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Histamine Intolerance during the menopause & HRT

Histamine Intolerance and menopause

Histamine Intolerance is underdiagnosed and poorly recognised in the medical profession. Frequently, individuals have grappled with various symptoms stemming from elevated histamine levels throughout their lives, yet often without a diagnosis or comprehension of the condition. These symptoms can worsen during the perimenopause or when starting HRT.

Histamine is a biological amine produced from Histidine through the action of the L-Histidine decarboxylase enzyme, with Vitamin B6 serving as a vital cofactor. It is synthesized and stored in several cell types, including mast cells, basophils, platelets, neurons, and ECL cells in the gastrointestinal tract (ECL - enterochromaffin-like cells).

Biological Functions of Histamine:

  1. Immune system: Mast cells attract white blood cells to combat pathogens in tissues, initiating an inflammatory response.

  2. Regulation of Physiological Functions in the Gut: Histamine influences gastric acid production, aiding in protein digestion.

  3. Neurotransmitter: Histamine impacts wakefulness, circadian rhythms, and cognition.

Histamine, once synthesized, is either stored or broken down by two enzymes:

  • DAO-(Diamine Oxidase) in the gut.

  • HNMT -(Histamine-n-methyltransferase) in the nervous system and lungs

Histamine Intolerance (HIT)

This condition arises when there is an imbalance between histamine production and breakdown, resulting in a toxic response within the body. The primary cause often involves impaired DAO activity, either due to gastrointestinal diseases or inhibition of DAO enzymes by substances such as green tea, black tea, alcohol and certain medications. Additionally, some individuals possess a genetic predisposition resulting in reduced DAO and HNMT enzyme production, leading to decreased histamine breakdown.

Triggers for HIT vary among individuals and may include:

  1. Consumption of histamine-rich foods or DAO-blocking foods (green & black tea, alcohol, ibuprofen, antidepressants)

  2. Gut inflammation, including conditions like leaky gut, SIBO, and infections such as H. pylori, Coeliac disease, and Crohn's disease

  3. Chronic stress, which can increase HPA activity (Hypothalamic-pituitary-adrenal axis) activates mast cells, and boosts histamine release

  4. Genetic predisposition resulting in reduced DAO or HNMT enzyme production and, consequently, decreased histamine breakdown

Symptoms of HIT

Symptoms of HIT are diverse, intermittent or continuous, and often mimic allergic reactions. They encompass:

  • Skin: Itchiness, redness, flushing, rash/eczema, hives, itching, rosacea, and psoriasis

  • Gastrointestinal Tract: Acid reflux, diarrhoea, constipation, bloating, wind, nausea, vomiting, and intolerance to certain foods (particularly high histamine foods)

  • Respiratory: Sinusitis, runny nose, asthma, chronic cough, and shortness of breath

  • Vascular: low blood pressure, dizziness, fainting, tachycardia, oedema, migraines, headaches, fluid retention, easy bruising

  • Neurological: Insomnia, anxiety, memory loss, brain fog, poor concentration, ADHD, panic attacks, and chronic fatigue

  • Hypersensitivity: Reactions to certain drugs, such as NSAIDs, aspirin, codeine, and some antidepressants

  • Gynaecological: Painful periods, miscarriages, progestogen sensitivity, and a potential link with endometriosis

Family History

The genetic variant associated with HIT is present in approximately 2-3% of the population. Among individuals with a genetic predisposition for the condition, 80% are women, 80% exhibit joint hypermobility, and 30% suffer from interstitial cystitis. A family history of similar symptoms is common.

It's important to note that HIT is not an allergy and does not lead to anaphylactic shock, which is a life-threatening reaction. HIT arises from a gradual accumulation of excess histamine in the body and, while not life-threatening, can significantly affect one's quality of life.

Sources of Histamine

Histamine is either synthesised within the body by mast cells, basophils, platelets, neurons, and gut cells, or it is introduced through food and beverages. Certain foods, such as green tea, black tea, and alcohol, can block DAO activity, while others contain high histamine levels or trigger histamine release.

Leftover foods should be avoided by HIT sufferers as bacterial growth post-cooking elevates histamine levels. However, the same food consumed freshly cooked may have lower histamine content. Fermented foods like kefir, yogurt, and sauerkraut should also be avoided.

Histamine Breakdown

Histamine is metabolised in the gut by the enzyme DAO and in the blood and tissues by HNMT. Genetic variations can reduce the production of these enzymes, and certain medications prescribed for HIT symptoms can inadvertently exacerbate the condition. These medications include antidepressants and NSAIDs, while some general anaesthetics can elevate histamine levels, leading to post-operative discomfort.

Impact of Histamine on Hormones

Histamine and oestrogen are closely interconnected. Oestrogen levels peak during adolescence, ovulation, and the perimenopause phase when hormonal fluctuations, including elevated oestrogen, are common. Histamine and oestrogen mutually stimulate each other, creating a potential cycle of increased histamine production and elevated oestrogen. This relationship can manifest in high histamine symptoms during menstrual cycles and perimenopause, including headaches or diarrhoea mid-cycle, painful heavy periods, endometriosis, miscarriages, and challenges in finding suitable hormonal contraceptives & HRT.

During pregnancy, high histamine levels are counteracted by a significant increase in Diamine oxidase (DAO) production, protecting the foetus. Consequently, histamine levels normalize, and symptoms typically resolve during pregnancy.

Histamine in the menopause & HRT

Perimenopausal women often experience symptoms resembling high histamine effects. While most non-HIT sufferers respond well to hormone replacement therapy (HRT), women with HIT may not fare as favourably due to progestogen sensitivity, which can exacerbate histamine levels and symptoms.


Diagnosing HIT typically involves identifying two or more symptoms, symptom improvement during a four-week low-histamine diet, and when taking antihistamines. Keeping a food diary can be immensely helpful for tracking individual triggers.

Dietary Recommendations:

  • Avoid alcohol, tea, green tea, coffee, fermented foods, sauces, processed foods, citrus, avocados, spinach, aubergines, tomatoes, gluten, dairy, hard cheeses, strawberries, tropical fruits, and chocolate

  • Consider consulting a nutritionist or dietitian knowledgeable about HIT for guidance on managing the diet. We can work alongside Sil Brangold our associate nutritionist

  • Freshly purchased food is preferable to reduce histamine content

Treatment of Histamine Intolerance:

  • Reducing dietary histamine is paramount, which may be sufficient for those with normal DAO and HNMT production.

  • Individuals with low enzyme production may require antihistamines (H1 and H2 blockers) to alleviate symptoms.

  • Antihistamines like Fexofenadine (prescription-only) may be necessary.

  • Natural antihistamines like Vitamin C 250mg three times daily, L Glutamine (500mg daily), and Quercetin (500mg twice daily) may offer relief.

  • DAO supplements can be taken 30-60 minutes before meals to aid histamine breakdown

Many patients can manage symptoms through dietary and lifestyle changes, supplemented by regular use of antihistamines as needed.

Lifestyle Considerations

  • Stress reduction through practices like meditation and yoga

  • Exercise may impact histamine levels differently for each individual

  • HRT management for HIT sufferers may require consultation with specialists experienced in the condition

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