Diamine oxidase (DAO)

Enzyme supplement · also known as DAO enzyme supplement, Histaminase

Oral enzyme supplement intended to degrade histamine in the intestinal lumen before absorption.

How it relates to mast cells: Downstream of the mast cell
Types of studies cited: Randomised controlled trial
Randomised trials in: chronic spontaneous urticaria
Approved for: nothing — US dietary supplement — not FDA-approved as a drug

What this relationship means: Acts after mast-cell mediators are released rather than stabilising the mast cell itself. This includes treatments that block mediator receptors, degrade a mediator, or oppose the physiology of an acute reaction. It describes where the intervention acts, not its clinical importance.

Mechanism of action

Diamine oxidase is the enzyme responsible for degrading ingested histamine at the intestinal mucosa. The rationale for supplementing it is narrow and specific: in individuals with reduced intestinal DAO activity, orally administered enzyme is intended to act within the gut lumen on histamine from food, before it is absorbed.

Two boundaries are worth stating plainly. The proposed action is confined to dietary histamine in the gut — it is not a mechanism for histamine that mast cells release into tissue, which is what defines mast cell activation. And the supporting literature concerns histamine intolerance, a separate condition from MCAS, which is why this entry is filed under a mechanism rather than an indication.

Sources

Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study Peer-reviewed study 2018 PMID 29698966 · link checked 22 Aug 2026
Histamine Intolerance-The More We Know the Less We Know. A Review Review article 2021 PMID 34209583 · link checked 20 Aug 2026
Histamine Intolerance Originates in the Gut Review article 2021 PMID 33921522 · link checked 20 Aug 2026

What this evidence cannot establish

Nothing in MCAS. This entry previously said the supporting studies were open-label; that was wrong. There is a randomised, double-blind, placebo-controlled crossover study — in chronic spontaneous urticaria, a different condition. The histamine-intolerance literature it otherwise rests on is open-label, and diagnosing histamine intolerance is itself unsettled: the reviews treat a good response to a low-histamine diet as the working criterion, which makes the diagnosis and the treatment response the same observation. Supplementation also usually begins alongside dietary change. Note too that serum DAO is not established to reflect DAO activity in the gut, and reduced DAO may be a marker of mucosal damage rather than a primary cause.

What this page does not say

No dosing, and no claim that this works. The entry describes a published mechanism, the cited study types, and what those studies cannot establish — nothing further. Why the site is built this way.

Recently verified. Verified 22 Aug 2026