The role of histamine in seasonal allergies

Seasonal allergies such as hay fever, also known as allergic rhinitis, are common and becoming increasingly so, both in the UK and across the globe.

A recent study by Allergy UK revealed that 49% of the UK population have had symptoms of hay fever with it officially affecting between 10-15% of children and 26% of adults.

It may appear to some to be just an inconvenience with the need for extra tissues or antihistamines but hay fever can be debilitating and can also have a knock-on effect on other aspects of health.

Up to 57% of adult patients and 88% of children with allergic rhinitis have sleep problems, including micro-arousals, leading to daytime fatigue, somnolence, and decreased cognitive function.

As we begin to enter the spring and summer, it is an important time to consider interventions that may support a healthier response to allergens. This blog looks at the response of the body when exposed to allergens, how the immune system is affected and the influence that histamine plays as well as looking at natural interventions to help individuals before and during the hay fever season.

What happens during an allergy?^1,2

1. An allergen, (in the case of hay fever, pollen), enters the body via the skin, respiratory tract or gastrointestinal tract, which are lined with epithelial cells. If the epithelial lining is compromised, then allergens are able to translocate across the lining, triggering the immune system.
2. Allergens are detected by antigen presenting cells, which they present to T helper cells and then, in turn, antibody producing B cells (producing IgE antibodies in response). This creates antibodies against pollen, initiating a more rapid and intense response to pollen upon the next exposure.
3. Pollen then binds with the antibody IgE, which activates receptors on mast cells (part of the innate immune system), prompting further immune response and releasing histamine.
4. Mast cells induce a further inflammatory response, initiating the production of chemical mediators such as proinflammatory cytokines and leukotrienes.
5. Other immune cells are recruited, including Th2 lymphocytes, eosinophils and basophils.

Both mast cells and basophils produce the chemical histamine, which is often a target of anti-allergic therapy. Histamine is part of the immediate reaction to an allergen and therefore medications target histamine as they can quickly reduce symptoms.

However, it can be seen from the above that supporting the epithelial lining and normal immune function should be an essential part of long-term intervention for allergic and atopic conditions.

What is histamine and what does it do?

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Histamine is a chemical mediator that is stored in granules within the cytoplasm of mast cells and basophils. It is an amine produced from the amino acid histidine by decarboxylation (removal of carboxyl group).^3,4

When it is released, it induces vasodilation and increased vascular permeability, which allows an increase of fluid into blood vessels leading to swelling and irritation. It also increases heart rate, cardiac contraction and glandular secretion, all of which, when in combination with other immune activation, have the potential to induce anaphylactic shock which can be fatal. However, in most people it will lead to symptoms associated with hay fever, including sneezing, itching and watery eyes and nose.⁴

Histamine not only acts locally and immediately but also activates other inflammatory molecules which can lead to a more sustained long-term inflammatory response; thus, symptoms can persist.

However, it should be noted that histamine interacts with 4 different histamine receptors. Where H1R is associated with allergy, other histamine receptors (H2-4R) are distributed differently across tissues and cells, and histamine triggers different signalling cascades when bound to these receptors.

Histamine is also recognised as a key player in immune regulation. Mechanisms include: ⁵

• Wound healing
• May dampen neuroinflammation in some instances
• Plays a role in gut homeostasis
• H2R may attenuate gut inflammation

Although much of histamine’s actions are inflammatory, we should not see it completely as the bad guy as many actions are also regulatory.

In seasonal allergies the immune response becomes inappropriate and therefore histamine release is hyperactivated, in this instance it is necessary attenuate excess histamine release.⁵ Therefore interventions that support immune function should be used in conjunction.

Histamine and the gut flora

It is well documented that the microbiome plays an essential role in the interaction with and modulation of the immune system. 70% of our immune tissue is found in the gut as gut associated lymphoid tissue (GALT), which is continuously influencing and interacting with the bacteria within the gut and visa versa.

Additionally, a healthy balance microbiome is fundamental for the integrity of the gut epithelium which is closely related to that of the skin and the respiratory tract. Hence, supporting a healthy microbiome is essential for maintaining the integrity of epithelial tissue and reducing the opportunity of sensitisation to allergen and the subsequent allergic immune response.

