Zinc in depression: From development to treatment: A comparative/ dose response meta-analysis of observational studies and randomized controlled trials.

BACKGROUND: A previous meta-analysis suggested that zinc status may be linked to depression status. However, it remains unclear whether zinc status can predict the risk of depression development, or whether the monotherapy of zinc is superior to the combination of zinc supplementation and antidepressant medications in the treatment of depression. Therefore, this meta-analysis aimed to clarify the impact of zinc status and supplementation on depression development and status across all available evidence. METHODS: PubMed, EMBASE, Scopus, and ISI web of science were searched, up to 14 May 2020, for relevant publications. Pooled relative risks (RRs) with 95% confidence intervals (CI) in observational studies, and mean and standard deviation (SD) for the change in depression score in RCTs were calculated using a random-effects model. RESULTS: The meta-analysis of RCTs indicated that zinc supplementation significantly lowered depressive symptom scores of depressed patients [weighted mean difference (WMD = -4.15 point; 95% CI: -6.56, -1.75 point; P < 0.01)], and the improvement in depression status occurred only when zinc supplementation was prescribed as a monotherapy. The cohort studies showed that the highest level of zinc intake was associated with a 28% reduced risk of depression (RR: 0.66; 95% CI: 0.50, 0.82; I2 = 13.90). Dose-response analyses revealed a significant non-linear effect of baseline mood status on depression score. CONCLUSION: Current evidence from observational studies and RCT's supports the potential benefits zinc to reduce the risk of, and alleviate, depression. However, further trials are needed to confirm the beneficial effect of zinc as a monotherapy versus adjunctive therapies.

Circulating levels of adropin and overweight/obesity: a systematic review and meta-analysis of observational studies.

The association between circulating adropin levels and overweight/obesity is currently unclear. The aim of this study was thus to investigate and seek to determine the association between circulating adropin levels and overweight/obesity using the meta-analysis approach of observational studies. A comprehensive literature search was carried out through the PubMed, Web of Science, and SCOPUS databases to identify relevant observational studies that assessed the relationship between circulating adropin levels and overweight/obesity up to September 2020. A random-effects model was used to compute the pooled weighted mean difference (WMD) with 95% confidence intervals (CI). The meta-analysis of five studies (n = 643 participants) showed that circulating adropin levels were significantly lower in the overweight/obese vs. the normal-weight participants (WMD = - 0.96 ng/ml, 95% CI = - 1.72 to - 0.19, P = 0.01; I2 = 88.4%). In subgroup analyses, lower circulating adropin levels in obese participants compared with normal-weight were observed in Asians (WMD = - 1.58 ng/ml, 95% CI = - 1.96 to - 1.21, P < 0.001; I2 = 0.00%), and in patients with metabolic disorders (WMD = - 1.26 ng/ml, 95% CI = - 1.76 to - 0.77, P < 0.001; I2 = 44.6%), respectively. Circulating adropin levels were significantly lower in overweight/obese vs. normal-weight participants, suggesting a possible role of this hormone in the development of obesity. However, the present research indicates that further studies are needed to conclusively confirm whether adropin is a viable marker of obesity.

The effect of vitamin C supplementation on mood status in adults: a systematic review and meta-analysis of randomized controlled clinical trials.

OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to clarify the effect of vitamin C supplementation on mood in both depressed and non-depressed populations. METHODS: A systematic search of PubMed, EMBASE, ISI web of science and Scopus databases was conducted, from inception to 1 March 2020. Random-effects meta-analyses were used to estimate the effect size (as Hedge's g) of vitamin C supplementation on depressive symptoms. RESULTS: Finding from 10 trials with 836 participants revealed no significant improvement in mood status in overall analysis (n = 10, Hedge's g = 0.09; 95% confidence interval: -0.15 to 0.33; P = 0.465). However, subgroup analysis showed beneficial effects of vitamin C supplementation in patients who were not prescribed antidepressants (subclinical depressed) (n = 5, Hedge's g: -0.18; 95% CI: -0.35, -0.01, P = 0.041; I2 = 0.00%,). CONCLUSIONS: Although no significant effect on mood status was observed in overall population, this meta-analysis tentatively suggests that vitamin C may produce mood-elevating effects in patients with subclinical depression. Further research is recommended to reach a firm conclusion. PROTOCOL REGISTRATION: The study protocol was registered in the international prospective register of systematic reviews database (http://www.crd.york.ac.uk/PROSPERO, registration no: CRD42018086677).

