The effect of oral supplementation of Paricalcitol on C-reactive protein levels in chronic kidney disease patients: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials.

BACKGROUND: Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature. METHODS: MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran's Q test and I2. RESULTS: Amongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I2 = 66.3% and P = 0.01). CONCLUSION: Oral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression.

Omega-3 fatty acids and endothelial function: A GRADE-assessed systematic review and meta-analysis.

INTRODUCTION: N-3 polyunsaturated fatty acids (PUFAs) supplementation has been reported to have an impact on flow-mediated dilatation (FMD), a conventionally used clinical technique for estimating endothelial dysfunction. However, its proven effects on endothelial function are unclear. This systematic review and meta-analysis were conducted to evaluate the effects of n-3 PUFAs supplementation on FMD of the brachial artery. METHOD: This study was performed following the PRISMA guidelines. To identify eligible RCTs, a systematic search was completed in PubMed/Medline, Scopus and Web of Science using relevant keywords. A fixed- or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). RESULTS: Thirty-two studies (with 35 arms) were included in this meta-analysis, involving 2385 subjects with intervention duration ranging from 4 to 48 weeks. The pooled meta-analysis demonstrated a significant effect of omega-3 on FMD (WMD = 0.8%, 95% CI = 0.3-1.3, p = .001) and heterogeneity was significant (I2 = 82.5%, p < .001). CONCLUSION: We found that n-3 PUFA supplementation improves endothelial function as estimated by flow-mediated dilatation of the brachial artery.

The effects of Quercetin supplementation on cardiometabolic outcomes: An umbrella review of meta-analyses of randomized controlled trials.

BACKGROUND: Quercetin is a bioactive flavonoid, but the effect of it on cardiometabolic factors has remained uncertain and previous findings from meta-analyses have been controversial. OBJECTIVE: To provide an overview of the effects of Quercetin on cardiometabolic factors based on meta-analyses of randomized controlled trials (RCTs). METHOD: MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched to identify eligible publications. As part of the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. A GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to rate the certainty of evidence. RESULTS: Five meta-analyses including 18 eligible RCTs plus 5 RCTs that were not included in previous meta-analyses were found. The results indicated Quercetin does not affect diastolic blood pressure (DBP), lipid profile, inflammation, anthropometric indices, fasting plasma glucose (FBG), and homeostatic model assessment for insulin resistance (HOMA-IR). However, Quercetin supplementation could significantly reduce systolic blood pressure (SBP) (weighted mean difference (WMD): -1.9, 95% CI = -3.2 to -0.6, I2 = 88.3%) and insulin level (WMD: -1.07, 95% CI = -1.9 to -0.1, I2 = 75.0%). The certainty of evidence ranged from very low to moderate. CONCLUSION: Quercetin supplementation has reducing effects on SBP and insulin levels but not other cardiometabolic parameters. More high-quality trials with longer follow-up durations may be required to obtain a more robust conclusion.

The effect of Spirulina supplementation on lipid profile: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials.

BACKGROUND: Cardiovascular diseases (CVD) are one of the most important causes of death worldwide. Dyslipidemia is one of the main causal risk factors for CVD that can be controlled by modifying lifestyle, which entails the use of healthy diets containing functional foods. The present study was conducted to summarize the effects of Spirulina on the lipid profile in previous randomized controlled trials. METHODS: MEDLINE, Scopus, Clarivate Analytics Web of Science, and the Cochrane Library databases were searched systematically until January 2023, for clinical interventions that investigated the effect of Spirulina supplementation on plasma lipid profile concentrations. RESULTS: ooled results of 20 studies (with 23 arms and 1076 participants) indicated that Spirulina intervention significantly reduced LDL-C (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05), TC (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05) and TG (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05) levels while HDL-C levels were significantly increased (SMD: 0.3, 95% CI: 0.0, 0.6, P<0.05). CONCLUSIONS: The findings of the present meta-analysis and review show the usefulness of supplementing with Spirulina in improving serum levels of TC, TG, LDL-C, and HDL-C.

