Jay Feldman 0:05
If you've been diagnosed with hypothyroidism and you're treating this as a thyroid problem, there's something you need to know, and we'll be going over exactly that in today's episode of the energy balance podcast, where we dig into the physiology behind the bioenergetic view of health and teach you everything you need to know to maximize your cellular energy. Today's episode is part one of our hypothyroidism series where we'll be going over why hypothyroidism is not the root cause of your issues, why TSH, on its own, is not a good marker of thyroid status, the importance of thyroid hormones for hormone production, gut health and immune function. We'll be going over T three's effects on autophagy, mitochondrial biogenesis and on coupling, and we'll be discussing whether low thyroid activity is beneficial for longevity and aging, and when a high TSH level may actually be a good sign. As always, if you're looking for the studies, articles or any other relevant links from this episode, head over to the show notes at Jay Feldman wellness.com/podcast, and with that, let's get started.

All right, so when it comes to hypothyroidism, for one it's an incredibly common diagnosis, yet it still can be argued, and I think should be argued, that it's still extremely under diagnosed. So this is something that is widely regarded, or at least documented, to affect at least 5% of the total population, which is huge. When it comes to a chronic health condition, that's a huge percentage. It is typically more common in women. So in women, it'll be as high as 10% and again, this is something that, especially the diagnosis, increases with age, so it's much more common as somebody who gets older. And this is something that I would say, and as we'll talk about, can be responsible for so many different symptoms that we can experience, and is also a relatively transient state and a situation that I think could describe what a ton of different people are experiencing. And I think again, the 5% diagnosis rate is very underdiagnosed. And one of the worst parts about this diagnosis is that the people who get this diagnosis are told that this is a genetic issue and that there's nothing that you can do, and they're prescribed t4 which is levothyroxine, which is the second most prescribed medication in the United States by most accounts, and as we'll talk about throughout the series, it's generally pretty ineffective for resolving the issue, resolving the hypothyroidism. So we've got this conglomeration of problems here, of this extremely common issue that is not properly diagnosed. We'll talk about why that is. We'll talk about blood markers and all and other symptoms and measures that you can use to that are indicators of your thyroid status, but it's also very poorly treated. And so just to kind of list some of the symptoms here that that are directly related to thyroid health. Thyroid activity, one of the most central ones is our metabolic rate. So how much you know, normally, it's measured in calories, how many calories you burn in a day, how much energy you expend, that's going to be dependent on on thyroid activity, as well as the amount of energy we produce, and that then translates to how much food you can eat while maintaining your weight. And along with that, if you're dealing with hypothyroidism, you'll be very prone to weight gain due to a low metabolic rate. You'll also be very prone to fatigue, low energy, low cognitive function, low mood, low immune function, low body temperature, low pulse rate, a handful of other symptoms as well, more physical symptoms like dry skin, dry hair, hair loss. Gut issues are extremely common as well. Small intestinal bacterial overgrowth. We'll be talking about SIBO as something that's directly tied or very highly correlated with hypothyroidism. Slow gut motility is another very common one, or constipation, you know, being the kind of main presentation of that there's a almost any symptom or chronic health issue you can think of as going to be tied back to thyroid activity. You know, this comes back to cardiovascular health, high blood pressure, high cholesterol. So many of the other things that we treat as independent issues can come back to thyroid health. So this isn't a ubiquitous problem, and, yeah, something that is extremely important to talk about. So we'll dig into that. We'll also talk in a moment about what hypothyroidism actually is in the biological context, what it actually means. But first, Mike, I'll let you chime in if you have anything else you want to add.

Mike 4:35
First, yeah, I think that, uh, I think Dr. Broto Barnes, so that's the main physiologist and MD that Dr. P talks about in terms of thyroid function. He's discussed that hypothyroidism being like a much larger problem than is actually commonly thought to the five to 10% being low, and the diagnosis and the treatment of these things are based on. So looking at people not from a symptomatic perspective, but looking at people from purely from a lab test perspective, and just going based off the and we'll dig into the lab tests, the main one being TSH, so I think that if you start to understand thyroid physiology, you start to understand what's actually going on in the body, how the hormones are being converted, and at the tissues and how they're being converted in different circumstances, you start to understand that the diagnosing of hypothyroidism is wholly inadequate and even in the literature, you're starting to see researchers talk about subclinical hypothyroidism and the different values of hypothyroidism, and essentially the way that previous researchers, like Dr bro Barnes looked at this was they looked at they didn't have as great lab testing. They were looking at like, I think, iodine indexes and things along those lines, which wound up being not as valid for testing hypothyroidism. And then TSH came out, and they that was been the gold standard, kind of ever since. But they were looking at what people are actually experiencing in their daily life. They're looking at actual physical measures of metabolic function. And so those things being body temperature, those things being says, like susceptibility to infection, premenstrual disorders, digestive issues, et cetera. And then kind of treating with thyroid empirically, and seeing, Oh, is this? Are these things getting better? Is temperature increasing and then going from there? So they, I think those methods, actually, despite the lack of, like, technological advancement in them, were much more sufficient, because you're getting to see the effects of something in real time. And I think the reason I bring this up specifically here is there's a lot of people are, well, a lot of people who come to the bioenergetic sphere. Kind of question like, do I really need all thyroid supplementation? What's with all these people taking thyroid and using thyroid? And it's because it can have such a profound effect on health, and it can help people dig themselves out of the hole, and it can provide, like, a huge relief for stress in conjunction with diet. So it's definitely a huge tool to have in the toolbox. It can be extremely helpful for people. And I think that it's much more than just this drug treatment to treat a lab range. It can be like a general health substance and so that's the changing how we view hypothyroidism, which we're going to dig into in just a second, but changing how we actually view what hypothyroidism is, and like the value of thyroid hormones in different treatments, I think can be a is, is really important to do in terms of improving your health and coming from this bioenergetic perspective.

