Mast Cell Activation Syndrome: Everything You Need to Know

by Dr. John Gannage | Nov 12, 2024 | Blog, General Wellness, Histamine, Integrative Medicine

Have you been experiencing widespread symptoms that are seemingly not connected yet are affecting your daily life in a significant way? I’m talking about headaches, fatigue, rashes, digestive symptoms.

You may be experiencing symptoms of mast cell activation syndrome (MCAS). MCAS is a multi-system, complex health issue that can affect a number of organs and bodily systems in your body causing widespread, chronic symptoms. If you have MCAS, your chronic symptoms could all be connected and treated together. If you receive the correct diagnosis, you can finally address the root causes of your issues and support your body to reduce symptoms and regain your health.

In this article, I want to go over everything you need to know about mast cell activation. You will learn what mast cells and mast cell activation syndrome are. You will understand the symptoms, triggers, and causes of mast cell activation issues. You will understand the difference between mast cell activation syndrome and histamine intolerance. Finally, I will share my top recommendations for mast cell activation issues.

What Are Mast Cells?

Your mast cells are a type of white blood cells that store inflammatory mediators or chemicals, including histamine, leukotrienes, heparin, serotonin, and other inflammatory chemicals called chemokines and cytokines. Mast cells can be found in your respiratory tract, digestive system, urinary tract, skin, brain, and blood. Essentially they are all over your body!

Mast cells are the first responders of your immune system. When your body encounters an allergen, environmental toxin, infection, stress, or another trigger, it will result in mast cell activation. This means that your mast cells will let your immune system know about the potential danger. To protect you, your mast cells will release histamine and other chemicals to fight off the invaders and protect you.

Mast cells are important for your health and mast cell activation is a critical protective mechanism to help fight allergens, infections, toxins, and other harm. Their mechanism is also responsible for many of the symptoms you get when you are sick or have an infection. However, while these symptoms can be uncomfortable, they are also part of your recovery process and a reminder that your immune system is doing a great job.

What Is Mast Cell Activation Syndrome?

While mast cells are critical for your health, dysregulated or overactivated mast cells can cause issues. Mast cell activation syndrome or MCAS refers to a condition when your mast cells release too much histamine and other chemicals leading to widespread symptoms (1, 2).

If you are dealing with overactive or dysregulated mast cells, it often means that your body will release inflammatory chemicals even if there is no danger in sight. You can start reacting to foods and substances that you previously enjoyed or well-tolerated or the general population has no issues with.

This can create havoc in your system. You may experience constant mast cell activation, chronic reactions or symptoms, or severe symptoms. Symptoms of mast cell activation syndrome can be widespread and chronic.

Putting the finger on this and understanding the cause of your chronic symptoms can be difficult unless you are working with a healthcare professional who is experienced in mast cell activation issues. Unfortunately, mast cell activation syndrome is still lesser known and misunderstood, so it can take a long time to find a diagnosis and appropriate treatment.

Symptoms of Mast Cell Activation Syndrome

Symptoms of MCAS include:

Rashes
Hives
Itching
Headaches or migraines
Chest pain
Heart palpitations
Low blood pressure
Weakness
Dizziness
Weight changes, including rapid weight loss or weight gain
Digestive trouble, including diarrhea, nausea, and vomiting
Loss of appetite or low appetite
Fatigue
Anxiety
Vision changes

Triggers of Mast Cell Activation Syndrome

Triggers of mast cell activation include:

Allergens, including insect bites and certain foods
Mold, including mold in the air and food
Heavy metals, including mercury from dental work and heavy metals in foods, tap water, and various products
Chemicals and other toxins, including conventional beauty, body, and cleaning products
Infections and viruses, including Epstein-Barr virus and COVID-19
Smells, such as perfumes and other conventional beauty products
Certain medications, including antibiotics, ibuprofen, and opiate pain relievers
Alcohol and tobacco
Stress-related issues, including anxiety, exercise, pain, lack of sleep, and rapid temperature changes
Hormonal changes, including those related to your menstrual cycle and perimenopause
Mast cell hyperplasia, which is a very rare condition that may occur due to certain chronic infections or cancers

If you have MCAS and encounter these triggers on a regular basis, it can lead to constant mast cell activation and related histamine and chemical release. Moreover, this can also increase the risk of histamine intolerance, which I will touch on later in this article.

