What is Histamine Intolerance?
You may have landed here from one of our previous posts on histamine and histamine intolerance. If so, then you know that people with histamine intolerance don’t have enough diamine oxidase (DAO), the enzyme that breaks histamine down in the gut. As a result, when they eat foods that contain histamine, it crosses into their blood, and they experience inflammation.
If you need a primer, check out these posts first:
- What is Histamine? Definition, Effects, Receptors & DAO
- Histamine Intolerance Symptoms: Could You Be Sensitive?
Benefits of a Low Histamine Diet
One strategy for managing a histamine intolerance is simply to avoid foods that contain high amounts of histamine. Many foods – especially cured and fermented meat and fish – are rich in histamine and other bioactive amines. For an extended list of foods that are high and low in histamines, check out this post .
1) Manages Chronic Headaches & Migraine
Histamine is a well-known cause of headaches and a possible culprit behind migraines. Some researchers suspect type 3 and 4 histamine receptors are responsible for migraines, but specific studies are lacking [1, 2, 3].
One study found that a diet low in vasoactive amines improved chronic headaches in 73% of patients. In this same study, histamine-rich foods were reintroduced and reliably caused headaches to occur again [4, 5].
2) Reduces Itching & Rash
Histamine also allows fluid and white blood cells to leak out of the capillaries and lymphatic vessels and into the skin tissue, creating a rash. Antihistamine medication is often used to control itching and skin rashes for this reason [6, 7, 8].
One study reported that 27 out of 44 (61%) people had a significant improvement in hives, skin swelling, and itching on a diet low in dietary amines, although foods containing additives or naturally high in salicylates were also restricted .
3) Reduces Skin Swelling
As mentioned in the previous point, histamine allows fluid and white blood cells to leak out of the capillaries and lymphatic vessels and into surrounding tissues. When this fluid builds up in the deep layers of the skin, it creates a painless, puffy swelling called angioedema [10, 8].
Angioedema usually requires medical treatment, but a low histamine diet may also help. People with angioedema used less antihistamine medication while eating a histamine-reducing diet compared to a control group that eliminated artificial sweeteners from their diet .
4) May Improve Some IBS Cases
Irritable bowel syndrome (IBS) is a condition in which certain foods trigger gut inflammation, abdominal discomfort, and poor stool quality. People with IBS often have far more mast cells in their intestines than normal, suggesting that histamine is at least partially responsible for some of the symptoms of this disease [12, 13].
A low FODMAP diet is well-researched for improving IBS. This diet, in part, works by lowering histamine. But despite its overlap with a low histamine diet, it still allows certain histamine-containing foods (such as spinach, tomatoes, and kefir) [15, 16].
Surprisingly, no studies have yet investigated the effect of a low histamine diet in people with IBS. Given the involvement of mast cells in this condition, however, it may be worth a try. If you decide to test the effect of reducing histamine on your IBS, keep a diary of your symptoms and make sure to be honest with yourself .
5) May Relieve Menstrual Pain
Estrogen and histamine interact strongly with each other: histamine increases the production of estrogen (through H1R). Estrogen then stimulates the release of prostaglandin F2α, a hormone that makes the muscles of the uterus contract, producing painful cramping. This is probably why women with histamine intolerance often have severe cramps during their periods .
To make matters worse, estrogen may also increase sensitivity to histamine. Women are more sensitive to histamine skin-prick tests during ovulation, when estrogen peaks, than at any other time [18, 19].
A low histamine diet has not specifically been tested in women with menstrual headaches and cramps. However, given histamine’s potential involvement in menstrual pain, it seems worth a try .
During pregnancy, DAO is produced at very high concentrations by the placenta, and its concentration may rise to over 500 times normal. DAO breaks down histamine. Its increased activity may be the reason why women with food intolerance frequently go into remission during pregnancy .
How to Prevent Histamine Release
Unfortunately, if you’re intolerant, it may not be enough to avoid foods rich in histamine. To prevent a bad reaction, you also need to avoid triggering histamine release from your mast cells.
