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Histamine Intolerance Issues - why?

Histamine intolerance is not an illness but rather a symptom of underlying health conditions.

It is when the accumulation of histamine is beyond the body’s capacity to process it. The root cause needs to be found and treated. Eating histamine free foods is not treating the root cause. Finding out why the body makes too much histamine, or doesn’t break it down well is finding out the root cause.


What is Histamine and why do we get intolerance issues?


A vasoactive amine that dilates our blood vessels allowing for an inflammatory response to occur. It plays an important role in the early acute inflammatory response. When we are exposed to substances our body decides shouldn't be there, stored Histamine is released by white blood cells. Those cells can be mast cells which are quick acting and can be anaphylactic. Other cells include basophils and platelets when required. This can be when there is tissue injury; constriction of smooth muscle in our bronchioles (asthma); or constriction of smooth muscle in the uterus (period cramps & pain).


Histamine is required to stimulate gastric secretions (HCl), to stimulate mucous secretion and to stimulate oestrogen. It is also a neurotransmitter that controls and regulates other neurotransmitters. In the brain, it is an excitatory neurotransmitter and there are potential links with excitatory mood issues.


It is when histamine is out of balance that we have issues. A low grade, chronic inflammatory response can cause excess histamine for example, and this can happen if our body is trying to remove substances it has determined shouldn't be present, over a long period of time. Some of our modern lifestyle factors can contribute to this.


Histamine Intolerance symptoms


Many varied symptoms as the graphic shows, including migraines, nasal congestion, anxiety, hives, chronic reflux, insomnia, heart palpitations, nausea, bloating, digestive issues, irregular menstrual cycle, painful menstrual cycle, dizziness, asthma, sinus issues, gas and bloating and many more.

Picture showing the body and the multiple issues Histamine intolerance can present as
Histamine Intolerance can show signs all over the body.

What are the many and varied causes of Histamine Intolerance?


The graphic shows how Histamine Intolerance can begin. Additionally, the long list below gives an insight into the process of determining the root cause. It can be a slow process to uncover the cause.

Graphic showing the multiple causes behind Histamine Intolerance
The multiple causes behind histamine intolerance.

When we start investigating the root cause of histamine intolerance, we start in the gut.

As Hippocrates said - "All disease begins in the gut".

1. Imbalance of Gut Bacteria – the majority of people have gut issues, where we get increased histamine, and have a reduction of DAO enzyme that breaks Histamine down. Initially we may have gut issues (reflux, bloating, cramping, diarrhoea), and if histamine breaks through gut to the bloodstream we may get hives, migraines, heart palpitations, anxiety, insomnia, and vertigo. Types of gut issues include:

a. SIBO (Small intestinal bacterial overgrowth), or dysbiosis in the small intestine. Bacteria lodge in the small intestine. They are usually found in the large intestine producing healthy short chain fatty acids - SCFA, and whose job is to break down vegetables/ starches. If they have relocated to the small intestine, and break down fibres, they produce gas (hydrogen, methane, hydrogen sulphide). Hence we can experience bloating, belching, flatulence, abdominal pain, nausea, constipation, diarrhoea, malabsorption, weight loss, and malnutrition. The gases produced reduce the DAO enzyme that is responsible for breaking down histamine, as the gases damage the microvilli in our gut wall that stores DAO. Additionally, excessive harmful bacteria release LPS (lipopolysaccharides) that increases the Histidine conversion to Histamine so this results in an increase in Histamine. LPS can trigger an immune reaction, that triggers inflammation, that damages gut wall cells, that leads to 'leaky gut' allowing histamine to cross into the bloodstream. Zonulin regulates the gut integrity, and it gets released upon insult. Histamine intolerance is therefore related to increased zonulin levels.

b. SIFO (Small intestinal fungal overgrowth) - Yeast and Candida contain oxalates that cause tissue damage and subsequent histamine release. Additionally, fungus can act like penicillin antibiotic so it can alter the gut microbiome, and increase histamine release from mast cells.

c. Starch and Carbohydrate Malabsorption – Dysbiotic bacteria ferment FODMAP foods (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols) in the small intestine when this should normally happen in the large intestine. As a result, inflammation can occur in the small intestine.

