Many people suffer from histamine intolerance or “histamine sensitivity”. Histamine intolerance is estimated to affect up to 1% of the population, 80% of which is said to be middle aged women. However this is likely to be an underestimate given the limited studies done on histamine intolerance and the complexity and expense involved in doing such studies.
What is histamine intolerance?
Histamine is a biogenic amine which is synthesised from histidine by vitamin B6 containing, L-histidine decarboxylase (HDC). Histamine is produced in mast cells, basophils, platelets, some neurons and by gut bacteria. Like other neurotransmitters, it is stored in vesicles and released on stimulation.
We consume histamine through many of the foods we eat. Foods, medications and other stimuli can also trigger the release of histamine within the body. These are often referred to as “histamine liberators”.
When there is an imbalance between the level of histamine in the body and the bodies ability to break it down and get rid of it, this is referred to as a histamine intolerance or sensitivity. Another term used to refer to this situation is “histamine overload”.
Common Symptoms of Histamine Intolerance
Conditions associated with histamine intolerance
DAO production can be reduced where there is damage to the enterocytes that make up the gut wall. Gut conditions that have been linked to reduced DAO enzyme activity and raised histamine levels include;
- Allergic enteropathy
- Colorectal polyps and carcinomas
- Crohn’s Disease
- Food allergies
- Irritable bowel syndrome (IBS)
- Small intestinal bacterial overgrowth (SIBO)
- Ulcerative colitis
Asthma has been linked to histamine intolerance with reduced activity of the enzyme histamine N-methyl-transferase (HNMT) responsible for degrading histamine in the respiratory system.
Histamine and the hormone estrogen influence each other bidirectionally. Histamine increases estrogen production and estrogen increases histamine levels. By increasing estrogen and prostaglandin, histamine can promote painful contractions of the uterus. Reproductive conditions linked with histamine intolerance include painful periods and cyclical headaches. Multiple miscarriages have also been reported anecdotally.
- Painful periods
- Cyclical headaches
- Multiple miscarriages
Other conditions linked with histamine intolerance
- Renal failure
- Viral hepatitis
- Hepatic cirrhosis
- Chronic urticaria
- Mood disorders
- Anxiety disorders
- Sea sickness
How is histamine intolerance diagnosed?
Some factors that clinicians may consider when ruling out histamine intolerance;
- Are there at least 2 symptoms of histamine intolerance?
- Do symptoms improve after taking antihistamine medications?
- Do symptoms improve on a histamine elimination diet?
- Are diamine oxidase (DAO) levels reduced?
- Is histamine level raised in plasma?
- Is there increased N-methyl histamine in the urine?
- Have other possible conditions been ruled out?
What causes histamine intolerance?
Histamine has beneficial roles in the body and we don’t want to have too much or too little. The enzyme Diamine Oxidase (DAO) helps to keep things balanced by breaking down histamine coming into the body from histamine rich foods. When there isn’t enough of this enzyme available to break down histamine we can experience symptoms of histamine overload.
Deficiencies in nutrients like vitamin B6, vitamin C and copper, needed for DAO enzyme activity, can contribute to histamine intolerance. Histamine N-methyl transferase (HNMT) is another important enzyme which helps to breakdown histamine within cells.
Damage to the intestinal lining, associated with a range of different gastrointestinal conditions including inflammatory bowel diseases, can lead to reduced production of DAO enzyme.
Mutations in the gene that makes the DAO enzyme have also been found and can be linked with conditions like food allergies and Inflammatory bowel disease. Other genetic mutations that can affect histamine metabolism include the Histamine N-methyl transferase (HNMT) gene, the Catechol-o-methyl-transferase (COMT) gene which impacts histamine level through its effects on estrogen metabolism, and genes like MTHFR which affect the activation and function of the above genes.
How is histamine intolerance treated?
- Following a histamine elimination diet
- Avoiding alcohol and drugs which raise histamine levels
- Using antihistamine medications or supplements
- Taking DAO enzyme supplements
- Reducing exposure to allergens
Environmental and food allergens contribute to histamine intolerance by increasing histamine levels. Avoiding or limiting exposure to these allergens where possible can help to increase a persons threshold for histamine intolerance. Immunotherapies that promote desensitisation to allergens are also available. Additional approaches, which aim to address the root causes of histamine intolerance, include;
- Correcting nutritional insufficiencies (e.g. vitamin B6, copper, vitamin C)
- Nutrigenomic therapy
- Gut repair and treatment of gut dysbiosis
Addressing nutritional insufficiencies such as in vitamin B6, copper and vitamin C that are needed for DAO production is an important step to reduce histamine sensitivity. Gut repair and addressing underlying conditions such as dysbiosis and small intestinal bacterial overgrowth (SIBO) can help to reduce histamine production and improve DAO production. Treating existing genetic mutations related to histamine intolerance using nutrigenomic therapy is another approach that aims for long-term resolution.
Maintz, L., Bieber, T. and Novak, N. (2006). Histamine intolerance in clinical practice. Deutsches Arzteblatt International, 103 (51-52), 3477-3483.
Munoz-Esparza, N.C., Latorre-Moratalla, M.L., Comas-Baste, O., Toro-Funes, N., Veciana-Bogues, M.T., and Vital-Carou, M.C. (2019). Polyamines in food. Frontiers in Nutrition, 6,(108), 1-11.
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