Hello everyone! I know it has been a while, but I have been busy with helping some clients with some very interesting symptoms. The more and more I read about histamine, allergies and gut health, the more I am discovering about this interesting phenomenon.

Do these symptoms sound familiar to you?

Common Symptoms of Histamine Intolerance

• Abdominal cramps
• Anxiety
• Arrhythmia, or accelerated heart rate
• Difficulty falling asleep
• Difficulty regulating body temperature
• Fatigue
• Flushing
• Headaches/migraines
• Hives
• Nasal congestion, sneezing, difficulty breathing (especially after eating certain foods)
• Nausea, vomiting
• Tissue swelling
• Vertigo or dizziness
• In a Human Study, it was observed that the most common clinical symptoms of histamine intolerance are diarrhoea, nausea and vomiting, headache, itchy skin, oral allergy syndrome as well as red eyes and swollen eyelids (≥50%) (Pinzer et al., 2018).

 

    Let’s start at the beginning:

What is histamine

Histamine is a biogenic amine that is naturally found in some foods and also produced by the body (Smolinska et al., 2014). Histamine and its 4 complex receptors represent a complex system of immunoregulation, they are thought to regulate both innate and adaptive immune response cells (Ferstl et al., 2012; Smolinska et al., 2014).

Histamine can have both pro-inflammatory and anti-inflammatory effects on immunoregulatory processes, depending on which histamine receptor is activated.

Normal response: When in balance, histamine helps protect the body from foreign invaders.

In BALANCE, Histamine is meant to PROTECT our bodies in numerous ways:

1) When the immune system detects a threat:

During an invasion from external pathogens histamine is released from Mast cells and other innate immune cells. This triggers smooth muscle contraction in the intestines (often causing cramps and diarrhea), expansion of blood vessels (causing low blood pressure), mucus secretion in the nasal passages and GI tract, and many other physiologic effects (allergy-like symptoms) that are intended to fight off invaders (Maintz & Novak, 2007).

Once the perceived threat is over, histamine levels are reduced back to normal, and symptoms subside. Normally the body has two enzymes that are capable of degrading histamine: N-methyltransferase (HNMT) and diamine oxidase (DAO) or it accumulates in the body.

2) Enterochromaffin-like cells in the stomach:

Histamine is also released from cells in the stomach, where it triggers acid secretion from parietal cells, increasing the acidity of the stomach (Smolinska et al., 2014), which helps to fight off ingested pathogens.

3) Histaminergic neurons in the brain:

Histamine is produced in the brain (specifically, in the tuberomammillary nucleus of the hypothalamus), where it acts as an excitatory neurotransmitter and plays a role in regulating the sleep-wake cycle (Scammell et., 2019).

Also, mast cells respond to neurotransmitters (in the brain) and synthesize and secrete molecules (histamine) that modulate neural responses as well (Corticotropin releasing hormone, serotonin, nerve growth factor, etc.) (Martinez et al., 2012).

 

What Is Histamine Intolerance?

Histamine intolerance  is thought to result from an incorrect balance between accumulated histamine and the capacity for histamine degradation/breakdown (Smolinska et al., 2014; Pinzer et al., 2018)

This is a perpetual build-up of inflammatory and/or immune responses eventually causes symptoms that are very similar to an allergic reaction.

It is estimated that 1% of the population has histamine intolerance, and most of those are middle-aged women – 70% of histamine interlace is due to under active Diamine Oxidase (DAO). (Manzotti et al., 2016; Maintz & Noval, 2007).

Why women?

Studies have shown that estrogen regulates histamine receptors in the brain, as well as liberates histamine release from mast cells (cells that exist in the lining of our tissues), and in contrast progesterone inhibits it (Vasiadi et al., 2006). Therefor, those experiencing estrogen dominance could be suffering from histamine intolerance as well.

As you can see, histamine and its receptors are responsible for many body functions:

 

What Causes Histamine Intolerance?

