BCAAs acutely drive glucose dysregulation and insulin resistance: role of AgRP neurons.

BACKGROUND: High-protein diets are often enriched with branched-chain amino acids (BCAAs) known to enhance protein synthesis and provide numerous physiological benefits, but recent studies reveal their association with obesity and diabetes. In support of this, protein or BCAA supplementation is shown to disrupt glucose metabolism while restriction improves it. However, it is not clear if these are primary, direct effects of BCAAs or secondary to other physiological changes during chronic manipulation of dietary BCAAs. METHODS: Three-month-old C57Bl/6 mice were acutely treated with either vehicle/BCAAs or BT2, a BCAA-lowering compound, and detailed in vivo metabolic phenotyping, including frequent sampling and pancreatic clamps, were conducted. RESULTS: Using a catheter-guided frequent sampling method in mice, here we show that a single infusion of BCAAs was sufficient to acutely elevate blood glucose and plasma insulin. While pre-treatment with BCAAs did not affect glucose tolerance, a constant infusion of BCAAs during hyperinsulinemic-euglycemic clamps impaired whole-body insulin sensitivity. Similarly, a single injection of BT2 was sufficient to prevent BCAA rise during fasting and markedly improve glucose tolerance in high-fat-fed mice, suggesting that abnormal glycemic control in obesity may be causally linked to high circulating BCAAs. We further show that chemogenetic over-activation of AgRP neurons in the hypothalamus, as present in obesity, significantly impairs glucose tolerance that is completely normalized by acute BCAA reduction. Interestingly, most of these effects were demonstrated only in male, but not in female mice. CONCLUSION: These findings suggest that BCAAs per se can acutely impair glucose homeostasis and insulin sensitivity, thus offering an explanation for how they may disrupt glucose metabolism in the long-term as observed in obesity and diabetes. Our findings also reveal that AgRP neuronal regulation of blood glucose is mediated through BCAAs, further elucidating a novel mechanism by which brain controls glucose homeostasis.

Effects of quercetin supplementation on endothelial dysfunction biomarkers and depression in post-myocardial infarction patients: A double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Endothelial dysfunction and depression are highly prevalent in patients who have experienced a myocardial infarction (MI). Epidemiological studies have pointed out that a diet rich in flavonoids, e.g., quercetin, can prevent the development of these biological phenomena. Therefore, we aimed to investigate the effects of quercetin supplementation on the levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and on depression in post-MI subjects. METHODS: Eighty-eight post-MI patients who had experienced their first MI (body mass index ≤35 kg/m2, age 30-65 years) were recruited from the Rasool-e-Akram and Afshar Hospitals, Iran, and included in this randomized, placebo-controlled, double-blind parallel study. The participants were randomly assigned to receive a daily dose of 500 mg quercetin (n = 44) or placebo (n = 44) for 8 weeks. Serum concentrations of ICAM-1 and VCAM-1 were quantified by ELISA and depression levels were assessed using the Beck's Depression Inventory (BDI-II) questionnaire at baseline and at 8-week follow-up. RESULTS: Seventy-six participants completed the study, but the intention-to-treat (ITT) analysis was conducted for all 88 participants who were randomized into the intervention groups. No significant changes in serum concentrations of ICAM-1 or VCAM-1 (P = 0.21 and P = 0.80, respectively) were observed after 8 weeks of quercetin supplementation versus placebo. In addition, depression levels did not differ significantly between the quercetin and placebo groups. CONCLUSION: Our findings demonstrated that in post-MI patients, daily supplementation with quercetin (500 mg/day) for 8 weeks did not affect endothelial dysfunction biomarkers and depression levels. This trial was registered at IRCT.ir as IRCT20190428043405N1.

Oxidative balance score and dietary phytochemical index can reduce the risk of colorectal cancer in Iranian population.

BACKGROUND: No previous study has assessed the association between oxidative balance score (OBS) and dietary phytochemical index (DPI) with colorectal cancer (CRC) simultaneously. Therefore, this study investigated the association between OBS and DPI with the odds of CRC among the Iranian population. METHODS: This hospital-based age and sex-matched case-control study was conducted between September 2008 and January 2010 (142 controls and 71 cases were entered for analysis). New diagnosed CRC cases were selected from the Cancer Institute, Imam Khomeini Hospital of Tehran. Dietary intakes were determined by a semi-quantitative food frequency questionnaire (FFQ). Then, dietary indices were calculated by food items and nutrient intake. Logistic regression was utilized for assessing the tertiles of OBS and DPI. RESULTS: In multivariate analysis, OBS was associated with a 77% reduction in CRC odds in the last tertile than the first tertile (odds ratio (OR) = 0.23, confidence interval (CI): 0.07-0.72, Ptrend = 0.017). Also, we found a 64% reduction in CRC odds in the last tertile of DPI compared to the first tertile (OR = 0.36, CI: 0.15-0.86, Ptrend = 0.015). CONCLUSIONS: A diet rich in phytochemicals and anti-oxidants, including fruits and vegetables (citrus fruits, colored berries, and dark-green leafy vegetables) and whole grains, may reduce the CRC odds.

