The Dr. Hyman Show - How Brain Inflammation Drives Depression, Alzheimer's, and Parkinson's

Episode Date: July 8, 2026

For decades, we've thought about conditions like Alzheimer's disease, depression, and 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 day. As part of our summer series, we're revisiting some of the most important conversations we've had 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. 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 the choices we make, the environments we create, and the ways we care for our bodies long before symptoms ever appear. View Show Notes From This Episode Sign up for Dr. Hyman’s Brainshaping Academy to learn how to nourish the biological systems that support your mental, emotional, and cognitive health https://drhyman.com/products/brainshaping?utm_source=dr_hyman_show&utm_medium=newsletter&utm_campaign=may_27&utm_content=link Get Free Weekly Health Tips from Dr. Hyman https://drhyman.com/pages/picks?utm_campaign=shownotes&utm_medium=banner&utm_source=podcast Sign Up for Dr. Hyman’s Weekly Longevity Journal https://drhyman.com/pages/longevity?utm_campaign=shownotes&utm_medium=banner&utm_source=podcast Join the 10-Day Detox to Reset Your Health https://drhyman.com/pages/10-day-detox Join the Hyman Hive for Expert Support and Real Results https://drhyman.com/pages/hyman-hive This episode is brought to you by Timeline, Sunlighten, Seed, BIOptimzers, Paleovalley, and Pique. Support healthy aging and get 20% off at timeline.com/drhyman with code HYMAN. Discover why so many people are using sunlighten.com and save up to $2,100 today and free shipping with code HYMAN. Make your microbiome part of your daily routine with seed.com/hyman and save 25% with code 25HYMAN. Go to bioptimizers.com/hyman and use code HYMAN to save 15% off your order, plus get a free gift.  Shop nutrient-rich foods and supplements at paleovalley.com/hyman and save 15% off your first order. Elevate your daily wellness ritual at piquelife.com/hyman and enjoy 15% off for life plus free gift (0:00) Understanding brain dysfunction, inflammation, and lifestyle interventions (0:21) Heavy metals, toxins, and Parkinson's disease (3:30) Introduction to the summer series on brain health (4:02) The MIND diet, precision nutrition, and brain-healthy fats (9:06) Vitamins, supplements, and caloric intake for cognitive health (11:23) Vitamin D, B complex, and reversing mild cognitive impairment (14:05) Additional supplements and intensive lifestyle interventions (17:18) Importance of magnesium and metabolic health (18:24) Multimodal treatments, hormone replacement therapy, and individualized care (26:49) Biopsychosocial factors, stress, and the gut-brain connection (32:30) Inflammation, energy dysregulation, and metabolism in brain health (42:33) Parkinson's disease: causes, history, and environmental factors (46:02) Leaky brain, blood-brain barrier, and Parkinson's as a whole-body disease (49:00) Closing remarks, disclaimer, and gratitude to sponsors

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 are depressed have inflamed brains. Autism has inflamed brains. Alzheimer's in a flame brain. If you look at multimodal lifestyle intervention that included exercise, nutrition, vitamins, supplements. Sleep.

Sleep. Stress management. stress management, keeping the brain engaged, learning something new. Intensive lifestyle intervention. Of all the interventions that we tried, move the needle the most. More than any of these billion-dollar amyloid drug study. 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. And the myth is that it's just a brain disease. It's a whole body disease, Mark. People ask me all the time what supplements I take personally. I'm constantly evaluating new research, new compounds, and new products. The truth is, there aren't many that make the cut. One that does is timeline powered by mitochondrial. If you follow my work, you've heard me talk about mitochondrial health.

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We're asking what do the underlying systems need to actually function? And one of the tools I keep coming back to in my own routine is my sunlight and sauna. Infraint therapy is one of the most. underrated recovery inputs out there. And I say input intentionally the same way I talk about sleep and nutrition. Not a luxury. It's a condition your body can use. What separates sunlight specifically is there pulse IQ technology?

It delivers red light plus near, mid, and far infrared wavelengths independently. So you're not just getting blended wavelengths plus heat. You're getting a targeted personalized session. Now, if you're already dialed in on food and exercise, this is the piece most people are missing. Go to sunlight.com and use it to go to high menu. you'll save up to $2,100 plus get free shipping. 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? Merging science is revealing that many of the factors driving cognitive decline, mental illness, and neurodegenerative disease may begin far outside the brain itself. And 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 doctors 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 the mind diet, which is Mediterranean.