Jay Feldman 7:41
Yeah, and a great point that you brought up there was that the testing that was used prior to TSH was, there was the protein bound iodine test. There's, I think, one other and repeat had detailed this history where these tests that were later found to be totally inaccurate had been used for a long time to determine hypothyroidism, and based on the what was deter based on the percentage of diagnosis of the population using these inaccurate tests, that same percentage was assumed to be the case when they transitioned toward other testing. So what I mean by that is, let's say, with the protein bound iodine test, they found that 5% of the population had hypothyroidism when they then switched to the TSH Test and looked at the population's TSH levels, they said, Oh, well, 5% of the population has hypothyroidism. So we're going to determine the, you know, top 5% of TSH levels, and that's going to be how we determine our range. But because that earlier test was inaccurate, that entire proportion of people with that should be diagnosed with hypothyroidism was thrown off, and that's part of the reason why, finally, there's some shift in what's considered to be normal in terms of TSH. The values used to go, you know, that was used to be not an issue, until you're at, you know, a TSH of 10. That was when hypothyroid diagnoses would start, and that's come down over time. But we'll dig into that when we talk about the thyroid blood testing more specifically, but to zoom out here, when we're talking about hypothyroidism, it's really helpful to get the broader biological context of what this means, what our thyroid activity means, and its relevance. And so, in essence, our thyroid glands is our metabolic dial. And so what it's doing is it's sensing, it's sensing the status of the environment, the energetic capability or availability of the environment. And based on that, it's adjusting our metabolism, adjusting our metabolic rate, and all of the things that go with it, which we'll talk about. And so if we have high thyroid activity, it that means that we're going to have have a higher metabolic rate, and that our authority is going to be responding to an environment that could support a higher metabolic rate. And when we when we have low thyroid activity that's happening as the result of our body through our handful of hormones that we'll discuss, among other things, sensing that the environment is not energetically favored. Bowl, and so it decides to turn down its metabolism to best adapt to that environment. And so this is central to the bioenergetic view. This is why you were talking about it in terms of something that Ray discussed quite a bit. Because when we're talking about energy availability to our bodies, our thyroid is a is basically the primary indicator of that. And so what this means in terms of hypothyroidism is that hypothyroidism is not a disease that you have or don't have, and it's not anything that's permanent. It's not necessarily genetic. Of course, there can be genetic factors here, but the important point here is that this is a transient state that can fluctuate throughout the day. It does fluctuate throughout the day, but it can also fluctuate on a larger, you know, broader context, month to month, year to year, week to week, and it will do so based on what sort of signals we're giving our bodies, in terms of food availability, in terms of light, in terms of all sorts of things. And so the good news there is that we are not doomed if we get a diagnosis, if we even want to think of it as a diagnosis of hypothyroidism. But rather, this is just saying that this is a state of a generally low metabolism, and that's exactly how it used to be diagnosed. So you mentioned that with Broda Barnes, and he detailed this and prior, I mean, since right around 1900 and earlier, they were using things like the basal metabolic rate as a primary determinant of thyroid state, as well as different reflex tests that we'll talk about. So that's kind of the, I would say the most important thing when we're talking about hypothyroidism is considering it as a general state of the body that's responding to the energetic capacity of the environment, and basically it's a part of our adaptation to our environment. There's two other things I want to mention here. So we will talk a little bit about the autoimmune side of hypothyroidism. It really isn't all that different from a non autoimmune hypothyroid state. There's, of course, some nuances that we'll discuss, but it really results from the same environment. So we will discuss that situation and what can lead to that autoimmune state, which is generally considered to be the most common driver of hypothyroidism. But again, it's not quite that clear. We'll discuss those nuances. There's two other things I wanted to add in. One is that we mentioned this earlier about hypothyroidism is because it is a state of the body of a low energy state. It's associated with virtually every other chronic health condition we talked about, the different symptoms, but you also have conditions like fatty liver disease and heart disease and depression and obesity and infertility and all sorts of other chronic health issues that are going to be directly tied to, of course, our underlying energetic state, which is why that's what we discussed throughout this podcast, and therefore are going to be directly tied to our thyroid state. And the last piece I do want to mention here that I think is particularly important from the way that thyroid health is looked at from the bioenergetic lens, is that the state of our thyroid, whether it's hypothyroid or euthyroid, meeting normal or hyperthyroid or any fluctuation there is a product of the state that our body's in and the environment that we're putting our bodies in. It's not the underlying driver of anything. It's not a root cause of our gut issues, because there is a root cause beneath the hypothyroidism. There's something that's driving that hypothyroid state. So we'll talk about what this means and why. This does not mean that we just want to jump to thyroid hormone supplementation or anything like that. We want to be aware of the context of when to use these things. And we also like I always think it's important to be careful with our nomenclature here and how we discuss it, and I'm always, I tend to prefer not to call a hypometabolic state hypothyroidism or a low energy state hypothyroidism, because that the hypothyroid. I mean, you can't, you can. It's not that it's incorrect, but it's just that is the surface level, that is the symptom. That's not actually the driver of that state. The driver of all the symptoms that we discussed, the chronic health issues, from this bioenergetic view, is the lack of energy and the things that are putting us in that situation, the things that inhibit our ability to produce energy, the things that increase the usage of energy to an excessive amount, those are what drive the hypothyroid state. And the hypothyroid nomenclature is just a way to characterize it in terms of the activity of the thyroid gland, but it's not actually the deepest level of what's going on.

Mike 14:24
So I just wanted to make that clarification before we dig in... I think the different diagnoses and the things that go with them are a product of like, the current medical system. Instead of viewing things as a systemic issue that has multiple factors involved, they kind of view things as like, all right, thyroid is not functioning, so it's a thyroid problem. So we need to focus in on the thyroid. But as we'll start to dig through some of the elements in the research here, what you start to see is that the thyroid is integrated at so many different levels with the stress systems and things going on with the gut and inflammatory systems, that's hard to say that a hypothyroid issue or low thyroid function is. Is a product of just an issue at the thyroid. You could have many things like, for example, an estrogen excess could be driving low thyroid. Excess cortisol could be driving low thyroid. Gut issues and inflammation, elevated cytokines could be driving low thyroid. So it's like, yes, you could directly treat thyroid, but I think what you're getting at here is that we may not need to directly treat thyroid if you can correct those other underlying issues that can take the breaks off your own thyroid production. Now, in that process, it's possible that using thyroid could be something that could be helpful to move things along and help shift the balance in the right direction. But again, it's, it's it's not that there's a singular it's not like a singular organ problem of the thyroid. It's it's a general, overall systemic issue, and it's kind of about ferreting that out at the end. The the one, I guess, underlying piece of all this is that when there are those general systemic issues, it's usually breaks down into a question of energy, what is blocking energy? What is is energy flowing? What? What are all the factors around that? Energy metabolism and a thyroid function is a key piece of that, but it's just one piece in that overall picture, one piece of the puzzle, right?

Jay Feldman 16:16
 Exactly, yeah, and I would basically say that it's not a thyroid problem, it's an energy problem. That's where we want to put. Want to put our focus. But of course, today we are talking about that in terms of the thyroid So let's dig into that in terms of the basics of thyroid physiology, the thyroid hormones production, regulation and all of that. We'll keep these parts relatively brief, but just going is at least worth going over some of the basics here, because it becomes relevant when we when we want to talk about the things that are going to affect thyroid activity and the downstream effects as well, and how you know why it's so important, how it's so important. So in terms of the basics here, we've got a few different hormones. Mike, do you want to start by walking us through them?

Mike 16:58
Sure. So the, I guess the easiest way to think about it is directly in the peripheral tissue, like at the body, or coming from the thyroid. You have two hormones that are produced. The main one is t4 and then the secondary one, in terms of amount that's produced, is t3 so t4 is produced in large amount, and then you have t3 now t4 can kind of be seen, be seen, as a pro hormone, to some extent, in the sense that it doesn't have the potent activity that t3 does. So what happens is, t4 has to be converted into t3 to have that active effect. And then, so essentially, the the body, the thyroid, is releasing t4 and then, depending on what's going on in the body, what, what the state of the body is, the body is converting that pro hormone, t4 into t3 so if you're in a good metabolic state, you you'll you can convert into larger amounts of t3 t3 being the hormone that's driving that metabolic activity. And now, if the body's not in such a great state, what can happen is the t4 can actually be converted into reverse t3 so this is another hormone. Now, reverse t3 is not active like t3 it actually competes with t3 at binding sites, and then it also, it can interact with some of the deiodinase enzymes in not an ideal way. So t3 is kind of inactive, or, excuse me, reverse t3 is kind of inactive, and then t3 is that active hormone, and t4 is the pro hormone. So now those are coming from the thyroid gland. Now you have another layer of regulation over that system, and that's at the brain level, with the hypothalamus and pituitary. And the hypothalamus and pituitary essentially can signal to the thyroid gland. Hey, I don't think we have enough thyroid hormone here. Hey, we have more that we're good on thyroid hormone here, and that it signals through TSH. So TSH is thyroid stimulating hormone, and that's the brain basically reading what's going on inside the body and then signaling down to the thyroid and saying, Hey, we need this, or we need that in terms of thyroid hormone production. So there's multiple layers of regulation of the thyroid hormones. You have the brain overarching kind of reading the environment and saying, Hey, we thyroid we need more thyroid hormone. You need less. The thyroid is producing thyroid hormone in the form of t4 and t3 largely t4 and then the body can take that t4 depending on its state, and say, Hey, we're not doing so hot here. We'll take this t4 we'll turn into reverse t3 it's not really, it's not active. It doesn't have that potent metabolic stimulating effect. If anything, possibly a decrease, can decrease metabolism a bit. And then on the flip side, if the body's doing well, could take that t4 and say, Hey, let's make t3 let's increase our energy expenditure, etc, etc, etc. So there's, it's a multi layer system of control that allows the body to fine tune ly, adjust. It's the metabolic rate using these hormones.

