Effect of carbohydrate restriction on body weight in overweight and obese adults: a systematic review and dose-response meta-analysis of 110 randomized controlled trials.

Introduction: Carbohydrate-restricted diets are one of the most effective dietary interventions for weight loss. However, the optimum carbohydrate intake for implementing the most effective weight-loss interventions is still being discussed. We aimed to determine the optimum carbohydrate intake for short- and long-term weight loss in adults with overweight and obesity. Methods: We searched PubMed, Scopus, Web of Science, and CENTRAL from inception to May 2021 for randomized controlled trials examining the effect of a carbohydrate-restricted diet (≤45% of energy intake) as compared to a control diet (carbohydrate intake >45% of energy intake) on body weight in adults with overweight/obesity. A random-effects dose-response meta-analysis was conducted to calculate the mean difference for each 10% decrease in carbohydrate intake at the 6-month follow-up (1 to 6 months), 12-month follow-up (6 to 12 months), and follow-up longer than 12 months. The shape of the dose-dependent effects was also evaluated. The certainty of the evidence was rated using the GRADE approach. The minimal clinically important difference (MCID) threshold was defined as 5% weight loss (equal to 4.39 kg). Results: A total of 110 trials were selected for the present meta-analysis. In the linear dose-response meta-analysis, each 10% decrease in carbohydrate intake reduced body weight by 0.64 kg (95% CI: -0.79 to -0.49; n = 101 trials with 4,135 participants, high-certainty evidence) at the 6-month follow-up and by 1.15 kg (95% CI: -1.61 to -0.69; 42 trials with 2,657 participants, moderate-certainty evidence) at the 12-month follow-up. Non-linear dose-response meta-analyses indicated a monotonic reduction in body weight with the decrease in carbohydrate intake, with the greatest reduction at 5% at the 6-month follow-up (mean difference 5%: -3.96 kg, 95% CI: -4.92 to -3.00) and 10% at the 12-month follow-up (mean difference 10%: -6.26 kg, 95% CI: -10.42 to -2.10). At follow-up longer than 12 months, dose-response analyses suggested a non-linear effect, wherein carbohydrate intakes higher than 40% and lower than 30% were not effective for weight loss. Discussion: Carbohydrate restriction is an effective dietary strategy for important weight loss in adults with overweight and obesity. At 6-month and 12-month follow-ups, body weight decreased proportionally, more than the MCID threshold, along with the decrease in carbohydrate intake. At follow-up longer than 12 months, there was a non-linear effect, with the greatest reduction at 30% carbohydrate intake. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315042.

The effect of whole grape products on blood pressure and vascular function: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Grape consumption-associated improvements in cardiovascular health have received significant attention over the last few years; however, major gaps have remained in the meta-evidence related to this topic. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to explore the effect of whole grapes and its products on blood pressure, endothelial function, heart rate, and pulse rate. METHODS AND RESULTS: Four database (PubMed, Scopus, Web of Sciences, and the Cochrane Library) were searched until the 14th of January 2022. The pooled effect size of interested outcomes was calculated using the random-effects model. Thirty eligible RCTs were identified. Pooled results indicated that compared to the control group, consumption of grape products significantly decreased systolic blood pressure (SBP) (WMD = -3.17 mmHg; 95% CI: -5.36, -0.99 mmHg; P = 0.004; I2 = 64%; P-heterogeneity<0.001); while, vascular cell adhesion molecule-1 (VCAM-1) increased (WMD = 34.11 ng/ml; 95% CI: 0.98, 67.25 ng/ml; P = 0.04; I2 = 2%; P-heterogeneity = 0.4). Although, the certainty of evidence was low and very low, respectively. No significant effect was observed on diastolic blood pressure, endothelial function, heart rate, pulse rate, and soluble intercellular adhesion molecule-1 (sICAM-1). In a subgroup analysis, consumption of whole grape products (raisin and grape powder) induced a significant decrease in SBP (WMD = -2.69 mmHg; 95% CI: -4.81, -0.57; P = 0.01; I2 = 18.1%; P-heterogeneity < 0.001), while grape juice did not. CONCLUSION: The low certainty of evidence from RCTs revealed that consumption of grape products, especially in whole forms, resulted in a small reduction of SBP but did not influence other markers of cardiovascular health. PROSPERO REGISTRATION CODE: CRD42022379231.

