What is Histamine Intolerance?
People with histamine intolerance have too much histamine: they either create it in excess or they can’t break it down quickly enough .
As a result, when they eat foods that contain histamine, it crosses into their blood, and they experience inflammation; by contrast, a healthy person would break down most dietary histamine before it ever reaches the bloodstream [1, 2].
Approximately 1% of the population has histamine intolerance. In contrast to food allergies, in which even a small amount of the allergen causes a reaction, the cumulative amount of histamine is crucial to inducing a reaction .
Histamine intolerance mimics an allergic reaction. Symptoms may include diarrhea, headaches, stuffy and runny nose, eye redness, asthma, low blood pressure, arrhythmia, hives, itching, and flushing .
Histamine intolerance can emerge as a result of one or more factors including genetics, gut damage, alcohol, drugs/supplements, or microbiome imbalances; if you have too many bacteria producing histamine and not enough that degrade it, your enzymes may have a hard time keeping up [1, 4, 1].
Histamine also increases estrogen during menstruation. Histamine-intolerant women often suffer from menstrual cramps and headaches. The reverse is also true: peaks in estrogen during ovulation can lead to flare-ups by increasing histamine .
In pregnancy, DAO is produced at very high concentrations by the placenta, and its concentration may become elevated by 500 times. This increased DAO activity may be the reason why women with food intolerance frequently go into remission during pregnancy .
If a lack of DAO is the sole cause of your histamine issues, then all you need to do is take the enzyme.
Joe suspects, however, that many people who complain of histamine intolerance don’t always have issues with the enzyme alone. Rather, Joe believes that such people are Th2 dominant and produce excess histamine after meals.
Histamine intolerance and reduced DAO levels can lead to allergy-like symptoms, including:
- Skin problems such as rashes, itching, hives, flushing, eczema, psoriasis, and even acne 
- Chronic headaches 
- Painful menstruation (dysmenorrhea) 
- Flushing 
- Gastrointestinal symptoms 
- Reactions to histamine-rich food and alcohol 
- Nasal mucus 
- Asthma attacks 
How Much Histamine is Too Much?
Blood histamine levels above the normal range (0.3 to 1.0 ng/mL) produce certain negative effects.
For example, levels of 1 to 2 ng/mL increase stomach acid secretion and heart rate. A level of 3 to 5 ng/mL leads to flushing, headaches, hives (urticaria), and skin itching (pruritus). The airways dangerously tighten causing bronchospasm at 7 to 12 ng/mL, and heart attacks occur at 100 ng/mL .
Thus, large amounts of ingested histamine can cause significant symptoms in otherwise healthy individuals. For example, eating spoiled fish can lead to flushing, sweating, hives, gut symptoms, palpitations, and in severe cases bronchospasm .
This condition, known as scombroid poisoning, occurs when bacteria in the fish convert high levels of histidine into histamine. These bacteria thrive during improper storage and high temperatures, gradually spoiling the fish. Cooking the fish destroys the bacteria but not the histamine. Tuna and mackerel are common culprits .
Tolerant vs. Intolerant People
Although 75 mg of liquid histamine can provoke symptoms in healthy volunteers, defining the safe threshold level in sensitive individuals is difficult. Canned sardines, which are very likely to trigger symptoms in intolerant people, have as much as 20 mg per 100 g, but some people react to foods that contain much less [11, 12, 13, 1].
Some foods may also provoke the release of histamine from your mast cells; such foods may increase blood and tissue histamine even if they don’t contain very much .
Negative Effects of High Histamine
Elevated histamine can wreak all sorts of havoc on your body. In addition to the common, acute symptoms of intolerance described above, histamine can contribute to mental illness, reduced bone density, and even cardiovascular disease.
Most if not all of these negative effects are interconnected: they tend to come back to inflammation. In theory, histamine intolerance could contribute to any or all of these if it is left unchecked and untreated for a long period of time.
In general, histamine favors the Th2 response, but H1R can also promote Th1 immunity. As a result, people who are Th2 dominant may have a stronger reaction to histamine. For a complete discussion of Th1 & Th2 dominance, check out this post [14, 15, 16].
Itching, Pain & Inflammation
1) Causes Skin Itchiness
Activation of H1R and H4R induces itching, whereas activation of H3R decreases itching. By the same token, drugs that block H1R or H4R (antihistamines) can be used to manage itch, while H3R blockers generally aggravate the itch [17, 18].
2) Increases Inflammation
Through H1R activation in the blood vessels and airways, histamine can quickly cause acute rhinitis, airway constriction, conjunctivitis, cramping, diarrhea, and skin inflammation. Unsurprisingly, then, blocking H1R with antihistamines can decrease inflammation before and during an allergic reaction .
Through H4R activation, histamine also contributes to chronic inflammation .
3) Contributes to Asthma
Histamine generally promotes Th2 responses, which are involved in some types of asthma; it also causes airway narrowing and coughing .
People with asthma have histamine in their lungs even during periods without symptoms; those with more severe asthma have more histamine in their airways, and vice versa .
