I’ve been getting quite a few clients who are dealing with histamine intolerance. So this protocol is dedicated to them.
- Executive Summary
- What Does Histamine Intolerance Come From?
- Do You Have Histamine Intolerance?
- Scientific Evidence For Harm Caused by Histamine and Biogenic Amines
- Amine and Histamine-Rich Foods
- Introduction to Mast Cells
- Histamine and IgE Allergies
- Histamine and Biotoxin Illness/CIRS
- Mast Cells and Infections
- Histamine and Lectins
- Leptin, Mast Cells, and Histamine Intolerance
- Nerve Growth Factor (NGF) Activates Mast Cells
- Ghrelin Activates Mast Cells
- Mast Cells and Fluoride
- Histamine and Mast Cell Stabilizers
- Histamine and Antihistamines
- Histamine and Bradykinin
- Histamine and Histidine Decarboxylase
- Histamine and Probiotics
- Supplements That Increase DAO Production
- Histamine and Erythropoietin
- Flushing: Histamine, MSH or Both?
- Be Wary of These Supplements
- Genetics of Histamine Intolerance
- Testing For Histamine Intolerance
- Disclaimer and Caveats
‘Histamine intolerance’ is a condition that results in high histamine levels.
It’s technically caused by a deficiency of an enzyme that breaks histamine down called diamine oxidase (DAO).
Anything that causes histamine to increase will contribute to this condition.
Often a variety of food chemicals can cause a spike in inflammation and histamine, as was the case in myself.
One of the biggest contributors to histamine intolerance is chronic HPA activation.
If you have histamine intolerance, some potential therapeutic options include:
- Reduce lectin and tannin consumption.
- Distress and reduce HPA activation.
- Quercetin to stabilize mast cells.
- Take 2-3 caps DAO enzymes to break down histamine
- Take probiotics: B infantis (R), B longum (R), L Plantarum (R) to degrade histamine.
- Stay away from fermented and cured foods.
- Take Allegra in the morning or Benadryl at night to block histamine receptors. Benadryl increases DAO as well (R).
- 1000mg Vitamin C 2X a day (R). One blogger notices a difference in the source of their vitamin C and only uses the linked version. (R)
- Vitamin B-6 (R) (Caution: also increase histidine decarboxylase)
If you have histamine issues in general, then do the following:
- Use Cromolyn as a mast cell stabilizer. Effective when used right before or during a reaction.
- Take 1 cap Forskolin (R) as a mast cell stabilizer.
- Take 1 cap 2X a day EGCG to inhibit histidine decarboxylase and stabilize mast cells.
- Experiment with other substances below and in the Th2 dominance page.
What Does Histamine Intolerance Come From?
Histamine intolerance comes about as a result of too little histamine-degrading enzymes in your gut (DAO).
The result is accumulated histamine. This causes numerous symptoms that resemble an allergic reaction
It can come from gut damage, alcohol, drugs/supplements or a microbial imbalance.
If a lack of DAO is the sole cause of your histamine issues, then all you need to do is take the enzyme.
I suspect, however, that many people who complain of histamine intolerance don’t always have issues with the enzyme in particular. Rather, I believe such people are Th2 dominant and just produce excess histamine after meals.
For this post, I will discuss all the ways in which you can reduce histamine overall, not only ways to increase the enzyme.
Do You Have Histamine Intolerance?
Reduced DAO levels can also lead to the following symptoms:
- Skin problems such as rashes, itch, hives, flushing, eczema, psoriasis, and even acne (R).
- Chronic headaches (R)
- Dysmenorrhea (R)
- Flushing (R)
- Gastrointestinal symptoms (R)
- Intolerance of histamine-rich food and alcohol (R)
- Nasal mucus (R)
- Asthma attacks (R)
Scientific Evidence For Harm Caused by Histamine and Biogenic Amines
When blood histamine levels are raised above the normal range (0.3–1.0 ng/mL) this produces certain effects. For example a level of 1–2 ng/mL causes increased stomach acid secretion and heart rate, with, flushing, headache, hives (urticaria), itching skin (pruritus) and a high heart rate occurring at a level of 3–5 ng/mL), bronchospasm at a level of 7–12 ng/mL and cardiac arrest occurring at levels of 100 ng/mL [R].
Thus large amounts of ingested histamine can cause significant symptoms in otherwise well individuals. For example symptoms of flushing, sweating, hives (urticaria), GI symptoms, palpitations and in severe cases bronchospasm may occur following the consumption of spoiled fish [R]. This condition, known as scombroid poisoning, occurs due to the high level of histidine in certain fish species being converted into histamine by marine bacteria [R].
