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What can we do about the aging process? You know, in the 21st century, are we any closer to cracking the code on aging? When we're talking about longevity, a lot of the people that are in the space have hacks and tricks. And in fact, one of my questions is about hacks and tricks and shortcuts. Our next guest is gonna talk about longevity hacks and how he's dispelled them.
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When you start to look into the research of resveratrol, it's a pretty wild story. It was hoped that by using resveratrol to activate Cytuin-1, a so-called longevity gene, that we could see these amazing benefits. That's where the excitement came from. Now, when other researchers tried to reproduce those results in terms of giving resveratrol to first yeast to see if it activates Cytuin-1, it didn't.
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Brad was graduated from the University of Auckland with a Bachelor of Medicine and Surgery. He specializes in primary care and practices at the Tuakau Health Center, again in Auckland, New Zealand. His YouTube channel has 204,000 subscribers. And on that channel, he shares the latest preventative care guidelines. Looking at the research over the past four years fairly intensively while I've been running my YouTube channel,
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I've not seen anything that will get us to 150, 100, what, 200. There's a lot of hype about all sorts of different cellular processes and, you know, the big one is cellular reprogramming at the moment. But speaking with other experts within the field that don't hype things up, I think it's decades if ever.
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Hi, my name is Chris Burris. I'm a longevity expert and the chief scientist at a lab focused on a longevity molecule. My primary focus is to help people live longer and better lives with science. Make sure to subscribe and share so you and your friends can live longer and better. Well, actually, so you and your friends can live beyond the norms. Dr. Stanfield, welcome. Thanks, Chris. Yeah, it's a pleasure to be here.
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All right. So before we jump into dispelling a lot of the longevity hacks, can you tell us a little bit about your background? So obviously you're in medicine and then there's kind of two phases, like first getting into medicine and then actually kind of stepping up and sharing with people the research. I don't even want to call it dispelling, just sharing the research that you found and how important.
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That informs your decision whether certain protocols you're going to take. But first medicine. And then then like how how did you get into longevity space? Yeah, so I graduated in 2015, as you said. So I've been a doctor for sort of eight years now. I originally got into medicine because I wanted to do something challenging, something that I could speak with people about and make a difference in the world. And so medicine kind of ticked all those boxes.
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And when I graduated from medicine and I started working in the hospitals, that's when I noticed some wrinkles around my eyes. And that got me interested in what can we do about the aging process? You know, in the 21st century, are we any closer to cracking the code on aging? So that got me interested in the field in the first place. And I looked at, you know.
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podcasts such as Joe Rogan, and that's when I came across David Sinclair. And looking at that podcast in particular, it sounded like we were on the cusp of these amazing breakthroughs in aging. And so I started my channel to sort of talk about that research. And the more that I delved into it, the more I realized that
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We actually are still quite a long way, if ever, of cracking the code on aging, but there's a truckload that we can do to prevent disease today. So that's sort of more the focus of my channel now is what can people do today that's evidence-based to prevent disease? And that's what I do in my clinic as well with my patients. So as you said, I'm a primary care physician. So every day in the clinic, I'm seeing patients
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And we're talking about what, you know, what diet can we do? What exercise can we do? What medications can we take now to prevent heart attacks and strokes rather than treating heart attacks and strokes? So that's my bread and butter. And again, my YouTube channel is there to talk about those guidelines because people go onto, you know, channels such as YouTube to figure out how can they be healthy? And unfortunately, there's a lot of misinformation out there. So my channel focuses in, again, on those preventative care guidelines and what the latest clinical research shows.
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Was there anything in particular? Did you already have a YouTube channel? Was there anything particular is like, wow, I need to have a voice on this particular subject. Was there one driving force behind that? So I was through high school. I was always very interested in sports. So I started taking things like creatine supplements, omega-3.
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So I was interested to see, you know, what the research showed there and I wanted to present that research. So that was the initial kicker or start for my channel was talking about, yeah, creatine supplements. And that's, you know, led me onto other things like metformin, resveratrol, any men, and you're looking at the research there. So,
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That was the initial reason, I think, to start the channel. What other things can we do in addition to diet and exercise to help with the aging process and to be stronger in terms of our muscle performance? I think we have, at least in that regard, a similar plan. What sports were you participating in typically?
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So I played rugby, athletics, cricket, tennis, all sorts at high school. So there's no time for sports now, unfortunately, aside from gym work and going up for runs to keep fit. But yeah, I used to play all sorts back in the day.
