{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:42:40Z","timestamp":1791690160639,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hestia Investments"},{"name":"Clinical Research Facility"},{"name":"Sheffield Biomedical Research Centre, Sheffield, UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/nu17132130","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T03:33:25Z","timestamp":1750995205000},"page":"2130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dietary Carnosine Supplementation in Healthy Human Volunteers: A Safety, Tolerability, Plasma and Brain Concentration Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6339-4076","authenticated-orcid":false,"given":"Ali N.","family":"Ali","sequence":"first","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2TN, UK"},{"name":"Combined Community and Acute Care Group, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Su","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2TN, UK"},{"name":"Department of Psychiatry, University of Cambridge, Cambridge CB2 1TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4848-7391","authenticated-orcid":false,"given":"Jillian","family":"Newton","sequence":"additional","affiliation":[{"name":"Biomolecular Science Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8011-892X","authenticated-orcid":false,"given":"Amy K.","family":"Grayson","sequence":"additional","affiliation":[{"name":"Biomolecular Science Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4165-5989","authenticated-orcid":false,"given":"David","family":"Taggart","sequence":"additional","affiliation":[{"name":"Glycyx MOR, Inc., San Francisco, CA 94121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2781-6478","authenticated-orcid":false,"given":"Simon M.","family":"Bell","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheharyar","family":"Baig","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Gardner","sequence":"additional","affiliation":[{"name":"Translational DMPK Science, Certara UK Limited, Sheffield S1 2BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8760-2511","authenticated-orcid":false,"given":"Barbora","family":"de Courten","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology University, Melbourne 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad","family":"Majid","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1152\/physrev.00039.2012","article-title":"Physiology and Pathophysiology of Carnosine","volume":"93","author":"Boldyrev","year":"2013","journal-title":"Physiol. 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