BACKGROUND: Zinc L-carnosine promotes the transition from the inflammatory to the proliferative phase of wound healing by reducing the expression of pro-inflammatory signals and enhancing the expression of anti-inflammatory signals. This prospective cohort study aims to test the effect of a zinc-L-carnosine mouthwash in promoting oral surgical wound healing.
METHODS: From October 2022 to February 2023, the authors enrolled healthy adult volunteers who needed the extraction of bilateral molars at the Unit of Dentistry of the University of Bari. The authors studied the baseline wound healing of each patient after the first extraction. Three months later, the patients underwent the second extraction and rinsed their mouths with zinc-L-carnosine mouthwash twice per day for the following 28 postoperative days. For a month after each extraction, the patients received weekly follow-up visits by an oral surgeon blinded about the study to record the modified healing index score of the wounds (range 0-6 points). For statistical analysis, we used the one-tailed t-test for paired samples with a significance level set at p < 0.05 to compare the baseline scores with those recorded during the exposure to the zinc-L-carnosine mouthwash.
RESULTS: The authors enrolled four women and six men (mean age = 44.60 ± 19.22 years). On the seventh and fourteenth postoperative days, the mean difference between the modified healing index scores obtained by using the zinc-L-carnosine mouthwash and the baseline was not significant. On the twenty-first postoperative day, the mean score obtained by using the mouthwash was 5.2 ± 1.3 points and was significantly higher than the 4.7 ± 1.8 points of the baseline (p = 0.026). On the twenty-eighth postoperative day, the mean difference was significant as well (5.9 ± 0.3 points and 5.4 ± 1.1 points, respectively).
CONCLUSIONS: The preliminary results of this study showed that the zinc-L-carnosine mouthwash improved the quality of oral surgical wound healing.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with intestinal epithelial barrier impairment. Polydatin (PD), a natural product isolated from Polygonum cuspidatum, is known to have an anti-inflammatory, antioxidant, and antiapoptotic effect. We attempted to compare the protective impact of PD pretreatment on alterations to the intestinal epithelial barrier and the colonic wall\'s ultrastructure accompanying ulcerative colitis to other conventional drugs in practice, primarily L-carnosine, which has not been addressed before. The rats were divided into 5 groups; 3 of them were treated with sulphasalazine (500 mg/kg), L-carnosine (30 mg/kg), and PD (45 mg/kg). All groups were administered their respective drugs 3 days before the UC was induced by acetic acid intra-rectally, and the treatment was continued until the 11th day. The disease activity index (DAI) was estimated, and a macroscopic scoring was established for the harvested colonic tissue. The tissues were extracted and processed for hematoxylin and eosin staining, caspase-3 immunohistochemical staining, electron microscopy, and biochemical analysis evaluating proinflammatory markers (IL-1β, TNF-α, and IL-6), myeloperoxidase (MPO), oxidative stress, and lipid peroxidation. Histopathological examination of colonic tissue showed that PD pretreatment effectively restored mucosal epithelial cells, intercellular tight junctions, goblet cells, and maintained the intestinal epithelial and endothelial barriers. PD suppressed MPO, proinflammatory markers, and malondialdehyde but enhanced superoxide dismutase and glutathione levels. It also hampered apoptosis, as evidenced by a reduction in caspase-3 expression. PD showed a significantly better response in preserving the intestinal epithelial barrier against acetic acid-induced colitis as compared to sulphasalazine and L-carnosine. These findings demonstrate the therapeutic role of PD for patients with UC.

