Functional Medicine: Beyond Traditional Thyroid Treatment - Episode 320
22 Jan 2026 · 47 min
In this episode of the Gladden Longevity Podcast, host Dr. Jeffrey Gladden interviews functional‑medicine clinician Dr. Justin Marchegiani about a systems‑based, root‑cause approach to thyroid disorders, hormone optimization, and longevity. The conversation begins with a discussion of cholesterol as the raw material for steroid hormones and the importance of high‑quality fats. They then explore how gut dysbiosis (SIBO, fungal overgrowth, H. pylori, Candida) drives autoimmunity, especially Hashimoto’s, and why gut health is the first therapeutic target. The duo contrasts conventional endocrinology (TSH‑driven synthroid prescriptions) with functional strategies that address underlying inflammation, nutrient deficiencies, and stressors (physical, chemical, emotional, spiritual). They dive deep into insulin resistance, describing two‑hour glucose tolerance tests with concurrent insulin curves, continuous glucose monitors, and the hidden risk of hyper‑insulinemia even when fasting glucose looks normal. Genetic and epigenetic factors that modulate hormone metabolism (DIO2, estrogen hydroxylation pathways, methylation capacity) are highlighted, along with the need to measure urine estrogen metabolites rather than just serum levels. Hormone replacement philosophy is debated: they argue for physiological dosing, careful monitoring of SHBG, free testosterone, and avoidance of blanket aromatase blockade. Environmental endocrine disruptors (phthalates, glyphosate, organochlorines) and detoxification strategies (mercury clearance, sauna, charcoal) are presented as prerequisite steps before adding therapeutics. Cardiovascular risk assessment is expanded beyond LDL to include oxidized LDL, Lp‑PLA2, myeloperoxidase, fibrinogen, homocysteine, Lp‑a, and glycocalyx integrity, with discussion of PCSK9 inhibitors, nattokinase, and reverse cholesterol transport metrics. Exercise prescription is detailed: zone‑2 for beginners, zone‑3 plus high‑intensity intervals for VO₂max improvement, and the role of cardio in raising Klotho. Finally, they outline practical tools—resting metabolic rate testing, metabolic carts, DIO2 genotyping—to fine‑tune thyroid therapy, and provide contact information for Dr. Marchegiani’s practice and resources. The episode blends clinical anecdotes, specific biomarker protocols, and a holistic, systems‑thinking mindset aimed at longevity‑focused clinicians and informed patients.
Chapters
Then coming on, looking at the hormones, I think it's a big deal. We've had a low fat, low cholesterol kind of dog milk for a while. And you being a cardiologist, you probably have been preached that for a bit. But cholesterol is the raw material building block for all your hormones. Right outside of your peptide hormones, which are going to be your insulin growth hormone, most of your hormones are going to be steroid based. And that's a cholesterol backbone. And so you need that healthy cholesterol building block from healthy fats and proteins that aren't oxidized, ideally, right. Grass fed, good quality, or going to be key, but that's going to be the building block for that raw material. The gut's a major role. And I can't tell you how many patients I see that have different infections, whether it's sibo, right? Sifo, right. Small intestinal bacterial overgrowth, small intestinal fungal overgrowth, or candida overgrowth, or H. Pylori or other infections. And these kind of infections play a big role because 80% of your immune system is in the gut. And so anytime we have autoimmunity, which is like the fastest, most diagnosed, diagnosed disease really, you see, is autoimmune issues, any kind of weird new disease you see today, it's like it's a new autoimmune condition. Your body's destroying itself in another unique way. It's like, well, the gut plays a big role because 80% of all your immune cells are in the galt, in the gastric, the mucosal associated lymphoid tissue that's in the small intestine. And so we know that. And so when we deal with inflammation and autoimmunity, we have to really focus at the gut.
Welcome to the Gladden longevity podcast with Dr. Jeffrey Gladden, where our passion is helping you to become an age hacker. On this show, we want to help you optimize your life energy, longevity, health and human performance with impactful and actionable information by answering four questions. How good can we be? How do we make 100 the new 30? How do we live well beyond 120? And how do we live young for a lifetime? Now, here's today's episode of the Gladden Longevity Podcast.
Welcome everybody, to this edition of the Gladden Longevity Podcast. I'm your host, Dr. Jeffrey Gladden, and today we're going to be talking to Justin Margiani. However, the podcast, as you know, is devoted to answering five big questions. How good can you be? How do you make 100 to new 30. How do you live well beyond 120? How do we live young for a lifetime? And how do we develop a 300-year-old mind? And the conversation with Justin today, he's a chiropractor who went into functional medicine with a passion for hormone optimization. Thyroid optimization becomes an interesting conversation. You'll see his approach, and then you'll see the. Some of the additions that we. That we have in addition to some of his thought process. Kind of rounds out the podcast, but I think you'll enjoy this. It should be interesting for you to. To hear somewhat of the different and complementary approaches that we have, and, and you can decide for yourself what you think is best. Welcome, everybody, to this edition of the Gladden Longevity Podcast. I'm your host, Dr. Jeffrey Gladden, and I'm here today with Dr. Justin Marchiani. I don't think I pronounced your last name correct. Why don't you say that for us, Dr. J.
You got it. Dr. Justin Marchegiani. Marchegiani. You got it.
Marchegiani. We were close.
Very close right there.
Okay, good. Yeah. In the neighborhood, at least. So, Justin, you know, you kind of have started out in the chiropractic world and transitioned into a functional medicine kind of thought process and approach, and I think that's led you into a real fascination with hormone and thyroid and things like that. Do you want to talk us a little bit through your. Your journey of how you got to where you are?