The effects of grapes and their products on immune system: a review.

Immune system plays a significant role in preventing and controlling diseases. Some studies reported the beneficial effects of grapes and their products on immunity. However, their results are controversial. This review aimed to discuss the effects of grapes and their products on immune system and their mechanisms of action. Although various in-vio and in-vitro studies and some human studies suggested that grapes and their products may help to improve the immune system's function, clinical trials in this area are limited and inconsistent.In conclusions, although, consumption of grapes and their products may help to having a healthy immune syste, further studies particularly human studies are required to clarify the precise effects of them and their mechanisms regarding immune system.

Circulating levels of adropin and diabetes: a systematic review and meta-analysis of observational studies.

OBJECTIVE: Adropin, a newly identified regulatory protein has garnered attention given its potential role in metabolism regulation, especially glucose metabolism and insulin resistance. However, studies on the association between adropin and type 2 diabetes mellitus (T2DM) are equivocal. The aim of this study is to assess the association between serum adropin levels and T2DM using a systematic review and meta-analysis of observational studies. METHODS: PubMed, Scopus, ISI Web of science, and Google Scholar were searched, up to August 2022, for studies that reported the association between serum levels of adropin in adults with T2DM compared to a control group without diabetes. A random-effect model was used to compute the pooled weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: Meta-analysis of 15 studies (n = 2813 participants) revealed that the serum adropin concentrations were significantly lower in patients with T2DM compared with the control group (WMD= -0.60 ng/mL, 95% CI: -0.70 to -0.49; I2 = 99.5%). Subgroup analysis also found lower concentration of adropin in patients with T2DM who were otherwise healthy compared to a control group (n = 9; WMD=-0.04 ng/ml, 95% CI= -0.06 to -0.01, p = 0.002; I2 = 96.4). CONCLUSIONS: Our study showed adropin levels are lower in patients with diabetes compared to a control group without diabetes. However, the limitations of observational studies challenge the validity of the results, and further investigations are needed to confirm the veracity of these findings and additionally explore possible mechanisms.

Effects of probiotic/synbiotic supplementation on body weight in patients with diabetes: a systematic review and meta-analyses of randomized-controlled trials.

OBJECTIVE: The aim of the present study was to assess the effect of probiotic/synbiotic supplementation on anthropometric measures in adults with diabetes, independent of body weight. METHODS: PubMed, Scopus, Web of Sciences and the Cochrane Library were searched for randomized controlled trials (RCTs) up until December 14, 2022. The effect sizes were pooled using an inverse-variance random-effects model. The methodological quality of studies as well as the quality of evidence was assessed using standard tools. RESULTS: Thirty-two RCTs met the established inclusion criteria. Overall, compared with the respective control groups, probiotic/synbiotic supplementation resulted in a significant reduction in body weight (weighted mean difference [WMD]: -0.50 kg; 95% CI: -0.83, -0.17; I2 = 79.8%, n = 27 studies]), body mass index (WMD: -0.24 kg/m2; 95% CI: -0.39, -0.09; I2 = 85.7%, n = 30 studies), and waist circumference (WMD: -0.90 cm; 95% CI: -1.13, -0.52; I2 = 0%, n = 11 studies). However, hip circumference and waist to hip ratio were not significantly improved. CONCLUSIONS: Our analysis revealed that probiotic/synbiotic supplementation may assist with weight management in patients with diabetes, especially when consumed at higher doses, in younger adults, and in participants with obesity. However, more studies are needed to elucidate the anti-obesity effects of specific strains of probiotics/synbiotics.

Oral vitamin D supplementation and body weight in children and adolescents: a systematic review and meta-analysis of randomized controlled trials.

