Brain Inflammation | Stop These Three Diseases Before They Start

The narrative needs to be there is something wrong with this person's brain or body or combination of the two that is causing dysfunction or dysregulation that can be fixed.

The brain only has so many ways of saying ouch. When it's inflamed, you don't feel it. People who are depressed have inflamed brains. Autism has inflamed brains. Alzheimer's has an inflamed brain.

If you look at multimodal lifestyle intervention that included exercise, nutrition, vitamins, supplements, sleep, sleep modification, stress management, keeping the brain engaged, Social connection. Yep. Intensive lifestyle intervention, of all the interventions that we tried, moved the needle the most.

More than any of these billion-dollar amyloid drug studies. Because coal was what they used to heat and do industry with, and that's full of mercury and lead.

And so we look in the brains of people with Parkinson's, they have high levels of heavy metal.

There's a big myth about Parkinson's, and the myth is, is that it's just a brain disease. Yeah. It's a whole-body disease, Mark.

For decades, we thought about conditions like Alzheimer's disease, depression, Parkinson's disease as disorders of the brain. But what if that's only part of the story? Emerging science is revealing that many of the factors driving cognitive decline, mental illness, and neurodegenerative disease may begin far outside the brain itself. In our metabolism, our immune system, our gut microbiome, our hormones, and even the environment we're exposed to every single day. As part of our summer series, we're revisiting some of the most important conversations we have on the topic of brain health. In this special compilation episode, you'll hear from leading experts Dr. Richard Isaacson, Dr. Chris Palmer, and Drs. Ray Dorsey and Michael Okun as they explore the new science of brain health and what it means for preventing cognitive decline, supporting mental health, and protecting our brains as we age. Now, what I find most encouraging about this research is that it challenges the idea that brain decline is simply an inevitable part of aging. Instead, it suggests that many of the biggest drivers of brain health are things we can influence through choices we make and the environments we create and the ways we care for our bodies long before symptoms ever appear. So let's dive in.

Let's talk about nutrition. There's a, there's the Mind Diet, which is Mediterranean. And, you know, like the way I think about it is, is, is, you know, if food is medicine, what's the drug? What's the dose? What's the duration? Right? And I think, yes, the Mind Diet, which is a sort of a modified Mediterranean diet, lots of omega-3 fats and anti-inflammatory foods. Great. But it, there's, there's different levels that you can push on the gas pedal to get more effect. I had a patient once who had MCI, mild cognitive impairment. She had a whole bunch of problems, the 21 things, and we fixed all them. Her thyroid was off, she has heavy metals, she was pre-diabetic, she had had methylation issues and high homocysteine. She had low omega-3 fats. I mean, just the list went on and on and we fixed everything and her cognitive function dramatically improved. And then after like 3 or 4 years, she started noticing a little bit of the dwindling. And I said, geez, why don't we try a ketogenic diet? Because I've been reading about ketogenic diets and changing the metabolism of the brain by cutting out all sugar and starch and carbohydrates pretty much and eating 75% fat. And we did it and like the lights came back on. And I was like, holy cow. So again, how do you approach diet with all this?

Yeah.

Well, so, so, you know, nutrition and dietary patterns versus single or multiple nutrients, like this is a, this is a long topic and you and I both have written books about this and we could talk about this probably for an hour. But to me, different diets, you know, we're not in the realm yet where precision nutrition is like easy off the shelf, straightforward, but different people, I believe, need to follow different dietary patterns. And, and I too, back in, I think 2007, 2007 was the first time that I put someone on a ketogenic diet and, and saw something that I just did not think was possible. But then I've had other people where I put on ketogenic diets and like things kind of went the wrong way. And, and to me, um, you know, it's— we're not— we're going to get there very soon where one day we'll have, you know, whether it's a blood test or a genetic test or something where we could put into a computer and the computer will spit out exactly what the person could eat. And until, until we get to that time, I think you think about the big bucket. So the Mediterranean-style diet, fatty fish, brain-healthy fats, omega-3 fatty acids, especially people with one or more copies of the APOE4 gene. Like, we have to have enough omega-3 brain-healthy fats. Otherwise, people will have cognitive decline and the synapses—

because a lot of your brain is made up of DHA, which is 60% as far as I remember, which is—

and DHA and EPA are the two most brain-healthy fats. And DHA is especially important for people with one or more copies of the APOE4 variant. So brain healthy fats, that's PUFAs, polyunsaturated fat. Then you have monounsaturated fats. Monounsaturated fats, like if you want to drink olive oil, like an ounce or two a day and your doctor says, okay, that's like anti-Tau protein. Like that is good for—

but it's gotta be good olive oil. It's gotta be bitter and burn the back of your tongue. Otherwise it doesn't have the polyphenols.

