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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.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.Overall, meta-analysis of 11 trials (Our main findings suggest that probiotics may be effective in elevating BDNF levels in patients with depression and neurological disorders, and a mixed of

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.

Objective The aim of the present study was to assess the effect of probiotics/synbiotics supplementation on anthropometric measures in adults with diabetes, regardless of body weight. Methods PubMed, Scopus, Web of Sciences and the Cochrane Library were searched for randomized controlled trials (RCTs) up to February 10, 2021. The effect sizes were pooled with the use of an inverse-variance random-effects model. The methodological quality of studies as well as quality of evidence was assessed using standard tools. Results Twenty-seven RCTs met the inclusion criteria. Overall, compared with their respective control groups, probiotics/synbiotics supplementation resulted in a significant reduction in body weight (weighted mean difference [WMD]: -0.62 kg; 95% CI: -0.97, -0.28; I2 = 81.1%, n = 23 studies]), body mass index (WMD: -0.20 kg/m2; 95% CI: -0.33, -0.07; I2 = 78.4%, n = 25 studies), and waist circumference (WMD: -0.93 cm; 95% CI: -1.34, -0.53; I2 = 0%, n = 8 studies). However, no significant improvement was observed for hip circumference and waist to hip ratio. Conclusions Our analysis revealed that probiotics/synbiotics supplementation may assist with weight management in patients with diabetes, especially when used at higher doses, in younger adults, and in participants with obesity. However, more studies are needed to elucidate the anti-obesity effects of specific probiotic/synbiotic strains.

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).

The aim was to systematically review and meta-analyze prospective cohort studies investigating the relation between maternal dietary patterns during pregnancy with pregnancy and birth outcomes. PubMed, Scopus, and ISI Web of Science were searched from inception until October 2019 for eligible studies. Studies reporting relative risk, ORs, or incidences (for binary data) or means ± SDs or B-coefficients (for continuous outcomes) comparing the highest and lowest adherence with maternal dietary patterns were included. Dietary patterns were categorized as “healthy,” “unhealthy,” or “mixed.” No language restrictions were applied. Study-specific effect sizes with SEs for outcomes of interest were pooled using a random-effects model. Quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Sixty-six relevant publications were included. A higher maternal adherence to a healthy diet was associated with a reduced risk of gestational hypertension (14%, P

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 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-alpha, 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. info:eu-repo/semantics/publishedVersion

Summary Background Although several randomized controlled trials (RCTs) have supported the beneficial effects of higher meal frequency (MF) on cardiometabolic risk factors, the putative effects of higher MF on health remain inconclusive. This study systematically reviewed the evidence from RCTs of the effect of higher compared with lower MF on the blood lipid profile, glucose homeostasis, and adipokines. Methods PubMed, Scopus, ISI Web of Science, and the Cochrane database were searched up to October 2020 to retrieve relevant RCTs. A DerSimonian and Laird random effects model was used to pool mean differences and 95% CI for each outcome. The quality of studies and evidence was assessed through standard methods. Results Twenty-one RCTs (686 participants) were included in this meta-analysis. Overall results showed a significant improvement in total cholesterol [weighted mean difference (WMD) = −6.08 mg/dl; 95% CI: −10.68, −1.48; P = 0.01; I2 = 88%], and low-density cholesterol (LDL-C) (WMD = −6.82 mg/dl; 95% CI: −10.97, −1.60; P = 0.009; I2 = 85.7%), while LDL-C to high-density cholesterol ratio (LDL-C: HDL-C) increased (WMD = 0.22; 95% CI: 0.07, 0.36; P = 0.003; I2 = 0.0%) in higher MF vs. lower MF. No significant effects were found on measures of glycemic control, apolipoproteins-A1 and B, or leptin. In subgroup analyses, higher MF significantly reduced serum triglyceride (TG), and increased HDL-C, compared with lower MF in interventions > 12 weeks, and decreased serum TC and LDL-C in healthy participants. A significant reduction in LDL-C also was observed in studies where the same foods given both arms, simply divided into different feeding occasions, and in feeding studies, following higher MF compared to lower MF. Conclusion Our meta-analysis found that higher, compared with lower MF may improve total cholesterol, and LDL-C. The intervention does not affect measures of glycemic control, apolipoproteins-A1 and B, or leptin. However, the GRADE ratings of low credibility of the currently available evidence highlights the need for more high-quality studies in order to reach a firm conclusion.

