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Histamine Intolerance

Summary: Histamine Intolerance develops when the amount of histamine in your body is greater than the amount of histamine your body can eliminate. Common symptoms can include anxiety, insomnia, abdominal pain, diarrhea / constipation, hives, headaches, and sinus congestion.

Histamine is an organic nitrogenous compound critically important for a variety of physiological functions. Most importantly, histamine is integral to the inflammatory response associated with the immune system attacking infections. However, excess histamine causes several serious maladies. Dramatic histamine excesses are a key concern in people with mastocytosis, which could be considered the far end in a spectrum of histamine conditions. On the complete opposite end of the spectrum would be the trivial histamine increases seen after a mosquito bite. There are also histamine-related health issues that develop between these extremes. Such histamine-caused symptoms may include headaches, abdominal pain, anxiety, insomnia, and joint pain. Histamine intolerance is a condition in which an individual’s ability of normally metabolizing histamine is compromised. It has been estimated that as many as 1% of people have an intolerance that can be managed, in part, by reducing exposure to high histamine foods.


Individuals with histamine intolerance have decreased ability to degrade histamine. After histamine is synthesized from histidine, it normally is broken down by one of two enzymes: diamine oxidase (DAO) and histamine N-methyl transferase (HNMT). DAO is the predominant enzyme present in the GI tract, degrading histamines present in ingested foods. HNMT is only active within cells. (Maintz & Novak 2007). Histamine intolerance occurs when accrued histamine concentrations exceed ability for normal enzymatic degradation.


There are several conditions associated with excesses histamine. These include chronic inflammation of joints or the lining of the intestinal tract. Rheumatoid arthritis is an extreme example of a common chronic inflammatory condition. Other conditions with the potential for causing histamine excesses include hormone imbalances, dysbiosis, and specific gastrointestinal diseases (inflammatory bowel disease [IBD], irritable bowel syndrome [IBS], Crohn’s disease, or infection due to bacteria, viruses, fungi, or parasites). It has also been suggested that emotional issues, physical stresses, extreme temperatures, dehydration, or high altitude can cause release of hormones and other chemicals, including histamine.


Since the histamine content of food varies dramatically, this may be a source of inflammation for some individuals. Avoidance of foods recognized as having high histamine concentrations may be beneficial. Altering a diet to foods with low histamine content for an individual suspected as having histamine intolerance is one of the few non-pharmacologic therapies available. High histamine concentrations are found in fermented foods such as aged cheese, yogurt, sauerkraut, still wine, sparking wines, and processed meat. Foods that may initially be low in histamine, may develop much higher concentrations over a few days. Therefore, one needs to be conscious of “safe” foods that cannot be consumed as leftovers. Spinach, avocados, pineapple, and tomatoes are examples of fruits and vegetables that contain relatively high histamine concentrations. Artificial coloring, preservatives, chocolate, and cinnamon are also high in histamines.


Fish that have not been cleaned, cooked, and eaten immediately after being caught tend to contain high amounts of histamine. The World Health Organization released a report saying that the high levels in fish may be too high for people who have allergies and immune system problems when accompanied with alcohol. Alcohol deactivates DAO. The two in combination can bring on a severe allergic reaction.


Genetics likely plays a key role in development of histamine intolerance. Early studies indicate the presence of genetic polymorphisms involved in developing deficient concentrations of diamine oxidase (DAO). The genetic component to this syndrome is supported by diagnosing histamine intolerance in family members. (www.deficitdao.org)


Histamine symptoms drastically reduce during pregnancy. It has been known that maternal blood serum levels of diamine oxidase (DAO) activity increases 1000 times during the first 20 weeks of pregnancy. DAO is produced at very high concentrations by the placenta. These findings temporarily relieve histamine intolerance symptoms until the baby is born. (Marintz, Schwarzer, Bieber, Van Der Ven, Novak 2008).


Is it possible for histamine intolerance to be an iatrogenic syndrome related to use of certain pharmaceuticals? Some drugs are known to either directly enhance histamine concentrations or to inhibit histamine breakdown by reducing concentrations of DAO. It has been estimated that more than 90 drugs may be involved in either inhibiting DAO or increasing histamine concentrations. Some implicated drugs include antidepressants, bronchodilators, anti-mycotics, anti-bacterials, and NSAIDs. A more complete list can be found on the website of the Swiss Interest Group Histamine Intolerance (SIGHI), (www.deficitdao.org) (Joneja 2017)


The common clinical symptoms associated with histamine intolerance include many assumed to be associated with inflammation. The inflammation associated with this condition has been explained as being the result of an individual’s “bucket being full.” In other words, the body has reached a level of histamines in excess of the ability for them to be efficiently metabolized and cleared from the body. Excess histamines then cause symptoms. Symptoms can include anxiety, insomnia, abdominal pain, diarrhea / constipation, hives, headaches, and sinus congestion. Listed are recognized symptoms associated with the common organ system that has become inflamed:


Central Nervous System

  • Headache

  • Anxiety

  • Panic disorder

  • Circadian rhythm disruption (arousal), insomnia

  • Vertigo

  • Tinnitus

  • Contribution to the regulation of body temperature, food intake, locomotion, learning and memory

  • Nausea/vomiting

Cardiovascular System

  • Hypotonia (low muscle tone), hypertension, hypotension

  • Anaphylaxis (severe reaction, such as to a bee sting)

  • Arrhythmia (irregular heart rhythm)

  • Tachycardia (heart rate that is too fast)

Physical

  • Pain in the temporomandibular joint

  • Neck pain

  • Joint pain

Skin

  • Pruritus

  • Flush

  • Urticaria (hives)

  • Edema (swelling) around eyes, lips, and throat

Respiratory Tract

  • Congestion of nose, rhinorrhea, sneezing

  • Bronchoconstriction, dyspnea (shortness of breath)

Gastrointestinal

  • Diarrhea

  • Constipation

  • Stomachache, cramps, bloat from inflamed gut

  • Heartburn, reflux

Uterus

  • Dysmenorrhea – painful periods

Acute allergic reactions, such as those seen with IgE release, cause immediate symptoms following even the smallest exposure to the offending item. Histamine intolerance, by contrast, is a chronic condition that can result in similar symptoms. Complicating the diagnosis of histamine intolerance is that excesses in histamines are known to occur secondary to other conditions. For example, carbohydrate malabsorption is seen with histamine intolerance (Enko 2016). Lectin and/or night shade sensitivities may also occur concurrently. The amine “sulfite,” present in many wines, may cause histamine-like (allergic) symptoms. Pairing wine with low histamine but high sulfite foods such as fruit juice, frozen vegetables and lettuce may cause serious allergic reactions. (Mainztz & Novak 2007). Antihistamines give only temporary relief by preventing histamine from reaching cells by blocking receptors. They are especially helpful in acute conditions, such as panic attacks or severe hives. Antihistamines do not enzymatically degrade histamine, but they can provide profound short-term relief.

Proper diagnosis is important. Ruling out Mast Cell Activation Syndrome by doing a Tyramine blood test is helpful. Since blood histamine and DAO levels fluctuate wildly during the day, blood tests tend to not be sensitive enough for proper histamine intolerance diagnosis.(HealingHistamine.com). An elimination diet consisting of foods with little to no histamine is the gold standard for both diagnosis and treatment of histamine intolerance (Joneja 2017). After beginning a low histamine diet, decreases in symptomatology can occur as early as a few weeks but may require as long as 2 to 6 months. The next step is determining what may be causing the histamine intolerance and if possible, eliminate that item from the diet, body, or environment. A nutritionally balanced antihistamine diet can be maintained long term if necessary. All types of stress release histamines and activate mast cells. Reducing stress is a must. Meditating daily is a great way to lower stress as is practicing moderate exercise such as yoga or walking.


Intense/strenuous exercise has been shown to increase stress, therefore, increasing histamine levels. Moderate exercise is ideal. Quercetin acts as an antihistamine which will degrade histamine. If magnesium is deficient, in just four days histamine rises dramatically. Supplementing with magnesium is critically important. Supplementing with a quality Diamine Oxidase before eating has been very helpful for some people. Since histamine is released during the digestive process, intermittent fasting not only gives your digestive tract time to heal but reduces your overall level of histamines.


References:

Enko, D., Meinitzer, A., Mangge, H., Kriegshauser, G., Halwachs-Baumann, G., Reininghaus, E., Bengesser, S., Schneidl, W., Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption. Canadian Journal of Gastroenterology and Hepatology; (Nov. 30, 2016) Published online doi: 10.1155/2016/4893501


Goldman, L., Schafer, Andrew I. (2012). Goldman’s Cecil Medicine. (24th ed.). Philadelphia, PA: Elsevier Saunders.


Maintz, L., Novak, N. Histamine and Histamine Intolerance. American Journal Clinical Nutrition 2007 May;85(5):1185-96


Marintz, L., Schwarzer, V., Bieber, T., Van Der Ven, K., Novak, N. Effects of histamine and diamine oxidase activities on pregnancy: a critical review. Human Reproduction Update; Oxford Vol. 14, Iss. 5, (Sep/Oct 2008): 485-95


Joneja, J. Histamine Intolerance, The Comprehensive Guide for Healthcare Professionals. Berrydales Books. 2017

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