Preventing Brain Fog and Dementia: Why Nootropics Often Fail

Dr. Steven Noseworthy (00:25.072)
Yeah, every

Hello everyone and welcome back to the Inflammation Nation, where as I always say, we like to stay up to date in how science can help you craft your own wellness journey. just a reminder.

Hey guys, and welcome back to The Information Nation, where we like to stay up to date on how science can help you craft your own wellness journey. Don't forget to hit that subscribe or follow button so you don't miss any new content. And of course, that helps me reach more people with the message of science informed wellness. If you're new to the podcast, sometimes I do put graphics and diagrams up on the screen. So if you like the visual side of things, the full video and the visuals are going to be on YouTube.

Now, if you have been, or if you are someone who is, if you are someone who is struggling with chronic brain fog, poor memory, word finding difficulty, possibly anxiety, changes in your mood control, and you're just generally looking for ways to sharpen your mind. Maybe you're concerned about long-term brain health. and that might be amplified if you have a family history of things like dementia or Alzheimer's disease.

Then this particular episode should be of great interest to you, particularly if you are following online health trends recently over the last year or so. You've probably seen the masses, massive push for cognitive enhancers or pneotropics, or nicotine patches, or transcranial electrical stimulation. All of these promise to instantly unlock your frontal lobe, your

Dr. Steven Noseworthy (02:10.25)
Executive function and protect your brain from dementia. And maybe you've tried some of these shortcuts. Maybe in the beginning you felt a brief surge of stimulation and better function, but then maybe a few hours or days later the fog rolls back in heavier than before, and you're left feeling mentally drained, more irritable, and like your brain has just crashed. And the question is: why do these brain boosting shortcuts?

Cuts fail for so many people. And there's certainly no doubt there are people out there that can take a nootropic, some kind of a brain stimulant, maybe buy one of those fancy transcranial headsets and actually derive benefit from it. But many people do those strategies, and not only do they not get better, they actually, in some cases, can get worse. Well, the reason is because brain fog and cognitive decline are not simple deficiencies.

In these things. You don't have a deficiency in a particular nootropic or a smart drug because pharmaceutical companies are trying to develop these. The brain itself doesn't operate in isolation from the rest of your body. And what happens in the rest of your body has everything to do with your brain health. When your body and your cells experience persistent systemic inflammation, maybe you're insulin-resistant or poor thyroid hormone conversion or.

Changes in your sex hormone, reproductive hormone balance, your brain's resident immune cells become primed. I'll explain that here in a bit. And the blood flow to your brain gets uncoupled. And I'll explain that in a bit. And what that essentially means is that inflammation and poor blood flow to your brain is a recipe for neurological disease.

Dr. Steven Noseworthy (04:10.846)
start the whole thing over, shall we? Hey guys, and welcome back to the Inflammation Nation, where we like to stay up to date on how science can help you craft your own wellness journey. As always, don't forget to hit that sub.

Dr. Steven Noseworthy (04:30.178)
Hey guys, and welcome back to The Inflammation Nation, where we like to stay up to date on how science can help you craft your own wellness journey. Don't forget to hit that subscribe or follow button so you don't miss new content. And of course, that helps us reach more people with the news and the message of science-informed wellness. If you're new to the podcast, sometimes I do put diagrams and information up on the screen. So if you like the visual side of things, check out the full video on YouTube. Now, today's topic is

About brain and about brain health. And that's a that's a large topic just in and of itself. We're going to slice it down to a couple of things that are very common, and that is things like brain fog, as well as people's concern over brain health as they age and whether or not they're marching down the path towards dementia or they're doing everything they can to stop that. And I think this is particularly important because if you follow health trends online, more than likely you've seen a a massive

Push for cognitive enhancers, things like nootropics, and these are drugs or even supplements that can enhance cognitive performance. and this all falls under the moniker or the general umbrella of brain biohacking. A lot of times you'll see influencers promoting, you know, smart drug stacks or smart supplement stacks, which might be high-dose GABA or nicotine patches, or even.

Transcranial electrical stimulating headsets. And all of these promise to, you know, magically unlock your executive function, your frontal lobe function, so that you can think clearly and make decisions and be motivated and set goals and actually take action to accomplish those things. And I think the overriding concern is none of us want to get older and lose our minds. We don't want to have Alzheimer's disease or some other form of dementia.

Maybe you've tried some of these things and maybe you've had some short term benefit. everyone's going to respond to these things a little bit differently. But today I want to ask the question for those people who try these things or are considering trying these things, why is it so often that these shortcuts to brain health fail so many different people? And the the simple answer is because brain cog brain brain brain cog.

