What You Need To Know About Histamine
This is a work in progress. Please send all comments and corrections to StevenLColeman42@gmail.com
The Cause Of Excessive Levels of Histamines
Lowering and Blocking Histamine Production
Avoid the blocking of DAO (The Avoid List):
Bacteria that produce histamines:
VitaMonk Low Histamine Probiotics
FoodsForGut Histamine Reducing Formula
N-methyltransferase (HNMT) enzyme
Inhibitors of HNMT (Avoid List):
Blocking/Reduction of Histamine production
Histamines are used by the body for signaling in various situations, with the primary cases of Immune Defense and Neurological. You need a certain level of histamines at all times but having too much can lead to many health problems including extreme immune responses and even psychiatric issues. People that have a very high level of histamines or lack the ability to reduce their histamine burden may have a condition known as Histamine Intolerance (HIT). Another condition called Mast Cell Activation Syndrome (MCAS) is also highly associated with Histamine Intolerance and high histamine levels in the blood.
There are several causes to consider when trying to figure out why someone has an excessive level of histamines in their system. There can be multiple reasons simultaneously and each needs to be explored to understand the individual's situation and the best course of action.
Environmental allergies often elevate the level of histamines due to an over exuberant immune response to common allergens. Once the immune system becomes sensitized to these environmental elements (antigens) then avoidance is generally the main recourse other than the use of medications to help block the effects.
When a parasitic, bacterial, or fungal infection takes hold the immune cells (Mast Cells, Basophils, Enterochromaffin-like (ECL) Cells, and Eosinophils) will release histamines to signal for other immune responses to take place. This signalling helps ramp up the immune response against any invading organism. One must test and research carefully to determine which of these might be exacerbating the current situation.
There are several variants for the AOC1, C314T, and A595G genes needed to produce the enzymes (see below DAO,HNMT) that are needed to reduce histamines in their system. A mutated variant may lead to the inability to eliminate histamines from the system. If a person has excessive histamines, it might be a good idea to get genetic testing for these variants.
Talk to your doctor to see what genetic tests are available to you. If no prescribed test is available to you, then some people have done their own genetics profile with a company like 23andme.com or Ancestry and then have downloaded/uploaded their genetic information into another service.
https://previmedica.com/shop-all/
If you order The Histamine intolerance (AOC) test alone ($250 when writing this), you will receive a swab kit rather than a blood draw kit.
https://mygenefood.app/reports/histamine
Cheek swab collection kit $249
Upload raw data from 23andme or Ancestry $149
Add Health Intelligence option $149 - premium report and ongoing access to research updates
\https://static.selfdecode.com/report_samples/Histamine%20-%20Sample.pdf
Upload $318.88 : Then $119.88 / year
SelfDecode Kit $714.95 : Then $119.88 / year
DNA Complete Pro kit $495
Upload membership $1/week
Upload your raw DNA data from AncestryDNA, 23andme, or MyHeritage.
Unlimited lifetime traits report is $75.
They supposedly decode all autosomal DNA, which does include the AOC1 gene, but so far I have not seen anything related to this gene in the unlimited traits report.
Reports cost $15
Appears to have AO1C gene but not the other HNMT ones
https://athenslab.gr/en/exetaseis-prolipsis/histamine-intolerance-genetic-testing-2194
https://eshop.athenslab.gr/en/exetaseis-prolipsis/mygenomix-gonidiakes-exetaseis-prodiathesis/histamine-intolerance-genetic-testing-2194#:~:text=Histamine%20Intolerance%2C%20Genetic%20Testing%20%2D%20myGenomiX%C2%AE%20%2D,Purchase%20the%20test%20online%20%7C%20Diagnostiki%20Athinon.
https://www.genechron.com/en/project/nutrigenetics/
GENETIC TEST FOR HISTAMINE INTOLERANCE: AOC1 A594 A/T (rs2268999), AOC1 4586G/T (rs2052129), AOC1 4106C/G (rs1049793), AOC1 995C/T (rs1049742); AOC1 47C/T (rs10156191), HDC 1932A/C (rs2073440), HNMT 939A/G (rs1050891), HNMT 314C/T (rs11558538).
