Estifanos Baye

Physiological and therapeutic effects of carnosine on cardiometabolic risk and disease.

Obesity, type 2 diabetes (T2DM) and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. They represent major public health threat to our society. Increasing prevalence of obesity and T2DM contributes to escalating morbidity and mortality from CVD and stroke. Carnosine (β-alanyl-l-histidine) is a dipeptide with anti-inflammatory, antioxidant, anti-glycation, anti-ischaemic and chelating roles and is available as an over-the-counter food supplement. Animal evidence suggests that carnosine may offer many promising therapeutic benefits for multiple chronic diseases due to these properties. Carnosine, traditionally used in exercise physiology to increase exercise performance, has potential preventative and therapeutic benefits in obesity, insulin resistance, T2DM and diabetic microvascular and macrovascular complications (CVD and stroke) as well as number of neurological and mental health conditions. However, relatively little evidence is available in humans. Thus, future studies should focus on well-designed clinical trials to confirm or refute a potential role of carnosine in the prevention and treatment of chronic diseases in humans, in addition to advancing knowledge from the basic science and animal studies.

Carnosine and the processes of ageing

The causes of ageing are usually regarded as multifactorial; thus effective regulation might be achieved by intervention at multiple sites. It has been suggested that the endogenous dipeptide carnosine, also available as a food supplement, possesses anti-ageing activity and may achieve its reported age-alleviating effects via a number of mechanisms. Carnosines possible anti-ageing mechanisms are therefore discussed; the evidence suggests that inhibition of the mechanistic target of rapamycin and carbonyl scavenging may be involved.

Consumption of diets with low advanced glycation end products improves cardiometabolic parameters: meta-analysis of randomised controlled trials

Studies examining the effects of consumption of diets low in advanced glycation end products (AGEs) on cardiometabolic parameters are conflicting. Hence, we performed a meta-analysis to determine the effect of low AGE diets in reducing cardiometabolic risk factors. Seventeen randomised controlled trials comprising 560 participants were included. Meta-analyses using random effects models were used to analyse the data. Low AGE diets decreased insulin resistance (mean difference [MD] −1.3, 95% CI −2.3, −0.2), total cholesterol (MD −8.5 mg/dl, 95% CI −9.5, −7.4) and low-density lipoprotein (MD −2.4 mg/dl, 95% CI −3.4, −1.3). There were no changes in weight, fasting glucose, 2-h glucose and insulin, haemoglobin A1c, high-density lipoprotein or blood pressure. In a subgroup of patients with type 2 diabetes, a decrease in fasting insulin (MD −7 µU/ml, 95% CI −11.5, −2.5) was observed. Tumour necrosis factor α, vascular cell adhesion molecule-1, 8-isoprostane, leptin, circulating AGEs and receptor for AGEs were reduced after consumption of low AGE diets with increased adiponectin and sirtuin-1. Our findings suggest that diets low in AGEs may be an effective strategy for improving cardiometabolic profiles in individuals with and without type 2 diabetes.

Treatment with high dose salicylates improves cardiometabolic parameters: Meta-analysis of randomized controlled trials

INTRODUCTION There is conflicting evidence regarding the efficacy of high dose salicylates in improving cardiometabolic risk in healthy and type 2 diabetes patients. We aimed to determine whether treatment with salicylates at an anti-inflammatory dose (≥1g daily) would improve cardiometabolic risk in healthy individuals and type 2 diabetes patients, compared to placebo. METHODS Medline, Medline-in-process, Embase, and all EBM databases were searched for studies published up to December 2016. Twenty-eight articles from 24 studies comprising 1591 participants were included. Two reviewers independently assessed the risk of bias and extracted data from included studies. Meta-analyses using random-effects model were used to analyze the data. RESULTS High dose salicylates (≥3g/d) decreased fasting glucose (MD -0.4mmol/l, 95% CI -0.54, -0.27) and glucose area under the curve (MD -0.41mmol/l, 95% CI -0.81, -0.01). Salicylates (≥3g/d) also increased fasting insulin (MD 2.4 μU/ml, 95% CI 0.3, 4.4), 2-h insulin (MD 25.4 μU/ml, 95% CI 8.2, 42.6), insulin secretion (MD 79.2, 95% CI 35, 123) but decreased fasting C-peptide (MD -0.11nmol/l, 95% CI -0.2, -0.04), insulin clearance (MD -0.26l/min, 95% CI -0.36, -0.16) and triglycerides (MD -0.36mmol/l, 95% CI -0.51, -0.21) and increased total adiponectin (MD 1.97μg/ml, 95% CI 0.99, 2.95). A lower salicylate dose (1-2.9g) did not change any cardiometabolic parameters (p>0.1). No significant difference was observed between those receiving salicylates and placebo following withdrawal due to adverse events. CONCLUSIONS High dose salicylates appear to improve cardiometabolic risk factors in healthy individuals and type 2 diabetes patients. PROSPERO REGISTRATION NUMBER CRD42015029826.

