The Effect of Selenium, Zinc, and their Combined Supplementation on Cardiometabolic Biomarkers-comparing their Effects in the Energy Restriction and High-fat Diet Methods in Obese Rats.

INTRODUCTION: The fat distribution in the body determines the risk of cardiometabolic problems such as heart disease and diabetes. Some dietary supplements, such as selenium and zinc, possess lipolytic and anti-angiogenic functions, which may be a useful strategy in reducing the risk of cardiometabolic complications. This study evaluated the effect of zinc (Zn), selenium (Se), and their combined supplementation on cardiometabolic risk factors in male Wistar rats in two nutritional models, including caloric restriction (CR) and high-fat diet (HFD). METHODS AND MATERIALS: The 48 male Wistar rats were divided into three diet groups (HFD and CR and normal diet (ND)). The HFD group was subdivided into four groups (N=8 rats in each group) that received (HFD+Se), (HFD+Zn), (HFD+Zn+Se), and HFD alone as the control group, respectively. After 8 weeks of intervention, biochemical tests were performed on serum levels, including measurement of lipid profile (triglyceride, Cholesterol, LDL and HDL) and glycemic indices (fasting blood sugar, insulin and insulin sensitivity markers). RESULTS: The results showed that supplementation significantly improved the lipid profile (P <0.001). A comparison of glucose homeostasis indices in the study groups also showed a significant difference. The serum level of glucose was higher in the HFD group than in the intervention groups (P <0.001). Also, the rate of improvement of lipid profile and glycemic indexes in the group receiving the combination of two supplements showed a better trend than those receiving zinc and selenium alone. However, the values were statistically significant only for glucose homeostasis indices (P <0.001). CONCLUSION: Although obesity is a multifactorial condition, controlling other risk factors, zinc and selenium and their combined supplementation can lead to promising solutions for the treatment of obesity-induced glucose and lipid homeostasis disorders.

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 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.

Beneficial effects of Se/Zn co-supplementation on body weight and adipose tissue inflammation in high-fat diet-induced obese rats.

This research investigated the effect of co-supplementation of selenium with zinc on weight control and the inflammatory and oxidative status in relation to obesity. Male Wistar rats (N = 32) were randomly divided into four groups after induction of obesity model: 1) "Zn" was supplemented with zinc sulfate (15 mg/kg BW), 2) "Se" supplemented with selenium as sodium selenate (0.5 mg/kg BW), 3) "Zn + Se" which received Zn (15 mg/kg BW) + Se (0.5 mg/kg BW), and 4) "HFD" as the control group. The intervention was done for eight weeks. At the end of treatment, serum and tissue level of Zn, Se, SOD, GSH-Px, MDA, leptin, TNF-α, and IL-6 was evaluated. Weight and food intake were significantly reduced in the Se group(p < .001), while in the Zn group, weight gain due to obesity was prevented compared to the control group (p = .48). There was a significant and stronger increase in SOD, GSH-Px levels and a remarkable decrease in MDA, leptin, TNF-α, and IL-6 in the group receiving the combination of two supplements than either alone(p < .001). Leptin had a positive correlation with inflammatory factors and lipid peroxidation marker and showed an inverse relationship with Zn and Se levels and anti-oxidative enzymes(p < .05). The analysis showed the mediating role of leptin in the effects of zinc. Co-supplementation of selenium and zinc may have a synergistic effect in reduction of oxidative and inflammatory markers. Regarding the effect of zinc on inflammatory factors and lipid peroxidation, leptin can play a mediating role.

Effect of ginger (Zingiber officinale) on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.

The aim of this systematic review and meta-analysis was to investigate the efficacy of ginger supplementation on circulating levels of C-reactive protein (CRP), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), soluble intercellular adhesion molecule (sICAM), and interleukin-6 (IL-6) concentrations in randomized controlled trials (RCTs). The search included PubMed-Medline, EMBASE, Scopus, Web of Science and Cochrane Library databases to identify randomized clinical trials on the effect of ginger supplementation on circulation levels of CRP, hs-CRP, IL-6, sICAM, and TNF-α published up until February 1st, 2020. We did not restrict articles based on language of publication. Standard mean differences and 95% confidence intervals were calculated for net changes in inflammatory mediators using a random-effects model. Sixteen RCTs comprising 1010 participants were found to be eligible for this meta-analysis. There was a significant reduction of circulating CRP (SMD: -5.11, 95% CI: -7.91, -2.30, I2 = 98.1%), hs-CRP (SMD: -0.88, 95% CI: -1.63, -0.12, I2 = 90.8%) and TNF-α levels (SMD: -0.85, 95% CI: -1.48, -0.21, I2 = 89.4%) following ginger supplementation. However, meta-analysis results did not show any significant impact of ginger supplementation on IL-6 (SMD: -0.45, 95% CI: -1.29, 0.38, I2 = 89.2%), and sICAM levels (SMD: -0.05, 95% CI: -0.36, 0.26, I2 = 00.0%). This systematic review and meta-analysis of RCTs demonstrates a significant impact of ginger in lowering circulating CRP, hs-CRP and TNF-α levels. Large-scale RCTs are still needed to draw concrete conclusions about the effect of ginger on other inflammatory mediators.