I also want to emphasize that viruses are one of the potential triggers of mast cell activation. This includes COVID-19 as well. In fact, mast cell activation syndrome may play a role in long-COVID symptoms and should be addressed to support recovery.

Causes of Mast Cell Activation Syndrome

The causes of mast cell activation syndrome are not well understood and are not completely clear yet. According to a 2013 study published in PLoS One, around 74 individuals with MCAS also have a first-degree relative with mast cell activation issues (3). This suggests that genetics likely plays a role in developing mast cell problems.

Moreover, MCAS often goes hand in hand with other issues, including autoimmune conditions, Ehlers Danlos syndrome, postural orthostatic tachycardia syndrome (POTS), irritable bowel syndrome (IBS), Celiac disease, chronic fatigue syndrome, eosinophilic esophagitis, gastroesophageal reflux disease (GERD), long COVID, and anxiety.

While the connection is not completely clear, it seems that these health issues may trigger or increase the risk of mast cell activation problems, or in other cases, MCAS can trigger the development of any of these other diseases. These conditions potentially share the same root cause issues resulting in the development of both or the multitude of connected complex health issues.

Mast Cell Activation Syndrome vs Histamine Intolerance

Many articles on the internet that talk about mast cell activation also talk about histamine intolerance. The symptoms and mechanisms behind the two are similar. They can be connected and overlap. And they can be easily confused when only looking at the symptoms. However, mast cell activation syndrome and histamine intolerance are not the same!

Histamine is one of the chemicals your mast cells release during mast cell activation and during inflammation. It is a chemical that supports your immune system by getting rid of allergens that it encounters. To protect you from allergens and toxins, your immune system releases histamine and other chemicals. Depending on the type of allergen attacking your system, histamine acts on various areas of your body, including your nose, throat, lungs, skin, eyes, or digestive tract. This action will result in symptoms of allergy.

Besides supporting your immune system and protecting you from allergens and other foreign substances, histamine also aids your gastrointestinal health. It supports your digestion by releasing hydrochloric acid. It also serves as a neurotransmitter that allows communication between your brain and other parts of your body. Thus, it is critical for your brain, neurological, and mental health (4).

Clearly, histamine plays a critical role in your health. However, too much of a good thing can turn into a major problem. Having too many chemicals triggering a response can cause chronic histamine release and chronic symptoms. Too many high-histamine foods, environmental toxins, stress, and other factors can lead to an increased release of histamine in your body. If your body has too much histamine and is unable to deal with it, it will lead to histamine buildup. This histamine buildup, called histamine intolerance, can affect your entire body and cause widespread symptoms (5, 6, 7, 8).

Symptoms of histamine intolerance may include:

Headaches and migraines
Eczema, dermatitis, acne, and other skin issues
Hives
Fatigue and sleep issues
Red eyes
Dizziness or vertigo
Heart palpitations or racing heart
Brain fog, confusion, memory issues
Irritability and mood swings
Anxiety or panic attacks
Blood pressure changes
Allergies
Asthma
Congestion or runny nose
Acid reflux, bloating, diarrhea, and other digestive symptoms
Abnormal menstrual cycle and premenstrual syndrome (PMS)

As you see, symptoms of MCAS and histamine intolerance can be similar, but the two conditions are not the same. MCAS refers to the overactivation of mast cells which leads to the release of histamine and other chemicals and related symptoms. Histamine intolerance means that your body has a buildup of histamine because it cannot break down excess histamine from a high-histamine diet and other high-histamine lifestyle factors.

While MCAS can lead to histamine intolerance, it might not lead to histamine intolerance in all people. This is because of the other chemicals mast cells store and release when triggered. There are over 200 of them, and just like histamine, the others can cause inflammation and symptoms. Histamine intolerance doesn’t lead to MCAS. Some people have both conditions, others only struggle with one.

