This is very simplified information about histamine and histamine intolerance – there are more resources available at the end of the page for further reading for those who are interested in knowing more.
What is histamine?
Histamine is a nitrogen compound found naturally in many plants, animals and micro-organisms. It is mildly toxic but it’s normal to find it widely distributed all over the body. It is found in higher concentrations in the skin, the gastric tract and the lungs. Histamine is completely natural and is an essential part of a normal functioning immune system. Histamine is a biogenic amine and is also referred to by some sources as a vasoactive amine.
Where is histamine made in the body?
Most histamine in the body is made by mast cells in places where your body encounters your environment, so the eyes, mouth, nose, skin, lungs and digestive system.
What does histamine do in the body normally?
In simplified terms, your immune system monitors for foreign bodies and releases histamines from mast cells when they are encountered. Histamines then bind to histamine receptors and starts an immune reaction. Blood vessels in the damaged area become leaky which allows more immune cells to get to the area and attack the foreign body. This is normal immune function, causing redness, swelling and itching (due to increased blood flow) in a localised area.
How does histamine work in an allergic reaction?
Allergic reactions are considered to be an overreaction of the immune system to an allergen. In food allergy this would be a food protein and in pollen allergies this would be a pollen allergen. This is why it is difficult, especially in young children, to determine whether a rash is an allergic reaction to food or pollen or the immune system acting normally by reacting to common viruses or bacteria.
When histamine is released it binds to a family of receptors on target cells in lots of different tissues in the body. These sets of receptors have different effects on the body including smooth muscle contraction, vascular dilation, mucus secretion, tachycardia, low blood pressure, heart arrhythmia and stimulation of gastric acid secretion.
What are histamine receptors and how do they affect allergy symptoms?
Histamine receptors are categorised by their function, location in the body and affinity for histamine. The importance of these distinctions can be in using the right medications for the right symptoms. We have to acknowledge here that histamine has multiple functions in the body aside from immune response.
- The H1 histamine receptor is associated with allergic inflammation. It is a low affinity receptor which means the bond between histamine and the receptor is more easily disrupted.
H1 Receptors are found all over the body but notably in the nerves, the lining of the lungs, skin cells and smooth muscle cells.
- The H2 histamine receptor is associated with gastric acid secretion. It is also a low affinity receptor and is associated with excessive gastric acid secretion and mucous production in other areas.
H2 Receptors are found in heart cells, smooth muscle, the brain and lungs.
- The H3 histamine receptor is associated with neurotransmission, so involved in sleep and inflammation. They are a high affinity receptor, meaning the bond between histamine and the receptor is more difficult to disrupt. They are associated with central nervous system disorders, ADHD, narcolepsy, Alzheimer’s, schizophrenia, generalised pain and rhinitis
H3 Receptors are found in the Central Nervous System, heart and lungs.
- The H4 histamine receptor is associated the immune response and inflammation. This is another high affinity receptor. Associated with inflammatory conditions, rhinitis, asthma and inflammatory pain.
H4 Receptors are found in the intestines, and are expressed in bone marrow and eosinophils, neutrophils, T cells, basophils and mast cells.
Histamine Receptors is a large topic, covering mast cells and T Cells, there are more resources at the bottom of the page if you are interested in learning more.
How do antihistamines work?
After ingestion antihistamines go through the bloodstream and bind with H1 and H2 receptors. This stops the receptors from being used by histamine and relieves the symptoms we associate with allergy or normal immune function.
How do H2 blockers work?
They are also called histamine H2 receptor antagonists – they are a group of medicines that help reduce the amount of acid produced by the cells in the lining of the stomach, treating symptoms like acid reflux. They bind specifically to H2 receptors, blocking them from receiving more histamine and reducing symptoms. H2 blockers include medications like omeprazole, lansoprazole and rabeprazole.
How does epinephrine work with histamine?
When made by the body, epinephrine is known as the hormone adrenaline and is made naturally by the adrenal glands in response to stress. Adrenaline and epinephrine have a significant role in contraction and relaxation of muscles and in the intense feeling of energy, fear and hyper-awareness, an often-overlooked symptom of anaphylaxis. In anaphylaxis the immune system is flooded with chemicals including histamine which can cause the blood pressure to drop and the airways and smooth muscle in the lungs to constrict, blocking the airways.