Jay Feldman 19:54
Yep, yeah, exactly, exactly. And it's important to and. We'll keep kind of discussing here some of the feedback mechanisms and conversion between the different hormones and everything. So we've got this graphic, which shows some of the basic feedback within the hypothalamic pituitary thyroid axis. So the first signal that is produced to increase thyroid hormone production is going to be TRH from the hypothalamus, and that's thyrotropin releasing hormone. The reason it's called that is because TSH, which so I'll back up TRH. The thyrotropin releasing hormone gets released from the hypothalamus. It acts on a pituitary and tells the pituitary to increase TSH, which is thyroid stimulating hormone. TSH is also known as thyrotropin so that's where you get the TRH name from. And so that will, again, that'll increase the TSH production from the pituitary, which will tell the thyroid to produce thyroid hormones, the t4 and t3 and so we have a pretty basic negative feedback loop here, although we'll talk about some of the details and why it can cause some issues when it comes to blood markers. And also, there's some nuances here, some details here, that that will come into play.

Mike 21:10
 Yeah, it's not as simple as just those hormones are inhibiting everything. There's other factors involved that we're going to dig into.

Jay Feldman 21:18
Yep, but the basics here is that the more t4 and t3 that are available, that's going to inhibit  the production of TRH and TSH. So the general idea here is, if you have more thyroid hormone, you'll have less TRH and lower TSH and and then vice versa. So if there's very low amounts of thyroid hormone that are being sensed, you'll have higher amounts of TRH and then higher amounts of TSH. So that's kind of the basic system. Here the basic axis. There are a couple of nuances, though, as I was saying. So one of the important nuances has to do with the actual sensing within the hypothalamus and the pituitary. So within each of those they are not actually able to sense as much the t4 levels. So if there's a lot of t4 in the pituitary or a lot of t4 in the hypothalamus, that won't necessarily turn off the production of TRH and TSH, they actually need to have t3 within those organs to turn off to provide that negative feedback. And this is one of those intricacies, which is that the production of t3 within those organs is relatively independent and separate from the rest of the body. So the rest of the body can have very low t3 but as long as the pituitary and hypothalamus are getting some t4 they'll be able to convert it to t3 regardless of what's going on in the rest of the body. And this is what can cause some issues with the negative feedback loops, where you can have low TSH, low TRH, but the body can be in a state of low t3 and so we'll be talking about that as we dig in deeper.

Mike 22:59
And what exactly is going on there, how that can affect our, you know, our approach. Before you move on to something to mention with that Jay, is that it's not only across the like in the pituitary, but in different portions of the body. Different tissues can also have different concentrations of of the active hormone or thyroid hormone signaling. So it's not just like t3 you have t3 it's in the blood, and everything is all good it. You can have different different tissues that will have different concentrations. And you can have, you can technically have some tissues that are in a hypothyroid state, while others are maintaining a degree of EU thyroid state throughout the body. So the other thing is, the other thing to point out is that at the hypothalamus. Not only is t3 regulating them, I guess we'll dig into this, but there's other factors that will directly hit the hypothalamic level that can mask a hypothyroid state by lowering that hype the hypothalamic pituitary signaling to the thyroid gland. So if you're gonna just look at TSH as a value and say, like, oh, thyroids good or bad, based on that, you can miss quite a bit of, quite a bit of, like, what's going on in terms of thyroid function, and a lot of, I don't know. I'm sure you've seen it as well, but you I've had many clients who will come with TSH suppressed, like, it's actually in the bottom of the reference range, and then t3 and t4 will also be quite low. And the doctor will have told them, oh, you're you thyroid, your thyroid function is fine. But when you're looking at their t3 and their t4 you're like, this is definitely not fine. This is like, borderline low. So they can make interpretation a little bit sketchy, because because of the nuances, you really need to understand what's going on at these different levels, and that's kind of why we're breaking this out,

Jay Feldman 24:44
 Yep, and as you're getting at that's why we cannot use just TSH on its own as a marker of thyroid status. Yeah. So we'll dig into that in some more detail. All right, just a quick interruption here to mention that if you're dealing with a lot of the. The common symptoms of hypothyroidism, low energy, fatigue, chronic pain, weight gain, digestive symptoms, brain fog, poor sleep, hormonal imbalances, or any other low energy symptoms. Then head over to Jay Feldman wellness.com/energy, where you can sign up for a free energy balance mini course, where I'll go over all of the different things that you can do from a diet and lifestyle perspective, to maximize your cellular energy, improve hypothyroidism and resolve these symptoms and any other chronic health conditions. So again, head over to Jay Feldman wellness.com/energy, to sign up for that free energy balance mini course. And now back to the episode. As far as the basics of thyroid hormone production, there's a couple things I want to mention. So one is that there's a primary enzyme involved that's also the rate limiting step step of thyroid hormone production, other than iodine availability, which is called thyroid peroxidase TPO. And so we'll be coming back to that, because there's certain regulation that can happen within thyroid peroxidase. But the important part to know there is that that is involved with the production. Involved with the production of the thyroid hormones. And another important piece here is that that thyroid peroxidase requires hydrogen peroxide for its enzymatic function. And so what that means is that they the thyroid tends to be in a highly a state that's highly prone to oxidation, because there has to be a decent amount of hydrogen peroxide available, and so that's something that we'll be digging into later, where that can be thrown out of balance very easily and create a lot of oxidative stress. A couple other things that I wanted to mention here. So as far as the thyroid hormone production, you mentioned, Mike, that most of the thyroid production in the thyroid is going to be t4 about 93% of the thyroid hormone produced is t4 and about 7% is t3 and most of the t3 that gets produced is going to be produced peripherally. So the t4 is going to be converted to t3 in other tissues and then be used in those tissues, or it'll actually be sent back out from those tissues to be used throughout the bloodstream, through circulation, in total throughout the day, normally, the thyroid is producing about somewhere between 85 and 100 micrograms of t4 and only about six micrograms of t3 and then we have another around 26 micrograms of t3 that gets Produced peripherally from the conversion of t4 to t3 so and so. That could be relevant as far as dosing thyroid, which we'll talk about later. And just as a reference, that tends to be about the equivalent of two grains per day of thyroid hormone production.

