– Let’s dive right into this trendy topic. Not a day goes by that we don’t hear something about GLP-1.
– Sure.
– But for our listeners, what the heck is it and why is everybody talking about it?
– Yeah, so GLP-1 is a short form for glucagon-like peptide. This is a in incretin-based hormone that, you know, so in our body to regulate the glucose responses about the pancreas as two kind of cells, the beta cells that make insulin and the alpha cells that make glucagon and they kind of, you know, keep each other in check. Insulin spikes up to regulate glucose levels. And just so you don’t go into hypoglycemia, glucagon is made to sort of keep the insulin levels in check as well. And so glucagon-like peptide-1 is a peptide and it’s in incretin as I mentioned hormone that basically keeps also the glucagon levels in check. In obesity, GLP-1 levels are known to go down and regulates gastric emptying, also hits the sort of the, what we call the gut-brain axis. So keeps not only the hunger away and the satiety in control, but connects to the brain’s reward center. And so it’s like a two-pronged approach to hit diabetes and obesity. So that’s why they, you know, it was initially discovered as a anti-diabetic medication and all the trials were done in that field. And over time, they’ve sort of repurposed it to see its big effects in obesity.
– Since this is a natural hormone.
– Yeah.
– What are we doing wrong that our modern diets have disrupted this natural communication system and this natural control system?
– Well, we are doing a lot wrong starting with eating a lot of processed fast food. And I mean our gut microbiome, there’s a big connection as I mentioned to the gut-brain axis, eating a lot of fat-enriched diet, the wrong fat kind of, you know, also induces a lot of inflammation in the body. So it’s essentially, you know, hitting on this gut microbiome dysbiosis. And if you were eating a lot of fiber and you had a lot of Akkermansia or the good bacteria that are also stimulants of GLP-1 production in your body, then you wouldn’t really have a problem, right? And if you exercise itself is known to stimulate GLP-1, certain fasting regimens also. So if you ate the right calories in moderation and, you know, did your exercise and ate your fiber and probiotics and then, you know, postbiotics, which we’ll get into it, you would really not have an issue. But we are all kind of, you know, fast-tracked our life into easy reward system. So we eat fast food and whatever we get our hands on, stress, all that upsets our gut microbiome and upsets GLP-1 physiology.
– Let’s fast forward to GLP-1 targeting drugs. Hopefully, I mean you can’t go on the internet without or seeing a TV commercial without seeing these and our audience probably has two or three friends or they themselves might be on these drugs. So how do these drugs work? Are they just supercharged GLP-1 or talk us through the mechanism?
– Yeah, so these are agonists. So, these are what we call GLP-1 agonists, which means they will really boost the action of the GLP-1 incretin hormone. And that will regulate satiety, that will regulate glucose levels. And a lot of early clinical trial data showed that, you know, compared to the, let’s say the first and second generation medications to counter diabetes, for example, they had a much safer profile, because they weren’t really inducing hypoglycemia, et cetera, things like this. So that’s how they were developed. And then they started finding, you know, because it hits this gut-brain axis as we were, through reward center, people started studying it further. It really delays gastric emptying, lowers appetite. And people started to lose weight in these trials and then they ran bigger trials and saw that in 12 months to 15 months, people would lose 15% of their body weight, was, you know, so that’s how all the crazes started. And I still say it as a clinician, where double up for a certain class of patients and people healthy body should not be taking it. But that’s where, you know, the things have moved.
– I tell my patients that to date, there has never been a safe weight loss drug long-term. Everyone has failed for various reasons, often dangerous reasons. But one of the things that I think I’m concerned about and a lot of patients are concerned about is some of these trials show a fairly dramatic loss of muscle as part of the weight loss. Can you talk about some of those trials? ‘Cause I think that needs to be talked about a lot more and that’s one of the reasons I wanted you on the program.
– You nailed it. Not all weight loss is healthy, right? So what was seen in these trials done, I think in the first ones really came out about three years back in the New England Journal of Medicine. These are called the STEP 1 studies and the SUSTAIN studies. And what they saw in these cohort of about 2,000 patients as they looked at their body composition over time, you know, longitudinally was they were, you know, these are very good drugs for the target they’re known to and they result in 15% weight loss. But out of that 15%, 10% is fat loss and 5% is muscle mass loss. Now if you quantify that in terms of kilograms, just to give you an idea, that you’re losing about 10 to 15 pounds of muscle compared to 20 pounds of fat in about a year to year and a half timeframe. Now if you look at the trajectory of muscle loss during aging, for example, you lose 1% every year, and over 10 years of your aging process, you lose 10%. So you’re kind of turbocharging that sort of, not only the fat loss but the muscle loss that will accompany. And if you’re young, overweight, this may be okay, you may be able to recover, but if you’re older, 50, 60, 70-year-old, you’re really at risk of inducing, what we call it in the clinical field is sarcopenia and frailty.
