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Histamines: Friend or Foe?

Allergies, IBD, IBS, Mast Cells, DAO, HNMT, and the Top Natural Antihistamine Supplements. What you NEED to know.

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Histamine acts through its four histamine receptors, in affecting appetite, arousal, learning, motivation, sexual activity, and sleep.

Histamines act as neurotransmitters involved with attention and arousal, while also responsible for various digestive processes along with inflammatory responses.

Having a wide array of other actions, it’s important to understand how histamine can be your friend or foe.

What are Histamines?

As a biogenic amine, histamine is a multi-functional compound we produce in the body.

Histamines can be “goldilocks” compounds in the body, and some suggest excess histamine to be a factor in anxiety, with histamine deficiency as a contributing depression factor.

Sufficient histamine levels are protective, while excessive histamine levels can wreak havoc.

[Related Article: The Top 9 Science-Backed Immune System Supplements]

Because of common antihistamine medications, many are familiar with the word histamine.

Histamine reaction arises when the function of histamine has gone awry, with overproduction and imbalance of histamine.

Excessive chronic histamine can promote an array of negative side effects from allergic symptoms and more.

Histamine releases hydrochloride or HCl as the first stage of gastric acid from the stomach to breakdown food.

Understanding the function of histamine allows us to see the role of histamine and improve its function in the body.

Histamine Receptors and Histamine Function

Histamine acts as a neurotransmitter in our nervous system.

It is a main role player in appetite, learning, memory, motivation, sexual behavior, and our sleep-wake cycle or circadian rhythm.

Histamine stimulates stomach acid (HCl), to begin the early stages of digestion.

Increasing the immune response, histamine controls smooth muscles and airways, promotes blood vessel dilation, while turning on nerve cells acting in pain and itchiness.

The Four Histamine Receptors

As a chemical, known as a biogenic amine, histamine has four histamine receptors, H1R, H2R, H3R, and H4R.

H1R and H4R increase allergies and inflammation, and H2R stimulates stomach acid (HCl), while H3R counteracts all three of them thus regulating histamine release.

[Related Article: The Top 9 Science-Backed Gastrointestinal Supplements]

These four histamine receptors often maintain opposing actions.


  • Increases wakefulness and thirst
  • Lowers appetite
  • Excessive activation can promote allergic reactions, such as airway obstruction, anaphylaxis, hives, itching, pinkeye, redness, runny nose, and swelling.


  • Increases airway and blood vessel smooth relaxation
  • Increases heart rate, and stomach acid (HCl) production
  • Lowers bone density and Th1 and Th2 immune response


  • Counterbalances other histamine receptor activity inhibiting histamine release
  • Increases sleep and desire for alcohol
  • Lowers itching, acetylcholine, dopamine, GABA, glutamate, norepinephrine, and serotonin


  • Activates inflammatory response with white blood cells and cytokine release (Th2 cytokines: IL-4, IL-5, IL-13, and IL-17)


Histamine Release: (Allergies and Mast Cell Activation)

As histamine can build up in the body with the histamine system becoming “dysfunctional” in those with histamine intolerance, IBD, IBS, food allergies, and more can occur.

These allergies and food intolerances, along with mast cell activation or histamine reaction, are complications that can arise from histamine release.

[Related Article: The Top 9 Science-Backed Respiratory System supplements]

While this condition only affects 1 percent of people, individuals may hold certain genes that increase their histamine sensitivity.

A Variety of Cells Produce, Release, and Store Histamine

  • Histidine decarboxylase (HDC) from the amino acid histidine
  • Histaminergic histamine-releasing neurons
  • Mast cells and basophils
  • Brain, gut, immune cells when needed

When out of balance, excessive histamine can promote allergies and inflammation, causing all the inflammatory symptoms most who suffer from this can identify.

As this shift gains momentum, we can experience compromised cellular immune balance and gut barrier health.

The Two Histamine Metabolizing Enzymes (DAO) (HNMT)

The two enzymes which breakdown histamine are diamine oxidase or (DAO) and histamine N-methyltransferase (HNMT).

If either of these histamine enzymes becomes ineffective, histamine levels can rise tremendously.

No reliable tests exist for DAO and HNMT.

As enzymes break down histamine, we can only estimate DAO and HNMT activity.


Acting as the main histamine-metabolizing enzyme in the brain and in lesser amounts in other major organs, HNMT breaks down cellular histamine to prevent histamine release into the bloodstream.

Histamine and Methylation (MTHFR)

Because HNMT metabolizes histamine by methylating it, many MTHFR writers claim those with low blood histamine are “over-methylators”, while those with high blood histamine are “under-methylators”.

The methylation histamine explanation is not likely what is occurring across the body simultaneously, as our individual reactions are likely organ and/or tissue-specific.

Instead, individuals could have low gut HNMT activity with normal brain HNMT activity.

