Traumatized: How Severe and Traumatic Brain Injury Can Cause or Worsen Dementia

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Thank you, Heather, pleasure to be here.

Heather Sandison, N.D. 

So I wanna dive right in to, actually, one of the things that I’ve seen where you’ve really shone a light for me in terms of helping support patients, which is TBIs. So traumatic brain injuries can create inflammation in the brain. They can create poor vascular supply and perfusion, lots of things can start going wrong if somebody gets in a motor vehicle accident or hit over the head with a baseball bat or has a football injury. You have this really amazing individualized approach that you take. Where do you start? How do you create these individualized approaches?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Sure, so in the world of neurology, when you do a physical examination and usually wanna listen to patient’s history. So usually the areas of complaints a patient has tells you whatever is the brain may have been injured. And the interesting thing with brain injuries, there’s been a lot of research with it. And what we’re realizing is this phenomenon, they call it chronic traumatic encephalopathy, CTE, really turns on the same protein messengers that lead to Alzheimer’s disease, the top protein, , and even the neurofibrillary tangles. And there’s really overlap between the pathophysiology of Alzheimer’s disease and that traumatic brain injury can then perpetuate that process or can contribute to that process, overlap, . 

So the key things where we start is we try to look at what the patient’s deficits are. And many times when it’s traumatic brain injury, that’s a factor. The deficits don’t happen directly after the brain injury. One of the basic thoughts in the past was you get a brain injury and go, “Well, how do you feel?” And then maybe for the first few days, you feel a bit off and maybe after a week you’re normal, and all the symptoms have gone away, but really, in fact, what’s happening is there’s an injury in the brain, and those cascades take place. And sometimes seven to 10 years, the clinical presentations show up. 

So, for example, if someone injures their frontal lobe, then we know they have issues down the road with focus, attention, concentration, being able to stay on task, executive functions like planning and following through with stuff. Some patients hit the back of their head into their cerebellum. And years later, they started to have dizziness and vertigo and instability. Some patients injure the parietal lobe. They’ll notice that they’re falling more, they’re tripping more on from the opposite side. They’re not as coordinated. If they close their eyes, they may not be able to notice where their limbs are in place. 

Some people injure the temporal lobe where they’ll have difficulty with hearing if there’s any background noise, or even get spontaneous tinnitus or tinnitus, people say. So really a lot of times just kind of listening to the patient and just noticing what their deficits are. Now, unfortunately, the healthcare model, most people will just hear the deficit and they go, “Well, that’s just you’re getting older. “That’s just your personality,” but it’s not. So these things happen slowly over time. So it could be your handwriting change, getting sloppier. It could be having a hard time remembering phone numbers and recall. It could be totally dependent on a navigation system. all of a sudden, or not all of a sudden, but over a few years. So those are the first things we look at just from the history, kind of to where the deficits are. We don’t associate any loss of function to personality. We don’t try to label it as aging. So that’s one of the first important things. And then secondly, we do an exam. And then when you do a neurological exam, there are two types of findings. One are what they call hard neurological signs. 

And the other one they call the soft neurological signs. The hard neurological signs would be like you close your eyes with a test called Romberg’s, for example, where you check your balance and you fall over. That’s like a positive Romberg’s, and a soft version of that would be you don’t fall over, but you just titubate and sway just to one side, and it’s pretty consistent every single time. And those are soft signs. So when we’re trying to do brain rehabilitation, we’re trying to look for all these different soft signs. So when people get things like chronic traumatic injury or some degree of early neurodegeneration or late neurodegeneration, they don’t completely lose all function. 

They start to lose some function. And those soft signs are typically ignored when people do a neurological exam, because the emphasis is to really look for these hard, clear pathological signs. And that’s not really how the brain works. The brain doesn’t just go from white to black. There’s shades of gray. So we try to find the areas of the brain where there’s shades of gray, and then we try to activate it. So when neurons are injured, if a neuron’s injured, and this neurons healthy, this neuron’s can branch over the injured one which is called plasticity. And we try to create a diet, nutrition, lifestyle environment where plasticity can be optimized. And then we have to activate those pathways with exercises. 

And if you don’t know what kind of exercises to do, if you’re just listening to this, basically whatever you can’t do is what you do. So if you’re bad with numbers, then you do numbers. If your balance is bad, then you focus on your balance. So that’s a simplified version of it, but that’s what we call a functional neurology rehabilitation approach to supporting the brain.

Heather Sandison, N.D. 

A lot of patients that come to me, they’ve been to a neurologist and the neurologist says, “There’s really not much we can do.” As your brain ages, as you mentioned, this is expected. You should have less and less function. And our expectation is that that just progresses, and, sorry, good luck with that. What you’re saying is very, very different. It’s this concept of neuroplasticity. So, how can we change our brains in positive ways as we age? How can we take control of this process?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, and I just wanna mention a few things. Every practitioner is gonna have their bias based on their training and based what they’re seeing. So, for example, if you went to a physical therapist that works with traumatic brain injury all the time, they’re gonna be like pushing the plasticity, of course, you can get things to change, versus if you go to a person who’s only looking at serious lesions and dealing with just diagnosing and not really working with the rehabilitation part of it. So that’s important to know if you’re suffering from a brain issue too, because each practitioner has bias. And sometimes you would think, “Well, maybe the head of neurology “at this department would be the expert in this,” but you have to realize they’re seeing only one part of the big picture. So when it comes to diet, nutrition impacting the brain, and when it comes to rehabilitation like the brain, you really should talk to people that are doing that. 

