Exercise and Carnosine Modulate Microbiota-Derived Metabolites, Myokines, and Cardiometabolic Profiles in Rats: A Randomized Controlled Trial.

Bozbay K, Çınar V, Akbulut T, Yasul Y, Yalçın MH, Orgun MC, Aydın S, Lee DY

Biomedicines22 Nov 2025

PMID41462868PMCIDPMC12730646DOI10.3390/biomedicines13122853PepBankPUB-41462868

Summary

Background/Objectives: Carnosine and exercise independently improve metabolic health, yet their combined effects on myokines and microbiota-derived metabolites remain underexplored. This study evaluated the synergistic impact of carnosine supplementation and exercise intensity on microbiota-derived metabolites, as well as skeletal muscle and myocardial expression of irisin and myonectin, focusing on lipid and glycemic regulation. Methods: A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA). Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks. Blood samples were collected post-decapitation; plasma was analyzed for lipid profile, glycemic parameters, and microbiota-derived metabolites using enzymatic and ELISA methods. Irisin and myonectin levels were assessed in plasma and myocardial and skeletal muscle tissues via ELISA and immunohistochemistry. Results: The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index. Irisin and myonectin levels in skeletal muscle and myocardium were also highest in HICT_CA. The trimethylamine N-oxide (TMAO) was lowest and S-equol highest in HICT_CA, whereas indoxyl sulfate (IS) peaked in HICT and was lowest in the C group. Principal component analysis revealed strong positive associations between HICT_CA and cardiometabolic biomarkers. Conclusions: High-intensity training combined with carnosine may reduce weight gain, improve lipid and glycemic profiles, and enhance myokines and microbiota-derived metabolites.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study13

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone13

In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking L-carnosine.

01AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, high-intensity training with carnosine produced the lowest body weight among study groups.
In plain wordsIn rats, high-intensity training with carnosine produced the lowest body weight among study groups.
Peptide
L-carnosine
Outcome
DecreaseBody weight
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286801
02AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, high-intensity training with carnosine produced the highest HDL-C among study groups.
In plain wordsIn rats, high-intensity training with carnosine produced the highest HDL-C among study groups.
Peptide
L-carnosine
Outcome
IncreaseHDL-C
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286802
03AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, high-intensity training with carnosine produced the lowest LDL-C among study groups.
In plain wordsIn rats, high-intensity training with carnosine produced the lowest LDL-C among study groups.
Peptide
L-carnosine
Outcome
DecreaseLDL-C
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286803
04AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, high-intensity training with carnosine produced the lowest total cholesterol among study groups.
In plain wordsIn rats, high-intensity training with carnosine produced the lowest total cholesterol among study groups.
Peptide
L-carnosine
Outcome
DecreaseTotal cholesterol
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286804
05AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, high-intensity training with carnosine produced the lowest triglycerides among study groups.
In plain wordsIn rats, high-intensity training with carnosine produced the lowest triglycerides among study groups.
Peptide
L-carnosine
Outcome
DecreaseTriglycerides
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Lipids · Metabolic and weight
Source sentences
Summary
The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286805
06AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, high-intensity training with carnosine produced the lowest atherogenic index among study groups.
In plain wordsIn rats, high-intensity training with carnosine produced the lowest atherogenic index among study groups.
Peptide
L-carnosine
Outcome
DecreaseAtherogenic index
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Lipids · Cardiovascular
Source sentences
Summary
The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286806
07AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Mechanism
In rats, skeletal muscle irisin was highest with high-intensity training plus carnosine.
In plain wordsIn rats, skeletal muscle irisin was highest with high-intensity training plus carnosine.
Peptide
L-carnosine
Outcome
IncreaseSkeletal muscle irisin
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
Irisin and myonectin levels in skeletal muscle and myocardium were also highest in HICT_CA.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286807
08AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Mechanism
In rats, myocardial irisin was highest with high-intensity training plus carnosine.
In plain wordsIn rats, myocardial irisin was highest with high-intensity training plus carnosine.
Peptide
L-carnosine
Outcome
IncreaseMyocardial irisin
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
Irisin and myonectin levels in skeletal muscle and myocardium were also highest in HICT_CA.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286808
09AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Mechanism
In rats, skeletal muscle myonectin was highest with high-intensity training plus carnosine.
In plain wordsIn rats, skeletal muscle myonectin was highest with high-intensity training plus carnosine.
Peptide
L-carnosine
Outcome
IncreaseSkeletal muscle myonectin
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
Irisin and myonectin levels in skeletal muscle and myocardium were also highest in HICT_CA.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286809
10AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Mechanism
In rats, myocardial myonectin was highest with high-intensity training plus carnosine.
In plain wordsIn rats, myocardial myonectin was highest with high-intensity training plus carnosine.
Peptide
L-carnosine
Outcome
IncreaseMyocardial myonectin
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
Irisin and myonectin levels in skeletal muscle and myocardium were also highest in HICT_CA.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286810
11AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Mechanism
In rats, TMAO was lowest with high-intensity training plus carnosine.
In plain wordsIn rats, TMAO was lowest with high-intensity training plus carnosine.
Peptide
L-carnosine
Outcome
DecreaseTMAO
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Source sentences
Summary
The trimethylamine N-oxide (TMAO) was lowest and S-equol highest in HICT_CA,
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286811
12AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Mechanism
In rats, S-equol was highest with high-intensity training plus carnosine.
In plain wordsIn rats, S-equol was highest with high-intensity training plus carnosine.
Peptide
L-carnosine
Outcome
IncreaseS-equol
Study
ratn: not reported in source
Sprague Dawley rats
Comparator
Other study groups
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Source sentences
Summary
The trimethylamine N-oxide (TMAO) was lowest and S-equol highest in HICT_CA,
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286812
13AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Other
In rats, principal component analysis linked high-intensity training with carnosine positively to cardiometabolic biomarkers.
In plain wordsIn rats, analysis linked high-intensity training with carnosine positively to cardiometabolic biomarkers.
Peptide
L-carnosine
Outcome
Not applicableCardiometabolic biomarker associations
Study
ratn: not reported in source
Sprague Dawley rats
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Source sentences
Summary
Principal component analysis revealed strong positive associations between HICT_CA and cardiometabolic biomarkers.
2 context sentences(design, population, supporting numbers)
Summary · context
A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA).
Summary · context
Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Show in the study text Report a problemFND-4146286813

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

Subjects

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Keywords

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