Do You have a Histamine Problem?

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Histamine intolerance is gaining ground as a potential cause of many problems from asthma to acid reflux. While it’s good that more people are aware of this, the information related to histamine issues isn’t wide spread and, in many cases, it’s incomplete.

Unfortunately, I’m not going to be able to solve that problem in this post because it’s an incredibly complex topic. However, I’m having the conversation with more and more clients about histamine being a potential issue for them, so I wanted to be sure I shared some info with you as well.

As always, let’s start at the beginning and work our way through to possible solutions…

What is histamine and what does it do?

Histamine is a small amine, meaning it is a molecule that contains carbon and nitrogen that has multiple impacts throughout the body.

First, it is “vasoactive”, meaning it affects the blood vessels. When histamine is present, it causes blood vessels to dilate, which allows more fluid into that particular section, and it makes the blood vessel more permeable, which means fluid can escape from the blood vessel into the surrounding tissue. In this role, histamine is an important part of our immune reaction as it enables white blood cells to get to and heal problems within the body.

Second, histamine is a neurotransmitter, a molecule that is passed between neurons in the nervous system in order to trigger a specific response. Within the brain, histamine has been shown to increase excitability. At the end of the day, the hypothalamus decreases the brains sensitivity to histamine, which allows us to fall asleep and makes histamine an important modulator of the sleep/wake cycle. (As a side note, this is why taking an antihistamine makes so many people sleepy… although it wakes me up, so I’m not sure what that says about my brain!) Seemingly contradictory to this excitatory capability, histamine  also reduces seizure activity.

In the brain, histamine also communicates with the hypothalamus about releasing several hormones including vasopressin (controls blood pressure), oxytocin (the “love” hormone), prolactin (stimulates milk production in mothers and is involved in male and female reproductive health), adrenocorticotrophic hormone (ACTH; regulates cortisol levels), β-endorphin (a natural pain reliever), and those that suppress hunger.

Third, histamine in the stomach stimulates the H2 receptors which ultimately triggers the release of hydrochloric acid, a powerful digestion substance. In this role, histamine is an important part of our digestive system.

In short, histamine has many functions within the body and is a necessary part of living.

Where does histamine come from?

This is where things start to get a little tricky as histamine comes from several different places.

1. Histamine is produced by our own tissues, with most of it coming from mast cells within tissues and basophils in the blood.

Almost every tissue in the body can produce histamine through conversion of the amino acid histidine, which isn’t surprising given its aforementioned roles in the body. Even though it can come from any tissue, most of it is released by mast cells and basophils, two types of white blood cells.

When histamine is released from these white blood cells, the rest of the immune system is triggered to respond to an impending threat, and the blood vessels are opened up to allow fluid to carry immune cells and healing proteins in to the damaged or endangered areas. During an allergic reaction, this mechanism causes watery eyes, a stuffy and runny nose, and wheezing due to increased fluid in the lungs. Histamine can also cause hives (i.e., urticaria) and itching of the skin during an allergic reaction, as fluid is released from the blood vessels into skin tissues.

In times of physical injury or trauma, histamine is also released having the same effect on the blood vessels and the immune system as when an allergic reaction is occurring. In these situations, the hurt area of the body may swell and feel warm as fluid rushes in.

In addition to immune system activation, the body releases histamine based on:

  • Stress, whether on-going or extreme, and
  • Periods of hormonal fluctuation such as puberty, pregnancy, ovulation, menstruation and menopause (For example, if you get headaches or hay fever worse at certain times during your cycle, this can indicate a histamine issue.)

2. Histamine is produced by some bacteria, including some of the good ones that live in our guts.

Although this is somewhat controversial as there is lots of disagreement on what substances different bacteria produce, I have seen a difference in clients’ symptoms based on changing their probiotic. Plus, we know that much of the histamine in food comes from bacterial fermentation, so we know that at least some bacteria produce histamine. As such, it’s worth mentioning here that your own microbiota could be contributing to your histamine load.

In general, people agree that Lactobacillus casei and Lactobacillus bulgaricus produce histamine.

Some people say that Lactobacillus lactisLactobacillus acidophilus and Lactobacillus helveticus also produce histamine while other people say that they don’t.

Finally, these bacteria seem break down histamine, thus contributing in a positive way to histamine balance: Lactobacillus rhamnosus, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus plantarum, and possibly Lactobacillus reuteri. (This last one is a “maybe”, as it does produce histamine but it seems to be a different type of histamine that decreases inflammation.)

