Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial

Abstract Carnosine is an endogenous dipeptide that buffers intracellular pH and quenches toxic products of lipid peroxidation. Used as a dietary supplement, it also supports exercise endurance. However, the accumulation and distribution of carnosine after supplementation has not been rigorously eval...

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Main Authors: Shahid P. Baba, Alok R. Amraotkar, David Hoetker, Hong Gao, Daniel Gomes, Jingjing Zhao, Michael F. Wempe, Peter J. Rice, Andrew P. DeFilippis, Shesh N. Rai, C. Arden Pope, Aruni Bhatnagar, Timothy E. O’Toole
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Language:English
Published: Springer 2024-08-01
Series:Amino Acids
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Online Access:https://doi.org/10.1007/s00726-024-03414-5
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author Shahid P. Baba
Alok R. Amraotkar
David Hoetker
Hong Gao
Daniel Gomes
Jingjing Zhao
Michael F. Wempe
Peter J. Rice
Andrew P. DeFilippis
Shesh N. Rai
C. Arden Pope
Aruni Bhatnagar
Timothy E. O’Toole
author_facet Shahid P. Baba
Alok R. Amraotkar
David Hoetker
Hong Gao
Daniel Gomes
Jingjing Zhao
Michael F. Wempe
Peter J. Rice
Andrew P. DeFilippis
Shesh N. Rai
C. Arden Pope
Aruni Bhatnagar
Timothy E. O’Toole
author_sort Shahid P. Baba
collection DOAJ
description Abstract Carnosine is an endogenous dipeptide that buffers intracellular pH and quenches toxic products of lipid peroxidation. Used as a dietary supplement, it also supports exercise endurance. However, the accumulation and distribution of carnosine after supplementation has not been rigorously evaluated. To do this, we randomized a cohort to receive daily supplements of either placebo or carnosine (2 g/day). Blood and urine samples were collected twice over the subsequent 12 week supplementation period and we measured levels of red blood cell (RBC) carnosine, urinary carnosine, and urinary carnosine-propanol and carnosine-propanal conjugates by LC/MS–MS. We found that, when compared with placebo, supplementation with carnosine for 6 or 12 weeks led to an approximate twofold increase in RBC carnosine, while levels of urinary carnosine increased nearly sevenfold. Although there were no changes in the urinary levels of carnosine propanol, carnosine propanal increased nearly twofold. RBC carnosine levels were positively associated with urinary carnosine and carnosine propanal levels. No adverse reactions were reported by those in the carnosine or placebo arms, nor did carnosine supplementation have any effect on kidney, liver, and cardiac function or blood electrolytes. In conclusion, irrespective of age, sex, or BMI, oral carnosine supplementation in humans leads to its increase in RBC and urine, as well as an increase in urinary carnosine-propanal. RBC carnosine may be a readily accessible pool to estimate carnosine levels. Clinical trial registration: This study is registered with ClinicalTrials.gov (Nucleophilic Defense Against PM Toxicity (NEAT Trial)—Full Text View—ClinicalTrials.gov), under the registration: NCT03314987.
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spelling doaj-art-9373a884d0d247a780738f3bc613583e2024-12-22T12:34:37ZengSpringerAmino Acids1438-21992024-08-0156111510.1007/s00726-024-03414-5Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trialShahid P. Baba0Alok R. Amraotkar1David Hoetker2Hong Gao3Daniel Gomes4Jingjing Zhao5Michael F. Wempe6Peter J. Rice7Andrew P. DeFilippis8Shesh N. Rai9C. Arden Pope10Aruni Bhatnagar11Timothy E. O’Toole12Christina Lee Brown Envirome Institute, University of LouisvilleChristina Lee Brown Envirome Institute, University of LouisvilleChristina Lee Brown Envirome Institute, University of LouisvilleChristina Lee Brown Envirome Institute, University of LouisvilleChristina Lee Brown Envirome Institute, University of LouisvilleChristina Lee Brown Envirome Institute, University of LouisvilleDepartment of Chemistry, Kentucky State UniversitySkaggs School of Pharmacy and Pharmaceutical Sciences, University of ColoradoDepartment of Medicine, Vanderbilt University Medical Center, University of VanderbiltChristina Lee Brown Envirome Institute, University of LouisvilleDepartment of Economics, Brigham Young UniversityChristina Lee Brown Envirome Institute, University of LouisvilleChristina Lee Brown Envirome Institute, University of LouisvilleAbstract Carnosine is an endogenous dipeptide that buffers intracellular pH and quenches toxic products of lipid peroxidation. Used as a dietary supplement, it also supports exercise endurance. However, the accumulation and distribution of carnosine after supplementation has not been rigorously evaluated. To do this, we randomized a cohort to receive daily supplements of either placebo or carnosine (2 g/day). Blood and urine samples were collected twice over the subsequent 12 week supplementation period and we measured levels of red blood cell (RBC) carnosine, urinary carnosine, and urinary carnosine-propanol and carnosine-propanal conjugates by LC/MS–MS. We found that, when compared with placebo, supplementation with carnosine for 6 or 12 weeks led to an approximate twofold increase in RBC carnosine, while levels of urinary carnosine increased nearly sevenfold. Although there were no changes in the urinary levels of carnosine propanol, carnosine propanal increased nearly twofold. RBC carnosine levels were positively associated with urinary carnosine and carnosine propanal levels. No adverse reactions were reported by those in the carnosine or placebo arms, nor did carnosine supplementation have any effect on kidney, liver, and cardiac function or blood electrolytes. In conclusion, irrespective of age, sex, or BMI, oral carnosine supplementation in humans leads to its increase in RBC and urine, as well as an increase in urinary carnosine-propanal. RBC carnosine may be a readily accessible pool to estimate carnosine levels. Clinical trial registration: This study is registered with ClinicalTrials.gov (Nucleophilic Defense Against PM Toxicity (NEAT Trial)—Full Text View—ClinicalTrials.gov), under the registration: NCT03314987.https://doi.org/10.1007/s00726-024-03414-5CarnosineCarnosine propanolCarnosine propanalMeasurement
spellingShingle Shahid P. Baba
Alok R. Amraotkar
David Hoetker
Hong Gao
Daniel Gomes
Jingjing Zhao
Michael F. Wempe
Peter J. Rice
Andrew P. DeFilippis
Shesh N. Rai
C. Arden Pope
Aruni Bhatnagar
Timothy E. O’Toole
Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial
Amino Acids
Carnosine
Carnosine propanol
Carnosine propanal
Measurement
title Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial
title_full Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial
title_fullStr Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial
title_full_unstemmed Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial
title_short Evaluation of supplementary carnosine accumulation and distribution: an initial analysis of participants in the Nucleophilic Defense Against PM Toxicity (NEAT) clinical trial
title_sort evaluation of supplementary carnosine accumulation and distribution an initial analysis of participants in the nucleophilic defense against pm toxicity neat clinical trial
topic Carnosine
Carnosine propanol
Carnosine propanal
Measurement
url https://doi.org/10.1007/s00726-024-03414-5
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