Dr. Steven Noseworthy (06:51.564)
And the simple answer is because brain fog and cognitive decline are not deficiencies in these nootropic supplements or smart drugs. And that's clear, like we all understand that. The brain itself doesn't operate in isolation from the rest of the body. And what happens in the rest of the body has everything to do with the health of the brain. When your body, your cells experience chronic inflammation, maybe there's some insulin resistance or

Low thyroid hormones, or maybe there's imbalances in your reproductive hormones. It creates an environment where the brain's resident immune cells become primed and blood flow to the brain gets uncoupled. And what that means is that brain inflammation and poor blood flow is a recipe for neurological disaster. We'll come back and define those terms about primed immune cells and neurovascular uncoupling here in a second. If you try to stimulate

A brain that is inflammatory, or when you try to stimulate a primed, inflamed, and metabolically starved brain with supplements or drugs that are nootropics, it's like throwing bacon grease on a kitchen fire. It doesn't really fix anything. It actually just accelerates the burn. So today we're going to look past all the biohacking hype.

We're going try to connect trending issues like brain fog, anxiety, depression, and dementia prevention directly to core metabolic control. Simple things like blood sugar, thyroid hormone conversion, sex hormone balance, and inflammation, and map out what it takes to actually protect your brain moving forward. But before we dissect the advanced neuroimmunology of the brain.

I want to address something under the heading of too simple, often overlooked. And this is something I'm going to continue to do as we go forward in episodes because there's so many things that are just simply overlooked for the sake of expediency or because it's a flashy new thing. We all love to dive deep into complex concepts like microglial priming, blood brain barrier integrity, synaptic plasticity, and as well, we should, because those are important topics.

Dr. Steven Noseworthy (09:10.594)
But sometimes people spend so much time searching for complex hidden causes or finding unique, new, flashy shortcuts that they step over the most basic fundamental laws of human physiology, and in this case, brain function and brain health. And one of those foundational rocks is basic energy balance and calorie deficits. When you're dealing with chronic brain fog or cognitive fatigue, your baseline calorie mechanics.

matter immensely. If you are constantly overconsuming calories, even clean, say organic calories, you predictably overload glucose and insulin handling capacity, and that will generate systemic inflammation and oxidative stress that can cross into the brain environment and directly interact with the brain. Conversely, we see the opposite extreme just as often. People who are always in a calorie deficit,

Or who have intermittent low blood sugar episodes, what we might call functional or reactive hypoglycemia, these people tend to trigger fight or flight responses, which are essentially your brain saying, hey, I'm I'm in starvation mode and this is not good for me. You cannot ignore the simplistic nature of simple things like energy balance, managing your calorie intake cleanly, avoiding avoiding both metabolic overload and prolonged cellular starvation.

is a fundamental metabolic prerequisite for brain health. So again, never step over simplistic foundational inputs like calorie balance just to chase complex, expensive, nootropic medications or supplements. You have to fix the fundamentals first. Now I'm not going to go into calorie deficits. I've I've done that in so many different episodes. in fact I've dedicated several to blood sugar control alone. You can just go back in the list and search for those and in

You know, grab yourself a whole bunch of information about how that works and why it might affect your brain. All right, let's let's move on to some of the deeper stuff. And the first thing I want to tackle is actually two things together because they are linked. And that is microglial priming and neurovascular uncoupling. And you may have heard of some of these things. You probably have heard of microglial priming. You probably have not heard of neurovascular uncoupling. It's a relatively recent topic in.

Dr. Steven Noseworthy (11:35.147)
Neurophysiological research. And by relatively recent, that could mean in the last seven to ten years, but it takes so long for research to make it into the hands of clinicians in the educational system and certainly to the public. But while your brain needs many things to be healthy, we can express things that it doesn't need as well. For example, your brain doesn't need to be inflamed, and it doesn't need anything to reduce its blood flow.

So let's take those one at a time. Inside your brain, surrounding your neurons, is a specialized team of supporting cells called glial cells. And these are not the cells that you think and move and feel with, those are your neurons. But these glial cells are there to support your thinking, moving, feeling neurons, both structurally as well as chemically. And there are different types of glial cells. And one type of glial cell is called a microglial cell.

These are essentially your brain's resident immune cells, which are separate and distinct from the immune cells and the rest of your body. I'm going to go ahead and put a graphic up here on the screen for those of you who are watching, say, on YouTube. In a healthy brain, these mycoglia act as, let's call them gentle housekeepers. They clean up cellular debris, they prune old synaptic connections, those connecting points between different neurons, and they also secrete growth factors like.