The present study sought to evaluate the effect of resveratrol supplementation on mRNA expression levels of peroxisome proliferator-activated receptor alpha (PPARα), p53, p21, p16, and serum levels of cluster of differentiation 163 (CD163) to TNF-like weak inducer of apoptosis (TWEAK) ratio in patients with type 2 diabetes. In this double-blind randomized controlled trial, 71 patients were randomly assigned to receive either 1,000 mg of trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Expression levels of genes of interest, and serum levels of sCD163 and sTWEAK were assessed at baseline and at the end of the study. Resveratrol supplementation significantly increased mRNA expression levels of p53 and p21 genes, compared with the placebo group (fold change of p53 = 1.29, p = .04; fold change of p21 = 1.46, p = .006). However, no significant effect on expression levels of PPARα and p16 genes was observed after supplementation. In addition, resveratrol significantly reduced serum levels of sCD163/sTWEAK ratio compared with the placebo group (p = .003). Resveratrol supplementation resulted in significant changes in p53 and p21 genes expression, while serum levels of sCD163/sTWEAK ratio also improved in the resveratrol group, without any significant change in adjusted sCD163 levels. More research is needed to confirm the beneficial effects of resveratrol for patients with diabetes.

The present study sought to investigate the effect of micronized resveratrol supplementation on serum levels of asymmetric de-methyl-arginine (ADMA) and paraoxonase-1 (PON1) activity in patients with type 2 diabetes (T2D). In this double-blinded randomized trial, 76 patients with T2D were recruited. Participants were randomly assigned to consume 1,000 mg resveratrol or placebo capsules (methylcellulose) per day, for 8 weeks. Serum levels of ADMA and PON1 enzyme activity were measured at the beginning and end of the intervention using the enzyme-linked immunosorbent assay method. In total, 71 participants completed the study. Our results showed that resveratrol significantly decreased serum levels of ADMA (-0.16 ± 0.11, p < .001) and improved PON1 enzyme activity (15.39 ± 13.99, p < .001) compared with placebo, after adjusting for confounding factors (age, sex, and baseline body mass index). Our findings suggest that 8-week resveratrol supplementation may produce beneficial effects on serum levels of ADMA and PON1 enzyme activity in patients with T2DM. However, further research is needed to confirm the veracity of these results.

The aim of this study was to determine the effect of zinc supplementation on anthropometric measures. In this systematic review and dose–response meta-analysis, we searched PubMed, Scopus, ISI Web of Science, and the Cochrane Library from database inception to August 2018 for relevant randomized controlled trials. Mean differences and SDs for each outcome were pooled using a random-effects model. Furthermore, a dose–response analysis for zinc dosage was performed using a fractional polynomial model. Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Twenty-seven trials (n = 1438 participants) were included in the meta-analysis. There were no significant changes in anthropometric measures after zinc supplementation in the overall analysis. However, subgroup analyses revealed that zinc supplementation increased body weight in individuals undergoing hemodialysis (HD) [3 trials, n = 154 participants; weighted mean difference (WMD) = 1.02 kg; 95% CI: 0.38, 1.65 kg; P = 0.002; I(2) = 11.4%] and decreased body weight in subjects who are overweight/obese but otherwise healthy (5 trials, n = 245 participants; WMD = −0.55 kg; 95% CI: −1.06, −0.04 kg; P = 0.03; I(2) = 31.5%). Dose–response analyses revealed a significant nonlinear effect of supplementation dosage on BMI (P = 0.001). Our data suggest that zinc supplementation increases body weight in patients undergoing HD and decreases body weight in individuals who are overweight/obese but otherwise healthy, although after normalization for study duration, the association observed in subjects who are overweight/obese disappeared. Although more high-quality studies are needed to reach a definitive conclusion, our study supports the view that zinc may be associated with body weight.

Background Therapeutic exercise for scapular muscles is suggested to be effective in reducing shoulder pain in patients with rotator cuff disorders, whereas its effectiveness on scapular position and motion has remained unclear. Therefore, the aim of this systematic review was to investigate whether exercise therapy improves scapular position and motion in individuals with scapular dyskinesis. Methods This study is a wide systematic review including any type of clinical trial in which the effect of any type of therapeutic exercise, including scapular muscle strengthening, stretching, and scapular stabilization exercise, is investigated in adult participants. Results Twenty studies were included in this systematic review. Studies were categorized on the basis of the techniques they used to measure scapular position and motion and the included participants. Methodologic quality of the studies was assessed by the Cochrane tool of assessing the risk of bias. Eight studies used 3-dimensional techniques for measuring scapular motions. Among them, 5 studies showed significant effects of exercise on scapular motion, of which 3 studies investigated individuals with subacromial impingement syndrome (SIS). The other 12 studies used 2-dimensional measurement techniques, of which 8 studies reported significant effects of exercise on scapular position and motion both in SIS patients and in asymptomatic individuals. However, their methodologic quality was debatable. Therefore, there was conflicting evidence for the effect of exercise on scapular dyskinesis. Conclusion There is a lack of evidence for beneficial effects of exercise in improving scapular position and motion in individuals with scapular dyskinesis. However, exercise is beneficial in reducing pain and disability in individuals with SIS.

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; I2 = 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.

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., 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.

