Histamine Intolerance: Understanding the Science

histamine intolerance
In this post we take an in-depth look at the science behind the food sensitivity reactions caused by histamine. We’ll explore:

  • the fascinating world of biogenic amines
  • how histamine forms inside and outside of our bodies
  • how histamine affects our physical and mental health
  • why some people, especially women, are more sensitive to histamine than others
  • and why reactions to high-histamine foods can be so unpredictable and confusing

If you’d like to skip ahead, choose a heading from the menu below:

To read about the practical aspects of Histamine Intolerance, such as diagnosis, prevention, treatment, food choices, food handling/storage, and medications to avoid, please see my companion post: Freshness Counts: Histamine Intolerance.

The Alchemy of Biogenic Amines

Histamine belongs to an important class of molecules called biogenic amines—potent signaling molecules made from amino acids (amino acids are the building blocks of all proteins—see my protein page for more information). HistAMINE, for example, is made from the amino acid HistIDINE.

Biogenic amines are used by all kinds of plants and animals to regulate important bodily functions. Cells capable of making biogenic amines generate and release them in very tiny quantities to attach to specific receptors on nearby target cells, triggering unique responses within those cells. As soon as their message is delivered, biogenic amines are destroyed by neutralizing enzymes to keep their influence under control.

In order to turn a garden variety amino acid into a powerful biogenic amine, all you have to do is remove its “carboxyl group.” This unceremonious amputation requires special enzymes called decarboxylases (fancy word for “enzymes that chop off carboxyl groups”).

Decarboxylase enzyme transforms amino acid into a biogenic amine

The decarboxylase enzyme transforms your garden variety amino acid into a powerful biogenic amine by removing its carboxyl group.

That’s all well and good, but biogenic amines like histamine aren’t just created by special cells within our bodies to do good deeds. Many species of bacteria and yeast also contain decarboxylases, and they enjoy using them to make biogenic amines out of the proteins in foods we like to eat. Meats, fish, poultry, and dairy products are rich in protein, so they are chock full of amino acids. Whenever a high-protein food like meat, poultry, or fish is not immediately consumed or frozen, microorganisms in the environment get straight to work munching on it, fermenting it, breaking down its proteins into ever-smaller, stranger, and often smellier compounds, including biogenic amines. In living organisms, biogenic amines are destroyed by neutralizing enzymes almost immediately after they are created. Unlike in living tissues, biogenic amines produced during meat fermentation are not destroyed—so they accumulate. This is why the older a food is, the higher its biogenic amine level becomes.

Some biogenic amines have strong unpleasant odors, which can be useful in figuring out whether a food has gone bad, but histamine itself has no flavor and is odorless, so you can’t use the “smell test” to detect its presence.

To make matters worse, we silly humans actually go out of our way to ferment foods on purpose. We add bacteria to milk to make cheese and yogurt. We add yeast to grapes to make wine. We add bacteria to meat to make salami. In the process, foods like milk, grapes, and meat—which in their fresh forms are virtually histamine-free—can become very high in histamine and other biogenic amines.

So, histamine can come from inside our bodies or from outside our bodies—from the foods we eat. They can also come from bacteria in our gut as they ferment the foods we digest.

Here is a list of the most common biogenic amines and the amino acids they are made from. Those in bold are the major players in food sensitivities. You’ll notice that a couple of them have ghastly names, worthy of a Vincent Price voiceover: putrescine and the perfectly ghoulish cadaverine—mwaaah ah ah…

Amino AcidBiogenic Amine
ArginineAgmatine, Putrescine , Spermine,Spermidine
HistidineHistamine
LysineCadaverine
OrnithinePutrescine , Spermine, Spermidine
PhenylalaninePhenylethylamine
TryptophanTryptamine, Serotonin
TyrosineTyramine

Say Hello to Histamine

Histamine is an important messaging molecule responsible for a staggering number of biological effects in our bodies, helping to regulate bodily functions as diverse as digestion, sleep, sexual function, blood pressure, and brain function. How does this one molecule do so many different things? The secret to histamine’s versatility is that it can cause a variety of different responses in neighboring cells, depending on what kinds of cells are nearby, and which receptors are on their surfaces.

Only certain cells in our bodies are capable of making histamine:­1)Kovacova-Hanuskova 2015 Allergol Immunopathol (Madr) 43(5):498-506

  • Immune system: Mast Cells and Basophils
  • Digestive system: Gastric Enterochromaffin Cells and certain Gut Bacteria
  • Nervous system: Histaminergic Neurons (in the brain and body)

Histamine can bind to four different kinds of receptors, and each receptor responds in its own special way to histamine.2)Seifert 2013 Trends Pharmacol Sci 34(1)

Histidine to Histamine to Four Receptors

The histidine decarboxylase enzyme (HDC) transforms histIDINE into histAMINE. The histamine molecule then binds to one of four different receptor types—H1, H2, H3, and H4—located in different places and performing different functions throughout the body. (Illustration by Suzi Smith)

By mixing and matching cell locations, receptors, and target cells, tiny histamine can accomplish a wide variety of tasks.3)Maintz 2007 Am J Clin Nutr 85:1185–96

For example, when histamine binds to special cells in the stomach called parietal cells, stomach acid is produced. When histamine binds to receptors on the surface of large blood vessel cells, arteries dilate, lowering blood pressure. When it binds to smaller vessels called capillaries, they become leaky and fluids ooze out of them, which can lead to runny nose, watery eyes, and puffy skin/fluid retention.