If your body has too much histamine and can’t handle it, it can result in histamine intolerance. This usually happens due to a high-histamine diet. However, stress, poor sleep, environmental toxins, certain medications, and other factors can add to your histamine bucket as well. If your body has trouble breaking down the extra histamine, it will lead to histamine build-up and histamine intolerance. Working with a functional medicine practitioner can help you figure out if you are dealing with histamine intolerance, MCAS, both, or any other chronic health issues.

If you want to learn about histamine intolerance, I recommend this article which offers a great overview of the issue. This article also links to all my other articles on histamine intolerance, related problems, and recommendations.

Why Is MCAS So Misunderstood?

If you are experiencing symptoms of MCAS, you probably know how hard it is to navigate this condition, get a diagnosis, and find the right treatment. While there is more and more attention to mast cell issues and you can find some mainstream articles discussing the issues, especially in relation to long-COVID, it can still be difficult to navigate the issue in the conventional healthcare system. Many doctors are not well-versed in mast cell activation issues. They don’t have a good understanding of the complexities of the condition due to a variety of issues including:

A “New” Condition

Though MCAS and mast cell issues are certainly not new, MCAS is still a relatively newly recognized condition. Though awareness, research, and knowledge have grown a lot over the past decades, many doctors haven’t received a formal education or training in MCAS, or at least not enough to address all the layers of the condition.

Specialized Medicine

Most doctors are incredibly specialized. They are highly trained in specific areas of your body and know everything about their specialty, such as gastroenterology, orthopedics, neurology, cardiology, or dermatology.

This has a lot of benefits. If you need hip surgery, you can go to a highly-specialized, great hip surgeon instead of a generalist who focuses on everything from your hip to your heart. However, when it comes to complex and multisystem conditions, such as MCAS, it can be hard to navigate.

Since mast cell activations can affect multiple organs and body systems, including your gut, respiratory system, skin, brain, and cardiovascular system, you may visit many different specialists. Each will focus on the symptoms and areas of your body that are specific to their own expertise without anyone connecting the dots. It can take a long time to find someone to realize that all your symptoms are related to the same issue.

Evolving Diagnostic Guidelines

The diagnostic criteria for MCAS have evolved a lot over the years. While this is a good thing to reflect new research and understanding of the condition, new guidelines haven’t been integrated well enough into clinical practice yet. Many healthcare providers are simply not aware of all the symptoms, criteria, and tools that can be used for diagnosis.

Primary Focus on Symptom Management

In conventional medicine, the main focus tends to be on managing or reducing symptoms instead of looking for the underlying issues behind them. This is true for mast cell activation issues as well. If your doctor is not looking for underlying issues, such as gut microbiome imbalances or environmental toxin overload, behind your overactive mast cells, and doesn’t address these root causes, they cannot effectively reduce your symptoms.

Why Choose Functional Medicine?

Functional medicine and integrative medicine practitioners are more keenly trained to look at multisystem, complex health conditions, identifying the root cause of the problem, and addressing underlying issues to improve your health. They also tend to have more time and willingness to listen.

Recommendations for Mast Cell Activation Syndrome

Though symptoms of MCAS can be chronic and uncomfortable, they can be improved through some simple dietary and lifestyle strategies. Here is what I recommend to improve your symptoms of MCAS.

Reduce Your Triggers of Mast Cell Activation

If you want to reduce your symptoms of mast cell activation issues, reducing your exposure to your triggers is an important step. Avoid chemicals, heavy metals, and environmental toxins. Instead of using conventional cleaning, body, and beauty products, choose organic, natural, or homemade options. Reduce or avoid the use of plastic, especially BPA, and choose glassware, bamboo and cotton cloths, and silicone products instead.

Choose organic food whenever possible to avoid exposure to pesticides, herbicides, added hormones, artificial ingredients, and chemicals. Avoid tap water and use a high-quality water filtration system. Make sure that your home is free of mold. Use a high-quality air filtration system to improve your indoor air.