However, the flora within the gut also plays a role in the production of histamine, with a recent study highlighting the key role of microbe-derived histamine in the host response. Histamine-secreting bacteria (Escherichia coli, Lactobacillus vaginalis, and Morganella morganii) are found at higher frequency in faecal samples from asthmatic patients, with a possible contribution to their atopic phenotype, as microbial-derived histamine is indistinguishable from the human-produced form.⁴

Beneficial species, including Lactobacillus rhamnosus, support normal histamine production by regulating SCFA (short-chain fatty acid) production, supporting GIT integrity and modulating histamine degradation. Therefore, supporting the microbiome with a multi strain probiotic is essential for ameliorating symptoms of allergy. Additionally, ensuring the intake of prebiotic fibre to support a diverse microbiome as well as the production of short chain fatty acids, which act as a fuel for repair and integrity of epithelial cells, is also very helpful.⁴

Histamine in foods

Some foods are naturally high in histamine and some individuals may be sensitive to these foods. If you are experiencing allergies such as allergic rhinitis it can be useful to try avoiding high histamine foods. It has also been shown to be a useful intervention in some who experience long-term low-grade inflammation.

Histamine intolerance

Those who are particularly reactive to histamine are described as having histamine intolerance, this is usually due to the lack if the enzyme which breaks down histamine, diamine oxidase (DAO).

As DAO is produced in the gut it is hypothesised that histamine intolerance is strongly associated with dysfunction of the gastrointestinal tract such as dysbiosis and leaky gut.⁶

It should be noted that histamine intolerance is more likely to be associated with gastrointestinal disorders than seasonal allergies. However, if you are intolerant to histamine, high histamine containing foods as well as dysbiosis can exacerbate seasonal allergies. Therefore, it is a good idea to consider avoiding foods high is histamine.

Foods that are high in histamine include:

• Alcohol
• Aubergine
• Pickled or canned foods – sauerkrauts
• Matured cheeses
• Smoked meat products
• Shellfish
• Beans and pulses – chickpeas, soy flour
• Long-stored nuts – e.g peanuts, cashew nuts, almonds, pistachio
• Chocolates and other cocoa based products
• Rice vinegar
• Ready meals
• Salty snacks, sweets with preservatives and artificial colourings

Nutrients that support the allergic response

There are 2 arms to supporting individuals who are experiencing seasonal allergies:

Firstly, it is important to build resilience by supporting normal immune response, this includes supporting the integrity of the epithelium and mucosa, supporting the balance of the microflora in the gut, skin and respiratory tract as well as providing nutrients which support immune balance. The main focus of this blog in on histamine however long-term support should also include:^7,8

• Provide nutrients which modulate immunity – Vitamin C, vitamin D3, N-acetyl cysteine
• Support the microbiome – live bacteria supplements and prebiotic fibre
• Support epithelial integrity- vitamin A, vitamin D3, zinc, glutamine, lactoferrin
• Support mucosal tissue – N-acetyl cysteine, marshmallow, slippery elm
• Reduce inflammation – curcumin, ginger, omega 3 fatty acids, quercetin

It is important that these interventions are implemented before the hay fever season to prime the body in being able to manage the assault from seasonal allergens during the spring and summer months. These interventions are also appropriate for other allergies.

Secondly, we can manipulate the production of histamine in the body by providing nutrients that have natural antihistamine properties.

Natural antihistamines

• Vitamin C has been widely discussed as an important anti-allergy nutrient. It has antioxidant properties and hence may provide a beneficial role in fighting free radicals in respect of allergic reactions. Oxidative stress contributes to damage to the epithelium and therefore sensitisation.^9,10Vitamin C contributes to the normal function of the immune system, and it is reported to have natural antihistamine properties by breaking down the molecular structure of histamine, therefore decreasing its volume in the blood.¹¹

• Quercetin is found in a variety of fruits and vegetables and is probably the most talked about bioflavonoid with respect to hay fever and allergies. It is a potent antioxidant and also promotes a healthy inflammatory response. Quercetin counteracts the allergic response by suppressing IgE antibody formation, thereby acting at a very early step in the allergic response. It inhibits the release of histamine and proinflammatory substances implicated in allergic reactions. Quercetin also has membrane stabilising properties and can have an anti-inflammatory effect on the mucous membranes.¹²