Histamine is a substance produced by the body during digestion. Some subjects following the intake of foods that lead to a high production of histamine (example, chocolate, citrus fruits, dried fruit) show a reaction similar to an allergy. To know if you are sensitive to histamine allows you to monitor the consumption of these substances and manage its symptoms.
Some people develop food sensitivities which disturb the intestinal immunological barrier and set up a chain reaction making them produce less enzyme than needed to combat these histamines.
Some Common Food Intolerances: Histamine, oxalates, tyramine, salicylates, amines, glutamates
Histamine signalling works by binding to a specific histamine receptor in order to to affect the specific signaling pathway intended. Antihistamines generally try to block the histamine from attaching to this receptor and thus to block that specific effect. Different receptors have different purposes and so histamine has many roles in the body. It's important to understand what roles affect what systems so you don’t have unintentional consequences when trying to reduce specific symptoms with arbitrary medications.
Primarily found in smooth muscle cells, endothelial cells, and neurons. They are responsible for mediating allergic reactions, such as bronchoconstriction, vasodilation, and increased mucus production.
See the section on antihistamines below because those target the H1 receptor directly.
Located in the stomach lining and heart. Histamines there stimulate gastric acid secretion and increase heart rate.
The primary drugs in this class are cimetidine, famotidine, nizatidine, and ranitidine. Blocking this pathway can inadvertently increase the number of H2 receptors and thereby increase the amount of histamines released. This can cause a rebound effect and even increase MCAS symptoms.
Note: If you are taking these PPIs specifically for histamine reasons, and not gastric reflux, then you should consider taking Betaine HCL to re-increase stomach acid to kill off any incoming bad bacteria and help with protein digestion. These bad bacteria will cause gas reflux and heighten the level of histamines that you absorb. The undigested proteins will only feed the bad bacteria and let things get out of control.
Present in the brain and gastrointestinal tract. They regulate the release of histamine and other neurotransmitters.
Pitolisant: (Wakix): This is the first approved drug that targets the histamine H3 receptor, functioning as an inverse agonist/antagonist to treat narcolepsy and excessive daytime sleepiness. There are considerable side effects and only minimal gains for histamine reduction.
Found in white blood cells (eosinophils, dendritic cells, T-lymphocytes, neutrophils and natural killer (Nk) cells) in the bone marrow. H4 receptors are involved in inflammation and immune responses
There are many drugs being researched, but blocking the H4 receptor pathway can cause even more histamines to be released, so this is not likely a pathway to finding relief. See Thioperamide as an example of this.
Antihistamines will temporarily block the effects of histamines while the histamines are actually being reduced by enzymes (DAO, HNMT) elsewhere in the body. Antihistamines do not resolve the problem but rather put it off to a later time. There are many types of antihistamens just as there are many histamine receptors, but when someone uses the word antihistamine they generally mean something that blocks the H1 receptor.
Antihistamines can be broken down to first-generation and second-generation products. The first generation products generally cause drowsiness while the second-generation products generally do not.
These antihistamines do cross the blood-brain barrier so they often cause drowsiness or sedation. The second-generation antihistamines are now recommended over any of these except in specific cases. We include these only for completeness.
It is on the American Geriatrics Society (AGS) BEERS Criteria List, which means it should not be used regularly by people over the age of 65.
It is on the AGS BEERS Criteria List, which means it should not be used regularly by people over the age of 65.
This antihistamine, sold under the name brand Benadryl, actually blocks DAO production (see DAO discussion below) so it should never be used long-term. It is on the AGS BEERS Criteria List, which means it should not be used by people over the age of 65.
It is on the American Geriatrics Society BEERS Criteria List, which means it should not be used regularly by people over the age of 65.
This antihistamine has the strongest vasodepressor effects so this will relieve swelling in the neck, inner-ear, and throat and may relieve symptoms of vertigo caused by this swelling. It is also on the American Geriatrics Society BEERS Criteria List, which means it should not be used regularly by people over the age of 65.
