The Hidden Link between MCAS, Orthostatic Intolerance/dysautonomia, and Interstitial Cystitis (IC)

Brandy Searcy
  • 3.8 (4)
  • Alternative Health
  • Weekly

Deep dives into the physiology driving mast cell activation syndrome (MCAS), histamine intolerance, POTS, dysautonomia, orthostatic intolerance, interstitial cystitis (IC), and chronic UTI symptoms with research scientist Brandy Searcy.

  1. Oct 27

    Does COVID drive mast cell activation?

    Did you become more reactive after COVID—or find that symptoms you already had became harder to live with? In this episode, research scientist Brandy Searcy explores the connection between COVID and mast cell activation: how SARS-CoV-2 and its spike protein activate mast cells in experimental studies, what researchers have found lingering in the body months after infection, and why persistent viral material deserves attention as a potential driver of ongoing symptoms. You’ll hear about findings from human intestinal biopsies, studies detecting circulating viral proteins, and experiments tracing how spike triggers the release of inflammatory mediators. Together, this research gives us a reason to ask: What is continuing to stimulate your immune response after the initial infection has passed? Explore the physiology beneath your symptoms in my free 7-day course, The Physiology Driving POTS and MCAS. Choose the track that fits what you’re experiencing: MCAS and histamine intolerance: https://theflowtoheal.com/mcas-and-histamine-intolerance POTS and dysautonomia: https://theflowtoheal.com/pots-and-dysautonomia References Zollner A, et al. (2022). Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases. Gastroenterology. https://doi.org/10.1053/j.gastro.2022.04.037 Swank Z, et al. (2023; published online 2022). Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciac722 Peluso MJ, et al. (2024). Plasma-based antigen persistence in the post-acute phase of COVID-19. The Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(24)00211-1 Tan JYJ, et al. (2023). Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19. Journal of Clinical Investigation. https://doi.org/10.1172/JCI149834 Wong AC, et al. (2023). Serotonin reduction in post-acute sequelae of viral infection. Cell. https://doi.org/10.1016/j.cell.2023.09.013 Brogna C, et al. (2021). Toxin-like peptides in plasma, urine and faecal samples from COVID-19 patients. F1000Research. Version 2. https://doi.org/10.12688/f1000research.54306.2 Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration. (2024). Journal of Inflammation Research. https://doi.org/10.2147/JIR.S456000 Wu ML, et al. (2021). SARS-CoV-2-triggered mast cell rapid degranulation induces alveolar epithelial inflammation and lung injury. Signal Transduction and Targeted Therapy. https://doi.org/10.1038/s41392-021-00849-0 Tsilioni I, Theoharides TC. (2023). Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms24119487 Zhang S, et al. (2025). Spike proteins of coronaviruses activate mast cells for degranulation via stimulating Src/PI3K/AKT/Ca2+ intracellular signaling cascade. Journal of Virology. https://doi.org/10.1128/jvi.00078-25 Augustin M, et al. (2026). Persistent Gut-Immune Axis dysregulation in long-term Post-COVID Syndrome: Insights from a prospective, observational, cross-sectional case-control study. Mucosal Immunology. https://doi.org/10.1016/j.mucimm.2026.03.002 University of Pennsylvania coverage mentioned in this episode Penn Today. (October 17, 2023). Viral persistence and serotonin reduction can cause long COVID symptoms. https://penntoday.upenn.edu/news/penn-medicine-viral-persistence-and-serotonin-reduction-can-cause-long-covid-symptoms

  2. Oct 23

    Is there a connection between recurrent UTI symptoms and mast cell activation?

    Burning, urgency, negative urine cultures, and maybe even a diagnosis of interstitial cystitis? Research scientist, Brandy Searcy, dishes on the link between interstitial cystitis and MCAS. Burning and urinary urgency that has you mapping every bathroom between home and the grocery store, and a urine culture showing nothing? If that sounds familiar, this episode is for you. I'm Brandy Searcy, a research scientist who lived with chronic UTI and interstitial cystitis (IC) symptoms for years before I decided management was not an option. In this episode I dig into whether interstitial cystitis and recurrent UTI symptoms are connected to mast cell activation syndrome (MCAS), a condition where mast cells, the immune cells that release histamine and other inflammatory compounds, fire far more easily than they do in a healthy body. In this episode: Why the bladder wall holds so many mast cells, and what happens when they sit on a hair trigger How histamine release produces burning, urgency, and pain that feel exactly like an infection Why some IC diets help The overlap between IC, MCAS, and Hashimoto's If your bladder is only one of the places your body keeps sounding the alarm, my free guide, The Physiology Driving MCAS, walks through what's happening underneath the reactions: https://theflowtoheal.com/mcas-and-histamine-intolerance More from me: brandysearcywellness.com YouTube: youtube.com/@feelbetterthanfine This episode is for educational purposes only and is not medical advice. NOTE: There's some wind noise during the first couple of minutes of this episode. Skip forward to around minute 3 to get past that.

  3. Sep 16

    Are proteolytic enzymes helpful or harmful for MCAS and POTS/Orthostatic Intolerance/Dysautonomia?

