Ep. 367 The Metabolic Health Crisis & GLP-1s with Dr. Anurag Singh
- June 5, 2024
- No Responses
I am delighted to reconnect with Dr. Anurag Singh today, the Chief Medical Officer at Timeline Nutrition. He joined me once before on Episode 268.
I invited Dr. Singh back to discuss the latest research on GLP-1 agonists like Wegovy, Semaglutide, and Ozempic, which are gaining significant traction with projected sales exceeding $100 billion by 2030, potentially affecting 9% of the US population.
In our conversation, we explore the contributors to our metabolic health crisis by looking at the research surrounding GLP-1 agonists, the physiology of GLP-1 peptides, and the influencing elements Dr. Singh refers to as the trifecta. We dive into the loss of muscle mass and strength, sarcopenia, and frailty associated with these drugs, and Dr. Singh shares his concerns about their impact on bone health, the gut microbiome, and their use in younger patients. We also get into lifestyle measures, mitochondrial health, hallmarks of aging, Akkermansia, and the importance of advocacy and patient empowerment.
Today’s compelling and invaluable discussion with Dr. Anurag Singh highlights crucial insights into GLP-1 agonists and their broader health implications. I know it will provide significant value for our listeners.
“We have two hormones to regulate glucose levels; insulin made by the beta cells in the pancreas and alpha cells that make the glucagon, and they essentially counteract each other.”
– Dr. Anurag Singh
IN THIS EPISODE YOU WILL LEARN:
- Dr. Singh breaks down what GLP-1 agonist drugs are and how they work.
- How our modern-day lifestyles contribute to poor metabolic health
- The benefits and side-effects of using GLP-1 agonist treatments for improving metabolic health
- Why strength training is essential for preventing muscle loss and frailty in middle-aged women
- What are the potential long-term effects of SARMs on muscle mass and health?
- Why dietary counseling is essential for those taking GLP-1 agonist drugs
- The benefits of supplements for boosting mitochondrial health
- Dr. Singh discusses a research study on combining lithium with GLP-1 agonists to improve the muscle quality of those with muscle-wasting conditions.
- Why akkermansia is essential for GLP production
Connect with Cynthia Thurlow
- Follow on Twitter
- Check out Cynthia’s website
- Submit your questions to support@cynthiathurlow.com
Connect with Dr. Anurag Singh
- Timeline
- Mitopure
- Email Dr. Singh: asingh@amazentis.com
Previous Episode Mentioned
Transcript
Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness podcast. I’m your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
[00:00:29] Today, I had the honor with reconnecting with Dr. Anurag Singh. He is the Chief Medical Officer at Timeline Nutrition. He last joined me on Episode 268. I asked him to join me to speak specifically to emerging research and information on GLP-1 agonist. We know now that 12% of adults have taken a GLP-1 agonist. These are drugs like Wegovy, semaglutide, Ozempic and 6% are currently taking one.
[00:01:01] Interestingly enough, Medicaid in 2022 indicated that these drugs represented 4.6% of gross Medicaid spend and in the third quarter of 2023 they reached 6.7%. More interestingly enough, JP Morgan research forecasts that these drugs will exceed $100 billion by 2030 and that 30 million people in the US may use the drugs by then, representing about 9% of the population. Today, Dr. Singh and I spoke at great length about the metabolic health crisis, the physiology of GLP-1 peptides, what is contributing to our metabolic health crisis, including what he refers to as the trifecta, research surrounding these drugs and the loss of muscle mass, the impact on sarcopenia, frailty, and strength and indicating that we lose muscle strength 10 times faster on these drugs, the concerns he has for using these in younger patients, the impact on bone health, falls, frailty, fractures, and more, the role of GLP-1s in the gut microbiome, the importance of lifestyle measures, including nutrition, the impact on mitochondrial health and hallmarks of aging including emerging research on urolithin A and lastly specific information surrounding Akkermansia, a keystone bacteria and the need for advocacy and empowerment in patients. This is a fascinating conversation, one that you will find invaluable and one that for me was a personal pleasure to restart the conversation with Dr. Singh.
