current meta-analysis. Moreover, subgroup analysis showed that TAC measurement index, geographical area, dietary assessment tool, health status and gender were potential sources of heterogeneity.

The interaction effect of aerobic exercise and vitamin D supplementation on inflammatory factors, anti-inflammatory proteins, and lung function in male smokers: a randomized controlled trial.

BACKGROUND: This study aimed to investigate the interaction effect of aerobic exercise and vitamin D supplementation on inflammation (TNF-α, IL-6, CC16, SP-D, and CC16/SP-D ratio) and lung function (FEV1, FVC, and FEV1/FVC ratio) in male smokers. METHODS: After applying inclusion criteria, a total of 40 healthy male smokers were recruited in this study. The participants were randomly divided into four groups as follows: Aerobic Exercise + vitamin D Supplementation (AE + VitD, n = 10), Aerobic Exercise (AE, n = 10), vitamin D Supplementation (VitD, n = 10), and Control (C, n = 10). The participants in the AE + VitD and AE groups performed aerobic exercise training (running) up to 50% of the maximum heart rate, three times a week for four weeks. Participants in AE + VitD and VitD groups received 6000 IU/w vitamin D3 for four weeks. The participants in control group did not receive any intervention. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, Clara cell protein (CC16), surfactant protein (SP)-D, CC16/SP-D ratio, and lung function (FEV1, FVC, and FEV1/FVC ratio) were measured before and after four weeks of intervention. RESULTS: Serum levels of TNF-α, IL-6, and CC16 decreased significantly in AE + VitD, VitD, and AE groups after four weeks (P < 0.05). Serum SP-D level decreased significantly only in the AE + VitD group (P = 0.011). In addition, FEV1 and FVC increased significantly (P < 0.05) in AE + VitD and AE groups after four weeks of intervention. However, the interventions did not have a significant effect on CC16/SP-D ratio and FEV1/FVC ratio (P > 0.05). Furthermore, serum levels of 1,25-dihydroxyvitamin D increased significantly in AE + VitD and VitD groups (P < 0.05) after four weeks of intervention. However, except for TNF-α, between-group comparisons showed no significant differences in levels of IL-6, CC16, SP-D, CC16/SP-D ratio, FEV1, FVC, FEV1/FVC, and 1,25-dihydroxyvitamin D (P > 0.05). CONCLUSIONS: The results of present study were that aerobic exercise combined with vitamin D supplementation can reduce serum inflammatory factors and anti-inflammatory proteins and improve lung function after four weeks of intervention. Further trials with larger sample size and longer duration are suggested to confirm these results. Trial registration Retrospectively registered. IRCT20180513039637N4. Registration date: 2020/10/20. URL: https://www.irct.ir/search/result?query=IRCT20180513039637N4.

An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults.

This systematic review and dose-response meta-analysis was conducted to summarize data from available clinical trials on the effects of α-lipoic acid (ALA) supplementation on glycemic markers including glucose, hemoglobin A1c (HbA1c), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-ß, and quantitative insulin check index in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase and SCOPUS from inception to February 2020. Among all of the eligible studies, 28 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran's Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eight eligible studies with a total sample size of 1,016 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced insulin (WMD: -0.64; CI: -1.287 to 0.004, P = .04), HOMA-IR (WMD: -0.48; 95% CI: -0.79 to -0.16; P = .002). No change in glucose or HbA1C was reported. Moreover, the effect of ALA on insulin was duration-dependent (Pnon-linearity = 0.04). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on other markers. The subgrouping revealed that ALA dosage and duration of ALA supplementation, health status of participants, geographic locations and the studies' quality are possible sources of heterogeneity. In summary, ALA supplementation improves serum insulin and insulin resistance in a two-class and duration dependent non-linear analysis.

