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Antihistamines and Their Role in Managing Mast Cell Activation Syndrome (MCAS)

Updated: Jun 14

Mast Cell Activation Syndrome (MCAS) is a condition characterised by the inappropriate and excessive release of mast cell mediators, leading to a variety of chronic symptoms affecting multiple organ systems . Effective management often requires a combination of medications, including antihistamines, mast cell stabilisers, and other therapeutic agents. Let's touch on different types and classes of antihistamines, their combinations, and other medications used in MCAS management, specifically focusing on those available in Australia.

Types and Classes of Antihistamines

Antihistamines are medications that block the action of histamine, a key mediator released by mast cells. They are classified into two main categories:

H1 Antihistamines:

  • First-Generation H1 Antihistamines (Sedating): These older antihistamines are known for their sedative properties because they can cross the blood-brain barrier. Examples available in Australia include diphenhydramine, chlorpheniramine, and promethazine (Phenergan) .

  • Second-Generation H1 Antihistamines (Less Sedating): These newer antihistamines are less sedating as they do not readily cross the blood-brain barrier. Examples available in Australia include cetirizine, loratadine, and fexofenadine.

H2 Antihistamines:

  • H2 antihistamines target histamine receptors in the stomach lining, reducing acid production. They are commonly used to manage gastrointestinal symptoms in MCAS. Examples available in Australia include famotidine.

Combination Therapy

For many patients with MCAS, a combination of H1 and H2 antihistamines is necessary to achieve adequate symptom control. This dual approach helps address a broader range of symptoms, from skin reactions to gastrointestinal issues.

  • Example Regimen: A typical combination might include cetirizine (10 mg twice daily) for H1 receptor blockade and famotidine (20-40 mg once or twice daily) for H2 receptor blockade. These are taken at the same time . Standard lower doses are not effective for MCAS.

Other Medications Used in MCAS

In addition to antihistamines, several other classes of medications are commonly used to manage MCAS:

Mast Cell Stabilisers:

  • These include cromolyn sodium, and ketotifen. They help prevent the release of mast cell mediators and are available only through compounding chemists in Australia .

Leukotriene Inhibitors:

  • Leukotrienes are another type of mediator released by mast cells. Medications like montelukast 10 mg once a day are available in Australia and can help manage symptoms related to leukotriene release .


  • In low doses, aspirin can inhibit the production of prostaglandin D2, a mast cell mediator involved in inflammatory responses. However, it is used with caution due to potential sensitivity, gastric erosion, or bleeding .


  • These anti-inflammatory medications, such as prednisone, are used for short-term management of severe flare-ups. Long-term use is generally avoided due to potential side effects .


  • Medications like omalizumab have been used off-label for MCAS. These drugs target IgE, a key antibody involved in allergic reactions and mast cell activation .

Lifestyle and Dietary Modifications

In addition to pharmacological treatments, lifestyle and dietary modifications can play a significant role in managing MCAS. Patients are often advised to:

  • Identify and Avoid Triggers: Common triggers include certain foods, stress, temperature changes, and environmental factors .

  • Follow a Low-Histamine Diet: This can help reduce the overall histamine load in the body, minimising symptoms .

  • Maintain a Symptom Diary: Tracking symptoms and potential triggers can aid in identifying patterns and adjusting treatment plans accordingly.

  • Probiotics:

Supporting gut health can be crucial for managing MCAS .

Supplements and Vitamins

Certain supplements and vitamins can play a supportive role in managing MCAS. These can help reduce inflammation, stabilise mast cells, and support overall health:

Slow-Release Vitamin C:

  • Dosage: 500-2000 mg per day, divided into smaller doses to maintain consistent blood levels and to avoid stomach upset. Maintenance dose for individuals with MCAS is generally around 500 mg to 1,000 mg per day. Start low and build up

Other useful supplements are:

Vitamin D and Vitamin K:

  1. Vitamin D Dosage: 1000-5000 IU per day.

  2. Vitamin K2 Dosage: 90-120 mcg per day .

  3. Quercetin: Dosage: 500-1000 mg twice daily .

  4. B Vitamins: Particularly B6 and B12, essential for proper immune function and stress reduction .

  5. Magnesium: Dosage: 200-400 mg per day .

  6. Omega-3 Fatty Acids: Dosage: 1000-3000 mg per day .


Managing Mast Cell Activation Syndrome requires a comprehensive approach that includes various classes of antihistamines, mast cell stabilisers, supplements, vitamins, and other supportive medications. Combination therapy is often necessary to address the multifaceted nature of the condition. Working closely with a knowledgeable clinician is crucial to tailor treatment plans to individual needs and optimise symptom control.

If you or someone you know is struggling with MCAS, consult with a healthcare provider to develop a personalised management plan. With the right combination of medications, supplements, and lifestyle adjustments, many patients can achieve significant relief and improve their quality of life.

By Dr Purity Carr

GP & Menopause Doctor

Harvey WA, 6220

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