Mike 27:33
Yeah, before you move forward, just a couple things. So just to clarify for people, the thyroid gland is producing about 85 to 100 micrograms of t4 a day, and it then producing six micrograms of t3 so that's what's actually coming out of the thyroid gland, that another 26 micrograms of t3 is being converted from the t4 produced by the thyroid by the body's cells and tissues, largely At the liver. So you're that extra t3 is coming from conversion outside of the thyroid gland, from the t4 that's produced. So that's a, just an just an important point, I think. And then the next thing I just want to touch on with the hydrogen peroxide and thyroid peroxidase is that the the thyroid gland is actually set up in a way that, because of this reaction that it has, like a special space inside the actual gland to protect the cells from the oxidative stress. So it like, kind of exports the thyroglobulin and then the adequate iodine and whatnot into this space that the thyroid peroxidase undergoes this highly oxidative enzyme or enzymatic process, and creates thyroid hormone, and then the thyroid hormone is taken back in from the cells. So it is a very it's kind of like a it's like you're having a nuclear, nuclear power plant in your town, like you have to be really careful around the like the energy production, or the nuclear energy that's produced there. So, like, the thyroid glands, kind of like that as this, like special area that's designated for this reaction because of how powerful the oxidative reaction is. So that's why it become that's why it's so susceptible to oxidative stress. If that stuff starts getting out of control, you can that's when the hydrogen peroxide can directly damage the cells. It's essentially like, we kind of think of it like, I guess, like a bleach in the cell to some extent. So you're very careful with, yeah, with that.

Jay Feldman 29:32
The nuclear reactor was a good analogy, So we've been talking about this t4 to t3 conversion, as you were clarifying Mike, between the thyroid produced the t3 produced at thyroid versus t3 produced systemically or peripherally. And so there are some details that can be helpful to go over here will actually are going to be really helpful, because the conversion of thyroid hormones is going to be one of the main things that gets affected. By different things in our environment. And so just understanding the basics here of what are called the diode ace enzymes is going to be really helpful. So the diode NAS enzymes are the enzymes that convert different thyroid hormones. And they're called diode aces because they're removing an iodide from the thyroid hormone. And so the there are three primarily, they're called diode and Ace one, two and three, very creatively named. And the there's a couple important things to consider. So when we have t4 to basically be converted into two different thyroid hormones. One is the active t3 that we talked about that has all the metabolic and genomic and all the effects. Then the other is the reverse t3 and reverse t3 not only doesn't have those effects, but it has some inhibiting effects. So when so there are a couple different enzymes that will that occur in different tissues, or are found in different tissues, and that are going to be primarily responsible for converting that t4 in either direction. In general, deiodinase one and 2d. One and d2 are the primary ones that are going to convert t4 to t3 and in general, d3 or deiodinase three, is the main enzyme that's going to convert t4 to reverse t3 so this is the most that's, you know, if you take nothing else from this part, that is the most important thing, because what we're going to see is a lot of different factors that can up regulate the conversion of t4 to t3 by d1 or b by d2 and things that can up regulate or down regulate the conversion of t4 to reverse t3 via d3 The other important point here is that these different, as I mentioned, the different diodense enzymes, occur in Different areas different tissues and so we were talking about this a little bit with the Pituitary and the hypothalamus. But essentially there are the d1 and d2 enzymes, the ones that convert t4 to t3 are found in different areas. D1 is mostly found in the liver and kidney and some other tissues that is basically going to be these are basically the areas that are going to produce a lot of t3 to release into circulation. So the liver and kidney will convert that t4 to t3 and then release it back out. So you have more circulating t3 d2 is primarily used in tissues that don't send that t3 back out. They just use the t3 within the tissues. So it's going to be going to be very commonly found in the muscle, and then also in the brain, the Pituitary and the hypothalamus. And there are different things regulating d1 and d2 so what we'll find later on is that different environmental stresses and factors will inhibit d1 but they won't inhibit d2 and so what that will mean is that our liver and kidneys won't be producing a lot of t3 that will be circulating, but our pituitary and hypothalamus specifically will have enough t3 so they'll be turning off our TSH production, say, and basically telling your doctor, hey, you've got enough thyroid hormone, even though there is not very much t3 circulating. And so that's the kind of most important point here, as I mentioned earlier, there is another important point when it comes to reverse t3 which is that the reverse t3 also competes with the t4 to be converted via d1 so or d2 So, if you see here at the bottom, reverse t3 can be converted to t2 and it requires the same d1 and d2 enzymes that the t4 to t3 conversion requires. So when you have a lot of reverse t3 it's going to compete there and reduce the amount of t3 that gets produced. And as we also talked about, it can have some blocking effects on the actual activity of t3 so that's kind of a you know, again, another reason why we want to be making sure that we're not creating a lot of reverse t3 which, as we'll talk about, is something that will happen in cases of low...

Mike 33:48
Of low what? Low carb diets, that's probably like one.

Jay Feldman 33:50
Yeah, low carb diets, I was going to say an environment that's not energetically favorable, or a low energy environment, but, yeah, low carb diet is certainly one of those. For sure. Another thing to mention here as well is that just, you know, it's, it's very prominent that selenium is required for d1 activity. We'll be talking about other nutrients that are required for different steps here. But that's just a particularly important one. And as you know, as we're alluding to, to, again, we want that t4 to be converted toward t3 via these two enzymes, that's going to be happening in a state of low stress, high energy and then the t4 to reverse. T3 via d3 is going to be happening in the high stress, low energy state. Yeah,

Mike 34:31
Yeah, there's a couple of things I wanted to add here, specifically, uh, just minor pieces. But another thing is up regulation of d3 will take t3 and convert it to t2 so the increasing d3 will also metabolize your t3 to more inactive thyroid hormone, which is t2 another piece is that reverse t3 is kind of like a triple whammy, because it's using your t4 so that you don't have t4 to be converted to t3 it's it's competing. With t4 at the d1 and d2 enzymes, and then it's also having an interaction at the cellular level with versus t3 in terms like a blocking some of the effects. So it's kind of overall, like you're seeing elevations of that there's like you're basically impairing thyroid function to three levels. Now it's not the reverse t3 is this terrible thing. It's what reverse t3 is indicating is the metabolic state of the body. It's saying, Hey, we have some like metabolism right now isn't so hot. And in certain circumstances, you don't want to ratchet up thyroid hormone if the body can't handle it. So it's gonna it has these, basically disposal pathways, or the this regulation system that's developed to protect itself from trying to ratchet up thyroid hormone in states where maybe so the states where you generally see low t3 and increase in reverse t3 are critical illness, significant stress, starvation, ketogenic diets, low carb diets, et cetera. So in those states, you wouldn't want to really push the pedal on, on energy metabolism. So it's a protective effect, and it's telling us these things are giving us an idea of what's going on in the body. And so you can look at this is when you look at labs, when you look at somebody in a you saying, Okay, you have high reverse t3 and low t3 maybe TSH is suppressed, then you're basically saying, Okay, there's something going on metabolically. And maybe you came from a carnivore diet, maybe you just came out of significant periods of stress. Maybe you've been exercising ridiculous amounts on a on a crazy basis, or came out of like, a very restrictive, low calorie diet. So then the solution isn't to just dump thyroid hormone into that, it's to reverse the other factors, diet, lifestyle, et cetera, so that you can then support your own t3 production. And then once you kind of have things on board appropriately, then it's like, okay, maybe adding a little thyroid can help kick start the system if it's been a chronic issue or whatnot. So again, it's not that these factors are terrible. It's not like cortisol, it's this terrible thing, it's just indicative of what's going on with the state of the body. And they're there for in general, for a particular reason, right?

