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Dao3.5
Diamine Oxidase (DAO) Research
Too few graded studies
13 peer-reviewed studies
What the evidence says
Too few graded studies
Diamine Oxidase (DAO) doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from mixed-quality randomised trials published 2011–2026 with a typical study size of 39 participants.
Based on 13 studies · 6 RCTs · 493 total participants
Confidence
Moderate confidence
By outcome
Histamine intolerance
Mostly mechanism / observational10 studies
Pain & analgesia
Too few graded studies2 studies
Women's health
Too few graded studies2 studies
Migraine & headache
Too few graded studies1 study
Skin & urticaria
Too few graded studies1 study
Sleep & insomnia
Too few graded studies1 study
Safety profile
Too few graded studies1 study
Active research area
7 studies in the last 5 years
201120182026
1CrossoverCited 48×n=39 · small study2011
In plain English: The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014).
Komericki P et al. · Wien Klin Wochenschr (2011)
Four-centre randomised, double-blind, placebo-controlled crossover in 39 people with suspected histamine intolerance who had reacted to an open challenge with 75 mg of liquid histamine
Taking DAO capsules reduced the total histamine-associated symptom score compared with placebo (P = 0.014)
Single symptoms were not reproducible on repeat blinded challenge, so the authors suggest a global symptom score rather than single symptoms for diagnosis
In plain English: One month of DAO supplementation has demonstrated a positive trend in the improvement of migraine but more studies with a longer treatment period are needed to better assess the efficacy of DAO supplementation.
Izquierdo-Casas J et al. · Clin Nutr (2019)
Randomised, double-blind, placebo-controlled one-month trial in 100 people with episodic migraine and low serum DAO (below 80 HDU/ml)
Attack duration fell from 6.14 to 4.76 hours within the DAO group (p = 0.0217). The placebo group fell from 7.53 to 6.68 hours, not significant within the group
The authors state the placebo reduction could explain the lack of significant differences between the two groups, so the trial did not show DAO beat placebo
In plain English: HIT was excluded in 50 patients (84.7%).
Bent RK et al. · J Allergy Clin Immunol Pract (2023)
Diagnostic study, not a DAO intervention: a single-blind placebo-controlled histamine challenge in 59 people referred with suspected histamine intolerance. No DAO supplement was given or tested
Histamine intolerance was excluded in 50 of 59 (84.7%). 37 (62.7%) reacted to placebo
Only 4 had objective symptoms after histamine and not after placebo, and 5 more were judged possible cases
In plain English: Supplemental therapy with DAO caused a 3.8 ± 1.2 point mean ± SEM UAS-7 score reduction in patients with low serum DAO levels at time 0 (p = 0.041 compared to placebo).
Yacoub MR et al. · Int Arch Allergy Immunol (2018)
Double-blind, placebo-controlled crossover in 22 people with chronic spontaneous urticaria not fully controlled by antihistamines, 20 of whom completed. DAO was one capsule twice daily, 15 minutes before a meal, for 30 days
Urticaria activity (UAS-7) fell 3.8 points with DAO in people with low serum DAO at baseline (p = 0.041 versus placebo). That is the result reported, and the abstract gives no result for the whole group
The lower the baseline DAO, the larger the improvement (p = 0.019). Participants on DAO slightly reduced their daily antihistamine dose (p = 0.049)
In plain English: Patients in both study groups experienced favorable changes during the evaluation period as indicated by their final FIQ and PCS scores, particularly in the DAO group in the latter questionnaire.
Okutan G et al. · J Clin Med (2023)
100 women with fibromyalgia were randomly assigned to DAO or control on top of their usual drug treatment for 8 weeks
Both groups improved on the Fibromyalgia Impact Questionnaire and the Pain Catastrophizing Scale. The full text reports no significant difference between groups on the main questionnaire
Lower fatigue, anxiety, depression and burning scores in the DAO group are described only qualitatively. Drug use for pain, depression and anxiety differed between the groups
In plain English: Decreases in ISI scores were similar in both groups, but severe insomnia at day 28 was higher in the placebo group (5.9 % vs. 2 %).