Great question. So I have an autoimmune thyroid disease myself, Hashimoto's. And so I wrote the book, I spent the last 10 years writing a book called the Thyroid Reboot, all on kind of the root causes and in regards to Hashimoto's and thyroid dysfunction. And most people think about thyroid, they just see their conventional endo. Here you got high tsh. Here's some Synthroid. Let's bring that down. And then you're normal. But you could have a whole bunch of other symptoms. And when you understand root cause physiology, you know that you didn't fix all the other physiological imbalances in the background. You didn't fix the gut inflammation, you didn't fix nutrient deficiencies, you didn't fix any of the stress physiological hormone imbalances that wasn't touched. But conventional medicine feels really good that they did their job, which I get. You don't want overly high TSH that causes problems. And so I was on this journey of trying to help my own health issues. And before that, I worked in a surgery center where I would help position patients that had limb amputations because of chronic high blood sugar. And then the more you go down the functional medicine kind of pathways, you see how insulin resistance, high blood sugar, oxidative stress is part of kind of the root cause of most conditions, especially your background being a cardiologist. Insulin Problems Number the 1. Number 1 root cause of cardiovascular issues in that area, especially a lot of the blockages and such.
Yeah, we see that all the time in our practice because we're doing two hour glucose tolerance tests with insulin curves on everybody. And it's really dramatic when you do that to see somebody that has what looks like a normal hemoglobin, A1C and even a normal fasting insulin when they get challenged. Oh my gosh, they, you know, they either their insulin shoots way up or, and they cover the glucose or their glucose and insulin shoot way up and they're diabetic for an hour or two.
Correct.
And it's really dramatic in terms of the, the health, you know, destroying impacts of that. Right. You get increased senescent cells and destroying the glycocalyx and the arteries. And so it's, it's a, it's a big deal. It's one of these things that I call it, it's looking behind the curtain, behind the curtain. And then to your point, in traditional medicine, it's just not. People look at the, at the first, at the first curtain, they never open that. And then they never open the curtain behind that curtain to see what's really going on. So, yeah, that's kind of how we see that.
Correct. And what do we need to remove from a diet and lifestyle standpoint, what nutrients and supports can we do to accelerate it? Versus hey, what drugs can we do to downregulate, block reuptake ports, put a brake on physiology, to control symptoms versus hey, how can we upregulate and support the healing of physiology? So one's a allopathic model. Right. And the other one's a vitalistic, your body to heal kind of model.
I think you made a good point about the first thing that we see that typically needs to be done is to think about what needs to be removed. What do you take out? Right. When you're taking this functional approach, people are always wanting to know, well, what are you going to do for me? What are you going to put in? What are you, what are you going to do? Because medicine, that's usually what they do. They write a prescription and put something into the system. But many times it's about what you take out. You know, how you either improve detox capabilities, up regulate detox, genetics, you know, lots of things like this that we look at in great detail and how you get certain things out of the body before you actually start putting stuff in. And it can be done simultaneously when you see there's obvious deficiencies. But it's really important for the audience to understand that what you take out is as important as what you're putting in.
Correct. You know how I look at it and many functional medicine doctors do. I look at the underlying stressors, physical, chemical and emotional stressors that broke the person down. The problem is what broke them down in the beginning then creates imbalances in their body systems. It could be hormones, it could be gut detox, immune, it can create nutrient deficiencies, it can create inflammation systemically in the vasculature and then that creates symptoms downstream. And so it's really easy to be hyper focused on all the symptoms, the fatigue, the high cholesterol, the depression, the brain fog, but then forget to go upstream to see what symptoms or what systems are not working well. Right. We want a system based approach versus symptom based and then also go back to the underlying stressors that preceded that started the whole domino rally. And so if you look at it like that, you have a much better physiological, I should say philosophical kind of framework where you're going to catch all the root causes that started this whole domino cascade along the way here.
Yeah, I think it's another good point you're making around the stressors. And to your point, they can be physical or chemical or whatever, but many of them can be psychological and even psych, spiritual. And so in our world, the life energy circle, we have five circles over here. The life energy circle is really the one that binds all the other four together because it's, it's the most important. If people are carrying around a lot of toxic thoughts or you know, lots of psychological trauma that they're living in reaction to, it has a massive impact on their biology 100% and. Right. And understanding the genetics that actually makes somebody more susceptible to the trauma in the first place and knowing how to actually make them more resilient by augmenting genetic function, SNP function, we find that to be super helpful at help moving people, in other words, setting them up physiologically to then benefit from the psychological inputs and the spiritual, you know, revelations and things like that. It's like, it's like creating the substrate so you can actually handle the healthy things that are, that you want to do so. I mean, that's true with addiction as well, right. There are people that are genetically much more prone to alcoholism per se. Once you understand what genes they have, you can go in and actually manipulate those to where they're less prone to be addicted. Now you can actually start to work on the rehab.
Right. And so when you look at, and you manage your physical, chemical, emotional stressors, that's activating like we talked about, the epigenetics that's going to activate the genes, right? Because just because you have a certain gene for something it doesn't necessarily have to express because the epigenetics play the role on which genes flip on or off. And like we talked about, you mentioned the emotional stress side of it. It's very hard if you're in chronic pain to be emotionally present. When you're in pain, you're just so focused on the pain, it's going to be hard for you to process the different stressors. Right. Or if you don't sleep, you don't sleep last night and now you're in chronic pain, good luck trying to deal with your taxes the next day or good, good luck trying to have a, you know, difficult conversation with your wife or kids. You're just not going to be able to handle it as if you had a good night's sleep and your body feels good. And so the physio, the physiological, structural side of the fence, plus the chemical that all feeds into the emotional. And of course, if the emotional is good, right. And you're feeling good and you're loving your relationships and loving your job, that's going to allow better healthier chemistry and that's going to allow better healthier body. But they all kind of feed in and the more you, you work on that three legged stool, the better balance you have.