Inhaled and intravenous histamine causes airway constriction that can be inhibited by H1R antihistamines .
Regardless, antihistamines are not very effective in asthma treatment compared to anti-inflammatory corticosteroids. Antihistamines can still help by decreasing the Th2 immune response and suppressing the accumulation of inﬂammatory cells .
4) Worsens Eczema
Patients with severe eczema (atopic dermatitis) have higher blood histamine. They also spontaneously release more histamine in response to environmental cues and food; furthermore, when they consume histamine, it worsens their symptoms. In one study, when people with atopic dermatitis followed a histamine-free diet for 2 weeks, their symptoms reduced .
In addition, some patients with atopic dermatitis have lower diamine oxidase (DAO) activity, which is to say that they can’t break down histamine as effectively as a healthy person .
5) Contributes to Anaphylaxis
Anaphylaxis is a severe, whole-body allergic reaction that can be fatal without medical intervention. Histamine contributes to this response by opening up blood vessels and increasing heart rate [14, 20].
6) Triggers Headaches
Histamine causes headache by releasing nitric oxide and increasing inflammation. It can induce headaches in healthy people as well as in those with migraine .
Many migraine patients have histamine intolerance, reduced DAO activity, and elevated histamine during both attacks and symptom-free periods. Food rich in histamine triggers headaches, while histamine-free diet and therapy with antihistamines alleviate headaches in these people .
Bones & Joints
7) Decreases Bone Density
Histamine decreases bone density. Patients with osteoporosis tend to have higher levels of histamine; in mice, histamine deficiency increases bone density and reduces the rate at which bone tissue is broken down .
8) May Contribute to Arthritis
Histamine increases inflammation, and thus can contribute to the development of arthritis. In mice, histamine deficiency reduces the symptoms of inflammatory arthritis .
Paradoxically, rheumatoid arthritis patients actually have lower histamine levels in their circulation and joint fluid. A possible explanation is that they “consume” more histamine, preventing its levels in the blood from getting too high. It could also be that other inflammatory markers (such as TNF-a) are much more important than histamine in rheumatoid arthritis [16, 22].
Mental Illness & Neurological Disorders
9) Increases Anxiety
Histamine is a danger response signal; increased brain histamine promotes anxiety. The activity of histamine-releasing nerves is increased in stressful situations, and blocking this activity reduces anxiety .
Blocking H1R reduces fearful behaviors in animals, while blocking H3R increases anxiety. Strangely, however, global histamine deficiency increased anxiety in mice .
10) May Contribute to Schizophrenia
People with schizophrenia tend to have increased histamine activity in their brains. Famotidine, an H2R blocker, may reduce so-called “negative” symptoms of schizophrenia, such as the inability to feel positive emotions or pleasure [24, 25, 26, 27].
11) May Contribute to Parkinson’s Disease
In mice with Parkinson’s, blocking H3R with thioperamide can restore a normal sleep cycle, improve memory. This drug also increases wakefulness in mice with narcolepsy. Disrupted sleep worsens cognitive deficits, so H3R blockers may help prevent these symptoms .
12) May Contribute to Multiple Sclerosis
T cells from H1R-deﬁcient mice produce signiﬁcantly less IFN-gamma, and these mice develop less severe autoimmune diseases. Both H1R- and H2R-deficient mice with multiple sclerosis develop less severe symptoms [19, 14, 16].
However, MS is worse in mice with global histamine deficiency or H3R deficiency. Therefore, the relative abundance of the histamine receptors 1, 2, and 4 may cause harm, rather than histamine or H3R [16, 14].
13) Impairs Balance
HR1 and H3R activity contribute to motion sickness. H1R antihistamines, such as cyclizine, meclizine, and dimenhydrinate (Gravol) effectively treat motion sickness and vomiting. Betahistine, a drug frequently prescribed for motion sickness and vertigo, strongly inhibits H3R and weakly activates H1R [31, 32].
14) Contributes to the Hardening of the Arteries
Histamine increases inflammation and causes small blood vessels, such as capillaries, to swell, but large arteries to contract. In addition, histamine thickens blood vessel walls, a process that contributes to the hardening of the arteries. People with hardened arteries (atherosclerosis) have more histamine in their blood .
15) Worsens Damage After Heart Attacks
In the six days after a heart attack, blood histamine may rise to more than twice as high as normal, while H2R activity increases .
16) High Levels Cause Ulcers
Through H2R activation, histamine increases stomach acid secretion, thereby damaging the stomach lining and increasing the risk of gastric ulcers; H2R inhibitors are used to treat peptic ulcer disease .
Additionally, H4R inhibitors were protective in animals with gastric ulcers .
17) Causes Scombroid Poisoning
A number of bacteria in fish produce histamine (including Morganella morganii, Enterobacter aerogenes, Raoultella planticola, Raoultella ornithinolytica, and Photobacterium damselae) .
To avoid scombroid poisoning, the fish must be carefully handled and stored. Cooking spoiled fish won’t help, as it only kills the bacteria but doesn’t lower the histamine .
