The Science of Lookmaxxing with Dr. Noc

Introduction to looks maxing

0:00Loved me some Dr. Knock. He's great, isn't he? Oh, man, and he told us how to not look old. Yeah, looks maxing, baby. Not that I need it. You may need creatine. Now, that I might need. All right, coming up, Dr. Knock on everything that you think is wrong with you, but might not be, on StarTalk Special Edition.

0:18Welcome to StarTalk, your place in the universe where science and pop culture collide. StarTalk begins right now.

0:31This is StarTalk Special Edition. We're thinking today about what everybody does to look different, although they would think to look better. Neil deGrasse Tyson here. You're a personal astrophysicist. It's Special Edition. That means... Me. Hey, how you doing, man? I'm good. All good now. All very good. Gary O'Reilly from the UK. Yes. Ours now. Yes. Good. And we got Chuck Nice. That's right. Chuck a baby. Hey, how's it going, guys? I'm good, man.

1:01Chuck nice. We're talking about looks maxing. Ooh. You mean you guys are discussing me? What? Looks maxing. Let's figure out what this is all about. So, Gary, get us buried here. All right. What's going on? We've all thought it. What if I looked better? Seemed younger. Shaved off a few pounds. Couldn't hurt, could it? No, not really. From, as you said, looks maxing to biohacking. Your biological age. So, to perfecting your body composition, modern science has offered us a whole new litany of quick fixes.

1:33Or so it would seem. But are people doing more damage than good in the pursuit of perfection? What are the facts? What is the fiction? And most importantly, is there something you can prescribe me to get back to my glory day so I can get back out on the field?

Meeting guest Morgan McSweeney

1:48So, Neil, please introduce our guest. I will. Making a second appearance on StarTalk. Our returning champion. An undefeated champion, the one and only Morgan McSweeney, Dr. Knock. Yes. Morgan, welcome back to StarTalk. Well, I'm surprised I got invited back, but I'm happy to be here. Yeah, we took some debate on our side. It was fine. Yeah, man. You have an academic background in pharmacology and immunology? That's right. Pharmaceutical sciences and immunology. This is a thing that matters now to everybody.

2:20It does. It is. Especially since we're all going to die in another pandemic because everybody has abandoned the safety precautions from the last one because, you know, you won't tell me what to do anyway. Feel better? Did you get that off your chest? Chuck, okay. You are a—the term, I think, is med-influencer. You're online. I am. Combating all the misinformation that we're flooded in.

2:51And the big challenge is how does someone know that you are not the misinformation and the misinformation itself isn't real? It will accuse me even further of being totally AI-generated sometimes. So your job is to vouch for the fact that I'm sitting here. I think it's your perfect diction that causes that to happen. And it's perfect hair. And it's hair. Yeah, exactly. So let's lead off. It's clear that everyone wants a quick fix. No one wants to do the hard work, whatever that is. Yeah. And I remembered I was in middle school, and I wrote a book report on Ponce de Leon.

3:24Oh. Yes, yes. I don't know what you say his name. Ponce de Leon. Look at that. Yes. And he came to South America, I think it was, in search of the fountain of youth. Fountain of youth. And I was a geeky kid, so I said, was he an idiot? You drink from the thing and you never—doesn't he know better than this? Yes, and maybe he didn't back centuries ago where anything was possible and there were deep religious convictions. And so the supernatural and forces beyond our knowledge or control were not an extreme thought.

3:58But I would learn that that urge persists to this day within us. Nobody wants to go to the gym for six months. They want a pill. They want an injection. And the closest thing we have lately, the—

GLP-1 drugs and weight loss

4:10GLP-1s. The GLP-1s. So let's start there. What has that done to the people who are not diabetic, where it was a medicinal treatment for their health condition? You have all kinds of other people injecting themselves. What is the consequence of that on our culture, on our civilization? Yeah. I think there's two things, culturally and medically. Medically revolutionary category of drugs. They are peptide drugs. We can talk about other peptides later. Oh, peptides. Okay, definitely want to go there.

4:41Yeah. So it's kind of the knight in shining armor story for peptides, along with insulin is one of them. But, I mean, I think they're a medical revolution. They're going to prevent a huge amount of chronic disease that otherwise never would have been prevented through lifestyle interventions alone. No matter how much you talk about it, you've got to get good sleep and physical activity and you've got to eat right. We've seen in practice for decades that even if you know that, it can be very hard to do in the context of real life. And for some people, even impossible, just given their own inability to focus or devote.

5:11Or challenges, everyone's coming from. Well, that's well, sure, sure. Yeah. And so now to augment, you still do those things, but in combination with these drugs, right, you're going to see huge reductions in chronic disease as a result. So I think that's a very good thing. Culturally, I think it has shifted what it means to lose weight. And it's, I don't want to say it's easier now, but, you know, with the medicines, it's more likely to happen for a lot of people. There's this familiarity with, you know, sometimes injecting yourself with medicines, which many people who previously never took injectable medicines now maybe are with GLP-1s.

5:47And maybe some of that familiarity is leading into being comfortable with injecting other things like all the other types of peptides that aren't as well studied. All right, so what about, I mean, I don't want to distract ourselves on this, but I'd want it to be there somewhere in the backdrop.

Understanding visceral fat risks

6:03Before the GLP-1s, there was a movement to be comfortable in your own body. There'd be people overweight, but not morbid. Body positivity. Body positivity. They were not morbidly overweight. They're just a little chubby. And now you can just get rid of that. And are we resorting to the skinny person mindset and the body positivity is no longer a thing? I think it's shifting self-perception for sure. And so there's two separate things. There is the health impact of particularly visceral fat, which is different from the health impact of subcutaneous fat, which is the part you can see in Pinch and Everything.

6:41We need to talk about that because people need to know that the visceral fat is the really dangerous fat. It is. It's the fat that forms around your organs and, you know, which you can't necessarily see from the outside. Whereas a subcutaneous fat is when you look in the mirror and go, I got a loose weight. Yeah. Which is not as much of a health risk. So there's separately sort of the health side of reducing visceral fat is generally good for your health. Totally different from do I feel good when I look at myself in the mirror? I think what we know very clearly is even people who you would consider to be, you know, thin or athletic looking can look in the mirror and still not feel great about themselves.