[00:02:53] Dr. Singh, so good to have you back on the podcast. Welcome.
Dr. Anurag Singh: [00:02:57] Yeah, thanks for having me, Cynthia.
Cynthia Thurlow: [00:02:59] Absolutely. We were speaking before we started recording about the impact of metabolic health and the obesity epidemic. And I think one of the probably emerging topics that’s coming up with greater frequency are these new drug classes, this GLP-1 agonists. And I would love for you to break down what these drugs are and the fact that we also make them endogenously in the body. So, I think many people don’t realize that, but it’s actually a substance that we make in the body on our own. And then we also have these drugs which are emerging with greater popularity as we navigate this metabolic health crisis.
Dr. Anurag Singh: [00:03:40] Sure. Yeah. So, these class of drugs are, as you mentioned, GLP-1. GLP stands for glucagon-like peptides. So, in our body, essentially regulate glucose levels. We have two hormones. We have insulin made by the beta cells in the pancreas and then we have the alpha cells that make the glucagon, and they essentially counteract each other. So, when insulin presses glucose down too much, then glucagon steps up and tries to push glucose levels higher up. And this is in diabetics, seen not as such a good thing, because and so, the body is obviously making these peptide GLP-1 endogenously as you mentioned. But as we all get older or we have metabolic disturbances or even gut microbiome makes a lot of GLP-1 endogenously.
[00:04:27] We all lose the amounts of natural GLP that we make. And so, these GLP-1 or glucagon-like peptide hormones, these are essentially peptides right? So, these were developed initially as anti-diabetic drugs. That’s where most of the initial research is, because the idea, if you can keep glucagon in check, you’ll kind of found another way to keep glucose levels in check, essentially, in diabetes. And so that’s where it all started. Now they have found another home in the obesity field and we can talk about that.
Cynthia Thurlow: [00:04:58] Yeah, and it’s really interesting to me because over the course of the past 25 years, I’ve really been privileged, like many of us have been, to watch this evolving obesity epidemic. And so, what is it about our modern-day lifestyles that is contributing to poor metabolic health?
Dr. Anurag Singh: [00:05:15] Well, I think it’s a trifecta of things. One is our diet. Our diets, instead of being fresh fruit and vegetables and high in fiber, has changed dramatically. We eat a lot of fast food, processed food. Our gut microbiome has changed drastically. And we know that the metabolic health is intricately linked to gut microbiome health. So, that’s one, diet is one factor. Second fact is our physical activity levels. So, exercise is normally good enough to regulate your metabolic health because it contributes in different aspects of metabolic health. So, we all have started doing these jobs where we sit and don’t move around. And our steps that we need to be taking in a day, we don’t do that. So, these two are. then the third thing I think that has really contributed is poor mitochondrial health and we can get into it, or poor cellular health as I call it, because that’s sort of it. So, the trifecta of these three things, poor diet, less physical activity, and then poor mitochondria, or aka cellular health, has contributed to, yeah, poor metabolic health.
Cynthia Thurlow: [00:06:14] Yeah, it makes a great deal of sense. And I just recently had the honor of reconnecting with Dr. Casey Means in her new book, Good Energy. She speaks a great deal about mitochondrial health. But perhaps for listeners that may not be as familiarized with that terminology, how can we unpack mitochondrial health, talking about different uses of fuel substrates and how that impacts, how we navigate our day-to-day lives? Like, as an example, I like to always think about the fact that our bodies are intrinsically designed to be able to use different types of fuel to fuel our bodies.
[00:06:48] And with our modern-day lifestyles, with the ultra-processed foods and the sedentary nature of our lifestyles, that has definitely adversely impacted things. But I also think, really, at the root is this poor metabolic health piece. And I think the more that people can understand how to take care of their mitochondria, that then leads to better lifestyle-related decision making.
