Healing The Brain-Gut Connection

Steven Gundry, MD

Yes, and that’s great. Dale, it’s great to see you again. You and I, through the years, with our interest in the ApoE4, have become very good friends, and almost not a week goes by that you’re sending me a paper or I’m sending you a paper, and yes, you’re right, it is frustrating for people to understand or to not understand that these processes are stoppable. If we get to it early enough, it’s reversible, and people need to hear this message. I’ll give you the example of just a couple of weeks ago. I saw a young woman, young in her early 40s, who was diagnosed with Parkinson’s about six months ago, and she initially noticed it as a pretty impressive tremor in her left arm. She fit all the criteria and was started on the usual medications, which may have made things a little bit better, but maybe not. 

Anyhow, the one thing she told me from her first interview was that I’ve always had a funny stomach, and if I have heard it once, I’ve heard it now tens of thousands of times. But she said, I’ve always had a funny stomach, and my mother told me that I was lactose intolerant as a child—bad lactose intolerance, blah, blah, blah. As part of my workup, now invariably I do leaky gut tests. For anyone listening, please. Leaky gut or intestinal permeability is not pseudoscience. It’s not quackery. It was well-established by a professor of pediatric gastroenterology, Alessio Fasano, who’s now at Harvard, and the mechanisms of how leaky gut occurs. We understand that intestinal permeability can be measured. You and I both know that Hippocrates said that all disease, including dementia and other neurologic diseases, is rooted in the gut, despite dysbiosis and intestinal permeability. This lady had a leaky gut. We discovered, I think, the reasons why she had it. 

We’re now six months into her treatment. The exciting thing is that her tremor is virtually not noticeable anymore. It’s just. Yes, and she’s, I remember her, and I remember her like this. Now she says, Look, yes, maybe there’s a little something. But she saw this night and day and she said, I was all set to, have the most miserable life possible, 42 years old. I’ve got Parkinson’s. and now, she said, look at this. Look at me and know what’s changed except teaching her how to eat. That’s what’s so exciting. This is a young woman facing a horrible future. If she had stayed in, our allopathic medicine model of treating Parkinson’s.

Dale Bredesen, MD

Absolutely. Of course, you just continue the degenerative process, unfortunately.  No matter what you do in cinema and what you have, you’re going downhill in the long run. It’s great to get to the source. Let’s talk about some specifics. Well, certainly, we know that both in Alzheimer’s and Parkinson’s, there are changes in the gut microbiome. Question one would be: What do you like to do to heal the gut? Are you a probiotic as a person, or are you a specific probiotic that you like? Are you a bone broth person? What are the sorts of things that have given you the best results?

Steven Gundry, MD

Well, in my new book, I come down pretty hard on bone broth because it has a sugar molecule called Nue5Gc, which can unfortunately leak through the blood-brain barrier and produce neuroinflammation. You and I don’t exactly like neuroinflammation. I’m much more interested in people taking glutamine for a while. I don’t like it long-term, but certainly, three months’ worth is good. But when I teach people how to heal leaky gut, and I even make a supplement called Total Restore Gundry M.D., it works well, but what I tell people is, look, we can heal your leaky gut, but if you keep swallowing razor blades every day, then you’re just going to rip it open, and Dr. Terry Wahls, who’s become a good friend of mine, both of us agree that lectins and other plant defense compounds are mischievous for most of us. 100% of my people with leaky gut have antibodies to the various forms of wheat, including gluten, including wheat germ gluten, and 70% of them have antibodies to corn. Many people who go on a gluten-free diet are eating corn and thinking it’s perfectly safe. Well, it’s not. 

It’s a 1/2 punch. Yes. We do want to heal the leaky gut, but we do want to stop swallowing these things that keep opening it up. Now, to your point on butyrate, one of the things that, when I wrote Gut Check, just surprised me, it shouldn’t have, is that people who carry the ApoE4  mutation, and there’s 25–30% of people who carry it. Their genes prevent them from having short-chain fatty acids, producing bacteria in their gut in sizable numbers. You and I have talked about this, and it’s amazing how many of these people do not lack butyrate-producing bacteria in their guts, and they almost always lack the keystone species Akkermansia. There are certainly many others, like Clostridium butyrate, and producing and getting them to take supplements that now can deliver these and then feeding these bacteria the foods they want in prebiotic fiber and postbiotics makes a world of difference for these people.