Evidence for antidepressant effects of L-Carnosine was shown in some experimental studies. In this study we tried to evaluate the efficacy and tolerability of L-Carnosine combination therapy in treatment of patients with major depressive disorder (MDD).
Fifty-eight patients with MDD (DSM-V) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 400 mg twice daily L-Carnosine or placebo in addition to citalopram (maximum dosage of 40 mg/day) for six weeks in a randomized double-blind, and placebo-controlled study. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6.
Fifty-two patients completed the trial. General linear model repeated measure showed significant difference for time × treatment on HAM-D score [F = 3.17, df = 2.39, p-value = 0.03]. Significantly greater improvement was detected in HAM-D score of the L-Carnosine group compared with the placebo group from baseline to weeks 2, 4 and 6 [Ps = 0.013, 0.028 and 0.023; respectively]. Patients in the L-Carnosine group experienced significantly greater response and remission rate than the placebo group [Ps = 0.023 and 0.012; respectively]. There was no significant difference between the two groups in baseline parameters and frequency of side effects.
Short follow-up period and small population size were two important limitations of this study.
L-Carnosine combination therapy with citalopram can effectively improve symptoms of patients with major depressive disorder. Rapid-onset antidepressant effects of L-Carnosine were also shown which need further investigation.

This study aimed to investigate the efficacy and tolerability of l-carnosine as an add-on to methylphenidate in management of children with attention-deficit/hyperactivity disorder (ADHD).
This was an 8-week, randomized, double-blind placebo-controlled study. Fifty-six drug-free children and adolescents aged 6-17 years old with a diagnosis of ADHD entered the study. The patients were randomly assigned to l-carnosine (800 mg/d in two divided doses) or placebo plus methylphenidate (0.5-1.5 mg/kg/d) for 8 weeks. Children were assessed using the Teacher and Parent ADHD Rating Scale-IV (ADHD-RS-IV) at baseline and at weeks 4 and 8 postbaseline.
Fifty patients completed the study, and all had two postbaseline measurements. Using the general linear model repeated measures, significant effect was observed for time × treatment interaction on total and inattention subscales of the Parent ADHD-RS (Greenhouse-Geisser corrected: F = 3.783, df = 1.444, p = 0.041 and F = 4.032, df = 1.600, p = 0.030). Improvements in the Teacher ADHD-RS were not significantly different between the two groups in total (Greenhouse-Geisser corrected: F = 0.200, df = 1.218, p = 0.705), as well as inattention and hyperactivity subscale scores (p = 0.956 and 0.281, respectively). The frequency of side effects was not significantly different between the two treatment arms.
l-carnosine, as a supplementary medication, might be beneficial in treatment of children with ADHD. However, further investigations and different doses of l-carnosine are required to replicate these findings in children with ADHD.

Since l-carnosine has shown effectiveness in improvement of cognition in patients with schizophrenia, this 8-week, randomized, double-blind, placebo-controlled pilot study was conducted. Sixty-three patients with chronic schizophrenia, who were clinically stable on a stable dose of risperidone, entered the study. The patients were randomly assigned to l-carnosine (2 gr/day in two divided doses) or placebo for eight weeks. The patients were assessed using the positive and negative syndrome scale (PANSS), extrapyramidal symptom rating scale (ESRS), and Hamilton depression rating scale (HDRS) during the study course. Sixty patients completed the trial. L-carnosine resulted in greater improvement of negative scores as well as total PANSS scores but not positive subscale scores compared to placebo. HDRS scores and its changes did not differ between the two groups. Both groups demonstrated a constant ESRS score during the trial course. Frequency of other side effects was not significantly different between the two groups. In a multiple regression analysis model (controlled for positive, general psychopathology, depressive and extrapyramidal symptoms, as well as other variables), the treatment group significantly predicted changes in primary negative symptoms. In conclusion, l-carnosine add-on therapy can safely and effectively reduce the primary negative symptoms of patients with schizophrenia.

