I’ve written extensively about MCAS, including its links to other conditions like Ehlers-Danlos Syndrome and toxic mold exposure. And while we’ve certainly come a long way in understanding this barely discussed disease, it remains a frustrating condition with no definitive cause or treatment.
But recent research indicates the emergence of a new therapeutic target for MCAS – toll-like receptors. Here, we’ll discuss how toll-receptors contribute to MCAS as well as the various treatment methods for this disease.
Mast Cells in Innate and Adaptive Immunity
Your immune system has two main branches of response: innate and adaptive immunity.
Innate immunity is a rapid, nonspecific response system that is your first line of defense against invaders. Think cough reflex, your skin, stomach acid, or mucus. All of these are designed to actively clear or eliminate pathogens.
The second response is called adaptive immunity. This is a slower but precisely targeted response mediated by lymphocytes called B and T cells. Adaptive immunity develops over a period of time, but results in the generation of effector cells. Some of these effector cells persist after the infection and form the basis of lifelong immunological memory of the invading pathogen. Commonly, people think of these as the antibodies that are created after we are exposed to an illness for the first time.
The two response systems were once considered separate, with adaptive immunity thought of as more sophisticated and potent of the two. However, researchers are noticing they are extensively interdependent – and one of the key players in this crosstalk is a class of proteins called toll-like receptors.
What Are Toll-Like Receptors?
If mast cells can be thought of as peacekeepers (like our soldiers and police), then toll-like receptors (TLRs) are likely the equivalent of a smart home security system. Similar to how today’s security systems are packed with sensors that alert you to intruders as well as natural disasters, TLRs recognize foreign invaders in your body and send out signals that activate mast cells.
TLRs accomplish this feat by detecting and binding to structurally-conserved molecules unique to foreign microbes, called pathogen-associated molecular patterns (PAMPs). Essentially, TLRs latch on to PAMPs to call attention to them.
These PAMPs are found among many microbes, and include:
- Bacterial lipopolysaccharide (LPS) – A toxin found on membranes of gram-negative bacteria.
- Lipopeptides – Structurally-diverse metabolites produced by bacteria and fungi, helps them during colonization of new habitats and during formation of biofilms.
- Lipoteichoic acid – Cell wall component of gram-positive bacteria that plays important roles in infection and inflammation.
- Peptidoglycan – A bacterial cell wall component.
- Bacterial flagellin – A globular protein that is a significant contributor to bacterial invasion, and has also emerged as a potent immune activator.
Most microorganisms – viruses, fungi, bacteria, and protozoa – express PAMPs, which means TLRs are able to sense just about any infection we might encounter. This is a valuable aspect of our immune systems because backup sensors don’t provide sufficient protections against most infections when TLRs are absent.
Let’s take a look at how toll-like receptors help your body fight infections.
Toll-Like Receptors: The Link Between Innate and Adaptive Immunity
Mast cells express multiple classes of pattern-recognition receptors (PRRs), including TLRs. Most people’s mast cells express TLRs 1–10, although there have been variations seen in studies.
Upon binding to PAMPs, all known human TLRs except TLR3 activate downstream signaling. This results in cascading reactions where mast cells mount an immune response. Mast cells can participate in direct defense against the pathogen in two ways: phagocytosis and reactive oxygen species (ROS) production.
Mast cells can also produce antimicrobial peptides or extracellular traps to kill organisms. However, due to the relatively small number of mast cells, indirect effects of coordinating host innate and adaptive immune responses may be more important.
In the indirect method, mast cells initially release small sacs called granules, which contain inflammatory mediators like histamine. These mediators can increase blood flow to the site of infection or enhance epithelial cell mucus production which can physically expel the pathogen. This is followed by the secretion of cytokines, chemokines, and lipid mediators, initiating the process of inflammation.
The secretion of chemokines and cytokines activate the T cells and B cells of the adaptive immune system. Mast-cell derived cytokines and chemokines enhance the migration of dendritic cells to the site of infection, where they ingest the pathogen. This is the start of the adaptive immune response.
In other words, TLRs act as a link between your innate and adaptive immunity.