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It's interesting that you say that. So my sport of choice, which is not typical for an American, was soccer. I was playing soccer when it was literally described as a commie sissy sport. And it's very exciting to see how soccer has kind of excelled. I, too, at some point, kind of just in working out,
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Uh, it was turned on to creatine and I don't, you know, that's probably reading a magazine, like a muscle magazine and, and didn't, I don't know that I would have started a YouTube channel, but you're, you're just of a different era where you had that option. Cause you, when I was doing that, that, you know, coming onto the scene in that regard, I didn't have that, uh,
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that advantage, that availability to do the YouTube channel. So it's fascinating that you dig in, you dive into this, and you're clearly a person who's interested in sharing whatever knowledge you have. I mean, you know, if we're on YouTube, there has to be some sort of vanity involved in it, right? Whatever that means. But I think it's more altruistic in, hey, I've got this information, let me share it, because there's other people, you potentially had a hard time finding it. So let me share that. That's pretty awesome.
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So what's been the most surprising thing for you as your, we'll call you again, a longevity debunker? What's the most surprising thing? Yeah, I don't think I'd classify myself as a longevity debunker. I think there's a truckload that we can do today, again, to prevent disease and to lead healthy, long lives. So, yeah, I'm not sure about the debunking part, but I suppose...
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When I went into the longevity community, as it were, I was a bit naive. I think I was hoping that this community was grounded in science, that there wouldn't be too much hype, that we would be focusing in again on the preventative care guidelines.
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with some preclinical work that was exciting that people were talking about. I didn't expect the amount of hype and people shilling supplements and their latest so-called longevity protocols that aren't science-based. So I think with any community, you're always going to have a few people that spoil it for the majority, and that's the same in the longevity space. The surprising things, I suppose, is that there's some core pillars that people talk about within the longevity space.
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It's things like metformin, intermittent fasting, NMN. I was surprised because there's a lack of evidence for those interventions. Also, the low-protein diet as well is one of the big ones. So, yeah, I spend a bit of my time on my channel speaking about that research and about why potentially those methods aren't great for people. If anything, they might be harmful.
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um and and then trying to shift the attention towards the things that actually matter so it's actually a high protein diet it's resistance and cardio exercise making sure that you're a healthy weight and then there are again a few other supplements like creatine which we've mentioned that do make a difference to people's health um and their lifespan hopefully so yeah that that's that again that's the shift in my thinking around this space
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Well, and we're going to jump into that because from some of your videos, my kind of position on metformin is certainly a little more aware, I think, in MN. Let me get that the right way. And then resveratrol, I'd like you to speak about those. Yeah.
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In fact, let's let's jump into Metformin. Right. Give give the background of why Metformin came onto the scene. I think you're you're probably well versed in that. And then what was that turning point? Because I think you said you you took Metformin for a while. It was on it was actually on your protocol for a while.
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Yeah, that's right. So metformin has been used for decades and every day at the clinic, I'm prescribing metformin for my pre-diabetic and type 2 diabetic patients. So what we're talking about here is non-diabetics using metformin. So the hope from some initial mice studies was that it would extend lifespan and it would do that by activating AMPK and making us more insulin sensitive.
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And there was initial excitement from the human research as well, because there were a couple of papers showing that type 2 diabetics who only needed metformin to control their diabetes seem to have lower rates of heart disease compared to non-diabetics. So again, that fueled the excitement about metformin. And again, since it's so widely used and there aren't that many side effects,
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for diabetics, people were, again, excited about it and wanting to take it to extend their own lifespan and prevent disease. So it's a noble cause. The trouble is we've now had multiple other papers showing that there's actually no benefit for non-diabetics. So if we start with the preclinical work, the initial mice studies were...
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They were done in inbred mice who developed high blood pressure. So if you're an inbred mouse with high blood pressure, maybe metformin's a good idea. But for the mice who are genetically diverse with no pre-existing health issues, when they were tested in the interventions testing program, there was no lifespan benefit seen. So the preclinical work, in my view, for non-diabetics doesn't support the idea that we should be using metformin.
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I think I know where you're going next. So I just want to outline this. Right. So the reasons to be excited about metformin. Right. It's inexpensive. Like that's one of the key ones. Extremely well documented to have low side effects. And and conceptually, if you have people who are in a diabetic group, which is typically more of a health challenge group.
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they were outperforming or doing better than some of their cohorts without diabetes. Like you're checking the checkbox of like this logically makes sense. And then you're saying, well, hold on, because in healthy rats, it's not making that much of a difference. And now here, I think, is where you start to lean on some additional data more related to humans. And I think this is I just wanted to outline that. And yeah, go ahead.
