A diet low in histamine may help manage intolerance related symptoms like headaches and a rash, but can it stop your mast cells from activating and releasing histamine of their own? Read on to discover the benefits and limitations of the low histamine diet.
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].
If you suspect that you have histamine intolerance, we strongly recommend talking to your doctor about it. Your symptoms may have a different underlying cause, and if histamine is the culprit, a medical professional can help guide you through the appropriate management strategies, which may include a low histamine diet.
1) Chronic Headaches & Migraine
Histamine is a well-known cause of headaches and a possible culprit behind some people’s 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) Itching & Rash
Histamine is best-known for its ability to induce itching and skin rashes. Once released by mast cells, histamine stimulates C fibers, the types of nerves that make us feel itchy [6, 7, 8].
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 [9].
3) 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 [11].
Other Potential Benefits Lacking Evidence
Some researchers believe that low histamine diets can have benefits in other cases based on human physiology, but these have not specifically been the subject of clinical trials. Talk to your doctor about whether decreasing dietary amines could be appropriate in your case.
4) 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].
Fifty-eight percent of adult patients with irritable bowel syndrome (IBS) believe that foods rich in vasoactive amines, such as wine, beer, salami, and cheese, are a cause of their symptoms [14].
A low FODMAP diet is well-researched for improving IBS. This diet works, in part, 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 [17].
5) 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 [1].
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 [20].
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 [18].
Women with histamine issues tied to their menstrual cycles may also consider supplements that increase DAO production and activity, such as vitamins C and B6 [21].
Factors that May Affect Histamine Release
Unfortunately, if you’re intolerant, it may not be enough to avoid foods rich in histamine. A bad reaction may also result simply from the activation of 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. It’s important to talk to your doctor about symptoms of excess histamine; a medical professional can accurately diagnose any underlying conditions and help develop an appropriate treatment or management plan.
1) Stress
Whenever the stress response is set off, the 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. The stress pathway has opposing effects on histamine [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].
2) IgE Allergens
According to some studies, Th2 immunity may exacerbate issues with histamine: B cells produce IgE antibodies, which in turn stimulates mast cells to release histamine [33, 34].
If you have histamine problems, you may want to make lifestyle and diet changes and take supplements to suppress your Th2 system. Talk to your doctor about allergy tests and strategies to reduce histamine.
3) Infections
Sometimes, if people have chronic infections, they may develop high histamine, possibly from excessive activation of mast cells. Mast cells get activated by parasites through IgE responses, for example [35, 36].
4) Leptin
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 [37].
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 [38, 39].
Leptin may increase mast cell activation in children with asthma who exercise [40].
For more information on leptin, chronic inflammation, chronic fatigue, and weight, check out this post.
5) 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 [41, 42].
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 [43].
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, are characterized by high NGF and more mast cells in affected tissues [43, 44, 45].
6) Bradykinin
Bradykinin is a protein that causes blood vessels to dilate (enlarge) and therefore causes blood pressure to fall [46].
Bradykinin triggers histamine release, possibly via an increase in calcium within our cells [47, 48].
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 [49].
Other Potential Factors Lacking Evidence
Some animal and cell research suggests a possible role for the factors in this section, but these have not been investigated in humans. Talk to your doctor about the extent to which any of these may be involved in your health.
7) Mold
According to some researchers, exposure to molds may induce histamine release from mast cells [50, 51].
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 cause reactions [51].
Not only mold, but also algae, bacteria, volatile organic compounds (VOCs), and other chemicals from the mold can be activators of histamine-mediated inflammation [52, 53].
8) Lectins
According to some researchers, lectins can bind to the lining of the intestine and increase its permeability; that is, they can make your gut “leaky.” Undigested lectins can then enter the bloodstream [54, 55].
Lectins such as concanavalin A (ConA) are among the best-studied food components that trigger mast cells and basophils in a lab setting [56].
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 [56].
The following lectins have been found to increase histamine release in cell studies:
- White potatoes and unmodified potato starch, which activate both mast cells and basophils. People who eat more potatoes may experience more symptoms of food sensitivity [56].
- Tomatoes. Tomato lectin is similar to potato lectin [56].
- Soy. Soybean agglutinin (SBA) directly triggers mast cells to release histamine [57, 58].
- 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 [59, 60].
- 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 [58, 61]
9) Fluoride
Fluoride may potentiate the activation of mast cells, at least according to cell studies. 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 [62, 63].
10) Ghrelin
Ghrelin is a hormone that induces hunger, anxiety, and possibly mast cell activation. This hormone may help explain why anxiety often goes together with histamine intolerance [64].
Who Should Try a Low Histamine Diet?
Above all, it’s important to talk to your doctor before making any significant changes to your diet. Discuss any symptoms that have led to you believe that you are histamine intolerant and make sure that you address any underlying conditions. A medical professional can help guide you through a transition to a new diet and ensure that you avoid any nutritional deficiencies and other unexpected adverse effects.
That being said, certain people are more likely than others to benefit from cutting histamine from their diets. Again, your doctor can help you determine whether you might benefit.
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 [65, 66].
If you have been diagnosed with histamine tolerance, you may be the ideal candidate to try a diet low in histamine and mast cell triggers [66].
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 [2].
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
Some prescription medications interfere with histamine metabolism; most often, they inhibit the enzymes that break histamine down [67, 68].
If you are experiencing allergy-like side effects from any of the following drugs, you may benefit from a low histamine diet. Talk to your doctor about whether this is a likely side effect and whether avoiding dietary amines is an appropriate management strategy.
- Opioid painkillers, including morphine and codeine [69, 70]
- Some blood pressure medications, including verapamil, alprenolol, and dihydralazine [66]
- Some antibiotics, including cefuroxime and cefotiam [66]
- Antimalarials, such as chloroquine [66]
- Monoamine oxidase inhibitors (MAOIs, the first class of antidepressants) [71]
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 [72].
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 [73, 74, 75].
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. Do not attempt to replace your doctor’s recommendations with a low histamine diet [76].
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
Takeaway
The low histamine diet reduces dietary histamine; however, inflammatory symptoms may also be caused by other triggers that activate mast cells.
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. Talk to your doctor to determine the most appropriate management plan for you.