Due to the nature of the symptoms caused, reactions involving vasoactive amines may, therefore, be incorrectly diagnosed as a food allergy.
One study found that a diet low in vasoactive amines alleviated chronic headache in 73% of patients [R].
Another study reported that 27/44 (61%) of subjects had a significant improvement in idiopathic urticaria, angioedema and pruritus on a diet low in dietary amines, although foods containing additives or high in natural salicylate were also restricted [R].
Subjects with chronic hives or angioedema had a marginally significant reduction in their use of antihistamines on a histamine-reducing diet compared to a control group who eliminated artificial sweeteners from their diet [R].
In a placebo-controlled study, one study found no correlation between wine histamine content and wine intolerance and concluded that other vaso-active amines or sulfites may be more relevant in intolerance to wine [R].
It has been proposed that other foods may be able to cause histamine release directly from tissue mast cells although evidence for this is lacking [R].
Amine and Histamine-Rich Foods
Histamine is considered a ‘biogenic amine’. Biogenic amines are commonly found in fish, fish products, meat, dairy products, wine, cider, and beer (R), as well as spinach, tomatoes and yeast products (R).
Biogenic or vasoactive amines are produced by bacteria during fermentation, storage or decay (R).
They include beta-phenylethylamine, tyramine, tryptamine, putrescine, cadaverine, spermine, and spermidine, but histamine is the one most frequently linked to food-related symptoms (R).
Citrus fruits are histamine “liberators” and should likewise be avoided (R).
In general, foods likely to contain high levels of these biogenic amines are fermented foods or foodstuff exposed to microbial contamination during storage (R).
Histamine, tyramine, cadaverine, spermine, spermidine, putrescine, tryptamine, and agmatine are considered to be the most important biogenic amines occurring in foods (R).
Biogenic amines have a negative reputation, but in reality, some like spermidine are quite healthful.
Spermidine prolongs the life span of several model organisms including yeast, nematodes, and flies and reduces oxidative stress. Spermidine induces autophagy in cultured cells and flies (R).
The main bacteria responsible for biogenic amine production in fermented food are lactic acid bacteria (LAB) (R).
These bacteria can break down amino acids into amine-containing compounds. Bacteria produce these compounds as defense mechanisms to withstand acidic environments (R).
Biogenic amines play critical roles within the human body (R).
Some countries place limits for histamine in wine such as Germany (2mg/l), Holland (3mg/l), Finland (5mg/l), Belgium (5–6mg/l), France (8mg/l), Switzerland, and Austria (10mg/l) (R).
According to one study, mean levels of histamine were 3.63 mg/L for French wines, 2.19 mg/L for Italian wines and 5.02 mg/L for Spanish wines (R).
The histamine content varies widely even in foods with supposedly high histamine levels (R).
The following foods generally have high histamine levels:
- Fermented products: Sauerkraut, kombucha, alcoholic beverages (except distilled), pickles, fermented soy products, yogurt, buttermilk, kefir, mature cheese,
- Cured, smoked, and fermented meats: sausage, pepperoni, salami, etc.
- Watch out for canned fish products (R).
- Tomato paste (R)
- Spinach and yeast products (R).
- Citrus fruits are histamine “liberators”, which increase histamine release, and should likewise be avoided (R).
Introduction to Mast Cells
Mast cells release histamine, but also serotonin, superoxide (causes brain fog, low T3), heparin (anticoagulant), tryptase, thromboxane (clot forming), PGD2 (constricts airways, cause baldness) and PAF (causes atherosclerosis).
Mast cells are present in most tissues surrounding blood vessels and nerves. They are especially present in areas that interact with the outside world: the skin, lungs, digestive tract, mouth, eyelids, and nose. (R)
Mast cell activation plays a central role in asthma, allergic rhinitis, anaphylaxis, eczema, itching, hives, pain, and autoimmunity. They also suppress fertility and sperm motility in males. (R)
Mast Cells, Histamine, and Stress
Whenever your stress response is set off, your hypothalamus releases Corticotropin Releasing Hormone (CRH), which results in an increase in cortisol release.
People think that cortisol is the villain. Chronically elevated cortisol is certainly bad, but chronically elevated CRH is even much worse.
So we see that activation of your stress pathway has opposing effects on histamine. But eventually, you become insensitive to cortisol and the histamine reducing effects of cortisol are diminished, while CRH stays elevated.
Some people produce high levels of CRH and lower levels of cortisol, and this will cause a lot of histamine issues.