They have a different perspective, because they live in a different world, but so what can you do? Well, there’s lots of things you can do. And the great thing about the brain is what’s so fascinating is even if neurons get injured, even if neurons degenerate, the concept of plasticity is neurons branch over it. So, in a clinical setting, whenever we see someone, for example, has traumatic brain injury, or neurodegenerative disease, we try to identify what things are promoting the neurodegenerative disease. And there’s lots of noticing the well-published factors. 

Some can be modifiable, not on the patient’s compliance issue, but the controlling blood sugar levels, controlling insulin resistance, avoiding pre-diabetes, getting physical activity in, optimizing vascular health and blood pressure and blood flow, increasing antioxidant status, reducing mechanism, what they call, brain inflammation, neuro inflammation, increasing antioxidant status, taking compounds that increase blood flow. There’s a lot of variations, and, you can say, some general concepts about them. That’s why I wrote my book, “Why Isn’t My Brain Working,” was each section like goes into a different mechanism. 

One is on blood sugar, one’s on brain inflammation, and one’s on essential fatty acids, and you really have to kind of combine those for the person, but it definitely requires an active patient. Like you’re brain is not going to get better on your own. Your brain is certainly gonna get better by taking any medication. And your brain’s not gonna get better just by taking a supplement. It’s really a complete diet and lifestyle, and then activation approach that really makes the biggest difference.

Heather Sandison, N.D. 

That’s consistent with what we’ve seen, both at Marama and for me clinically, that there are a lot of patients we can help. And the ones that aren’t getting better, there’s usually something we’re missing. There’s some part that they don’t feel confident in, whether it’s the diet, or they don’t like to swallow pills, or they have a big stressor in their life, or nobody’s looked at their thyroid. There’s usually a component missing. And when we get as comprehensive as possible, my confidence certainly goes way up in the results we see.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, it’s one of those things too is sometimes, well, compliance is absolutely necessary that when you look at brain rehabilitation and brain optimization, it definitely requires a active participant from the patient, and the higher their level of motivation, the better that can get. But the scary thing about it is sometimes like, for example, the frontal lobe will degenerate to the point they don’t have any more motivation, drive, or executive function, so they really can’t do it even. So there’s a point of like almost no… There’s a point where they need assistance when it gets really bad, but also at that point, the prognosis is really poor. 

Sometimes they can’t swallow, because their vagal pathways are impaired , and they feel like they can’t swallow, which is a red flag. Anytime someone can’t swallow lets us know their brain to gut access to starting to degenerate. That’s the unfortunate thing. There is a period of time, so if you’re suffering from a brain-related… If you like start to have mild cognitive impairment and you notice it, and things really started to change for you, time is of the essence.

You really need to jump on top of it. There could be a point where you get enough degeneration where you pass this. There’s a threshold that once you pass it it’s really hard to get some kind of change. And right before you reach it, it can be tremendous change where you can kind of stay where you are and even improve, and then really delay the time it takes to get to that degenerative change. And that is probably the most important principle for most people to know about and understand.

Heather Sandison, N.D. 

Yeah, that the sooner we can act, the better. And in fact, what we should be doing is preventing this from ever happening at all. With TBIs, I’m curious what your thoughts are. Sometimes we’re seeing patients where it was decades ago that they had an injury, and sometimes it’s just been days. So if you can intervene within days, does the treatment plan change?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, acute brain injury that we know we’re in the first six months, things like hyperbaric oxygen therapy can make a huge impact for them. But once they get past that six month window, like a year later, we don’t see that same degree of change. Studies have shown in the acute stages of brain injury, for example, progesterone has been shown to be very protective, and even hormones at the early stages can really dampen neuro inflammation. And there’s been multiple studies now published on survival outcomes and function in emergency rooms after TBI is when they use hormones, and testosterone and progesterone being really very powerful, ’cause they have a very powerful anti-inflammatory effect in the acute brain stage, and they help with setting the stage for healing. 

So those are immediate protocols that there’s some evidence for when someone gets an acute brain injury. And then once they’re out of the acute phase, things change. Now, one of the phenomenons that takes place with brain injury is this concept called microglia priming. So neurons actually change, not neurons, but microglia. There’s two sets of cells in the brain, neurons and microglia. After traumatic brain injury, these microglia cells, they changed their shape into what they call an opioid shape, and they start moving and circulating and staying in that one area. 

They’re very hyperactive to inflammation. So at that point, the person, wherever the brain injury is, that area of their brain becomes extremely sensitive to inflammation. So, when you look at inflammatory mechanisms, even when you look at not just the TBI world, but the Alzheimer’s disease world, air pollution, that impacts the pulmonary brain access, the microbiome, the gut-brain access, inflammatory diets, it breaches the blood-brain barrier, infections, environmental, chemical load. Those things can then amplify and add fuel to the fire. And if you have areas of the brain where there’s the traumatic brain injury, those microglial cells that have been traumatized from that injury are just there, and they’re very reactive to these inflammatory responses, and that perpetuates the degeneration, that area at a faster rate, and then you have other regions of the brain, because of that initial trauma.

Heather Sandison, N.D. 