Unfortunately, many probiotics and probiotic foods contain one or more of the Lactoballius strains that contribute to a higher histamine load.

3. Some foods contain histamine.

Most foods that contain histamine are fermented, and fermentation is done by bacteria, which we know from above can produce histamine. Although there is no definitive list for foods that are rich in histamine because fermentation is not a perfectly consistent process and living things are always unique, the following are generally accepted as being high histamine foods:

  • Some fish (tuna, mackerel, skipjack, bonito, herring, sardines, marlin, and anchovies, especially canned versions) due to marine bacteria which can turn histidine in the fish into histamine! Unfortunately, histamine is resistant to heat, so cooking the fish does not destroy it. Fortunately, refrigeration and proper handling of fish can prevent the build-up of histamine.
  • Aged cheese (gouda, camambert, cheddar, emmental, parmesan)
  • Aged or fermented meat (sausage, salami, fermented ham)
  • Sauerkraut and other fermented vegetables, including pickles
  • Vinegar
  • Ketchup
  • Fermented drinks like kombucha, cider, wine, champagne and beer
  • Olives
  • Spinach
  • Eggplants / aubergines
  • Tomatoes
  • Avocados

4. Some foods cause histamine to be released. 

Most often these foods that cause histamine to be released by the body are those that cross-react with different types of pollen, meaning that if a person has a pollen allergy which causes histamine to be released, eating these foods may also trigger the mast cells to release histamine as they become “confused” and think the pollen is present. Unfortunately, this is where things get really muddy because not everyone will cross-react with all foods so it may be difficult to figure out your specific food triggers. With that said, these are the common cross-reactive foods, keeping in mind that birch-pollen cross-reactivity is the most common and those that are most often found to be culprits during studies are in bold:

  • Birch pollen cross-reactors: carrot, celery, potato, apple, apricot, cherry, kiwi, nectarine, peach, pear, plum, almond, hazelnut, tree nuts
  • Birch/mugwort cross-reactors: celery, carrot, sunflower seed, honey, spices
  • Grass cross-reactors: potato, Swiss chard, tomato, melon, orange, watermelon, peanut
  • Ragweed cross-reactors: cucumber, zucchini / courgettes, banana, watermelon and other melon
  • Plane cross-reactors: green beans, lettuce, maize, apple, kiwi, melon, peach, chickpeas, hazelnut, peanuts
  • Latex cross-reactors: avocado, celery, pepper, potato, tomato, chestnut, banana, kiwi, mango, papaya, passion fruit

Additional foods that have been shown to trigger mast cells to release histamine, not necessarily due to a pollen cross-reactivity, include pork, egg white, chocolate, spinach, tomatoes, pineapple, strawberries, alcohol, citrus fruits and licorice. And in mice, long-chain fats caused more histamine to be released than medium-chain fats, like those found in coconut oil and full-fat dairy products.

Finally, artificial dyes, colors and preservatives can also trigger histamine release.

5. Food-dependent exercise-induced anaphylaxis (FDEIA) can trigger histamine release from mast cells.

FDEIA is anaphylaxis that occurs either when exercising after a certain food has been consumed or vice versa.

Wheat is the most commonly reported cause of this condition, but crustaceans (shellfish), tomatoes, peanuts, maize, soy, celery, alcohol, cheese, and strawberries have also been implicated via research.

How is histamine broken down?

There are two main pathways in the body by which histamine is broken down:

Diamine oxidase (DAO) is an enzyme found primarily in the small intestine, large intestine and kidneys which degrades histamine from food, our microbiota, and histamine released into the intestines by our own mast cells.

Histamine-N-methyltransferase (HNMT) is the other enzyme and is found in most tissues of the body, with the greatest concentration in the kidneys, liver, spleen, large intestine, prostate, ovaries, spinal cord, bronchi and trachea.

As mentioned above, there are some bacteria that can break down histamines as well. But they can only help with those histamines that make it all the way to the large intestine where they live. Most of the histamine in food will be degraded by enzymes or absorbed into the body higher up in the digestive tract. As such, we shouldn’t be relying on our gut bugs to break down histamine for us.

How does histamine intolerance happen?

Histamine intolerance is really having too much histamine in the system. Essentially, we are getting or producing more histamine than our enzymes can break down. When this imbalance happens, we get symptoms associated with excess histamine in the body and this looks like histamine intolerance. (These symptoms are listed below.)