Mast cells are white blood cells present in most tissues surrounding blood vessels and nerves. They are especially abundant in areas that interact with the outside world: the skin, lungs, digestive tract, mouth, eyelids, and nose [22, 23].
When mast cells are activated, they release histamine and a handful of other compounds. Mast cell activation plays a central role in asthma, hives, hay fever, anaphylaxis, eczema, itching (pruritus), pain, and autoimmunity. It also suppresses fertility and sperm motility in men [22, 24, 25, 26].
This section will discuss common triggers to avoid if you want to stabilize your mast cells, preventing them from freeing histamine.
1) Reduce Stress
Whenever your stress response is set off, your hypothalamus releases corticotropin-releasing hormone (CRH), which in turn triggers the release of cortisol. CRH also activates mast cells, which indirectly cause an increase in the release of histamine. Cortisol, by contrast, may block histamine secretion in cells to keep the immune system in check. We know this because corticosteroid drugs lower inflammation by mimicking the effects of cortisol. Therefore, your stress pathway has opposing effects on histamine. Eventually, CRH takes over [27, 28, 29, 30].
CRH also activates brain mast cells to release inflammatory cytokines such as IL-6 and IL-8; it stimulates monocytes to release IL-1, another inflammatory cytokine. This process increases the permeability of the blood-brain barrier; that is, more compounds can cross from your blood into your brain [31, 32].
Some people produce high levels of CRH and lower levels of cortisol, and this causes a lot of histamine problems. Through his consults, Joe realized that many people’s histamine issues are most impacted by chronic activation of the stress response, i.e. too much activity in the hypothalamus, pituitary, and adrenal glands (the HPA axis).
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.
2) Reduce IgE Allergies
If you have histamine problems, you may want to make lifestyle and diet changes and take supplements to suppress your Th2 system.
3) Resolve Infections
4) Avoid Lectins
Lectins target sugar molecules in IgE antibodies, which can then trigger histamine release. In the diagram below, the Ys are IgE antibodies, the red dots are the sugar molecules, and the purple egg is a lectin. This process is called “cross-linking the glycans of cell-bound IgE.”
The cited study was performed with potato lectins, but many other lectins would likely have a similar effect. Cooked potatoes still retain about half of the biological activity of their lectins, so even cooking them won’t get rid of the problem, but it does improve it to a large extent .
The following lectins increase histamine release:
- White potatoes and unmodified potato starch, which activate both mast cells and basophils. People who eat more potato may experience more symptoms of food sensitivity .
- Tomatoes. Tomato lectin is similar to potato lectin .
- Soy. Soybean agglutinin (SBA) directly triggers mast cells to release histamine [40, 41].
- Grains that contain gluten, which in turn contains wheat germ agglutinin (WGA). However, this evidence is contradictory. It could be that WGA increases histamine release, but when histamine is released the stores get used up for a bit, and histamine is inhibited [42, 43].
- Legumes. Concanavalin A (ConA) binds to manganese, calcium, and carbohydrates in that order; once it is completely bound, it triggers histamine release from mast cells [41, 44]
5) Lower High Leptin Levels
Leptin, a hormone that reduces appetite and promotes weight loss, may have to do with histamine intolerance. Leptin and leptin receptors can be found in mast cells in your skin, lungs, gut, and urogenital tract .
As leptin levels increased in people with metabolic syndrome, so did the number of mast cells in their fat tissue, suggesting that leptin may stimulate mast cells to multiply. Leptin may also increase the activity of mast cells and make them more inflammatory [46, 47].
For more information on leptin, chronic inflammation, chronic fatigue, and weight, check out this post.
6) Lower High Ghrelin Levels
7) Reduce Lower Inflammation from Nerve Growth Factor (NGF)
Nerve growth factor (NGF) activates mast cells and triggers the release of histamine, BDNF, and other neurotrophins. This is one of the mechanisms by which NGF worsens inflammation and increases sensitivity to heat and pain [50, 51].
During mentally or emotionally stressful events, NGF is released in the hypothalamus and bloodstream. Thus, NGF contributes to the effects of stress on histamine release and inflammation .
