You are currently viewing Histamine Intolerance : Symptoms, Causes, And Treatment

Histamine Intolerance : Symptoms, Causes, And Treatment

If you suffer from food allergies, then you’ve likely experienced the following scenario. If so much as one crumb of the offending fare lands on your tongue – it can feel like your immune system is hunkering down for war. Cue abdominal pain, uncontrollable diarrhoea, hives, and even potentially fatal symptoms like shortness of breath. All these are typical food allergy symptoms. But wait. Why do you also struggle with chronic headaches, sleep disturbances, and unexplained anxiety attacks? Well, here’s a thought. What if your so-called food allergies aren’t food allergies… but a sign of histamine intolerance instead? Hista–what? Don’t worry.

This article will cover everything you need to know about the condition so you can determine if you have indeed been struggling with food allergies–or have something new to consider (i.e. histamine intolerance).

An introduction to histamine

Chances are, you’ve popped an antihistamine pill or two (e.g. Zyrtec, Claritin, and Allegra) at some point in your life, and already have an idea of what histamine is. Regardless. Histamine is a chemical your body makes that plays several different roles, but its primary function is to help your body eliminate allergens. Here’s how it works.

When you come across an allergen/harmful substance, your immune system launches a chain reaction to protect you. First, it sends a chemical signal to the ‘mast cells’–a type of white blood cell found in connective tissue–in your skin, lungs, nose, mouth, gut, and blood to release histamines (along with other mediators, including tryptase and heparin). And once released, histamines boost blood flow in the area of your body affected by the allergen; this causes inflammation. The result? If your nose is affected (e.g. pollen), histamines prompt your membranes to produce more mucus. This helps ‘flush out’ the offending allergen.

What is histamine intolerance?

As explained earlier, histamine’s actions are great for protecting your body against allergens. Unfortunately, though, this doesn’t hold for individuals with histamine intolerance. Just so you know: histamine intolerance is not a sensitivity to histamine as implied by its name, but an indication that too much of it has built up in the body. This condition is relatively rare; it impacts an estimated 1% – 3% of the population. However, scientists postulate an increase in prevalence as medical experts (and the society at large) increasingly becomes aware of histamine intolerance.

Histamine intolerance symptoms

As histamine can influence various parts of your body (skin, lungs, nose, mouth, gut, and blood), symptoms of an intolerance are broad and can easily be confused for other things. For instance, food allergies. That said, some of the most common histamine intolerance symptoms to be aware of include:
  • Itchy skin, eyes, ears, and nose
  • Eczema or other types of dermatitis
  • Red eyes
  • Hives
  • Facial swelling or other tissues swelling
  • Tightness in the throat
  • Difficulty regulating body temperature
  • A drop in blood pressure when standing up quickly
  • Vertigo or dizziness
  • Fast heartbeat
  • Heart palpitations
  • Sleep disturbances
  • Anxiety or panic attacks
  • Runny nose and congestion
  • Headaches and migraines
  • Digestive issues like diarrhoea and acid reflux
  • Abnormal menstrual cycle
Less common symptoms also include low blood pressure, tremors, and loss of consciousness.

What’s causing your histamine intolerance?

Your body contains 2 different enzymes that work to break down histamine: diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). Following this line of thought, histamine intolerance generally occurs when either–or both–of these enzymes aren’t working correctly, which can lead to a histamine build-up. In addition to the reduced enzymatic activity of DAO and HNMT in the body, another factor is simply an abnormal increase in the amount of histamine the body produces. To sum it all up, histamine intolerance can be attributed to disequilibrium of accumulated histamine and the body’s capacity for histamine degradation.

Below, find the common causes of histamine intolerances–and how it leads to the condition, specifically (i.e. does it decrease the efficiency of DAO/HNMT or increase the amount of histamine the body produces?)

Mastocytosis

>Mastocytosis is a rare immune disordertypically caused by a genetic mutation. There are 2 main types of mastocytosis: cutaneous and systemic. Cutaneous mastocytosis occurs when mast cells accumulate in the skin; systemic mastocytosis, on the other hand, occurs when mast cells accumulate in the internal organs, including the liver, spleen, small intestine, or bone marrow. Here’s something important to remember, mast cells are responsible for producing histamine. What happens when an individual with mastocytosis is exposed to an allergen/harmful substance? That’s right. An abnormally high histamine release (due to the huge numbers of mast cells present in the body).

Gut infections

Gut infections (be it microbial or fungal) and histamine intolerance often go hand in hand and can take different forms. Find a brief discussion of the various gut infections that have been linked to histamine intolerance below:
  • Helicobacter Pylori (H. pylori) – A common type of bacteria that grows in the digestive tract and affects roughly 50% of the adult population. Although research into the connection between H. pylori and histamine is in its initial stages, studies have shown that the bacteria can cause the gut lining’s mast cells to produce more histamine (i.e. an underlying factor of histamine intolerance).

