Mold, Lyme, Gut Health, and the Mystery of Histamine Intolerance

Summary

Podcast Summary: The Dr. Hyman Show Episode: Mold, Lyme, Gut Health, and the Mystery of Histamine Intolerance
Release Date: April 21, 2025

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Introduction

In this enlightening episode of The Dr. Hyman Show, Dr. Mark Hyman delves deep into the complex world of histamine intolerance, its connection to gut health, mold, Lyme disease, and the broader implications for chronic illness management. Joined by experts like Todd LePine, Dr. Amy Shah, Dr. Peter Attia, Dr. Will Cole, and Dr. Satish Rao, the discussion unpacks the enigmatic nature of histamine-related disorders and highlights the functional medicine approach to diagnosing and treating these conditions.

Understanding Histamine Intolerance and Mast Cell Activation Syndrome (MCAS)

The conversation kicks off with Dr. Amy Shah explaining the role of histamine in the body. Histamine isn't just involved in allergic reactions; it also acts as a neurotransmitter influencing sleep-wake cycles and mood.

Dr. Amy Shah [02:11]: "Histamine is found naturally in the body... it works as a neurotransmitter... it's involved in the sleep-wake cycle."

Mast Cell Activation Syndrome (MCAS): Dr. Shah introduces MCAS, a condition where mast cells release excessive histamine, leading to a cascade of symptoms. Unlike traditional allergies, MCAS can manifest with a wide range of non-specific symptoms, making it challenging to diagnose.

Symptoms and Impact of Histamine Intolerance

Histamine intolerance can present with diverse and often misunderstood symptoms, including:

• Dermatological Issues: Hives, rashes, and dermatographism (a condition where scratching the skin leads to raised welts).

  Todd LePine [03:33]: "You can write your name on your back and it'll have raised like letters."

• Neurological Symptoms: Headaches, migraines, brain fog, and dizziness.

• Gastrointestinal Distress: Abdominal pain, bloating, diarrhea, and constipation.

• Systemic Effects: Fatigue, anxiety, heart palpitations, and temperature regulation issues.

Diagnosis of Histamine Intolerance and MCAS

The panel discusses various diagnostic methods to identify histamine-related disorders:

1. Blood Tests: Measuring histamine levels and tryptase.

   Dr. Amy Shah [11:40]: "You can measure histamine in the blood... You can also measure tryptase."

2. DAO Deficiency Testing: DAO (diamine oxidase) is an enzyme responsible for breaking down histamine. Deficiency can lead to histamine accumulation.

   Todd LePine [12:26]: "DAO is an enzyme that helps break down histamine... if this enzyme is lacking, you will have problems detoxifying histamine."

3. Dermatographism Test: A clinical test where scratching the skin indicates mast cell reactivity.

4. Immunological Markers: Anti-CDTB and anti-vinculin antibodies can indicate autoimmune involvement linked to gut health.

5. Functional Diagnostics: Assessing for leaky gut, dysbiosis, and genetic markers influencing histamine metabolism.

Dietary Approaches: Low Histamine Diet

A cornerstone of managing histamine intolerance is dietary modification. The experts outline a phased approach to adopting a low histamine diet:

1. Phase One: Initial Restrictions

   • Eliminate High-Histamine Foods: Aged cheeses, cured meats, fermented foods (sauerkraut, kimchi, yogurt), alcohol (especially beer and wine), and leftovers.

     Dr. Amy Shah [15:04]: "Leftovers... fermented foods... have high histamine."

   • Emphasize Fresh Foods: Fresh meats, freshly caught fish, non-citrus fruits, eggs, and gluten-free grains like quinoa and black rice.

2. Phase Two: Further Restrictions

   • Remove Additional Fermented and Processed Foods: Canned and smoked fish, pickled vegetables, soy sauce, and artificial additives like sulfates and MSG.

3. Phase Three: Advanced Restrictions

   • Restrict Certain Plant Foods: Avocado, spinach, tomatoes, pineapple, and citrus fruits.

   Todd LePine [17:21]: "Foods like papayas and chocolate... may really cause increased histamine production."

Key Dietary Recommendations:

• Avoid Antihistamine Blockers: Certain foods and beverages like alcohol, black and green tea, energy drinks.
• Incorporate Histamine-Lowering Foods: Freshly prepared meals, non-fermented plant-based oils, and animal proteins.

Dr. Amy Shah [17:58]: "Work with a nutritionist... what to eat, what to avoid, and what supplements to take."

Connection Between Histamine Intolerance and Lyme Disease

The episode highlights the intricate link between histamine intolerance and Lyme disease:

• Lyme Disease as a Trigger: Lyme bacteria reside in connective tissues, activating mast cells and exacerbating histamine release.

  Dr. Amy Shah [07:13]: "Lyme disease is also associated with histamine intolerance... Lyme bacteria reside in the connective tissues... activate mast cells."

• Case Studies: Patients with undiagnosed Lyme often present with chronic fatigue, brain fog, and mast cell activation symptoms. Advanced testing, such as specialized T cell ELI spot tests, can reveal underlying Lyme infections not detected by conventional lab tests.

Irritable Bowel Syndrome (IBS) and Gut Health

The discussion transitions to IBS, emphasizing its multifaceted nature:

• Functional vs. Conventional Medicine: Traditional approaches often overlook the gut’s role in systemic symptoms, whereas functional medicine seeks root causes like leaky gut, dysbiosis, and histamine imbalance.

  Dr. Amy Shah [10:12]: "When you have dysbiosis, some bacteria cause more histamine production."

• Post-Infectious IBS: A significant percentage of IBS cases stem from past food poisoning incidents, leading to autoimmune reactions impacting gut nerves and motility.

• Gut Microbiome Dysbiosis: Imbalanced gut bacteria can increase histamine production and lead to chronic inflammation.

Functional Medicine vs. Conventional Medicine

The panel contrasts the two medical paradigms:

• Conventional Medicine:

  • Focuses on symptom management using antihistamines, corticosteroids, and mast cell stabilizers.

  • Often fails to address underlying causes, leading to temporary relief without resolution.

    Dr. Peter Attia [30:07]: "Traditional medicine... throws a lot of medication at it... it's just massive symptoms."

• Functional Medicine:

  • Emphasizes personalized, root-cause treatments.

  • Utilizes comprehensive diagnostic tools to uncover underlying issues like mold exposure, heavy metals, hormonal imbalances, and gut health.

  • Advocates for dietary modifications, enzyme supplementation, stress reduction, and detoxification protocols.

    Dr. Peter Attia [30:37]: "Functional medicine helps start to think about the symptoms and do a deeper dive."

Treatments and Management Strategies

Effective management of histamine intolerance involves a multifaceted approach:

1. Dietary Interventions:

   • Adopting a low histamine diet in phased stages.
   • Ensuring fresh, non-fermented, and minimally processed foods.

2. Supplementation:

   • DAO Enzymes: Aid in breaking down dietary histamine.

     Dr. Amy Shah [13:01]: "There are enzyme products... and patients respond very well."

   • Natural Antihistamines: Quercetin and nettles have shown efficacy in reducing histamine levels and alleviating symptoms.

3. Medications:

   • Antihistamines: Over-the-counter options like Allegra, Claritin, and Zyrtec.
   • Mast Cell Stabilizers: Medicines like cromolyn sodium or natural alternatives like butterbur for migraines.
   • Antibiotics for SIBO: Rifaximin is commonly used for bacterial overgrowth, sometimes in combination with neomycin or metronidazole for methane-producing archaea.

4. Addressing Underlying Causes:

   • Lyme Disease Treatment: Antimicrobial therapies tailored to eliminate Lyme bacteria.
   • Gut Healing: Protocols to repair leaky gut and restore microbiome balance.
   • Environmental Detoxification: Reducing exposure to mold and heavy metals.

Gut Microbiome: Bacterial and Fungal Overgrowth

A substantial portion of IBS cases involves an imbalance in gut microbiota:

• Small Intestinal Bacterial Overgrowth (SIBO):

  • Types: Hydrogen, methane, and hydrogen sulfide-producing bacteria.
  • Diagnosis: Breath tests evaluating gas production.
  • Treatment: Antibiotics like rifaximin tailored to specific bacterial profiles.

