Association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with metabolically healthy obesity.

BACKGROUND: Among the Toll-like receptors (TLR) that are dependent of myeloid response protein (MyD88), the TLR4 and TLR2 are directly associated with low-grade chronic inflammation; however, they are not been investigated in subjects with metabolically healthy obesity (MHO). Thus, the objective of this study was to determine the association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with MHO. METHODS AND RESULTS: Men and women with obesity aged 20 to 55 years were enrolled in a cross-sectional study. Individuals with MHO were allocated into the groups with and without low-grade chronic inflammation. Pregnancy, smoking, alcohol consumption, intense physical activity or sexual intercourse in the previous 72 h, diabetes, high blood pressure, cancer, thyroid disease, acute or chronic infections, renal impairment, and hepatic diseases, were exclusion criteria. The MHO phenotype was defined by a body mass index (BMI ≥ 30 kg/m2) plus one or none of the following cardiovascular risk factors: hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol. A total of 64 individuals with MHO were enrolled and allocated into the groups with (n = 37) and without (n = 27) inflammation. The multiple logistic regression analysis indicated that TLR2 expression is significantly associated with inflammation in individuals with MHO. In the subsequent analysis adjusted by BMI, TLR2 expression remained associated with inflammation in individuals with MHO. CONCLUSION: Our results suggest that overexpression of TLR2, but not TLR4 and MyD88, is associated with low-grade chronic inflammation in subjects with MHO.

Association of the triglycerides and glucose index and the homeostatic model assessment of insulin resistance with lipoprotein(a), apolipoprotein AI, and apolipoprotein B concentrations in children with normal-weight.

The aim of this study was to compare the association of the triglycerides and glucose (TyG) index and homeostatic model assessment of insulin resistance (HOMA-IR) with lipoprotein(a) (lp[a]), apolipoprotein AI (apoAI), and apoliprotein B (apoB) concentrations in children with normal-weight. Children with normal weight aged 6-10 years and Tanner 1 stage were included in a cross-sectional study. Underweight, overweight, obesity, smoking, alcohol intake, pregnancy, acute or chronic illnesses, and any kind of pharmacological treatment were exclusion criteria. According to the lp(a) levels, children were allocated into the groups with elevated concentrations and normal values. A total of 181 children with normal weight and an average age of 8.4 ± 1.4 years were enrolled in the study. The TyG index showed a positive correlation with lp(a) and apoB in the overall population (r = 0.161 and r = 0.351, respectively) and boys (r = 0.320 and r = 0.401, respectively), but only with apoB in the girls (r = 0.294); while the HOMA-IR had a positive correlation with lp(a) levels in the overall population (r = 0.213) and boys (r = 0.328). The linear regression analysis showed that the TyG index is associated with lp(a) and apoB in the overall population (B = 20.72; 95%CI 2.03-39.41 and B = 27.25; 95%CI 16.51-37.98, respectively) and boys (B = 40.19; 95%CI 14.50-65.7 and B = 29.60; 95%CI 15.03-44.17, respectively), but only with apoB in the girls (B = 24.22; 95%CI 7.90-40.53). The HOMA-IR is associated with lp(a) in the overall population (B = 5.37; 95%CI 1.74-9.00) and boys (B = 9.63; 95%CI 3.65-15.61).   Conclusion: The TyG index is associated with both lp(a) and apoB in children with normal-weight. What is Known: • The triglycerides and glucose index has been positively associated with an increased risk of cardiovascular disease in adults. What is New: • The triglycerides and glucose index is strongly associated with lipoprotein(a) and apolipoprotein B in children with normal-weight. • The triglycerides and glucose index may be a useful tool to identify cardiovascular risk in children with normal-weight.

The Triglycerides and Glucose Index is Negatively Associated with Insulin Secretion in Young Adults with Normal Weight.

