Understanding Histamine

Understanding Histamine

Welcome.

In this guide, we're going to be talking about Histamine. The information in this document has been prepared for you to understand the role of histamine in some of the symptoms you may be experiencing such as headaches, migraines and allergies. We’ll also discuss histamine intolerance and associated genes, and most importantly how to address a histamine intolerance.

You can find out more about histamine, and many other topics in the MTHFR Support Patient Knowledge Centre (PKC). The PKC is my membership site filled with educational webinars and resources for people who want to take control of their health and better understand how they can improve their health outcomes.

Hello, I’m Carolyn

I’m the founder of MTHFR Support Australia. I am a naturopath, herbalist and nutritionist who has a Bachelor of Health Science (Naturopathy) Honours, Bachelor of Herbal Medicine, Bachelor of Naturopathy, Advanced Diploma of Naturopathy and Diploma of Nutrition, also having studied courses in genetics at Duke University and The University of Maryland in the US.

I’m a results-oriented health expert who has the ability to provide straightforward and practical advice to address your specific health issues, working with you through the entire course of your healing. My key focus is looking at how your genes impact your health and make you more susceptible to disease. You can read more about me here.

Understanding Histamine

What is histamine and why is it significant?

Histamine is like a messenger in your body. It helps your immune system fight off unwanted things like germs and allergens But sometimes, histamine can cause problems if there's too much of it or it can’t be broken down properly.

Histamine is a bioactive amine that is both synthesised in the body from the amino acid, histidine, and absorbed from food and bacteria. Histamine is found in nearly all tissues in the body, stored in the highest concentration in vascular tissue, specifically in the granules of mast cells and basophils

Most well-known for its role in allergic and inflammatory processes, histamine plays an important role in a range of physiological functions.

Histamine isn't just about allergies. It also helps control things like how awake you feel, how your stomach digests food, and even how you breathe But when there's too much histamine or it can’t be broken down properly, it can lead to headaches, migraines, tummy troubles, and other issues.

Histamine is found in many foods and drinks, like aged cheese, wine, and certain fruits. It's also released in your body in response to stress, infections, and allergies.

Understanding histamine and how it affects your body can help you manage symptoms and feel better. By making small changes to your diet and lifestyle, you can help keep histamine levels in check and enjoy better health.

What is histamine and why is it significant?

Do you know that allergies, headaches and migraines affect more than 34% of the population at some point in their lives? Australia has one of the highest rates of allergies in the world.

Why?

We believe that allergies, headaches and migraines are primarily caused by a histamine excess. Histamine is a signalling molecule that is triggered by some sort of inflammatory response – it may be triggered by mast cells due to exposure to mould, viruses similar to COVID-19, bacterial toxins such as (Lipopolysaccharides or LPS) due to gut bacteria and much more.

For some of you, your genes make these reactions worse. For example, you may not be able to break histamine down effectively, or you may not produce enough diamine oxidase enzyme in the gut to help you break food-based histamine down, which leads to reactions and symptoms when this histamine is triggered.

What are Mast Cells?

Mast cells, often referred to as the guardians of the immune system, are specialised cells crucial for the body's defence against pathogens. These cells are strategically positioned in various tissues throughout the body, particularly in areas where the body interacts with the external environment, such as the skin, lungs, and digestive system One of their primary roles is to initiate the inflammatory response as a part of the immune system's defence mechanism.

Mast cells are equipped with granules containing a variety of potent substances, including histamine, which is a key player in allergic reactions. When the body detects a potential threat, mast cells release these granules, triggering a cascade of immune responses While this process is essential for combating infections and promoting healing, an overactive or hypersensitive mast cell response can lead to chronic inflammation and a range of health issues.

Mechanism of action - Mast cells and histamine

Histamine, released by mast cells, is particularly noteworthy due to its involvement in allergic reactions and inflammatory responses. In individuals with histamine intolerance or mast cell disorders, even mild stimuli can lead to an excessive release of histamine, contributing to symptoms such as itching, hives, digestive issues, and respiratory distress.

Understanding the intricate role of mast cells and histamine in the immune system is crucial for unravelling the complexities of histamine-related conditions and developing effective strategies for management.

Understanding Histamine

Histamine Intolerance

After histamine is consumed and/or released by mast cells, it is broken down by specific enzymes. In the central nervous system, it is metabolised by histamine N-methyltransferase (HNMT), while in the digestive tract, it is broken down by diamine oxidase (DAO).

Histamine intolerance describes a condition in which histamine is unable to be catabolised faster than it is either consumed or released, leading to histamine-mediated adverse reactions. This is thought to be due to a deficiency in DAO enzymes.

Histamine may build up in the body due to ingested histamine from foods, from foods that liberate histamine from mast cells and/or in response to an allergen.