• Small Intestinal Fungal Overgrowth (SIFO):

  • Identification: Challenging due to lack of reliable non-invasive tests; requires endoscopic sampling.
  • Common Species: Candida albicans, Candida glabrata, among others.
  • Treatment: Antifungals such as fluconazole or natural alternatives.

  Dr. Will Cole [45:58]: "Hydrogen sulfide is the new kid on the block... when you get rid of it, patients feel better than they've ever felt."

Preventing Recurrence and Long-Term Management

To sustain improvements and prevent relapse:

• Prokinetics: Medications that enhance gut motility, ensuring regular cleaning waves to prevent bacterial overgrowth.

  Dr. Will Cole [53:34]: "We get patients on prokinetics to space their meals and stimulate cleaning waves."

• Dietary Maintenance: Transitioning from a strict low histamine diet to a more balanced approach, incorporating tolerated foods gradually.

• Regular Monitoring: Ongoing assessments to detect and address potential triggers early.

• Lifestyle Modifications: Prioritizing stress reduction, adequate sleep, and regular exercise to support overall health and immune function.

Conclusion

This episode of The Dr. Hyman Show underscores the intricate interplay between histamine intolerance, gut health, and chronic conditions like Lyme disease and IBS. By adopting a functional medicine approach—focused on personalized diagnostics, dietary interventions, and holistic treatments—patients can achieve lasting relief and enhanced well-being. The collaborative insights from the panel highlight the importance of addressing root causes rather than merely managing symptoms, paving the way for a more comprehensive and effective healthcare paradigm.

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For those interested in exploring these topics further or seeking personalized care, Dr. Mark Hyman encourages listeners to visit the Ultra Wellness Center and engage with functional medicine practitioners who can guide them through their health journeys.

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Notable Quotes:

• Dr. Amy Shah [03:24]: "When you actually totally block histamine, you actually get sleepy. It'll actually involved with the sleep wake cycle."
• Todd LePine [05:30]: "I remember when we started doing this decades ago, doctors would laugh at the concept of leaky gut."
• Dr. Will Cole [37:00]: "We never seen antibiotic resistance to rifaximin so far, knock on wood."
• Dr. Peter Attia [51:22]: "Traditional medicine doesn't do a very good job of this and throws a lot of medication at it."

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Resources:

• Low Histamine Diet Handout: Available in the show notes for listeners to implement dietary changes.
• Ultra Wellness Center: For personalized functional medicine consultations and treatments.

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Disclaimer: This summary is for informational purposes only and does not constitute medical advice. Consult a healthcare professional for medical recommendations.

Transcript

[Dr. Mark Hyman]

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[Todd LePine]

Yeah, we talk about fermented foods being so good for you, like sauerkraut and kimchi and natto and miso.

[Dr. Amy Shah]

And this is where these really good foods in someone who has historical intolerance is like putting gasoline on a fire. And they're like, well, I'm getting worse. It's like, well, no, you should be getting worse. These are good foods for you. No, you have histamine problem.

[Dr. Mark Hyman]

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[Todd LePine]

Now, before we jump into today's episode, I'd like to note that while I wish I could help everyone by my personal practice, there's simply not enough time.

[Dr. Peter Attia]

For me to do this at scale.

[Todd LePine]

And that's why I've been busy building several passion projects to help you better understand. Well, you. If you're looking for data about your biology, check out Function Health for real time lab insights. And if you're in need of deepening your knowledge around your health journey, check out my membership community, the Hymen Hive. And if you're looking for curated and trusted supplements and health products for your health journey, visit my [e-mail] for my website store for a summary of my favorite and thoroughly tested products.

[Dr. Amy Shah]

Histamine is. Is found naturally in the body. The body makes histamine. We also consume histamine. And the interesting thing about histamine is it is also part, it's released by mast cells as part of our first response to offending organisms. Like.

[Dr. Peter Attia]

So mast cells are like a white blood cell.

[Dr. Amy Shah]

Type of. Exactly, yes. Type of white blood cells, yeah. And the also interesting thing is that histamine actually works as a neurotransmitter. And when you think about this, this is really an interesting thing. And as I was preparing for this, I sort of stumbled upon some things which I thought was really quite fascinating. Is that when you take antihistamine, what you get drowsy. Exactly. So histamine, when it's, when it's at high enough levels, it stimulates the brain. Histamine is actually involved in the sleep wake cycle.

[Todd LePine]

And well, I mean, you know, Tylenol PM or Advil pm, it's. It's Tylenol, Advil plus.

[Dr. Amy Shah]

Right.

[Todd LePine]

Benadryl, which is an antihistamine.

[Dr. Will Cole]

Right.

[Dr. Amy Shah]

So. So, so it's a balance. Like, you know, too much histamine is bad, too little histamine is also bad. So when you actually totally block histamine, you actually get sleepy. It'll actually involved with the sleep wake cycle. And Modafinil, which is the, the drug that take. That actually works on histamine.

[Todd LePine]

It's part of Provigil.

[Dr. Amy Shah]

Provigil, exactly. We're actually part of that works on, on the histamine. So it, it keeps the histamine levels higher. So it keeps your brain sort of awake, if you will.

[Todd LePine]

Incredible. So most people, you know, are familiar with certain histamine conditions.

[Dr. Peter Attia]

Right.

[Todd LePine]

If you get hives.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

If you have a peanut allergy.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

If you have this condition we call dermatographia, which sounds weird, but essentially it's. If you scratch your fingernail on your skin, it'll create a red welt.

[Dr. Amy Shah]

Yes, yes, that's it. That's a, that's a.

[Todd LePine]

You can literally write your name on your back and it'll kind of have raised like letters.

[Dr. Amy Shah]

And that's, that's actually a poor man's way. And oftentimes we'll use that with patients to determine how much histamine their body, they're having in the connective tissue because the mast cells are in, are the type of white blood cells that are in the connective tissue of the body. And when they have excess amounts of histamine in them or they release histamine too easily, you will get this thing called dermatographism where you can take your. Your finger and stroke on and you will form a red line and it'll stay there. And sometimes it'll get really wealthy and raised. And that will tell you that there is a problem with excess amounts of histamine in the body.

[Todd LePine]

Yeah. And it's something that, you know, we've all experienced. You know, when you get a bee sting or something like that, you'll see this raised. Well, but, but, but what happens for some people, they don't necessarily get the hives and they don't get the. These raised welts on their skin, but they do suffer a whole range of symptoms. So when someone walks in your office, what are the clues that alert you to the fact that they might have a histamine problem? Because, by the way, most traditional doctors don't even know anything about this syndrome. Yeah. If you have allergies taken in histamine, but that's about it. But there's a whole host of problems that people suffer from that are mostly misdiagnosed, poorly treated, and create so much suffering, which is unnecessary.

[Dr. Amy Shah]

Yeah. And there's a term out now which, when I was in medical school, we didn't even have it. It's now called mcas. Mast cell activation synd.

[Todd LePine]

That gets a real medical diagnosis.

[Dr. Amy Shah]

It's a real medical diagnosis. I mean, we're seeing a lot of it now. And the question is, is why are we seeing so much mast cell activation? It's. It's a really, It's a. And I've been puzzling on this myself.

[Todd LePine]

Yeah, I never took that class in med school.

[Dr. Amy Shah]

I know, right, Exactly.

[Todd LePine]

But it's true. It's a big thing now.

[Dr. Amy Shah]

We're seeing. We're seeing a lot of it. And, and, and it's not like it's. It's. There's one cause for mast cell activation. There are multiple causes. And, And I actually, even in. When I deep dived into the literature, one of the things that I stumbled upon was the effects of EMF on emf. EMF is electromagnetic frequency.

[Todd LePine]

So, like your cell phone, cell towers, WI fi.

[Dr. Amy Shah]

Absolutely, absolutely. And there's some. There's some work by a woman, Johansson, out of. I think it's Sweden, who's done some work on the effects of EMFs on mast cell degranulation. And there's some good studies showing that EMFs are one of the things in susceptible individuals that cause their mast cells to release more histamine, that drives this allergic inflammatory response.