Several studies have supported the usefulness of the triglycerides and glucose (TyG) index as a surrogate measure of insulin resistance; however, it has not been evaluated in insulin secretion. The aim of this study was to assess the association between the TyG index and insulin secretion in young adults with normal weight. Apparently healthy non-pregnant women and men, aged 18 to 23 years, were enrolled in a cross-sectional study. Overweight, obesity, pregnancy, smoking, alcohol consumption, diabetes, liver disease, renal disease, cardiovascular disease, and neoplasia were the exclusion criteria. Normal weight was defined by a body mass index (BMI)≥18.5<25.0 kg/m2 and the TyG index was calculated as the Ln [fasting triglycerides (mg/dl) x fasting glucose (mg/dl)]/2. A total of 1676 young adults with normal-weight, 1141 (68%) women, and 535 (32%) men were enrolled. Of them, 269 (16%) individuals exhibited insulin resistance; 213 (12.7%) women and 56 (3.3%) men. The linear regression analysis adjusted by gender, BMI, and waist circumference showed a significant association between the TyG index and HOMA-B (B=-35.90; 95% CI:-68.25 to-3.54, p=0.03) in the overall population. An additional analysis adjusted by BMI and waist circumference revealed that the TyG index is significantly associated with HOMA-B in subjects with and without insulin resistance (B=-104.73; 95% CI:-204.28 to-5.18, p=0.03 and B=-74.72; 95% CI:-108.04 to-41.40, p<0.001). The results of this study showed that the TyG index is negatively associated with insulin secretion in young adults with normal weight.

Effect of glucagon-like peptide-1 receptor agonists on renal function: A meta-analysis of randomized controlled trials.

AIMS: The objective of this meta-analysis was to examine the impact of the GLP-1 RA on renal function parameters in randomized controlled trials. METHODS: A systematic search was performed in PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Meta-analysis was performed using a random-effects model and sensitivity analysis. RESULTS: Data from 18 randomized controlled trials involving 12 192 subjects, showed that treatment with GLP-1 RA had no effect on serum creatinine levels (weighted mean difference [WMD]: 0.00 mg/mL, 95% confidence interval [CI]: -0.01, 0.01, P = .83, I2 = 0%) and glomerular filtration rate (WMD: 1.01 mL/min/1.73 m2 , 95% CI: -1.61, 3.63, P = .45, I2 = 75%). On the other hand, a significant reduction in urinary albumin excretion (WMD: -18.01 mg/day, 95% CI: -31.20, -4.82, P = .007, I2 = 23%) and albumin-to-creatinine ratio (WMD: -6.74 mg/g, 95% CI: -12.64, -0.85, P = .03, I2 = 68%) was detected after GLP-1 RA therapy. CONCLUSION: Results of our meta-analysis revealed that GLP-1 RA treatment decreases urinary albumin excretion and albumin-to-creatinine ratio but it did not cause significant changes in creatinine levels and glomerular filtration rate.

Clinical Efficacy of Botulinum Toxin in the Treatment of Plantar Fasciitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy of botulinum toxin A (BTX-A) for the treatment of plantar fasciitis through a meta-analysis of randomized controlled trials (RCTs) focusing on pain and functional outcomes since current literature has supported a potential benefit of BTX-A. DATA SOURCES: The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched until December 2020 for RCTs reporting the effects of BTX-A injections on plantar fasciitis. The complementary literature search included Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and greylit.org. STUDY SELECTION: Only RCTs assessing the effect of BTX-A injections on pain, functional improvement, or plantar fascia thickness in patients with plantar fasciitis were included. Multiple researchers carried out the screening process of the 413 records. DATA EXTRACTION: Data were extracted independently and in duplicate using a standardized data extraction format. Information was contrasted by a third observer. DATA SYNTHESIS: BTX-A injections resulted in significant pain relief (mean difference, -2.07 [95% CI, -3.21 to -0.93]; P=.0004; I2=97%) and functional improvement (standardized mean difference, 1.15 [95% CI, 0.39-1.91]; P=.003; I2=87%). A subanalysis indicated that pain relief was sustained at 12 months while functional improvement remained significant after 0-6 months. The results were not affected by a single study after sensitivity analysis. The site of injection and the use or not of ultrasound-guided injections may account for potential sources of interstudy heterogeneity. CONCLUSIONS: This meta-analysis suggests both a statistically significant and a clinically meaningful improvement on plantar fasciitis symptoms after BTX-A treatment.