BDNF, which stands for brain derived neurotropic factor. And these things support learning, they support memory. And the combination of cleaning up degree debris and pruning these synaptic connections and secreting growth factors is part of how we protect the brain from degrading and degenerating over time. And they promote what we call neuroplasticity, which is actually physical, structural, and chemical changes to your brain that enhances connectivity and communication. And these are all good things.

course. And again, under normal healthy circumstances, when needed, these normally gentle housekeepers can turn into a well controlled and well trained tactical force whose job now becomes to find and eliminate any threats to the brain. When you're healthy, these microglial cells can accurately identify some kind of an intruder. They can tell the difference between an intruder and you and your own tissues.

Dr. Steven Noseworthy (14:01.11)
And when the job is done and they've eliminated the threat, they go back to cleaning the house. Of course, these are analogies, you understand that. But if these microglial cells get primed, they transform not into a well-controlled tactical force, but an out-of-control band of mercenaries who don't really care who's the bad guy and who's the good guy. They just like to go out and wreak havoc and destruction. And so this thing called microglial priming.

Is an immunological state of hypervigilance, hyperreactivity. And primed microglial cells really don't want to go back to those other jobs. They don't want to go back to the well-trained tactical force, and they certainly don't want to go back to being just the simple housekeepers. And the net result is that primed microglia drive a constant state of brain inflammation that is most often experienced.

By people who have it as brain fog and depression. And we can throw in their cognitive to fatigue. You can only use your brain for so long before your brain gets tired. And over time, with this microglial priming and brain inflammation, this promotes faster rates of neurodegeneration. So the general rule is that an inflamed brain is going to degenerate faster than a non-inflamed brain. And maybe it's obvious, but

A history of head injury can also certainly prime the microglial cells. This is well proven in neurological research. In fact, microglial priming is a core neurometabolic feature of head injury and concussion. And while I'm at this, like don't discount having had some kind of a milder head impact in the past where you didn't pass out, maybe you just had your bell rung, but you certainly didn't lose consciousness. Those things count as well. The literature is very clear on that.

And to make matters worse, if you've had several of these smaller injuries over a period of time, each one adds more priming to the one before. And so maybe the first one didn't really result in a microglial priming, but then you have a second one, and that increases the probability. And then by the time you have a third mild impact, all of a sudden you have a majorly inflamed brain as if you had had a one.

Dr. Steven Noseworthy (16:22.85)
serious head injury that was so great and so significant that you did lose consciousness consciousness. So don't discount the the milder head impacts where you didn't really think about it because you never had any post concussive symptoms that lasted for any given period of time, or again, maybe you didn't lose consciousness.

Dr. Steven Noseworthy (16:47.948)
And to make matters worse, if you had several smaller head injuries, each one adds more priming to the one before. So maybe you didn't ever have a big concussion where you lost consciousness. But maybe you just had a handful of smaller impacts, which we call mild traumatic brain injury, that you discounted because it wasn't a big impact and you didn't lose consciousness. But each one gets added to the ones before, and you can end up down the road as if your brain

did have a major injury because it behaves that way chemically. But you can have primed microglial cells in your brain causing neuroinflammation even without a concussion. And that's because there are some things that happen in the body that can affect the brain by closet crossing the blood brain barrier.

smoldering systemic inflammation from say an infected leaky gut or stealth infections like Epstein Barr. We've talked about Epstein Barr recently, or maybe it's Lyme disease or some kind of environmental toxin exposure, maybe it's mold. the metabolics of the impacts of insulin resistance, more. All of these can cause the microglia to shift into the prime state where they're acting like those heartless mercenaries. And once these microglia are primed into that mercenary state,

The gentle breeze of a minor strip minor stressor or a poor night's sleep or a small drop or spike in blood sugar causes the alarms to blare at full volume. And now everything gets turned on again. And so primed microglia, they spew out massive amounts of inflammatory cytokines, things like interleukin 1 beta and TNF alpha. Along with that comes a hefty dose of free radicals. And this localized neuroinflammation.

slows down electrical conduction between neurons, produces the brain fog, promotes cognitive fatigue, and if all those things happen, particularly in the frontal lobe, it shifts you into a state of depression. And to make matters worse and to connect this with the second item that we want to talk about, brain inflammation changes how blood flow to your brain behaves. And research calls this neurovascular uncoupling. This part can get

Dr. Steven Noseworthy (19:07.436)
A little bit complicated, so track with me for a minute. In a healthy brain, blood gets diverted to whichever part of the brain needs it most. If you're thinking hard about a complex topic, you're going to get more blood flow to your frontal lobe, which is what you use to think with. If you're working out and you need more blood flow to the brain networks that are involved in contracting muscles and moving your joints and so on. And your brain coordinates this by using another type of glial cell called an astrocyte.