Histamine receptors and effects diagram

Tiny histamine is responsible for a staggering number of biological effects, which vary based on receptor, cell location, and target cell. (Diagram adapted from Maintz 2007 Am J Clin Nutr 85:1185–96)

Histamine’s Destiny

Histamine is promiscuous, lives fast and dies young. As soon as it delivers its special chemical message to its target cell it is instantly destroyed to keep it from running amok. No respect–but that’s what it gets for being the cad that it is.

If we eat something with histamine in it, say an aged steak or a piece of ripened cheese, we have special enzymes in our gut ready to destroy the histamine in that food before it can be absorbed into the bloodstream.

The cells lining the small intestine and the upper stretch of the colon (ascending colon) are constantly releasing a histamine-busting enzyme called Diamine Oxidase (DAO) into the gastrointestinal tract, creating the first line of defense against excessive histamine exposure from foods and beverages.

Any histamine that makes it past DAO will have to contend with another histamine-destroying enzyme, histamine-N-methyltransferase (HNMT), which is located inside of the cells lining the gut.

degradation of histamine in the gut by DAO and HNMT

Most of the histamine that we consume is neutralized by DAO released into the gastrointestinal tract or HNMT located in the cells that line the gut. These enzymes prevent excess histamine from entering the bloodstream. [Illustration by Suzi Smith; Adapted from Kovacova-Hanuskova 2015 Allergol Immunopathol (Madr) 43(5):498-506]

Most cases of Histamine Intolerance are thought to be due to inadequate levels or activity of these enzymes, most importantly DAO.4)Kovacova-Hanuskova 2015 Allergol Immunopathol (Madr) 43(5):498-506 5)Grandy 2007 Pharmacol Ther 116(3): 355–390 If enzymes are deficient, histamine can cross into the bloodstream and cruise around the body willy-nilly, having its way with our cells.

Histamine Reactions

Under normal circumstances, tiny amounts of histamine are quietly, safely conducting the daily business of the body. But there are plenty of scenarios that can lead to excessive, abnormal histamine exposure.

The Dose Makes the Poison

As with any toxin, “the dose makes the poison.” Healthy individuals are supposed to be able to handle foods that contain about 50 to 100 mg/kg of histamine,6)Byun and Mah 2012. Journal of Food Science 77(12) but people with Histamine Intolerance generally react to much lower levels. The kinds of reactions we have to histamine depend primarily on how much histamine we are exposed to and which area of the body is affected. Reactions fall into five general categories; the first four scenarios can happen to anyone:

  1. Anaphylaxis—massive internal release of histamine into the bloodstream by an allergic trigger
  2. “Scombroid Poisoning”—food poisoning caused by eating spoiled fish (typically containing >500 mg/kg histamine)
  3. Localized allergic reactions (sinus congestion, hives, etc.)
  4. Histamine overload—eating too much histamine at once and overwhelming healthy defenses (typically >50 mg/kg)
  5. Histamine Intolerance—uncomfortable symptoms with exposure to histamine even at low doses (<50 mg/kg). This only happens to sensitive individuals.

Anaphylaxis

If you are allergic to peanuts and you sink your chompers into a peanut butter cup, your immune cells will throw a fit and flood your bloodstream with histamine, wreaking all kinds of havoc—from hives to low blood pressure to difficulty breathing. This is histamine in crisis mode. Histamine isn’t supposed to be coursing recklessly through your bloodstream in large quantities, and it can be deadly.

Scombroid Poisoning

fish-scombroid poisoning

Most of us have at some point in our lives gotten sick with food poisoning after eating bad seafood. “Scombroid Poisoning” is an extreme reaction to spoiled fish that is very high in histamine, typically greater than 500 mg/kg:7)Hungerford 2010 Toxicon 56:231–243

“The onset of Scombroid poisoning is typically from 10 min to 1 h following consumption of poisonous fish. The symptoms are variable and include peppery or metallic taste, oral numbness, headache, dizziness, palpitations, rapid and weak pulse (low blood pressure), difficulty in swallowing, and thirst. Noteworthy as allergy-like are symptoms such as hives, rash, flushing and facial swelling. Symptoms involving the central nervous system (CNS) such as anxiety are less frequently observed. Less specific symptoms such as nausea, vomiting, abdominal cramps and diarrhea are also experienced. Recovery is usually complete within 24 hours.” [Hungerford 2010]8)Hungerford 2010 Toxicon 56:231–243

However, the relationship between histamine levels and degree of toxicity is not straightforward; it seems that two other biogenic amines may also play a role in these severe reactions: putrescine and cadaverine. [It figures…leave it to Smelly and Spooky.] Both of these ghastly biogenic amines interfere with DAO activity, and therefore make it easier for histamine to get into our bloodstream.