    My own personal experience with proteolytic enzymes (from those that support gluten breakdown to the wildly popular nattokinase and serrapeptase) is much different than I expected. Here's what you need to know (whether you're taking these or considering these) even if you don't have: gluten intolerance (and cheat occasionally by popping a handful of enzymes) mast cell activation orthostatic intolerance/dysautonomia (with or without tachycardia) interstitial cystitis Long COVID migraines/severe headaches (and especially if you do). This segment is lifted directly out of Reclaim Wellness Intensive, the program I wish I'd had when I first started struggling with these symptoms (yes, I had all of these at once). P.S. You'll find much more detail about how each of these proteases behaves in the body (whether by upregulating matrix metalloproteinases or the body's own endogenous proteases) inside an upcoming post. P.P.S. For the tau protein part of this episode, proteases are known to cleave tau protein and those fragments are problematic (see references 5, 6, and 7 below). References for this episode: Biancheri P, Di Sabatino A, Corazza GR, MacDonald TT. Proteases and the gut barrier. Cell Tissue Res. 2013 Feb;351(2):269-80. doi: 10.1007/s00441-012-1390-z. Epub 2012 Mar 20. PMID: 22427120.Van Spaendonk H, Ceuleers H, Witters L, Patteet E, Joossens J, Augustyns K, Lambeir AM, De Meester I, De Man JG, De Winter BY. Regulation of intestinal permeability: The role of proteases. World J Gastroenterol. 2017 Mar 28;23(12):2106-2123. doi: 10.3748/wjg.v23.i12.2106. PMID: 28405139; PMCID: PMC5374123.Fedorowski, A., Sutton, R. Autonomic dysfunction and postural orthostatic tachycardia syndrome in post-acute COVID-19 syndrome.Nat Rev Cardiol 20, 281–282 (2023). https://doi.org/10.1038/s41569-023-00842-wFoote CA, Soares RN, Ramirez-Perez FI, Ghiarone T, Aroor A, Manrique-Acevedo C, Padilla J, Martinez-Lemus L. Endothelial Glycocalyx. Compr Physiol. 2022 Aug 23;12(4):3781-3811. doi: 10.1002/cphy.c210029. PMID: 35997082; PMCID: PMC10214841.Boyarko B, Hook V. Human Tau Isoforms and Proteolysis for Production of Toxic Tau Fragments in Neurodegeneration. Front Neurosci. 2021 Oct 21;15:702788. doi: 10.3389/fnins.2021.702788. PMID: 34744602; PMCID: PMC8566764.Nübling G, Levin J, Bader B, Israel L, Bötzel K, Lorenzl S, Giese A. Limited cleavage of tau with matrix-metalloproteinase MMP-9, but not MMP-3, enhances tau oligomer formation. Exp Neurol. 2012 Oct;237(2):470-6. doi: 10.1016/j.expneurol.2012.07.018. Epub 2012 Aug 6. PMID: 22890115.Kostiuchenko O, Kravchenko N, Markus J, Burleigh S, Fedkiv O, Cao L, Letasiova S, Skibo G, Fåk Hållenius F, Prykhodko O. Effects of Proteases from Pineapple and Papaya on Protein Digestive Capacity and Gut Microbiota in Healthy C57BL/6 Mice and Dose-Manner Response on Mucosal Permeability in Human Reconstructed Intestinal 3D Tissue Model. Metabolites. 2022 Oct 26;12(11):1027. doi: 10.3390/metabo12111027. PMID: 36355110; PMCID: PMC9696696.

    Are proteolytic enzymes helpful or harmful for MCAS and POTS/Orthostatic Intolerance/Dysautonomia?

  4. 06/27/2024

    Is adrenal fatigue causing your estrogen dominance?

    In this episode, you'll discover why adrenal fatigue causes estrogen dominance. For more on hormone health check out: https://brandysearcy.com/the-secret-reason-youre-sick

  5. 06/17/2024

    Detecting cortisol dysregulation

    How do you know if your cortisol's high or low without a lab test? Find out in this episode. For more, subscribe to youtube.com/@feelbetterthanfine Connect with Brandy at hey@rainorganica.com or shesbalanced@gmail.com

  6. 04/11/2024

    Could this be causing your symptoms?

    We often chase things that don't matter when seeking wellness. I myself have chased low estrogen, migraines, fatigue, weight gain, and chronic UTI symptoms. At the end of the day, the one thing causing all those symptoms was the same...my body couldn't meet energy demands. If you're tired of living life limited by symptoms and frustrated with chasing those symptoms, this episode's for you. Click to listen. Ready to break free of your symptoms? Claim your seat in From Gaslit to Resilient here: brandysearcy.lpages.co/from-gaslit-to-resilient

  7. 04/03/2024

    Is TSH enough to test for thyroid function?

    What tests are necessary to properly evaluate thyroid function? This episode discusses the markers necessary. Hint, some are thyroid hormones and some aren't 🤯 Download that lab test here: brandysearcy.lpages.co/is-tsh-enough-to-determine-low-thyroid And, save your spot in from Gaslit to Resilient here: brandysearcy.lpages.co/from-gaslit-to-resilient

  8. 02/17/2024

    What does the Mira Fertility monitor reveal about your health?

    Quantitative fertility monitors are new(er) on the scene, and they're powerful tools for empowered health! Sylvia Kang, founder of Mira Care joins me in this episode to talk about Mira the fertility monitor I use daily. Get the Mira monitor here: mira-fertility.pxf.io/rainorganica Save your spot at the summit here: tinyurl.com/flourish-beyond-40

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3.8
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Deep dives into the physiology driving mast cell activation syndrome (MCAS), histamine intolerance, POTS, dysautonomia, orthostatic intolerance, interstitial cystitis (IC), and chronic UTI symptoms with research scientist Brandy Searcy.

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