Histamine Intolerance and Mast Cell Activation – Could They Be Affecting Your Health?

Histamine is a natural compound in the body that plays a role in immunity, digestion, and the nervous system. However, when histamine levels become imbalanced, it can cause a wide range of symptoms.

Bloating, digestive upset, reflux or heartburn, headaches, sinus issues, itchy skin, anxiety, fatigue, brain fog, dizziness, joint or muscle pain — these can all be signs that histamine is playing a bigger role in your health than you realize.

Two of the main conditions that sit under the “histamine umbrella” are Histamine Intolerance (HIT) and Mast Cell Activation Syndrome (MCAS). While they share overlap, they are not the same.

What is Histamine and Why Does it Matter?

Histamine is a natural chemical made in the body. It plays many important roles, including:

• Supporting the immune system (helps fight infections)

• Controlling stomach acid for digestion

• Acting as a neurotransmitter in the brain (affecting mood, sleep, and focus)

• Helping with wound healing and circulation

In short, histamine isn’t “bad”—we need it. The problem comes when histamine levels become too high or too low, or when the body can’t break it down properly.

What Happens When Histamine is Out of Balance?

Histamine works through different receptors around the body. That’s why excess histamine can cause a wide range of symptoms:

• Sinuses → hay fever, blocked nose, excess mucous

• Eyes → watery, itchy, or red eyes

• Gut → reflux, bloating, nausea, diarrhea or constipation

• Skin → eczema, acne, hives, itching, flushing

• Heart → racing pulse, changes in blood pressure

• Lungs → asthma or chronic cough

• Brain → anxiety, irritability, insomnia, migraines

Some people feel their symptoms flare at certain times—like around ovulation (due to higher oestrogen) or after eating high-histamine foods.

High Histamine Symptoms

This is the most common pattern and may include:

• Headaches or migraines

• Fatigue, anxiety, or irritability

• Nausea (including morning nausea)

• Gut pain, bloating, digestive upset, reflux, or food sensitivities

• Insomnia or restless sleep

• Asthma or shortness of breath

• Sinus congestion or frequent “allergy” symptoms

• Skin reactivity (rashes, hives, eczema, flushing, bug-bite reactions)

• Joint pain, muscle aches, connective tissue pain (via inflammatory pathways)

• Low blood pressure, dizziness, palpitations

• Menstrual issues (PMS, endometriosis, heavy or painful periods)

Low Histamine Symptoms

Less common, but can still cause issues such as:

• Weak digestion (low stomach acid, constipation)

• Cold hands and feet

• Low mood, brain fog, or fatigue

• Low libido

• Poor wound healing or immune response

  
  

Why Does Histamine Become a Problem?

There are a few main reasons:

1. Too much histamine coming in (from food, gut bacteria, infections, mould, or even oestrogen surges)

2. Poor breakdown of histamine (due to genetics, enzyme deficiencies, gut issues, or certain medications)

3. Mast cell over-activation (mast cells release histamine in response to triggers like stress, infections, mould, or allergens)

Normally, enzymes like DAO (diamine oxidase) and HNMT (histamine N-methyltransferase) help clear histamine. But if these pathways aren’t working well—often due to nutrient deficiencies, gut imbalances, or genetic factors—histamine builds up.

HIT vs MCAS – What’s the Difference?

• HIT → A problem with breaking down histamine (too much builds up).

• MCAS → A problem with mast cells releasing histamine and other mediators inappropriately.

Both can overlap, and some people may actually have both conditions.

Histamine Intolerance (HIT)

This platter is a histamine overload!

HIT occurs when your ability to clear histamine is reduced. This can be from:

• Low DAO enzyme activity (due to genetics, gut damage, or nutrient deficiencies)

• High-histamine foods (fermented, aged, leftover foods, alcohol, etc.)

• Medications or alcohol that block histamine breakdown

Symptoms tend to flare after meals or during hormonal shifts (such as ovulation, PMS, or perimenopause).

Mast Cell Activation Syndrome (MCAS)

MCAS is different. Here, your mast cells (a type of immune cell) become overactive and unstable, releasing not just histamine but also prostaglandins, leukotrienes, cytokines, and other inflammatory chemicals.

This means MCAS symptoms are usually broader and less predictable. Triggers can include foods, stress, temperature changes, infections, mould exposure, or even strong smells.

Underlying Triggers of Histamine Overload or Mast Cell Instability

Histamine overload or mast cell instability is rarely an isolated issue. It often connects with other root causes, including:

• Mould toxicity – mycotoxins can trigger mast cell activation and histamine release.

• Post-viral activation syndromes – after infections like COVID-19 or Epstein-Barr virus, immune dysregulation can persist, leading to histamine and mast cell issues.

• Gut imbalances – dysbiosis, candida and leaky gut can increase histamine production and reduce DAO activity.

• Nutrient deficiencies – vitamin B6, zinc, copper, vitamin C, and magnesium are all important for histamine breakdown or balance.

• Methylation issues -

  One key piece of the puzzle is methylation—a process that controls how our genes work and how well we clear chemicals like histamine.

  • If methylation is working well → histamine is broken down properly.

  • If methylation is sluggish → histamine builds up, leading to symptoms.

  • Certain genetic variations (like MTHFR) can make this process less efficient.

  Nutrients such as active B vitamins (especially B12 and folate), magnesium, zinc and copper play important roles in methylation and histamine clearance.

  
  

Why Antihistamines Aren’t a Complete Solution

Antihistamines (like H1 or H2 blockers) can temporarily reduce symptoms by blocking histamine receptors, but they don’t reduce overall histamine levels in the body. Long-term, they can sometimes worsen the imbalance, as the body may compensate by producing or releasing more histamine.

A more sustainable approach involves supporting histamine breakdown, stabilizing mast cells, and addressing underlying causes.

Next Steps – What You Can Do

If you suspect histamine intolerance or MCAS, here are some helpful directions to consider:

1. Track symptoms and diet – keeping a food/symptom diary can reveal hidden triggers.

2. Trial a low-histamine diet – this should be short-term and guided by a practitioner, not a permanent restriction.

   

3. Consider medications that can worsen histamine issues - e.g. NSAIDs (ibuprofen, aspirin, diclofenac, naproxen), Antidepressants (SSRIs, tricyclics like amitriptyline), Painkillers (metamizole, tramadol, morphine), Antibiotics (clavulanic acid, isoniazid, ciprofloxacin, doxycycline, metronidazole).

4. Support gut health – improve microbiome balance and gut lining integrity. Be careful of certain probiotics that can liberate histamine such as Lactobacillus acidophilus, L. caesi and L. bulgaricus.

5. Reduce triggers – address mould exposure, past infections, or chronic stress.

6. Stabilize mast cells naturally – nutrients like zinc, vitamin C, quercetin, luteolin, perilla and curcumin can help.

7. Check hormone balance – especially oestrogen dominance or perimenopausal shifts.

8. Work with a knowledgeable practitioner – to rule out other causes and tailor treatment safely.