The symptoms of scombroid poisoning are variable and may include :
- A peppery or metallic taste
- Mouth numbness and difficulty swallowing
- Dizziness and low blood pressure
- Palpitations and rapid and weak pulse
- Hives, rash, flushing, and facial swelling
- Nausea, vomiting, and diarrhea
These symptoms are typically rapid in onset, and recovery is usually complete within 24 hours, but in rare cases can last for days .
Scombroid poisoning is treated by antihistamines. Corticosteroids are ineffective .
18) May Worsen Irritable Bowel Syndrome
Histamine has been associated with symptom severity in irritable bowel syndrome (IBS). IBS patients with abdominal pain have more mast cells and more histamine activity near gut-associated nerves .
In one study, 58% of the patients with IBS experienced gut symptoms from histamine-releasing food items and foods rich in biogenic amines. In some of these patients, a new carbon-based adsorbent (which binds to histamine in the gut, preventing it from crossing into the bloodstream) reduced symptoms .
Furthermore, elevated levels of H1Rs and H2Rs are found in the stomachs of people with IBS. The H1R inhibitor ketotifen reduces some IBS symptoms .
Testing for Histamine Intolerance
Markers to Check
Tryptase is a marker of mast cell activation, so you should test for tryptase if you want to see how active your mast cells are. Doctors can also test for blood histamine shortly after a reaction [35, 36].
Sensitivity to vasoactive amines is usually diagnosed through history and dietary exclusion; however, some studies have suggested that the measurement of diamine oxidase (DAO) levels may be helpful .
In one study, people with DAO levels under 3 kU/mL were more likely to negatively react to high-histamine foods, whereas histamine intolerance was unlikely when DAO was over 10 kU/mL .
According to another study, the size of the wheal in the “histamine 50-skin-prick test” is a useful diagnostic indicator: 82% of people with histamine intolerance maintained a wheal size greater than 3 mm, compared with 18% of controls .
It might also be a good idea to get a breath test to check if you’ve got H. Pylori. H. pylori infects about 52% of Americans; infection increases histidine decarboxylase, which in turn increases histamine .
If you suspect you are histamine intolerant, Joe suggests taking the DAO enzyme to see how you feel before you order any blood tests. If you have histamine intolerance, some natural therapeutic options include:
- Reducing lectin and tannin consumption
- Destressing and reducing HPA activation
- Quercetin to stabilize mast cells
- Taking probiotics like B infantis, B longum, and L Plantarum to degrade histamine [41, 42]
- Staying away from fermented and cured foods
- Talking to your doctor or pharmacist about taking Allegra in the morning or Benadryl at night to block histamine receptors. Benadryl increases DAO as well 
- Taking 1,000 mg of vitamin C twice a day 
- Vitamin B-6 (Caution: this also increases histidine decarboxylase) 
If you have histamine issues in general, then you may want to try the following:
- Talk to your doctor about taking Cromolyn as a mast cell stabilizer. It is effective when used right before or during a reaction.
- Take 1 capsule of forskolin as a mast cell stabilizer .
- Take 1 capsule twice a day of EGCG to inhibit histidine decarboxylase and stabilize mast cells.
- Experiment with other substances in the Th2 dominance page.
Sulfation: Joe’s Experience
Anecdotally, some people have trouble with sulfation, an important detox pathway for clearing certain drugs, neurotransmitters, and hormones (including thyroid hormones and estrogens) from the body. The culprit might be low activity of an enzyme called phenol sulfotransferase or lack of dietary sulfur [45, 46].
In Joe’s experience, people who have a sensitivity to certain supplements, foods, and chemicals because of this often also develop histamine issues.
Joe recommends avoiding certain phenolic and high salicylate foods, which may place less stress on the sulfation process and subsequently lower histamine.
MSM, cysteine (NAC), methionine, and Epsom salts may also help with histamine issues by supplying sulfur to the body. Caution: some people cannot convert the sulfur in MSM to the needed sulfate form; Epsom salts supply sulfur in the sulfate form directly. You can also try glucosamine sulfate and chondroitin sulfate.
More About Histamine
This is the third post in a six-part series on histamine, histamine intolerance, and how to manage it. To learn more, click through the links below.
- Part 1: What is Histamine? Definition, Function, Receptors & DAO
- Part 2: 17 Histamine Health Effects: Cognition, Inflammation & Sleep
- Part 4: Low Histamine Diet: Does It Work? + Who Should Try It
- Part 5: Foods High & Low in Histamine + Other Mast Cell Triggers
- Part 6: Natural Antihistamines to Prevent Histamine Reactions
Irregular Histamine Levels?
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Histamine intolerance symptoms emerge when there’s too much histamine for your body to handle – either because you’re producing too much or not breaking down enough. People who don’t break down histamine well enough often have low diamine oxidase or DAO.
Histamine can trigger itching, rash, pain, gut inflammation, and headaches in the short term. If histamine levels are high for a long period of time, they may contribute to mental illness, brain damage, weak bones, and heart disease.
Diets low in both histamine and mast cell triggers can help manage intolerance, as can natural and pharmaceutical antihistamines.