Toll-Like Receptors and Mast Cell Activation Syndrome
Chronic exposure to environmental pathogens like toxic mold can trigger the activation of TLRs, which activates mast cells that start the inflammatory process. Without removal of the trigger, mast cells can become overactive in some individuals, leading to the development of mast cell activation syndrome (MCAS).
The chronic inflammation that results from this vicious cycle could explain some of the symptoms we see often in patients with MCAS, such as brain fog, fatigue, skin rashes/hives, and swelling/edema.
9 Treatments for Mast Cell Activation Syndrome
While there is no cure for MCAS there are a number of tools you can put into place. Which work best differ from person to person, so it’s best to experiment.
Many are able to gain control of their MCAS with trial and error. Identifying and avoiding triggers that cause MCAS to flare up is of utmost importance. People with a non-aggressive form of MCAS usually see improvements within the first four weeks of treatment.
Here are some treatment options I recommend for patients with MCAS. If you know an environmental toxin is your trigger, then some of these suggestions might not apply to you.
1. Eat a Low-Histamine Diet
First things first, you need to get your histamine levels under control. One way to do this is by doing a “low-histamine diet,” which is an elimination diet with the goal of reducing the histamine from the foods and beverages you consume.
For my patients, I suggest keeping a daily health journal, where they can jot down all the specific foods they ate along with symptoms as they appear. If you’re interested in doing a health journal, It’s best to make these notes in chronological order, so you can identify any patterns and deduce the source of your symptoms.
Now, you’re probably wondering: Which foods are approved for a low-histamine diet?
There’s no one list that serves as a go-to reference when it comes to low-histamine diets. I list general food rules for patients with MCAS in my article, Mast Cell Activation Syndrome (MCAS): When Histamine Goes Haywire.
Note that these lists should only serve as a foundational guideline. There is no guarantee that you will see benefits or that all of the “allowed” foods will not trigger your MCAS symptoms because you have your own list of sensitivities. What makes one person sick may not affect you in any way, so the best thing you can do is to track your own responses as best as possible.
To avoid the risk of malnutrition, confusion, or overwhelm, you may want to seek the help of a registered dietician or a physician who is familiar with treating MCAS. It’ll take some experimentation and a lot of patience, but a low-histamine diet could help you understand and identify some patterns in your sensitivities.
As someone who’s had to work through my own personal food sensitivities, I promise taking the time to get to the bottom of this is worth it. Your health and wellbeing are worth it!
2. Use a DAO Enzyme Supplement
Diamine oxidase (DAO) is the main enzyme responsible for degrading histamine. However, in patients with DAO deficiency, this degradation activity is impaired, leaving histamine to run amok. The resulting symptoms are those we often associate with an allergic reaction or MCAS.
That’s where DAO supplements come in.
Similar to how lactase enzyme supplements relieve symptoms of lactose intolerance by raising lactase levels, DAO supplements increase the DAO levels in the digestive tract. By reducing the level of histamine entering the bloodstream, the total level of histamine in the body also decreases. This can provide some people with symptom relief.
There are a number of DAO supplements available over the counter, but be careful – ordering from Amazon may be convenient, but it’s also where fake and/or poor-quality supplements run galore. Whenever you buy supplements, I recommend buying professional-grade products directly from the producer or one of their trusted suppliers.
The DAO supplement I approve of for my patients is Histamine Blocker. With 20,000 Histamine Degrading Units (HDUs) per serving, this unique patented formula replenishes the DAO levels in your body so you can combat excess histamine in your food.
For more information on the mighty DAO enzyme, read my article, Boost Your DAO Levels to Fight Histamine.
3. Use Antihistamines and Mast Cell Stabilizers
Because DAO in supplements has such a short half-life, it cannot enter the bloodstream to reduce the amount of histamine produced within the body. This means that excess endogenous histamines need to be addressed by other methods, such as natural antihistamines and mast cell stabilizers.
You’re probably more familiar with antihistamines like Benadryl. These drugs provide relief from allergy symptoms by competing with histamines for occupation of histamine receptors on cells. While you may want to keep medications handy in case you need immediate symptom relief, some reports suggest that the body can build a tolerance to these drugs, requiring more potent medications. If possible, try to start with natural sources of antihistamines and try to address the underlying causes.