Exactly. And 60%, one study I read of the alcohol, of the olive oil out there is corrupt. Exactly. So, you know, getting quality olive oil, like literally taking a shot of it, one or two shots a day, or pouring it on everything. You know, I have olive oil stashed in different parts of the house and just pour it on, pour it on whatever I can get it in because I need it. And if it burns the mouth, yep, that's exactly the proxy. Has a taste to it. So avocados, olive oil, fatty fish, brain-healthy fats are like so critical. Green leafy vegetables. So, you know, berries, you know, half a cup of strawberries or blueberries 2 to 3 times a week. Nurses Health Study published over a decade ago showed you could delay cognitive decline just by eating eating berries on a regular basis by 2 years just from one intervention.

That's why I gave you a berry shake this morning.

You did. It was good with goat milk whey, which was a first for me. So I appreciate it, which is really nutritious and actually tasted really good. So, you know, green leafy vegetables, high antioxidants. People should be eating mostly plant-based. You know, I would call it plant-rich. Yeah.

Plant-rich.

Yeah. Plant-rich. Plant-rich. And, you know, there's totally different—

because plant-based is vegan.

Yeah.

Oh no, no. That might be problematic for people who want to build muscle.

Mostly plant-rich.

Okay.

Yeah.

That's a better—

and I wouldn't maybe, maybe Yeah, I don't know the exact terminology, but you know, and then like meat is all not created equal. Like, like red meat, grass-fed beef is totally different than other beef that isn't, you know, whatever. So I think people need to eat, you know, where they feel comfortable with, whether ethically or otherwise, they need to get protein levels, whether it's through whey protein, through goat or whey protein through regular milk from cows. I think each person needs their own individual kind of thing. And some people may be more sensitive to one thing versus the other. And there's lots of different—

and I saw you putting like cocoa polyphenols in your—

oh yeah, I travel. I travel with dark cocoa powder, which is completely ridiculous, but I never leave home without my dark cocoa powder. And yeah, I have coffee in the morning with dark cocoa powder because to me, actually caffeinated coffee I think is brain healthy and has been shown to have better brain outcomes. Dark cocoa powder, again, it has to be like pure and not have the heavy metals in it and things like that. But dark cocoa powder can help with insulin regulation, blood pressure control, and has shown to be beneficial for brain health too.

So Richard Isaacson starts his morning with a mocha.

I do. A mocha for your memory. In the morning.

And it's funny cuz MOCA is actually one of the names for a test we use, the Montreal Cognitive Assessment test, which is the actually something you can actually do at home. It's something you download on the internet and it's a pretty good way of tracking your, your brain health.

Exactly.

Yeah.

We don't want people to do it too much at home cuz then they practice and the doctors see the doctor and they memorize the test. But I, I don't disagree. Yeah. For, yeah, for sure. There are definitely ways to, to track, track.

So fatty, fatty foods, omega-3 fats, monounsaturated fats, berries, leafy greens.

Yeah. You know, nut, nuts and seeds, antioxidants, nuts and seeds, you know, balancing the omega-6 with omega-3s. I'm there, there's so much nuance with nutrition, but I think that's it. Also the ELF diet.

What's that?

Oh my, did eating moss in the Arctic Circle. I, I just stumped Dr. Mark Hyman on a dietary pattern that he's never heard of.

Wow.

This is, this is a great day. I'm never gonna forget this day.

I've never heard of it.

The ELF diet. Eat less food.

Oh, eat less food. Yeah.

Yeah.

Like Michael Pollan, eat food, not too much, mostly plants, right?

Yeah. So just less, like people just eat so much in excess. Like it's, it's crazy. And you know, there was a study out of Mayo that showed that people that ate, like, I think the cutoff was like 2,100 calories a day, less than 2,100 or more, have, you know, delayed cognitive decline. And, and again, this is like imprecise.

So the Okinawa principle, right? Harihachibu, which is eat 80% full.

Exactly. Harihachibu. That's a That's exactly it. So the take-home here is though, if you're trying to gain muscle, oh, you better eat sufficient protein and calories because you need both carbs and protein to build muscle and you don't want to like just starve yourself and there's good carbs and bad carbs and know the difference. That's really key.

Berries and leafy greens are carbs, right?

Exactly.

Yeah.

And you know, some whole grains in moderation I think are okay, but not if a person's not active, you know? So anyway, Yeah, nutrition's tricky. Vitamins, we talked about omega-3 fatty acids, but vitamin D, especially people with one or more copies of the APOE4 variant, we check vitamin D. And just like you mentioned earlier, we don't just tell everyone to take vitamin D, but I think the statistic in Miami, as an example, 60% of the people in Miami, even with sun exposure, are deficient in vitamin D. So we check vitamin D and we—

Well, you have to be naked between 10 and 2 in the morning, 2 in the afternoon for 20 minutes. And if you're not, you're not going to get enough vitamin D. If you're a lifeguard, you will, but otherwise forget it.