Greater histamine intake and histamine production along with lower DAO activity can be major factors.


DAO the primary histamine enzyme.

Lower DAO activity is the most common cause of histamine intolerance and histamine reaction.

We find DAO in the gut, and also kidneys and other organs and tissues.

We release DAO into the bloodstream, allowing it to break down extracellular histamine.

Degrading other biogenic amines such as putrescine and spermidine, DAO is an important enzyme.

Many common medications such as antidepressants and acid reducers suppress DAO and HNMT function.

The Function of Histamine: (Health Benefits)

Histamine is critically vital to the body’s daily activities in support of the following activities.

  • Allergies (Food)
  • Aging
  • Anorexia (Excessive histamine)
  • Antibacterial protection
  • Anxiety (Excessive histamine)
  • Cognition
  • Cognitive decline
  • Desire for alcohol
  • Depression (Insufficient histamine)
  • Gastrointestinal inflammation
  • Hormone release
  • Management of stress
  • Motivation and drive
  • Pain
  • Regulation of appetite
  • Regulation of temperature
  • Sexual behavior
  • Sexual reproduction
  • Seizure prevention
  • Thirst
  • Wakefulness (Circadian clock)


Histamine Reaction Causes

A histamine reaction or mast cell activation occurs when inflammatory symptoms are triggered as one has excessive histamine in the body along with a deficiency of histamine-metabolizing enzymes.

These allergy-like symptoms present themselves in an array of issues, with the avoiding foods with high histamines in favor of a low histamine diet, as the preferable diet strategy.

This condition affects roughly 1 percent of the population, however, it increasingly appears many more conditions and individuals can be affected.

There may be individuals with genetic traits that increase their sensitivity to histamine.

Symptoms of Histamine Intolerance

Those with allergy-like reactions to high histamine foods may be suffering from histamine intolerance.

Histamine intolerance could be involved with the following conditions.

  • Anaphylaxis
  • Anxiety
  • Arthritis
  • Atherosclerosis
  • Asthma
  • Balance issues
  • Bone density issues
  • Eczema
  • Heart Attack Damage
  • Inflammation
  • Irritable bowel syndrome (IBS)
  • Itchy skin
  • Migraines and chronic headaches
  • Multiple sclerosis
  • Parkinson’s disease
  • Schizophrenia
  • Ulcers


Drugs which can interfere with DAO and HNMT Function

  • Alcohol
  • Antibiotics
  • Antidepressants
  • Antipsychotics
  • Cardiovascular medications
  • Diuretics
  • Gastrointestinal medications (proton pump inhibitors: especially Prilosec)
  • Malaria and TB medications
  • Muscle relaxers
  • Pain medications (aspirin, diclofenac, naproxen, indomethacin, and others)
  • Theophylline


Are Antihistamine Medications Safe?

Antihistamine medications can function as histamine blockers or as mast cell stabilizers for Mast Cell Activation Syndrome (MCAS).

We have created an array of antidepressants and antipsychotics from the antihistamine medication structure.

Best used at night because of its increase of drowsiness, Benadryl is a common H1 receptor antagonist which also increases the production of diamine oxidase (DAO) production.

Benadryl may also act similar to SSRI antidepressants in lowering anxiety because of an increase of serotonin in the brain.

Other options, such as fexofenadine (Allegra), don’t trigger drowsiness because of its lack of crossing the blood-brain barrier as effectively as these “first-generation” antihistamines such as Benadryl (diphenhydramine).

Recently, Harvard Medical School in Harvard Health warned against the long-term use of many antihistamine medications amongst other sedatives, along with other common medications containing anticholinergic actions.

This is because many antihistamine medications deliver negative long term anticholinergic effects on the brain.

Foods with High Histamines: (Low Histamine Diet: Low FODMAP Diet)

An emerging theory is foods with high histamines cause our cells to release histamines as the bigger factor.

We are now seeing a connection between conditions such as SIBO and histamine intolerance, making the low FODMAP Diet popular, lowering histamine levels by 8 times.

For this reason, the low histamine diet such as the Low FODMAP Diet and elimination of these foods has become a popular treatment.

If one is on a low histamine diet, because of histamine intolerance, they should avoid the following foods with high histamines.

  • Alcohol products: (beer, liquor, and wine)
  • Cold cuts: (ham, salami, sausages)
  • Eggplant
  • Fermented dairy products: (buttermilk, cheese, kefir, sour cream, and yogurt
  • Fermented vegetables: (kimchi, pickles, sauerkraut)
  • Kombucha
  • Processed Fish: (canned, frozen, salted such as sardines and tuna)
  • Soy products miso, natto, soy sauce, and tempeh
  • Sourdough bread
  • Spinach
  • Tomato Ketchup and tomatoes
  • Vinegar

*Also, one should avoid collagen and bone broth if one suffers from histamine intolerance.