Dr. Anurag Singh: [00:07:09] Yeah, sure. So, mitochondria or think of mitochondria as the batteries in your Tesla car. If your batteries are not being used and your car is just sitting there lying, it’s not going to get charged itself. So, these are like, and of course, everybody’s heard that mitochondria are the powerhouses of the cell. So, the food we eat, the mitochondria, are actually symbiotic. Originally, if you look at evolutionary mitochondria are evolutionary bacteria that develop this symbiotic relationship. The host, which is us as humans, and the idea that whatever we are eating, these ancient bacteria that integrated with our cells, they could then metabolize these substrates, like glucose, for example, or protein, into smaller breakdown products, and they give out energy that we, as a human host, need.
[00:07:54] But these mitochondria are very essential because they are key to breaking down protein synthesis. They are key to collagen synthesis. They are key to using how we use glucose. I mean, essentially, that’s the whole crux of metabolic health. So, these are very important cellular organelles. Every cell type in our body has them except the red blood cell, and the more metabolic the organ. So, the muscle for example, we’re all walking around. So, the muscle needs a lot of energy to just get up from a chair and walk around. It needs a lot of mitochondria to do that. The brain cells to think clearly, you need a lot of mitochondria in your neuron cells, heart. So, these are very metabolic organs. They have a lot of high demand of mitochondria, not just generating energy, but using substrate, as you said, using glucose and breaking down fats. And so, if you stress these using with a lot of glucose, that happens in diabetics or obesity. These mitochondria start to get damaged. So, they’re not the classical structure of a mitochondria. It is like a round-shaped organelle with a lot of internal wirings inside it that just becomes spaghetti like. And that’s what happens with poor metabolic health.
Cynthia Thurlow: [00:09:08] And it’s interesting to me because I think many people don’t realize that at the basis of most chronic disease states is mitochondrial dysfunction, and that after the age of 40 it is, we are much more likely to have an impairment in the autophagy, the waste and recycling process in the body of getting rid of diseased and disordered organelles. And then on top of it, we add in the chronic stress and the poor sleep and the ultra-processed foods, and it really just creates the perfect recipe for metabolic health dysfunction. But let’s pivot a little bit and talk about how these GLP-1 agonists are being utilized to help augment poor metabolic health.
[00:09:48] I think that, yeah, there’s definitely a camp of individuals that are prescribing it very appropriately for people that are either insulin resistant or they have metabolic health disorders including insulin resistance. And then there’s a whole other subset of population of people that are using them to take an edge off their appetite. And I use that in a non-pejorative manner. But there are definitely people I’ve spoken to in the health and wellness space where it makes me chuckle that, we’re getting to a point where these drugs are becoming much more commonplace. I think people are more familiarized with the vernacular. But what is it about these drugs that can lead to some of the side effects that I think, for those of us that work in the metabolic health space, we get very concerned about?
Dr. Anurag Singh: [00:10:28] Sure, sure. Well, first I’d like to say these are great drugs. They were meant to treat diabetes and the way now, sort of the other aspect of how they work on obesity is that the second mechanism of action is they lower the appetite. So, they hit two ways. They delay gastric emptying. So, the food is sticking around longer and you feel less hungry. And they hit this appetite control center in the brain, which controls how frequently you eat. So, these drugs are great for two, of course, reasons, which is being if you’re diabetic and nothing’s working, you get on these drugs. And if you are obviously obese, then you can get on these drugs. And if you look at the most recent data, even they affect heart failure and obese. So, these will be one of the most prescribed drugs. The problem is, you very clearly pointed out, is that they’ve become lifestyle medicines. So, everybody’s taking it to look good, and etc., etc.
[00:11:24] And if you look at the first set of data that was published in the new England Journal of Medicine, what was very clear is that if you’re on these GLP-1 or as they call Ozempic and Wegovy, which is the same drug, semaglutide, in about 15 months, you drop 15% of your body weight. Let’s say 15% is around 40 pounds roughly. You lose 25 kilo of fat mass, but you’re also losing 25 pounds of fat mass, but 15 pounds of muscle mass. So, that’s the problem. The main side effects so far that people have seen is GI effects.
