Top 10 Tips for Calming Mast Cell - Histamine Response

top 10 tips to calm mast cells


We have deep dives on mast cell activation pathways but we wanted to get to the toolkit for offsetting this whole process below.

First...the mast cell cheat sheet:

what causes mast cell activation

Now, a quick look at the tools found in research that can actually reverse this hyperactivation of our immune system response without tolerance, addiction, and side effects.

Otherwise, we're just creating a worse problem in the future!

We'll run the gamut from steroidal hormones (especially important for women 40's and older) to unwinding the effects of past trauma/infection (very exciting).

Here's a quick list of tips for mast cell mitigation!: 

  • Progesterone - the original histamine calming agent
  • Early trauma and infection (even in utero or past generations)
  • Gut inflammation and vagus nerve - the inflammatory thermostat
  • Magnesium glycinate - our mineral mast cell offset
  • CBD isolate - leveraging the endocannabinoid system to dial down mast cells
  • Vitamin D - the steroid we get from the sun and histamine response
  • PEA - a powerful backup mast cell stabilizer
  • Medicinal mushrooms - using our distant cousins to remodulate histamine response
  • Berberine - a powerhouse gut remodulator and histamine
  • The mast cell grab bag - NAC, Omega 3s, Quercetin, B vitamins

Let's get started! 

Progesterone - the original histamine calming agent

For women, you have to start with progesterone.

We have a deep dive but understand that progesterone is the master calming agent for immune response including histamine and mast cells.

In fact, estrogen drives the immune system while progesterone calms it.


do steroidal hormones affect mast cells


It all goes back to pregnancy!

The amniotic sac is actually created by the father's DNA and as such, it's seen as a foreign entity by the mother's immune system which wants to attack it (the main role of histamine by the way!).

Progesterone calms this response..disabling the alarm so to speak.

That's why the autoimmune diseases can go into remission during pregnancy and 

Check out our autoimmune review.

Also...huge ties to preemie births and low progesterone (immune system is winniing!)


Here's the issue…

Progesterone drops by 50% by age 40! It continues down from there but the vast majority of sufferers from mast cell activation diseases are…women!


And the percentage creeps up during the 40s and beyond. Hmmm.

Make sure it's bioidentical and oral. Prometrium (or generic) is an option. Work with your naturopath but progesterone is a total game changer for mast cell activation. 

Interestingly for men, testosterone calms immune function as well (just not as pronounced)!

Okay… let's look at issues that apply to everyone (unfortunately). 

Early trauma and infection (even in utero or past generations) 

This is the big one. The newer research is all around the immune system and epigenetic changes.

Don't leave! We'll explain it all.



trauma and mast cells


Early trauma and/or infection (in utero or even past generations) can upregulate inflammation in the body.

Don't take our word for it: 

“We found that stress at different times had different effects – chronic exposure to stress is where we saw the significant differences in mast cell activity in the brain,”

A 30% increase in mast cell activity but this is only one aspect of a litany of insults from early stress and trauma: 

  • Reduced GABA (calming "brake" pedal)
  • Reduced serotonin - repair and stress response
  • Increased stress hormones
  • Increased inflammation


Much of what we talk about below is either unwinding this heightened immune response longer term or calming the immediate histamine response now.

Our experiences (good and bad) affect the epigenome which turns our genes on and off.


does early trauma infection affect mast cells


Think of it as an equalizer for music. Dials (say bass or treble) get moved up and down and directly affect the sound of the music.

Your mast cell response is the music and we need to change those dials!

Check out our review on trauma or how the immune system is the key to mental health (and histamine response).

One more stop before we get into the tools. 

Gut inflammation and vagus nerve - the inflammatory thermostat 

The gut is our early detection system for outside intruders which makes sense since it's the site for first contact for most bacteria/fungi etc free-riding on our food.

The problem is that our gut constantly deals with chemicals and substances it has no clue what to do with.

  • Glyphosate and other pesticides
  • Artificial flavors, preservatives, colors, and other chemicals


Check out our review on CBD and the gut barrier to learning more.

The gut barrier is critical because when it's weakened, bacteria can escape into our bodies and the immune response including histamine is fast and furious.