Jay Feldman 37:10
And we don't want to encourage a state, but that will increase that situation, that'll increase high levels of cortisol or reverse t3 so that's a it's a really good point, a really great distinction to make. And something I wanted to mention earlier, when we were talking about this larger context of hypothyroidism, which is that hypothyroidism is the proper response to a low energetic environment, like a non energetically favorable environment, whether that is a low carb diet or, as you said, illness or starvation, or any of those cases, those are situations where we want to turn our metabolism down to ensure survival and ensure function to whatever extent we can. And it's basically this is our way of saying that we want to turn down our metabolic dial. In that case, it's really, really important that we can do this. If we can't, we would be in major trouble in the same way that if we didn't have stress hormones like glucagon and cortisol and adrenaline, which directly affect the thyroid system, as we'll discuss. If we didn't have those things, we would be in major trouble, because those help to turn down they do a couple things. They'll turn down our metabolism through certain effects on the thyroid system, which will help deal with future stress or reserve energy for future stress, and they'll also mobilize resources for the immediate stress at the same time. But the point is that these things are super important. It's great that we have them. That's part of why we're here. But that does not mean we want it doesn't mean that they're all benign we It doesn't mean we want to do things to increase cortisol or adrenaline or glucagon. It doesn't mean we want to do things to increase reverse t3 so yeah, that's that's that kind of context that's so important.

Mike 38:38
Yep, exactly. We're trying. We know these things have different effects in different areas. They're there for a reason. But we also can look at this and say, well, we don't want to optimize for those things. We want to optimize for an increase in energy and keeping those things on the lower side overall.

Jay Feldman 38:56
Yeah, exactly. There's a couple other kind of minor points I want to mention here that will come into play later, because, again, other factors can affect these aspects of the thyroid system. One is the transport through the circulatory system. So thyroid hormones don't tend to be free in the circulation. Instead, they tend to be bound with certain proteins. The main one is called TBG, which is thyroid binding globulin, or thyroxin binding globulin, that transports most of the thyroid hormone, about 74% 75% of the t4 and then to a smaller extent, we have transdirectant and albumin. Those will also help to transport t4 and t3 to different extents, there are certain things that will inhibit the thyroid hormones from binding to these different binding proteins. So that's why they'll become important later on. Is there anything else you want to mention regarding those?

Mike 39:51
The only other thing is just that if you have alterations in the production of these binding proteins, you can also see negative impacts on thyroid function. So this Jay. Generally you would see in like with liver problems. If you're having issues with liver and you're having issues with production of these binding proteins, you can see not only aberrations of thyroid hormone, but aberrations in multiple hormonal systems. Because a lot of these binding proteins, as you see, like as an example for transdiretin, binds both t4 and retinol, and then albumin is kind of like this ubiquitous carrier protein and plasma protein that you see all throughout the blood that carries and has multiple functions. So yeah, if you have any dysfunction going on to that extent, you can see general alterations of the hormones in terms of carrying and then also with the liver, specifically with metabolism, which we'll talk I guess just a side point. I don't know if we were going to get to get to it later. If it was part of the D we kind of briefly mentioned it in the deodina system, but the liver is one of the main areas where you have the d1 enzyme that's increasing the production of t3 from t4 so if you have any impairment at the liver level, then you can see alterations in the bind the binding proteins. Now that's usually more severe, but you can see changes in the metabolism of t4 to t3 versus t4 to reverse t3

Jay Feldman 41:07
Yeah. And you were saying that you won't really see decreases in the binding protein availability unless the issue with the liver is more severe.

Mike 41:14
Yeah. Usually you're seeing, like significant liver issues before you start to see drastic adjustments and production of things like albumin and whatnot. It's not like just fatty liver causes that. Now, there are other mechanisms where, like with fatty liver, if you have elevated endotoxin, which we'll get to that can alter thyroid hormone signaling, but that that's not severe enough by itself, usually, to just cause this, like drastic down down regulation or production of the transport proteins.

Jay Feldman 41:44
Yeah. And then the last piece, or I guess second last piece, I want to touch on in terms of the basic thyroid hormone activity and physiology. Well, not activity, we'll talk about that. But in terms of like production and transport and everything, there's another factor, which is the actual uptake of the thyroid hormones into the cells, and so the uptake of t3 and t4 are both considered to be active processes, and what that means is that they're energy dependent, so they require ATP in order for the cell to take up t3 and t4 and more specifically, The t4 and also reverse t3 require much more energy to be taken up than t3 so this is going to be particularly important as we talk later on about the energetic state of the cell, where if the cell is low on energy, it's not going to be able to take up t4 very easily, or t3 but more So t4 both of these require adequate energy, and obviously all the things that can inhibit our ability to produce energy, all the things that could create that mitochondrially dysfunctional state, will then impair our ability to use thyroid hormone. So that's an important piece here. And normally this uptake is considered to happen via different protein channels, and, you know, other kind of transporters along the membrane, of course, from the more bioenergetic view of the cell, through the association induction hypothesis, this wouldn't be as specifically relevant, but I think you can basically take the same claim, which is that not which is basically that it doesn't require energy to literally transport it across the membrane, but rather, the cell has to be in a state of having adequate energy in order to uptake the thyroid hormones. And this is, you know, just based on structural conformational changes. So again, that's the case when we talk about any anything related to like cellular uptake, or cellular membrane receptors and things like that. But yeah, that's this is one that's certainly going to be something that we'll talk about throughout the series.

Mike 43:46
 And this is a this is actually in conjunction with the idea of the deiodinase enzymes controlling production of our conversion of t4 to t3 versus reverse t3 Oh, or one of the major problems with t4 only monotherapies, where you're in this low energy state and you're not converting the t4 over to active thyroid hormone, and then you're also not able to uptake that t4 into the cell appropriately. Then you can be taking all the t4 that you want, and you'll be technically, largely or possibly suppressing your TSH, because you won't have that change in the d2 d2 diet deiodinase enzyme at the pituitary and then hypothalamus. But so you you'll GSh will be suppressed, and everything will look good from that perspective. And t4 levels may be high enough, but you still going to technically be in a cellular hypothyroid state because the rest of the cells of the body aren't able to affect aren't converting t4 to t3 and aren't able to uptake the t4 appropriately. So this can explain, for a lot of people why, when you hop on levothyroxine, t4 only monotherapy, that you're not really you're not really experiencing these drastic changes if you're if somebody is using thyroid hormone, if they. You should technically see, maybe, if you're maintaining your regular caloric intake whatnot, start to see a decrease in weight, maybe a decrease in water, maybe an increase in body temperature, improvements in digestion. So if you're not seeing that on your current thyroid therapy, there could be other reasons to explain it, and we'll talk about some of these things with nutrient requirements. And as we go throughout the rest of this this video, but if you're not seeing that, then I would start to question if maybe to t4 only therapy is best for you. And I think, I think there's a section later where we dig into this a little bit.

