Effectiveness of Diamine Oxidase (DAO) Enzyme Supplements for Histamine Reactions
DAO enzyme supplements may provide modest symptom relief for individuals with histamine intolerance, particularly those with documented low serum DAO levels, but the evidence is limited and more rigorous studies are needed before recommending them as a primary treatment.
Understanding Histamine Intolerance and DAO
Histamine intolerance results from an imbalance between accumulated histamine and the body's capacity to degrade it. This condition occurs when:
- Histamine accumulates in the body from dietary sources or endogenous production
- There is reduced activity of diamine oxidase (DAO), the main enzyme responsible for metabolizing ingested histamine in the gastrointestinal tract 1
- The resulting histamine excess causes symptoms that mimic allergic reactions
Evidence for DAO Supplementation
Clinical Studies
Recent research provides some support for DAO supplementation:
- A randomized, double-blind placebo-controlled study showed that oral DAO supplementation reduced symptom severity in chronic spontaneous urticaria patients with low baseline serum DAO levels 2
- An open-label interventional pilot study demonstrated significant reduction in histamine intolerance symptoms during 4-week DAO supplementation, with symptoms returning during the follow-up period without supplementation 3
Important Limitations
The evidence has significant limitations:
- Small sample sizes in existing studies
- Limited number of randomized controlled trials
- Lack of standardization in DAO supplement formulations
- Uncertain bioavailability of oral DAO supplements
A laboratory study evaluating porcine DAO found that commercially available supplements may not contain sufficient enzyme activity for meaningful histamine reduction, with some products showing histamine reduction through adsorption rather than enzymatic degradation 4. This raises concerns about the efficacy of currently available supplements.
Management Approach for Histamine Reactions
First-line Approaches
Antihistamines:
Low-histamine diet:
- Avoid histamine-rich foods (fermented foods, aged cheeses, processed meats)
- Maintain diet for at least 4 weeks to evaluate effectiveness 5
- Identify and avoid triggers of histamine release (temperature extremes, alcohol, certain medications)
Role of DAO Supplementation
Consider DAO supplementation as an adjunctive therapy:
- Most appropriate for patients with documented low serum DAO levels 2
- Take before meals containing potential histamine-rich foods
- Monitor response over 4 weeks to assess effectiveness 3
- Be aware that the quality and activity of commercial DAO supplements vary significantly 4
Diagnostic Considerations
Before considering DAO supplementation, proper diagnosis is essential:
- Rule out IgE-mediated allergies and mastocytosis
- Consider measuring serum DAO activity if available
- 24-hour urinary N-methylhistamine measurement provides a more stable assessment of histamine levels 5
- Normal levels of tryptase or histamine don't rule out histamine-mediated conditions
Cautions and Limitations
- DAO supplements should not replace appropriate medical treatment for severe allergic reactions
- The quality and potency of commercially available DAO supplements vary significantly
- A prospective, double-blind, randomized controlled trial is currently underway to better evaluate the efficacy of low-histamine diet and DAO supplementation 7
- For severe histamine reactions, especially anaphylaxis, epinephrine remains the first-line treatment 6
Conclusion
While preliminary evidence suggests potential benefits of DAO supplementation for histamine intolerance symptoms, particularly in those with documented low DAO levels, the current evidence is insufficient to recommend it as a primary treatment. A comprehensive approach including antihistamines, dietary modifications, and possibly DAO supplementation as an adjunctive therapy may provide the best symptom management for individuals with histamine intolerance.