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.

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.

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.

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.

The Effect of Curcumin Phytosome on the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem with increasing prevalence among overweight and obese patients. It is strongly associated with conditions of insulin resistance including type 2 diabetes mellitus (T2DM) and obesity. It has detrimental consequences ranged from simple steatosis to irreversible hepatic fibrosis and cirrhosis. Curcumin is a dietary polyphenol with potential effect in improving NAFLD. Therefore, the aim of this trial was to examine the effect of curcumin supplementation on various aspects of NAFLD. In this trial, a total number of 80 patients were randomised to receive either curcumin at 250 mg daily or placebo for 2 months. Lipid profiles, hepatic enzymes, anthropometric indices and hepatic fat mass were assessed at the baseline and the end of the trial, and compared within the groups. The grade of hepatic steatosis, and serum aspartate aminotransferase (AST) levels were significantly reduced in the curcumin group (p = 0.015 and p = 0.007, respectively) compared to the placebo. There was also a significant reduction in high density lipoprotein (HDL) levels and anthropometric indices in both groups with no significant differences between the two groups. Low dose phospholipid curcumin supplementation each day for 2 months showed significant reduction in hepatic steatosis and enzymes in patients with NAFLD compared to placebo. Further studies of longer duration and higher dosages are needed to assess its effect on other parameters of NAFLD including cardiovascular risk.

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.

Curcumin and Piperine Combination for the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind Randomized Placebo-Controlled Trial.

BACKGROUND: Experimental and clinical studies have revealed that curcumin may be an effective therapy for non-alcoholic fatty liver disease (NAFLD). Hence, the aim of this study was to assess the effect of curcumin plus piperine administration on NAFLD. METHODS: Adults 18-65 years-old diagnosed with NAFLD by liver sonography were randomly allocated to curcumin (500 mg/day) or placebo groups for 2 months. All participants received both dietary and exercise advice. Anthropometric and biochemical measurements as well as hepatic ultrasound were performed at baseline and final conditions. RESULTS: Seventy-nine participants were recruited and randomly allocated into the curcumin (n = 39) or placebo (n = 40) groups. There were no significant differences between placebo and curcumin groups for demographic and clinical characteristics and NAFLD grade at baseline. After the treatment period, the curcumin group exhibited lower alkaline phosphatase (-16.2 ± 22.8 versus -6.0 ± 22.5 mg/dL, p = 0.04) concentrations and severity of NAFLD compared with the placebo group (p = 0.04). CONCLUSION: Results of this clinical trial suggest that short-term treatment with curcumin plus piperine administration improves NAFLD severity.

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 green tea on inflammatory mediators: A systematic review and meta-analysis of randomized clinical trials.

Catechin in green tea might be able to reduce inflammatory mediators; therefore, in this study, we aimed to indicate green tea effects on inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6). The advanced search methods of electronic databases were used to find randomized clinical trials that assessed green tea effect on inflammatory mediators among adult population. Google Scholar, PubMed/Medline, EMBASE, SCOPUS, and ISI Web of Science were searched until January 2019. Delphi checklist was used for assessing the quality of included articles. Mean changes in serum inflammatory biomarkers were calculated by subtracting endpoint values from the baseline in each study arm. Then the effect size for each selected study was estimated as the difference between mean changes in the intervention and control groups. We included 16 articles in our meta-analysis and 17 articles in systematic review. Our results indicated that green tea could not significantly decrease serum CRP levels and significantly increased IL-6 and significantly decreased TNF-α levels. In conclusion, green tea might not be able to change inflammatory mediators especially in diseases with low inflammation, but scientists who want to assess green tea effect on inflammatory mediators should perform their study on patients with high inflammation. Studies exclusive on male or female and considering nutrients intake as a confounding factor are a necessity.

Effect of Phytosomal Curcumin on Circulating Levels of Adiponectin and Leptin in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and changes in serum adipocytokine levels. The aim of the current study was to evaluate the effect of phytosomal curcumin on serum adiponectin and leptin levels in patients with NAFLD. METHODS: In this randomized double-blind, placebo-controlled trial, 65 eligible patients were randomly allocated into curcumin and placebo recipient groups using a blocked randomized technique. Parameters of weight, height, body mass index (BMI), fasting blood sugar (FBS), lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), adiponectin, leptin, and the leptin:adiponectin ratio were measured at baseline and eight weeks after intervention. RESULTS: High-density lipoprotein cholesterol (HDL-C) levels increased significantly in the curcumin group compared to the placebo group (p=0.01). Serum adiponectin levels increased significantly (p<0.001) and serum leptin levels decreased significantly (p<0.001) with a decrease in the leptin: adiponectin ratio in the curcumin group compared to the placebo group after 8 weeks of intervention. CONCLUSIONS: Non-alcoholic fatty liver disease was associated with changes in serum adipokines levels. Phytosomal curcumin effectively improved leptin and adiponectin levels. It is possible that curcumin efficacy will increase with long-term use of higher doses of this substance.