Considering the pathologic importance of metabolic disturbances, advanced glycation end products (AGEs), and chronic inflammation in diabetes mellitus and ameliorating potentials of l-carnosine in hampering these detritions and because these effects have not been investigated in patients with type 2 diabetes (T2D) so far, we conducted the current study. We hypothesized that l-carnosine would improve glycemic control, lipid profile, AGE, soluble receptor of AGEs (sRAGE), and inflammatory markers. In a randomized, double-blind, placebo-controlled clinical trial, 54 patients with T2D were recruited and assigned into either intervention group (n=27, receiving 2 capsules of l-carnosine 500 mg each) or control group (n=27). Blood samples and dietary intakes information were collected at baseline and after 12 weeks of intervention. l-Carnosine supplementation resulted in significant decrease in fat mass and an increase in fat-free mass in the intervention group compared with the placebo group (1.5% and 1.7%, respectively) (P<.05). A significant reduction in fasting blood glucose (13.1 mg/dL); glycated hemoglobin (.6%); and serum levels of triglycerides (29.8 mg/dL), carboxymethyl lysine (91.8 ng/mL), and tumor necrosis factor-α was detected in the l-carnosine group compared with the placebo group (P<.05). In the l-carnosine group, a significant reduction in serum pentosidine levels (2.8 ng/mL) was observed compared with those at baseline (P<.05). No significant differences were observed in dietary intake, body mass index, systolic and diastolic blood pressure, fasting insulin levels, homeostasis model assessment of insulin resistance and secretion, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, sRAGE, interleukin (IL)-6, and IL-1β levels between the groups after adjusting for baseline values and covariates (P>.05). Collectively, l-carnosine lowered fasting glucose, serum levels of triglycerides, AGEs, and tumor necrosis factor-α without changing sRAGE, IL-6, and IL-1β levels in T2D patients.

This study aimed at investigating the efficacy and tolerability of l-carnosine as an add-on to risperidone in the management of children with autism.
This was a 10-week, randomized, double-blind, placebo-controlled study. Seventy drug-free children aged 4-12 years old with a diagnosis of autism spectrum disorder (ASD), according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. (DSM-5) who had an Aberrant Behavior Checklist-Community (ABC-C) scale irritability subscale score of ≥12, entered the study. The patients were randomly assigned to l-carnosine (800 mg/day in 2 divided doses) or placebo in addition to risperidone titrated up to 2 mg/day (based on body weight) for 10 weeks. The children were assessed by using ABC-C at baseline and weeks 5 and 10 post-baseline. The primary outcome measure was the mean change in the ABC-C irritability subscale score, and other subscale scores were defined as secondary outcomes.
Using the general linear model repeated measures, no significant effect was observed for time × treatment interaction on the irritability subscale scores. However, significant effect was detected on the hyperactivity/noncompliance subscale [F (1.62, 64.96) = 3.53, p-value = 0.044]. No significant improvements were obtained on the lethargy/social withdrawal, stereotypic behavior, and inappropriate speech subscale scores. Significantly greater score reduction in the hyperactivity/noncompliance subscale occurred in the l-carnosine group compared with the placebo group at the end of the trial. Extrapyramidal Symptom Rating Scale Scores and its changes did not differ between the two groups. The frequency of other side effects was not significantly different between the two groups.
Although no significant difference was detected on the irritability subscale scores, l-carnosine add-on can improve hyperactivity/noncompliance subscales of the ABC-C rating scale in patients with ASD.

Dysregulation of glutamate is implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Consistently, glutamate-modulating agents, such as riluzole and memantine have been used in OCD treatment. Previous research has identified some neuroprotective role for L-carnosine potentially via its modulatory effect on glutamate. Here, we assessed the efficacy of L-carnosine as adjuvant to fluvoxamine in OCD treatment.
Forty-four patients diagnosed with moderate to severe OCD were recruited in a randomized double-blind trial. Patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10 weeks. The Yale- Brown Obsessive Compulsive Scale (Y-BOCS) was used for assessing the severity of symptoms at baseline and at weeks 4, 8, and 10.
General linear model repeated measure showed significant effects for Time × Treatment interaction on total Y-BOCS [F (2.10, 88.42) = 8.66, p < 0.001], obsession [F (1.88, 79.34) = 4.96, p = 0.01] and compulsion [F (1.88, 79.11) = 4.57, p = 0.01]. At week 10, the change from baseline in Y-BOCS scores was 8.86 ± 2.89 (mean ± SD) in the L-carnosine group compared to 5.86 ± 2.88 in the placebo group.
L-carnosine results in significant reduction of obsessive-compulsive symptoms when used as an adjuvant to fluvoxamine.