Reduce stress and anxiety with the help of meditation, breathwork, journaling, therapy, and other strategies. Move your body throughout the day and exercise regularly, if tolerated. Spend plenty of time in nature and get daily sunshine as the weather allows it. Aim to get 7 to 9 hours of restorative sleep a night.

Detoxify Your Body

If you are dealing with mast cell activation issues or any other chronic health problems, detoxifying your body is a critical step. Since environmental toxins, mold, chemicals, heavy metals, and viruses can all trigger mast cell activation, detoxification is especially important with MCAS.

I recommend drinking lots of purified water to hydrate your body and support detoxification through urine and sweat. You may improve your sweating and detoxing through the skin by infrared sauna use and exercise. Glutathione is a great protector of your mitochondria from oxidative stress (9).

Toxin binders, such as activated charcoal and zeolite, can absorb toxins and help eliminate various toxins and heavy metals (10). I will touch on gut health in the next section, but supporting your gut with high-quality probiotics and a gut-friendly, anti-inflammatory diet is also critical for both detoxification and gut health.

Improve Your Gut

Gut microbiome imbalances, leaky gut syndrome, and other gut health issues are potential underlying problems behind mast cell activation issues. Triggering of the gut-based mast cells is known to occur in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), such as colitis. With MCAS, digestive symptoms are common, and can also involve disturbances of the microbiome, as occurs with IBS and IBD (11, 12, 13, 14). This is why a lab test for microbiome mapping can often be helpful, followed by treatments to address imbalances in the gut flora.

The management of dysbiosis (microbiome imbalances) is relevant in mast cell patients and integratively can include all of prebiotics, enzymes, herbs, and even pharmaceuticals if your healthcare provider is well-versed and able to thoughtfully combine these different approaches.

DAO enzymes are mainly made in your small intestines and low levels of DAO can increase the risk of mast cell-related histamine intolerance. Improving your gut health can help to improve DAO enzyme levels and functions.

Probiotics and fermented foods are usually the first recommendation for gut health issues. If you don’t have histamine intolerance, this could be a good option for gut problems with MCAS. However, if you are dealing with both MCAS and histamine intolerance, fermented foods may not be right for you. Probiotic-rich fermented foods are high in histamine and are not appropriate for histamine intolerance. Probiotics supplementation can help, but certain strains can trigger histamine intolerance, while other strains may reduce the risk of histamine reactions and support your recovery.

If you have histamine intolerance, you want to avoid Lactobacillus casei, Lactobacillus Bulgaricus, Streptococcus thermophilus, Lactobacillus delbrueckii, and Lactobacillus helveticus. Look for probiotics specifically designed for people with histamine intolerance. Specific probiotics that are helpful and safe for histamine intolerance include Bifidobacterium strains, Lactobacillus rhamnosus, and some other strains of Lactobacillus (15, 16, 17, 18). This article can help you select the right probiotics.

Additionally, following a gut-friendly, nutrient-dense, anti-inflammatory diet is also beneficial. Some people benefit from digestive enzymes to support digestion and the absorption of nutrients. As I touched on the importance of detoxing and cleaning already, if you are dealing with environmental toxins, heavy metals, or mold, you might benefit from a detoxification protocol as well. You can learn more about detoxing in this article.

If you are dealing with SIBO, SIFO, H. pylori, parasites, or other microbial overgrowth, I recommend working with a functional medicine doctor to address your specific gut microbe imbalances. Finally, some people may also benefit from a short-term low-FODMAP diet to address their gut problems, as outlined in this article (19).

You can also sign up for my 7-Day Histamine Gut Reset here to improve your gut microbiome and reduce gut-related mast cell and histamine issues. This program is completely free and a great place to start your journey.

Address Histamine Intolerance

Not everyone has histamine intolerance with mast cell activation issues. However, if you are or suspect that you have histamine intolerance due to mast cell activation problems, I recommend that you address your histamine intolerance with a low-histamine diet and by reducing your histamine bucket.