The effects of spinach-derived thylakoid supplementation in combination with calorie restriction on anthropometric parameters and metabolic profiles in obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: There is a promising outlook regarding the potential effect of spinach-derived thylakoids in the management of obesity and its associated metabolic disturbances. This research aimed to evaluate the effects of spinach-derived thylakoids supplementation combined with a calorie-restricted diet on anthropometric and metabolic profiles in obese women with the polycystic ovary syndrome (PCOS). METHODS: In a 12-week double-blind placebo-controlled randomized clinical trial, 48 females with obesity and PCOS were randomly allocated into either intervention (5 g/day thylakoid) or placebo (5 g/day cornstarch) groups along with calorie-restricted diets. Anthropometric measures, physical activity levels, dietary intakes, insulin resistance markers, as well as serum levels of insulin, fasting blood glucose (FBG), non-esterified fatty acids (NEFA), and sex hormones including dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were evaluated pre-and post-intervention. RESULTS: After the 12-week intervention, there were significant decreases in weight (- 6.97 ± 0.52 vs. -3.19 ± 0.72 kg; P < 0.001), waist circumference (- 7.78 ± 2.50 vs. -3.73 ± 1.40 cm; P < 0.001), fat mass (- 5.19 ± 0.53 vs. -1.36 ± 0.39 kg; P < 0.001), and insulin levels (- 5.40 ± 1.86 vs. -1.19 ± 0.85 µU/mL; P < 0.001) in the spinach-derived thylakoid group compared to the placebo group. Furthermore, insulin resistance markers and serum levels of testosterone decreased significantly in the thylakoid group compared to the placebo group (P < 0.05). The changes in other parameters did not show significant differences between the two groups. CONCLUSIONS: Spinach-derived thylakoid supplementation resulted in more favorable improvements in anthropometric indices and insulin sensitivity compared to the calorie restriction alone. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Research Vice-chancellor of Tabriz University of Medical Sciences, Tabriz, Iran, and was registered in the Iranian Registry of Clinical Trials (registration ID: IRCT20140907019082N9 ).

The effects of powdered black cumin seeds on markers of oxidative stress, intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in patients with Hashimoto's thyroiditis.

OBJECTIVE: Oxidative stress plays an important role in the pathogenesis of Hashimoto's thyroiditis. Because of the major anti-oxidant properties of black cumin, the current study aimed to evaluate the effect of powdered Nigella sativa seeds on markers of oxidative stress, endothelial dysfunction and serum lipids in patients with Hashimoto's thyroiditis. METHODS: Forty patients with Hashimoto's thyroiditis, aged between 22 and 50 years old, participated in the trial and were randomly allocated into two groups of intervention and control receiving powdered N. sativa or placebo daily for 8 weeks. Changes in markers of oxidative stress, including total anti-oxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and biomarkers of endothelial dysfunction including Intracellular Adhesion Molecule (ICAM)-1, Vascular Cell Adhesion Molecule (VCAM)-1 and serum lipids were also evaluated. RESULTS: Treatment with N. sativa, significantly increased serum TAC, SOD and reduced MDA concentrations with no significant change in GPX (P < 0.05). A significant reduction in VCAM-1 (P = 0.0012), body mass index (P = 0.002), serum concentrations of low density lipoprotein cholesterol (P = 0.002) and triglyceride (P = 0.02) were also reported in N. sativa-treated group after 8 weeks; while serum high density lipoprotein cholesterol (HDL) also significantly increased (P < 0.05). No change in other parameters were reported. CONCLUSIONS: Giving attention to the potent beneficial effects of powdered black cumin seeds in improving oxidative stress, endothelial dysfunction, serum lipids and anthropometric features in patients with Hashimoto's thyroiditis, this medicinal plant can be considered as a therapeutic agent in management of Hashimoto-related metabolic abnormalities. TRIAL REGISTRATION NUMBER: Iranian registry of clinical trials (registration number IRCT2015021719082N4).

Cocaine and amphetamine-regulated transcript prepropeptide gene (CARTPT) polymorphism interacts with Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals.

