Mast cell activation improving with circadian optimization

Mast cell activation syndrome(MCAS) is a condition where mast cells release histamine and other inflammatory mediators that cause allergic-type reactions in the body. As a results, people begin experiencing allergic-type reactions when they consume foods high in histamine or its precursors. Many people dealing with chronic mast cell activation spend a loooooooong time trying to address it.

Often times the issue with mast cell activation can begin in the gut, but the adrenals contribute as well. Optimizing circadian rhythms is by far the most bang-for-your-buck approach to addressing gut problems. Plus, the risk of side effects is extraordinarily low.

Today we’re going to discuss the results seen by a 39 year old female from my Stop Leaky Gut Challenge. She has been dealing with MCAS, adrenal fatigue and hypothyroidism for 11 years.  Over time, restrictive dieting has led to a progressively declining food list.

This list has dramatically expanded since the challenge, and even further since beginning the Circadian Retraining Program. There are several lines of evidence that indicates circadian rhythms can impact histamine intolerance. Mast cells have their own circadian clock that regulates plasma histamine.

The gut and adrenals in mast cell activation syndrome

Another study implicates cortisol as a factor that regulates the mast cell clock. Cortisol inhibits histamine release, which is why allergic reactions tend to be worse at night. Nighttime is when the cortisol is lowest due to circadian variation.

Histamine also plays a role in gut disorders such as IBD and IBS. Thus, I believe her improvements fit in to 2 neat little buckets that I’ll use to describe what’s going on. These buckets are adrenal specific and gut specific. 

To be clear, these are not separate issues, they’re simply easy to categorize that way.  The gut affects the adrenals and the adrenals affect the gut. However, the adrenal hormone cortisol acts as an anti-inflammatory throughout the body, and decreases our sensitivity to histamine

The gut is a significant source of histamine. An inflamed gut causes histamine to leach out in to the blood. Additionally, beneficial bacteria from the microbiome make histamine from the foods we can consume. Other bacteria, the bad guys, cause our gut to release histamine.

Image result for histamine intolerance
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Correcting mast cell activation via the adrenals

Properly synchronized circadian rhythms are critical for adrenal function. Properly synchronized circadian rhythms set the daily variation in cortisol, which helps set your level of arousal throughout the day. 

High cortisol levels in the morning help wake you up and make you alert. Cortisol normally declines throughout the day, reaching the lowest at night. This helps you fall asleep.

This daily rhythm also helps set your sensitivity to stressors throughout the day.  But it’s important to point out that your behavior also plays a role in your daily cortisol rhythm.  This is why watching a scary movie at night or worrying about your finances 24/7 can negatively impact your sleep.

Adrenal improvements from circadian optimization

All that said, a combination of optimizing circadian rhythms and managing stress is the ideal way to address adrenal problems.  Addressing it in this manner, this participant saw some major adrenal improvements including:

  • Improved sleep – “falling asleep immediately when I go to bed, no matter what my day has been like.”
  • A significant decrease in inflammation – “previously the slightest activity would sideline me for days with severe inflammation that was both painful and sapped all my energy.
  • Fewer spikes in heart rate and sudden drops in blood pressure, particularly while standing or sitting still.
  • Improved resilience for physical activity

This is all a fantastic development for this woman.  She even described a situation where she traveled across time zones to visit family. She kind of went off the wagon for a few nights. 

Normally, this would sideline her for days. But since she was compliant for 10 weeks, she felt fine. She slept fine, and was even able to do things with her kids without 4 days of inflammation afterwards.

The key word here is resilience.  She put in the time and work, and now she’s on her way to feeling and functioning better.

Correcting Mast cell actvation from the gut

While she only mentioned 2 gut improvements, both are an indication of diverse improvements:

  • A significantly improved ability to handle high histamine foods- No heart palpitations or cortisol surges.
  • My urine is much darker, which means I have much better bile. (It was completely clear)

The first improvement in gut function is something I expect to see universally for digestion.  I feel many people believe their poor digestion is from low digestive enzyme output. But this is likely only part of the problem. 

A bigger issue not addressed by taking digestive enzyme is the mucus layer in the small intestine isn’t thick enough. Therefore, digestive enzymes don’t have enough time to act on your food.

The mucus layer changes throughout your gut.  The stomach and colon have a dense inner mucus layer and a loose detached outer mucus layer. 

But in the small intestine, there’s only one loose detached mucus layer so we can absorb nutrients.  Enzymes are dispersed in to that mucus layer to act on your food.

Improved mucus layer through circadian optimization

When this mucus layer is inadequate, enzymes don’t have enough time to breakdown our food. Then, bacteria can come closer to the epithelial cells that make up the intestinal barrier. 

To build up an adequate mucus layer, we need enough energy and time to build it up.  This, as you can probably imagine, is regulated by circadian rhythms.

So this woman saw improvements in her ability to handle higher histamine foods. But this probably has more to do with a thicker mucus layer. And less to do with increased diamine oxidase(DAO) synthesis which breaks down histamine.

The increased darkness in her urine is an indication of either improved bile flow or a change in the microbiome.  The color of your urine and poo are caused by bacterial action on bile pigments.

So moving from clear urine to yellow is a sign that you are making more bile. That, or her microbiome is becoming more enriched in commensals that transform bile pigments.  (NOTE: Cortisol plays a role in bile acid recycling so this may be linked to the improvements in cortisol)


Circadian rhythms play a big role in regulating gut and adrenal function.  The modern world drives us towards behaviors that cause circadian disruption which can lead to dysfunction in both.

But it doesn’t have to be this way.  We can optimize our circadian rhythms by changing this behavior. Though, it requires more work than playing around with blue light glasses and time-restricted eating for most.

Tinkering around with light exposure and the feeding/fasting cycle can lead to moderate improvements for some people. But deeper problems require more complex solutions. 

The more comprehensive 18-point Stop Leaky Gut Challenge was just what the doctor ordered for this participant. And her results are indicative of her efforts.

For more information on the Stop Leaky Gut Challenge, click here.

3 thoughts on “Mast cell activation improving with circadian optimization

  1. lavendelblauen says:

    Its horrible how much trouble leaky gut is resposible for. The only drawback I found in the article is the infographic incorrectly lists Endometriosis as a “symptom” of histamine intolerance…Endo is 100% genetic. I can understand the reasoning though, histamine can cause worsening of symptoms with IBS & menstual pain flares to go haywire because of gut permiability–but it is NOT the origin of Endo lesions. (Perhaps I misunderstood the graphic, appologies if I mixed that one up. I get a little upset when I see misinformation about Endo ☺️.)

    • cincodm says:

      I think what they are referring to is that if you are genetically susceptible to endometriosis, histamine intolerance will exacerbate it. The same for asthma, migraines, etc. IMO, histamine intolerance is an “environmental”issue that can draw out genetic weak links.

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