The effect of L-carnitine on inflammatory mediators: a systematic review and meta-analysis of randomized clinical trials.

AIM AND BACKGROUND: Reducing inflammation by nutritional supplements may help to reduce the risk of many chronic diseases. Our aim in this meta-analysis was to determine the effect of L-carnitine on inflammatory mediators including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). METHODS: Our systematic search to find relevant randomized clinical trials (RCTs) was performed up to October 2018 using ISI Web of Science, Google Scholar, PubMed/Medline, and SCOPUS. In this meta-analysis, the weighted mean differences (WMD) with standard errors (SE) were used to pool the data. WMD was calculated by subtracting change-from-baseline mean values in the control group from change-from-baseline mean values in the intervention group in each study. To identify heterogeneity among studies, the I2 statistic was employed. The protocol was registered with PROSPERO (No. CRD42019116695). RESULTS: Thirteen articles were included in our systematic review and meta-analysis. The results of the meta-analysis indicated that L-carnitine supplementation was significantly associated with lower levels of CRP in comparison to controls (WMD = -1.23 mg/L; 95% CI: -1.73, -0.72 mg/dL; P < 0.0001). Also, a slight but statistically significant decrease was observed in IL-6 and TNF-α levels (WMD = -0.85 pg/dL; 95% CI: -1.38, -0.32 pg/dL; P = 0.002 and WMD = -0.37 pg/dL; 95% CI: -0.68, -0.06 pg/dL; P = 0.018, respectively). CONCLUSION: Our results indicate that L-carnitine reduced inflammatory mediators, especially in studies with a duration of more than 12 weeks. Further studies with different doses and intervention durations and separately in men and women are necessary.

Effect of Vitamin D on Non-Alcoholic Fatty Liver Disease: A Systematic Review of Randomized Controlled Clinical Trials.

New evidence suggests that low serum Vitamin D may cause nonalcoholic fatty liver disease (NAFLD). Hypovitaminosis D is associated with the severity and incidence of NAFLD. The objective of this study was to conduct a systematic review on randomized controlled trials (RCTs) assessing the effect of Vitamin D on serum metabolic profile among NAFLD patients. Databases including PubMed, Institute for Scientific Information Web of Science, Scopus, and Google Scholar were searched up to November 2016. RCTs which studied Vitamin D effect on metabolic profiles and liver function, and conducted among adults were included. Six articles were eligible to be considered in this systematic review. According to the result, Vitamin D supplementation might improve lipid profile and inflammatory mediators when compared with placebo. No article indicated significant effect of Vitamin D on liver enzymes except one article which revealed that Vitamin D together with calcium carbonate can reduce liver enzymes. Vitamin D supplementation may not improve anthropometric measures and glycemic index variables among patients with NAFLD. Vitamin D supplement might improve NAFLD symptoms, especially inflammatory mediators. More RCTs in different parts of world with different forms and doses of Vitamin D are necessary.

The effect of alpha-lipoic acid on inflammatory mediators: a systematic review and meta-analysis on randomized clinical trials.

Alpha-Lipoic Acid (ALA) is a natural antioxidant compound which is naturally found in plant sources. New evidence revealed that ALA can reduce inflammation. Our objective in this meta-analysis was to conduct a systematic review and meta-analysis on randomized controlled trials to indicate ALA effects on serum inflammatory mediators concentration such as tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin-6 (IL-6). In order to find relevant articles we performed a systematic research up to June 2018 using EMBASE, ISI web of science, Scopus, PubMed, and Google scholar. The overall treatment effect for each inflammatory marker was calculated as weighted mean differences (WMD) and corresponding 95% of confidence interval (CI) between changes in intervention and control groups. Changes for each parameter were calculated by subtracting baseline values from the final mean values. The I2 statistic was used to examine between-study heterogeneity. When heterogeneity was > 25%, random effect model was run to estimate pooled effect size. There had been nineteen articles in our meta-analysis and twenty-one articles in systematic review. Our meta-analysis results indicated that ALA significantly decreased serum CRP levels (WMD= -0.29, 95% CI: -0.46, -0.12; I2 =97.6%, P < 0.0001), IL-6 (WMD= -3.02, 95% CI: -4.03, -2.01; I2 =99.7%, P < 0.0001) and TNF-α levels (WMD= -1.71, 95% CI: -2.30, -1.13; I2 =99.0%, P < 0.0001). Our results indicated possible decreasing effect of ALA on inflammatory mediators especially in high dose. More randomized clinical trials (RCTs) are necessary with different intervention duration and on women and men separately.