7:20So I think it's a little bit deeper than necessarily just the number on the scale. I think a lot of people struggle with that, especially in, you know, the era of Snapchat filters and social media and unrealistic expectations. I think we'll get into the psychology and the imposition of certain body shapes that people say you must adhere to this body shape rather than the one that you have. But take a step back with GLP-1s. How much clinical data is there that we have? Because we're seeing right there for, as you said, diabetes.

7:51We're now looking at it as a weight loss drug. And it's sold mainly as a weight loss drug, regardless of your conditions, if you have or haven't any. Do we think there are other downstream benefits? Do we think, hang on a minute, this could cause problems, not just have a list of benefits? Yeah, so certainly it's always... When we turn 70, do we grow a second head or something, you know? I want one of those. I mean, if the drug has not been in civilization for more than a certain amount of time, you don't know what that will do as people age beyond that.

8:23Right. So what do you know? You know taking these medicines can lead to weight loss on the order of 10%, 20%, depending on where you're starting, depending on your dose. What do we know about carrying, you know, in some cases, extra body weight? It increases your risk for a long list of diseases. We're talking even dementia. People are surprised about that one sometimes. Your cardiometabolic health, which is influenced by your visceral fat, influences your risk for brain disease, obviously for heart disease. And so what we do know is it helps people lose weight if it was medically indicated for them to lose weight.

8:55Therefore, we can predict it's probably going to help reduce risk for the long list of chronic diseases that we know are associated with carrying excess weight for a long period of time. Okay. We don't know what will happen in 20 or 30 years. But is that enough rationale to wait 20 or 30 years to start taking them when we know there are some concrete benefits we could kind of act on now? I'm going to wait 30 years and then I'll start. So GLP-1, semaglutide, am I pronouncing that? Is that a naturally occurring peptide within the body?

9:26No. So the GLP-1 signaling pathway is endogenous to the body.

9:33Endogenous. It's in your body. Thank you for that. Okay. They're different molecules. So the ones that you inject as the pharmaceutical versions, they're longer lasting. It's obviously more controllable. But when you eat a meal, you do have hormone signaling going on to tell your brain, okay, you're feeling full. You don't need to eat more right now. Right. So that was the... So that's what he's saying. Yeah. You already have... Your gut tells your brain to... Time to eat. We're done. I'm hungry. I'm hungry. I'm hungry. And then your gut tells your brain... No, it's Thanksgiving. It doesn't do that.

10:03So it's an amplification of certain messaging. That's right. And so those hormones, they respond differently to different types of food that you eat. If you eat something rich in whole foods and particularly plant-based foods with dietary fiber and protein, you're going to feel more satiated for longer. You're going to feel fuller for longer. If you're eating often ultra-processed foods that are rich in sodium and added sugars but not particularly fiber or protein, you're not going to feel as full for longer, which is totally separate from the nutritional effect of those foods. So I got a question. For the longest while, there are these herbal supplements to your health that would make claims.

10:40None of them were verified by the FDA. All right. Have we transitioned from that era to an era where science actually is accomplishing what everyone was thinking was getting accomplished by herbal cures that they were told would either... Support metabolic health. Support metabolic health. Support metabolic health. Support metabolic health. You've got the lingo. Support metabolic health. Support your sex life, your social life. Yeah. You know, these claims were all extraordinary.

11:11And are the scientific circles, the pharmaceutical circles, learning how to do that but with authentic science? Is it the snake oil that actually works? Ooh. I think there probably is something to that. I don't know how the supplement market has shifted after the introduction of GLP-1s. I think you're probably right that you've probably seen decreased interest in, you know, the bottles you can buy that support weight loss or support metabolic health with no efficacy numbers attached to like, oh, these drugs actually have clear clinical data on both the benefits and the risks.

11:44My guess is you've probably seen a flip in those. Yeah. So people are believing the science? Or are they getting to the point where they're ready to believe the science or they're demanding more science? There comes a time where science rises up to a level where it cannot be ignored. There you go. And I think you are both underestimating the utter stupidity of who we are as people. There is always that element. There's always that. Okay. Yeah. Okay. You're right, Chuck. Because, listen, one of the things that happens is that people see the results for themselves.

12:16So with GLP-1s, I think for everybody out there. Everybody's got a friend. Everybody's got a friend. And here's what you saw with that friend. It works. What happened, man? Look at you. Are you sick? Do you, like, you know. Right, right. In the old days. In the old days, I'd say, hey, I don't know. Have you seen Jimmy lately? Man, he lost a lot of weight, man. I don't know, man. I'm worried about him. Unexplained weight loss. Unexplained weight loss. I looked at the data on that. Unexplained weight loss, you're dead in six months. Okay. But now you say, and your friend, you're like, oh, my God, that works.

12:48You're on GLP-1. Right? It works. Live five years longer. So there's, like, these walking testimonies now that says this stuff works. Yeah, yeah, yeah. Space fact. So life doesn't simply require the sun. It requires a source of energy. One source of energy is Earth itself in the form of hydrothermal vents. Places at the bottom of the ocean where heat is coming out.

13:21And there we find life forms as alien as anyone has ever dreamt of, thriving on geochemical energy from the depths of the Earth. If you like that fact, you can find 4,999 more in Lost in Space. 5,000 facts to help navigate the universe. Lost in Space is now available wherever you get your books.

What are peptides

14:09So what is this with peptides? Just introduce me. I learned it in high school biology, and I forgot it. So just catch me up on what a peptide is and why you guys care. Yeah. So peptides are closely related to proteins. You can think of them as really small proteins almost. There's a short number of amino acids, which is the fundamental building block of proteins. And if you've got between 2 up to around 40-ish, depending on the definition, amino acids, that's a peptide. Okay. And so functionally, that's the scale where they're not really doing complex three-dimensional folding on each other like larger proteins would.

14:44But they're still busy and useful. They are, yeah. And so you make them in your body. They have critical signaling functions and hormonal functions, like the GLP ones, like insulin. Insulin's a little bit bigger, I think around 50. Are they more easily absorbed through the biological barriers, which makes them more effective? You still have to inject them. With any peptide or any protein, if you eat it, your body is going to break it down. Your body acid will destroy it. Yeah. And then you'll still absorb the amino acids. So you have to bypass your digestive tract in order to get it into your bloodstream. That's right. Okay. For most of them.

