Effects of purified anthocyanins supplementation on serum concentration of inflammatory mediators: A systematic review and dose-response meta-analysis on randomized clinical trials.

Anthocyanins, due to their antioxidant effects, are candidates to reduce inflammation and the risk of inflammatory diseases. Therefore, through conducting a systematic review and meta-analysis, we tried to find the effect of purified anthocyanins on serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Databases including, ISI Web of Science, Scopus, ClinicalTrials.gov, PubMed, and Cochrane Library were searched up to June 2023. The meta-analysis was done by calculating mean differences and their standard deviations. Calculating the statistical heterogeneity of intervention effects was performed through I-squared statistics and Cochran's Q test. The pooled estimate showed a significant decrease in serum levels of CRP, TNF-α, and IL-6 (weighted mean difference (WMD) = -0.12 mg/L, 95% confidence interval (CI) = -0.21 to -0.02, p = 0.013; WMD = -1.37 pg/mL, 95% CI = -1.79 to -0.96; p < 0.001; WMD = -1.43 pg/mL, 95% CI = -1.87 to -1.00; p < 0.001, respectively). Subgroup analysis results revealed purified anthocyanins significantly decreased serum levels of CRP among participants with serum levels of CRP≥1.52 mg/L, at-risk/unhealthy status, and in trials with intervention duration ≥84 days, anthocyanins dose ≥320 mg/day, and sample size ≥85 subjects. Regarding TNF-α and IL-6, out results showed that there was a significant effect of purified anthocyanins on serum levels of TNF-α and IL-6 in most subgroups. The results of our study indicated that purified anthocyanins significantly decreased serum levels of CRP, TNF-α, and IL-6. However, further high-quality studies are needed to firmly establish the efficacy of purified anthocyanins.

The Effect of Parenteral Selenium Therapy on Serum Concentration of Inflammatory Mediators: a Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials.

Selenium can protect against inflammation through its incorporation in selenoenzymes; therefore, in this study, we assessed the effect of parenteral selenium on C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) through a systematic review and meta-analysis on randomized controlled trials (RCTs). A systematic search was performed in the databases, including PubMed, Scopus, Cochrane, clinicaltrials.gov, and ISI Web of Science, up to October 2022, with no limitation in study location or publication time. We calculated the effect size by the mean change from baseline in serum concentration of selected inflammatory mediators and their standard deviations. DerSimonian and Laird random effects model was used to estimate the heterogeneity and summary of the overall effects. Included studies in this systematic review and meta-analysis were 10 and 8 RCTs, respectively. Our results revealed parenteral selenium significantly decreased serum IL-6 (Weighted Mean Difference (WMD) = -3.85 pg/ml; 95% confidence interval (CI) = -7.37, -0.34 pg/ml; p = 0.032) but did not significantly change serum levels of CRP (WMD = 4.58 mg/L; 95% CI = -6.11, 15.27 mg/L; P = 0.401) compared to the comparison groups. According to our results, parenteral selenium supplementation might reduce serum levels of inflammatory mediators.

A systematic review and dose-response meta-analysis of the effect of selenium supplementation on serum concentration of C-reactive protein.

BACKGROUND: Despite conducting new studies on the potential effect of selenium in reducing inflammation; results held contradictory weights and turns into an intriguing area of research. Concerns have been raised on this matter on hand to reach conclusive/consistent results. Therefore, this study seeks to address this scientific gap by assessing randomized controlled trials (RCTs) investigating the effect of selenium intake on C-reactive protein (CRP). METHOD AND MATERIALS: To find all the relevant English-language RCTs, databases including SCOPUS, Web of Science, Clinical Trials.gov, PubMed, and Cochrane Library were searched with no time limit (up to June 2022). Based on the mean changes for both comparison and intervention groups, the effect sizes were calculated. Further, DerSimonian and Laird random-effects model was performed to determine the summary of overall effects and their heterogeneity. RESULTS: Fifteen studies were selected for systematic review and thirteen studies were known to be eligible for meta-analysis. Meta-analysis results indicated a significant effect in serum CRP concentrations compared to the control group (weighted mean difference (WMD)= -0.22 mg/L 95 % confidence interval (CI): - 0.39, - 0.04; p = 0.014). CONCLUSION: In conclusion, our study confirms the downward effect of selenium on the serum concentration of CRP. On a wider level, further research is also needed to assess the selenium effect on other inflammatory mediators.

