Are you suffering from histamine intolerance?
Have you been instructed to follow a low-histamine diet, but are feeling a little confused about what that means?
We get it! There are so many things to think about.
Which foods do you need to avoid? What can you actually eat? Is there anything else you can do to start feeling better?
This comprehensive article will explain the science behind histamine intolerance and help you understand the best diet for managing your symptoms.
Let’s dive in!
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What Is Histamine?
Histamine is a chemical that is naturally found in some foods and also produced by the body.
Histamine In Food
Histamine forms when certain bacteria or yeasts transform the amino acid histidine into histamine (1).
This means that any food containing protein can form histamine under the right conditions.
Generally speaking, aged and fermented foods or beverages contain the highest levels of histamine, while fresh foods contain almost none.
Histamine In the Body
Our bodies also naturally produce histamine.
It is one of the most versatile molecules in the body, inducing a wide variety of effects, depending on where it is released (51).
Some of the places that histamine is released include:
1) From immune cells when the immune system detects a threat.
Histamine can be released by many cells of the immune system, including basophils and mast cells.
When released, it triggers 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 (2).
Once the perceived threat is over, histamine levels are reduced back to normal, and symptoms subside.
2) From enterochromaffin-like cells in the stomach.
Histamine is also released from cells in the stomach, where it triggers acid secretion from parietal cells, increasing the acidity of the stomach (52).
3) From histaminergic neurons in the brain.
Histamine is also produced in the brain (specifically, in the tuberomammillary nucleus of the hypothalamus), where it acts as an excitatory neurotransmitter and plays a role in regulating the sleep-wake cycle (53).
The body has two enzymes that are capable of degrading histamine: N-methyltransferase (HNMT) and diamine oxidase (DAO) (2).
HNMT exists only in the cytoplasm, so it is responsible for breaking down any histamine found inside of cells.
The highest concentrations of HNMT have been found in the kidney and liver but it also exists in many other tissues.
DAO, on the other hand, is produced and stored by epithelial cells (cells that line our organs and blood vessels).
When stimulated, it is secreted into the bloodstream and gut where it picks up and degrades any histamine that might be floating around.
DAO is produced in large amounts within the intestines, but also by the placenta during pregnancy.
However, in some people histamine degradation doesn’t work the way it should, causing a condition known as histamine intolerance.
What Is Histamine Intolerance?
Histamine intolerance occurs when more histamine accumulates in the body than we are able to break down effectively (54).
This build-up eventually causes symptoms that are very similar to an allergic reaction.
It’s unclear why women are more often affected than men, but one theory is that an imbalance of female sex hormones may cause the body to produce more histamine than it normally should.
So, if the amount of estrogen being produced is higher than the amount of progesterone, more histamine is released.
Histamine Intolerance Symptoms
Symptoms of histamine intolerance can vary depending on the person and the amount of histamine that has accumulated.
- Itching, redness, hives and/or swelling of the lips, tongue, or skin
- Red eyes
- Swollen eyelids
- Atopic eczema
- Sneezing and nasal congestion
- Low blood pressure
- Heart arrhythmia
- Abdominal pain
- Sleep disturbances
- Menstrual irregularity
- Chronic fatigue
These symptoms are very general, so experiencing them is not enough to confirm a diagnosis of histamine intolerance. Further investigation is usually needed.
What Causes Histamine Intolerance?
Histamine intolerance may occur for several reasons:
1. The body has produced too much histamine (due to immune reactions or a condition like mastocytosis, in which the body has too many mast cells that release histamine).
2. Too much histamine is ingested (through food or alcohol).
3. The degradation of histamine is impaired (due to genetics, medications, or other medical conditions).
It is thought that the main cause is the impaired breakdown of histamine due to alterations in DAO activity.
While the exact causes of DAO deficiency are unknown, there may be a genetic component that explains why some people experience insufficient DAO activity.
In this case, the most relevant SNPs are rs10156191 Thr16Met, rs1049742 Ser332Phe, and rs1049793 His645Asp (15).
With genetic testing, it is possible to determine if you have some of these SNPs, but simply having a SNP does not necessarily mean that you will experience histamine intolerance.
People with histamine intolerance tend to have less “good” Bifidobacteria in their intestines, more “bad” Proteobacteria, and less microbial diversity than healthy controls, suggesting that the microbiome may also play a role in the development of histamine intolerance (58).
In a mice model, histamine-producing bacteria in the gut induced an immune response in the lung, suggesting that histamine in the gut can trigger symptoms elsewhere in the body (although human research is needed) (59).
In many cases, it may be possible to reverse histamine intolerance by healing the gut or removing whatever is inhibiting DAO activity (2).
Who Should Follow a Low-Histamine Diet?
A low-histamine diet (also sometimes called a histamine intolerance diet) can be helpful in both the diagnosis and management of histamine intolerance.
