Enhancement of subunit vaccine delivery with zinc-carnosine coordination polymer through the addition of mannan.

Vaccines represent a pivotal health advancement for preventing infection. However, because carrier systems with repeated administration can invoke carrier-targeted immune responses that diminish subsequent immune responses (e.g., PEG antibodies), there is a continual need to develop novel vaccine platforms. Zinc carnosine microparticles (ZnCar MPs), which are composed of a one-dimensional coordination polymer formed between carnosine and the metal ion zinc, have exhibited efficacy in inducing an immune response against influenza. However, ZnCar MPs' limited suspendability hinders clinical application. In this study, we address this issue by mixing mannan, a polysaccharide derived from yeast, with ZnCar MPs. We show that the addition of mannan increases the suspendability of this promising vaccine formulation. Additionally, since mannan is an adjuvant, we illustrate that the addition of mannan increases the antibody response and T cell response when mixed with ZnCar MPs. Mice vaccinated with mannan + OVA/ZnCar MPs had elevated serum IgG and IgG1 levels in comparison to vaccination without mannan. Moreover, in the mannan + OVA/ZnCar MPs vaccinated group, mucosal washes demonstrated increased IgG, IgG1, and IgG2c titers, and antigen recall assays showed enhanced IFN-γ production in response to MHC-I and MHC-II immunodominant peptide restimulation, compared to the vaccination without mannan. These findings suggest that the use of mannan mixed with ZnCar MPs holds potential for subunit vaccination and its improved suspendability further promotes clinical translation.

The Cost-Effectiveness of Supplemental Carnosine in Type 2 Diabetes.

In this paper, we assess the cost-effectiveness of 1 g daily of carnosine (an over the counter supplement) in addition to standard care for the management of type 2 diabetes and compare it to standard care alone. Dynamic multistate life table models were constructed in order to estimate both clinical outcomes and costs of Australians aged 18 years and above with and without type 2 diabetes over a ten-year period, 2020 to 2029. The dynamic nature of the model allowed for population change over time (migration and deaths) and accounted for the development of new cases of diabetes. The three health states were 'Alive without type 2 diabetes', 'Alive with type 2 diabetes' and 'Dead'. Transition probabilities, costs, and utilities were obtained from published sources. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. Over the ten-year period, the addition of carnosine to standard care treatment resulted in ICERs (discounted) of AUD 34,836 per YoLS and AUD 43,270 per QALY gained. Assuming the commonly accepted willingness to pay threshold of AUD 50,000 per QALY gained, supplemental dietary carnosine may be a cost-effective treatment option for people with type 2 diabetes in Australia.

PHoral: Effects of carnosine supplementation on quantity/quality of oral salivae in healthy volunteer and in subjects affected by common oral pathologies.

BACKGROUND: Diseases of the oral cavity (OC) with an infectious trigger such as caries and periodontal disease are extremely common in the general population and can also have effects at the cardiovascular level. The oral salivary flow, with its buffering capacity, is able to regulate the pH of the OC and, therefore, significantly contribute to the ecological balance of the microenvironment in which the oral microbiome (OM) develops. On the other side, when the quality/quantity of salivary flow is altered it is supposed the disruption of this balance with the potential increase in oral pathogens and triggered diseases. Among the endogenous substances able to exert a significant effect on the salivary flow and its characteristics, carnosine (Car), a dipeptide originally isolated in skeletal muscle, represents, thanks to the known buffering properties, a promising principle. METHODS: We aimed this protocol to evaluate the quantitative/qualitative characteristics of the salivary flow in healthy volunteer subjects (n = 20) and in subjects suffering from common OC pathologies (n = 40), before and after 7 days of supplementation with SaliflussTM (Metis Healthcare srl, Milan, Italy), a Class I medical device on the market as 400 mg mucoadhesive oral tablets that has Car as the main ingredient. DISCUSSION: Combining the characteristics of saliva with the OM and comparing them with OC pathologies, we expect to clarify their reciprocal relationship and, using quantitative proteomics techniques, to help clarify the mechanism of action of Car.