[Todd LePine]

So that's fascinating. And so what when one of the set of symptoms that you see people.

[Dr. Amy Shah]

Coming in with, well, they oftentimes will react to every food. They're sort of the people who. They can't. They have a more and more restricted diet because the more foods that they eat, it'll trigger. Because lots of foods contain histamine or will get broken down. Histidine is an amino acid. And that when you. And you consume foods that are high in histidine, things like meats have a lot of histidine, your body will actually break it down into histamine. And normally the body can process that, but when you have problems with either too much ingestion or too much production of histamine or not enough breakdown of the histamine, then you'll have problems with histamine intolerance. And these are, you know, typically a lot of people who have food allergies. And Mark, I think you've done this yourself.

[Todd LePine]

Yeah.

[Dr. Amy Shah]

This is really interesting is the old, old way of treating food allergies was what, Chromalin sodium.

[Todd LePine]

Yeah.

[Dr. Amy Shah]

Right. Remember using that and that. It's actually quite. It's actually a pretty good treatment for people who are really, really reactive to foods. And the way that chromalin sodium. Because chromolin is actually used for patients with asthma.

[Dr. Peter Attia]

Yeah.

[Todd LePine]

You inhale. It's an inhaler.

[Dr. Amy Shah]

It's inhaler. Exactly. And it's a. It's a very effective drug for really bad cases. Chromosodum can be very, very helpful for patients who have severe histamine responses to foods.

[Todd LePine]

And it's true. And people can come in with all sorts of weird symptoms that just are misdiagnosed. They have headaches, they get migraines, nasal congestion, sinus issues, fatigue, brain fog. Brain fog, digestive problems, menstrual cycle problems, nausea, vomiting. And if it's really severe, you can get really bad cramping, you can get edema, tons of fluid retention, palpitations, anxiety, your temperature regulation's off, dizziness. So a lot of people come in with all these weird symptoms. I don't know what's wrong. Taking any depressant.

[Dr. Amy Shah]

Yeah, exactly.

[Todd LePine]

So, so. But there is a. There is a way to diagnosis. And so if you're suffering from any of these issues, it may be that there may be a chance that it could be a histamine issue.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

And. And you know, when you have someone who comes in with all these symptoms. And by the way, a lot of people have edema and fluid retention. You can just stick your finger in their body and their tissue, it's puffy and swollen. You can get edema in the legs. You can see just people carrying a lot of extra weight and fluid.

[Dr. Amy Shah]

Yep.

[Todd LePine]

Is often some type of histamine activation there?

[Dr. Amy Shah]

Well, sure, Because. Well, the mast cells, which are the one. The cells that contain the histamine, they're actually found in the spaces, the interstitial spaces in the connective tissue of the body. So that's why they get puffy, because those are where those cells that are high in histamine reside.

[Todd LePine]

And it can. It can really be something that leads to chronic fatigue syndrome. This mast cell activation issue, it's a big deal. And most of the time, it's just completely missed.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

I mean, if you ask the average doctor, say, doc, I think I have mast cell activation syndrome. Can you please get me the test and diagnose me? They're going to. Yeah, you know, let me check your histamine levels. So. So when you have a patient with this, how do you begin to think about diagnosing this? Because, you know, it can. It can be a big. It can be a big deal for people. And I want to share a case later. You're going to share some cases of some patients who suffered for decades. Decades. And finally get better when we treat them.

[Dr. Amy Shah]

Yeah. Well, again, we talked on the last podcast about the role of leaky gut in the microbiome. Interestingly, when you have dysbios, some of the bacteria will actually cause more of your. Your body to produce excess amounts of histamine. So that's another thing where when the histamine is in excess in the digestive tract, that can be related to food consumption, which are high foods in the histamine, or the bacteria are actually causing the breakdown of histidine as an amino acid to go into histamine. So dysbiosis is one of the things that can trigger excess.

[Todd LePine]

Amy, the old nasty gut thing again, we're always talking about the gut here on the Doctor's Pharmacy podcast, and especially in our House Call episodes, because it's such a fundamental thing and it's connected to everything. And the microbiome is. Is so critical in so many aspects of our health. And I remember when we started doing this, Todd, decades ago, and we'd say, oh, people have a leaky gut, or there's problems with their gut floor. They have dysbiosis. They would just laugh at us. They literally would just. Doctors would just laugh at us and think we were completely crazy, insane.

[Dr. Peter Attia]

And.

[Todd LePine]

And yet it is now one of the most important areas of research in medicine is the microbiome and understanding leaky gut. And you see all kinds of papers and sc. Scientific literature using the term leaky gut. Wow.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

This is. I remember sitting. It was. It was in 1997, and I was at Canyon Ranch, and I was having dinner with some guests, and there was some doctors in the crowd, and we were having nice dinner, and we were. I was talking about leaky gut. And the woman. This woman was an allergist, so her specialty was allergy and things like history. And she looked at me and she said, you're just completely nuts. There's no such thing as leaky gut. You know, this is just a bunch of, you know what. And I just looked at her like, oh, boy. You know, and it's now, you know, 25 years later.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

And medicine's really come along. It takes a long time, but people are still struggling. And, you know, and I think the obvious. You know, the obvious. The worst sort of case scenario of a histamine reaction is obviously anaphylaxis.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

But. But that doesn't have to be that. So talk about how. How we begin to diagnose it. We look at what test besides a SIBO test.

[Dr. Amy Shah]

Well, you can measure histamine in the blood. You can also measure Tryptase, which is another marker for mast cell activation. You can also measure. There's another test. My preparation for this, I've not measured. I haven't found the lab that does it. But it can be measured as N methyl histamine, which is a breakdown product of histamine. That is another one that can be done. And then again, I think one of the tests for me is dermatographism. I find that a very helpful clinical test to determine if a person's mast cells in interstitial spaces are overly reactive and releasing lots of histamine.

[Dr. Peter Attia]

Yeah.

[Todd LePine]

And we also do a test for DAO deficiency.

[Dr. Amy Shah]

Yes. Yeah.

[Todd LePine]

So talk about what that is. DAO is an enzyme, right?

[Dr. Amy Shah]

Yes. So DAO is a diamine oxidase. So this is an enzyme that our body has, and it helps to break down histamine. So histamine has to be, you know, consumed, it's used, and then it has to be detoxified. And if this enzyme is lacking in a person, for whatever reasons, the enzyme may be turned off, you will have problems with detoxifying Histamine, especially in the gut. So. And there are enzyme products that you can use. Dao enzymes that you can use that patients respond very, very well to this.

[Todd LePine]

Yeah, we do that here at the Ultra Wellness Center. You give people histao and enzyme support. And it's interesting. There's a lot of things we do every day that block Dao production.

[Dr. Amy Shah]

Absolutely.

[Todd LePine]

Alcohol, black tea, green tea, which is a good thing, mate. Energy drinks, these all block Dao production. So it's going to increase your histamine intolerance.

[Dr. Amy Shah]

Yeah, exactly, yeah. And then, you know, you can, you can use his antihistamines. And the other thing, we had another pot podcast earlier on migraines and this is, I found this also very interesting is one of the things that is a histamine blocker is butterbur. And butterbur is used in migraines. And the reason why butterbur works in migraines is it actually is working on an antihistamine level because you can get an allergic brain, if you will. You know, we know, we know about that, where you get fuzzy in the head and you get, you can get headaches and things like that. So excess amounts of histamine has an impact on the brain.

[Dr. Peter Attia]

Yeah.

[Todd LePine]

And you know, there. And so when you see these patients, you can do some of the genetic testing, look for these DAO deficiency issues, you can look at histamine levels, you can look at some of these byproducts, you can do tests for Dao deficiency, you can look at some of the other factors that may be causing it, like leaky gut, food sensitivities. All that is really part of what we do here at the Ultra Wellness center. When we check these patients history and we look at their lab tests and then, you know, so when they come in and you sort of, you have this suspicion because sometimes it's hard to diagnose. You have a suspicion like, like it's pretty easy to sort of test and try different approaches that allow people to see if it's an issue. So what are the dietary things that we'd start with? Because a lot of histamine triggers are in the diet.