Natural sources of antihistamines are:
- Vitamin C
- Stinging nettle
- Local raw honey
On the other hand, mast cell stabilizers prevent degranulation and stabilize the cell, preventing the release of antihistamines. Quercetin is a powerful, well-known, natural compound that exhibit mast cell stabilizing activities. Other mast cell stabilizers you might be familiar with include resveratrol, luteolin, and curcumin.
Having to take so many supplements can be overwhelming, especially if you’ve just been diagnosed with MCAS. I get it. Nobody wants to spend hundreds of dollars on dozens of supplements each with different directions. You’d be spending all day taking them! You don’t have time like that.
That’s why I recommend Hist Assist, a blend of flavonoids, antioxidants, enzymes, and botanicals that provide you with a comprehensive support for relief from MCAS symptoms.
4. Identify Sources of Toxins
There is no one single factor that has been shown as the definitive cause of MCAS. However, various microbes can disrupt the immune system and cause mast cells to go haywire.
One of the biggest environmental triggers of MCAS is mold, which I’ve written about in my article, Mold is a Major Trigger of Mast Cell Activation Syndrome. For patients with MCAS, it’s absolutely essential to reduce the body’s microbial burden. This could mean eliminating the source of the toxins or removing yourself from the building.
5. Increase Exercise & Sweating
You don’t have to spend thousands of dollars on trips to remote islands to experience the benefits of detoxification. Once you minimize inflow of toxins or triggers, you can take steps to mobilize toxins and enhance toxic outflow.
One of the best ways to “distress” the toxins in your body is to get the blood pumping through exercise. Sweating has been receiving a lot of attention in the recent years, with experts disagreeing on its ability to remove toxins from your body.
While it may not remove all pollutants, there are studies that show sweating is an effective and safe method for removal of:
In general, adults should aim for at least 30 minutes of moderate exercise every day. You can also try to sweat more with regular sauna sessions.
6. Promote Good Gut Health
The gut microbiome is another topic I’ve written extensively about. And although we’re still in the early stages of understanding the gut microbiome and its impact on our health, many experts agree that a skewed microbiome often results in illness, including inflammation.
Therefore, moving beyond calming hyperactive mast cells, restoring balance to body’s microbiome is essential. Diet is a huge factor, and I emphasize the importance of eating organic foods if and whenever possible. A plant-centric, low-carb diet will starve the bad bacteria while providing the good guys with energy to thrive.
To get a boost in restoring a healthy intestinal microecology, you can take a probiotic supplement like Probiotic Daily Essentials. Each capsule of this four-strain probiotic supplement is sealed in nitrogen-purged aluminum blister packs, protecting it from factors that compromise stability of probiotics.
7. Get Enough Sleep
In a world that idolizes intense productivity and doing “all the things,” it’s tempting to sacrifice sleep. But doing so can upset the circadian clock of mast cells, which regulates the severity of allergy symptoms throughout the day.
An interesting facet of allergic diseases is the variation in symptom severity throughout the day. Earlier studies showed that serum mast cell histamine levels were lower in the afternoon and highest at night. This is why many patients with allergies report experiencing “morning attacks” or sleep disruptions.
With irregular sleep patterns or poor sleep quality, mast cells can lose their rhythmicity, which means mediator release becomes uniform throughout the day. The bottom line here is that cultivating a good, regular sleep schedule and sticking to it can help keep your mast cells in check.
8. Reduce Stress
Chronic stress can kick your immune system into overdrive and allow troublemaking microbes to flourish. Stress can also contribute to mast cell degranulation, which causes them to release mediators like histamine. It only makes sense, then, for patients with MCAS to minimize stress as much as possible.
Triggers for MCAS patients can be wide-ranging, from physical or emotional stressors to the smell of perfume or even a change in room temperature. The reality is, MCAS is highly variable in its behavior. Thus, stress management for patients with the disease also needs to be personalized.
Similar to what I discussed in the “Eat a Low-Histamine Diet” section, I recommend that patients keep a daily journal of any emotions, events, or activities that triggered their symptoms. And remember, the devil is in the details. If you suspect that you are suffering from MCAS, it’s crucial that you provide your physician with a detailed list of triggers and symptoms.
Stress is a major problem for most of us, and many of us don’t have a healthy way of managing it. But it doesn’t have to be difficult, expensive, or time-consuming. For my tips on how to reduce stress, check out my article, Be Happier & Less Anxious with 7 Minutes a Day.