Effect of Oral carnosine supplementation on urinary TGF-ß in diabetic nephropathy: a randomized controlled trial.

BACKGROUND: Activation of the transforming growth factor beta (TGF-ß) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is a dipeptide that can inhibit TGF-ß synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-ß levels among patients with diabetic nephropathy. METHODS: We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30-299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-ß level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-ß. RESULTS: The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-ß and renal function measurements. Urinary TGF-ß significantly decreased with carnosine supplement (- 17.8% of the baseline values), whereas it tended to increase with placebo (+ 16.9% of the baseline values) (between-group difference P < 0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects. CONCLUSIONS: These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-ß level that serves as a marker of renal injury in diabetic nephropathy. TRIAL REGISTRATION: Thai Clinical Trials, TCTR20200724002 . Retrospectively Registered 24 July 2020.

Effects of Carnosine, Ankaferd, and Silver Sulfadiazine on an Experimental Burn Model: Roles of Irisin and HSP70.

In this study, the effects of carnosine, ankaferd, and 1% silver sulfadiazine applied topically on second-degree burns were investigated and the roles of irisin and Heat shock protein 70 (HSP70) in this healing process were evaluated. Ninety male albino rats were used and divided into five groups. The groups were classified as control, burn, burn + carnosine (CAR), burn + ankaferd (ABS), and burn + silver sulfadiazine (SS). It was found that level of irisin increased in the first week and decreased in the second week in the burn and CAR groups. In the ABS and SS groups, the level of irisin was determined that started to increase in the first week and continued to increase in the second week. The level of HSP70 was found to increased in the first week in burn and CAR groups and decreased in the second week, but started to increase in the second week in ABS and SS groups. Both levels of irisin and HSP70 were observed to decreased in all treatment groups in the third week. In this study, it was shown that ankaferd and silver sülfadiazine treatments cause an increase in the irisin levels in the early period and a gradually increase in HSP70 levels in the later period in burns. The inflammatory response was observed to be limited in the early period in the ankaferd and sulfadiazin groups. It was concluded that these findings were effective in early wound healing in burns.

Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: A multi-institutional randomized controlled trial.

Oral mucositis is a common and distressing complication in patients receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). We reported previously in a single-center retrospective analysis that zinc-L-carnosine (polaprezinc [PZ]) reduced the incidence of oral mucositis associated with HSCT. To verify the accuracy of the prophylactic effect of PZ against oral mucositis, we carried out a multi-institutional prospective randomized controlled study. Patients were randomly allocated to either the prevention group, in which PZ lozenge treatment was started before chemotherapy, or the control group, in which administration of PZ lozenges was initiated immediately after the onset of Grade 2 oral mucositis. Oral mucositis was evaluated daily from the start of chemotherapy to 35 days after transplantation. A total of 91 patients were enrolled, and 88 patients (47 in the control group and 41 in the prevention group) were eligible for data analysis. The incidence of Grade ≥2 but not Grade ≥3 oral mucositis was significantly reduced in the prevention group compared to the control group (44.7% in control group vs 22.0% in the prevention group, P = .025). There were no significant differences in the incidence rates of other adverse events or the rate of engraftment (95.6% vs 97.2%, P = .693) between the two groups. These findings suggest that PZ lozenge is effective for prophylaxis against Grade ≥2 oral mucositis associated with chemotherapy in patients undergoing HSCT without any influence on the HSCT outcome.

Dietary supplementation with L-carnosine improves patient-reported outcomes, autonomic nervous system performance, and brain metabolism in 3 adult patients with multiple sclerosis.