Quality of life of patients treated with opium tincture or methadone: A randomized controlled trial.

OBJECTIVE: Quality of life (QoL) is an increasingly recognized patient-centered treatment outcome in individuals with opioid use disorder. There is a gap in literature on the impact of opium tincture (OT) on patients' QoL compared to standard treatment options such as methadone. This study aimed to compare the QoL of participants with opioid use disorder receiving OAT using OT or methadone and identify the factors associated with their QoL during treatment. METHODS: The opium trial was a multicenter non-inferiority randomized clinical trial in four private OAT outpatient clinics in Iran. The study assigned patients to either OT (10 mg/ml) or methadone sirup (5 mg/ml) for a follow-up of 85 days. QoL was assessed using the brief version of the World Health Organization Quality of Life instrument (WHOQOL- BREF). RESULTS: A total of 83 participants, 35 (42.2%) in the OT arm and 48 (57.8%) in the methadone arm, completed the WHOQOL-BREF in full and were included in the primary analysis. The mean score of patients' QoL showed improvement compared to baseline, but differences were not statistically significant between OT and methadone arms (p = 0.786). Improvements were mainly observed within the first 30 days of receiving treatment. Being married and lower psychological distress were associated with an improved QoL. Within the social relationships domain, male gender showed significantly higher QoL compared to females. CONCLUSION: OT shows promise as an OAT medication, comparable to methadone in improving patients' QoL. There is a need to incorporate psychosocial interventions to further sustain and improve the QoL in this population. Identifying other social determinants of health which affect QoL and the cultural adaptation of assessments for individuals from various ethnocultural backgrounds are critical areas of inquiry.

Effect of soy isoflavones on C-reactive protein in chronic inflammatory disorders.

New evidence suggests that soy products might reduce chronic systemic inflammation. Therefore, we aimed to summarize the effect of soy isoflavones on serum concentration of C-reactive protein (CRP) among participants with chronic inflammatory disorders by conducting this study. Cochrane Library, Scopus, ISI Web of Science, clinicaltrials.gov, and PubMed were searched to identify randomized clinical trials (RCTs) published up to December 2020. The effect size was calculated by the mean change from baseline in concentrations of CRP and its standard deviation for both intervention and comparison groups. DerSimonian and Laird random-effects model was used when the heterogeneity test was statistically significant. In total, thirteen RCTs involving 1213 participants and ten RCTs involving 1052 participants were eligible for our systematic review and meta-analysis respectively. Study duration ranged from 4 to 96 weeks and soy isoflavones dose varied from 33 to 132 mg/day. Overall effect size indicated a non-significant effect on serum concentration of CRP following soy isoflavones intake (weighted mean differences (WMD)=-0.15 mg/L, 95% confidence interval (CI): -0.54, 0.23; p=0.430). Subgroup analysis revealed that soy isoflavones significantly reduced serum concentration of CRP in studies among participants with age >57 years and baseline CRP levels >3.75 mg/L. The present study proposed that soy isoflavones could not significantly reduce serum CRP levels. It seems more RCTs on participants with age more than 57 years and higher levels of CRP is necessary.

A systematic review and meta-analysis of almond effect on C-reactive protein and interleukin-6 in adults.

BACKGROUND: The previous articles have shown that the almond might reduce the serum concentration of inflammatory mediators. Therefore, the studies reported in this article aimed to assess the almond effect on serum concentration of C-reactive protein (CRP) and interleukin-6 (IL-6) in adults. METHOD AND MATERIALS: To find the related English-language studies, an electronic search was run in databases including Web of Science, PubMed, SCOPUS, ClinicalTrials.gov, and Cochrane library with no time limit (up to August 2022). The effect sizes were calculated based on the mean changes for both intervention and comparison groups. DerSimonian and Laird random-effects model was used to determine the summary of overall effects and their heterogeneity. Cochran's Q test and I-squared statistic were used to explore the statistical heterogeneity. RESULTS: In total, eleven studies were included in this study. The overall estimate indicated that the almond consumption had no significant effect on serum CRP level (weighted mean difference (WMD) = -0.28 mg/l, 95 % confidence interval (CI): - 0.81, 0.25; p = 0.29). Regarding IL-6, almond consumption significantly decreased serum IL-6 level (WMD = -0.1 pg/ml, 95 % CI: -0.15, -0.05; p < 0.001). CONCLUSION: The overall results support the beneficial effects of almond consumption on serum concentration of IL-6; but even so, our study revealed that the almond consumption non-significantly reduced serum concentration of CRP. We still need more well-designed trials to confirm the beneficial effects of almond.