Most are without drowsiness, but some minority of people may have this as a symptom with some of the below as noted. All will treat allergy symptoms and rhinitis. Recent studies raise questions about reduced cognitive function when on high doses.
This is called Benadryl Allergy Relief in the UK without a prescription and is marketed as Semprex-D in the US, but has not been manufactured since 2008. It generally comes with pseudoephedrine as part of the formulation so it has become a regulated prescription in the US. It has considerable side effects to consider. In recent studies it was found not to be cognitively impairing at normal doses but more impairing at higher than recommended doses.
The most selective binding antihistamine to the H1 receptor. The half-life in the bloodstream is from 6.5-10 hours. It helps with dermatitis and urticaria better than any of the other alternatives. It partially crosses the blood-brain barrier so a minority of people may report drowsiness with this product, so do test carefully before driving. Commonly reported side effects of cetirizine include headache, dry mouth, drowsiness, and fatigue, while more serious, but very rare, adverse effects reported include tachycardia and edema. The sudden discontinuation of cetirizine after prolonged use may cause itching, so slowly weaning off of this medication is recommended. Has an anti-inflammatory effect.
Levocetirizine is the active levorotary enantiomer of cetirizine. Levocetirizine is more potent than cetirizine because it binds more strongly to the H1 histamine receptor. Like Cetirizine the sudden discontinuation after prolonged use may cause itching, so slowly weaning off of this medication is recommended. Has an anti-inflammatory effect.
Not recommended in children less than two years old. Urticaria is among the specific symptoms that it can treat, but it is not quite as good at that as Cetirizine. Common side effects include sleepiness, dry mouth, and headache. Serious side effects are rare and include allergic reactions, seizures, and liver problems. Do not take with ketoconazole, erythromycin, cimetidine, and furanocoumarin. In recent studies it was found not to be cognitively impairing at normal doses but more impairing at higher than recommended doses.
Prescription only. The major metabolite byproduct of Loratadine (above). desloratadine has
been shown to have the highest H1 receptor binding affinity.
Has an anti-inflammatory effect.
Fexofenadine was also shown to inhibit histamine-induced wheal and flare symptoms. In recent studies fexofenadine demonstrated the least cognitive impairment of all tested second-generation antihistamines. Has an anti-inflammatory effect. Recent studies showed that fexofenadine was not cognitively impairing even at higher than recommended doses.
Prescription only from a licensed Compounding Pharmacy to your physicians exacting prescription requirements, potentially void of dyes or fillers. This is an antihistamine that also acts as a Mast Cell Stabilizer so it can actually prevent mast cell degranulation and the subsequent histamine release. It can come as a capsule or liquid. If you think you have MCAS then this might be the right antihistamine for you, but check your insurance coverage first and talk to your doctor. It is not easy nor cheap to get your hands on this medication because of the compounding. Do not take ketotifen concurrently with [Amifampridine, Bupropion, Clomipramine, Donepezil, Hydroxychloroquine, or Pitolisant].
The potency of second generation histamine antagonists is (from strongest to weakest) desloratadine (Ki 0.4 nM)
levocetirizine (Ki 3 nM)
cetirizine (Ki 6 nM)
fexofenadine (Ki 10 nM)
terfenadine
loratadine
Mizolastine: a review of its use in allergic rhinitis and chronic idiopathic urticaria
For urticaria, cetirizine and mizolastine demonstrate superior suppression of wheal and flare.
For atopic dermatitis, as adjunctive therapy to reduce pruritus, cetirizine, ketotifen, and loratadine are effective.
Note: astemizole, ebastine, and terfenadine can accumulate and cause heart beat regulation issues.
Second-generation antihistamines: a comparative review
Diamine oxidase (DAO) is a natural enzyme that plays a crucial role in the metabolism of histamine. DAO enzyme breaks down histamine, reducing its levels in the body. This reduction helps to prevent excessive histamine accumulation, which can lead to symptoms such as flushing, headaches, nausea, and gastrointestinal issues. DAO is involved in regulating immune responses by controlling excessive histamine levels and prevents excessive inflammation and reduces allergic reactions. Deficiency in DAO can lead to histamine intolerance, while supplementation with DAO may help to reduce systemic histamine-related symptoms.
