April is Autism Awareness Month. There isn’t a better way to mark this occasion but to discuss lesser-known factors that may play a role in autism spectrum disorder (ASD). Though there are countless studies on the connection between mast cells and autism, the role and prevalence of mast cell activation are not part of the daily conversation when discussing the causes, symptoms, and treatment strategies for autism. Let’s change that.

Mast cell activation syndrome (MCAS) and histamine intolerance can affect your entire body and cause widespread symptoms. One of the potential symptoms of mast cell activation is brain inflammation. Brain inflammation due to increased mast cell activity may lead to brain fog, memory issues, concentration troubles, insomnia, headaches, migraines, depression, anxiety, and so on.

It may not be surprising that mast cell dysregulation may be involved in the development and symptoms of autism spectrum disorder. In this article, I want to discuss the role of mast cells in autism and what to do about increased mast cell activation. 

What Is Autism

Autism spectrum disorder (ASD) or autism is a term used for a range of conditions that can result in social, behavioral, and communication challenges. In Canada, about 1 in 66 children are diagnosed with autism (1). In the US about 1 in 44 children have an autism diagnosis (2). Adult diagnosis of autism is increasingly prevalent as well with about 2% of adults having an autism diagnosis (3, 4). Since the diagnosis can come with both emotional and financial challenges and is not available for everyone, the actual number of children and adults with autism are likely higher than official statistics.

Autism has various subtypes. Subtypes, symptoms, and characteristics may be influenced by both genetic and environmental factors. The symptoms of autism can widely vary between different individuals. For example, for some individuals with autism, social interactions are incredibly difficult, while for others, not so much. Learning, thinking, and problem-solving abilities can greatly vary from highly gifted to average to severely challenged. Many individuals with autism can lead a healthy and productive life without support. Other ASD patients need some or a lot of outside support in their daily lives for their entire life.

Though we understand autism more and more, research is ongoing. We gain a deeper understanding of the disorder and treatment options every day. There are many factors that may influence the development, symptoms, and treatment of autism, including genetic, family history, other mental health or behavioural conditions, other medical issues, environmental factors, nutrition, and lifestyle factors. 

One of the less talked about factors that may influence autism is your mast cells. Addressing mast cells and mast cell activation may help to improve the symptoms and the quality of life of some people with autism. Before I get into the connection between autism and your mast cells, I want to briefly go over what your mast cells are.

What Are Mast Cells

Your mast cells are white blood cells found in your connective tissues, including your digestive tract, skin, respiratory tract, urinary tract, reproductive organs, surrounding your nerves, and near your blood vessels and lymph vessels. Your mast cells store histamine and other inflammatory mediators. When your body is exposed to an allergen, pathogens and microbes, or some chemical it will lead to an immune response. Your mast cells can release these inflammatory mast cell mediators to protect you from harm.

Your mast cells are absolutely necessary for a healthy immune system and a healthy body. However, overactive mast cells can lead to problems. Overactive mast cells may increase the risk of mast cell disorders, including mast cell activation syndrome (MCAS). This may result in chronic and widespread symptoms and health issues, including hives, itching, eczema, skin issues, headaches, migraines, fatigue, nervous system symptoms, digestive issues, and bladder problems (5, 6, 7, 8).

Mast Cells and Autism

When discussing the connection between your mast cells and autism, we have to talk about the blood-brain barrier (BBB). The blood-brain barrier is a semipermeable border of your endothelial cells. It prevents toxic substances from your blood from crossing over to your brain and nervous system. You clearly want your blood-brain barrier to be healthy and protect your brain. 

Research has shown that the blood-brain barrier and your gut are closely connected and influence each other (9, 10). I’ve written about the importance of the gut-brain connection in autism in this and this article. I will come back to the importance of the gut-brain axis later, but let’s start with mast cells in your brain first.

Mast cells are located in large concentrations in your brain surrounding your blood-brain barrier. They play a role in protecting your brain from toxins and pathogens. Mast cells in this area are essentially your brain’s gatekeepers (11). They are part of the decision-making process of what molecules can cross into your brain. 

Your mast cells are also responsible for allowing molecules into your brain that trigger microglia. Microglia are cells found in your central nervous system (CNS). They are responsible for cleaning up damaged neurons and infections to maintain CNS health and balance. Increased microglia tends to come with increased brain inflammation. A 2013 study published in JAMA Psychiatry has found excessive microglial activation in those with ASD (12). A 2005 study published in the Annals of Neurology has found increased microglial activity and neuroinflammation in patients with autism (13). 

When your mast cells create inflammation they want to protect you from allergens, infections, toxins, and other harm. However, too much inflammation can be a bad thing. Mast cells can release molecules that activate microglia which then release pro-inflammatory mediators to your brain. Over-reactive mast cells and increased mast cell activation can increase microglia activity and increase inflammation. Too much inflammation can lead to a leaky blood-brain barrier. According to a 2009 review published in Expert Opinions in Pharmacotherapy, mast cell activation can result in gut-blood-brain barrier disruption, which may lead to neuroimmune problems and symptoms of autism (14). 