The effect of l-carnitine supplementation on mortality and clinical outcomes in ventilator-dependent critically ill patients with obesity and COVID-19: Protocol for a randomized double-blind placebo-controlled trial.

Background: Coronavirus disease 2019 (COVID-19) still remains a pandemic accounting for at least 15% of intensive care unit (ICU) admissions. Recently, it has been observed that l-carnitine levels, which play an important role in fatty acid metabolism, have an inverse association with the severity of COVID-19 and its complications, hence a potential role for supplementing with this nutraceutical has been suggested. The current protocol describes a trial aiming to an evaluation of the effect of l-carnitine intervention on mortality and clinical outcomes in ICU-admitted patients with COVID-19. Methods: This parallel-group, randomized, placebo-controlled, and double-blind clinical trial involves 50 participants and will be performed at the ICU of Artesh (AJA) Hospital, Mashhad, IRAN. Eligible participants will be randomized into two groups: 1) the intervention group will receive 1000 mg l-carnitine capsules 3 times a day, and 2) the placebo group will receive 1000 mg placebo capsules 3 times a day. Assessments will be performed at baseline, 7 and 28 days after study initiation. The primary outcome includes changes in serum levels of C-reactive protein (CRP). Secondary outcomes include the length of stay in the ICU, ICU mortality, hospital mortality, 28-day mortality, duration of mechanical ventilation (MV), and the neutrophil-lymphocyte ratio (NLR). Conclusion: Based on previous evidence, l-carnitine may reduce inflammation and oxidation stress and improve respiratory function. However, the effects of l-carnitine on ventilator-dependent COVID-19 critically ill patients have not been assessed yet, justifying the necessity to conduct a clinical study in this field. c.

The effects of curcumin-containing supplements on inflammatory biomarkers in hemodialysis patients: A systematic review and meta-analysis.

In the past decade, the effect of curcumin or turmeric supplementation on many aspects of health status in different populations has been evaluated. In the present study, a systematic review and meta-analysis were conducted to estimate the effect of curcumin administration on inflammatory markers in hemodialysis (HD) patients. A systematic search was performed in MEDLINE, EMBASE, Scopus, and Clarivate Analytics Web of Science databases from 1997 until June2022 for terms related to curcumin/turmeric and hemodialysis (HD). Randomized, double-blind/single-blind studies examining the effects of curcumin/turmeric on the inflammation of HD participants older than 18 years were considered eligible for inclusion. Data were pooled using the weighted mean difference (WMD) and 95% CI as the summary statistic, considering a random-effects analysis model. The data that were pooled from nine studies with 472 patients indicated that curcumin-containing supplement had significant effect on serum C-reactive protein (CRP) levels (WMD = -3.3 mg/L; 95% CI: -5.4 to -1.3; p < 0.001, I2  = 76.7%, 8 studies, 467 participants), and interlukine-6 (IL-6) levels (SMD: -0.4; 95% CI: -0.8 to -0.07; p = 0.02, I2  = 31.6%, 3 studies, 153 participants) compared control group. Although curcumin intervention could not change tumor neurosis factor-α (TNF-α) concentration (SMD = -0.3; 95% CI: -0.7 to 0.04; p = 0.08, I2  = 25.3%, 3 studies, 153 participants), when compared with the placebo group. Our study's main limitations were small number of studies, overall high risk of bias in the included trials, and high heterogeneity in some results. The present meta-analysis suggested that intervention with curcumin-containing supplements was associated with a significant reduction in serum hs-CRP and IL-6 concentrations in HD patients. The curcumin intervention in the reduction of hs-CRP levels was greater than the minimal clinically important difference (MCID) for CRP (0.5 mg/L), which can be helpful in physicians' clinical decisions.

Effect of beetroot or beetroot plus vitamin C supplementation on cardiovascular function in patients with coronary artery disease: protocol for a double-blind, placebo-controlled, randomised trial.

