brain and skeleton

Autism and Mast Cell Activation Syndrome

Mast Cell Activation Syndrome and Histamine Intolerance can cause different types of brain inflammation.

Do you have any of these symptoms?

  • Insomnia
  • Brain fog
  • Short term memory issues
  • Trouble recalling words, trouble with attention
  • Headaches, migraines
  • Depression or anxiety
  • Dizziness
  • Tinnitus
  • Sweating, temperature changes

If so, there very well may be a Mast Cell and Histamine connection for you. 

There is a significant link between Mast Cell Activation Syndrome and Autism too. In fact, mast cell dysregulation is likely involved in 75% or even more cases of Autism. This includes all Autism Spectrum Conditions, such as Asperger’s.

I’ve written this article specifically about Autism. But if you or someone you love has any type of brain inflammation, this article will give you a lot of helpful information.

There is quite a lot of research on mast cells and autism. Dr. Theoharides is a mast cell researcher who has done pioneering work in this area. And now, there are hundreds of research articles since January 1, 2018, that mention autism and mast cells. What’s more, there are thousands of articles mentioning autism and mast cells since January 1, 2010.

I covered this topic on Mast Cell Activation Syndrome and Autism with Karen Thomas on the live radio show and podcast; Naturally Recovering Autism. You can listen to the show recording here:

Incorporating this knowledge about Mast Cell Activation Syndrome into Autism Protocols can make a world of difference for those with ASD. I have a teenage client with Autism who had been suffering with severe urinary pain for several months. He was given multiple rounds of antibiotics with little to no improvement in the urinary burning. The antibiotics were making his gut worse. And gut issues are a major issue with Autism. He was also dealing with agitation and sleep issues. He was pacing and unable to sit still in my office from agitation and the pain of the urinary burning. I wanted to help him get relief as quickly as possible.

I had suspected this client had Mast Cell Activation Syndrome after reviewing his health history, symptoms, and genetics. He had previously been prescribed supplements that can worsen Mast Cell Activation Syndrome. Chronic antibiotic use can also make Mast Cell issues much worse. And the antibiotics didn’t seem to be helping at all. He was also on supplements that can worsen Autism symptoms when there is mast cell involvement. His mother discontinued the antibiotics and contraindicated supplements.

Meanwhile, we ran an Organic Acid Test and found significant Candida overgrowth in his gut. He also had high levels of oxalates. Both Candida and oxalates can worsen Mast Cell Activation Syndrome and symptoms of Autism. There are many mast cells in the brain. And Mast Cell Activation can cause agitation. We started him on an oxalate reduction protocol that was also mast cell friendly. This worked great and his urinary burning was reduced significantly in just a few weeks. His agitation was reduced. What other practitioners worked on for months, we were able to clear up in just a few weeks.

However, it isn’t really the fault of the practitioners that this client didn’t get better. Health Care Practitioners do the best they can with the knowledge they have. But Mast Cell Activation Syndrome is not well known by health care providers. It only received a diagnosis code in 2016. So, most health care practitioners were never trained in it.

Could Mast Cell Activation Syndrome Be Hijacking Your Autism Protocols?

Parents of children with Autism and adults with autism themselves often spend a huge amount of money on healthcare. When autism protocols aren’t working, it is often because the mast cell piece hasn’t been addressed. Autism protocols need to be mast cell friendly.

If parents of children with Autism don’t make sure the Mast Cell piece is addressed, they may be wasting a lot of time, money, and energy. I get clients who bring their children into my office after spinning their wheels for years. Some have even seen their children get worse over time. This is because many healing protocols that work well for some people can actually increase brain inflammation in those with Autism. Some of these things are:

  • Lots of fermented, high histamine foods
  • Lots of bone broth
  • High levels of Methylfolate
  • High levels of B12
  • Niacin

Bone broth and fermented foods increase histamine levels and can worsen Mast Cell Activation in Autism. We have to exercise caution for those on the spectrum. The same with high levels of methylfolate and B12. I have seen these work well for clients who are undermethylators for a period of time. But high doses tend to backfire after several months. And for overmethylators, these high doses can spell disaster. Niacin leads to histamine release and may not be the best form of B3 for everyone with Autism.

