Updated: 28 Jan 2019
Histamine is a hormone involved in digestion, immune & nervous system function. While anti-histamine drugs are often prescribed for asthma, they are also given to those with food allergies.
Anti-histamine drugs can be life-saving in times of crisis. At the same time if one doesn’t deal with what causes the reaction at 1st place she/he is trying to put off a fire by removing the battery from the fire alarm.
Which raises the question “What helps histamine intolerance?”
What is histamine intolerance?
Histamine is a hormone with varying functions in different tissues.
Histamine intolerance symptoms are due to histamine’s relation with the immune system. Histamine activates immune cells (basophils & mast cells) while causing blood vessels to dilate so that immune cells can be quickly transferred to kill pathogens. In that sense you can think of histamine as a fire alarm.
“Histamine intolerance is a fire alarm going on when there is no fire.”
To be more precise histamine intolerance results from an imbalance between accumulated histamine and the capacity to break it down. In most cases it is due to limited histamine breakdown capacity. Like all hormones histamine needs to be eliminated from the body when it has done its job. While it is broken down by a few different enzymes (HNMT, NAT1,2 & DAO), it is the DAO (Maintz, L. and Novak, N., 2007) responsible for the breakdown of ingested histamine.
Digestion & histamine
Gastrointestinal problems are very common among those with histamine intolerance.
While histamine is necessary for proper gut function excess levels can cause digestive complications. Below are a few facts highlighting the link between histamine intolerance and gut health:
a. all 4 histamine receptors H1R-H4R are found in the digestive tract and they have excitatory actions there (Breunig E. et al., 2007).
b. In a study conducted in Italy, 13 out of 14 subjects (with food intolerances) reported benefits in at least 1 food after DAO supplementation (Manzotti G. et al., 2015).
c. The capacity of both histamine breakdown pathways: HNMT and DAO have been reported to be reduced in those with food intolerances (Kuefner MA et al., 2004).
d. Elevated levels of histamine in the brain have been shown to suppress appetite. (Malmlöf, K. et al., 2005)
“Diet can help histamine intolerance in 2 ways: i. reduce the histamine load ii. support histamine breakdown”
Histamine intolerance: foods to avoid
There are 2 categories of foods those with histamine intolerance need to avoid: a. Those that contain histamine & b. those that can cause the release of histamine in the body although they don’t contain histamine (Maintz, L. and Novak, N., 2007)
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Histamine intolerance : diet
The fresher the food the lower it is in histamine. Vitamin C supplementation has also been shown to reduce histamine levels (Hemilä, H., 2014).
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Blood sugar regulation and histamine intolerance
The link between histamine and diabetes goes back to 1950 (Pini A et al., 2016).
Plasma histamine was shown to reduce after insulin administration in diabetic rats (Hollis T. et al., 1985). Two of the mechanisms through which insulin and histamine interact was that the activation of histamine 3 receptors (H3R) in pancreatic beta cells was shown to: a. inhibit insulin secretion (Nakamura T et al., 2014) b. reduce glucagon production in non-hyperglycemic state (Nakamura T et al., 2015). While the mechanisms of interaction between diabetes and histamine intolerance are currently not clear the correlation appears to be positive (Pini A et al., 2016).
To that extent a state of insulin resistance should be addressed in cases of histamine intolerance together with any other protocol.
Breathing & histamine
Histamine release is involved in seasonal allergies. A recent novel clinical trial (Casale E. et al., 2018) has shown that the inhalation of small dosages of CO2 can suppress the symptoms of seasonal allergies.
CO2 can suppress histamine release in mast cells by increasing intracellular Calcium levels (Strider J et al., 2011). While no studies so far has tested the use of breathing exercises to suppress seasonal allergies, it is well documented and clinically confirmed that certain breathing exercises can increase the levels of CO2 in the body. Based on that it is well worth considering to use breathwork for histamine intolerance.
How to test for histamine intolerance?
Prior to treating any condition it is wise to diagnose it first. By measuring the levels of DAO enzyme in your blood you can assess your body’s capacity to breakdown histamine. The cut-off level of serum DAO activity (for probable histamine intolerance) is <10 U/mL (Manzotti G. et al., 2015)
Labs that offer this service are:
23andme results & histamine intolerance
23andme results can be useful in identifying potential blockages in the pathway of histamine. At the same time it is dangerous to drive conclusions solely from one’s genetic makeup, let alone one gene. In many cases a person may have no SNPs in the gene that produces the DAO enzyme (AOC1 gene) and at the same time experience histamine-like reactions after the consumption of red wine for instance. The case bellow is such an example.