And, you know, like, the way I think about it 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 there's different levels that you can push on the gas pedal to get more effect. I had a patient once who had MCI mal-cogyn impairment. She had a whole bunch of problems, the 21 things, and we fixed all. Her thyroid was off.

She has heavy metals. She was pre-diabetic. She 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 three or four 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 nutrition and dietary patterns versus single or multiple nutrients. It's like 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 I, too, back in, I think 2007 was the first time that I put someone on a ketogenic diet 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 to me, you know, 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 genetic test or something where we could put into a computer and the computer will spit out exactly what the person could eat. 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 APOE-4 gene. And like we have to have enough omega-3 brain-healthy fats. Otherwise, people will have cognitive decline in the synops. 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 APO-E-4 variant.

So brain-healthy fats, that's Pufa's polyunsaturated fat. Then you have mono-unsaturated fats. Mono-insaturated fats, like, if you want to drink olive oil, you. like an ounce or two a day, and your doctor says, okay, that's like anti-tow protein. Like, that is good for... But it's got to be good olive oil. It's got to 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, we're pouring it on everything. You know, I have olive oil moustached 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, um, 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. That's why I gave you a berry shake this morning. You did. It was good with, with, with goat milk way, 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. I would call 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, yeah, I don't know the exact terminology. But, you know, and then, like, meat is all not created. equal, 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 way protein,

through goat, or way 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 mouth 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 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 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 Isaac starts his morning with a mocha. I do. A mocha for your memory in the morning. And it's funny because mocha is actually one of the names for a, test we use, the Montanil 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 brain health. Exactly. Yeah. We don't want people to do it too much at home because then they practice and the doctor see the doctor and they memorize a test, but I don't disagree. Yeah, for yeah, for sure. There are definitely ways to track track. So fatty foods, omega-3 fats, monocytes, berries, leafy greens. You know, nuts and seeds. Antioxies, balancing the omega-6 with omega-3s. them. There's so much nuance with nutrition, but I think that's it. Also, the elf diet. What's that? Oh, my. Depp. Eating moss in the Arctic Circle. I just stuck. Dr. Mark Hyman on a dietary pattern that he's never heard of. Well, this is, this is a great day. I'm never going to forget this day.

The elf diet. Eat less food. Oh, eat less food. Oh, eat less food. Yeah, yeah. Like, Michael Paul, they eat food, not too much, mostly plants, right? Yeah, so just less. Like, people just eat so much in excess. Like, it's crazy. And, you know, there was a study out of Mayo that showed that people that ate, like, I think of the cutoff was like 2100 calories a day, less than 2100 or more, have, you know, delayed cognitive decline. And again, this is like imprecise. So the Okinawa principle, right? Harihachi boo, which is eat take-on-fus. percentful, exactly. Hari-hachibu, that's exactly it. So the take home here is, though, if you're trying to gain muscle, well, you better eat sufficient protein and calories because you need both carbs and proteins. and protein to build muscle and you don't want to 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, 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, you know, tricky. Vitamins, we talked about, you know, mega three 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.

We have to be naked between 10 and 2 in the afternoon for 20 minutes. And if you're not, you're not gonna get out of vitamin D. If you're a lifeguard, you will, but otherwise, forget it. Exactly. People wear sunscreen now. People are indoors. And yeah, you know, I usually tell people you need 15 minutes of 12 to 15 minutes between the hours of 11 and 1 to try to split the difference on a

want to, you know, it's hard to know for sure. But, you know, we, 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 is 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, for me, it was a paper published a number of years going to jammer in England journal I read where a pure homo system was over 14, the year 50% more likely to get Alzheimer's or dementia. And that's, again, something we test that function health and also methamelotic acid, which is a marker B12 function. And 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 methamalotic acid, which is a marker B12, which are probably better than measuring folate and B12 in the blood. Probably had a double MTH of our mutation. And she did.

She had the genetics that made her having trouble with her metabolic pathways. 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. People think of 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 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 methylpholate and some B6, some of these methylating nutrients, and completely cured her MCI. Now, it's not that everybody with MCI are. pre-dementia has that problem. It's just that she had that problem. And then a number of years later, probably five 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's, well, I'm going for a trek in Bhutan. She's 85. And I want to know what I should be doing

and 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, you know, Kirkham and the active ingredient curry. I think in certain people, especially with elevated amyloid levels in the blood, you know, 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. But I mean, the list just, I mean, the list is really long. So, I mean, 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 a plant 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 that I can talk about because 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 uh keeping the brain engaged learning something new yep seeing a doctor on a regular basis to make sure their blood pressure cholesterol uh you know blood sugar is all modified and in an optimal range for specifically for them when you when you put all those together but no um drugs if you look at the the groupings of of the categories of the people we followed so intensive lifestyle intervention intensive lifestyle intervention of all the interventions that we tried move the needle the most more than any of these billion-dollar amyloid drug studies.

