Study: DAO might play a critical role in cognitive symptoms of ADHD

By Nikki Hancocks

- Last updated on GMT

© iLexx / Getty Images
© iLexx / Getty Images

Related tags DAO Adhd Attention-deficit hyperactivity disorder Cognitive health

AB Biotek Human Nutrition & Health (HNH) has spotlighted new research suggesting a connection between diamine oxidase (DAO) enzyme deficiency and comorbidities and cognitive dysfunction in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD).

The new research, conducted by researchers in Madrid, Spain and published in the Journal of Clinical Medicine, ​concluded that while no relationship between ADHD severity and DAO deficiency was found, some gene variants associated with DAO deficiency were related to several meaningful medical comorbidities.

The team also reported a strong association between DAO activity and the intelligence quotient, particularly in working memory.

"Our results give some support to our hypothesis that DAO deficiency, an enzyme which metabolizes histamine extracellularly, might play a critical role in the pathophysiology of ADHD," the report stated. "Thus, decreased DAO activity might lead to an accumulation of histamine, which could explain both ADHD symptoms and comorbid disorders, such as atopy."

Dr. Carlos de Lecea, RD&A director at AB Biotek HNH, told NutraIngredients: “The conclusions suggest supplementation with DAO may offer an alternative to drugs, or possibly may work in combination with the drugs, to reduce the dosage or the length of treatment required."

The firm sells the supplement DAOfood, containing the enzyme Diamine Oxidase, for the dietary management of DAO deficiency and histamine intolerance. Its R&D team has carried out in vitro​ research​, which indicates the supplement is safe to be taken in tandem with ADHD drugs.

Dr. de Lecea highlighted one research finding as "most startling".

"This study showed 80% of kids with ADHD had a genetic pre-disposition to produce less DAO," he said. "What’s more, the higher the deficit in DAO, the worse outcome in terms of cognitive capacity impairment.

"This is quite compelling. There’s really been nothing new in the management of ADHD for quite some time, so there’s an opportunity to raise attention to this and improve protocol with supplementation."


ADHD is the most prevalent neurodevelopmental disorder worldwide. DAO is responsible for the histamine gastrointestinal degradation so its deficient functioning can lead to an excess of histamine in the body.

An excess of histamine (histamine intolerance, HIT) has been related with a growing number of diseases and pseudo-allergic symptomatology. Interestingly, most of the disorders associated with DAO deficiency are also frequently reported in people diagnosed with ADHD, the new study noted. However, data on the relationship between the DAO enzyme, HIT and ADHD are lacking.

The main objective of the new observational study was to analyze the prevalence of the four most relevant SNP variants of the AOC1 gene affecting DAO enzyme functionality in a sample of patients diagnosed with ADHD attending child and adolescent mental health services.

New data

Researchers obtained data from 303 children and adolescents with a primary diagnosis of ADHD following treatment at the Child and Adolescent Mental Health Services (CAMHS) at Puerta de Hierro University Hospital, Majadahonda (Madrid, Spain).

In total, 65 patients had none of the four studied SNP variants associated with reduced DAO activity, whereas 238 patients had at least one of these variants.

The team collected several sociodemographic and clinical data using the Wechsler Intelligence Scale for Children-Fourth Edition, which measures general cognitive ability, intellectual functioning in verbal comprehension, perceptual reasoning, working memory and processing speed, as wells as the Histamine Intolerance Clinic Questionnaire (HICQ), measuring 21 gastrointestinal, respiratory, dermatological and cardiac symptoms typical of HIT.

The prevalence of genetic DAO deficiency (the presence of at least one minor allele associated with DAO deficiency in the SPNs analyzed) was 78.5%.

"The close relationship between atopy and ADHD may have something to do with the high prevalence of 'genetic DAO deficiency', an underlying cause of HIT, in our sample (78.5%; 82.94% in females, and 77.06% in males)," the researchers wrote. "Unfortunately, there is no previous literature regarding the prevalence of DAO deficiency in either ADHD samples or even the general population."

They added that blood histamine does not pass the blood–brain barrier (BBB), and therefore, DAO deficiency should not influence brain functioning. However, the BBB is permeable to histamine during development.

"Accordingly, a DAO deficiency may influence some processes in the brain, such as learning and memory, and the development of some disorders such as ADHD by allowing for the permeability of histamine into the central nervous system during critical developmental periods," the study stated.

DAO deficiency prevalence

EFSA released a scientific opinion​ noting that, based on limited published information, while no adverse health effects are observed after exposure to 50 mg of histamine for healthy individuals, below detectable limits can lead to a reaction for those with histamine intolerance.

The paper called for further research to  explore the scale of histamine intolerance in the population and to improve monitoring of histamines in the food system.

Dr. de Lecea said that his team is making inroads in sizing the problem and finding out how many people could benefit from supplementation.

The company will host its virtual DAO Congress ​on April 11 to build awareness of DAO deficiency and map the future of DAO with presentations on the latest research and market insights.

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