* Other biogenic amines such as cadaverine, putrescine, spermidine, spermine, tryptamine, and tyramine are created by food storage bacteria growth, making lengthy and unrefrigerated leftovers to be avoided.

*Food additives can also trigger histamine release.

DAO Enzyme Co-Factors (We NEED These Micronutrients for Optimal Function)

  1. Copper

2. Iron

3. Vitamin B6

4. Vitamin B12

5. Vitamin C

*Magnesium, Manganese, Zinc are also important for Histamine Metabolism.

*Copper/ Zinc balance is important. Daily zinc intake over 40 mg can lower copper absorption.

Top 5 Natural Antihistamines

We find plant-based antioxidants in foods and supplements, certain herbal supplements, probiotic strains, and vitamins and minerals, such as B6, magnesium, and zinc to work as a natural histamine blocker.

Making histamine from the amino acid histidine, mast cells use an enzyme called histidine decarboxylase (HDC) to release histamine, in responding to an array of histamine triggers including food and more.

These histamine blocker supplements and foods can block this histamine creating enzyme, thus stopping mast cells from releasing histamine, and/or assisting the body in the more efficient metabolism of histamine.


Quercetin, the rising coronavirus star, a believed zinc ionophore with potent antivirus, antioxidant, and anti-inflammatory actions, also offers histamine blocker actions.

Naturally occurring in a variety of plant-based foods such as apples, berries, black tea, green tea, peppers, some vegetables, and red wine, studies find it buffers respiratory side effects through lowering respiratory airway inflammation.

As an antioxidant and plant flavonoid, we identify quercetin as one of the top natural antihistamines out there.

While drugs typically work faster than natural supplements, in one study we find quercetin more effective than the pharmaceutical Cromolyn, the mast cell-stabilizing drug.

As quercetin and stinging nettles do not cross the blood-brain barrier, we can use it without the negative short- and long-term side effects common with antihistamine medications.

Dosage: One capsule three times daily. Capers are the densest quercetin food source, with apples being the most common quercetin food source. Green tea is another quality quercetin source. Dividing dose is key with its short half-life.

Stinging Nettle

Thought to be equally effective as quercetin, stinging nettles are also a top antihistamine supplement, as we often find the two combined in natural histamine blocker supplements.

Like quercetin stinging nettle is also a top coronavirus, antioxidant, anti-inflammatory, and antiviral natural supplement receiving much attention.

As a common natural supplement, stinging nettle shows natural antihistamine actions in a study wherein 58% experience symptom relief, along with 69% reporting it superior to placebo.

Dosage: Studies use 300 mg of stinging nettles daily. Nettle root is used for men’s issues such as BPH, and urinary issues. In this indication and all others, nettle leaf should be used.

Vitamin C

Vitamin C is also a top natural antihistamine.

As the coronavirus spotlights vitamin C, we see much more use for it than ever before, beyond solely its histamine blocker actions.

Studies find high vitamin C intravenous doses as reliably reducing allergy symptoms.

Another shows 2,000 mg of daily vitamin C as effective against hay fever.

We now believe a vitamin C deficiency may promote allergy-related issues because of the needed role of vitamin C as the body’s powerful anti-inflammatory and antioxidant.

1,000 mg vitamin C lowers histamine in all participants in a small study with histamine levels rising along with the subsequent drop in vitamin C levels.

Dosage: Oral vitamin C can typically only promote vitamin C levels within the 70–120 micromol/L range. The great Linus Pauling and Orthomolecular Medicine show we absorb 90% of the first 250 mg of vitamin C, making this the “most important.” While some suggest there might be a negligible difference between 400 mg to 2.5 g of vitamin C, other researchers suggest otherwise. We also are seeing high-absorption vitamin C products available such as buffered and liposomal vitamin C available. New studies suggest much as in the case of high dose 10 mg of melatonin, high dose vitamin C might further complicate major inflammatory conditions, such as rheumatoid arthritis.

EGCG (Green Tea)

As a polyphenol from green tea, epigallocatechin gallate (EGCG) shows actions as a mast cell stabilizer and is also receiving much attention for its believed zinc ionophore activity.

EGCG as a top natural histamine blocker, also reduces ongoing mast cell count, while blocking mast cell division and movement from the blood and into other body parts

Through inhibiting histidine decarboxylase (HDC), the histamine producing enzyme, EGCG is a likely potent natural antihistamine supplement.

We find green tea contains roughly 2.75% quercetin.

Dosage: Limited evidence shows 800 mg of EGCG as toxic to the liver. The average green tea has 50 to 100 mg of EGCG. Consuming green tea might be a more optimal strategy as more research shows other green tea components, such as its beta-carotene and PQQ content, make it one of the top lung supplements with powerful lung cancer evidence. Matcha tea is said to contain a much greater percentage of antioxidants over standard green tea.


