Host: Dr. Ryan Cole | Guest: Dr. Keith Berkowitz
What happens when the immune cells meant to protect you start overreacting?
Dr. Ryan Cole, IMA Head of Medical and Scientific Affairs, is joined by Dr. Keith Berkowitz, IMA founding member and founder and medical director of the Center for Balanced Health, to discuss mast cell activation syndrome (MCAS).
Symptoms keep showing up in different parts of the body, and nobody connects them. The pulmonologist treats the wheeze. The ENT treats the sinuses. The allergist runs a panel, finds nothing, and says it can’t be an allergy. By the time someone with mast cell activation syndrome reaches Dr. Keith Berkowitz, they have typically seen eight or nine doctors.
Part of the problem is that MCAS does not behave like the conditions medicine is trained to catch. It crosses organ systems, its triggers can arrive days late, and the standard tests can read normal on any day the patient is not actively reacting. Dr. Berkowitz has spent six years treating it in long COVID and post-vaccination patients, and he has arrived at a treatment sequence: nervous system first, then gut, then the mast cells themselves.
He also brings a clinical observation worth hearing. An integrative internist and IMA founding member, Dr. Berkowitz measures two cytokines that few practices check, and he describes a pattern in his sickest patients that he believes helps explain why they stay sick. Dr. Cole brings the pathologist’s view of the cell itself: what it is, where it lives in tissue, and what switches it on.
Meet the Experts
Keith Berkowitz, MD, MBA
Founder and Medical Director, Center for Balanced Health; IMA founding member. Board-certified internist combining conventional and complementary medicine. Formerly Medical Director of the Atkins Center for Complementary Medicine and a faculty member in the Department of Medicine at North Shore University Hospital. Offers telehealth in New York, New Jersey, Florida, and California.
Ryan Cole, MD
IMA Head of Medical and Scientific Affairs; Senior Fellow, Pathology. Board-certified anatomic and clinical pathologist whose work has focused on tissue pathology, immune function, and vaccine safety. He has spent a career identifying mast cells under the microscope, which gives the conversation its grounding in what the cell actually is and where it lives in the body.
1. The Mothership and the Fighter Pilots: What Mast Cells Actually Do
Mast cells are white blood cells that leave the bloodstream almost entirely. Born in the bone marrow, they migrate into tissue and stay there for years: skin, gut, bladder, around nerves, lining blood vessels. Dr. Cole, who has spent a career looking at them under a microscope, calls them sentinels of the innate immune system.
Mast cells in skin (purple) and gut (brown).
Long-lived tissue residents, not circulating blood cells.
Click any slide to enlarge.
Almost anything can set them off, such as an allergen, a drug, a stress hormone, or a change in temperature, and when they fire they release granules of inflammatory mediators. Histamine is the famous one. Tryptase, heparin, and prostaglandins ride along.
Mast cells are supposed to fire when the moment calls for it. When they refuse to stop, that is where MCAS may be at play. Dr. Cole compares a healthy mast cell to his border collie barking at the gate: you want the bark when a jogger passes, and you want it to end. Signals like TGF-beta and interleukin-10 are supposed to tell the cell to stand down.
Allergy is one switch among many. Click to enlarge.
Dr. Berkowitz adds his own image. Mast cells are the mothership; histamines are the fighter pilots. The distinction that matters for diagnosis is timing.
“The main difference between the two is histamine or allergic reaction is an immediate reaction. It doesn’t last. Where mast cell activation syndrome is a chronic inflammatory process. It keeps on going and going and going… It’s almost like the body feels it’s always under attack.” — Dr. Keith Berkowitz
2. Eight or Nine Doctors: Why MCAS Gets Missed
The triggers are the first problem. Dr. Berkowitz described a patient whose reaction arrived a full week after anesthesia, and another who reacted to an afternoon in the sun. In long COVID and vaccine injury, Dr. Berkowitz regards spike protein as the persistent irritant. A trigger that shows up seven days late does not look like a trigger.
The second problem is that patients are routed by organ. Each specialist treats one system. The allergist’s panel comes back clean, so the patient is told they have no allergies and therefore cannot have a mast cell problem.
The third problem is the labs. Serum tryptase is treated as the gold standard, but Dr. Berkowitz points out it may be normal unless blood is drawn within roughly four hours of a reaction. Urine N-methylhistamine and prostaglandin D2 share the limitation. Draw them on a calm day, which is the day most patients get bloodwork, and they can read normal. Diagnostic criteria weigh symptoms, a rise in mediators relative to the patient’s baseline, and response to treatment; a single normal result rules nothing out.