15:15Actually, there is, I think semaglutide now has an orally available pill. Yeah, yeah. But the bioavailability, it's like 2% of it. Ends up making it into your actual system compared to injected where, much more obviously. 100%. People prefer oral to injection. Right. All right. Let's go back to the enemy, visceral fat. How do we manage that with, say, a peptide? Or do we have another route of approach? Visceral fat, and this is one of the unique places where our biology is on our side. When you lose a little bit of weight, visceral fat comes off disproportionately first.

15:48It's also disproportionately risky to your health. And so, you know, losing even a couple percent of total body fat, you'll see much more of your visceral fat go. And the reason you care about that is it is crazily associated with risk for future cardiometabolic health. UK Biobank did an interesting study. If you compare people who were overweight, you know, by looking in the mirror, looking at the total body weight scale versus normal weight, but people who are normal weight with a lot of visceral fat, because that can happen. You can be overweight on the scale, but not have much visceral fat.

16:18The normal weight people with a lot of visceral fat had like a 6% chance of getting type 2 diabetes. It was like 2% for the people who were overweight, but with low visceral fat. So a threefold difference in the opposite direction of what you would expect by looking at somebody. So visceral fat has, it's a disproportionate impact on your health. But when you go to either lose weight, you actually don't have to lose weight to lose visceral fat. If you just increase aerobic activity, you have to increase it kind of a lot. Like the threshold is 150 minutes. Minutes?

16:48Per week. Oh. I was going to say that's a long workout. The gym tells me I can only sit on this thing for 30. I know, right?

16:58But you don't have to lose, the number on the scale doesn't have to change for your visceral fat to be going down meaningfully. You can do body recomposition. If you're doing more aerobic activity, the fact that it is so metabolically hot works to your advantage that it can go off first, even if not much changes in your whole body. You said body recomposition. Yeah. Okay. What is that? Exactly. So, you know, say I'm 193 pounds and say I'm going to add more strength training. Right. I'm going to be eating, you know, my total energy intake is going to be, it's going to

17:28keep me right at 193 pounds, but I'm going to be eating enough protein and I'm going to be doing strength training. Right. What's going to happen is maybe my body fat is going to go down a little bit, but my muscle mass is going to go up. So you're going to weigh the same, but your body is going to be re-comprised in such a way that you're more lean and muscular at the same weight. That's right. Okay. We used to call that conditioning. Conditioning. Yeah. Yeah. What if I'm that lazy ass guy that says you got a peptide for that?

Creatine and muscle recovery

17:55Oh yeah. So how, how do we attack our visceral fat and we want to get lean muscle mass? There's got to be a go-to peptide. There is. So anytime you're going to lose even a little bit of total body fat, the visceral fat is going to come off first. So the GLP-1s are going to kind of by nature, reduce your visceral fat while you're reducing total body fat. Separate from that, I mean, it's all the boring stuff we all know. It's the sleep. It's the proper nutrition. It's doing the strength training. It's doing the aerobic activity. I'll remind you of the lazy ass sentence.

18:28Maybe the sleep. Yeah. Sleep I'm good at. I can do that. Yeah. And then, you know, quite a few tiers down from the GLP-1s, you can take creatine to amplify your strength training. Right. And so we can get into that. But the way the... Creatine is a what? Protein. It is a supplement. A protein supplement. It is a dietary supplement. It's not... I don't think of it as like a protein powder. It's totally different. No, it's not a protein powder. But apparently, if you are weight training specifically, not the only thing, but weight

19:01training, it really helps with your recovery and to help build muscle, supposedly. Yeah. So the way it works, we actually make creatine kind of natively. We make about a gram per day. You get about another gram per day through dietary sources if you're omnivorous. A typical supplemented dose for weight training is on the order of five grams per day. That's hardly anything. Yeah. So you're going up about threefold-ish from like the native endogenous. I mean, it's just... I'm just... I just don't know how little five grams is. Oh, it's a small total amount. It's a tiny little... You can't just jump into the... It's a fraction of an ounce.

19:32Yeah. When you actually add it to whatever you're going to supplement... I mean, whatever food, it's literally... It looks like a thimble. Yeah. Okay. Yeah. The thing is, if you take a dosage that is way above because you think, you know what, I'm going to really... Yeah, because why take a low dose if you can take a high dose? Yeah. So you end up with a shock in some capacity in your body. Gastrointestinal. Yeah. Yeah. So then you're just not in balance with your own biology. Got it. Yeah. And you know what? While we're on that, maybe as a doctor, you can tell people... Scientist. I'm sorry. As a scientist, you can tell people... It's a doctor or scientist. Doctor or scientist.

20:03Just because this much of something works doesn't mean two times that works twice as good. Oh, yeah. There is a threshold effect with creatine as a very good example. I mean, the way it works in your muscle cells is when you're going to be doing a set of 10 reps of bench press or whatever it is, you've got kind of this quick-acting energy system with ATP. While you're doing it within the first few seconds, you blow through that. And your cells have to say, okay, we've got to recharge energy here. So you've got this battery system in your cells that has creatine phosphate.

20:37And so you can kind of increase the size of that quick-acting battery by supplementing with creatine. And the order of effect here is about 10%, 20%. So instead of being able to do 10 reps on the bench press, now you're going to do 11 reps. And so you get a little bit more growth stimulus. You get a little bit more out of your workouts. You can work out with a little more intensity. And that's the entire mechanism for how supplementing with creatine leads to more lean mass gain when you're doing training. The stimulus, though, is still coming from training. That's a misconception. People think, if I take creatine, I'm going to start hulking up.

21:09Now back up. I'm on a creatine and ice cream diet.

21:13Back up. Just remind us about ATP. ATP, yeah. So in your cells, they need a way to quickly get energy. And so the way that works is you're going to be burning the macronutrients. You're going to be burning carbohydrates, preferentially, or you're going to be using fat, or at least, ideally, you're going to be using protein. When they get combusted in your body, they can take the phosphate, and through a complex series of molecular events, you result in molecules called ATP, ATP, which is what your mitochondria in your cells use for the energy to do whatever they're going to do, in the case of muscle cells, you know, to contract.

