The low histamine diet: why you might need it

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Finding out that you have a histamine intolerance may be something of a relief. Finally, an explanation for those itchy eyes and runny nose!

But you may also be wondering what to do about it.

For most people, the best solution is a low-histamine diet. But what is that exactly? What foods are low in histamine and what foods are not? What even IS histamine?

We’ll explain all that - and more.

What is Histamine?

Histamine is a chemical known as an autacoid, which means it acts like a local hormone near where it is synthesized in the body. The highest concentrations of histamine are found in your intestinal mucosa, skin, and bronchial tissues. Histamine is also present in many foods.

Scientifically speaking, histamine is a tissue amine and chemical molecule that is biosynthesized by the decarboxylation of the amino acid, histidine. The biosynthesis of histamine is catalyzed by the presence of L-histidine decarboxylase and the cofactor pyridoxal 5’-phosphate or the active form of B6. Of all biogenic amines observed in foods, the excessive levels of histamine and tyramine are considered highly toxic and can produce unwanted effects in the human body.

Biosynthesized histamine is stored in basophils, mast cells, gastric enterochromaffin cells, lymph nodes and thymus.

Histamine is involved in several physiological functions, including gastric acid secretion, lowering of blood pressure, inflammation, increased vascular permeability, cytokine production, smooth muscle contraction and vasodilation. Histamine is also synthesized in the brain, specifically in the neurons present in the posterior region of the hypothalamus.

As a neurotransmitter, it maintains wakefulness and carries impulses like pain and itching sensations. Of all G-protein-coupled receptors, H1, H2, H3 and H4 interact with histamine and activate the signal transduction pathways, thereby initiating the biological mechanisms.

Histamine also participates in local immune response, immunomodulation, hematopoiesis, day-night rhythm, wound healing effects and regulation of histamine- and polyamine-induced cell proliferation and angiogenesis in various tumor models and intestinal blood supply. As per the concentration of histamine present in the plasma, different activities are exhibited as mentioned in Table 1 below (Adapted from Mainz et al., Am. J. Clin. Nutr. 2007).

Table 1. The pharmacological and clinical effects of plasma histamine concentration (ng/ml)

Why Do We Need Histamine?

Although an inflammatory reaction can be quite unpleasant, histamine is very important in protecting your body from potential harm. It acts like an armed guard, sounding the alarm to let your body know that something foreign has entered and that it needs to be fought off.

This causes your immune system to respond with inflammatory chemicals that help get rid of the invader - known as an allergen - that’s bothering you.

When produced during a local immune response, histamine’s main role is to cause inflammation. Its release causes your capillaries to become more permeable to white blood cells and other proteins, which allows the white blood cells to target and attack foreign bodies in the affected tissue.

As one of the most versatile molecules in your body, histamine can cause a huge range of effects depending on where it’s released.

Immune Cell Release

Histamine is produced as part of your immune system’s response to trigger inflammation. Basophils and mast cells secrete histamine when your body detects one of these invaders. These cells reside in connective tissue and act as potent effector cells of the innate immune system.

Mast cells are the major producer of histamine and express many receptors on their surface. These receptors are activated through stimulants such as allergens, complement peptides, and neuropeptides, which cause the mast cells to release various inflammatory mediators including histamine.

When released, histamine causes smooth muscle contraction in the intestines (often causing cramps and diarrhea), expansion of blood vessels (often causing low blood pressure), mucus secretion in the nasal passages and GI tract, and many other physiologic effects that are intended to fight off invaders.

Stomach Cell Release

Histamine is also released from enterochromaffin-like cells in the stomach, triggering acid secretion from parietal cells. This increases acidity in the stomach to kill off any dangerous invaders.

Brain Cell Release

Histamine is also produced in the hypothalamus. It acts as an excitatory neurotransmitter and is involved in regulating the sleep-wake cycle.

How is Histamine Broken Down in the Body?

There are two important pathways in histamine metabolism: one involves diamine oxidase (DAO) and the other involves histamine N-methyl transferase (HNMT).

DAO converts histamine into imidazole 2-acetaldehyde, followed by imidazole acetic acid and finally, imidazole acetic acid riboside is formed. Conversely, histamine is metabolized in the presence of HNMT to obtain methylimidazole acetic acid through the production of intermediate methylimidazole acetaldehyde.