BACKGROUND: Epidemiologic studies show that cocaine- and amphetamine-regulated transcript prepropeptide (CARTPT) gene polymorphism modifies diet-obesity relationships. However, the interaction between CARTPT gene polymorphism and diet quality indices have not been investigated yet. The current study was aimed to evaluate the interaction between major dietary indices including Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI)-2015 and CARTPT gene rs2239670 variants among apparently healthy obese Iranians. METHODS: This cross-sectional study was carried out by employing 288 apparently healthy obese adults aged 20-50 years with a BMI of 30-40 kg/m2. Diet quality was evaluated by Diet Quality Index-International (DQI-I) and Healthy Eating Index-2015 (HEI-2015) using a 132-items semi-quantitative validated food frequency questionnaire. The CARTPT gene rs2239670 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Blood concentrations of glycemic markers, lipid profile, α-melanocyte stimulating hormone (MSH) and agouti-related peptide (AgRP) were also measured. ANCOVA multivariate interaction model was used to analyze gene-diet interactions. RESULTS: The significant interactions were identified between CARTPT gene polymorphism and HEI, affecting BMR (PInteraction = 0.003), serum glucose (PInteraction = 0.009) and high density lipoprotein cholesterol HDL concentrations (PInteraction = 0.03) after adjusting for the effects of sex and age. Also we found gene-diet interaction between CARTPT genotypes and DQI-I in terms of fat mass (FM; PInteraction = 0.02), waist circumference (WC; PInteraction < 0.001), body mass index (BMI; PInteraction < 0.001), basal metabolic rate (BMR, PInteraction < 0.001), serum fasting glucose (PInteraction < 0.01) and AgRP (PInteraction = 0.05) in individuals even after adjusting for potential confounders. CONCLUSION: Current study showed the effects of interaction between CARTPT genotype with adherence to HEI and DQI-I scores on obesity-related anthropometric and metabolic risk-factors.

Powdered black cumin seeds strongly improves serum lipids, atherogenic index of plasma and modulates anthropometric features in patients with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis is associated with serious alterations in serum lipids and glucose homeostasis. The aims of the current study were to evaluate the effect of powdered Nigella sativa on serum lipids, glucose homeostasis and anthropometric variables in patients with Hashimoto's thyroiditis. METHODS: Forty patients with Hashimoto's thyroiditis, aged between 22 and 50 years old, participated in the trial and were randomly allocated into two groups of intervention and control receiving powdered Nigella sativa or placebo daily for 8 weeks. Serum lipids, glucose homeostasis, and anthropometric variables were evaluated at baseline and after intervention. RESULTS: Treatment with Nigella sativa significantly reduced body weight and body mass index (BMI). Serum concentrations of low density lipoprotein cholesterol (LDL) and triglyceride (TG) also decreased in Nigella sativa-treated group after 8 weeks; while serum high density lipoprotein cholesterol (HDL) significantly increased after treatment with Nigella sativa (P < 0.05). None of these changes had been observed in placebo treated group. Serum Nesfatin-1 concentrations was in inverse relationship with serum triglyceride (TG) (r = - 0.31, P = 0.04). CONCLUSIONS: Giving attention to the potent beneficial effects of powdered black cumin seeds in improving serum lipid profile and anthropometric features in patients with Hashimoto's thyroiditis, this medicinal plant could be considered as a beneficial herbal supplement alongside with the disease- specific medications including Levothyroxine in management of Hashimoto's thyroiditis- related metabolic abnormalities. TRIAL REGISTRATION: Iranian registry of clinical trials (registration number IRCT2014090819082N2 - Registered 2014-09-29).

The effects of vitamin D administration on brain inflammatory markers in high fat diet induced obese rats.

BACKGROUND: Obesity induced brain inflammation is associated with cognitive disorders. We aimed to investigate the influence of vitamin D on hypothalamus and hippocampus inflammatory response in high-fat diet induced obese rats. METHODS: In the beginning of the study, 40 rats were divided into two groups: control diet and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: N, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. IL-6, IL-1ß, NF-Kß and acetylcholine (ACH) and brain derived neurotropic factor (BDNF) concentrations in hippocampus and hypothalamus homogenate samples were measured by commercial ELISA kits. RESULTS: Vitamin D administration, reduced food intake and weight gain in studied groups (P < 0.001). Vitamin D reduced hippocampus acetylcholine concentrations in ND + vitamin D group (P < 0.001). High fat diet increased hippocampus IL-6 concentrations significantly (P < 0.05) compared with normal diet receiving groups. Vitamin D could not have significant effects on IL-6 concentrations. Vitamin D administrations reduced IL-1ß, NF-Kß and acetylcholine concentration and BDNF concentrations in ND + vitamin D compared with ND group. These reductions were not significant in HFD + vitamin D versus HFD group. CONCLUSION: According to our results, vitamin D reduced food intake and weight gain and modulated the HFD induced inflammatory response in hippocampus and hypothalamus of high fat diet induced obesity. Therefore, this neurosteroid, can be suggested as a supplemental therapeutic tool in prevention of obesity related cognitive and neurodegenerative problems.

