The other day I was reading an article that discussed histamine as it pertains to allergies to pollen, like sneezing and itchy eyes. It made me realize that almost everyone assumes histamine causes allergies and nothing else. This is simply not true. 

Histamine can certainly cause allergies, and it is found in hundreds of foods that you consume daily, but an allergy is different than what I want to share with you today. An allergy causes an almost immediate reaction to the food you just ate, whereas an “intolerance” is a reaction that occurs later. Why later?  Because the blood levels of histamine need to spike for the reaction to take place, you are reacting to histamine, not the food itself.  See the difference? 

High blood histamine levels will cause chronic health conditions, which could be life-long. In contrast a true food “allergy” results in symptoms within a few minutes like lip swelling, itchiness, sneezing, hives, diarrhea and possibly anaphylaxis.

Histamine is associated with many problems so read on, this could be life-changing information for some of you.  In fact, I’ll just tell you right now that eating leftover meats can produce too much histamine and you’d never sneeze from that. The histamine is produced because bacteria act on your leftovers and produce histamine, then you eat it.

A problem with histamine break-down can cause many disorders that you would never connect to histamine (since you associate histamine with sneezing and runny nose). For example, people who are directed to eat fermented foods, common with Hashimoto’s, can experience a worsening of their thyroid condition due to high histamine found in fermented foods and the inability to break it down! I’ll circle back to this later.

Anxiety and irregular menstrual cycles is very common in women with high histamine. It causes blood vessels around your brain to swell, increasing pressure in your head causing migraines and cluster headaches.

If your face turns red when you drink wine, histamine is to blame.

It’s not that you have an “allergy” like you would to pollen, it’s more that you have an intolerance. So use the right word when discussing this with your physician.

Histamine is a naturally-occurring compound that your immune system produces when faced with antigens like pet dander, pollen and other allergens. This is where antihistamines like Claritin and Zyrtec work.  They reduce excessive amounts of histamine which is released like crazy from cells called “mast” cells.  So a person with hyperactive mast cells will dump a lot more histamine than they should. 

I want you to know that histamine is not bad, in fact, it acts as a neurotransmitter. A certain type of histamine helps you make stomach acid, which helps you break down food during digestion. It is this area where Zantac and Pepcid work, they reduce histamine 2.   

Histamine levels can get out of control and it’s ironic that you associate high histamine with your head (all the sneezing, itchy, red eyes, scratchy through, mucus and so forth) the truth is the high histamine can stem from intestinal problems.  It can also stem from your genetic profile (your SNPs) which I’ll cover shortly.

First the gut problems.

Gut problem termed SIBO (small intestinal bacterial overgrowth) can lead to elevations in histamine as well as serum cobalamin. The colonization of germs in your small intestine will increase histamine levels and therefore symptoms. So will an ulcer (it’s due to GI bleeding). High histamine may also be the result of a very permeable intestinal wall (leaky gut as we affectionately call it).  Eating histamine-rich foods can also jack up levels rather quickly.

That expensive bottle of 1998 vintage Petrus Pomerol is not worth the $1500 a bottle if you have an activated DAO SNP! Main point, having the SNP in your gene pathway doesn’t mean you have histamine intolerance, but you are pre-disposed. You may be active, but it’s not a 100% certainty okay. Let me assume for the purpose of my blog today that you have the SNP and it IS active so you have a chronic health condition of some sort.  

Skip the red wine, especially the expensive ones, they are still often full of sulfites. That smoked turkey sub and yogurt you had for lunch is also high in histamine. So is anything fermented like kefir, bleu cheese or sauerkraut. I included a comprehensive list of histamine-rich foods, as well as histamine-provoking foods in my Headache Free book in case you have that. 

Let’s talk about your genes now.  SNPs for DAO can easily be tested for, usually a salivary test. A homozygous SNP in DAO can produce histamine intolerance.

Histamine intolerance can be the result of a Diamine Oxidase (DAO) deficiency. FYI, I have 2 heterozygous SNPs in the DAO gene myself. Having several active SNPs in your DAO gene pathway could cause a DAO deficiency. DAO breaks down histamine in the gut. It’s like a big ax that chops it up, so if you don’t have the ax you can’t chop it up. Histamine backs up in your bloodstream and causes discomfort and illness. People with DAO problems have an intolerance, not a true “allergy.”   The problem is so grand that I’m betting it costs our healthcare system millions of dollars. 

Another SNP in the HNMT gene (histamine-N-methyl transferase) will cause histamine to build up. This is the gene that encodes for an enzyme that reduces histamine into another compound called N-methylhistamine, which subsequently requires the MAO (monoamine oxidase) enzyme to further break it down.  MAO runs by having enough riboflavin (actually the biologically active form called FAD).

