How Brain Inflammation Drives Depression, Alzheimer's, and Parkinson's

Mark Hyman, MD

Dr. Mark Hyman is leading a health revolution—one focused on using food as medicine to support longevity, energy, mental clarity, happiness, and so much more. Mark Hyman, MD is a practicing family physician and an internationally recognized leader, speaker, educator, and advocate in the field of Functional Medicine. He is the founder and director of The UltraWellness Center, Founder and Senior Advisor for the Cleveland Clinic Center for Functional Medicine, a sixteen-time New York Times best-selling author, and Board President for Clinical Affairs for The Institute for Functional Medicine. He is the founder and chairman of the Food Fix Campaign, dedicated to transforming our food and agriculture system through policy.

He is a co-founder and the Chief Medical Officer of Function Health. He is the host of one of the leading health podcasts, The Dr. Hyman Show with 150+ million downloads. Dr. Hyman is a regular medical contributor to several television shows and networks, including CBS This Morning, Today, Good Morning America, The View, Fox, and CNN.

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Full Transcript

Automatically generated. Please forgive any typos or errors in the following transcript. It was generated by a third party and has not been subsequently reviewed by our team.

Dr. Chris Palmer
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.

Dr. Mark Hyman
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 is inflamed brain.

Dr. Richard Isaacson
If you look at multimodal lifestyle intervention that included exercise, nutrition, vitamins, supplements Sleep. Sleep sleep stress management. Stress management, keeping the brain engaged, learning you have intensive lifestyle intervention. Of all the interventions that we tried, moved the needle the most.

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

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

Dr. Michael Okun
Is there's a big myth about Parkinson, and the myth is is that it's just a brain disease. Yeah. It's a whole body disease, For

Dr. Mark Hyman
decades, we thought about conditions like Alzheimer's disease, depression, Parkinson's disease as disorders of the brain.

Dr. Mark Hyman
But what if that's only part of the story?

Dr. Mark Hyman
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 Doctor. Richard Isaacson, Doctor. Chris Palmer, and Drs.

Ray Dorsey and Michael Okin 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. Yeah. There's there's the MIND diet, which is Mediterranean.

Dr. Richard Isaacson
And, you know, like,

Dr. Mark Hyman
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 modified Mediterranean diet, lots of omega three 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 MSCI impairment. She had a whole bunch of problems, the 21 things, and we fixed all of Her thyroid was off. She had heavy metals. She was prediabetic.

She had methylation issues and high homocysteine. She had low omega three fats. I mean, just the list went on and on. And we fixed everything, and her function dramatically improved. And then after, like, three or four years, she started noticing a little bit of the dwindling.

And I said, jeez, 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 with all this?

Dr. Richard Isaacson
Yeah. Well, so so, know, nutrition and and and dietary patterns versus single or multiple nutrients, like, 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 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 kinda went the wrong way.

And and to me, you know, it we're not we're gonna 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. Until until we get to that time, I think you you think about the big bucket. So the Mediterranean style diet, fatty fish, brain healthy fats, omega three fatty acids, especially people with one or more copies of the APOE four gene, like, we have to have enough omega three brain healthy fats, otherwise people will have cognitive decline in the synapses.

Dr. Mark Hyman
Because a lot of your brain is made up of DHA, which is 60% as far as I remember, which

Dr. Richard Isaacson
And 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 eight zero eight four variant. So brain healthy fats, that's PUFAs, polyunsaturated fat. Then you have monounsaturated fats. Monounsaturated fats, like, if you wanna 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

Dr. Mark Hyman
But it's gotta be good olive It's gotta be bitter and burn the back of your tongue, otherwise, doesn't have the polyphenols.

Dr. Richard Isaacson
Exactly. And 60%, one study I read of the of the 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 moustache in different parts of the house and just pour it

Dr. Mark Hyman
on Me too.

Dr. Richard Isaacson
Pour it on whatever I can get it in because I I need and if it burns the mouth, yep, that's exactly the 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 two to three times a week. Nurses' health study published over a decade ago showed you could delay cognitive decline just by eating berries on a regular basis by two years, just from one intervention.

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

Dr. Richard Isaacson
You did. It was good with with with goat milk whey, which was a first for me.

