Carnosine and Beta-Alanine Supplementation in Human Medicine: Narrative Review and Critical Assessment

Cesak, Ondrej; Vostalová, Jitka; Vidlář, Aleš; Bastlová, Petra; Študent, Vladimír

doi:10.3390/nu15071770

Cited by 17 publications

(3 citation statements)

References 107 publications

(163 reference statements)

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“…Intriguingly, a negative correlation between alanine levels and age was observed in AF patients. Alanine supplementation has been documented to improve fatigue, increase strength, and enhance cognitive function in the elderly [ 40 , 41 ]. These health benefits of alanine for the elderly suggest its plausible benefits in age-related AF.…”

Section: Discussionmentioning

confidence: 99%

Amino acid profile alteration in age-related atrial fibrillation

Huang,

Lin,

Zhou

et al. 2024

J Transl Med

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Background Amino acids (AAs) are one of the primary metabolic substrates for cardiac work. The correlation between AAs and both atrial fibrillation (AF) and aging has been documented. However, the relationship between AAs and age-related AF remains unclear. Methods Initially, the plasma AA levels of persistent AF patients and control subjects were assessed, and the correlations between AA levels, age, and other clinical indicators were explored. Subsequently, the age-related AF mouse model was constructed and the untargeted myocardial metabolomics was conducted to detect the level of AAs and related metabolites. Additionally, the gut microbiota composition associated with age-related AF was detected by a 16S rDNA amplicon sequencing analysis on mouse fecal samples. Results Higher circulation levels of lysine (Student’s t-test, P = 0.001), tyrosine (P = 0.002), glutamic acid (P = 0.008), methionine (P = 0.008), and isoleucine (P = 0.014), while a lower level of glycine (P = 0.003) were observed in persistent AF patients. The feature AAs identified by machine learning algorithms were glutamic acid and methionine. The association between AAs and age differs between AF and control subjects. Distinct patterns of AA metabolic profiles were observed in the myocardial metabolites of aged AF mice. Aged AF mice had lower levels of Betaine, L-histidine, L-alanine, L-arginine, L-Pyroglutamic acid, and L-Citrulline compared with adult AF mice. Aged AF mice also presented a different gut microbiota pattern, and its functional prediction analysis showed AA metabolism alteration. Conclusion This study provided a comprehensive network of AA disturbances in age-related AF from multiple dimensions, including plasma, myocardium, and gut microbiota. Disturbances of AAs may serve as AF biomarkers, and restoring their homeostasis may have potential benefits for the management of age-related AF.

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Section: Discussionmentioning

confidence: 99%

Amino acid profile alteration in age-related atrial fibrillation

Huang,

Lin,

Zhou

et al. 2024

J Transl Med

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“…Carnosine is a dipeptide endogenously synthesized from β-alanine, a non-proteogenic amino acid, and L-histidine, an essential amino acid. Carnosine is found in the human body in relatively high concentrations in excitable tissues (brain and skeletal muscle) but also in lower quantities in other tissues (kidney, gastrointestinal tract, adipose tissue, heart, and liver) ( Cesak et al., 2023 ). Due to its several modes of action, carnosine supplementation has promise as an additional therapy for the treatment of sepsis ( Bonaccorso et al., 2023 ).…”

Section: Antioxidant Treatmentmentioning

confidence: 99%

Exploring the role of antioxidants in sepsis-associated oxidative stress: a comprehensive review

Sahoo,

Wong,

Patani

et al. 2024

Front. Cell. Infect. Microbiol.

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Sepsis is a potentially fatal condition characterized by organ dysfunction caused by an imbalanced immune response to infection. Although an increased inflammatory response significantly contributes to the pathogenesis of sepsis, several molecular mechanisms underlying the progression of sepsis are associated with increased cellular reactive oxygen species (ROS) generation and exhausted antioxidant pathways. This review article provides a comprehensive overview of the involvement of ROS in the pathophysiology of sepsis and the potential application of antioxidants with antimicrobial properties as an adjunct to primary therapies (fluid and antibiotic therapies) against sepsis. This article delves into the advantages and disadvantages associated with the utilization of antioxidants in the therapeutic approach to sepsis, which has been explored in a variety of animal models and clinical trials. While the application of antioxidants has been suggested as a potential therapy to suppress the immune response in cases where an intensified inflammatory reaction occurs, the use of multiple antioxidant agents can be beneficial as they can act additively or synergistically on different pathways, thereby enhancing the antioxidant defense. Furthermore, the utilization of immunoadjuvant therapy, specifically in septic patients displaying immunosuppressive tendencies, represents a promising advancement in sepsis therapy.

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“…In fact, carnosine is not toxic per se, as demonstrated in several human studies where a transient increase in the carnosine concentration in blood was promoted without negative effects [ 58 , 59 , 102 ]. Conversely, carnosine’s beneficial properties have been extensively reviewed, and many authors advocate the use of such a molecule as a food supplement in sport or as a potential therapeutic agent in human disease [ 17 , 82 , 83 , 90 , 103 , 104 , 105 , 106 , 107 ].…”

Section: Human Serum Carnosinase In Human Diseasementioning

confidence: 99%

State of the Art in the Development of Human Serum Carnosinase Inhibitors

Regazzoni

2024

Molecules

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Human serum carnosinase is an enzyme that operates the preferential hydrolysis of dipeptides with a C-terminus histidine. Only higher primates excrete such an enzyme in serum and cerebrospinal fluid. In humans, the serum hydrolytic rate has high interindividual variability owing to gene polymorphism, although age, gender, diet, and also diseases and surgical interventions can modify serum activity. Human genetic diseases with altered carnosinase activity have been identified and associated with neurological disorders and age-related cognitive decline. On the contrary, low peripheral carnosinase activity has been associated with kidney protection, especially in diabetic nephropathy. Therefore, serum carnosinase is a druggable target for the development of selective inhibitors. However, only one molecule (i.e., carnostatine) has been discovered with the purpose of developing serum carnosinase inhibitors. Bestatin is the only inhibitor reported other than carnostatine, although its activity is not selective towards serum carnosinase. Herein, we present a review of the most critical findings on human serum carnosinase, including enzyme expression, localization and substrate selectivity, along with factors affecting the hydrolytic activity, its implication in human diseases and the properties of known inhibitors of the enzyme.

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Carnosine and Beta-Alanine Supplementation in Human Medicine: Narrative Review and Critical Assessment

Cited by 17 publications

References 107 publications

Amino acid profile alteration in age-related atrial fibrillation

Amino acid profile alteration in age-related atrial fibrillation

Exploring the role of antioxidants in sepsis-associated oxidative stress: a comprehensive review

State of the Art in the Development of Human Serum Carnosinase Inhibitors

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