Eric Balcavage 0:00
Hey, everybody, it's Dr Eric Balcavage. We're back for another edition of Thyroid Answers Shorts, and this episode is called The Thyroid - GLP-1 Trap, and I want to talk today about why optimizing your thyroid physiology and taking a GLP-1 can be a trap that actually sabotages your health and your well being. So here's a scenario I'm seeing more and more, and you've been told, maybe you've been told your thyroid is optimized. You've been put on T4 and or T3 medication, and whatever lab value your doctor cares about is now been optimized.
Eric Balcavage 0:52
But you're still struggling with weight issues, your fatigue issues, your blood sugar issues, and your doctor says, you know what, we've optimized your thyroid physiology. Now we think it's time for you to take a GLP-1 drug, and if we give you the GLP-1 drug, this should help you regulate your blood sugar and lose weight. And maybe for some of you, this sounds familiar. Maybe for some of you, you're already working through this process. And I think it's a challenge. I think it's a problem. And these, GLP-1 drugs are all the craze now, even those people, some of the people in functional and integrated medicine, are pushing these really heavily. So I want to dig into what this is all about, why this could really become a more significant issue. So let's get started with some content on some of the basics, what GLP-1 is, and how it could potentially have an impact on your physiology.
Eric Balcavage 1:58
So GLP one is glucagon, like peptide one, and is it's a hormone that's made by the L cells in your intestines, in the upper part of your colon. And what it does is, within minutes of eating your intestinal L cells release GLP-1. And what GLP-1 does is it goes to your pancreas and it stimulates the release of insulin that's already pre formed in the pancreas, so that as soon as the glucose starts coming into the blood, into the bloodstream from the GI tract, the GLP-1 stimulates the pancreas to release insulin, to push it into the cells and tissues.
Eric Balcavage 2:41
The other thing that GLP-1 does at the pancreas is it actually reduces the pancreatic production and release of glucagon. Now, why is that important? It's important because when you eat, your body is bringing glucose in. When you're in a fasted state, your liver primarily is generating glucose for you. So you can regulate your glucose levels in the blood on a continual basis, even in a fasted state. So, this is what GLP one does, is it helps you release insulin and reduce the production of liver glucose into the bloodstream. Those are the primary functions we'll get into more here in a second.
Eric Balcavage 3:31
The other thing that's really important is that GLP-1 production is intimately connected to thyroid hormone function.Those L cells in your GI tract that make GLP-1 , they are metabolically active powerhouses that depend heavily on T3 inside the cells for optimal function. So if you don't have optimal T3 levels, not just in the blood, but actually in the intestinal L cells, it's going to have an impact on GLP-1 function.
Eric Balcavage 4:06
So in a healthy person with good thyroid function, how does T3 support GLP-1 production? Someone in true homeostasis, not just optimized labs, but genuine cellular balance, low stress state, homeostatic regulation. I talk about this all the time, that most people who have thyroid issues aren't in homeostasis, they're in allostasis, which is an adaptive response.
Eric Balcavage 4:52
But here we're talking about somebody who's in homeostasis, they would have appropriate levels of T4 and T3 in the blood. They'd have appropriate levels of T3 in their intestines and in the intestinal L cell. That T3 enhances GLP-1 production in several key ways. First, T3 boost mitochondrial function in the L cells. More mitochondrial energy means better GLP-1 synthesis and secretion after meals. Second, T3 supports healthy gut motility. That way the gut moves food through the GI tract, not too fast, not too slow, which ensures that nutrients reach the distal ileum, where most L cells live, giving them the signals they need to produce appropriate GLP-1.
Eric Balcavage 5:50
T3 enhances nutrient absorption and the expression of the receptors for these intestinal L cells that respond to fats, amino acids and short chain fatty acids. All these triggers for GLP-1 release. So the GLP-1 cells have to have appropriate receptor function, and T3 helps support it.
Eric Balcavage 6:15
And finally, T3 supports vagal tone. So your vagus nerve is this big nerve as part of your parasympathetic nervous system that drives the function and physiology of the gut. So T3 supports vagal tone and the gut brain connection, amplifying GLP-1's effectiveness throughout the body.
Eric Balcavage 6:33
Now it's important to know and keep in mind that you make GLP-1 when you're in homeostasis. So if somebody's telling you that you need GLP-1, what does that tell us? That you probably aren't in homeostasis. You're in allostasis, not homeostasis, which means that your body's adaptively down regulating, GLP-1 production and function.