Yeah, that's right. For us it's, yeah, we, that's the approach we take is you can't leave any part out. And it's one of the problems with medicine in general is that it becomes too siloed. You know, I was a cardiologist. People get trained or specialized in certain things and it's, it's really does an injustice to the entire system, if you will, to just focus on one aspect of one organ system. So yeah, I think, I think we're, we're synchronized on that. Talk to me a little bit about your approach to thyroid disorders because you talked a little bit about Hashimoto's.
Yeah. So I got a book, the Thyroid Reboot. And in that book Most we talk about, you know, the root underlying factors that drive thyroid issue. And it's not just a, hey, you have this high tsh, here's some level thyroxin tintoroid. Look, it's good. Now we look at the underlying issues and most thyroid issues. There's an autoimmune component that means your immune system is attacking your thyroid gland. And then over time that can create scar tissue that can decrease the functional capacity of your thyroid gland. Uhm, that also can impact the hormones from working and binding to the receptor sites. Now conventional medicine, as you know, when it has comes to autoimmune issues, what does conventional medicine typically do? It's pretty straightforward. They're going to steroids, they're going to some kind of a biologic, whether it's like Remicade or Humira or some kind of a immunosuppressant. Right. Those are the big three. Now when it comes to thyroid autoimmunity, those side effects of those medications are kind of like maybe not appropriate for autoimmune thyroid issue. Like they would be for Crohn's or some kind of RA condition. So they do nothing. So they don't even look under that rock because they have nothing to do to it. There's not a ICD10 or CPT code they can do to get billing for us. They just leave it alone. But in the functional medicine world, there's a lot we do right. We can look at supporting healthy selenium levels, we can work out supporting healthy vitamin D and glutathione because these all produce inflammation, they help balance your T regulatory system. We can look at dealing with dysglycemia, that blood sugar rollercoaster. You said patients can be, you know, diabetic for an hour or two after each meal. I see it all the time. I have patients run what I call functional glucose tolerance. I have them give them a blood sugar meter. I have them take their blood sugar right fasting and then one hour, two hours later, they should be no higher than 120 in the first hour, back below 100 with an hour two. I can't tell you how many patients are still diabetic in two hours. They're still above 126. It's like that is not good. And what that's doing, like you talked about, right, the, the, the glycohelics and the cross linking of your proteins in your vasculature, what that's doing to the interleukins, that's driving more autoimmunity. What that's doing to your adrenals. Because your adrenals, you got this blood sugar. So your blood sugar goes up, your pancreas, beta cells make a bunch of insulin, right. The more resistant you are, the more insulin you make. That does a whole bunch of bad things to your hormones. If you're a guy, it's more aromatization. If you're a female, it's causing more testosterone. Not good either way. That's causing your blood sugar to drop. When your blood sugar drops, especially suddenly, that's called reactive hypoglycemia. That can create more cortisol, that can create more adrenaline issues and make you feel anxious and jittery. And I call it the blood sugar rollercoaster. Blood sugar up, too much process, too much inflammation. Beta cells come out, knock the blood sugar down, adrenaline, cortisol, bring it back up, and then you're in this blood sugar kind of spiral.
Yeah, no, I think that's. That's right. I would say that it's nice that you're doing the functional glucose tolerance test with the, you know, with a CGM continuous glucose monitor or whatever device you're using. I will just let you know, though, that there are people that will never spike their sugar above 120, have significant insulin issues. So when we do the insulin curve, as well as looking at the glucose, we see that people will have a high resting insulin level. Should be around 2 or 3, maybe 12 or 13. We'll see that their blood sugar may go from 90 to 118. But instead of going from 2 or 3 up to 10 to control that, or 10 or 15 to control that, they may shoot up to 60. And so that super high spike in insulin while it's controlling the blood sugar is also driving risk of cancer, it's driving aging, it's driving cell formation, it's stiffening arteries, it's doing all kinds of things behind the scenes. And that's why I say the curtain behind the curtain, behind the curtain is really interesting. And then when you look at the genetics behind that, you can say that some people just are built not to actually get the signaling when they consume glucose through the incretin system, to actually tell their, their pancreas to start making or releasing insulin. And so for those people, they're going to spike and then they're going to crash it on the back end. So there's many, many, many, many curtains to look behind to actually piece it together. Point being, once you do it, you can actually start from the genes and work forward. Now you Know, oh, well, this person will respond better if we do this and this and this. And you can kind of build it from the ground up, if you will. And that's how we think about, you know, helping people with this.
Yeah, I think fasting insulin is really important to look at. I think you can really tell a lot in that first hour after a meal because your blood sugar's got to go up that then pituitary sees that and then you got this huge beta cell production. So that first hour usually you're going to get a pretty good window. I like finger pricks because I find that the interstitial fluid assessment, which is like your CGM, like your Freestyle Libre 3 or Dexcom, that's using interstitial fluid and it tends to just give you a little bit more of a delay. It doesn't give you that fast immediate response. So it's a little bit delayed, which it's fine if you're type one or you want to do it over a long period of time just to see. I think it's good, but I think you get a faster look at it when you just do the blood by itself. Do you see, do you see that blood sugar go up though, in that first hour or so? And then you see the big insulin?