d. Inflammation – Inflammatory 'pathogens' stimulate the release of histamine and cause leaky gut allowing histamine into our blood stream causing systemic symptoms. It requires a well functioning immune system. The majority of our front-line immune response is in our gut known as secretory IgA and if you are low in this, your ability to defend is low.

e. Leaky gut - Histamine release can damage the microvilli enabling undigested foods to pass into the bloodstream and cause an inflammatory response.

f. Overgrowth of histamine producing bacteria – LPS (lipopolysaccharides toxins) that are present on the outer membrane of Gram-negative bacteria e.g H. pylori, E. coli, Klebsiella, Pseudomonas, Campylobacter, Salmonella), can increase histamine.


2. H.pylori – Gram-negative bacteria that releases LPS with subsequent mucosal damage that stimulates mast cells to release histamine.


3. Digestive Enzyme Insufficiency – Digestive enzymes prevent a build-up of histamine as Hydrochloric acid (HCL), pancreatic juices and bile are all antimicrobial. HCl is secreted by stomach, is lovely and acidic, and breaks down food. It also then stimulates bile and pancreatic juices (that contain sodium bicarbonate which is alkaline). They pour into the Small Intestine which is where we want it to be alkaline. An acidic environment in the small intestine is favourable for bacteria we don't want there, so we want good enzymes to help create an alkaline environment. Less HCl breakdown of food = more food for bacteria to eat, enabling them to dominate, and it leads to SIBO. SIBO increases inflammation, reduces DAO activity, leading to increased histamine. In this situation, once histamine is released, THEN HCl gets released that leads to reflux at the WRONG time. Dietary changes can assist improve this.

4. Gluten intolerance – gluten resists digestion, and can cause Zonulin to be released, not only in people with Coeliac Disease. Zonulin can then disassemble tight junctions in our small intestine, and lead to leaky gut. Unwanted pathogens can get through the gut wall, cause inflammation, and histamine can get released. The causes are firstly Coeliac disease, where there is flattened microvilli where DAO is located, so there is a reduced ability to breakdown histamine. Wheat allergy is another cause. Wheat is recognised by the body as an antigen, and the body makes IgE. The IgE binds to receptors on mast cells and basophils, and histamine released (rapidly). This is known as a Type I hypersensitivity reactions (rapid) – that can lead to anaphylaxis, asthma, atopic dermatitis, hives. A Type IV (12-72 hours) reaction can also occur in those people that are non-coeliac gluten sensitivity, and gut inflammation and leaky gut are present.


5. Mast Cell Activation Syndrome (MCAS) - MCAS can occur from mould, heavy metals and glyphosate exposure. Glyphosphate is a weed spray used on crops. It is normal for mast cells to release histamine, but in MCAS they’re hyperactive and release histamine, cytokines, prostaglandins, interleukins, heparin which are all inflammatory. This hyperactive state can’t be switched off, hence chronic inflammation persists and histamine intolerance develops.


6. Oxalates – are found in foods. We also make them when our bodies are under stress, and Candida can produce them. Oxalates can bind up our nutrients and make us deficient. We can become deficient in Calcium, magnesium, and Vitamin B6. You can also get kidney stones from oxalates. Interestingly, unabsorbed fat from bile insufficiency also binds to calcium, and given bile insufficiency can also occur in people with histamine issues, it can become interesting to tease apart. Oxalates can also occur in kidney stones. Interestingly oxalates can get stored in connective tissue where there may be previous injuries that over time get even more painful. It may not been an autoimmune issue with joint pains, but rather an oxalate issue.


7. Candida – Candida comes from a high sugary diet and can liberate oxalates.


8. Inflammatory Bowel Disease (IBD) – inflammation from it leads to a reduction of DAO enzyme, and a subsequent increase in histamine release. More histamine with little ability to break it down.


9. High Histamine Containing Foods – high histamine foods, foods containing other biogenic amines, histamine liberators, and DAO enzyme inhibitors (like alcohol and chocolate can prevent our DAO enzyme from breaking down histamine). A lot of us have resorted to nut milks, and nut flours which all contain oxalates which as we've seen above can cause histamine issues. Enjoy foods in moderation, and eat foods that are seasonal. Live like our ancestors did.