Dale Bredesen, MD

Yes, great point. Do you have a favorite probiotic, then?

Steven Gundry, MD

Well, I like Pendulum Life. Interestingly enough, the one I start everybody on now is the one called Metabolic Daily. It’s a combination of Akkermansia and other butyric acid-producing bacteria, and it’s also the most affordable of their three, and I’ve got no skin in that game. But that’s what I start people with, and that’s a good start. Most of the butyrate-containing compounds, in my humble opinion, are fairly worthless, but nano-encapsulated butyrate does work. I have one at Gundry M.D., but other people have it. It’s called Bio-Complete 3, and the folks at Pendulum are big fans of nano-encapsulated butyrate because butyrate has to get delivered down to the colon, and most of the butyrate compounds never make it that it’s digested before it ever gets there. 

Dale Bredesen, MD

Yes, great point. The other question I wanted to ask you about is when you look at the cellular and molecular biology and signaling in Alzheimer’s disease in cognitive decline beyond that also vascular dementia, Lewy body disease, things like that, you come back again and again and again to three major things. You come back to energetics, which are suboptimal. It’s very much related to what you’ve been talking about. You come back to inflammation from various insults, various toxins, etc., and you come back to toxicity. Of course, Christopher Palmer has written a book called Brain Energy all about mental health and energy.  We certainly see the same thing with Alzheimer’s disease. If you’ve got low vascular flow or poor mitochondrial function, you’re going to be at increased rates. The question is how to get that back. What do you like, for example, for NAD? How do you like to increase NAD in your patients?

Steven Gundry, MD

Well, any time going way back 20 years and how I initially gave everybody the ApoE4

mutation plain old niacinamide and because it was based on a few papers in rats showing that niacinamide increased in NAD plus and it does. It’s dirt cheap now. I like NR and NMN. They are a bit pricey so a lot of times I’ll see Medicaid patients and a lot of times these supplements are just out of their reach. But niacinamide is not out of people’s reach. It’s a good work. 

Dale Bredesen, MD

It works. 

Steven Gundry, MD

Yes. We can say, well, which works better, but it works. There’s very good evidence for that. I like to give it at night. The reason I like to give it at night is it works better at raising HDL cholesterol and lowering LDL cholesterol if you give it at night it’s still very effective at lowering Lipoprotein A, which is one of the biggest causes of vascular dementia. Anything we can do to decrease LP-A activity seems to me to be worth it. But to get back to your point, the mitochondria in memory loss and all of these diseases of the brain are dysfunctional. You and I have said, a ketogenic diet is something that we should look at with these folks. You’ve documented how well that works. I agree that ketones are superb signaling molecules to make mitochondria uncouple, and we won’t go into that today. But I like my mitochondria uncoupled. But during the signaling, you tell mitochondria to repair themselves, to have mitophagy, and to build more mitochondrial mitogenesis. I’m very impressed with this new compound Urolithin-A.

Dale Bredesen, MD

I asked you about that. I’m glad you brought it up.

Steven Gundry, MD

I talk a lot about it in the book. It’s been formulated by a company out of Switzerland called Timeline Nutrition. I’ve seen some impressive effects on my patients. Again, it’s unfortunately a bit pricey. But when we’re talking about the brain, at some point you’ve got to say price is way down on the list of what we should be worried about. A daily dose is cheaper than a cup of coffee. That’s how we have to look at some of these supplements because the evidence is very impressive about Urolithin-A’s ability to produce mitophagy and mutagenesis.