It is worth noting that the conversion of histamine into different by-products is the protective role of DAO and HNMT against excess histamine, either from ingested foods or produced by the intestinal microbiota. Therefore, both enzymes DAO and HNMT help balance and maintain optimum levels of histamine in the human body.

Histamine Intolerance

Histamine intolerance - also known as histaminosis - is an impaired ability to metabolize ingested histamine. It is a disorder which originates from a decreased histamine degradation capacity in the intestine due to diminished DAO activity. This lower DAO activity results in the accumulation of histamine in plasma and creates adverse effects.

As the body’s histamine receptors are throughout smooth muscle, endothelial cells, adrenal medulla, heart, and central nervous system, an intolerance triggers a range of symptoms including nasal congestion, rhinorrhoea, the dilation of blood vessels and inflammation of airways.

Because histamine plays so many different parts in how your body functions, symptoms of histamine intolerance are broad and can easily be confused for other things, such as food allergies.

Some of the most common symptoms of histamine intolerance to be aware of include:

Digestive issues

Abdominal cramping, bloating, diarrhea, and other gastrointestinal discomforts. Histamine plays a part in breaking down food. If your body isn’t able to do this properly, you’ll end up with symptoms like gas, bloating, diarrhea, and stomach pain.

Headaches and dizziness

Histamine can cause the blood vessels in your brain to dilate, which can lead to headaches and lightheadedness.

Respiratory issues

Nasal congestion, sneezing, and other respiratory problems. Again, dilated blood vessels in the nasal passageways tend to cause sneezing and congestion. Histamine can also affect other parts of your respiratory system beyond your nose, including your airways. In extreme cases of histamine intolerance, you may have trouble breathing.

Dermatological problems

Rashes, eczema, and itchy skin are also a result of inflammatory reactions in the skin.

Cardiovascular reactions

A racing heart or palpitations is caused by histamine acting directly on cells in your heart.

Other symptoms of histamine intolerance include:

Abdominal cramps
Irregular menstrual cycle
Anxiety
Arrhythmia or increased heart rate
Trouble falling asleep
Difficulty maintaining body temperature
Fatigue
Flushing
Headaches and/or migraines
Hives
Blocked nose, sinus congestion, sneezing, difficulty breathing
Nausea, vomiting
Swelling of tissues
Vertigo or dizziness

What is Histamine Intolerance Caused by?

There are several reasons intolerance can develop.

Your body is producing too much histamine. This can happen during an immune reaction or due to a health condition such as mastocytosis, in which mast cells increase in number and as a result, cause the body to produce higher amounts of histamine.

You are consuming high-histamine foods or drinks.

Your body is not breaking down histamine properly. This may be due to genetics, medications, or other medical conditions. In most cases, this is due to impaired DAO activity. Studies have shown that people with histamine intolerance tend to have lower serum DAO activity.
Poor gut health due to stress, infection, dysbiosis or inflammatory bowel diseases (such as Crohn’s disease). Inflammation in intestinal cells may lead to a decrease in DAO production. Those with histamine intolerance tend to have less “good” gut bacteria

What is Histamine Intoxication or Histamine Poisoning?

Although histamine is involved in many physiological mechanisms in our bodies, the ingestion of foods containing high levels of histamine causes damaging effects on the body. The balance of histamine is reliant on the body’s histamine degradation systems functioning properly; this is required for the body to appropriately regulate the excess levels of histamine.

Histamine intoxication is also a type of food poisoning that can happen after the consumption of foods with high histamine levels (higher than 500 mg/kg) which actually subjugates the degradation mechanisms. In 2018, a meta-analysis was performed to identify the foods which typically cause histamine intoxication.

The study covers research data between 1959 and 2013 that focus on several studies of histamine intoxication and revealed that the causative food in 98% of the cases accounted for was fish and the remaining cases were due to cheese.

Histamine intoxication is essentially characterized by a short incubation period with low to moderate severity and subsiding in a few hours. The symptoms of histamine intoxication affect the skin, gastrointestinal tract, hemodynamic and neurological functions.

The adverse effects of histamine intoxication are listed below.