Remember that glial cells are not neurons, and their job is to support the neurons that we use to think, move, and feel. And each astrocyte is connected up to 20 different neurons. And when those neurons activate, because you're using the part of the brain where that neuron lives, the astrocytes in that region sense the increased neuronal activity and they release chemicals that cause small blood vessels that V feed the tissue of the brain.

To dilate and to deliver more blood to the working neurons. But when your brain is inflamed for whatever reason, when you try to use the inflamed parts of your brain, blood flow becomes uncoupled from the demand because the astrocyte's ability to sense the activity and coordinate increased blood flow gets compromised. Essentially, when you use an inflamed brain, your neurons fire and demand more fuel, but the local blood vessels

fail to dilate, which means that within a short period of time of engaging, say in mental effort, you experience like word-finding difficulty or heavy brain fog, mental confusion. It's difficult to think through problems or situations or make decisions. And it's this precise scenario where taking brain stimulants or enhancers like nootropics fails for some people, because adding a stimulant

To an inflamed brain that can't coordinate blood flow on demand only increases the demand for blood flow. And so the gap between the metabolic demand and supply gets wider and wider and wider. But understand this point, and this helps us segue into the next core concept. Understand why blood flow is necessary not just to the brain, but to all living tissue. Blood carries the essentials of life, which are oxygen and a fuel source, like glucose or fats.

Dr. Steven Noseworthy (21:28.812)
And the reason why shutting off blood flow to the brain is bad is because it def deprives the brain of the fuel sources and oxygen which it needs to make ATP or energy. And brain cells need that to stay alive. So poor blood flow means low oxygen and low fuel, which means lower ATP at the neuron level, lower energy production, which means poor function. And if you shut it off altogether, of course, we call that stroke and brain death. That's obviously the extreme.

So, what if you have decent blood flow, but maybe you have a blood sugar problem that deprives the brain of a potential fuel source? Well, that can prime glial cells too. So let's talk about what I like to call metabolic pivot points that affect the brain health. If these are working in your favor, you'll tend to have a better brain. But if there is an imbalance or a problem with one or more of these pivot points, you tend to have a bad brain. So this next

Concept is about metabolic control relating to blood sugar control, specifically insulin resistance, and what researchers have in recent years been calling type 3 diabetes. So that first major metabolic pivot point for the brain is blood sugar stability and central insulin resistance. Again, we'll take these one at a time and I'll pop something up on the screen for you to take a look at.

There are different types of blood sugar stability issues, but the focus here, just for this episode, is on states of high blood sugar and high insulin, what we call insulin resistance. And I'm sure you've heard of that. Maybe you haven't. Let me simplify this because it is a little bit of a complex topic. When you're healthy and you're eating food containing glucose, you're eating carbohydrates, the rise in blood sugar causes the production of insulin from your pancreas.

And insulin's job is to help clear glucose, extracting it from your bloodstream and transporting it into your cells, where your cells can either burn it for energy right away or store it for later use in the form of what's called glycogen. With insulin resistance, that process doesn't work, which means glucose stays in the bloodstream and causes even more insulin to be produced. The net result, at least in this context, is that high glucose and high insulin trigger.

Dr. Steven Noseworthy (23:45.249)
A downstream inflammatory cascade. And as a result, consistently high blood sugar and insulin cause systemic inflammation. And this is very well understood and very well documented. And on a simplistic level, the inflammatory chemicals from the insulin resistance can cross the blood brain barrier and get into the brain, where they can prime your microglial cells. And now you have brain inflammation coming from a body-based problem.

In this case, handling blood sugar and handling insulin. Furthermore, the inflammation of insulin resistance can impair the blood brain barrier, which opens the brain environment to any number of potential threats. The blood brain barrier is there to keep certain things out of the brain. And when it fails, you get what's called neuroinvasion, which sets up another way to prime your brain's microglial cells. Either way,

Brain inflammation from bad blood sugar control manifests again as brain fog, depression, and brain fatigability. When we use terms like insulin resistance, we're talking about the mechanism by which someone becomes a type 2 diabetic. Now you can be insulin resistant and never become a type 2 diabetic, but if you do become a type 2 diabetic, it's because you have somewhere along the way developed insulin resistance.

