Mast Cell Activation Syndrome (MCAS) – The Root Cause of Histamine Intolerance?

Is mast cell activation syndrome responsible for your histamine intolerance?

While I'm going to try to help you to answer this question today, one thing is for certain: you probably have histamine intolerance if you've landed on this article!

Especially if you're living with, and likely can't find resolution to your symptoms like chronic runny nose, digestive upsets, headaches or migraines, or are feeling tired all the time despite getting enough rest. In addition to this, you are likely experiencing multiple other, seemingly unrelated, medical conditions that crop up when you are exposed to histamine-containing foods, or factors that increase your body’s histamine concentration.

The question you want to answer is not related to how or what, but why. Why is this happening to you, when it doesn’t seem to be happening to anyone else around you?

Is MCAS the underlying cause of histamine intolerance symptoms?

Histamine intolerance isn’t so much a diagnosis in itself. It's more a collective description that covers a group of symptoms related to increased levels of histamine in the body.

In order to be more specific with what the root cause is, and why you have developed histamine intolerance, we need take a deeper dive to find out what's really going on.

When you're looking to try to identify the mechanism responsible for your histamine levels rising, there are several possibilities. You may have a predisposition to increased histamine production (by certain types of gut bacteria, for example), or you might have a reduced capacity to make the histamine degrading enzymes HMNT or DAO due to genetic changes or reduced liver capacity.

Or, it could be that your mast cells are too active, being triggered when they're really not supposed to be.

Mast Cell Activation Syndrome (MCAS) is a term commonly being used as the more accurate diagnosis for chronic histamine intolerance when it relates to various factors increasing histamine in the body, not just from the intake of food. In other words, you can have a condition called histamine intolerance, but you can also have MCAS when the condition becomes more complex and leaves you with a wider range of complicated symptoms relating to a higher sensitivity to histamine (1).

So, let’s explore this condition and find out whether it's the reason for the current range of symptoms you're experiencing as a result of an increased sensitivity to histamine.

What Are Mast Cells? And How Do They Relate to Histamine?

To recap, mast cells are primary cells of the immune system, found in all tissues that we have (2). They interact with potentially threatening compounds, which is why they are more prevalent and concentrated in areas that are in constant contact with the environmental, namely in the gut, the lungs and skin (3).

When these cells encounter a threat, it's their job to defend the body. They do this by releasing histamine and other chemical compounds to increase inflammation in the tissues, which sounds like a bad thing, but it is actually a protective mechanism. It's one that helps to deal with and neutralize a potential threat that could otherwise damage the tissues (4,5,6).

The problem is, in some people, there are simply too many mast cells. What’s worse, is these people tend to have slightly altered DNA, which causes the mast cells to malfunction.

This mutation causes the cells to release too many inflammatory chemicals as well as histamine, which can end up affecting every organ in the body. It is for this reason that MCAS is associated with so many diverse and debilitating symptoms (7), such as obesity, chronic skin conditions, irritable bowel syndrome, mental health disorders, menstrual irregularities and even diabetes (8,9). Any of these sound familiar?

MCAS wasn’t a recognized condition until 2007, and even when they knew it was an official diagnosable condition, it took a further 3 years for scientists to propose the criteria for diagnosing it (10). Since 2010, however, there has been a significant amount of progress in understanding the condition and its causes (11).

The research is by no means complete, but the medical community has a few ideas...

 

Get the Low Histamine Diet

 

Mast Cell Activation Syndrome and Its Potential Causes

There’s still much we need to learn about MCAS. There are a number of causes of histamine intolerance, however, two widely accepted reasons for the onset of MCAS are:

1. Too many heavy metals in your system
2. Invasion by bacteria, parasites, viruses, fungi or mold 

Let's break each one down.

Heavy metals:

The body is able to tolerate low levels of heavy metals. After all, we're exposed to a significant amount of them through our environment, including our food and drinking water. Normally the body is able to get rid of them through our detoxification pathways, but when we're exposed to higher amounts our our detoxification pathways aren't working as well, their build up in the body can be quiet destructive. Heavy metals are toxic to many of your organs, and your immune system is no exception. Aluminium, lead and mercury, in particular, have been shown to destabilize mast cells, which causes them to be overzealous in their activity, being triggered by other non-threatening factors when they're not supposed to be (12).

Bacteria, parasites, viruses, fungi and mold:

Any microorganism that is not supposed to be present in the body can cause an infection. Some of the most common infections we associate with MCAS are as a result of too many or too little bacteria, an overgrowth of fungi or exposure to mold that typically disrupts the balance in your gut, which is where 80% of your immune reactions stem from. When your gut microorganisms are out of balance or under threat, the large contingent of mast cells housed in the gut are also disrupted. Whether it is a bacterial, viral, parasitic, or even a fungal or mold infection, your mast cells may begin to flare up as a result of their presence. Even the toxins they release into the body can cause your immune system to become hypersensitive and cause flares to other non-threatening compounds, activating mast cells and causing histamine intolerance symptoms.

For example, studies confirm that both Helminth parasites, the candida yeast infection as well as chronic mold toxicity can have strong effects on mast cells (13,14,15).

So, what can you do?

In order to stabilize your mast cells, there are two important interventions that focus on these two root causes.

Discovering the Root Cause of Your Histamine Intolerance and MCAS

There are two things I would recommend you do as a starting point for discovering whether heavy metals or an infection is playing a role in the reason you have MCAS and are suffering from all of the nasty histamine intolerance symptoms.