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; I

Background: Gestational diabetes mellitus (GDM) is known as a degree of glucose intolerance that occurs for the first time during pregnancy. There is paucity of evidence regarding the effect of oat bran on GDM. Oat as a source of β-glucan can be effective in reducing the blood sugar levels. This study aimed to investigate the effect of oat bran on fasting blood sugar (FBS) and glycosylated hemoglobin (HbA1c) in patients with GDM. Method: This single-blind clinical trial was conducted on 90 pregnant women with GDM. The experimental group (EG) consumed 30 g of oat bran daily with 100 g of low-fat yogurt before lunch and dinner for 4 weeks. The control group (CG) consumed only low-fat yogurt and both groups received nutrition counseling. The present study investigated the FBS, HbA1c, and weight gain at the beginning and after four weeks of intervention. Results: Out of 90 patients, 80 completed the study. FBS decreased in the EG (P = 0.04, -2.75 ± 8.22), whereas, it increased in the CG (P = 0.003, 4.37 ± 8.72). No significant difference was observed between the two groups in terms of HbA1c levels. Weight gain was controlled more efficiently in the EG than the CG (P = 0.001). Conclusion: The use of oat bran for four weeks decreased the FBS,; whereas, it did not affect HbA1c levels. Weight gain was controlled better in the EG than the CG.

The present study sought to evaluate the effect of resveratrol supplementation on mRNA expression levels of peroxisome proliferator-activated receptor alpha (PPARα), p53, p21, p16, and serum levels of cluster of differentiation 163 (CD163) to TNF-like weak inducer of apoptosis (TWEAK) ratio in patients with type 2 diabetes. In this double-blind randomized controlled trial, 71 patients were randomly assigned to receive either 1,000 mg of trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Expression levels of genes of interest, and serum levels of sCD163 and sTWEAK were assessed at baseline and at the end of the study. Resveratrol supplementation significantly increased mRNA expression levels of p53 and p21 genes, compared with the placebo group (fold change of p53 = 1.29, p = .04; fold change of p21 = 1.46, p = .006). However, no significant effect on expression levels of PPARα and p16 genes was observed after supplementation. In addition, resveratrol significantly reduced serum levels of sCD163/sTWEAK ratio compared with the placebo group (p = .003). Resveratrol supplementation resulted in significant changes in p53 and p21 genes expression, while serum levels of sCD163/sTWEAK ratio also improved in the resveratrol group, without any significant change in adjusted sCD163 levels. More research is needed to confirm the beneficial effects of resveratrol for patients with diabetes.

Although obesity has been associated with an increased cancer risk in the general population, the association in patients with type 2 diabetes (T2D) remains controversial. We conducted a dose–response meta-analysis of cohort studies of body mass index (BMI) and the risk of total and site-specific cancers in patients with T2D. A systematic literature search was conducted in PubMed, Scopus, and Medline until September 2020 for cohort studies on the association between BMI and cancer risk in patients with T2D. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models. Ten prospective and three retrospective cohort studies (3,345,031 participants and 37,412 cases) were included in the meta-analysis. Each 5-unit increase in BMI (kg/m2) was associated with a 6% higher risk of total cancer (RR: 1.06, 95% CI 1.01, 1.10; I2 = 55.4%, n = 6), and with a 12% increased risk in the analysis of breast cancer (RR: 1.12, 95% CI 1.05, 1.20; I2 = 0%, n = 3). The pooled RRs showed no association with prostate cancer (RR: 1.02, 95% CI 0.92, 1.13; I2 = 64.6%, n = 4), pancreatic cancer (RR: 0.97, 95% CI 0.84, 1.11; I2 = 71%, n = 3), and colorectal cancer (RR: 1.05, 95% CI 0.98, 1.13; I2 = 65.9%, n = 2). There was no indication of nonlinearity for total cancer (Pnon-linearity = 0.99), however, there was evidence of a nonlinear association between BMI and breast cancer (Pnon-linearity = 0.004) with steeper increases in risk from a BMI around 35 and above respectively. Higher BMI was associated with a higher risk of total, and breast cancer but not with risk of other cancers, in patients with T2D, however, further studies are needed before firm conclusions can be drawn.