The good news is, I see children on the Autism Spectrum improve much faster and for way less money when Mast Cell supports are integrated into the protocol. It is critical that Autism protocols consider the Mast Cell involvement in brain inflammation. I get great success with clients with Autism by:

  • Discovering the individual root factors underlying symptoms
  • Doing extensive genetic analysis of 10,000+ variants
  • Support nutrients where needed: vitamins, minerals, amino acids
  • Work on lifestyle, environmental, and diet changes

So, if you or a loved one has Autism, be sure to read on to learn more about how addressing Mast Cell Activation can help. It may, in fact, make all the difference in the world in reducing brain inflammation and other debilitating symptoms.

What are Mast Cells?

The mast cells are very important immune cells in the body. They are the first line defenders for any kind of infection or allergen. Mast cells help protect us from viruses, bacteria, parasites, and fungal infections. The mast cells’ job is to surround and isolate the invader and signal to other immune cells that there is a problem here. The other immune cells mobilize them and move in to clean up the infectious agent or allergen.

I like to think of the mast cells as the front-line guards to a castle, where the castle is the body. The mast cells are there to make sure nothing gets into the castle that shouldn’t be there, but also to allow things that are okay to enter. The mast cells should be able to recognize when there is a problem and take a break where there isn’t a problem.

The way the mast cells work is that they have a number of different types of receptors on the surface of the cells. Certain things can dock on those receptors – like for example, chemicals produced by the Lyme bacteria or the excretions from a mosquito bite – and the mast cells will go into action. They are incredibly intelligent cells in that they can selectively release over 200 different chemicals. The most well-known of these chemicals is histamine. The mast cells can also release other inflammatory mediators, including different types of cytokines and prostaglandins. They can even release serotonin. These different chemicals cause a cascade of immune signaling to protect the body.

What is Mast Cell Activation Syndrome?

Any kind of chronic infection like mold toxicity, Lyme, other chronic infections, even other continual activation like ongoing EMF exposure, chemical exposure, and metal toxicity can cause dysregulation of the mast cells.

When the mast cells become dysregulated, if we go back to the castle and the guard metaphor, in Mast Cell Activation Syndrome, the mast cells start attacking things that are not harmful to the body. They can start to over fire at the invaders, which is where you see things like large reactions to bug bites. And they also start shooting at things that are okay to enter, like butterflies. The butterflies can be things like foods, low levels of chemicals that wouldn’t normally bother other people, and so on. Or they may get so busy shooting at butterflies and dragonflies that they miss firing at the Lyme infection, and some Lyme bacteria slips in. In Mast Cell Activation Syndrome, the mast cells aren’t able to do their jobs correctly.

Mast Cell Activation Syndrome (MCAS) occurs when the mast cells become over-reactive and over release inflammatory chemicals into the body. This can happen due to genetic predisposition combined with chronic triggering of the mast cells, or it can be acquired due to chronic infection, mold toxicity, hormone imbalances, and so on. Mast Cell researchers estimate anywhere from 10-17% of the general population have Mast Cell Activation Syndrome, and we don’t know yet how common it is in Autism, but I suspect it may be as high as 75%.

We want to differentiate a little here between Mast Cell Activation Syndrome and some of the other Mast Cell Disorders. There are other mast cell issues, like Mastocystosis, which is a very rare disorder that acts like a cancer where there are way too many mast cells. In Mast Cell Activation Syndrome, there are normal numbers of mast cells, but they are over reactive.