Symptoms associated with histamine intolerance may include:

Sneezing

Headaches especially after eating certain foods or alcohol

PMS and period pain

Anxiety

Migraines triggered by your menstrual cycle

Eczema

Fatigue

Hives

Runny watery eyes

Itchy eyes

Runny nose when exposed to cold air

Stomach cramps after eating certain foods

Explosive diarrhoea after eating certain foods

Flushed red face when you drink alcohol

Genes and Histamine Understanding Histamine

DAO

The enzyme diamine oxidase (DAO) is the major enzyme involved in histamine metabolism and is responsible for ensuring a steady histamine level required for the balance of numerous chemical reactions taking place in the body.

DAO is the key enzyme responsible for the degradation of extracellular (free) histamine, regardless of whether the histamine originates from allergy-induced processes in the body or is consumed with food

The activity of DAO determines the rate of histamine breakdown.

If the activity of DAO is inhibited, histamine will accumulate in the blood.

The DAO enzyme is dependent on vitamins B6, B12, iron, copper and vitamin C, so it would be helpful to increase their intake. Copper and Vitamin C are crucial components of the DAO enzyme and Vitamin B6 is a key cofactor that enables DAO to degrade histamine Copper deficiency is another possible cause for low DAO activity, as copper is a central atom of the DAO and is thus essential for its function. Together with the copper levels, zinc levels should be checked at the same time, as zinc prevents intestinal copper absorption.

Medications/Drugs affecting DAO enzymes

The changed production of DAO enzyme can be a consequence from the use of certain medications, including;

Non-steroidal anti-inflammatory drugs (Ibuprofen, Aspirin)

Antidepressants (Cymbalta, Effexor, Prozac, Zoloft)

Immune modulators (Humira, Enbrel, Plaquenil)

Antiarrhythmics (Propanolol, Metaprolol, Cardizem, Norvasc)

Antihistamines (Allegra, Zyrtec, Benadryl)

Histamine (H2) blockers (Tagamet, Pepcid, Zantac)

Understanding Histamine

HNMT

Histamine N-methyltransferase (HNMT) is the other gene that plays an important role in regulating histamine.

HNMT breaks down the histamine intracellularly and it inactivates histamine by transferring a methyl group from S-adenosyl-L-methionine to histamine (aka N-methylation).

HNMT is expressed in many human tissues, with the highest levels found in the liver. HNMT is expressed in the kidneys, bronchi and trachea and is responsible for degrading endogenous histamine.

А single nucleotide polymorphism (SNP) in the HNMT gene can prevent efficient histamine catabolism and result in histamine build up.

Medications/Drugs affecting HNMT

Medications that block Histamine N-Methyl Transferase (HNMT):

Chloroquine (Amodiaquin, an antimalarial)

Hydroxychloroquine

Pyrimethamine

Promethazine

Chloroguanil

Diphenhydramine (H1 antihistamine, Benedryl, but can slightly increase DAO activity also)

folate antagonists such as metoprine (HNMT requires folate for activity)

Tacrine (anticholinesterase, early Alzheimer's drug)

Do you want to check your genes to see if you have a histamine problem? Purchase our complete GENE test to find out. I want to test my genes

Why is histamine intolerance becoming more

of a

concern in people? Understanding

There are numerous reasons for this; a few of the main presenting reasons are:

Hormone imbalances - Mast cells have oestrogen receptors and when they bind, histamine is released. In women who are genetically predisposed to oestrogenic conditions, are exposed to xenoestrogens or hormonal contraceptives, this action can be exacerbated. Oestrogen can also downregulate DAO enzyme activity, aggravating the situation. At times of the menstrual cycle when oestrogen is higher, symptoms associated with histamine intolerance are more likely to appear. Women with oestrogen conditions, such as endometriosis, menstrual migraines and dysmenorrhoea are more likely to suffer from allergic diseases.

Gut dysfunction - gut dysbiosis, specifically SIBO, can disrupt the gastrointestinal mucosa and subsequently reduce DAO activity, leading to a build-up of histamine. Another mechanism by which gut dysbiosis leads to histamine excess is due to high levels of decarboxylase-containing bacteria that enhance the synthesis of histamine from histidine.

“Healthy diets” - Many of the foods that are considered universally healthy are also high in histamine. This is generally not a problem if you are not managing histamine intolerance or you have a varied diet. A paleo diet, for instance, is high in histaminecontaining and liberating foods, such as nuts, chilli, tomatoes, soy, spinach, bacon, liver, tinned fish etc. Add on top of this that fermented foods are more readily available than ever before; sauerkraut, kombucha and bone broth may all be contributing to histamine buildup.

