The Genetics of Histamine Intolerance

Digital models of DNA structure with problem element on abstract blue background. 3d render genetics of histamine intoleranceAre genetics involved in histamine intolerance? The research says, “yes.” However, genes aren’t the be all and end all when it comes to this state or condition. There are many things we can do to turn off the effects of genes and live with good health and vitality. This post will be most useful to those who have done genetic testing through 23 and Me or another service. Be sure to postmark this information otherwise. 


There are certain variations of DNA building blocks that can set you up for histamine issues. These Single Nucleotide Polymorphisms, or SNPs (pronounced “snips”), have been the subject of much research in recent years as we try to understand what makes one person react to particular drug, environmental exposure, food, et cetera, and another not to react. It’s what makes us all unique, biologically. Histamine is a regular part of our immune response as well as our nervous systems –acting as a neurotransmitter. It becomes a problem when it doesn’t get broken down, and high levels accumulate in the body. There are two enzymes that control the breakdown of histamine in the body: HNMT (histamine N-methyltransferase) and DAO (diamine oxidase). If there are genetic mutations (SNPs) in these genes, histamine may not be broken down properly, leading to a build-up and the resulting unpleasant symptoms.


Histamine levels are regulated in part by the enzyme, Histamine N-methyltransferase (HNMT). The HNMT activity is encoded in the gene called C939T. Having the variation AA causes increased histamine levels in the body.


Diamine Oxidase (DAO), as I have spoken of before, is the enzyme that helps break down histamine. An allele is an alternative form of a gene that comes from a mutation. Each “T” allele that you have within the AOC1 gene indicates reduced DAO activity. Even if you find out you’re TT for AOC1 and have severely reduced DAO enzymes, you can boost it to an extent, with food. I learned through my research that there are certain foods that naturally boost DAO levels, and so I created recipes around those foods which you’ll find in my 28 Histamine Reset and cookbooks


The HDC gene encodes for the enzyme, histidine decarboxylase (also HDC), which produces histamine from the amino acid, histidine. SNPs in this gene could change how easily histamine in produced from histidine. In two separate studies, allergic rhinitis was more common in individuals with a SNP in this gene.


Monoamine Oxidase (MAO) is an enzyme that breaks down N-methylhistamine to N-methylimidazole acetic acid. SNPs in the gene that encodes for this enzyme can cause histamine levels to stay high rather than be degraded.


This widely discussed gene is vital for regulating methylation, an important process in the body which is involved in detoxification, the immune response, inflammation, brain chemistry, energy production, and repair. The MTHFR gene encodes an enzyme by the same name, Methylenetetrahydrofolate reductase (MTHFR). This enzyme is also needed to reduce histamine in the body. The A1298 mutation in the MTHFR enzyme lessens the conversion of BH2 to BH4.  Less BH4 lowers nitric oxide (NO) formation, which may result in increased mast cell degranulation and histamine flares.


Keep in mind, though, that while there are certain genetic SNPs that can predispose you to histamine intolerance or any number of other diseases, illnesses, syndromes, or intolerances, there are other factors involved. While genes may load the gun, environmental factors pull the trigger. Epigenetics has been a major subject of interest in recent years. Epigenetics is the study of how external factors affect the ways genes function –turning them on or off. Nutrigenomics refers specifically to the effect of food on our genes. There are a lot of things that we can do about our environmental (diet and lifestyle) factors that can help to offset our genetic susceptibilities. Chances are, you’ve removed toxic personal care and cleaning products from your life already. Discovering which foods are helpful or harmful is the next step. Reducing histamine producing foods and adding in those that are anti-inflammatory or raise your levels of DAO can go a long way toward swinging your environment more in the direction of healing. For a comprehensive and step-by-step guide on how to use your dietary and lifestyle choices to offset your genes and heal from histamine intolerance, including supplement recommendations, check out my 28-Day Histamine Reset. For an excellent overview of genetics I highly recommend Dr. Ben Lynch’s ‘Dirty Genes’ book now for sale on Amazon. ———- REFERENCES ———— Haenisch, B., Nöthen, M. M., & Molderings, G. J. (2012). Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics. Immunology, 137(3), 197–205. Maintz, L. et al. (2011). Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Allergy, 66(7), 893-902. Retrieved from: Smolinska, S. Jutel M, Crameri R, O’Mahony L. Histamine and gut mucosal immune regulation. Allergy 2014; 69: 273–281. Retrieved from: Smuda, C., & Bryce, P. J. (2011). New Developments in the Use of Histamine and Histamine Receptors. Current Allergy and Asthma Reports, 11(2), 94–100.
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