Ali, A.N. orcid.org/0000-0001-6339-4076, Su, L. orcid.org/0000-0002-6347-3986, Newton, J. orcid.org/0000-0003-4848-7391 et al. (7 more authors) (2025) Dietary carnosine supplementation in healthy human volunteers: A safety, tolerability, plasma and brain concentration study. Nutrients, 17 (13). 2130. ISSN 2072-6643
Abstract
Background: Carnosine is a multimodal pleotropic endogenous molecule that exhibits properties that make it a compelling therapeutic agent for further evaluation in a number of diseases. However, little data currently exists on its pharmacokinetic profile, maximum tolerated doses, side effects and whether oral administration can lead to elevated brain concentrations. Method: To investigate this, sixteen healthy volunteers underwent a single dose-escalation study of oral carnosine to establish safety, tolerability, and pharmacokinetics. A subset (n = 5) underwent Proton Magnetic Resonance Imaging (MRI) spectroscopy to evaluate the effect of oral dosing on brain carnosine concentrations, and another subset (n = 4) completed a long-term (4-week) dosing study. Results: Oral carnosine was safe and well tolerated up to a dose of 10 g. At doses of 15 g, the frequency of adverse events became unacceptably high, with 77% of participants experiencing side effects, most commonly headache (43.5%), nausea (21.7%) and paraesthesia (21.7%). While pharmacokinetic profiles varied between individuals, peak plasma concentrations occurred within the first hour of dosing. Little circulating carnosine was detectable beyond 4 h. Brain carnosine concentration increased at 1 h post-dose but reverted to baseline values by 5 h. Long-term dosing at 5 g twice daily did not result in any adverse events. Conclusions: Our data will inform dosing interventions in future clinical trials of this exciting agent.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | carnosine; histidine; safety and tolerability; pharmacokinetics; brain concentration |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 14 Jul 2025 11:59 |
Last Modified: | 14 Jul 2025 11:59 |
Status: | Published |
Publisher: | MDPI AG |
Refereed: | Yes |
Identification Number: | 10.3390/nu17132130 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:229151 |