This study was designed to ascertain whether oral vitamin D supplementation (oral supplementation and fortified foods) is associated with changes in body weight measures in children and adolescents, using a systematic review and meta-analysis of randomized controlled trials (RCTs). PubMed, Scopus, Cochrane, and Web of Science databases were searched from inception to October 28, 2022. The mean difference and corresponding 95% confidence interval (CI) of interested outcomes were pooled using a random-effects model. Twenty-one RCTs were included in the meta-analysis, and the results showed a significant decrease in body mass index (BMI) following vitamin D supplementation in children and adolescents (n = 9 studies, 1029 participants; weighted mean difference: - 0.43 kg/m2, 95% CI: - 0.79, - 0.08; P = 0.02; I2 = 58.5%). Overall, oral vitamin D supplementation had no significant effect on body weight and other anthropometric indices, including fat mass, lean mass, waist circumference, BMI Z-score, and height. Although results of body weight changed to significant after sensitivity analysis (WMD = 0.39 kg, 95% CI = 0.01, 0.78; P = 0.04; I2 = 0%, P-heterogeneity = 0.71), we also found significant weight gain in healthy pediatric population, and when the dose of vitamin D supplementation was up to 600 IU/day, the certainty of evidence was very low for weight, moderate for height and BMI, and low for the remaining outcomes. CONCLUSION: Our results suggest that vitamin D supplementation may lead to a statistically significant weight gain in children and adolescents, while BMI was reduced. Although no significant change was observed in height, it seems vitamin D supplementation may elicit these changes by increasing skeletal growth; however, this remains to be verified. Further high-quality RCTs, with longer duration and larger sample sizes, are needed to yield more certain evidence in this regard. WHAT IS KNOWN: • Available evidence indicates an inverse association between body weight/fat mass and vitamin D status in children and adolescents; however, findings regarding the effect of vitamin D supplementation on anthropometric measurements in children are controversial. WHAT IS NEW: • Our results showed a significant decrease in BMI following vitamin D supplementation in children. • A significant weight gain also was observed after sensitivity analysis, and in healthy pediatric population, and when the dose of vitamin D supplementation was up to 600 IU/day.

Resveratrol may mildly improve renal function in the general adult population: A systematic review and meta-analysis of randomized controlled clinical trials.

Whether renal health biomarkers can benefit from resveratrol supplements is unknown. Thus, we conducted a systematic review and meta-analysis to summarize evidence from randomized controlled trials investigating the effect of resveratrol supplementation on renal health biomarkers. We hypothesized that resveratrol supplementation is associated with improved renal health biomarkers. Four electronic databases, including PubMed, Scopus, and Institute for Scientific Information Web of Science, and Cochrane Central, were searched for relevant articles up to February 2023. The pooled effect sizes were estimated using a random effects model and expressed as weighted mean difference (WMD) and 95% CI. In total, 32 articles were eligible for inclusion in the current meta-analysis. The pooled results indicated that resveratrol significantly decreased blood urea nitrogen (weighted mean difference [WMD]= -0.84 mg/dL; 95% CI, -1.48 to -0.20; P = .01; I2 = 64.4%) and creatinine levels (WMD = -1.90 µmol/L; 95% CI, -3.59 to -0.21; P = .03; I2= 52.1%), and increased glomerular filtration rate (WMD = 7.58 mL/min/1.73 m2; 95% CI, 5.25-9.91; P < .001; I2 = 0%). The favorable change of blood urea nitrogen was significant in studies with short follow-up duration (12 weeks or less), with lower doses of resveratrol (less than 500 mg/d), and those conducted in patients with diabetes. However, higher doses of resveratrol are needed to observe significant reductions in creatinine. No significant change was observed in albumin, total protein, and uric acid concentrations. This meta-analysis provides a low certainty of evidence indicating a mild renal protective effect of resveratrol in adults. Further high-quality evidence in patients with impaired renal function and estimates of mortality risk in these patients is required before resveratrol can be advocated as an adjuvant therapy.

The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials.