[Dr. Amy Shah]

Yeah, right.

[Todd LePine]

And so we can have a low histamine diet. So what, What's a low histamine diet? Well, foods or what actually are. Well, put this way, what are the foods that have the highest histamine that we should be avoiding?

[Dr. Amy Shah]

Yeah. So so basically the way to think about it is bacteria produce histamine. So if you have food that's old, if you have Food that's sitting in the refrigerator for a couple of days, guess what happens? The bacteria actually break down histidine, the amino acid, into histamine.

[Todd LePine]

So no leftovers.

[Dr. Amy Shah]

Leftovers, exactly. Leftovers, exactly.

[Todd LePine]

Just like the next day.

[Dr. Amy Shah]

And then fermented foods. Fermented foods are fermented by bacteria. So anytime we have food that's old or fermented, things like parmesan cheese, aged meats, et cetera, cured meats, etcetera, they. They have high histamine, and that's part of the fermentation process.

[Todd LePine]

And yet we talk about fermented foods being so good for you, like sauerkraut and kimchi and natto and miso and.

[Dr. Amy Shah]

Exactly.

[Dr. Will Cole]

And this is where.

[Dr. Amy Shah]

This is yogurt. This is where these really good foods in someone who has histamine intolerance is like putting gasoline on a fire. And they'll say, well, I'm getting worse. It's like, well, no, you should be getting worse. These are good foods for you. No, you have histamine problems.

[Todd LePine]

What is that saying was good for the gooses and good for the gander? Right. I think this is so critical, what we're talking about here, Todd, because functional medicine is personalized medicine.

[Dr. Will Cole]

Absolutely.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

It's precision medicine. And it's not only medicine, it's precision nutrition.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

So it's really important to understand that even though this way of eating may be great for some people with fermented foods and eating avocados and having, you know, delicious shellfish.

[Dr. Amy Shah]

Bone broth. Bone broth, that's another one.

[Todd LePine]

Right. We think all these are great foods, but you might be killing yourself. Of course. Alcohol and beer and all that is a problem. Wine. But, but, you know, we.

[Dr. Will Cole]

We are.

[Todd LePine]

We're. We're really here focused on what is right for you.

[Dr. Will Cole]

Yeah.

[Todd LePine]

And I think dietary dogma really interrupts personalization and approach to nutrition. Some people do great on vegan diets. Some people do terribly. Some people do great on keto, and some people do terribly.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

So there's no one size fits all approach. And what really frustrates me, Todd, and probably, I imagine you too, is that, you know, there's all these people out there on the web and Internet and promoting this and that approach and this and that diet, and they're not seeing patients.

[Dr. Amy Shah]

Yeah.

[Dr. Peter Attia]

And.

[Todd LePine]

And, and the thing about seeing patients is it's incredibly humbling if you've seen tens of thousands of patients. You know, you. You can't be dogmatic.

[Dr. Will Cole]

Absolutely.

[Todd LePine]

You can't say this is the Way you have to be vegan or you have to eat meat, or you have to eat fermented foods or. Yeah. It's like you go, wait a minute. Everybody's different. Different.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

And what works for one may not work for another.

[Dr. Amy Shah]

Yeah. One man's food is another man's poison.

[Dr. Mark Hyman]

That's right.

[Todd LePine]

And even good, quote, good foods, you know, we're talking about good foods.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

And so I think, I think this is a really important point. Particularly people have histamine issues, which is a lot of people at some level or another, they should consider trying a histamine free diet. And also other other foods that we think are also great, maybe triggering histamine. Like papayas and chocolate. Oh, my God. Chocolate, which I love would be terrible to get this condition.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

Dried fruit, certain nuts, food dyes, additives, you know, wheat ger, wheat germ. It's supposed to be health food. Right. Tomatoes, bananas, all these things may really cause increased histamine production. And sadly, in order to get this under control, sometimes you need to be restricting some of these foods for a while for your body to heal.

[Dr. Amy Shah]

It's not forever. That's the thing. I think you're absolutely right. An elimination diet is not something that you do forever. And a low histamine diet is also something that you don't necessarily have to do forever. And I think that the key thing is really working with a really good, well trained, experienced, functional medicine, nutrition, who can help you navigate all of the nuances of what to eat, what to avoid, what, what to take, as in terms of supplements can be very, very helpful.

[Todd LePine]

Absolutely. You know, the things that we want to focus on if you have histamine intolerance are foods that are low in histamine. Like fresh, really fresh food is the key. Right. Not old food, like you said, fresh meat, freshly caught fish, not fish has been sitting around for a while. Or canned fish is not as very good fruit. That's not citrus fruits. Eggs are great. Great.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

Not gluten, grains get away from the gluten. But quinoa and, and black rice. Not dairy. Avoid dairy. But you can have coconut milk or almond milk, lots of veggies, but no tomatoes, avocado, spinach or eggplant.

[Dr. Will Cole]

Right.

[Todd LePine]

So you got to be smart about this and it's a little complicated and often you need help with the nutritionist.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

All the good oils and fats that we like, those are all great. So you, you know, it's pretty much how I eat. I mean, I, I do eat avocados. And certain things, but I really pretty much eat protein vegetables, and it works so well for these patients. So, Todd, when you see a patient like this, tell me about a. Where it sort of kind of got you thinking about this and allowed you to really drive down into really the diagnosis and the treatment.

[Dr. Amy Shah]

Well, you bring up an interesting thing because, you know, as I have seen more and more patients, and I think we are seeing more patients who have, you know, histamine intolerance, call it mast cell activation syndrome, to what degree is. There are certain individuals who can be a little bit more predisposed towards this. So people who have Ehlers Danlos syndrome, you know, the hypermobile people, can actually, for whatever reasons, will have a higher incidence of histamine intolerance. The other thing in the case I recently had was a patient who came into me with severe mast cell activation syndrome. It was on a whole bunch of different medicines, including chromium, which we talked about earlier to decrease food reactions to histamine. And I saw the patient, and he gave a very interesting history, had this skin lesion which sort of like morphed into this almost like a. An scarring type ulcerated lesion on his back area. He saw multiple dermatologists, had a biopsy, had part of the area removed, and was ultimately diagnosed with a. Some type of form of a scleroderma, sort of like a malignant scleroderma, which is sort of interesting and like, oh, what's, what's that related to? But he was also having all of these. These histamine type reactions. And then when I asked him a bunch of questions, you know, I started thinking about, well, guess what? Lyme disease is also associated with histamine intolerance. Because Lyme bacteria resides in the connective tissues in the body, it sort of hides there, and that in turn can actually activate those mast cells. Which mast cells are the first line defense or one of the first lines of defense against infectious agents. And when I asked him, because he had a lot of, you know, fatigue and brain fog type symptoms too, but, you know, maybe that was related to something. So I asked him about, you know, potential exposure. So, lo and behold, he ended up having a low CD 57 count, which is oftentimes a marker. It's not diagnostic of Lyme, but it tells you that the immune system is not working so well. And when I did advanced testing on him, he had actually had conventional lab testing. I think we talked about that in another podcast. How regular conventional lab testing for Lyme disease is not that helpful. But I did a specialized T cell ELI spot test on him, and his Lyme Eli spot test lit up like a Christmas tree.

[Dr. Peter Attia]

Wow.

[Dr. Will Cole]

Right.

[Todd LePine]

So he had Lyme disease.

[Dr. Amy Shah]

He had Lyme disease, which was actually triggering a lot of his Mast cell activation type symptoms. So I've been working with him for a while, and he did very well. I put him on a supplement which is a combination of quercetin, which can help with.

[Todd LePine]

It's like a natural antihistamine.

[Dr. Amy Shah]

Natural antihistamine.

[Todd LePine]

Turns out it's really good, too.

[Dr. Will Cole]

It's.

[Dr. Amy Shah]

Yeah, yeah, exactly. Very, very powerful. Phytochemical. And I. He did very well by adding nettles along with quercetin as a sub in supplement form. He also worked with the nutritionist, got on a low histamine diet, dramatically made a huge, huge improvement. His brain was working better and his energy was better, but he still wasn't 100% better. So that's where I went. Went to the next level. And he's, you know, currently actually being treated for Lyme time. And it's in the medical literature. And I sort of stumbled upon this because I had this patient come into me and she had the same thing. She was. Had severe Mast cell activation. She was on zolaire.