As another potent antiviral plant, astragalus is a primary Chinese medicine medicinal plant delivering protection for those suffering from histamine reaction.

Astragalus active compound astragalin provides a potent mast cell stabilizing antioxidant within both the nasal airways and the gut, making it a possible top option for gut-related histamine intolerance.

We find astragalus effective against allergic rhinitis in research studies.

While we have no evidence of histamine blocker astragalus actions, we can find its effectiveness on par with pharmaceutical non-sedating antihistamines.

Dosage: Similar to vitamin C, we find the best effects in the use of intravenous astragalus. This leads to believe like the other natural antihistamines, a divided dosing strategy throughout the day might prove most effective. We see astragalus used in kidney disease studies restoring kidney function at dosages from 7.5 to 15 grams daily and presume this might be the upper level of safe dosages. Chinese medicine books describe daily doses of 9 to 15 grams.

Natural Antihistamine Foods

These plant-based food sources can provide natural antihistamine benefits.


Preventing mast cell activation, apigenin, an anti-inflammatory apple, grape, and parsley flavonoid reduces histamine release.



Also, a top option for allergies, and like apigenin, fisetin, an apple and strawberry flavonoid lowers histamine release through inhibiting mast cell release.



As a polyphenol from cruciferous vegetables, such as broccoli, cabbage, and kale, kaempferol delivers similar anti-mass cell activity as apigenin and fisetin.



Suppressing lung and nasal inflammation, luteolin is a broccoli, celery, and parsley, and flavonoid, which stabilizes mast cells and is also a top selection for allergies and asthma.



Stabilizing mast cells, while lowering blood clotting and inflammation, myricetin is a common polyphenol we find in wine, vegetables, tea, and berries.



As another mast cell stabilizer, rutin from apples, buckwheat, and passionflower, carries similar anti-inflammatory and blood vessel health protection, as myricetin.


Top 12 Notable Natural Antihistamine Supplements

  • Allicin (Pure extract from garlic only)
  • Berberine
  • Black Seed Oil (BSO)
  • Boswellia
  • Bromelain (Extract from pineapples not pineapple whole food)
  • Butterbur
  • Forskolin
  • NAC (N-acetyl-cysteine)
  • Neem
  • Oil of Oregano (OOO) (Always dilute and cycle on and off)
  • Olive Leaf Extract (Oleuropein)
  • Omega-3 (Algae oil, cod liver oil, fish oil, krill oil)


Other Natural Antihistamine Supplements

CoQ10, vitamin B6, magnesium, zinc, carnosine, cinchona bark, diamine oxidase, saccharomyces boulardi, bifidobacterium, (L. Plantarum LP299v), Andrographis, cat’s claw, enzymes, naringenin, l- theanine, curcumin, reishi, skullcap, peppermint, lemon oil, lavender, apple cider vinegar, spirulina, chamomile, terminalia chebula seed, propolis, bee pollen, mangosteen, grape seed extract, pycnogenol, pine bark, resveratrol, pterostillbene, hesperidin, marshmallow root, ginger, papaya, capsicum, algae, evening primrose oil, echinacea, burdock, mullein, goldenseal, acerola, camu camu, rosemary, ma Huang, white pine, eyebright, B. longum Moringa (BB536), B. infantis, erythropoietin, eleuthero, tulsi (holy basil), mucuna, palmitoylethanolamide (PEA), SAM-e, valine, basil, jewelweed, fennel, thyme, carraway seed oil, clove oil, lemon balm.

Conclusions on Histamines

Clearly for all health optimizers, consuming more plant-based antioxidants such as apigenin, fisetin, kaempferol, luteolin, rutin, and myricetin can support our health.

Many dealing with symptoms of histamine intolerance or histamine reaction, might benefit from avoiding foods with high histamines in favor of the low histamine diet.

Researchers believe specific histamine-producing probiotic bacteria might be valuable.

CoQ10, magnesium, omega-3’s, vitamin B6, vitamin C, and zinc appear to be essential micronutrients involved with the proper function of histamine.

As previously suggested many times, most use a daily caffeine source, so why not drink daily matcha tea?

Look for common medications which might decrease the function of your histamine metabolizing enzymes, DAO, and HNMT.

Antihistamine medications give significant cause for concern for long-term use due to their negative anticholinergic effects on the brain, with a recent warning by Harvard Medical School.

The top natural antihistamine supplements:

  1. Quercetin
  2. Stinging Nettle
  3. Vitamin C
  4. EGCG (Green Tea)
  5. Astragalus


What’s your favorite antihistamine supplement?


Your Friend in Health

Mark Stein

[Get The Essential 3 Sugars and Fat for Every Health Optimizer]

One thought on “Histamines: Friend or Foe?

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