Certainly a traumatic brain injury is a type of trauma. Stress is also a type of trauma like psychological or emotional stress. How does that impact the brain and how is that different from a physical trauma?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

In research, they have linked psychological as trauma too, and they have this priming effect as well. There’s different explanations for it. Some of the secondary, we know, I’ll just explain it from a stress model, where when you get stressed out, your cortisol levels go up, your stress hormones go up. That tends to activate an immune pathway called IL-16, 17, which activates these glial cells that promotes inflammation. And in the world of neuro immunology, there’s a concept called neurogenic inflammation, where the brain itself can promote inflammation throughout the body. That inflammation throughout the body can then trigger inflammatory responses. So high stress environments activates this neurogenic inflammatory response. So, the combination of traumatic brain injury and stress is really big deal, but I just wanna point out with traumatic brain injury, you don’t have to lose consciousness. 

I mean, a past car accident that catches up with you, playing an active contact sport for many years and having a couple blows, they can be a factor. And the other major key thing to understand about traumatic brain injury is it’s not how hard you hit your head. It’s how, what they call, primed your glial cells were before the injury. So your immune cells have a certain degree of inflammation at any given time. But if you take, let’s say, two people, person one, person, A, person B, and I’m gonna say person A here, they’re a smoker, they’re a diabetic. 

These are increasing inflammation, a really bad diet. They really don’t eat any kind of healthy, antioxidant-based foods. All these things increase the inflammatory load. And let’s say this person’s not those things, and they have decreased inflammatory triggers. Well, they may both get the same impact to their brain, but this one with a greater degree of already preexisting inflammation is gonna have far reaching effects down the road. So that’s the other key thing is it’s not just how hard you hit your head, ’cause sometimes very trivial impacts can cause the devastating effects, even long-term, on the brain based on how much inflammation the brain had before the injury.

Heather Sandison, N.D. 

I’m curious, another summit guest had mentioned that it’s not just the brain either, that also spinal cord injuries can have a similar effect on cognition and, of course, physical function and create this microglial activation that can set you up for a poor cognition later, 10 decades down the road. And so I’m curious your insights about we think of them as TBIs, traumatic brain injuries, but what if it’s another part of the central nervous system?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, so there’s a concept of anything presynaptic to the neuron can cause diathesis and postsynaptic pull, which is neurology term for basically meaning you have a receptor. So it’s, first of all, first concept is this neuron has to fire to this neuron to keep it healthy. And this neuron has to fire to the next neuron to keep it healthy. So neurons are like muscles. They have to constantly activate each other. When they activate each other, there’s cellular processes that take place, there’s single mitochondria that’s formed. Their energy production becomes active, and they basically function. 

So if this neuron no longer fires, so this neuron which then fires down to the other neuron like a domino effect, then you start to have a degenerative change that takes place. So you could have someone who has a spinal cord injury, and the motor pathways that impact the frontal lobe can get impacted in the cerebellum. They have cognitive issues. You can have someone who ends up hindering their hearing, ’cause they’re listening to loud music their whole life, and they’re a roadie at concert or something. Then all of a sudden their temporal lobe starts to degenerate much, much faster. Any type of receptor site degeneration leads to lack of activation of neurons downstream over a period of time. Those pathways just kind of degenerate, or went away to some degree. So they call that intrograde degenerative changes that take place, moving forward. So it does happen. 

So the injury can be anywhere. And then the effects are downstream many times somewhere else. In a world of a physical exam and functional neurology model, we can know where the injury is and then kind of start looking at an entire pathway postsynaptically and kind of see what’s happening, but that is really common to have.

Heather Sandison, N.D. 

Another thing that seems to exacerbate dementias and memory loss is when people lose their hearing or their vision as well. So they’re not getting those inputs into the brain. Is that another sort of way that this is happening where you’re getting degeneration, because the nervous system isn’t firing? Those neurons aren’t firing, because they’re not getting the inputs.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

– Yeah, I mean, it depends also on the age too. If you, for example, lose your hearing or your vision at a certain age, then you have this ability for synaptic connectivity, what they call synaptic pruning, and then you can just make up for it. What happens later in life, you don’t have the same output. If it happens later in life, you don’t get to have those refigurations and connections. Then that area of the brain is no longer getting stimulated. And then, again, it does start to generate just like if you tied your arm up and never moved it for six months. This arm is gonna be totally atrophied, right? So same thing with areas of the brain. If they’re not getting input and activation, those proteins also don’t get activated and they start to degenerate.

Heather Sandison, N.D. 

You mentioned young brains. So what can we do early on even for like a developing brain, a child say, to help prevent Alzheimer’s from happening in their lives?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, and I can tell you I have a daughter, and for me, my goals in Alzheimer’s prevention was, how do I optimize my daughter’s brain to take over the world? What are the strategies? There’s a lot of things I wanted to do my wife wouldn’t let me do like putting my daughter on oxygen and do therapy as soon as she was born and do stuff. But I was able to do some other things, but the point is, what can you do? Well, I think first of all, activation in the brain’s really important. It’s very important for kids to have physical exercise, activity with as much coordination and reflexive movement as possible. So that’s critical for developing motor development, and motor development helps cognitive development. So a sport, especially a sport that requires a lot of movement, coordination, timing, planning is ideal for brain development. They have to learn a language. So basically sports, language, and music.

Heather Sandison, N.D. 

Multiple languages, would you recommend that?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, even better, but you gotta activate language centers of the brain, so the process of going to learning language. It’s the process of listening to music. Playing a music instrument is important. So I think every kid should be focused on learning a language. Multiple languages is great. Playing a physical sport that requires most intense motor coordination, if possible, if they enjoy that sport. And then obviously learning how to play a musical instrument. 