And this is the one that's related to diet and lifestyle choices and is both preventable and reversible. And in this context,

Dr. Steven Noseworthy (25:20.588)
And this is in contrast to type 1 diabetes, which is an autoimmune problem that usually ends up with someone having to take insulin every day. But in 2005, researchers started to use the term type 3 diabetes to describe what happens in the brain of Alzheimer's disease. And now it's important to note that this is not an official diagnostic term, but it's a description of what's happening in the brain of people with Alzheimer's. You don't have to be a diabetic of any type to get Alzheimer's.

But what happens inside the brain with Alzheimer's includes insulin resistance in the brain itself. Now, insulin is not just a blood sugar storage hormone for your liver and your muscle cells, it's also a critical neurotransmitter and a growth factor inside your brain. So there are two things to know about insulin and your brain. The first is that insulin receptors are found throughout the entire brain, but they're not equally distributed. Some parts of the brain

And some cell types, like the neurons that we think, move, and feel with, have more insulin receptors than, say, the supporting glial cells. So changes in insulin sensitivity will affect certain parts of the brain and certain types of cells more than others. But the role of insulin in the brain is less about controlling glucose, like we see in the body, especially in the liver and muscle. And it's more about insulin's role as a neurotransmitter. And in this role,

Good insulin signaling supports synaptic plasticity, neuronal health, and survival of brain cells. And one of those parts that's packed with insulin receptors is called the hippocampus. And this is a core part of the brain that's responsible for memory formation, among some other things. And it's also the first site of impairment in the development of Alzheimer's and dementia. So when the brain becomes insulin resistant,

Specific regions of the brain, like this hippocampus, are much more likely to be affected because of the density of insulin receptors in that area compared to other parts of the brain. And the bottom line is that it's bad, bad, bad, bad for your brain to have a blood sugar and insulin issue. Right. And in most cases, the effects of this can be prevented and perhaps reversed with proper diet and lifestyle and some targeted nutritional support. You cannot.

Dr. Steven Noseworthy (27:41.965)
Biohack your way out of this. You can't biohack your way out of central insulin resistance with nootropics, whether that's a drug, a smart drug, or a supplement stack. If you want to clear your brain fog and work to prevent dementia, and you have systemic and brain-based blood sugar and insulin problems, you have to fix those first. That brings me to our metabolic pivot point.

Number two, which is thyroid and sex hormones. The brain has the second pivot point.

Dr. Steven Noseworthy (28:25.176)
And that brings me to the second metabolic pivot point that involves the thyroid and reproductive hormones. And while it is more complex than this, let's say for now that the effects fall into two broad categories: genomic or genetic, and non-genomic effects. And that's just a scientific way of saying that active thyroid hormones like T3, particularly free T3.

And all the reproductive hormones impact how the genes of the neurons in your brain behave, and they impact non-genetic processes such as the regulation of growth factors like the BDNF that we talked about before, brain-derived neurotropic factor. For the last 16 years or so, I've taught a three-day functional medicine course to doctors called Mastering Brain Chemistry. And we typically start the entire weekend talking about dementia and neurodegeneration.

And in the course of that introduction section, I typically make this statement that one of the fastest ways to degenerate the brain is to deprive it of thyroid hormones. While thyroid and reproductive hormones play a role in activating the DNA of your neurons, the thyroid does most of the heavy lifting there. It's the one that's primarily responsible for these genomic effects. And in fact, two important roles of

The active horm hormone T3 in the brain are regulating gene expression to support neuronal survival and health, and stimulating mitochondrial biogenesis and function for better brain energy mechanics, which means that it's critical that you have enough thyroid hormones, especially in the form of T3 or free T3, to support that. Now, if you are

somehow hooked into the thyroid algorithm of social media platforms, you're going see no shortage of practitioners with 90-second clips about how your thyroid makes most of the mostly inactive thyroid hormone called T4, and how that needs to be converted to the active form of T3 to be useful. And that's true. They will also typically state that in order for your body to convert T4 into active T3, you need the nutrient selenium. That is also true.

