Do you have runaway histamine? Looking for alternatives to antihistamine drugs? We’ve collected a list of the best mast cell stabilizers, HDC blockers, as well as HNMT and DAO boosters nature has to offer. Read on to discover the ideal one for you.

What Causes Histamine Reactions?

You may have gotten here from one of our previous articles on histamine intolerance. If so, then you know that having too much histamine in your body and not enough of the enzymes that degrade it can give you symptoms of histamine intolerance.

These allergy-like symptoms can range from skin rashes to headaches, and you can manage them by avoiding histamine-rich foods and substances that activate your mast cells.

If you haven’t already read our previous posts, you may want to check them out before reading on:

  1. What is Histamine? Definition, Function, Receptors & DAO
  2. 17 Histamine Health Effects: Cognition, Inflammation & Sleep
  3. Histamine Intolerance Symptoms: Could You Be Sensitive
  4. Low Histamine Diet: Does It Work? + Who Should Try It
  5. Foods High & Low in Histamine + Other Mast Cell Triggers

Natural Antihistamines

Mast cells use an enzyme called histidine decarboxylase (HDC) to make histamine out of the amino acid histidine. They then release histamine in response to a host of different triggers, including some foods, alcohol, insect bites, and more.

Many natural compounds can interrupt this process, either by inhibiting HDC or stabilizing mast cells and preventing them from releasing histamine. In this post, we will explore these natural antihistamines so you can find the right one for you.

Plant-Based Antioxidants

1) Fisetin

Fisetin is a flavonoid pigment found in strawberries and apples. This compound reduces histamine release by preventing IgE from binding to and activating mast cells. It’s a good choice if you suffer from allergies. Plus, it may promote longevity [1, 2, 3].

2) Forskolin

Forskolin is a compound extracted from a member of the mint family called Coleus forskohlii. It is most often used to promote weight loss, but it is also great for preventing asthma. It stabilizes mast cells and relaxes muscles in the lungs comparably to two common asthma drugs, sodium cromoglycate and beclomethasone [4, 5, 6, 7, 8].

3) Luteolin

Luteolin is a flavonoid found in celery, parsley, and broccoli. It stabilizes mast cells and suppresses inflammation in the lungs and nose, which makes it another good choice for asthma and seasonal allergies [9, 10, 11, 12].

4) Apigenin

Apigenin is a common anti-inflammatory flavonoid found in parsley, grapes, and apples. It prevents IgE from binding to and activating mast cells and thereby prevents histamine release [9, 13, 14].

5) EGCG

Epigallocatechin gallate (EGCG) is a polyphenol found mainly in green tea. Besides stabilizing mast cells, EGCG has the added benefit of reducing the number of mast cells present at any time [15, 16].

EGCG also inactivates histidine decarboxylase (HDC), the enzyme that makes histamine. Finally, it prevents mast cells from dividing and traveling out of the bloodstream and into other tissues [17].

With its multi-pronged effect on mast cells, EGCG is among the best natural antihistamines.

6) Kaempferol

Kaempferol is a polyphenol found in cruciferous vegetables, Delphinium plants, witch hazel, and grapefruit. Like many other polyphenols on this list, it prevents mast cells from releasing histamine [18, 1].

7) Myricetin

Myricetin is a polyphenol common in berries, teas, wines, and many vegetables. It also stabilizes mast cells and more broadly prevents inflammation and excessive blood clotting [1, 19, 20].

8) Rutin

Rutin is an antioxidant and anti-inflammatory flavonoid found in large quantities in buckwheat, apples, and passion flower. It stabilizes mast cells, reduces inflammation, and strengthens blood vessels [1, 21, 22, 21, 23].

9) Theanine

Theanine is an amino acid found most abundantly in green and black tea and some fungi. Unlike most chemicals, it can cross the blood-brain barrier and act directly on the brain, where it increases serotonin, dopamine, and GABA levels. Theanine also stabilizes mast cells and prevents histamine release [24, 25, 26, 27].

10) Methylxanthines

The methylxanthines are a group of related compounds that include caffeine, theobromine, and theophylline. Xanthine occurs naturally in the human body, while the methylxanthines, which stabilize mast cells, can be used to treat asthma [28, 29].

Dietary sources of methylxanthines include coffee, tea, chocolate, maté, and guarana. You can drink coffee, eat chocolate, or supplement with theobromine, but attempting to supplement with theophylline is not recommended [30, 31, 32, 33].

Note, however, that chocolate also contains some histamine, and researchers suspect that it may encourage histamine release. The net effect of cocoa is unknown; we recommend that you test your own individual response and see what it does for you. Importantly, organic chocolate contains fewer biogenic amines than non-organic chocolate; choose organic options when possible [34, 35, 36].

11) Naringenin

A bitter compound found in grapefruit, naringenin inhibits histidine decarboxylase and prevents histamine from being formed. Naringenin is also a deep-acting anti-inflammatory and helps prevent liver damage and metabolic syndrome [37, 38].