Opium tincture versus methadone for opioid agonist treatment: a randomized controlled trial.

AIM: To test if opium tincture (OT) was non-inferior to methadone in retaining participants in opioid agonist treatment (OAT). DESIGN: A Phase III, multi-centre, parallel-group, non-inferiority, double-blind randomized controlled trial with an allocation ratio of 1:1. Participants were provided treatment and followed for a period of 85 days. SETTING: Four OAT clinics in Iran. PARTICIPANTS: Two hundred and four participants with opioid use disorder [mean age (standard deviation) = 37.4 (9.3); female 11.3%] recruited between July 2017 and January 2018. INTERVENTIONS: Participants were assigned to either OT (102) or methadone (102) using a patient-centred flexible dosing strategy. MEASUREMENTS: Treatment retention over 85 days was the primary outcome. Self-reported opioid use outside treatment and occurrence of adverse events (AEs) were the secondary outcomes. FINDINGS: Remaining in treatment at the end of the follow-up were 68.6% in the methadone arm and 59.8% in the OT arm. The relative retention rate of methadone to OT was 1.15 (0.97, 1.36) in both intent-to-treat and per-protocol analyses; non-inferiority was not supported statistically, as the upper bound of the confidence interval exceeded our pre-specified non-inferiority margin (1.25). Opioid use outside treatment was reported by 30.3% of OT (n = 152) and 49.4% of methadone (n = 168) patients, a difference in proportions of -19%: 90% confidence interval (-28%, -10%). The total count of AEs in the OT arm (22 among nine individuals) was significantly higher (P = 0.04) than that in the methadone arm (three among two individuals). Nausea was the most common side effect. CONCLUSION: While this study could not conclude the non-inferiority of opium tincture (OT) to methadone for retaining patients in opioid agonist treatment, OT retained 60% of participants to end of follow-up (85 days) and was superior to methadone in reducing self-reported opioid use outside treatment.

Investigating the Effect of Zinc on the Prevention of Acute Peripheral Neuropathy in Cancer Patients Treated with Taxanes.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major complication of many chemotherapeutic agents, including taxanes. Here, we aimed to investigate the effect of zinc on CIPN. Materials and Methods: This is a double-blinded controlled clinical trial that was performed in 2020-2021 in Isfahan on 55 cancer patients. We collected the data regarding CIPN, its severity, presence of abnormal deep-tendon reflexes, paresthesia, restriction in daily activities, and restriction in self-care and pain. Patients were divided into two groups: Patients in the first group were treated with capsules of zinc sulfate 25 mg daily and the control group received placebo. The duration of treatments was 3 months. Patients were visited 6, 9, and 12 weeks after study initiation. Results: There was a statistically significant decrease in the frequency of CIPN in the intervention group (37.03% vs. 14.8%, P < 0.001). The evaluation of the severity of neuropathy and presence of abnormal deep-tendon reflexes also demonstrated significant decrease in the intervention group during the study (P < 0.001 for both), but no significant changes were observed in the placebo group (P > 0.05). The activity limitations and pain severity improved significantly both in the intervention and placebo groups (P < 0.001 for both groups and items). The intervention group, however, had significantly lower frequencies of activity limitation and lower pain severity within compared to the control group during the study (P < 0.001). Conclusion: Zinc supplement therapy resulted in reduced frequency and intensity of CIPN in patients undergoing chemotherapy with taxanes.

The beneficial effect of tart cherry on plasma levels of inflammatory mediators (not recovery after exercise): A systematic review and meta-analysis on randomized clinical trials.

