Histamine is a chemical that is produced by the body's immune system. It is most commonly recognised for the role it plays in allergic reactions, but it also has other functions, including regulating blood flow, digestion, and sleep.
In recent years, there has been growing interest in the role of histamine in the menstrual cycle. Some studies have shown that women with menstrual problems, such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), may have higher levels of histamine than women without these conditions. There may also be a link between inflammation and endometriosis.
This blog post will explore the role of histamine in the menstrual cycle, including the scientific evidence, how to test for histamine intolerance, and the signs and symptoms that may indicate a problem.
If you have any questions at all please drop me a comment or email.
Love Andrea
Your favourite period acupuncturist in Hertfordshire
A short story of histamine
Histamine is a chemical messenger that at its heart regulates inflammation. It is derived from histidine (an amino acid found in protein foods) which then converts to histamine but it can also be found endogenously in mast cells.
Two main histamine metabolic pathways are known in humans, involving the enzymes diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT). I promise this will become important, as we learn how we might need to detox any excess of histamine!
DAO is responsible for deamination and HNMT for methylation.
DAO is responsible for the degradation of extracellular histamine and is restricted to certain tissues, mainly the small intestine, ascending intestine, placenta, and kidneys. In the intestine, DAO activity increases progressively from the duodenum to the ileum and is located mainly in the intestinal villi. DAO plays a major role in protecting the body against exogenous histamine, whether originating from ingested food or generated by the intestinal microbiota.
HNMT is expressed in a wide range of human tissues, above all in the kidneys and liver, and also the spleen, intestines, prostate, ovaries, spinal cord cells, and the trachea and respiratory tract. HNMT is responsible for the inactivation of intracellular histamine and can be synthesized in the cell itself or incorporated from the extracellular space by binding to a receptor or by membrane transporters.
Histamine's key roles
Raising inflammation appropriately: When we are injured it creates the appropriate response (heat, oedema, swelling, itching) and sends the appropriate response to help repair the injury
Plays a key role in gastric acid secretion and digestion
Acts as a neurotransmitter in the nervous system. Upregulates glutamate, serotonin, dopamine, and adrenaline.
Blood clotting via platelets and wound healing
Histamine has different receptors and this is important as these receptors can impact many systems within the body hence why signs and symptoms of histamine intolerance can be wide-ranging.
H1R - allergy & inflammation (CNS, respiratory tract, epithelium). Smooth muscle constriction, increased vascular permeability, oedema, prostacyclin, platelet activating factor, mucus.
H2R - Gastric acid secretion, increased heart rate, mucus production, vascular permeability, relaxation of airways, uterus, vascular smooth muscle cells, regulation of intestinal bacteria.
H3R - CNS, negative feedback, modifying release of histamine, noradrenaline, dopamine, serotonin, acetylcholine, GABA affecting sleep, cognition, inflammation, metabolism, energy (implicated in satiety/obesity). Problems with H3R can increase leptin and insulin
H4R: migration/recruitment of eosinophils, mast cell allergy, amplifying inflammation.
Signs and Symptoms of Histamine Intolerance
The signs and symptoms of histamine intolerance can vary from person to person. However, some common symptoms include:
Hives
Sneezing
Runny nose
Itchy eyes
Nausea
Vomiting
Diarrhea
Headache
Fatigue
Difficulty sleeping
Mood swings
Anxiety
Depression
If you are experiencing any of these symptoms, it is important to see a doctor to rule out other possible causes.
How can histamine become unbalanced?
Each individual has a unique and constantly changing tolerance level influenced by the overall level of inflammation, hormones, gut microbiome, and stress.
Food: For a full list of high-histamine foods click here, however, some examples are cured meats, cheeses, yoghurts, kiwis, avocado, spinach, bone broth, kefir,
Allergens: dust mites, viruses, bacteria, stings, mold, pollen, dander
Hormones: oestrogen (and possibly progesterone), stress hormones
Toxins: environmental toxins, alcohol
Gut microbiome: A higher ratio of Proteobacteria genus may predict dysbiosis and/or impaired intestinal epithelial function
How Histamine Affects the Menstrual Cycle
During the menstrual cycle, there are a number of changes in hormone levels. These changes can affect the production of histamine.
The changes in histamine levels during the menstrual cycle can affect a number of different functions, including:
Blood flow: Histamine can cause blood vessels to dilate, which can lead to increased blood flow to the uterus. This can cause pain and cramping during menstruation.
Digestion: Histamine can stimulate the production of stomach acid, which can lead to nausea, vomiting, and diarrhea.
Sleep: Histamine can interfere with sleep by stimulating the brain. This can lead to difficulty falling asleep and staying asleep during the night.
Higher levels of inflammation: might be a co-factor of signs and symptoms in PMS and PMDD
Oestrogen
When oestrogen binds with ESR1 (the oestrogen receptor) this starts the degranulation of the mast cell and the release of histamine. The reason for this is it supports embryo implantation in pregnancy.
Progesterone
It has been found that in the luteal phase when progesterone and oestrogen are aggregately at their highest there can be a proliferation of mast cells. This therefore will coincide with a higher incidence of histamine.
DAO
When an embryo is implanted and pregnancy begins, DAO, will increase dramatically. This is to protect the pregnancy from adverse inflammatory effects.
How to Test for Histamine Intolerance
There is no definitive test for histamine intolerance. However, there are a number of tests that can be used to assess whether you may have a problem with histamine. These tests include:
Blood test: This test measures the levels of histamine in your blood.
Saliva test: This test measures the levels of histamine in your saliva.
Elimination diet: This is a diet that excludes foods that are high in histamine. You would need to do this for between 4-8 weeks. If you feel better when you follow this diet, it may be a sign that you have a histamine intolerance.
What are my next steps if I think I have a histamine imbalance?
Identify and avoid triggers (immunological/non-immunological)
Testing
Support detoxification of histamine - HNMT and DAO (Vitamin C, copper, or vitamin B6 supplementation) as appropriate.
Anti-histamines - stinging nettle leaf, H1 antagonists
Investigate/support gut - esp. microbiome (bacterial histamine), gut wall integrity.
Wider systems imbalances, especially stress/dopamine, oestrogen, general inflammation, and wider toxic load (especially alcohol).
Low histamine diet (4-8 weeks) - food and symptom diary.
Conclusion
The role of histamine in the menstrual cycle is still not fully understood. However, there is some evidence to suggest that histamine may play a role in the development of PMS, PMDD, and endometriosis. If you are experiencing symptoms of histamine intolerance, it is important to see a doctor to get a diagnosis and treatment.
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