Hyperuricemia is Associated with the Presence of Metabolically Obese Normal-Weight and Metabolically Healthy Obese Phenotypes.

BACKGROUND: It is well-recognized that hyperuricemia is a common abnormality among individuals with metabolic syndrome. AIMS: The objective of this study was to determine whether hyperuricemia is associated with the metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) phenotypes. METHODS: Men and women equal or greater than 18 years of age were enrolled in a cross-sectional study. Normal-weight subjects were allocated into the MONW or healthy normal-weight (HNW) groups; while obese individuals were divided into the MHO and metabolically unhealthy obese (MUO) subgroups. MONW phenotype was defined by body mass index (BMI) <25.0 kg/m2 accompanied by at least one cardiovascular risk factor (hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol), and MHO phenotype was considered in obese subjects (BMI ≥30 kg/m2) without metabolic abnormalities. RESULTS: A total of 567 individuals were enrolled; of them, normal-weight subjects were allocated into the MONW (n = 101) and control (n = 72) groups, whereas obese individuals into the MHO (n = 61) and MUO (n = 333) groups. The multiple logistic regression analysis adjusted by age, gender, and body mass index revealed that hyperuricemia is significantly associated with MONW (OR = 5.14; 95% CI: 1.37-19.29) and MHO (OR = 0.34; 95% CI: 0.14-0.82) phenotypes. CONCLUSION: Results of our study showed that hyperuricemia is associated with both MONW and MHO phenotypes.

The Triglycerides and Glucose Index Is Associated with Mild Cognitive Impairment in Older Adults.

BACKGROUND: It has been reported that insulin resistance is related to cognitive decline. The triglycerides and glucose (TyG) index, is a reliable and inexpensive surrogate test for detecting insulin resistance. AIMS: The goal of this study was to evaluate the association between the TyG index and the mild cognitive impairment (MCI) in older adults. METHODS: A total of 135 individuals, men and women aged 60 to 90 years, were enrolled in a case and control study. Individuals with a diagnosis of MCI (n = 65) were allocated into the case group and compared with individuals without MCI (n = 70) in the control group. Alcohol intake, diabetes duration ≥5 years, diagnoses of cerebrovascular disease, brain injury, folic acid deficiency, dementia, moderate or severe CI, major depressive disorders, and thyroid disease were exclusion criteria. RESULTS: Individuals in the case group exhibited higher waist circumference (97.9 ± 13.9 versus 93.5 ± 13.0, p = .001) and TyG index (5.0 ± 0.3 versus 4.1 ± 0.2, p = .001) than individuals in the control group. The TyG index ≥4.68 (OR 6.91; 95% CI 2.05-11.68) and waist circumference (OR 1.03; 95% CI 1.01-1.06) were positively associated with MCI, while education level (OR 0.44; 95% CI 0.30-0.61), occupation (OR 0.75; 95% CI 0.59-0.61), and exercise (OR 0.34; 95% CI 0.22-0.52) were inversely associated with MCI. After controlling for sex, age, waist circumference, education level, occupation, and exercise, a TyG index ≥4.68 remained significantly associated with MCI (OR 2.97; 95% CI 1.12-14.71). CONCLUSION: The TyG index is independently associated with the presence of MCI in older people.