Ferrer-Garcia J et al. · Sleep Med X (2026)
Exploratory randomised, double-blind, placebo-controlled 28-day trial in 101 adults with insomnia symptoms and variants of the AOC1 gene, which encodes DAO. DAO product 12.6 mg/day (n = 50) or placebo (n = 51)
The Insomnia Severity Index fell by a similar amount in both groups
Sleep quality (PSQI) change was -1.62 with DAO versus -1.47 with placebo. Sleep efficiency and sleep medication use improved significantly only against baseline, within the DAO group in the once-daily regimen
In plain English: Lastly, current challenges are discussed, including the lack of standardised diagnostic methods, limitations in supplementation efficacy, and gaps in the regulatory framework.
Alemany-Fornés M et al. · Int J Biol Macromol (2025)
Narrative review of DAO biology, DAO deficiency, the clinical trials of DAO supplements and the differences between supplements from different enzyme sources
Names the lack of standardised diagnosis, limits on supplement efficacy and regulatory gaps as current challenges
Two of the four authors are full-time employees of a DAO supplement manufacturer
In plain English: Limited clinical evidence reflects the difficulty of dietary management and suggests a beneficial role of DAO supplementation on the clinical manifestations associated with HIT.
Jackson K et al. · Int J Mol Sci (2025)
Narrative review of diet and DAO supplementation for histamine intolerance
Notes there is no validated biomarker, so diagnosis rests on clinical assessment and response to a low-histamine diet with reintroduction
Reports that DAO activity in supplements varies with cofactors and enzyme origin, and that the clinical evidence for a benefit is limited
In plain English: The dietary supplement that contains a pig kidney extract did not show DAO activity.
Kettner L et al. · J Food Sci (2020)
Laboratory study of porcine DAO in simulated digestive fluids
Free porcine DAO had a half-life of about 19 minutes in fed-state simulated intestinal fluid. About 50 nkat, the amount from roughly 100 g of pig kidney, was needed to break down about 90% of the histamine in a typical histamine-containing meal (75 mg)
A commercial pig-kidney-extract supplement showed no DAO activity. The small histamine reduction seen (18.9%, falling to 12.1% after simulated gastric fluid) was attributed to histamine binding to a capsule component
In plain English: Concurrently, the DAO activity significantly increased 11-fold from the baseline, coinciding with symptom relief.
Duelo A, Sánchez-Pérez S, Pellicer-Roca S, Sánchez-Buxens S, Comas-Basté O, Latorre-Moratalla ML, Vidal-Carou MC · J Clin Med (2025)
Prospective observational study in 30 women with histamine intolerance, with serum DAO activity and symptoms assessed before, during and 2 months after pregnancy. No DAO supplement was given
Symptoms improved during pregnancy in 27 of 30 women (p < 0.001), and serum DAO activity rose about 11-fold from baseline
Two months after birth symptoms tended to return and DAO activity fell in every participant
In plain English: Inactivation of exogenous histamine is not driven by enzymatic degradation and kidney filtration.
Karer M et al. · Inflamm Res (2022)
Mice lacking DAO showed no difference from normal mice in body temperature or plasma histamine after oral or injected histamine
This questions the premise that low DAO activity is what makes dietary histamine harmful
Recombinant human DAO given to the mice did reduce histamine levels and histamine-induced symptoms, which is a different preparation and route from oral supplements
13ObservationalCited 68×n=14 · very small study2016
In plain English: Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation.
Manzotti G et al. · Int J Immunopathol Pharmacol (2016)
Retrospective review of 14 allergy-clinic patients who had benefited from a low-histamine diet, published as a letter
10 of 14 had serum DAO activity below 10 U/mL. Mean activity was 7.04 U/mL against 39.50 U/mL in 34 healthy controls (P = 0.0031)
13 of 14 subjectively reported benefit in at least one symptom after DAO supplementation. There was no control group and no blinding