Adipose Tissue Inflammation and Oxidative Stress: the Ameliorative Effects of Vitamin D.

Obesity is a low-grade inflammatory disease and is associated with numerous comorbidities. The current study was aimed to evaluate the effects of vitamin D administrations on markers of inflammation and oxidative stress in adipose tissue of high-fat diet-induced obese rats. In the beginning of the study, 40 rats were divided into two groups: normal diet and high-fat diet (HFD) for 16 weeks; then, each group was subdivided into two groups including ND, ND + vitamin D, HFD, and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-ß and IL-6 concentrations and markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) concentrations in adipose tissue of rats were determined using ELISA kits and spectrophotometry methods, respectively. Vitamin D treatment led to a significant reduction in adipose tissue TNF-α concentrations in both ND + vitamin D and HFD + vitamin D groups (P < 0.05). Adipose tissue MCP-1 concentration also reduced in HFD + vitamin D group compared with HFD group. Among markers of oxidative stress in adipose tissue, SOD and GPx concentrations significantly increased in adipose tissue of HFD + vitamin D treated group compared with other groups (P < 0.05). Reduced food intake and weight gain was also occurred after vitamin D treatment. Vitamin D improved adipose tissue oxidative stress and inflammatory parameters in obese rats. Vitamin D treatment was also associated with decreased food intake and decreased weight gain in animals under a high-fat diet. Further studies are needed to better clarify the underlying mechanisms.

Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats.

BACKGROUND: Obesity is associated with numerous metabolic and inflammatory disorders. The current study was aimed to evaluate the effects of vitamin D administration on the markers of oxidative stress and inflammation in the cardiac tissue of high-fat diet induced obese rats. METHODS: In the beginning of the study, 40 male Wistar rats were divided into two groups: normal diet (ND) and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: ND, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. Tumor necrosis factor (TNF)-α concentration and markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) concentrations in the cardiac tissue and serum concentrations of lipids in rats were determined using ELISA kits and spectrophotometry methods respectively. RESULTS: According to our results, GPx activity in ND and ND + vitamin D group was significantly higher compared with HFD group. Similarly, SOD activity was also significantly increased in ND + vitamin D group compared with ND and HFD groups. Moreover, vitamin D administration, significantly reduced catalase activity in ND + vitamin D and HFD + vitamin D groups (P < 0.05). TNF-α concentration in heart tissue in ND + vitamin D group significantly reduced compared with ND group. Cardiac tissue MDA concentration in baseline or after vitamin D administration did not changed significantly. CONCLUSION: Vitamin D improved cardiac oxidative stress and inflammatory markers in HFD induced obese rats. Further studies in human models are needed to further confirm the use of this nutrient in daily clinical practice.

The effects of Spirulina Platensis on anthropometric indices, appetite, lipid profile and serum vascular endothelial growth factor (VEGF) in obese individuals: a randomized double blinded placebo controlled trial.

BACKGROUND: In recent years, a great attention has been focused on Spirulina platensis as a source of potential valuable nutrients for prevention and treatment of chronic diseases. The objectives of the current study were to determine the effects of Spirulina platensis on anthropometric parameters, serum lipids, appetite and serum Vascular Endothelial Growth Factor (VEGF) in obese individuals. METHODS: In the current study sixty four obese individuals aged 20-50 years were enrolled and randomly allocated into two groups of intervention and placebo. Intervention group (n = 29) received each 500 mg of the Spirulina platensis a twice-daily dosage while the control group (n = 27) received two pills daily starch for 12 weeks. Anthropometric parameters and serum VEGF and lipid profile were measured in fasting blood samples at the beginning and end of the study period. Dietary intakes were assessed by a 24-h recall method and appetite was measured using standard visual analogue scale (VAS). RESULTS: Body weight and body mass index (BMI) were decreased in intervention and placebo treated groups although the mean reduction in Spirulina platensis-treated group was significantly higher (P < 0.05). Serum total cholesterol (TC) significantly reduced in intervention group (P < 0.05). Also, treatment with Spirulina platensis significantly reduced appetite (P = 0.008). Mean serum VEGF, low density lipoprotein-cholesterol, and triglycerides did not change significantly after intervention. Serum high density lipoprotein-cholesterol concentrations (HDL-c) significantly increased in both groups while no difference in mean difference of this change has been observed. CONCLUSION: Spirulina supplementation at a dose of 1 g/d for 12 weeks is effective in modulating body weight and appetite and partly modifies serum lipids. This can further confirm the efficacy of this herbal supplement in control and prevention of obesity and obesity- related disorders. TRIAL REGISTRATION: Iranian registry of clinical trials (IRCT registration number: IRCT2015071219082N7 ; Date registered: September 12, 2015).

