Peptides, including GLP-1s, are everywhere you turn these days. They are being recommended for several different conditions. You may be wondering, what is the role of GLP-1s in mast cell activation syndrome (MCAS)? Let’s break it down.
What is MCAS?
Mast cell activation syndrome is an immune system condition where mast cells, the white blood cells that release histamine and other chemicals during an allergic reaction, become overly sensitive. When mast cells become overly sensitive, they release histamine too often or too much. The overactivation of the mast cells contributes to a wide variety of symptoms across many organ systems. While symptoms vary person to person, some symptoms include skin reactions (itching, hives), digestive issues (bloating, diarrhea, nausea), respiratory symptoms (wheezing, coughing), neurological symptoms (headaches, brain fog), and cardiovascular symptoms (heart palpitations, low blood pressure).
What are the GLP-1s?
GLP-1, or glucagon-like peptide 1, is a hormone made in the human gut that helps slow digestion, contributes to feelings of satiety after meals, and helps manage blood sugar. While we use the term GLP-1s to describe the medication, the medication are in fact, GLP-1 RAs, GLP-1 receptor agonists, synthetic versions of the hormone that act on the GLP-1 receptors in the human body. This class of medication is being studied for a variety of applications.
Beyond appetite and digestion, GLP-1 RAs are being looked at for their anti-inflammatory benefits. The thought is that one of the mechanisms by which GLP-1 RAs may be working on cardiovascular disease risk, type 2 diabetes management, and sleep apnea symptoms is by lowering inflammation. Thus, the possible anti-inflammatory potential of these medications may be of use for individuals with MCAS.
Furthermore, GLP-1 receptors have been identified on mast cells. If the GLP-1 RA medications bind directly to these receptors, it is hypothesized that a signal will be sent to stabilize the mast cell. Through stabilizing the cell, the medications may limit the release of inflammatory chemicals such as histamine, tryptase, and prostaglandins, ultimately lowering the symptoms associated with MCAS.
A recent case-series highlighted that use of the GLP-1 RAs was associated with clinical benefit for 89% of patients (42 of the 47 patients) with MCAS, with participants reporting significant multisystem improvements.
While promising, it is important to note that GLP-1 RAs are not yet approved for the treatment of MCAS. The study mentioned was a case series rather than a randomized controlled trial so the quality of evidence is lower and there may be several other factors contributing to the findings.
The authors of the study do acknowledge that GLP-1 RA therapy alone will likely not be sufficient for maximal improvement of MCAS symptoms and that a multi-pronged approach will be of most benefit.
Similar to the general population, the medication is only one tool in the toolbox and should not replace other lifestyle components, such as nutrition, movement, sleep, and stress management.
While more understanding is needed to know the exact risks and benefits of GLP-1 RA for MCAS patients, there is promise.
Some considerations if exploring GLP-1 RA for MCAS:
If you or someone you know is considering this medication class to manage MCAS, we recommend:
- Make an informed decision with support of your medical team, with all of the risks and benefits discussed.
- Meet regularly with your team and get routine lab work to assess for nutritional deficiencies and monitor inflammatory markers
- Meet with a registered dietitian who specializes in nutrition for GLP-1, alongside nutrition for MCAS, to ensure you are getting and maintaining adequate nutrition.
- In addition to weight trends, also consider measuring changes in body composition to trend lean mass over time.
The team at LCWNS is here to support you on your MCAS and GLP-1 journey.
To learn more about GLP-1s and nutrition, check out our podcast Eat Kale and Cupcakes, particularly episode 3 on GLP-1 RAs.
Also, check out our GLP-1 Master Class.
Schedule a session with one of our RDs for an individualized approach.
References:
Afrin LB, Weinstock LB, Dempsey TT, Aschenbrenner K, Blitshteyn S, Schofield JR. Utility of glucagon-like-peptide-1-receptor agonists in mast cell activation syndrome. Am J Med Sci. 2025;370(4):377-382. doi:10.1016/j.amjms.2025.07.006