Then outside of that, it’s basically keeping the inflammation down, making sure they’re eating healthy diet, making sure they are getting a lot of healthy fats in their diet, making sure they’re not eating the standard American diet, which is all processed fats and fats, making sure gut microbiomes are really, really healthy. So like my daughter, she starts every morning up and she takes resveratrol and turmeric and fish oils, big stuff for her microbiome. And she has a little drink we make where we blend up like 30 different fibers in a food processor, give a couple of scoops of that. And that’s just been her routine since she was a little kid, and she’s keeps her brain really active, and she’s learning a language and plays an instrument.

Heather Sandison, N.D. 

What’s her instrument?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

She plays piano. And she also likes to sing. So she kind of has combination of those things, and that’s been great for her.

Heather Sandison, N.D. 

And so would you recommend the same things on the other end of the spectrum? Is that the foundation?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, that’s the foundation, but here’s the thing, whatever you don’t like to do when you get older is what you have to do. So you’re gonna have a tendency to not wanna do it. Like if you’re bad at math, you don’t wanna do math. So when you work with patients that are starting to get neurodegeneration, I’m like, “Yep, I know you’re 50, “but you’re gonna have to open up the fourth grade math app “and go over your multiplication tables and divisions.” And now they have all these games where they play games and it’s like math and so forth. Or, “You gotta do a word recall, or word matching “or image matching.” So we try to use a lot of apps to help them. 

And then also, a lot of the online platforms like Lumosity and different cognitive tools are very helpful for people that start to do on a daily basis, or at least two or three times a week, and they could keep a score. But that’s been a nice trend to see that the commercial environment has got into where they have these subscriptions where they can start doing some cognitive tasks, but cognitive tasks are really important. And also like physical movement. If you don’t have physical movement, your brain has no chance. Sedentary lifestyles sets you up to stage with very little chance of improving your brain and say, “Well, just go for walk.” Honestly, it’s not enough. You need to do more. It’s just like they say with diabetes, if you just walk, keep your blood sugar under control, yeah, but this statistically significant research study, but not really clinically relevant. 

So you really want to move as much as you can, play as much as you can, dance. Dancing is phenomenal for the brain. And so motion and movement. Even trying to learn a new language. You may never learn it. You might wanna say, “Hey, I wanna learn German “or learn French.” You may never get to the point where you can actually speak it fluently. It doesn’t matter. It helps your brain stay healthy, helps your brain develop. So it does apply to adults. And maybe as an adult, you go, “Hey, I wanna learn how to play the guitar.” It doesn’t even matter if you are good at it. The task of doing it is very therapeutic for the brain. And I think we tend to think of like, “What’s my end goal “if I’m never gonna speak French, “I’m never gonna play the guitar? “Then I shouldn’t do it. “I’m not gonna compete in a dance contest.” It doesn’t really matter. So those things can be social, and they can really important, but sedentary lifestyle with lack of activation, like vegging out on Netflix or watching TV all day, or just gossiping all day is not going to help the brain.

Heather Sandison, N.D. 

We’ve seen that as people move into Marama. a lot of times they’re addicted to TV. It’s almost like a sugar addiction. They’re asking every day, all day long. “Oh, well, can we turn the TV on? “I really wanna see the news.” And I’ve walked into other care facilities where there’s a TV on each wall, and one’s got the news on. Another one’s blaring advertisements. The other’s got a sports game. And like my brain doesn’t work when it’s under that much, inundated by that much auditory stimuli. And so I can just imagine if you were searching for a word, or if you’re trying to remember someone’s name, that that would really throw your brain off track and be hard. Yeah, certainly not only hard to hear, but just hard to function.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Most people don’t realize when people go into some of these retirement homes, they’re really designed for the staff to not deal with the patient. They’re put in a place where they’re sedated and now watch all this, be entertained, leave us alone. And that really creates environment for brain degeneration and brain aging. So be aware that if you’re taking family members somewhere, you really wanna be in a place where it encourages activation and learning and stimulation and have healthy food. Yeah, I mean, I’ve been to visit retirement homes where exactly that, like there’s no stimulation for the people there. It’s very little. It’s voluntary and, of course, their brains are too tired for teaching them all and volunteer and do anything. And then the food is horrific. Like the worst things for the brain, processed food, microwave food, no nutrient quality. And of course, of course, that’s gonna create the stage for accelerating neurodegeneration.

Heather Sandison, N.D. 

So what role does diet play in neurotransmitter balance? I’d love to dive into neurotransmitters. Acetylcholine, of course, dopamine, GABA, serotonin, all of these have a lot to do with mood, cognition, and diet, of course, is the building block, so that we can produce those neurotransmitters. So the ideal diet, how do you feel about keto?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Well, yeah, ketogenic diet is shown, without question, in multiple studies, very effective for reducing brain inflammation, improving fuel to the brain. And for someone who is starting to notice cognitive decline, it’s really a phenomenal way to make a big change, a game changer once you get into ketosis. And new studies have shown that the theory with ketosis, you start using fats for energy, and fats or ketones are better fuel source for the brain. So it’s easier to function with a better fuel source, but ketones are actually anti-inflammatory and actually dampen inflammation, which is one of the key mechanisms of all neurodegenerative diseases, whether it’s traumatic brain injury causing degeneration, or Parkinson’s disease, or Alzheimer’s disease. 

So ketogenic diets are really, really important. We use it all the time with patients that are suffering from brain injuries in the recovery phase, and for people that are sort of get cognitive declines, it’s a key thing. And obviously it’s important to take a break from it, like every month or so, and then take a few days off then. And some patients don’t, They’re like, “If I go off it, “I’m gonna feel awful for four days, “and I don’t wanna feel that way.” And then others are like, “Well, I can last three weeks. “I can’t do a month. “And then I need my a couple of days off.” I mean, okay, fine, whatever works for you. But if you can have same time in ketosis, it can be very, very beneficial. So ketosis is very important. And then, when you look into neurotransmitters, there is research that shows things like taking amino acids, like 5-hydroxytryptophan or different precursors can help support some neurotransmitter activity. And it has an effect that’s short-term, but the bigger changes will be physiological factors like blood sugar control. 

So insulin surges and blood sugar spikes can really disrupt all neurotransmitters and neurotransmitters signaling pathways and neurotransmitter transport proteins. There’s a very important one called LNAA, large neutral amino acid transport that is completely dysregulated with insulin surges and insulin spikes. A lot of research continues to show the microbiome has a huge impact on neurotransmitter activity and things like lipopolysaccharides and various bacteria produce what are called postbiotics, or different versions of polysaccharides, which have an impact on brain and neurotransmitter function. 

So we are just starting to understand it, but we definitely know having a really healthy microbiome and a diverse microbiome is critical, in ketosis, really critical. So, we use something we call a keto microbiome diet where they’re in ketosis, but we don’t let them have like their diet pure saturated fat and fried food all the time. And we actually remove dairy. Dairy seems to be very inflammatory. So we do a ketogenic diet, and we encourage a lot of diverse and fermented vegetables that are low-glycemic, so they can stay in ketosis. The combination of really helping the microbiome stay healthy and then get into ketosis, seems to work really well.

Heather Sandison, N.D. 

That’s amazing. So the integrity of the gut that is also a factor in brain function, right? Leaky brain, leaky gut, they usually come together. So does the ketogenic diet help with that, or what’s your approach to healing a leaky gut or leaky brain?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Okay, so there’s clinical mechanism and what’s been published. There’s differences in those as well. But first of all, I would say that studies show that when you have intestinal permeability, there’s a higher chance that you have a blood-brain barrier permeability. We published a study in 2020 International Journal of Molecular Science where we took patients that had inflammatory bowel disease also disease in Crohn’s, and we measured the blood-brain barrier permeability proteins as S100B, aquaporins, different markers of the blood-brain barrier, and we found like a linear relationship. If you had leaky gut, you had blood-brain barrier, and we measure something called a R value, which is if you guys aren’t familiar with statistics that are listening, it’s a way to measure that association, and it was like the highest you can have is one-to-one, and it was pretty high, close to one to one. And I’ll go over papers to see if that connection existed, and it was very, very prominent, other relationships shown similar things. 

So typically when you have a leaky gut, leaky blood-brain barrier, and that just sets up the stage for inflammation happening in the gut, and inflammation in the gut has been shown to activate inflammation of brain through multiple pathways, and then inflammation in the brain is really gonna accelerate all types of neurodegeneration and disrupt your transmitter signaling. So both are important. Now what do you do basically? Ultimately, you heal the gut, you improve their diet. You get rid of inflammatory foods. Certainly ketogenic diet can be helpful, ’cause you immediately stop insulin surges from going up. So insulin is very inflammatory. It activates something called a RAGE react. It’s called receptor advanced glycation end product reactions. 

They call it RAGE for short. It triggers that, and once that RAGE reaction’s triggered, you’re gonna have significant neuro inflammation, and it’s been directly linked to risk factor for Alzheimer’s. So the advantage of ketosis is insulin levels sometimes drop by 50% in people, at least 25 to 30%. So that immediately dampens inflammation. It helps the blood brain-barrier heal, helps to get heal And obviously there’s lots of nutraceuticals you can take to support those pathways, which are mostly antioxidants, anti-inflammatories, and things like that. We talked about them in my brain book in great detail.

Heather Sandison, N.D. 

Yeah, I’m curious about your brain book. You published this in 2013 and here we are, it’s 2021. It hasn’t even been a decade, but, man, the research has just exploded. I mean, there is so much that… Well, I’m wondering, I guess that’s my question, what’s changed, and what’s been the same? What would you add to that book if you were writing it today?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

I would just add a chapter on ketosis and intermittent fasting. That has more and more research come up. Outside of that, like I know like the Bredesen protocol’s pretty popular. Yeah, we were doing that 20 years ago. Functional medicine community. I know it’s like now a new thing, but it’s like, yeah, every single step you’re talking about in that program, we did 20 years ago, and we actually published it at least in that book 10 years ago. So for us, it’s not new, for us to get information on the brain is new. I think it was, I think Dr. Bredesen, who I really admire, has been a phenomenal molecular Alzheimer’s disease researcher. He was able to show some key studies where these things change. And for people who’ve never seen that, they’re like, “Oh my God, “you can actually change cognitive decline?” And we’re like, “Yeah, all the time every day.”

Heather Sandison, N.D. 

