ABSTRACT
Background: Diamine oxidase (DAO) deficiency plays a pivotal role in histamine intolerance (HIT), a condition driven by impaired histamine degradation. HIT manifests through a spectrum of gastrointestinal, dermatologic, and neurologic symptoms often misdiagnosed as allergic or inflammatory disorders. Objective: This review synthesizes emerging literature on the mechanisms, diagnostic challenges, and therapeutic strategies related to DAO deficiency. Methods: Following PRISMA 2020 guidelines, a comprehensive search was conducted across PubMed, Scopus, and Web of Science (2018-2025). Studies examining DAO activity, genetic variants, microbiome interactions, and supplementation outcomes were included. Results: Genetic polymorphisms, nutrient deficiencies, intestinal inflammation, and pharmacologic inhibition emerged as major contributors to DAO dysfunction. Clinical interventions, particularly DAO supplementation and low-histamine diets, demonstrate consistent symptom relief across multiple studies. Conclusion: DAO deficiency bridges gut physiology, immune modulation, and systemic health. Integrative approaches incorporating nutrition, genetics, and microbiome science offer a pathway toward personalized management of HIT.