[Todd LePine]

She was on injections for like, 20 grand a year.

[Dr. Amy Shah]

Yeah, yeah, exactly. Yeah, 20 grand a year. 20 grand.

[Todd LePine]

The histamine, which could be controlled by diet and these other things.

[Dr. Amy Shah]

Exactly. And. And her condition actually turned out to be the same thing. It was actually undiagnosed Lyme disease. And this is, I think, you know, one of those. You have to think about it. Not that Lyme disease causes everything, but Lyme disease is such a tricky condition that you've got to be thinking about it. Anybody who comes in.

[Todd LePine]

Masquerader.

[Dr. Amy Shah]

It's like syphilis. Exactly. It's like the great masquerader. And people can come in. I've seen people with Parkinson's symptoms. I've seen people with brain fog. I've seen people with rheumatoid, you know, seronegative. Rheumatoid arthritis.

[Todd LePine]

Kris Kristofferson at Alzheimer's, quote, Alzheimer's. Lyme disease.

[Dr. Amy Shah]

Exactly. I had one patient with fibromyalgia who is, quote, unquote, fibromyalgia, whatever that means. It means just. It means you heard all over. And so Lyme can actually mimic fibromyalgia. So you really got to think about it. And it doesn't present as one neatly neat little boxed diagnosis. It's really? You gotta. Really?

[Dr. Peter Attia]

Well, that sort of speaks to the. One of the foundational concepts of functional.

[Todd LePine]

Medicine is that one disease can have many causes.

[Dr. Amy Shah]

Yeah, right.

[Todd LePine]

Like histamine intolerance could have many causes.

[Dr. Amy Shah]

Yeah.

[Todd LePine]

And one cause, like Lyme disease can create many diseases. Like, you know, Lyme disease can cause neurologic issues and joint issues and skin issues and chronic fatigue and Alzheimer's and mast cell activation syndrome and, you know, you know, pots and all these weird diagnoses that doctors treat as if they're the thing, but actually it's something else.

[Dr. Will Cole]

Right.

[Dr. Satish Rao]

Like some symptoms of histamine intolerance will increase, will include things like. Like headaches or migraines, congestion, congestion after you eat, especially digestive issues are really high on the list. Abdominal pain and bloating, diarrhea, constipation. We talked about the rashes that can happen. Urticaria, hives, rashes that can happen. But we also know that histamine intolerance or high levels of histamine can cause a lot more systemic things as well, so. Or other systemic symptoms. So things like low blood pressure, heart palpitations, dizziness, vertigo, feelings, anxiety. So sometimes people will feel more anxious when their histamine levels are high. Chronic fatigue. And so, you know, histamine intolerance, you.

[Dr. Peter Attia]

Get a lot of nasal congestion. Right. And. And sometimes even asthma symptoms and.

[Dr. Satish Rao]

Absolutely, right, Absolutely.

[Dr. Peter Attia]

People, brain fog, and it's like everything, right? So it can often be dismissed as, you know, people don't put the dots together, and the doctors don't often put the dots together. And these symptoms are often seen as disparate or not connected, but they're all really connected, right?

[Dr. Satish Rao]

They are, right? They are. And, you know, to be honest, I've often not put the dots together. Right. So it is not always easy. We're always like, oh, oh, this person has headaches. Why are they getting headaches? Or they're having digestive issues. And then all of a sudden you go, oh, this is all related. And I've got to be thinking about histamine. And so we've learned a lot over the years, too, to be able to help people as well. So I think of mast cell activation syndrome, it's more systemic. There can be a lot more things going on. And. And when we say the word histamine intolerance, we're really thinking a lot about that reaction that happens from eating a food and that histamine reaction or that histamine imbalance that occurs after a meal where there is just too much histamine around, and the body's not able to break it down. But you know what? It's often a clinical diagnosis, Right. So it's often based on looking at that person's story and understanding, you know, really understanding their timeline and what their symptoms are and looking for those interconnections that can really help us to determine if this is what's going on for them. Because the testing is imperfect.

[Dr. Peter Attia]

Yeah, that's right. I mean, like, in terms of traditional medicine, what would be the traditional approach to diagnostics testing and then treatment? And then let's sort of talk about how we would approach this from a functional medicine perspective.

[Dr. Satish Rao]

Right. So, you know, you can measure histamine levels, right? So whether you can measure histamine levels in the blood, so you can measure something called histamine and tryptase in the blood, and you can measure histamine in the urine. It's called a. It's a methyl histamine urine test that's done. And that test is often done both both functionally and conventionally. And it can be. It can be helpful if the levels are high. So if the levels are high, you go, oh, this person has an issue with histamine. But what's a problem with this test is that the levels fluctuate a lot during the day. And depending on what you just ate and the amount of food you ate and how. We'll talk about this later.

[Dr. Peter Attia]

It's not super reliable, right?

[Dr. Satish Rao]

No, it's not. And so a lot of times these tests come back negative, meaning they look normal. But that doesn't mean the person doesn't have issues with histamine. So just because these tests are negative, it doesn't mean, oh, you can check that box and say, histamine's not an issue. So in addition to those tests, you know, we're always looking a little deeper. So we can measure things like. We can now measure things like DAO levels. So you can actually measure that enzyme level, which is many times helpful. We can look at things like, is there increased intestinal permeability, you know, by doing some tests that look at antibodies against zonulin and lipopolysaccharides, because that can give us an indication that this may be an issue. And we also.

[Dr. Peter Attia]

Zonulin is like the gluten marker for excess gluten. And lipopolysaccharides are toxins that bacteria make that create inflammation. So those are bad things that happen in your gut, and that can trigger this.

[Dr. Satish Rao]

Right. And then when the body makes antibodies against Them that means that there is increased intestinal permeability. So it's a test that we do to give us a sense of is there increased intestinal permeability and is that where we need to work to help improve this person's health? And we also look at genetics. We look at genetic markers all the time. You know, that can influence how well you make that DAO enzyme, as well as how well you break down histamine through methylation. So there's a bunch of different genetics, genetic SNPs we will evaluate for that will also give us some information about, like, how much is this person at risk for having issues with histamine.

[Dr. Peter Attia]

Yeah, it's interesting. And, you know, I think, you know, people have even weird symptoms like dramatic graphism where you kind of scrape your skin with a fingernail and it'll just like welt up and look bad. So you can write stuff on your skin and it's like graffiti, right?

[Todd LePine]

But these are really a whole host.

[Dr. Peter Attia]

Of really disparate symptoms. And again, this is a spectrum, right? Histamine intolerance, mast cell cell activation syndrome. They're all part of a continuum of dysfunction of your immune system, overreaction of the allergic response in the body, and triggers all this cascade of downstream symptoms. The problem is traditional medicine doesn't do a very good job of this and throws a lot of medication at it. Antihistamines, things like Allegra, Claritin, Zyrtec, or what we call H2 blockers, another histamine receptor like Pepcid or Tagamet. And then they use, know, mast cell stabilizers, which actually I think are. Can be helpful like chromoly and sodium.

[Todd LePine]

Which we, which we use.

[Dr. Peter Attia]

And you can take it orally as a, as a liquid before you eat to kind of decrease any reactions to food. And I find that extremely helpful during safe medication. But there's more serious ones like Singulair for leukotriene inhibitors, which are. Which are, you know, strong medications, steroids. So that's really kind of the. The toolkit. And it's a very limited toolkit and often doesn't really solve the problem. It's just massive symptoms. So the beauty of functional medicine is that it helps start to think about the symptoms. And as you mentioned, we do a deeper dive. We look for things like leaky gut for food intolerances. We look at dysbiosis, what's happening in the gut. We also look at mold and environmental toxins and hormone levels and all the things that we know really Are, are relevant when it comes to sort of trying to understand the root causes of, of overactive histamine response. So I, I think it's, it's an area I think we have a lot of success with and a lot of different approaches than traditional healthcare. I think the interesting thing about histamine is that it also is in food. So people have to eat. You make histamine in your body, but you also get histamine from various foods. Maybe you could share, you know, what initial approach would be from a functional medicine perspective. You know, we do with the deep diagnostics as we mentioned. You know, look for leaky gut, look for dysbiosis, look for hormone imbalances, toxins, look for food sensitivities, look for mole issues. We do, you know, genetic testing to look at histamine related enzymes like Dao and maybe even urinary histamine levels. So we do a whole range of tests. But then, you know, once we find out someone has this, what's kind of the general approach you would take to dealing with the root causes?