BACKGROUND: Chronic inflammation has been classified as one of the most important threats to health. Scientists suggested that tart cherry (TC) can reduce plasma levels of inflammatory mediators. Therefore, the aim of this study was to summarize the effect of TC on circulating C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) among adult participants in non-exercise randomized clinical trials (RCTs). METHODS AND MATERIALS: The eligible English-language RCTs were found by searching databases including PubMed, Web of Science, Cochrane Library, Scopus, and clinical Trials.gov up to May 2022, with no time limit. We used the mean change from baseline and its standard deviation for both intervention and comparison groups to calculate the effect size. The random-effects model proposed by DerSimonian and Laird was used to estimate the overall summary effect and the heterogeneity. We used PRISMA 2020 guidelines to report this study. RESULTS: Ten RCTs were included in this study. The results demonstrated that TC had a significant decreasing effect on plasma CRP level compared with the comparison group (weighted mean differences (WMD) = -0.55 mg/L; 95% confidence interval (CI): - 1.03, - 0.06; p = 0.029), but had no significant effect on plasma IL-6 compared with comparison group (WMD = 0.08 pg/mL; 95% CI: -0.02, 0.17; p = 0.10). The effect of TC consumption on plasma TNF-α level was evaluated in only three studies that showed no significant effects (p>0.05). CONCLUSION: Our results confirmed a significant decreasing effect of TC on CRP. Regarding IL-6 and TNF-α, our study did not present any significant effect of TC.

Grain yield and micronutrient concentrations of maize parental lines of new hybrid genotypes affected by the foliar application of micronutrients.

It is important for the breeders to find how genetic differences may affect crop grain yield and nutrient uptake affected by micronutrient fertilization. Accordingly, with respect to our published research, the foliar application of the most deficient micronutrients (Fe, Zn and Mn) in the arid and semi-arid areas of the world affecting grain yield and nutrient concentration of maize parental lines of new hybrid genotypes was tested in a two-year experiment (2016-2017). A split plot experiment (randomized complete block design) with seven maize parental lines (G1-G7, sub-plots), and eight micronutrients treatments (main plots) including control (without spraying, M1), Zn (M2), Mn (M3), and Fe (M4) at 3 g L-1, Mn + Zn (M5), Fe + Zn (M6), Fe + Mn (M7), and Fe + Mn + Zn (M8) at 1.5 g L-1, sprayed at the growth stages of V8 and the full appearance of the plant organs (R1) was conducted. Plant height, cob height, 1000 grain weight, grain yield, number of rows per cob, number of grains per row, grain crude protein content, and micronutrient (Zn, Fe and Mn) concentrations were determined. Micronutrients significantly affected Fe (27.68-62.55 mg. kg-1) and Zn (33.34-55.73 mg. kg-1) concentrations. A3 (12,600 kg. ha-1) and A5 (8900 kg. ha-1) resulted in the highest and least grain yield, respectively. M7 (11,470 kg. ha-1) had the highest grain yield significantly different from control (5510 kg. ha-1). Interestingly, just Mn significantly affected grain crude protein (9.63-12.92%). Correlation coefficients indicated Mn and Fe as the least and the most correlated micronutrients with the growth of maize parental lines. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01160-0.

Substance of choice, impact of heroin or opium on treatment retention in a multicentre randomised controlled trial in Iran.

INTRODUCTION: In the Middle East and Asia, illicit opioid use exists across a spectrum between heroin and opium. The impact of primary opioid of choice on opioid agonist treatment retention has not been well evaluated previously, especially for opium tincture, an increasingly popular form of opioid agonist treatment in Iran. This study investigates the relationship between primary opioid of choice, namely heroin or opium, and retention in opium tincture and methadone treatment. METHODS: Participants with opioid use disorder (n = 204) were randomised to receive opium tincture or methadone. All participants were categorised as mainly using opium or heroin. Bivariate analyses between treatment retention and primary opioid of choice (P < 0.05) and logistic regression were conducted. RESULTS: Among the 191 participants included in this analysis, heroin was the primary substance of choice for 135 participants (70.7%) and opium for 56 (29.3%). Bivariate analysis showed that the opium group was more likely to be satisfied with family situation, employed and retained in treatment than the heroin group while less likely to experience incarceration and use multiple substances. When adjusting for covariates, primary opioid of choice was not significantly associated with retention in either methadone or opium tincture treatment arm. DISCUSSION AND CONCLUSIONS: Positive factors, such as employment, housing and family support, seem to collectively explain the higher retention in treatment among those who primarily use opium compared to those who use heroin. To optimise retention in opioid agonist treatment, biopsychosocial care models should be further evaluated to improve psychosocial functioning.