This pilot trial reports the effects of L-carnosine administration on autonomic nervous system performance, brain metabolism, and various patient- and clinician-reported outcomes in a case series of patients with multiple sclerosis (MS). We hypothesized that medium-term L-carnosine supplementation would improve selected patient- and clinician-reported outcomes in MS patients, with no negative effects on self-reported side effects. L-carnosine (2 g/day) was administered orally for 8 weeks in 2 women and one man suffering from MS. The intensity of symptoms and signs of MS after L-carnosine administration diminished in 5 out of 7 domains in CASE 1, in 3 out of 7 domains in CASE 2, and one domain in CASE 3; general fatigue was reduced in all 3 cases at the follow-up. This was accompanied by an improved walking distance to exhaustion in all patients, with values improved for 51.1% in CASE 1, 19.5% in CASE 2, and 2.1% in CASE 3 at 8-week follow-up. Tests of autonomic cardiovascular reflexes demonstrate normalized parasympathetic modulation and balanced sympathetic function after L-carnosine intervention in all MS cases. An increase in serum total antioxidant capacity (TAC) was found at 8-week follow-up in all patients (from 4.6 to 49.6%); this was accompanied by lower blood lactate at post-administration in all cases (23.5% on average). Single-voxel 1.5 T MR spectroscopy revealed increased brain choline-contained compounds (18.9% on average), total creatine (21.2%), and myo-inositol levels (12.3%) in girus cinguli at 8-week follow-up in all MS cases. This case study demonstrates that an 8-week intervention with L-carnosine appears to be a safe and beneficial therapeutic strategy with regard to the reduction of presence and severity of symptoms of MS.

Effect of L-Carnosine as adjunctive therapy in the management of children with autism spectrum disorder: a randomized controlled study.

L-Carnosine is an amino acid that acts as an anti-oxidant, anti-toxic and neuroprotective agent. There is a paucity of data about the effectiveness of L-Carnosine in the management of autism spectrum disorder (ASD) in children. This study aimed at investigating the effectiveness of L-Carnosine as adjunctive therapy in the management of ASD. This was a randomized controlled trial. Children aged 3-6 years with a diagnosis of mild to moderate ASD were assigned to standard care arm (occupational and speech therapy) and intervention care arm (L-Carnosine, 10-15 mg/kg in 2 divided doses) plus standard care treatment. The children were assessed at the baseline and the end of 2 months for the scores of Childhood Autism Rating Scale, Second Edition-Standard Version (CARS2-ST), Autism Treatment Evaluation Checklist (ATEC), BEARS sleep screening tool and 6-item Gastrointestinal Severity Index (6-GSI). Of the sixty-seven children enrolled, sixty-three children had completed the study. No statistically significant difference (p > 0.05) was observed for any of the outcome measures assessed. Supplementation of L-Carnosine did not improve the total score of CARS2-ST, ATEC, BEARS sleep screening tool and 6-GSI scores of children with ASD. Further investigations are needed with more objective assessments to critically validate the effectiveness of L-Carnosine on ASD children for more decisive results.

Pre-dialysis serum creatinine as an independent predictor of responsiveness to zinc supplementation among patients on hemodialysis.

BACKGROUND: To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD). METHODS: We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of < 80 µg/dL three months after the study began. Patients were divided into two groups: late response (serum zinc level < 80 µg/dL) and early response (serum zinc level ≥ 80 µg/dL). Factors independently associated with a late response to zinc supplementation were determined using inverse probability of treatment weighting (IPTW) multivariate logistic analysis. RESULTS: Of 91 patients, 86 continued to receive zinc supplementation after three months. The mean pre-dialysis SCre level was 10.0 mg/dL. The number of patients with a late response and response to zinc supplementation was 32 and 54, respectively. There was a significant negative correlation between the pre-dialysis SCre and the Δserum zinc change for 3 months. (r = - 0.284, P = 0.008). IPTW multivariate analysis showed that a pre-dialysis SCre level ≥ 10.0 mg/dL (odds ratio, 3.71; 95% confidence interval; 1.24-11.1, P = 0.022) was an independent factor associated with a late response to zinc supplementation. CONCLUSIONS: Pre-dialysis SCre level was independently associated with responsiveness to zinc supplementation after three months in patients on MHD.

Effect of carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and insulin resistance: A systematic review and meta-analysis of long-term randomized controlled trials.

