Curcumin effects on glycaemic indices, lipid profile, blood pressure, inflammatory markers and anthropometric measurements of non-alcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: Curcumin has antioxidant properties and has been proposed as a potential treatment for NAFLD. The aim of current systematic review and meta-analysis was to evaluate previous findings for the effect of curcumin supplementation on glycaemic indices, lipid profile, blood pressure, inflammatory markers, and anthropometric measurements of NAFLD patients. METHODS: Relevant studies published up to January 2024 were searched systematically using the following databases: PubMed, SCOPUS, WOS, Science Direct, Ovid and Cochrane. The systematic review and meta-analysis were conducted according to the 2020 PRISMA guidelines. The quality of the papers was assessed the using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Pooled effect sizes were calculated using a random-effects model and reported as the WMD and 95% CI. Also, subgroup analyses were done to find probable sources of heterogeneity among studies. RESULTS: Out of 21010 records initially identified, 21 eligible RCTs were selected for inclusion in a meta-analysis. Overall, 1191 participants of both genders, 600 in the intervention and 591 in the control group with NAFLD were included. There are several limitations in the studies that were included, for instance, the results are weakened substantially by potential bias or failure to account for potential adulteration (with pharmaceuticals) or contamination (with other herbs) of the curcumin supplements that were tested. However, previous studies have reported curcumin to be a safe complementary therapy for several conditions. Our study indicated that curcumin supplementation in doses of 50-3000 mg/day was associated with significant change in FBG [WMD: -2.83; 95% CI: -4.61, -1.06), I2 = 51.3%], HOMA-IR [WMD: -0.52; 95% CI: -0.84, -0.20), I2= 82.8%], TG [WMD: -10.31; 95% CI: -20.00, -0.61), I2 = 84.5%], TC [WMD: -11.81; 95% CI: -19.65, -3.96), I2 = 94.6%], LDL [WMD: -8.01; 95% CI: -15.79, -0.24), I2 = 96.1%], weight [WMD: -0.81; 95% CI: -1.28, -0.35), I2= 0.0%] and BMI [WMD: -0.35; 95% CI: -0.57, -0.13), I2= 0.0%] in adults with NAFLD. There was no significant change in HbA1C, plasma insulin, QUICKI, HDL, SBP, DBP, CRP, TNF-α and WC after curcumin therapy. Subgroup analysis suggested a significant changes in serum FBG, TG, SBP, WC in RCTs for intervention durations of ≥ 8 weeks, and SBP, TG, LDL, HDL, BMI, WC in RCTs with sample size > 55 participants. CONCLUSION: Curcumin supplementation in doses of 50-3000 mg/day over 8-12 weeks was associated with significant reductions in levels of FBG, HOMA-IR, TG, TC, LDL, weight and BMI in patients with NAFLD. Previous studies have reported curcumin as a safe complementary therapy for several diseases. We would suggest that should curcumin supplements be used clinically in specific conditions, it should be used with caution. Also, difference in grades of NAFLD may effect the evaluated outcomes, so it is suggested that future studies be conducted with an analyses on subgroups according to their NAFLD grade. Furthermore, because of the failure to conduct independent biochemical assessment of the turmeric/curcumin product used in most studies as well as potential sources of bias, results should be interpreted with caution.

Effects of Selenium Supplementation on the Indices of Disease Activity, Inflammation and Oxidative Stress in Patients with Rheumatoid Arthritis: a Randomized Clinical Trial.

The aim of study was to evaluate the effect of selenium supplementation on disease activity, inflammation, and oxidative stress in patients with rheumatoid arthritis (RA). This study was a randomized double-blind placebo-controlled trial on 59 patients with RA. Participants were randomly divided to receive 200 µg/day of selenium or a placebo for 12 weeks. The disease activity score (DAS.CRP and DAS.ESR), erythrocyte sedimentation rate (ESR), serum levels of C-reactive protein (CRP), fasting blood glucose, lipids, antibodies to cyclic citrullinated protein (anti-CCP), nitric oxide, glutathione, and total antioxidant capacity were assessed. The mean of DAS.CRP and DAS.ESR decreased significantly within both study groups after the intervention. However, the between-group comparisons revealed no significant differences. The CRP levels decreased significantly in the selenium group, and this decrease was near the significance level compared to the placebo (P = 0.05). However, after adjusting for baseline values, the observed difference between groups did not remain significant. In addition, the values of ESR and anti-CCP decreased significantly within the selenium group. Although, between-group comparison did not statistically significant, the change in ESR and anti-CCP in the selenium group was small clinically relevant compared to the placebo [the effect size (95% CI) for ESR: 0.38 (- 0.14, 0.89), and for anti-CCP: 0.32 (- 0.2, 0.83)]. Our study showed that selenium caused a small clinically relevant improvement in some RA biomarkers such as ESR and anti-CCP. Future studies that evaluate the effects of novel forms of supplements such as selenium nanoparticles on the clinical symptoms and biomarkers of RA are suggested. Trial Registration: At www.irct.ir as IRCT20190924044869N1 on 2020-06-14.

Dietary Magnesium Intake and Proteinuria: Is There a Relationship?