1. The body has produced too much histamine: due to immune reactions or a condition like allergies or mastocytosis, in which the body has too many mast cells that release histamine (Horney et al., 2018; Smolinska et al., 2014).
2. Too much histamine is ingested (through food or alcohol): we consume a large number of biogenic amines that we are often unaware of in the form of toxins, pesticides, and preservatives (etc). If not broken down histamine accumulates in the body, which creates a viscous circle of inflammation that eventually reduces intestinal membrane permeability, dysbiosis and leaky gut (Pinzer et al., 2018; Smolinska et al., 2014; Martinez et al., 2012).
3. The degradation of histamine is impaired: Not enough N-methyltransferase (HNMT) and diamine oxidase (DAO) to break down histamine due to genetics, medications, or other medical conditions (Smolinska et al., 2014).

 

Our Microbiome is associated (of course):

They have found:

• Specific microbes within the microbiota have been described to release the biogenic amine histamine (Smolinska et al., 2014).
• Microbia that inhabit the large intestine are able to convert the amino acid histidine found in protein foods into histamine, thereby contributing to internal levels (Kohn, 2014).
• In a mice model, histamine-producing bacteria in the gut induced an immune response in the lung, suggesting that histamine in the gut can trigger symptoms elsewhere in the body (Barcik et al., 2019).
• In one study, people with histamine intolerance tend to have less “good” Bifidobacteria in their intestines, more “bad” Proteobacteria, and less microbial diversity than healthy controls, suggesting that the balance of the microbiome, its diversity and intestinal barrier dysfunction (leaky gut) are related to the development of histamine intolerance (Schink et al., 2018).

 

Histamine is liberated by STRESS!

In the GI tract, mast cells (Mast cells synthesize Histamine) are activated during a stress response (any). Mast cells respond to and produce corticotropin-releasing hormone (Cortisol- Key modulator of Stress response) (Wallon et al., 2008). Upon activation they release numerous pro-inflammatory mediators (including histamine), similarly to the immune response (but there is not always a foreign invader).

Mast cell activation has been link with stress-induced mucosal barrier impairment (leaky gut), which in turn creates more mucosal inflammation (Martinez et al., 2012; Smolinska et al., 2014).

 

This is where the viscous circle begins…

In summary: Chicken or egg scenario

Stress, high histamine (biogenic amine) foods, and certain conditions (allergies etc.) can cause our immune system to release more histamine than is needed, which eventually leads to dysbiosis and leaky gut as it accumulates in the gut. It is ALSO suggested that people who already have dysbiosis (from other reasons- eg. antibiotics or candida overgrowth) are at high risk for developing histamine intolerance as our immune system is over stimulated.

 

HOW do we know it is HIT?

The accurate diagnosis of histamine intolerance (HIT) should be based on the well-documented association between food consumption and symptoms, identification of food causing symptoms, determination of histamine content of the food causing the symptoms, exclusion of other causes (e.g., allergy, toxins, metabolites), oral histamine provocation (if possible), determination of DAO and HNMT contents and activity in intestinal mucosa (not in peripheral blood), and the analysis of DAO and HNMT genetic polymorphisms (Smolinska et al., 2014). There is no specific blood testing diagnostic tool for histamine intolerance, the span of time it takes for histamine to build up in the body is usually longer than what is allowed during testing (Kohn, 2014).

What can we do?

It is noted in the literature that the food industry needs to be more honest about the content of biogenic amines in foods and prevent patients’ misunderstanding (Martin & Garicano, 2016).

1. Try a low histamine diet for 30 days
2. Heal your gut lining
3. Incorporate low- histamine probiotics
4. Possibly use some supplements that support Histamine breakdown (DAO)
5. Add chlorella to your diet, as it inhibits histamine-mediated allergic response (Min-Jung et al., 2013)

In many cases, it may be possible to reverse histamine intolerance by healing the gut or removing whatever is inhibiting DAO activity (Maintz & Noval, 2007).

