I feel histamine is most well-known because of anti-histamine drugs than its actual effect on the body, certainly not IBS. It’s no wonder as allergic rhinitis, or hay fever, is thought to affect ten to thirty per cent of the worldwide population, and that was ten years ago.[1]
We’ve all been affected by histamine actions on the body at one stage in our lives, but hay fever and skin rashes aside, there are more profound effects of histamine in the digestive system and the brain that you might not be as clear. Most of my patients are surprised about how intrinsic this amine is, and this intimate relationship is exactly what we will explore in this article.
What is Histamine?
Histamine was discovered over one hundred years ago and is considered a master amine. It plays critical roles in immune defence, neurological activity, growth and development, fertility and nutrition.[2]
It wasn’t actually until 1927 that scientists realized that it played a role in anaphylaxis when they compared histamine levels in the lungs before and after an episode of shock.[3] The majority of the advances in our understanding of histamine following have come from discovering different histamine receptors in various cells throughout the body.
Any easy way to think of receptors is the lock part of a lock and key mechanism where different functions are “opened”, forming some type of response from a cell or a tissue. There are four different types of histamine receptors that help histamine create different outcomes in the body. Contrary to popular belief, histamine can be both inflammatory and anti-inflammatory. Let’s explore the role of each of the four of these receptors a little more.
A variety of histamine receptors allow histamine to interact with the body diversely.
Histamine 1 receptors, or H1R, drive the movement of cells, the detection of a painful stimulus, dilation of the blood vessels, something that decreases blood pressure and bronchoconstriction or the tightening of the lungs.[4] H1R is the receptor responsible for the more classic allergy symptoms we’re familiar with.
The histamine 2 receptor, or H2R, plays a role in producing your gastric juices in the stomach, mucus production in your airways (hello allergies!), and the ability of blood vessel walls to allow molecules like nutrients, water and white blood cells to pass through.[5]
The histamine 3 receptor plays a role in neuro-inflammatory disease, which we will discuss further later in this article, and the histamine 4 receptor is involved with allergy inflammation differently from the H1R.[6] We’ll come back to explore this H4R a little more later as this particular receptor is involved in more chronic inflammatory conditions.
Often, we think that histamine results from an allergic response, but foods high in histamine provide a disproportionate amount of histamine in our bodies.[7]
This high consumption of histamine based foods has seen many successful outcomes for people on low histamine diets who either have a large amount of it in their daily diets or have trouble circulating it out of their bodies. Let’s look at some foods with the highest amount of histamine.
Foods that are high in histamine:[8]
- Meats and Seafood such as Pork, Mackerel, Anchovies and Tuna
- Fermented foods such as soybean paste, kimchi, yoghurt and cheese
- Instant and fast foods
- Tomatoes
- Nuts including peanuts
- Alcohols including wine
- Green tea
- Chocolate
- Grapes
- Bananas
- Strawberries
- Citrus fruits such as lemons, oranges and tangerines.
This list was taken from an interesting study around a low histamine diet and the treatment of chronic urticaria. However, this article explores how histamine interacts with the gut and the brain. Let’s start with the brain first.
Histamine in the brain
Initially, scientists didn’t think that histamine travelled past the blood-brain barrier, so it was the last organ in the body that histamine was discovered to play a role. We know that the histaminergic (means working on the histamine system) network plays a crucial role in various brain and central nervous system functions, such as sleep and wake cycles, learning and memory, feeding and energy balance.[9]
Based on these interactions in the brain, researchers are now investigating the role of this histaminergic system in neuropsychiatric conditions such as Alzheimer’s disease, Parkinson’s disease, Tourette’s syndrome, narcolepsy and schizophrenia.[10] For example, brain histamine levels are lower in Alzheimer’s disease patients, where exponentially higher levels of histamine are found in the brains of people living with Parkinson’s disease and schizophrenia.[11]
Histamine can drive the intensity and direction of your behaviour
One of the more interesting papers around histamine and the brain has more to do with how histamine can affect the motivation that drives human behaviour.[12]
There has been lots of speculation that there is such a thing as a “high histamine personality,” a quick search on Pubmed shows very little research confirming the hypothesis. This absence of journals doesn’t necessarily mean that it is not the case, just that we are yet to understand if it is true or not. In saying that, early research is now linking histamine and serotonin together as another potential sustaining factor in depression.[13] Sorry, I get distracted.