Jay Feldman 45:35
Yeah, we'll be talking a lot about that. And most people who are on t4 only third like therapy do not have improvements, and their TSH goes down, and their doctor says, you're totally fine. But as we've been saying, that does not mean you're actually fine. And part of the reason could be because you're not converting that t4 to t3 effectively, part of it can be because you're in a state of low energy production, so your cells can't take up the t4 so they can't convert it to t3 anyway, because in order, even for the liver and kidney to produce the t3 for the rest, you know, for to put out in circulation, which they're responsible for, more of that than the thyroid, is they need to be able to take up the t4 so there's a whole host of ways that we will have low t3 despite intervention, and this is one of the main ways. So, yeah, we'll definitely be discussing that more detail. The last thing to mention here is just some of the nutrients that are involved in the production and conversion of the thyroid hormones. I mentioned. Selenium is involved in the conversion. But again, we're just, I'm just going to kind of touch on these. There are details as far as where each of them are used, but the kind of short of it is that we need to make sure we have enough of pretty much any nutrient for anything to work, and this is because a lot of different nutrients are involved with a lot of processes, and thyroid hormone production and conversion is no exception to that. So when it comes to the production, this is going to depend on having enough iodine and tyrosine as well as things like selenium, zinc, vitamin E, different B, vitamins b2, b3, b6, are particularly important. Vitamin C, Vitamin D, Vitamin A and iron are also all involved in the production of thyroid hormone. So we'll be talking about those a little bit later. And just in general, this is a lot of these are recommended as supplements if somebody's dealing with hypothyroidism, unless there's a clear deficiency, they tend not to make a major difference, but it could depend on the context, and they might be worth addressing. We'll talk about that later on, in terms of our approach of what to actually do when it comes to a hypothyroid state. And then the last thing, as far as conversion of the thyroid hormones go, selenium, zinc and vitamin A are particularly important there.

Mike 47:38
Yeah, I think it's with the nutrients, a lot of people ask me, like, what is the one nutrient? There's this idea that there's, like, this high dose vitamin C or this really high dose vitamin E, like, those are the things that are gonna make this massive difference. And what the response that I always wind up giving is something along the lines of, like, all of these things work together. So you in order, as we're talking about throughout this whole situation, you need adequate energy metabolism in order to respond well to thyroid hormone and then also to convert appropriately. So that's going to require a vast majority of the B vitamins, just that alone. And that's then you have what you actually need for the iodine ace enzyme function, what you need for the antioxidant enzymes inside the thyroid gland, because, again, you have that high amount of oxidative stress from thyroid peroxidase, then you need. What do you need for thyroid hormone to function at the cell? That's where you start talking about vitamin A. And so it just, it basically is like, yeah, you need everything. That's not like nutrients are maybe more involved, but because everything is so integrated, you're just you wind up needing everything and if you start to actually like detail all the different pathways, you basically just come with the basic idea that you need to have a nutrient dense diet and overall. Now the other thing to keep in mind here is super dosing. Everything isn't necessarily ideal either, because there can be problems with taking too high doses of certain things, which we'll talk about as an example, iodine and even selenium. And really high intakes can cause problems as well. So again, it's not it's not about like taking the like, most high value supplement possible for all these different things. You can get a lot of these things from the diet and then kind of sharing up some areas where you could be deficiencies, and then using some things, possibly in higher dosages that are safe at higher dosages, and kind of being there's a nuance to the nutrient stuff, but a lot of it comes down to that nutrient dense diet that's going to be that foundational piece here to cover these different bases.

Jay Feldman 49:40
Yep, definitely, and we'll talk about that too, because overdoing it with some of these different nutrients can actually inhibit thyroid activity as well. So it is an important consideration to make for sure, just because iodine is necessary for thyroid hormone production does not mean that you want to go supplementing iodine, especially with the kinds of doses that many people use for it. So definitely want to be. Careful with all of that, and we'll discuss some details. And of course, it's the same for things like iron and vitamin A and all of that.

Mike 50:06
And I see that so often, the iodine one specifically, it's like, oh, yeah, thyroid labs weren't good, so I started taking, like potassium iodide, or lugals, or like seaweed, a large amounts of seaweed, and it's like, you need iodine, but you don't, maybe don't need that much.

Jay Feldman 50:23
Yeah, yeah, definitely, yeah. So let's talk a little bit about the direct effects of mostly t3 because t4 doesn't really have those direct effects, but in terms of what t3 is actually doing when it is available, when it does reach the cell, and so the most basic thing that it does is it stimulates mitochondrial respiration. It stimulates our energy production. This is, of course, the thing that we talk about all the time as the driver, the foundational component that drives our health. And so that's why hypothyroidism is so important. Here it's why thyroid activity is important. That's why having enough t3 is particularly important. And so this is also why t3 is the so particularly responsible for where metabolic rate is at, how much, you know, calories we're burning on a daily basis. So that's the first part here. The second part I want to mention, it comes back to our hermesis discussion, which, of course, is another thing that kind of has influence everywhere. And so one thing that thyroid hormone, or t3 specifically, can do is it can activate some of the things that people try to activate with hormesis without the stress. So t3 can directly activate uncoupling, as well as stimulate autophagy and mitochondrial biogenesis, but it does this while simultaneously increasing ATP production. And so if you are trying to accomplish those things under some guise that you need lots of autophagy or lots of mitochondrial biogenesis all the time, which I don't think is necessarily the case, but even if you wanted to do it, we talked about this dichotomy in those hormesis episodes, which I'll link to, where you could do that through a high energy state or a low energy state. In the low energy state, you block energy production, you increase oxidative stress, the production of lots of reactive oxygen species, and you decrease ATP production, and that causes defensive reactions that will increase uncoupling, autophagy, mitochondrial biogenesis, and on and on. And we would argue, basically, that is not an ideal thing to encourage. On the contrary, you can also stimulate the same processes by increasing ATP production, which does also increase reactive oxygen species, but it doesn't in a different context where there's high ATP and high CO two, which directly protects the cell from oxidative damage and also doesn't lead to the accompanying stress hormone production and the systemic signals to decrease metabolism. And one of the factors in this latter state of activating these things in a high energy state is t3 because the t3 can specifically and uniquely activate these processes in a high energy state. So just wanted to mention those couple of things, which I think are particularly important when it comes to t3 activity. But there's a couple other very important effects of t3 if you want to touch on those...

Mike 53:11
So another major beneficial effect of t3 is increasing steroidogenesis, and the way that it does this is t3 will first increase the LDL receptors on cells. So basically it'll let LDL receptor specifically for LDL cholesterol. It allows the cells to uptake that cholesterol. So the next thing it does is Jay already talked about, is it stimulates mitochondrial respiration, which is important because the mitochondrial respiration is key in that energy production is absolutely key for the production of steroid hormones. Which thyroid hormone also increases the influx of that cholesterol into the mitochondria. So not only is thyroid bringing the cholesterol from circulation into the cell, it then takes that cholesterol and brings it to into the mitochondria. The protein that it does that is through the steroid acute regulatory protein, or star protein, and that is the first initiating step that is important for the conversion of cholesterol into pregnenolone and then subsequently all the other hormones downstream. So the thyroid hormone is going to drive that mitochondrial respiration. It's going to increase the number of mitochondria, and then it's also going to increase the steroidogenic output of those mitochondria. And it's also one of the things that you see in people who are hypothyroid, is this increase in serum cholesterol. The thyroid hormone actually is driving that cholesterol into the cells as well. So, and that's what you want to happen, right? You want the cholesterol to be converted into these, these steroid hormones, the cholesterol, a lot of people, I think, when you first come into, like, the low carb sphere and whatnot, it's like, oh, cholesterol, it's not this demon. It's actually the precursor to all of these beneficial hormones, and then it has a whole host of functions inside the cell. So thyroid is key in bringing that cholesterol into the cell and in converting into these. Hormones. And this is why in states of hypothyroidism, you can see problems with fertility. You can see problems with androgenic hormone production. You can see problems with elevated cholesterol levels. I think some people we've worked with have had cholesterol levels coming off low carb and intermittent fasting, one on the three hundreds and four hundreds, and then you bring you bring carbs on board. You don't even bring thyroid hormone on board. You just bring carbohydrate back on board, and the cholesterol numbers drop precipitously. And it's a function of increasing that thyroid hormones function and signaling and conversion of t4 to t3 production, et cetera. So, and you're seeing this is like we get to see it in real time, essentially, the effects of having adequate thyroid hormone, and the effects of not exogenous thyroid hormone, but of dietary and lifestyle changes on increasing thyroid hormone function and then subsequently having these specific effects. So I guess just a quick recap, we're seeing an increase in metabolic rate. We're seeing an increase in mitochondrial biogenesis, or production of new mitochondria. We're seeing a lowering of serum cholesterol, and we're seeing a conversion of that cholesterol into the steroid hormones from from t3 so these are very obviously, these are all pretty potent effects, especially when you start to consider the effects of some of these other steroid hormones and the value of energy production of the mitochondria and adequate ATP from this general model that we work through.