Histamine Intolerance

Another related issue is Histamine Intolerance. But it is a little different from Mast Cell Activation Syndrome. Histamine is responsible for a number of activities in the body, such as immune response, triggering stomach acid release, and also as a neurotransmitter. Histamine is made and released from mast cells, but we also consume histamines in some types of foods. Some foods are much higher in histamine than others. For example, all aged and fermented foods, beef, and spinach are all very high histamine. There are different enzymes in the body responsible for breaking down histamine when histamine levels rise too high. Histamine Intolerance is when those enzymes aren’t able to keep up with the histamine load in the body, so the histamine levels keep building. Symptoms develop when the histamine levels cross a certain threshold in the body. Histamine Intolerance has a genetic predisposition component, and can develop due to gut infections, certain medications, and a few of the same triggers as Mast Cell Activation Syndrome.

Mast Cell Activation Syndrome is usually more severe and debilitating than Histamine Intolerance, but there are also exceptions to that. In Mast Cell Activation Syndrome, you get a larger breadth of triggers, like fragrance in the laundry detergent aisle at the grocery. Or people may have symptoms as soon as they put food in their mouths or smell food. Or there may be strong reactions to stress. People can have either Mast Cell Activation Syndrome or Histamine Intolerance. Or they can be like me and have both. People with Mast Cell Activation Syndrome are often called the canaries in the coal mine because they react to low levels of things that are toxic to everyone, but people with Mast Cell issues react much more quickly. Mast cell dysregulation and Autism are showing us that our world has become much, much too toxic.

Symptoms of Mast Cell Activation Syndrome

The mast cells are in most tissues in the body, so the symptoms can be quite varied depending on which systems are affected. This is a big part of why this syndrome was such a mystery for so long. There are way too many possible symptoms to talk about today, but people can go to and click on “MCAS” to see a more complete list.

Symptoms are usually grouped by body systems. Here is a rundown of just a few of the symptoms:

General: overall fatigue and feeling bad, food, drug, environmental, and chemical sensitivities, inflammation, swelling

Muscles/Skeleton: pain that moves around, general muscular and bone pain, hyperflexible joints

Skin: flushing, hives, ruddy/reddish or a pale complexion, itching, burning sensations, dermatographia (persistent redness or white marks after scratching skin), psoriasis, eczema

Heart: fast heartbeat, heart palpitations, dizziness and lightheadedness when standing up, low blood pressure

Digestion: diarrhea, cramping, abdominal pain, nausea, vomiting, reflux, trouble swallowing, throat tightness, bloating, food sensitivities and food allergies, irritable bowel syndrome

Brain and Nervous System: brain fog, short-term memory issues, trouble recalling words, headaches, migraines, depression, nerve pains, anxiety, insomnia, dizziness, ear ringing, temperature changes

Lungs: congestion, coughing, wheezing, increased mucous production, frequent throat clearing, asthma

Eyes: eye pain, redness, trouble focusing, inflammation in the eyes

Reproductive System: painful periods, hormonal imbalances

People don’t have to have all of these symptoms at all to have Mast Cell Activation Syndrome. Usually, at least 2 systems are affected. So, for example, digestion and skin symptoms or insomnia and chemical sensitivities. Some people may only be aware of symptoms in just one system, but still have Mast Cell Activation Syndrome.

How is Mast Cell Activation Syndrome related to Autism?

We don’t have time to cover all the ways Mast Cells are involved in Autism, but I’ll hit on the highlights. First, there are large concentrations of Mast Cells in the brain. It is the job of Mast Cells to create inflammation to protect us. But when there is too much inflammation from over reactive mast cells, those inflammatory compounds are known to cause leaky blood brain barrier.

Levels of mast cell mediators have been shown in research to be higher in cerebrospinal fluid of those with ASDs. ASDs are associated with immune dysfunction, which often involves mast cell issues. Mitochondrial dysfunction is also common, and the oxidative stress and inflammation that arises from mitochondrial dysfunction increases mast cell activation as well. Anxiety is very common with those with ASDs and the increase in stress from anxiety increases mast cell activation, creating more blood brain barrier disruption.