Normal saline injection produces a therapeutic effect in patients with plantar fasciitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Injectable therapies have been increasingly investigated to treat plantar fasciitis in randomized controlled trials (RCT) where normal saline injections are frequently used as placebo. The purpose was to quantify the effect of saline injections and compared against available minimal clinically important difference (MCID) criteria specific for plantar fasciitis to assess if changes were clinically meaningful. METHODS: RCT including a placebo group (normal saline) and reporting changes in pain and functional outcomes in plantar fasciitis were identified through a search in MEDLINE, Embase, Web of Science, and Scopus to February 2022. PRISMA guidelines and a registered protocol (PROSPERO: CRD42020214035) were followed to conduct the study. RESULTS: Pooled analysis of 13 RCT (379 subjects) included for analysis revealed a significant improvement on pain (P < .00001) and functional scores (P < .00001) after normal saline injections. These changes exceeded the established MCID criteria. CONCLUSIONS: Normal saline injections in plantar fasciitis showed a therapeutic effect with statistically and clinically meaningful improvement when administered in the setting of an RCT for up to 12 months. The control of potential confounders influencing the effect of saline injections is required for future research.

Effect of sodium-glucose co-transporter 2 inhibitors on hepatic parameters: A systematic review and meta-analysis of randomized controlled trials.

Previous studies have suggested that sodium-glucose co-transporter-2 (SGLT2) inhibitors may improve hepatic function; however, the evidence is scarce. Hence, we performed a meta-analysis of randomized controlled trials to evaluate the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on hepatic parameters. PubMed, Web of Science, Scopus, and Google Scholar databases were searched to identify randomized controlled trials examining the effect of SGLT2 inhibitors on hepatic parameters. Meta-analysis was performed using a random-effects model and sensitivity analysis. Meta-analysis revealed that SGLT2 inhibitors therapy significantly lowered alanine aminotransferase (ALT) (WMD: -4.79 U/L, 95 % CI: -6.10, -3.47, I2 = 62 %, p < 0.00001), aspartate aminotransferase (AST) (WMD: -2.49 U/L, 95 % CI: -3.30, -1.68, I2 = 54 %, p < 0.00001), alkaline phosphatase (AP) (WMD: -1.13 U/L, 95 % CI: -2.03, -0.22, I2 = 23 %, p = 0.02), and gamma-glutamyl transferase (GGT) (WMD: -7.77 U/L, 95 % CI: -9.33, -6.21, I2 = 5 %, p < 0.00001). Additionally, SGLT2 inhibitors showed a significant increase in bilirubin levels (WMD: 0.64 U/L, 95 % CI: 0.27, 1.00, I2 = 53 %, p < 0.0006. Finally, no significant changes were found on albumin levels (WMD: 0.13 U/L, 95 % CI: -0.06, 0.32, I2 = 53 %, p < 0.0006) after SGLT2 inhibitors treatment. In conclusion, our results suggest that treatment with SGLT2 inhibitors exerts a beneficial effect on liver function tests through decreased ALT, AST, AP, and GGT concentrations.

The Fat-to-Lean Mass Ratio Is Associated with Hyperinsulinemia in Healthy Mexican Adolescents.

Objective: To evaluate whether the Fat-to-Lean Mass (FyM) ratio is associated to hyperinsulinemia in healthy adolescents.Methods: Apparently healthy adolescents aged 10 to 15 years that according to sex, age, and percentiles of body fat percent, were included and allocated into the groups with elevated (body fat percent ≥85 percentile) and normal total body fat (body fat percent <85 percentile). The FyM ratio was calculated as total lean mass (kg)/total body fat (kg) and hyperinsulinemia was defined by fasting insulin levels ≥20 µUI/mL.Results: A total of 1,299 adolescents, 665 (51.9%) girls and 634 (48.1%) boys, were enrolled and allocated into the groups with high (n = 439) and normal (n = 860) body fat. The FyM index remained significantly associated with hyperinsulinemia (OR 5.58; 95%CI: 1.54-28.10) after logistic regression analysis adjusted by sex, age, body-weight, body mass index, and waist circumference.Conclusion: The FyM index is highly associated to the presence of hyperinsulinemia in adolescents, emerging as a useful tool from anthropometric measurements for identify insulin abnormalities.

Impact of glucagon-like peptide-1 receptor agonists on adiponectin concentrations: A meta-analysis of randomized controlled trials.