In our study that we've, 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-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, you know, 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-1's 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.

Bloading gas, irregularity are often brushed off as minor issues, but they can really interfere with your quality of life. I see this all the time with patients who feel uncomfortable after meals, worried about digestion when they travel, are frustrated that nothing it tried actually works. That's one reason I continue to recommend seed. Their DSO-1, daily symbiotic, was designed differently from most probiotics in the market. Many probiotics don't survive digestion, but DSO1 uses a capsule in-capsule delivery system designed to help the strains survive and reach a colon where they can actually do their job. It's a 24-strain probiotic and prebiotic clinically shown to improve regularity, reduce bloating, and alleviate gas.

And what Presby most is the level of scientific rigor behind the product, which is what led me to join Seeds Clinical Board. Go to cede.com slash hymen and use the code 25 hymen to get 25% off your first month. That's s e-ed-com slash hymen and used to go 25 hymen. Summer is supposed to be the season where we feel more energized, travel, and heat, and schedule changes in longer days can actually throw off sleep, recovery, and stress levels pretty quickly. That's one reason I recommend magnesium with so many patients is involved in hundreds of biocchemical reactions in the body,

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Plus get a free travel-sized bottle of their best-selling mass zyme, digestive enzyme, while this applies last. Well, they improve metabolic health, and there's no. many roads to roam 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 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 GLP1s. There would be no difference in any of the biology. That's my funny. 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 neurodegenerate disease. So you're testing, not guessing. We test everything. You're like, here, let me try these 20 things and let's cross our fingers and maybe do like a sort of semi, semi-subjective objective test, which is a bunch of questions. You try something. You're actually looking at blood tests that show changes. Try one thing. We repeat it. We don't try 10 things. 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. 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 one studies, we'll try a GLP1 and we'll check. we'll try hormone replacement therapy.

Like hormone replacement therapy, bioidentical hormones for women during the paramedipos transition, in the right woman at the right dose, the women 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 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, 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 study that you could use H. Harmon replacement therapy. And then there was a

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 talk to the GYN and we talk to the doctors, hormone replacement therapy during the paramount of post-transition has helped improve brain biomarkers associated with Alzheimer's and neurogenital disease risk. It's been striking. So this is more than just what it's 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 changed and improved. prove the blood bond markers that are associated with neurodibis disease. That's a big deal. And the other thing I want to just say is that the consensus, most of that I've heard is that 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. What, end early?

I want to start. Both. Both. Both. Yes, start early. Does that mean every woman should be on porn replacement therapy? Like, what are the implications here? Yeah, this is, 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? 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, oh, you don't feel good. Oh, you're having brain fog. Oh, okay. Sorry. You know, we'll see you back in six 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, no, this is a medical condition. Like, really, or 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 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, at the right duration and collaboration with the 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 paramedopause transition, to me, is one of the most impactful tools that we can use to reduce the risk of cognitive decline dimension, Alzheimer's disease, and 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, 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 if you're not symptomatic. Well, I think if you're symptomatic, it's 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, estradial 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, Ptow 217 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 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 Ptow 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 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 amyloids 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 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, follow it closely. I think women pre-menopause

should probably get checked every six the 12 months for these brain biomarkers and hormones. So essentially what you're saying is if you're symptomatic, don't suffer. And if you're non-symptomatic and you have a lot of risk factors and some of these blood biomarkers that are emerging are abnormal, then it's better again out 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 two 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, you know, the back of my mind, like, 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 very low cost, we've dramatically reduced the cost. You can get all these biomarkers, including APE4 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. What do we know now about those? causes and one of 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 thinking 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, even autism spectrum. If an infant is severely neglected or abused, that infant is at much higher risk of developing autism. Because that infant will never learn appropriate social skills. But every label in DSM-5TR is increased. Your 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 score, the more likely you 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 know the biology of this. 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 Bruner'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. We can use diet and nutrition. We can 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. One thing I've learned over the years

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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 diet and other therapies, right? Yes, that's the way I think about it. So I think...