This study aimed to evaluate the effect of resveratrol on liver biomarkers in adult participants, using systematic review and meta-analysis of randomized controlled trials. PubMed, Scopus, Web of Science and Cochran Library was searched, up to October 2021. The pooled effects were calculated using a random-effects model and expressed as weighted mean difference and 95% confidence interval. The methodological quality of studies as well as certainty of evidence were assessed by standard tools. Thirty-seven relevant trials were found. Although overall analysis found no significant change, subgroup analysis showed a significant improvement in alanine aminotransferase (ALT; -7.79 U/L) and glutamyl transferase (-6.0 U/L) in patients with liver disorders, and ALT (-2.22 U/L) in younger adults; however, high-dose supplementation (>1,000 mg/day) appeared to increase alkaline phosphatase concentration (+5.07 U/L). ALT also increased in older adults (+2.33 U/L) following resveratrol supplementation. We found resveratrol did not have a significant effect on liver health in the general population. However, resveratrol could be effective in patients with liver disorders. Our findings also suggest that high-dose resveratrol administration and supplementation in older adults should be performed with caution. Further high-quality clinical trials are also needed to firmly establish the clinical efficacy of resveratrol.

Probiotics supplementation and brain-derived neurotrophic factor (BDNF): a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: An emerging body of evidence has demonstrated the beneficial effects of probiotics on various mental health conditions. In this systematic review and meta-analysis, we sought to examine the effects of probiotics supplementation on brain-derived neurotrophic factor (BDNF) in adults. METHODS: PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to April 2021, for eligible randomized controlled trials (RCTs). We pooled mean differences and standard deviations from RCTs using random-effect models. RESULTS: Overall, meta-analysis of 11 trials (n = 648 participants) showed no significant changes in serum level of BDNF following probiotics. However, subgroup analysis revealed that probiotics increased BDNF levels in individuals suffering from neurological disorders (n = 214 participants; WMD = 3.08 ng/mL, 95% CI: 1.83, 4.34; P = 0.001; I2 = 7.5%; P-heterogeneity 0.34), or depression (n = 268 participants; WMD = 0.77 ng/mL, 95% CI: 0.07, 1.47; P = 0.032; I2 = 88.4%; P-heterogeneity < 0.001). Furthermore, a significant increase in BDNF levels was found in studies that administered the mixture of Lactobacillus and Bifidobacterium genera, and were conducted in Asia . CONCLUSION: Our main findings suggest that probiotics may be effective in elevating BDNF levels in patients with depression and neurological disorders, and a mixed of Lactobacillus and Bifidobacterium appear to show greater efficacy than the single genus supplement. The low quality of evidence reduces clinical advocacy, and indicates that more large-scale, high-quality, RCTs are needed to facilitate reliable conclusions.

The Mediterranean, DASH, and MIND diets and the incident of hypertension over a median follow-up of 7.4 years in the Tehran Lipid and Glucose Study.

BACKGROUND: Despite the favorable effects of well-known dietary patterns in the treatment of hypertension (HTN), such as the Mediterranean (MED) and Dietary Approach to Stop Hypertension (DASH) diets, it is uncertain if adherence to these diets can reduce the risk of HTN, especially in non-Mediterranean populations. Moreover, none of the previous studies evaluated the association between the MED-DASH Intervention for Neurodegenerative Delay (MIND) diet adherence and the incidence of HTN. Therefore, we aimed to assess the association of adherence to these diets with the development of HTN in adults. METHODS: This prospective study included 2706 adults free of HTN who were selected from the Tehran Lipid and Glucose Study. The MED, DASH, and MIND diet scores were computed at baseline using dietary information collected with the food frequency questionnaire. Associations between the dietary indices and risk of HTN over a median follow-up of 7.4 years were examined using Cox proportional hazards regression analysis. RESULTS: The baseline mean age of participants was 37.9 ± 12.5 years (age range: 20-79 years), and 52.4% were women. During the 18262 person-years follow-up, 599 incidents of HTN were identified. There was no significant relationship between the dietary scores and the risk of HTN, either as continuous or categorical variables, even after excluding individuals with early/late HTN diagnosis, prehypertension, diabetes, or chronic kidney disease at baseline. A significant interaction was found between body mass index (BMI) and DASH (P-interaction < 0.001). Stratified analyses based on baseline BMI status revealed an inverse association between DASH and HTN risk in individuals with normal-weight (HR = 0.84, 95% CI = 0.71-0.98, P = 0.031), although this association did not reach statistical significance across the tertiles of DASH. CONCLUSIONS: In this study, MED, DASH, and MIND showed no significant association with the occurrence of HTN in adults. Further prospective studies on diverse populations are required to assess whether adherence to the MED, DASH, and MIND diets is an effective strategy for reducing the occurrence HTN.