OBJECTIVE: Glucose disorders and dyslipidemia are closely associated with obesity and metabolic disease. The purpose of this study was to investigate the effect of Carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and Insulin resistance. METHOD: MEDLINE/PubMed, Scopus and Web of sciences were investigated to identify relevant articles up to June 2019. The search strategy combined the Medical Subject Heading and Title and/or abstract keywords. The combined effect sizes were calculated as weight mean difference (WMD) using the random-effects model. Between study heterogeneity was evaluated by the Cochran's Q test and I2. RESULTS: Four RCTs studies investigated Carnosine use versus any control for at least 2 weeks were identified and analyzed. Overall results from the random-effects model on included studies, with 184 participants, indicated that carnosine intervention reduced HbA1C levels in intervention vs control groups (WMD: -0.92 %, 95 % CI: -1.20, -0.63, I2:69 %). Four studies, including a total of 183 participants, reported TG changes as an outcome measure variable, but combined results did not show significant reduction in this outcome (WMD: -14.46 mg/dl, 95 % CI: -29.11, 0.19, I2:94 %). Furthermore, combined results did not show any significant change in HOMA-IR, Cholesterol, fasting blood sugar, or HDL-C. CONCLUSION: Carnosine supplementation results in a decrease in HbA1C, but elicits no effect on HOMA-IR, Cholesterol, fasting blood sugar, TG and HDL-C. Future studies with a larger sample sizes, varied doses of carnosine, and population-specific sub-groups are warranted to confirm, and enhance, the veracity of our findings.

The neuroprotective properties of carnosine in a mouse model of manganism is mediated via mitochondria regulating and antioxidative mechanisms.

Objective(s): Manganese (Mn) is an essential trace element physiologically incorporated in the structure of several vital enzymes. Despite its essentiality, excessive Mn exposure is toxic with brain tissue as the primary target organ. There is no specific and clinically available therapeutic/preventive option against Mn neurotoxicity. Carnosine is a neuropeptide with several physiological roles. The neuroprotective properties of this peptide have been evaluated in different experimental models. The current study was designed to investigate the effect of carnosine supplementation and its potential mechanisms of action in an animal model of Mn-induced neurotoxicity. Materials and Methods: Male C57BL/6 mice received Mn (100 mg/kg, s.c) alone and/or in combination with carnosine (10, 50, and 100 mg/kg, i.p). Several locomotor activity indices were monitored. Moreover, biomarkers of oxidative stress and mitochondrial function were assessed in the brain tissue of Mn-exposed animals. Results: Significant locomotor dysfunction was revealed in Mn-exposed animals. Furthermore, brain tissue biomarkers of oxidative stress were significantly increased, and mitochondrial indices of functionality were impaired in Mn-treated animals. It was found that carnosine supplementation (10, 50, and 100 mg/kg, i.p) alleviated the Mn-induced locomotor deficit. Moreover, this peptide mitigated oxidative stress biomarkers and preserved brain tissue mitochondrial functionality in the animal model of manganism. Conclusion: These data indicate that carnosine is a potential neuroprotective agent against Mn neurotoxicity. Antioxidative and mitochondria protecting effects of carnosine might play a fundamental role in its neuroprotective properties against Mn toxicity.

Effects of Anserine/Carnosine Supplementation on Mild Cognitive Impairment with APOE4.

BACKGROUND: Oral supplementation of anserine/carnosine helps preserve cognitive functions in healthy older adults. Mild cognitive impairment (MCI) is a transition between cognitive-normal and dementia. Therefore, it needs to investigate whether anserine/carnosine supplementation (ACS) has effects on subjects with MCI. METHODS: A randomized, double-blind, placebo-controlled 12-week trial was performed. Fifty-four subjects with MCI were randomized to an active group ingesting 750 mg of anserine and 250 mg of carnosine per day or a placebo (1:1). Evaluation of cognitive change was conducted utilizing a psychometric test battery. RESULTS: The score improvement in the global Clinical Dementia Rating (gloCDR) was superior in the active group than placebo (p = 0.023). No beneficial effect in the active group was detected in the other psychometric tests including the Mini-Mental State Examination (MMSE), the Wechsler Memory Scale, and the Alzheimer's Disease Assessment Scale (ADAS). When APOE4 positive (APOE4 (+)) or negative (APOE4 (-)) subjects were separately analyzed, beneficial change in the APOE4 (+) subjects was observed in MMSE (p = 0.025) as well as in gloCDR (p = 0.026). CONCLUSIONS: The present study might suggest that protective effects against cognitive decline in APOE4 (+) MCI subjects exist.