Certain species of fish are more likely to be associated with scombroid poisoning, and the majority of them are dark-fleshed fish which are especially rich in the parent amino acid histidine:9)Hungerford 2010 Toxicon 56:231–243

AmberjackMackerelTuna
AnchoviesMahi MahiSalmon*
BluefishMarlinSwordfish*
Cape YellowtailPilchards
HerringSardines

[*Salmon and Swordfish are also commonly associated with Scombroid poisoning despite not having particularly high levels of histidine in their tissues.]

Localized Allergic Reactions

In humans, histamine is best known for its role in the body’s allergic response. If you are allergic to pollen, and you go romping through a field of flowers, the cells lining your sinuses will overreact and release too much histamine, causing watery eyes, sneezing, and so forth. Or if your skin is exposed to an irritating product you may develop hives. Many people with allergies take an antihistamine medication to block the effects of excess histamine.

Histamine Overload

Most healthy individuals can tolerate a total of about 50 to 100 mg/kg of histamine in foods per sitting,10)Byun and Mah 2012. Journal of Food Science 77(12) but consuming more than that can cause symptoms even in people with healthy histamine defenses. Our natural capacity to neutralize histamine varies widely, so some people can get away with lots of high-histamine foods while others are more sensitive.

Histamine Intolerance

“The term ‘histamine intolerance’ was introduced as common denominator for symptoms such as abdominal pain, flatulence, diarrhoea, headache, pruritus (itching), blepharedemas (puffy eyes), urticaria (hives), rhinorrhea (runny nose), dysmenorrhea (menstrual cycle problems), respiratory obstruction (difficulty breathing), tachycardia (racing heart), extrasystoles (palpitations) and hypotension (low blood pressure) occurring after the consumption of histamine-rich foods.” [Komericki 2010]11)Komericki 2011 Wien Klin Wochenschr 123: 15–20

Histamine Intolerance affects at least 1% of the population, and 80% of those affected are (ahem)…middle-aged.12)Maintz 2007 Am J Clin Nutr 85:1185–96

What Causes Histamine Intolerance?

Most cases of Histamine Intolerance are thought to be due to abnormally low levels/activity of diamine oxidase (DAO), an enzyme that destroys histamine.

histamine block

A DAO supplement can be effective in limiting the effects of histamine in food when taken 15 minutes before eating.

DAO is located only in certain organs in the body: the small intestine, ascending colon, kidney, liver and placenta. Therefore, anything that causes temporary or permanent damage to any of these organs could potentially affect DAO function, particularly damage to the intestines, because that is where DAO is most active (in non-pregnant individuals). Examples include chemotherapy, Crohn’s Disease, Celiac Disease, kidney disease, liver failure, or surgery. Genetic abnormalities in DAO also play a role in certain cases of Histamine Intolerance.13)Kovacova-Hanuskova 2015 Allergol Immunopathol (Madr) 43(5):498-506

DAO requires vitamin B6, vitamin C, copper, and zinc in order to function properly, so if you are deficient in any of these, you may experience Histamine Intolerance.

HNMT, by contrast, is found in almost all organs in the body, including in the brain and red blood cells. Problems with HNMT function are not thought to play a significant role in most cases of Histamine Intolerance.

SIBO (small intestine bacterial overgrowth) can lead to high levels of histamine in the gut, overwhelming our enzymes.

HER-stamine?

HER-stamine? Histamine Intolerance is more common in women

About 80% of people with Histamine Intolerance are women.14)Maintz 2007 Am J Clin Nutr 85:1185–96 This may be because estrogen and histamine reinforce each other, meaning that estrogen increases histamine levels and vice versa. Since women have higher levels of estrogen than men, they also naturally have higher levels of histamine than men. It stands to reason then that it would take smaller amounts of high-histamine foods to overwhelm histamine-destroying enzymes.

Histamine is known to increase estrogen production. This is very important to think about, because eating different amounts of histamine from day to day can put women on a hormonal roller coaster of fluctuating estrogen levels.

Women may be more sensitive to histamine in foods during the points in their cycles when estrogen levels are higher (ovulation and pre-menstrual phase) or if they are taking estrogen supplements. Histamine triggers nitric oxide release in the arteries surrounding the brain, which can lead to migraine headaches. “Menstrual migraines” may be due to the fact that estrogen levels peak during the pre-menstrual phase, stimulating a rise in histamine.

Women have a higher number of H1 receptors in their brains than men do, which means that women’s brains are naturally more sensitive to histamine (see mental health section below). 15)Yoshizawa 2009 Biol Psychiatry Feb 15;65(4):329-35

One of the many natural roles of histamine in the body is to stimulate contraction of the uterus. This explains why Histamine Intolerance can cause or worsen pre-menstrual cramps.16)Maintz 2007 Am J Clin Nutr 85:1185–96

Especially fascinating is that pregnant women typically experience relief from allergies and Histamine Intolerance during pregnancy because the placenta produces up to 500 times the normal amount of DAO, the enzyme that destroys histamine, in order to protect the fetus from histamine toxicity.