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Yeah, that's right. So the initial human studies that were developing a lot of the excitement about metformin, they were observational studies. So they're just taking the population and observing them to see what happens. So it's not a particularly strong piece of evidence. What we ideally want to rely on is a randomized controlled trial. And that's what was done by the Diabetes Prevention Program. So this study started in the late 1990s, where they took individuals who were overweight,
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Half of them received metformin and the other half a placebo, and the participants didn't know which one they were taking. And these participants were followed up for about 10 to 15 years.
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was no benefit seen in terms of mortality or death rates. There was no improvements in cancer rates and heart disease. In essence, there was no benefit seen for those non-diabetics. And again, those non-diabetics were high risk because they started the trial as overweight. So the MICE studies don't support the idea that we should be using metformin for otherwise healthy rats.
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The human research doesn't suggest that there's any benefit. And I wouldn't make such a song and dance about this if we don't actually see downsides to metformin. So there are downsides. It's not without risk. The downsides of metformin is that it does lower testosterone levels.
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And we've got multiple human studies now showing that if you take metformin, you blunt the positive effects of exercise. And how we know this, again, using randomized controlled trials, one group was taking metformin, the other group were taking a placebo, and both groups were exercising. And what they could see at the end of this 12-week study...
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is that the group who didn't take the metformin, they had a higher VO2 max, which is a marker of fitness compared to the people who were taking metformin. So it was roughly half the benefit that the metformin group were getting. So they were knocking the exercise performance gains by half. So it's not without its risks. So that's why I talk about it on my channel because
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People, again, want to be healthy, but by taking metformin, you're probably making the situation worse. You're probably worsening your health. And it had an additional, you're talking about VO2 max, which is really a good indication when you start thinking about longevity. But it also has a negative impact on gains associated with building muscle, right? The actual muscle mass.
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Yeah, that's right. That's right. So you're not as strong, you're not as fit, and you've got lower testosterone levels by taking metformin for non-diabetics. Now, again, those risks, they're vastly outweighed by the benefits for diabetics and pre-diabetics. So again, that's why I prescribe metformin every day at the clinic.
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Um, but again, for non-diabetics who are taking it for longevity purposes, you're probably doing more harm than good. And again, that's why I highlight this on my channel. So, so excellent. I think that's a lot of people are not slowing down and looking at all of those details. And, um, it'd be interesting to see somebody have a rebuttal. I don't have one.
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Right. Like this feels like solid research. You're talking about placebo controlled double blind studies. I don't know if they were double blind, but they're at least single blind, if not double blind. So it's a pretty phenomenal and important foundational report.
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This is why the preventative care clinical guidelines don't suggest using metformin for non-diabetics. So again, as medical practitioners, we've got guideline databases basically telling us exactly what the latest treatments are for various diseases. And ideally, most doctors should be following those guidelines word for word, because again, that's the latest and best ways to treat
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do not suggest using metformin. So that's why on my channel, I really try and emphasize what the preventative care guidelines show because those guidelines are fantastic. And I wish that more people would follow them because we would be a truckload healthier compared to what we are as a community now. Excellent. And I'll probably jump into some more questions about that. Let's move on to resveratrol. So was resveratrol something that you did have in your stack at one point?
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Coming back to the beginning of my channel, this is when I was a bit naive and trusted what people were saying rather than actually looking at the research myself. When you start to look into the research of resveratrol, it's a pretty wild story.
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So the excitement came in the early 2000s around a group of enzymes called cetirins. It was hoped that by using resveratrol to activate cetirin-1, a so-called longevity gene, that we could see these amazing benefits. Yeah, that's where the excitement came from. Now...
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When other researchers tried to reproduce those results in terms of giving resveratrol to first yeast to see if it activates the two-in-one, it didn't. When other researchers tried to give resveratrol to mice to see if it extended their lifespan, it didn't. And that was over and over again shown.
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Now that original resveratrol research was bought by GSK for $720 million, all based on hype that was unreproducible, again by multiple different labs. And GSK spent millions more trying to develop so-called Situin activators,
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And they spent about five years heavily researching and investing in this field. And they just couldn't get anything to work, including separate molecules that were specifically designed to activate situins. Again, no benefits were seen. So about five years after they spent that $720 million, they shuttered the doors. Now, unfortunately, resveratrol is still available today and it's hyped heavily by certain individuals. Right.