21:50I have in my head that that stands for adenosine triphosphate. That's right. Does it still stand for that? As far as I know. I didn't check this morning. Let's visit this sort of, you know, you go big with the dosage.

Peptide stacking and animal studies

22:03Yeah.

Peptide stacking and animal studies

22:04All right. So jump back into peptides, stacking. So if I'm stacking, it's not one peptide, but you're multiple different peptides coming in at the same time. That's become very popular, but how, A, does that work, and B, how? I'm not sure it does work. So this is a totally separate class of peptides. So the GLP-1s went through the route you would want them to go through, big clinical studies, thousands of people. You get a clear idea of benefits and risks. The peptides I think we're talking about now when people talk about stacking with BPC-157 or TB-500,

22:37there's very, very little, in some cases zero, human clinical data on either the benefits or the risks of these peptides. Those two peptides you mentioned, they're the wolverine stack. The wolverine stack. And so it's touted for, with very little evidence, some animal evidence, but not much human evidence. And anyone who's been in biology for a long time can tell you how many times we've cured cancer in mice and how many times we've solved every disease in animal models of disease that have failed to translate to humans. I think the stat is among drugs that start clinical studies, actual clinical studies.

23:10On humans? On humans, only about 10% of them make it all the way through, make it to market. It's even lower in cancer. I think it's about 5%. And 100% of those were tempted by their results from animal research. Right. So you're starting out. They didn't just pull it out of their ass and say, let's give it to people. They had some evidence that it might work. Right. Enough to convince. But how do you explain that? If mice are actually quite close to us genetically, what is the fundamental divide between us then? Yeah. I mean, there's phenomenal differences, even coming from non-human primates, maybe as a more striking.

23:46Sure, sure. You'd think it's almost identical. Go there. Go there. Yeah. There was a really tragic clinical study started for an antibody years back at this point called TGN-1412, which was supposed to be a powerful treatment for autoimmune disease. It was supposed to turn up the types of immune cells in your body that help damper down the immune response. Just before we had a cure for AIDS? Was that? I don't know the exact timeline. I think it was from the 2000s. But the idea was, we're going to turn up these helpful immune cells that work against autoimmune disease. And they tested it in non-human primates.

24:17And then they said, okay, based on that non-human primate dose, everything looked fine. We're going to scale it down 100-fold, 200-fold, I forget what it was, and try it in humans. They put it into the first six humans. I think it was either all of them or five out of the six first people who were tested, within minutes, started going into this severe inflammatory response. Their organs started shutting down. One of them lost, I think, a few fingers or something. Damn. And afterwards, what they found out was, oh, actually, in this non-human primate model, this type of T cell doesn't have the exact same marker that is present in human T cells.

24:50And it turned up the wrong type of inflammatory T cells in humans that wasn't visible, even in non-human primates, let alone rats or mice. So it caused like a cytokine response instead. It did. It causes huge inflammatory response acutely. That's really unfortunate. So unexpected stuff happens all the time. See, that's why we should just test everything on humans to begin with. What you're saying is we should expect unexpected things. Right. Which is why, I mean, that's why clinical trials are structured the way they do. And actually, in response to that, now instead of dosing all six people at the same time,

25:23and six is already a small number to be starting with, now they do called sentinel dosing, where it's like you start with one person, and you wait and see what happens to that one or pair of people, and then you kind of scale it up. And you might handpick your person who is in a really dire strait. In the case of cancer, absolutely. Right. So that the upside, the potential upside is way good for them relative to some bad happening in the drug. That is how it's done in cancer. For a lot of other drugs, they actually start with a maximally healthy person to minimize

25:53the odds. Like, if it is going to do something bad, maybe it's not going to tip them over the edge. Oh, it might knock them off. And with the cancer, unfortunately, it really isn't just dire. Like, my mother died of cancer, and she had bone cancer, and it was resistant to every treatment. That's right. And there were some new drugs coming on the market, and I had some friends at a foundation. I said, hey, and they actually wanted to help, but she was too old. And basically, they were like, the information that we get from her is not usable because

26:26of her age. Interesting. Are peptides that people are using for their body composition naturally occurring in our bodies? Are they being pharmaceutically developed and then introduced? Most of them are modified based on naturally occurring molecules, is my understanding. So they're changing the signaling. And so if I want to reduce fat, you make the signal of reducing the fat and triggering the chemicals in the body. To make it more powerful, to make it last longer.

26:57Now, for these, what could be compounded peptides, and I think these very differently from the type of peptides like GLP-1s, the ones we're talking about that have minimal human data, that have animal data, that people are self-dosing with kind of through the gray market. I'm very concerned about that. There's two big types of risks. The first one, which is the one that people talk about the most, is the less concerning risk. That's where it's being made in these for research use only applications, but they're actually marketing it to people for personal research. The risk is, well, maybe they didn't do a good job of being sterile in their preparations.

27:28Maybe there's some inflammatory endotoxin from the bacteria they use to produce the peptides. Maybe what's in the vial isn't safe to inject. That type of risk you can mitigate by bringing it domestically. In, you know, regulated pharmacies, compounding it here. The second type of risk is much more concerning to me, which is that some of these peptides, they're touted for things like tissue repair, like BPC-157. It gets pitched as, oh, it's going to help you recover from your tendon injury or your muscle injury or whatever. Athletes would be very interested in that. Right.