– A couple things about that, one of the things that I tell my patients is that muscles are really the customer that insulin sells sugar to. And obviously if you’re a salesperson, you would like to have a very large customer base to buy your product. And in fact, my patients don’t realize that their weight loss with this muscle mass means that, okay, great, you’ve lost some weight, but if you ever go off these drugs, you all of a sudden have a whole lot less customers to sell what you’re eating to. Is that a good way, number one to describe it?
– Yeah, I couldn’t have said it better. I think that’s what you’re hitting on is these are expensive drugs. They cost about 1,000, 1,500 month. So you’re looking at spending about 12 to 20K a year to keep your lose weight. And then once you lose weight, people say, “Oh, okay, I’m gonna get out of this because I’ve already achieved my target.” The important thing is in these studies that have followed up, they’ve seen that if you get wean off these drugs, the fat comes back very fast, right? And it comes back, but the muscle will never come back. And so you are gonna have a bigger problem at hand of what I call sarcopenic obesity, because you’re gonna just take the good muscle away and you’re gonna, you know, replace it with more fat that will come once you wean off. So I think there needs to be an education both from the healthcare practitioners and I mean these companies, the pharmaceutical companies know the side effects, right? They are already looking for the next generation of these medicines that have a muscle sparing effect. It kind of reminds me like the statins that people knew had mitochondrial toxicity to a certain, and then, you know, of course. So that’s where we are in the field.
– Yeah, so let’s go back to sarcopenia.
– Yeah.
– You’re right. I think many people, particularly overweight people, will say, “My thighs, I wear the same size pants that I wore when I was 30. I still got great muscle in there.” But if we ever do, like, MRIs or even CT scans of these people and compare the same circumference leg of a, say a 60-year-old to a 30-year-old, lo and behold the leg size may be the same size, but now the muscle mass is dramatically reduced and it’s been replaced by fat. And I think the other thing that people unfortunately don’t understand is that this fat can weave itself between muscle cells and muscle fibers and you have a well-marbled piece of beef and it’s this marbling that actually makes among other things muscles more insulin resistant and harder to deliver the glucose into them. So it’s like a one-two punch that you really don’t want to have happen. So now I have heard, and I’ve seen that there are actually companies saying, “Well, that’s easy to fix. All you gotta do is eat more protein and the more protein you eat, the more muscle you’ll build.” And I see it on the internet every day. Talk us through, “Really? All I have to do to make muscle is eat protein?”
– No, so, you know, I’ve been in the, running clinical trials, randomized trials in the nutrition field for a good 20 years now, and a lot of them initially were high protein supplementation in older adults. They don’t work, they don’t show anything unless you add exercise on top. You have to give the body some stimulus to synthesize the protein. And that’s why I don’t get the high protein fad so much, because they say, “Oh, take 10 grams,” and then you have another company selling 20 grams, then somebody sells you 40 grams of protein. It’s not the amount, it’s A, the quality of the protein. And B, at a certain age you hit what is called as anabolic resistance to really absorbing, you know, the protein and your body, which is really the mitochondria are the sites of protein synthesis. So unless you have your mitochondria in shape, unless they are, muscle quality is better, the high protein is not gonna do anything. So I think what the recommendation with these, at least these GLP-1 drugs should be under supervised clinical care, should they be given to the target population. And during sort of the weaning, there should be a very good dietary counsel, very good physical activity counseling to these folks. You know, how to keep the fat away and keep the muscle preserved. I think it’s a very powerful word, muscle preservation.
– And I just want to reiterate that somehow it makes great marketing sense to say, “Well, okay, we know that you’re going to lose muscle on these drugs, let’s admit it.” All the clinical trials show that that happens. And since muscles are made of protein, all you gotta do is eat more protein. I’m a fan of Christopher Gardner, who’s head of nutrition at Stanford. He makes some very logical points. Number one, most of the protein we eat is not turned into muscle fiber and is not used in repair and bone. Most of the protein we eat, and we can argue, you know, it’s around maybe 20% of the protein we eat is actually utilized with a nitrogen molecule on it, but the rest is stripped off into primarily glucose. And that glucose can either be used by the mitochondria directly or if the mitochondria don’t need anymore, it’s shifted into fat. And that’s the sad thing about this, that even eating all this protein will just make more fat and it’s…
– Yeah, yeah.
