Diamine oxidase supplementation

Diamine oxidase supplementation

adiDAO® is a diamine oxidase (DAO) enzyme developed to support histamine metabolism in the gastrointestinal tract. adiDAO® is proven to break down food-derived histamine and helps manage digestive discomfort linked to low DAO levels. Supported by clinical studies evaluating its benefits for discomforts related to histamine intolerance. 4.2 mg per serving.

adiDAO® - Key features

  • Highly active DAO enzyme, low dose

  • Supports digestive health by helping the body break down dietary histamine and supporting normal DAO levels 
  • Available in three grades: animal-derived (original extract), plant-based (vegetable alternative), and microencapsulated (enhanced enzyme protection and performance)
  • Patented ingredient for use and application in various clinical manifestations related to histamine intolerance

Science supporting adiDAO®

More than 18 years of scientific research have been dedicated to the characterisation and clinical validation of adiDAO® in supporting histamine metabolism. The clinical benefits of adiDAO® in digestive comfort and gut function have been demonstrated in a randomised, double-blind, placebo-controlled trial. Its efficacy is supported by application patents and regulatory recognition, including EU Novel Food and GRAS status. 

Characterisation

adiDAO® is a diamine oxidase (DAO) enzyme obtained through controlled physical processes. It delivers high enzymatic activity and is available from two sources: adiDAO® original from pig kidney extract and adiDAO®Veg from pea sprouts. Both sources are carefully processed to preserve enzyme integrity and ensure consistent activity.

Composition
•    adiDAO®: Protein extract from pig kidney
•    adiDAO®Veg: Dehydrated powder from pea sprout

Enzymatic activity
•    adiDAO®: ≥0,25 mU/mg of ingredient (≥12.000 HDU/mg of ingredient)
•    adiDAO®Veg: ≥0,17 mU/mg of ingredient (≥8.160 HDU/mg of ingredient)

Recommended daily dosage: 4.2 mg per serving, up to 3 servings a day before meals

Microcapsules: A Strategic Solution for DAO Combination Products
We provide a microencapsulated form of adiDAO®, obtained through a dual-layer encapsulation process that creates two protective barriers. This innovative approach ensures optimal protection and functionality of the enzyme within complex formulations.

Key Advantages of Microencapsulation:

  • Enzymatic Isolation: Prevents direct interaction between DAO and other active ingredients, preserving its structural integrity and enzymatic activity.
  • Moisture Barrier: Protects DAO from humidity, improving product stability and reducing the risk of bacterial contamination.
  • pH Resilience: Enhances resistance to pH variations within the formulation and throughout the digestive tract, supporting consistent enzyme performance.

Histamine intolerance

Histamine is a biogenic amine naturally produced by the body, essential to the immune, digestive, and nervous systems. While endogenous histamine has a positive biological role, exogenous histamine from food (e.g. fermented products, wine) can cause discomforts if not properly degraded. 

Diamine oxidase (DAO) is a functional enzyme that breaks down histamine derived from dietary sources. Under normal conditions, exogenous histamine is metabolised by the enzyme diamine oxidase (DAO) in the small intestine. However, when DAO activity is reduced, histamine from food can accumulate instead of being efficiently degraded.

This imbalance is known as histamine intolerance (HIT) and leads to digestive and extraintestinal discomforts, such as skin reactions, headaches, and respiratory discomfort. 

A recent study found 79% of individuals with clinical manifestations of histamine intolerance carry genetic variants associated to a reduced DAO activity.
The study determined the prevalence of associated discomforts in 100 subjects with histamine intolerance:

Gastrointestinal, nervous system, and musculoskeletal issues are among the most common. Headache, bloating, and fatigue affect more than 60% of people, while pruritus, flushing, rhinitis, muscle pain, constipation, and low blood pressure are also frequent. On average, individuals experience eight different clinical manifestations, and 99% had three or more at the same time, making histamine intolerance a challenge that affects overall quality of life. 

This highlights the importance of nutritional strategies that help maintain histamine balance, creating opportunities for innovative ingredient solutions such as DAO supplementation. 

Duelo et al., 2024

KEY INSIGHTS

  • DAO activity is influenced by genetics, gut disorders, diet, and certain medications.
  • 66% of the population may have a genetic predisposition to DAO deficiency.
  • Up to 88% of individuals with HIT report digestive discomfort.
  • Elevated histamine levels can overwhelm even normal DAO function.