27:59Which, you know, on the benefit side, that could be great. One of the things is, you know, they say it may promote angiogenesis, the growth of new blood vessels, which is good in the context of tissue repair, where you need to get nutrients in and immune cells to help. Yeah, I can see that, yeah. On the flip side, cancer biologists think of angiogenesis in a very different light. Absolutely. And so, if you have a particularly well-vascularized tumor, that can lead to runaway tumor growth in a way that wouldn't happen. Wow. Because you're feeding the tumor. Wow. Wow. Not to say that, you know, it causes cancer or that it exacerbates cancer among people

28:29who have cancer who take it. Right. But I wouldn't rule that out. Yeah, that risk is definitely there. Yeah, for sure. So, I mean, clearly they have biological activity, but having biological activity is not a compliment when it's coming from a biologist. It could have benefits. It could have risks. I would want to see a very carefully studied and objectively studied weighing of those benefits and risks in formal clinical studies before I would take any of these types of... Is there a list of the good guys and the bad guys when it comes to peptides? Yeah, so all of the ones that you're going to be buying from these gray market, research-grade

29:04sources, I wouldn't touch them for the reason of both of those risks. Because some of them, you can even buy like retitrutide or trzepatide or semaglutide, the ones that are the real GLP-1 drugs. And it may be cheaper to get it through these unofficial sources, but I'm not 100% sure that

Future of computational drug discovery

29:19what's in the vial is what they say it is. I want to pivot to the anti-aging movement. But before I do that, to learn, at least for me for the first time, that a peptide is some transitional place between an amino acid and a full-up protein, and so much happens in our body or is prevented from happening in our body based on what proteins do, how they fold, how they behave. And given that AlphaFold just got the Nobel Prize for the AI application to solving the

29:54protein folding problem. It's AlphaFold 3, I think. AlphaFold 3. Yeah. In principle, if these molecules are so fundamental to everything we are, is that the future of our health? Just some brilliant people in the lab finding out how to- Puzzle these together. Puzzle these together. Yeah. And whatever is your need, this new chemistry gets introduced. There's some combination to address it. And then I don't have to go to the gym, I don't have to put on makeup, we'll get to

30:25that in a minute. I don't have to do any of these things, I can just sit with my ass on the couch and watch TV. I mean, I would be surprised if medicine didn't continue to get better and better. I would be astonished if these were the last peptide drugs that were ever approved. They're not the first either, I should say. There's something like 80 FDA-approved drugs that are peptides. So there will be more. Probably they will be better. Probably they'll be designed better, sort of with an in-silico approach, maybe with the use of AI. What's in-silico? Everybody knows what that means.

30:56Why are you even asking? Oh, I'm sorry. Chuck was on behalf of the people out there who may not know. What is in-silico? Yes, I mean, believe me, I know. Drug development is you take this library of 3,000, 10,000 compounds from microbes and from soil and from all different places, often natural compounds, and you've got a target. You know you want to modulate in the body, and so you screen 10,000 compounds, and you're looking for the hits. And then from those hits, which often came from a natural starting point, you modify them to say, okay, can we make it a little bit better activity, a little bit better safety?

31:29That's been kind of the cornerstone of traditional drug development. Or you vaccinate a mouse against something, and then you look through all its antibodies, and you try to find the best one, and you sequence that, and you turn that into a drug. I still consider that to be from a natural type of origin. Increasingly, as we understand kind of how you rearrange all these different building blocks, people can start to predict that using computational methods that I know nothing about. But I think we will see more power from those computational approaches, you know, with better computing potential and with better understanding of the biology itself.

32:00What does that have to do with in-silico? Oh, in-silico means in the chip, so like computer-based. Oh, computer. Oh, computer-based. Oh, computer helping you. Oh, look at that. Oh, I didn't get that. I didn't get that. So to Neil's point about anti-aging, all these peptides, all of these skincare regimes that are now coming through, playing straight into a vanity. Yes. A need to comply with the body type, the skin regime, whatever it is.

32:32I mean, is that just a human condition that we will hijack it just to look better? I think so. Look younger. Yeah, rather than it being, you know what, I need this for my health, dude. No, I just want to look more better. Well, I think it's, I mean, I think we all, we choose to present ourselves, like we've all made conscious decisions about how we're showing up here today. Today, right. What's curious to me, to Gary's point, is that we are rejecting wholesale the natural aging phenomenon of the human body.

33:02Mm-hmm. And I dropped an explainer on getting old. And I have strong thoughts about that. Mm-hmm. And I don't want people who are old to be viewed as something you never want to be, or never want to look like. Too late. It feels wrong to me. It is wrong. Socially, culturally. We've forgotten the respect your elders conversation we as young people had. Yeah, I see two things here.

Aging trends and bone density

33:30One is looking older and being older. And the second thing is, we know there's some stuff that happens as you get older. If you are 30 years old, you can bet, you're pretty sure, that with every passing decade, you're going to lose somewhere between 3% to 8% of your muscle mass. Muscle mass. Your cardiorespiratory fitness is going to be trending down. Your bone density, particularly in women around menopause, is going to be going down. Right. We know these things are going to happen. Let's not even talk about the prostate. Jeez. Yeah. Why do you always got to bring your prostate into all these conversations? Can you not tell that I am going through something, man?

34:04Okay, I didn't mean that. Okay, fine. Thank you. So what I was going to say is, those trends, you can never escape those trends. You're not going to go up in total muscle mass or bone density, probably, or cardiorespiratory fitness from age 30 to age 80. But you can totally influence the slope of that change. And so when I do videos, I'll talk about bone density or strength training or cardiorespiratory fitness and VO2 max. And it's not just pitched at people who are 50, 60, 70, 80, who are starting to worry about these things very acutely. It's also for if you're 30.

34:34Right. And you're in maximal control of what is the slope going to be over the course of decades. And VO2 max, that's the uptake rate of oxygen into the metabolism of your system. That's right. I'm going to say that correctly. Yeah. It's your total, if you're going max all-out effort, how much oxygen can you use? I think of it like, you know, if you're a car, it's the size of your engine. And having a bigger VO2 max engine means you have a better cardiorespiratory fitness total health. It's very highly predictive of your total health, total mortality.

35:06You increase it as you would expect by doing more aerobic training. So now going back to younger people, is health like saving money? Where if you start earlier, do you bank benefits later on in your life? Or is it something where it's like, Were you just a lazy-ass person? You're trying to get back in right now. Hey, man, what can I say? You can get back in now. There's no point. Get back in the game? I had some foolish years. That's all I can say. There's a really interesting study in people in their 90s who started doing a strength training program.