[00:11:58] A lot of people feel nausea, gastric effects. That’s the one sorf of immediate effects. But the long-term effects, which folks like me, who have been in the muscle longevity space for a long time, are raising a little red flag to, is the extremely fast muscle loss that happens. And what is known is that people who take these for 15-18 months, these are expensive drugs, so you can’t forever be on them in your whole life’s trajectory. People who stop them, well, the weight, the fat mass comes back very rapidly in three to four months, because, again, you haven’t really changed your diet, your activity, and you think these are the magic drugs, but the muscle doesn’t come back.
[00:12:38] And that for a 50, 60-year-old who’s on it is a big problem because that essentially means you’re predisposing them to frailty, sarcopenia, which are muscle loss disease as we get old.
Cynthia Thurlow: [00:12:48] Yeah. And that’s a catastrophic change, especially as women are navigating menopause and men are navigating andropause. Those are real hormonal shifts in the body. And what’s interesting is, as I’ve gotten more familiarized with the research surrounding sarcopenia, understanding that prior to muscle loss, people are losing strength, and that generally creates this. You lose muscle strength, and then you start asking, as an example, I have teenagers, can you help me open up this can? And I stopped doing that because I kept saying to my husband, that’s what we don’t want, is that loss of strength precedes muscle loss. And then each decade, we’re losing 3 to 8% of muscle mass if you’re not actively working against it.
[00:13:36] And so, I think when we’re looking at this metabolic health crisis, it’s with the understanding that the drugs are, in many instances, really necessary. I think for many people, they need the help of the medications to be able to get on top of these lifestyle-mediated concerns. But it’s with the understanding, like, it can’t just be about the drugs. Traditional allopathic medicine in many ways, they have a symptom, they have a drug to treat the symptom. But we have to be thinking long term. We have to be thinking that if you’re using the medication, you have to also be prescribing strength training. You also have to be prescribing other lifestyle medicine measures. Otherwise, as you very appropriately stated, the fat mass that we’ve lost returns, and then you never get back the muscle mass that you lost.
[00:14:22] And I can speak as a middle-aged woman that it is exquisitely challenging to maintain and build muscle if you’re not actively working towards that goal on a daily basis. And so, when we start thinking about 40s, 50s, 60s, the degree of frailty, what are the concerns you have as a longevity expert that maybe listeners are not aware of, that this loss of strength, muscle mass, frailty, leads to other sequelae that people may not even be considering, that are at the life stage that they’re at now. You and I are both aware of those, because we’ve worked in medicine for a long time, but always those concerns about long term locomotion, mobility, etc.
Dr. Anurag Singh: [00:15:06] Sure. No, I mean, as you aptly put it, after our 40s, we are losing about 5 to 10% in that range of strength and muscle mass also with every 10 years of passing life. And this process even accelerated after our 60s and 70s doubles up. So, now you have these medicines that are inducing 10% of muscle strength loss in about a year. So, it’s 10 times faster. And when I thought about it, I said, well, when you’re in your 30s and 20s and even early 40s, when you have the muscle mass that, and you can think about eating well and etc., maybe there is a way sort of hormesis that body can adapt and still use the remaining muscle mass and strength.
[00:15:51] But when you’re in your 50+, you’re not only losing muscle mass, but if you actually see that people are losing bone mineral density in these also. So, now you’re creating the scenario where, as you mentioned, what is the global impact on locomotion, you’re creating a sequence of events that I think that you’re going to start diagnosing sarcopenia and frailty much earlier. Normally, when I’ve done these trials in sarcopenia in older people, around 70, 75, is when you really start seeing frailty or prefrailty that progresses to frailty or pre-sarcopenia that progresses sarcopenia, I think you’re going to see a shift earlier on in early 60s. And what that is going to mean is that people are going to have more falls, more fractures, you’re going to spend more, and this is a chain of events.
[00:16:38] Once you have a fall and a fracture and you go to a hospital, you never really recover. Most older adults have multiple falls and I think that’s the worrisome part. So, as you said, well, just don’t give the drug, give lifestyle advice, give dietary counseling, pair them up with dietitians and think about it. How you do resistance exercise, pair them up with trainers. So, I think that’s how the society, if at all, bringing them as lifestyle drugs, that we need to think about it.