Dr. Steven Noseworthy (30:43.33)
And they might so go so far as to say that's because the Deiodinase enzymes, we usually call these D1, D2, or D3, these enzymes that drive the conversion of T4 to T3 are selenium-dependent. True again. But this kind of leaves you with the impression that in order to make more active T3 hormones, all you need to do is take more selenium. And that's where the truth-telling stops. It turns out that having

Enough active T3 is so critical to driving genetic expression and mitochondrial function in both your brain and your body, that the natural intelligence of your body prioritizes these T4 to T3 converting enzymes over most other things. In other words, even as your selenium levels start to fall, if that's happening, these enzymes continue to work efficiently because that natural intelligence in your body preserves their function.

reserving selenium for those enzymes and taking it away from things that are less critical, even in the face of suboptimal levels. It's only when you become severely selenium deficient that these enzymes become dysfunctional. Yet there are many practitioners on social media, and there's one that I'm thinking of right now. I could put his picture up, but I'm not going to do that. But he states that he puts all of his thyroid patients on five specific supplements before they do anything else.

And selenium is number one or number two on his list. And this highlights an alarming trend among low information, maybe inexperienced practitioners, where they might go to a seminar and they learn a basic truth, a fact that these converting enzymes are selenium-dependent, which again they are, but they then construct a clinical approach based on surface-level knowledge. Because the deeper information says, yes, while these are selenium-dependent.

They are prioritized by the natural intelligence of your body. And so you have to have a severe selenium deficiency for that for that to have an impact on that system. And of course, it would be easy for you as a social media consumer, not a seasoned practitioner, to listen to something that someone says, especially if they say it with confidence and assume that it's true. Especially if you hear more than one person saying it. But just because more than one person repeats a mostly true statement.

Dr. Steven Noseworthy (33:10.892)
Doesn't make it entirely true. So, what does affect the conversion of inactive T4 to active T3 to the benefit of both body and brain? Well, I'm going to toss up a short list on the screen if you're watching this on YouTube. There are several key nutrient factors with differing effect sizes. We just talked about selenium. It probably has the most, the greatest impact in talking specifically about selenium deficiencies.

But studies show that selenium's effect on how these converting enzymes work has an inverted U-shape curve, meaning that not only does low selenium cause these problems of converting inactive T4 to active T3, so does too high selenium. So if your selenium is normal and you start supplementing with selenium because you heard someone say, you need to be taking selenium for your thyroid, and you end up having more selenium than you need.

You actually create the very thing that you're trying to fix. And that's not good for your thyroid. It's certainly not good for your brain. Some other things that nutrients that can have an effect, iron, low iron status, which we measure by something called ferritin, has a moderate effect here. Although ferritin and iron has effects in other parts of the thyroid system. Just talking about the T4 to T3 conversion, it has a moderate effect if you're deficient there. And the weakest effect is related to zinc.

It's probably the least of our concerns, although there might be concerns with low zinc as it relates to things like your immune system. We also have biological or metabolic factors that affect T4 to T3 conversion. And don't lose sight of why we're even talking about this. All of a sudden we're talking about the thyroid in a little bit of detail, but it's because the thyroid is so critical to your brain. So, what are the biological or metabolic factors that can derail T4 to T3 conversion? Well, high strength.

High cortisol, what we call stress chemistry, and the pairing of inflammation and oxidative stress, which by definition, if you have a bad brain and you have brain fog, depression, and fatigability, we know that your brain is inflamed. And maybe that's coming from systemic inflammation that's affecting your thyroid. And now we have poor T4 to T3 conversion, which by the way, we can easily identify this just by doing a simple blood test, right? This is not.

Dr. Steven Noseworthy (35:32.513)
Rocket science, this part. This is actually easy, basic fundamental diagnostics. And then finally, there are some environment environmental factors that can have an impact here. a whole class or different, I should say, different classes of environmental toxins, and we can include heavy metals, especially mercury and lead, can impair this conversion as well. And the reality is that we all have these things in our body. The question is, is it really causing a problem for you? And again.

If we want to know if somebody is converting T4 to T3 efficiently, we just simply run a thyroid panel that includes those things. Very simple, very easy. And the patterns, if you know what you're looking for, are quite easy to find. But while active thyroid hormones are the most potent driver of brain health from a gene activating standpoint, they are also, or they also play a role in neuroprotection by activating growth factors like BDNF.

BDNF again is a compound that the brain uses to repair neurons and to create greater connectivity between the neurons, which is the key aspect of what we call plasticity. And neuroplasticity is the antidote to neurodegeneration. Let me say that last part again. Neuroplasticity is the antidote to neurodegeneration.