Not necessarily what we, we see it, we see all kinds of combinations. So for example, we'll see somebody where their blood sugar doesn't go up at all and yet their insulin will go up dramatically. So they control the blood sugar extremely well. That's not the issue.
So you'd see it on a fasting insulin, though. You probably see it there on insulin.
Nope, the fasting insulin is not enough.
So how are you picking up?
Well, you do a two hour glucose tolerance test with an insulin curve. So you measure glucose and insulin, 75 grams of glucose. Measure it again both at an hour and both again two hours. Now you actually can see what's, what's actually happening in both, both with the insulin and the glucose. And we find that that gives us tremendous insight. You know, you take somebody with cancer because, you know, insulin is a driver of malignancy. And so you can see who's susceptible to more insulin release. You also get an idea of just how much insulin resistance they have. So it's, it's, it's really been phenomenal. We just saw a gentleman this morning and, you know, typical story, you know, fasting blood sugar was normal. Fasting insulin was elevated at about 14. His blood sugar went up to 185. And his fasting or his one hour insulin went up to I think over 70. And then at two hours his fasting insulin was even higher. It was like 80 or 90 and his blood sugar was coming back down. So you see all kinds of permutations to let you know kind of the extent of the insulin resistance. And we find that super helpful.
I think it's good. There's a lot of ways to do it. So when I do it, I just do patients meals and so that way we can test their meals and see how it does throughout the weeks. I've had a patient last week where they were coming in in that first hour at 180 and within hour two they were at 140, still incredibly elevated. Just a little tweak of the diet and we had them, you know, below that 120 in the first hour and back below 100. So I like that because I'll have patients test three different random meals. The functional, the glucose tolerance you're talking about is nice. You have a lab and you can do that. My only concern is, you know, some people, even if they're healthy, that's 75 grams of sugar, they may still not be able to handle it. Even if they're, even if they're on point, just because that's such a stress to their body. That may be too much for most people. But I think either way, blood sugar is such an important thing to look at and the more tools or windows you can use is vital.
Yeah, no, I think that's right. I think you wanna, you wanna understand as best you can. And then we, we are big users of CGMs. Just because people don't like to prick their fingers that much and you can continuously see what's happening, it's still a good tool. We find them very useful. One of the things that I wish they would create though, and I've talked to several manufacturers, is actually an insulin sensor.
It's saying it for a decade. I'm like, once we get insulin on there, we're considering be amazing. Even if like, you know, I got the keto mojo. It's got a strip for ketones, it's got a strip for insulin. Just give me a strip for insulin, man. And I'm like, I am tickle pink.
Exactly. Yeah, it's really, it's kind of a deficit. I think in the field that we don't have the ability to have a sensor for insulin, that we have to, you know, go through a laboratory test to get it.
But it's gotta be coming. Like if I were to do a startup right now, I'd be like, let's find a way to do insulin with that. That'd be amazing. It's gotta be being researched now. But I agree. And again, insulin's a big deal, especially for guys listening, right? That's gonna upregulate aromatase, that's gonna cause more of your t. Testosterone to go to estrogen. And for women listening, right, that upregulates the 1720 LIAS enzyme, which causes more of your female hormones to go to androgens, which, which is the root cause of infertility in most women, right? You have this elevation of prolactin, high amounts of androgens, that causes ovarian cyst, right? That's why the major medication for treating pcos, right, is what. It's glucophage metformin. It's an insulin sensitizing compound. So insulin impacts both sexes equally, but in different ways.
Yeah, yeah, no, I think that's, that's a really good point that you make. And I would just point out to men that what we find is that genetically, again, people have different predispositions, whether they're male, male or female, to aromatize testosterone and estrogen. So there are some women that are fairly low aromatizers, generally speaking, and some men that are very high aromatizers. And it's important to understand, you know, where you fall and then to measure the actual levels. Because what we find as well is that the concept of replacing testosterone or boosting testosterone and trying to block estrogen production is really, it's really foolhardy in our case, because men need estrogen just as much as women need estrogen. Especially if you have APOE4 genes and you have a predisposition for Alzheimer's, estrogen is godsend to your brain. And so actually bone density is more related to estrogen than it is to testosterone. So you really. Men need estrogen. It's just that we need it in a different balance. And so the idea of crushing estrogen production is really, I think, kind of a fool's errand. But.
Well, you see lots of, yeah, you see lots of doctors, you know, prescribing HRT for men, I think, way too willy nilly. Number one, they, when they prescribe it, they prescribe way outside of the physiological norms. Your typical guy makes about 6 to 8 milligrams per day and the average doctor starting at 150 milligrams per week. And they don't, they don't even dose it. Physiologically appropriate I say the more you can dose it daily if you have to. First off, guy in your 20s, 30s, 40s, even 50s, if you're doing the right thing, you should be able to get the aromatization in check, get your diet in check, and you shouldn't have to need testosterone. Let's say, for instance, you're doing all the right things, all the principles, all the herbs, all the nutrients and you need it, fine, but it should come later into the game and it should be used within that physiological norm. Start low, the lowest possible, right, maybe 4 or 6 milligrams per day. Try to do it every day or every other day at the lowest level. And ideally, if you're having a compound Arimidex and use estrogen blockers, you're not doing it right, you're lazy. You need to do with the right physiological levels. As you know, the major reason why most bodybuilders have heart issues, it's not necessarily because of too much testosterone. It's because they're taking estrogen blockers that destroy their heart. Right? You, like you mentioned earlier, estrogen is very cardio protective on the heart. And if you lower estrogen too much with drugs like Arimidex or uhm, which what you see, I see a lot of doctors prescribing testosterone with Arimidex or estrogen blockers in the compounds and that can cause a lot of cardiovascular problems. And again, we're not talking dim or you know, glutathione or sulfur that naturally helps clear it out. We're talking about, you know, blocking drugs, if you will. Comments on that, what do you think? Yeah, so what?