The Impact of Vitamin D Supplementation on Neurodegeneration, TNF-α Concentration in Hypothalamus, and CSF-to-Plasma Ratio of Insulin in High-Fat-Diet-Induced Obese Rats.

There is growing evidence that obesity can lead to neurodegeneration induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF-α). Moreover, obesity is associated with reduced transport of insulin through the blood-brain barrier (BBB). Insulin deficiency in the brain especially in the hypothalamus region has neurodegenerative and obesity-promoting effects. Because of the anti-inflammatory and neuroprotective effects of vitamin D, in the current experimental study, we aimed to investigate the effects of vitamin D supplementation on neurodegeneration, TNF-α concentration in the hypothalamus, and cerebrospinal fluid (CSF) to serum ratio of insulin in high-fat-diet-induced obese rats. At the first phase of the study, the rats were divided into two groups: (1) normal diet (ND, 10% fat) and (2) high-fat diet (HFD, 59% fat) and were fed for 16 weeks. In the second phase, each group was subdivided into four groups including the following: ND, normal diet + vitamin D, HFD, and HFD + vitamin D. Weight was measured and recorded weekly. Vitamin D supplementation for 5 weeks at 500 IU/kg dosage was used. One week after vitamin D supplementation, daily food intake was recorded. At week 22, blood was collected to determine fasting serum glucose, vitamin D, and insulin concentrations, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. CSF samples were also collected to measure insulin concentrations, and the hypothalamus was dissected to determine TNF-α concentration. HFD significantly increased TNF-α concentrations and degenerated neurons in the hypothalamus (P = 0.02). We also observed a significant reduction of CSF-to-serum ratio of insulin in HFD group (P = 0.03). The HOMA-IR test indicated significant increment of insulin resistance in HFD-fed rats (P = 0.006). Vitamin D supplementation in HFD group significantly reduced weight (P = 0.001) and food intake (P = 0.008) and increased CSF-to-serum ratio of insulin (P = 0.01). Furthermore, vitamin D decreased insulin resistance in the HFD group (P = 0.008). Vitamin D had no significant effect on degenerated neurons and TNF-α concentration in the hypothalamus. According to our findings, vitamin D improved brain insulin homeostasis and modulated food intake and body weight in high-fat-diet-induced obese rats. Further studies are needed to better clarify the underlying mechanisms.

The effects of Nigella sativa on thyroid function, serum Vascular Endothelial Growth Factor (VEGF) - 1, Nesfatin-1 and anthropometric features in patients with Hashimoto's thyroiditis: a randomized controlled trial.