Eric Balcavage 6:58
Now let's talk about what happens in thyroid allostasis, this is the adaptive state where the body reduces T4 to T3 conversion has a protective mechanism. This is where things get interesting, because in allostasis, which is the body's protective response to some type of cellular stress, threat, reduced energy level, a bacterial infection, viral infection, toxicity, whatever the excessive stress is. That stress is excessive, the body senses danger, and it shifts into this adaptive state. We call this excessive cell stress, the cell danger response. And part of that cell danger response is the adaptive down regulation of T4 to T3 and to some level, as this cell stress response becomes chronic, it triggers immune activation and even the thyroiditis.
Eric Balcavage 7:48
Now it's important to keep in mind that this is not broken physiology. Many people will tell your your thyroid gland forgot how to work, or you forgot how to convert t4 to t3 that's that's not true. This is an adaptive response. The body is saying we need to slow the metabolism down to deal with the threat and then start the repair process. But once we enter the cell danger response and this thyroid allostasis, it creates a cascade of effects on your GLP-1.
Eric Balcavage 8:23
The L cells will start to have reduced levels of local T3 inside them. Because of this decreased conversion of T4 to T3what happens is their mitochondrial output drops. They make less energy. They have less mitochondria, and with less energy, they can't produce GLP-1 efficiently, even with appropriate nutrition coming into the system, because of the lower state of T3.
Eric Balcavage 8:54
Gut motility slows so the nutrients don't reach the L cells effectively to stimulate GLP-1.
Eric Balcavage 9:03
Nutrient sensing becomes sluggish, and the L cells become less responsive to normal meal cues, the vagal tone drops, disrupting the gut brain signaling that normally coordinates GLP-1 release. The result, impaired GLP-1 production, even though the person is eating well and trying to do everything right.
Eric Balcavage 9:29
Many of you are in that situation where I'm eating right, I'm doing the right things, I'm exercising, I'm doing all this stuff right. Why can't I lose weight? Why is my metabolism slow? It's because your body's operating in this cell danger physiology, this Allostatic regulation, and people say, but I've optimized my T4 or I've optimized my TSH, or I've optimized my T3. It won't matter if you optimize the blood levels, because at the tissue level, where it really matters, you're not going to utilize that thyroid hormone the way you want it to so this is where it gets really problematic.
Eric Balcavage 10:08
What happens when we give thyroid medication to somebody to optimize their labs when they're in an Allostatic state?This is a trap that so many people fall into when you give T4 medication during thyroid allostasis, you might improve TSH. You might improve T4 levels, at least on paper. But the body often continues shunting T4 into reverse T3 to maintain the protective low T3 state. So you get misleading lab improvement while the L cells in your intestines are still low in T3.
Eric Balcavage 10:50
GLP production remains impaired, but now you've also suppressed the body's natural thyroid regulation, because when you add more T4 in this situation, the body doesn't make more T3. Instead, it deactivates the T4 to T3 you actually worsen the cellular T3 state many times by adding more and more T4 to a system that didn't want it or need it.
Eric Balcavage 11:18
Some people would say, well, since T3 does all the work. Why shouldn't we just give T3? Shouldn't that fix it? T3 does get into the cells easier, but the T3 medication can be even more problematic if you're in an Allostatic state, because you're forcing metabolism in tissues that are trying to down regulate their physiology for protection. This can increase oxidative stress in those vulnerable L cells, potentially making them even more dysfunctional. You create what I call a metabolic mismatch, pushing energy production in a system that's still in defense mode. You actually create more damage to the cells, and you can actually worsen the GLP-1 production.
Eric Balcavage 12:10
And then many of these same people, because they've been "optimized" with thyroid hormone, and they're still struggling with metabolism issues, they're still struggling with blood sugar issues, they're still stuck struggling with weight issues, get prescribed a GLP-1 medication. But that can compound the problem. It can almost become like the perfect storm for more significant dysfunction. If you have someone in thyroid allostasis, their gut is already sluggish, their GLP-1 production is impaired, and now you add exogenous GLP-1 medication that further slows their gastric emptying and intestinal transit time. Now this the combination of the reduced T3 in the cells, which slows everything down, and the GLP-1 medication that slows it down, the combination of these things can lead to severe constipation, even functional ileus, which is where the bowel essentially can become more paralyzed.
