Best Supplements for Mast Cell Activation Syndrome
Mast cell activation syndrome (MCAS) can be a challenging condition to manage, particularly for those with postviral conditions like ME/CFS and long-haul COVID. Following a viral infection, it is not uncommon for the immune system to remain in a heightened state, leading to overactive mast cells and a range of symptoms, from skin rashes and itching to more severe reactions like digestive distress, headaches, and autonomic issues. While supplements can offer support, it’s important to approach them thoughtfully and prioritize overall gut health, which may help reduce the need for supplements altogether.
How Does MCAS Develop?
Mast cells are a part of the immune system that help the body respond to threats by releasing chemicals like histamine. However, in MCAS, mast cells become overactive, releasing too much histamine even when there is no real danger. This can result in chronic inflammation and a variety of symptoms.
An imbalanced gut microbiome (dysbiosis) can contribute to this overactivity. Certain gut bacteria help produce diamine oxidase (DAO), an enzyme that breaks down histamine in the gut. When dysbiosis occurs, DAO production can drop, leading to higher histamine levels and increased mast cell reactivity. By restoring eubiosis—a healthy balance of gut bacteria—you can support natural DAO production and help stabilize mast cells. You may find that your mast cells naturally calm down, reducing the reliance on supplements.
What About Medications?
Standard medical treatments for MCAS often involve a multi-faceted approach to reduce histamine levels and stabilize mast cells. Antihistamines, both H1 and H2 blockers, are commonly used to block histamine receptors and alleviate symptoms. Non-sedating H1 blockers include cetirizine, fexofenadine, loratadine, desloratadine, and levocetirizine, while sedating options include diphenhydramine, hydroxyzine, cyproheptadine, doxepin, and ketotifen. These can be used in combination and titrated up to four times the recommended dose under medical supervision.
H2 blockers such as ranitidine, cimetidine, and famotidine are often combined with H1 blockers to provide a synergistic effect, particularly for gastrointestinal symptoms.
Other medications used in MCAS management include zileuton (to inhibit the synthesis of inflammatory mediators), aspirin (in low doses to manage prostaglandin-related symptoms), sodium cromoglycate (to prevent the release of mast cell mediators), and anti-IgE treatments to reduce mast cell degranulation.
While medications can provide relief, addressing underlying triggers, including gut dysbiosis, is an essential part of a comprehensive MCAS management strategy in the long term.
Let’s look at some supplements that may help.
Key Supplements for Mast Cell Activation Syndrome
Certain supplements can offer targeted support for managing MCAS symptoms. However, many of these supplements face bioavailability challenges—meaning the body may not absorb them well. Using advanced formulations like liposomal, emulsified, or nanoparticle-based supplements may improve absorption.
Here are some of the best research-backed options:
1. Vitamin C
How It Helps: Vitamin C is a natural antihistamine that can help stabilize mast cells, reducing the release of histamine and other inflammatory mediators. It also has antioxidant properties that support overall immune balance.
Food Sources: While citrus fruits, strawberries, and kiwi are traditionally rich in vitamin C, they are also high in histamine, which may not be suitable for those with MCAS. Instead, low-histamine sources of vitamin C include broccoli, bell peppers, and cauliflower.
Supplement Tips: Liposomal vitamin C can enhance bioavailability. Doses often range from 500-2,000 mg daily, but higher doses may be necessary for therapeutic effects.
2. Quercetin
How It Helps: Quercetin is a flavonoid with strong antihistamine and anti-inflammatory properties. It can stabilize mast cells and reduce histamine release.
Food Sources: Found in apples, onions, capers, and berries.
Supplement Tips: Quercetin’s bioavailability is limited, so forms like quercetin phytosome or liposomal quercetin may be more effective. Typical dosages range from 500-1,000 mg twice daily. Read more about quercetin’s other effects in this blog post.
3. Supplemental DAO (Diamine Oxidase)
How It Helps: DAO is an enzyme that breaks down histamine in the gut. Taking DAO supplements before meals can help manage histamine from dietary sources.
Supplement Tips: Since DAO is not found in foods, it must be supplemented. Follow product instructions, usually taken about 15 minutes before meals. You can find this over-the-counter in most places. It is also available in the FullScript store for US-based readers.
4. Skullcap
How It Helps: Skullcap (Scutellaria baicalensis) is an herb known for its anti-inflammatory and antihistamine effects. It can help calm overactive mast cells.
Supplement Tips: Absorption of herbal supplements can vary, and extracts or tinctures may offer better bioavailability.
5. Perilla
How It Helps: Perilla seed extract is rich in polyphenols and can help inhibit histamine release from mast cells.
Food Sources: Perilla leaves and seeds are used in Asian cuisine. Perilla leaves pictured above.
Supplement Tips: Perilla supplements often come in oil or capsule forms. Look for high-quality extracts for better absorption.
6. Resveratrol
How It Helps: Resveratrol is a potent antioxidant with anti-inflammatory properties. It can help reduce mast cell activation and support overall immune balance.
Food Sources: Grapes, red wine, berries, and peanuts contain resveratrol. However, it is important to note that many of these foods, particularly red wine and certain berries, are also high in histamine. This makes them potentially problematic for those with MCAS, despite their resveratrol content. Opting for resveratrol supplements may be a better choice to avoid histamine exposure.
Supplement Tips: Resveratrol’s bioavailability is quite low, but micronized or liposomal formulations can improve its effectiveness.
The Importance of Dosage and Realistic Expectations
While supplements can play a role in managing MCAS, many studies on these agents are in vitro (in a lab setting), which doesn’t always translate to the same effects in the human body. It’s important to recognize that getting the right dose is crucial—often, higher doses are needed to see therapeutic benefits. Working with a healthcare provider can help ensure safety and effectiveness. Keep in mind supplement toxicity can be a real concern. Read more about that here.
The Bigger Picture: Prioritizing Gut Health
While these supplements can be valuable tools, they shouldn’t overshadow the importance of gut health. Focusing on a diet rich in prebiotics, non-histamine-producing probiotics, and gut-healing polyphenols can help restore eubiosis. Over time, this approach may reduce mast cell overactivity and, in turn, the need for supplemental support.
Conclusion
For those with mast cell activation syndrome, particularly those with ME/CFS or long-haul COVID, supplements like vitamin C, quercetin, DAO, skullcap, perilla, and resveratrol can offer relief from symptoms. These may be used in conjunction with prescribed medications in some cases. However, the ultimate goal should be to create an internal environment where these supplements are needed less and less. By focusing on gut health, you can take meaningful steps toward managing MCAS naturally and effectively. Remember, while supplements and medications can provide immediate relief, addressing the root cause through gut health is the most sustainable path forward.
References
Sumantri S, Rengganis I. Immunological dysfunction and mast cell activation syndrome in long COVID. Asia Pac Allergy. 2023;13(1):50-53. doi:10.5415/apallergy.0000000000000022
Kaag S, Lorentz A. Effects of Dietary Components on Mast Cells: Possible Use as Nutraceuticals for Allergies?. Cells. 2023;12(22):2602. Published 2023 Nov 10. doi:10.3390/cells12222602
Anogeianaki A, Castellani ML, Tripodi D, et al. Vitamins and mast cells. Int J Immunopathol Pharmacol. 2010;23(4):991-996. doi:10.1177/039463201002300403