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But again, I wouldn't make such a song and dance about it if there weren't risks involved. So just like metformin, it blunts the positive effects of exercise and it lowers testosterone levels. How it actually seems to work, and this was based on a 2020 CRISPR paper, so using the latest technology to see exactly the effect that resveratrol has on human cells, it stresses them. So basically, it's a poison, it's a microdose of poison, and when you start to...
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increase that dose, you start to get more and more side effects. So again, no benefits. You're just micro-poisoning yourself by taking resveratrol. So again, that's why I make a song and dance about it because people want to be healthy, but they might be taking a molecule that's worsening their health.
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And they might even be taking more, right? Like I think resveratrol certainly fits into this kind of band of, hey, probably more is better as a thought process for users. And in reality, that's not true. Like you're taking a microdose of poison and you're actually increasing it. So that would be counterproductive.
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Yeah. And unfortunately, the resveratrol story has kind of morphed into people saying, okay, well, there might be a hormetic effect. So just like exercise, you stress your body. And therefore, that signals to your body that you need to become more efficient. What about if we apply that same logic to resveratrol, where if we give microdoses, so microdose typically in the 50 milligram or 100 milligram dose of resveratrol, maybe that will offer benefits.
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And again, that's a nice theory, but there's no evidence to suggest benefit. There's no randomized placebo-controlled trials that robustly show benefits by taking that dose of resveratrol. If there was good evidence, we would see it in the preventative care guidelines. But again, we don't. And those guidelines specifically say or recommend to not take resveratrol, again, because it's a poison.
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It's interesting. You talk about the hype. I think certainly what was first hyped about resveratrol was that it's found in red wine. And so now red wine is good for you. And I have no doubt that the preventative guidelines say that red wine is not good for you. I don't think there's really anybody around who's saying that it's good for you. You mentioned that it had a dampening effect right on similar to metformin. Is it better or worse or was it on par? Yeah.
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It was roughly on par. So it blunted the positive effects of exercise again by about 50%. So that's roughly in line with what metformin did. So again, if you start to stack these so-called longevity interventions on top of each other, you are drastically worsening your health. You can only, like, I use, when I first started my channel, I used to take metformin and resveratrol. And I was wondering why I was feeling rubbish at the gym. And it was because I was taking these molecules.
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So again, people want to be healthy. It's just unfortunate that a lot of misinformation online is out there from hypesters that's actually worsening people's health. Yeah, no, that's, yeah, that's, I mean, one of the big reasons that I wanted to have you on this summit. I think next on the list is NMN, right? Nicotinamide mononucleotide. I think I'm really close on that.
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Yeah. So again, this is a, um, it's a really interesting idea. So one of the central molecules to our metabolism is NAD. And there's a suggestion that NAD in certain tissues in our body, um, goes down as we age. So if we can replenish NAD, we can hopefully make our metabolism more resilient so we can be more resilient against diseases and age-related diseases. Um,
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So it's quite an easy concept to explain to people. And if you take these precursors, so NMN or NR or nicotinamide, you can replenish your NAD levels and ideally be healthier. So that's where a lot of the hype around NMN started, again, from the similar people who were promoting metformin and resveratrol.
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Does NAD also affect sirtuins? Is that associated or is it a different thing altogether? There are many different processes and enzymes within our cells that use NAD. So sirtuins are one of them, but there's many, many others. So if you boost NAD, in some experiments, you can see more activity of sirtuins, but that doesn't mean that the NAD itself is activating
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Okay. And so NMN, it has this impact. You're looking at NAD, which is something that drops off as we age, right? And like so many things- Well, even that is controversial. So to take a step back and to actually figure out how sound this theory is, there was a recent study in humans that came out. Again, this is an observational study, so we can't be too rock solid about the results, but they found some
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They took muscle biopsies from younger adults, so they were in their early 20s, and then they took muscle biopsies from older adults. Now, some of the older adults were regularly exercising, they were doing resistance training, they were going out for runs, and other older adults weren't. And what they found is that the older adults who were exercising, their muscle NAD was very, very similar to younger adults, whereas the older adults who weren't exercising, that's when the NAD was starting to go down.
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So there's a strong possibility that if we simply focus in on a good diet and regularly exercise, our NAD levels will be absolutely fine because we've got the salvage pathway within our cells to recycle NAD. So again, my thinking about this is that it's likely that we don't need these precursor molecules. All we need to do is have a good diet and regularly exercise,
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It sounds like I'll never forget. I read an article, I think it was in Men's Health Magazine, and the title of the article, and this is some 15 plus years ago, was that your metabolism slows down as you age, which really frustrated me because I don't want to read that. I don't want to hear that.