Serum irisin levels in metabolically healthy versus metabolically unhealthy obesity: A case-control study.

Background: Metabolically healthy obese (MHO) individuals appear to be protected or more resistant to the progression of obesity-related metabolic disorders. Hormonal regulation associated with adipose or muscular tissues such as irisin and leptin may facilitate the healthy metabolic profile of MHO cases. In this case-control study, the differences between serum level of irisin was investigated in metabolically unhealthy obese (MUO) and metabolically healthy obese (MHO) individuals. Methods: The study participants included obese individuals with metabolic syndrome (MetS) (n=51) and 2 control groups that included weight matched cases without MetS (n=51) and normal weight cases without MetS (n=51). Diagnosis of MetS was made based on the Adult Treatment Panel III (ATPIII) criteria. Serum levels of leptin and irisin were determined by enzyme-linked immune-sorbent assay (ELISA) kit. Receiver Operator Characteristic (ROC) curve, multiple linear regression, and one-way ANOVA analysis were used in SPSS 16 software. Significant level was set at 0.05. Results: Based on the statistical analysis, serum levels of irisin were 2.91±1.6, 3.14±1.4, and 4.47±3.23 (ng/mL) in MUO, MHO, and nonobese metabolically healthy participants, respectively (P = 0.001). Also, serum levels of leptin were 14.06±12.4, 11.2±9.3, and 7.09±7.1 (ng/mL) in MUO, MHO, and nonobese metabolically healthy cases, respectively (p=0.002). After adjusting for demographic variables, a significant association was found between irisin and study groups (ß = 0.77, P = 0.001), weight (ß=-0.03, p=0.014), BMI (ß=-0.11, p=0.006), TG (ß=-0.003, p=0.025), fat mass (ß=-0.04, p=0.046), and fat free mass (ß=0.08, p=0.014). Conclusion: Obese patients with/without MetS had lower level of irisin than normal weight participants.

Effect of DASH diet on oxidative stress parameters: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND AIMS: Oxidative stress (OS) is one of the main risk factors for several chronic diseases. The Dietary Approaches to Stop Hypertension (DASH) contain many antioxidants and may contribute to managing OS. OBJECTIVE: To perform a systematic review and meta-analysis to examine the impacts of the DASH diet on OS parameters. METHODS: A comprehensive electronic search in MEDLINE, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials was performed through September 2020 to find related studies evaluating the impact of the DASH diet on OS parameters. Standardized mean differences were pooled using random-effects meta-analysis. RESULTS: Eight studies with a total of 317 subjects met our inclusion criteria. Four studies included in meta-analysis model with 200 participants (100 in treatment and 100 in control group). The DASH diet was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD: -0.53; 95% CI: -0.89, -0.16; I2 = 42.1%), and a significant increase in glutathione (GSH) (SMD: 0.83; 95% CI: 0.36, 1.03; I2 = 42.1%). Meta-analysis found no statistically significant effect of DASH diet on nitric oxide (NO) (SMD: -1.40; 95% CI: -0.12, 1.93; I2 = 92.6%) or total antioxidant capacity (TAC) levels (SMD: 0.95; 95% CI: -0.10, 1.99; I2 = 87.6%). CONCLUSION: Our results demonstrated that a DASH diet could significantly increase GSH and decrease MDA levels. Furthermore, there is a trend to improve TAC, NO, and f2-isoprostanes by the adherence to the DASH diet. However, long-term, large sample size and well-designed randomized clinical trials are still needed to draw concrete conclusions about DASH diet's effects on OS parameters.

