Herbs: Histamine Intolerance & Mast Cell Activation

Lately I have been seeing more sensitive patients. These patients are eating only a handful of ‘safe’ foods, they have a long list of supplements that they react to and their symptoms are unusual and hard to pin down to one precise thing. 

Histamine intolerance or sensitivity is a major player in many of these patients’ presentations and it shows up in a multitude of ways. Runny or stuffy noses, chronic sinusitis and itchy eyes tend to be the more common symptoms with headaches, migraines and sore lymph nodes coming in a close second. For a primer on how histamine affects your digestion check out a previous article Histamine Intolerance & the Gut.

My approach to treating histamine intolerance ranges from client to client but today I wanted to share some top herbal medicines that I might choose to include in a protocol.

Herbal Medicine & Histamine Intolerance 

There is the difference between herbs that I use and have observed helping clients with histamine intolerance and digging up every obscure reference in the scientific literature. I prefer to use tried and tested therapies first. If we are having trouble getting results I will do a deep dive into the literature to find more supportive treatments. 

I will list the following histamine intolerance herbs in order of priority. The ones I find more effective and use frequently will be listed first. 

Baical skullcap for histamine intolerance 

Baical skullcap is a popular herb in Chinese Medicine. 

I frequently use baical skullcap as a potent antiviral, inflammation modulating, antimicrobial and anti-allergy herb. 

When focusing in on the allergy side of things baical skullcap has been shown to inhibit anaphylactic-like reactions, stabalise mast cells and inhibit plasma histamine release in animals. 

The fascinating image below shows a mast cell from a rat (A). They then introduced a potent mast cell degranulation mix that forces mast cells to release upwards of 90% of their histamine (C) Finally in the bottom left box (D) we can see a mast cell that had been pretreated with the baical skullcap extract that then had the mast cell degranulation mix added (1).

Pictures really are worth a thousand words!

Image taken from: Scutellaria baicalensis Inhibits Mast Cell-Mediated Anaphylactic Reactions  

This same effect has been noted in another study where they found the flavonoids to be the most potent mast cell stabilising constituents in the herb (2).

This is interesting as quercetin, which we will cover in a future article on the supplements I use for histamine intolerance and mast cell activation, is a flavonoid.  From the supplement side of things quercetin is my top therapy for allergic and histamine related conditions.   

Finally, research has shown that baical skullcap decreases inflammatory mediators of the allergic response and helps to modulate the Th1/Th2 balance (3).

Clinical note. I use baical skullcap frequently in patients with histamine intolerance and mast cell activation syndrome. It is a very cold herb so should be formulated with warmer herbs to balance the coldness and prevent loose, sticky stools.

Perilla for histamine intolerance

Perilla frutescens is a top anti-allergy herb I turn to when histamine intolerance is evident. This herb is a member of the mint family and has a tradition of use as a food and medicine in China, Japan, Korea, Vietnam and India for a range of conditions (4).

Image of perilla leaf from the Byron Herbalist dispensary. We source the best quality herbs available in Australia to make into tinctures or powder them for sensitive patients. 

There have been over 270 different phytochemicals isolated from the perilla plant ranging from polyphenols, volatile compounds, fatty acids and even tocopherols (4).

This is why it can be so hard to pin down exactly how a plant is having an effect on a person. Sometimes I have found it helpful to use isolated and refined extracts that can be found in perilla, specifically luteolin and rosmarinic acid, but the whole herb is a great place to start and build up from there.   

One animal study showed perilla could inhibit the release of histamine and upregulate cyclic AMP from rat mast cells (5).

In an in vitro study luteolin, a polyphenol flavonoid found in perilla, was shown to inhibit proinflammatory messenger molecules from human mast cells. Animal studies showed luteolin to reduce histamine release from mast cells that had been stimulated by a histamine liberator (6).

Image taken from: Anti-Inflammatory and Antipruritic Effects of Luteolin from Perilla (P. frutescens L.) Leaves

Nigella sativa for histamine intolerance

Black cumin or nigella is a herbal medicine that has always attracted me. There is something to this plant that is hard to pin down. A properly extracted herbal tincture has an oily and earthy taste, somewhat muted compared to other essential oil rich herbs and just a touch of acridness on the back of the throat.

We could spend the next 10 articles reviewing the long history and extensive research on black cumin but I will keep it brief.

Used by cultures around the world, Nigella sativa is known by many different names. In Prophetic Medicine of Islam it was said that nigella could cure anything but death (7).

One review outlined nigella’s actions on the body as ‘antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti≠inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro protective and antioxidant properties’ among others (8).

The seed of nigella has a number of active constituents including fixed oils, volatile oils and even pyrazole alkaloids, vitamins and minerals. Much of the research focuses on thymoquinone which makes up between 30-48% of the volatile oils in nigella (9).

Interestingly nigella seeds also contain thymol and carvacrol some of the major active constituents in both thyme and oregano which we commonly use in the Byron Herbalist clinic to treat methane and hydrogen SIBO, overgrowths and infections in the large bowel and even lung infections.   

Image taken from: Preclinical and clinical effects of Nigella Sativa and its constituent, thymoquinone: A review

Summarising the antihistamine in vitro and animal studies we see that thymoquinone, the principle active constituent in nigella, improved allergic conjunctivitis, blocked histamine receptors in the trachea and inhibited histamine release in an animal model of colitis (10).

