Histamine is a naturally occurring chemical that is involved in several physical functions, including allergic and inflammatory reactions. It is also found to varying degrees in food and drinks.
In histamine intolerance, there is an imbalance between levels of histamine and the body’s ability to break it down. This can occur as a result of various factors including elevated histamine levels and/or lower levels of the enzymes that metabolize it.
There are two primary enzymes that are involved in breaking down histamine: histamine N-methyltransferase (HNMT) and diamine oxidase (DAO).
DAO is the primary enzyme that is responsible for breaking down dietary histamine. If DAO levels are reduced, or the proper function of DAO enzymes is inhibited, the body may begin to display physical reactions indicative of histamine intolerance. Scientific research supports this connection between DAO deficiency and symptoms of histamine intolerance (1).
This article explains more about DAO and histamine intolerance, and how to keep DAO levels healthy.
Histamine Intolerance and DAO
When the amount of histamine rises above normal levels, and it can’t be broken down completely or quickly enough, histamine intolerance may occur and cause adverse effects. Some of the many possible indicators of histamine intolerance include:
Digestive issues (IBS, constipation, stomach pain, diarrhea)
Nausea or vomiting
Menstrual pain & heavy periods
Migraines, headaches, and dizziness
Racing heart or palpitations, high or low blood pressure
Skin issues (psoriasis, hives, itching and dry skin)
Fibromyalgia and muscle aches
To reduce the risk of histamine intolerance, it is important for DAO to be present at adequate levels and for the enzymes to be able to function properly.
What Causes Reduced DAO Activity and Histamine Intolerance?
There are a number of things that can inhibit DAO activity and contribute to histamine intolerance, but one of the most common causes is increased intestinal permeability (leaky gut syndrome).
Most of the DAO in the human body is produced in the gut, so when gut health is compromised, there is less DAO available to manage histamine levels.
Therefore, following a diet focused on gut health is imperative for maintaining healthy levels of DAO and preventing the buildup of histamine.
In addition, genetics plays a role in proper DAO functioning. People who have certain SNPs, or genetic mutations, in their DAO genes have a lower ability to break down histamine.
Estrogen dominance has also been linked to histamine intolerance, because estrogen is thought to activate histamine release from mast cells (2). If a woman has higher than normal levels of estrogen, she may therefore also have an overabundance of histamine, making it difficult for the histamine breakdown enzymes to keep up with the metabolic demand.
Finally, certain foods, drinks, and medications may block the production of DAO or inhibit its activity. The following section goes into more detail on dietary choices that support healthy DAO levels.
How to Maintain Healthy Levels of DAO
In functional medicine, diet is frequently used to address health concerns, including histamine intolerance and low levels of DAO.
1. Follow a low histamine diet.
Another way to avoid an imbalance where DAO enzymes cannot keep up with excess histamine is to follow a diet that is focused on foods that are lower in histamine.
In essence, a low histamine diet consists of fresh poultry, fresh fish, non-citrus fruits, and vegetables, with the exception of tomatoes, avocados, eggplant, and spinach. Gluten-free grains and dairy substitutes are also acceptable.
The foods to be avoided include foods that contain naturally occurring histamine, foods that trigger histamine release, fermented foods and ripened fruits and vegetables.
Some foods also block the production or function of DAO, like alcohol, energy drinks, and black and green tea. Alcohol is especially harmful for DAO functioning, so consumption should be eliminated or dramatically reduced in the case of histamine intolerance (3).
This article provides a complete overview of a low histamine diet, as well as additional tips and tricks for other ways to manage histamine levels. A low FODMAP diet, explained here, may also help with histamine intolerance.
2. Focus on gut health.
Several gastrointestinal conditions may interfere with DAO production and functioning. These include:
Small Intestine Bacterial Overgrowth (SIBO)
Leaky Gut Syndrome
Inflammatory gastrointestinal conditions (IBS, Crohn’s disease)
This article goes more in depth about how gut imbalances can influence DAO levels.
Therefore, eating a diet focused on gut health is another way to ensure adequate DAO production and activity. This means reducing consumption of highly processed foods, sugar, and unhealthy fats, and ensuring that your diet is high in fiber, plant-based foods, and lean protein. Additional gut health supports like probiotics may also be helpful.
3. Consider checking levels of DAO cofactors. Although research is limited, DAO is thought to depend on a number of vitamins and minerals to function properly. These include:
Some functional medicine tests, like the Spectracell micronutrient test, can look at your levels of these and other vitamins and minerals, and help you to determine whether or not supplementation with any of these cofactors may be advisable.
While these nutrients can be obtained through food sources, keep in mind that some of these food sources may violate the low histamine diet.
4. Be mindful of the relationship between medications and DAO functioning.
Certain medications may interfere with DAO activity, as explained in this article. If possible, limit the use of NSAIDs (non-steroidal anti-inflammatory drugs) such as Advil and Aleve, as well as antihistamines like Benadryl. Other medications, including antidepressants, antacids and antibiotics, may also block DAO, but it is important to speak to your physician before making any changes to the dosage or frequency of your medications.
Supplementing With DAO
The use of oral DAO supplements has been shown to be effective in reducing multiple health concerns related to histamine intolerance, including disorders related to the skin and the gastrointestinal, cardiovascular, and respiratory systems (4). Make sure to consult with your physician before introducing any new supplements.
If you’re looking for more personalized guidance related to histamine intolerance, request a consultation with Dr. Gannage.