When taking a DAO supplement the enzyme, measured in HDU units, will work to degrade the histamines in the gut before they can ever be absorbed into the bloodstream. This will reduce the overall level of histamines in the blood and for those with IBS-D symptoms will alleviate the cramping and diarrhea.
Taking DAO 15 minutes prior to a meal can help reduce your overall histamine burden, as it is an enzyme that destroys histamines coming from foods and gut bacteria before it can be absorbed into the bloodstream.
Those same histamines in the gut, if left unchecked before absorption, will cause inflammation of the intestinal lining and thereby breach your immunological barrier. If the immunological barrier gets breached then larger molecules of undigested food can make their way into the bloodstream and cause a cascade of immunological consequences. Unfortunately your serum level production of DAO is inversely proportional to your intestinal permeability, so fixing the inflammation at the source will often help correct your proper serum levels of DAO.
DAO Products by Cost Effectiveness
A source of naturally occurring DAO is bean sprouts, which can be much cheaper than the commercial supplements if you have the time to devote to sprouting and processing your own. The very best of the supplements are made from pea/lentil sprouts only they just purify an extract from it. Any whole food or natural food store will have peas and lentils that are able to be sprouted. Place in a wet container in a dark and cool place and once they sprout start counting the days. On exactly the sixth day remove the sprouts from the container, rinse, puree, abortion, and freeze in units that can be thawed for use just prior to each meal. Consume this mixture 15 minutes before your meal for the maximum benefit. Alternatively you can just use fresh beansprouts on your salad, but if you keep them in the refrigerator the natural DAO will begin to degrade, so use quickly if fresh.
Oleic Acid (CAS:112-80-1)
Oleic acid, the fatty acid of triolein, can actually increase serum levels of Diamine Oxidaze (DAO). Olive oil is high in oleic acids, and general purpose Oleic Acid is available on Amazon in various forms and purity.
- Take zinc, magnesium, phosphorus, iron, and vitamin B12
Foods: Alcohol, energy drinks, black tea, green tea (ECG and EGCG)
Note: Both ECG and EGCG are known to block the production of histamines, but they both also appear to block production of DAO. More research is needed to see which is more beneficial, but logically you don't need to degrade something that does not exist. I therefore lean towards green tea extract EGCg being more beneficial than not because it has many other beneficial purposes as well. This is obviously something that each individual should be aware of and test very carefully.
Avoid these Drugs that Inhibit DAO Production or Processing
Amitriptyline, Cymbalta, Effexor, Prozac, Zoloft, Cardizem, Metoprolol, Norvasc, Propafenone, Dihyrdalazine, Enbrel, Humira, and Plaquenil, Aspirin, Ibuprofen, Diclofenac, and Indomethacin , Naproxen, Acetylcysteine, Metoclopramide
Note: Amitriptyline studies are somewhat mixed as to whether it helps or hurts. This obviously needs more research
MAO inhibitors: (monoamine oxidase inhibitors): Are used for depression and can slow down the breakdown of histamine.
Antibiotics: A few antibiotics can reduce the activity of the DAO Metronidazole, Cephalosporins (cefotiam, cefuroxime)
Contraceptives with oestrogen: Can reduce DAO activity and thus influence the breakdown of histamine.