Dale Bredesen, MD

It’s a good point. If you look at the average American who dies of Alzheimer’s, that’s 15% of the population. It’s very common. They are going to spend on average about 300 dollars, and that’s before inflation. It’s probably now more like 400 – 450 thousand dollars before dying. That’s, of course, a lot of that going to a nursing home. Yes, if you can get rid of that. In our argument, we’ve just had a paper accepted that’s going to be coming out showing documented, sustained improvement for over 10 years. That’s never been seen before. People have never documented this. As you and I both know, these people can get better, and then they can stay better. One of the interesting things we learned is that often they’ll go for several years and then begin to have a secondary decline. Lo and behold, you find out what’s causing that. They go back and then write it back up again. If you can keep people out of nursing homes, spending a little bit on a supplement is just not going to be an issue. It’s a great investment as part of an overall plan to keep you out of the nursing home, save you a great deal of money, and, of course, save your brain as well. So I think there’s no question that these are critical things.

Steven Gundry, MD

Something I think we neglect to mention is becoming the caregiver of someone in cognitive decline or with Parkinson’s. Is being a caregiver oftentimes harder than the person who is getting the care? Unfortunately, I  see these people every day. Yes, it’s nothing else. Think of your family or your loved one who’s going to have to provide the care. Again, the exciting news, as you and I know, is that we can stop this in its tracks. Given the circumstances, we can reverse it. You’ve now spent your career trying to convince people of this, and I’m behind you.

Dale Bredesen, MD

Yes, we’ll get there. I think the two biggest problems are that number one, people don’t believe it. Or number two, they want to wait till the end stage. We had a person just recently as a physician who went to his neurologist, and this guy was into the fourth stage, passed, SCI, MCI into dementia, and the doctor of neurologist told him this is normal aging. This is one of the things that I think is changing. We’ve changed. This is part of 21st-century medicine. Don’t wait for a lot of symptoms. Look at risk and look at the earliest changes. This is why we recommend anyone who’s 40 or over. Please get a Cognoscopy. It’s easy. You can get a blood test. You can get a simple online evaluation. If you have symptoms, you can get an MRI with volume metrics. But if you don’t, you don’t have to worry about that. 

But the reality is that very few people need to get this disease. Unfortunately, everybody, so many people are coming down with it. It’s going to dwarf the pandemic. We’ve got over a million people dead from the pandemic in the United States. About 45 million statistically slated to die from Alzheimer’s among the currently living Americans. Let me go there for a moment. Steven, what are you seeing and what are you doing? We’re now in a new bloom, unfortunately, of COVID-19, and certainly Long COVID has so many parallels with what ultimately becomes Alzheimer’s. ongoing inflammation, ongoing mitochondrial damage, ongoing brain fog, and dysfunction. There are just too many parallels. It’s quite scary. What are you telling your patients who are getting COVID now, typically the JN1; I guess it is now a variant.

Steven Gundry, MD

Well, I’m one of the people who thinks that most Long COVID originates from the leaky gut caused by the COVID virus. Initially, 25 to 30% of people with COVID’s presenting symptoms are GI. Whether it’s nausea, whether it’s abdominal pain, or whether it’s diarrhea. Viruses are notoriously good at producing leaky gut, and through the years, many of my patients will describe a viral illness that started their autoimmune disease. I think I mentioned to you just last week that I saw two people with nuance of Crohn’s in their 40s following a COVID-19 infection. Neither of their GI people even considered that that was one. What happens, I think, is that COVID-19 opens the door for all of these pathogens to come out through the gut to cause neuroinflammation. then it’s a hard process to stop. One of the things that is frustrating, I think, probably to you and me, is that once you activate the microglia, thinking that they need to protect the neurons, it’s hard to tell them, Hey, relax. Trouble is not coming on the way. That’s where I think you’ve been so effective. My patients’ current treatment is aimed at reducing chronic inflammation. I think COVID is a great way to start the process.

Dale Bredesen, MD

It’s interesting. We’re seeing that the amyloid that people have vilified in this disease is part of the innate immune system. Essentially, it’s part of an innate immune system memory, essentially like a long-acting cytokine anti-microbial peptide. As you say, as long as you are triggered, whether it’s by COVID, whether it’s by a vaccine, whether it’s by a cold infection, eating too much saturated fat, having a leaky gut, or having a change in your oral microbiome, just going down the list. Any of those things that are triggering this are going to put you in that category. So I know we’re coming up on time here, but I want to hit you with a couple of rapid-fire questions at the end here so that we all have something actionable to remember. You mentioned Urolithin-A.