Effects of probiotic/synbiotic supplementation on body weight in patients with diabetes: a systematic review and meta-analyses of randomized-controlled trials.

OBJECTIVE: The aim of the present study was to assess the effect of probiotic/synbiotic supplementation on anthropometric measures in adults with diabetes, independent of body weight. METHODS: PubMed, Scopus, Web of Sciences and the Cochrane Library were searched for randomized controlled trials (RCTs) up until December 14, 2022. The effect sizes were pooled using an inverse-variance random-effects model. The methodological quality of studies as well as the quality of evidence was assessed using standard tools. RESULTS: Thirty-two RCTs met the established inclusion criteria. Overall, compared with the respective control groups, probiotic/synbiotic supplementation resulted in a significant reduction in body weight (weighted mean difference [WMD]: -0.50 kg; 95% CI: -0.83, -0.17; I2 = 79.8%, n = 27 studies]), body mass index (WMD: -0.24 kg/m2; 95% CI: -0.39, -0.09; I2 = 85.7%, n = 30 studies), and waist circumference (WMD: -0.90 cm; 95% CI: -1.13, -0.52; I2 = 0%, n = 11 studies). However, hip circumference and waist to hip ratio were not significantly improved. CONCLUSIONS: Our analysis revealed that probiotic/synbiotic supplementation may assist with weight management in patients with diabetes, especially when consumed at higher doses, in younger adults, and in participants with obesity. However, more studies are needed to elucidate the anti-obesity effects of specific strains of probiotics/synbiotics.

Revisiting the Role of Vitamins and Minerals in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia that affects millions of individuals worldwide. It is an irreversible neurodegenerative disorder that is characterized by memory loss, impaired learning and thinking, and difficulty in performing regular daily activities. Despite nearly two decades of collective efforts to develop novel medications that can prevent or halt the disease progression, we remain faced with only a few options with limited effectiveness. There has been a recent growth of interest in the role of nutrition in brain health as we begin to gain a better understanding of what and how nutrients affect hormonal and neural actions that not only can lead to typical cardiovascular or metabolic diseases but also an array of neurological and psychiatric disorders. Vitamins and minerals, also known as micronutrients, are elements that are indispensable for functions including nutrient metabolism, immune surveillance, cell development, neurotransmission, and antioxidant and anti-inflammatory properties. In this review, we provide an overview on some of the most common vitamins and minerals and discuss what current studies have revealed on the link between these essential micronutrients and cognitive performance or AD.

Probiotics supplementation and brain-derived neurotrophic factor (BDNF): a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: An emerging body of evidence has demonstrated the beneficial effects of probiotics on various mental health conditions. In this systematic review and meta-analysis, we sought to examine the effects of probiotics supplementation on brain-derived neurotrophic factor (BDNF) in adults. METHODS: PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to April 2021, for eligible randomized controlled trials (RCTs). We pooled mean differences and standard deviations from RCTs using random-effect models. RESULTS: Overall, meta-analysis of 11 trials (n = 648 participants) showed no significant changes in serum level of BDNF following probiotics. However, subgroup analysis revealed that probiotics increased BDNF levels in individuals suffering from neurological disorders (n = 214 participants; WMD = 3.08 ng/mL, 95% CI: 1.83, 4.34; P = 0.001; I2 = 7.5%; P-heterogeneity 0.34), or depression (n = 268 participants; WMD = 0.77 ng/mL, 95% CI: 0.07, 1.47; P = 0.032; I2 = 88.4%; P-heterogeneity < 0.001). Furthermore, a significant increase in BDNF levels was found in studies that administered the mixture of Lactobacillus and Bifidobacterium genera, and were conducted in Asia . CONCLUSION: Our main findings suggest that probiotics may be effective in elevating BDNF levels in patients with depression and neurological disorders, and a mixed of Lactobacillus and Bifidobacterium appear to show greater efficacy than the single genus supplement. The low quality of evidence reduces clinical advocacy, and indicates that more large-scale, high-quality, RCTs are needed to facilitate reliable conclusions.

Effect of extra virgin olive oil consumption on glycemic control: A systematic review and meta-analysis.

AIMS: Several health benefits are contributed to extra virgin olive oil (EVOO). The polyphenol fraction of EVOO may be responsible for its cardioprotective impacts. This systematic review and meta-analysis aimed to investigate the effect of EVOO intake on glycemic parameters. Electronic literature searched through 1 September 2020 across MEDLINE/PubMed, Web of Science, and SCOPUS databases to find all clinical trials that reported the effect of EVOO intake on glycemic parameters [FBS(fasting blood glucose), insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and HbA1c (glycated hemoglobin A1c)] vs. control. DATA SYNTHESIS: We pooled standardized mean differences (SMD) and 95% confidence intervals (CIs) from randomized clinical trials (RCTs) using random-effects models. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). We found 13 related trials comprising a total of 633 subjects. In pooled analysis, EVOO intake had no effect on FBS (SMD: -0.07; 95% CI: -0.20, 0.07; I2 = 0.0%), insulin (SMD: -0.32; 95% CI: -0.70, 0.06; I2 = 38.0%), and HOMA-IR (SMD: -0.32; 95% CI: -0.75, 0.10; I2 = 51.0%). However, a decreasing trend was observed in these effects. Subgroup analysis based on age, health status, dose, and EVOO intake duration also did not significantly change results. CONCLUSION: Although EVOO seems a promising hypoglycemic effects, we did not find any significant evidence that EVOO consumption impacts glucose homeostasis. Furthermore, well-designed RCTs with longer durations are still needed to evaluate the EVOO's efficacy on glycemic parameters.