[Dr. Satish Rao]

So, right, we want to calm down the body and calm down this reaction, this overreaction that's happening in the body. And so we will often do a trial of a low histamine diet. And it can be very effective, as I mentioned, with this patient with migraines and how effective it was, was. But what's important, I think really important to just start off with is this is not a lifelong diet because there's a lot of really healthy foods that have histamine in it, right. Or even can cause histamine to be released in somebody's body. So what we ultimately want to do is decrease the body's reaction to these foods and heal leaky gut. But let's start talking about this low histamine diet because it is a really great tool that we are using often. And just it's for, for a bunch of reasons. One, to see how much is this, is histamine related to this person's symptoms and then how can we help? Start to calm down the body's immune reaction and then over time we work to relax the diet. So what, what we always do is we do phases so we're not overly restricting foods. And it's, you know, because it's important to recognize that the amount of histamine in a food varies significantly depending on how long that food has been sitting there, how long that food is, you know, how long since it's been picked or caught or prepared. We know that foods that have been. The longer they've been sitting there, histamine levels will go up. And so it's important to think about a lot of different things when we're doing a low histamine diet. So in terms of the phases, what we start with first is removing alcohol, especially beer and wine and champagne. Those, as you mentioned earlier, are foods or drinks that are high in histamine, and they also block the body's ability to break down histamine. So we pull those away first. And we also work with people to make sure that they are not keeping a lot of leftovers around. They're eating foods that are fresh, very newly prepared. If they do have leftovers, they want to freeze those foods right away, because the longer the food is sitting there, the more histamine it will produce. For example, we also know with fish, for example, you want to try to eat fish 30 minutes after it's been caught. Well, because that will have the lowest meat. Exactly. That's so hard to do. So a lot of times people will have frozen fish, which is good because those fish are often frozen very quickly after.

[Dr. Peter Attia]

Oh, that's interesting. Yes, that's interesting.

[Dr. Satish Rao]

And they're going to be lower in histamine. But the key is when you defrost your fish, you want to. You want to prepare it right away and consume it right away, because the longer it's being defrosted or the longer that, you know, if you eat that food two diet, two days after you prepared it, there's going to be higher levels of histamine in it. So all of that can be really complicated. So I will always recommend. And, you know, we do this at the Ultra Wellness Center. You know, we have, what, seven nutritionists now? You know, I always recommend people work with the nutritionist. I work with the nutritionist because. Because it can be such a complex process to figure out and to remove. And you want to do it in a healthy way where you're not overly restricting. But, you know, it can be really helpful. So you want to have fresh foods, minimally processed foods, and you want to have foods without those additives in it that, like sulfates and msg, things that can trigger more of a histamine response in the body.

[Dr. Peter Attia]

Just like, you know, the aged cheeses, fermented foods, alcohol. Those are all really full of histamines. You have to be really careful with those.

[Dr. Satish Rao]

Absolutely. We put a lot of those in phase two. So phase one isn't enough to calm down the body. Body. Then we'll move and pull away the canned and smoked fish, anchovies, which unfortunately is one of my favorites. But again, this is not a lifelong meal. Food restriction. Processed and fermented meats, we pull away aged cheeses, pickled and fermented foods, which like sauerkraut, kimchi, yogurts, kefir, mustard, ketchup, vinegar, soy sauce. You know, a lot of these, as we talked about earlier, are really healthy foods. So we want to be able to add them in in the future. But sometimes, again, we pull them out for a period of time to see how much that helps somebody's symptoms improve. And they typically will see improvements in two to four weeks. So it's like a two to four week removal to get a sense of how much things calm down in the body. There is even a phase three where we have to restrict even more and pull away some plant foods like avocado, spinach, tomatoes, pineapple, citrus foods that can also trigger some histamine reactions in some people's body. And so again, we do it in phases and we can, you know, we can attach this handout, I think, right Mark to the, for a few people.

[Dr. Peter Attia]

In the show notes, we'll put a handout on the different phases. Phases so people can listen in and actually figure out what to do. By looking at this handout that we have provided at the Ultra Wellness center, we'll put a link to it and I think it's kind of a good guide on how to get started on your own. But one of the challenges is that even if you do all that stuff, I always say we need to figure out not what you're sensitive to, but why you're so sensitive. And that's sort of the next phase. You can get people immediate relief by removing histories histamine and by giving them, you know, DL enzyme and maybe some other things that sort of are mitigating symptoms, you know, whether it's antihistamines or cromolyn or whatever you're going to give them. But at the end of the day, to really resolve this, you have to dig deep into the root causes and to try to deal with those things that we really are good at in functional medicine but are not so great at in traditional medicine. And, you know, and that involves everything from optimizing and fixing the gut, whether it's bacterial overgrowth, fungal overgrowth, growth, leaky gut inflammation, healing and repairing the gut, which, you know, we have a whole program 4 and 5R program in functional medicine. I've done many podcasts on the gut optimizing nutritional status that affects their Immune system, whether it's vitamin C, B6, magnesium that support histamine metabolism. And also the stress reduction part, which is really key because that activates everything. Getting regular sleep, exercise, but then also diving, seeing, well, do you have mold? Do you have environmental toxins? Do we have heavy metals causing this? Do we have something else going on that we need to treat directly? And how do we upregulate your detoxification system? So we really treat both the histamine syndrome itself, but also then dive into root cause treatment so that people don't have to suffer with this their whole life.

[Dr. Will Cole]

We now believe that, and sort of brought this up as part of the introductions is that we now believe that food poisoning starts the whole process. So you. And eating is part of it. You know, back in the day, meaning like 40, 50 years ago, when we were in kindergarten, we would sit in a sandbox and eat the sand. Now we eat salad out of a bag until we go to Club Med. And for the first time in our life, we see salmon or we go somewhere and we get traveler's diarrhea or we get food poisoning or whatever. We start to explore the world of food. But food poisoning triggers this. And we now have identified the toxin in food poisoning, the CDTB toxin that trips off some antibodies in the human body that then cause your nerves of the gut to fail or to be impaired. And so when the flow of the gut, gut is slowed by this impairment, bacteria build up. And there's two bacteria that just flourish when it's a little more swampy. So I used to watch Survivor shows on TV and Discovery Channel, you probably watch those. And they always say, I like the loss.

[Dr. Peter Attia]

I used to watch Loss, which was kind of like Survivor.

[Dr. Will Cole]

It's a little bit different. There's a little more raunchiness with Survivor. You're just kind of trying to make it to a roadside somewhere. But the point was that he always, this guy on the Survivor show would always say, if the water's not moving, don't drink it. If the water is flowing fast, drink it because it's cleaner. And the same thing with the small bowel. If the small bowel stagnates, it becomes swampy and bacteria grow in it. And the same thing is happening in the human small intestine. And so it's a sequence. So food poisoning, the antibody bodies, and then you develop the bacterial buildup.

[Todd LePine]

So you're almost saying it's like an.

[Dr. Peter Attia]

Autoimmune disease of the nerves of the gut that develops that kind of sluggish.

[Todd LePine]

So this is a kind of a.

[Dr. Peter Attia]

Radical idea that irritable bowel is an autoimmune disease, isn't it? I mean, this is kind of not what most doctors typically think of when they think of ibs. They think of IBD or inflammatory bowel disease, but they don't think of, you know, irritable bowel being auto.