Try a Low-Histamine Diet

I recommend starting out with a low-histamine diet for 3 to 4 weeks with plenty of anti-inflammatory, nutrient-dense, low-histamine foods. Avoid high-histamine foods that can trigger histamine release, histamine-liberating foods, and foods that act as diamine oxidase or DAO enzyme blockers. Additionally, avoid inflammatory foods, such as refined sugar, refined oil, artificial ingredients, gluten, heavily processed foods, and junk food.

Eat plenty of 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. For patients in my clinical practice, this diet change on its own has oftentimes resulted in marked improvement in symptoms. You can use the food list in this article and use this article as a guide.

Reduce Your Histamine Bucket

Besides high-histamine foods, other factors can contribute to your histamine diet, so following a low-histamine diet may not be enough to reduce your histamine-related symptoms. I recommend decreasing your histamine bucket by paying attention to other lifestyle and environmental factors. Avoid medications, chemicals, environmental toxins, heavy metals, and other irritants that could trigger histamine release. Reduce your stress and anxiety. Exercise and move your body regularly. Improve your sleep.

Improve Your DAO Enzyme Levels

DAO enzymes help to break down histamine in your body. If your body is not making enough DAO enzymes, it won’t be able to break down excess histamine. This can result in histamine buildup, histamine intolerance, histamine reactions, and histamine-related symptoms.

Certain vitamins and minerals, including vitamin B6, vitamin C, zinc, and copper, play a role in the production and function of DAO enzymes. Deficiencies in these micronutrients may increase the risk of low levels of DAO enzymes. On the other hand, getting enough of the micronutrients through food and supplementation are used to help to improve your DAO enzyme levels and functions (20, 21).

Assess DAO and HNMT Genetics

Lab testing for histamine intolerance can include an assessment of susceptibility involving DNA testing. The goal here is to determine if your genes that code for enzymes involved in histamine metabolism, such as DAO and HNMT, are displaying variants that predispose you not to make enough of these histamine breakdown enzymes (22, 23, 24).

This would mean that if your body is dealing with histamine, say through food or by triggering mast cells as with allergies, the histamine will not be cleared efficiently and hang around longer at your receptors. This leads to a cascade of inflammation and symptoms. Genetic testing is often a simple procedure, with a sample of cheek cells obtained from a cotton tip swab inside your mouth. And helps guide long-term management. Your functional medicine practitioner can help you access the test, which can provide valuable information beyond histamine genetics.

Try Mast Cell-Stabilizing Foods and Supplements

Since mast cell activation is one of the potential underlying issues behind histamine intolerance, stabilizing your mast cells is a good idea to improve your health. Try foods that can 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 (25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36).

Using vitamin C and vitamin B6 can also allow better DAO enzyme action (30, 31, 32). I recommend using supplementation with natural antihistamines and mast cell stabilizers, such as quercetin, resveratrol, curcumin, nettle leaf, and luteolin (37, 38, 39, 40, 41, 42, 43). DAO enzyme is another option for reducing mast cell-related histamine intolerance (44, 45, 46, 46, 47, 48, 49).

Avoid Vitamin D Deficiency

Vitamin D is a fat-soluble vitamin. It is critical for immune function, calcium absorption, and bone health. It helps decrease inflammation, playing a role in preventing diseases like osteoporosis and certain cancers. Vitamin D production is triggered by sunlight exposure in the skin. However, it can also be obtained from foods and supplements, which is particularly critical in darker and colder climates.

Vitamin D deficiency all on its own is a mast cell activator (50, 51). It’s why I routinely measure levels and want my patients to correct any deficiencies with appropriate supplementation on an ongoing basis. This is particularly important in climates where sun exposure year-round is difficult to come by. Vitamin K2 helps the absorption and work of vitamin D in tandem. I recommend daily supplementation with vitamin D3 and K2 to reduce and improve deficiencies.

Consider Intravenous Vitamin C

Vitamin C offers immune-boosting and anti-inflammatory benefits that can help to call down your mast cells and reduce histamine intolerance. Eating foods rich in vitamin C and taking vitamin C supplements orally is fantastic. However, using higher doses of vitamin C in an intravenous (IV) may be more effective. In a recent study, 7.5 g of vitamin C administered intravenously in 89 patients with allergies or upper respiratory infections caused a significant reduction in serum histamine (52). I’ve written about the benefits of IV nutrient therapy in this article and I offer intravenous nutrient infusions at my practice.

