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Diamine Oxidase (Histamine-Degrading Enzyme)
An oral enzyme, usually from pig kidney or pea sprouts, taken just before meals to break down histamine from food in the gut. Small trials in people with suspected histamine intolerance report fewer symptoms, but the trials in migraine, urticaria, fibromyalgia and insomnia mostly failed to show a clear difference from placebo.
What the evidence says
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 confidenceBy outcome
Emerging 3.5: one small placebo-controlled crossover and one open-label pilot report fewer histamine-intolerance symptoms, but the larger placebo-controlled trials in migraine, fibromyalgia and insomnia did not show a clear difference from placebo, the urticaria benefit was reported in a low-DAO subgroup of a 20-completer crossover, product activity is unverified, and no systematic review exists.
Diamine oxidase (DAO) is the main enzyme the gut uses to break down histamine taken in with food. Histamine intolerance is the proposed condition in which too little DAO activity lets dietary histamine cause headaches, digestive complaints, flushing or hives.
DAO supplements are taken shortly before a meal so the enzyme is in the gut when the food arrives, and they act there rather than being absorbed. The clinical evidence is small.
A 39-person placebo-controlled crossover found fewer symptoms after a histamine challenge with DAO capsules (P = 0.014), and an open-label pilot of 28 people reported symptom improvement that reversed when DAO was stopped.
In migraine with low DAO, attack duration fell within the DAO group but the trial did not show a difference from placebo. In chronic urticaria, a 3.8-point fall in the UAS-7 activity score with DAO (p = 0.041 versus placebo) was reported in people with low serum DAO, in a crossover of 20 completers.
Fibromyalgia and insomnia trials found similar improvement with DAO and placebo on their main scales.
Two further findings limit confidence: a laboratory test found no DAO activity in a commercial pig-kidney capsule, and a placebo-controlled histamine challenge excluded histamine intolerance in 85% of people referred with it. No systematic review or meta-analysis exists.
DAO oxidises histamine from food in the gut lumen, which is proposed to lower the amount absorbed after a histamine-containing meal.
The enzyme is taken just before a meal to work alongside the food in the intestine. In simulated intestinal fluid free porcine DAO had a half-life of about 19 minutes, so timing relative to the meal matters.
Mice lacking DAO were not more sensitive to oral histamine, and serum DAO is not a reliable diagnostic marker, so how much low gut DAO explains symptoms in people is not settled.
Most DAO supplements are pig-kidney extracts. Plant-source (pea sprout) products exist.
Not studied as a supplement in pregnancy or breastfeeding. DAO rises naturally in pregnancy: in one study of 30 women with histamine-related symptoms and low DAO activity, serum DAO activity rose about 11-fold and symptoms eased in 27 of 30 during pregnancy. Ask a clinician or pharmacist before use.
The condition is often not confirmed on placebo-controlled testing, so have other causes of the symptoms checked rather than self-treating long term.
Reviews of histamine intolerance list drugs that release histamine or block DAO as triggers of symptoms in people with the condition. Such drugs could offset a DAO supplement. Ask a pharmacist whether a regular medicine is one of them rather than stopping it.
Tip: Avoid the product if allergic to its source and choose a different source if needed
Diamine Oxidase (DAO) has an evidence score of 3.5/10 — emerging evidence based on 13 indexed studies. An oral enzyme, usually from pig kidney or pea sprouts, taken just before meals to break down histamine from food in the gut. Small trials in people with suspected histamine intolerance report fewer symptoms, but the trials in migraine, urticaria, fibromyalgia and insomnia mostly failed to show a clear difference from placebo. Representative study: PMID 29475774.
Dosing for Diamine Oxidase (DAO): One capsule about 15 minutes before a histamine-containing meal, up to twice daily, as in the urticaria trial. Strength is labelled in histamine-degrading units (HDU) or mg of extract and varies by product, so capsule counts are not comparable across brands. An insomnia trial gave 12.6 mg/day of a DAO product. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take Diamine Oxidase (DAO) is with meals. Take it with food. DAO works on histamine in the food as it passes through the gut, so it is taken shortly before the meal it is meant to cover.
Diamine Oxidase (DAO) is generally well-tolerated and considered safe for most healthy adults at recommended doses. Reported side effects include allergic reaction to the source protein (pork or pea). How often they occur is not established for all of them. Use caution if any of these apply to you: Allergy to pork or pea protein, depending on the enzyme source.
Lactase
Too few graded studiesA digestive enzyme taken with dairy to break down lactose. Small placebo-controlled challenge trials mostly show less breath hydrogen and, in most, fewer symptoms in people with lactose malabsorption, but responses vary widely between people and products and no pooled analysis in adults exists.
Digestive Enzymes
Too few graded studiesEnzyme blend that helps break down proteins, fats and carbohydrates. Small trials suggest less discomfort in functional dyspepsia, but the evidence for everyday bloating is mixed.
Oral Proteolytic Enzymes
Too few graded studiesCombinations of protein-cleaving enzymes (trypsin, chymotrypsin, papain, bromelain), often with rutoside, taken between meals for joint pain and swelling. In osteoarthritis they were non-inferior to diclofenac in two 6-week trials designed to test that, and a pooled reanalysis reported fewer adverse events than diclofenac, but placebo-controlled evidence is mixed and a 721-person ankle sprain trial found no benefit.
AN-PEP
Mostly mechanism / observationalAn oral enzyme from the mould Aspergillus niger that breaks down gluten in the stomach. Small trials show it lowers the gluten reaching the small intestine after a meal, but it is not a treatment for coeliac disease and does not make gluten safe for people with coeliac disease to eat.
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Reviewed by Dr. Baher Al Hakim · Last reviewed October 2026 · evidence from 13 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.