INTRODUCTION: Coronary artery disease (CAD), classified into the atherosclerosis category, is a prevalent cardiovascular disease worldwide that is associated with serious comorbidities and death. The purpose of this study was to evaluate the effect of beetroot/beetroot plus vitamin C on cardiovascular health status and function in patients with CAD. METHOD AND ANALYSIS: A randomised, placebo-controlled, double-blind clinical trial to recruit 90 patients with CAD at the cardiac outpatient clinic and Imam Reza Hospital, Mashhad, Iran. Participants will be divided into three groups: (1) Those who receive 500 mg three times a day of beetroot capsules, (2) Those who receive 500 mg three times a day of beetroot plus vitamin C capsules, and (3) Those who receive placebo capsules three times a day for 4 weeks. Pulse wave velocity, Augmentation Index, heart rate, volume of oxygen (VO2) max/VO2 peak, peak heart rate, blood pressure, interleukin 6 (IL-6), high sensitivity C reactive protein, intercellular adhesion molecule, vascular cell adhesion molecule, lipid profile and anthropometry will be measured at the beginning and end of the intervention. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.MEDICAL.REC.1399.717). All participants will be asked to complete the consent form at the beginning of the study. The results will be actively disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: Iranian Registry of Clinical Trials, IRCT20210217050393N1 (registered 16 May 2021).

The effects of saffron supplementation on the measures of renal function indicators: a systematic review and meta-analysis.

CONTEXT: Saffron (Crocus sativus L.) has been proposed as a potential agent to improve renal function in animal studies. But, due to insufficient evidence in human research, further investigation is needed. OBJECTIVE: To fill this knowledge gap, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of saffron supplementation on the measures of renal function indicators in adults. Renal function was assessed based on serum urea, blood urea nitrogen, and creatinine levels. METHOD AND MATERIALS: A systematic search in PubMed/Medline, Scopus, Web of Science, Embase, and Google Scholar databases was done until March 2021 using relevant keywords. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine RCTs were included in the meta-analysis, and their quality was assessed using the Cochrane risk of bias tool. RESULTS: The pooled analysis showed that saffron supplementation had no significant effect on serum urea concentrations (WMD: - 1.05 mg/dl; 95% CI - 5.1 to 3; P = 0.6, I2 = 93%, P < 0.001) and serum creatinine levels (WMD: - 0.006 mg/dl; 95% CI - 0.08 to 0.06; P = 0.8, I2 = 79%, P < 0.001) when compared to the placebo group. In the dose-response analysis, we observed a significant non-linear relationship between the duration of saffron supplementation and serum urea and creatinine levels. CONCLUSIONS: Based on our findings, Saffron supplementation had no significant effect on renal function markers, including urea and creatinine. However, further trials are required to determine the actual effect and safety of saffron intervention in human studies. PROSPERO SUBMISSION ID: 248081.

