Mast cell activation syndrome treatment: Time’s on your side

Mast cell activation syndrome(MCAS) treatment normally centers around blocking histamine. You’ve likely heard of histamine as the release of histamine from mast cells causes allergic symptoms. Symptoms such as sneezing, runny nose, cough, and things of that nature.

Mast cells are cells of the immune system that help protect the body against foreign invaders. Activation of mast cells causes degranulation: the release of histamine and other inflammatory compounds that signify an invader is present. In mast cell activation syndrome and allergies, they are inappropriately activated.

This is what causes the classic allergic symptoms. Mast cells also contain histamine receptors. When histamine binds to this receptor, it causes mast cell degranulation. Antihistamines work by binding this receptor and preventing this response.

Circadian synchronization: A key to mast cell activation syndrome treatment

Like most other cells in the body, mast cells are under circadian control. Every one of our cells has an internal timekeeping mechanism that changes how they work throughout the day. This concept, known as a circadian rhythm, simply means that a cells function changes throughout the day to meet our needs.

Circadian rhythms are incredibly important for our health and overall well-being. We did a video blog you can check out here if you need a rundown of what they do in general.

As far as mast cells go, circadian rhythms play an important role in their number and sensitivity to stimulation. Mast cell numbers in mice reach their minimum early in their subjective day, and peak in their subjective night.

Immunglobulin E(IgE) and interleukin-33(IL-33) play an important role in activating mast cells. When these molecules bind to their receptors on mast cells, they cause degranulation.

Fortunately, our circadian rhythms help control the sensitivity of mast cells to these compounds. During the daytime, mast cells contain fewer receptors for IgE and Il-33 which decreases the sensitivity of mast cells to degranulation.

At night, these receptors increase, making mast cells more sensitive to degranulation. This is likely why MCAS and allergic symptoms tend to be highest at night. This is the basis for a recent review on the circadian control of mast cells.

Mast cell activation syndrome treatment: Circadian rhythms play a role

Which signals set the mast cell clock?

Each one of us has our own, personal circadian rhythm. While it typically runs close to 24 hours, it’s not exact. Luckily, environmental cues help reset our clocks every day AND help synchronize all of the clocks in our body to one another. This keeps our cells on the same time.

From a mast cell perspective, this is incredibly important. When the mast cell clock is disrupted, this causes daytime mast cell activation to resemble the night. In other words, they become more sensitive to activation during the day.

So which signal or signals help keep time in your mast cells? It seems that part of it is regulated by the stress hormone cortisol. In addition to being an important stress hormone, cortisol also plays an important role in our circadian rhythms.

Cortisol follows a circadian rhythm, peaking right before we wake up. This causes us to wake up, which led researchers to refer to this as the cortisol awakening response. This cortisol awakening response may be the key to resetting your mast cell clock every day.

The cortisol awakening response is primarily regulated by chronic light exposure. When we wake up and expose our eyes to sunlight, this creates a timing cue that sets the cortisol awakening response.

Additionally, since mast cells are considered a peripheral clock, they may be sensitive to when we eat our first meal. Evidence shows that while our master clock is primarily regulated by light exposure, most of our peripheral clocks are regulated by when we eat.

Mast cell activation syndrome treatment: Other circadian factors

Many people are becoming exposed to the importance of circadian rhythms. As such, many have begun regulating their light exposure and tinkering with time-restricted eating to find their optimal feeding window.

However, there are other important factors to consider. What we eat plays an important role in our circadian rhythm as well as mast cell activation.

Magnesium is essential for our circadian rhythm AND acts as a mast cell stabilizer. In addition, many nutrients, especially ones that play a role in gene regulation, are necessary for healthy circadian rhythms

Finally, our gut contains a majority of the mast cells in our body. Our gut also has its own circadian clock that interacts with another circadian clock in our microbiome. This causes circadian variation in different metabolites such as short chain fatty acids(SCFA).

One SCFA in particular, butyrate, is created when microbes in our gut ferment fiber and some amino acids. Butyrate decreases activation of mast cells by regulating the sensitivity of IgE receptors on mast cells. Another SCFA, propionate, does the same.

Therefore, the circadian clocks in our gut AND microbiome, which are regulated by what and when we eat, are also critically important to proper mast cell circadian rhythm.


Mast cell activation syndrome and other conditions with improper mast cell activation are likely worsened significantly in people with circadian disruption. As such, practicing good circadian habits may be an essential part of mast cell activation syndrome treatment.

In addition, a diet supportive of healthy circadian rhythms is important. Generally speaking, a Mediterranean diet is likely the best choice for this given what we know about how the gut works. However, for many with gut issues, this may be tricky as the microbiome can activate mast cells as well.

Furthermore, many may not have the metabolic machinery in their microbiome to degrade fiber to butyrate. Therefore, a short term elimination diet such as Keto or Carnivore followed by reintroduction can help an individual find the diet that’s best for them. Spoiler alert: It’s likely gonna contain fiber and polyphenols.

Note: An individual in our circadian program saw major improvements in their mast cell activation syndrome by optimizing her circadian rhythms and addressing all of this. You can check out her story here.

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