Skin - local inflammation, edema, redness, rash, urticaria and pruritus
Gastrointestinal tract –diarrhea, nausea and vomiting
Hemodynamic function – hypotension
Nervous system – headache, tingling and palpitations

How Do Genetic Mutations Affect Histamine?

Studies have shown that single-nucleotide polymorphisms (SNPs) of enzymes may influence histamine intolerance. More than 50 SNPs in the DAO-encoding gene have been detected to date. Some of the key SNPs (namely rs10156191, rs1049742, rs2268999 and rs1049793) discovered in Caucasian people could produce a protein with impaired activity.

Individuals of Asian and African descent may be more affected by SNPs rs45558339 and rs35070995 which have also been reported to show DAO enzyme deficiency. On the other hand, the main SNP related to HNMT (rs11558538) has been associated with reduced HNMT activity.

Overall, these SNPs lead to reduced or deficient enzyme activity, which increases the levels of histamine in the plasma and is then typically followed by a histamine intolerance reaction (particularly in these individuals with DAO and HNMT SNPs – or genetic mutations).

The Link between DAO deficiency and the symptoms of histamine intolerance

Numerous studies have shown that histamine intolerance is most often linked to DAO deficiency. A study involving 100 healthy individuals found that 79% who had symptoms of histamine intolerance also had one or more of the four SNPs associated with reduced DAO activity.

In another study with 27 patients who had headache symptoms, DAO deficiency was reported in 23 patients. Further, the study claimed that 85% of individuals might show histamine intolerance due to the DAO deficit. In the same study, researchers found that patients with a low histamine diet for four weeks had revealed a notable increase in DAO activity and 90% of patients showed the reduction or remission in the frequency of headaches.

Histamine in Food

Histamine is a byproduct of the amino acid histidine. It’s created when certain strains of bacteria or yeasts convert histidine into histamine.

Histidine is present in most protein-rich foods such as meat, fish, eggs, soy, whole grains, beans, and nuts. Although most protein-containing foods can form histamine under the right conditions, the foods containing the highest amounts are aged and fermented foods. Fresh foods contain very little or zero.

Histamine and other biogenic amines such as tyramine, putrescine and cadaverine are present in varying concentrations in different foods, which increases as they age. The following determines the formation of biogenic amines in food:

availability of free amino acids
presence of decarboxylase-positive microorganisms
ideal conditions for bacterial growth and
decarboxylase activity

Plenty of bacterias and a few yeast types demonstrate high L-histidine decarboxylase activity (assisting the conversion of histidine into histamine). This increases histamine production. It’s worth noting that high levels of histamine and other biogenic amines are typically found in products of microbial fermentation which include processed meats, aged cheeses, sauerkraut and wine, also in microbially spoiled food.

So, the presence of histamine, tyramine, putrescine and cadaverine are all considered as indicators of food quality.

Other biogenic amines can combine with histamine and cause intolerance or adverse effects. Besides histamine-rich food, several foods such as citrus fruits, a few types of fish and liquorice can stimulate a histamine release from mast cells. The concentration of histamine in various food categories is presented in Table 2.

Table 2. Histamine content in various types of food categories (Adapted from Bover-Cid et al., 2014).

Food types	N	Histamine content (mg/kg)
		Average	Maximum

Fruits, plant-based products and vegetables

Cereals	28	0.12	0.89
Chocolate	25	0.58	0.56
Fruits	136	0.07	2.51
Legumes	11	ND	ND
Nuts	41	0.45	11.86
Spices	12	ND	ND
Vegetables	98	2.82	2.51

Alcoholic beverages

Beer	176	1.23	21.60
Red wine	260	3.81	55.00
White wine	83	1.24	21.60

Fish and other meat products

Canned fish	96	14.42	657.05
Fresh fish	136	0.79	36.55
Semi preserved fish	49	3.48	34.90
Fresh meat	6	ND	ND
Cooked meat	48	0.30	4.80
Cured meat	23	12.98	150.00
Dry fermented sausages	209	32.15	150.00

Dairy Products

Pasteurized milk cheese	20	18.05	162.03
Raw milk cheese	20	59.37	389.86
Unripened cheese	20	ND

How to Treat Histamine Intolerance?

Avoiding both high-histamine foods and histamine-releasing foods is the best place to start (more on this below).

