Abstracts

Originally published in Naturopathic Doctor News and Review (NDNR) on May 6, 2016.

Histamine Intolerance: A Common Cause of Chronic Complaints

Krista Moyer, ND

Dermatology can be annoyingly difficult to navigate, since each condition can have so many different presentations. My goal in this article is to introduce you to the possibility that histamine intolerance may be the root cause of many cases of atopic dermatitis.

Histamine is a well-known cause of seasonal allergies and pruritic rashes; however, there is a whole other world of bodily functions that can be caused by histamine dysregulation (Table 1).

Histamine is a neurotransmitter that is a part of the immune system, and is released by mast cells. There are 2 main enzymes that break down histamine. The enzyme in the central nervous system is histamine N-methyltransferase (HMT), and the enzyme within the digestive system is diamine oxidase (DAO). This article will focus on dysfunction of the DAO enzyme.

Histamine Dysregulation

Diamine Oxidase

Many patients seek out naturopathic doctors because of gastrointestinal (GI) dysfunction, estrogen dominance, anxiety, chronic urinary tract infections, and rashes. An imbalance in histamine can cause any of these to occur, either simultaneously or intermittently.

In a healthy person, a large production of histamine is normally produced within the GI system. However, impairments within the intestinal lining can cause the DAO enzyme to be produced in insufficient quantities by the enterocytes, resulting in excessive concentrations of histamine.

This elevated level of histamine will promote inflammation in the GI tract, and its most obvious outcome will be diarrhea. So, even if histamine is being secreted at an appropriate rate, once the DAO enzyme levels decrease, histamine remains elevated, causing further inflammatory damage to the lining. The same goes for the urinary tract, especially if there is a history of digestive complaints, as this will lower the DAO enzyme, further increasing the concentration of histamine in the urinary tract and resulting in inflammation and degradation of the tissue. Excessive histamine within the body can then advance to cause further systemic dysfunction.

Estrogen & Histamine

Estrogen is ubiquitous in today’s environment, and with the generally heavier load on the liver from our toxic world, it is important to decrease exposure whenever possible. Estrogen has an important and interesting relationship with histamine: High levels of estrogen will increase histamine, and high histamine levels will increase estrogen.1 Combine this with an inflammatory digestive disorder, where the DAO enzyme isn’t being produced in sufficient quantities, and both estrogen and histamine levels will rise further. During pregnancy, women generally notice a significant decrease in their symptoms from high histamine, as the placenta also produces the DAO enzyme.1 But once pregnancy is over, the symptoms return.

Medications & Histamine

Certain drugs can directly induce histamine release, while others can decrease the effectiveness of the DAO enzyme.1 Non-steroidal anti-inflammatory drugs (NSAIDS), aspirin, and some diuretics have been associated with decreased effectiveness of the DAO enzyme.1

Histidine

Histidine is an amino acid that transforms into histamine by the enzyme histidine decarboxylase. Certain bowel bacteria can produce this enzyme, which would increase the production of histamine in the GI tract. The histamine can then pass through the intestinal wall, transferring to other areas of the body.

Foods highest in histidine are mostly animal source: meats, dairy, eggs. Consequently, consuming a diet high in protein can temporarily exacerbate symptoms in a person with histamine intolerance. Furthermore, the histidine content of protein foods slowly transforms into histamine the longer it sits,2 raising histamine exposure in overly sensitive patients. This goes for both cooked or uncooked foods, but is particularly prevalent in meats and fish.

Diagnosing Histamine Dysfunction

So, how do you decide if histamine, rather than some other dysfunctional pathway in the body, is causing your patient’s issues? This is where being a good detective and taking a thorough case history is important. It is crucial to establish what types of treatments the patient has tried in the past.

If they have already had customary treatments for their condition that failed, those failures can help guide you toward a diagnosis of histamine intolerance. A classic example would be that the patient did IgG food sensitivity testing and removed all of the reactive foods for 3 months, but only experienced slight improvements. IgG testing is not necessarily going to reveal a reaction to all of the high-histamine foods, or histamine-liberating foods, or a deficiency of the DAO enzyme. In such a case, the patient could have removed an inflammatory component, but still have the majority of their pathology present.