Going back to that three-day seminar that we teach, the first day is really talking about this relationship between neurodegeneration and neuroplasticity. From the moment you're born, you start losing brain cells. And we lose brain cells at different rates as we age through the decades, but we can offset that by creating greater connectivity with the neurons that are still surviving. And so you can have a very functional 80, 90-year-old person who's lost a ton of brain mass.

but they've retained their plasticity and their connectivity, which means that they can still function. Right. And then you can have other people who don't really have a lot of neurone loss, but they didn't develop a lot of plasticity and they're going to suffer greater loss as they continue to age.

Dr. Steven Noseworthy (37:40.835)
While thyroid hormones do play a role in supporting plasticity, the real drivers are the reproductive hormones. In fact, when we look at the impacts of optimized hormones in a general sense, we see the following three or four things. We see lower brain inflammation because these hormones help to control your primed glial cells. We see better brain energy production and better utilization of fuel sources like glucose or even fats and ketones.

And we see a dampening of stress chemistry and oxidative stress and cortisol. And there's other things that we could throw into that list as well, but those are probably the most common ones that we encounter clinically. And while we could isolate each of these reproductive hormones and tease out precise details of what each individual one does, it's better to look at them collectively, especially since clinical strategies like hormone replacement therapy are best employed.

With a whole system approach. Doctors who really know what they're doing with hormone replacement therapy rarely prescribe a single hormone without considering how they all work together. And the bottom line is this: to bring things full circle to the main topic today, if you try to treat hormone-driven brain fog and prevent dementia with brain stimulants or nootropics when the brain is inflamed and has bad blood flow, you are ignoring the

Core physiological physiological drivers, the root cause disruptors, if you will, that created the bad brain to begin with. And you have to address those before you can expect the biohacks to be successful. So, what's the final word on restoring central nervous system capacity? How do we break the cycle? How do we calm down primed glial cells? How do we improve blood flow to the brain? How do we protect long-term cognitive health? Well,

Again, I teach a full three-day course on this to clinicians. So there's a lot more than what I'm going to give you now. But I'm I want to give you some quick tips and strategies that maybe you can start thinking about the situation that you're in for yourself. But the the first thing is this stop being random. Like you have to have a plan, you have to have a strategy, you have to understand what it is you're dealing with. And I think your plan has to respect the hierarchy of function, meaning that some things are more fundamental than others.

Dr. Steven Noseworthy (40:09.932)
So here's part of the step-by-step framework that I teach and that I use clinically. Number one is, and this is up on the screen, by the way, establish baseline energy mechanics. You have to have good blood flow, you have to have good aerobic energy metabolism, and you have to be eating sufficient calories to fuel your brain function. You have to unprime your microglial cells.

And there's many studies on different bioflavonoids, things like luteolin or epigenin, curcumin, as well as good antioxidants like glutathione can help control inflammation and oxidative stress. And they do it in part by calming down the glial cells. There's other mechanisms, but that's in the context of today what we're interested in. The next thing is you have to restore metabolic control. You have to have good blood sugar control. You have to be insulin sensitive.

You have to restore T4 to T3 conversion problems if they exist for you. And again, it's not just about taking selenium. And you have to have good optimized reproductive hormone balance. And let's add in the last thing here, which is targeted neuroplastic stimulation. And there are different strategies that we can use with this. But once the brain is no longer inflamed and it's got good blood flow and good energy metabolism and balanced hormones in the environment.

Then we can use different, let's call them brain training or brain exercises, brain rehab, whatever you want to insert into that empty space there to actually drive activation and use of these things, which is required for plasticity. And the brain operates on this simple rule: if you don't use it, you're going to lose it. Now that's not a complete list, but it's a good start. When you fix your metabolic foundation and you calm microglial activation, your brain naturally

regains its focus and its clarity and its resilience, even without resorting to brain stimulants, which again, for some people can backfire. I would love for you to stop spending time and money on internet-based biohacks that try to shortcut your brain's basic physiology. Brain fog, anxiety, depression, fatigability, dementia risks. They're not deficiencies in supplements. They're biological

Dr. Steven Noseworthy (42:34.21)
Neurometabolic and hormonal states that demand a systematic evaluation of your fundamental chemistry and your metabolic control. You can't outhack a metabolically starved brain that's plagued by inflammation in things like hormone imbalances. As I've said before, crafting wellness is not the same thing as just simply using biohacks. It requires identifying your unique root cause disruptors.

Evaluating your foundational systems and moving step by step through a real structured three-stage health journey. My personal coaching clients that work with me, they work only through me through this three-stage journey. And if you personally are ready to address your actual root cause mechanisms and things that are driving your brain fatigue and your anxiety and your brain fog.