1. Consider heavy metal testing.

It's worthwhile getting a heavy metal test performed, in addition to reviewing your individual possibility of infection.

If you often eat fish, have dental fillings, or use aluminium lined cookware, for example, the heavy metal concentrations in your body might be a problem for you. This is particularly true if your liver is already operating sub-optimally, limiting its ability to detoxify these agents. 

2. Assess your risk of a bacteria, viral, parasitic, fungal or mold infection.

If you travel frequently - or even travelled to a country only once where sanitation is questionable and you've had a gut bug - it's quite possible that you've been exposed to foodborne microorganisms. It would be likely especially if you’ve eaten foods where you have little information regarding the source or its freshness. You may also have even been exposed to impurities in the water you drink or bathe in while travelling, without even realizing it. As I mentioned, even one exposure and a foodborne illness resulting from this exposure could be the cause.

Other causes of infections and gut imbalances are frequent use of antibiotics, as this leaves your body and especially your gut exposed to opportunistic infections by potentially bothersome microorganisms that can disrupt the delicate balance of your gut and immune system.

Once you uncover if any of these factors are the cause of your badly behaving mast cells, you can target it with specific therapies. In the meantime, I also recommended that you begin following a low histamine diet. It's one of the best things you can do to reduce the overall load of histamine that your body has to deal with.

Not sure what to eat? Here is a great list of foods to eat and those to avoid to get you started.

Want to step it up a notch while you go about finding out the root cause of your illness? Vitamin C, turmeric and other natural therapies have also been found to be helpful in the treatment and management of histamine intolerance and MCAS. See a list of our top 7 supplements we suggest for histamine intolerance. You can either incorporate them into your routine as supplements, or aim to include them in food sources as part of your diet.

While you’ve likely been pushed from pillar to post in your mission to find out what exactly is wrong with you and why you’re suffering from these debilitating symptoms, there is finally a light at the end of the tunnel. When you discover where things have gone oh-so wrong, there’s an opportunity to make them right.

With more information about what might be going on and what you may need to look for as the underlying cause, it gives you more to speak to your doctor about, and potentially get the right testing (16).

By figuring out the underlying cause of your mast cell dysfunction and high histamine load, you can begin to put practices in place that bring about balance to your system so that you may once again get your health back on track and start enjoying life as you’ve so desperately wanted to.

 

Get the Low Histamine Diet

 

References:

1. Valent, P., Akin, C., Nedoszytko, B., Bonadonna, P., Hartmann, K., Niedoszytko, M., … Metcalfe, D. D. (2020). Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine. International Journal of Molecular Sciences, 21(23), 9030. doi:10.3390/ijms21239030
2. Da Silva, E., et al. Mast Cell Function. J Histochem Cytochem. 2014 Oct;  62(10): 698–738. 
3. Metcalfe DD, Boyce JA. Mast cell biology in evolution. J Allergy Clin Immunol. 2006 Jun; 117(6):1227-9. 
4. Jutel, M., et al. Histamine, histamine receptors and their role in immune pathology. Clin Exp Allergy. 2009 Dec;39(12):1786-800. 
5. Galli S., et al. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol. 2011 Oct 19; 12(11):1035-44. 
6. Weller C., et al. Mast cells in health and disease. Clin Sci (Lond). 2011 Jun; 120(11):473-84. 
7. Moon, T., et al. Mast Cell Mediators: Their Differential Release and the Secretory Pathways Involved. Front Immunol. 2014; 5: 569. 
8. Anand P, Singh B, Jaggi AS, Singh N. Mast cells: an expanding pathophysiological role from allergy to other disorders. Naunyn Schmiedebergs Arch Pharmacol. 2012 Jul;385(7):657-70.
9. Rao K., & Brown M. Mast cells: multifaceted immune cells with diverse roles in health and disease. Ann N Y Acad Sci. 2008 Nov; 1143():83-104. 
10. Akin, C., et al. Mast Cell Activation Syndrome: Proposed Diagnostic Criteria. J Allergy Clin Immunol. 2010 Dec; 126(6): 1099–104.e4. 
11. Gulen, T. Using the Right Criteria for MCAS. Curr Allergy Asthma Rep 24, 39–51 (2024). https://doi.org/10.1007/s11882-024-01126-0
12. Bent, S., et al. The effects of heavy metal ions (Cd2+, Hg2+, Pb2+, Bi3+) on histamine release from human adenoidal and cutaneous mast cells. Agents and Actions. June 1992, Volume 36, Supplement 2, pp C321–C324. 
13. Lopes, J., et al. Opportunistic pathogen Candida albicans elicits a temporal response in primary human mast cells. Scientific Reports volume 5, Article number: 12287 (2015) 
14. Saluja, R., et al. Role and Relevance of Mast Cells in Fungal Infections. Front Immunol. 2012; 3: 146.
15. Lee, T., et al. Mast cell responses to helminth infection. Parasitol Today. 1986 Jul;2(7):186-91.
16. Valent, P., & Akin, C. (2019). Doctor, I Think I Am Suffering from MCAS: Differential Diagnosis and Separating Facts from Fiction. The Journal of Allergy and Clinical Immunology: In Practice, 7(4), 1109–1114. doi:10.1016/j.jaip.2018.11.045