In fact, a range of very common diseases are showing signs of bacteria influence including ones you wouldn't suspect: 

  • Dementia
  • Arteriosclerosis (plaques have bacterial signature DNA)
  • Prostate cancer (brand new research)
  • Autoimmune
  • PCOS (brand new research!!)


Remember, the core role of histamine is to rid the body of foreign intruders!

This becomes a constant signal of intrusion across the body and it all starts from the gut (and occasionally the mouth, urinary/reproductive tracts).

Some of the tools below really focus on the gut inflammation states and the protection of the barrier.

Let's get into it! 

Magnesium glycinate - our mineral mast cell offset 


does magnesium calm mast cell activation


Mag is awesome and so many people don't get enough since the conveyor belt from soil to food (ground bacteria and fungi) has been broken from pesticides and monocrop rotation.

Mag acts like a powerful calming agent across the body including its support of GABA, our primary "brake" pedal.

In fact, histamine and GABA are opposing forces in the sleep/wake cycle which is why histamine is so tied to insomnia (more here).

Mag deficiency directly drives mast cell activity (where histamine comes from).

Check out the review on magnesium glycinate. We focus on glycinate since it crosses the blood brain barrier and is key for mental health, sleep, and a range of excitability issues such as migraines.

We take 3 - 100mg daily to keep migraines at bay.

One note…when you're under stress, you just dump out magnesium via urine. It's a primary stress response buffer!

As for mast cells when mag drops: 

many investigators have recognized the same symptoms in relation to degranulation of mast cells with a release of histamine and inflammatory mediators

Check out the big review on magnesium glycinate with practical guidance.

Next up…the system that balances our immune response. 

CBD isolate - leveraging the endocannabinoid system to dial down mast cells 

CBD isolate for mast cells

We have huge reviews on CBD and mast cells or CBD as a mast cell stabilizer.

CBD isolate works within our endocannabinoid system which is tasked with balancing other key systems including the immune system (which features histamine).

The best part is that it doesn't push in one direction but calms histamine response when too high.

Speaking to this balance (don't worry…we'll translate!): 

Together, the results suggest that CBD may induce activation of PPARγ in mast cells leading to secretion of G-CSF and consequent MDSC mobilization.

PPAR is a powerful pathway for "resolving" inflammation including histamine.

MDSCs are the counterbalance to mast cells. They basically push back on histamine response to bring it in balance.


Resolution! Again, this fits right into the endocannabinoid system's wheel house.

One important note…full spectrum CBD can have opposite effects due to the plant material.


is cbd isolate better for mast cells


There is a very different response between CBD isolate (by itself) and full or broad spectrum. More on full spectrum CBD versus isolate for histamine.

We take between 100mg-300mg daily as part of our regiment.  CBD Isolate here.  More on CBD for histamine here.

Also, check out CBD and asthma or CBD and psoriasis (autoimmune).

Next up…the forgotten steroid. 

Vitamin D - the steroid we get from the sun and histamine response 

Vitamin D is actually a steroid. It governs over 1000 different processes in the body including DNA repair and yes…immune function.

In fact, it's a master regulator of immune response on both the good (fighting cancer/infection) and bad side (histamine and mast cell response).

Recent research from the pandemic sheds direct light on it: 

Late mast-cell activation leads to the release of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α. Vitamin D is required to maintain the stability of mast cells, and Vitamin D deficiency results in mast cell activation

Goodness. "Vitamin D deficiency results in mast cell activation"

For that reason, your doctor has been testing Vitamin D levels for years, right?

Wrong!!   So many people are Vitamin D deficient and that's based on the ridiculous RDA levels of under 30 ng/ml. Endocrinologist want us closer to 70-80.

See our full review on Vitamin D (huge for sleep and mental health as well). Get tested. Get your levels up.

One more stop at our endocannabinoid system.

PEA - a powerful back up mast cell stabilizer 

PEA is a backup player called in when the primary endocannabinoids (anandamide and 2ag) are running low. Exhausted.

Anandamide, named after the hindu goddess of "bliss" is a powerful backup when inflammation runs high.



does anandamide help with mast cells


It's there to "resolve" or bring it back down. CBD supports anandamide, which act like a big wet blanket of inflammation including histamine.

PEA is a backup backup to anandamide. Calling in the reserves!