Testing for Histamine Dysregulation

Testing your patients for histamine intolerance is not a matter of a simple blood test. You can test for the levels of the DAO enzyme, but the results may not be all that helpful. If the enzyme is low, it could be because histamine levels are not elevated. And if it is high, it could be that there is a greater level of histamine in the body, and the DAO enzyme is appropriately elevated at that time to degrade the extra histamine. You could also do genetic testing; however, it will not reveal a histamine intolerance. The patient would still need to find a practitioner who is trained in genetic mutations and able to interpret the raw data, as there is currently no simple test to demonstrate a defect in the gene that codes for the DAO enzyme.

Foods to Avoid

1. High-Histamine Foods

These foods naturally contain high concentrations of histamine.

• Anything fermented
• Meat, poultry, fish (unless freshly caught, gutted, and cooked within 1 hour, or immediately frozen after processing)
• Canned foods
• Raw eggs (a moderate amount of cooked eggs, especially the yolks, can be tolerated)
• Any fermented dairy products (the longer the fermentation process, the higher the histamine level)
• Cured meats
• Shellfish
• Chocolate
• Tomatoes
• Avocado
• Eggplant
• Spinach
• Dried fruit
• Citrus fruits
• Alcohol
• Fermented soy
• Vinegar
• Yeast products
• Nuts (especially peanuts, cashews, walnuts)

2. Histamine-Liberating Foods

These foods can induce histamine release from mast cells, etc, independent of DAO.

• Chocolate
• Alcohol
• Bananas
• Strawberries
• Nuts
• Citrus
• Papaya
• Tomatoes

3. High Biologic Amine Foods

Other biogenic amines than histamine preferentially compete with DAO for degradation. As a result, a higher concentration of biogenic amines can cause a temporary decrease in histamine breakdown. Some of these amines (including medications such as H1 anti-histamines) are also capable of directly causing histamine-like symptoms.

• Legumes (beans, lentils, soy)
• Wheat germ
• Peanuts
• Pineapple
• Grapefruit
• Orange
• Banana
• Papaya
• Kiwi
• Pears
• Raspberries

4. DAO Enzyme-Blocking Foods

These foods slow the breakdown of histamine by inhibiting the DAO enzyme.

• Alcohol
• Tea (both green and black)
• Energy drinks

Diet & Supplements

Long-term treatment of histamine intolerance involves limiting high-histamine foods, as well as histamine-liberating foods. Healing the gut is essential. Supplements that are helpful will depend on the patient’s symptoms. Examples include: quercetin, vitamin C, DAO, and vitamin B6 (required to make the DAO enzyme). During the initial treatment of histamine intolerance, these supplements will be needed at higher dosages, and can be decreased or even eliminated once the patient has stabilized. Even using an anti-histamine, such as loratidine, only during the initial stages of treatment, will help to greatly decrease the load of histamine in the body and alleviate the aggravating symptoms more quickly. Long-term use of an OTC anti-histamine is not advisable, as it will disrupt gastric acid production, potentially leading to a full host of digestive disturbances and further complications.

Treating patients with histamine intolerance is life-changing. Patients generally have gone to many doctors, and have tried many different medications, dietary changes, and creams to alleviate their atopic dermatitis, among their other possible conditions. Once the anti-histamine diet is initiated, you should know within 4-6 weeks whether they have histamine intolerance, as most, if not all, of their symptoms will have subsided significantly. And they will finally have achieved relief from years of aggravating symptoms, with you to thank!

Table 1. Histamine-Related Symptoms

• dysmenorrhea
• symptoms subside during pregnancy

• rashes
• erythema
• severe sweating
• eczema
• urticaria
• acne
• pruritis

• diarrhea
• constipation
• flatulence
• GERD
• stomach cramps
• nausea & vomiting

Head

• headaches
• migraines
• vertigo
• flushing
• watery eyes/nose
• sinusitis
• hair loss
• tinnitus

• chronic fatigue
• foggy thinking
• edema
• insomnia
• anxiety
• syncope
• chronic swollen lymph glands

Cardiovascular

• asthma
• edema
• low blood pressure
• tachycardia

Urinary

• interstitial cystitis

• chronic joint or body pain
• difficulty exercising
• numbness & tingling in extremities

References

1. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85(5):1185-1196.
2. Ganowiak Z, Gajewska R, Lipka E. [Histidine decarboxylase activity and free histidine and histamine levels in fish meat. Rocz Panstw Zakl Hig. 1990;41(1-2):50-57. [Article in Polish]