Jamie Martin
Welcome to Life Time Talks in our series on performance and longevity with MIORA. I’m Jamie Martin. I’m here with Jim LaValle. He is the chief science officer at Life Time as well as a longtime clinical pharmacist, the co-chair of the American Academy of Anti-Aging Medicine, and the chair of the International Peptide Society. And we’re coming back to a topic that we’ve talked a few times about on the podcast.

We’re talking about GLP-1s and really the reality of what it is like to be on one, but also what’s emerging in terms of benefits and also risks. So Jim, like kind of give us a state of the state on GLP-1s. Where are we right now? I mean, it’s been a few years since they’ve really risen to mainstream knowledge. Where are we?

Jim LaValle
Yeah, I think it’s a moving target. I think the science that’s evolving is pretty amazing. A lot more is being kind of characterized as what I call the pleotropic or the multi-systems benefit that a GLP-1 has. And at the same time, there are going to be people that have side effects. Yeah. And they have to be cautious and make sure they’re aware of that.

But I think I’m gonna go out on a limb here. I’m gonna say I think they may be one of the most important drug categories discovered in the last hundred years. Especially for Americans.

Jamie Martin
Yes. Okay, so why especially for Americans, Jim?

Jim LaValle
Well, fifty percent of our population is either insulin resistant or have diabetes, forty-two percent obesity, right? And we are moving to fifty percent, with well in the upper 70% of people being overweight. A lot of that is due, not all of it, but a lot of that’s due to this glitch that’s developed in our glucose and insulin regulation with unopposed glucagon production, which is one of our hormones.

I don’t know a drug that’s more important because when you get weight down and you lower diabetes issues, guess what happens to our accelerated comorbidities and risks? Right. They go down dramatically. Now, the million dollar question is are we gonna learn how to, I think, do them more personalized. Create all the other lifestyle factors and maybe other nutrients people need in order to really get their metabolism corrected.

But I mean, the state of the state is 18% of people in the US reported trying it, I think this last year. Right. 12% remained. I think it’s tragic that a lot of the people that tried it because they didn’t get good guidance now won’t want to go back on it. Right.

Jamie Martin
Right.

Jim LaValle
And I think that’s unfortunate. And then there’s folks that are buying them on their own without guidance, getting research use only peptides, which by the way, messing with your glucose regulation is a pretty big deal. Like you can become hypoglycemic, and then all the other side effects if you’re dosing incorrectly. And the thing that people don’t realize when they’re buying all these things online, all the dosages, the concentrations, they’re different. So now I gotta—

Jamie Martin
Complicated.

Jim LaValle
I gotta figure out, how many am I really supposed to do? Yeah. And I had a physician a month ago call my office and he reported, “I read the syringe wrong. I took three times the amount of the GLP.” And you know, because I’ve got dietitians, physicians, PAs in my practice. And he said, “What can I do?”

And I said, I guess—because he’s real nauseous, right? Yeah. I said, well, you can suck on some Tums or if you’re really nauseous, you’re gonna need a script for some Zofran, which is a medication for nausea that’s really bad. Because once you put it in there, it’s in there and it’s creating that signal and it’s gonna be going on for six days.

So anyway, I think those are the things that are interesting is that they’re becoming more acceptable. I think it’s no longer a stigma. I don’t think of people thinking of it as cheating anymore. Yep. I do believe we’re still woefully, woefully behind on what to do. I know we’ve been teaching now for five years at the American Academy of Anti-Aging Medicine in our Peptide Society course, a two-day course on how to use GLP-1s effectively in weight loss. I mean, it’s not like a little two-hour session or one-hour session. Right. This is a full two-day certification course with physicians and healthcare providers teaching various aspects of what you need to do in order to be successful.

Jamie Martin
Right. And we’re gonna try and get into some of that. I don’t know, we’re gonna be able to go have two days worth of content, but we’ll get into that. I do think it’s important to note what those benefits and potential risks are, the emerging benefits and risks. Let’s delve into that a little bit. First we’re starting with the emerging benefits that we’re starting to see and that probably still need more research and validation.

Jim LaValle
Right. So here’s the one that’s most unlikely that people may or may not have heard about is that GLP-1s improve mitochondrial density and numbers. Now, I went with the tough one first, right? So mitochondria. Why? Because that’s the powerhouse of every cell of our body. And we start to make more energy when we have more mitochondria and they’re more dense.