Just for the audience to understand what we're talking about here, it's important to realize that testosterone is turned into estrogen both for men and women, and then the body ends up detoxing the estrogen through three different pathways. They're called hydroxylation pathways. So there's a 16, a 4 and a 2 hydroxy pathway. And the 2 hydroxy is really the safe pathway. And then you need to be able to methylate that hydroxy compound for the second stage of detox. And some people are poor methylators. So we go in and genetically look at that and then see how well they're able to methylate. And there are many things we can do to boost methylation capacity. So that being said, we want to decrease the 4 hydroxy which is the most toxic for both men and women. It increases breast cancer risk, prostate cancer risk, et cetera. And then the 16 hydrostic is good, but not quite as bad as the 4. So the dim comment is that we can push those metabolites of estrogen, estrogen through estrogen and then down through the two hydroxy pathway preferentially. So that's important. And these drugs, the Arimidex is referring to, blocks the enzyme that takes testosterone and turns it into estrogen in the first place. So when you're thinking about hormone optimization, it's so important not to simply measure blood levels. It's so important actually measure the urine metabolites in our world to actually understand how is somebody metabolizing these things, because it's different. And it's genetically driven in part, but it's also driven by what people are eating or what they're taking or how much stress they're under and things like that. So you can't just look at the genetics and get it right either. It can give you an idea where you might have a leverage point. But you've got to measure those urine metabolites to know what you're dealing with, to keep somebody safe. That's the way we think about it.
Yeah, I'll use some of the precision analytics testing a lot to look at testosterone, the estrogen, the 2, 4, the 16, the 2 methoxy, 2 hydroxy pathways. That's important. And as I was talking about earlier, a lot of doctors use estrogen blocking medication because they give way too high of hormonal dose for someone. And it's just they're lazy, they don't want to adjust the dose, they want to give it weekly, they want maximal compliance, they don't want to have to worry about fine tuning. And in functional medicine world, hormones, they're measured in picograms and nanograms. That's right to the, you know, to the 9th degree or to the 12th degree. So these are very potent things. And so I try not to use hormones unless someone absolutely needs them or we're using precursor hormone support. And so for instance, guys are given testosterone way too early. And also testosterone can thicken the blood, as you know, can increase your platelets, make your cells more sticky. And then of course, we have to be using physiological norms. And so if I give testosterone to recommend it, we're giving it to guys that are older, that have already maxed out everything regarding sleep, movement, exercise, nutrient deficiencies, zinc, selenium, you know, some of the herbs that have a really good impact on LH and fsh. And then if we have to, then we can recommend that. But I'd say 95% of guys that Come to me that have some of these issues, whether it's muscle, libido, mood, we're able to avoid having to go that bioidentical T route. And if we have to, there's microdosing strategies that work far better and keep you within the physiological range in that top 25% or so.
Yeah, I think that's a good point. You know, the other thing for people to realize as they listen to this is that everyone's aware that women go through menopause, which essentially means that the lifecycle of the ovary for releasing eggs on a monthly basis has diminished. And the Leydig cells inside the testicles that make testosterone also have a shortened life expectancy compared to your own life expectancy.
Correct.
If you, if you live long enough, odds are that the Leydig cells will eventually poop out. And so you may end up needing testosterone. But there are many, many things that can be done for a woman in her 30s who's experiencing, you know, not even pre menopause, but sort of pre, pre menopausal kind of changes and symptoms to kind of optimize the biology. And the same is true for men that are experiencing, you know, low T symptoms in their 30s. And one of the things we find is that there are a lot of environmental bioregulators that get in the way.
Oh yeah.
A lot of plastic and things like this. So we're testing for all of that in our people as well to see what are they, what, what are they exposed to, what, you know, what do we need to detox. Not only get the detox system to work, but what do we need to sort of get out of their environment or out of, you know, the soap they're using or the plastic bottles they're drinking from or whatever they're doing. Right. So it's a, it's a complex arena here and there's so many endocrine disruptors or hormone disruptors in these chemicals that we're exposed to every day that a lot of the problems for a 35 year old can be both stress related as well as environmentally related. It's kind of how we think about it.
Yeah, I agree. And I'm seeing lots of guys come in to me in their 20s and 30s and they're being recommended testosterone, which I think is a, it's crazy. It's a miscarriage. Number one, two, these guys potentially could be infertile because as you increase testosterone, you're going to take the fsh, which talks to the Sertoli cells that make Sperm and then your cells, the leydig is the lh ones that make testosterone. And do you silence that? That's why guys, notoriously, you know, get atrophy of their testicles because of testosterone. And so that happens too long. You may not be able to reestablish that feedback loop and you're gonna have low sperm and you may be infertile. And so most people aren't thinking about that. And so from a functional medicine standpoint, how you treat a 60 year old is gonna be different than how you treat a 20 or 30 year old. And so I just want want the guys to know that. And with my females too, of course, you know, there's different guys kind of have this andropause that's kind of more slower and steady, as you mentioned, doc, regarding the Sertoli cells or the cells of Laydig kind of pooping out a little bit, a little bit more slow and gradual where women are a little bit more punctuated in that late, late 40s, early 50s with their follicular reserve kind of going dry, if you will. And so there may be a greater need for a female hormone intervention on the hormone side. So we like to treat, you know, the sexes and, you know, a little bit differently in that because how their physiology works. We gotta meet them where their physiology is.