Clinically supported benefits

Double-blind, randomised, placebo-controlled study.

LOCATIONS

Madrid, Spain
Research Center in Nutrition and Health (CINUSA Group)

YEAR & DURATION 2023
8 weeks
POPULATIONS

100 women
Age: 33-61 years old

PARAMETERS

Pain Catastrophising Scale (PCS)

Clinical manifestations related to gastrointestinal discomforts and Bristol stool scale

INTAKES

GASTRO-RESISTANT TABLETS
4.2 mg of adiDAO® or placebo
3 tablets per day, 20 min before main meals

adiDAO® has been demonstrated to significantly reduce the intensity of gastrointestinal heartburn and flatulence.

Changes in heartburn intensity between subjects supplemented with adiDAO vs placebo.

 

Changes in heartburn & flatulence intensity between responders (>20% improvement in FIQ scores after supplementation) and non-responders pre- and post-supplementation.


This study highlights the potential of adiDAO® supplementation to support histamine metabolism, with demonstrated relevance for complex wellness strategies.

 

adiDAO® is safe.

No adverse event linked to adiDAO® supplementation has been recorded.

adiDAO®Veg has undergone safety testing:

  • Study on 30 healthy subjects, a daily dose of 10x/20x/50x the daily recommended dose was administered. No adverse effect recorded on clinical and biological parameters: heart rate monitoring, haematology, clinical chemistry, coagulation, urinalysis.

  • In a group of 10 women with clinical manifestations of histamine intolerance, the administration of escalating doses of adiDAO®Veg - up to 100.8 mg/day over 8 weeks - was well tolerated and raised no safety concerns. No changes were observed in vital signs or biochemical parameters.

Unlock the Potential of DAO with adiDAO®

We offer a full spectrum of solutions, from raw material to finished product, designed to meet the evolving needs of healthcare and nutraceutical markets.

At the heart of our offering is adiDAO®, a high-purity diamine oxidase enzyme available in animal-derived, plant-based, and microencapsulated formats. Designed for stability and compatibility, adiDAO® is the foundation for a wide range of digestive and histamine-regulating applications.

Semi-Finished Formats for Custom Development

Accelerate your development pipeline with our ready-to-integrate delivery systems:

  • adiDAO® Tablets: Gastro-resistant tablets containing the DAO enzyme.
  • EFICAPS adiDAO® capsules - Vitamin C & QuercetinGastro-resistant tablets with controlled-release DAO in the intestine and immediate-release of complementary active ingredients such as vitamin C and quercetin.
  • EFICAPS adiDAO® capsules – Caffeine & B VitaminsCombines DAO enzyme with caffeine, folic acid, vitamin B6, and vitamin B12 , which act as complementary ingredients to promote optimised function.

Our semi-finished delivery systems are engineered to optimise enzyme protection and targeted intestinal release. Offered in bulk, blister, and dispenser formats, they provide a versatile foundation for custom product development.

Interested in semi-finished formats?

Contact us to discuss your formulation needs

Regulatory & Certifications

adiDAO®: Non-GMO, gluten-free
                 Authorised Novel Food Ingredient, Self-affirmed GRAS

adiDAO®Veg: Non-GMO, Halal, Kosher, gluten-free, suitable for vegetarians.
                       Self-affirmed GRAS, under NDIN 

References

COMPETITOR ANALYSIS
Alemany-Fornes et al. bioRxiv. 2023

CLINICAL TRIALS
Molina Perelló P et al.; Int J Transl Med. 2025
Fortes-Marín et al. Genes, 2025
Duelo et al.; Nutrients, 2024
Okutan et al.; J. Clin. Med. 2023
Izquierdo Casas et al.; Clin Nutr. 2019
Izquierdo-Casas et al.; J Physiol Biochem, 2018

PATENTS
EP2686004, Composition comprising diamine oxidase for use in the treatment or prevention of fibromyalgia or chronic fatigue syndrome, 2014
EP2686006, Composition comprising diamine oxidase for the prevention of hangover symptoms, 2013
EP2844277, Diamine oxidase for use in the treatment or prevention of attention deficit hyperactivity disorder (ADHD)
EP2686005, Topical compositions comprising diaminooxidase for the treatment or prevention of diseases associated with high histamine levels which involve an increase in pain, 2016
EP2685841, Functional foods comprising diamine oxidase and uses thereof, 2014

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