35:40They saw like a doubling in strength. Tremendous improvements in muscle. Like there's no point where it's, oh, it's too late for me to do this type of training. People, once they hit a certain age, men in particular, get bombarded with testosterone commercials. You've got to have it. It's going to be beneficial on a number of different aspects of your life. You'll like it, and she'll like it too. She'll like it more. Oh, that's right. Right, right, right. I still like it more. Okay, so possibly it's for the lead in your pencil, but that's other effect.

36:10Wait, what? It has other effect. What? I've never heard that before. Who gave me permission to say that?

36:22It's back in the game. Oh, that was hilarious. Really? Oh, that's so good. Okay, fine. It just depends who you write to. Anyway, that's enough of the jokes from me. Lead in your pencil. Is it that situation where you do naturally have diminishing testosterone over the years, or just is everybody different? Everybody is different, certainly. It's also a highly predatory market, and it's not just for older men, right? You see people 20, 30 years old on social media talking about being on testosterone. Yeah, but are they being led towards that by an influencer of sorts?

36:53Yeah, there's this optimization culture where even people who, you know, if you asked a clinician, you know, do they need to have more testosterone, and they would give you the answer of no. There's these hormone clinics who are trying to convince you that, oh, your testosterone may be in the normal range, but maybe it should be a little bit higher in the normal range, which is very not backed by evidence. The percent of people under 60... I like that. Very not backed by evidence.

37:22The percent of people under 60 who actually have low testosterone is on the order of 1%. Right. In their 60s, it's like 3%. In their 70s, I think it's about 5%. When they tried to recruit people for the big clinical studies, they pooled 51,000 people, 65-plus men, who thought they had symptoms of low testosterone. If they tell you that enough on an ad, then you'll believe it. That's just it, isn't it? If you hear it enough times, it must be true. But you have to understand that those ads are positioned in the same way like the Zodiac is.

37:52They give you very general traits that we all share. Do you feel tired sometimes? Do you feel tired sometimes? It's like, we all share these traits, and then they say, you must have low T. Does your chest go up and down when you breathe? Yeah. Yeah. I mean, 51,000 people who thought they had symptoms of low testosterone, six in seven of them did not. Only one in seven did. And so if you expand that out to the general population, it does happen. For people who do have low levels, replacement into the normal range can improve some things,

38:25particularly sexual symptoms, desire, libido, erection quality. Oh, really? Maybe some improvements in mood. There's a couple ingredients there, nitric oxide and, surprisingly, cardiovascular health is super important. But if you do have truly low testosterone, replacing back into the normal range can help some sexual symptoms. Maybe it can help mood a little bit. It can help bone density. A lot of the stuff, though, that you hear, or that you would, like, you're not going to hulk up from replacing into the normal range.

38:56If you think about, like, bodybuilder testosterone, steroid cycling, that's going well beyond the replacement dose, which is a totally different ballgame with much greater risks. And we've seen some of those risks with the Roy Raids, et cetera.

Testosterone replacement market

39:10So my issue about the aging wasn't just what happens to you metabolically or physiologically. It's just the overall appearance. Look at how much we invest in what we look like to look younger. Nobody's looking at your visceral fat. They're looking at your face, your skin, your... Well, we have a youth culture, that's why. And the reason we have a youth culture is because this may not still be the case, but I read an article about the psychologists that work on Madison Avenue and what they found...

39:41For advertisers. For advertisers, specifically. Right. So the deal is that in the surveys that they took, people over the age of 30 and pretty much every year after that become far more rigid in their purchases. And which means you have to spend a lot more money to get them to switch from Ford to Toyota or from Tide to Dash. And so the result is spend all your money at people who are 13 to 25 because those people

40:18haven't made up their mind. And if you can get them on board with you at that time, then the other advertisers have to spend money to get them later on. Brand loyalty. Brand loyalty. If I can get a younger person into my brand, then the chances of me keeping them further down the line is much, much higher. But the result has been, very quickly, all of our movie stars... You know, I grew up in a time where all the movie stars were old people. They were like middle-aged people. They're not now. They all look like Timothee Chalamet.

40:50You're sports stars, of course, because you've got to be young to play the sports. You're pop stars, all the music. So all of the cultural-like influences in our society are now owned by young people for the sake of advertising to those young people. So everybody else is like, well, I don't want to look old. Look at how everybody looks young. I don't want to look old. But what they forget, and this is what advertisers will never tell you, so you take it from me, all right? Young people are dumbasses.

41:22Stupid as hell.

41:25You don't want to look stupid, do you? See, that's my commercial. Okay. All right.

41:36So add to the list of things that happen as you age are these sort of horrific fate of the mental functioning of so many people in the form of Alzheimer's, in the form of dementia.

42:06These are clearly age-tagged ailments. And what kind of progress can we hope for these going forward?

Dementia risk factors

42:14There is some hopeful news here. The big one is there actually is a long list of risk factors that we know influence your risk for future dementia. Now, of course, even if you do all of them perfectly, you can still get dementia. Can we get to the drugs part? How much doing drugs does it mess up your... Check it out. Again, you check it for someone else. Yeah, yeah. The list, so I guess what I was trying to communicate was you can do all these things perfectly, you can still get dementia. So it's not a moralism about...

42:44It's the statistical risk factors that people don't know how to think fluently about. But yeah, it's a risk factor. It's a risk factor. And is heredity a big part of it? It is part of it. The ones I'm thinking about, so there's kind of three clusters. One is cardiometabolic risk factors. If you have better control of your blood lipids, your blood pressure, your blood sugar. So this is going back to the visceral fat discussion. Your cardiometabolic health, your brain, as it turns out, is a highly vascular organ. And the health of those blood vessels to your brain influences your odds for brain disease later. That's the first bucket.

43:14The second bucket I think of as environmental. So things like air pollution we know is associated with increased risk of brain disease later. I'm going to forget all of them. There's a list of 14 risk factors. The third bucket is things like social contact, which is linked to, you know, if you have challenges with hearing, getting that corrected reduces your risk for progression to dementia because it's linked to, you know, you may be shying away from social interactions, right? So they all kind of play together. Wow. But if you combine all these things together, I forget the exact number.

