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Stress Busters: Rhodiola & L-Theanine

Body Wisdom

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Mast Cell Activation Support

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Mast Cell Activation Syndrome (MCAS) How It Is Diagnosed - And What Science Says About Supportive Supplements Mast Cell Activation Syndrome, or MCAS, is a condition where part of your immune system becomes overly reactive. It can be confusing, frustrating, and difficult to diagnose - because symptoms can affect many different parts of the body. Let’s break it down clearly. What Are Mast Cells? Mast cells are immune cells found throughout your body - especially in your: Skin Gut Lungs Blood vessels Nervous system Their job is protective. When they detect a threat, they release chemical messengers like: Histamine Prostaglandins Leukotrienes Cytokines These chemicals help fight infection and coordinate healing. But in MCAS, mast cells release these chemicals too easily, too often, or in excessive amounts - sometimes without a clear trigger (Molderings et al., 2011; Castells & Butterfield, 2019). What Are the Symptoms of MCAS? Because mast cells live in many tissues, symptoms often affect multiple systems at once. Common symptoms include: Flushing, itching, hives (skin affected) Nasal congestion or wheezing (sinuses or lungs affected) Abdominal pain, bloating, diarrhea (gut affected) Headaches or brain fog (brain affected) Rapid heart rate or lightheadedness (heart and blood vessels/cardiovascular system affected) Fatigue (brain and nervous system affected) Sensitivity to foods, smells, medications, heat, or stress (nervous system and more affected) Symptoms often flare and settle. They can resemble allergic reactions or even anaphylaxis. How Is MCAS Diagnosed? Diagnosis is not based on symptoms alone. International expert guidelines require all three of the following criteria (Weiler et al., 2019; Valent et al., 2024; Parente et al., 2023): 1. Recurrent attacks affecting at least two organ systems Episodes usually resemble allergic or anaphylaxis-like reactions. For a diagnosis to be made, symptoms must involve more than one body system at the same time. For example, someone might experience digestive symptoms along with brain symptoms such as dizziness or brain fog, or skin symptoms like hives along with gut or cardiovascular symptoms. 2. Objective evidence that mast cells were activated during the episode This is the key laboratory step. The most important test is serum tryptase , drawn within about 4 hours of a flare and compared to your baseline level. Doctors use what is called the “120% + 2 rule” : Event tryptase must be ≥ baseline × 1.2 + 2 ng/mL (Valent et al., 2024; Weiler et al., 2019; Beck et al., 2019). If tryptase does not rise, other supportive tests may include urine measurements of: N-methylhistamine Leukotriene E4 (LTE4) Prostaglandin D2 metabolites These are collected a few hours after symptoms and compared with baseline levels (Voelker & Pongdee, 2024; Hamilton, 2024). 3. Clear improvement with mast-cell–directed treatment Improvement with medications such as: H1 antihistamines H2 antihistamines Cromolyn Leukotriene blockers supports the diagnosis (Weiler et al., 2019; Parente et al., 2023). If baseline tryptase is persistently elevated or other concerning features are present, doctors may test for a more severe version of mast cell activation called clonal mast cell disease (mastocytosis) using: KIT D816V genetic testing Bone marrow biopsy Specialized mast cell markers (Romantowski et al., 2021; Navarro-Navarro et al., 2025). Standard Medical Treatment Comes First First-line therapy for MCAS typically includes medications that: Block histamine (H1 and H2 blockers) Stabilize mast cells (cromolyn, ketotifen) These are considered foundational (Molderings et al., 2011; Molderings et al., 2016; Castells & Butterfield, 2019). Supplements are sometimes used as adjuncts - meaning add-ons to medical treatment - not replacements for it. Some people choose to try supplements on their own if they have symptoms of mast cell activation but do not meet the full diagnostic criteria for MCAS and are therefore not prescribed medication. In either case, it is important to understand what the science actually says about these supplements before using them for symptom support or disease management. A Reality Check About Supplements Before discussing nutrients, it’s important to understand: Most supplement research is not specific to MCAS Many studies are