Anyway, a polymorphism that blocks HNMT prevents the break down of histamine, just like a SNP in the DAO enzyme will cause histamine to accumulate.  Either SNP, your histamine builds up too high. 

What if you don’t have a SNP, is it still possible to have these enzymes malfunction, and thus have histamine build up? 

You betcha! That’s what you have me for. I’m a pharmacist, so I know medications like the back of my hand. And I can assure you that certain medications will act as “drug muggers” on a pathway, stealing the very nutrients you need to make that pathway run. If you run out of a nutrient that runs a specific pathway, then the pathway stops working. It’s kind of like a double homozygous SNP that is expressing, but it occurs from medicines you take (that rob the necessary nutrients).  I call it a “Medication-Induced SNP” or MIS because that’s exactly what it is.  Take a look at this pathway I drew.
Screen Shot 2015-10-17 at 2.45.58 PM
As you can see from my diagram, the DAO enzyme is dependent on vitamin B6, B12, iron, copper and vitamin C.  Diuretics, hormone replacement drugs, vibrates and statins (and others) deplete these nutrients thus causing a MIS… the acronym for “medication induced SNP”  and the first letters form “MIS” as you can see. 
Yes I made that up, but you will see me using that term from now on. 

So a Medication-Induced SNP can happen in the absence of an actual gene SNP. The medication is acting like the homozygous polymorphism, only worse. You see, having a polymorphism doesn’t mean you will have expression of the SNP, whereas (and this is highly unfortunate) taking a medication is a slam dunk for expressing what looks like a SNP! It is definitely going to be a ‘drug mugger’ of nutrients, thus it is definitely going to hinder your pathways and either upregulate or downregulate a biochemical pathway. How much did I make to discover this?  
Zero, but my research will hopefully make your life better and spark discussions all over the world. If you have more interest in how medications are inducing SNPs, I’ve created the world’s first resource and this is especially handy for practitioners, and savvy consumers. It’s laminated pathways on a keyring, with all the medications embedded on the pathways. You can click here to learn about my keyring pathyways.

In the case of the HNMT and MAO enzyme, the following drugs deplete riboflavin which is needed to run that enzyme: Hormone replacement, diuretics and certain antidepressants.  Those categories of drugs cause a MIS “medication induced snp” and effectively cause histamine to build up in your bloodstream. 

This part is huge: 
If your physician doesn’t tease these problems (either a  DAO block or an HNMT block) caused by medications you take, or by polymorphisms you have, then the following may happen to you:

* You might get a diagnosis for “migraines” or “cluster headaches” and you are given a lazy-Susan of drugs to reduce headache frequency. For example:
1) Triptans like Imitrex or Zomig
2) Pain-killers like Vicodin or Dilaudid
3) Anti-inflammatories like Naproxen

Do you know that cluster headaches (extremely painful and disabling) are also called “the histamine headache” because they are so commonly associated with high levels of histamine.

* You might get a diagnosis of anxiety and be prescribed a benzodiazepine drug (alprazolam for example). Anxiety is very prevalent among vegans, and I suspect it’s due to their high consumption of tofu and tempeh two fermented foods that are extremely high in histamine. Vegans who are prone to anxiety or other mood instability problems should consider a trial diet where they eliminate the fermented foods altogether (every one of them including kombucha, sauerkraut and tofu/tempeh). See how you feel after a month or two.  You don’t have to eat animals if you don’t want, but at least animal protein is not fermented, it’s better for you than the manufactured fermented stuff.

* You might experience a worsening of Hashimoto’s thyroiditis  if you have histamine intolerance. It’s sad but true that many Hashi patients are told to eat certain foods to help repair their gut, but the recommended foods are fermented. That’s dangerous to a Hashi patient. The problem is that fermented foods are extremely high in histamine. Hashimoto’s patients all have inflamed “leaky” guts with too many bad bacteria and yeast, and too few healthy bacteria. This imbalance predisposes you to more food sensitivities so when you eat fermented foods (or any other food high in histamine for that matter), you make yourself sicker.

More specifically, experts that recommend diets high in fermented foods (with good intentions to support gut health), cause a low-grade inflammatory cytokine problem in their Hashi patients. The reason it backfires is due to increasing the histamine levels (from the foods eaten), combined with a problem breaking down the histamine consumed. This could be from a SNP in your DAO gene or histidine decarboxylase gene. It could be a Medication-Induced SNP too, if the patient takes a drug that mugs any of the nutrients needed to run DAO. Remember, DAO breaks down histamine in the intestines (it doesn’t help you with allergens like dust).