There are also a large number of mast cells anywhere the body meets the outside world, including the skin and the entire GI tracts. Many children with autism have gut issues that are strongly correlated with mast cell activation.

A 2017 study in Nature showed histamine signaling genetic variants in ASDs, particularly for those coding for a histamine degrading enzyme called HNMT, those coding for the 4 types of histamine receptors, and for the enzyme that converts the amino acid histidine to histamine.

There was a paper published in 2018 on Autism and Pain related to Hypermobility disorders like Ehlers-Danlos Syndrome (EDS), which are connective tissues disorders of the joints that cause chronic pain. Mast cells are concentrated in the joints and are involved in these hypermobility disorders that are common in autism.

Many people with autism have mercury toxicity, and mercury at even low levels has been shown to cause mast cell activation and increased mast cell related inflammation as part of the body’s response to the mercury. Particularly, this increases something called Vascular Endothelial Growth Factor or VEGF that is involved in creating leaky blood brain barrier, but also many of the other mast cell inflammatory mediators. Many children with severe ASD have increased urinary porphyrins associated with mercury toxicity – these porphyrins are cause from disruptions of the heme pathway, are very toxic themselves, and cause further mast cell dysregulation – so you get these downward spirals.

There is a very well established connection that if we keep digging down into the root factors and issues at the cellular level in Autism Spectrum disorders, we will most likely find that mast cell dysregulation is involved and is a very significant factor.

How can you know if you or your child might have Mast Cell Activation Syndrome?

Look for things like:

  • Flushing
  • Rashes
  • Hives
  • More swelling from mosquito bites or other bug bites than other children have
  • Skin that gets red easily or raises up from being scratched
  • Wheezing, excess phlegm, coughing, asthma
  • GI issues
  • Food sensitivities
  • Anxiety
  • Insomnia

Also, if the root triggers we discussed are there, it is worth looking into Mast Cell Activation Syndrome.

What can cause Mast Cell Activation in children with Autism Spectrum Disorders?

There are many possibilities, but I’ve found the most common for those with Autism Spectrum Disorders are:

  • Food triggers (beyond just histamine) – I always look at the diet first. Some of the food triggers can be glutamates, oxalates, salicylates, lectins, even chemicals in the foods like sulfites, preservatives like sodium benzoate, pesticides like glyphosate – I like to look at a child’s food diary, health history, and genetics to get a sense of what these might be for each child. It is so common for children on the spectrum to have limited diets, so I also have to be practical here. If a child will only eat 2 foods, we can’t take those foods away. But it is still important to investigate because often as the mast cells calm down and sensory issues improve, we can start to introduce more foods.

We have to take a look at supplements and fillers in supplements too – some of these can be triggers for those with Mast Cell Activation as well. Niacin can trigger histamine release, especially in those who are undermethylators. Too much methylB12 and methylfolate can stimulate mast cells through some indirect processes and too much methylfolate can cause too much glutamate release in those with glutamate sensitivity.

  • Infections and Toxicity – like Lyme, Epstein Barre, Mold Toxicity, Systemic Candida infections – these are all big triggers and any chronic infection really can contribute to mast cell activation. Also, toxicity from environmental toxins like pesticides, off gassing of new materials, cleaners, chlorine in tap water and swimming pools can contribute to mast cell activation too. I screen for mycotoxins, chemical toxins, candida, and I like for people to have bacteria and virus panels to rule out those kinds of infections.
  • Genetic Factors (like detox and inflammation issues) – there are thousands of genes that can contribute here. Dr. Bob Miller did a great job in his interview talking about some of the genetics, and his work with the NOX enzyme that stimulates mast cells has been groundbreaking in this area. Some of the others include methylation variants, acetylation variants involved in histamine breakdown and detoxification, any detoxification variants really, including glutathione, Diamine Oxidase variants to break down histamine, and more, as there are many specific to mast cells as well. We have the technology and knowledge now to do really comprehensive genetic analyses, thanks to Dr. Bob Miller. We’re up to over 10,000 genetic variants involved in these types of challenges like Autism and Mast Cell Activation. There is no single genetic variant for Autism or for Mast Cell Activation Syndrome. We have to be thinking functionally and holistically in looking at genetic factors because these genes and the enzymes they code for are a complex interplay of processes involved in health and optimal functioning.
  • Nutrient Deficiencies for nutrients the mast cells need and nutrients that are cofactors for enzymes that degrade histamine, break down toxins, etc. Some of these include:
    Iron in the bioavailable form
    Sulfur compounds, etc.