Histamine Intolerance Diagnosis
Histamine intolerance should be considered in people who have the signs and symptoms but test negative for allergies and other disorders like celiac disease, gut infections, etc.
The gold standard for diagnosis is a double-blind placebo-controlled oral challenge after a histamine-free diet. This requires following a very strict low-histamine diet for 4 weeks and then reintroducing a few high histamine foods to see if symptoms develop (2).
Other than the oral challenge, there are no reliable tests to diagnose histamine intolerance.
One study found that a histamine skin prick test that measures the rate of reaction resolution showed 79% sensitivity and 81% specificity in diagnosing histamine intolerance, but this test is still considered experimental and is not commonly used (19).
No test is perfect, so trying a low-histamine diet is often the simplest and most effective option!
Reducing Histamine Intolerance Symptoms
One of the most effective ways to manage histamine intolerance symptoms is to follow a low histamine diet.
Foods to Avoid
On a low-histamine diet, it is important to avoid foods that contain high amounts of histamine.
The longer food has been aged, the more amino acids have been converted to histamine. So, fermented foods have the highest levels (2).
Keep in mind that histamine levels in food can vary significantly depending on aging, storage time, and how it is processed (20).
In general, aged and fermented items are much higher in histamine than fresh foods.
In severe cases, it may also be helpful to try cutting back on histamine-releasing and DAO-blocking foods (see below).
High Histamine Foods List
Foods that are generally high in histamine include:
- Aged cheeses
- Alcohol of any kind (red wine tends to have ~3x more histamine than white wine, and wine on tap is higher in histamine than bottled wine) (62)
- Avocado (63)
- Dried fruits
- Eggplant (63)
- Fermented/aged meats (salami, sausages, pepperoni, lunch meat, hot dogs, canned meats/fish)
- Fermented beverages (kombucha)
- Fermented dairy (yogurt, kefir, sour cream, buttermilk, cottage & ricotta cheese)
- Fermented vegetables (kimchi, sauerkraut, pickles, miso, natto)
- Fish and seafood, especially if leftover, smoked, salted, or canned (levels can vary widely) (64)
- Soy sauce, tamari, coconut aminos, liquid aminos
- Spinach (boiling causes histamine to leach into the water, reducing histamine content by 83%) (63)
- Spoiled food/old leftovers
- Tea (black/green/white)
- Yeast products
*Note that measured histamine levels can vary widely from study to study, even for the same foods. This can make it very difficult to pinpoint which foods might be problematic.
Following a structured elimination diet under the care of a registered dietitian or other nutrition professional who is knowledgeable about adverse food reactions can help immensely.
Some foods are also thought to be “histamine releasers.”
Currently, there is not enough scientific support for histamine-releasing foods, so more research is needed before limiting these foods can be recommended routinely (26).
Foods that may be histamine releasers include:
- Citrus fruits (lemon, lime, grapefruit)
- Egg whites
- Some spices
There are other foods that are called “DAO blockers” because they inhibit the activity of DAO.
- Alcohol (7)
Since alcohol is both high in histamine AND slows its breakdown, it should definitely be avoided by people with histamine intolerance.
Foods to Enjoy
Generally, fresh foods have the lowest amounts of histamine.
Low Histamine Foods List
Some low-histamine foods to try include:
- Fruits: apples, apricots, blackberries, blueberries, cherries, coconut, melons, peaches, plums, pomegranate, and raspberries, among others.
- Vegetables: arugula, 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, and zucchini, among others.
- Grains: gluten-free options like amaranth, corn, millet, quinoa, rice, teff are less likely to exacerbate an irritated gut than gluten-containing grains.
- Fresh herbs
- Olive oil
- Fresh animal proteins: chicken, beef, lamb, goat
Please note that just because a food is low in histamine does not mean that it will be tolerated well by your body.
Other types of adverse food reactions like allergies, sensitivities, and intolerances are always possible. Listen to your body first!
Food Purchasing and Preparation Tips
Since histamine forms as food ages and ferments, there are some tips for keeping food fresh and reducing the amount of histamine produced.
1. Purchase Fresh Proteins
When purchasing animal-based proteins, the fresher the better. Check the “packaged on” date when shopping for meat, and choose the freshest.
Also look for meat that has been butchered and frozen quickly. Check with local meat suppliers for the best options.
Additionally, whole cuts may be better than ground meats, since the grinding process spreads bacteria throughout the meat, increasing their ability to create histamine.
If buying fish, look for the “frozen-at-sea” (FAS) label.
When shopping, select your animal proteins at the end of your grocery shopping trip and keep in a cooler on your way home.
2. Try Freezing
Freezing food prevents or slows down the development of histamine (27).
Buying fresh meat or other foods and freezing in individual portions allows for quick thawing and minimal histamine accumulation.
