The number of patients who come into my office that complain of hive-like reactions and severe mood changes has been significantly increasing. What is going on here? My own research has led me to believe that more and more people are suffering from histamine intolerance.

What is histamine?
Histamine is a molecule derived from the amino acid histidine. There are two places in the body where histamine is found – the digestive tract and the brain. Histamine play a variety of different roles in the body, from causing a classic reaction of itchy skin to more serious reactions like anaphylaxis.
Some other roles of histamine include:
- Modulating glutamate NMDA receptors
- Being a part of arousal and anxiety
- Activation of the sympathetic nervous system
- Causing the release of stress-related hormones from the pituitary gland
- A role in water retention
- Supporting digestion and movement of bowels
As you may be thinking, each of these areas can then be enhanced or suppressed if you have too much or too little histamine. So, we want to achieve a balance of histamine levels.

Given that histamine is found in the brain, can it affect mood?
Histamine is utilized in the brain, which can result in change of mood. The mechanism as to how this affects mood isn’t 100% clear. However, a correlation has been found between the amounts of histamine found in the brain and state of mood. For example, researchers observed that low levels of histamine are often associated with depression while high levels are associated with mania.
To balance histamine in the brain, we want to do 2 things:
- Ensure we are consuming enough of the amino acid histidine
- Make sure that our body has the ability to successfully break down and remove histamine
Any other areas we can commonly see an increase of histamine?
- Atopic Dermatitis
- Asthma
- ADHD
- Chronic urticaria
How is histamine broken down?
With any biochemical pathway, numerous agents are involved. For histamine, there are 3 pathways and numerous enzymes and cofactors.
There are three main genes that are paramount to processing histamine:
- HNMT
- DAO
- MAO
If any one of these genes are compromised, then the removal of histamine is decreased and symptoms of histamine intolerance occur.
Key cofactors needed to support these genes
- SAMe
- Vitamin B6
- Copper
- B2
- Iron
- B5
Are there other reasons why histamine may be accumulating?
- An excess of histidine
- Excess histamine can actually block DAO (see in Atopic Dermatitis)
- If have leaky gut, then will pass and acts as a vasodilator
- Taking too many methyl donors such as methylfolate and methylcobalamine with compromised MAO genes. This can result in increasing methylation which in turn can increase the production of methylated histamine, therefore; cause an overabundance or trapping of methylhistamine.
- Other genetic polymorphisims: MTHFR, PEMT
- Gut bugs – some produce histamine and some block methylation (Pseudomonas aeruginosa
- Haemophilus spp, Enterobacter aerogenes, Clostridium perfringes)
- Deficiency in the cofactors
- Long term medication use of antibiotics, antacids and even antihistamines
- Life style: stress, anxiety, lack of sleep, excessive alcohol consumption
- Hormonal imbalance such as excess estrogen (use MAO)
- Diet: eating an abundance of fermented foods, aged foods, leftovers, citrus, fish, high protein intake
- Environmental burden
- Compromised digestive health: IBS, IBD, leaky gut, SIBO
Overview of all the roles histamine plays in our bodies:

Here are foods you should AVOID if you think you have a histamine intolerance
- aged, spoiled, leftovers
- alcohol
- fish
- pickled foods à saurkrawt
- canned foods
- aged cheeses
- smoked meats
- shellfish
- beans
- nuts: walnuts, cashews
- citrus, wheat, vinegar

What are ways to help overcome newly acquired reactions to foods?
- DAO enzyme
- Reducing histamine foods (see above)
- Watching which probiotics you are taking (bifido vs lactobacillus spp)
- Supporting digestive health
- Addressing dysbiosis

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