I screen for micronutrients, and especially in those on limited diets to see which enzymes might be affected because even if there aren’t any genetic variants for a particular enzyme, if you don’t have the raw materials to make the enzyme, you won’t be able to make it.

  • Hypoxia (low oxygen) – it is really important to look at airway obstructions in children. I do a basic screen and then refer to an airway specialist if there might be a problem. Look for things like a forward head posture, snoring, narrow dental arch, scalloping on the edge of the tongue
  • Hormone Imbalances – low cortisol and high estrogen can contribute to mast cell activation.
  • Stress and/or Early Trauma – We live in a very stressful world to begin with, and being on the Autism Spectrum is even more stressful because most of the world is set up for people who are Neurotypical. Just walking into a waiting room with a TV on can be stressful to children with ASD. Early Trauma can even include medical trauma. Because of this, I try to avoid blood draws as much as possible, unless we have a good case for a draw or the child is more amenable to it. Otherwise, I try to rely on urine, saliva, and stool sampling when we can get reliable results through those. Stress also activates mast cells through many of the mechanisms that were discussed in the earlier interview I did on the HPA Axis.

EMFs from cell phones, tablets, computers, even from Bluetooth in the car, TVs, and refrigerators are another big trigger – There is an unpublished study by Dr. Theoharides where he exposed mice to just the amount of radiation emitted from initiated a cell phone call and there was immediate brain mast cell degranulation – meaning the mast cells starting releasing inflammatory molecules.

It is really important to keep children at least 2 feet away from electrical devices and use EMF shielding devices for electronics, hard wire the house, and turn off the router or at least turn it off at night. I like using EMF shielding bedding or bed canopies so they can at least be shielded at night.

What are the next steps if a parent suspects their child may have Mast Cell Activation?

  1. The most important step is to identify the root causes. I do this through extensive health history and symptom analysis and often lab and genetic evaluation.
  2. Clean up diet if possible and environmental toxins and EMFs.
  3. Reduce or eliminate as many triggers as possible while calming and reducing mast cell activation.
  4. Address things like infections and nutrient deficiencies
  5. Address the genetic variants
  6. Balance hormones if needed
  7. Address any airway issues
  8. Support the mast cells in normalizing so they aren’t so sensitive with individualized supplements, specific foods to introduce, tailored stress relieving techniques.

It sounds simple, but this really has to be tailored for each child. It is in the individualized approach, looking at comprehensive genetic analysis, and finding all the root triggers where I really see results for kids with autism.

Importance of Mast Cell Friendly Autism Protocols

Some common diets and supplements used with Autism can make Autism symptoms worse if there is Mast Cell Activation involvement. What are some things that need to be adapted with Mast Cell Activation Syndrome?

When there is mast cell involvement, we want to make sure we are taking that into account in autism protocols. That may mean using supplements that can both address, say mold toxicity, and has simultaneous mast cell stabilizing effects. For example, steering away from some of the antimicrobial supplements like clove that could lead to more mast cell issues in those susceptible. I’m always thinking about how to keep the mast cells stabilized while doing detoxification support, nutrient support, etc.

Pay attention if you are trying GAPS diet or other types of diets that use a lot of bone broth and fermented foods. These are perfect for some kids, but if there is Histamine Intolerance or Mast Cell Activation, you may see itching, flushing, rashes, diarrhea, increased trouble sleeping, or increased stimming.