Eric Balcavage 13:24
And here's the issue, the GLP-1 medications reduce glucose intake by slowing digestion and reduce the glucose production by suppressing glucagon. In someone with thyroid allostasis, who already has impaired fat oxidation and ketone production, where are they getting glucose from?
Eric Balcavage 13:52
Right? Because if I'm in a fasted state, my liver should be pumping out glucose. In a fed state, I turn off the liver because I'm getting most of the glucose from the GI tract. But if I have decreased T4 to T3 conversion. I'm probably going to have decreased absorption of glucose potentially to begin with because of decreased GLP-1. That's going to decrease glucose coming into the bloodstream. And I've also taken this exogenous GLP-1 that's going to turn off the liver. So where's the glucose coming from? How am I getting glucose to run the system? I can't rely on the ketones and and fats for energy, because if I'm in a thyroid Allostatic state, the fat oxidation and ketone production are going to be decreased anyway. So how am I getting energy?
Eric Balcavage 14:49
The body becomes metabolically trapped. Essentially, it can't efficiently use dietary glucose because digestion is too slow and absorption is reduced. It can't make glucose from the liver because glucagon is suppressed, and it can't switch to burning fat or making ketones because thyroid allostasis has impaired those pathways. So the body turns to muscle catabolism, breaking down precious lean tissue to make amino acids that can be converted into glucose. It also results in up-regulation of the Cori cycle, where muscles perform inefficient anaerobic metabolism, producing lactate that the liver has to convert back into glucose at a huge energy cost, and this is in somebody who's already not making energy efficiently. So this can easily wind up causing lots of fatigue. You end up with muscle wasting, metabolic insufficiency and worsening fatigue, all while, somebody might say your labs have been optimized. This sounds like a recipe for making people worse, not better.
Eric Balcavage 16:03
So what should people be looking for that they have a problem here if they're taking both thyroid medication and they're taking the GLP-1 drug? Some of the warning signs include severe constipation or bloating after starting the GLP-1 medications, weight loss, but worsening body composition. You're losing more muscle than you are fat. Increasing fatigue, despite better looking thyroid labs, weakness, poor exercise recovery and persistent hypoglycemic symptoms despite eating. So you're getting more of those kind of hangry symptoms.
Eric Balcavage 16:46
The key insight is that we need to address the root cause driving the cell danger response and thyroid allostasis before trying to optimize hormones or add metabolic medications.
Eric Balcavage 17:04
So here's what I want you to take away from today's podcast. I want you to understand that your body's not broken. It doesn't matter to me if somebody's diagnosed you with Hashimotos and autoimmune condition, your body's not broken. Your immune system is not trying to destroy you or kill you. If you're in thyroid allostasis, your body is adapting to protect you.
Eric Balcavage 17:28
If your GLP-1 production is is low, there's a reason. It doesn't mean you should just be taking more. The solution isn't to override these protective mechanisms with medication that force normal looking labs or pharmacologically replace hormones. The solution is to ask, what is driving my body into this protective state? What cellular stressors need to be addressed? Focus on resolving the inflammation, focus on resolving the excessive stress load. And as you reduce the excessive stress load, you'll reduce the inflammation. You'll improve your T4 to T3 conversion. And yes, your thyroid gland can start to make appropriate thyroid hormone levels again. Your GLP, one production can improve. Your thyroid physiology can improve.
Eric Balcavage 18:31
If you're just trying to manage lab values and just force more hormones into a system that didn't want it, you may get some short term benefit, but it's going to be in problem somewhere down the road. You have to remember, we're not trying, or we shouldn't be trying, especially in functional medicine, to just manage your lab values.
Eric Balcavage 19:02
What my role is and what it should be in functional medicine is that we're trying to restore your physiology back to homeostatic regulation. We're trying to identify what's causing you to be in this Allostatic state, in this adaptive state. And when we identify what's causing which or what's contributing to the excessive stress, load from diet, lifestyle, organisms, toxins, and we reduce or eliminate those things, you can restore your physiology. You can restore your GLP-1 signaling, and you can restore your health in general. So that's it for today's thyroid shorts. I hope this resonates with you. Share it with someone who might be stuck in this optimization trap until next time, trust your body's wisdom.