Histamine and Mental Health

Histamine doesn't cross the blood-brain barrier

Although histamine molecules are found in both the body and the brain, they do not cross the blood-brain barrier. However, Histamine Intolerance may still create mental health symptoms.

Histamine acts as an important neurotransmitter in the brain, where it helps to regulate the stress response, alertness, sexual function, sleep-wake cycles, attention, learning, and memory.

While I am not aware of any scientific findings specifically proving a formal connection between Histamine Intolerance and mood disorders, people with Histamine Intolerance commonly experience symptoms such as panic, insomnia, anxiety, and fatigue. It is intriguing to think about, because histamine is not thought to cross the blood-brain-barrier.17)Haas 2008 Physiol Rev 88(3):1183-1241 Therefore, if you eat a high-histamine diet, and some of that histamine makes it into your bloodstream, it shouldn’t be able to enter your brain. How then do we understand the psychological symptoms associated with Histamine Intolerance?

One possible explanation is that the majority of the anxiety symptoms people with Histamine Intolerance notice are not generated in the brain, but rather in the body, via histamine’s ability to raise levels in the bloodstream of other important signaling molecules, most importantly adrenaline.

Adrenaline is the body’s “fight-or-flight” hormone. It does not cross the blood-brain barrier, but in the body, it can trigger panic symptoms such as racing/pounding heart, anxiety, nausea, sweating, insomnia, shortness of breath, shaking, etc.

Another interesting possibility: histamine raises estrogen levels in the body, and estrogen DOES cross the blood-brain barrier. As any woman knows, estrogen can have powerful effects on mood—sometimes positive, sometimes negative (the relationship between estrogen and mood is very complicated). Once inside the brain, estrogen stimulates histamine release, so this could be one way that a high-histamine diet in sensitive people might affect energy and concentration levels.

If you have anxiety or sleep problems and want to understand how your diet may be causing your symptoms, I recommend reading my Psychology Today article 5 Foods Proven to Cause Anxiety and Insomnia.

What About the Other Biogenic Amines?

In foods, histamine is never alone. It is always accompanied by significant amounts of other biogenic amines. This makes symptoms and diagnosis of Histamine Intolerance complicated and sometimes rather unpredictable.

Putrescine and cadaverine in foods can cause trouble by interfering with DAO activity, making it harder for us to detoxify histamine in our gut. This can raise the level of histamine we are exposed to. The higher the levels of putrescine and cadaverine in a food, the higher the effective level of histamine.18)Ruiz-Capillas 2004 Critical Reviews in Food Science and Nutrition 44:489–499

Tyramine is broken down not by Diamine Oxidase (DAO) but by a different enzyme called Monoamine Oxidase (MAO). Tyramine is therefore notorious for causing problems in people taking old-fashioned antidepressants called “MAO-inhibitors” like Nardil and Parnate, which block tyramine destruction. If tyramine accumulates, severe headaches and dangerously high blood pressure can occur.

True tyramine intolerance, unlike Histamine Intolerance, doesn’t seem to be a concern except in people taking MAO-inhibitor medications or in rare cases of genetic MAO deficiency. But here’s the rub: putrescine and cadaverine both interfere with MAO activity and therefore behave as mild MAO-inhibitors! Smelly and Spooky strike again…you just can’t trust those two…this is why aged foods can trigger migraines and high blood pressure even if you don’t have Histamine Intolerance.

It’s Not Just About Histamine… Other Factors

It is no easy task figuring out whether or not you have Histamine Intolerance. In addition to the fact that other biogenic amines can influence how a particular food affects you, there are MANY other variables that determine how you will feel when you eat a high-histamine food:

It’s impossible to know how much histamine is in a given food, and the same food will contain different amounts of histamine under different circumstances:

  • Some medications interfere with DAO activity, including NSAIDS such as Ibuprofen19)Maintz 2007 Am J Clin Nutr 85:1185–96 20)Kovacova-Hanuskova 2015 Allergol Immunopathol (Madr) 43(5):498-506
  • Estrogen levels stimulate histamine production21)Maintz 2007 Am J Clin Nutr 85:1185–96
  • Stress and physical injury trigger immune cells to release histamine and other pro-inflammatory substances22)Kovacova-Hanuskova 2015 Allergol Immunopathol (Madr) 43(5):498-506
  • Alcohol interferes with DAO activity23)Wackes 2006 Inflamm Res 55(Suppl 1):S67-S68
  • Low-histamine “trigger foods” directly stimulate mast cells to release histamine24)Vlieg-Boerstra 2005 The Netherlands Journal of Medicine 63(7):244-249
  • There is a handful of low-protein, low-histamine plant foods naturally rich in the amino acid histidine (which turns into histamine under the right conditions)25)Maintz 2007 Am J Clin Nutr 85:1185–96
  • Some species of gut bacteria contain histidine decarboxylase and therefore can generate histamine from proteins in the foods we eat. This is more likely to occur with foods that are difficult for us to completely digest on our own, because such foods travel further down in our digestive system into the colon, where bacteria live. This is just one reason why it makes sense to minimize “fermentable” foods such as legumes and foods high in proteins such as gluten and casein, which humans don’t possess the capacity to break down.