Exactly. People wear sunscreen now, people are indoors, and yeah, I usually tell people you need 12 to 15 minutes between the hours of 11 and 1 to try to split the difference. I don't want to, you know, it's hard to know for sure, but we check vitamin D and supplement if needed. We also talk a lot about B-complex vitamins, and B-complex vitamins again are not something that's one size fits everyone. The VITACOG study, which was published over a decade ago, showed that when people had a marker in their blood called homocysteine, if homocysteine is high, the people that took B-complex vitamins, B12, folic acid, and a tiny little bit of B6, those people not only did they have slightly improved memory function on cognitive testing, but those people actually also had slower shrinkage of the memory, sorry, of the total shrinkage of the total brain size.

So yeah, I mean, it was a paper published a number of years ago in JAMA or New England Journal I read where if your homocysteine was over 14, You're 50% more likely to get Alzheimer's or dementia. And that's again, something we test at Function Health and also methylmalonic acid, which is a marker of B12 function.

Yeah.

And I, I remember a patient who came to me who was, you know, a very successful businesswoman, was on multiple boards. She was in her early 80s and she's like, I got diagnosed with MCI, mild cognitive impairment, early dementia. And she was pretty upset. And I'm like, well, I don't know, let's see what we find. And she had extremely high homocysteine and high methylmalonic acid, which is a marker of B12, which are better, probably better than measuring folate. Leading B12 in the blood.

Probably had a double MTHFR mutation.

And she did.

She had the genetics that made her having trouble with her metabolic pathways.

Maybe some diet issues.

Yeah. And she was older and probably not absorbing B12, which is common. As you get older, you get less stomach acid and so on and so forth. There are people that get acid blockers. They don't get B— I mean, that's what, that may drive me crazy. I mean, there's the third most leading prescribed drugs after statins and psychiatric drugs is the acid blocking drugs, which are now over the counter. And they're dangerous to take long-term. Fine short-term, but long-term. And so I, I said, I found this and I gave her B12 shots and I gave her high dose of methylfolate and some B6, some of these methylating nutrients, and completely cured her MCI. Now, it's not that everybody with MCI or pre-dementia has that problem. It's just that she had that problem. And then a number of years later, probably 5 years later, I got a call from her and I thought, oh, she's probably going downhill and I'm a little worried about her. And I saw her on my schedule and I'm like, what's going on? She says, well, I'm going for a trek in Bhutan. She's 85 and I want to know what I should be doing to prepare and take and blah, blah, blah. And I'm like, okay, great.

Amazing.

Yeah. What else supplements? What other supplements? Vitamin D, fish oil, the B vitamins. Yeah.

I mean, turmeric, I think curcumin, the active ingredient in curry, I think in certain people, especially with elevated amyloid levels in the blood, we usually, we sometimes use this. And I think in terms of like the big picture, those are like the One size fits many ones.

Yeah.

But I mean, the list just, I mean, the list is really long. So I mean, there's, there's definitely other things people can do. But, but the take home here is, you know, we check it in the blood, we do the history, and then we personalize the plan for them. So I think nutrition is, is really nutrition and exercise are like critical, critical levers. And, you know, in our research study that we presented data on that I can talk about, cuz we presented this at the 2025 Alzheimer's Association International Conference in July 2025. And we showed that when you looked at, and I'll talk about different interventions in a moment, but if you look at multimodal lifestyle intervention that included exercise, nutrition, vitamins, supplements, sleep, sleep, sleep, stress management, keeping the brain engaged, learning something new, seeing a doctor on a regular basis to make sure their blood pressure, cholesterol, blood sugar is all modified in an optimal range for specifically for them. When you, when you You put all those together, but no drugs. If you look at the groupings of the categories of the people we followed.

So intensive lifestyle intervention.

Intensive lifestyle intervention of all the interventions that we tried moved the needle the most.

More than any of these billion-dollar amyloid drug studies, right?

In our study that we've, and this hasn't been fully published, but I can talk about it because we presented an abstract form. There are people that, for example, took GLP-1 drugs and GLP-1 drugs are tricky because, you know, I believe that too high a dose, if you're not eating right and doing the right thing, you can lose muscle and have all the things. Lower dose, you know, I'm more of like the microdose crew when it comes to GLP-1s. GLP-1s, positive effect on biomarkers, you know, in my opinion, based on our results, you know, impressive results when used in the right person at the right dose for the right duration of time.