Proteus, Enterobacter, Serratia, Citrobacter, Raoultella, Vibrio, Acinetobacter, Plesiomonas, Pseudomonas, Aeromonas, Photobacterium, Clostridium, Morganella, Lactobacillus, Staphylococcus, and Klebsiella
Lactobacillus Gasseri
https://www.amazon.com/Swanson-Lactobacillus-Metabolism-Acid-Resistant-Designed-Release/dp/B00OLQLS64?th=1
Lactobacillus plantarum
https://www.amazon.com/Vitamatic-Lactobacillus-Plantarum-Digestive-Prebiotic/dp/B0CJQLC9P5?source=ps-sl-shoppingads-lpcontext&ref_=fplfs&psc=1&smid=A2BWIK2HM93SR4&gPromoCode=sns_us_en_10_2025Q1&gQT=1
PaeniBacillus polymyxa (aka Bacillus polymyxa)
Available for agricultural use - no ingredients listed so not for human use
https://www.marknature.com/products/bacillus-polymyxa?variant=41681159651503&country=US¤cy=USD&com_cvv=8fb3d522dc163aeadb66e08cd7450cbbdddc64c6cf2e8891f6d48747c6d56d2c
Dietary Paenibacillus polymyxa AM20 as a new probiotic: Improving effects on IR broiler growth performance, hepatosomatic index, thyroid hormones, lipid profile, immune response, antioxidant parameters, and caecal microorganisms
https://www.sciencedirect.com/science/article/pii/S0032579123007587
Virgibacillus campisalis (Vietnamese fish sauce)
https://www.researchgate.net/publication/369305888_Histamine-degrading_halophilic_bacteria_from_traditional_fish_sauce_Characterization_of_Virgibacillus_campisalis_TT85_for_histamine_reduction
Ingredients: Bifidobacterium infantis, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium lactis, Lactobacillus salivarius, Lactobacillus plantarum
Ingredients: Saccharomyces boulardii, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus rhamnosus, Bifidobacterium breve, Bifidobacterium lactis, Lactobacillus plantarum
https://www.foodsforgut.com/product-page/histamine-reducing-formula-1
Ingredients: B. Longum Bl-05, B. Lactis UABla-12, B. Bifidum Bb-06, L. Gasseri Lg-36*, L. Salivarius Ls-33, L. Rhamnosus Lr-32
N-methyltransferase (HNMT) is an enzyme that inactivates the neurotransmitter histamine by adding a methyl group from S-adenosylmethionine (SAM) to it, creating N-methylhistamine. It plays a critical role in regulating histamine levels in various tissues, including the brain, gut, and airways, and is the sole enzyme responsible for terminating histamine's action as a neurotransmitter in the central nervous system. Disruptions in HNMT function due to genetic variations or deficiency have been linked to neuropsychiatric disorders, including intellectual disability and Parkinson's disease, and can affect aggressive behavior and sleep patterns,
HNMT is expressed in the brain. Clinical studies suggest that single nucleotide polymorphisms of the human HNMT gene are associated with several brain disorders such as attention deficit hyperactivity disorder.
Take B12, folate, S-adenosylmethionine (SAMe)
Drugs to Avoid: Diphenhydramine, Amodiaquine, Chloroquine, Dimaprit, Etoprine, Metoprine, Quinacrine, Tacrine
Histidine decarboxylase is the enzyme that produces histamine in humans, and research[1] shows that it can be blocked to actually prevent the production of histamine. The enzymatic synthesis of human derived histamine can be blocked by two common types of natural molecules:
Eugenol can reduce the amount of histamine in the blood by preventing mast cells from releasing histamine and causing anaphylaxis . It can reduce itching caused by histamine and atopic dermatitis. Eugenol has anti-inflammatory, antioxidant, antimicrobial, antifungal, and antiviral properties. It has historically been used in folk medicine for dental care, as an antiseptic, and as an analgesic and may be available through those channels. It also helps lower hyperglycemia (t2dm) but should not be taken in combination with insulin, or blood thinners. With high concentrations (>10 mg kg-1) you may run a risk of liver damage or seizures, but at normal therapeutic concentrations it is generally considered safe.
Available naturally from Clove, Nutmeg, Cinnamon, Basil and Bay leaf. Supplemental forms are available as clove oil extract.
ANTIANAPHYLACTIC PROPERTIES OF EUGENOL
ANTI-INFLAMMATORY ACTIVITY OF EXTRACTED EUGENOL FROM OCIMUM SANCTUM L. LEAVES
From Green Tea, buckwheat, and grapes. Supplemental forms are available as EGCg (green tea extract).
Epicatechin Gallate (ECG), like the more studied EGCG, is a tea polyphenol that can inhibit histamine release from mast cells. It Interacts with mast cell membranes, potentially affecting the signaling pathways involved in degranulation.