Dr. Mark Hyman
So I

Dr. Richard Isaacson
I appreciate it, which is really nutritious and and actually tasted really good. So, you know, green leafy vegetables, high antioxidants. People should be eating mostly plant based. Know, I I would

Dr. Mark Hyman
call it plant rich.

Dr. Richard Isaacson
Yeah. Plant rich. Yeah. Plant rich. Plant rich.

And, you know, there's

Dr. Mark Hyman
totally diff because plant based is vegan. Yeah. I know. That might be problematic for people who wanna build muscle.

Dr. Richard Isaacson
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 or otherwise. They need to get protein levels, whether it's through whey protein through goat or 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

Dr. Mark Hyman
And I saw you putting, like, cocoa polyphenols in your

Dr. Richard Isaacson
Oh, yeah. This morning. 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 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, 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 for brain health too.

Dr. Mark Hyman
So Richard Eisenhower starts his morning with a mocha.

Dr. Richard Isaacson
I do. A mocha for your a mocha for your memory in the morning.

Dr. Mark Hyman
And it's funny because mocha is actually one of the names for a test we use, the Monterell cognitive assessment test, which is 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.

Dr. Richard Isaacson
Exactly. Yeah. We don't want people to do it too much at home because then they practice, the doctors see the doctor, and they memorize a test. But I I don't disagree. Yeah.

For For sure. There are definitely ways to to track track.

Dr. Mark Hyman
So fatty fatty foods, omega three fats, monosage fats, berries, leafy greens.

Dr. Richard Isaacson
You know, nuts and seeds.

Dr. Mark Hyman
Antioxus nuts and seeds.

Dr. Richard Isaacson
You know, balancing the omega six with omega threes. There there's so much nuance with nutrition, but I think that's it. Also, elf diet.

Dr. Mark Hyman
What's that?

Dr. Richard Isaacson
Oh my Eating moss in

Dr. Mark Hyman
the Arctic I

Dr. Richard Isaacson
I just saw Doctor. 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

Dr. Mark Hyman
day. The

Dr. Chris Palmer
elf diet.

Dr. Richard Isaacson
Eat less food.

Dr. Mark Hyman
Oh, eat less food. Yeah. Yeah. Like Michael Pollan, they eat food, not too much, mostly plants. Right?

Dr. Richard Isaacson
Yep. 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? Eat eat Hari Hachibu, which is eat take percent full. Percent full.

Exactly. Hari Hachibu. That's exactly it. So the the take home here is, though, if you're trying to gain muscle, well, you better eat sufficient protein and and and calories because you need both carbs and protein to build muscle and you don't wanna, like, just, you know, 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 and, you know, some whole grains in moderation, think, are okay, but but not if a person's not active.

You know? So so, anyway, yeah. Nutrition's, you know, tricky. You know, vitamins, we we talked about, you know, omega three fatty acids, but vitamin d, especially people with one or more copies of the APOE four variant, we check vitamin d. Just like you mentioned earlier, we don't just tell everyone to take vitamin d, but I think the statistic in Miami, as a as an example, sixty percent of the people in Miami, even with sun exposure, are deficient in vitamin d.

So we check vitamin d and

Dr. Mark Hyman
Well, you have to be naked between ten and two in the in the morning, two in the afternoon for twenty minutes. And if you're not, you're not gonna get enough vitamin d. If you're if you're if you're a lifeguard, you will. But otherwise, forget it.

Dr. Richard Isaacson
Exactly. People wear sunscreen now. People are indoors. And, yeah, you know, I usually tell people you need fifteen minutes of of twelve to fifteen minutes between the hours of eleven and one to try to split the difference. I don't wanna you know, it's it's it's hard to know for sure.

But, you know, we we check vitamin d and and and supplement if needed. We also talk a lot about b complex vitamins, and 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 Yeah. Homocysteine is high, the people that took b complex vitamins, b twelve folic acid, a tiny little bit of b six, 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 the shrinkage of the total brain size. Yeah.

Dr. Mark Hyman
There was a paper published a number of years ago in JAMA or a New England Journal I read where if your homocysteine was over 14, you're 50 more likely to eat Alzheimer's or dementia. And that's again something we test at function health, and also methamylonic acid, which is a marker of b 12 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 eighties, 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, is a marker of b 12, which are better probably better than measuring folate and b 12 in the blood.