Effects of quercetin supplementation on inflammatory factors and quality of life in post-myocardial infarction patients: A double blind, placebo-controlled, randomized clinical trial.

Myocardial infarction (MI) is one of the leading causes of death in the world. Epidemiological studies have shown that dietary flavonoids are inversely related to cardiovascular morbidity and mortality. The study aimed to determine whether quercetin supplementation can improve inflammatory factors, total antioxidant capacity (TAC) and quality of life (QOL) in patients following MI. This randomized double-blind, placebo-controlled trial was conducted on 88 post-MI patients. Participants were randomly assigned into quercetin (n = 44) and placebo groups (n = 44) receiving 500 mg/day quercetin or placebo tablets for 8 weeks. Quercetin supplementation significantly increased serum TAC compared to placebo (Difference: 0.24 (0.01) mmol/L and 0.00 (0.00) mmol/L respectively; p < .001). TNF-α levels significantly decreased in the quercetin group (p = .009); this was not, however, significant compared to the placebo group. As for QOL dimensions, quercetin significantly lowered the scores of insecurity (Difference: -0.66 (12.5) and 0.00 (5.55) respectively; p < .001). No significant changes in IL-6, hs-CRP, blood pressure and other QOL dimensions were observed between the two groups. Quercetin supplementation (500 mg/day) in post-MI patients for 8 weeks significantly elevated TAC and improved the insecurity dimension of QOL, but failed to show any significant effect on inflammatory factors, blood pressure and other QOL dimensions.

Effect of soy products and isoflavones on oxidative stress parameters: A systematic review and meta-analysis of randomized controlled trials.

Soy products and isoflavones intake have been shown to exert antioxidant effects. There are several randomized control trials (RCTs) that evaluated the effect of soy products intake on oxidative stress (OS) parameters. The aim of the present systematic review and meta-analysis was to summarize the results of RCTs evaluating the effect of soy products and isoflavones intake on OS parameters. Randomized trials that assessed the effect of soy products and isoflavones intake on OS parameters in adults were identified through searching in electronic databases: Cochrane clinical trial center, Embase, PubMed, Scopus, and Web of Sciences up to April 2020. Random effects model was used to calculate the effects sizes of soy intake on OS parameters. Twenty-four trials with 1,852 participants were eligible and were included in the meta-analysis which measured OS parameters. Soy intake compared to control group significantly reduced MDA levels (SMD: -0.53; 95% CI: -0.86, -0.19; I2 = 88.3%), increased GSH levels (SMD: 0.51; 95% CI: 0.13, 0.88; I2 = 72.4%), SOD activity (SMD: 0.53; 95% CI: 0.08, 0.99; I2 = 84.1%), TAC (SMD: 0.54; 95% CI: 0.27, 0.82; I2 = 49.3%) and TRAP (SMD: 1.74; 95% CI: 0.82, 2.65; I2 = 81.3%) significantly compared to control group. Soy products and isoflavones intake are effective in improving OS parameters in adults compared with controls; thus, it could be a valuable advise to control OS progress in chronic diseases.

The Association between Maternal Dietary Protein Intake and Risk of Gestational Diabetes Mellitus.

BACKGROUND: The amount and type of dietary protein affect glucose metabolism. However, the association between dietary protein intake and gestational diabetes mellitus (GDM) risk is vague. We examined this association. Methods: We included 152 GDM and 168 non-GDM participants (total 320), age 18-45 years from Arash Women's Hospital, Tehran, Iran. Protein intake was ascertained from 168-item Food Frequency Questionnaire at 24-40 weeks' gestation. GDM was defined as fasting blood sugar >95 mg/dL and/or oral glucose tolerance test >155 mg/dL. Dietary data were assessed using N4 software and statistical analysis was performed using SPSS 21. We tested the association between the amount of protein consumed from red and processed meat, poultry, dairy, egg, seafood, and vegetable plus sociodemographic and lifestyle covariates and GDM risk using multivariate logistic regression analysis. RESULTS: There was a significant association between the physical activity (P < 0.035), socioeconomic status (P < 0.013), body mass index, age, and each trimester's weight (P < 0.001), and risk of GDM. No significant association was observed between the intake of protein from major protein sources and risk of GDM. The only significant association was observed for egg consumption which was lower in GDM participants (P = 0.004), yet this association turned nonsignificant after adjustment for confounders, except for the fourth quartile (odds ratio: 0.43, 95% confidence interval: 0.208, 0.893). CONCLUSIONS: According to our findings, dietary intake of total and major protein sources could not affect the GDM risk. Differences between Iranian and Western population and the reverse causality might be the main reasons for this nonsignificant association.