People with Histamine Intolerance can even experience high blood pressure or low blood pressure, depending on the circumstances! Histamine itself lowers blood pressure in most cases. However, histamine also triggers the release of other substances in the body that affect blood pressure, most importantly adrenaline, which raises blood pressure.

It’s complicated.

People with Histamine Sensitivity and their doctors can easily become very confused. The same food can cause different symptoms, or no symptoms, from one day to the next, depending on the circumstances. It is not simply about how much histamine is in a food. Which other biogenic amines were in that food? Did you drink alcohol that day? Did you take an NSAID like Aleve or another medicine that can raise histamine levels? What else did you eat that day? Did you eat any histamine triggering foods? How stressed were you? If you are a woman, where were you in your monthly cycle?

I see you throwing your hands up in the air. How are you supposed to know whether you have Histamine Intolerance or not? If you suspect you have Histamine Intolerance, what should you do? Fear not, help is on the way!

Please see my companion post all about the practical aspects of Histamine Intolerance—diagnostic tests, food choices, food storage/handling, and medications to avoid: Freshness Counts: Histamine Intolerance.

You can also listen to my new podcast interview with Yasmina Ykelenstam, the Low Histamine Chef, about the connection between Histamine Intolerance and mental health.

Update: Recommended Resource

I have received numerous inquiries from people wanting to learn more about Histamine Intolerance. One resource that I found particularly helpful was a textbook entitled: Histamine Intolerance: Histamine and Seasickness by Reinhart Jarisch. Since it is a textbook, it is written in an academic voice and is expensive (although available to rent on Kindle), but goes into depth about many of the topics discussed in my two-part histamine series and includes many helpful food tables.

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  • tessmck

    Thank you, Dr. Ede — that was an excellent short treatment of a very complex subject. Also a reminder to me, that feeling poorly “out of the blue” is SO OFTEN a histamine issue!

    • Thank you, tessmck! And yes, it is often true for me too!

  • Dr. J

    Excellent review of a complex topic. Unfortunately, most MD’s are not up to date on the latest advances in knowledge about histamine intolerance or MCAS. It is nice to see a “member of the guild” talking about these things, to help establish the credibility of these debilitating conditions that have been considered psychosomatic for too long. Thank you!

    • Thank you Dr. J! Rule number one of doctoring: BELIEVE YOUR PATIENTS:)

  • KrisTea

    So many pieces of the puzzle has fallen into place before my eyes. Thank you. Seeing the science behind the symptoms is what I love to see the most. I’ll be anticipating even more articles like this one, even more detailed would be fine.

    • Dear KrisTea (that’s a fun name by the way)

      Hooray for puzzle solving! l love the details too–can never have too many details!

  • Ali Bamford

    So, can we have an article on the elements that are natural antihistamines and how to increase the DAO or MAO producing bacteria/heal the gut…..?

  • Rainey

    I believe I have histamine intolerance, as I can’t touch anything that’s high histamine but my problem is worse …I can’t seem to digest any cooked food whatsoever. Is cooked food higher in histamine? I am also very limited to just a few raw foods ..I do raw eggs very well, but can’t touch cooked. I have to eat my meat raw ..but it’s 100% grass fed and organic so it’ safe — I’ve had no problems eating it since 2009, but the only other foods I can eat is raw celery juice, bananas, raw honey, and avocados. For awhile I was able to tolerate berries, apples, onions and cheese …then I added in some pasteurized grass fed butter because I couldn’t afford it raw, and it’s like my whole system has reverted to back when I was at my sickest ..can’t digest anything now except the few things I listed. When I eat the foods I shouldn’t, I start going in shock, and have to do rapid and deep breathing to prevent going out …this is usually followed by a three day long excruciating headache which sometimes switches to the other side for another three days following one day of no headache. This went on for years until I found out I could get rid of the headaches and trashed digestion and shock by eating the few raw foods I mentioned …but I am GETTING SICK OF THIS DIET …I can’t eat anything that has any flavor without getting sick. I must have vitamin and mineral ..especially mineral deficiencies because of my cravings. For a short while last summer I was able to get raw grass fed goat milk and that seemed to work wonders …then I wasn’t able to get it anymore …I looked into the GAPS diet, but with all the fermented stuff and bone broth, I’d go in shock and die the first day. But on these few raw foods, for the first time in my life, my digestion is perfectly normal …no more consitpation alternating with diarrhea …that is until the butter. I imagine it will take some time to get things balanced back out ..but what can I do? This condition has disabled me as I am so histamine sensitive that I seem to be allergic to my own stress hormones …I can’t tolerate stress ..or at least not for long. On top of this, I am autistic. But I live on $1120 per month and can’t afford to see a doctor …or pay for health insurance. Obamacare didn’t help a bit. I can’t afford medicare …of course I could if I lived on the junk food diet one is expected to live on with this amount of money, but I would literally die if I tried it. Grass fed raw meat is expensive, and so is all the organic celery …commercial makes me sick. The eggs also have to organic, or I get sick. The honey must be completely unheated …I use Really Raw brand which is very expensive. I have completely run into a wall and have no idea what to do.