Dr. Richard Isaacson
Probably had a double MTHFR She

Dr. Mark Hyman
had the genetics that made her having trouble with Yeah. Her metabolic And she was older and probably not absorbing b 12, 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 I mean, that's what that made 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 they're 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 b twelve shots, and I gave her high dose of methylfolate and some b six, 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 a number of years later, probably five years later, 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 wanna know what I should be doing to prepare and take and blah blah blah.

I'm like, okay. Great. Amazing. Yeah. What else supplements?

What other supplements? Vitamin d, fish oil, the b vitamins?

Dr. Richard Isaacson
Yeah. I mean, turmeric, I think, you know, curcumin, the active ingredient in curry. I think in certain people, especially with elevated amyloid levels in the blood, you know, we usually we we we sometimes use this. And I think in terms of, like, the the the big picture, those are, 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 the take home here is, you know, we check it in the blood, we do the history, and then we personalize the plant for them. So I think nutrition is is real nutrition and exercise are like critical critical levers. And, you know, in our research study that we presented data on that that I can talk about because we presented this at the, twenty twenty five 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. Stress management, keeping the brain engaged, learning

Dr. Mark Hyman
Social connection.

Dr. Richard Isaacson
Yep. Seeing a doctor on a regular basis to make sure their blood pressure, cholesterol, you know, blood sugar is all modified in in in in a in a in an optimal range for specifically for them. When you when you put all those together, but no drugs, if you look at the the groupings of of the the categories of the people

Dr. Mark Hyman
we followed So intensive lifestyle intervention.

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

Dr. Mark Hyman
More than any of these billion dollar amyloid drug studies.

Dr. Richard Isaacson
In our in our study that we've and now this hasn't been fully published, but I can talk about it because we present an abstract form. There are people that, for example, took GLP one drugs. And GLP one 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, you know, lose muscle and have all other things lower dose. You know, I'm I'm more of like the microdose crew when it comes to GLP ones. GLP ones, positive effect on biomarkers, you know, in my opinion, based on the our results, you know, impressive results when used in the right person at the right dose for the right duration of time.

Dr. Mark Hyman
Well, improve metabolic health, which and there's many roads to roam to do that. Right? If you radically improve your diet. I mean I mean, before GLP ones were on the market, was reversing diabetes, getting people to lose 200 pounds, 100 pounds, 150 pounds. You 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 ones and the same diet that you would eat if you were on GLP ones, there would be no difference in any of the biology. That's my feeling.

Dr. Richard Isaacson
So while multimodal treatments, you know, obviously 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

Dr. Mark Hyman
you're testing, not guessing?

Dr. Richard Isaacson
We test everything.

Dr. Mark Hyman
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.

Dr. Richard Isaacson
We try something.

Dr. Mark Hyman
We're actually looking at blood tests to show changes.

Dr. Richard Isaacson
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 gonna try a drug, we're gonna 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. But and and and we just try to do things as as as rigorous as as humanly possible.

And what we show is that when we do these tests, what call these n f one studies, we'll try a GLP one and we'll check. We'll try hormone replacement therapy. Like, replacement therapy, bioidentical hormones for women during the perimenopause trans transition. In the right woman at the right dose, the 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.

We've had, I'll just say what I feel like I should say, amazing success with using hormone replacement therapy. And when that rapid drop of estrogen comes in a genetically susceptible woman, know, we did this whole women's brain imaging study at 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. Yeah. But it had never really been proven in a in a study that you could use h hormone replacement therapy.

And then there was this that woman's health study that used, like, synthetic hormones and horse urine derived whatever. Like, when you use a bio identical patch and you use progesterone, and we talk to the GYN, we talk to the doctors, hormone replacement therapy during the paramental post transition has helped improve brain biomarkers associated with Alzheimer's and neurodegenerative disease risk. It's been striking. So So

Dr. Mark Hyman
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 and improve the the blood biomarkers that are associated with neurodegenerative disease. And that's a big deal. And 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 actually start it later.

Dr. Richard Isaacson
What what end early. I I wanna start Both.

Dr. Mark Hyman
Both. See. Yes. Start early. Does that mean every woman should be on hormone replacement therapy?

Like, what what are the implications here?

Dr. Richard Isaacson
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?