The effect of soy protein containing soy isoflavones on serum concentration of cell adhesion molecules: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Soy protein in combination with soy isoflavones might reduce the serum concentration of inflammatory mediators. In this study, we attempted to summarize the effect of soy protein combined with soy isoflavones on circulating E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in adults. METHODS: Clinicaltrials.gov, Web of Science, Cochrane Library, PubMed, and Scopus were searched for English articles with no time limit regarding publication up to December 2020. Thereafter, the mean changes from baseline and their standard deviations (SDs) for both intervention and comparison groups were used to calculate the effect size. We used DerSimonian and Laird random-effects model if the heterogeneity test was statistically significant. Cochran's Q test and I-squared statistic were also used to calculate the statistical heterogeneity of the intervention effects. RESULTS: Eight articles were found as eligible for this study. The treatment duration was between 6 and 24 weeks. Soy isoflavones dose was in a range of 30-112 mg/day and soy protein dose was in a range of 11.25-52 g/day. Overall, taking soy protein supplements containing soy isoflavones was not associated with changes in cell adhesion molecules, E-selectin, ICAM-1, or VCAM-1 (WMD = 0.65, 95 % CI: -2.58, 3.89; p = 0.692; WMD = 2.68, 95 % CI: -0.98, 6.34; p = 0.151; WMD = 2.66, 95 % CI: -6.28, 11.61; p = 0.559, respectively). CONCLUSION: The combination of soy protein and soy isoflavones was not significantly associated with changes in levels of E-selectin, ICAM-1, and VCAM-1. However, we need more studies with a large sample size and more participants with different age categories in this regard.

Beneficial effect of soy isoflavones and soy isoflavones plus soy protein on serum concentration of C-reactive protein among postmenopausal women: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Scientists suggest that soy isoflavones or the combination of soy isoflavones and soy protein may have beneficial effects on inflammation. Thus, the present study aims at conducting a systematic review and meta-analysis on randomized controlled trials (RCTs) in which the effect of soy isoflavones and the combination of soy isoflavones and soy protein on serum concentration of C-reactive protein (CRP) among postmenopausal women is assessed. METHODS AND MATERIALS: A literature searching was done to identify a breadth of related references in PubMed, Scopus, ISI Web of Science, Cochrane Library, and Clinicaltrials.gov up to December 2020. The mean change from baseline in the CRP concentrations and its standard deviation (SD) for both intervention and comparison groups were used to calculate the effect size. The summary of the overall effects and heterogeneity was estimated by using the DerSimonian and Laird random effects model. The protocol was registered in PROSPERO (No. CRD42020166053). RESULTS: This study considered 23 articles for systematic review and 19 articles for meta-analysis. The overall effect presented a non-significant effect of soy isoflavones on serum CRP concentrations (WMD = 0.08 mg/L, 95 % CI: -0.08, 0.24; p = 0.302) and the overall effect of the combination of soy isoflavones and soy protein indicated non-significant effect in serum levels of CRP (WMD= -0.02 mg/L 95 % CI: -0.12, 0.08; p = 0.715). CONCLUSION: Published RCTs did not provide strong evidence regarding beneficial effect of soy isoflavones or the combination of soy isoflavones and soy protein on serum CRP concentration among postmenopausal women.

The effect of soy isoflavones and soy isoflavones plus soy protein on serum concentration of tumor necrosis factor-α? A systematic review and meta-analysis of randomized controlled trials.

In this study, we summarized the effect of soy isoflavones and soy isoflavones plus soy protein on serum concentration of tumor necrosis factor-alpha (TNF-α) among adult participants. We systematically searched Scopus, ISI Web of Science, Cochrane Library, PubMed, and clinicaltrials.gov for articles published up to May 2020. Effect size was calculated by mean change from baseline of TNF-α concentrations and its standard deviation (SD) for intervention and comparison groups. If the heterogeneity test was statistically significant, DerSimonian and Laird random effects model was used to estimate the summary of the overall effects and its heterogeneity. Nineteen and fourteen randomized clinical trials were included in our systematic review and meta-analysis, respectively. The result of overall effect size indicated a non-significant effect in serum concentration of TNF-α following soy isoflavones intake (WMD = 0.2 pg/ml, 95% CI: -0.13, 0.53; p = .226) and the combination of soy isoflavones and soy protein intake (WMD = 0.02 pg/ml, 95% CI: -0.02, 0.06; p = .286). Subgroup analyses revealed no significant change in circulatory levels of TNF-α following soy isoflavones plus soy protein intake. In conclusion, the present systematic review and meta-analysis found insufficient evidence that soy isoflavones or the combination of soy isoflavones and soy protein significantly reduce serum concentration of TNF-α.

Can soy isoflavones plus soy protein change serum levels of interlukin-6? A systematic review and meta-analysis of randomized controlled trials.