Carnosine supplementation does not affect serum concentrations of advanced glycation and precursors of lipoxidation end products in autism: a randomized controlled clinical trial.

BACKGROUND: Abundant evidence indicate the increased levels of oxidative stress in patients with autism. Advanced glycation end products and advanced lipoxidation end products and their precursors play a major role in increased oxidative stress in numerous metabolic and neurologic diseases. Carnosine is a natural dipeptide with antiglycation effects. The aim of this trial was to examine the effects of carnosine supplementation on the advanced glycation end products and the precursors of advanced lipoxidation end products in patients with autism. METHOD: This randomized double-blind, placebo-controlled clinical trial was conducted on 36 autistic children, 18 in the carnosine group and 18 in the placebo group. The groups received a daily supplement of 500 mg carnosine or placebo for two months, respectively. Plasma concentrations of glycation and precursors of lipoxidation markers were evaluated by enzyme-linked immunosorbent assay method. RESULTS: In all, 63.9% of the autistic children had normal nutritional status. Carnosine supplementation did not significantly alter plasma concentrations of advanced glycation end products and precursors of advanced lipoxidation end products in autistic children. CONCLUSION: The findings indicate that supplementation of carnosine could not change advanced glycation end products and precursor of advanced lipoxidation end products in autistic children.

Carnosine and Histidine Supplementation Blunt Lead-Induced Reproductive Toxicity through Antioxidative and Mitochondria-Dependent Mechanisms.

Lead (Pb)-induced reproductive toxicity is a well-characterized adverse effect associated with this heavy metal. It has been found that Pb exposure is associated with altered spermatogenesis, increased testicular degeneration, and pathological sperm alterations. On the other hand, it has been reported that Pb-induced reproductive toxicity is associated with increased reactive oxygen species (ROS) formation and diminished antioxidant capacity in the reproductive system. Hence, administration of antioxidants as protective agents might be of value against Pb-induced reproductive toxicity. This study was designed to investigate whether carnosine (CAR) and histidine (HIS) supplementation would mitigate the Pb-induced reproductive toxicity in male rats. Animals received Pb (20 mg/kg/day, oral, 14 consecutive days) alone or in combination with CAR (250 and 500 mg/kg/day, oral, 14 consecutive days) or HIS (250 and 500 mg/kg/day, oral, 14 consecutive days). Pb toxicity was evident in the reproductive system by a significant increase in tissue markers of oxidative stress along with severe histopathological changes, seminal tubule damage, tubular desquamation, low spermatogenesis index, poor sperm parameters, and impaired sperm mitochondrial function. It was found that CAR and HIS supplementation blunted the Pb-induced oxidative stress and mitochondrial dysfunction in the rat reproductive system. Thereby, antioxidative and mitochondria-protective properties serve as primary mechanisms for CAR and HIS against Pb-induced reproductive toxicity.

Carnosine supplementation reduces plasma soluble transferrin receptor in healthy overweight or obese individuals: a pilot randomised trial.

Abnormalities of iron homeostasis have been linked to insulin resistance, type 2 diabetes and cardiovascular disease. Carnosine, an over-the-counter food supplement with chelating properties, has been shown to decrease serum iron and improve glucose metabolism in diabetic rodents. We have previously demonstrated that carnosine supplementation prevented worsening of glucose metabolism in healthy overweight and obese middle-aged adults. Yet, the impact of carnosine on markers of iron metabolism in humans has not been investigated. We aimed to determine whether carnosine supplementation has an effect on iron parameters in overweight and obese, otherwise healthy adults. We included 26 participants, who were randomly allocated to receive 1 g carnosine (n = 14) or identical placebo (n = 12) twice daily for 12 weeks. Iron parameters including iron, ferritin, transferrin, soluble transferrin receptor, total iron binding capacity and iron saturation were measured in serum or plasma by standard commercial assays. Carnosine supplementation decreased plasma soluble transferrin receptor compared to placebo (mean change difference ± standard error: - 0.07 ± 0.03 mg/l, p = 0.04). None of the other iron parameters were different between carnosine and placebo groups. At follow-up, soluble transferrin receptor was associated inversely with urinary carnosine concentrations and positively with serum carnosinase-1 activity (both p < 0.02). Our findings suggest that carnosine may modulate iron metabolism in high-risk groups which could ameliorate insulin resistance and prevent type 2 diabetes. Larger human clinical trials are required to confirm our results.

