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Identifying Histamine Intolerance: Causes, Symptoms and Diagnosis of Food Intolerances

Overview of Laboratory Services

Histamine intolerance (HIT) is a common but non-immunological metabolic disorder that is often classified as a pseudoallergic reaction due to its symptomatology, which resembles that of an IgE-mediated food allergy. The condition arises from an imbalance between the tissue hormone histamine and its degradation in the body.

The organism must manage elevated histamine levels in various scenarios:

  • following the release of endogenous histamine (produced within the body),
  • through excessive intake of dietary histamine (exogenous histamine), or
  • as a result of increased microbial histamine synthesis by the intestinal microbiota.

Two enzymes are responsible for histamine in the body:

  1. Diamine oxidase (DAO) (formerly known as histaminase) – continuously produced and released by cells in the intestine, kidneys, and placenta. DAO is primarily responsible for degrading dietary histamine.
  2. Histamine-N-methyltransferase (HNMT) – this enzyme is active in most body tissues and is responsible for breaking down endogenous histamine.

When does histamine intolerance develop?

Reduced enzymatic activity of DAO in the intestine may result from various causes, either congenital or acquired:

  • Genetic predisposition
  • Lack of cofactors
  • Use of medications (which inhibit enzyme activity)
  • Excessive histamine levels/insufficient enzyme levels
  • Inflamed intestinal mucosa

Symptoms of Histamine Intolerance

The hallmark symptoms of histamine intolerance include:

  • Headaches
  • Flushing (skin redness)
  • Nausea
  • Shortness of breath

Additional accompanying symptoms may include:

  • Diarrhoea
  • Skin eczema (itchiness)
  • Urticaria flare-ups
  • Low blood pressure (below 100/60 mmHg)
  • Nasal mucosal inflammation
  • Asthma attacks

Foods that Trigger Histamine Intolerance

Histamine is primarily formed during prolonged storage or ageing of foods due to microbial metabolic activity. The following table offers a brief overview of foods that are either low or high in histamine:

Food Category

Low in Histamine

High in Histamine

Meat/sausages

Fresh fish, minced meat

Smoked, cured, dried, marinated meats; raw ham; salami

Cheese

Fresh cheeses (e.g. mozzarella, butter cheese, feta)

Aged cheeses (e.g. Edam, Emmental, Gouda, Tilsit, Parmesan, Camembert)

Vegetables

Fresh lettuce, courgette, pumpkin, cucumber, peppers, potatoes

Sauerkraut, avocado, spinach, tomatoes (including ketchup and tomato paste)

Treatment for Food-related Histamine Intolerance

Once food-related histamine intolerance is diagnosed, a strict change in diet forms the foundation of effective therapy. In the elimination phase, high-histamine foods should be avoided for approximately 2 weeks. During the challenge phase (lasts up to 6 weeks), suspected trigger foods are gradually reintroduced to identify individual tolerance levels. In the final maintenance phase, a personalized long-term diet plan should reflect the patient’s known histamine tolerance.

Laboratory Diagnostics for Histamine Intolerance

Depending on clinical presentation and diagnostic questions, a range of tests may be used to investigate histamine intolerance. Relevant analyses include:

  • Histamine in plasma
  • Histamine in whole blood
  • Histamine in stool
  • DAO activity
  • DAO genotype (genetic test)
  • DAO cofactors – vitamin B6, copper, zinc, small blood count
  • Histamine metabolism