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And then the entire article went on to say, no, your metabolism doesn't drop as you age. You slow down and that slows down your metabolism. Right. So we talked about playing sport. I've always felt like as you get older, you tend to do other sports because you have more control. You tend to do like running or triathlons because you could control when you train. Right. One of the reasons I stopped playing soccer was I just wanted my Saturdays back.
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Because if I'm playing soccer, you know, certainly as I got older, it was an entire Saturday was gone because of soccer. Like if some of it was the exhaustion after the game.
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And I wanted that back. So I ended up now I train and my wife and I run half marathons. So so that entire article was like, yeah, no, you just slow down. And in every case, when those elderly people who had, quote unquote, slow metabolisms started getting more active, their metabolism sped up. And it sounds like that's what you're describing with NAD.
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Yeah, I think, again, there's a lot of hype about NMN or NR supplements or nicotinamide. The other thing that people need to know about is that we've used these precursor molecules for decades in medicine. So back in the day, we used to use niacin to lower LDL cholesterol levels. Now, that's no longer used because niacin has got some other toxic side effects at the higher dosages, so it's no longer used.
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We know a truckload about boosting NAD by using these molecules. And there's a reason why it's no longer used in medicine because there's no benefit seen. We always want to have a bit of a shortcut. And there are a couple of shortcuts in terms of, you know, things like creatine and whatnot, but the fundamentals of preventative medicine is a great diet and regular exercise. And I'm not convinced that mega dosing these NAD precursor supplements is
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has much of a role or any benefit for humans. You are enjoying, well, at least I hope you're enjoying, the Live Beyond the Norms podcast. Make sure you subscribe, make sure you follow, and make sure you share. But don't be that annoying guy, whatever you do. Don't share it with people who aren't actually interested in living beyond the norms. So you've got a good...
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consistent story with metformin, right? Like, so, hey, we've got the data. Really, it's not beneficial. And not only is it not beneficial, it's detrimental. A lot of people will say that berberine is a good replacement for metformin. So maybe you don't want to do this off-label prescription drugs.
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And you do berberine. How does berberine fit with kind of your logic? Yeah, so berberine is a weak AMPK activator compared to metformin. So if we wanted to activate AMPK, I think we should do it pharmacologically because we know the dosages. We know the dose response. We can make sure that the product that you're taking is pure. So I'm not too excited about that side of the story.
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Berberine has another effect, which is on cholesterol levels. So it does act as kind of a weak PCSK9 inhibitor. So it does have a slight cholesterol-lowering effect. So...
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The PCSK9 inhibitors in terms of the drugs today, they are incredibly expensive. So some patients, if they wanted to explore supplements because they have, for their own personal reasons, definitely don't want to take drugs, but they want to turn to supplements.
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Um, berberine is something that they might consider, but again, the, if we really wanted to take a scientific approach to this, and if we wanted to take something to lower our cholesterol levels, in addition to diet and exercise, we've got fantastic medication options available today that are cheap, that are very effective and that are proven to lower cardiovascular disease. So again, I, I'm not excited by berberine because it's, um, it's, it's, it's, it's, it's, it's,
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it we've got better drugs to do the same uh effects are you talking about statins or did i get am i kind of one cholesterol molecule off like are statins what you're comparing them to or may or no no there's there's a separate class of cholesterol-lowering medication called pcsk9 inhibitors um so so they're injections at the moment that you give you know either fortnightly uh monthly or six monthly so they're they're
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They're brilliant medications with a very low side effect profile that do lower your cholesterol levels. They do lower cardiovascular disease, but they are incredibly expensive. So berberine looks like it works in a similar way, but just not as effectively. So that's the other effect that berberine has.
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Okay. And actually, I kind of brought it up myself. Statins is something that I've read that I think that there's some good data on longevity. Are you aware of that and where does that sit? Yeah. So statins online have got a terrible reputation. A lot of people online who will say, you know, statins cause all sorts of side effects. They are terrible for your testosterone levels, that they wreck all sorts of processes in your body and they should be avoided like the
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Clinical medicine has a very, very different opinion. And that opinion, again, is based on the sound scientific research that we've got in the form of randomized controlled trials. So statin medications, they lower your LDL cholesterol levels, and they've been shown overwhelmingly to reduce cardiovascular disease and mortality rates.
