By Maryann Walsh, RD, CDCES, CMNCS
MCAS, POTS and EDS
If you have been diagnosed with or are suspected to have Mast Cell Activation Syndrome (MCAS), Postural Orthostatic Tachycardia Syndrome (POTS), or hypermobile Ehlers-Danlos Syndrome (hEDS), you already know that your body does not follow the standard rulebook. You have probably tried elimination diets that made things worse, removed foods based on a test your doctor shrugged at, or been handed a low-histamine foods list and sent on your way.
The problem is not you. The problem is that the nutrition care model was not built for your biology.
These Conditions Are Deeply Interconnected — And So Are Their Nutritional Needs
MCAS, POTS, and hEDS are increasingly recognized as a clinical triad. A 2024 review published in Current Opinion in Gastroenterology examined the proposed association between hypermobile EDS and disorders of mast cell activation, noting that these patients present with a complex array of co-existing diagnoses including GI dysfunction, postural orthostatic tachycardia syndrome, and food intolerances that significantly affect dietary tolerance and quality of life (Penny et al., 2024).
What ties them together at the root level is connective tissue. In hEDS, abnormalities in collagen structure affect not just joints, but the integrity of the gut wall itself. A 2025 AGA Clinical Practice Update confirmed that in hEDS, changes in collagen structure or extracellular matrix molecules may lead to alterations in intestinal motility, tone, sensation, and permeability, all of which directly affect how food is tolerated (AGA, 2025).
Mast cells live in connective tissue. When connective tissue is structurally compromised, mast cells can become hyperreactive, releasing histamine, prostaglandins, leukotrienes, and cytokines in response to foods, scents, stress, and temperature changes. This is not a typical food allergy. It is a fundamentally different immune event, and it requires fundamentally different testing.
Testing for Food Allergies and Intolerances
When a patient with MCAS presents with food-triggered symptoms, the conventional response is to order IgE allergy testing or an IgG food sensitivity panel. Both often come back unremarkable, and the patient is told they have no allergies. Meanwhile, they continue to react.
Here is why this happens: MCAS-driven food reactions do not rely on IgE or IgG pathways. Mast cells can be directly degranulated through complement activation, cell-mediated mechanisms, and non-immune pathways that antibody-based testing is completely blind to. A clean IgG panel does not rule out food-triggered mast cell reactivity. It just means the test was measuring the wrong thing.
A 2024 cross-sectional study published in the American Journal of Gastroenterology found that dietary alterations in hEDS patients were independently associated with MCAS (OR 2.05), functional dyspepsia, ARFID-positive screening, and reflux — highlighting that food reactivity and dietary restriction in this population are a real, measurable clinical problem that demands a targeted approach (Topan et al., 2024).
For patients with MCAS or POTS-dominant presentations, the most mechanistically sound food sensitivity test may be the Mediator Release Test (MRT).
Unlike antibody-based tests, MRT exposes your white blood cells, including mast cells, basophils, monocytes, and eosinophils directly to food antigens in a laboratory setting. It then measures whether those cells release inflammatory mediators in response. The newest generation instrument, MRT III, uses advanced flow cytometry combined with a patented impedance-based Ribbon Method to measure volumetric changes across four white cell populations simultaneously, capturing reactivity regardless of which immune pathway triggered it.
This is a critical distinction. A patient who has never eaten a particular food can still test reactive on MRT because the reactivity lives in the immune cell itself, not in the antibody history. For a MCAS patient on a severely restricted diet, this means you can map inflammatory food triggers across 170 foods and food chemicals even when their diet is down to ten safe foods.
For an additional layer of workup, especially in patients with prominent GI symptoms, serum DAO enzyme activity and 24-hour urine methylhistamine can help distinguish histamine intolerance from mast cell activation and guide dietary histamine management alongside MRT findings.
When gut barrier compromise is suspected and in this population it almost always should be Cyrex Array 2, which measures antibodies to intestinal permeability markers including LPS, occludin, and zonulin, providing a useful upstream picture of whether antigen translocation is driving systemic immune reactivity.
What Nutrition Intervention Actually Looks Like
Testing is only the starting point. The goal is building a structured, individualized eating plan based on your specific reactive foods not a generic elimination diet copied from a blog post.
For MCAS and POTS patients, this typically means:
Starting with your safest foods. The LEAP (Lifestyle Eating and Performance) protocol, built on MRT results, begins with a short list of the patient’s lowest-reactive foods and expands systematically. For patients with significant food fear which research confirms is common in this population this structure also provides psychological safety alongside physiological benefit.
Addressing fluid and electrolyte needs. POTS patients require substantially higher sodium and fluid intake than standard recommendations suggest. Nutrition support in this area is often underprescribed and can have a significant impact on symptom burden.
Rebuilding nutritional adequacy. A 2024 study found that 61% of hEDS patients were taking nutritional supplements, and 25.3% had received some form of nutritional support — yet research confirms that expert dietitian involvement remains rare in this population (Topan et al., 2024). Restricted diets, GI dysmotility, and malabsorption create real risk for micronutrient deficiencies including B12, vitamin D, iron, and magnesium that must be proactively assessed and corrected.
Working with a Dietitian for MCAS, POTS and/or EDS
If you have been living with MCAS, POTS, or hEDS and have never worked with a dietitian who understands the immunological complexity of these conditions, you are not alone and you are not out of options.
I often work with patients who have been dismissed, misguided, and told their symptoms are in their head. They are not. They are in your mast cells, your connective tissue, and your gut — and there is a clear, evidence-based nutritional path forward.
Ready to stop guessing? Reach out to me:
Reach out at info@mwalshnutrition.com
Maryann Walsh, RD, CDCES, CMNCS is a Registered Dietitian, Certified Diabetes Care and Education Specialist, and Certified Medical Nutrition Consultant in private practice. Based in Jupiter, FL and Rhode Island.
References
- Penny HA, et al. Mast cell activation and nutritional disorders in patients with hypermobility. Curr Opin Gastroenterol. 2024;40(3):225–232.
- AGA Clinical Practice Update on GI Manifestations and Autonomic or Immune Dysfunction in Hypermobile Ehlers-Danlos Syndrome. Clin Gastroenterol Hepatol. 2025.
- Topan R, et al. Comprehensive assessment of nutrition and dietary influences in hypermobile Ehlers-Danlos syndrome. Am J Gastroenterol. 2024;119(4):727–738.
- Oxford Biomedical Technologies. MRT III: The Future of Food Sensitivity Testing. nowleap.com. 2023.
- Shah ND. Nutritional Considerations for Hypermobile Ehlers-Danlos Syndrome. Practical Gastroenterology. May 2024.