Effects of zinc, vitamin D, and their co-supplementation on mood, serum cortisol, and brain-derived neurotrophic factor in patients with obesity and mild to moderate depressive symptoms: A phase II, 12-wk, 2 × 2 factorial design, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: The aim of this study was to investigate the effects of zinc, vitamin D, and their co-supplementation versus placebo on changes in the Beck Depression Inventory II (BDI-II) score, serum cortisol level, and brain-derived neurotrophic factor (BDNF) in obese/overweight patients with depressive symptoms. METHOD: This 2 × 2 factorial, double-blind, randomized, placebo-controlled trial with obese/overweight patients with depressive symptoms was conducted in the Endocrinology and Metabolism Research Center (EMRC), Vali-Asr, Emam Khomeini Hospital between July 2016 and February 2017. The intervention period was 12 wk. There were 140 randomized participants who were obese or overweight (mean ± SD, 38.35± 6.70 y of age; mean ± SD body mass index, 30.1 ± 3.78 kg/m2) with BDI ≥ 10. Participants were randomly assigned to one of four groups in a 1:1:1:1 ratio: 2000 IU/d vitamin D + zinc placebo; 30 mg/d zinc gluconate + vitamin D placebo; 2000 IU/d vitamin D + 30 mg/d zinc gluconate; or vitamin D placebo + zinc placebo for 12 wk. RESULTS: We analyzed 125 participants, and a significant decrease in BDI-II was found among those who received zinc, vitamin D, or joint zinc-vitamin D supplements compared with the placebo group (P < 0.001). Zinc was significantly more effective than vitamin D on decreasing the depression score. Supplementation with zinc, vitamin D, or a combination of the two had no significant effects on serum cortisol (P = 0.974) or BDNF (P = 0.076). Fifteen patients discontinued participation owing to pregnancy (n = 1), severe anemia (n = 1), and unspecified unwillingness to continue (n = 13). CONCLUSION: Supplementation with zinc, vitamin D, or in combination for 12 wk yielded significant beneficial effects on the BDI-II score in obese or overweight patients with BDI-II ≥10.

Comparing serum concentration of spexin among patients with metabolic syndrome, healthy overweight/obese, and normal-weight individuals.

Background: There are many factors related to etiology of metabolic syndrome (MetS) including obesity. Spexin, a peptide hormone released from adipose tissue, is the most down-regulated gene in obese, compared to non-obese adipose tissue. Hence, it potentially contributes to the progression and development of metabolic diseases. This study was designed to evaluate serum concentration of spexin in patients with MetS compared to weight-matched and normal-weight controls. Methods: In this case-control study, 153 participants (51 per group) were collected from October 2014 to June 2016. The study groups were all matched for age and sex and included overweight/obese individuals with MetS and 2 control groups without MetS (including weight-matched and normal-weight participants). Body composition and serum concentration of spexin and leptin were measured. Results: Serum leptin and spexin levels were significantly higher and lower, respectively, in normal-weight compared to overweight/obese groups with/without MetS (p< 0.02). No significant difference was observed in serum leptin and spexin concentrations between the overweight/obese groups with/without MetS (p≥ 0.05). Also, spexin, with cutoff value of 4.6, had 78% sensitivity and 82% specificity for diagnosing overweight/obese from normal-weight participants. Spexin had 78% sensitivity and specificity, with cutoff value of 4.35, in diagnosing MetS participants from normal-weight group. Conclusion: This study found no correlation between the circulating level of spexin and MetS development. Higher serum concentration of spexin in normal-weight adults compared to the obese participants illustrated the potential role of this novel peptide in obesity.