Epinephrine works by binding to specific receptors on immune cells and suppressing further chemical release. It also causes all the muscles and blood vessels to relax, causing the blood vessels to dilate, improving blood flow throughout the body, normalising blood pressure and relaxing the muscles in the throat which has caused it to constrict.
What causes a histamine intolerance?
Most food intolerances are usually the result of a lack of metabolic enzymes. You can read more about them on the Food Intolerance Page
. Histamine intolerance is caused by reduced production of an enzyme called diamine oxide, commonly referred to as DAO. Some medications inhibit DAO production, this type of intolerance is temporary and the effects can be limited by modifying your diet.
What does DAO do in the body normally?
Diamine oxide (DAO) is made in the mucous membranes in the intestines and kidneys. This enzyme breaks down excess histamine in the body, blocks it from receptors and reduces the amount of histamine moving from the intestines to the bloodstream. DAO only breaks down histamine from food and drink.
What is N-methyltransferase?
Also called Histamine N-methyltransferase (HNMT). This is another enzyme made by the body which breaks down histamine produced by the body (and not histamine that has been consumed). This is produced in the Central Nervous System.
Can you be allergic to histamine?
The simple answer is no, food intolerances are linked to a dysfunction of the gastrointestinal system. A true food allergy is a dysfunction of the body's immune system, however as histamine is a key part of the immune system response it can have the symptoms of a classic IgE allergic reaction.
What are the symptoms of a histamine intolerance?
The symptoms of histamine intolerance are different to other food intolerances in that can it also affect the skin and sinuses as well as the gastrointestinal system. Symptoms may include:
Blocked or Runny Nose
Rashes, Itching or Flushing
Which foods contain histamine?
Histamine is mostly found in pickled and overripe foods. They include:
Processed and Cured Meats
Processed and Cured Fish
Fresh Fish (increases in histamine as it becomes less fresh)
Pickled Fruits and Vegetables
Fermented Soya Products (but not fresh soya)
Certain cheeses (soft cheeses which are processed for shorter times are lower in histamine)
This food list is not exhaustive, the Cross Reactivity page will have the most up to date food lists. You can read more about any of these foods from the dedicated Food Allergy Index
What is a histamine liberator?
This is a theory from the 1950s, that certain foods when eaten can release histamine which is naturally produced by the body. How histamine liberators might work has still not been established over 70 years later. Diets with extensive lists of histamine liberators may be encouraging unnecessary dietary restrictions without much evidence of effectiveness.
Why do different sites have different opinions on which foods contain histamine?
Some foods contain other biogenic amines aside from histamine, but have a similar effect on the body, these are occasionally listed as high histamine foods. Putrescine is another biogenic amine found in citrus fruits, chocolate, tea and nuts. It is also found in high histamine foods, so these are often included in histamine food lists. Other foods (and more frequently medications) work the other way, by inhibiting the natural production of the enzyme DAO which breaks down consumed histamine.
Is histamine bad, do I need to avoid foods containing them?
No, if your body is working normally then there is no need to avoid high histamine foods. Low histamine diets are usually recommended for people with a histamine intolerance and this does not apply to the general population.
Can we inactivate histamine in the food we eat?
Some food allergens can be destroyed by processing, high heat or freezing. This is not the case with histamine as it is not an allergen and the amount of histamine in foods is not reduced by further processing.
Allergy UK - Histamine Intolerance
Histamine Intolerance Awareness
Patient UK - Antihistamines
Patient UK - H2 Blockers
Allergic Living - How does epinephrine work?
Science Direct – Histamine N-Methyltransferase
Science Direct – Histamine Receptor
Articles and Journals
Chitosan edible coating: a potential control of toxic biogenic amines and enhancing the quality and shelf life of chilled tuna filets, 2023
Low-Histamine Diets: Is the Exclusion of Foods Justified by Their Histamine Content? 2021
Food Intolerance: The Role of Histamine, 2021
Histamine, histamine receptors, and anti-histamines in the context of allergic responses, 2019
The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets, 2018
Methodologies to Identify and Analyze Genetic Polymorphisms for Human Histamine Receptors, 2017
Histamine, histamine receptors and antihistamines: new concepts, 2010
Histamine and histamine intolerance, 2007