AIMS: Previous studies have reported an elevation in adiponectin concentrations using glucagon-like peptide-1 receptor agonists (GLP-1 RA) therapy; however, this possible pleiotropic effect is still uncertain. Thus, the objective of this meta-analysis of randomized controlled trials was to assess the impact of GLP-1 RA on adiponectin levels. METHODS: This systematic review and meta-analysis included randomized controlled trials investigating the effect of GLP-1 RA on circulating adiponectin concentrations. Studies from PubMed, Web of Science, Scopus, and Google Scholar databases were included. A random-effects model and a sensitivity analysis using the leave 1-out method were conducted. RESULTS: A meta-analysis of 20 randomized controlled trials involving 1497 individuals demonstrated a significant increase in adiponectin levels after GLP-1 RA administration (weighted mean difference [WMD]: 0.59 µg/mL, 95% confidence interval [CI]: 0.10, 1.08, P = .02). Particularly, liraglutide had a significant effect on adiponectin (WMD: 0.55 µg/mL, 95% CI: 0.04, 1.06, P = .04), while exenatide did not affect these concentrations (WMD: 0.60 µg/mL, 95% CI: -0.23, 1.42, P = .16). CONCLUSION: GLP-1 RA treatment is associated with an increase in adiponectin levels.

Effect of hydroxychloroquine on glucose control in patients with and without diabetes: a systematic review and meta-analysis of randomized controlled clinical trials.

PURPOSE: The aim of this meta-analysis of randomized controlled trials was to evaluate the effect of hydroxychloroquine on glucose control. METHODS: Randomized controlled trials examining the impact of hydroxychloroquine on glycemic markers were searched in PubMed, Web of Science, Scopus, and Google Scholar databases. Meta-analysis was performed using a random-effects model and sensitivity analysis through the leave-one-out method. RESULTS: Meta-analysis revealed a significant reduction of fasting glucose (WMD: - 8.05 mg/dl; 95% CI: - 11.17, - 4.93; I2 = 75%; p ˂0.0001), 2-h postprandial glucose (WMD: - 15.52 mg/dl; 95% CI: - 20.61, - 10.42; I2 = 53%; p ˂0.00001), and glycated hemoglobin (HbA1c) values (WMD: - 0.19%, 95% CI: - 0.37, - 0.02; I2 = 94%; p = 0.03) after hydroxychloroquine treatment. Otherwise, meta-analysis showed no significant effect of hydroxychloroquine on insulin levels (WMD: 16.52 µUI/ml; 95% CI: - 16.35, 49.40; I2 = 90%; p = 0.32) and HOMA-ß (WMD: - 14.62; 95% CI: - 45.84, 16.59; I2 = 0%; p = 0.36). CONCLUSION: The present meta-analysis revealed that treatment with hydroxychloroquine improves glucose control through the reduction of fasting glucose, 2-h postprandial glucose, and HbA1c values. Given that the effect of hydroxychloroquine on beta-cell function is based only on two clinical trials, it is not possible to draw definitive conclusions.

The triglycerides and glucose index is strongly associated with hepatic steatosis in children with overweight or obesity.

Given the worldwide increase prevalence of overweight, obesity, and nonalcoholic fatty liver disease (NAFLD), the objective of this study was to evaluate whether the triglycerides and glucose (TyG) index is associated with hepatic steatosis in children with overweight or obesity. Apparently healthy children aged 5­17 years were included and allocated into the groups with and without hepatic steatosis. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Hepatic steatosis was diagnosed by ultrasonography. A total of 177 children, 66 (37.3%) girls and 111 (62.7%) boys, were included in the study. According to the hepatic ultrasonography, they were allocated into the groups with (n = 100) and without (n = 77) hepatic steatosis. The adjusted analysis by gender, body mass index, and waist circumference revealed that HDL-C (OR 0.96; 95% CI: 0.93-0.99), triglycerides (OR 1.005; 95% CI: 1.001-1.009), AST (OR 1.03; 95% CI: 1.008-1.07), ALT (OR 1.03; 95% CI: 1.01-1.05), and TyG index (OR 4.07; 95% CI: 1.26-13.15) remained associated with hepatic steatosis.Conclusion: Compared to other biochemical markers, the TyG index is highly associated with the presence of fatty liver in children with overweight and obesity. What is known: • The triglycerides and glucose (TyG) index is effective in predicting high risk for incident nonalcoholic fatty liver disease (NAFLD) in adults. What is new: • Compared to other biochemical markers, the TyG index is highly associated with the presence of fatty liver in children with overweight or obesity. • The triglycerides and glucose index may be a useful tool to detect children at high risk of fatty liver.