So GLP-1s help at the cellular level to get you back to making energy and then being able to store that energy in your muscle so you get better glycogen storage, right? Yep. So now you can call on that versus breaking muscle down and adding fat into your muscle, which is what happens to people that are insulin resistant and have diabetes. Right.

Then the next important thing is that they actually don’t make you—it’s clear. They don’t make you lose lean mass. You lose lean mass because you don’t eat enough. Right. And actually, they do have some cell signaling effect on skeletal muscle that would help you if you add enough protein and you exercised to maintain lean mass and even gain. Okay. So second big benefit that’s interesting.

Now the more clinical ones that people are more familiar with, less risk of heart disease, less risk of, if you have a heart attack, it being as severe. Improvement in lipids, so you’re remodeling your lipids. Yep. Glucose and insulin regulation obviously is better. Right. And you’re losing fat, and visceral fat is where it’s an engine for what’s called adipokines. You make a bunch of inflammatory compounds that drive everything from skewed hormone production. So you make more androgens in your fat.

You make more something called angiotensinogen, which makes your blood vessels get more stiff because you convert angiotensin one to angiotensin two. That’s why we take drugs called angiotensin inhibitors. Right. To stop that. Yep. So blood vessels improve, endothelial function improves. So the blood vessels get more pliable. You’re less prone to plaque. You’re less prone to an acute event. Your kidney function will improve.

And then there’s improved cognition, right? So there’s a lot of talk about the improvement in dementia risk, which makes sense because dementia was called type three diabetes. So I don’t know why everybody thinks it’s such a big surprise. Like, it might help dementia. Well you’re controlling blood sugar. Right. It’s gonna help dementia by default.

Jamie Martin
Yep. My gosh.

Jim LaValle
Yeah. And then reports for alcohol consumption, right? Reducing.

Jamie Martin
Right.

Jim LaValle
So reducing kind of a little bit of that reward behavior as to why people eat, the obvious of food noise. Some people are starting to report a little bit of better neurotransmitter function. So things like their attention deficit might improve.

Jamie Martin
Their ability to focus on some of those people.

Jim LaValle
This is better. So there’s a lot of improvements. You know, previous episode we talked about polyendocrine, metabolic, ovarian syndrome, formerly PCOS, and doctors are now using GLP-1s in PMOS because it helps to regulate insulin, which is one of the key drivers of what goes on in PMOS. Right. Weight gain, lipids are off, metabolic syndrome, type 2 diabetes. Makes sense that a GLP-1 would help that. Yep.

And so I think there’s that understanding—if you understand that insulin and glucose, how your cells make energy, how you store glycogen, is at the center of every signal and communication you have. It’s no wonder when you use a GLP-1 and you regulate energy and normalize it, and you no longer are generating inflammation because of excessive insulin or too much glucose in your bloodstream. Right. Well, yes, a lot of different conditions are going to get better.

Recently there was the discussion of cancer. Is it a cancer treatment? And I’m glad to hear that they didn’t say it’s a treatment for cancer. But what they did say—so when you have cancer, typically you have something called the Warburg effect going on. You have too much glucose going into your cell and you’re feeding those cancer cells, right? That’s how they put radio labeled water, run it in you, take a picture, and that’s called a spec scan, and they can look at that and go, we see that light up.

When you use a GLP-1, you’re regulating glucose, and regulating glucose for cancers that are very sensitive to glucose issues, well, of course it’s going to help because it’s getting to the core of that issue—maybe not why the cancer was developed, but how the cancer is feeding itself.

Jamie Martin
Well right. So it’s another tool in like your treatment plan, could be another tool in your treatment.

Jim LaValle
It’s promising. We’re talking about those potential benefits, right? On the horizon. Yep. Now, where are the risks? Yes. And I’m gonna say the risks that were first out were people got nauseous, they got diarrhea, they got constipation. If they dehydrated really bad, it could affect their kidneys. Right. They could get pancreatitis if they are overdosing. So what happened is they would lose forty percent of their weight and lean mass.

Yeah. And see, that lowers your resting metabolic rate. That lowers your resting energy expenditure. So when you end up dropping all that lean mass, well, what if you come off of it and you start to gain weight back again and now you want to re-reactivate your metabolism? You got less—

Jamie Martin
Yeah.