10. Oestrogen – if we are constipated, we may experience detoxification issues with oestrogen, as we need need daily bowel movements to eliminate detoxified hormones. Unfortunately, B-glucuronidase enzymes from certain bacteria in our gut can deconjugate, or uncouple bound up oestrogen, histamine and bile that was ready for elimination. This then results in recirculating oestrogen, now in excess as new oestrogen has been produced by the body. Excess oestrogen down-regulates the DAO enzyme. Oestrogen can also stimulate the release of histamine from mast cells. Histamine also stimulates the ovaries to make even more oestrogen. This cycle goes round and around. Oestrogen leads to Histamine release, that leads to recirculating oestrogen etc. Think of this if you have high oestrogen symptoms like endometriosis, painful and heavy menstrual cycles etc.


11. Methylation issues – if you have histamine issues, gut issues and oestrogen excess, then you won’t be methylating properly, and methylation is required for many purposes in the body. In relation to histamine, methylation is required for the HNMT enzyme (which breaks down histamine in the brain) and COMT enzyme (which detoxifies oestrogen in the liver).


Methylation BREAKS DOWN Histamine, and Methylation requires good nutrition.

Methylation is needed to break down histamine but without clearing high histamine first, methylated folate, B12 and SAMe supplements can make your histamine issues worse. We take this slowly in treatment.


12. Genetic polymorphisms – MTHFR, DAO, HNMT, COMT are genes that code for enzymes that perform functions in our bodies. Methylation is required for HNMT and COMT to work. If COMT is not working, you can get oestrogen detoxification issues, and increased oestrogen can lead to increased histamine. DAO in particular impacts how sensitive you are to the environment, particularly food and toxins. It impacts your response to histamine, which in turn can influence how sensitive or allergic you are to various foods. Issues with DAO can create itchy skin, hives, runny nose, leaky gut, food sensitivities, SIBO, migraines, nausea/indigestion, pregnancy complications, and irritability.

The wonderful news is that genetics can be altered through dietary and lifestyle changes (this is the science of Nutrigenomics).

13. Medications - can interfere with histamine breakdown.


14. Nutritional deficiencies - The DAO enzyme that breaks down extra-cellular histamine needs calcium and copper. The HNMT enzyme that breaks down intracellular histamine in our brain needs good methylation (that needs folate and Vitamin B12 to produce SAMe). The MAO-B enzyme needs Vitamin B2 to continue the HNMT breakdown. Many other vitamins and minerals are required to drive the bodily processes. To make it worse, the methylation process suffers under high histamine conditions as it is in high demand. The required cofactors get easily consumed. Our neurotransmitters, and our most powerful antioxidant Glutathione can start suffering. We can see signs of this on blood tests with our Homocysteine levels. It is easy to see why histamine issues present with so many symptoms.


15. Vigorous exercise - Finally, you may get really itchy or flush easily when you exercise intensely. Who needs an excuse not to exercise so hard?


Radial chart showing diversity of symptoms caused by Histamine and organs in the body it impacts
A reminder of the diversity of Histamine Symptoms and their effects

Image from: Maintz, L & Novak, N, (2007) 'Histamine and Histamine Intolerance'


How to test for Histamine Intolerance?

Find out the root cause. Don't jump to conclusions. Not everyone has Mast Cell Activation Syndrome from mould exposure. Start by testing the gut microbiome first as the majority of histamine intolerance stems from inflammatory issues in the gut. Inflammation drives histamine issues. With the majority of our immune system in our gut monitoring us for inflammation, you can understand why testing starts first in the gut. Many, many further additional tests are available depending on your signs and symptoms, and how much information you want to know. It is best to take the investigation of histamine issues step by step and narrow it down. Working with a qualified naturopath who is experienced in dealing with histamine issues can help with this. I can do that for you.


Histamine Intolerance Issues - Beyond the why to what next?

Once confirmation of the cause has been found, we can work together to repair the situation. A lot simply comes down to dietary and lifestyle changes. If you would like to discuss your Histamine Intolerance issues with me, please make a booking on my website bookings page via the booking link below. I'd only be too happy to assist you.


My pathology background means I am very experienced in interpreting general pathology and more detailed functional test results. I can simplify the results so you understand what is going on easily. We can then start assisting you early and with confidence!


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