Zac Spiritos, MD, MPH on neurogastroenterology with Dr. Tania Dempsey on Mast Cell Matters

This episode features gastroenterologist Dr. Zac Spiritos in conversation with mast cell expert Dr. Tania Dempsey about neurogastroenterology in patients with MCAS, POTS/dysautonomia, and hypermobility/EDS. They describe how common and severe GI symptoms are in this "trifecta," and how traditional GI labels like IBS, GERD, SIBO, and functional dyspepsia often miss the underlying drivers: mast cell activation, autonomic dysfunction, disordered motility, and pelvic floor dysfunction. Dr. Spiritos is skeptical of over-focusing on SIBO or parasites and instead prioritizes why motility is impaired and why mast cells are overactive. Both doctors explain why standard endoscopy and CD117 mast-cell staining are imperfect for diagnosing MCAS, and why symptom patterns, comorbidities (migraines, menorrhagia, joint hypermobility, POTS), and response to mast-cell–targeted treatment can be more revealing. A major part of the discussion is the emerging use of GLP‑1/GIP agonists such as tirzepatide and semaglutide at very low “microdoses” as powerful mast cell stabilizers that can rapidly reduce food reactions, brain fog, reactive hypoglycemia, edema, and other MCAS symptoms, often with little or no weight loss at those doses. They contrast this with older mast cell drugs (cromolyn, ketotifen, LDN), which may help but often take months and cause more side effects. Nutrition is approached pragmatically: avoid making already-restricted diets even stricter unless clearly needed; support motility with gentle fibers like partially hydrolyzed guar gum; and distinguish mast-cell–driven post‑meal flares from pure motility problems like gastroparesis or vascular issues like MALS. They also highlight the role of pelvic floor dysfunction and visceroptosis in EDS-related constipation and mixed bowel patterns. Throughout, both clinicians stress individualized, multi-system care, close follow-up, and validating patients whose tests are "normal" but who are severely impacted by these interconnected conditions.