Does supplementation with carnosine improve cardiometabolic health and cognitive function in patients with pre-diabetes and type 2 diabetes? study protocol for a randomised, double-blind, placebo-controlled trial

Introduction Carnosine, an over-the-counter food supplement, has a promising potential for the prevention and treatment of chronic diseases such as type 2 diabetes (T2DM), cardiovascular and neurodegenerative diseases through its anti-inflammatory, antiglycation, antioxidative and chelating effects. We have previously shown that supplementation with carnosine preserves insulin sensitivity and secretion in non-diabetic overweight and obese individuals. The effect of carnosine on cardiometabolic risk and related cognitive outcomes in patients with pre-diabetes and T2DM has thus far not been studied. We therefore aim to investigate whether supplementation with carnosine improves cardiometabolic health and cognitive function in patients with pre-diabetes and T2DM. Methods and analysis We will employ a parallel design randomised controlled trial. Fifty participants with pre-diabetes (impaired fasting glycaemia and impaired glucose tolerance) and T2DM (with HbA1c level < 8%) aged between 18 to 70 years will be randomly assigned to the intervention or control group. At baseline, participants will undergo a medical review and series of tests including anthropometric measurements (body mass index, a dual X-ray absorptiometry and peripheral quantitative computed tomography scan), an oral glucose tolerance test, cardiovascular measurements (central blood pressure, endothelial function and arterial stiffness), cognitive function, physical activity measurement, heart rate variability and liver fibroscan as well as questionnaires to assess dietary habits, sleep quality, depression and quality of life. The intervention group will receive 2 g of carnosine daily in two divided doses while the control group will receive identical placebo capsules for 14 weeks. All baseline measurements will be repeated at the end of the intervention. The change in glycaemic, cardiovascular and cognitive parameters as well as other measures will be compared between the groups. Ethics and dissemination This study is approved by the Human Research Ethics Committee of Monash Health and Monash University, Australia. The findings will be disseminated via peer-reviewed publications and conference presentations. Trial registration NCT02917928; Pre-results.

Carnosine Supplementation Improves Serum Resistin Concentrations in Overweight or Obese Otherwise Healthy Adults: A Pilot Randomized Trial

Adipokines play an important role in the regulation of glucose metabolism. We have previously shown that carnosine supplementation in overweight or obese non-diabetic individuals improves glucose metabolism but does not change adiponectin concentrations. However, its effect on other adipokines has not been investigated. Herein we further determined the effect of carnosine supplementation on serum adipsin, resistin and leptin. Twenty-two overweight or obese otherwise healthy adults were randomly assigned to receive either 2 g of carnosine (n = 13) or identically looking placebo (n = 9) for 12 weeks. Serum adipsin, leptin and resistin were analyzed using a bead-based multiplex assay. Carnosine supplementation decreased serum resistin concentrations compared to placebo (mean change from baseline: −35 ± 83 carnosine vs. 35 ± 55 ng/mL placebo, p = 0.04). There was a trend for a reduction in serum leptin concentrations after carnosine supplementation (−76 ± 165 ng/mL carnosine vs. 20 ± 28 ng/mL placebo, p = 0.06). The changes in leptin and resistin concentrations were inversely related to the change in concentration for urinary carnosine (r = −0.72, p = 0.0002; r = −0.67, p = 0.0009, respectively), carnosine-propanal (r = −0.56, p = 0.005; r = −0.63, p = 0.001, respectively) and carnosine-propanol (r = −0.61, p = 0.002; r = −0.60, p = 0.002, respectively). There were no differences between groups in change in adipsin concentrations. Our findings show carnosine supplementation may normalize some, but not all, of the serum adipokine concentrations involved in glucose metabolism, in overweight and obese individuals. Further clinical trials with larger samples are needed to confirm these results.