43:46I think it's roughly a halvening of your total risk for dementia is accountable to these various risk factors. The sum of them together will have your risk. In theory. So there is stuff you can do. It happens to be the exact stuff you already know you should be doing for every other chronic disease. But the idea that kind of it's totally up to fate is an incorrect one. There are things you can do to modify your risk. Okay. Is there anything we've discussed today in terms of a peptide or a supplement that is showing

44:18any signs of... You got something you can give us on the side when we turn off it? Yeah. You want to just slide one across the table? You know, you just kind of move it, you know, like across the table. It's going to take a long time for the data to give an answer either way. All right. I would be surprised if the GLP-1 drugs in improving all those cardiometabolic risk factors didn't give some reduction in risk for brain disease in the future. It's going to be a while before we come to that answer. But my guess right now is that improving those cardiometabolic risk factors now, maintaining

44:49it for decades, will probably reduce your risk for brain disease later. That's my guess. All right. So for creatine, there's very clear evidence that it can increase your benefits from strength training, build more lean mass on the order of 10 to 20%. Separately, what people often pitch it for is cognitive benefits. And so there, the evidence is much less clear, not particularly compelling as of yet. It could turn out in the future. Right now, what we have are small-scale heterogeneous studies that aren't often controlled. There was one last year that people bang on about on podcasts and social media.

45:24It was a group of 20 patients with Alzheimer's giving creatine and no placebo group, by the way, so uncontrolled. And their outcome of interest was performance on this cognitive test over time. And so they saw some improvements on some of the outcomes or processing speed on those test measures as they took the test time and time again. But one thing about taking tests time and time again, sometimes you get better at that test. So, you know, the authors of that paper are saying- They took the same test. I'm not sure if it was the exact same test instrument or the same type.

45:54But the authors are saying, you know, maybe this is an effective practice, which is well known, sort of in the cognitive testing space. So the authors are framing it as, it's feasible to give it to people with Alzheimer's. You increase the creatine stores in the brain. We're going to have to do bigger, better studies to show whether or not there is a benefit in amelioration of symptoms or people who don't have dementia yet in terms of reducing risk of getting dementia. That's what the authors are hedging. And then on social media, you'll see, take creatine. It's going to solve Alzheimer's disease. It's not going to be an issue. So there's this huge disconnect where the data are legitimately very uncertain as it

46:28relates to cognitive outcomes from these small studies. But people pitch it as it's going to solve all your trouble. And the main risk with that for me is knowing there is this long list of risk factors we do know influence your risk of dementia. What happens if people start thinking, all they have to do is take a scoop or two scoops or three scoops of creatine. If that in any way reduces the effort you're putting towards the risk of stuff we know matters, then that's going to be an indirect harm of taking creatine and thinking it's, even if it's not causing direct toxicity, you know, I consider that the absence of other actions.

47:00Right. Which I see as the main sort of category harm of supplements in general. NAD as an anti-aging. Now, I think it's nicotinamide, something like that, but I'm going to mangle whatever I think it is, but you're going to be able to tell me exactly what it is. NAD? NAD. NAD. NAD, adenine dinucleotide. Thank you. Everybody knew that. Wow. Apart from me. Nicotinamide. We are in an uncertain place where we know that, first of all, what does it do? It's important in energy cycling within your cells.

47:31It takes an electron, like when you burn sugar, it takes the electron, carries it to your mitochondria. It cycles that way many times in your body. The second thing it does is it's broken down by some enzymes related to DNA repair and inflammatory responses and stress that are pitched as like longevity enzymes called serjuins. Or things that people will want to have. Yeah. So this is all mechanistic. And this is a big, I write about this all the time. I talk about this in my videos all the time. There's a difference between improvements in some number on a lab test or a very compelling mechanism about why something should be important and showing that it's important in a clinical

48:05outcome. And so for NAD, what we see is clearly if you, as you get older, as you look at cohorts of people over time, levels go down. What you also see is if you supplement with nicotinamide supplements, levels go up very measurably. What people have not shown except for one particular case is that getting those levels to go back up improves outcomes in any meaningful way. Right. The one case where there is clinical data to show it is useful to have that happen is very niche. It's among people who are at high risk for skin cancer.

48:38In the study, they had had two skin cancers in the last five years or something. So not representative of the general population who took nicotinamide supplement. That's the one trial where they showed something like a 20 to 25% relative risk reduction of another skin cancer diagnosis. And so that's totally different from what you see on social media, which is the story of your levels go down as you get older. Therefore, take more. Take this. Right. Which, you know, in a cancer model in mice, actually, taking nicotinamide supplements led to worse outcomes. Oh. You can imagine all your cells in your body, you know, have this dependence on energy cycling.

49:12Maybe in some cases, that could be a bad thing depending on where you're starting from. Not to say it does cause cancer or exacerbate cancer if you have it and start taking it. More to say, I'm not particularly convinced. I know the answer to that. So people pitch you on this mechanism. On the numbers going down, you should make it go up again. What I would want to wait to see is how is it going to influence a clinical outcome in, you know, in a placebo-controlled study in a way that I care about. Interesting. So there's this noise out there in society that's coming from influences from social media

49:44that is affecting how we currently see our bodies, how we see the supplements and treatments. I mean, is that more a comment now on where we are as a society? How we've built up this pressure and people are just so, on occasions, ashamed of their bodies? Or they are needing to find a new way to look younger or, in their own mind, better looking? I did an experiment yesterday, actually. It's still running on my Instagram story.

50:16An experiment's a strong word for what it is. It's more of like a game. And the prompt was, okay, your goal, and maybe we can do this now, actually, before I give you the answer. So think of it as if you were answering it. And your goal is to make the options on this poll 95% option A and 5% option B. And so you click one of the two buttons, and you only see the answer from everybody else after you have chosen. Okay. Your prompt is, as a group, you have to make it so the answer is 95% people have chosen A and only 5% of people have chosen B.

50:46But you have to cast your own individual vote in that poll. And the poll is just A or B. I don't really know any. It's just A or B? It's just A or B. A or B. That's it. Well, I'm going with B. You know why? Because screw you.

51:00Forget the 95%. I don't ever want to be a part of 95% of anything. So I'm going with... So you're dealing with some skeptics here. Yeah. I'm going with B. Who are inherently difficult in their nature. So I think it's a B. Letters as a sequence in the alphabet happen to also be letters that you're graded in school where you're better or worse. So we have value judgments placed on whether something's an A or a B. That's true. And so... See, I never got that first letter, so it's not my problem. I think most people would want to be A. A. Yeah. B or A. You said want to be A.