– I’m sorry. Don’t shoot the messengers. That’s just the basic physiology.
– Yeah.
– So how do we get the mitochondria, which is your interest and my interest, how do we get them more interested in manufacturing protein?
– Yeah, I think it’s really improving the quality of the muscle and the quality of your mitochondria. And there are certain ways to improve mitochondrial health. We know that. And you can improve the efficiency of the mitochondria. So you can take the pool of healthy mitochondria you have and basically get them to produce more ATP, which is the currency of energy. There’s ways to create newer healthy mitochondria in another biological way to improve mitochondrial health that we call mitochondrial biogenesis. And they are compounds, the NAD boosters, good old respiratory, all these hit this pathway. And then the molecule, the prebiotic molecule we’ve been studying, it’s a totally new vel conserve pathway called mitophagy. And that’s basically taking out the damaged mitochondria out from the cellular system, which in overweight obesity that I can tell you, we’ve looked at the muscle in the mitochondria, there’s a lot of these faulty mitochondria. So it basically takes the bad mitochondria out and replaces them with newer healthy ones. And that sort of gives you new batteries to turbocharge your mitochondria, which end up processing protein and better protein synthesis.
– One of the things I’ve been impressed with through the years now with Timeline Nutrition is that you guys do these clinical trials. This is not conjecture on your part and this is, you know, this is not dreaming on your part. Are there promising studies about this topic that you can share with us?
– Yeah, sure. I mean, as you said, I mean we’ve been at it for 17 years now. If I count the years, 17 years of research, and the word research is a fascinating, actually my MD and PhD advisor told me it’s actually two words, re and search, you have to keep going back under, that’s what, you know, he used to say, and I have his voice always in my head. It’s never one trial, never two trials. You have to, you know, look in different populations. So we looked in older adults that were very sedentary, overweight, probably a good population to take these GLP-1 like drugs. And we looked at the mitochondria and they were in such bad shape. And we then did randomized clinical trials in these very sedentary, overweight older adults where we gave them different increasing doses of Urolithin A, which is also called Mitopure versus placebo. And we saw we could actually reverse the mitochondria into looking like what a 50, 60, 70-year-old’s mitochondria who’ve been training all their life for half marathons would look like. And building on there, we went to even younger 50-year-olds who were overweight, obese, and we saw that giving, without changing physical activity or diets drastically in those populations for two to four months, we saw improved in So improving sort of the mitochondrial consumption of how a mitochondria utilize energy and better strength and endurance. So that’s the studies we have run and just finished the study even in athletes where you would think in athletes going to Olympics, they’ll probably have best mitochondria. Overtraining in these athletes induces mitochondrial dysfunction and inflammation. And we see even there we can have big effects in recovery.
– I want to hear that again, because we are always looking for exercise in a bottle, but your studies have actually shown that you can take non-exercising individuals and actually improve their muscle quality. Am I saying that correctly?
– Yeah, I think we are hitting the same biology as regular exercise or calorie restriction of about 15% reducing a calories would hit, which is basically the mitochondria, you know? The mitochondria gets stressed if you eat too much, if there’s too much sort of nutrient utilization that they get burnt out as they call them. And so this is what this molecule is, what we are seeing is doing is hitting the same biology.
– Yeah, I wrote a whole book about it called “The Energy Paradox” and you’re right, it’s literally, there’s rush hour, I use LA terms, there’s rush hour almost 24 hours in our mitochondria and because of our constant overeating. And you’re right, these guys burn out and fuel production literally, you know, falls in a tank. So you’ve gotta rev these guys up, and again I think you’re seeing with Urolithin A, Mitopure, these same effects that intermittent fasting does, that exercise does. And, you know, and I think I’ve shared with you or I’ve shared at least on my podcast or before I started Urolithin A, I’ll turn 74 in a couple months and my wife and I are actually avid hikers and we think nothing of hiking eight to 12 miles every day in hills in Italy or France or outside our home. And yet I noticed, oh, in my late 60s, early 70s, that if nothing else, my balance wasn’t as good on these rocky terrains and I wasn’t as interested I might say. And my wife at one point said, “Well, you know, look at all these old people. They’re using poles, they’re using hiking sticks, maybe it’s time, get yourself a pair of hiking sticks.” And I’m going, “Yeah, yeah, maybe I should.” Well, I actually happened upon Urolithin A through Mitopure and started taking it and one of the things that actually changed within months was my balance dramatically improved. And now to think that I need hiking sticks is kind of laughable. In fact, there’s a straight up trail in the south of France outside of Nice, which is called Nietzsche’s Trail and it’s in Eze. And it’s literally straight up, supposed to take you an hour. We’ve had friends that we’ve taken along and we have a really good friend who says, “Oh, I can make it under an hour.” And we go, “Boy, that’s really moving.” And two months ago we did it in 50 minutes, which was actually our record.