Cynthia Thurlow: [00:17:06] Yeah, I think it’s so important. And for anyone that’s listening, I can’t tell you how many patients I saw in cardiology. Sometimes, they were even close to my age, that they would have a bedside toilet called a bedside commode, and we would encourage them to use the bedside commode if they weren’t strong enough to be able to get to the bathroom. And I just recall how many patients in their 50s didn’t have strong enough quadricep muscles, this is now 15+ years ago, to get off the bedside commode. And you just realize that it really becomes this slippery slope of less physical capability, less strength, more likely to fall. We know that breaking a hip in and of itself is a poor prognostic indicator that your morbidity and mortality goes up quite significantly within a one-year timeframe.
[00:17:52] So, that doesn’t mean that that necessarily becomes the trajectory for every patient. But for me, when I start seeing loved ones or family or friends talking about their parents falling and breaking hips, it really is not a benign entity. It’s not as simplistic. The orthopedic surgeon goes in and does surgery and fixes the bone or the hip. It is far more significant than that. And what are your concerns? You mentioned that typically when you’re doing research, it’s really looking at the 70s are when you start to see the significant decline in muscle mass. What per se is going to happen when we have, in some instances, teens and young adults using these drugs and not realizing that the potentiality exists if they’re not actively working against it, that they could end up becoming sarcopenic? I think that’s, to me, seems like a catastrophic side effect.
Dr. Anurag Singh: [00:18:44] Yeah. And there’s so many unknowns right now with these medications, what it means for healthy people to be taking it, how’s it impacting our gut? How are these medicines– we all know if you just look at the statins, I think there’s a very similar story. Statins were again great drugs, lowered cholesterol in the same amount of time. But they were also a bit, how I say it, mitochondrial toxins. Because a lot of people were put on the early generation statins. Later on, it was found that they had all these muscle problems. They would come into the doctor’s office with cramps, etc., and utilize that after 10+ years of these statins were launched.
[00:19:20] So, I think we are in the same early trajectory where we don’t know what the effect on the gut microbiome is of these drugs. Are they actually shutting down the natural endogenous GLP-1 production from the gut microbiome? We don’t know how they are, for example, acting on our immune cell muscle is a longevity organ. It’s the site, a lot of immune cells to be interacting with muscle cells and muscle inflammation, and we don’t know anything about it. So, I think as a society, especially if you put early people in their 20s and 302 on these for life, I think you’re going to see massive health economic impacts down the road. That’s my personal feeling. Now, again, research is two words, reinsert, so you need to follow [Cynthia laughs] people over to really find the effects. But that’s where my gut instinct tells me.
Cynthia Thurlow: [00:20:06] No. And it certainly makes sense. And where does nutrition play a role in conjunction with these weight loss drugs? Because one of the concerns that I have is when I talk to patients who’ve been prescribed GLP-1 agonists by other providers, they tell me they just aren’t hungry enough to eat. And so, they eventually, if I ask them to track their macros, and not so much focused on calories, but just tracking their macros, what I find is that most of them are eating maybe 600, 800 calories a day because they just don’t have the hunger mechanisms or the interest in eating. And so, how do we maintain or even try to reverse or address this muscle loss if we aren’t consuming enough nutrient-dense food?
Dr. Anurag Singh: [00:20:52] Yeah, I mean, that’s the big problem. You just highlighted it. I mean, they’re not going to eat enough protein, for example, good quality protein. We all know you need about a gram per kilo of body weight. And as you get older, you need to up it up to 1.2 to1.4 g/kg because the body needs losing so much muscle mass. And I think here they need to be guided on dietary, on how to put more protein, more fiber, because they also need to think, as I said, about the gut microbiome, that’s absolutely key for that.
[00:21:25] And then thinking about the rapid muscle strength and mass loss, I think mitochondria, the impact of such a high–, losing so much muscle means you’re also losing a lot of mitochondria that are in the muscle. And the impact of such changes reminds me, actually, I was talking to somebody who studies GLP-1, and they said, well, the effect looks very much like starvation, because if you put somebody in a starvation for six months, they drop 15% of their body weight. And if you look at their face, it looks exactly like the people are seeing or dermatologists are seeing what they’re calling Ozempic face. So, it’s almost like starving yourself. And I thought that resonated with me so much because you’re not– so that’s where I think a lot of dietary counseling would be very helpful for people getting on these GLP-1 drugs.
