Low Dose Naltrexone (LDN)
Low‑dose naltrexone (LDN) is a low dose of naltrexone that is thought to briefly block opioid receptors to boost natural endorphins and support immune balance.
Mast Cell Activation Syndrome (MCAS) is a complex disease made up of varying triggers and unpredictable reactions. Typically requiring lifelong management and drug therapy, its root cause is unknown. MCAS symptoms involve multiple body systems because mast cells are everywhere, located in organs and tissues protecting against foreign invaders/allergens. In response to a threat or trigger, mast cells activate and release chemical mediators like histamine.
In MCAS, mast cells become hyper-reactive and unstable, responding to a combination of stressors that may seem utterly benign to the average immune system. The body responds in a dysregulated and outsized manner with inconsistent flares of reactivity that are difficult to predict and control.
MCAS patients tend to be highly sensitive to medication excipients, making compounded therapies a desirable option for disease support. A multimodal approach is often required: antihistamines for mast cell activation syndrome to block histamine receptors, compounded ketotifen as a mast cell stabilizer, cromolyn or cholestyramine for gut related issues, and low dose naltrexone to mitigate the inflammatory response.
Our MCAS Medications
Ketotifen Fumarate (Clear) MCC
Ketotifen is a first‑generation antihistamine and a mast cell stabilizer that can gradually reduce the reactivity of mast cells, preventing the release of additional chemical mediators beyond histamine.
Cholestyramine
Cholestyramine is a nonabsorbable resin that binds bile acids in the intestine to block their reuptake, increase fecal bile salt loss, and support non‑systemic effects.
About Mast Cell Activation Syndrome (MCAS)
Causes
While the actual cause of the disease is unknown, it’s thought that 7 root causes of mast cell activation syndrome exist. These 7 factors are not root causes but triggers, commonly known to precipitate sensitivity reactions in many MCAS patients. Physical, emotional, and environmental stressors can lead to a variable response – not every patient will react in the same way. Exposure to one trigger alone may not prompt a reaction initially, but the additive effect of two or more could elicit a different response. Avoidance is key for disease management.
Physical triggers
Hot or cold temperatures, insect stings and bites, as well as exercise are physical stressors that can result in flushing or hives.
Medications and excipients
The active pharmaceutical ingredient may be well tolerated, while the inactive ingredients (excipients) can be activating for mast cells.
Specific foods or substances
Foods high in histamine such as leftovers or alcohol can result in gastrointestinal symptoms because mast cells line the GI tract.
Emotional stress
Trauma, stress-induced overwhelm, or sleep deprivation activates the body’s stress response and mast cells.
Hormonal fluctuations
Perimenopause, menstruation, and pregnancy can all impact estrogen and progesterone levels and lower the activation threshold of mast cells.
Environmental exposure
Odors, mold, or even cleaning products can induce unpredictable reactions.
Infection
Viruses, bacterial, and chronic inflammation trigger an immune cascade involving cytokines that sensitize and (activate) mast cells.
Symptoms
MCAS symptoms are due to mast cell mediator release and can vary significantly patient to patient. The underlying mechanism is not like a standard allergic reaction. Wildly unpredictable, responses range from mild to extreme, encompassing minor inflammation to major life-threatening anaphylaxis. An MCAS diagnosis is associated with problems that may span the entire body:
- Cardiovascular: Rapid heart rate, blood pressure changes, passing out
- Gastrointestinal: Nausea, diarrhea, vomiting, abdominal discomfort, reflux
- Genitourinary: Cramps/bleeding, bladder problems
- Neurological: Brain fog or cognitive issues, headache, mood changes
- Respiratory: Nasal congestion, throat itching/swelling, difficulty breathing or wheezing
- Skeletal: Bone or muscle pain
- Skin: Flushing of the face and neck, rashes or hives, itching
Therapies
MCAS patients are commonly recommended to avoid dyes and certain preservatives because ingredients considered inactive can be biologically active for patients with the disease. Custom compounds are formulated with limited additive ingredients, a significant benefit for highly sensitive patient populations.
Antihistamines for mast cell activation syndrome are a mainstay of therapy and include first and second generation H1 antihistamines like hydroxyzine and ketotifen respectively, as well as H2 antihistamines such as famotidine. These drugs target different histamine receptors, controlling different effects of histamine release:
- H1 antihistamines are designed to limit symptoms related to a stereotypical allergic reaction, such as itching and flushing.
- H2 antihistamines help reduce GI effects and immune signaling while helping maintain proper blood vessel function.
- Both are often taken together as MCAS medications to limit downstream effects of histamine.
Compounded ketotifen as an oral capsule can do more than block histamine – it is a mast cell stabilizer, gradually reducing the reactivity of mast cells. Ketotifen may also prevent the release of additional chemical mediators beyond histamine. Its dual mechanism of action helps address immediate MCAS symptoms and can benefit long-term management of the condition.
Low dose naltrexone (LDN) provides an antagonistic effect on toll-like receptor 4 (TLR4) found on macrophages, immune cells in charge of the body’s first line of defense. This receptor is involved in mast cell activation and other inflammatory signaling. By acting as an immune modulator, LDN can inhibit TLR4 and decrease mast-cell reactivity and inflammation. Patients may also find their day-day pain diminished and experience better cognitive function and state of mind. Additionally, LDN therapy is known to upregulate endorphins and has promise for improving quality of life for patients plagued with fatigue.
Cromolyn can prevent localized mast cell degranulation in the gut. Degranulation is the process during which mast cells release their chemical mediators. For MCAS patients with GI discomfort and bloating connected to food, cromolyn can offer symptom relief.
Cholestyramine can bind bacterial and mold related toxins in the gut and help remove them, reducing MCAS triggers. Because mast cells are so highly concentrated in the gut, GI irritation can continuously provoke a state of activation and worsen overall symptoms.
Commonly Asked Questions About MCAS
Mast Cell Activation Syndrome (MCAS) is a collection of immune system issues where mast cells become hyper-reactive and unstable. Normally, mast cells activate and release chemical mediators like histamine in response to foreign invaders. In MCAS, mast cells respond in a dysregulated manner to a combination of triggers that may appear benign to the average immune system. As a result, patients experience inconsistent flares of reactivity that are difficult to predict and control.
MCAS diagnosis involves an expert evaluation of symptoms, clinical exam, and lab tests. Symptoms of mast cell activation syndrome can vary patient to patient, and other conditions usually need to be excluded beforehand. Lab tests can be a challenging diagnostic tool because some need to be drawn soon after a flare and compared to baseline, like with specific marker serum tryptase.
MCAS and postural orthostatic tachycardia syndrome (POTS) are often connected. Mast cells release chemical mediators that impact blood vessels and nerves, making it harder for the body to regulate heart rate and blood flow while standing. These autonomic signaling problems are characteristic of POTS. Patients can be diagnosed with both and experience overlapping symptoms. It’s important to investigate the presence of MCAS in patients diagnosed with POTS, because underlying mast cell dysregulation can exacerbate POTS symptoms and make it harder for patients to experience symptom relief.