I think for you and I, it’s not shocking that these things work? What we’re doing is very common sense. We’re creating an environment where every cell function’s better. So, of course, the brain is going to work better. And if you take away all of the crap that doesn’t allow it to work well, then, of course, it’s going to work better. And that’s really what you detail. And I think in just preparing for this conversation and in chatting with you over the past couple of years, when I’ve gone back to that book, I’ve been kind of surprised like, wait, he’s been doing this for… This is not brand new. And really right now, I think what our job is is to tell everyone, because they’re still getting that message from neurology. It’s like, here, try some Namenda and good luck with that. It doesn’t work great, but it’s what we’ve got.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

And to give credit, and then honestly, I think we’re in the world of a preventative medicine, lifestyle medicine, we are lacking clinical trials. So I do have some understanding why conventional neurology’s not so open-minded to it, because in the world of research, you have to have some degree of evidence to sway things. We don’t have, for example, any really good clinical trials that have been published. So all we have are these little case studies and clinical trials. And that really requires an extensive amount of time, energy, and money to incorporate. But one of the things that’s become very clear is that treatment for the brain in things like Alzheimer’s, dementia, it’s a multivariate model. multivariate model means you can’t just take one single thing and then expect an outcome. 

So when you design a clinical trial, the typical approach is you get two groups, you randomize them. So their age and weight and height and everything is equal between those two groups. And that accounts for what they call confounders where things that can change, and they give one person a treatment and one person, the intervent, a placebo. And they just monitor them over time. They have like an end point. The end point may be, we’re gonna check your Montreal cognitive assessment form, or we’re gonna check your memory recall, wherever it is. 

That’s how they do it. And every single drug that’s been used as a treatment for Alzheimer’s has really failed in that model for the most part. And the problem with the clinical trial is that a multivariate model with potential, lots of various confounders, they can’t be just accounted for by randomization, makes it hard. So, when you’re looking at improving the brain, for some people improving the brain would be you really have to control the blood sugar and the pre-diabetes and really improve their vascular health and get them to move. For someone else that’s an athlete who’s overtraining and has too much oxidative stress. and they have like a mycotoxin exposures all over their house, and they’re really getting sick. and they have respiratory disease, and they’re not getting blood flow to the brain.

It’s totally different set of variables. So when you put them into clinical trial, you can’t really match for them, and it’s not enough randomizations. The difficulty is… So again, with all credit, if you’re looking at clinical trials for the level of evidence, we don’t have them. So it’s understandable why a lot of really hardcore research-based neurologists and major departments would be like, “Mm, I’m not convinced yet.” And they’re not, because there hasn’t been done. So that’s-

Heather Sandison, N.D. 

We’re working on it. Right now, at my clinic, we are still recruiting for a clinical trial, and it’s an observational trial. We’re not splitting them into two groups, because I think that’s where we are at this stage in the research. What we need to do is add more… We’ll take a cohort through, which hasn’t been published quite yet. Hopefully by the time this goes live, Dr. Bredesen’s group of 30 will have gone through that, and that will be published, but we’ll add another 25 to that. 

And then the next step is probably these controlled trials where you have two arms and you can compare what happens if you don’t do these individualized treatments versus when you do put together a comprehensive, integrative individualized approach. And I mean, I don’t think you or I will be surprised by what pops up there, but you really can’t blind it. And the conclusion that you come to is that, well, it’s not humans that can’t do this. It’s that the model, the scientific model, and that kind of inquiry doesn’t match the complexity of the brain and the human system.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, that’s a really good point. The study design limitations of not being able to do a placebo and having multivariates and lots of different confounders that are not gonna be able to be completely satisfied accurately with the clinical trial is what makes it really hard. So this is where we have the disconnect and gap between people that are not really promoting this type of diet, because they don’t have the evidence they want, but the truth is they don’t understand. You can’t really create the best study design for that. Now we definitely in the field can do more. 

It’s great you’re doing studies and other people are doing studies as well, so that’ll be great, but then that can be satisfied unless there’s a multi thousand multicentered trial with two arms and placebo controlled, which is gonna be very, very difficult to organize properly. And because of so many different variables of confounders, in order to reach statistical significance, you’re gonna need to have such a high number, which that makes it cost prohibitive. So, that’s the frustration. The frustration is practitioners and people that work with brain relation see changes every day. It’s like not even a surprise to them. It’s almost expected when they see that.

Heather Sandison, N.D. 

In my practice, if somebody is not getting better, I go, “What am I missing? “Like this definitely affected that you get better. “So let’s dig deeper. “Let’s figure it out. “Let’s find out what we’re missing, “because it’s not that you can’t get better. “That is not the answer.”

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Right, so that’s one side, and the other side is like, “I don’t see this , “so I can’t even…” But everything you’re saying is anecdotal. And the patient’s in between that, and I know what to do, ’cause I talked to this very prestigious person at this department and these people I really trust, and they’re experts in the field, but they’re telling me, and then I went to this alternative person, and they’re telling me, “You can do all these things.” I don’t want any snake salesman stuff. And they’re kind of frustrated, and they’re not sure what to trust. But at the end of the day, nothing’s gonna happen if you improve your diet and nutrition and lifestyle and move and optimize your brain function. It’s not like it’s gonna hurt you. And it may actually have a huge impact on your health. So, why not?

Heather Sandison, N.D. 

Well, and billions of dollars and decades of time have been spent studying these medications. And oftentimes what they discovered is that when you remove the beta amyloid plaques, when you remove the tail proteins, you can be successful at that using the medications, but you actually get an increase in cognitive decline. So you get a worsening of the symptoms. The model is broken, the model that we’re using. And at some point, patients are going… They just won’t put up with it. Like they’re going to continue to ask for solutions. And hopefully we will have the studies soon enough before the baby boomers kind of hit this. There’s so many people. There are millions and millions of people that are expected to be diagnosed with Alzheimer’s over the next 10, 15, 20 years. And I think those people are clamoring for solutions.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yep, it’s very true. And also, with the Alzheimer’s disease, the plaques may also have a protective role like maybe dampening inflammation. We published a study in Journal of Alzheimer’s Disease, 2017, where we were looking at all the different pathogens that cross-react and how actually the plaques themselves are protective, and they reduce the inflammatory cascade all over the place. There’s also things that then trigger the abnormal apolipic protein expression, which is pathogenic, but it’s not just always bad, and it’s a model of a single agent, not a multivariate, but just one variable that’s involved. And then you wanna generalize really for the entire disease process. 