In the present review, we aimed to summarize the effect of soy isoflavones plus soy protein on circulating interlukin-6 (IL-6) in adult participants. Databases including ISI Web of Science, PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched up to 23 March 2020. The mean change from baseline of IL-6 concentrations and its SD for intervention and comparison groups were used to calculate the effect size. If the heterogeneity test was statistically significant, DerSimonian and Laird random effects model was used. Cochran's Q test and I-squared statistic were also used to compute the statistical heterogeneity of the intervention's effects. Eighteen studies were known to be eligible for systematic review and 14 studies were selected for meta-analysis. Our meta-analysis results indicated a non-significant effect in serum IL-6 concentrations compared to the comparison group (WMD = 0.03 pg/ml, 95% CI: -0.06, 0.12; p = .459). In subgroup analysis, based on soy isoflavones dosage, it was observed that this combination could reduce IL-6 levels in studies that used isoflavones with dose >84 mg/day (WMD = -0.12 pg/ml 95% CI: -0.24, -0.004; p = .042, I2 = 82.7%) and in articles with a good quality (WMD = -0.15 pg/ml 95% CI: -0.24, -0.05; p = .003, I2 = 62.3%). Performing well-designed intervention studies using a high dose of soy isoflavones is recommended to confirm the beneficial effects of soy ingredients on IL-6.

Effect of resistant starch type 2 on inflammatory mediators: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Inflammation is the main cause in the development of chronic diseases. The enhancement of pro-inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) is the main risk factor in chronic diseases. Resistant starch type 2 (RS2) is non-gelatinized granules which their enzymatic hydrolysis is very low. RS2 might be able to reduce inflammatory mediators, therefore; our aim for this study was indicating RS2 effects on inflammatory mediators such as IL-6, TNF-a, and CRP among healthy and unhealthy subjects. METHODS: Articles which assessed RS2 effect on IL-6, TNF-α, and hs-CRP were found by advanced search methods. Electronic databases including Google scholar, ISI web of science, SCOPUS, and PubMed, were searched up to October 2019. Treatment effect was the mean difference between changes in serum levels of inflammatory biomarkers in each arm of the clinical trials. To pool the effect of resistant starch on inflammatory biomarkers, we used random effects model. RESULTS: We included eight articles in systematic review and meta-analysis. The overall effect illustrated no significant change in serum levels of hs-CRP, IL-6, and TNF-α in intervention group compared with the control group (WMD: -7.18 pg/mL, 95% CI: -27.80, 13.45; P = 0.495, I2 = 100.0%, WMD: -0.003 pg/mL, 95% CI: -0.07, 0.06; P = 0.919, I2 = 98.1%, WMD: -0.003 pg/mL, 95% CI: -0.004, -0.001; P < 0.0001, I2 = 98.0% respectively). CONCLUSION: In conclusion, we found that RS2 could not reduce inflammatory mediators, but we still need more RCTs with longer intervention duration, higher dose, and studies in different countries.

A pilot study of the effect of curcumin on epigenetic changes and DNA damage among patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND: The enhancement of oxidative stress in non-alcoholic fatty liver disease (NAFLD) patients may cause mutation in DNA by deamination of cytosine to 5-hydroxyuracil or uracil. This study aimed to discover the effects of curcumin on NAFLD progress, DNA damage caused by oxidative stress, and promoter methylation of mismatch repair enzymes. MATERIAL AND METHODS: in this study, 54 NAFLD patients were randomly devided into two groups, according to a double blind parallel design either phytosomal curcumin (250 mg/day) or placebo for 8 weeks. Fasting blood samples and anthropometric measures were taken twice, once at the baseline and once at the end of the study. Promoter methylation and 8-hydroxy-2' -deoxyguanosine (8-OHdG) concentration as DNA damage mediator were measured by restriction enzymes and enzyme-linked immunosorbent assay, respectively. RESULT: Analysis was performed on 44 patients. According to our between groups analysis, curcumin significantly reduced the methylation in MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) promoter regions. The within-group comparison revealed that anthropometric variables significantly decreased. However, the result of the between groups comparison indicated no significant changes in the anthropometric variables except for BMI. Liver enzymes and 8-OHdG did not significantly change at the end of the study, neither in curcumin group nor in placebo group. CONCLUSION: Curcumin might be able to reduce the risk of mismatch base pair in DNA among the NAFLD patients. However, it did not change the DNA damage mediator and liver enzymes. For confirming these results, more studies with longer duration, more numbers of examined genes, higher dose of curcumin, and larger sample size are required.