51:32Sorry, sir. Sorry. Don't hit me. Okay. So I... Gary, what's your answer? I'll go with B because I just... I'm difficult. This is what I found. It was something like 24% of people chose option B. And so my reading, like clearly, like the logical answer is probably you should be choosing A for any individual person to get it as close as possible to 95-5 split. So I thought it might err on the side actually of above 95% being A, like you were thinking of. 24% instead of being 1 in 10, that's like 1 in 4. And so we see ourselves...

52:04And so behavioral psychologists will make fun of me for this interpretation probably and for calling this a study. But my reading of it, very amateurishly, is we see ourselves as exceptional, as not one of the crowd. Like, oh, everybody else is going to be voting for A. I've got to counterbalance it to get that 5% up there. But then we way overshoot beyond that. So I think there's something to that where, you know, it's like, well, I acknowledge that the clinical data for everybody else may tell this story. But what if I'm different? Yeah. Yeah. But see, those people are dumbasses. I'm sorry.

52:35What did you vote for? No, I'm not talking about that because that's just, that's really, psychologically, what your poll is also asking is, do you see yourself as a part of a crowd? Do you see yourself as a part of a group? Yeah. And there are a lot of people out here, believe it or not, who feel like they don't fit in anywhere. And so if you ask them, do you fit in? They're going to say, no. I happen to be one of those people who's always felt throughout my life, I don't really fit in. Like, I know how to get in, but I don't know how to fit in. Chuck, you fit in here with family. And I mean, I swear I'm not there here, Neil.

53:06All right. I'm sorry. Are we here? I mean, all right, I'm not qualified to analyze it as a psychologist, but you have body dysmorphia with a growing number of people. Are they the group that are 24% of the votes and there's pressure for them to look like the people in group A and they can't and they're shamed. And why is this even happening in society? Yeah. I think part of it is you feel like you are alone often in today's, like you're scrolling

53:42by yourself. There's not as much social connection as we have. And so you may not realize that there's actually a lot of other people out there who are voting be with you who may be feeling very similar to you in that respect, but you're not connected, you know, to each other. I think there probably is something to that. B people unite. Let's get together, B people. We got two t-shirts, one A, one B. One B, an A and B t-shirt. Oh, on the dysmorphia, there's a really interesting, there's like a Snapchat dysmorphia in the Journal of Plastic Surgery or something where they were writing about how people come in, you know, they're asking them what they want to look like.

54:13And they show them an image of themselves with a Snapchat filter on it. Oh, God. And so just fundamentally, like the disproportionate expectations from what can be possible in the real world is just being blown way out of proportion by what we see all the time, which increasingly is on our screen and not actual real people in the real world. So before we wrap this up, Neil, if I may, what are we more likely to get rid of? Of the obsession with looking young and the possibility of being old or unattractive?

54:43What one are we likely to get rid of? Or are we now in a one-way street? I can give you my answer for myself. I have an answer too, but go on. Sure. Which, for me, I'm focused on the stuff I can control, which is doing the strength running, doing the aerobic activity, doing the nutrition, improving my sleep. My sleep got a lot better in the last year. I'm sleeping 45 minutes per night more this year compared to last year. Good for you, lazy son of a gun. And the glow in your face shows. You lazy son of a gun, you. We'll save it for next time, what those changes are to sleep better.

55:14For me, that's what I'm focusing on. Like, I know otherwise my muscle mass is going to go down, my bone density is going down, my cardiometabolic fitness is going down. I know that by improving those things, I will feel better as I'm older. I'll be able to do more things with my daughter for a longer period of time. That's what I care about. All right. That's great.

Social media influence and integrity

55:30So the way you phrased that, I would have added a third option. Okay. Because you made it like it's only two directions on the street. Must we force ourselves to look younger or must we just get old? Accept getting older. And maybe looking old can be beautiful. Mm-hmm. Yes. I'd think so. Can you, in just a few sentences, convince an audience why they should pay attention to you online and not all of the noise competing with you in the very same space?

56:06What you'll notice is that when we talked about creatine, I didn't recommend a particular product. There's no affiliate code. Mm-hmm. When we talked about compounded peptides, there's no affiliate link. That's very not true on social media. Often people telling you to take creatine are saying, use my code. And by the way, behind the scenes, there's often a 30% to 50% affiliate kickback they're getting. Whoa. Neil, we got to start affiliating, man. We're in the wrong business. We got to get another game. We're going to get it on this action, guys.

56:37Yeah. Okay. You know, what I can say, like my business model, I run it, like there's a newsletter I do, a Substack newsletter. I have no ads. I have no affiliate deals. I have no sponsors on the letters. It's entirely reader supported. And so the reason for doing it that way, and I thought for a long time about this, is that means like my motivation is to give them the best information possible so they keep funding the newsletter. It is not to pitch the more expensive version of creatine that it doesn't matter compared to the less expensive version. It's not to pitch the more expensive air purifier just because I have a discount code.

57:11And so to me, that's kind of the only way that you can expect someone to believe what you have to say if they're telling you to do a particular action. Okay. Very helpful. And we're delighted to share your expertise with our audience. And I know they would eat it up. I mean, they're all scientifically literate. Yeah. And to get some physiological insights into our lives from especially you is of great benefit to us all. Yeah, you do a great service, I have to say.

57:41I watch all your videos. And I just love the fact that you bring peer-reviewed science and the best available information. You're not conjecturing. You're not trying to tell people anything that isn't just in the literature, which is great, but you make it accessible so they can understand it. So it's really a great service. I appreciate that. And this episode is brought to you by the Big Bang Never Happened Vitamins.

58:07Have you optimized your Big Bang?

58:10Nicely done. We've got a whole company. All right. Let me tell you something. I'd buy that product. All right. So we out. Again, Dr. Nock, thanks for coming back to us. Thank you for having me. Chuckie, baby. Always a pleasure. All right. Gary. Hey, my friend. Neil deGrasse Tyson here for another installment of StarTalk Special Edition. Until next time, keep looking up.