Supplementing with DAO may also be beneficial. Studies have shown that DAO may be a therapeutic approach to increase dietary histamine degradation in people who have a deficiency or impairment of the DAO enzyme in the intestine.

The adverse effects of histamine intoxication are listed below.

antihistamines (histamine receptor antagonists)
avoiding drugs/substances that inhibit DAO and HNMT enzyme activity (i.e. chloroquine, clonidine, isoniazid, diclofenac, cimetidine, verapamil, vitamin B1 and vitamin C)
supplementing with a DAO enzyme to increase its activity in the body (which in turn decreases histamine levels)

Diagnosis of Histamine Intolerance

Some options for determining whether you have histamine intolerance may include:

dentification list of foods that trigger the symptoms
Determining the histamine content for the foods which cause symptoms
Exclusion of other causes including allergic, metabolic and toxic concerns
Analysis of DAOSNPs (or genetic mutations)

o rs45558339

o rs35070995

o rs10156191

o rs1049742

o rs2268999

o rs1049793

Analysis of HNMTSNPs (or genetic mutations)

o rs11558538

o rs1050891

o rs758252808

o rs745756308

Determining the DAO and HNMT content in the plasma using ELISA-type immunoassay and radioimmunoassay tests as well as their activity levels in the intestinal mucosa.

Histamine intolerance testing

If you have the signs and symptoms of histamine intolerance but no apparent allergies or gastrointestinal disorders, it’s important to seek a proper medical diagnosis.

The gold standard for a histamine intolerance diagnosis begins with a strict low-histamine diet for four weeks.

You will then ‘introduce’ a few high histamine foods and observe your physiological reaction.

A registered dietician or other healthcare professional can help guide you through a structured elimination diet.

It’s also a good idea to keep a food diary for a few weeks and record everything you eat and drink, along with any symptoms.

When is a low histamine diet recommended?

The first step in managing histamine intolerance and reducing symptoms is to follow a low-histamine diet. Studies have shown that reducing intake of histamine also reduces symptoms of intolerance, and may even help to increase DAO levels in the blood.

It’s generally accepted that if your tolerance level for histamine is naturally low, you are likely to react when you eat or drink something containing histamine.

Histamine levels in foods increase with maturation, which means they have been fermented in some way. This includes aged cheeses, yogurt, kefir, sauerkraut, processed meats, aged meats, and alcoholic drinks such as wine, champagne, and beer. Reactions also appear to correlate with the degree of processing.

Alcohol- Red wine can have up to three times more histamine than white wine. Wine ‘on tap’ contains higher amounts of histamine than bottled.
Avocado
Dried fruits
Eggplant
Fermented or aged meats: salami, sausages, pepperoni, lunch meat, hot dogs, canned or smoked meats/fish
Fermented beverages: kombucha
Fermented dairy products: yogurt, kefir, sour cream, buttermilk, cottage cheese, ricotta
Fermented vegetables: miso, kimchi, sauerkraut, pickles, natto
Fish and seafood, especially smoked, salted, canned, or leftover
Matured cheeses
Beans and pulses: chickpeas, soy
Nuts prone to mold: peanuts, cashews, almonds
Chocolates and other cocoa-based products
Seitan
Rice vinegar
Instant or packaged meals
Snacks and sweets with preservatives and artificial additives
Soy sauce, tamari, coconut aminos, liquid aminos

Histamine liberators

Symptoms can also be brought on by “liberators”: foods that don’t actually contain histamine but can trigger your cells to release it. These foods include:

Most citrus fruits, including lemon, lime, oranges
Cocoa and chocolate
Walnuts, peanuts
Papaya, pineapples, plums, kiwi, bananas
Legumes
Tomatoes
Wheat germ
Most vinegars
Additives – benzoate, sulfites, nitrites, glutamate, food dyes

NOTE: Symptoms may be triggered by certain foods, but histamine intolerance is not the same as a food allergy. Symptoms may not be immediate; rather, you may react any time your “threshold” is reached. This makes it very difficult to pinpoint a particular food as the culprit.

DAO blockers

Foods that inhibit the activity of DAO should also be avoided - especially alcohol. Alcohol contains high levels of histamine and also slows DAO’s ability to break it down.