So the goal is to reduce our intake of and improve our ability to degrade histamine.

What interferes with my ability to degrade histamine?

Unfortunately, a person can have a deficiency in either or both of the aforementioned enzymes due to genetic SNPs! That means that the body won’t produce enough of the enzyme to handle the work load of the histamine present. Basically, we can’t empty the histamine-tolerance cup very quickly.

As well, some foods and medicines interfere with DAO’s ability to work, including:

  • Alcohol
  • Energy drinks
  • Black tea, green tea and mate tea
  • Muscle relaxants: pancuronium (Pavulon), alcuronium, D-tubocurarine
  • Narcotic: thiopental (Trapanal)
  • Analgetics: morphine, pethidine (Demerol), NSAIDs (ibuprofen, etc), acetylsalicylic acid (aspirin), metamizole (dipyrone)
  • Local anesthetic: prilocaine (Lidocaine)
  • Anti-hypotonic: Dobutamine
  • Anti-hypertensive drugs: verapamil (Verelan, Calan, Covera-HS, and Isoptin), alprenolol, dihydralzaine
  • Anti-arrhythmic: propafenone (Rythmol)
  • Diuretic: amiloride (Midamor)
  • Gut motility: metoclopramide (Reglan)
  • Antibiotics: cefuroxime, cefotiam, isoniazid, pentamidin, clavulanic acid, choroquine
  • Mucolytics: acetylcysteine (Acetadote), ambroxol
  • Broncholytic: aminophylline
  • H2-receptor antagonist: cimetidine (Tagamet)
  • Cytostatic: cyclophosphamide (Cytoxan, Neosar)
  • Antidepressant: amitriptyline (Elavil)

What happens when we have too much histamine in our bodies?

At its worst, excess histamine can cause anaphylaxis, as too much fluid gets into the tissues surrounding the airways causing over-expansion and preventing oxygen from getting in. However, it can also cause several lesser problems as well, including:

  1. Asthma (Unfortunately, asthma can also be life-threatening, although thankfully it usually isn’t.)
  2. Nasal congestion
  3. Sneezing
  4. Difficulty breathing or shortness of breath
  5. Migraines or headaches
  6. Anxiety and panic attacks
  7. Flushing or itching of the skin
  8. Hives or urticaria
  9. Arrhythmia
  10. Coronary artery spasm which can lead to some cases of variant angina pectoris
  11. Hypotension (low blood pressure) and sometimes hypertension
  12. Vertigo or dizziness
  13. Low appetite
  14. Acid reflux / heartburn
  15. Abdominal cramps
  16. Nausea or vomiting
  17. Diarrhea
  18. Intestinal diseases such as Crohn’s disease and ulcerative colitis (although it’s not clear to me from the literature which is the cause and which is the effect)
  19. Difficulty falling asleep or insomnia, especially between 2 – 4 am
  20. Abnormal menstrual cycles (because it increases the production of estradiol with no affect on progesterone)
  21. Conjunctivitis (pinkeye)
  22. Trouble regulating body temperature
  23. Raynaud’s disease
  24. Joint pain or swelling (especially for those with rheumatoid arthritis or fibromyalgia)
  25. Glaucoma (eventually due to the constant increase in intra-ocular pressure)

Of course, none of these symptoms are truly specific to histamine overload, meaning they can be caused by any number of underlying problems. If you aren’t sure, work with a qualified healthcare practitioner (like me) to figure out if it’s a histamine problem or something else.

How do I know if I’m histamine intolerant?

As mentioned above, histamine intolerance is essentially an imbalance between the amount of histamine present and the body’s ability to break it down. The result is that we have more histamine than we need and the excess can cause troublesome symptoms throughout the body.

If you have more than one of the above symptoms on a regular basis, you may have difficulty breaking down histamine. Or at least have trouble breaking down as much histamine as you are producing and consuming.

People with chronic idiopathic hives are often deficient in DAO (the enzyme that works in the digestive system). A deficiency of this enzyme is correlated more closely with GI symptoms and food allergies.

People with asthma or other bronchial related issues are often deficient in HNMT due to a genetic SNP. Also, an HNMT deficiency is associated with methylation issues or a SNP in the MTHFR gene.

As an interesting side note, children whose behavior issues got better when food additives were removed from their diets often showed a SNP in the HNMT gene. This implies that a build up of histamine could be a true root cause of behavior problems, rather than it being from the food additives directly. (Although I wouldn’t rule that out either because food additives are just chemicals that add to our toxic load.)