  • Small intestinal bacterial overgrowth (SIBO) – A serious condition involving an abnormal increase in the overall bacterial population in the small intestine, particularly types of bacteria not commonly found in that part of the digestive tract. The gut microbes of an individual diagnosed with SIBO may produce large amounts of histamine. When this happens, the DAO and HNMT enzymes may fail to break down all the released histamine–in turn, causing histamine intolerance.

  • Intestinal parasites – Organisms that infect the small and large intestine, including worms (e.g. roundworms, tapeworms, pinworms, and hookworms), protozoa, and yeast. Remember how your mast cells release histamine–in addition to other inflammatory agents–during an immune response? Well, your immune system sees parasites as a threat, too. That means they’ll signal your mast cells to continue releasing histamine as long as the parasites are present. In turn, leading to histamine intolerance as the histamine breakdown rate is unable to match its release.

Certain medications

Some evidence also suggests that agents in certain medications–including nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, and antibiotics–can block DAO from doing its job in the body or prevent the production of the enzyme, which might cause an uptick in histamine levels.

How to determine if you have a histamine intolerance

Unfortunately, a reliable lab test or procedure that can provide a firm histamine intolerance diagnosis doesn’t exist – yet. Generally, you’ll need to experience at least 2 or more typical histamine intolerance symptoms (e.g. chronic migraines and heart palpitations) before your doctor will even consider the possibility of the condition. And even then, he/she will need to rule out other potential causes.

Your doctor might also collect a blood sample to analyse if you have a DAO deficiency. According to a 2015 review published in Clinical and Translational Allergy, individuals with DAO levels under 3kU/mL were more likely to react to high-histamine foods. In contrast, histamine intolerance was unlikely when DAO was over 10 kU/mL. Another way to ‘diagnose’ histamine intolerance is through a prick test. Researchers in a 2011 study published in ISRN Allergy pricked the skin of 156 participants–then applied a 1% histamine solution. 82% of individuals with histamine intolerance maintained a wheal size greater than 3 mm that didn’t resolve within 50 minutes, in contrast to only 18% in the controls group.

However, this bears repeating: neither of the tests mentioned above can definitely diagnose an intolerance. Your doctor will have to consider the results of your tests (if any) in conjunction with your food diary, health history, and any other relevant medical data.

Treatment and prevention of histamine intolerance

The treatment of histamine intolerance hinges on introducing a histamine-elimination diet (which will be covered more in-depth in a bit). There are also medications and other tactics you could use in coordination with diet modifications.

Histamine-elimination diet

A histamine-elimination diet is a type of elimination diet that tries to pinpoint ‘trigger foods’ by slowing taking out histamine-rich foods and logging symptoms. For instance, suppose you notice an improvement in your symptoms after removing a trigger food (e.g. cheese). In that case, you can omit that food temporarily and attempt to add it back to your diet after a month. Only, at a reduced amount and frequency, depending on how you react to it. Your tolerance and symptoms determine the rate at which you eliminate and add foods back into your diet.

It’s important to note that ‘histamine-rich’ foods can be further categorised into 3 primary groups:

  • High-histamine foods – Foods that contain a high amount of histamine, so they are most often very problematic for those with histamine intolerance. Examples include:
    • Blue cheeses, mould cheeses
    • Processed cheese
    • Yoghurt
    • Dried meat
    • Wild meat
    • Avocado
  • Histamine liberators – Foods that are not high in histamine, but they cause histamine release in the body. Examples include:
    • Egg white
    • Entrails
    • Innards
    • Lobsters
    • Oysters
    • Sunflower seeds
  • DAO-blocking foods – As the name implies… Foods that block DAO, the enzyme needed to break down histamine. Examples include:
    • Energy drinks
    • Black tea
    • Sparkling white wine
    • Ethanol
    • Rum
    • Alcoholic beverages in general

It’s important to note that besides these 3 primary groups, there are also foods that rapidly form histamines as they’re highly perishable–and those that contain biogenic amines, which affect the intestinal permeability (which then stimulate the release of histamine from mast cells).

Addressing Histamine Intolerance

Typically a histamine-free diet is recommended for histamine intolerance, in combination with antihistamines to combat the symptoms (to be taken for a short period).

Nutritionists often recommend some key supplements to improve DAO function (and hence, histamine intolerance). These supplements seek to ensure adequate intake of nutrients involved in breaking down histamine, including copper and vitamins B6 and C. Studies also suggest that an adequate intake of healthy fats and other nutrients – Including phosphorus, zinc, magnesium, iron, and vitamin B12–may play a role in enhancing DAO activity. As such, scientists believe that having a deficiency in the vitamins/minerals mentioned above could be a potential cause of histamine intolerance.