Dr. Mark Hyman
Because we have a misogynistic research infrastructure. Like,

Dr. Richard Isaacson
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, Oh, okay.

Sorry. You know, we'll see you back in six months. Perimenopause is a neurological disease. Like, you're just gonna have a woman suffer. These are these are symptoms that are treat 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 like, 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, it's normal.

Well, no. Optimal is where we want a brain protein. Normal, 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 and I think, you know, it's 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.

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

Dr. Richard Isaacson
Well, I think if you're symptomatic, it's it's like, how like, how could you not? I think it's like, you know, it's unethical not to try to figure out how to. In our cohort, we track estrogen, estradiol levels, and other hormone levels, you know, I mean, women 21 and above. We also this is crazy, but like, you know, 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?

P tau two seventeen changes, and these other markers change too. How has this never been done before? So we have women. We have, like, vol thank you. Thank you.

I'm not gonna say their their code numbers in in our research study. They get six blood draws on day one, on day three, on day seven. Like, we get six 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, we've seen women in their early forties, 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 gonna 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, we 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 and if your doctor says tough it out, like, go to another doctor. If you're presymptomatic, follow it closely. I I think women pre menopause perimenopause should should probably get checked every six to twelve months for these brain biomarkers and hormones.

Dr. Mark Hyman
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 that are emerging are abnormal, then it's better to get out early even if you're not symptomatic.

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

Dr. Mark Hyman
This this is honestly, Richard, why we cofound and function, and and I 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 APOE four and some of these brain biomarkers. And then you can kind of start to decide what to do and and take control of your own health.

Dr. Chris Palmer
The narrative needs to be there is something wrong with this person's brain or body or a 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.

Dr. Mark Hyman
So what do we know now about those causes? 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 root 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 and yet, we're not treating it. So can you talk about what are those causes in in a little bit more depth, and and how do we start to begin thinking about fixing those, and even diagnosing them?

Dr. Chris Palmer
So the the part of the field that I really want to embrace, which has been around for, you know, fifty, sixty 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. Mhmm.

If if you if if a 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 five TR is increased. You're increased risk from adverse childhood experience. What else do adverse childhood experiences increase risk for? Obesity, type two diabetes, cardiovascular disease, autoimmune disorders, all sorts of other physical metabolic health conditions.

Dr. Mark Hyman
Yeah. Anybody listening, you should go online and look up the ACE questionnaire, ACE, 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 a 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.

Dr. Chris Palmer
And interestingly, can change your gut microbiome. So we just had a paper out, research study out in last year showing that amygdala activation, so this is your threat system in the brain. The amygdala actually activates a certain 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.

Dr. Mark Hyman
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?

Dr. Chris Palmer
Yes. That's the way I think about it. So I I think There

Dr. Mark Hyman
are many roads to roam 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 is an inflamed brain.

All the psychiatric illnesses, their brains are literally inflamed on fire, but we we don't feel it except as as psychiatric symptoms, and we think of it 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.

Dr. Chris Palmer
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. And on and on. COVID infection caused severe neuroinflammation.

Dr. Mark Hyman
I mean, 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 suet It really is.

Dr. Chris Palmer
The depression part is common. 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 wanna 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's 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 in my mind, those are all adaptive responses. The that 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 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 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

Dr. Mark Hyman
Yeah.

Dr. Chris Palmer
From the neuroinflammation. Yes. And and people getting all of the constellation of symptoms.

Dr. Mark Hyman
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, and refined carbs, which, you know, affects everybody. I mean, ninety three percent of Americans are metabolically healthy at some level. You know, I I would say most of those have some degree of insulin resistance.

We're figuring out how test for it. And Function Health, the company I started with with a bunch of folks, we actually can measure insulin resistance, and we can see the degree. It's probably over ninety percent of people who we test have some degree of insulin resistance. It's it's pretty striking. You know, 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 you kind of think is 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 in 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 grow on this, but it the final dysfunction is very similar, and the the therapies can be cross diseases very effective. So whether you have fibromyalgia, whether you have, you know, 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.

Dr. Chris Palmer
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

Dr. Mark Hyman
We're on the edge of our seat.

Dr. Chris Palmer
Is that biological, like, wide range of biological

Dr. Mark Hyman
All the

Dr. Chris Palmer
way through. It's infections or, you know, hormones, like, sorts of things. Gut microbiome, diet, biological, psychological, social, and environmental, In particular, environmental toxins. All of those four buckets are the root causes of chronic disease. Those four buckets.