Impact of synbiotic supplementation on cardiometabolic and anthropometric indices in patients with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Probiotic and synbiotic products are being widely used by a large number of patients and clinicians; however, effects on cardiometabolic indices in patients with the metabolic syndrome remain unclear. This meta-analysis aimed to evaluate the effects of a synbiotic intervention on lipid profile, insulin resistance, blood pressure, anthropometric parameters, and inflammatory markers. METHODS: We searched MEDLINE, Scopus, and Clarivate Analytics Web of Science by October 2021. Studies were selected if they reported the effectiveness of the synbiotic intervention on cardiometabolic and anthropometric indices. The weighted mean difference was calculated as the effect size using a random-effects model. Subgroup analyses were conducted to determine sources of heterogeneity. Dose-dependent effects were assessed using a dose-response meta-analysis of differences in means. RESULTS: Five trials (1049 participants) were finally included in the meta-analysis. Synbiotic intervention significantly reduced serum insulin levels (WMD, -6.39 µU/mL; 95%CI, (-7.2 to -5.4); p = 0.001, I2 = 88.2%, N = 5), triglycerides (WMD, -20.3 mg/dl; 95%CI, (-32.7 to -7.8); p = 0.001, I2 = 87.7, N = 5), total cholesterol (WMD, -7.8 mg/dl; 95%CI, ( -12.5 to -3.02); p = 0.001; I2 = 66.7%, N = 5), low-density lipoprotein cholesterol (WMD, -9.02 mg/dl; 95%CI, (-10.8 to -7.2); p < 0.001, I2 = 0%, N = 5), waist circumference (WMD, -4.04 cm; 95%CI, ( -4.9 to -3.08), p < 0.001; I2 = 22.7%, N = 3), body weight (WMD, -4.3 kg; 95%CI, (-6.2 to -2.5); p = 0.001; I2 = 0%, N = 2), systolic blood pressure (WMD, -1.8 mmHg; 95% CI, (-2.8 to -0.7); p = 0.001; I2 = 0%, N = 3), and serum interleukin-6 concentrations (WMD, -0.2 pg/mL; 95%CI, (-0.3 to -0.08); p = 0.001, I2 = 39.8%, N = 2), and increased high-density lipoprotein cholesterol levels (WMD, 2.3 mg/dl; 95%CI, (0.2-4.4); p = 0.03; 03; I2 = 93.1%, N = 5). Synbiotic administration did not significantly affect fasting plasma glucose, homeostatic model assessment for insulin resistance, body mass index, diastolic blood pressure, heart rate, and serum C-reactive protein concentrations. CONCLUSIONS: The present findings suggest that synbiotic intervention effectively improves cardiometabolic risk factors in patients with metabolic syndrome.

The effect of beetroot inorganic nitrate supplementation on cardiovascular risk factors: A systematic review and meta-regression of randomized controlled trials.

OBJECTIVES: Inorganic nitrate is one of the most effective compounds in beetroot for improving cardiovascular function due to its conversion to nitric oxide in the body. This review and meta-analysis aimed to investigate the role of beetroot inorganic nitrate supplementation on adults' cardiovascular risk factors. METHODS: We conducted a systematic literature review of articles published without time limitation until November 2020 in PubMed, Embase, ISI Web of Science, Scopus, Cochrane Library, and gray literature databases. We included the original randomized clinical trials (RCTs) in which the effect of beetroot inorganic nitrate supplementation on endothelial function, arterial stiffness, and blood pressure was studied. RESULTS: 43 studies were included for qualitative synthesis, out of which 27 were eligible for meta-analysis. Beetroot inorganic nitrate supplementation significantly decreased Arterial Stiffness (Pulse Wave Velocity (-0.27 m/s, p = 0.04)) and increased Endothelial function (Flow Mediated Dilation: 0.62%, p = 0.002) but did not change other parameters (p > 0.05). CONCLUSION: Beetroot inorganic nitrate supplementation might have a beneficial effect on cardiovascular risk factors. Further high-quality investigations will be needed to provide sufficient evidence.

Vitamin D supplementation effects on the clinical outcomes of patients with coronary artery disease: a systematic review and meta-analysis.

In this systematic review and meta-analysis our aim was to assess the effect of vitamin D supplementation on cardiac outcomes in patients with coronary artery disease (CAD). The search terms were performed from January 2000 to January 2018, only randomized clinical trials (RCT) in human subjects were considered, with no language restrictions. The electronic databases used in this study were: PubMed; Cochran library; Embase; and Scopus. Two independent expert reviewers carried out data extraction according to Cochrane recommendations. Only four RCTs were found in relation to the effects of vitamin D supplementation on the coronary artery disease. In these 299 patients, vitamin D supplementation had significant favorable effects on Diastolic Blood Pressure (DBP) (- 2.96, p = 0.02) and Parathyroid hormone (PTH) (- 4.05, p < 0.001). However, it had no significant effects on hs-CRP mean difference (- 0.04, p = 0.25), total cholesterol (TC) (- 0.46, p = 0.83), triglyceride (TG) (0.68, p = 0.89), low-density lipoproteins (LDL) (2.08, p = 0.56), and high-density lipoproteins (HDL) (- 2.59, p = 0.16). In conclusion, the use of vitamin D was associated with improvements in some cardiac outcomes of CAD patients with vitamin D deficiency. Also, further research is needed to clarify these results.