cell-based or animal studies Dedicated large MCAS trials are limited People with MCAS often react to fillers or additives (Schofield & Afrin, 2019) Higher doses are not always better Supplements should be individualized and supervised by a clinician familiar with mast cell disorders. Palmitoylethanolamide (PEA): A Key Mast Cell Modulator PEA is a fatty acid compound your body naturally produces to help calm inflammation. It works by: Activating PPAR-alpha receptors Modulating the endocannabinoid system Reducing mast cell activation Early human research showed PEA can directly reduce mast cell activation - a mechanism sometimes called the “ALIAmide” effect (Facci et al., 1995; Skaper et al., 2013). Human Evidence Relevant to Mast Cells Functional dyspepsia (upper gut discomfort) Functional dyspepsia is a digestive condition where you have ongoing upper stomach discomfort without an ulcer, infection, or visible problem on standard tests. Common symptoms include burning or aching pain in the upper abdomen, feeling overly full after small meals, bloating, nausea, or early fullness when eating. It is sometimes described as chronic “indigestion” with no clear structural cause. Researchers found patients with functional dyspepsia had impaired natural PEA release and increased mast cell activation. Adding PEA to biopsy tissue reduced mast cell activation and pain signaling (Sarnelli et al., 2020). Mastocytosis Altered PEA metabolism has been observed in patients with systemic mastocytosis (Ferrara et al., 2019). Irritable Bowel Syndrome A randomized trial found PEA reduced abdominal pain, even though mast cell numbers did not change - suggesting calming effects rather than elimination (Cremon et al., 2017). Allergic rhinitis A placebo-controlled trial showed reduced histamine and inflammatory markers with PEA supplementation (Briskey et al., 2023). Typical Doses Studied 300–600 mg per day is most common Some trials use up to 1200 mg short term Systematic reviews suggest higher doses do not always add benefit (Gabrielsson et al., 2016; Bortoletto et al., 2024; Galla et al., 2024). Other Nutrients That Influence Mast Cells 1. Flavonoids (Plant Compounds) Certain plant compounds strongly inhibit mast cell mediator release in lab and animal studies. Notable examples: Quercetin Luteolin Resveratrol Curcumin EGCG (green tea) Quercetin and luteolin are among the most studied dietary mast cell inhibitors (Theoharides & Bielory, 2004; Kaag & Lorentz, 2023). Most human quercetin trials use 500–1000 mg/day (500 mg once or 500 mg twice daily) for up to 12 weeks. In human studies, luteolin supplements are usually taken in amounts of about 50 to 100 mg per day for several weeks or months. There is no official recommended dose, and we do not yet have strong long term safety data for higher amounts. EGCG has shown dose-dependent mast cell stabilization in animal models (Islam et al., 2025). For adults, most research suggests keeping total supplemental EGCG around 200 to 300 mg per day. Doses above 800 mg per day are generally not recommended because higher amounts have been linked to potential liver stress or toxicity. Human MCAS-specific trials remain limited. 2. Vitamins and Minerals Vitamin D Helps stabilize mast cells. Deficiency is associated with increased spontaneous activation (Liu et al., 2017). Vitamin C Helps degrade histamine and reduce mast cell degranulation (Molderings et al., 2011). Vitamin B6 May work synergistically with vitamin C to inhibit mast cell release (Kazama et al., 2022). Magnesium and zinc Have shown mast cell–stabilizing effects in experimental models (Kazama et al., 2025). 3. Gut-Derived Metabolites Your gut microbiome influences mast cell behavior. Butyrate and propionate , produced by healthy gut bacteria, strongly inhibit human mast cell activation through epigenetic mechanisms (Folkerts et al., 2020). Certain amino acid combinations may also reduce mast cell mediator release in gut models (Uranga et al., 2020). The Bottom Line MCAS is diagnosed using three required criteria : Recurrent multi-system symptoms Laboratory evidence of mast cell mediator rise during flares Improvement with mast-cell–targeted therapy (Weiler et al., 2019; Valent et al., 2024; Parente et al., 2023) Standard medications remain foundational. Research suggests that several supplements - especially PEA - may help calm mast cells at a biological level. Other supportive nutrients include flavonoids, vitamin D, vitamin C with B6, magnesium, zinc, and gut-derived short-chain fatty acids. However: Dedicated MCAS trials are limited Individual tolerance varies Supplements should be adjunctive, not replacements Professional supervision is essential Mast cell biology is complex - and personalized care matters. If you see yourself in these symptoms, know that you are not alone, and with the right testing, guidance, and personalized support, it is possible to better understand your body and calm the cycle of mast cell activation. References Molderings G et al. Mast cell activation disease: diagnostic workup and therapy. J Hematol Oncol. 