“My average patient has seen eight to nine doctors.” — Dr. Keith Berkowitz
That puts weight on history. Dr. Berkowitz calls MCAS a symptom-driven diagnosis, and the pattern he looks for is several systems misbehaving at once. The clusters he sees most:
- Neurological: panic, anxiety, a body stuck in fight-or-flight, brain fog, headaches, migraines. He finds these the most dramatic and the most overlooked.
- Gastrointestinal: bloating, gas, diarrhea, constipation, and the increased gut permeability people call leaky gut.
- Skin: hives and angioedema, the textbook presentation, though many patients never show it in the exam room.
One of his favorite tells: a patient who sneezed every time he ate and thought nothing of it. Dr. Cole cited studies suggesting 10 to 15 percent of the population may have some degree of mast cell activation. If that is close, most physicians are already treating patients with it.
3. The Seesaw: What Dr. Berkowitz Is Seeing in Long COVID and Post-Vaccine Patients
Dr. Berkowitz did not think about mast cells before COVID. What drew him in was a pattern: an immune system tied up with mast cell activation seemed unable to clear the virus or keep old infections in check. So he began treating MCAS early, and looking for a way to measure what standard markers miss.
He settled on two cytokines. Interleukin-8 is the pro-inflammatory signal, sent when the body is stressed by infection, cancer, or autoimmune disease. Interleukin-10 is its counterweight, the signal that says the threat is handled. In a healthy response they move like a seesaw. In his post-COVID and post-vaccine patients, IL-8 is very high and IL-10 is low, and they have stopped moving together.
The numbers he shared are stark. Against a normal value he put at around 66, Dr. Berkowitz saw an IL-8 result of 25,000 the day of the recording. The low IL-10 worries him more. His reading is that a body unable to generate the stand-down signal never registers that it is sick.
“Interleukin 8 is the one causing the mess. Interleukin 10 is the cleanup crew that they never come.” — Dr. Keith Berkowitz
Even after IL-8 normalizes, he often finds IL-10 still depressed. He is careful to call what follows his own thinking, but he wonders whether that pattern is behind several things clinicians have puzzled over:
- Patients catching COVID again and again despite repeated exposure.
- Reactivation of old infections: acute Epstein-Barr in a 95-year-old, Lyme positives in people with no tick exposure.
- Antivirals failing in patients whose immune systems cannot finish what the drug starts.
It also gives him a theory about ivermectin and hydroxychloroquine: both, he notes, lower IL-8 and support IL-10. Dr. Cole tied the pattern to the literature, citing a Dutch study on innate immune reprogramming after two Pfizer doses that circulated as a preprint for three years before clearing peer review, and a 2025 Yale preprint describing an immune system that revs hard and then burns out.
The most severe cases share one more feature: nervous system involvement. Histamine, he explained, drives neuroinflammation directly, and he described a vaccine-injured young woman whose psychotic episodes reliably break when the ER gives her an H1 and an H2 blocker.
4. Nervous System First: The Order of Operations
Ask Dr. Berkowitz where treatment starts and he does not start with the mast cells. His rule for any chronic illness is to stabilize the nervous system, digestion, and blood sugar first. He calls it setting the patient up for success.
Six years in, he has settled on an order, and the nervous system leads. A body locked in fight-or-flight cannot recover, and an immune system running on stress hormones cannot recalibrate. His most reactive patients, the ones who react to probiotics, to low-dose naltrexone, even to ivermectin, are the majority of his practice, and they need calming before anything else goes in.
“I think one thing I’ve learned over the last six years is there is an order. And to me, the nervous system should always be first.” — Dr. Keith Berkowitz
The brake he reaches for is GABA, the body’s main inhibitory neurotransmitter. His starting tools are magnesium glycinate and L-theanine: supportive rather than direct, helpful for cortisol and sleep, and magnesium in particular is the best tolerated of anything he uses. Some patients do not tolerate theanine. GABA itself can come later.
What he does not start with is methylation. Many of his MCAS patients carry MTHFR variants, and the intuitive move is methylated folate and B12. In his experience it is too stimulating up front. Support GABA, then revisit.
Blood sugar and sleep round out the foundation. Insulin is inflammatory, he notes, and blood sugar swings block the same GABA pathway. Poor sleep, in his view, is the most common feature of anyone at high risk for chronic disease.
His pharmaceutical toolkit has narrowed over time:
- H1 plus H2 blockers: two histamine receptors, one whole-body disease. Blocking only the allergy receptor leaves the gut receptor untouched.
- Ketotifen: H1 blocker and mast cell stabilizer in one, but weight gain is common and it can worsen anxiety in an unsettled nervous system.
- Low-dose naltrexone: his favorite immunomodulator, titrated up gradually.