Pickle Consumption is Associated with Body Mass Index and Blood Pressure among Iranian Female College Students: a Cross-Sectional Study.

Pickle is consumed in high amount among Iranians. Pickle consumption may be related to body mass index (BMI) and blood pressure (BP) but limited evidence exist in this regard. The aim of current study was to determine the association between pickle consumption and risk of overweight, central obesity and BP among Isfahanian female youths. A cross-sectional study was conducted on 289 female students aged 18-27 years randomly selected from students of Isfahan University of Medical Sciences, Isfahan, Iran. Diet was assessed by a validated and reliable food-frequency questionnaire. Mean pickle consumption was 15.1 ± 2.2 g/day. Individuals in the highest tertile of pickle consumption had a significantly higher BMI, systolic and diastolic BP (p = 0.001, 0.03, and 0.03, respectively), whereas we did not observe significant association for waist circumference (p = 0.21). Total energy intake (p = 0.02) and consumption of carbohydrate (p = 0.01), protein (p = 0.03), and fat (p = 0.05) in the upper tertile was higher than lower tertiles. There was a significant association between pickle consumption and obesity and BP among Iranian female youths. Further prospective studies are needed to confirm this association.

The Effect of n-3 Polyunsaturated Fatty Acids Supplementation on Serum Irisin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Diabetes refers to a group of metabolic diseases with blood glucose of higher than normal ranges. Furthermore, n-3 polyunsaturated fatty acids are necessary for the regulation of the activity of human function. The effect of n-3 PUFA on diabetes has been investigated in animal studies, yet, the exact amount has not been set, to date. Irisin, as a new myokine, is released from skeletal muscle and Irisin levels decrease as a result of physical inactivity, overweightness, and obesity. Also, the reduction of serum irisin level is associated with development of insulin resistance and type 2 diabetes. This study was performed to assess the effects of n-3 PUFA supplementation on serum irisin level in patients with diabetes. METHODS: This randomized clinical trial included 43 patients with type 2 diabetes (21 patients in the placebo group and 22 patients in the n-3 PUFA supplement group). They were randomized to groups, one receiving 10 weeks of either n-3 PUFA supplement and the other the placebo (1250 mg capsule, three times per day). Samples were also matched by age, gender, and body mass index (BMI) in the 2 groups. Anthropometric measurements, demographic information and dietary intakes were obtained both before and after the intervention. Serum irisin levels were measured before and after the intervention using human irisin enzyme linked immunosorbent assay (ELISA) kit. Independent t-test was used to compare the mean outcomes between groups. RESULTS: At baseline, irisin serum levels were not significantly different between the placebo and n-3 PUFA supplementation groups (P > 0.05). However, a significant change was observed between the groups after intervention (P = 0.04). Also there was a significant difference in mean change (after versus before the intervention) (P = 0.05). Compared to the placebo, n-3 PUFA supplementation decreased serum FBS and HbA1C (P = 0.036 and 0.001; respectively). Also, there were significant differences between changes of diastolic blood pressure and HOMA-IR after the intervention between the groups. The duration of illness was not considered as a confounding factor because there was no significant association between irisin level (after versus before the intervention) and the illness duration. CONCLUSIONS: The current study indicated that n-3 PUFA supplementation with a dosage of 1250 mg three times per day, resulted in increased serum irisin level of diabetic patients.

Omega-3 Fatty Acid Could Increase One of Myokines in Male Patients with Coronary Artery Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Omega-3 fatty acids have a protective role against cardiovascular disease and these protective properties are attributed to its anti-inflammatory effects. Myokines have anti-inflammatory properties and thereby reduce low-grade inflammation. Irisin, as a myokine, is considered to be therapeutic for human metabolic diseases. This study was conducted to determine the effects of Omega-3 fatty acids supplementation on serum irisin in men with coronary artery disease (CAD). METHODS: This study was an 8-week randomized, double-blind, placebo-controlled trial. Forty-eight CAD male patients (Omega-3, n = 24; control, n = 24) were randomly assigned to either Omega-3 or control groups by permuted block randomization method. Only the participants with more than 50% stenosis in at least one major coronary vessel were included.  A total of 3 participants in the control group were excluded from the study. Forty-five participants (Omega-3, n = 24; control, n = 21) completed the study. Participants took Omega-3 fatty acids supplement (720 mg eicosapentaenoic acid plus 480 mg docosahexaenoic acid) or placebo (edible paraffin) for 8 weeks. Serum irisin, high-sensitivity C-reactive protein (hs-CRP), lipid profile and anthropometric indices, body composition, and food intake were assessed before and after intervention. Statistical analyses were performed using SPSS software. Paired t-test was used for evaluating within-group effects from baseline. Variables with normal distribution were compared by independent t-test between 2 groups. RESULTS: Compared to placebo, Omega-3 fatty acids increased serum irisin (P = 0.044) and decreased serum hs-CRP (P = 0.018) and LDL cholesterol (P = 0.031). Omega-3 fatty acids supplementation did not result in any significant changes in anthropometric measurements, blood pressure, serum lipids except for serum LDL, fasting blood glucose, body composition or serum insulin levels (all P > 0.05). CONCLUSION: Omega-3 fatty acids supplementation could elevate serum irisin in male patients with CAD. Also, these fatty acids may able to decrease serum hs-CRP and LDL cholesterol.