Gut Health Understanding Histamine

The histamine content of foods increases over time as a result of microbial fermentation This process is facilitated by some species of bacteria found in the gut (a.k.a. histamineproducing bacteria) such as:

- Lactobacillus species: Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus delbrueckii, Lactobacillus lactis, and Lactobacillus reuteri.

- Enterococcus species: Enterococcus faecalis, and some types of E coli

- Klebsiella

- Enterobacter and citrobacter

To maintain balance, certain types of bacteria degrade histamine.

These histamine-degrading bacteria are:

- Bifidobacteria species: particularly Bifidobacterium infantis.

- Lactobacillus species: Lactobacillus gasseri, Lactobacillus Plantarum, Lactobacillus rhamnosus, and Lactobacillus salivarius.

If the histamine-producing bacteria proliferates and outnumbers the histamine-degrading bacteria, histamine build-up occurs This overwhelms the ability of the histamine-degrading bacteria to break down the excess histamine which causes the symptoms of histamine intolerance to appear.

This gut flora imbalance is otherwise known as gut dysbiosis or SIBO, which stands for Small Intestine Bacterial Overgrowth. SIBO is one of the main reasons why histamine intolerance has become prevalent over the past 20 years

Gastric Secretion

Histamine is found in large amounts in the stomach lining where it also plays a role in gastric acid secretion.

Gastric acids facilitate digestion of proteins and the absorption of vitamins and minerals. They also inhibit bacterial growth, which helps prevent enteric infections and SIBO. A peptide hormone called gastrin elicits the release of histamine which stimulates the cells to secrete gastric acids. This is the basis of using histamine blockers in the management of gastrointestinal ulcers, gastrinoma, and gastritis.

Histamine and Food Sources Understanding Histamine

Blood histamine concentrations of 0.3-1.0 ng/ml are considered normal (however from a functional medicine range we are looking more at 0.3-0.6 ng/ml being the norm), and anything higher gives rise to histamine-mediated symptoms.

Even healthy individuals with no gastrointestinal problems can develop symptoms (i.e. severe headaches, allergy-like symptoms, hives, rashes, redness, sneezing) due to ingestion of excessive amounts of histamine.

Some foods are not high in histamine but may also trigger symptoms by causing histamine levels to rise. These foods are known as histamine liberators and they include food substances such as additives, crustaceans, citrus fruits, and egg whites.

Unlike true food allergies or sensitivities, the symptoms of histamine intolerance do not develop immediately. The response to the intolerance is concentration-dependent and cumulative, meaning it is triggered only when the threshold is reached. This is what makes histamine intolerance a bit challenging to recognise.

It can also be difficult to pinpoint which particular food triggers the symptoms, especially since the amount of histamine in food varies and is dependent on the foods ripeness, processing, and duration of storage.

Understanding Histamine

How to address a histamine intolerance

Thankfully, histamine intolerance is usually transient and is dependent on the consumption of allergens and/or high-histamine foods.

Think of histamine as a build-up, the filling up of a cup. Only once the cup is full, should symptoms appear This cup is easily filled by known allergens that trigger an IgE-mediated allergic response, but filling the cup with histamine-containing or liberating foods is generally a much slower process.

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Understanding Histamine

Methods to reduce histamine build-up:

Reduce inflammation – using nutrients such as quercetin, resveratrol, turmeric

Address why the mast cells are activated – Lyme, mould, bacteria, viruses, allergies

Support healthy detoxification

Eliminate toxins, including xeno-oestrogens

Address gut dysbiosis & restore gut function

Support key nutrients (B6, SAMe, L-methionine, zinc, betaine hydrochloride)

Reduce high histamine foods and consume only low histamine foods and non-liberator foods until symptoms have reduced. See our ‘Fixing Your Histamine Problems eBook inside our Ultimate Allergy, Headaches and Histamine Solutions Bundle’. This guide includes food plans, recipes and high-histamine food lists.

Consider natural antihistamine supplemvents and herbs;

> Quercetin

> Skullcap

> Eyebright

> White mulberry

> Bromelain

> Vitamin C

> Calcium

> Stinging nettles

Discovertheunderlyinggenetics,nutrientdeficiencies,hormonal andimmuneimbalancescausingyourrecurringproblemsand howtotreatthemNATURALLY.

Foods High in Histamines

The following foods contain high levels of histamines;

Fermented alcoholic beverages, especially wine, champagne and beer

Fermented foods: sauerkraut, vinegar, soy sauce, kefir, yoghurt, kombucha, etc.

Vinegar-containing foods: pickles, mayonnaise, olives

Cured meats: bacon, salami, pepperoni, luncheon meats and hot dogs

Soured foods: sour cream, sour milk, buttermilk, soured bread, etc.