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Well, they improve metabolic health, which, and there's many roads to Rome to do that, right? If you radically improve your diet. I mean, I mean, before GLP-1s were on the market, I was reversing diabetes, getting people to lose 200 pounds, 100 pounds, 150 pounds. You can do it. It's just, it's just, and I think my guess is that they would do a head-to-head comparison of GLP-1s and the same diet. That you would eat if you were on GLP-1s, there would be no difference in any of the biology. That's my feeling.

So while multimodal treatments, you know, I would say work the best, the other categories that worked exceptionally well, that meaning exceptionally well to me means statistically significant improvements in a variety of pathologic proteins that are associated with neurodegenerative disease.

So, so you're testing, not guessing.

We test everything.

Okay. Let me try these 20 things and let's cross our fingers and maybe do a, like a, a sort of semi semi-subjective objective test, which is a bunch of questions.

We try something.

You're actually looking at blood tests that show changes.

Try one thing, we repeat it. We don't try 10 things at— well, for multimodal interventions, we try a group, and then if we're going to try a drug, we're going to recheck the 150 biomarker proteins. We check the proteins on different machines in duplicates. Every blood test we do, we run twice. This is not normal. This is not cost-effective. We do it anyway because we care about quality, not about anything else. Um, but, and, and, and We just try to do things as rigorous as humanly possible. And what we show is that when we do these tests, we call these n-of-1 studies, we'll try a GLP-1 and we'll check, we'll try hormone replacement therapy, like hormone replacement therapy, bioidentical hormones for women during the perimenopause transition in the right woman at the right dose. The women in our, in our little hormone replacement therapy group, believe it or not, the age ranges from 42 to 67. We have multiple women that have actually started on hormone replacement therapy with approval and agreement by the GYN and the primary care doctor in our, in our team. Um, we've had, uh, I'll just say what I feel like I should say, amazing success with using hormone replacement therapy. And, and when that rapid drop of estrogen comes in a genetically susceptible woman, you know, we did this whole women's brain imaging study at Cornell and spent, you know, millions and millions of dollars on this. Women that had, you know, hormone replacement therapy on board had better brain volumes and less amyloid, but it had never really been proven in a, in a study that you could use hormone replacement therapy. And then there was this, that Women's Health study that used like synthetic hormones and horse urine derived, whatever. Like when you use a bioidentical patch and you use progesterone and we talked to the GYN and we talked to the doctors, hormone replacement therapy during the perimenopause transition has helped improve brain biomarkers associated with Alzheimer's and neurodegenerative disease risk. It's been striking.

So, so this is more than just what has been done before, which is population-based studies, which can't really directly look at cause and effect. You're actually looking at blood biomarkers that change, that improve the, the blood biomarkers that are associated with neurodegenerative disease. That's a big deal. And the other thing I, I wanted to say is that the consensus most of that I've heard is that it's, it's important to start right away after your menopausal transition. But what I hear you saying is that you can She started later.

What, end early? I want to start both.

I would say yes, start early. Does that mean every woman should be on hormone replacement therapy? Like, what, what are the implications here?

Yeah, this is, these are, these are really, you know, and by the way, why hasn't this been better studied? Why are we the only group to my knowledge?

Like, because we have misogynistic research infrastructure.

Like, it's, it's just so, it's demoralizing. It's just so wrong that women are taught that like, oh, you're having night sweats.

Oh, oh, you don't feel good.

Oh, you're having brain fog.

Oh, okay. Sorry. You know, we'll see you back in 6 months. Perimenopause is a neurological disease. Like, you're just going to have a woman suffer? These are, these are symptoms that are treated. Oh, go change the temperature in your room and maybe you'll sweat less, or maybe change your sheets, get better sheets. Like, like, no, this is a medical condition. Like, really? Or get like, you know, the cooling thing.

Like, okay.

Or a weighted blanket. Fine.

Okay.

Treat the problem. And what we've shown is that, you know, through ridiculous amounts of time, effort, money spent, and research, which needs to be quadrupled or, or probably increased even much more than that, we've shown that when we use hormone replacement therapy in the right woman at the right dose, the right duration, in collaboration with a multidisciplinary team, when we start seeing the estrogen drop, even if the symptoms are very mild, You get the estrogen back up, the tau starts coming down, even though the tau wasn't elevated to a degree where we're like, uh-oh, sky is falling. But the tau is higher than it should be in that woman who's 47 years old. And this whole concept of like, you know, uh, it's normal. Well, no, optimal is where we want a brain protein. Normal, uh, a little borderline, a little high. Like, no, in order to have the most benefit We need to make these incremental changes and hormone replacement therapy during the perimenopause transition to me is one of the most impactful tools that we can use to reduce the risk of cognitive decline, dementia, and Alzheimer's disease in women. And I think, you know, it's tricky. I think there's risks and benefits with every one of these decisions, but, you know, I've just seen too many women suffer and it's just not fair.