Jim LaValle
—activity. Yes. So big issue there. I think a lot of people understand that now. I’m proud to say I actually submitted and taught two case studies of clients that went through the Miora program, one with 39 pounds weight loss and only two pounds of lean mass loss, and another with 41 pounds—no names, the de-identified data for educational purposes for physicians. I gotta add that in.

Jamie Martin
Yeah, that can be a little—

Jim LaValle
Okay.

Jamie Martin
—significant.

Jim LaValle
Big difference. And so I think the way you do GLP-1s is becoming more important than whether they’re good or bad. Right? Like let’s get past that. They’re good for some people. Sometimes people aren’t candidates for them. If you don’t have that much weight to lose, you may need to try other things. You’re probably not going to qualify. If you’re hypoglycemic, you’re probably not going to qualify. But other than that, I think we’ve finally moved past good or bad.

Yeah. No, it’s not cheating. The problem is if you don’t make enough incretin hormones and you have this lipids, metabolic syndrome, diabetes, you die a slow death. Right? Yeah. Of chronic illness. It’s chronic illness that takes place. You know, when you take another pancreatic hormone out, insulin, that’s more acute. People have to have—

Jamie Martin
You need to have that to survive. Yep.

Jim LaValle
The incretin hormones, the GLP-1s, are helping you to manage your health and wellness. The big risk factors for dying are cardiometabolic risk factors. And dementia, right? Yep. And cancer. So if I can help that, great. So people with, you know, multiple endocrine disorders, they can’t use it. People with endocrine thyroid cancers can’t use it. Okay.

So if it’s a multiple endocrine neoplasia, meaning a cancer in your thyroid, that’s not like PMOS where it would be good to use. So the point being is that I think for people now, if they need to be on it, how do they use it as a part of their lifestyle? Can you wean them off as they become diligent about their health? They start to exercise, they train right, they find the food that they need to eat, they get adequate sleep.

They establish a lifestyle that’s well for them as they’re weaning themselves down from probably a much smaller dose that initiated one to two pounds of weight loss a week. Now, when I go to get rid of that and titrate down, the receptors aren’t so understimulated. In essence, the receptor’s going, “Hey, where’d all the GLP-1 med go?” Yeah. Right? Because you had such a big dose.

Now you have a reduced amount of signaling to that receptor. And guess what? People can get off of it if they follow through with lifestyle. And sometimes they need to use maybe a botanical or something as their maintenance.

Jamie Martin
Right. So let’s actually talk a little bit about the lifestyle pieces. We’ve covered this in other episodes, but this is so critical. We talk about the importance of strength training, of nutrition, and there’s certain supplements and things you recommend as part of an overall protocol. Right. We’ll get to that.

When somebody starts a GLP-1, are there certain changes they’ll typically see? And let’s say it’s a GLP-1 that’s at the right dosage for them. What are the things they’re gonna start to notice, and what might surprise them about what happens over the course of the first few months?

Jim LaValle
Yeah, that’s a great question. So if you’re doing it in a titration fashion, you’re gonna start low. They may not feel a lot the first two weeks.

Jamie Martin
Got it.

Jim LaValle
But what you’re doing is you’re prepping the body to get used to this signal while you’re hopefully starting to change your diet. Right. And then the magic that happens is people go, “I’m not hungry.”

Jamie Martin
Yeah. That signaling that—

Jim LaValle
The food noise is gone. Yep. You have to be careful not to overstimulate that. So they still want to eat food. And then it’s, “Hey, I have better energy. Gee, I’m thinking clearer. My stamina seems to be improved”—if they’re eating and exercising. Right. If all they do is take the drug and they’re not doing anything, I don’t think some of those changes happen as dramatically. Got it.

And you know, it doesn’t have to be—you don’t have to become a gym rat in order to make it happen, right? Right. But you should train resistance training two to three times a week. Yep. And if you’re not used to that, you should get guidance. Dynamic personal trainers at Life Time are fantastic at being able to put together programs for individuals. Yep. I think that’s great.

And what the conversation needs to be about is not about fat loss. It’s not even about how much weight did you lose. It’s how much lean mass did you spare? Because if we’re talking about it in the context of longevity, right, muscle is the currency of longevity. Yep. And so it’s more about, did you lose the weight healthy? Did you maintain that lean mass? Did you feel strong? Don’t just focus on a number that, you know, “Hey, I feel miserable. I’m tired. I can’t hardly move, but gee, my weight’s down.” Right? But you’ve lost a lot of metabolic capac—

Jamie Martin
At what cost? Again, it kinda comes down to what’s the cost of that. Like, yeah, great, the number on the scale is different, but you still feel terrible.