2011. PMID: 21306600. Castells M, Butterfield J. Mast cell activation syndrome and mastocytosis. J Allergy Clin Immunol Pract. 2019. PMID: 30910418. Weiler C et al. AAAAI Mast Cell Disorders Committee Work Group Report: Mast Cell Activation Syndrome (MCAS) Diagnosis and Management. J Allergy Clin Immunol. 2019. PMID: 31537491. Valent P et al. Reversible Elevation of Tryptase Over the Individual's Baseline. Curr Allergy Asthma Rep. 2024. PMID: 38521914. Parente R et al. Secretory and Membrane-Associated Biomarkers of Mast Cell Activation. Int J Mol Sci. 2023. PMID: 37109806. Beck S et al. Biomarkers in Human Anaphylaxis. Front Immunol. 2019. PMID: 31057633. Voelker D, Pongdee T. Urine Mast Cell Mediators in MCAS. Curr Allergy Asthma Rep. 2024. PMID: 38331348. Hamilton M. Mast Cell Activation Syndrome and Gut Dysfunction. Curr Gastroenterol Rep. 2024. PMID: 38520738. Romantowski J et al. Application of Allergy Diagnostic Methods in Mast Cell Disorders. Int J Mol Sci. 2021. PMID: 33668645. Navarro-Navarro P et al. Improved diagnostic screening of clonal mast cell diseases. Blood. 2025. Molderings G et al. Pharmacological treatment options for MCAD. Naunyn Schmiedebergs Arch Pharmacol. 2016. PMID: 27180236. Schofield J, Afrin L. Medication excipient reactivity in MCAS. Am J Med Sci. 2019. PMID: 31097234. Facci L et al. Mast cells express a peripheral cannabinoid receptor. Proc Natl Acad Sci USA. 1995. PMID: 7724575. Skaper SD et al. Glia and mast cells as targets for palmitoylethanolamide. Mol Neurobiol. 2013. PMID: 23440402. Sarnelli G et al. Impaired duodenal PEA release underlies mast cell activation. Cell Mol Gastroenterol Hepatol. 2020. PMID: 33189806. Ferrara AL et al. Altered endocannabinoid metabolism in mastocytosis. J Immunol Res. 2019. PMID: 31281611. Cremon C et al. PEA and polydatin in IBS. Aliment Pharmacol Ther. 2017. PMID: 28083828. Briskey D et al. PEA supplementation in allergic rhinitis. Nutrients. 2023. PMID: 38066668. Gabrielsson L et al. PEA pharmacokinetics and efficacy. Br J Clin Pharmacol. 2016. PMID: 26817640. Bortoletto R et al. PEA supplementation systematic review. Brain Behav Immun Health. 2024. PMID: 38719586. Galla R et al. Dose-dependent effects of PEA. Int J Mol Sci. 2024. PMID: 39201487. Theoharides TC, Bielory L. Mast cells as targets of dietary supplements. Ann Allergy Asthma Immunol. 2004. PMID: 15328675. Kaag S, Lorentz A. Dietary effects on mast cells. Cells. 2023. PMID: 37960888. Islam M et al. EGCG stabilizes mast cells in vivo. Inflammopharmacology. 2025. PMID: 39962387. Liu Z et al. Vitamin D and mast cell stabilization. Allergy. 2017. PMID: 28261828. Kazama I et al. Pyridoxine and vitamin C synergism. Cell Physiol Biochem. 2022. PMID: 35383741. Kazama I et al. Magnesium and zinc stabilize mast cells. Cell Physiol Biochem. 2025. PMID: 40023811. Folkerts J et al. Butyrate inhibits human mast cell activation. Allergy. 2020. PMID: 32083336. Uranga J et al. Nutraceutical regulation of mast cells. Molecules. 2020. PMID: 33023128.

Dr. Patricia's Core Supplements

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Candida & Yeast Support

This Fullscript community plan that I specially created for you reflects the standalone protocol Dr. Carolyn Dean used during her years in medical practice —and the one she reports seeing the most consistent improvements with when supporting patients with yeast overgrowth, particularly in the gut. The approach combines nano silver , used for its broad antimicrobial properties, with Saccharomyces boulardii , a beneficial probiotic yeast that helps displace pathogenic yeast, support gut barrier function, and restore microbial balance . Dr. Dean discusses this protocol, including when and how she used it clinically, in my interview on the Wild Wisdom Show . 🎥 Watch the full conversation here: https://ca.fullscript.com/plans/drpatriciamills-candida-yeast-solution As always, this plan is shared for educational purposes and reflects Dr. Dean’s clinical experience rather than a one-size-fits-all recommendation.