So if they're symptomatic or if you do evaluations and you have a higher risk based on your Alzheimer's risk score, which you developed, then maybe it's a good idea. But even if you're not symptomatic—

Well, I think if you're symptomatic, it's like, how could you not? I think it's unethical not to try to figure out how to. In our cohort, we track estrogen, estradiol levels and other hormone levels. I mean, women 21 and above. We also, this is crazy, but like, this hasn't been done before to my knowledge. We do multiple blood draws through the menstrual cycle to try to figure out, like, as estrogen and progesterone change during the cycle, guess what? PTAL217 changes and these other markers change too. How has this never been done before? So we have women, we have like, thank you, thank you. I'm not going to say their code numbers in our research study. They get 6 blood draws on day 1, on day 3, on day 7. Like, we get 6 blood draws during the menstrual cycle. We're just trying to figure out, like, What should the P-tau be at? What, depending on what day the blood was drawn, we need to correct for what the tau level should be based on where the estrogen and progesterone is. Like, these are things that just haven't been figured out yet. And these are the types of questions we're asking. And these are the types of things that need to be figured out. And when you take this approach, precision, personalized, individualized approach, um, we've seen women in their early 40s, like 42 is the earliest we've started, where we've seen the estrogen going down, and we've seen the amyloid going up. Well, maybe they're a little symptomatic, but it's not really bothering them. But we're going to start on low-dose hormone replacement therapy if everyone is in agreement. And guess what? She feels better. Her cholesterol comes down. That's interesting. Her amyloid is improving, even though it wasn't abnormal. And this is really the key. Like, we have to personalize these therapies and we have to, you know, also just monitor for a change. We've been monitoring these women for so long. We see the change and then you intervene. And so, so to me, it's if symptomatic, like, please talk to your doctor. And if your doctor says tough it out, like, go to another doctor. If you're pre-symptomatic, um, follow it closely. I think women pre-menopause, perimenopause should, should probably get checked every 6 to 12 months for these brain biomarkers and hormones.

So essentially what you're saying is if you're symptomatic, don't suffer, right? And if you're not symptomatic and you have a lot of risk factors and some of these blood biomarkers that were, are emerging or abnormal, then it's better to get on early even if you're not symptomatic.

I believe that specifically in people that are at the high, women that are in the highest risk category, which are APOE4 positive, especially women with 2 copies of the APOE4 variant. Some of the most striking improvements. Actually, one woman is actually lives in Austin. One woman is in California. I mean, I know these cases like the back of my mind. You just start and you see everything improve.

This is honestly, Richard, why we co-founded Function. And I don't mean to kind of oversell it here, but these tests are not things that your doctor likes to order or often will order. And for a very low cost, we've dramatically reduced the cost. You can get all these biomarkers, including ApoE4 and some of these brain biomarkers And then you can kind of start to decide what to do and take control of your own health.

The narrative needs to be, there is something wrong with this person's brain or body or combination of the two that is causing dysfunction or dysregulation that can be fixed. If we can ask the question, what might be causing the problem? And we can systematically look for causes.

So what do we know now about those causes and what are the mechanisms that are going on that are causing this brain dysfunction because it's things like insulin resistance, inflammation, oxidative stress, mitochondrial dysfunction, all these fundamental concepts that are rooted in functional medicine thinking that we've been talking about for decades. It's happening in the brain and we know what's causing it and yet we're not treating it. So can you talk about what are those causes in a little bit more depth and how do we start to begin to think about fixing those and even diagnosing them?

So the part of the field that I really want to embrace, which has been around for you know, 50, 60 years is this concept of biopsychosocial, biological, psychological, and social. Those are the root causes and we know it. So adverse childhood experiences, if they occur early enough in life, they increase risk for all of the mental disorders and even autism spectrum. If you, if an infant is severely neglected or abused, that infant is at much higher risk of developing autism because they— that infant will never learn appropriate social skills. But every label in DSM-5-TR is increased. You're increased risk from adverse childhood experience. What else do adverse childhood experiences increase risk for? Obesity, type 2 diabetes, cardiovascular disease, autoimmune disorders, all sorts of other physical metabolic health conditions.

Yeah.

Anybody listening, you should go online and look up the ACE questionnaire, ACE, it's Adverse Childhood Events, and get your score. And it'll tell you what your score is. And the higher your score, the more likely you are to have your health issues driven by what happened to you. Because it's what happens to you is not just an emotional thing. It actually gets written in your epigenome and written in your biology in a way that changes everything and drives inflammation. So when you have adverse events happening to you, it literally turns on different genes that drive different metabolic pathways that drive inflammation and oxidative stress and even things like insulin resistance. We, we know the biology of this.