Cynthia Thurlow: [00:22:14] Yeah, I think it’s so important. I mean, obviously, I’m in the intermittent fasting space, and this is where I’m not a fan of OMAD, one meal a day for exactly that same issue. But it’s interesting across social media and as I was preparing for our conversation today, that concept of Ozempic face is really becoming problematic. In fact, I feel like the individuals that spend far too much time paying attention to what celebrities are doing, in someways they’re targeting these individuals who may very privately be making the choice to utilize the drugs, which is their own choice, but really speaks to the fact that there are side effects. That in many ways we’re thinking short term and not thinking long term.
[00:22:56] And as you appropriately stated, as we’re getting older, we have to be thinking about more protein, not less. We know that it requires more protein to stimulate muscle protein synthesis than it does in my teenagers. We know that leucine threshold has to be met in terms of amino acid profiles. And are you a fan of, again not pejorative, but are you a fan of protein shakes even if it’s a high-quality protein shake? or do you prefer that when you’re working with individuals or doing research really counseling them on consuming real whole foods?
Dr. Anurag Singh: [00:23:26] Well, I think it has to be a mix of both. You need to tell them to get as much, I’m a vegetarian and I’m aware that diet is not enough at least for me from being a vegetarian to get exposed to a lot of. And so, I have to rely on high-protein supplementation, at least 15-20 g of protein, which is the deficit I probably have in my diet. So, I think it’s a mix of both. And if you’re eating a well-balanced diet with a lot of animal protein and you think you’re getting, as I said, 1 g/kg body weight, then perhaps you don’t need to do that extra high-protein supplementation. You can just eat your cottage cheese or skyr or Greek yogurt and get enough protein that way as well.
Cynthia Thurlow: [00:24:06] Well, I think it’s really important to have you say that because in many individuals it’s really about meeting patients and clients where they are. And for some people they may be eating two or three meals a day and they’re still falling short in their protein intake. So, I do think there’s a place for clean protein shakes. Now what is the emerging research with regard to targeting muscle quality via mitochondrial nutrients and things like urolithin A in particular?
Dr. Anurag Singh: [00:24:34] Sure. Yeah. So, in the field today, and I think the field of mitochondria health is in this buzzword of hallmarks of aging, a lot of people have heard about these, used to be 9, now there are 12 of them. What I find amazing is that all of them are linked to genomic alterations or epigenetic alterations or poor nutrient sensing. But the one that is actually amenable to intervention is mitochondrial health. So, as we age, our mitochondria, as I was mentioning, they accumulate a lot of damage. They stop our balance between good mitochondria and bad mitochondria, shifts in the direction of more bad mitochondria in all the organs that have a high metabolic demand. So today, there are three ways you can boost mitochondrial health. You can actually take nutrients such as NAD boosters.
[00:25:19] So, these are compounds such as nicotinamide, riboside, or even resveratrol. These are known to help create newer, healthy mitochondria. So, that’s what we call biogenesis. It’s a nerdy scientific term, but it’s just a way to create mitochondria. Then you can take your pool of healthy mitochondria and make them more efficient. And so, CoQ10, creatine, or L-carnitine. These are compounds that can make mitochondria produce more energy. What happens with aging is actually the clearance of the faulty mitochondria slows down. And that’s what we got started talking about mitophagy. Now, if you could get mitophagy activated, which is the garbage disposal machinery in your house, if I can call it that. It’s just that as we age, the garbage disposal truck stops showing up at the door. And so, you are just keeping collecting waste in your house, and that’s exactly what’s happening.
[00:26:08] So, what this nutrient we have discovered, called Urolithin A or Mitopure, basically activates this cleaning process. And so now you’re taking these bad, faulty mitochondria, and they become building blocks of healthy new mitochondria. So, you could do a mix of all three. But what we have seen is that by using Urolithin A in multiple randomized trial, we see that it’s enough to clean the bad mitochondria out and grow new mitochondria and give you more energy and strength.