100%. Yeah, 100%. It's just that a lot of men are aware of the fact that women go through menopause, but they're not aware that they also are on a timeline and that they will go through andropause at some point.
Correct.
So that being said, we have people, clients in their 70s, who still have, you know, quite healthy testosterone and free testosterone levels. Right. That's another thing that's not looked at is sex hormone binding globulin and free testosterone. Because it's not the, it's not the testosterone number that really matters, it's what's the free testosterone. Right. That's really what's doing the work. Yeah. So again, it's a sophisticated. It's not just walk into a T clinic, oh, your tea is low. We'll give you tea and give you an aromatase inhibitor. I think that is such a disservice to not only the person, but really to humanity on some level because of the sperm counts and the other things you're mentioning.
And it's not uncommon for me to be able to help the men that come and see me and double their testosterone. Double it. Because the first thing is we have to look at all of the xenoestrogens in our environment have to be removed. So whether it's the phthalates in your soaps or in your dishwashing detergents or the little tree car freshener or the Glade plug in, those are all a soup of estrogen. All right? And estrogens. And also the organochlorine pesticides, the glyphosate. When you have estrogens or xenoestrogen compounds, that comes into your system and that shuts down lh, that shuts down luteinizing hormone. So the feedback loop from the pituitary that tells the cells of Leydig to make testosterone drop. So the first thing you have to do is get rid of the chemicals in the environment that's screwing up that feedback loop. That's number one. Even if you're going to use testosterone or herbs or whatever, or nutrients, you have to reestablish healthy feedback loop. And the first thing is get the environmental toxins down.
That's right. Again, it's back to what we said at the beginning. One of the earliest comments you made was beginning by looking at what it is that needs to be taken out. Right, Right. Yeah, it's really key. You can't. In other words, you can put in all day long, but if you're not taking out the stuff that needs to come out, you're kind of, you know, trying to breach a wall that's unbreachable.
So, yeah, when people tell me, they're like, well, what should I do for detoxification? Well, the first thing is let's just work on removing stuff, like, from our environment. Just that.
That's right.
Because it's so much easier to detoxify once you've pulled out all the crud. Now, your system can work so much better once the, you know, junkie food's out.
That's right. And to your point about that is that if you're. If you're still being exposed to all those toxins, even though you're on a good detox protocol. Right. It's coming in as fast as you're getting it out.
Yeah, exactly.
We see that with mercury all the time. You can actually look at the rate of mercury clearance through a quicksilver test, and you can see whether or not people are actually getting rid of it faster than they're accumulating it, or vice versa. So we've been able to detox people of mercury without having to go to chelation, But a lot of it involves getting the mercury out of their System, whether it's the fish they're eating or the coal plant that's up the road or whatever it else where it's coming from, getting the air purifiers in. And then when they get in the sauna and you give them the charcoal and you give them the metal free and the other things that help them pull it out through the gut as well as the skin, we see mercury levels go back down to normal very quickly. So it's pretty cool.
Yeah, yeah, absolutely. And then coming on, looking at the hormones, I think it's a big deal. We've had, you know, a low fat, low cholesterol kind of dogma for a while. And you being a cardiologist, you probably have been preached that for a bit. But cholesterol is the raw material building block for all your hormones. Right. Outside of your peptide hormones which are going to be your insulin growth hormone, most of your hormones are going to be steroid based and that's a cholesterol backbone. And so you need that healthy cholesterol building block from, from healthy fats and proteins that aren't oxidized ideally. Right. Grass fed, good quality. So they be key. But that's going to be the building block for that raw material.
Yep. No, that's, that's right. I think, you know, there we went through a phase where we demonized cholesterol, we all know this. And then we went to the low fat, low everything and we robbed ourselves of a lot of things. Also, you know, the C15 molecule which shows up in fat, dairy and things like that.
Right.
People were losing a great deal of that and turns out that C15 tends to be associated with longevity. So there's beyond that. Cholesterol, as you point out, is needed for lots of steroid based hormone synthesis. And so you don't want your cholesterol to be too low. In fact, if you look at population data, people that have cholesterols, total cholesterols below about 220 actually have a higher mortality relative to people that have a cholesterol of around 220 or 240. And obviously if it's too high and it can be that increases mortality as well. But this is where for us in the cardiology world it really boils down to focusing on the glycocalyx and the nitric oxide system to be able to keep an artery healthy and then decreasing insulin resistance, high blood sugar spikes like ocalyx, things like that. So all that becomes super helpful as well.
Yeah, no, I think that's really important. And when we look at things like statins, for instance. Right. A statin is an HMG CoA reductase inhibitor. Right. When you look at most medications, they just inhibit. It's a PPI proton pump inhibitor, an ACE inhibitor, angio retention receptor site blocker. Right. You know, all these medications, right. They just inhibit, inhibit, inhibit. But when you look at that, one of the. What's the major thing that stimulates that HMG CoA reductase enzyme, the major compound, the major hormone that stimulates its insulin. Right. Because we know most cholesterol is made by the body and your body can overproduce it if you're in a insulin resistant state. And if you're overly inflamed, cholesterol can go up. And so I'd be curious to know your kind of ranges. I don't typically worry too much about cholesterol until it starts going into the three hundreds. But if I start to, if I'm really trying to rule out risk factors, we're going to look at things like oxidized ldl, small dense ldl, make sure that cholesterol is not oxidizing. We're going to look at clotting factors because we know most cardiovascular incidents. Right. Most mis. It's not necessarily a blockage, it's a clot being thrown. 60% of clots being thrown. So we'll look at D dimer fibrinogen, we'll look at homocysteine. We'll at look, we'll look at fasting insulin. We'll look at LP, PLA2, which is an inflammation marker in the blood vessels. And I'll, I'll do that to kind of weigh, kind of, you know, the balance of where these lipids are at. And also just making sure that trig to HDL ratio, ideally as close to 1 as possible for healthy.