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Um, but essentially that there's a big trend going on at the moment in clinical medicine, that the lower your cholesterol levels, the better in terms of the more protection you have against heart disease and strokes. So, um, I, I take a low dose statin called, um, resuvastatin. So I take resuvastatin five milligrams. And the reason why I take resuvastatin is that it's incredibly targeted to the liver
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So that's where the statin should be acting to lower your cholesterol levels. And it doesn't get into places that it shouldn't. So it doesn't get into your brain or your muscles or your fat. And there's also a truckload of evidence showing that statins have no effect on your hormone levels. So they've got no effect on your estrogen levels, on your testosterone levels. So there's, again, a lot of misinformation online.
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um about statins if you take a low dose statin particularly one such as rosuva statin which is off patent it's incredibly cheap i i pay nine dollars for my three month subscription um or prescription uh again you can lower your cholesterol levels prevent cardiovascular disease and the studies show live longer
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Is there any kind of LDL too low? Like the current mindset is a lower LDL is always better. Yeah. So we've got studies going out about three to five years looking specifically at that question. What happens if you have a super low LDL cholesterol level? So say below 30 and they looked at hormone profiles. They looked at, you know, cognitive performance. There was no downside seen. So it looks like there is no downside.
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downside to lowering your LDL cholesterol. Now, for some patients, say with statin medications, there are some side effects that we do need to talk about. So some patients, even if they take a low dose resuvastatin, there's a small chance about one in a hundred patients that will get muscle aches.
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So some patients will get muscle aches. And that's kind of the biggest side effect. The other side effect, if you start to boost the dose of your statin, there is a slightly higher chance of developing type 2 diabetes. So we do need to know about those side effects. But again, for most patients, if they use resuvastatin at a very low dose, it's highly unlikely that you're going to get any of those side effects. And if that low dose of the resuvastatin is not enough, there's many other factors that
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cholesterol-lowering medications that we can use combined with that statin. So we can use, for example, another one called ezetimibe, which prevents your gut from absorbing as much cholesterol. So that works really well together with the statin if you combine it because it's working on different pathways to lower your LDL cholesterol levels. So again, there's many things that we can do now to prevent disease. And yeah, I hope that more and more people get on that bandwagon.
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of preventing disease rather than waiting for something to go wrong and treating it. So you mentioned that that second drug would actually block the absorption of cholesterol in the gut. In my mind, like at first we're like, hey, you have high cholesterol, you need to cut out all fats and everything that had been kind of rewritten and that it's actually other things that are causing these higher LDLs. Talk to me a little bit about that.
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Yeah, so this is a common point of confusion that I see in the clinic. So there's a distinction between dietary cholesterol, which is often found in things like eggs, and saturated fat, which is found in fatty cuts of meat or animal fats. So...
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overwhelmingly if you the evidence shows from cochrane reviews and randomized controlled trials if you lower your saturated fat intake you will lower your ldl cholesterol levels but if you lower your dietary cholesterol again dietary cholesterol is different to saturated fat if you lower your dietary cholesterol levels for most patients they won't see much of an effect yes there's a small minority of people that are hyper absorbers of dietary cholesterol but they're relatively rare
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So if people lower their dietary cholesterol levels, that doesn't have much of an effect in terms of your blood cholesterol. So that's the distinction and that's where people often get confused. So in terms of how azetamide, which is the medication that we're talking about, works, so your gut or your liver also produces a lot of cholesterol that is then reabsorbed by the gut. So if you block that reabsorption process, again, you can lower your cholesterol level. So it's not...
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It's not so much to do with what you're taking in. It's more what the rest of your body is doing in terms of producing its own cholesterol. Okay. It just happens to be at the gut, but it's not necessarily from the food that you've consumed. Correct. Yeah. Excellent. Let's get on to the next one, which I think is one, the origin story of rapamycin is just amazing. If anybody out there doesn't know the origin story...
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I first heard it on a podcast called Radiolab, and it's just an absolutely amazing story. But you're supporting a rapamycin study. Talk about rapamycin, what's behind it, and this study that you're supporting.
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Yeah, so rapamycin is a really interesting molecule because of the preclinical work that we've got. So overwhelmingly, whenever rapamycin is tested in mice, it extends both male and female lifespan by over 20%, which is huge. And that is a reproducible finding.
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The trouble is rapamycin has got a bit of a dirty name in clinical medicine. So it's used in clinical medicine to help prevent organ rejection. So if you have a kidney transplant, for example, one of the medications that you'll commonly be on is rapamycin to prevent your own immune system from destroying that donated organ.