[Dr. Will Cole]

The interesting thing about contrasting IBD to ibs, so the antibody that we discovered is an autoantibody that is directly related to the pathology. So the higher that antibody is, the sicker you are. The antibodies in IBD are markers of ibd. They're not directly implicated in the pathophysiology. The antibody to vinculin that we discovered is directly related to the pathophysiology. We can make rats have IBS just by giving them this talk toxin. And so that. That's very cool because it allows us to study new drugs and new therapies coming in.

[Dr. Peter Attia]

Not so cool for the rats, though.

[Todd LePine]

So this is fascinating.

[Dr. Peter Attia]

So you were saying there are different kinds of bacteria. Can you explain what are the kinds of bacteria and then what type of food poisoning is it? Any, like, if you get Giardia or if you get Salmonella shigella, Campylobacter or entamoeba or like, you know, what are the kinds that typically cause the problem?

[Dr. Will Cole]

Well, the four horsemen of the apocalypse of IBS are Campylobacter, Salmonella shigella, and some E. Coli. Food poisoning type of E. Coli. Pathogenic E. Coli. Giardia can do it too. It turns out it has vinculin in its structure. And so maybe that's how you get the antibodies from Giardia. The viruses are less likely to precipitate ibs. So the four horses horsemen, Campylobacter, Salmonella shigella, and E. Coli. So that's, that's.

[Todd LePine]

And.

[Dr. Will Cole]

And it occurs about. Starts to occur about three months after you get sick. Patients will remember, some don't remember, and they'll say, well, you know, they have a couple of days of diarrhea and they don't pay much attention to it, but they remember going on a trip to Hawaii and they end up in the hospital with bloody diarrhea. And then ever since then, nothing's been the same.

[Dr. Peter Attia]

I have heard that story so many times. You know, I went to. To Thailand or India or, you know, Jamaica and like, and sort of trip. The whole thing going.

[Dr. Amy Shah]

Yeah.

[Dr. Will Cole]

Or the taco truck in Venice. Yeah. So a lot of possibilities.

[Dr. Peter Attia]

Wow. So. So this explains like sort of 60%, you say, but, you know, not all of it. Right. What are the other things that may be driving irritable bowel syndrome? And are they also related to sibo or is it. Is it all. All something else?

[Dr. Will Cole]

Well, so based on culturing the bowel, we've been able to isolate that 60% of IBS is SIBO. The other 40% is a mixed bag. So, for example, and you probably talk about this now, Ehlers Danlos syndrome, Potts syndrome, we're starting to recognize those illnesses as characteristically GI centric, at least in their early presentations as well. So some of the leftover 40% have Ehlers Danlos syndrome or POTS, or some of them are celiac that we've missed. Some of them are food sensitivities, some of them are histamine sensitivities, some of them. So it's a mixed bag of a number of other disorders, and some of them are fungal overgrowth. So we see that in about 6 to 10% of that hundred pie. So there's still more to unpackage. We're not ignoring the other 40. We're trying to figure the rest stout. But it's. It's a little bit harder to unravel.

[Dr. Peter Attia]

So let's pause there for a minute because you just said something that I think might slip by, which is this whole idea of fungal overgrowth, or what often is referred to as sifo, small intestinal fungal overgrowth. You know, and in my coming of age as a functional medicine doctor, basically people would laugh when we talked about yeast overgrowth or anything like that and candidiasis. And it was just like a quacky alternative, alternative concept. But it seems to be now understood as potentially playing a role in some of these cases. Can you talk about the current understanding of this and actually some of the treatment? And then I'll sort of loop back to the. How do we start to treat and think about IBS differently?

[Dr. Will Cole]

Yeah, I mean, Satish Rao, Dr. Satish Rao in Georgia has done a lot of the seminal work in this, but more recently we've done shotgun sequencing of the small intestine, and we've been seeing this fungal overgrowth.

[Dr. Peter Attia]

That doesn't mean you shoot somebody in the gut with a shotgun.

[Dr. Will Cole]

Shotgun sequencing means we sequence every single piece of DNA we can find and then characterize it and see what organisms it represents. Yeah, and it represents fungus about 10% of the time, and that when the fungus is higher, the patients are experiencing more abdominal pain and more diarrhea. So there is a subclass of these patients that it is fungal, but it's smaller than some would like to believe, but larger than those who are naysayers, as you've probably heard. And so it is there. It's real and. But it's a little more challenging to identify. There's no breath test for it. You got to go in and chase it. And that's the challenge.

[Dr. Peter Attia]

Chase it by doing stool cultures or.

[Dr. Will Cole]

Well, chase it could be by stool, but if you want to find small intestinal fungal overgrowth, you got to get into the small intestine. And that's really sample it, endoscopy and all of that. That's how Dr. Ross Rao identifies it.

[Dr. Peter Attia]

Yeah. And. And any particular species of fungus, or is it sort of a broad array?

[Dr. Will Cole]

So what we found in this, quote, shotgun sequencing is Candida albicans is a big part, and a little bit of Candida glabrata and there's a few other Malassezia and all these other organisms that are very minor, but they generally aren't at a high number that we think are as consequential as the first two dimension.

[Dr. Peter Attia]

Yeah, no, I definitely have seen that on cultures and. No, you know, in my experience, maybe it's not universal, but it tends to lead to more constipation. And so people tend to have more constipation. And also I can tell because they might have other fungal symptoms. They might, you know, eat tons of sugar and starch. They might actually have fungal rashes on their skin or dandruff or other kind of clues that they have kind of a yeasty kind of situation going on. But I think it's important that it's been identified. And going back to kind of the treatment of that, how would that normally be treated?

[Dr. Will Cole]

Well, yeah, generally in allopathic medicine, we try an antifungal. There are natural antifungals as well, and you're probably better versed in those than I am. But we do use fluconazole. We do use nystatin. Occasionally we use more radical, more advanced antifungals, but those are the typical first two choices.

[Dr. Peter Attia]

Yeah, sometimes you can take what we used to call amphoterable, which is a horrible first generation antifungal, but it's not absorbed. So if you take it orally, it's not absorbed. And that can totally be, you know, and then. And in terms of the bacterial stuff, you know, you talked about these three different bacteria, right? You've got methane producing, hydrogen producing, sulfide producing, and they all are a little bit Different. And, you know, said the methane producers are not really bacteria, they're archaea.

[Todd LePine]

But, you know, for, you know, simplicity's.

[Dr. Peter Attia]

Sake, let's call them bacteria. And, and I don't, I don't think most people know what ARCA is. It's arcane, Right?

[Dr. Will Cole]

So it's arcane. Yeah.

[Todd LePine]

So what, what is your approach to starting to kind of differentiate these and.

[Dr. Peter Attia]

Then how do you determine what the right treatment is for a patient and can kind of, kind of guide us through what to do both in terms of, you know, lifestyle, diet, and any kind of supplements that might be helpful and medication.

[Dr. Will Cole]

Yeah. So first of all, we helped develop the first three gas breath tests. So just full disclosure, but it's changed my practice because there are patients who fell through the cracks without knowing hydrogen sulfide. So unpacking each. The hydrogen positive breath test patients are generally. We actually just published this paper. It came out literally yesterday. There are two bugs. That's it. That cause the hydrogen overgrowth. It's Escherichia coli, the non pathogenic one, and Klebsiella pneumoniae, those two characters, when they come into town, everybody leaves because they're so opportunistic and bullies. And we think they produce even toxins to the other bacteria around them to try and get rid of the inhabitants. So it's like you've got a gang that comes into the small town and everybody leaves. So it's a disruptor of the microbiome and then they rise very high in number. So that's the hydrogen one. The second category is the methane or methanogens. And those characters live both in the colon and the small bowel. And we have a paper coming out showing exactly where they're living. And it's pretty universal in a lot of these papers, patients. So hence we call it intestinal methanogen overgrowth and not sibo methane, because it's not just the small bowel, it's colon also. And when they produce methane, it gives you a lot of constipation, a lot of gas, and you can't pass the gas. And these people are quite miserable. And then the third is the hydrogen sulfide, which is the new kid on the block, which has changed my practice because some of those patients we didn't know. Breath test is normal, everything looks fine. And then the hydrogen sulfide's positive, we get rid of it and all of a sudden they feel better than they have in their life. And for some reason, when you get rid of hydrogen sulfide, it doesn't Come back so quickly, which is beautiful. I have patients who've gone a year, just one treatment and they're done. And so I'm really excited about that. So, I mean, I could talk about the treatments if you like now or.