Histamine Degrading Probiotics

Optimizing gut bacteria is vital for overall health and disease prevention. Unfortunately, that’s not easy to do for those with histamine intolerance because probiotic foods (yogurt, kefir, kombucha, etc.) are high in histamine and should be avoided.

It’s important to choose probiotic supplements containing bacteria that do not produce histamine.

The following strains may be helpful because they have been found to break down (Biogenic Amines) or reduce the formation of histamine:

• Lactobacillus plantarum (link)
• Lactobacillus rhamnosus (link)
• Bifidobacterium infantis (link)
• Bifidobacterium lactis (link)
• Bifidobacterium longum (link)

These strains should be avoided because they produce histamine in the GI tract:

• Lactobacillus brevis (link)
• Lactobacillus casei (link)
• Lactobacillus delbrueckii (link)
• Lactobacillus hilgardii (link)
• Lactobacillus lactis (link)
• Enterococcus faecium (link)
• Streptococcus thermophilus (link)

See the photo from the Swiss Interest Group Histamine Intolerance for the foods that can be related to each of the histamine imbalances.

For a full comprehensive list or if you are concerned about your symptoms, please connect!

Wishing you a wonderful day!

Kaley
RN BN MN CNC 200YTT
If you would like to know the specifics of this diet or if you have questions about your health, please subscribe to ‘WhatsApp Wellness’ at www.vitalityhealthsolutions.org and find solutions to your health concerns.

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References:

Bae, M. J., Shin, H. S., Chai, O. H., Han, J. G., & Shon, D. H. (2013). Inhibitory effect of unicellular green algae (Chlorella vulgaris) water extract on allergic immune response. Journal of the Science of Food and Agriculture, 93(12), 3133-3136.

Barcik, W., Pugin, B., Brescó, M. S., Westermann, P., Rinaldi, A., Groeger, D., … & Ferstl, R. (2019). Bacterial secretion of histamine within the gut influences immune responses within the lung. Allergy, 74(5), 899-909.

Esposito, F., Montuori, P., Schettino, M., Velotto, S., Stasi, T., Romano, R., & Cirillo, T. (2019). Level of biogenic amines in red and white wines, dietary exposure, and histamine-mediated symptoms upon wine ingestion. Molecules, 24(19), 3629.

Ferstl, R., Akdis, C. A., & O’Mahony, L. (2012). Histamine regulation of innate and adaptive immunity. Front Biosci, 17(1), 40-53.

Horny, H. P., Reiter, A., Sotlar, K., & Valent, P. (2018). Mastocytosis. In Encyclopedia of Pathology (pp. 1-11). Springer, Cham.

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Liu, Q., Huang, Y., Zhang, R., Cai, T., & Cai, Y. (2016). Medical application of Spirulina platensis derived C-phycocyanin. Evidence-based complementary and alternative medicine, 2016.

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Martínez, C., González-Castro, A., Vicario, M., & Santos, J. (2012). Cellular and molecular basis of intestinal barrier dysfunction in the irritable bowel syndrome. Gut and liver, 6(3), 305.

Manzotti, G., Breda, D., Di Gioacchino, M., & Burastero, S. E. (2016). Serum diamine oxidase activity in patients with histamine intolerance. International journal of immunopathology and pharmacology, 29(1), 105-111.

Martin, I. S. M., Brachero, S., & Vilar, E. G. (2016). Histamine intolerance and dietary management: A complete review. Allergologia et immunopathologia, 44(5), 475-483.

Pinzer, T. C., Tietz, E., Waldmann, E., Schink, M., Neurath, M. F., & Zopf, Y. (2018). Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls. Allergy, 73(4), 949-957.

Rahmani, J., Miri, A., Mohseni-Bandpei, A., Fakhri, Y., Bjørklund, G., Keramati, H., … & Khaneghah, A. M. (2018). Contamination and prevalence of histamine in canned tuna from Iran: a systematic review, meta-analysis, and health risk assessment. Journal of food protection, 81(12), 2019-2027.

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