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So it's quite difficult to get trials underway in otherwise healthy people looking at rapamycin to see if we can use it to help prevent disease and extend human lifespan. So one of the things that I'm really interested in is what can we do to prevent muscle wasting as we get older? Because that's one of the biggest risk factors for frailty, right? So the patients that I see in the clinic,
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If they can't, you know, do the hobbies that they want to do, if they can't toilet themselves, if they can't get up from a chair, that's massive. And if we can, you know, prevent that muscle decay from happening, that's huge in clinical medicine.
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So the trouble is when, as we get older, we seem to over activate an enzyme called mTOR. So people who go to the gym generally want to activate mTOR because that's the muscle building switch, if you like. If you activate mTOR, you will build up your own proteins and build up your own muscles. Um...
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So given that we're over-activating mTOR in our muscles as we get older, you'd expect our muscles to be getting stronger. But the opposite happens. And the trouble is when you're over-activating mTOR, you're never allowing your cells to activate another process called autophagy. So that's the cell clearance process. So what seems to happen is that we're building up all of these old damaged components.
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and never giving our body a chance to get rid of them. And that's where rapamycin comes in. So rapamycin works by switching off mTOR. So the theory goes that if we can have periods of time where we use rapamycin to switch mTOR off, we can get rid of these old damaged components so that when we start exercising, we can rebuild new components and hopefully that way we can improve muscle performance. So that's the trial that I'm setting up, that people will take rapamycin
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Not every day. They'll take it intermittently. And then other periods of time, they'll be exercising. So you're switching mTOR on and then switching it off again and on and off. And hopefully we will see muscle performance improvements. So yeah, we're still fundraising for that trial. But hopefully we'll have it funded by the second half of 2024. That's the goal. So yeah, it's exciting. That's very cool.
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I find it fascinating. MTOR, right? It stands for a mammalian target of rapamycin. So it's actually a component in our body that's named after a drug found in an island. Like it's just a fascinating story of MTOR. With rapamycin, are there any concerns? Like I heard first about it probably in 2019. And the context of the conversation is like, there's some crazy people out there taking rapamycin, right? Yeah.
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And I think my understanding was like getting too much of it was dangerous, but extremely dangerous. What are the concerns with rapamycin at this point? Yeah. So as I mentioned previously, rapamycin is used to prevent your own immune system from attacking donated organs. So it's used in medicine as a immunosuppressant, right? So you're suppressing your immune system. So one of the concerns is if you're taking rapamycin, particularly at dosages that are too high, will you be more susceptible to cancers or other infections?
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So there was a randomized placebo-controlled trial looking at mTOR inhibitors, so again, blocking mTOR, to see what effect they would have on the response to the influenza vaccine. The hope was that if we can use mTOR inhibitors to clear away the old components of our immune system, maybe we would have an improved immune response.
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Now, unfortunately, that trial failed because it didn't show an improvement, but crucially, the mTOR inhibitor group, they had just as much response to the influenza vaccine. So I think so long as we dose rapamycin correctly, I'm not particularly concerned about the immunosuppressant effects. So in the trial that I'm designing,
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And we're still trying to work out the exact details about how often we want to dose rapamycin. But we're thinking that we only want to dose rapamycin once a month. And that's because rapamycin in the current forms that we've got, it's got a really long half-life of about three days. So if you take rapamycin once, it lasts in your body a really long time. So yeah, we think that if you just take it once a month, that will offer all of the benefits that you need or that you'll get from rapamycin without the side effects.
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That's fascinating. Right. So then you could take it infrequently. And I don't need a specific answer to this question. I'm just kind of interested. Is there anything that your intuition is driving you to consume above like the current research? Like it sounds like if you had easy access to rapamycin, you might be taking it even though the- No, I wouldn't take rapamycin. No, I wouldn't take rapamycin.
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No, we don't know enough about rapamycin. So it's a really interesting molecule. The preclinical research is fairly sound. There's not enough human research in healthy individuals looking at rapamycin and what the effects might be. Again, coming back to metformin, we were so excited about metformin, but actually it caused more harm than good. So I'm a bit conservative with rapamycin. I think it needs to be studied and those studies need to be funded.
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But until those studies are completed and showing a true benefit, I personally wouldn't take it. That makes sense. All right. So I feel like we could have a lot more to talk about and maybe we'll talk off air of maybe bringing you back.