    • Esmée La Fleur

      You are not the only one, but the ONLY FOOD I can eat is fresh raw beef.

      • Rainey

        Wow! How did you figure it out? I was searching online and found out about Aajonus Vonderplanitz’s book, We Want To LIve.

    • Dear Rainey

      What an ordeal! I’m glad Esmee responded herself because I was just going to recommend her excellent site to you. Whenever anyone writes to me about extreme food sensitivities, the first thing I suggest is trying an all-meat diet for at least a few weeks. From everything I’ve learned about food, this diet is the least likely to irritate the human body. From there you can try adding one food back at a time, but there is no need to add anything else back, and it is likely that you will feel even better without the honey and so forth. It’s not the most exciting diet in the world but without carbohydrates, most people lose their cravings for other foods.

      • Rainey

        Hi Dr. Ede,

        I have tried cutting out carbs but I start feeling really acidic and toxic when I do. Every morning I drink a smoothie with banana, avocado, raw egg, and raw honey ..which always seems to balance me back out and soothes my digestive system. Should I just allow the acidity? I really crave those smoothies too. When I get one of those headaches, it helps get rid of the pain much faster ..the pain is too intense on just meat ..but then I have never allowed myself to go just on meat for more than a day, so maybe I should try it? I swear I would give my left arm to be able to eat normal food again. I hate this.

      • Esmée La Fleur

        Rainey – It might help you to know there is a 1-2 month adaptation phase that takes place when a person transitions to an all-meat diet. You can feel pretty lousy during this time, especially if you eat a lot of sugar like honey before beginning. This is because you body has to upregulate enzymes designed to burn fat for energy, rather than carbs for energy and this upregulation does not happen overnight. It is also very important to make sure you are eating enough fat. Everyone’s capacity for fat is a little different, but it is usually between 65-85% of total calories. I personally feel best at about 70-75% fat by calories. If you do not get enough fat, you will eat too much protein and this will definitely make you acidic and you will feel bad. So, the key is to find the right balance. This takes a little time and experimentation. The best cuts of meat are fatty ribeye, New York strip, and chuck roast. But not all steaks have enough fat on them because our butchers today tend to cut off the extra. You have to actively seek out and request fatty meat. There are a lot of great articles and testimonials on my website where you can learn more about this, and you can join us in our Facebook Group Principia Carnivora where you can ask questions and we will try to help you. As far as why so many of us seem to be having trouble with salicylates and histamines, this is my theory: just as everyone has a different capacity for carbs (some can handle very few, while others can handle a lot) before getting diabetes, I believe that the same thing applies to salicylates and histamines. I was a vegan who ate only plant foods and lots of fermented foods for about 15 years, and I think I simply burned out my capacity to metabolize salicylates and histamines. I hope this helps.

        • Rainey

          Yes Esmee, it does! Thank you. I joined your group …I am Angela R. …I see a bunch of my Primal Diet friends are in there! haha! I am aware of the need for fat, and I think it is the majority of my calories …raw egg, avocado, and the meat I eat is ground grass fed with 15% fat. With every meat meal I eat either egg, avocado or both. My morning smoothie consists of 1 banana (probably one banana too much 🙁 ), 2 avocados and 4 raw eggs, and 1 tablespoon raw honey …so it is a lot of fat, but also a lot of carbs. I have pondered going keto for quite awhile, but didn’t know how to get safely through the transition without pain or hurting my teeth. I have severe bone loss around my teeth, and though my teeth themselves are in good shape ..only a couple cavities my entire life, several are quite loose as a result of the bone loss. But I noticed that when my digestion is working better, my teeth tighten up and feel better. So, I need to get through the transition smoothly. This past summer I found I did really well health and teeth-wise on raw grass fed goat milk, but my supply ran out, and the benefits from drinking it slowly faded away …I highly suspect if I had continued the milk, though, it would have gone the same way as everything else I try to add in …eventually I would have started to get sick …though I’d sure like to know for sure. Anyway, I’ll get in the group, and ask these questions about how to transition more smoothly. Thank you for taking the time Esmee, and Dr. Ede. It was quite a surprise to find someone who even knew what I was talking about re the meat …knowledge is spreading! Finally!! LOL

    • linxall

      Dr. F. Batmanghelidj states water is the only remedy for histamines and that unrefined salt is needed to help the body’s hydration. If your circumstances are histamine related I suggest you learn from him either from reading his books or from watching his YouTube videos.

  • Esmée La Fleur

    Absolutely stellar article! The best I have read so far. Merci Beaucoup ⭐️⭐️⭐️⭐️⭐️

    • Thank you so much, Esmee; that’s high praise coming from you! For those of you are not familiar with Esmee’s work, I highly recommend her wonderful site: http://zerocarbzen.com/

  • Phil C

    Hi Dr Edes, I love this site, it’s helped me so much on my own journey to figuring out what foods bother me and has thus improved a lot of my symptoms. Thankyou 🙂

    I was wondering if you’ll be doing a post on SIBO – many people suffer histamine intolerance because of this which you touched on in this post. It seems that SIBO can be what’s causing fructose malabsorption for many, and inability to eat fibrous vegetables as they feed the SIBO. I wonder if this is a larger part of many peoples issues than they realize.