Jim LaValle
That’s it.

Jamie Martin
Right? Like that’s not worth—is it worth it, I guess. I don’t know.

Jim LaValle
I personally don’t think it’s worth it ’cause I’m all about wanting people to feel better. Right. I think someone who’s lost fifty pounds has still lost fifty pounds. Yeah. But if they’re not vital and they can’t enjoy their life because they’re always nauseous, or they’ve got side effects or symptoms, well, it kind of defeats the purpose.

Jamie Martin
Yep. I think the point about energy—like if you’re doing both, right, you’re starting a GLP-1, it’s titrating to the right dosage for you, and you’re incorporating or maintaining lifestyle habits that we talk so often about, the movement, strength training, eating well, making sure you’re eating. Because that is one of the things I do get concerned about—I will hear people say, “I’m just not hungry.” And we really do need them continuing to eat and nourish their bodies. That’s what’s really gonna help them thrive in the long run.

Jim LaValle
Yeah, I think it’s one of the core questions I know we ask is, how’s your appetite? If you’re just not hungry, but you are losing weight, maybe that dose needs to come back a little bit. Yeah. Because you do need to get that one point six to two point two grams per kilogram of protein a day. You’re gonna have to divide it up.

Jamie Martin
Right. You’re not taking this all at once.

Jim LaValle
Right. You’re gonna have to divide it up smaller amounts ’cause you’re not gonna be as hungry. And then use other tools like creatine or using a protein powder. You have to get that protein source in. It’s so important for success.

And I do think that even just people getting moving, ’cause many times they haven’t been—I think there’s two kinds of folks that really reach out for this. You’ve got the person who’s really obese and they’ve had very little success. They haven’t been moving a lot over the last several years. And then you got the person who is moving, they’re trying to eat well, and they’re still 30 pounds overweight. Mm-hmm. And it’s not budging no matter what they do. Chemistry.

Jamie Martin
Right.

Jim LaValle
I think that person, it’s a little easier for them because they’re not having to think about movement again. How do I cook?

Jamie Martin
It’s relearning skills and adopting new habits in one case where some of these are already established, right? Exactly.

Jim LaValle
Yeah. And so I think we’ve got those two types of populations that you have to talk to maybe a little bit differently. Absolutely. Right. To make sense. You know, I’ve seen so many cases of people that are more on this side of, “I’m working out. Look at what I’m eating. I’m not moving the scale. What’s wrong?” Right.

Well, first of all, it could be other things like cortisol levels are up. Maybe your sex hormones are out of balance, maybe your gut’s permeable, because we know gut permeability leads to weight gain. But even at that, most of those things that are triggering inflammation, metabolic inflammation leads to insulin receptor resistance. Right. It all—

Jamie Martin
So kind of comes back to the same.

Jim LaValle
—comes back to it. In my opinion, it all comes back to glucose, insulin, and how our nervous system is feeding that information to it. And then all the other systems have to figure it out from there.

Jamie Martin
Right. But to your point, understanding what is going on with you is so important too, which is why the metabolic code that you do at Miora and elsewhere—understanding what your body needs, what’s missing, where a system might not be functioning as optimally as it could. And I think that that is also maybe baseline, right? Before we would want to consider like, the GLP-1 is for sure the tool, but do you understand what your body is actually telling you right now?

Jim LaValle
I don’t think people should try a GLP-1 until they have a lab and understand where they’re at. Yeah. So you’re not missing something that you may want to work on at the same time. But more importantly, what if you already have elevated pancreatic enzymes and you don’t know it? Right. It’s not good to have—

Jamie Martin
Might be counter for you.

Jim LaValle
It could be a problem. It could increase some risk. So absolutely get a lab test. And I think you really need guidance if you’re not familiar with how much resistance training you should do. ‘Cause the trainer should be asking, right, “Hey, how’s your energy?” Because if your energy is lower because your caloric intake is down, the trainer’s gotta modify that a little bit. It’s not about how much you do, it’s that you’re doing it. Yeah. And so—

Jamie Martin
So—

Jim LaValle
—that part I think is real valuable, that you have a team, a trainer that’s keeping an eye on you. Are you losing weight too fast? Make sure you’re getting on that bodycomp scale. Are you starting to lose lean mass too fast? Better dial back dose, improve protein intake. You know, I think all those variables need to be looked at for the individual if they’re going to be in a successful program.