And interestingly can change your gut microbiome.

Hmm.

So we just had a paper out, research study out in the last year showing that amygdala activation, so this is your threat system in the brain, the amygdala actually activates assert specific pathway in the vagus nerve, which then lands on something called Brunner's glands in your digestive tract that secrete an enzyme that changes the acidity of your gastrointestinal tract that within an hour changes your gut microbiome. And so stress and trauma impact your gut microbiome, which can then impact whole body health, mental health, all of it. But as you might know, what you eat also impacts your gut microbiome. And so we need to put it together. So even if stress or trauma is causing changes in your gut microbiome that then increase your risk for a disorder, we can use diet and nutrition to treat those changes in your gut microbiome. To restore a healthier gut microbiome, which will then reduce your risk for disease or improve your health.

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Just one, one note on that, because it's really important. It seems to me a final common pathway is anything that triggers inflammation, whether it's toxins, your diet, psychological stress, changes in your microbiome, allergens, infections, anything can drive changes that drive inflammation that ends up in your brain that causes mitochondrial dysfunction. And that becomes part of the root dysfunction in the brain that you fix with the changes that you do with diet and other therapies, right?

Yes. That's the way I think about it. So I, I think—

There's many roads to Rome and there's many things that can drive it, but the brain only has so many ways of saying ouch. And so when it, when it's inflamed, you don't feel it. But when you look at the science, people who are depressed have inflamed brains. Autism has inflamed brains. Alzheimer's and inflamed brain. All the psychiatric illnesses, their brains are literally inflamed on fire, but we don't feel it except as psychiatric symptoms. And we think of that as something that is, like you said, genetic or because of it's in our head as opposed to it's in our body. And there's something we can do to find the root cause and fix it.

I think about inflammation. I mean, the way that I think about it really is that there are a series of pathways. That are all connected, like a series of dominoes that are connected. And so inflammation is one of those dominoes. It is not the only domino because all of us get inflamed when we get a cold. And that includes brain inflammation. And yet most people don't become psychiatrically ill from a cold. Some do, but not most don't. Went on and on. COVID infection caused severe neuroinflammation.

I mean, I remember when I had COVID, I got severely depressed afterwards and I could feel my brain and I'm like, wow, I've never felt this before. And I felt suicidal and I actually took exosomes and it was gone like literally in a day.

So the— the depression part is common and, and a lot of people don't think about that, but researchers have been talking about this for decades. High levels of inflammation cause behavioral motivational changes in most animals. So if you get the flu, you have a decrease in energy. You have a decrease in confidence. You are less likely to take risks. And what does that do? That drives you to want to go to your bedroom. Get under the covers and hide from the world and stay away from the world. You are less interested in reproduction, less interested in sex. Even if the opportunity is right there, you're like, get the hell away from me. Leave me alone. I'm sick. I don't feel well. Leave me alone. Let me recover. And in my mind, those are all adaptive responses that your body is hardwired to have this response. And the response is conservation of energy because your body is expending tremendous amounts of energy on your immune system right now. It is waging war on this thing that is infecting you and trying to take your life. It is waging war and it is spending every ounce of energy possible to create new immune cells, antibodies, cytokines, other things that are all trying to defend end your life. And it is telling you as an organism, do not spend an ounce of energy that is unnecessary. Get into bed, go into that cave and hide from the world. Don't challenge anyone right now. Don't go out and get into a fight where you have to fight or flee. Don't do anything. Stay away, hide from the world. The suicide out. So that part is actually really common.

Yeah.

With infections and high levels of inflammation. The suicidality part is not, and that's where I think about the brain becoming dysregulated.

Yeah.

From the neuroinflammation.

Yeah.

And, and people getting all of the constellation of symptoms.

Well, you talk about, you know, the genetic vulnerabilities, but then there's a lot of inputs that can drive the same final common pathway of energy dysregulation in your brain cells, right? Diet, sugar, refined carbs, which affects everybody. I mean, 93% of Americans are metabolically unhealthy at some level. I would say most of those have some degree of insulin resistance. We've figured out tests for it. At Function Health, the company I started with a bunch of folks, we actually can measure insulin resistance and we can see the degree. It's probably over 90% of people who we test have some degree of insulin resistance. It's pretty striking. Chronic stress and trauma. So psychological traumas can be transmuted into biological signals. Sleep deprivation, substance use, toxins. We talk about microplastics in a minute. Not exercising and being sedentary drives inflammation. And anything like infections or allergens, microbiome changes, all those kind of lead to this final dysfunction, which you kind of think is at the root of it. And when you look at things like Alzheimer's or autism, which are not psychiatric particularly diseases, the same phenomena is going on. Suzanne Goh, who's been on the podcast, talks about mitochondrial dysfunction autism and treating kids by treating their mitochondria and helping them with autism. And you're doing the same thing with mental illness. So can you talk about this kind of final common pathway of energy dysregulation and how it ties everything together? Because there's a lot of ways to go on this, but it— the final dysfunction is very similar and the therapies can be cross-diseases very effective. So whether you have fibromyalgia, whether you have alcohol use disorder or eating disorder, whether you have Alzheimer's, autism, depression, bipolar, schizophrenia, anxiety, PTSD, these can be impacted by changing your diet.