– Wow.
– And so the only thing really that’s changed, my training hasn’t changed, I’m older, but my muscles clearly got younger and unfortunately I blame it on Mitopure.
– Oh, thanks for sharing, that’s a great story.
– I don’t endorse things that I don’t, number one personally try and number two that I haven’t read the, you know, the literature and the studies, so you guys are really to be congratulated on developing this. What else is in the pipeline?
– Yeah, so 17 years in, we think we’re just getting started. The thing is when you publish really top line and do the hard yards, people like you and other top scientists are really recognizing those efforts and they’re starting to look into it. At least three groups have started looking at the effect on cognition and how this helps in things like delaying the progression of cognitive decline that happens with aging. And they’ve all come up, you know, they’ve all, like, screened hundreds and thousands of natural compounds, drugs that can delay dementia, all these dementia, Parkinson’s disease. The root cause is mitochondrial dysfunction.
– Absolutely.
– And so that’s where we’re getting a lot of interest and we are embarking on a study to see how we can improve brain metabolism and that, how that can result in better cognitive ability. We are just wrapping big study on immune aging, because that’s one area where people have not really appreciated the role of mitochondria. As you get older, your T cells, this sort of the guardians that keep the flu, the COVID, and the cancers away, they go away. You know, these sort of youthful T cells go away. And so we have been studying how rewiring the mitochondria of these immune T cells can sort of bring them to a more youthful state. So that’s something that you will hear soon. Very exciting stuff. And then we’re looking at skin aging as well through topical ways of delivering Mitopure to see, you know, can we do, like, a 360 approach to longevity?
– I’ve gotta say that my wife loves your topical Urolithin A so I think you’re onto something as well.
– Yeah.
– Is Urolithin A, is Mitopure one of the pieces to keep these drugs from damaging what you don’t want to damage?
– No, absolutely. I think it’s something I believe very strongly that, you know, this sort of muscle preservation aspect of sort of the muscle sparing effect and so that there needs to be a thought process on what is this ozempic support protocol, right? And that should be, you know, as I mentioned, having a nutritionist or a dietician give sort of good dietary counseling to these folks who have been taking Ozempic for a certain period of time that needs to be a physical activity guidance through personal trainers, et cetera. But there is a very big space for nutrition companion products and I know you mentioned it, a lot of high protein selling companies have, are positioning themselves as that companion product. And I think boosting muscle mass is not the solution at all. And we’ve all gone down that road and I think really focusing on your muscle quality by improved mitochondrial health and energetics is sort of the nutrition companion approach. And we actually, I forgot to mention we are running a study now with actually the lady at National Institute of Aging who discovered GLP-1 where she wants to go into pre-diabetics and see how Mitopure is actually regulating glucose metabolism in GLP-1 production. So we think this is a very good, you know, sort of support protocol.
– Great. Well, yeah, I think that’s well overdue and, you know, again, for anybody listening and you’re on these drugs or considering these drugs, you absolutely have to do everything you can to support your muscle wasting, ’cause if you don’t, it’s gonna happen, and you will be sorry for the effects. I see it in my clinics and of course, there are Ozempic faces and some of my plastic surgeon colleagues just think that Ozempic is the best thing that ever happened to them, but we won’t go there. So I understand that you’ve got a discount for those who want to try Mitopure.
– Sure, yeah, I think folks listening on to the podcast and will listen to this, I think it’s GUNDRY10 and they’ll get a 10% discount on the products.
– Timeline.com/gundry, and yeah, 10% off your first purchase, that’s great.
– Yeah, yeah.
– I don’t endorse anything that I haven’t tried, haven’t read the literature, and my personal experience has been nothing but superb with this. And I, you know, I congratulate you for doing all this and keep up the good work. Thanks for watching, but don’t go anywhere. The next episode of the Dr. Gundry Podcast is waiting for you now. And the way the stomach determines whether all the protein has been digested is the acid in your stomach is used up in digesting the protein.