BACKGROUND: Hashimoto's thyroiditis is an autoimmune disorder and the most common cause of hypothyroidism. The use of Nigella sativa, a potent herbal medicine, continues to increase worldwide as an alternative treatment of several chronic diseases including hyperlipidemia, hypertension and type 2 diabetes mellitus (T2DM). The aim of the current study was to evaluate the effects of Nigella sativa on thyroid function, serum Vascular Endothelial Growth Factor (VEGF) - 1, Nesfatin-1 and anthropometric features in patients with Hashimoto's thyroiditis. METHODS: Forty patients with Hashimoto's thyroiditis, aged between 22 and 50 years old, participated in the trial and were randomly allocated into two groups of intervention and control receiving powdered Nigella sativa or placebo daily for 8 weeks. Changes in anthropometric variables, dietary intakes, thyroid status, serum VEGF and Nesfatin-1 concentrations after 8 weeks were measured. RESULTS: Treatment with Nigella sativa significantly reduced body weight and body mass index (BMI). Serum concentrations of thyroid stimulating hormone (TSH) and anti-thyroid peroxidase (anti-TPO) antibodies decreased while serum T3 concentrations increased in Nigella sativa-treated group after 8 weeks. There was a significant reduction in serum VEGF concentrations in intervention group. None of these changes had been observed in placebo treated group. In stepwise multiple regression model, changes in waist to hip ratio (WHR) and thyroid hormones were significant predictors of changes in serum VEGF and Nesgfatin-1 values in Nigella sativa treated group (P < 0.05). CONCLUSIONS: Our data showed a potent beneficial effect of powdered Nigella sativa in improving thyroid status and anthropometric variables in patients with Hashimoto's thyroiditis. Moreover, Nigella sativa significantly reduced serum VEGF concentrations in these patients. Considering observed health- promoting effect of this medicinal plant in ameliorating the disease severity, it can be regarded as a useful therapeutic approach in management of Hashimoto's thyroiditis. TRIAL REGISTRATION: Iranian registry of clinical trials (registration number IRCT2015021719082N4 - Registered March-15-2015).

Vitamin A supplementation reduces the Th17-Treg - Related cytokines in obese and non-obese women.

OBJECTIVE: The objective of the present study was to investigate the effect of vitamin A supplementation on serum Th17 (IL-6, IL-17, IFNγ) and Treg (TGF-ß, IL-10) related cytokines in obese and non-obese women. SUBJECTS AND METHODS: In a randomized double blind placebo controlled design, 56 obese women were randomly assigned to receive either an oral dose of 25,000 IU retinyl palmitate or placebo per day for 4 months. Twenty eight ages matched non-obese women were also received vitamin A. At the study entry, anthropometric variables were measured and serum Th17 and Treg related cytokine profile were determined at baseline and 4 months after intervention. RESULTS: Significantly higher baseline concentrations of IL-6 were observed in obese compared with non-obese women (P < 0.05). However, the initial concentrations of other cytokines were not significantly different between groups. The mean concentrations of IL-17 and TGF-ß were significantly decreased after vitamin A supplementation in non-obese and obese women respectively. Positive relationships between IL-17 and IL-10 (r = 0.42, P < 0.001), TGF-ß and IL-17 (r = 0.35, P < 0.001) and between IL-10 and IFN-γ (r = 0.41, P = 0.002) in total participants were also observed. CONCLUSIONS: The results of the present study showed for the first time that vitamin A supplementation reduces serum concentrations of IL-17 and TGF-ß in reproductive age women. Further studies are needed to explore the possible underlying mechanisms.

The effect of enriched chicory inulin on liver enzymes, calcium homeostasis and hematological parameters in patients with type 2 diabetes mellitus: A randomized placebo-controlled trial.

BACKGROUNDS AND AIMS: Type 2 diabetic mellitus (T2DM) as one of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities. In the current study we aimed to evaluate the effects of enriched chicory inulin supplementation on liver enzymes, serum calcium and phosphorous concentrations and hematological parameters in patients with T2DM. METHODS: Forty-six diabetic females patients were randomly allocated into intervention (n=27) and control (n=22) groups. Subjects in the intervention group received a daily dose of 10g of chicory and subjects in control group received a placebo for two months. Anthropometric variables, glucose homeostasis, hematological parameters and metabolic indices including serum alanine aminotransfersae (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), calcium and phosphorous as well as creatinine concentrations, glomerular filtration rate (GFR) and blood pressure were assessed at the beginning and end of the trial. RESULTS: Significant reductions in fasting serum glucose (FSG), Hb A1C, AST and ALP concentrations were observed in chicory-treated group. Systolic and diastolic blood pressures were also reduced in chicory-treated group. Serum calcium significantly increased after chicory supplementation but no change in placebo treated group has been occurred (P=0.014). Supplementation with enriched chicory for two months significantly reduced hematocrit and mean corpuscular volume (MCV) values (P<0.05). Changes in serum insulin, creatinine and GFR were not significant. CONCLUSION: The present study showed beneficial effects of oligofructose-enriched chicory on the improvement of the glucose and calcium homeostasis, liver function tests, blood pressure and reduction in hematologic risk factors of diabetes in female patients with T2DM. Further studies in both genders are needed to generalize these findings to total population.