Yeah, good. So we, we do that. We take probably a little bit different approach in that we're looking at markers of inflammation.
Yep.
Including LPPLA2, but myeloperoxidase as well. We're also looking at oxidized LDL, F2X, prostane, ADMA, SDMA, because. And also microalbumin, creatinine. This is a really sensitive marker for vascular inflammation. So you put those together, it turns out that inflammation is what drives events. And then we look at genetics around clotting because some certain people are more predisposed to clotting. And when they are, we'll put them on things like nattokinase.
Yeah.
Actually helps in the blood, Right. And so. And then LP is very important. So we look at that because that's a big driver of cardiac events. And the problem with LP is that when it's elevated and it's genetically determined, it decreases your ability to dissolve a clot that might form in your blood. So let's say you're having a heart attack, and normally your body would try to dissolve that clot. If you've got LP around, it blocks your ability to dissolve that, so you end up having a bigger heart attack. And it also potentiates plaque formation in the first place. So we're looking at lp.
What supplements are you using to help bring down the lp?
There isn't any that actually work. So we go to the PCSK9 inhibitors. That seems to bring it down. And then we're also looking at, you know, there's lots of talk about niacin, but quite honestly, it's never really proven to be that effective. So then the other thing we look at is the APO A family, which is all the good guys, and the APO B family, which is all the bad guys. We look at small, dense ldl, as you mentioned. But the thing that's more important than almost anything except lp, and what we've talked about is what's the ability for reverse cholesterol transport? Because if you can actually get cholesterol out of a plaque or out of a cell membrane back to the liver, you're actually much more protected than if you don't have the ability to do reverse cholesterol transport. And that becomes a function of plasmalogen levels, it becomes a function of phosphatidylcholine levels. And so we're measuring all these, and we help people augment their ability to do reverse cholesterol transport. Because if you have a healthy glycocalyx and you have good reverse cholesterol transport, you can have a cholesterol of 240 and you're okay. But if you don't have good reverse cholesterol transport, and a high HDL is not indicative of reverse cholesterol transport because a lot of that HDL is dysfunctional. So you've got to actually have a metric to look at reverse cholesterol transport. So in a Cleveland Heart Lab study that we do profile, it does give us at least an algorithm to look at reverse cholesterol transport. So we look at all of that, and then we actually have a glycocheck scope where we can actually, under the tongue, we can look at the microcirculation and actually measure the thickness of the glycocalyx and where it's. Where it's failing or where it's not. So it's. We have a, we have many, many lenses to look at the cardiovascular system.
And what mark are you looking at to look at hdl? Because, I mean, HDL is the bus that brings the cholesterol back from the artery back to the liver to recycle. And ldl, the reverse. What's the, what's the marker?
Well, the HDL is, is part of the Apaway family. And as I mentioned, HDL can be dysfunctional. So just because you have an HDL 70 or 90 doesn't mean it's actually doing the job.
Is that based on oxidation? What's the marker to look at dysfunctional? This.
There's, there's an algorithm that looks at subtypes of HDL to basically calculate what the actual capacity is for reverse cholesterol transport. It's available on equ. Hard lab profile.
Yep.
Okay.
I mean, the good old fashioned way to bump up HDL and make it more functional is what it's going to be, really. Just trying to choose healthy fats and proteins that aren't oxidized. Correct.
And cardio. Cardio.
Oh, yeah. And yes. Yes. Any particular type? Are you more interval Zone two. A combination of the two.
Yeah. This is interesting too. So we measure cardiopulmonary exercise tests on every. Every client. So we actually measure VO2max and anaerobic threshold. And you're probably aware that VO2max for longevity is one of the strongest indicators for longevity. Right. Even stronger than muscle mass by a factor of two and a half. So how do you train for VO2 max? Well, there's a lot of misinformation out there around zone two. We find zone two is. I've been doing it for over 20 years now, measuring cardiopulmonary exercise tests and training people for VO2 max optimization. And what we found is that zone two is good in a couple situations. Zone two, you can, if you're listening to this, zone two is essentially a form of exercise where you can carry on a conversation. Right. So you're walking, you know, you're. You're lightly doing.
You're at that threshold right at that top end. That's that.
Yeah, that's zone two. And if you are over training, zone two is great. If you are just coming off the couch, zone two is great. But if you're actually reasonably athletic, to build VO2, what we found is you need zone three. And you need zone three three days a week for about 45 minutes. And then you need interval training where you're at zone five, which is all in, so to speak. For about interval training, it would be like one minute intervals or 90 second intervals or maybe even 30 second intervals. Maybe six to eight of those within a 20 minute period where you're kind of going all in. Then you have a 90 to 122nd recovery. So you do that twice a week, and you do the zone three three days a week. And we see, we routinely always see VO2 go up, but people will tell us that, oh, I'm doing orange theory now, and I'm getting plenty of cardio. My trainer says we're getting plenty of cardio. I do some cardio before I lift my weights, and then I'm doing circuit training. My heart rate's always elevated. It's like, great, let's. Let's measure your VO2. It always goes down. Always. I've never seen it go up. And it's not that I didn't want it to go up. It's just went down. It's like, well, okay, well, then we need to come up with a strategy that actually works. And cardio will raise not only hdl, but it also raises Clotho. And Clotho is God's gift to your kidneys, your heart, your brain from a stand, and longevity. So lifting weights lowers Clotho and, and cardio raises Clotho. So really, there's so many benefits to cardio when it comes to cardiovascular health and longevity. Makes sense.