• Beta 1-3, 1-6 Glucan is best known for its immune supporting properties, with extensive research indicating it may optimise the function of the immune system. Put simply, Beta 1 3, 1 6 Glucan ‘primes’ the immune system, alerting the body to help defend itself against foreign invaders.¹³In terms of allergies, Beta 1-3, 1-6 Glucan is capable of binding to receptors on the surface of innate immune cells, and this action is suggested as playing a role in reducing the symptoms caused by IgE production, especially histamine release. Beta Glucan ‘down-regulates’ sensitivity and immune over reaction, as seen in allergies.¹⁴

• Spirulina is a blue-green algae and a nutritional powerhouse, providing protein, vitamins, minerals, essential and non-essential amino acids, fatty acids, trace elements and the carotenoids beta carotene, beta cryptoxanthin and zeaxanthin.
  In the support of allergies, spirulina has been shown to relieve inflammation in the nasal cavity as well as decreasing histamine levels, thereby reducing itching, nasal discharge, nasal congestion, and sneezing. One study even demonstrated that spirulina was more effective than the antihistamine medication cetirizine at improving the symptoms of allergic rhinitis.^7,15,16

It is best to begin the above interventions before experiencing seasonal allergic symptoms as in this event the immune system is already triggered, and it may be more difficult to ameliorate the symptoms.

Hence this time of year is an excellent opportunity to support a healthy immune response to allergens such as pollen.

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References

1. Guryanova S V., Finkina EI, Melnikova DN, Bogdanov I V., Bohle B, Ovchinnikova T V. How Do Pollen Allergens Sensitize? Front Mol Biosci. 2022;9:900533. doi:10.3389/FMOLB.2022.900533/BIBTEX
2. Charles A Janeway J, Travers P, Walport M, Shlomchik MJ. Effector mechanisms in allergic reactions. Published online 2001. Accessed February 28, 2024. https://www.ncbi.nlm.nih.gov/books/NBK27112/
3. Borriello F, Iannone R, Marone G. Histamine Release from Mast Cells and Basophils. Handb Exp Pharmacol. 2017;241:121-139. doi:10.1007/164_2017_18
4. Branco ACCC, Yoshikawa FSY, Pietrobon AJ, Sato MN. Role of Histamine in Modulating the Immune Response and Inflammation. Mediators Inflamm. 2018;2018. doi:10.1155/2018/9524075
5. Thangam EB, Jemima EA, Singh H, et al. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets. Front Immunol. 2018;9(AUG):1873. doi:10.3389/FIMMU.2018.01873
6. Schnedl WJ, Enko D. Histamine Intolerance Originates in the Gut. Nutrients. 2021;13(4):1262. doi:10.3390/NU13041262
7. López-Enríquez S, Múnera-Rodríguez AM, Leiva-Castro C, Sobrino F, Palomares F. Modulation of the Immune Response to Allergies Using Alternative Functional Foods. Int J Mol Sci. 2023;25(1). doi:10.3390/IJMS25010467
8. Bland J et al. Textbook of Functional Medicine.; 2008.
9. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9(11). doi:10.3390/NU9111211
10. Bendich A, Machlin LJ, Scandurra O, Burton GW, Wayner DDM. The antioxidant role of vitamin C. Advances in Free Radical Biology and Medicine. 1986;2(2):419-444. doi:10.1016/S8755-9668(86)80021-7
11. Ghalibaf MHE, Kianian F, Beigoli S, et al. The effects of vitamin C on respiratory, allergic and immunological diseases: an experimental and clinical-based review. Inflammopharmacology. 2023;31(2):653. doi:10.1007/S10787-023-01169-1
12. Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and Its Anti-Allergic Immune Response. Molecules. 2016;21(5). doi:10.3390/molecules21050623
13. Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E. Effects of beta-glucans on the immune system. Medicina (Kaunas). 2007;43(8):597-606. doi:10.3390/medicina43080076
14. β‐Glucan supplementation, allergy symptoms, and quality of life in self‐described ragweed allergy sufferers – PMC. Accessed February 29, 2024. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951572/
15. Souyoul SA, Saussy KP, Lupo MP. Nutraceuticals: A Review. Dermatol Ther (Heidelb). 2018;8(1):5-16. doi:10.1007/s13555-018-0221-x
16. Cingi C, Conk-Dalay M, Cakli H, Bal C. The effects of spirulina on allergic rhinitis. Eur Arch Otorhinolaryngol. 2008;265(10):1219-1223. doi:10.1007/S00405-008-0642-8

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Last updated on 13th March 2024 by cytoffice