By Lori Allen, RPh, ISEAI Diplomate, owner of Mixtures Pharmacy

Have you ever walked into a friend’s home and started to sneeze, or got itchy eyes, and then found out that your friend has cats? Are you able to tell what trees are in season because your nose gets congested and you have problems breathing? Do you have to scan ingredient lists, or ask about how foods are prepared when you eat out, because you know you’ll get diarrhea and stomach cramping if you mistakenly eat a particular food? If so, you’re likely affected by histamine.

Most of us know that when we have an allergy, histamine is the primary culprit that causes our eyes to water and our nose to run. This little protein molecule is stored primarily in mast cells and when released through a process called degranulation, can signal inflammation and itching. Histamine is found almost everywhere in the body and is particularly abundant in tissue prone to injury like our arms, legs, skin and blood vessels.

When we’re exposed to invading pathogens (like a virus or bacteria), allergens (like pollen or animal dander), or toxins (mosquito bites, snake bites, or mold), our immune system releases antibodies called immunoglobulin E (IgE) into the blood stream. The IgE then causes histamine to flood the area. How we experience this histamine reaction depends on the receptor(s) the histamine bind to.

There are 4 different histamine receptors in our body labeled H1, H2, H3, and H4 receptors. The H1 receptors are primarily found in the smallest blood vessels called capillaries, which allows the capillaries to become more leaky and can make the surrounding area appear puffy. The H1 receptors also work on smooth muscle contraction, primarily in the digestive and bronchial muscles, which presents as breathing problems like asthma and stomach issues like cramping. Over-the-counter (OTC) and prescription antihistamine like diphenhydramine (Benadryl) block the H1 receptor.

When they are turned on by histamine, H2 receptors cause increased secretion of hydrochloric acid in the stomach. They can also cause a slight increase in vasodilation (flushing), but more slowly than the H1 receptors do. H2 stimulation may also inhibit the release of a brain hormone called prolactin. Medications that block the effect of histamine on the H2 receptors (such as the OTC medications cimetidine, famotidine, ranitidine, nizantidine) are used for acid reflux.

The H3 receptors reduce histamine release in the brain, the peripheral nervous system, and elsewhere in the body. They also affect other brain neurotransmitters such as dopamine and may be implicated in Tourette’s syndrome. No drugs have been developed to specifically block or enhance this receptor, but researchers suspect that H3 receptor inhibition (or activation) may be useful in certain neuropsychiatric conditions. The H4 receptors are found in the bone marrow and on white blood cells and have effects on eosinophils and mast cells. No drugs have been developed for H4 receptors, but blocking H4 receptors might be useful in asthma and allergies.

Symptoms of mast cell activation syndrome (MCAS)

(Used with permission from Dr Sandeep Gupta and Dr Jill Carnahan

Now I have painted a picture that makes histamine out to be a pretty good villain. But like some of our favorite villains they can sometimes have a good side.

  • Histamine can act as a neurotransmitter in our brain, which can increase and decrease other neurotransmitters like norepinephrine, serotonin, dopamine and acetylcholine.
  • Histamine is important in controlling our sleep-wake cycle. It may decrease GABA levels and increase norepinephrine and epinephrine levels, causing increased wakefulness.
  • Histamine influences the release of brain hormones that control things such as behavioral state, biological rhythms, energy metabolism, thermoregulation, fluid balance, stress and reproduction.
  • Elevated histamine may affect thyroid function and thyroid hormone may reduce mast cells and histamine.
  • Histamine may play a role in neurocognitive function. (Haas, 2008)
  • Histamine reduces seizure activity in humans and animals that have an increased number of H1 receptors in some types of human epileptic foci.
  • Histamine has been found to contribute to the physiological control of appetite. (Hough, 1999)

As you can see, we don’t want to completely get rid of the villain, or we also miss out on its benefits.

How does your body control histamine? It is broken down through two processes: (1) oxidative deamination and (2) N-methylation. These enzymatic processes control the breakdown of histamine in different areas of the body. In the gut, the body makes an enzyme called Diamine Oxidase (DAO). The job of DAO is to break down histamine and keep it from binding to too many receptors. If your body doesn’t make enough DAO or if it can’t keep up with the demand for DAO after you eat something that causes a reaction, you can take an OTC product that contains DAO to help counter the allergic (histamine) reaction. DAO generally stays in the gut.

The enzyme that processes N-methylation is called N-methyltransferase. There are some self-help strategies to support and improve this methylation process:

  • Diet: eliminate sugar and alcohol and packaged/processed foods.
  • Sleep: your body needs that time to rest and restore.
  • Stress reduction: the methylation cycle is very sensitive to stress. To see how stressed you are, do the questionnaire on Dr Wilson’s Adrenal Fatigue site.
  • Supplements: Add a good B vitamin complex and minerals. These provide the nutrients needed for the enzymes to work, the cofactors to support the methylation cycle and the methyl groups to methylate the histamine. As a bonus, a good B complex can give you a nice boost of energy; just remember to take it with food.

How can you prevent a histamine response? There are medications that can keep histamine from being released by the mast cells in the first place. These are called mast cell stabilizers. There are several mast cell stabilizers that can be used systemically: cromolyn sodium, ketotifen and tranilast. Other medications provide more localized treatments for the eyes and sinuses.

Several natural supplements can also be effective, such as quercetin and vitamin C. These can be used together. Just make sure you get a quality professional supplement! Curcumin is another natural supplement that some people find helpful for their histamine problems, but this isn’t as universally helpful as quercetin or vitamin C are. Be aware that curcumin makes the histamine problem worse in some people, instead of better.

Most of us occasionally experience the discomfort of seasonal allergies or a reaction to a particular food or foods, which can be dealt with on a seasonal or as needed basis. If you are more affected than the average person, and despite eating a low histamine diet and avoiding your triggers, still have lots of issues, know there are clinicians available to help you. As with all medical conditions, it is important to find the right practitioner who can help figure out a treatment plan for your histamine intolerance (HIT) or mast cell activation syndrome (MCAS). ISEAI is a wonderful resource for finding a practitioner to guide you through the answers to help you live your life to its fullest.

  1. Haas, H. S. (2008). Histamine in the Nervous System. Physiol Rev, 1183-1241. PMID 18626069
  2. Nakazawa, H. S. (1994). Viral respiratory infection causes airway hyperresponsiveness and decreases histamine N-methyltransferase activity in guinea pigs. American Journal of Respiratory and Critical Care Medicine, 1180-1185. PMID 8173757
  3. Hough LB. Histamine Actions in the Central Nervous System. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999. Available from:
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