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But I want to kind of get to our wrap up questions. And the first one is, how long do you like what's your target age for living? Like how old do you want to live to? I want to live a healthy 105 year life and there will always be the eventual decay. So I'd imagine living to about 110. Yeah.
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So that's kind of the goal that I've got in my mind. And I look at, say, for example, the reason why I'm taking a statin medication. So if you look at the trials, they're generally over a five-year period in terms of the statin trials, and they do show a reduction in cardiovascular disease. But the absolute risk reduction isn't actually that much. But when you compound that over a really long time, that's when you see a significant benefit.
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of resuver statin. So yeah, that's kind of my goal and my thinking. That makes sense. So between 105 and 110, do you have a picture? So David Sinclair in his book is like, the levers have to be there, right? And I think he makes a compelling argument for that. Do you have a sense of what is the, like, are we ever going to get to 150, 200, maybe infinite lifespan? What's your thoughts there? Yeah.
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Looking at the research over the past four years fairly intensively while I've been running my YouTube channel, I've not seen anything that will get us to 150, 100, what, 200. There's a lot of hype about all sorts of different cellular processes. And the big one is cellular reprogramming at the moment. But speaking with other experts within the field that are…
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that don't hype things up. I think it's decades if ever away. Let's share, if you could, two to three protocols, habits, mindsets. We'll call them shortcuts because everybody likes shortcuts. Two longevity and a long health span that you would share.
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Yeah. So I think coming back to diet and exercise. So one of the biggest misconceptions in diet is around protein. Ideally, we want to be having 1.6 grams of protein intake per kilogram of body weight per day. Now that is a lot. So say for an 80 kilogram person, that's about 128 grams of protein. All right, let's say 80 kilogram. Let me work that into pounds because most of my audience...
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I'm an engineer by education and even that. So that puts out about 176 pounds. So in terms of getting that protein intake, so let's take beef for an example. 100 grams of beef is about 25 grams of protein. So to reach the protein targets, you'd be having around half a kilogram of beef every day. Now I'm not saying that you should do that. I'm just trying to give that as an illustration about how difficult it is to reach those protein targets.
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So with my patients that I see in the clinic, every meal, I want them to make a conscious thought about where's my protein coming from in this meal. Am I having chickpeas, lentils, beans? Am I having tofu, chicken, fish? Where is your protein coming from in each meal? And most of the time, I'm suggesting to my patients to take protein shakes. So just make sure it's a no sugar option.
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from the observational human research that we've got, people who have higher protein intakes live longer and they're also stronger. That 1.6 gram of protein intake, that target comes from the exercise studies that we've got showing that there doesn't seem to be much, if any, further benefit beyond that 1.6 gram target in terms of your muscle performance and the gains that you get from resistance exercise. So I think that's the biggest one that is often...
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Yeah, misunderstood. People need to be getting more protein. And then on the flip side is exercise. People need to be doing resistance exercise. Ideally, so if a lot of patients at the clinic, they'll tell me that they go for walks or they do gardening, which is great. I certainly want them to continue doing that.
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But the advantage of resistance exercise is that you can push yourself to near failure. So what I mean by that is, say, if you're doing push-ups and you're getting to the point where you can no longer do one more push-up, that's failure. And when you approach that point, that's a powerful signal to your muscles to become stronger, that they need to adapt to that stress that you're putting them under. So yeah, I think those are the two crucial things that I think people need to do to significantly extend their health span.
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I've been hearing a lot about, you know, doing much shorter to failure exercise where you actually don't even need to spend as much time. If you were like me, sometimes I would spend one to two hours in the gym and I, you know, one, I don't have the time now and two, it's just not an efficient use of the time that I do have. And so that that makes a lot of sense. All right, Dr. Stanfield, how can people contact you? And I'm assuming like give them some guidance on getting to that rapamycin study for funding.
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Yeah, so I've got my website, drstanfield.com. I'm on YouTube. If you search up Brad Stanfield, I'm there as well. And also on Twitter. So yeah, a couple of places you can reach me. All right. And last question. What in the near future are you excited about?
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Rapamycin. If we can show that by using rapamycin, we can stop or even reverse the age-associated decline in strength, that's pretty game-changing. So rapamycin. That's pretty good. All right. So you can find him, drstanfield.com. And you can also find him on Instagram, which is bradstanfield, right? If they're looking on Instagram. I don't have Instagram just yet, but Twitter and YouTube, you can find me. Yeah.
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Excellent. Dr. Stanfield, thank you so much for joining us. Cool. It was a pleasure. Thanks, Chris.
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