Cynthia Thurlow: [00:26:38] Yeah, it’s really interesting to me. And when research subjects or individuals are taking Urolithin A, what is the timeframe where they generally will start seeing benefits? Is it three months? Is it six months? Based on the research where people following?
Dr. Anurag Singh: [00:26:54] So, our early studies, we were actually comparing to folks who were either doing also even fasting or a regular exercise. We’ve put 15 years of research behind it, we started seeing that it was hitting this pathway that exercise and intermittent fasting does. And so in about a month, you start seeing mitochondria turn. So, with that, I mean, that mitochondria going from bad mitochondria to healthy mitochondria, and then about two to four months’ timeframe is when you start seeing physiological benefits to people. If you make them do exercise, they have more [unintelligible [00:27:28] they have more energy reserves to keep on going longer. About four months in, they have more endurance and better strength. So, round about the two-to-four-month timeframe is when people really start seeing effects.
Cynthia Thurlow: [00:27:41] It’s really interesting because for me, where it has really shown up is with jetlag. I had been out of the country twice in the past month and zero jetlag. And it drove my family crazy because I could fall asleep effortlessly, stay asleep for eight or nine hours, woke up refreshed every day, came back to The States, went back to Europe, had no issues whatsoever. And that for me was definitely one of those things that was such a profound difference for me that I was completely humbled. But many of my patients will talk about energy, just overall energy, but for me, it has really shown up as the lack of jetlag and being able to switch that biological clock because normally it would take 1 hour would be one day.
[00:28:29] And so, by the time I caught up with myself, I’d be heading home from somewhere. So, certainly for me, the jetlag piece was certainly quite humbling. I mean, there’s no other way to describe it because I’ve always suffered when I’ve traveled. As much as I love traveling, I would be the person that would be falling asleep all day long. And now that’s really not an issue. I’m curious, is there any research that’s ongoing or planned looking at the utilization of Urolithin A concomitantly with GLP-1 agonists?
Dr. Anurag Singh: [00:29:00] We can, of course, and we are doing this in some models of muscle loss. If we were to do a trial with a pharmaceutical drug with a nutritional supplement, the way trials are seen by regulatory agencies, it will be seen as a drug trial. So, we are actually now, well, completing soon with the bit more famous muscle wasting, researcher is called Stu Phillips. He’s a professor at McMaster and studies how high protein affects muscle mass and muscle quality. So, what we have used is a model in young collegiate students where you actually make them immobile. So, you put a knee brace, which basically takes them from doing 10,000 steps a day to 1000 or 2000 steps a day.
[00:29:45] And by doing that in just two weeks of immobilization, it’s like getting injured and being in a hospital for two weeks, and they lose about 8 to 10% of their muscle very rapidly. So, it’s a model of muscle atrophy. And so that’s mimicking what these GLP-1 drugs would do in a real-world setting. And so, what we are trying to show is that high protein has a use. And so, in one arm, we are giving high protein and in the second arm, where we think we’ll see an even better effect is where we’re combining high protein with Urolithin A or Mitopure, because we think that’s going to improve muscle quality by improving the energetics. And the protein obviously is going to work much better. So, there’ll be less atrophy, the muscle will better. And so, yeah, that’s the one way we have found how to do that research in muscle atrophy that could be applied to the GLP-1 space.
Cynthia Thurlow: [00:30:34] I think it’s really exciting because as this conversation has really identified one of the greatest concerns, not just with aging overall, but the accelerated muscle loss with these drugs, at the expense of fat mass loss and probably very likely changes in insulin sensitivity, vis-à-vis the fat loss, we have this profound net impact on muscle health. And so, are there other supplements that are in the works or things that you’re working on that can help with GLP-1 agonists or just GLP-1 support endogenously in the body right now?