The woman is in her mid-40s, vegetarian with a more or less healthy lifestyle. She carries only 1 homozygous polymorphism in the AOC1 gene which has been shown to be beneficial.
While there seems to be no burden on the production of DAO if you look at the entire pathway you will see that she carries SNPs in the HNMT and MAOB genes. Both of which can tax DAO’s function.
How can this information be useful?
For this woman supporting the function of HNMT and MAOB can help with histamine symptoms. For HNMT methylation support as well Salacia Oblonga (Oda, Y et al., 2015) can be used while for MAOB vit B2.
This Nutrigenomics analysis would not be possible without access to Opus23 analytics.
Breunig, E., Michel, K., Zeller, F., Seidl, S., Weyhern, C.W.H.V. and Schemann, M., 2007. Histamine excites neurones in the human submucous plexus through activation of H1, H2, H3 and H4 receptors. The Journal of physiology, 583(2), pp.731-742.
Casale, T. B., Onder, R. F., Berkowitz, R. B., & Korenblat, P. E. (2018). Nasal Carbon Dioxide Used As Needed in the Symptomatic Treatment of Seasonal Allergic Rhinitis. The Journal of Allergy and Clinical Immunology: In Practice, 6(1), 183-189.
Hemilä, H., 2014. The effect of vitamin C on bronchoconstriction and respiratory symptoms caused by exercise: a review and statistical analysis. Allergy, Asthma & Clinical Immunology, 10(1), p.58.
Hollis, T.M., Kern, J.A., Enea, N.A. and Cosgarea, A.J., 1985. Changes in plasma histamine concentration in the streptozotocin-diabetic rat. Experimental and molecular pathology, 43(1), pp.90-96.
Kuefner, M.A., Schwelberger, H.G., Weidenhiller, M., Hahn, E.G. and Raithel, M., 2004. Both catabolic pathways of histamine via histamine-N-methyltransferase and diamine oxidase are diminished in the colonic mucosa of patients with food allergy. Inflammation Research, 53, pp.S31-S32.
Malmlöf, K., Zaragoza, F., Golozoubova, V., Refsgaard, H.H.F., Cremers, T., Raun, K., Wulff, B.S., Johansen, P.B., Westerink, B. and Rimvall, K., 2005. Influence of a selective histamine H3 receptor antagonist on hypothalamic neural activity, food intake and body weight. International journal of obesity, 29(12), pp.1402-1412.
Manzotti, G., Breda, D., Di Gioacchino, M. and Burastero, S.E., 2015. Serum diamine oxidase activity in patients with histamine intolerance. International journal of immunopathology and pharmacology, p.0394632015617170.
Maintz, L. and Novak, N., 2007. Histamine and histamine intolerance. The American journal of clinical nutrition, 85(5), pp.1185-1196.
Nakamura, T., Yoshikawa, T., Noguchi, N., Sugawara, A., Kasajima, A., Sasano, H. and Yanai, K., 2014. The expression and function of histamine H3 receptors in pancreatic beta cells. British journal of pharmacology, 171(1), pp.171-185.
Nakamura, T., Yoshikawa, T., Naganuma, F., Mohsen, A., Iida, T., Miura, Y., Sugawara, A. and Yanai, K., 2015. Role of histamine H 3 receptor in glucagon-secreting αTC1. 6 cells. FEBS open bio, 5, pp.36-41.
Oda, Y., Ueda, F., Utsuyama, M., Kamei, A., Kakinuma, C., Abe, K. and Hirokawa, K., 2015. Improvement in Human Immune Function with Changes in Intestinal Microbiota by Salacia reticulata Extract Ingestion: A Randomized Placebo-Controlled Trial. PloS one, 10(12), p.e0142909.
Pini, A., Obara, I., Battell, E., Chazot, P.L. and Rosa, A.C., 2016. Histamine in diabetes: is it time to reconsider?. Pharmacological research, 111, pp.316-324.
Strider, J. W., Masterson, C. G., & Durham, P. L. (2011). Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels. Allergy, 66(3), 341-350.