DAO-blocking foods include:

Alcohol
Black tea
Energy drinks
Green tea
Mate tea

Low histamine diet-related clinical case studies

A prospective study was carried out for four weeks with a low histamine diet in 35 patients with headache and other secondary symptoms such as urticaria, arrhythmia, diarrhea and asthma to evaluate the plasma histamine levels and DAO activity. Interestingly, a 77% reduction in symptoms, a 73% increase in DAO activity, along with no changes in plasma histamine levels were found.

In another prospective study with 36 patients, the low histamine diet was supplemented for 2 weeks and a 33% reduction in atopic dermatitis was reported. One more prospective study comprising 45 patients was conducted for a low histamine diet over 4 weeks to evaluate chronic headache, dermatological and respiratory symptoms.

It reported that an 82% reduction in dermatological and respiratory symptoms and a 68% reduction in chronic headache was achieved.

The retrospective study on a low histamine diet was performed for 4 weeks in 157 patients to assess chronic idiopathic urticaria (CIU). The results revealed a 46% reduction in CIU. In another retrospective study evaluation of CIU along with gastrointestinal symptoms, an estimation of DAO activity was carried out in 56 patients kept on a low histamine diet for 3 weeks.

Notably, the study showed a significant 75% reduction of CIU and gastrointestinal tract symptoms, whereas there were no considerable changes in DAO activity in the plasma of the patients.

Focusing on gastrointestinal symptoms and DAO activity, another study involved 63 patients who were supplemented with a low histamine diet for 7-18 months,of which 79% reported a reduction in gastrointestinal symptoms and a 52% rise in DAO activity was noted.

Foods to eat on a low low-histamine diet

Fortunately, there are plenty of low histamine foods out there! Remember, foods with the lowest amount of histamine are fresh, natural foods.

Fresh fruits: apples, apricots, blackberries, blueberries, cherries, coconut, melons, peaches, plums, pomegranate, and raspberries, among others.
Most vegetables: asparagus, bell peppers, beets, bok choy, broccoli, brussels sprouts, cabbage, carrots, cauliflower, garlic, greens, leeks, lettuce, onions, rhubarb, rutabaga, shallot, summer squash, sweet potato, turnip, watercress, winter squash, zucchini.
Gluten-free grains (these are less likely to aggravate an irritated gut lining): amaranth, corn, millet, quinoa, rice, teff.
Fresh herbs
Olive oil
Fresh animal proteins: chicken, beef, lamb. Choose meat that has been butchered and frozen quickly, and preferably in whole cuts. Ground meat (such as mince) is more prone to bacteria being spread throughout the meat, allowing histamine to be created.

Again, note that everyone tolerates different foods differently. Even some low-histamine foods can cause adverse reactions.

Tips for preparing food on a low histamine diet

The key thing about histamine is that it forms as food ages, so it’s vital to keep all food and drink as fresh as possible. Keep a cooler in your car for groceries. Freeze food where possible: this prevents or slows the development of histamine.

Should you take antihistamines?

Over-the-counter antihistamines are medications designed to block the action of histamine, reducing symptoms. However, this is just a temporary fix: antihistamines will not get to the root of the problem, and will certainly not help boost DAO activity. Antihistamines are also known for causing drowsiness, dry mouth, dizziness, and even nausea.

Histamine intolerance supplements

While limiting histamine-containing foods is the most effective way to manage intolerance, it can be difficult to avoid histamine completely. That’s where supplements that support the degradation of histamine and reduce histamine in the body can be helpful.

Supplementation of the DAO Enzyme

Oral supplementation of DAO has been proposed by several researchers to improve the dietary histamine degradation system. In 2017, the European Commission provided the approval to launch DAO supplements as food for special medical purposes.

According to the literature on DAO enzymes, porcine kidneys are a major source of DAO. A number of studies have shown that porcine kidney-derived DAO enzymes degrade excessive levels of histamine and other biogenic amines in vitro. To date, only a few interventional studies have been reported for the pharmacological efficacy of DAO supplementation inpatients with histamine intolerance.

A randomized, double-blind, placebo-controlled, crossover provocation study, for 39 patients with histamine intolerance symptoms such as headache, gastrointestinal and skin related complaints, was executed using histamine-containing and histamine-free tea with DAO capsules or placebo.