So anyway, histamine builds up and may cause a worsening in a Hashi patient. This can also occur from antibiotic use, or other drugs that have chipped away at your microbiome like oral contraceptives and acid blockers. So I would never recommend the histamine-rich foods (listed below) if you have hypothyroidism or Hashimoto’s until you are certain that your blood histamine levels are well within normal levels, and also certain that you do NOT have a DAO snp.

* Stomachaches or Diarrhea. You may be told that you need to go off gluten, and not that this is a bad idea, but stomachaches could very well be related to high histamine levels. Diarrhea is extremely frequent in people who have elevated histamine levels. A simple blood test would reveal it. A histamine-free diet could relieve years of misery and reduce the need to ‘toilet map’ every time you go out. Results could be seen in as little as 3 weeks if you don’t cheat on the diet.

* Dermatographia. My son had this when he was young, and when I would scratch his back, thick raised lines would pop up on his skin.  I am homozygous for DAO, so I’m betting that he expresses the gene SNP even though I haven’t tested him. Persistent eczema is often tied to high blood histamine levels and all those expensive steroid creams won’t do you a bit of good unless you reduce histamine intake or improve tolerance. Supplements of DAO may help, I’ll tell you about that later.

* Vertigo and dizziness. This could result you going in for expensive MRIs to determine what is wrong, or rule out brain tumors. High histamine could be one simple cause though. Also vertigo and dizziness (and lightheadedness) are often associated with a condition called POTS which you can read about by clicking here.

* Abnormal or erratic menstrual cycles. Lowering histamine levels could make each month a little more comfortable and might result in you being able to avoid the drugs used to control PMS problems like expensive antidepressants and analgesics.



* Asthma. This category is HUGE. All the inhalers needed, and the fear associated with bronchospasm. It can be fatal of course. What if reducing histamine helped you, can you imagine how much better your life would be?!

* Core body temperature.  Histamine impacts your body temperature via two different mechanisms. It will cause it to drop below normal. How many of you are told you are hypothyroid when it is really histamine intolerance and dysregulation, I wonder about that.

* Pain. Histamine intolerance leads to more pain, controlled by NSAIDs, acetaminophen or opiate pain-killers. Do you have chronic fatigue or fibromyalgia that is unresponsive to typical medications that should help? Consider histamine elevations. Pain syndromes are often treated with NSAIDS.  Aspirin, ibuprofen, naproxen and other NSAIDS are known to cause elevations in histamine. So do other pain killers like the opiates (oxycodone, hydrocodone, etc). It’s definitely a conundrum. I think if it were me, and I needed these medications (any of them) then I would consider low dose DAO supplementation, but that is just me. I cannot advise what is right for you, okay, so have a candid discussion with your physician.

* Multiple Sclerosis (MS) and other Autoimmune diseases. Histamine is a crucial factor for both the initiation and maintenance of painful inflammatory disorders of the CNS (central nervous system). A 2013 study confirmed that the cerebrospinal fluid of patients with MS held much higher levels of histamine than normal participants.

* Hypertension. Blood pressure will rise in the presence of high histamine. Millions, no billions are spent in this country on anti-hypertensive agents, not to mention the cardiovascular complications that result from uncontrolled hypertension.

MTHFR and Histamine

Having the MTHFR mutation doesn’t necessarily mean you have a methylation defect, but it does raise your risk. I think most people with the mutation do have a methylation problem, but that is just my opinion.

Summary
Histamine isn’t a bad guy, it’s needed to create stomach acid and to perfect your gut motility so that you can get food through you properly. DAO or “diamine oxidase” is an enzyme that is outside the cell (termed “extracellular”) and it breaks down histamine in the intestinal tract. 

Foods and drinks can be high histamine such as wine or other alcohol, seafood, citrus fruits, berries, chocolate and leftovers that may have begun fermenting. In fact,  fermented foods and leftovers are very high in histamine, and when you eat that you have to have enough DAO enzyme on board to break down that histamine. A SNP in your DAO gene will hinder that process and cause histamine to build up in your bloodstream.

High histamine is prevalent and often undetected. It can lead to chronic inflammatory conditions. You see it frequently in skin disorders such as eczema, unexplained skin rashes, itchiness, hives or increased sweating.  Intolerance to alcohol is another clue. High histamine predisposes you to nausea and feeling woozy or developing sea sickness.

Reducing high histamine foods can help, as can taking DAO supplements to help you deal with a polymorphism in your DAO enzyme.  The supplements will help you deal with all that bloodstream (extracellular) histamine.  If you don’t take care of mitochondria, and have enough glutathione, the histamine levels will also rise. This causes a lot of inflammation. It’s unfortunate but inflammation runs rampant as cytokines build up in our body, histamine being one of them. It makes you chronically ill and no matter what you do, nothing will help until you reduce histamine.