What can I do to prevent histamine build up or my reaction to histamine?

As mentioned at the beginning, we need histamine in order to live. So the goal is not to eradicate all histamine from the body, but rather to ensure that our cup of histamine tolerance does not overflow. This means that we have to reduce the amount of histamine we are taking in or producing and/or increase our body’s ability to break it down.

So, for example, if you struggle with asthma, this likely means your body does not produce enough HNMT and, therefore, struggles to breakdown histamine inside the tissues. By reducing your intake of histamine containing foods or boosting your DAO activity, you may be able keep the total amount of histamine in your body at a tolerable level and reduce your asthma symptoms.

So here are the ways you can boost your histamine tolerance:

  1. Reduce your intake of histamine containing and releasing foods. I realize that seems like a monumental task because there are so many potential triggers. So my suggestion is to do an elimination diet with these foods for 3 – 6 weeks and then add them back in one at a time so you can determine which ones are affecting you. Of course, there’s no need to add back in artificial dyes, colors and additives as these chemicals don’t have any place in your diet anyway!
  2. Reduce your intake of foods and medications (as appropriate based on conversations with your doctor) that can block the action of DAO.
  3. Identify the foods to which you are sensitive (even if they weren’t mentioned above) so that your immune system is not constantly being triggered when you ingest them.
  4. Eat foods that seem to have an antihistamine effect including onions, blueberries, parsley, olive oil, pea sprouts, ginger, garlic, turmeric, and stinging nettle tea.
  5. Prevent your body from releasing too much histamine by using pharmaceutical or natural anti-histamines. As a dietitian, I prefer the natural ones like DAO enzymes, quercetin (be careful with this one if you have a COMT SNP), garlic and digestive enzymes.
  6. Change your probiotic to one that does not contain histamine producing bacteria. This is the one that I have used with success with my clients and I now use myself. It’s not cheap, but it is super high powered, so you can take it every other day or every third day.
  7. Fix any imbalance in your gut bugs.
  8. Heal your leaky gut, if you have one.
  9. Ensure you don’t have any nutrient deficiencies that could increase your sensitivity to histamine. Magnesium, niacin (B3), vitamin B6, vitamin C and methionine (an amino acid) deficiency have been shown to contribute to histamine-related problems.
  10. If you have an MTHFR SNP, consider taking the active versions of folate and B12. At the same time, be sure you are not getting too much folic acid or vitamin B12 which can increase histamine production.
  11. Drink plenty of water.
  12. Be sure you are getting enough sleep.
  13. Learn to manage your stress.

That’s a lot of information, I know! And I hope that helps you or someone you love to reach histamine balance.

 

Sources:
— Duquesne University. The functions of histamine. In Immune System. Accessed April 19, 2017.
— Gaby AR. Nutritional Medicine. Concord, NH: Fritz Perlberg; 2011.
— Gropper SS, Smith JL. Advanced Nutrition and Human Metabolism. 6th ed. Belmont, CA: Wadsworth Cengage Learning; 2013.
— Hall J. Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders Elsevier; 2011.
— Hough LB. Histamine Actions in the Central Nervous SystemBasic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Accessed on line April 19, 2017.
— Ji Y, Sakata Y, Li X, et al. Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2013 Apr 15;304(8):G732-40.
— Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. 9th ed. Philadelphia, PA: Elsevier Saunders; 2013.
— Maintz L, Novak N. Histamine and histamine intolerance. The American Journal of Clinical Nutrition. 2007 May 1;85(5):1185-96.
— OptiBac Probiotics. Which probiotic for histamine intolerance? In Frequently Asked Questions. Accessed April 24, 2017. [Note: This is not an endorsement for this product. I am linking to their page because they consolidated a nice article with references, so I wanted to give credit where credit is due.]
— Priyadarshani D, Mesthri W, Rakshit SK. Screening selected strains of probiotic lactic acid bacteria for their ability to produce biogenic amines (histamine and tyramine). International Journal of Food Science & Technology. 2011 Oct 1;46(10):2062-9.
— Skypala S, Venter C, eds. Food Hypersensitivity: Diagnosing and managing food allergies and intolerance. West Sussex, UK: John Wiley & Sons; 2009.
— Turner H. Dietary Histamines, Salicylates and other Natural Food Chemicals. In Integrative and Functional Nutrition Academy, Therapeutic Elimination Diets Track. Webinar. June 20, 2016.

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