12) Quercetin

Quercetin is a plant flavonoid and antioxidant. It is recognized as one of the best natural antihistamines out there. In some cases, quercetin even outperforms Cromolyn, a mast cell-stabilizing drug; quercetin works better for prevention, while Cromolyn works more quickly once the reaction has already started [39, 1].

Supplementing with quercetin may be a good natural alternative to taking Cromolyn.

13) Curcumin

Curcumin, a yellow compound found in turmeric, is one of the strongest plant-based anti-inflammatories. It suppresses an overactive immune system, which makes it a great supplement to fight allergies and autoimmunity; specifically, it prevents mast cells from releasing histamine [40, 41].

Curcumin may also reduce the activity of diamine oxidase (DAO), the enzyme that breaks down histamine in the blood. However, in this case, lower DAO in the blood may simply mean that cells in the intestinal lining are injured less frequently and, thus, need to release less DAO [42].

Herbal Supplements

14) Astragalus

Astragalus is a medicinal plant also known as milk vetch. Its active compound astragalin is a powerful antioxidant that can stabilize mast cells in the intestines and nasal passages, so it may be worth a try for histamine problems in the gut and nose [1, 43, 44].

15) Reishi

Reishi is a fan-shaped mushroom that prevents histamine release and strengthens immunity. Take care, however, as it may overstimulate the immune system [45, 46, 47].

16) Chinese Skullcap

The roots of the Chinese skullcap, a plant from the mint family, are important in traditional Chinese medicine. This plant’s active compounds significantly reduced histamine release in rat studies [48, 49, 47].

17) Eleuthero

Eleuthero, also known as Siberian ginseng, is a staple of traditional medicine in the Far East. In rats, an extract of eleuthero reduces mast cell activity and prevents histamine release [50, 51, 52].

18) Tulsi

Tulsi, otherwise known as holy basil, is an aromatic herb best known in Ayurvedic medicine as a tonic for stress and inflammation. In rats, tulsi seed oil blocks histamine release from mast cells [53, 54, 55].

19) Mucuna

Mucuna pruriens, also known as velvet bean, is a natural source of the dopamine precursor L-DOPA, a strong inhibitor of histidine decarboxylase (HDC). Taking Mucuna as a supplement may prevent your body from producing as much histamine [56].

Vitamins

Vitamins C and B6 both increase the production of diamine oxidase (DAO), which breaks down histamine in the bloodstream.

20) Vitamin C

In one study, 1 g of vitamin C directly decreased histamine in everyone it was given to; as vitamin C levels went back down, histamine levels increased. Oral doses can generally only get your blood vitamin C level up to 70-120 micromol/L; to this end, there’s not much of a difference between 400 mg and 2.5 g of vitamin C supplements per day [57, 58, 59, 60].

21) Vitamin B6

Vitamin B6 supports DAO production, but it also increases histidine decarboxylase (HDC), and may, therefore, increase total histamine production. Generally speaking, this vitamin is required for a healthy histamine metabolism; people with histamine intolerance may benefit from supplementing with B6 [57, 61].

Probiotics

Some species of beneficial bacteria colonize the intestine and degrade histamine while it’s still in the gut. These are recommended probiotics for people with histamine intolerance.

22) B. longum

People with histamine intolerance tend to have fewer bacteria of the Bifidobacteriaceae family than healthy controls. One species in this family, Bifidobacterium longum, effectively suppresses allergic reactions; it decreases expression of the H1R and HDC genes, which code for histamine receptor 1 and the histamine-producing enzyme histidine decarboxylase, respectively [62, 63].

As such, probiotics containing B. longum and other Bifidobacteriaceae may improve histamine intolerance and allergies.

23) B. infantis

Bifidobacterium longum ssp. infantis was previously thought to be a separate species from B. longum. This subspecies is sometimes included in probiotic blends that effectively reduce histamine [63].

24) L. plantarum

Some strains of Lactobacillus plantarum degrade biogenic amines, including histamine. However, this species more effectively degrades putrescine and tyramine; if you use L. plantarum, it should support other histamine-fighting strategies [64].

Potentially Deficient Compounds

Your body is full of chemicals that can help degrade histamine or stabilize mast cells. Aim to give your body the building blocks for creating these if you are deficient, or simply to improve the process.

25) Erythropoietin

Erythropoietin (EPO) is a hormone that stimulates red blood cell production, also called erythropoiesis. In a clinical trial of people with kidney disease, 8 out of 10 experienced a significant reduction of histamine and improvement in their itching symptoms during EPO therapy. Histamine levels increased again when the patients stopped EPO [65, 66].

You can read our list of natural ways to increase EPO here.