Nigellone, a carbonyl polymer of thymoquinone, has been shown to improve asthma and bronchitis due to its mast cell stabilising effects. Nigellone has also been shown to inhibit the 5-lipoxygenase enzyme which is the rate limiting enzyme in the pro-inflammatory pathway of leukotriene synthesis (11).

The research supporting the use of nigella in histamine intolerance and mast cell activation is sparse but don’t let that fool you. Nigella is in the top 5 herbs I recommend to support histamine intolerant patients. As with most herbs it doesn’t work for everyone but is well tolerated and effective for many.

Nettle leaf for histamine intolerance

Often I am attracted to herbs that are commonplace and considered boring by some. Nettle is one of those underappreciated herbs by some herbalists. We use the leaf, root and even the seeds for different conditions. 

As we are discussing histamine intolerance today we will be covering nettle leaf. 

It may seem like a bizarre herb to turn too as nettle leaf actually contains histamine. Nettle leaf can be poorly tolerated in a small number of histamine sensitive patients but I still frequently recommend trialling the herb in most. 

Nettle has been shown to inactivate and inhibit the H1 receptors (H1 blocking medications are used to treat allergies) and stabalise mast cells which prevents extra histamine being released in your body. The downstream effect is a reduction in the messenger molecules that contribute to inflammation and allergy symptoms (12).

Nettle leaf has also been shown to inhibit mast cell tryptase. Tryptase is an enzyme that speeds up the breakdown of proteins. It regulates mast cell degranulation, a process whereby mast cells release their pro-inflammatory and immune stimulating messengers. This humble leaf has also been shown to block COX-1 and COX-2 enzymes resulting in lowered prostaglandin synthesis (12).

Other Herbs For Histamine intolerance 

I like to start with strong and well studied antihistamine herbal medicines like perilla, baical skullcap, nigella and nettle leaf. Occasionally if a patient is very sensitive I will start with one herb at a time or even pair it back to the extract to start the process of stabilising mast cells and lowering the histamine load on the body. 

There are a number of other herbs that I will frequently use if I feel they will be tolerated. 

Ginger is potently anti-inflammatory, soothes the gut and stimulates motility. If a patient is constipated then histamine intolerance will be soooo much worse. 

Albizia can be very helpful and has been shown in invitro studies to lower histamine levels by downregulating gene transcriptions for histamine-1 receptors and the histidine decarboxylase enzyme (HDC below) which converts histidine to histamine. 

Image taken from: Ben Lynch’s pathway planners 

Demulcent herbs that help protect the gut lining and build up the beneficial mucous layer can be helpful with some. My favourites here are marshmallow root and licorice. Ribwort can be helpful and slippery elm is great but less sustainable and best avoided if possible. 

Image of ribwort which is not technically antihistamine but can help as a demulcent and as an anti-inflammatory primarily for the lungs but I have found it helpful in the gut too. 

Finally anti-Inflammatory herbal medicine can help patients with histamine intolerance 

The process of inflammation is complex. 

In the most basic summary, mast cell degranulation resulting in histamine liberation in the body is part of that inflammatory cascade. It is often caused by insult or damage to the body which then results in a spurring on of that inflammatory process. Many classic inflammation modulating herbs can be helpful as background support in histamine intolerance. 

My favourites are curcumin extracts from turmeric as well as boswellia. 

Approaching Histamine intolerance in practice

As a clinician my goal is to help people regain their health. 

When someone presents with histamine excess symptoms it is important to improve those symptoms by blocking or downregulating the inflammatory process. The most important thing is to find and address why the body has kicked over into an inflammatory reaction and address that. 

Sometimes correcting the root cause takes time but thankfully the herbal medicines listed here help many feel better and regain their tolerance to common food intolerances. 

References & Resources

  1. Scutellaria baicalensis Inhibits Mast Cell-Mediated Anaphylactic Reactions  
  2. Scutellariae Radix. X. Inhibitory Effects of Various Flavonoids on Histamine Release from Rat Peritoneal Mast Cells in Vitro
  3. Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin-induced allergic airway inflammation and mast cell-mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release
  4. Ethnomedicinal, Phytochemical and Pharmacological Investigations of Perilla frutescens (L.) Britt.
  5. Inhibitory Effect of Mast Cell-Mediated Immediate-Type Allergic Reactions in Rats by Perilla Frutescens
  6. Anti-Inflammatory and Antipruritic Effects of Luteolin from Perilla (P. frutescens L.) Leaves 
  7. Nigella sativa (Prophetic Medicine): A Review 
  8. A review on therapeutic potential of Nigella sativa: A miracle herb
  9. Preclinical and clinical effects of Nigella Sativa and its constituent, thymoquinone: A review
  10. Thymoquinone and its therapeutic potentials
  11. Preclinical and clinical effects of Nigella Sativa and its constituent, thymoquinone: A review
  12. Nettle Extract (Urtica dioica) Affects Key Receptors and Enzymes Associated with Allergic Rhinitis

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  1. Hi Tood, please explain why you wrote: “slippery elm is great but less sustainable and best avoided if possible”.
    I suffer from histamine intolerance and I also have leaky gut, I wanted to start a supplement that has different herbs including slippery elm but now I’m not sure. Is it better to take just L-glutamine?
    Thank you very much.

    1. Hi Gloria, thanks for your comment. I don’t prescribe slippery elm as much as I would if it was a more sustainable herb. If it helps you can still use it, this is more of an environmental/ethical stance.

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