    Interesting about the MAO connection…I have defective MAO-A genes (homozygous), and so MAO blocking things can affect me badly. It’s amazing how food can interact with our genes and bodily state.

    Please keep up the good work!

    • Hi Phil

      Thank you for your kind words and I’m so glad you’re finding the site helpful! I would love to explore the topic of gut bacteria, as I’m suspicious of some of the popular beliefs circulating lately about the need to feed our gut bacteria high-fiber and pre-biotic foods. I think it would take some work to get to the bottom of it, and I’m working on a few other projects right now for upcoming posts and presentations, but it is definitely on my list! In the meantime, if you haven’t seen my post about fructose malabsorption yet:

      http://www.diagnosisdiet.com/is-fructose-malabsorption-causing-your-ibs/

      Thanks for writing and for your support!

  • patstar5

    So do antihistamines have adverse effects on the body? I read that they could prevent weight loss.

    • Hello, Patstar5

      Great question. YES. As a psychiatrist I prescribe some medicines that block histamine receptors, and these medicines are notorious for causing drowsiness and weight gain as potential side effects.

  • Rainey

    Thanks for sharing. Do you have any idea what is causing this? I am so sick of nothing but cold wet flavorless meat I could scream. I HATE IT, LOL!

  • Lucinda

    Dear Dr. Ede, thank you for this website with great information. In this article you write about how the placenta produces up to 500 times the normal amount of DAO, in order to protect the fetus from histamine toxicity. I read that the placenta gets build in the first 12 weeks of pregnancy, and around 12 weeks it should be finished. Does that mean the body cannot protect the fetus from histamine toxicity in the first months? This worries me since I had bad histamine reactions very early in my pregnancy. Something else I wonder about is, why isn’t there a way for the body to produce more DAO when not pregnant, and having histamine intolerance, when there clearly is a way to produce more DAO when pregnant.

    • Dear Lucinda

      What a great question! In the excellent article linked to below, I discovered that placental DAO levels rise between week 2 and week 12, so levels are at their peak during the second trimester. Apparently the rise occurs earlier in women who have lower DAO levels in general, so your baby may have had more protection than during the average pregnancy in someone without histamine intolerance:

      http://humupd.oxfordjournals.org/content/14/5/485.long

      I don’t know why the body can’t ramp up DAO production in the gut but I’m guessing it has to do with damage to the gut lining that can happen over time to some of us.

      • Lucinda

        Thank you, really interesting!

      • D. Arro

        Hmm is that why morning sickness is so prevalent in the first few weeks? I know last night after a severe bout of histamine food poisoning I was empathizing with 1st trimester moms who get morning sickness. Makes me wonder if women with hyperemesis have issues with histamine and the placenta….

  • Lucinda

    Dear Dr. Ede, one more question: sometimes I take a DAO histamine digester capsule when eating high-histamine foods. I recently noticed that there’s shellac in these capsules. There’s not much information on the impact of shellac on the body, do you know something about this subject? The few information that I read about it wasn’t too positive about it so I’m not sure if it’s safe to take the DAO capsules. I would love to hear your thoughts on this.

    • Another fascinating question! Yes, I see that on my bottle of Histamine Block, shellac is listed as one of the capsule ingredients. Pharmaceutical grade shellac is different from the type of shellac sold in hardware stores. It is a natural plastic-like substance made from insects and is good at resisting stomach acid. I did a quick literature search and found only a few articles referring to cases of contact dermatitis from shellac in cosmetic products. This article finds little evidence of health problems associated with edible shellac with it but my guess is that it hasn’t been rigorously tested:

      http://www.drugs.com/npp/shellac.html

      • Lucinda

        Thank you for replying!

  • Scott Hamilton

    I have been taking L-arginine for some ten years after reading that it aids in the production of nitric oxide which in turn promotes endothelial cell repair/rebuilding.
    I had a heart attack in 2002 so this seemed a prudent thing to do.

    Is this quality of L-arginine more imortant than its contribution to histamine?

    • Dear Scott

      If you find that L-arginine triggers histamine intolerance symptoms for you, I suppose you’d have to weigh the risks and benefits depending on how uncomfortable those symptoms are in comparison to the possible benefits of L-arginine. I haven’t researched L-arginine and endothelial function, so I can’t speak specifically to its benefits. I am sorry to hear about the heart attack but you must be doing something right since that event was almost 15 years ago! What I do know is that, generally speaking, taking care of your blood vessels and heart has a lot to do with the quality of carbohydrates and fats in the diet. If you have not explored the benefits of a low-carb high-fat diet for cardiovascular health, that would be another way to protect your vessels and your whole system from excessive oxidative and inflammatory damage.

  • John

    Hi Doc, I have been reading this with quite a bit of interest. Just found out today by trial I probably have this going on. I had a couple of questions, first is this something that can be cured through an all meat diet? Second is there any evidence that you know of that would make bone broth high in histamines?