NGF-induced histamine release may also play a role in the development and progression of autoimmunity. A number of autoimmune conditions, such as multiple sclerosis and rheumatoid arthritis, have high NGF and more mast cells in affected tissues [52, 53, 54].
8) Reduce Fluoride
Fluoride potentiates mast cells to trigger more easily. Tap water is fluoridated in many countries, including the USA; in others, like China, tap water is not artificially fluoridated but may contain excess fluoride from other sources [55, 56].
9) Lower Bradykinin
ACE inhibitors or blood pressure-lowering drugs increase bradykinin. ACE inhibitors may 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-inhibiting drugs, unless absolutely necessary .
Supplements that block bradykinin include:
10) Address Mold Illness/Chronic Inflammatory Response Syndrome (CIRS)
Mold, which is in all of our homes to one degree or another, is among the most common biotoxins. Aspergillus, Stachybotrys, and other types of molds can all cause disease .
However, it’s important to note that it’s usually not just the mold, but also algae, bacteria, volatile organic compounds (VOCs), and other chemicals from the mold that are mass activators of inflammation, causing histamine issues as a side effect [66, 67].
Who Should Try a Low Histamine Diet
1) Diagnosed Histamine Intolerance
Doctors can diagnose histamine intolerance using skin prick tests, allergy-like symptoms (but no allergy), and medical history of reactions to foods or medications that make histamine levels rise [69, 70].
If you have been diagnosed with histamine tolerance, you should are the ideal candidate to try a diet low in histamine and mast cell triggers .
2) Chronic Headache or Migraine
If you have chronic headaches or migraines with unknown cause, you may want to try a low histamine diet and see if they improve. As we discussed at the beginning of this post, histamine receptors in the brain are probably involved in producing headaches and migraines .
3) Unexplained Rash or Itching
Histamine has a prominent role in skin rashes, itching, and swelling; people with these stubborn symptoms may benefit from a low histamine diet. Diets that reduce both histamine and salicylates have been successful for people with skin problems as well [6, 11, 9].
4) Histamine Reactions to Prescription Medication
If you are experiencing allergy-like side effects from any of the following drugs, you may want to try a low histamine diet to manage them:
- Opioid painkillers, including morphine and codeine [73, 74]
- Some blood pressure medications, including verapamil, alprenolol, and dihydralazine 
- Some antibiotics, including cefuroxime and cefotiam 
- Antimalarials, such as chloroquine 
- Monoamine oxidase inhibitors (MAOIs, the first class of antidepressants) 
For a more complete list of medications that may increase histamine, see this post.
5) H. Pylori Infection
Helicobacter pylori is a spiral-shaped bacterium that infects about half of all people around the world. Left unchecked, it can cause inflammation, ulcers, and even cancers of the stomach or small intestine .
H. pylori infection may increase inflammation in your gut by stimulating histamine-producing stomach cells. H. pylori also increases histidine decarboxylase (HDC), the enzyme that creates histamine [77, 78, 79].
A highly accurate breath test is used to diagnose H. pylori infection. If you have this bacterium in your stomach, it’s important to follow your doctor’s recommendations. You can also try the low histamine diet, natural antihistamines and these natural solutions to help manage it .
More About Histamine
This is the fourth 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 3: Histamine Intolerance Symptoms
- Part 5: Foods High & Low in Histamine + Other Mast Cell Triggers
- Part 6: Natural Antihistamines to Prevent Histamine Reactions
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.
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Also, make sure to check out the lectin avoidance diet, because histamine issues are often caused by various food components that cause inflammation.
The low histamine diet reduces dietary histamine; however, to prevent inflammatory symptoms, it’s also important to avoid triggers that activate mast cells. In people with histamine intolerance, this strategy can improve chronic headaches, itching, rashes, skin swelling, IBS, and even menstrual pain.
Besides food, aim to manage stress, infections, hormones, and biotoxin exposure to make sure you’re successful with a low histamine diet. If you are sensitive to lectins, avoiding them may also lessen your histamine problems.