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DAO Enzymes and Tyramine

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Their Connection and Impact to Health

Biogenic amines like histamine and tyramine play various roles in the human body. An imbalance in these compounds can lead to adverse health effects. One of the key enzymes involved in regulating biogenic amines is diamine oxidase (DAO).

This article will provide an overview of DAO and its connection to histamine and tyramine metabolism, and the impact this has on health.

Understanding Biogenic Amines

Biogenic amines are nitrogenous compounds formed by the decarboxylation of amino acids. They play diverse physiological roles depending on the amine and its concentrations in the body. Some of the most well-known biogenic amines include histamine, tyramine, tryptamine, and phenylethylamine.

These amines are found naturally in many foods and are also produced internally by bacteria, yeasts, and molds during fermentation or spoilage. Dietary biogenic amines can be absorbed in the gut and enter systemic circulation. When present in high amounts, they can trigger toxic reactions and adverse health effects like headaches, respiratory distress, changes in blood pressure, and heart palpitations. It’s important to understand how the body metabolizes these compounds.

The Role of Diamine Oxidase (DAO)

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DAO (also known as histaminase) is the main enzyme involved in the metabolism of ingested histamine. It breaks down histamine through oxidative deamination, which involves the removal of an amine group. DAO is found in high concentrations in the intestinal mucosa.

When histamine levels rise, DAO works to degrade and maintain healthy physiological amounts in the body. Impaired DAO activity can lead to an excess accumulation of histamine, resulting in symptoms like hives, headaches, vertigo, and gastrointestinal distress.

These factors can negatively impact DAO activity:

GeneticsDAO activity can be influenced by genetic factors, such as polymorphisms of the AOC1 gene.
Intestinal diseasesIntestinal inflammation and damage can reduce DAO activity, leading to histamine intolerance.
MedicationsCertain medications, such as NSAIDs, can inhibit DAO activity.
DietFoods high in histamine or histamine-releasing compounds and deficiencies in nutrients like zinc, copper, vitamin B6, and vitamin C can reduce DAO activity.
Alcohol and smokingAlcohol and smoking can reduce DAO activity, leading to histamine intolerance.
Hormonal changesHormonal changes, such as those during the menstrual cycle, can affect DAO activity and histamine intolerance.

Maintaining optimal DAO enzyme function is therefore essential for the effective degradation of dietary histamine and protection against adverse histamine-related reactions.

Tyramine: A Closer Look

Tyramine is a biogenic amine derived from the amino acid tyrosine. Foods that naturally contain tyramine include aged cheeses, fermented meats, and fermented soybean products. The chemical structure of tyramine includes a phenyl group, making it a phenylethylamine.

Tyramine acts as a neuromodulator when ingested and has the ability to release norepinephrine, inducing effects like elevated blood pressure and vasoconstriction. These effects are usually short-lived in healthy individuals as monoamine oxidases (MAOs) rapidly detoxify tyramine in the gastrointestinal tract and liver.

MAOs break down tyramine through oxidative deamination, which converts tyramine into non-biologically active compounds that are excreted. Impaired MAO function can lead to hypertensive effects from tyramine ingestion.

Histamine and Its Impact on Health

Histamine is involved in many physiological processes like gastric acid secretion, neurotransmission, and immune responses. It is synthesized by the decarboxylation of the amino acid histidine and stored in mast cells and basophils.

When histamine is released, it binds to specific receptors that mediate effects like smooth muscle contraction, increased vascular permeability, mucus secretion, and sensory neuron activation. This makes histamine a key mediator in allergic reactions and anaphylaxis.

However, histamine intoxication can occur in non-allergic individuals when high amounts of histamine from food overwhelms the enzymes that metabolize it. Symptoms like hives, headache, gastrointestinal upset, respiratory distress, and hypotension can manifest within minutes to hours after ingestion. Plasma histamine concentrations above 1 ng/mL are considered abnormal.

Foods and Histamine

Histamine levels can vary considerably between food types. In general, aged, fermented, pickled, cured, smoked, and marinated foods tend to be higher in histamine. These include sauerkraut, yogurt, kefir, kombucha, aged cheese, deli meats, sausages, canned fish, champagne, beer, wine, dried fruit, tomatoes, spinach, and eggplant.

Cooked, fresh, or frozen foods are lower in histamine. High histamine foods may trigger reactions in those with impaired histamine degradation capacity. Following a low-histamine diet helps control intake while supporting histamine-metabolizing enzymes.

The Connection Between DAO and Tyramine

While DAO metabolizes histamine, it does not appear to degrade tyramine to a significant extent. This is likely because the diamine structural motif of histamine is specific for DAO’s catalytic activity. The absence of a second amine group on tyramine means it is not an optimal substrate for DAO.

Instead, tyramine is primarily metabolized by MAOs through oxidative deamination like histamine. The lack of DAO’s involvement in tyramine breakdown highlights the specificity and importance of enzymatic reactions in amine metabolism. Other enzymes like histamine N-methyltransferase also play key roles in regulating histamine levels.

Addressing Histamine Intolerance

When histamine degradation falters, sensitivity and adverse reactions to ordinarily tolerated histamine doses can occur. Strategies to manage histamine intolerance include avoiding high-histamine foods, consuming fresh foods, following proper food handling procedures to prevent biogenic amine formation by microbes, increasing intake of DAO-rich foods like soybeans, supplementing with DAO enzymes like DAO-HIST, and identifying any medications that might hinder DAO activity.

DAO supplements can provide temporary digestive support by degrading incoming dietary histamine. However, they do not address underlying causes and long-term dietary adjustments and lifestyle modifications may be needed. Maintaining proper food safety and awareness of food chemicals is also beneficial.

Broader Implications

Histamines impact various aspects of health beyond just food reactions. Scombroid poisoning is a type of foodborne illness caused by the consumption of fish contaminated with high histamine levels produced by bacterial spoilage. Monitoring histamine concentrations is an important aspect of food and cosmetics toxicology.

The Food and Agriculture Organization has established guidance levels for histamine in fish and fishery products. In the United States, the FDA sets limits on histamine levels and requires hazard analysis from seafood producers. Understanding histamine and DAO can have far-reaching protective benefits.


In summary, DAO, histamine, and tyramine are intricately connected in human metabolism and physiology. While DAO specifically degrades histamine, MAOs are the primary enzymes that metabolize tyramine. An imbalance in any of these pathways can lead to adverse reactions, especially when ingesting high amounts from dietary sources.

Those experiencing sensitivity would benefit from limiting intake of high histamine/tyramine foods, supporting metabolic enzymes, and making dietary adjustments. Awareness of this system empowers us to make informed choices for optimal health and wellbeing.

Take Control of Your Health Today

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If you suspect you may be dealing with histamine intolerance or have reactions to histamine-releasing foods, there are solutions available to help you reclaim balance. Supporting your body’s DAO activity is key.

The DAO-HIST supplement from SeeBeyond Shop provides temporary digestive relief by increasing the enzymatic degradation of excess histamine from food sources. Our team can assess your symptoms and offer guidance on managing your histamine levels through proper dietary adjustments and lifestyle recommendations.

Get your DAO-HIST supplements today from SeeBeyond Shop to start addressing histamine intolerance from the root cause. Have additional questions? SeeBeyond Shop’s experts are ready to support you on your journey towards histamine balance and overall well-being. Call us at (914) 768-1658 or book a consultation online to get in touch.

We are offering 30 minutes for free to talk to one of SeeBeyond's Functional Medicine Practitioners to create a personalized regimen.

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