Jay Feldman 56:23
Yeah, and when you consider that decreases in these steroid hormones, and you know, testosterone for men, progesterone for women, is one of the main things correlated and driving aging and all those other issues. I mean, this is central to our health. So, yeah, huge component here. And to mention, also, just for reference, the star protein. I don't know if you mentioned this is the rate limiting step of steroid hormone production. So what that means is that, essentially, our thyroid hormone is the primary determinant of how well we're going to convert that cholesterol to these protective steroid hormones. So yeah, incredibly important if you're dealing with low amounts of those hormones, and as you said, also incredibly important if you're doing with elevated cholesterol levels, which, among other things, can be driven by low thyroid state due to a low conversion of cholesterol to the steroid hormones. And this is pretty well recognized in the literature, and we'll talk about some discrepancy later on to where t4 monotherapy, t4 monotherapy tends not to lower cholesterol like a combination therapy that includes t3 because you need this activity of the t3 and if somebody's not converting that t4 to t3 well then you don't have that effect. So yeah, that is those are some of those real central reasons why we want to have adequate thyroid hormone. And just a couple other things as well, is that it's got a very critical role in growth and differentiation and development, and it really has a critical role in pretty much any, any issue we can think about immune function, cardiovascular health, digestion, which will we don't have anything talking like any citations here, but I'll cite some in the in the show notes, and we've talked about this in previous episodes talking about gut health. About gut health and digestion, where t3 is the main thing needed to stimulate motility. It's needed to stimulate bile flow, to stimulate stomach acid production and if you have low amounts of all those, you're then going to be prone to microbial overgrowths, and more specifically, SIBO. And there's a very tight correlation between low thyroid activity and SIBO so and we've seen this as well. I know both of us have where the general approach for an issue like SIBO or an overgrowth is just kill it all off, but if you're not addressing the underlying energetic state of the organism, it's just going to come right back, because you're not actually fixing that context of what allowed for it in the first place. And low thyroid is one of the primary things that allows for that, yeah, and again, go ahead. Go ahead.

Mike 58:45
Well, I was gonna say is, you see in the alternative, like health spheres that, like all the gut officials, the gut aficionados, trying to target all of these different pathways, like increased stomach, stomach acid increase, like, kill everything in the small intestine with, like, antibiotics or whatnot, and then take a pro kinetic substance. It's like, and then people are people go through this process. Like, I have multiple clients, like, I took her Paxman, like, five times, and I didn't notice anything. Like, I got better, maybe, like, for two weeks, and then it came back. And it's like, you can do all these things in the meantime. They're not bad strategies. But when things work well, you shouldn't have to worry about small intestinal bacterial overgrowth. The thyroid hormone is going to take care of these things. Is going to take care of the stomach acid. It's going to take care of the bile acids. It's going to function as a prokinetic. It's going to increase the that motility. So it doing those things in the meantime, while you work on because it's kind of a sticky situation, right? If you're trying to increase thyroid hormone function, because you came off low carb, but every time you eat carbs, you're bloated to the high heavens, then, yeah, it's a little bit difficult to like you're not you may be having issues absorbing those carbs, or bacteria producing products that can cause issues as well. So you can use those things in the meantime, but at the. At the end of the day, what drove the problem? The first in the first place is most likely a state situation. What is the body state in and in bringing thyroid hormone or improving thyroid hormone function through diet, lifestyle measures, possibly using thyroid hormone, I think would probably help to have, like, a consistent resolution of this problem, instead of just constantly going through all these gut protocols. And I know we went through our gut protocol phases as well. Whereas, like, we the like most intense gut protocol, like all these herbal antimicrobials, biofilm disruptors, stomach acid support, etc, all this type of stuff. And realizing we did that a couple times and it didn't necessarily fix the problems until we started working on the other things behind the scenes.

Jay Feldman 1:00:42
Another thing to mention there that's associated you mentioned using Rifaximin multiple times, and one thing that's been found in people who have these recurrent issues after using Rifaximin is that they tend to have low steroid hormone production, which, again, is another correlating factor here with low thyroid activity. And we've referenced that in the past as well. And also, if somebody is dealing with those digestive issues and they're in that imbalanced state, or that difficult state where they can't eat a lot of things because of them, and so they're struggling incorporating certain, you know, carbohydrates, or whatever it is, I'll link back to a handful of episodes where we've discussed approaches there for how to deal with that situation. One last thing I wanted to mention here is in terms of the effects of thyroid hormones. Well, two things, one is the fact that this is directly implicated in virtually everything associated with aging. And so we can really think of the state of aging. And we talked about this in episodes where we discussed aging itself and how, basically, it's a state of lowering of the metabolism, and that is what drives the degeneration and disease processes that are seen. And low thyroid activity also correlates with that directly. And so there's a paper. The title is pituitary thyroid axis and immune system, a reciprocal neuroendocrine immune interaction, where they detail this in terms of the immune function that gets degraded with age. And so what they're basically talking about is that there was this idea that with age, your immune system just deteriorated. It just happened over time, and there was no idea that there was actually causative factors that could be identified or reversed. And so they're basically detailing here that one of those factors, the primary, crucial one, is thyroid hormone. So they state that all these findings clearly support the idea that the age related immune deterioration does not represent an intrinsic and irreversible event, but it is largely dependent on the age related defect of micro environmental factors, among which pituitary thyroid hormones certainly play a crucial role. So again, it's just very nicely stated, There very clear explanation of two things, one, the fact that it's not just age, but rather it's the environment, and the interaction between our organism and the environment that causes degenerative states and in this case, low immune function over time. And the other part is that there's a crucial role of thyroid hormone there, that it's one of the main intermediary factors. So you have anything you want to mention there. Mike?

Mike 1:03:09
 I just want to say, Jay, that you know that centenarians have higher TSH values, so, like, you should be hype. And then also, you know, if your metabolism is too high, you're just gonna, like, burn out all your cells and you're gonna go through your Hayflick limit and all that type of stuff. So clearly you need to be hypothyroid to age. Well,

Jay Feldman 1:03:29
Well, well, that, I mean, obviously you're joking, but that's literally the belief by many people who are suggesting things like fasting and caloric restriction for longevity. And we've spent a lot of time discussing why these sorts of things do not actually extend lifespan, and why it's actually the opposite of what you want to be doing. We discussed it in a series discussing aging and metabolism, and also in that hormesis series. So I'll link back to those where we kind of took apart those very prominent beliefs in the current sphere world, yeah,

Mike 1:04:01
well, I guess it's slightly tangential, but interesting is say this to the centenarians did have a higher TSH value. That doesn't necessarily mean that they were more hypothyroid than the the other population, because they maybe their TSH values were just elevating after however many years of their life, to basically say, like, hey, we need to increase thyroid hormone production, whereas the other groups, TSH was suppressed. But so is there t3 and t4 so just interesting look at that specifically, just thinking about that specifically in this context.