Adiponectin: An Indicator for Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, consider as a manifestation of obesity. However, a proportion of obese patients do not develop MetS. The aim of our study was to determine whether concentration of plasma adiponectin and leptin differ between metabolic unhealthy obese (MUO) patients and comparable age- and sex-matched control groups. METHODS: In this case-control study, we assigned 51 obese patients with MetS (MUO) in cases group and 102 metabolic healthy obese (MHO) and normal weight metabolic healthy subjects matched for age and gender to cases in control groups. The study was conducted between December 2014 and February 2016 in the Endocrinology Research Center of Tehran University of Medical Sciences, Tehran, Iran. We measured serum adiponectin, leptin, their ratio, and body composition in all subjects. RESULTS: No significant differences were observed between MHO and MUO in term of total fat mass and trunk fat (P>0.05). Compared to MHO and normal weight metabolic healthy subjects, MUO subjects had lower levels of plasma adiponectin (P<0.001) and lower plasma adiponectin to leptin ratio (P<0.001) and a higher level of plasma leptin (P<0.002). A Receiver Operator Characteristic curve was used to identify the ability of adiponectin and leptin level to predict the MetS. The area under the Receiver Operator Characteristic curve was 0.66 (P<0.01), 0.73 (P<0.001) and 0.75 (P<0.001) for leptin, adiponectin, and adiponectin/leptin ratio levels respectively. CONCLUSION: Our study introduced adiponectin and leptin as indicator of MetS and obesity respectively.

The Effects of Probiotics or Synbiotics Supplementation in Women with Polycystic Ovarian Syndrome: a Systematic Review and Meta-Analysis of Randomized Clinical Trials.

We searched bibliographic databases from inception through May 2018 to evaluate the effect of probiotics (or synbiotics) supplementation in women suffering from polycystic ovary syndrome (PCOS). Seven trials involving 236 women with PCOS and 235 controls were included in the meta-analysis. Comparing with the control group, probiotics (or synbiotics) may improve Quantitative insulin sensitivity check index (QUICKI) (standardized mean difference (SMD) 0.41, 95% confidence intervals (CI) 0.01 to 0.82, P = 0.04), decrease triglyceride (TG) level (mean difference (MD) - 17.51 mg/dL, 95% CI - 29.65 to - 5.36); fasting insulin: (MD - 2.14 µIU/mL, 95% CI - 4.24 to - 0.04), and increase high-density lipoprotein (HDL) (SMD 1.55 mg/dL, 95% CI 0.28 to 2.81). No significant effect of probiotics (or synbiotics) on homeostatic model assessment-insulin resistance (HOMA-IR), fasting plasma glucose (FPG), low-density lipoprotein (LDL), total cholesterol (TC), and anthropometric indices was found in women with PCOS. Although probiotic (or synbiotics) supplementation was effective on some metabolic indices, the effect was negligible and not clinically significant.

Depressive symptoms among metabolically healthy and unhealthy overweight/obese individuals: a comparative study.

Background: Although a growing body of evidence suggests an association between obesity and depressive disorder, the association remains inconclusive. Metabolically healthy obese (MHO) phenotype, defined by favorable lipid profile, and normal insulin sensitivity, blood pressure, may be considered as a possible explanation for these inconsistencies. Accordingly, this study aimed to compare depression score among metabolic unhealthy obese (MUO) and age- and sex-matched healthy controls. Methods: In this comparative study including 157 Iranian adults, we assigned participants into three groups (non-obese metabolic healthy group, MHO and MUO) according to the BMI cutoff and MetS criteria. Depressive symptoms were assessed by Beck Depression Inventory. Analysis was done using SPSS version 14.0. All variables are expressed as means ± SD. One-way ANOVA and multiple linear regression were used for data analysis. Results: After adjustment for sex, marital status and educational level, MUO participants had significantly higher Beck depression score (P= 0.036) compared to MHO and non-obese metabolic healthy groups. After adjustment for demographic variables, there was a significant association between waist circumference (ß = 0.142, p=0.023), BMI (ß= 0.347, p= 0.037), FBS (ß= 0.096, p< 0.001), and the number of MetS components (ß= 1.71, p= 0.002) with depression score. Conclusion: MHO was a benign phenotype in relation to depression.

Metabolic Syndrome Patients Have Lower Levels of Adropin When Compared With Healthy Overweight/Obese and Lean Subjects.

Metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, is a challenging public health issue. The aim of current study was to test the hypothesis that concentrations of plasma adropin and leptin differ between patients with MetS and comparable age- and sex-matched control groups. This case-control study involved 153 subjects (51 per group). The study group included obese subjects with MetS and the two control groups included weight-matched subjects without MetS ("healthy": obese) and normal weight subjects without MetS. Body composition parameters were measured using bioelectrical impedance analysis. Plasma levels of adropin, leptin, and their ratio were measured. Leptin was significantly different between obese patients with/without MetS groups and normal weight subjects. Patients with MetS had higher levels of leptin (14 ± 12.4) compared with those without MetS (11.2 ± 9.3 vs. 7 ± 7.1 obese and normal weight without MetS, respectively; p = .002). Compared with healthy obese and normal weight subjects, MetS subjects had lower levels of plasma adropin ( p < .001) and a lower plasma adropin to leptin ratio ( p < .001), which remained significant when adjusted for body fat mass by analysis of covariance ( p < .001). This study demonstrates low levels of adropin are correlated with MetS and hence identify it as a potentially protective agent against MetS development. Variation in adropin levels may partly explain the "healthy obese" phenomenon.

Diet quality in obese/overweight individuals with/without metabolic syndrome compared to normal weight controls.

BACKGROUND: Metabolic syndrome (MetS) is a serious public health concern worldwide; however, the pathogenesis of this disease has not been yet cleared. This study aimed to compare diet quality in obese/overweight participants with/without metabolic syndrome with normal weight controls. METHODS: This was a comparative study on 147 Iranian adults under treatment at the Endocrinology Center of Tehran University of Medical Sciences. They were assigned into three groups (normal weight, obese weight with/without MetS) according to the inclusion- exclusion criteria. Metabolic syndrome was defined according to the NCEP ATPIII consensus criteria. Healthy Eating Index Data were obtained from the validated FFQ to determine the diet quality index scores, using the Healthy Eating Index-2010. RESULTS: Our findings demonstrated that FBS, TG, SBP, WC and weight were higher among MetS patients compared to the both weight matched and non-weight matched participants, while HDL-c was lowest in this group (p<0.05). A statistically significant difference was found between healthy weight controls and obese/overweight participants with/without MetS in HEI-2010, and 9 of the 12 HEI-2010 components score (p<0.05). CONCLUSION: Our study revealed that low diet quality was a risk factor in developing MetS.

Positive evidence for vitamin A role in prevention of type 1 diabetes.

Type 1 diabetes mellitus (T1DM) as one of the most well-known autoimmune disease, results from the destruction of ß-cells in pancreas by autoimmune process. T1DM is fatal without insulin treatment. The expansion of alternative treatment to insulin is a dream to be fulfilled. Currently autoimmunity is considered as main factor in development of T1DM. So manipulation of the immune system can be considered as alternative treatment to insulin. For the past decades, vitamin A has been implicated as an essential dietary micronutrient in regulator of immune function. Despite major advantage in the knowledge of vitamin A biology, patients who present T1DM are at risk for deficiency in vitamin A and carotenoids. Applying such evidences, vitamin A treatment may be the key approach in preventing T1DM.

Adropin- A Novel Biomarker of Heart Disease: A Systematic Review Article.

BACKGROUND: Heart disease is one of the most common chronic disease and leading cause of morbidity and mortality worldwide. Adropin, a newly identified protein, is important for energy homeostasis and maintaining insulin sensitivity, and has been referred to as a novel regulator of endothelial cells. Endothelial dysfunction is a key early event in atherogenesis and onset of HD. Therefore, this review gives a systematic overview of studies investigating plasma adropin level in patient with heart disease. METHODS: Data carried out in PubMed, Scopus, Web of Science, Embase, Google scholar and MEDLINE, from the earliest available online indexing year through 2015. The search restricted to studies conducted in humans. The keyword search was adropin to apply in title, abstract and keywords. References lists of all original published articles were scanned to find additional eligible studies. RESULTS: Heart failure (HF), coronary atherosclerosis acute myocardial infarction and Cardiac Syndrome X (CSX) were type of heart disease acknowledged in this study. Majority of evidences introduced low adropin as an independent risk factor of heart disease. In a case-control study, the plasma level of adropin increased with the severity of HF. CONCLUSION: Adropinmay be a potential serum biomarker for early diagnosis of HD.