Of course, this doesn’t work for ALL foods, because some are not freezer-friendly.
3. Experiment With Different Cooking Methods
There’s also some evidence that the histamine levels in a food can change based on how it is cooked.
Frying and grilling tend to increase histamine levels, while boiling can maintain or decrease levels, but the difference is relatively small (28).
Other strategies include cooking with a pressure cooker, using quick thaw methods for frozen foods, freezing individual meals, and avoiding slow-cooked foods.
More Lifestyle Tips
While limiting histamine-containing foods is the most effective way to find relief from symptoms of histamine intolerance, low-histamine diets are definitely not easy to follow, and total avoidance of histamine is impossible.
To help reduce symptoms even further, some items can help support the degradation of histamine and reduce histamine in the body:
Antihistamines are sometimes used by those with histamine intolerance to block the action of histamine and quell symptoms.
However, antihistamines just mask symptoms and do not address the root cause.
They may provide temporary symptom relief, but it is expensive to routinely take antihistamines and they can cause side effects like excessive drowsiness.
Additionally, antihistamines do nothing to boost DAO activity, which is typically at the root of histamine intolerance.
2. Oral DAO
Another option is to take DAO enzymes orally.
These enzymes will enter the gut and help degrade histamine in food, much like the DAO naturally produced in your gut would.
DAO can be helpful for breaking down histamine from food, reducing the amount of histamine that gets absorbed.
It was previously believed that DAO taken orally would not be absorbed into the bloodstream, but a 2019 study found a small increase in serum DAO levels after taking it by mouth (64).
There has not been a lot of research on the effectiveness of DAO, but a few studies have shown beneficial effects.
One small (non-blinded, non-controlled) pilot study found that taking 0.3mg DAO before each meal, up to 3 times per day, for 4 weeks significantly reduced all symptoms of histamine intolerance, and those symptoms rebounded when the supplement was discontinued (65).
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3. Support Histamine Breakdown
There is also some evidence that vitamin B6, vitamin C, and copper increase the activity of DAO and aid in the breakdown of histamine; however, no randomized controlled studies have been conducted to confirm this (31, 32, 33, 34, 35).
Another study found that vitamin C administered by IV significantly decreased serum histamine concentrations in patients with allergies (32). The theory behind this is that vitamin C is actually able to degrade histamine (37).
The effect of copper on histamine has only been studied in vitro (in test tubes); researchers found that a copper solution inhibited the release of histamine from mast cells in a dose-dependent relationship (35).
Try consuming foods rich in vitamin B6, vitamin C, and copper and consider working with a dietitian if you have been diagnosed with a deficiency in one of these nutrients.
4. Histamine Degrading Probiotics
Optimizing gut bacteria is vital for overall health and disease prevention (37, 38). Unfortunately, that’s not easy to do for those with histamine intolerance because probiotic foods (yogurt, kefir, kombucha, etc.) are high in histamine and should be avoided.
Another option is to take oral probiotics, but it’s important to choose probiotics that do not contain histamine-producing.
The following strains may be helpful because they have been found to break down or reduce the formation of histamine:
- Lactobacillus plantarum (39)
- Lactobacillus rhamnosus (40, 41)
- Bifidobacterium infantis (42)
- Bifidobacterium lactis (43)
- Bifidobacterium longum (42)
These strains should probably be avoided because they produce histamine in the GI tract:
- Lactobacillus brevis (44)
- Lactobacillus casei (45, 46)
- Lactobacillus delbrueckii (45)
- Lactobacillus fermentum (47)
- Lactobacillus helveticus (47)
- Lactobacillus hilgardii (44)
- Lactobacillus lactis (47)
- Enterococcus faecium (47)
- Streptococcus thermophilus (48, 49)
These lists are not comprehensive, because this is still a new area of research, but they can be used to guide decisions about which probiotics to purchase.
Most people with histamine intolerance find relief after just a few days of following a low-histamine diet (7).
A generalized low-histamine diet should not be followed long-term, because it may be over-restrictive, increase the risk of malnutrition, and take some of the pleasure out of eating.
Instead, it is better to use the diet as a tool to determine an individual’s histamine tolerance, and craft a customized diet from there (50).
Start by following a low-histamine diet for 2 weeks, and then slowly reintroduce higher histamine foods while documenting symptoms. A tolerance threshold can be determined, which will help guide long-term dietary changes.
Additional measures can also be considered to help manage symptoms but should be done under the guidance of a physician or other healthcare professional familiar with your unique health history.
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Amy is a registered dietitian nutritionist and certified LEAP therapist. She received her Masters in Nutrition Diagnostics from Cox College and her Bachelors in Dietetics from Missouri State University. Her passion is finding ways to communicate nutrition research in an interesting and easy-to-understand way.