    • Hi John

      I don’t know if you can cure it with all-meat, although I suppose it’s possible, depending on what is causing your histamine intolerance. However, it is important to make sure that whatever meat you do eat is very fresh (or was frozen fresh and eaten soon after thawing).

      As for bone broth, the cooking process destroys the enzyme that generates histamine. If you use very fresh (or freshly-frozen) bones, prepare the broth right away, and then freeze or use the broth immediately, it should be fine. However, some people are in the habit of collecting bones over the course of a number of days in the refrigerator, then preparing broth from those older bones. Cooking will not destroy the histamine that was formed while the bones were sitting in the fridge. And some people store their broth in the fridge, where more histamine can form.

  • janmarbol

    I’ve taken DAO supplements and they’ve caused me to have extreme muscle aches, especially in my neck and shoulders. I have many intolerance/sensitivities to food but the DAO supplement caused me so much pain that I stopped taking it. Does anyone know why this can happen?

    • Dear Lisa Simpson,

      I am not sure why you’re having this side effect, but it could be due to an ingredient in the DAO supplement you are taking. When I was researching which supplement I was going to try myself, I came across some brands that seemed to be causing some consumers pain as a side effect. The one I take and that I link to in the post hasn’t caused me any problems, but that’s just me. I wonder if you might try experimenting with a few different brands to see if you can find one that doesn’t bother you. I have a lot of food sensitivities myself, so I believe you!

  • Jodi Owen

    A very interesting and informative article. What are your views on mast cell activation diseases (widening the scope beyond the branch of Histamine Intolerance) and the influence of epigenetics (i.e. over/under methylation)?

    You touched lightly on the connection between histamine and mental health, and mentioned being unaware of any ‘scientific findings specifically proving a formal connection between Histamine Intolerance and mood disorders.’ I’m wondering if you are familiar with the work of Dr. William Walsh at Walsh Research Institute? He’s done some eye-opening research over the years on the connection between histamine, methylation and mood disorders: http://www.corepsych.com/2014/09/overmethylation-depression-walsh/

  • Sally M

    This is a great explanation
    I suffered for years with histamine intolerance even though I was on a low amine low salicylate diet.

    I am on a low histamine diet

    I discovered that preservatives and additives and colours triggered release of my own histamines, especially sulfites. I also discovered that there is a lot of sulfites are not disclosed in labels. Dr Janice Vickerstaff, Canadian immunologist and dietician suggests sulfites may be in most processed food. I cook just about all my own food now, and I am symptom free. I take H1 and H2 blockers when I get a trigger reaction (bloated gut, low blood pressure, high pulse rate 1.5 hours after eating problem food) which works in about 30 mins. I also take vitamin c (2 grams +) daily which has made a big difference, for me.
    Carol Johnston, Arizona State University has many articles on the web about Vitamin C. One of her articles is “The Antihistamine
    Action of Ascorbic Acid published in Subcellular
    Biochemistry, Volume 25: Ascorbic Acid: Biochemistry and Biomedical cell
    biology, edited by J Robin Harris Plenum Press New York 1996
    Vickerstaff says Vitamin C works for some of her patients, but not everyone.

    I have gradually improved and now eat histamine rich food intermittently. I found that intermittent fasting helped. I tried the 5;2 diet for weight loss, 2 days a week only eating about 600 calories. I have kept on the diet because I find I can eat some histamine rich food on the other days . Maybe the fasting give my body a chance to catch up on DAO production.

    • Hi Sally

      Very interesting! Thanks for sharing your experience and your tips with us!

  • Erica

    Hi Dr Ede, Thanks for great website and information. I have been on ZC facebook for awhile now and due to what I believe to be severe histamine intolerance (among many others intolerence like all fruits, sals, ox and I think all grains in general) I have not been able to tolerate beef and lamb. Trust me I have tried all farmers, farmers, methods and freshness under the sun. Seriously nothing short of slaughtering the animal with my bare hands. I get super itchy, shaking from the insides and joint pain, like burning all over. Other meats are not a picnic either but compare to beef/lamb it’s a walk in the park. I read that you don’t tolerate beef well either. how much ounces of chicken, pork, fish are you having in a day then? and is it ok that I cannot find any chicken that is not finished with grains at all in my area. Also have you ever tried the all meat and water diet minus the beef? Thanks so much for the work you do

    • Hi Erica

      I eat a mostly-meat ketogenic diet (I like to call it meatogenic–ha ha), therefore I limit protein to about 60 grams per day. I tolerate lamb fine but I have heard that some people who don’t tolerate beef also have trouble with lamb, unfortunately.

      I personally wouldn’t worry about trying to only consume perfectly pastured poultry or other meats–I just do the best I can finding the best quality meats I can, but we live in an imperfect world where these things aren’t always available or affordable.

      Yes I have definitely tried a zero carb all meat diet before! I’m a big believer in that way of eating, and am a big fan of Esmee LeFleur and Amber O’Hearn’s work, but unfortunately for me, it was too hard to sustain given how much I have to limit protein in order to stay in ketosis. I may try it again in the future, but for now I do include a few plant foods in my diet.

      Thanks for writing!

  • Petra Mikat

    Where can I find reference no. 25 please?