- Steroids: largely abandoned. The cost to sleep, blood sugar, cortisol, and an already inflamed thyroid outweighs the relief.
The same logic reframes POTS. Patients with postural tachycardia are sent to cardiology; Dr. Berkowitz sees a nervous system stuck in fight-or-flight, and one of his first interventions is IV saline, which in his experience settles patients in a way drinking water alone often does not.
5. Calming the Gut: Diet, Microbiome, and the Complementary Toolkit
With the nervous system steadier, Dr. Berkowitz turns to digestion, and the foundation is a low-histamine diet, which he recalls React19 identifying years ago as one of the most effective interventions for the vaccine-injured. For those who struggle with it, or who want a night out, he adds a DAO enzyme with meals. He calls it his dating pill.
The gut is the most vulnerable surface in the body. The intestinal lining is one cell deep, with none of the layered defense skin has. Dr. Berkowitz compares inflammatory damage to taking braces off a set of teeth: remove the structure and the cells drift apart, letting mediators through.
Probiotics help, but he is emphatic about how. Some strains liberate histamine, and in an inflamed system even a strong anti-inflammatory can be too much. One at a time, weaker strains first:
- Saccharomyces boulardii: a yeast, histamine-friendly, and the one he introduces first.
- Lactobacillus rhamnosus
- Bifidobacterium infantis
He cites Dr. Sabine Hazan’s work finding near-total microbiome wipeout in some long COVID and vaccine-injured patients, and he has watched previously healthy patients become diabetic during the COVID years.
For mast cell stabilization without a prescription, the compounds he reaches for:
- Quercetin: antihistamine, mast cell stabilizer, crosses the blood-brain barrier, and antiviral.
- Luteolin: another natural mast cell stabilizer.
- Curcumin and resveratrol: broad immune stabilizers.
- Vitamin D and K: in his words, essential for everything.
For a recent infection, both agreed early treatment still matters: ivermectin or hydroxychloroquine given close to an acute infection dampens the post-viral response in a way that is much harder years later. Dr. Berkowitz’s caution about pacing all of this comes with a line he borrowed from William Osler: to recover from a disease, you have to recover from the disease and from the treatment.
“It’s calming down the nervous system. It’s calming down the gastrointestinal system. It’s calming down the immune system… You want the body to be in this calm state so that it can function for itself.” — Dr. Keith Berkowitz
Can MCAS Be Cured?
An attendee asked the question everyone in the chat wanted answered, and Dr. Berkowitz’s response comes back to what MCAS is. It is a secondary effect. The mast cells are reacting to something, and in long COVID and vaccine injury he believes that something is spike protein. Until the trigger is gone, the syndrome can wax and wane, quiet for weeks and then set off by a virus or the wrong meal. He is candid that medicine is still working around the spike protein rather than on it, with no good direct measure of it, which means much of what he does is symptom management. Patients who stop their medications often rebound, and so do patients who catch another infection. His benchmark is honest rather than triumphant: if a patient gets 80 to 85 percent better and functional, that is meaningful.
Dr. Cole added the other vitamin D: discipline. The hyperreactive pattern shifts only when a consistent new one is held long enough to take. Both of them want a part two.
The live chat made the case for one better than we could. A sample of what came in:
- Jeffrey G.: “So happy to see Dr. Berkowitz on here! I credit Dr. Berkowitz for saving my life two years ago. He figured out my issues and did all the proper blood tests that no one else knew to do.”
- Jeffrey G.: “Yep, Dr. Berkowitz found my thyroglobulin AB was through the roof. Praise to him!”
- Linda M.: “Dr. Berkowitz thank you for keeping your sense of humor. It is so appreciated and somehow a confidence builder.”
- Morimasa Y.: “Thank you Drs. Cole and Berkowitz, nice webinar today!!!”
- Vinny G.: “Thank you Drs for your genuine service ❤️”
Related Reading
- Video: Dr. Tina Peers: The Role of Mast Cell Activation in Long COVID & Vaccine Injury
- Guide: Allergy Guide: Allergens, Intolerances, Allergies & Histamine
- Guide: Gut & Metabolic Support: Foundational Nutrients for a Healthier Gut
- Peer-Reviewed Study: MCAS, POTS, Dysautonomia, and “Genetic Disorders” — Long COVID Observations
- Peer-Reviewed Study: Amlexanox: A Promising Alternative to Steroid and Antihistamine Dependence in Patients with Mast Cell Activation Syndrome, Allergies, Asthma, and Autoimmunity
- Protocol: I-RECOVER: Long COVID Treatment
- Protocol: I-RECOVER: Post-Vaccine Treatment