26) Palmitoylethanolamide

Palmitoylethanolamide, or PEA, is a fatty acid already found in your body. PEA is best known as a natural painkiller, but it also prevents histamine release from mast cells. It may be especially good for eczema and skin allergies [67].

27) Epinephrine

Epinephrine, or adrenaline, does not directly decrease histamine. Instead, it quickly acts against the effects of histamine. Epinephrine is the drug of choice in anaphylaxis for this reason; people with severe allergies carry an EpiPen or similar device that injects epinephrine into the thigh muscles if they have a reaction [68, 69, 70].

Epinephrine is considered a drug, but your body also makes it when you need to be alert. It is one of the hormones responsible for the “fight or flight” response to danger, and it increases dramatically during exercise and stress [71].

28) Pancreatic Enzymes

According to one study, supplementing with pancreatic enzymes may reduce histamine levels and improve the symptoms of histamine intolerance; the mechanism of this effect is unknown [35].

29) SAM-e

S-adenosyl-L-methionine, also known as SAM-e, is a compound that naturally occurs in your body and which donates methyl groups during methylation processes. Histamine N-methyltransferase (HMNT) inactivates histamine by methylating it; therefore, SAM-e might help HMNT work more efficiently [72, 73].

According to some studies, SAM-e supplementation does not increase histamine breakdown if the body already has sufficient SAM-e. However, many of these are decades-old mouse studies; we haven’t been able to find recent human studies to clearly answer the question [74].

Methionine also strongly inhibits histidine decarboxylase (HDC), so SAM-e may prevent new histamine from being formed [75].

Other Options with Mixed Effects

30) Carnosine

Carnosine is a naturally-occurring compound made from the amino acids beta-alanine and histidine. It is abundant in high-quality meat and inhibits histidine decarboxylase, thereby preventing new histamine from being formed [75, 76].

In pigs, however, carnosine inhibits diamine oxidase, which breaks histamine down in the gut. The net effect of carnosine on histamine in the human body is unknown; there are better antihistamine choices on this list [77].

31) NAC

N-acetyl cysteine (NAC) is an amino acid supplement and one of the strongest available antioxidants. In one study, it strongly inhibited histidine decarboxylase, the enzyme that makes histamine. But in other cell-based studies, it increased histamine release; this may explain some of NAC’s side effects [75, 78, 79].

NAC is a powerful and healthy supplement that you should consider if you have issues with oxidative stress as well as histamine, but it probably isn’t the best option solely for histamine intolerance.

32) Valine

Valine is an essential amino acid, meaning that we cannot make our own and therefore need to consume it in our diets. Valine weakly inhibits histidine decarboxylase (HDC); it’s important to make sure you get plenty in your diet. You can get valine from most foods, including meat, grains, vegetables, and milk and dairy products [80, 75, 81].

33) Oxaloacetate

Oxaloacetate is an organic compound and part of your body’s energy production and waste management systems. In the form of oxaloacetic acid, it also weakly inhibits HDC. Unfortunately, oxaloacetate quickly breaks down and is extremely difficult to stabilize in supplement form. Given this uncertainty, it’s probably best to look elsewhere [75, 82].

Want More Targeted Ways to Combat Inflammation?

If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation DNA wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.

SelfDecode is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thanks for your support.

Also, make sure to check out the lectin avoidance diet, because histamine issues are often caused by various food components that cause inflammation.

A Note on Synthetic & Pharmaceutical Antihistamines

Sometimes, pharmaceutical antihistamines are required to effectively and specifically control histamine reactions. Discuss these drugs with your doctor.

Antihistamines (H1-receptor antagonists) block type 1 histamine receptors to reduce the effects of circulating histamine [83].

Fexofenadine or Allegra is a drug that doesn’t cause drowsiness because it doesn’t cross the blood-brain barrier as efficiently as first-generation antihistamines like Benadryl (diphenhydramine) [84, 85, 83].

People taking Allegra at normal dosages don’t experience significant adverse effects when compared to a placebo [86].

Benadryl, an H1 receptor antagonist that also increases diamine oxidase (DAO) production, is better taken at night since it induces sleepiness. In fact, it is also sometimes used as an occasional sleep aid [87, 88].

Benadryl may also decrease anxiety and increase serotonin in the brain, similar to SSRI antidepressants. In fact, many antidepressants and antipsychotics were developed based on its chemical structure [89].

Takeaway

If you have runaway histamine problems, you may not need to turn to pharmaceutical antihistamines. Plant-based antioxidants, herbal supplements, vitamins, probiotics, and some other compounds can help you manage your symptoms without a big price tag.

The best natural antihistamines include forskolin, EGCG, quercetin, vitamin C, and probiotics containing Bifidobacterium longum.

These supplements and nutrients may inhibit the enzyme that creates histamine, prevent mast cells from releasing histamine, or help your body break more histamine down.

About the Author

Jasmine Foster, BSc, BEd

BS (Animal Biology), BEd (Secondary Education)

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

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