The way that I think about it, because some people think, oh, you know, Chris Palmer, you're being too reductionistic. You're saying everything's mitochondrial dysfunction. And so I really like— I'm struggling. How can I explain this so people understand what I'm really trying to say?

Yeah.

So what I'm really trying to say on the edge of our is that bio— biological like wide range of biological, whether it's infections or, you know, hormones, like all sorts of things, gut microbiome, diet, biological, psychological, social, and environmental, particular environmental toxins. All of those 4 buckets are the root causes of chronic disease, those 4 buckets. So there are lots of things that go into those 4 buckets, but they all converge at this central pathway called metabolism mitochondria. Mitochondria are regulating and controlling metabolism because they are, they are really mitochondria.

Give us a 60-second, like when you say metabolism, people, I have a slow metabolism. You're not talking about that.

I'm not talking about that.

Talk about what you mean by metabolism. 'Cause it's important for people to understand this.

So most people think of metabolism as burning calories. And yes, it is burning calories. Most people think of it as, well, it's metabolic syndrome, it's high blood pressure, high glucose, insulin resistance. That's metabolism. Yes, those things are tiny parts of metabolism, but metabolism in fact is a fundamental definition of a living organism. The ability to take food and turn it into energy or building blocks is a fundamental definition of a living organism. Virus cannot do that independently. And so many biological authorities will say viruses are not independent living organisms. They are not a life form unto themselves. They— so life, a living organism, whether it's a bacterium to a human being and everything in between, has to be able to take food, oxygen, nutrients and turn that into energy or building blocks to maintain life. And in fact, the absence of metabolism, the cessation of metabolism, is the definition of death. There are zero exceptions. There is no cause of death that does not involve the cessation of metabolism. Suffocate somebody, you're depriving them of oxygen, which stops metabolism. Starvation, toxins. You will not find any toxin that can kill a human being that does not disrupt metabolism.

Cyanide. That's what it does.

Boom.

You're dead in seconds because it interrupts.

It is a mitochondrial toxin. Arsenic, a mitochondrial toxin. Tylenol overdose, mitochondrial toxin. Toxin, alcohol poisoning, mitochondrial toxin. You can go on and on. And the reason is not— it's not, you know, when I first started doing this work, I was initially like shocked by what I'm saying. And I was a little bit in disbelief. I'm like, it can't be that simple. It is that simple. And why is it that simple? Because metabolism is a fundamental law. Like we don't really have laws like they do in physics. They have laws. And this is a law of biology. Metabolism is fundamental to life. The absence of metabolism is the definition of death. Dysregulation of metabolism. This is what I am proposing. Dysregulation of metabolism leads to chronic disease.

Yeah.

Dysfunction of mitochondria broadly leads to chronic disease.

Great. Michael, just sort of talking to me about, you know, Parkinson's, what is it? Give us a little background on, on the biology of it and then the, the increasing incidence of it and, and what you think are the major reasons why we're seeing this, this increasing, dramatic increasing incidence. It's like orders of magnitude. It's not just like a 10 or 20% increase.

Parkinson's, the first major description of the disease was by Dr. James Parkinson in 1817 in London. So he's 61, he's a, a surgeon actually. Yeah. And he's actually even a geologist and he sees something new on the streets of London, something so new that at 61 he bothers to write a case series. He basically writes his case series on 6 people, uh, 5, at least 5 of whom are men. They're all older and they have tremor, which has long since been described, but they have this stooped posture, this hunched, uh, posture, and this tendency to walk faster and faster and to fall forward. And he said in 1817, this has not been described in the medical literature.

Hmm.

Really?

This is 1817.

So in 1817, Dr. Parkinson says that park disease that became known as Parkinson's has not been described in the medical literature, ergo I'm describing something new.

And this was the beginning of the Industrial Revolution.

And this is the beginning of the Industrial Revolution. And where is it? It's in London.

Yeah.

And air quality in 1800 London is equivalent to what is in Delhi, India today. It's equivalent to what was over New York City with the Canadian wildfires. You remember 2 or 3 summers ago?

Yeah.

The skies turned orange. That was every day, 1800 London.

Yeah.