Jamie Martin
Right. And that really means a support system and regular connections with them. Right. I mean, I think that’s really what I’m hearing—that we need that support and connection on a regular basis.

Jim LaValle
I think when you’re losing weight—as I’ve said before in many episodes, growing up in a family that struggled with weight, my brother’s whole life, I mean, there were weight issues. My mother, my father—you’re a world famous chef, you gotta taste everything that he cooks, right? Right. I mean, you need a support mechanism or people fall back into their habits because life gets stressful. Stress triggers the need for reward, and reward is not found in broccoli. People want cookies and cake and chips.

And I guess I’ve worked at it long enough—man, steam some good broccoli, put some mold and sea salt on it, maybe drizzle a little bit of olive oil on that, you got something pretty good. Yep. But the point being is that you do need a support structure. Having someone that knows diet, a good dietitian, having a provider looking over your dosing, where you’re at, where you’re tracking, and most importantly, I still believe the fitness trainer is going to become the hub, the center of transformational health, especially in the US. Because—

Jamie Martin
Because of the regular connection points.

Jim LaValle
—of the regular connection point, they don’t have to prescribe, right? They don’t have to make those kind of recommendations, but they can ask the right questions. Yep. To see if you’re succeeding and help guide and then give feedback to the providers like, “Hey, did you know that Mary, for example—whoa, we had her on the inbody and she lost a fair amount of lean mass and she’s not saying she’s eating very much.” Yeah.

I really believe they’re at that pivot. They’re the hub point that really needs to be focused on if we’re gonna be successful, related to what I call medical fitness. It still comes back to that trainer. Got it.

Jamie Martin
Okay. I’ve got two quick questions for you, I think, and we’re gonna wrap this one up. If there is like one smart first step for someone who’s considering a GLP-1 but they’re feeling overwhelmed by it, what would that step be?

Jim LaValle
Talk to someone who’s done it successfully, right? Because there’s a lot of questions. How am I gonna feel? Gee, how’d you deal with the nausea? How much did you have to eat? What did you eat? Yeah. Try to find somebody—a friend. Because at this point, you know people.

And then I would say the very first step is you have to get a lab test. Yep. If you’re contemplating a GLP-1. If you’re feeling overwhelmed, I think that GLP-1s provide a lifeline. It’s the bridge to getting out of a path of chronic illness. Yep. Back to that chronic wellness. Yep. Right? That we’re looking for. So that’s why I think it’s really important.

Jamie Martin
Yep. Okay. I love that. And if there’s anything you would want people to understand about the reality and the future of GLP-1s, what would it be?

Jim LaValle
Well, the future is—we’re gonna continue to create more and more powerful ones as the population either gets resistant to the first generation or second generation meds. We’re now on to the third generation. Yeah. We now have oral ones. I mean there’s a lot of things that are shifting. It is a shifting science.

I would also say that you gotta find out which one’s right for you. Just because it’s, quote, “more powerful” doesn’t mean it works as well for you. You have to be careful of that. And I think that we’re gonna be looking at accessory drug therapies or secondary therapies that help the GLP-1s to do their job even better.

So the future is we’re managing metabolic syndrome and obesity and type two diabetes if we have a hope of health care in our country. And we’re gonna continue to see that movement towards what other ancillary drugs or nutrients are gonna be important for that progression. So the future’s bright for GLP-1s. There’s no shortage of people that need them.

Jamie Martin
Well, it seems like there’s gonna be ideally more personalization to understanding you as an individual. So—

Jim LaValle
Prices are coming down. Yep. So I think there’s a lot of things that are positive. It’s democratizing the ability to even have access to them. So I think that’s great too.

Jamie Martin
Anything we missed, you want to make sure to add before we wrap up?

Jim LaValle
You know, I wanna clear up and make sure people know: you don’t wanna lose excessive lean mass, you wanna lose all fat mass. Just remember when you’re using that GLP-1, your goal is to maintain as much lean mass as you can. Yep. So even if the weight loss is slower, be patient, you’ll get to your goal and you’re going to be able to really empower yourself to take control of your metabolism.

Jamie Martin
It’s a great way to end it. All right, focus on that lean mass. People want to learn more, they can visit Miora.lifetime.life, visit experiencelife.com to get all of our podcast episodes in this performance and longevity series. And Jim, thanks as always for joining me.

Jim LaValle
Much fun