A 2010 review published in Biochimica et Biophysica Acta has found that allergies, stress, and environmental triggers can trigger mast cell activation, increase inflammation, and delay the development of the gut-blood-brain barrier in ASD (15). According to a 2019 review published in the International Journal of Molecular Sciences, stress and environmental triggers can lead to mast cell activation and trigger the microglia. This may change the fear threshold of your amygdala (another part of your brain) resulting in an increased fight-or-flight response and stress, anxiety, and obsessive behavior in those with autism (16).

A 2009 review published in Frontiers in Endocrinology has also found that a disruption of the gut-immune-brain barrier axis may be one of the reasons  behind the wide range of symptoms of ASD (17). They also found that food allergies are common in ASD and may increase mast cell activation disrupting brain function and causing intestinal permeability. A 2019 article published in the International Journal of Immunopathology and Pharmacology has also explained that food intolerances and allergies can increase mast cell activation and disrupt the gut-blood-brain barrier (18).

A 2012 review published in BBA Molecular Basis of Disease and a 2019 review published in Frontiers in Cellular Neuroscience both explained that increased mast cell activation can increase the risk of gut inflammation and leaky gut syndrome (19, 20). Food sensitivities, food intolerances, and food allergies, which are common in autism, can also increase the risk of the leaky gut syndrome and other gut health problems (21, 22, 23, 24). 

Digestive symptoms are not only common in autism, but research has shown that gut microbiome imbalances, leaky gut syndrome, and other gut health issues can often play a role in autism (25, 26). A 2018 review published in the International Journal of Molecular Sciences has found that the interaction between the gut microbiome and the brain and the health of the gut-brain axis plays an important role in autism (27). Mast cell activation can affect both your gut and your brain, thus possibly increasing symptoms of autism in multiple ways.

Recommendations for Autism and Mast Cell Activation

The right nutrition, supplementation, and lifestyle can make a big difference in the symptoms of autism and mast cell activation. Everyone is different and you may need to make some tweaks based on your personal needs. This general guide should help you to get started.

Follow a Low-Histamine Diet

To improve mast cell activation and reduce histamine intolerance, I recommend following an anti-inflammatory, low-histamine diet. Avoid inflammatory foods, such as refined sugar, gluten, dairy products, refined oil, artificial ingredients, heavily processed foods, and junk food. Avoid high-histamine foods and foods that trigger histamine release, act as diamine oxidase or DAO enzyme blockers, or increase histamine levels. Follow a diet rich in low-histamine, anti-inflammatory, nutrient-dense whole foods, such as greens, vegetables, herbs, fruits, eggs, pasture-raised poultry, grass-fed beef, and wild-caught fresh fish. I recommend reading this article with a detailed list of what to avoid and what you can eat.

Follow a Sugar-Free, Gluten-Free, and Casein-Free Diet

I’ve found that following a sugar-free, gluten-free (GF), and casein-free (CF) whole foods diet can make a significant difference for children with autism spectrum disorders and other developmental disorders (28). Research has found that a large subset of children with ASD has gut permeability issues, or “leaky gut”, which may lead to poor nutrient absorption and deficiencies (29, 30). Gluten and casein, wheat and dairy protein respectively, may trigger gut permeability as well as mast cell activation. Additionally, I recommend checking for food intolerances, food sensitivities, and removing any triggering foods. Often I will recommend a GFCF food elimination diet for 3 months to best assess the role that dietary restriction might play in a carefully managed treatment plan.

Reduce Your Histamine Bucket

Beyond diet, lifestyle and environmental factors may also increase mast cell activation and fill up your histamine bucket. Avoid medications, chemicals, environmental toxins, heavy metals, and other irritants that may trigger mast cell activation. Improve your sleep. Lower your stress and anxiety as best as possible. Exercise and move your body regularly. 

Try Mast Cell-Stabilizing Foods and Supplements

You may benefit from trying some herbs and other foods that may help to stabilize your mast cells, including watercress, moringa, chamomile, Thai ginger, apples, Brazil nuts, peaches, nettle, onion, fiber-rich foods, and quercetin-rich foods (31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42). You may also benefit from supplementing with natural antihistamines and mast cell stabilizers, such as quercetin, resveratrol, curcumin, vitamin C, nettle leaf, and luteolin. DAO enzyme may be helpful if you are dealing with a DAO deficit (43, 44, 45, 46, 47, 48, 49).

Try Some Nutrients and Supplements for Autism

I’ve recently written an article about the potential benefits of nutrient therapy for autism. Vitamin B12, other B vitamins, glutathione, omega-3 fatty acids, carnitine, vitamin D, zinc, magnesium vitamin A, coenzyme Q-10 may also benefit those with autism (50, 51, 52, 53, 53, 54, 55, 55, 56, 57, 58, 59). You can learn more common nutrient deficits in autism and how these nutrients may help to improve autism by reading this article.

Next Steps

If you or your child are experiencing symptoms of autism or other neurodevelopmental disorders, you may benefit from looking into mast cell function and dysfunction. Working with a healthcare practitioner knowledgeable about autism, histamine intolerance and MCAS is the best way to get to the root cause of your symptoms and create an individualized treatment. I welcome you to start a personalized functional medicine consultation with me for further guidance to improve your health. You may book your consultation here.

Check out my Histamine Intolerance Course here. Learn on your own time, from anywhere. Get an inside look at the most helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common (and sometimes surprising) mast cell triggers, and learn what to eat, what to avoid, and why.

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