This paper named “histamine and motivation” discusses some of the roles that histamine can play in the types of behaviour that either bring us closer to something positive or away from something negative. The paper frames this by looking at drug addiction and what happens when dysfunction in the histaminergic system in the brain causes decreased motivation or apathy.[14]
My patients are often amazed at the extent to which histamine can affect the body. But what about the digestive system? If you are a regular reader on the site, you’ll know that the theme is always around the connection between the brain and the digestive system, and histamine’s role in the digestive system is worth looking at.
Histamine plays a prominent role in the digestive system and irritable bowel syndrome (IBS).
Suppose you’ve listened to Free and Inspired radio or read some of the articles concerning digestion and the immune system. In that case, you might have heard me mention a statistic that seventy per cent of the immune system resides in the gut. I offer this to patients and now you, the reader, more as a way of explaining how intimate the relationship between these two systems can be.
Another example of this intimate relationship is histamine’s effects on the digestive system and, most notably, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Two immune cells, mast cells and basophils, produce histamine. We know that histamine is present in exceptionally high amounts when an inflammatory response is underway.[15] These increased amounts would make sense considering one of histamine’s jobs is to mobilize inflammatory cells where they are needed.
There are three main functions for histamine in the digestive tract, two of which may heavily affect people trying to solve IBS.
The first is that histamine enhances gastric acid production. The second is the modulation of a process called motility,[16] which we’ve referred to as one of the causes of constipation oriented IBS and small intestinal bacterial overgrowth.
Here is some exciting news for those who have stumbled on this page because they think histamine is connected with their IBS or have other symptoms like allergies concomitantly. One of the critical reasons histamine is now an essential consideration in the management of IBS is that a low FODMAP diet has been shown to decrease histamine levels in the body.[17]
Whilst the study revealing this was small scale and the subjects only completed the low FODMAP diet for three weeks, it was randomized and showed promise for people who feel as if their IBS is unresponsive.
But wait, there’s more. There could be another reason why histamine affects your digestive system, and this is down to the uninvited guests who have set up colonies without you knowing.
Undesirable gram-negative bacteria from fish consumption can also produce histamine
In other articles, we’ve discussed how gram-negative bacteria may not be helping your digestive system. Least of all, if you are suffering from IBS. But did you know that some forms of fish can expose you to bacteria that create more histamine?
Examples include strains that often pop up in comprehensive stool testing, such as Morganella morganii, Enterobacter aerogenes, Hafnia alvei, Citrobacter freundi and Escheria colli.[18] In more extreme circumstances, bacteria like this can cause Scombroid poisoning around twenty-four hours after eating mishandled fish, with symptoms very similar to that of an allergy, such as mouth numbness, headache, difficulty swallowing, thirst, hives and facial swelling.[19]
Another consideration with the microbiome and histamine is that various probiotic strains from the Lactobacillus species can naturally create histamine as part of their generalized function.[20] Examples of these probiotic strains are Lactobacillus reuteri, Lactobacillus casei and Lactobacillus delbrueckii subsp, bulgaricus.[21] So even by taking a probiotic, you could be unintentionally increasing your histamine levels in your body. Compounding existing problems already present because of high histamine such as IBS.
All this without even mentioning allergy?
The focus of this article was to broaden your understanding of the role of histamine in IBS, the brain and digestion as a whole. This connection is just the tip of the iceberg regarding histamine’s varied and profound role within the body. Rest assured, we’ll be exploring more of this over the coming weeks and months. Still, I hope this article has increased your awareness of how even fish and probiotics can influence the global levels of histamine in your body, potentially making your IBS symptoms worse along with your focus, sleep, and memory!
Hope this helps.
[1] World Health Organization. White Book on Allergy 2011-2012 Executive Summary. By Prof. Ruby Pawankar, MD, PhD, Prof. Giorgio Walkter Canonica, MD, Prof. Stephen T. Holgate, BSc, MD, DSc, FMed Sci and Prof. Richard F. Lockey, MD.