Dr. Anurag Singh: [00:31:15] Yeah. So, you have to look at, there’s a lot of research. And first, I’ll start with the molecule I know very well for 10 years. We haven’t studied it, but right now I know at least a few groups that are looking at how to regulate insulin resistance and, for example, endogenous GLP levels by taking Urolithin A. Can Urolithin A boost these endogenous levels? I know, for example, we’ve done research looking at people who make Urolithin A are overweight, and people who don’t make Urolithin A via their microbiome or through the diet and are overweight, they have a completely different metabolic profile. So, we are studying the gut microbiome.
[00:31:56] And one group of bacteria that really shows up in people who can make endogenous Urolithin A and are protected from these metabolic shifts is people who have Akkermansia. This is the gut microbiome that, if you read the literature, is highly conducive to making endogenous and increasing endogenous GLP production. So, eating the right or getting right probiotics or getting right fermented foods and eating right fiber to promote the health of these gut bacteria. Taking advanced nutrients such as Urolithin A, I think, can really help in weaning off people or if you are already on these and you’re starting to think to get away, I think, of course, nothing can replace good dietary counseling and exercise training, but these are the tools available on the nutrition side that people can apply as a nutrition support for, really, so that muscle keeps being there.
Cynthia Thurlow: [00:32:52] Yeah. It’s so interesting. We had a podcast devoted to Akkermansia, the gut microbiome, which I found so interesting because in the context of keystone bacteria that are in the microbiome, the gut microbiome, I think many people, certainly when I was in school, we didn’t know much, if at all, anything related to the gut microbiome. And it really has exploded after over the last five to ten years. And for listeners understanding that Akkermansia plays a lot of different roles. It’s involved in short chain fatty acid production. It’s involved in the mucin lining within the small intestine. And for those that don’t know, this small intestine only has a one cell thick lining. So very, very important. And then also in this GLP-1 production in the body, so we do indeed make this peptide ourselves, but for a variety of different reasons I don’t fully understand it yet.
[00:33:43] There are some people that are more likely to have healthier, more robust Akkermansia keystone bacteria than others. And so, I’m so glad that you brought that up. Is there anything else that you feel like is important to this conversation? Maybe something we haven’t touched on that would be of great value to our listeners?
Dr. Anurag Singh: [00:34:01] Again, I think you have to first talk to your medical practitioner. How long should you be on these? Are you really a fit for this GLP-1 usage over long term? I think more and more you will see literature coming out on the safety and efficacy profile of these drugs. I think beyond high protein, people can actually think about branched-chain amino acids, for example, supplementation as you mentioned, leucine, even creatine is an excellent for muscle strength. So, keeping muscle in the mind that you’re not losing it all in the rapid amount of time. And I think that’s the only advice I can give, is think about nutrition as a complementary tool. And even if you go on these drugs long term.
Cynthia Thurlow: [00:34:44] Yeah, I think it’s really important to just be cognizant of the fact that for individuals, these drugs can be life changing in many ways. I have some colleagues that are using them in “micro doses.” They’re using them in very small doses and having a great reduction in size effects. And they have indicated and actually McCall McPherson, who’s a physician’s assistant, she was on and talking about how she’s really having great results using them in very small doses very judiciously.
[00:35:09] Well, it’s always a pleasure to connect with you. Please let listeners know how to connect with you. Obviously might appear is a podcast sponsor, so we’ll link up information about that as well. We’ll also link our past podcasts together. How can people connect with you if they want to learn more about your work?
Dr. Anurag Singh: [00:35:26] Sure, they can go to timeline.com. They can learn about all the different nutritional and topical products we have that potentially address not just signs of aging, but some of the side effects that we just talked about. They can obviously go to mitopure.com to learn more about the science. And yeah, if they’re more interested in ongoing studies, you can always write directly to me. My email is asingh@amazentis.com or timeline.com. So yeah, happy to get back to your audience on that.
Cynthia Thurlow: [00:35:54] Sounds great. Thank you so much.
Dr. Anurag Singh: [00:35:55] Sure. Thanks, Cynthia.
Cynthia Thurlow: [00:35:58] If you love this podcast episode, please leave a rating in review, subscribe and tell a friend.