Background: Altered scapular kinematics in individuals with rounded shoulder posture (RSP) may affect acromiohumeral distance (AHD). The purpose of this study was to compare AHD and scapular dyskinesis prevalence in individuals with and without RSP. Methods: A total of 44 women (RSP, n=21; control, n=23) participated in the study. RSP was assessed by measuring acromion to table distance (ATD) in supine position and forward shoulder angle (FSA) using a camera and the AutoCAD software from the lateral side. According to these measurements, ATD more than 2.6 cm and FSA equal or more than 52° were considered as RSP. AHD was measured via ultrasonography with the arm at rest and 90 º of active elevation in scapular plane (scaption). Also, scapular dyskinesis was assessed by Uhl yes/no rating system. Independent and paired t tests were used to compare AHD between and within groups’ comparisons, respectively. Chi-square test was used to compare the scapular dyskinesis prevalence in individuals with or without RSP. The data were analyzed using the SPSS statistical software version 17. Significance level was set at 0.05 Results: There were no statistically significant differences in participants’ AHD in rest position (dominant side, p=0.187, nondominant side, p=0.144) and 90° scaption (dominant side, p=0.144, nondominant side, p=0.182) in each side between the 2 groups. Also, the results of chi-square test showed that there were not any significant differences in the prevalence of scapular dyskinesis during shoulder flexion (dominant side, p=0.653, nondominant side, p=0.541) and shoulder abduction (dominant side, p=0.141, nondominant side, p=0.277) in individuals with and without rounded shoulder postures. Conclusion: According to our results, RSD cannot lead to reduced AHD and higher prevalence of scapular dyskinesis.

Ninety individuals were included in this case-control study:30 type 2 diabetes mellitus, 30 pre-diabetes and 30 healthy individuals (males and females, age: 25-65, body mass index: 25-35). MicroRNAs expression was determined by real-time polymerase chain reaction. Furthermore, plasma concentrations of tumor necrosis factor alpha (TNF-α) and interleukin 6 (Il-6) and fasting insulin was measured by enzyme-linked immunosorbent assay. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as an indicator of insulin resistance.

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.

Summary Objective The present study investigated the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on telomerase activity, mRNA expression of P16 INK , IL-6, and TNF-α considering Pro12Ala polymorphism in the PPARγ gene. Methods/Design In this double-blind randomized controlled trial, 72 PPARγ Pro12Ala polymorphism genotyped type 2 diabetic patients aged 30–70 years were randomly assigned to receive 2.4 gr of DHA-enriched fish oil or a placebo for 8 weeks. Genotyping of the Pro12Ala polymorphism in the PPARγ gene was assessed using polymerase chain reaction-restriction length polymorphism (PCR-RFLP), telomerase activity in the peripheral blood mononuclear cell (PBMC) was measured using PCR-ELISA based on the telomeric repeat amplification protocol (TRAP), and changes in the mRNA expression of P16, IL-6, and TNF-α were measured using real-time quantitative reverse transcription–polymerase chain reaction (RT-PCR). Results In the DHA group, telomerase activity was decreased (p = 0.001) during the intervention. In addition, between-group comparisons showed significant differences in the changes in telomerase activity (p = 0.003) and P16 mRNA expression (p = 0.028) and non-significant differences in TNF-α and IL-6 mRNA expression. The gene*DHA interaction could not affect changes in P16, IL-6, or TNF-α mRNA expression or in telomerase activity in PBMC. Discussion Short-time DHA-enriched fish oil supplementation caused increased levels of P16 expression and a decline in telomerase activity compared with the control group without modulating the effects of Pro12Ala polymorphism on the PPARγ gene. Because of the positive correlation between P16 activity and cellular senescence, the possibility of senescence stimulation by DHA is proposed.

IntroductionOver the past decades, the number of people with type 2 diabetes (T2D) has increased globally. One of the major complications in these patients is cardiovascular disease; it seems that the cell proliferation inhibition can improve vascular function in these patients. It is proposed that peroxisome proliferator-activated receptor alpha (PPARα) can induce cell cycle arrest via cyclin-dependent kinase inhibitor 2A (p16) activation. Also, it has been shown that phosphorylated tumour suppressor protein p53 is involved in cell senescence by cyclin-dependent kinase inhibitor 1 (p21) upregulation. Resveratrol is a natural polyphenol and appears to improve the vascular function through the mentioned pathways. We will aim to evaluate the effects of resveratrol supplementation on mRNA expression of PPARα, p53, p21 and p16 in patients with T2D. We will also measure serum levels of cluster of differentiation 163 (CD163) and tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as the indicators of cardiovascular status.Methods and analysisSeventy-two subjects suffering from T2D will participate in this double-blind randomised parallel placebo-controlled clinical trial. Participants will be randomly assigned to receive 1000 mg/day trans-resveratrol or placebo (methyl cellulose) for 8 weeks. The mRNA expression levels of PPARα, p53, p21 and p16 genes will be assessed using real-time PCR and serum CD163 and TWEAK levels will be measured using commercially available ELISA kits at baseline and the end of the study. Clinical outcome parameters (glycaemic and lipid profiles and body composition) will also be measured before and after study duration.Ethics and disseminationThe study is performed in agreement with the Declaration of Helsinki and is approved by the Ethics Committee of the Shahid Sadoughi University of Medical Sciences (no: ir.ssu.sph.rec.1396.120). The results will be published in scientific journals.Trial registration numberIRCT20171118037528N1; Pre-results.