Try Quercetin

Quercetin is a powerful flavonoid that can help to reduce inflammation in the body. It can also naturally lower histamine levels and the allergic response, which may be particularly beneficial if you have both MCAS and histamine intolerance.

Quercetin can be found in a variety of plant foods, including blueberries, cranberries, cherries, grapes, black currant, black plums, pepper, cruciferous vegetables, cabbage, romaine lettuce, kale, asparagus, snap pea, sprouts, olive oil, and various herbs. You will likely benefit from eating quercetin-rich foods. However, I also recommend taking a quercetin supplement if you are dealing with symptoms of histamine intolerance or mast cell activation (53).

Assess for and Treat Estrogen Dominance

For many reasons, a woman’s health is best supported with the appropriate balance between the various sex hormones. For mast cells, this is especially true for estrogen and progesterone.

The mast cell has receptors for estrogen hormone, and estrogen can be activating. Counterbalance with progesterone is important, especially after ovulation and leading up to a menstrual period. Progesterone is calming, both to the brain and the mast cell. Disturbance toward estrogen excess relative to progesterone not only aggravates premenstrual symptoms, but is associated with an excess of histamine symptoms, such as rashes (including hives) or migraines among others, and potential worsening of histamine intolerance (54, 55).

Treatments for addressing estrogen metabolism include specific herbal extracts, DIM, magnesium, SAMe, and B6. These will address phase 1 and phase 2 estrogen breakdown, if necessary (56, 57, 58, 59, 60). Consulting with a functional medicine practitioner well versed in hormone assessment and hormone balancing therapies, including bioidentical progesterone in some cases, can be very helpful.

Manage Excess Weight

Mast cells are produced in your bone marrow, and then move throughout the body to settle in tissues that come face-to-face with the outside world, where they can act as protectors while detecting threats. However, they are also produced in fat tissue. Being overweight allows for the production of a greater number of mast cells (61, 62).

When a greater number of unstable mast cells are produced and then triggered, the release of histamine, and the mast cell’s other many chemicals, can wreak havoc. Losing weight is an anti-inflammatory exercise! During COVID, obese patients had worse outcomes, in part due to the mast cell overproduction problem and the virus being a very significant trigger of mast cell activation.

Consider Medication for Mast Cell Activation

While I’ve seen a lot of success in improving mast cell activation issues without medication and it is always my aim to support your body with a nutrient-dense diet, healthy lifestyle strategies, appropriate supplementation, and complementary strategies, in some cases, taking medication can be beneficial or necessary.

Common medications for MCAS include mast cell stabilizers, antihistamines, leukotriene inhibitors, aspirin, NSAIDS, and other drugs that target your mast cells. One medication, repurposed at a lower dose i.e. low dose naltrexone, I have observed being particularly helpful for many patients with mast cell issues, as well as other conditions that have a chronic inflammatory component.

If natural strategies alone are failing you, consult your doctor to see if you can benefit from medications and what medications are right for you. If you are taking medications for MCAS, do this in conjunction with nutritional and lifestyle strategies to support your body and minimize the need for pharmaceuticals.

Follow My Histamine Intolerance Course

If you have both mast cell activation issues and histamine intolerance, I recommend checking out my Histamine Intolerance Course here. This is a particularly great investment if you can’t afford to work with a functional medicine doctor one-on-one or want to get started on your own. This course allows you to learn on your own time, from anywhere. You will learn about helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common mast cell triggers and what to eat, what to avoid, and why.

Next Steps

If you are experiencing symptoms of MCAS, I recommend following my tips in this article. If you need help in improving your symptoms of MCAS, I recommend reaching out for guidance.

If you are dealing with any chronic health issues and need advice on how to improve your nutrition and health, I welcome you to start a functional medicine consultation with me for further personalized guidance. I invite you to 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.

Learn more about working with Dr. Gannage