Effects of α-Lipoic Acid, Carnosine, and Thiamine Supplementation in Obese Patients with Type 2 Diabetes Mellitus: A Randomized, Double-Blind Study.

Type 2 diabetes mellitus (T2DM) is evolving to an epidemic of the modern world. T2DM is associated with a number of pathological complications, including cardiovascular disease that is mostly promoted by the increased oxidative stress in type 2 diabetic patients. We performed a randomized double-blind placebo-controlled trial to investigate the effectiveness of an individualized oral supplementation with α-lipoic acid (ALA), carnosine, and thiamine. For that purpose, 82 obese type 2 diabetic patients were randomly assigned to 2 groups, and were either supplemented daily with 7 mg ALA/kg body weight, 6 mg carnosine/kg body weight, and 1 mg thiamine/kg body weight or placebo for 8 weeks. An array of biochemical tests including the estimation of oxidative stress and platelet aggregation were performed at baseline and at follow-up. Moreover, the antiplatelet activity of each of the supplement's components was determined ex vivo at human and washed rabbit platelets. Glucose and HbA1c levels were significantly reduced after supplementation (135.7 ± 19.5 mg/dL vs. 126.5 ± 16.8 mg/dL and 8.3% ± 0.3% vs. 6.03% ± 0.58%, respectively, P < .05); however, insulin was significantly increased (3.6 ± 0.7 µIU/mL vs. 6.8 ± 0.2 µIU/mL, P < .05). The patients treated with the supplement recorded higher follow-up values for HOMA-IR and HOMA-ß, and a significant drop in serum hydroperoxide level. Only ALA inhibited platelets aggregation ex vivo through ADP, platelet activating factor, arachidonic acid, epinephrine, collagen, and thrombin pathways. Daily supplementation with an individualized ALA, carnosine, and thiamine supplement effectively reduced glucose concentration in type 2 diabetic patients, probably by increasing insulin production from the pancreas. In addition to that, the reduction of oxidative stress and inhibition of platelet aggregation could potentially provide greater cardiovascular protection. Further studies are needed to fine-tune the supplementation dose-response effects in T2DM patients.

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.

l-Homocarnosine attenuates inflammation in cerebral ischemia-reperfusion injury through inhibition of nod-like receptor protein 3 inflammasome.

We investigated the therapeutic effects of l-homocarnosine against inflammation in a rat model of cerebral ischemia-reperfusion injury. Rats were grouped into control, middle cerebral artery occlusion (MCAO), 0.5 mM l-homocarnosine + MCAO, and 1 mM l-homocarnosine + MCAO treatment groups. Superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, lipid peroxidation, and reduced glutathione (GSH) levels were measured. Neurological scores were assessed, and histopathology, scanning electron microscopy (SEM), and fluorescence microscopy analyses were conducted. The mRNA expression levels of nod-like receptor protein 3 (NLRP3), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) and protein expression levels of NLRP3 were assessed. l-Homocarnosine supplementation substantially increased SOD, catalase, Gpx, and GSH levels, whereas it reduced the levels of lipid peroxidation relative to MCAO rats. l-Homocarnosine significantly reduced the infarct area and neurological deficit score, as well as histopathological alteration, apoptosis, and necrosis in brain tissue. The mRNA expression levels of NLRP3, TNF-α, and IL-6 were increased in MCAO rats, whereas l-homocarnosine supplementation reduced mRNA expression by >40%, and NLRP3 protein expression was reduced by >30% in 1 mM l-homocarnosine-treated MCAO rats. We propose that l-homocarnosine exerts a protective effect in cerebral ischemia-reperfusion injury-induced rats by downregulating NLRP3 expression.