Through my consults, I’ve realized that a majority of people’s histamine issues are most impacted by chronic stress response activation i.e. too much HPA activity.
Psychological stress is only one of the dozens of reasons why your stress response is overactive. However, it’s often the most significant factor.
Read the full list of reasons for chronic stress pathway activation and see how many factors apply to you.
You can take a salivary Cortisol Rhythm test to get a better idea of what your stress response is like.
Mice who are exposed to acute stress more quickly develop Multiple Sclerosis, a disease with a leaky brain barrier. When these mice are lacking mast cells or CRH the effects disappear. (R)
Histamine and IgE Allergies
If you’re Th2 dominant, you will likely have issues with histamine.
This is because B-cells produce IgE antibodies, which in turn stimulates mast cells to release histamine (R).
Therefore, you should think about taking supplements to suppress your Th2 system.
Histamine and Biotoxin Illness/CIRS
People with biotoxin illness generally will have issues with histamine-rich foods, such as cured or fermented foods.
The most common biotoxin is mold, which is in all of our homes to one degree or another.
Mold is a broad category that includes the actual mold itself like Aspergillus, Stachybotrys, and others.
However, it’s important to note that it’s usually not just the mold, but also the algae, bacteria, VOCs, and chemicals from the mold that can be mass-activators of inflammation, causing histamine issues as a side effect.
This is why I make sure my histamine clients check for these 2 tests:
Mast Cells and Infections
Sometimes, if people have chronic infections, they can have histamine/mast cell issues. Mast cells get activated by parasites through IgE responses, for example.
Histamine and Lectins
Lectins such as ConA are probably the best-studied food components in triggering mast cells and basophils (R).
IgE antibodies contain sugar molecules that are a target of lectins. Lectins can then cause histamine to be released. (This works by “cross-linking the glycans of cell-bound IgE.”)
In the picture below, the Y’s are IgE antibodies, the red dots are the sugar molecules and the purple egg would be a lectin. This is what’s called “cross-linking the glycans of cell-bound IgE.”
The cited study was done with potato lectins, but many other lectins would likely have a similar effect.
Potato lectin is present in amounts of 5-8 mg per 100 g raw potatoes, and ∼0·5 mg per 100 g when cooked (R).
Cooked potatoes still retain about half of the biological activity of lectins (R), so even cooking them won’t get rid of the problem, but it does ameliorate it to a large extent.
Obviously, the dose makes the poison.
The following lectins increase histamine release:
- White Potatoes and certainly unmodified potato starch (STA) (R) “As potato lectin activates and degranulates both mast cells and basophils by interacting with the chitobiose core of IgE glycans, higher intake of potato may increase the clinical symptoms as a result of non-allergic food hypersensitivity in atopic subjects.”
- Tomatoes (R) “Tomato lectin behaves similarly to potato lectin in glycoprotein-binding assay, based on their structural homology and identical sugar specificity”
- Soy (SBA) (R)
- Gluten-containing grains (WGA) (R). Contradictory (R). It could be that WGA increases histamine release, but when histamine is released the stores get’s used up for a bit and histamine is inhibited (R). I don’t know.
- Legumes (ConA) (R)
Leptin, Mast Cells, and Histamine Intolerance
Leptin may have to do with histamine intolerance.
Leptin and leptin receptors in mast cells in human skin, lungs, gut and urogenital tract (R), suggesting that leptin has some effect on mast cells.
In metabolic syndrome patients, there was a positive correlation between leptin levels and the number of fat tissue mast cells, suggesting that leptin may stimulate mast cells (R).
It seems like leptin causes mast cells to be more inflammatory (R).
Leptin correlates with (probably increases) mast cell activation in children with asthma who exercised (R).
See my post on leptin: All About Leptin: It’s Role in Chronic Inflammation, CFS, and Weight.
Nerve Growth Factor (NGF) Activates Mast Cells
This may contribute to histamine intolerance.
A number of autoimmune conditions have high NGF as well as more mast cells (R).
NGF is one mechanism by which stress increases histamine intolerance, inflammation, and autoimmunity (R).
Ghrelin Activates Mast Cells
This hormone is another reason why anxiety often goes together with histamine intolerance.
Mast Cells and Fluoride
Fluoride potentiates mast cells to trigger more easily (R). People are exposed to more fluoride in the US because of fluoridation of water.
Histamine and Mast Cell Stabilizers
Histamine is released by immune cells called mast cells. When you stabilize these cells, histamine doesn’t get released.
When mast cells are activated they release a lot of other crap besides histamine.
Various herbs within the Th2 list are mast cell stabilizers and therefore prevent the release of histamine.
Mast cell stabilizers/histamine reducers
A relatively safe and effective drug that stabilizes mast cells is called Cromolyn (R). This drug works via multiple mechanisms in combating allergic disease (R). It’s available over-the-counter in the US.
- Quercetin (R) – more effective than cromolyn. Quercetin works better as a preventative and cromolyn works more quickly (R).
- Fisetin (R)
- Forskolin (R)
- Curcumin (R) (beware: curcumin decreases DAO (R))
- Luteolin (R)
- Apigenin (R)
- Astragalus/Astragalin (R)
- EGCG (R)
- Palmitoylethanolamide (R)
- Methylxanthines/Chocamine (R)
- Adrenaline (beta2-adrenergic receptor agonist) (R). Yohimbine and Adrenal glandular should work.
- Reishi (R)
- Chinese Skullcap (R)
- Eleuthero (R)
- Kaempferol (R)
- Myricetin (R)
- Rutin (R)
- Tulsi/Holy basil (R)
- Theanine (R)
Mast cells have a circadian rhythm (R).
Most of the supplements for Th2 dominance will decrease histamine release from mast cells.
Histamine and Antihistamines
Antihistamines (H1-receptor antagonists) block histamine receptors so that with a given amount of circulating histamine, the effects will be less severe.
Fexofenadine or Allegra seems like a safe drug that doesn’t cause drowsiness because it doesn’t cross the blood-brain barrier much. First generation antihistamines (Benadryl) do cross the brain barrier and cause fatigue.
Research on humans taking Allegra at normal dosages show no significant adverse effects when compared to a placebo. No deaths occurred in testing on mice who took 110X the maximum recommended dose for an adult human (R). I recommend speaking to your doctor to get a prescription.
Benadryl would be good to take at night since it induces sleepiness. It’s actually an FDA-approved sleep medication.
Benadryl has other positive effects besides blocking histamine receptors. It decreases anxiety (R), increases serotonin (R), increases dopamine and is useful for the treatment of OCD (R), which most people have to one degree or another.
Histamine and Bradykinin
Bradykinin is a protein that causes blood vessels to dilate (enlarge), and therefore blood pressure to fall.
ACE inhibitors or blood pressure lowering drugs will increase bradykinin.
ACE inhibitors also constrict our airways, which makes sense because histamine causes such effects.
Therefore, people with histamine issues would be wise to stay away from ACE inhibitors, unless absolutely needed.
Supplements that inhibit bradykinin:
Histamine and Histidine Decarboxylase
Histidine decarboxylase (HDC) is the enzyme that speeds up the reaction that produces histamine from the amino acid histidine. This enzyme is helped by vitamin B6.
If you inhibit the enzyme HDC, you decrease the production of histamine.
Inhibitors of HDC are:
- Magnesium deficiency (R)
- Glucocorticoids/Cortisol/Dexamethasone (R)
- EGCG/Catechins – found in tea (most concentrated in green tea), chocolate, kola nut, acai oil, peaches, raw apples, apricots, nectarines, pears and plums with skin, blackberries, red raspberries, cranberries, cherries, broad beans, vinegar (R)
- Tritoqualine AKA Hypostamin -A drug with no evident side effects. It seems that you need to get this prescribed by a doctor, though I doubt most docs have heard of it (R). Alibaba has it, but seems shady, so buy at your own risk.
- Naringenin (R)
- Mucuna/L-DOPA (Strong) (R)
- Homocysteine (Strong) (R) (ease up on the B-vitamins, perhaps)
- NAC (Strong) (R) – however, NAC increases histamine (R, R2).
- SAM-e (Strong) (R)
- Urocanic acid (Strong) (R) – Can get this by getting sun/UVB? (R)
- Carnosine (less strong) (R). However, carnosine seems to inhibit DAO in pigs (R).
- Valine (amino acid) (Weak) (R)
- Oxaloacetate (Weak) (R)
It might be a good idea to check if you’ve got H Pylori (breath) . H pylori infect about 52% of the American public. H pylori infection increases Histidine Carboxylase, which will increase histamine. (R)
Histamine and Probiotics
Some probiotics degrade histamine and are recommended for histamine intolerant people. I linked to 3 different probiotics because if you buy probiotic brands with a bunch of species, you will also be getting the probiotics that produce histamine.
Histamine degrading bacteria:
People with histamine intolerance generally do better with Bifido Probiotics.
Supplements That Increase DAO Production
Besides taking an enzyme, some supplements increase DAO.
The following increase DAO:
- Vitamin C (R). In one study, 1g of vitamin C also directly decreased histamine in everyone it was given to.. And histamine levels increase exponentially as the ascorbic acid level decreases (R). Vitamin C is rapidly excreted so at least 500-2000 mg needs to be taken periodically throughout the day for optimal effect.
- Vitamin B-6 (R) (Caution: also increase histidine decarboxylase)
- Benadryl (R)
- Pancreatic enzymes (R) – don’t know if it increases DAO, but it supposedly helps.
H Pylori inhibits absorption of vitamin C. (R)
Histamine and Erythropoietin
In a clinical trial with uremic patients, 8/10 people with pruritus had marked reductions in their pruritus scores during erythropoietin therapy.
The patients with pruritus had elevated histamine (20.7 nmol/l), compared with the patients without pruritus (4.2) and normal subjects (2.1).
Therapy with erythropoietin decreased histamine, and discontinuation of erythropoietin was accompanied by increases in histamine. (R)
Flushing: Histamine, MSH or Both?
People with histamine issues are most often underweight, have low blood pressure, have increased pain sensitivity and don’t display a fever generally even though they exhibit inflammation.
While, histamine has a role in these, activation of the melanocortin receptors can cause the same issues (MC4R) (R).
My guess is that both histamine and MC4R are causing flushing symptoms.
Be Wary of These Supplements
- Alcohol (R)
- Curcumin (R)
- Carnosine (R)
- Imidazoles – found in many plants – especially alkaloids (R). Alkaloids include caffeine, nicotine, and theobromine on cocoa.
- Cimetidine (R) – an antihistamine
Genetics of Histamine Intolerance
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Some HDC gene variants increase the risk of developing allergic rhinitis (R).
rs1050891: The HNMT gene known as C939T regulates histamine. “AA” will increase histamine.
If you have “AA”, don’t freak out, as ~56% of the population has this gene.
Food additives can exacerbate ADHD symptoms and cause non-IgE-dependent histamine release from basophils. (R)
“AA” for this gene indicates an increase in ADHD behavior for children when they have been exposed to certain food additives: sunset yellow, carmoisine, tartrazine, ponceau 4R, quinoline yellow, Allura red AC, and sodium benzoate. (R)
It’s believed that”AA” increases histamine levels and this is responsible for the ADHD behavior. (R)
Taking SAM-e should negate this gene, theoretically.
rs10156191 (DAO Gene)….Each “T” allele means you have reduced DAO activity. (R) A “T” allele means you’re more likely to get migraines (R) and you’re also going to be more sensitive to NSAIDs (aspirin, Ibuprofen). (R)
The number of H4R copies correlates to the incidence of arthritis, proteinuria, and antinuclear antibody abnormalities in systemic lupus erythematosus (SLE) (R).
A variant in H1R has been associated with Parkinson’s disease (R).
The MS4A2 (Membrabe spanning 4-domains A2) gene codes for a subunit of the IgE-receptor protein. The IgE-receptor protein is found of the surface of mast cells and plays an important function in allergen response. [R]
This gene encodes a protein that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the nervous system. It is associated with epilepsy and autism (R).
Testing For Histamine Intolerance
You can do a Histamine Test to check for elevated blood levels. You can also check your Tryptase levels, which is a marker for Mast Cell activation. (R)
The diagnosis of sensitivity to vasoactive amines is usually made through history and dietary exclusion; however, some studies have suggested that the measurement of diamine oxidase (DAO) levels may be helpful. One study found a DAO level <3 kU/mL was associated with reported symptoms to high histamine foods, whereas a level of >10 kU/mL indicated histamine intolerance was unlikely [R].
Another study reported that the size of the skin prick test wheal to histamine after 50 min, the ‘histamine 50-skin-prick test’, was a useful diagnostic indicator; 82% of subjects with histamine intolerance maintained a wheal size greater than 3 mm compared with 18 % of controls [R].
I suggest just taking the DAO enzyme and see how you feel.
Some people supposedly have trouble converting sulfur to sulfate (phenol sulfotransferase issue), and who have a sensitivity to certain foods and chemicals because of this, often times develop a high histamine level.
Avoiding certain phenolic and high salicylate foods may help the sulfation problem and subsequently lower the high histamine level.
MSM or Epsom salts also supply sulfur to the system and may be helpful. Some people cannot convert the sulfur in MSM to the needed sulfate form although other people can.