So there are lots of things that go into those four 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

Dr. Mark Hyman
Give us a sixty second. Like, when you say metabolism, people, I have a slow metabolism. You're not

Dr. Chris Palmer
talking about that. I'm not talking about

Dr. Mark Hyman
What you mean by metabolism? Because it's important for people to understand this.

Dr. Chris Palmer
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. Viruses cannot do that independently, and so many biological authorities will say viruses are not independent living organisms. They are not a life form under 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.

Dr. Mark Hyman
Cyanide. That's what it does. Boom. You're dead in seconds because it interrupts

Dr. Chris Palmer
mitochondrial toxin. Arsenic, a mitochondrial toxin. Tylenol overdose, mitochondrial 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. Disregulation of metabolism, this is what I am proposing, dysregulation of metabolism leads to chronic disease.

Dr. Mark Hyman
Yeah.

Dr. Chris Palmer
Dysfunction of mitochondria broadly leads to chronic disease.

Dr. Mark Hyman
Ray, 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 ten or twenty percent increase.

Dr. Ray Dorsey
Parkinson's, the first major description of the disease was by doctor 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 six people, five, at least five of whom are men. They're all older, and they have tremor, which has long since been described, but they have this stoop posture, this hunched posture, 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.

Dr. Mark Hyman
Really? This is 1817.

Dr. Ray Dorsey
So in 1817, Doctor. 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.

Dr. Mark Hyman
And this was the beginning of the Industrial Revolution. And it's the beginning

Dr. Ray Dorsey
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 in New York City with the Canadian wildfires, you remember, two or three summers Yeah. Sky has turned orange. That was everyday 1800 London. Yeah. So I think Doctor.

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

Dr. Mark Hyman
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.

Dr. Ray Dorsey
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 to air. The fancy term is particulate matter. Most of them we cough out or sneeze out, but some are so small, less than one thirtieth the width of our hair, they penetrate the nerve that hangs down the response for smell that hangs down on our nasal passages.

And hitchhiking on those pieces of dirt and soot are toxic metals.

Dr. Mark Hyman
Wow. So it's a superhighway from your nose to your brain.

Dr. Ray Dorsey
Exactly. It's the front door to your brain.

Dr. Mark Hyman
Wow.

Dr. Ray Dorsey
And it's the blood brain barrier, you remember from medical school, right, doesn't let let things in.

Dr. Mark Hyman
Well, kinda it does. Well, but it kinda does, but

Dr. Ray Dorsey
this It's

Dr. Chris Palmer
a little leaky.

Dr. Ray Dorsey
This this is the front door. This doesn't go through the blood brain barrier. It's just going through the olfactory nerve, the nerve response or smell that's hanging it, and it's hitchhiking are these metals, lead from gasoline, iron from brakes, platinum from catalytic converters. And so people with Parkinson's and Alzheimer's both have 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.

Dr. Mark Hyman
Yeah. We're exposed to I mean, listen. We're exposed to mercury in the fish we eat. Lead is, 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 because they're like, oh, that's nonsense. It's just, you know, you're quacking. 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 berry 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 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 because 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?

Dr. Michael Okun
Yeah. And you're absolutely, you know, spot on when you talk about leaky gut too. And it turns out the gut is also a pathway, you know, where you can hitchhike in and potentially cause Parkinson as well. And we talk about now brain first Parkinson and gut first Parkinson. And and so this leakiness, you know, this permeability to, you know, to stress and 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 kinda 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. Nothing's gonna get through this force field. 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.

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. And one other thing 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. 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

Dr. Mark Hyman
that are expressed in the body in Parkinson's.

Dr. Michael Okun
Absolutely. And so misfolded. Yeah. And misfolded. I mean, we have twice the risk of of malignant skin cancer, you know, melanoma in Parkinson disease.

Twice the risk of osteoporosis in Parkinson disease. This is a whole body disease. And as we think about it and I love, you know, kind of how you you describe yourself as someone that that, you know, thinks of everyone, thinks of the whole. We have to start thinking about Parkinson 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.

Dr. Mark Hyman
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Thank you so much again for tuning in. We'll see you next time on The Doctor 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.

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