[2] Chazot PL. Histamine pharmacology: four years on. Br J Pharmacol. 2013;170(1):1-3. doi:10.1111/bph.12319
[3] Parsons ME, Ganellin CR. Histamine and its receptors. Br J Pharmacol. 2006;147 Suppl 1(Suppl 1):S127-S135. doi:10.1038/sj.bjp.0706440
[4] 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;9:1873. Published 2018 Aug 13. doi:10.3389/fimmu.2018.01873
[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;9:1873. Published 2018 Aug 13. doi:10.3389/fimmu.2018.01873
[6] 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;9:1873. Published 2018 Aug 13. doi:10.3389/fimmu.2018.01873
[7] Schnedl WJ, Enko D. Histamine Intolerance Originates in the Gut. Nutrients. 2021;13(4):1262. Published 2021 Apr 12. doi:10.3390/nu13041262
[8] Son JH, Chung BY, Kim HO, Park CW. A Histamine-Free Diet Is Helpful for Treatment of Adult Patients with Chronic Spontaneous Urticaria. Ann Dermatol. 2018;30(2):164-172. doi:10.5021/ad.2018.30.2.164
[9] Cheng L, Liu J, Chen Z. The Histaminergic System in Neuropsychiatric Disorders. Biomolecules. 2021;11(9):1345. Published 2021 Sep 11. doi:10.3390/biom11091345
[10] Cheng L, Liu J, Chen Z. The Histaminergic System in Neuropsychiatric Disorders. Biomolecules. 2021;11(9):1345. Published 2021 Sep 11. doi:10.3390/biom11091345
[11] Nuutinen S, Panula P. Histamine in neurotransmission and brain diseases. Adv Exp Med Biol. 2010;709:95-107. doi:10.1007/978-1-4419-8056-4_10
[12] Torrealba F, Riveros ME, Contreras M, Valdes JL. Histamine and motivation. Front Syst Neurosci. 2012;6:51. Published 2012 Jul 4. doi:10.3389/fnsys.2012.00051
[13] Imperial College London. (2021, August 17). Histamine could be a key player in depression, according to study in mice. ScienceDaily. Retrieved January 12, 2022 from www.sciencedaily.com/releases/2021/08/210817111404.htm
[14] Torrealba F, Riveros ME, Contreras M, Valdes JL. Histamine and motivation. Front Syst Neurosci. 2012;6:51. Published 2012 Jul 4. doi:10.3389/fnsys.2012.00051
[15] Smolinska S, Jutel M, Crameri R, O’Mahony L. Histamine and gut mucosal immune regulation. Allergy. 2014;69(3):273-281. doi:10.1111/all.12330
[16] Fabisiak A, Włodarczyk J, Fabisiak N, Storr M, Fichna J. Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal. J Neurogastroenterol Motil. 2017;23(3):341-348. doi:10.5056/jnm16203
[17] McIntosh K, Reed DE, Schneider T, et al. FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial [published correction appears in Gut. 2019 Jul;68(7):1342]. Gut. 2017;66(7):1241-1251. doi:10.1136/gutjnl-2015-311339
[18] Smolinska S, Jutel M, Crameri R, O’Mahony L. Histamine and gut mucosal immune regulation. Allergy. 2014;69(3):273-281. doi:10.1111/all.12330
[19] Smolinska S, Jutel M, Crameri R, O’Mahony L. Histamine and gut mucosal immune regulation. Allergy. 2014;69(3):273-281. doi:10.1111/all.12330
[20] Schink M, Konturek PC, Tietz E, et al. Microbial patterns in patients with histamine intolerance. J Physiol Pharmacol. 2018;69(4):10.26402/jpp.2018.4.09. doi:10.26402/jpp.2018.4.09
[21] Schink M, Konturek PC, Tietz E, et al. Microbial patterns in patients with histamine intolerance. J Physiol Pharmacol. 2018;69(4):10.26402/jpp.2018.4.09. doi:10.26402/jpp.2018.4.09