As compared to placebo controls, a statistically significant reduction of histamine-elicited symptoms was observed in the group taking DAO supplementation. In another randomized double-blind clinical trial, 100 patients with episodic migraine were treated with DAO supplements for one month.The duration of migraine attacks was significantly reduced in the group taking the DAO supplements.

An open-label pilot study proved the efficacy of DAO supplementation for one month of intervention in 28 patients. The study was focused to assess the various symptoms including gastrointestinal, cardiovascular, respiratory and skin issues, together with reduced DAO levels. The study showed a significant improvement in all histamine intolerance symptoms. Concerning DAO plasma levels, 61% of patients revealed a modest increase in DAO levels.

Guidelines of the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Association of Allergologists (AeDA), and the Swiss Society for Allergology and Immunology (SGAI) suggested a phased approach (three-step dietary adjustment; presented in Table 3) which not only allows a person to determine their histamine tolerance but also helps them to avoid the intolerance symptoms.

Table 3. Three-step dietary adjustment (Adapted from Imke Reese et al., 2017).

Phase	Aim	Recommendation	Duration

I: Avoidance	Reduce symptoms to a great extent	A mixed diet emphasizing vegetables and reduced biogenic amine intake (specifically histamine)Nutrient optimizationChange in meal compositionBalanced diet	10-14 days
II: Test	Expansion of food choice under consideration of individual risk factors (stress, medication, menstruation, etc.)	Targeted re-introduction of suspected foodsDetermining individual histamine tolerance	Up to 6 weeks
III. Long term diet	A balanced supply of nutrientsGood quality of life	Individual nutritional recommendations

Vitamins to support the breakdown of histamine

There is also some evidence that DAO enzymes are dependent on vitamin B6, B12, iron, copper and vitamin C in order to function properly. Copper and Vit C play crucial roles in the function of the DAO enzyme, while B6 is a key cofactor that enables DAO to degrade histamine.

Several studies have shown that vitamin B6 deficiency is associated with reduced serum DAO activity, which may correlate with it may influence serum DAO activity.

One of the best ways to increase your intake of these nutrients is with a high-quality multivitamin such as a Methylated Multivitamin. This comprehensive multivitamin contains all the nutrients required for optimal methylation in the body.

The research-based formulation includes methylfolate and hydroxocobalamin to promote your body’s production of glutathione, your most powerful antioxidant.

The Methylated Multi supports energy production with a host of B vitamins and their cofactors, TRAACS® minerals, Vitamins A, D3, E and bioactive K2. It also contains a new ATP energy combination, NADH + MicroActive® CoQ10.

Methylation support

Antihistamines are also known for causing drowsiness, dry mouth, dizziness, and even nausea. Histamine is also involved in the methylation process, which can be problematic for anyone with defects of the MTHFR gene.

MTHFR helps regulate methylation, which is needed to reduce intracellular histamine. However, genetic defects can result in a malfunctioning MTHFR enzyme, which in turn can lead to imbalances in methylation status.

Research suggests that a MTHFR mutation(s) compromises your body’s ability to carry out methylation which can lead to a buildup of excess histamine.

Check out our recent article, High histamine: what it does and why it’s so complicated for more about this.

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As with taking any supplement, it is strongly advised that you consult with a qualified healthcare practitioner before beginning any treatment.

Methyl-Life™ provides free Methylation Protocols for download, so you can decide what’s best to take for your own methylation needs.

The Takeaway

Histamine intolerance can trigger various uncomfortable symptoms like itchy skin, urticaria, nausea, headaches, digestive problems etc. It has been reported that a histamine-free diet is very helpful in the treatment of chronic spontaneous urticaria.

Therefore, a low-histamine diet is highly beneficial for people who develop untoward effects in response to foods containing histamine. Many nutritionists and dieticians suggest that an individualized approach be taken for curbing histamine-induced allergic symptoms. T

hose suffering from histamine intolerance must ensure not to miss out on essential nutrients while following a low histamine or histamine-free diet and should seek advice from a dietician or nutritionist.

References

https://pubmed.ncbi.nlm.nih.gov/12875237/
https://pubmed.ncbi.nlm.nih.gov/12875237/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463562/
https://www.jacionline.org/article/S0091-6749(03)01877-3/fulltext
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859183/