Also, with histamine and mast cell issues, niacin often cause flushing and itching, so we need to use different forms of B3 that are better tolerated.

Some people think some of the symptoms occurring during detoxification or pathogen protocols are normal – if there is increased brain fog, diarrhea, itching, flushing, increased or decreased temperature, getting chills, but these types of symptoms are often histamine elevations and mast cell activation over-reaction – they are an indication that this protocol is too much for this body.

It can really throw a wrench into Autism protocols when trying to push through these kinds of reactions. Herx reactions and also histamine and mast cell reactions mean the body can’t keep up with what is happening. I always warn parents to never push through increases of symptoms during protocols unless there is a very, very good reason, like a serious acute infection, because doing so can make the kid worse. I’ve had a number of clients come into my office because they went downhill from protocols that were too aggressive for them. Mast cells have up to a 1 year life cycle, and it can take 6 months to 1 year for these dysregulated mast cells to die off. Sensitive systems require sensitive approaches.

Pushing through increases of symptoms can lead to a mast cell inflammation cascade – this happens in Mast Cell Activation Syndrome when the mast cells are already over reactive. As there is more release of inflammatory mediators, the surrounding mast cells start to release their inflammatory mediators, which triggers more mast cells to release inflammatory mediators. It becomes like a forest fire effect, where you start with just a spark in a few mast cells and things keep spreading and spreading until you have a forest fire. So, you really want to keep an eye out for these types of symptoms mounting up. It takes up to a year for over reactive mast cells to die off, so in Mast Cell Activation Syndrome, those cascades can go for a really long time once they start.

The other thing that can occur is development of Histamine Intolerance when fermented foods, bone broths, and other high histamine foods are continued when there are increases of symptoms like we’ve discussed. So, really be monitoring your kids. We have to make sure we are using the right interventions for kids, and it can be very different for each child on the spectrum.

What should you do next if you some you know has Autism?

The next step is to download my Mast Cell 360 Free Guide on the 7 Most Common Causes of Mast Cell Activation Syndrome. You can download it here:

You are welcome to reach out to me through the contact page there you have any questions. You may even be wondering if you or your other children might have Mast Cell Activation Syndrome – it often runs in families.

If you are ready for one to one help for you or your child, go ahead and schedule a case review here:

I want to thank Karen Thomas for having me on her show Naturally Recovering Autism to talk about the connection between Mast Cell Activation Syndrome and Autism. I’m so glad that we can come together here to help more parents and children put these mysteries together and regain their health.

Are you interested in working with a practitioner 1:1?  

If so, you can apply to see if the Mast Cell 360 Practice is a good fit for you. Click the button below: 

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It’s important you know that this blog post is for informational and educational purposes. It’s not meant to treat any health condition or to be prescriptive for anyone. Always be sure to work with your healthcare practitioner. 

Before you change your diet on your own, please make sure you’re working with a healthcare practitioner who can help you with this.  

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  1. Sasha

    Is inositol hexanicotinate an ok form of niacin for mast cell activation syndrome? Thanks

    1. Suz, Mast Cell 360 Team

      Yes, this form can be better tolerated than niacin because inositol doesn’t increase histamine levels. Still, if you haven’t tried it, try everything new slowly to make sure you are ok because other pathways will be addressed with it.

      1. Rosie M

        Hi there,
        I have been diagnosed with MCAS and have been taking 150mg of the flushing type of nicotinic acid every day. As I understood-the flushing was the result of histamine in the body, not the cause of it?
        But have I got this wrong? Am I actually causing further histamine release by taking this form?
        I would be really grateful if you could let me know your thoughts and the science behind it.
        Many thanks, Rosie

        1. Suz, Mast Cell 360 Team

          Hi Rosie,
          Niacin causes a histamine release which causes the flush.

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