That’s why I think people are confused, because you can’t answer some of the questions that people want on one side and other people are observing it. And they’re frustrated, ’cause they’re going, “Why aren’t these people jumping on board?” And it’s not like these people aren’t caring and want all the same things. They have a different way of thinking and a different standard for how they accept things. And this group is just like, “Well, what’s gonna matter if we just change our diet “and improve the lifestyle.” And then these, “Oh, you’re just giving false hope.” And there’s other like, “You’re not doing whatever,” and patients in between. That’s the environment, and it’s not gonna change anytime soon. It’s gonna change the next 10, 20 years. And were getting more and more research gonna come out. More people are gonna be open-minded. But I don’t think we’re gonna get the big, big change, because of these limitations.

Heather Sandison, N.D. 

If you could design a study that would illustrate what you’re seeing clinically, what would it look like?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Well, it would require a huge sample population. And then we’d have to do a lot of group analysis, and we’d have to have multiple end points. Those types of clinical trials, you’d need an entire hospital team. You couldn’t do it on your own. Like you have to get a recruiter. You have to monitor stuff. It would be very difficult. And at that point, you still can’t blind some people, will be very difficult, and because they’re know they’re getting treated, they know their doing it, exercise, for a study a group does not… So, again, that’s the problem. You can’t design. Now you can do some things. And I think like you’re doing some great work. You have a study out on the people working on a trial, but you’re like us, and you’re not gonna change the field of neurology, even if there’s a 30 person clinical trial.

Heather Sandison, N.D. 

But what about like a Framingham type trial or Framingham type study where it’s a big, large, huge-

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

There’s a retrospective. They’re gonna go, “Hey, it’s a retrospective study. “Retrospective study has problems, lots of confounders. “We need a randomized double blind clinical trial. The same issue. But this is a world of research, right?

Heather Sandison, N.D. 

Right, well, we contribute where we can, which you do a ton of.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

I just want to point that out. And the point about this is f you are a person suffering from cognitive decline, just know that this is the atmosphere, like this is what’s happening. Both groups have best intentions in mind, but each person has their biases and the way they think of things and how the world are seeing things from. So, know that there’s gonna be some of those different opinions and different approaches, and know that there there’s valid reasons for both sides, and then decide what you wanna do. Doing nothing is not a good idea. Without question, optimizing your health, make some strategies to improve your brain function and your overall health and physiology is gonna be good for you no matter what.

Heather Sandison, N.D. 

I really appreciate that perspective. The patients are who suffer. They are the ones that get caught in the middle of this argument. And it’s not about being right. It’s really about getting the help to the people who need it. And thank you for just-

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

I mean, I’m in a department of neurology at a hospital doing research, which is totally different, then I’m in the trenches doing alternative medicine, which is totally different. So it’s like, these are really, really great people. These are really, really great people. They think this way, they think this way, and then they have patient in the middle of “I don’t know what to do.” And you’re like, “Ah, sorry, but that’s frustrating.” Anyways, it’s important that people know that, because I think they just don’t end up knowing like it’s the atmosphere.

Heather Sandison, N.D. 

Right, right. And everyone is really trying to do their best to help.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yes.

Heather Sandison, N.D. 

Yeah. We’re gonna spend an entire day talking about toxins on the summit here and how they change cognitive function. But I would love for you to just weigh in on that topic. We hadn’t talked a ton about it. You mentioned pathogens, which could kind of act like a toxin as well, creating signaling that the brain needs to protect itself, but I’m wondering what your clinical experience has been around detox.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah. Also, I mean, I had several publications on chemicals, how they impact the brain, that we’ve published and made a contribution to the literature. And one of the things that we’ve talked to, there’s toxic chemicals that increase inflammation, they increase oxidative stress. They activate and promote the neurodegenerative process. I don’t think anyone doubts that anymore. I think it’s pretty accepted, but something that we contributed to was that it’s not really the amount of toxin you get exposed to, but whether you start to have immune reactions to the chemicals. 

So, we did some initial studies where we looked at, for example, BPA, BPA found a plastic products, and we found that certain toxic chemicals like BPA in plastic products and like in fire retardants, which is like in your furniture that’s sprayed and those types of compounds, everyday kind of compounds. For some people, they can bind to their proteins in their blood. We checked human serum albumin. And then when they bind to the protein, it changes the structure of their protein. And then their immune system starts to make antibodies against it. And then this is where a trace amount of the chemical can then cause these immune reactions. So our initial study that we did we published in the Journal of Applied Toxicology. We looked at 400 healthy blood donors and when we go, “Hey, .” And we randomized them to like race and age of the US population. So we get some clues of how to specify the healthy human population. 

This was a group of people who have no disease, but we found between 10 to 15% of them had chemical reactivity. So then we did some followup research and we go, “Well, these people have chemical reactivity, “how many of them have brain inflammatory markers “like myelo basic protein and myelo neurofilament?” And it was a high percentage of them. And so we published a lot of issues showing, even not the toxic level, but just these trace chemicals. If your body starts to react immunologically to them, that can actually cause auto antibody reaction in the brain and cause inflammation in the brain. 