Alpha-lipoic acid effect on leptin and adiponectin concentrations: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: New evidence suggests that dysregulation of adipocytokines caused by excess adiposity plays an important role in the pathogenesis of various obesity comorbidities. Our aim in this meta-analysis was to determine the effect of alpha-lipoic acid (ALA) supplementation on serum levels of leptin and adiponectin. METHODS: We searched Scopus, PubMed, Google Scholar, and ISI Web of Science from inception up to July 2019. Mean difference for leptin and adiponectin were calculated by subtracting the change from baseline in each study group. Summary estimates for the overall effect of ALA on serum leptin and adiponectin concentrations were calculated using random effects model. Results were presented as weighted mean difference (WMD) and their 95% confidence intervals (CI). Between-study heterogeneity was examined using the I2 statistics. RESULT: Eight studies were included in systematic review and seven studies in meta-analysis. The overall effect suggested a significant decrement in serum leptin concentrations (WMD = - 3.63; 95% CI, - 5.63, - 1.64 µg/ml; I2 = 80.7%) and a significant increase in serum levels of adiponectin (WMD = 1.98 µg/ml; 95% CI, 0.92, 3.04; I2 = 95.7%). Subgroup analyses based on age showed a significant reduction in leptin levels only in younger adults, and subgroup analysis based on duration indicated in studies with a duration of more than 8 weeks adiponectin levels increased significantly and leptin levels decreased significantly. CONCLUSION: Our results revealed ALA decreased leptin and increased adiponectin especially in studies lasted more than 8 weeks. We still need more studies with different ALA dose, intervention duration, and separately on male and female.

The effect of curcumin with piperine supplementation on pro-oxidant and antioxidant balance in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial.

Background The main causes of the progression of non-alcoholic fatty liver disease (NAFLD) are enhanced levels of reactive oxygen species and lipid peroxidation products. Therefore, the usage of antioxidant agents for the prevention and remedy of this disorder was recommended. Curcumin is proposed to treat NAFLD due to its high antioxidative activity. The aim of this study was to examine the effect of curcumin with piperine supplementation on oxidative stress in subjects with NAFLD. Methods In this double-blind, placebo-controlled trial, 55 subjects were randomly divided into two groups (curcumin with piperine and placebo). The participants received administrations of curcumin (500 mg) in combination with piperine (5 mg) and placebo daily for 8 weeks. Oxidative stress was assessed by measuring serum pro-oxidant and antioxidant balance (PAB) assay before and after the intervention. Results The serum PAB values did not significantly change between the treatment group vs. age and gender-matched placebo group after 8 weeks of supplementation. Also, curcumin in combination with piperine did not show a significant decrease (p = 0.06) in PAB levels compared to baseline. Conclusions The present study demonstrated that a dose of curcumin, co-supplied with piperine might be less than a dose in which curcumin can significantly decrease PAB values in these patients.

Comparing opium tincture and methadone for medication-assisted treatment of patients with opioid use disorder: Protocol for a multicenter parallel group noninferiority double-blind randomized controlled trial.

OBJECTIVES: This is the first study to compare the safety and efficacy of opium tincture (OT) with methadone for treatment of opioid use disorder. METHODS: In this multicenter, double-blind, noninferiority controlled trial, a stratified sample of 204 participants with opioid use disorder were recruited from community outreach, drop-in centers, and triangular clinics. Participants were excluded in case of active participation in another treatment program for opioid use disorder, hypersensitivity to trial medications, pregnancy, and certain serious medical conditions. They were randomized to receive either OT or methadone with an allocation ratio of 1:1 using a patient-centered flexible dosing strategy. Eligible participants were followed for a period of 12 weeks. Primary outcome is the difference in percentage of patients retained in the treatment. Secondary outcomes are craving, withdrawal symptoms, physical health, mental health, quality of life, and severity of substance use problems, cognitive function, safety profile, cost-effectiveness, and participants' satisfaction. Both intention-to-treat and per-protocol analyses will be conducted. The Ethics Board of the University of British Columbia and Tehran University of Medical Sciences approved the study. (clinicaltrials.gov; NCT02502175). RESULTS: To be reported after final analysis. CONCLUSIONS: If shown to be effective, OT will diversify the options for medication-assisted treatment of opioid use disorder.