The MCAS explosion

I am seeing a growing number of cases of Mast Cell Activation Syndrome (MCAS) in my practice. This condition causes an over-activation and proliferation of a type of immune cell termed a mast cell, leading to a range of symptoms such as dizziness, cardiovascular symptoms, skin rashes, abdominal pain, and fatigue.

I am seeing a growing number of cases of Mast Cell Activation Syndrome (MCAS) in my practice.  This condition causes an over-activation and proliferation of a type of immune cell termed a mast cell, leading to a range of symptoms such as  dizziness, cardiovascular symptoms, skin rashes, abdominal pain, and fatigue.  But for some, the condition can progress to produce really debilitating symptoms such as Postural tachycardia syndrome (PoTS), whereby the person’s heart rate increases in response to simply sitting or standing up.

The reason for the increase in the number of cases is that Covid-19 is thought to trigger MCAS for some individuals. But, MCAS is by now means a new condition and we had a very small number of cases pre-pandemic.

By the time I see many of these patients, they are very debilitated by this condition and already on a range of medications, supplements and an extremely restricted diet.  The exact cause of MCAS is not fully understood but we do recognise that it is a complex interplay between genetic, environmental and physiological factors that create a perfect storm to contribute to its development. So, even if Covid was the trigger, there would have already been an underlying susceptibility.

As functional medicine practitioners we have to work back to find the cause, rather than rely simply on using histamine blockers and removing low histamine foods from the diet.  For this reason, I do believe that testing becomes really important.

So, what are the key testing areas for this condition?

1.      Genetic testing:

Genetic testing can be interesting and we do often see a connection with other hereditary conditions such as Ehlers-Danlos Syndromes.  This will be helpful in understanding the stage that was set for the development of this condition and will also help in deciding whether we need to focus on things like the diamine oxidase (DAO), the enzyme that breaks histamine down in the gut.  However, genetics are never the full picture. Gene plasticity is the idea that our genes aren’t set in stone and can be changed by the world around us. Think of it like this: our genes are like a loaded gun, but it’s the environment that pulls the trigger and decides whether they will be fired or not. So even if you have a gene that makes you more likely to develop a certain condition, it’s things like what you eat, how you live, the toxins you’re exposed to that will determine if you end up getting ill or not.  With that in mind, your best bang for your buck in regards to testing will be in looking more closely into the environment.

2.      Trigger testing

Looking for the triggers that set the condition in motion is often where we will have the biggest success. Here we will want to take a thorough history and then decide on a testing strategy.  In my experience the most common last straw is often mould exposure, but prior to that there may have been a range of infectious or toxic exposures.  Patients often ask about testing for food and environmental allergies or sensitivities. While this can be very helpful in the short-term in reducing further cascading of these immune cells, it is only a short-term strategy as triggers change over time.

3.      Gut testing:

In nearly all cases of MCAS there is also a compromised intestinal and neurologic barrier function to hyperinflammation. Since nearly 80% of al immune cells reside within the gut, doing comprehensive gut testing is really helpful in MCAS. This often helps us understand the ecosystem from which the immune system is born and can identify infections, tell us about the health of the microbiome etc. Interestingly, a recent study showed that significant increases in duodenal mast cell densities often lead to additional non-gastrointestinal symptoms such as fatigue, dizziness, and muscle, joint, and chest pain. And this tells us that a large part of MCAS may be stemming from the GI tract.

Once triggers have been identified, it is then important to fully deal with these. So for instance, if there is any ongoing mould exposure, getting that remediated should be a number one priority.

Vagus nerve stimulation

In all cases of MCAS that I have ever seen, there is a level of vagus nerve dysfunction. This large nerve line connects the brain and the gut and is responsible for signalling to the nervous and immune system regarding threats such as toxins and infections. If your body thinks it’s under attack, your mast cells will be pumping out histamine and subsequent inflammation.  This will make it near impossible to get well, until you first stabilise the vagus nerve.

Recent studies have explored the use of non-invasive vagus nerve stimulation (VNS) as a potential treatment for MCAS. VNS has been shown to be effective in reducing mast cell activation and the release of mast cell mediators, providing significant relief for individuals with MCAS.

I have found auricular vagus nerve stimulation to be exceptionally effective in helping with this condition, even more so than diet and supplementation. This is especially so for patients who have tested high in cortisol.


Patients often do report improvements in their symptoms after following a low-histamine diet. One study found a significant increase in DAO levels in patients who strictly follow a low-histamine diet.  Another study with 146 participants found that a low-histamine diet and/or DAO supplementation can effectively reduce symptoms with histamine intolerance, with the best response in patients who have DAO levels between 3-10 U/ml.

Vitamin D has been found to play an important role in maintaining the stability of mast cells and has a connection to allergic disease. Getting vitamin D levels into the optimal range can often help reduce symptoms.

Functional medicine also focuses on increasing nutrient consumption for better immune health. Some foods that may possess anti-inflammatory properties include onions (rich in quercetin), moringa, chamomile, nettle, galangal, turmeric (high in curcumin), peaches, Brazil nuts(rich in selenium), fiber, and others. These foods have been found to regulate mast cell-mediated allergic reactions and decrease histamine release, among other benefits. Further research is required to fully understand the effects of these foods on the immune system.

In conclusion, this very tricky condition will respond well to a multi-pronged approach using vagus nerve stimulation, diet and carefully thought through supplements. But to really get a lasting effect, you do need to work your way back to the root cause and address that.