9. Low-Dose Naltrexone – The Surprising New Comer
Even with all the treatment methods outlined above, some people may continue to struggle with MCAS symptoms. Recent research shows that a novel use of low-dose naltrexone (LDN) may help some of these patients.
At first glance, LDN may seem like a strange drug of choice for treatment of MCAS. After all, naltrexone is a drug that was approved to help prevent narcotics and alcoholics from relapsing. As an opiate antagonist, naltrexone competes with opioid drugs for real estate on opiate and endorphin receptors. This helps patients feel less “high” from opioids or alcohol and reduce cravings.
So how does blocking opiate/endorphin receptors help MCAS patients?
LDN works in a different way. While it is still an antagonist for opiate/endorphin receptors, LDN appears to trick them into responding with an increased production of endorphins, the “feel good” chemical that is released during exercise.
More importantly, when LDN is used within a specific dosage window (typically between 0.5 mg and 4.5 mg), its binding of opiate receptors on immune cells can have a temporary immunoregulatory effect. The increased levels of endorphins stimulate the immune system by binding to regulatory T cells, which promotes an increase in T-lymphocytes. This upregulation of T-lymphocytes reduces cytokine and antibody production, restoring a more normal balance.
Additionally, LDN has anti-inflammatory effects. Recent studies have demonstrated this effect in patients with fibromyalgia, in which inflammation of the central nervous system is a common characteristic. When triggered by inflammation or infection, microglia and immune cells in the central nervous system increase their expression of TLR-4, which leads to an increase in the production of pro-inflammatory cytokines. As a TLR-4 antagonist, LDN blocks this cascade of inflammation. You can find out more information about LDN by reading my article, Low Dose Naltrexone: The New Treatment You’ve Never Heard Of….
In one 10-week pilot study, 8 women with fibromyalgia were given a 4.5 mg oral dose of LDN every night. The serum levels of several pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β, IL-2, IL-15, IL-17A, and tumor necrosis factor (TNF)-ɑ decreased significantly. Researchers also found that the patients who took LDN had a 15% reduction of fibromyalgia-associated pain and an 18% reduction in overall symptoms.
We have a lot to learn about LDN, and studies using LDN as a treatment option for MCAS is extremely limited. In a case study reported last year, one patient with severe MCAS and postural orthostatic tachycardia syndrome (POTS) experienced significant and sustained improvement using a combination of LDN and intravenous immunoglobulin (IVIg) therapy. The doctors overseeing her case hypothesize that by blocking TLRs that stimulate mast cell activities, LDN reduced the patient’s neuroinflammatory pain.
The doctors also reported successfully using LDN and antibiotics to treat another patient with POTS and MCAS.
Can LDN Treat Mast Cell Activation Syndrome?
Is LDN the inexpensive, safe, and effective therapy for MCAS we’ve been looking for all along? Of course, we’ll need more evidence, but based on the evidence so far, I believe LDN has the potential to treat a wide variety of conditions.
A word of caution when adding any supplements or medications: It might be tempting to take as many things as possible to relieve yourself of your symptoms, but people with MCAS can react to all sorts of things, even herbs. Slow down and take it easy. Start with one supplement or herb at a time and see how it affects your body.
Living with a chronic illness like MCAS can make you feel pretty discouraged. But there are things you can control. With the addition of healthy lifestyle choices and medications, you can stabilize mast cells and bring balance to your immune system.
Now I want to hear from you. Have you been diagnosed with MCAS? What have you tried for treatment of MCAS in the past? Have you ever tried low-dose naltrexone for MCAS or another condition? Let me know in the comments!
Many Lyme/MSIDS patients struggle with MCAS as their body is in a war.
https://madisonarealymesupportgroup.com/2017/04/17/mast-cell-activation-syndrome-lymemsids/ Not mentioned in the article by Dr. Carnahan is LDA/LDI. Many have improved with this treatment as it retrains the body not to react to substances. For more on that treatment: https://madisonarealymesupportgroup.com/2016/05/30/new-kids-on-the-block-ldaldi/
For more on MCAS: https://madisonarealymesupportgroup.com/2018/03/13/mcas-lyme-msids/