[Dr. Peter Attia]

Yeah, yeah, yeah, go through the treatments.

[Todd LePine]

Because I think they're all different.

[Dr. Peter Attia]

And this is important to understand for.

[Todd LePine]

People because, you know, just because you.

[Dr. Peter Attia]

Have a little bowel, it's not like a one side size fits all approach. You've got to differentiate what type it is. And, and These tests that Dr. Pennington developed, the tests for anti CDTB and anti viculin antibodies are really important. And then the, the breath test that allows you to look at hydrogen, methane and sulfur. So can you talk about what are the, you know, what are the different treatments for each of these?

[Dr. Will Cole]

Yeah, so I mean, if I have an IBS patient with diarrhea or a patient with diarrhea and bloat my practice now, I do the antibodies because I want to be able to say, was it food poisoning or not? And if the antibodies are really high, it makes it harder to treat. But also you travel, you better take prophylaxis because you could get into further trouble with these antibodies going higher. So I universally do that like prophylaxis.

[Dr. Peter Attia]

Like what? Like xifaxan.

[Dr. Will Cole]

So I give xifaxan prophylaxis. That's what I do in my practice. And a lot of the GIS now do that because if the antibody goes higher, the damage to the nerves of the gut is more intense or the effect on the gut is more intense. And at least that's what we're seeing in our clinic. So we're very careful with those patients who have the antibodies positive when it comes to. Then we do the 3 gas breath test in all of our patients. And if it's hydrogen, and we all know rifaximin got FDA approved for IBS with diarrhea on the basis that IBS was in part a microbiome disease. And now we understand that microbiome condition is serious fibo. So I give rifaximin for that. If it's methane. We have one double blind study that we can lean on and it's rifaximin plus either neomycin, which is what the double blind study covered, or rifaximin and metronidazole. And then the third category is hydrogen sulfide. And we give rifaximin, but we give it with bismuth because bismuth is an anti. It blocks some of the synthetic functions of Hydrogen sulfide in the sulfate reducing bacteria. Point is, the hydrogen sulfide goes down, the bacteria are reduced and therefore the patient's normal bacteria take over and things get better more permanently in that group, it looks like.

[Dr. Peter Attia]

And that's basically Pepto Bismol and Pepto Bismol. Yeah, yeah.

[Todd LePine]

Interesting.

[Dr. Peter Attia]

So in terms of diet, is there a different approach to each of these in terms of what you would recommend from a food point perspective?

[Dr. Will Cole]

We haven't sorted out or had time to sort out the different diet approaches, but I envision smarter people in me and diet will come up with a way. What we do now is what we call low fermentation eating. So we don't use low fodmap in our practice because you can't do it indefinitely. But low fodmap will reduce the amount of calories you're providing to bacteria and therefore they'll ferment less and less. And that might help. But long term, low fodmap hurts your microbiome and can cause nutritional deficiencies. So you can't stay on the full low fodmap indefinitely.

[Dr. Peter Attia]

And fodmap is like fermentable oligosaccharides that.

[Dr. Will Cole]

Yeah, fermentable oligosaccharides, monosaccharides and etc. And, and, and basically it's too restrictive. But you've probably, most people have probably read about fod low fodmap diet. It's very popular in the last few years. But we use what's called low fermentation eating. Not as restrictive. And the philosophy of that was with a low fermentation diet, you can go to any restaurant in the country and you'd find a meal. So it's, you know, you don't want to be the person at the table just because you have IBS that spends 10 minutes with the, with the, you know, trying to explain your dietary restrictions on a low fodmap diet. So, you know, that's part of the reason we want our IBS patients to feel as normal and as socially non isolated as possible. And that's part of it.

[Dr. Peter Attia]

What is a low fermentation diet?

[Dr. Will Cole]

So it's basically restricting non digestible carbohydrates, so low fiber, no dairy, and then none of the artificial sweeteners because of course they're easily fermentable. And then spacing your meals so you don't eat for five hours between meals because the damage of the nerves, we talked about that earlier, the damage to the nerves causes a reduction in cleaning waves of the gut. So the cleaning waves only occur when you're not eating. So your gut is sort of like got two computer programs, eating mode, cleaning mode. If all you do all day is spend time in the break room room taking a bite of a bagel that's in the break room, you never go into cleaning mode. So in addition to the construct of what to eat, we tell you when to eat and to try and space your meals out.

[Dr. Peter Attia]

So anyway, is it interesting? The typical dietary recommendation when I was in medical school for IBS was more fiber, like metamucil. Basically what you're saying is that you want to restrict soluble fibers that are diet digestible and low, low fiber diets seem to be, you know, it seems like a contrary notion when you want to create a healthy microbiome, because good bugs also live on fiber. So how do you, how do you navigate that?

[Dr. Will Cole]

Well, you know, I may be punished for saying something like this, but everything has fiber in it now. Even Cheerios, they put fiber in it because it prevents colon cancer and it's colon health and all this stuff for 20 years. How many, how much have we heard about colon health in fiber? What have we got now? We've got colon cancer happening in the 40s and we're doing screening colonoscopy at 45. Now, I'm not saying it's fiber causing that, but all the fiber we've been pounding and the cardboard we've been eating hasn't really done as much as we thought it might. So I'm a little unclear about fiber, but from the point of view of bacteria, you put more fiber, you're going to have more of the bacteria. If you had bad bacteria to begin with, there's going to be more of them. For a healthy person whose microbiome is healthy, no problem. But not for these patients with these microbial conditions.

[Todd LePine]

Now, if you've gotten, you know, these.

[Dr. Peter Attia]

Antibiotic treatments, you know, you've gotten diagnosed, you've gone through the testing, you've gotten the personalized treatment, you do the course of antibiotics. What prevents the bacteria from coming back? And in my experience, it often does. So how do we manage this sort of recurrence that occurs because you don't want to keep giving people antibiotics, because intuitively people go, wait a minute, antibiotics are bad for the gut. So why are we giving antibiotics to someone who's got a gut problem? It seems counterintuitive.

[Dr. Will Cole]

Well, I can answer that in two or three ways, but I'll try to touch on a little bit of each. We looked at rifaximin before and after treatment the small bowel. And when you get rid of the bullies in the town, all the inhabitants of the town come back. So it goes opposite of what people think. We're not not, you know, being cataclysmic. It's getting rid of the E. Coli and the klebsiella in sibo that allows the regular bacteria to reflourish, repopulate and take over again for a period of time. But remember, the problem is those cleaning waves are not working. So it is possibly going to come back. It depends how badly damaged. And that's where that antibody comes in. Because if the anti vinculin, which is that auto antibody for the autoimmune disease of IP IBS is very high, the neuropathy is more high or more intense and you're going to relapse or reoccur more frequently. So that's where we were able to have some further strategy. But first of all, take the antibiotics. They actually repopulate the town counter to what you think. We've never seen antibiotic resistance to rifaximin so far, knock on wood. It's a very unique chemical drug. And then we get them on the low fermentation eating diet. That's what we do. And for those where the antibody's high or those who relapse, we do put them on a prokinetic so they space their meals. Everything's going right. But we want to stimulate those cleaning waves at nighttime because that's the longest time you're not eating and make you clean up as much as possible at night so that the bacteria don't have a chance to come back. So we don't do all three things for everybody. It depends on, you know, if somebody relapses in two years, we don't need to put them on a drug every day to prevent. But if they relapse every three months, then we can stretch it out to a year by adding the prokinetic or doing more aggressive diet strategies.

[Dr. Mark Hyman]

If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at DrMark Hyman, please reach out. I'd love to hear your comments, comments and questions. Don't forget to rate, review and subscribe to the Dr. Hyman show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on the Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness center, my work at Cleveland Clinic, and Function Health where I am Chief Medical Officer. This podcast represents my opinions and my guests opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness center at ultrawellnesscenter.com and requ request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public, so I'd like to express gratitude to sponsors that made today's podcast possible. Thanks so much again for listening.