The possible relationship between dietary magnesium status and proteinuria has been suggested by a number of previous studies. However, human studies on this association are limited. Therefore, the present study aimed to investigate the independent relationship between dietary magnesium intake and urinary protein excretion. The present study was a post hoc analysis of the previous randomized clinical trial that evaluated the effect of dietary phosphorus restriction on proteinuria. The baseline data of 90 participants with proteinuria and chronic kidney disease was used to measure the association between dietary magnesium intake and proteinuria. Participants were asked to record their 24-h food intake for three days a week in a questionnaire. Urinary protein to creatinine ratio (UPCR) in a random urine sample was measured to be a marker for proteinuria. Out of 90 patients included in the study, 47 were men and 43 were women. The mean ± standard deviation of age and body mass index were 59.05 ± 14.16 years and 29.02 ± 5.54 kg/m2, respectively. The patients' average daily dietary intake of energy and magnesium were 2183 kcal and 169.44 mg, respectively. A significant inverse correlation was found between the dietary intake of magnesium and UPCR (r = - 0.219, p = 0.042). This association remained significant even after adjusting for confounding variables (ß = - 0.222, p = 0.028). The findings of the present study showed a significant inverse relationship between the magnesium intake and proteinuria. Although, the design of the current research was cross-sectional, it has provided a basis for conducting future longitudinal studies and trials to better elucidate such a relationship.

Effects of Folic Acid Supplementation on Liver Enzymes, Lipid Profile, and Insulin Resistance in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial.

Background: Previous evidence revealed an association between folate deficiency and non-alcoholic fatty liver disease (NAFLD). This study is the first one investigating the effects of folic acid on hepatic steatosis grade, liver enzymes, insulin resistance, and lipid profile in NAFLD cases. Materials and Methods: Sixty-six participants with NAFLD were allocated randomly to take either a placebo or one oral tablet of folic acid (1 mg) on a daily basis within eight weeks. Serum folate, homocysteine, glucose, aminotransferases, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and lipids were assessed. Ultrasonography was used for assessing the liver steatosis grade. Results: The serum alanine transaminase, grade of hepatic steatosis, and aspartate transaminase significantly were decreased within both study groups; however, the between-group comparison was not statistically significant. Of note, the decrease in ALT was more pronounced in folic acid compared with the placebo group (-5.45 ± 7.45 vs. -2.19 ± 8.6 IU/L). The serum homocysteine was decreased after receiving folic acid compared to the placebo (-0.58 ± 3.41 vs. +0.4 ± 3.56 µmol/L; adjusted P = 0.054). Other outcomes did not significantly change. Conclusion: Supplementation with folic acid (1 mg/d) for eight weeks among cases with NAFLD did not change significantly the serum levels of liver enzymes, the hepatic steatosis grade, insulin resistance and lipid profile. However, it was able to prevent the increase in homocysteine in comparison with the placebo. Conducting further research is suggested with the longer duration and different doses of folic acid, adjusted to the genotypes of methylenetetrahydrofolate reductase polymorphism, among NAFLD patients.

Nigella sativa supplementation and non-alcoholic fatty liver disease: A systematic review of clinical trials.

Objective: Based on the results of previous studies, the effects of N. sativa on some of the non-alcoholic fatty liver disease's (NAFLD) biomarkers were positive; however, there were conflicting results regarding other variables. Therefore, the present systematic review of clinical trials was designed to clarify whether N. sativa effectively prevents the progression of NAFLD. Materials and Methods: A search of four databases (Scopus, PubMed, Medline, and Google scholar) was conducted to identify the clinical trials that assessed the effects of N. sativa supplementation on NAFLD. The outcome variables of interest were biomarkers of hepatic steatosis, liver enzymes, insulin resistance, and inflammation. Results: Overall, four randomized clinical trials (RCTs) were included. In three studies, hepatic steatosis grade decreased significantly after N. sativa supplementation. Serum levels of liver enzymes reduced significantly in three of four included trials. In the only study that examined the effect of N. sativa on insulin resistance parameters, all variables related to this factor were significantly reduced. In two included studies that measured biomarkers of inflammation, the serum levels of tumor necrosis factor α (TNF-α), high-sensitive C-reactive protein (hs-CRP), and interleukin 6 (IL-6) decreased significantly after intaking N. sativa supplements. Conclusion: Although the efficacy of N. sativa on liver enzymes and the grade of hepatic steatosis was reported in some of the included studies, more well-designed clinical trials are needed to determine the definitive effects of N. sativa on NAFLD. The present study provides suggestions that help to design future studies in this field.

Association of Zinc Status with Matrix Metalloproteinases, Advanced Glycation End-Products, and Blood Pressure in Patients with Chronic Kidney Disease.

Inflammation, oxidative stress, and hypertension trigger the development of chronic kidney disease (CKD). Zinc is known to have antioxidant and anti-inflammatory properties and a possible role in regulating blood pressure. The aim of this study was to investigate the correlation of serum zinc with matrix metalloproteinase-2 and-9 (MMP-2, MMP-9), advanced glycation end products (AGEs), and blood pressure in patients with CKD. This cross-sectional study included 90 patients with CKD. Serum zinc and the levels of MMP-2, MMP-9, AGEs, and creatinine were measured using validated biochemical methods. Three 24-h food recalls were completed to evaluate dietary zinc intake. Systolic and diastolic blood pressure (SBP, DBP) were measured using a digital sphygmomanometer. Participants' mean age was 60.68 ± 8.81 years. The prevalence of zinc deficiency in our participants was 10%. Serum zinc was negatively correlated with MMP-9 (r = - 0.231, p = 0.032) and creatinine (r = - 0.304, p = 0.004). However, after adjusting for confounding variables, the association between serum zinc and MMP-9 was near the significance level (ß = - 0.174, p = 0.09) and zinc remained in the model as one of the predictors. Serum zinc was positively correlated with the dietary intake of zinc (r = 0.241, p = 0.025) and estimated glomerular filtration rate (eGFR) (r = 0.259, p = 0.015). In conclusion, our results showed that serum zinc might be one of the predictors of serum MMP-9 in patients with CKD. In addition, serum zinc was positively associated with its dietary intake and eGFR. Future longitudinal studies or clinical trials are required to reveal any causal association between zinc status and profibrotic or inflammatory biomarkers among patients with CKD.