You can contact me today. Just use the contact information that's in the episode description, or you can visit my website at drnosworthy.com. That's dr noseworthy.com. Thank you for listening to the inflammation nation. Put your big rocks in first, and I'll see you on the next episode.

Timestamps

• 01:12  Brain fog, memory issues, anxiety, and brain health concerns

• 01:42

   Why this episode matters in the context of online health trends

• 02:35

   Why brain-boosting shortcuts often fail

• 03:05

   Brain fog and cognitive decline are not simple deficiencies

• 03:34

   Inflammation, hormone imbalance, and blood flow as core drivers

• 04:30

   Re-introduction and episode setup

• 04:59

   Brain health, aging, and dementia concerns

• 05:28

   Nootropics, smart stacks, and brain biohacking

• 05:55

   Why people want to avoid losing mental sharpness

• 06:24

   Why shortcuts fail for many people

• 06:51

   Brain fog is not a nootropic deficiency

• 07:19

   Inflammation and low blood flow create brain problems

• 07:50

   Why stimulants can backfire on an inflamed brain

• 08:16

   The episode’s main framework: brain fog, mood, and dementia prevention

• 08:41

   The importance of simple foundational physiology

• 09:10

   Energy balance and calorie deficits

• 10:06

   Low blood sugar, starvation mode, and brain fatigue

• 10:36

   Why fundamentals come before expensive biohacks

• 11:05

   Microglial priming and neurovascular uncoupling

• 12:03

   What glial cells and microglia do

• 13:02

   Healthy microglia, learning, memory, and neuroplasticity

• 13:31

   How microglia become hypervigilant and destructive

• 14:31

   Brain inflammation, fatigue, and faster degeneration

• 15:27

   Head injury, concussion, and long-term microglial priming

• 17:37

   Systemic inflammation, toxins, and infection as drivers

• 18:07

   Neuroinflammation, cytokines, brain fog, and depression

• 19:07

   Neurovascular uncoupling and how blood flow should work

• 20:03

   How inflammation disrupts blood flow on demand

• 20:32

   Why stimulants worsen the gap between demand and supply

• 21:28

   Why blood flow and oxygen are essential to brain energy

• 21:58

   Metabolic pivot points for brain health

• 22:25

   Blood sugar stability and central insulin resistance

• 22:48

   What insulin normally does

• 23:15

   How insulin resistance drives inflammation

• 23:45

   Blood sugar problems, brain inflammation, and the blood-brain barrier

• 24:41

   Insulin resistance, type 2 diabetes, and brain fog

• 25:20

   Type 3 diabetes and Alzheimer’s-related brain insulin resistance

• 25:49

   Insulin’s role as a neurotransmitter in the brain

• 26:47

   Good insulin signaling, plasticity, and the hippocampus

• 27:13

   Why central insulin resistance is bad for the brain

• 27:41

   Why you can’t biohack your way out of insulin resistance

• 28:10

   Thyroid and sex hormones as the second pivot point

• 28:51

   How thyroid and reproductive hormones affect the brain

• 29:21

   Thyroid hormone deprivation and brain degeneration

• 29:48

   T3, gene expression, and mitochondrial function

• 30:12

   T4 to T3 conversion and selenium

• 30:43

   Why selenium is often oversimplified online

• 31:13

   How the body prioritizes T4 to T3 conversion

• 31:42

   Why “just take selenium” is incomplete

• 33:10

   What really affects T4 to T3 conversion

• 33:39

   Selenium’s inverted U-shape and why too much can be harmful

• 34:08

   Iron, ferritin, and zinc

• 34:37

   Metabolic factors that disrupt thyroid conversion

• 35:06

   Cortisol, inflammation, and oxidative stress

• 35:32

   Environmental toxins and thyroid function

• 35:59

   Why thyroid panels help identify the problem

• 36:29

   Thyroid hormones, BDNF, and neuroprotection

• 36:53

   Neuroplasticity as the antidote to neurodegeneration

• 37:40

   Reproductive hormones and brain support

• 38:10

   Why hormone treatment should be whole-system, not isolated

• 38:39

   Why nootropics fail when root causes are ignored

• 39:09

   How to break the cycle and restore capacity

• 39:39

   Stop being random: you need a plan

• 40:09

   Step 1: establish baseline energy mechanics

• 40:37

   Unpriming microglia and lowering inflammation

• 41:07

   Restore metabolic control and hormone balance

• 41:37

   Targeted neuroplastic stimulation

• 42:05

   Why the brain naturally regains clarity when foundations improve

• 42:34

   Why biohacks can’t outrun poor physiology