The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. OBJECTIVE: The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. METHODS: PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used to assess the presence of publication bias. RESULTS: Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p < 0.001; I 2: 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p = 0.206; I 2: 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p = 0.004; I 2: 0%). CONCLUSION: High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations.

Antidiabetic Properties of Curcumin: Insights on New Mechanisms.

Plant extracts have been used to treat a wide range of human diseases. Curcumin, a bioactive polyphenol derived from Curcuma longa L., exhibits therapeutic effects against diabetes while only negligible adverse effects have been observed. Antioxidant and anti-inflammatory properties of curcumin are the main and well-recognized pharmacological effects that might explain its antidiabetic effects. Additionally, curcumin may regulate novel signaling molecules and enzymes involved in the pathophysiology of diabetes, including glucagon-like peptide-1, dipeptidyl peptidase-4, glucose transporters, alpha-glycosidase, alpha-amylase, and peroxisome proliferator-activated receptor gamma (PPARγ). Recent findings from in vitro and in vivo studies on novel signaling pathways involved in the potential beneficial effects of curcumin for the treatment of diabetes are discussed in this review.

Protective Effects of Curcumin Phytosomes Against High-Fat Diet-Induced Atherosclerosis.

Curcumin has been shown to have beneficial effects on pathogenic factors involved in the development of atherosclerosis. The aim of this study was to assess the effects of curcumin phytosomes on atherosclerosis induced by high-fat diet in rabbits. A total of 16 adult male New Zealand white rabbits (1.8-2 kg) were fed with a diet containing 0.5% cholesterol for 4 weeks. The rabbits were randomly divided into four groups of four animals each. Group I orally received PBS for 4 weeks. Group II animals were treated with curcumin-phosphatidylcholine solid state dispersion (Meriva®, Indena, Italy) suspended in normal saline at doses equivalent to 100 mg/kg of curcuminoids per day p.o., for 4 weeks. Groups III and IV were treated with curcumin-phosphatidylserine solid state dispersion (Meriserin®, Indena, Italy) suspended in normal saline at doses equivalent to 10 and 100 mg/kg of curcuminoids, respectively, per day p.o., for 4 weeks. For atherosclerosis evaluation, histological examinations on aortic arch section were performed. Blood samples were obtained to determine lipid profile and high-sensitivity C-reactive protein (hs-CRP) levels. Curcumin-phosphatidylserine (100 mg/kg) therapy resulted in a significant reduction in grading of atherosclerotic plaque and intima/media thickness ratio (P < 0.05) and decreased presence of inflammatory cells in the atherosclerotic lesions compared to the control group. However, no significant differences were observed between the curcumin-phospholipid preparations and the control group regarding lipid profile and hs-CRP levels. Results of the present study revealed an atheroprotective effect of curcumin-phosphatidylserine (100 mg/kg) solid dispersion as revealed by a reduction in the development of atherosclerotic lesions.