The effect of almond intake on cardiometabolic risk factors, inflammatory markers, and liver enzymes: A systematic review and meta-analysis.

Almond intake may be correlated with improvements in several cardiometabolic parameters, but its effects are controversial in the published literature, and it needs to be comprehensively summarized. We conducted a systematic search in several international electronic databases, including MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov until April 2021 to identify randomized controlled trials that examined the effects of almond consumption on cardiometabolic risk factors, inflammatory markers, and liver enzymes. Data were pooled using the random-effects model method and presented as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Twenty-six eligible trials were analyzed (n = 1750 participants). Almond intake significantly decreased diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein (LDL), non-high-density lipoprotein (HDL), and very LDL (p < 0.05). The effects of almond intake on systolic blood pressure, fasting blood glucose, insulin, hemoglobin A1c, homeostatic model assessment of insulin resistance, C-peptide, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, C-reactive protein (CRP), hs-CRP (high sensitivity C-reactive protein), interleukin 6, tumor necrosis factor-α, ICAM (Intercellular Adhesion Molecule), VCAM (Vascular Cell Adhesion Molecule), homocysteine, HDL, ox-LDL, ApoA1, ApoB, and lipoprotien-a were not statistically significant (p > .05). The current body of evidence supports the ingestion of almonds for their beneficial lipid-lowering and antihypertensive effects. However, the effects of almonds on antiinflammatory markers, glycemic control, and hepatic enzymes should be further evaluated via performing more extensive randomized trials.

The effects of olive leaf extract on cardiovascular risk factors in the general adult population: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The aim of this systematic review and meta-analysis was to determine the effect of olive leaf extract (OLE) supplementation on cardiovascular-related variables, including lipid, glycemic, inflammatory, liver and renal-related factors, as well as blood pressure. METHODS: PubMed, ISI Web of Science, Scopus, and Cochrane library were searched, up to October 2021, for relevant controlled trials. Mean differences and standard deviations were pooled for all outcomes, using a random-effects model. The methodological quality, as well as quality of evidence were assessed using standard tools. RESULTS: Twelve studies (n = 819 participants) were included in our analyses. Overall analyses showed that OLE supplementation significantly decreased triglyceride (TG) levels (WMD = - 9.51 mg/dl, 95% CI - 17.83, - 1.18; P = 0.025; I2 = 68.7%; P-heterogeneity = 0.004), and systolic blood pressure (SBP) (WMD = - 3.86 mmHg, 95% CI - 6.44, - 1.28 mmHg; P = 0.003; I2 = 19.9%; P-heterogeneity = 0.28). Subgroup analyses also revealed a significant improvement in SBP (- 4.81 mmHg) and diastolic blood pressure (- 2.45 mmHg), TG (- 14.42 mg/dl), total cholesterol (TC) (- 9.14 mg/dl), and low-density lipoprotein-C (LDL-C) (- 4.6 mg/dl) measurements, in patients with hypertension. Significant reductions were also observed in TC (- 6.69 mg/dl), TG (- 9.21 mg/dl), and SBP (- 7.05 mmHg) in normal-weight individuals. However, no meaningful changes were seen in glucose hemostasis, liver and kidney, or inflammatory markers. CONCLUSION: The present study revealed that supplementation with OLE yielded beneficial effects for blood pressure and lipid profile in adults, especially in patients with hypertension. As the quality of evidence for glucose hemostasis variables, liver, kidney, and inflammatory markers, were low-to-very low, higher quality RCTs may impact the overarching results. This study was registered at PROSPERO with the code CRD42022302395.

