Diamine oxidase (DAO) is a key enzyme for metabolizing dietary histamine in the gastrointestinal tract. DAO deficiency can lead to histamine intolerance (HIT), manifesting as migraines, gastrointestinal disturbances, and allergic reactions. DAO supplementation has been shown to enhance histamine breakdown, alleviating these symptoms. This randomized, double-blind, single ascending dose (SAD) Phase I clinical trial aimed to evaluate the safety and tolerability of escalating doses of DAO supplementation in healthy volunteers. Thirty participants were enrolled and randomly assigned to receive DAO or placebo. Single doses of 42 mg, 84 mg, or 210 mg of DAO extract (adiDAO(R) Veg) were administered under fasting conditions. Vital signs, laboratory parameters, and adverse events (AEs) were monitored, and a follow-up visit assessed post-administration safety. All participants completed the study without discontinuations. No serious adverse events or clinically significant changes in vital signs, ECGs, or laboratory parameters were observed. The study demonstrated that even doses significantly exceeding typical recommendations were well- tolerated, with no safety concerns identified. This trial confirms the safety of high-dose DAO supplementation, supporting its potential use in managing DAO deficiency and HIT. Future studies are recommended to explore the effects of chronic high-dose administration and alternative dosage forms to improve convenience.

The authors have declared no competing interest.

NCT06715163

This study did not receive any funding

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Ethics committee of Fundacio de Gestio Sanitaria de l'Hospital de la Santa Creu i Sant Pau de Barcelona gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors