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How to Treat Histamine Intolerance and

High Histamine Levels
Ive been getting quite a few clients who are dealing with histamine intolerance. So
this protocol is dedicated to them.

Contents [hide]

1 Executive Summary
2 What Does Histamine Intolerance Come From?
3 Do You Have Histamine Intolerance?
4 Histamine Rich Foods
5 Introduction to Mast Cells
6 Mast Cells, Histamine and Stress
7 Histamine and IgE Allergies
8 Histamine and Biotoxin Illness/CIRS
 9 Mast Cells and Infections
10 Histamine and Lectins
11 Leptin, Mast Cells and Histamine Intolerance
12 Nerve Growth Factor (NGF) Activates Mast Cells
13 Ghrelin Activates Mast Cells
14 Mast Cells and Fluoride
15 Histamine and Mast Cell Stabilizers
o 15.1 Mast cell stabilizers/histamine reducers
16 Histamine and Antihistamines
17 Histamine and Bradykinin
18 Histamine and Histidine Decarboxylase
19 Histamine and Probiotics
20 Supplements That Increase DAO Production
21 Histamine and Erythropoietin
22 Flushing: Histamine, MSH or Both?
23 Be Wary of These Supplements
24 Other/Anecdotal
25 Genes
o 25.1 DAO
o 25.2 HNMT
26 Disclaimer and Caveats
o
26.0.1 Share this:
26.0.2 Related

Executive Summary
Histamine intolerance is a condition that results in high histamine levels.

Its 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.

The clearest sign of histamine intolerance is a bad reaction after eating fermented foods
like sauerkraut.

The biggest contributor to histamine intolerance is chronic HPA activation.

If you have histamine intolerance, some potential therapeutic options include:

DESTRESS and reduce HPA activation.

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:

Reduce lectin consumption. Only do this if you have histamine issues in general
and your issues arent resolved with taking DAO enzymes.
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.
Take 1 cap Bromelain and Quercetin to break down bradykinin (bromelain) and
stabilize mast cells (quercetin). Quercetin works best as a preventative. (or buy
bromleain separately and use this Quercetin+Vitamin C).
Experiment with other substances below and in the Th2 dominance page.

I recommend seeing a well-done flow chart that seems pretty comprehensive.

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)

You can theoretically check your levels of DAO enzymes, but its difficult and
expensive to do in the US.

I suggest just taking the enzyme and see how you feel.

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 your histamine issues are strictly as a result of a lack of DAO enzymes, then all you
need to do is take the enzyme.

I suspect, however, that many people who complain of histamine intolerance dont
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 headache (R)
Dysmenorrhea (R)
Flushing (R)
Gastrointestinal symptoms (R)
Intolerance of histamine-rich food and alcohol (R)
Nasal mucus (R)
Asthma attacks (R)

I recommend seeing a well-done flow chart that seems pretty comprehensive.

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).

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 a 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 (2 mg/l), Holland (3
mg/l), Finland (5 mg/l), Belgium (56 mg/l), France (8 mg/l), Switzerland, and Austria
(10 mg/l. (R)

The histamine content varies widely even in foods with supposedly high histamine
levels (R).

The following foods are generally attributed to 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, eye lids, 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)

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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.

Mast cells get activated by CRH, which leads to histamine release. (R) On the other
hand, cortisol inhibits histamine secretion. (R)
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.

CRH also activates brain mast cells to release inflammatory cytokines such as IL-6 and
IL-8. (R) Activation of mast cells by CRH increases Brain Barrier permeability. (R)

Some people produce high levels of CRH and lower levels of cortisol, and this will
cause a lot of histamine issues.

Through my consults, Ive realized that a majority of peoples 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, its 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)

Read why stress is bad.

Histamine and IgE Allergies

If youre 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 its important to note that its 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.

The most common markers of biotoxin illness are elevated C3a, C4a and TGF
beta. These inflammatory responses activate mast cells (R, R2), which causes blood
histamine levels to rise.

This is why I make sure my histamine clients check for these 3 tests:

Transforming Growth Factor Beta1 (TGFb1)

Complement C3a
Complement C4a

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 can bind to the lining of the gut wall and make it more leaky (R). Undigested
lectins can enter into the bloodstream (R).

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 Ys are IgE antibodies, the red dots are the sugar molecules
and the purple egg would be a lectin. This is whats 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 05 mg per
100 g when cooked (R).

Cooked potatoes still retain about half of the biological activity of lectins (R), so even
cooking them wont get rid of the problem, but it does ameliorate it to a large extent.

Obviously, the dose makes the poison. People who arent sensitive to lectins will look
upon those who are as crazy, since lectin sensitivity isnt a diagnosable disorder.

(Note to Self: Sialic acid and N-acetyl-glucosamine lectins seem to inhibit histamine
release.)

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 gets used
up for a bit and histamine is inhibited (R). I dont 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: Its Role in Chronic Inflammation, CFS and
Weight.

Nerve Growth Factor (NGF) Activates

Mast Cells
Nerve Growth Factor (NGF) activates mast cells, which causes the release of histamine.
BDNF and other neurotrophins, however, do not activate mast cells (R).

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

Ghrelin (and obestatin) induces hunger, anxiety and mast cell activation (R).

This hormone is another reason why anxiety often goes together with histamine
intolerance.

Mast Cells and Fluoride

Fluoride potenitates 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 doesnt get released.

When mast cells are activated they release a lot of other crap besides histamine.

People with mast cell activation from food allergies or whatever else can experience
brain fog. I believe this is because mast cells release superoxide (R), which is the
central cause of brain fog.

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). Its available over-the-counter in the US.

The following also stabilize mast cells:

Forskolin (R)
Quercetin (R) more effective than cromolyn. Quercetin works better as a
preventative and cromolyn works more quickly (R). One blogger notices a
difference in the source of their quercetin and uses this one instead. (R)
EGCG (R)
Palmitoylethanolamide (R)
Curcumin (R) (beware: curcumin decreases DAO (R))
Methylxanthines/Chocamine (R)
Adrenaline (beta2-adrenergic receptor agonist) (R). Yohimbine and
Adrenal glandulars should work.
Reishi (R)
Chinese Skullcap (R)
Eleuthero (R)
Fisetin (R)
Luteolin (R)
Apigenin (R)
Kaempferol (R)
Myricetin (R)
Rutin (R)
Astragalus/Astragalin (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 doesnt cause drowsiness because it
doesnt 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. Its 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.

Its used in studies to increase histamine levels (R). One potential mechanism by which
it increases histamine is via an increase in calcium within our cells. (R)

ACE inhibitors or blood pressure lowering drugs will increase bradykinin. A side effect
of ACE inhibitors is constriction of 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:

Bromelain (R),
Aloe (R)
Grape Seed Extract and polyphenols (R)

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 youve got H Pylori (breath) . H pylori infects ~52%
of the American public. H pylori infection increases Histdine 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:

B infantis (R)
B longum (R)
L plantarum (R)

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) dont know if it increases DAO, but it supposedly
helps.

H Pylori inhibits absorption of vitamin C. (R)

SAM-e may help break down histamine by methylating it. (R) Histamine N-
methyltransferase is an alternative to DAO in breaking down histamine and it uses
SAM-e to do that. (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

were accompanied by increases in histamine. (R)
Ways to increase EPO: Interval Exercise, Cobalt (R), Kidney glandular,
Rhodiola/Salidroside, Rehmannia/Catalpol, Astragalus, Phycocyanin, Emodin (R),
Arachidonic acid, Echinacea.

Flushing: Histamine, MSH or Both?

People with histamine issues are most often underweight, have low blood pressure, have
increased pain sensitivity and dont 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).

People with chronic stress and/or inflammation will have the MC4R receptor activated,
which then leads to flushing, weight loss, lower blood pressure and increased pain (R).

My guess is that both histamine and MC4R are causing flushing symptoms.

Be Wary of These Supplements

Histamine producing bacteria:

L casei (R)
L reuteri (R)
L bulgaricus (R)

DAO Inhibitors:

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

Other:

Supplements that decrease Th1/Increase Th2

Other/Anecdotal
Some people supposedly have trouble converting sulfur to sulfate
(phenolsulfotransferase 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.

Epsom salts supply sulfur in the sulfate form directly. Taking MSM or Epsom salts may
alleviate a histamine reaction. You can also try Glucosamine sulfate and Chondroitin
sulfate.

Genes
DAO
rs2052129 (DAO Gene). Having one T means you produce less DAO. (R) This is on
the old 23andme, not the new one.

rs10156191(DAO Gene).Each T allele means you have reduced DAO activity.

(R) A T allele means youre more likely to get migraines (R) and youre also going
to be more sensitive to NSAIDs (aspirin, Ibuprofen). (R)

rs1049742 (DAO Gene). Each T allele means you have reduced DAO activity. (R)

HNMT
Rs1050891: The HNMT gene known as C939T regulates histamine. AA will increase
histamine.

If you have AA, dont freak out, as ~56% of the population has this gene. G=25%.

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)

Its believed thatAA increases histamine levels and this is responsible for the ADHD
behavior. (R)

Taking SAM-e should negate this gene, theoretically.