Absolutely.
Yeah. Yeah. So what other things, what other things would you like to, to chat about?
Yeah, So I would say when we look at thyroid, we want to get to the root underlying issue of that, because we don't just want to rely tsa, rely on TSH as our underlying metric of thyroid health. I think it's important that we dial TSH in if we're overly high because that's your. A sign that your pituitary is freaking out. And we want a little bit more thyroid hormone most of the time, but we have to support the underlying factor. The gut's a major role. And I can't tell you how many patients I see that have different infections, whether it's sibo. Right. Sifo. Right. Small intestinal bacterial overgrowth, small intestinal fungal overgrowth, or candida overgrowth, or H. Pylori or other infections. And these kind of infections play a big role because 80% of your immune system is in the gut. And so anytime we have Autoimmunity, which is like the fastest, most diagnosed, diagnosed disease really, you see, is autoimmune issues. Any kind of weird new disease you see today, it's like it's a new autoimmune condition. Your body's destroying itself in another unique way. It's like, well, the gut plays a big role because 80% of all your immune cells are in the galt, in the gastric, the mucosal associated lymphoid tissue that's in the small intestine. And so we know that. And so when we deal with inflammation and autoimmunity, we have to really focus at the gut.
100%. 100%. I think that is the key place to start. Yeah. And so cleaning up the gut becomes really, really important. First you got to kill bad guys, then you got to rebuild the mucosa. Then you've got to basically keep people from destroying it. And so there's a lot that goes into that. Getting digestive enzymes. Right. Getting the food sensitivities. Right. And then we use peptides to help with that as well. Oral bpc.
Yep.
Kpv. Those are very helpful at rebuilding the gut. But I agree with you that a lot of autoimmunity occurs there. And that can, you know, show up as Hashimoto's and other forms of autoimmunity with dysregulation of Treg cells, et cetera, et cetera. One of the things that we do for thyroid is we do resting metabolic rates on everyone. And we've been stunned that blood work is useful, but really not accurate. For example, we see many people with normal TSHs, or even what most people would consider a good TSH, and they're still hypothyroid or they're hyperthyroid and they don't know it. And so we find that a resting metabolic rate is really, for us, the gold standard when it comes to dialing in thyroid. We've had many people come to us that are on thyroid and they just don't feel right. And the first thing we do is we do the blood work, of course, very comprehensive blood work, but we also do the rest of the metabolic rate, and all of a sudden, it's sitting right there in front of us.
How's that being tested?
With a metabolic cart. So it's the same way that.
Like a VO2 max.
Like a VO2 max. Just sitting in a chair. Yep. The other thing that's missed commonly is we're doing genetics on a DIO2 gene, which is basically the ability to convert inactive to active thyroid T4 to T3 in the brain specifically. So you can even have a normal resting metabolic rate. You can have normal systemic thyroid levels. T3, T4 free T3 free T4, TSH, reverse T3, all of those can be normal. And yet somebody can still not have adequate thyroid activity in the brain. And we've had cases where we've added a small amount of T3 only Cytomel and people brains come back on online. So it's really, really, it's a nuanced art I think to really dial in thyroid for an individual. And for us it really requires the DIO2 gene measurement as well as a resting metabolic rate.
Yeah, no, that makes sense.
Yeah. Good stuff. So it sounds like, it sounds like you've got a robust practice down there in Austin helping people. How do people get a hold of you if they'd like to make contact?
Yeah, my website is justinhealth.com I'm Dr. Justin so J-U-T-I-N H-E-A-L-T-H.com there's a.
Work.
With Dr. Jay button. I see patients all over the world so patients want to reach out and schedule. Also I got a book called the Thyroid Reboot. It was number one on Amazon for preventative medicine. Talk all about this and we kind of connect the dots and, and that's a great kind of opportunity to reach out, get more information. It's also podcast and YouTube channel. I got almost a hundred thousand subscribers on YouTube and doing this for 15 plus years. So I've been at it for a while and so just trying to provide lots of great information to the general public to help them kind of take control of their health more.
Yeah, no, it sounds great. Sounds great.
Well, I appreciate the podcast and nice chatting with you Dr. Jeff. It was nice.
Yeah, appreciate that. Okay, thanks.
Well, nice to meet you.
Thank you for listening to this week's episode of the Gladden Longevity Podcast. If you would like more information on what we've discussed or other topics, please reference the show notes or go to gladdenlongevitypodcast.com youm can also find us on Instagram, Facebook and Twitter by searching Gladden Longevity. If you've enjoyed this podcast, please subscribe to get future episodes delivered to you and share our podcast or this episode with someone in your life. Lengthy may find benefit. Thank you for listening. We'll be back next week with another exciting episode. The Glide and Longevity podcast is provided for informational purposes only. It does not constitute medical advice. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding your medical condition. The use of any information and materials linked to this podcast is at the listener's own risk.
More from Dr.


Dr. Jeffrey Gladden's Daily Longevity Routine: How He Trains for Strength, Mobility, and Energy - Episode 356