- Cancer prevention: Studies suggest it may inhibit cancer cell growth and proliferation in various types of cancers.
- Cardiovascular health: May help improve blood vessel function and lower cholesterol levels.
- Anti-inflammatory effects: Potential to reduce inflammation in the body.
- Weight management: Some studies suggest it may contribute to weight loss by promoting fat burning.
- Neuroprotective effects: Research is exploring its potential role in neurodegenerative diseases due to its antioxidant activity.
Note: high doses may cause gastrointestinal upset
Targeting of histamine producing cells by EGCG: a green dart against inflammation?
Energy drinks rich in caffeine and theine, such as coffee, tea and energy drinks can both release histamine and block DAO.
Alcohol can block the action of the DAO enzyme.
Chocolate is quite problematic, and you will hear various things that are in contradiction, such as the cocoa bean is naturally low in histamines, but that is only the unprocess ones. Processed cocoa contains a very similar molecule to caffeine, and that is naturally high in histamine due to the fermentation process. It may also trigger the release of histamine from immune cells, and the biogenic amines, such as tyramine and phenylethylamine will interfere with DAO utilization by competing with the enzyme binding sites. It does not appear to prevent the future production of DAO directly, so eating it may only have short term effects if you take it concurrently with supplemental DAO. There is a lower histamine version of chocolate called “wholy bean” in the UK, so this might be an alternative. Generally lower cocoa in the chocolate (e.g. milk chocolate) means less histamine, so white chocolate, unfermented cocoa, or home made tends to be better, if that works for your own personal cravings.
DAO products by cost effectiveness
Products at the top of the list are better than further down.
Note: Many people who are taking PPIs for acid reflux purposes actually have too low of stomach acids, and the bad bacteria living in their gut are creating gas that causes this reflux. What they actually need is more acids to kill these bad bacteria to alleviate their symptoms. Further decreasing their stomach acids with PPIs only prevent the proper digestion of proteins which then feeds the bad bacteria, thus making this underlying problem even worse. Talk to your doctor.
Novel inhibitors for histidine decarboxylase from plant components
Alchemilla vulgaris (Lady’s mantle) grass
Cydonia oblonga (Quince) fruit
Filipendula ulmaria (Meadowsweet) flower
Prunus armeniaca (Apricot kernel) seed
Prunus japonica (Japanese bush cherry seed) seed
Rosa roxburghii (Roxburgh rose) fruit
Rubus chingii (Raspberry) fruit
Solidago virgaurea (Goldenrod) grass
Artemisia capillaris (Capillary wormwood) flower
Cassia mimosoides grass
Senna alexandrina (Alexandrian senna) leaf
Alpinia officinarum (Lesser galangal rhizome) root
Polygonatum falcatum (Polygonatum rhizome) root
Nepeta cataria (Catnip) grass
Juglans regia (Walnut) seed
Artocarpus lakoocha wood
Bassia scoparia fruit
Terminalia chebula (Chebulic myrobalan) fruit
Eucalyptus (Eucalyptus leaf) leaf
Phyllanthus emblica (Amla) fruit
Rumex crispus (Yellow dock) root
Not a rumor, TCM ( traditional Chinese medicine) has used quail eggs for thousands of years as an allergy treatment.
?? Gallic acid, Pimentol,
lavonoid glucosides, ellagitannins
Histamine Intolerance: Unraveling the Complexities of Diagnosis and Management
GUT Bacteria vs DAO
[1] Histamine Intolerance: Unraveling the Complexities of Diagnosis and Management - 20 October, 2024
http://www.ijlbpr.com/uploadfiles/104vol13issue11pp597-603.20241125063729.pdf
[2]
Histamine in the regulation of wakefulness
https://pubmed.ncbi.nlm.nih.gov/20851648/
Histamine and histamine intolerance
https://www.sciencedirect.com/science/article/pii/S0002916523280533
(great diagram of immune relationships)
https://www.nahrungsmittel-intoleranz.com/en/histamine-intolerance-and-medication/