Dried fruit: apricots, prunes, dates, figs, raisins

Most citrus fruits

Aged cheese including goat cheese

Nuts: walnuts, cashews, and peanuts

Vegetables: avocados, eggplant, spinach, and tomatoes

Smoked fish and certain species of fish: mackerel, mahi-mahi, tuna, anchovies, sardines

Processed foods of all types – Preservatives are high in histamines

Understanding Histamine

Histamine-Releasing Foods

These foods do not necessarily contain histamine but they liberate histamine from mast cells and reduce DAO enzyme activity.

Alcohol

Bananas

Black tea

Chocolate

Cow’s Milk

Energy drinks

Nuts

Papaya

Pineapple

Shellfish

Strawberries

Tomatoes

Wheat

Germ

Many artificial preservatives and dyes

Yerba Mate tea

Green tea

Can you reduce histamine too much or not have enough histamine?

Histamine is generally found in low levels in the blood and due to it being able to be synthesised in the absence of food sources, low levels of histamine are uncommon. Due to its role as a neurotransmitter, histamine is involved in arousal, pain perception and helps regulate some stress hormones.

Clinically it has been observed that patients with low histamine levels present with symptoms such as low moods, poor motivation and anxiety. Specific conditions in which low histamine may be found include schizophrenia, alcoholism and dementia. This process, although theoretically and clinically interesting, has not been scientifically validated at this stage.

Low Histamine Foods

Eat these liberally.

Freshly Cooked Meat and Poultry

Freshly Caught Fish

Extra Virgin Olive Oil

Pasture-Raised Eggs

Gluten-Free Grains: brown rice & quinoa

Fresh Fruits: Other than citrus, avocado, tomato, pineapple, bananas and strawberries

Fresh Vegetables (except spinach and eggplant)

Coconut milk, Rice milk, Hemp milk, Almond milk

Coconut oil

Grass-fed Butter/Ghee

Organic coffee

Almond butter

Leafy herbs

Herbal teas

Going on a low histamine diet is the most logical solution if our intent is to lower overall histamine levels. Sticking to a low histamine diet for a considerable period of time (or until you can stabilise mast cells and maintain healthy histamine levels) has been proven to relieve symptoms of histamine intolerance in most cases. Identifying specific trigger foods by starting an accurate food diary instead of indefinitely going on a strict low histamine diet is also an option.

Understanding Histamine

References

1.

Comas-Basté, O. et al. (2020). Histamine Intolerance: The Current State of the Art. Biomolecules. 10(8). <https://www.mdpi.com/2218-273X/10/8/1181>.

2.

Galli, S.J. & Tsai, M. (2012). IgE and mast cells in allergic disease. Nat Med. 18 (5). <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597223/>

3.

Hrubisko, M. et al. (2021). Histamine Intolerance: the more we know the less we know. A review. Nutrients. 13 (2228). <https://www.mdpi.com/2072-6643/13/7/2228>.

4.

Krystal-Whittemore, M. et al. (2016). Mast Cell: A multi-functional master cell. Frontiers in Immunology, Vol. 6. <https://www.frontiersin.org/articles/10.3389/fimmu.2015.00620/full>.

Kunder, C.A. et al. (2011) Mast cell modulation of the vascular and lymphatic endothelium. Blood, 118 (20). <https://ashpublications.org/blood/article/118/20/5383/29763/Mast-cell-modulation-ofthe-vascular-and-lymphatic>.

5. Marrion, G. (2018). The relationship between histamine, oestrogen, progesterone and cortisol. FX Medicine. <https://www.fxmedicine.com.au/blog-post/relationship-between-histamine-oestrogenprogesterone-and-cortisol>.

6. Pal, S. et al. (2020). Emerging Roles of Mast Cells in the Regulation of Lymphatic Immuno- Physiology. Frontiers in Immunology. Vol. 11. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311670/>.

7. San Mauri Martin, I. et al. (2016). Histamine Intolerance and dietary management: A complete review. Allergologia et Immunopathologia, Vol. 44, Issue 5. <https://www.sciencedirect.com/science/article/abs/pii/S0301054616300775#>

8. Schink, M. (2018). Microbial Patterns in Patients with Histamine Intolerance. Journal of Physiology and Pharmacology, 69 (4). <https://www.deficitdao.org/wp-content/uploads/2018/12/MICROBIALPATTERNS-IN-PATIENTS-WITH-HISTAMINE-INTOLERANCE.pdf>

10.

9. Schnedl, W.J. & Enko, D. (2021). Histamine Intolerance Originates in the Gut. Nutrients, 13 (4). <https://www.mdpi.com/2072-6643/13/4/1262>.

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Thank you so much for taking the time to read this document. I hope it has been useful for you.

At MTHFR Support, we create better health through science and genetics, empowering you with knowledge and support of underlying issues, allowing you to gain back control of your health and live your best life.

I hope to meet you again soon,

Carolyn