So the contribution that I can kind of share with you that maybe other speakers haven’t is immuno reactive role that takes place. Now that the question is like, why does this happen to 10 to 15% of population, not the other percentage? And it really probably goes back to what’s called immune tolerance. So immune tolerance is the body’s ability to react to the environment, not to react to the environment, and that goes back to microbiome health and leaky gut and early T cell function. Those are the things that when they get disrupted cause you to react abnormally, have an exaggerated response to environmental things. And that’s where we believe that some of this trace amount of chemicals, even though it’s not high amount, can cause significant impacts on people. So everyone’s measuring them load. It’s like, “Hey, what’s your heavy metal load? “How much toxins you have? “How much mercury you have?” But it’s also good to measure chemical antibodies. So, for example, Cyrex has a panel called chemical rate 11, which I was on the team to help develop. And that measures for chemical antibody reactivity.

Heather Sandison, N.D. 

So this might also explain why a husband and wife, say, they’re in the same environment exposed to the same thing, but one of them is debilitated and the other isn’t, or even siblings, people in the same household. We see this come up a lot in the mold world, “Well, why is she sick, but I’m not? “And we’re in the same environment.” And that is a really great explanation for why. It’s because there’s a different immune response, because of other factors. And again, this is this multi variable kind of soup that we live in that that’s real life that you can’t separate all of these out, that they really come together to create either health or disease.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, and the field of immunology is called chemical tolerance. So if you have people at different degrees of chemical tolerance and chemical resilience, if you have people living in the same household, doesn’t mean they’re gonna have the same reaction. Someone can have a better tolerance than the other person. And this is why sometimes it’s frustrating for a person suffering through it, ’cause they go ahead and talk to the spouse and go, “This mildew and mold and these things don’t bother me. “It’s in your head. “Like I can’t feel it, so how could it be real for you?” But it is real for them, because they have a different immune system than they do.

Heather Sandison, N.D. 

Exactly. So what are the most harmful toxins when it comes to cognitive function? Can we separate this out? Is there something that we should really aim to avoid, or is it just like detox as much as you can and good luck? Good luck out there in that toxic world.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Obviously the more oxidative stress or inflammation it causes, for sure, those would be most toxic. And I’m sure you have speakers on that would have the list better than I do. But I think at this point, ’cause my focus has always been on the immunological response to chemicals, not so much the actual oxidative toxic load. But the most common’s obviously solvents, pesticides, the ones that were really like… Well, we’re not working in factories and getting exposed to magnesium metals in the air and breathing them in . We’re we’re around cigarette smoke. We’re in the freeway with car exhaust. We’re sleeping in beds that have lots of plastic compounds and sprayed with fire retardants. We’re eating and drinking food through plastic compounds. Those all play a role too. They’re not as toxic as, let’s say, mercury, for example, but they can definitely, especially if you’ve lost your tolerance, they can be a significant contributor to neuro inflammation.

Heather Sandison, N.D. 

One of the things that we see a show up is this overlap between anxiety and depression and then cognitive decline. I would love for you to talk about the role that mood plays in cognition and maintaining good cognitive function.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

I mean, when you look at that, so a lot of times that’s really related to frontal lobe degeneration. So the frontal lobe is where you have focus, attention, concentration, and your executive functions, but your frontal lobe also has a pathway that dampens an area in the brain called limbic brain, and these are called frontal striatal projections. When those frontal striatal projections start to degenerate, becomes very easy to get anxiety and you get nervousness. 

So, it’s not uncommon for people that have Alzheimer’s disease, or Lewy body dementia, or Parkinsonians, or whatever traumatic brain injury, CTE, they have these interests to frontal lobe. If they get the frontal striatal projections injured, or degenerated, they will absolutely have anxiety with depression, focus, and concentration issues. So, I don’t think it’s specifically a chemical, ’cause we see it when we do a thorough exam. We’re like, “Oh the frontal lobe’s not doing well,” “so we can rebuild that.” We rebuild the frontal lobe, we see those things change. So I don’t think it’s chemical-specific. I think it’s more of a pathway.

Heather Sandison, N.D. 

Well, this conversation has certainly been good for my brain. I think I’ve learned new things. It’s certainly made me a little happier, because it’s always a pleasure to talk to you. And I’ve learned just so much every time that I’ve interacted with you, every time I’ve opened one of your books and Dr. Kharrazian, I just can’t thank you enough for spending some time with us and sharing with all of our listeners. Where can they find out more about you? I don’t think I’ve tried, so I don’t think you’re taking patients anymore.

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, we just have a long waiting list. So that’s a problem, but, I mean, I work with patients every week, so, I mean, I still see patients. I work with them. My website is called Dr. K News, drknews.com We have lots of articles on brain health and applications. So if anyone’s interested, please check that out. And then obviously my book, “Why Isn’t My Brain Working,” it’s available at Amazon and bookstores,

Heather Sandison, N.D. 

And you providers as well, right, for any providers listening?

Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN

Yeah, so I do do postgraduate education. We have an education too called the Kharrazian Institute, my last name Institute. And if you’re interested in learning from a clinical perspective how to work with chronic diseases, you can always check out the kharrazianinstitute.com.

Heather Sandison, N.D. 

Do the satisfying work that we do, reversing dementia, reversing cognitive decline.