The effect of vitamin D supplementation on hemoglobin concentration: a systematic review and meta-analysis.

AIMS: The purpose of this review was to investigate the effect of vitamin D supplements on hemoglobin concentration in subjects aged 17.5-68 years old; using randomized controlled trials (RCTs). METHODS: Relevant RCT studies were identified from January 2000 to January 2019 by using MeSH terms in PubMed, Embase, Cochrane Library, Clinical trials, Scopus databases and gray literature. The studies were reviewed systematically, and quality assessments were evaluated by the guidelines of the Cochrane risk of bias. The effect of vitamin D supplements (n = 14) on hemoglobin concentration was considered as primary outcome, while its effects on the levels of ferritin, transferrin saturation and iron status were derived as secondary outcomes. In total, 1385 subjects with age range of 17.5 to 68 years old were examined for 3 h to 6 months; Mean (standard deviation) or median interquartile changes in the hemoglobin concentration in each treatment group was recorded for meta-analysis. RESULTS: Fourteen RCTs met the inclusion criteria. Current study findings propose that vitamin D supplementation leads to a non-significant reduction in hemoglobin levels in subjects (17.5-68 years old) [std. mean difference (SMD): 0.01; 95% CI: - 0.28, 0.29; P = 0.95], also it has no significant effect on ferritin concentrations [std. mean difference (SMD): -0.01; 95% CI: [- 0.20, 0.18; P = 0.91]. However, vitamin D supplementation demonstrated positive effects on transferrin saturation [mean difference (MD): 1.54; 95% CI: 0.31, 2.76; P = 0.01] and iron status [std. mean difference (SMD): 0.24; 95% CI: - 0.09, 0.39; P = 0.002]. CONCLUSION: Current review concluded that supplementation with vitamin D had no significant effect on hemoglobin and ferritin levels while positive effects on transferrin saturation and iron status were observed. Further clinical studies are required to determine the actual effect of this intervention on hemoglobin levels.

Vitamin D supplementation and serum heat shock protein 60 levels in patients with coronary heart disease: a randomized clinical trial.

BACKGROUND: The aim in this study was to investigate the effect of vitamin D (25(OH)D3) supplementation on heat shock protein 60 (HSP 60) and other inflammatory markers (IL-17, TNF-α, PAB) in patients with coronary heart disease (CHD). METHODS: In this double-blind, randomized clinical trial, we recruited 80 male and female patients aged 30-60 with CHD and 25(OH)D3 serum levels < 30 ng/ml from Rasool-e-Akram Hospital in Tehran, Iran. Serum levels of HSP 60 as primary outcome, and 25(OH)D3, IL-17, TNF-α, PAB, lipid profiles and parathyroid hormone (PTH) as secondary outcomes were measured at baseline and post-intervention. We randomly assigned eligible participants to a placebo group (N = 40) or an intervention group (N = 40) (50,000 IU/wk. vitamin D supplement) for eight weeks. RESULTS: The results demonstrated that vitamin D supplementation resulted in a significant increase in 25(OH) D3 serum levels in the intervention group compared to the placebo group (46.86 vs. 7.28 ng/ml). PTH levels decreased in the intervention group compared to the placebo group (- 19.81 vs. 2.92 pg/ml) after eight weeks of supplementation. Furthermore, we observed a significant change in waist circumference (- 0.97 vs. -0.26 cm), fat percentage (-.13 vs. 0.1%), systolic blood pressure (- 3.85 vs. -2.11 mmHg) and diastolic blood presure (- 4 vs. -1.86 mmHg) in the vitamin D group compared to the placebo group (all P values < 0.05). Other variables did not significantly change after the intervention. CONCLUSION: Based on our findings, weekly vitamin D supplementation of 50,000 IU for eight weeks in patients with CHD resulted in decreased systolic and diastolic blood pressure, waist circumference and fat percentage. No significant effect on HSP 60, inflammatory markers or lipid profiles was observed. TRIAL REGISTRATION: IRCT, IRCT201612122365N14. Registered 12 December 2016.