So I think Dr. Parkinson is describing the effect effects of chronic exposure to high levels of air pollution. And so Parkinson's, we think as a, as a—

and by the way, it was coal. Coal, because coal was what they used to heat and do industry with, and that's full of mercury and lead.

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Exactly. And so we look in the brains of people with Parkinson's, they have high levels of heavy metal. And so when you look at smog in LA, for example, you're seeing little pieces of dirt and soot that are suspended in the air. The fancy term is particulate matter. Most of them we cough out or sneeze out, but some are so small small, less than 1/30th the width of our hair. They penetrate the nerve that hangs down, the responsible for smell, that hangs down in our nasal passages. And hitchhiking on those pieces of dirt and soot are toxic metals.

Wow.

So it's a superhighway from your nose to your brain.

It's exactly— it's the front door to your brain.

Wow.

And it's the blood-brain barrier, you remember from medical school, right? Doesn't let things in.

Well, kind of does, but it kind of does.

But this is a little leaky. But this, this is the front door. This doesn't go through the blood-brain barrier, it's just going through the olfactory nerve the, the nerve response for smell that's hanging it and is hitchhiking are these metals, lead from gasoline, iron from brakes, platinum from catalytic.

Yeah.

Converters.

And so people with Parkinson's and Alzheimer's both have high, high levels of metals in their brain. No one's really been able to explain why, but I think one of the reasons why is air pollution, which is one of the toxins that are inhaled that lead to Parkinson's. Yeah.

And we're exposed to, I mean, listen, we're exposed to mercury in the fish we eat, lettuce, you know,, in their food. And, you know, if you eat a lot of kale that's grown in urban environments, it just picks up all the lead. You know, what, what, what you said was so interesting to me about the leaky brain, because, you know, when I was in, in sort of my early years of practicing, we were talking about a leaky gut and I used to get laughed at all the time by traditional doctors cuz they're like, oh, that's nonsense. It's just, you know, you're quack. And for a long time I've also basically been saying that there's a leaky brain. Well, you, Michael, you, you sort of just sort of brought this to attention because I think people don't really understand what that is. I mean, leaky gut is when the barrier breaks down and food and poop leak in and affect your immune system and then start to cause all kinds of havoc, you know? And, and as you mentioned, Michael, Michael, that you basically have this barrier, this blood-brain barrier, but it becomes permeable and then all of a sudden things get in from the outside. So it's not like a up like completely impenetrable barrier. And I think we're seeing increasingly things that cause a leaky brain, like stress and many other things like toxins. So maybe you could talk a little bit about this leaky brain phenomenon, cuz it's really how the toxins get into the brain that are causing all these problems. When you do biopsies and you're finding toxins and heavy metals in the brains, like what's happening?

Yeah. And you're absolutely, you know, spot on when you talk about leaky gut too. And it turns out the gut is also also a pathway, you know, where you can hitchhike in and potentially cause Parkinson's as well. And we talk about now brain-first Parkinson's and gut-first Parkinson's. And so this leakiness, you know, this permeability to, you know, to stress and other factors that can get across is really important. So if you think about the brain as having like a force field, if you're a Star Wars fan, you know, it's kind of got like a force field. And we've always kind of taught all the medical students, we've taught everybody in medicine that this is this impenetrable force field.

That's right.

Nothing's gonna get through this force field area. It's actually not correct. Not only is it not right, but as we develop, you know, treatments and as we develop, you know, different, you know, therapies, we're actually able to defeat the blood-brain barrier is what we call it, or the BBB. Yeah. We're able to defeat that. And, and it's so super important for us to remember that things can get through it. We can use that for therapeutics. We can also need to be thinking about that for cause and getting to the root cause of Parkinson's. And one of the things— treatment, and even treatment— but one other thing I just wanted to bring into the discussion, and, and I'm so glad that you mentioned the gut, is there's a big myth about Parkinson's. And the myth is, is that it's just a brain disease. Yeah, it's a whole body disease, Mark. And, and, and we see it in the gut, you know, we see the proteins in the gut, we see it in the skin, we see it in multiple systems. And so we—

proteins that are expressed in the body in Parkinson's.

Absolutely. And so misfolded.

Yeah.

And misfolded. I mean, we have twice the risk of malignant skin cancer, you know, melanoma and Parkinson's disease, twice the risk of osteoporosis and Parkinson's disease. This is a whole body disease. And as we think about it, and I love, you know, kind of how you describe yourself as someone that, you know, thinks of everyone, thinks of the whole whole, we have to start thinking about Parkinson's in a different way. It's not just a brain disease, and it's not just a disease of dopamine. There are certainly multiple circuits in the brain. And then, you know, this barrier that we, you know, have, you know, invested so much in, in all of our textbooks— we've got to rewrite them.

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