Anserine/Carnosine Supplementation Suppresses the Expression of the Inflammatory Chemokine CCL24 in Peripheral Blood Mononuclear Cells from Elderly People.

Our goal was to determine whether anserine/carnosine supplementation (ACS) suppresses chemokine levels in elderly people. In a double-blind randomized controlled trial, volunteers were assigned to the ACS or placebo group (1:1). Sixty healthy elderly volunteers (active, n = 30; placebo, n = 30) completed the study. The ACS group was administered 1.0 g of anserine/carnosine (3:1) for 3 months. A microarray analysis and subsequent quantitative real-time polymerase chain reaction (qRT-PCR) analysis of peripheral blood mononuclear cells (PBMCs) showed decreased expression of CCL24, an inflammatory chemokine (p < 0.05). Verbal memory, assessed using the Wechsler memory scale-logical memory, was preserved in the ACS group. An age-restricted sub-analysis showed significant verbal memory preservation by ACS in participants who were in their 60s (active, n = 12; placebo, n = 9; p = 0.048) and 70s (active, n = 7; placebo, n = 11; p = 0.017). The suppression of CCL24 expression was greatest in people who were in their 70s (p < 0.01). There was a significant correlation between the preservation of verbal memory and suppression of CCL24 expression in the group that was in the 70s (Poisson correlation, r = 0.46, p < 0.05). These results suggest that ACS may preserve verbal episodic memory, probably owing to CCL24 suppression in the blood, especially in elderly participants.

N-acetylcarnosine (NAC) drops for age-related cataract.

BACKGROUND: Cataract is the leading cause of world blindness. The only available treatment for cataract is surgery. Surgery requires highly-trained individuals with expensive operating facilities. Where these are not available, patients go untreated. A form of treatment that did not involve surgery would be a useful alternative for people with symptomatic cataract who are unable or unwilling to undergo surgery. If an eye drop existed that could reverse or even prevent progression of cataract, then this would be a useful additional treatment option.Cataract tends to result from oxidative stress. The protein, L-carnosine, is known to have an antioxidant effect on the cataractous lens, so biochemically there is sound logic for exploring L-carnosine as an agent to reverse or even prevent progression of cataract. When applied as an eye drop, L-carnosine cannot penetrate the eye. However, when applied to the surface of the eye, N-acetylcarnosine (NAC) penetrates the cornea into the front chamber of the eye (near to where the cataract is), where it is metabolised into L-carnosine. Hence, it is possible that use of NAC eye drops may reverse or even prevent progression of cataract, thereby improving vision and quality of life. OBJECTIVES: To assess the effectiveness of NAC drops to prevent or reverse the progression of cataract. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Allied and Complementary Medicine Database (AMED) (January 1985 to June 2016), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 June 2016. We handsearched the American Society of Cataract and Refractive Surgery (ASCRS) and the European Society of Cataract and Refractive Surgeons (ESCRS) meetings from 2005 until September 2015. SELECTION CRITERIA: We planned to include randomized or quasi-randomised controlled trials where NAC was compared to control in people with age-related cataract. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified two potentially eligible studies from Russia and the United States. One study was split into two arms: the first arm ran for six months, with two-monthly follow-up; the second arm ran for two years with six-monthly follow-up. The other study ran for four months with a data collection point at the start and end of the study only. A total of 114 people were enrolled in these studies. The ages ranged from 55 to 80 years.We were unable to obtain sufficient information to reliably determine how both these studies were designed and conducted. We have contacted the author of these studies, but have not yet received a reply. Therefore, these studies are assigned as 'awaiting classification' in the review until sufficient information can be obtained from the authors. AUTHORS' CONCLUSIONS: There is currently no convincing evidence that NAC reverses cataract, nor prevents progression of cataract (defined as a change in cataract appearance either for the better or for the worse). Future studies should be randomized, double-masked, placebo-controlled trials with standardised quality of life outcomes and validated outcome measures in terms of visual acuity, contrast sensitivity and glare, and large enough to detect adverse effects.