Effect of resveratrol supplementation on hepatic steatosis and cardiovascular indices in overweight subjects with type 2 diabetes: a double-blind, randomized controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are prone to develop non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). We aimed to investigate whether the resveratrol supplementation improves novel hepatic and cardiovascular indices in these patients. METHODS: We conducted a double-blind, randomized controlled trial for 8 weeks. Seventy-six patients with T2DM were randomly assigned to receive 1000 mg/day resveratrol or placebo. Levels of lipid accumulation product (LAP), visceral adiposity index (VAI), Castelli risk index I (CRI-I), CRI-II and atherogenic coefficient (AC) were measured at the beginning and after intervention. RESULTS: A total of 71 participants completed the trial. After adjusting for confounding factors including medications, diabetes duration, energy intake and physical activity, no significant difference was found between the intervention group and the control group in LAP (mean change: - 2.46 ± 23.3 vs. 1.43 ± 14.3; P = 0.43), VAI (mean change: - 0.25 ± 1.1 vs. - 0.02 ± 0.6; P = 0.47), CRI-I (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79), CRI-II (mean change: - 0.23 ± 0.7 vs. - 0.06 ± 0.6; P = 0.38) and AC (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79). CONCLUSIONS: Resveratrol supplementation had no effect on hepatic steatosis and cardiovascular indices. Further clinical trials, especially among subjects with dyslipidemia are needed to reach a firm conclusion. In addition, taking all medications should be controlled in future studies. Trial registration The protocol was registered on 29/12/2017 at the Iranian clinical trials website (IRCT20171118037528N1) with URL: https://en.irct.ir/trial/27734 .

The effect of probiotics/synbiotics supplementation on renal and liver biomarkers in patients with type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.

Despite the apparent beneficial effects of probiotics/synbiotics on glucose haemostasis, lipid profile and inflammatory responses, it is not clear whether these beneficial effects also impact renal and hepatic function in diabetes. Therefore, we sought to assess the effect of probiotics/synbiotics supplementation on renal and liver biomarkers in adults with type 2 diabetes mellitus (T2DM) using a systematic review and meta-analysis of randomised controlled trials (RCT). PubMed, Scopus, Web of Science and Cochrane Library were systematically searched, up to February 2021. The pooled weighted mean difference (WMD) was estimated using a random-effects model. The methodological quality of studies, as well as certainty of evidence, was assessed using standard scales. Fifteen related trials were identified. Meta-analysis of six trials, involving 426 participants, indicated that probiotics/synbiotics supplementation reduced serum levels of creatinine (WMD = -0·10 mg/dl, 95 % CI -0·20, -0·00; P = 0·01; I 2 = 87·7 %; P-heterogeneity < 0·001), without any significant effect on blood urea nitrogen (BUN), glomerular filtration rate or microalbuminuria. No significant improvement was found on liver biomarkers following probiotics/synbiotics supplementation. The subgroup analysis showed a significant improvement in BUN when follow-up duration lasted for 12 weeks or more (WMD = -1·215 mg/dl, 95 % CI -1·933, -0·496; P = 0·001) and in creatinine levels in patients with renal dysfunction (WMD = -0·209 mg/dl, 95 % CI -0·322, -0·096; P < 0·001). Our results are insufficient to advocate the use of probiotics/synbiotics for improving renal or liver function in patients with T2DM. Indeed, due to the low certainty of evidence, these findings need to be affirmed in further high-quality RCT.

The effect of vitamin D supplementation on serum levels of fibroblast growth factor- 23: A systematic review and meta-analysis of randomized controlled trials.