Jay Feldman 1:04:34
Yeah, we'll talk about it later. There's this graph that we have that basically shows initially, when you're having hypothyroidism. In the degeneration there, you'll have high TSH, but as it gets worse, your TSH actually goes down and gets suppressed, so that could actually be a sign of worse hypothyroidism. And I think both of us see that with clients as well. I know I do where I prefer a client who has a high TSH and hypothyroidism than a low TSH and hypothyroidism, because they're essentially closer to improve. Improvement, and they tend to respond much better to different different interventions, compared to someone who's in that state of suppressed TSH. They tend to be deeper into the stress state. And so yeah, we will discuss that a little bit when we talk about the blood markers.

Mike 1:05:12
I always see that stuff kind of as a spectrum with clients, where it's like, on one end you have suppressed TSH and suppressed thyroid hormones, t3 t4 and then you have an on the other end, you have a person who is maybe low t3 t4 who has, like, their TSH is elevated. And then you have somebody who could have, like, good t3, t4 and TSH is elevated. And you have somebody who's like, obviously in a more euthyroid state. And it's kind of weird telling people like, yes, your TSH is probably going to go up initially, coming from your low carb diet, but then we probably going to see it come back down once thyroid hormones come back into range. And it's like, because a lot of times like, Oh, my TSH is high now it's like, Yes, that's good. Because before your your hypothalamic and pituitary axis, we're not telling your thyroid to make thyroid hormone, and you also weren't making thyroid hormones. So it's just, yeah, very interesting with the interpretation of some of these things. It's always an interesting conversation to, like walk through how these things can adjust in kind of weird ways as you, as you start to improve some of these external circumstances to then subsequently improve, or not only external, but kind of accessory circumstances, not directly supplementing with thyroid to improve thyroid function.

Jay Feldman 1:06:24
Yeah. And just for reference, we're not like, making these things up in terms of suppressed TSH being something that occurs in hypothyroidism and severe stress states. This is well documented. We will be going through some of the research talking about cortisol, for example, suppressing TSH in a hypothyroid state and on from there. It's not just cortisol, but, yeah, this is not just something that we saw and came up with. This is something that, yeah, that where our our experience is corroborating what is going on with the physiology and the research.

Mike 1:06:51
Yeah. Well, come some of for me, some of it came from working with people and, like, initially going through some of the labs, like, right when I was first starting me, like, this is interesting and not and then, like, looking through the studies and being like, oh yeah, this quarter. Like, your cortisol is elevated, TSH is suppressed, t3 t4 are low. It's like, the researchers just speak about this, like, as if, right? They just say, like, well, this is known, and then this, but it's like, for the wider population, and even, I think for a lot of clinicians, it's like, this is not known. Somebody sees a normal, some of these normal values, like, something's in range, like, TSH, say, oh, that's fine. Like, for example, when you had the that close, the close family member who had the, like, super elevated TSH, and you were just like, This is not okay. And the doctor's like, oh yeah, it'll be just fine. It's kind of like that. Like, there's a little cartoon where the dog is sitting in the room and everything's on fire, and he just like, there's a quote. It's like, this is fine. That's kind of like, what the situation is.

Jay Feldman 1:07:50
Yeah. Well, that was a context. I believe TSH was around nine, and that doctor had a reference range up to 10, which now I almost never see. I mean, it's always, always, almost always, a reference range up to about three or four normally. Four is like typically conventional right now, but yeah, and it's not like the physiology changed in that time. When they changed the range, everyone who had the four and above TSH was very hypothyroid at that state. At that time as well. It didn't change, but they switched the reference range.

Mike 1:08:18
Now they're hoping they weren't before now, right now, the range is adjusted. Now they're hypothyroid Exactly, exactly.

Jay Feldman 1:08:26
And as we'll talk about, that range is nowhere near adequate. We'll talk about the fact that TSH of much lower can still indicate hypothyroidism, like we'll get into it, the research that actually shows what optimal TSH levels are, yep, even when they're not suppressed. The last thing I wanted to mention is just that, in terms of the many of the effects of t3 they do. This is, I think you mentioned this earlier, but when it comes to nutrients, this is an area where vitamin A is particularly important. A lot of the nuclear effects, where the t3 is bonding with the nucleus, require retinol as well the vitamin A. So yeah, just something you see a lot in the research. And again, this relationship between vitamin A and and thyroid is very close. They get transported together. They get used together and when. And it's also one we have to be very careful with, because excessive amounts of different thyroid hormones can cause elevated vitamin A. Excessive amounts of vitamin A can suppress certain thyroid hormones. We'll discuss that later, but it's another one where we want to be careful, but sufficiency is definitely important for thyroid activity

Mike 1:09:28
And  an adequate intake. So just kind of to clarify what you're saying is at inside the nucleus of the cell, when thyroid a lot of the effects of thyroid hormone are happening there which one t3 binds into the nucleus of the cell, it changes all of these effects at the cell. And the way that t3 binds in also requires something called the retinoid X or receptor, or the retinoid binding element. So they kind of like work together. So the t3 and the vitamin A kind of come together. They bind in, and then they have this effect at the nucleus. So that's why you need both. But as. You mentioned, as with a lot of these nutrients, like you need adequate iron, you need adequate vitamin A, too much vitamin A, or too much iron, or problematic, and then too little of each are also quite problematic. So that's why it's, again, it's important to have sufficiency as you I think that's a good term that you used, rather than just like super dosing large amounts of these different nutrients. It's kind of like there is actually ranges where, or like values where you know, like, this is an adequate amount and, dr, not, I guess. Dr, Chris masterjohn does have good work discussing, like, what some of these optimal ranges are and where some of these specific areas are. In case anybody, like, wanted to know, like, the very specifics of this stuff, he is a good resource for some of these.

Jay Feldman 1:10:47
All right, we're going to end that episode there and pick back up in part two, where we'll be discussing the factors that affect thyroid hormone production, conversion, transport and uptake, how high TSH levels can cause damage to the thyroid gland, high carb diets versus low carb diets for thyroid health, why restricting calories is not the way to go if you're struggling with hypothyroidism, the effects of PUFA and endotoxin on thyroid hormone activity and the problems with both deficiencies and excesses of iron, iodine and vitamin A for thyroid health. If you did enjoy this episode, please leave a like or comment if you're watching on YouTube and if you're listening elsewhere, please leave a review or five star rating on iTunes. All of those things really do a lot to help support the podcast and are very much appreciated. As always. Head over to Jay Feldman wellness.com/podcast to check out the show notes, where we'll link to the articles and any other references throughout today's episode, and if you're looking to reverse your hypothyroidism with clear action steps and strategies, along with personalized guidance from me, head over to Jay Feldman wellness.com/solution where you can find all the information for the energy balance Solution Program. This program includes customized health coaching, a video library that includes a video talking specifically about how you can evaluate your thyroid status using blood work and symptoms, as well as when you should supplement with thyroid hormones, how to dose them properly and how to pick the right product. The program also includes resources like a sample meal plan and supplement guide, as well as a private community so head over to Jay Feldman wellness.com/solution, to check out all the details, and I'll see you in the next episode.