Ultimately, if you suspect that you have histamine intolerance, you are advised to seek guidance from a registered nutritionist. Do not attempt to go on a histamine-elimination diet by yourself. A histamine-elimination diet is a form of restriction diet. More often than not, you will need to work with a professional, registered nutritionist to ensure that you’re getting adequate nutrients and avoid an unnecessary reduction in your quality of life while eliminating histamine-rich foods from your diet. Consulting a nutrition professional also ensures that you’re addressing all possible underlying causes of your histamine intolerance, including serious health conditions like mastocytosis and small intestinal bacterial overgrowth.

References

Carter, M. C., Metcalfe, D. D., & Komarow, H. D. (2014). Mastocytosis. Immunology and Allergy Clinics of North America, 34(1). https://doi.org/10.1016/j.iac.2013.09.001

Comas-Basté, O., Sánchez-Pérez, S., Veciana-Nogués, M. T., Latorre-Moratalla, M., & Vidal-Carou, M. del C. (2020). Histamine Intolerance: The Current State of the Art. Biomolecules, 10(8). https://doi.org/10.3390/biom10081181

Ghoshal, U. C., Shukla, R., Ghoshal, U., Gwee, K.-A., Ng, S. C., & Quigley, E. M. M. (2012). The Gut Microbiota and Irritable Bowel Syndrome: Friend or Foe? International Journal of Inflammation, 2012. https://doi.org/10.1155/2012/151085

Halliez, M. C. M., & Buret, A. G. (2015). Gastrointestinal Parasites and the Neural Control of Gut Functions. Frontiers in Cellular Neuroscience, 9. https://doi.org/10.3389/fncel.2015.00452

Klausz, G., Buzás, E., Scharek, P., Tiszlavicz, L., Gyulai, Z., Fülöp, A. K., Falus, A., & Mándi, Y. (2004). Effects of Helicobacter pylori infection on gastric inflammation and local cytokine production in histamine-deficient (histidine decarboxylase knock-out) mice. Immunology Letters, 94(3), 223–228. https://doi.org/10.1016/j.imlet.2004.05.005

Kofler, L., Ulmer, H., & Kofler, H. (2011). Histamine 50-Skin-Prick Test: A Tool to Diagnose Histamine Intolerance. ISRN Allergy, 2011. https://doi.org/10.5402/2011/353045

Leitner, R., Zoernpfenning, E., & Missbichler, A. (2014). Evaluation of the inhibitory effect of various drugs / active ingredients on the activity of human diamine oxidase in vitro. Clinical and Translational Allergy, 4(Suppl 3), P23. https://doi.org/10.1186/2045-7022-4-S3-P23

Lopez, C. M., Yarrarapu, S. N. S., & Mendez, M. D. (2020). Food Allergies. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK482187/

Maintz, L., & Novak, N. (2007). Histamine and histamine intolerance. The American Journal of Clinical Nutrition, 85(5), 1185–1196. https://doi.org/10.1093/ajcn/85.5.1185

Miyoshi, M., Ueno, M., Matsuo, M., Hamada, Y., Takahashi, M., Yamamoto, M., Yamamoto, I., Mikajiri, R., Tabuchi, S., Wakida, K., Yamanishi, M., Hirai, M., & Usami, M. (2017). Effect of dietary fatty acid and micronutrient intake/energy ratio on serum diamine oxidase activity in healthy women. Nutrition (Burbank, Los Angeles County, Calif.), 39–40, 67–70. https://doi.org/10.1016/j.nut.2017.03.004

Naganuma, F., Nakamura, T., Yoshikawa, T., Iida, T., Miura, Y., Kárpáti, A., Matsuzawa, T., Yanai, A., Mogi, A., Mochizuki, T., Okamura, N., & Yanai, K. (2017). Histamine N -methyltransferase regulates aggression and the sleep-wake cycle. Scientific Reports, 7(1), 15899. https://doi.org/10.1038/s41598-017-16019-8

Patel, R. H., & Mohiuddin, S. S. (2020). Biochemistry, Histamine. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK557790/

Schnedl, W. J., Schenk, M., Lackner, S., Enko, D., Mangge, H., & Forster, F. (2019). Diamine oxidase supplementation improves symptoms in patients with histamine intolerance. Food Science and Biotechnology, 28(6), 1779–1784. https://doi.org/10.1007/s10068-019-00627-3

Skypala, I. J., Williams, M., Reeves, L., Meyer, R., & Venter, C. (2015). Sensitivity to food additives, vaso-active amines and salicylates: A review of the evidence. Clinical and Translational Allergy, 5. https://doi.org/10.1186/s13601-015-0078-3

______________________________________________________________________________________________________

tracey-blog-profile-image-ibs-clinics  Posted by Tracey Randell | Lead Nutritional Therapist specialising in IBS and other gut-related issues.