The results: 

The anti-inflammatory effects of PEA have been for a long time related to its ability to regulate mast cell activation and degranulation, an action that is known as the ALIA mechanism (Aloe et al., 1993).

Full review here. You can supplement PEA here. CBD supports anandamide when low while PEA is a supplement to it.  Very different from THC which pushes too hard/long as it mimics anandamide.  This causes a rebound and tolerance longer term!

Let's turn to the gut now since it's a huge player in our histamine response. 

Medicinal mushrooms - using our distant cousins to remodulate histamine response 


are medicinal mushrooms good for mast cells


We have a huge review on Medicinal mushrooms.

Fascinating effects across the range of mushrooms with huge implications on modulating or balancing our immune response.

Just a few examples….


Results also indicated that inotodiol, a triterpenoid predominantly present in DF, played an active role as a mast cell stabilizer.


In conclusion, our results suggest that Cs-4 has the potential to alleviate immune hypersensitivity reactions in allergic rhinitis and asthma.

Again..we can go on and on as the a range of mushrooms show anti-inflammatory (including histamine) effects and powerful abilities to re-balance our immune system.

Read the big review here. We take a mix of medicinal mushrooms here.

Still in the gut…next up is berberine. 

Berberine - a powerhouse gut remodulator and histamine 


is berberine good for mast cells


Berberine is a natural analog for metformin.

Both have powerful effects on calming gut inflammation and protecting the gut barrier (so bacteria, etc can't escape into the body).

Akkarmansia, a unique probiotic that increases with berberine or metformin, may be at the heart of these effects but either way, it's beneficial for mast cell activation issues.

Berberine suppresses mast cell-mediated allergic responses via regulating FcɛRI-mediated and MAPK signaling 

This is the short term effect. The longer term effect is reducing the "assault" so that the immune system isn't always code red.

Big review on berberine and this is the one we take.

Finally…the war party so to speak. 

The mast cell grab bag - NAC, Omega 3s, Quercetin

These players may have some benefit and are generally good for health anyway. There's a good review of different mast cell stabilizers here but the potential rising stars… 

Let's jump in. 

NAC and mast cells

NAC supports glutathione, our primary detox pathway in the body.

Nitrous Oxide (NO) can suppress mast cell activity. 

NAC's result there: 

Furthermore, co-incubation with NAC allowed previously ineffective NO donors to suppress HCMC activation and thus suggested that NAC could increase the availability of NO from NO donors.



does glutathione affect histamine


Vitamin C supports the glutathione pathway as well. See glutathione or oxidate stress.

Omega 3's and Mast Cells

The "good" fat can have a powerful effect on inflammatory response via its alpha-linoleic acid metabolites: 

Taken together, omega-3 fatty acids might target mast cells to a greater extent than T cells to suppress Th2 cytokine expression by inhibiting GATAs for alleviation of allergic disease.


Fish oil is a great source of Omega 3 and watch out for the seed oils (and the highly industrial "vegetable" oil) with their Omega 6 profiles. Highly inflammatory.

We did a huge review on Omega 3's.

Quercetin and mast cells

Quercetin (and fisetin) are fascinating plant-derived substances with effects across the inflammatory spectrum including…mast cells!

Quercetin also exerts its anti-inflammatory properties by inhibiting mast cell degranulation and therefore all the pro-inflammatory compounds contained in granules, including tumor necrosis factor (TNF)


We really like "super" quercetin - called myricetin for it's powerful effect on dopamine!

That's a wrap!  We focused on substances that don't build tolerance but calm "excessive" histamine response.



natural tools for histamine


Keep in mind that histamine is a very important player in protecting us so we don't want to hammer it down (say with antihistamines) completely.  Histamine is excitatory in the brain and key to the sleep/wake cycle.

We need it to be alert and engaged during the day. These players are backups when there's imbalance and that's ideal in such a complicated web as the immune system.

Don't forget....

The Cheatsheet:

what causes mast cell activation

Related Research:

Best CBD for histamine

Mast cell stabilizers

Histamine and insomnia

Why histamine is so important for women



buy 1000mg cbd isolate no thc
buy 2000 mg cbd isolate online no thc

buy 6000 mg cbd isolate no thc online


Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.


Back to blog

Leave a comment

Please note, comments need to be approved before they are published.