A Functional Medicine Approach to Mast Cell Activation Syndrome (MCAS)

Mast Cell Activation Syndrome (MCAS) is a complex and often underdiagnosed condition in which mast cells—an essential part of the immune system—become dysregulated and release mediators like histamine, prostaglandins, and cytokines inappropriately. This can result in a wide array of symptoms ranging from fatigue and brain fog to skin reactions, gastrointestinal issues, and even anaphylaxis-like responses.

While conventional medicine typically focuses on antihistamines and mast cell stabilizers, functional medicine seeks to address the root causes and restore balance to the immune system. Below are three key tools often used in a functional medicine approach to MCAS: Low Dose Naltrexone (LDN), Ketotifen, and an Anti-Inflammatory Diet.

1. Low Dose Naltrexone (LDN): Calming the Overactive Immune Response

Low Dose Naltrexone (LDN) is a compounded medication that works by transiently blocking opioid receptors, which paradoxically results in an upregulation of the body’s natural endorphins and enkephalins. These molecules don’t just influence mood and pain—they also have immunomodulatory effects.

In MCAS, where the immune system is inappropriately reactive, LDN appears to help by:

• Reducing pro-inflammatory cytokines

• Modulating T-cell activity

• Stabilizing mast cells indirectly

• Improving resilience to triggers like stress, infection, or allergens

LDN is not a cure, but many patients report significant improvement in fatigue, brain fog, and inflammatory symptoms over time. Doses typically range from 0.5 mg to 4.5 mg, individualized to patient tolerance.

2. Ketotifen: Stabilizing the Mast Cells

Ketotifen is a lesser-known but powerful mast cell stabilizer and H1 antihistamine, typically available through compounding pharmacies in the U.S. Unlike common over-the-counter antihistamines, ketotifen has dual action:

• It prevents mast cell degranulation, reducing the release of histamine and other inflammatory mediators.

• It blocks histamine receptors, reducing downstream symptoms like flushing, hives, or gastrointestinal distress.

In functional medicine, ketotifen is often used as a bridge therapy to help control symptoms while deeper root causes—like gut dysbiosis, mold exposure, or chronic infections—are addressed.

Common starting doses are 0.5–1 mg at bedtime, with titration based on response and side effects. Some patients may experience drowsiness initially.

3. Anti-Inflammatory Diet: Lowering the Baseline Fire

Food is medicine—or it’s fuel for the fire. An anti-inflammatory diet is foundational in managing MCAS. Because mast cell activation can be triggered by inflammatory foods and gut permeability (leaky gut), removing dietary triggers is crucial.

Core Principles:

• Eliminate high-histamine foods: Fermented foods, aged cheeses, alcohol, and leftovers can exacerbate symptoms.

• Avoid common allergens: Gluten, dairy, soy, and artificial additives can be mast cell irritants.

• Focus on whole, nutrient-dense foods:

  • Fresh, organic vegetables and fruits (especially low-histamine options like blueberries, zucchini, and leafy greens)

  • Wild-caught fish (rich in omega-3s)

  • Healthy fats (olive oil, avocado, coconut oil)

  • Clean protein (pasture-raised meats, collagen peptides)

Supportive additions:

• Quercetin, Vitamin C, and DAO enzymes can support histamine breakdown and reduce reactivity.

• Gut healing protocols, including bone broth, L-glutamine, and probiotics, are often introduced after stabilization.

  
  

Final Thoughts

Managing MCAS requires more than simply suppressing symptoms. The functional medicine model offers a systems-based approach, aiming to rebalance the immune system, identify root triggers, and restore resilience.

Low Dose Naltrexone, Ketotifen, and an Anti-Inflammatory Diet form a triad that many patients with MCAS find transformative when personalized and used under professional guidance.

As always, work with a knowledgeable healthcare provider to tailor any treatment to your specific needs—especially when using compounded medications or navigating complex immune conditions.

Interested in personalized care for MCAS or other immune-related conditions?Schedule a consultation at Direct Integrative Care to explore functional medicine solutions tailored to you.

Dr. Kim offers telemedicine integrative & functional medicine services serving IL, MO, TX, GA, and FL. He has a special emphasis serving areas near Quincy IL - Hannibal MO - Carthage IL, Keokuk IA and Macomb IL.

Yoon Hang Kim MD.

www.yoonhangkim.com