Previous studies of the effect of vtamin D on serum levels of fibroblast growth factor- 23 (FGF-23) have yeilded an inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) sought to investigate the effect of vitamin D supplementation on serum levels of FGF-23. PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to November 2020, for RCTs that evaluated the effects of native or active vitamin D supplementation on serum levels of FGF-23 in adults. Weighted mean difference (WMD) were calculated and random effects meta-analysis was used to estimate the overall effects. Twenty-seven trials were included in the meta-analysis. Supplementation with native vitamin D (23 studies, n = 2247 participants; weighted mean difference [WMD] = 0.5 pg/mL, 95 % CI: -0.52 to 1.51, P = 0.33; I2 = 29.9 %), and active vitamin D (5 studies, n = 342 participants, WMD = 29.45 pg/mL, 95 % CI: -3.9 to 62.81, P = 0.08; I2 = 99.3%) had no significant effects on serum FGF-23 concentration. In subgroup analyses, supplementation with ergocalciferol (3 studies, n = 205 participants; WMD = 18.27 pg/mL, 95 % CI: 5.36-31.17, P = 0.006), and daily dosing regimens (9 studies, n = 1374 participants; WMD = 0.41 pg/mL, 95 % CI: 0.22 to 0.59, P < 0.001) increased serum FGF-23 levels compared to control. Overall, our findings revealed no significan effect of vitamin D supplementation on serum FGF-23 concentration. However, further high quality, large-scale studies are needed to better elucidate this relationship.

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.

Effect of saffron supplementation on oxidative stress parameters: A systematic review and meta-analysis of randomized placebo-controlled trials.

Oxidative stress (OS), the absence of equilibrium between prooxidants and antioxidants in the body, has been shown to play a pivotal role in the initiation and progression of many diseases. Saffron has been noted for its antioxidant capacity and can be used to improve OS parameters in unhealthy patients. Our aim was to evaluate the efficacy of saffron supplementation on OS parameters in unhealthy patients in randomized controlled trials (RCTs). We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science without language restrictions for RCTs up until April 2021. Studies were included if they compared any form of saffron supplementation to placebo or no supplementation on OS parameters in unhealthy patients. Using a random-effects model with calculated standardized mean difference (SMD) and 95% confidence intervals (CI), we quantitatively synthesized the data. Heterogeneity was assessed using Cochrane's I 2 values. Ten randomized controlled trials were eligible for this review. Seven were included in the meta-analysis and indicated an association between saffron intake and a statistically significant decrease in malondialdehyde (MDA) levels (SMD: -0.40; 95% CI: -0.63, -0.17; I 2 = 32.6%) and a significant increase in total antioxidant capacity (TAC, SMD: 0.24; 95% CI: 0.05, 0.42; I 2 = 00.0%). Saffron intake was shown to significantly impact MDA and TAC, indicating its beneficial properties in improving OS in unhealthy patients. However, additional RCTs are required to evaluate the effect on other OS parameters.

Effects of Calcium and Vitamin D Co-supplementation on the Lipid Profile: A Systematic Review and Meta-analysis.

PURPOSE: Calcium and vitamin D co-supplementation is common and widely used, but randomized, controlled trials (RCTs) have yielded inconclusive results concerning its impact on the serum lipid profile. METHODS: A comprehensive literature search of Medline, Web of Science, Scopus, Embase, Cochrane Central Register of Controlled Trials, and clinical trial registry databases was conducted to identify placebo-controlled RCTs that were published through September 2020 and that evaluated the impact of calcium and vitamin D co-supplementation on total cholesterol (TC), triglycerides (TGs), low- and very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C). Standardized mean differences (SMDs) were pooled using random-effects meta-analysis models. FINDINGS: Thirteen studies in a total of 2304 participants met the inclusion criteria. Calcium and vitamin D co-supplementation was associated with significant reductions in both TC (SMD, -0.81; 95% CI, -1.35 to -0.27; I2 = 94.6%) and TGs (SMD, -0.50; 95% CI, -0.91 to -0.08; I2 = 91.5%), and with a significant increase in HDL-C (SMD, 1.22; 95% CI, 0.60 to 1.83; I2 = 95.4%). However, calcium and vitamin D co-supplementation were not found to be associated with significantly decreased low-density lipoprotein cholesterol (SMD, -0.39; 95% CI, -0.78 to 0.01; I2 = 90.1%) or very-low-density lipoprotein cholesterol (SMD, -0.01; 95% CI, -0.70 to 0.69; I2 = 82.3%). IMPLICATIONS: The findings from the present systematic review and meta-analysis suggest that calcium and vitamin D co-supplementation has a beneficial effect on TC, TG, and HDL-C. Larger-scale, well-designed RCTs are needed to clarify the effect of calcium and vitamin D co-supplementation on all lipid-profile components.

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).