You may be sitting there thinking, “Fine I’ll just stop eating cheese and drinking wine” but it’s not that simple. The consumption of high histamine foods/beverages is just one simple scenario, and the plot thickens if you have a DAO SNP because then it’s like a one-two punch because you are eating histamine (first punch), yet you can’t break it down (second punch).

My plan for you would be as follows, and not necessarily in this order: 

1) If you have a chronic illness, I would test your blood levels of histamine, ask your doctor to order the test. Any physician can do this. If for some strange reason, you can’t make it happen easily, go ahead and order the test by yourself. Since I am a practitioner with Direct Labs, you can go through my private link by clicking here.

2) Realize histamine plays a role if you have chronic skin conditions, it is almost a given! For example, if you suffer with eczema, psoriasis, other skin rashes, hives, wheels or itchy bumps it is almost always tied to high histamine or a DAO block (like a SNP).  Realizing this puts you on the fast track to wellness. Almost as important are lung concerns like wheezing, chronic sinusitis, asthma and the sniffles.

3) Consider supplementation of DAO, sold nationwide and at many health food stores.

4) If you have hypothyroidism, or Hashimoto’s thyroiditis or Graves’ or any other auto-immune disorder such as Multiple Sclerosis, there is evidence to suggest lowering histamine can help you so I would eat a low-histamine diet, not a high one (this means no more histamine-containing foods, and no more histamine-producing foods). Many of these are fermented foods often mistakenly suggested to improve gut microbiome. You should be doing that with healthy probiotics and/or healthy yeast (ie Saccharomyces boulardii).

5) DAO is over-the-counter, but I don’t recommend self-treatment, and I can’t personally advise you. So even though you can buy these supplements anywhere, it’s always a good  idea to talk to your physician about using DAO instead of antihistamines. This is crucial for serious conditions like asthma, do NOT (repeat do NOT) go off your steroids and inhalers, as these may still be needed for your total recovery. DAO supplements are derived from pigs, in case you have allergies. DAO enzymes will dry you out, just like antihistamines. Some supplements are super strong, and some are mild, you’ll have to choose what you like as I cannot advise you. But do have a candid and open discussion about the possibility of histamine intolerance, and how it may apply to you.  

I know that I will be asked about dosages. It varies and you should use the lowest effective dose. Some of you can take a capsule just before eating a meal that is high in histamine and some of you need daily support. The dose varies, some of you may need half a capsule, others may need 1 or 2 capsules (20,000 to 40,000 HDU) taken daily.  
DAO supplements are usually taken before a meal, however, there are no hard fast rules.  Follow (or adapt) the directions stated on the label of the product that you purchase.

6) Consider the herb HOPS (follow label directions) to reduce histamine levels.

7) Consider quercetin (about 250 to 500 mg taken three times daily) in order to reduce histamine levels. This bioflavonoid is okay for people with normal or low dopamine, but not high dopamine as it will exacerbate that.

8) Avoid fermented beverages like wine, champagne, beer and kefir. Avoid fermented foods too like cheese, yogurt and sauerkraut. Remember fermented foods are high in histamine.

9) Go on a histamine-free diet and avoid the following:
Farmed seafood, including shellfish
Smoked meats
Tofu
Bologna
Eggs
Fermented dairy products like buttermilk, yogurt, cheese of any sort, aged cheese, kefir
Citrus fruits
Dried fruits: Apricots, cherries, cranberries, prunes, currants, raisins and dates
Tomatoes and tomato sauce
Spinach (it’s high in oxalates anyway, so keep this to a minimum)
Vinegar-containing foods like salad dressing, pickles, relish, etc
Sulfites 
Anything fake like a food additive (artificial colors, preservatives, benzoate’s)
Soy sauce or miso
Chocolate (boo hoo, sorry guys!)
Cola drinks 
Spices like cloves, cinnamon, chili and curry
There are other foods, this is not complete.

10) Feed your mitochondria if necessary, glutathione supplements may be critical for some of you. If you have poorly functioning mito, the histamine will be more apt to build up.



11) Look at your medication list to see if you are taking a medication that is causing a MIS (medication induced SNP). If you are interested in seriously cutting-edge information on genes, and how medications induce SNPs (and you have good understanding of pathways) you can check out my Keyring Pathways.

Finally, histamine travels throughout your blood, it is carried in the bloodstream, so histamine can affect  you anywhere, from your gut to your lungs, your brain, your heart, skin and central nervous system. Feel free to share your store and comments below. Keep in mind, I receive hundreds of questions and comments at this site each day and unfortunately I can’t answer them all. I’ll chime in as I can. Please help each other.