There's 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's inflamed, you don't feel it, but when you look at the science, people are depressed, have inflamed brains, autism has inflamed brains, Alzheimer's is in a flame 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 it as some, 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. And 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 suicide, 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 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, 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 in 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 out.

So that part is actually really common with infections and high levels of inflammation. The suicidality part is not. And that's where I think about the brain becoming dysregulated from the neuroinflammation and people getting all of the constellation of symptoms. Well, you talk about 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, you know, affects everybody.

I mean, 93% of Americans are metabolically healthy at some level. You know, I would say most of those have some degree of insulin resistance. We can get out tests for it. And function health, the company I started with a bunch of folks, we actually can measure in some resistance. And we can see the degree is probably over 90% of people who we test have some degree of and some resistance. 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 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 Go, 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 the final dysfunction is very similar. And the therapies can be cross-dise disease is 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. 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 around the edge of our season is that bio, Biological, like wide range of biological, whether it's infections or, you know, hormones, like all sorts of things. Got 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 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 what you mean by metabolism because it's important people 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. 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. Sinai, that's what it does. Boom, you're dead in seconds because it interrupts it. It is a 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. Do you have laws? And this is a law of biology. Metabolism is fundamental to life. The absolute.

of metabolism is the definition of death. Disregulation of metabolism, this is what I am proposing, dysregulation of metabolism leads to chronic disease. Dysfunction of mitochondria broadly leads to chronic disease. Ray, Michael, just sort of talking to me about, you know, Parkinson's, what is it?

Give us a little background on the biology of it, and then the increasing incidence of it, it. And what you think are the major reasons why we're seeing this is increasing, dramatic increasing incidence. It's like orders of magnitude. It's not just like a 10 or 20 percent 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 surgeon, actually, 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, and this tendency to walk faster and faster and to fall forward. And he said in 1817, this has not been described the medical literature. Really? This is 1817. So in 1817, Dr. Parkinson says that 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 it's the beginning of Industrial Revolution. And where is it? It's in London. And air quality in 1800 London is equivalent to what, as in Delhi, India today, is equivalent to what was over the New York City with the Canadian wildfires.

You remember two or three seven years ago? Yeah. The sky's turned orange. That was everyday 1800 London. Yeah. So I think Dr. Parkinson is describing the effects of chronic exposure to high levels of air pollution. And so Parkinson's, we think, as... And by the way, it was coal.

Coal. Because coal was what they used to heat and do it. with, and that's full of mercury and lead. 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 L.A., for example, you're seeing little pieces of dirt and soot that are suspended air. The fancy term is particulate matter. Most of them we cough out or sneeze out. But some are so small, less than one-thirt-th-th-width-width of our hair. They penetrate the nerve that hangs down, the response to 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 super highway from your nose to your brain. Exactly. It's the front door to your brain. And it's the blood brain barrier you remember from medical school, right? Doesn't let things in. Well, kind of does. But it's a little leaky. But this is the front door. This doesn't go through the blood brain barrier. It's just going through the olfactory nerve, the nervous on the smell that's hanging it. And it's hitchhiking are these metals lead from gasoline, iron from brakes, platinum from catalyst converters. And so people with Parkinson's and Alzheimer's, both have high levels of metals in our 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, we're supposed to, I mean, listen, we're exposed to mercury and the fish we eat, lettuce, you know, in their food. And, you know, if you eat a lot of kale, has grown in an urban environment, it just picks up all the left. You know, what, what you said was so interesting to me about the leaky brain, because, you know, when I, you know, when I, I was 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 quack. And for a long time, I've also basically been saying that there's a leaky brain. Well, you, Michael, you sort of just sort of brought this 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. 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 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 biopopsies 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 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 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 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. Nothing's going to 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, 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 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 I just wanted to bring into the discussion. And I'm so glad that you mentioned the gut. is there's a big myth about Parkinson. And the myth is that it's just a brain disease. Yeah. It's a whole body

disease, Mark. 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 need to. Proteins that are expressed in the body in Parkinson's. Absolutely. And so. And misfolded. Yeah. And misfolded. I mean, we have twice the risk of malignant skin cancer, you know, melanoma and Parkinson disease. Twice the risk of osteoporosis in 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, 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 the 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. If you love this podcast, please share it with someone else. you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman.

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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 guest's opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services.

If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center at Ultra Wellness. Center.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed health care practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public, so I'd like to express gratitude to sponsors that made today's podcast possible. Thanks so much again for listening.