Do you replace your PPQ with that or do you use both?

Steven Gundry, MD

I use both, yes. I think that they work in different ways.

Dale Bredesen, MD

Got it. What do you like? What is your vitamin D target?

Steven Gundry, MD

I want vitamin D’s. at least 100 nanograms per mil. The Cleveland Clinic says a 150 is perfectly normal. I agree with them. The University of California, San Diego, down the street from all of us, says that they have never seen vitamin D toxicity in a human being, even at 40,000 international units a day. That’s my experience as well. They think the average American should be taking 9,600 international units a day. That’s 10,000 a day.

Dale Bredesen, MD

Almost 10,000. Yes, exactly. Where do you like to see your B12?

Steven Gundry, MD

I like high B12. The reason I do that is because I follow people’s homocysteine. First of all, half of the population has at least one mutation of the MTHFR genes, and they do not have methyl groups that can be donated to homocysteine to inactivate or activate DNA. I think that’s a big missing link. We see lots of people with these mutations who have high homocysteine. That, to me, is just a marker that they’re bad methylators. I give them methyl B12 and methyl folate. I like TMG as well. Trimethylglycine. Another cheap methyl donor. One of the things that’s fascinating me is, folks, you got to put methyl B12 under your tongue. Some so many people lack the intrinsic factor that allows them to properly absorb oral methyl B12 they just put it under their tongue and it works miraculously.

Dale Bredesen, MD

You, as a cardiothoracic surgeon, may be the best person to answer this question. We hear all the time from cardiologists that we’d like to see your cholesterol as close to zero as there was one to get it low. Where would you like to see ApoB? Where do you like to see total cholesterol?

Steven Gundry, MD

Over the last few years, I’ve used to test what’s called oxidized phospholipid ApoB and I use Boston Heart to run that test for me on every human being. One of the things I can tell you is that despite all the talk out there, ApoB does not correlate with oxidized ApoB levels. Oxidized phospholipid ApoB, would be leveled. I have people with ApoB levels of 2 to 300 that do not have oxidized phospholipid ApoB and I have done CT coronary angiograms on these people, and they have absolutely no plaque. On the other hand, I have people who have very low ApoBs because they’re on high-dose statin drugs and they have ApoBs 50, and 40, and they oxidize their ApoB. Those are the ones I worry about because they’re the ones who keep getting stents and they go. I don’t believe it. My doctors got my LDL at 30, and I’m on testosterone because I don’t make testosterone anymore and I have to replace it. They are still getting stents. When we look at them, they have an oxidized PL ApoB. They go, What’s that? I go. Well, that’s still the best way to track it now.

Dale Bredesen, MD

Interesting. 

Steven Gundry, MD

It’s an $8 test. You can amaze your cardiologist with an $8 test.

Dale Bredesen, MD

Fantastic and very exciting. Thanks for all this great information, Steven. It’s always great to talk to you. Again, congratulations on your book, Gut Check. I heard the launch went well. 

Steven Gundry, MD

Yes. 

Dale Bredesen, MD

I don’t know if you saw 60 Minutes last night, but they had a piece on Alzheimer’s where they said that the way to go is to open the blood-brain barrier and deliver more anti-amyloid antibodies.

Steven Gundry, MD

Of course.

Dale Bredesen, MD

They had zero data on Cognition. Zero. This is the only thing to do, which is scary. We do need to continue to change the realization, get people on early treatment, get people on early prevention, or earliest reversal. I urge everybody: please do not wait. It’s not normal to have problems with cognition as you get a little older. You should be able to keep your cognition very good if you do the things that Dr. Steven Gundry tells you to do. Thanks very much, Steven, and I look forward to talking to you again.

Steven Gundry, MD

Thank you. Keep up the good work, and thanks for having me on. I appreciate it.

Dale Bredesen, MD

It was great to talk to you, Steven.