Therapeutic Effect of Curcumin in Women with Polycystic Ovary Syndrome Receiving Metformin: A Randomized Controlled Trial.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, for which the insulin sensitizer metformin has been used therapeutically. It has been shown that curcumin also exhibits insulin-sensitizing properties. Given that metformin acts as an ovulation inducing agent and both curcumin and metformin can reduce insulin resistance, the aim of the current study was to evaluate the effect of metformin with and without curcumin nanomicelles in the treatment of women with polycystic ovary syndrome. This clinical trial was conducted on 100 women with PCOS, diagnosed according to the Rotterdam criteria, who were sequentially recruited and randomly divided into two groups (n = 50 each). Group 1 received 500 mg metformin three times daily and group 2 received 80 mg/day capsule of curcumin nanomicelle and 500 mg metformin three times a day for 3 months. After collecting fasting blood samples, biochemical parameters including triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, plasma glucose, alanine amino transferase (ALT) and aspartate aminotransferase (AST) were evaluated based on enzymatic methods. Hormonal parameters were assessed using immunoassay kits. Insulin resistance (HOMA-IR) and insulin-sensitivity check index (QUICKI) were also assessed. After treatment, fasting insulin, HOMA-IR, and total testosterone in group 2 were significantly lower than those in group 1 (p < 0.05). Post-treatment LDL-C levels in groups 1 and 2 were 117.9 ± 24 and 91.12 ± 19.46 mg/dL, respectively (p < 0.01). In addition, HDL-C levels were increased with curcumin (group 1: 38.1 ± 4.36 mg/dL; group 2: 44.12 ± 7.3 mg/dL, p < 0.05). Total cholesterol was decreased with curcumin level (group 1: 207.9 ± 39.84 mg/dL; group 2; 159.7 ± 48.43 mg/dL, p < 0.05), with a decrease in triglycerides levels (group 1: 141.6 ± 9.57; group 2: 97.5 ± 8.8 mg/dL, p < 0.01). This study showed that curcumin has a synergistic effect with metformin in the improvement of insulin resistance and lipid profile in patients with PCOS. Therefore, the combined use of metformin and curcumin may have therapeutic utility in patients with PCOS.

Beneficial Effects of Plant-Derived Natural Products on Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease is becoming in one of the most prevalent liver diseases that leads to liver transplantation. This health problem is a multisystem disease with a complex pathogenesis that involves liver, adipose tissue, gut, and muscle. Although several pharmacological agents have been investigated to prevent or treat non-alcoholic fatty liver disease, currently there is no effective treatment for the management of this chronic liver disease. Nonetheless, the use of natural products has emerged as a alternative therapeutic for the treatment of hepatic diseases, including non-alcoholic fatty liver disease, due to its anti-inflammatory, antioxidant, antidiabetic, insulin-sensitizing, antiobesity, hypolipidemic, and hepatoprotective properties. In the present review, we have discussed the evidence from experimental and clinical studies regarding the potential beneficial effects of plant-derived natural products (quercetin, resveratrol, berberine, pomegranate, curcumin, cinnamon, green tea, coffee, garlic, ginger, ginseng, and gingko biloba) for the treatment or prevention of non-alcoholic fatty liver disease.

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.

Zinc deficiency is an independent risk factor for prehypertension in healthy subjects.

Objective: To assess whether zinc deficiency is associated with prehypertension (preHTN) in apparently healthy subjects. Design: Apparently healthy women and men, aged 20 to 60 years were enrolled into a case-control study. Individuals with and without preHTN were allocated into the case and control groups, respectively. Hypertension, liver disease, renal disease, smoking, pregnancy, diabetes, malignancy, hypernatremia, hypomagnesemia, medical treatment, and use of supplements containing zinc were exclusion criteria. PreHTN was defined by systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) of 120-139 mmHg and/or of 80-89 mmHg, respectively, and the zinc deficiency by serum zinc levels < 74 µg/dL in men and < 70 µg/dL in women. Results: In total, 142 subjects (90 women and 52 men) were enrolled and allocated in the case (n = 71) and control (n = 71) groups. In the overall population, the frequency of zinc deficiency was 11.1%; individuals in the case group showed significant higher frequency of zinc deficiency as compared with the control group (16.9% vs 5.5%, p = 0.04). The logistic regression analysis showed a significant association between zinc deficiency and preHTN (OR = 4.61; 95% CI: 1.24-17.12, p = 0.02). Conclusion: Our results suggest that zinc deficiency is associated with the presence of preHTN in apparently healthy subjects.