Nutrients · 2025
Dietary Carnosine Supplementation in Healthy Human Volunteers: A Safety, Tolerability, Plasma and Brain Concentration Study.
СтатьяНазвание и аннотация: Перевод в очереди
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Ali Ali N, Su Li, Newton Jillian, Grayson Amy K, Taggart David, Bell Simon M, Baig Sheharyar, Gardner Iain, de Courten Barbora, Majid Arshad
Аннотация
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.
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.