S05E99 Should I Take Rapamycin: The Fountain of Youth or Scientific Gamble?

Would you like to live 10, 15, or even 20 years longer just by taking a weekly pill? Join us as we dive into the buzzworthy world of rapamycin, a drug lauded by researchers as potentially the most powerful anti-aging treatment ever discovered.

Dr. Rhee shares his personal journey of considering rapamycin, offering an in-depth look at its history, how it works by inhibiting the mTOR pathway, and its promising results in extending lifespan in lab animals. Beyond just living longer, these animals stayed healthier, showing delays in age-related diseases including cancer. He also discusses the current evidence in human studies, potential benefits, and noteworthy side effects like mouth sores and metabolic changes.

Addressing the risks and practicalities of dosing, prescribing, and costs, Dr. Rhee reflects on why he is rapamycin-curious and the steps he might take if he began using it.

Whether you're new to the topic or deeply curious about longevity science, this episode provides a comprehensive overview of rapamycin's potential to help us stay youthful longer.

#Longevity #AntiAging #Rapamycin #HealthAndWellness #Biohacking #HealthyLiving #FitnessJourney #AgingGracefully #HealthyLifestyle #CrossFitLife #BotoxAndBurpees #health #movement

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S05E99 Should I Take Rapamycin: The Fountain of Youth or Scientific Gamble?

TRANSCRIPT

[00:00:00]

Sam Rhee: Hello, and welcome to Botox and Burpees. I'm Sam Rhee, your host, board certified plastic surgeon, CrossFit coach, who loves exploring where health, beauty, and fitness intersect. Thanks for tuning in.

Today, I want to talk about something that's been generating a lot of buzz in the longevity and anti aging world, a drug called rapamycin.

some researchers have even called rapamycin potentially the most powerful anti aging drug ever discovered. Now that's a huge claim, so let's dig into what that really means.

Now if you're watching on YouTube, you can actually see I'm holding up rapamycin. Which looks pretty ordinary actually, it's just some small white pills.

I had a physician prescribe it for me because I actually have been considering starting rapamycin myself, but I haven't started it yet.

Sam Rhee: But after one of my colleagues started rapamycin about six months ago and told me about the medication, I did a quick Google search and it's looked [00:01:00] great so far at first glance. But a couple weeks ago, when I got the medication before I was about to start it, I realized I really didn't know what this medication was all about.

And it was something that I was going to have to take for a long time to help me live longer. So before I actually decided to start, I wanted to actually research this medication, which I did.

And now I'm going to share what I found with you, my podcast audience.

Sam Rhee: All of us are looking to stay young, and it's obvious that it's very important to almost all of us. What's so funny is when I first brought the medication home, my spouse saw it and asked me what it was,

and when I said it was an anti aging drug, she immediately said, What? You're going to take a longevity drug and you aren't going to give any to me, so what, you're going to want me to die early and then you'll just keep living?

And I had to say, whoa, whoa, whoa, let's take a step back here. Sheesh. So in this episode, I'll be doing a deep dive into what rapamycin is and why people think it might help us live longer. I'll cover a bit of the [00:02:00] backstory. Of how it was discovered and first used in medicine, how scientists first found it could extend lifespan and lab animals and the mechanism behind how it works in ourselves.

I'll also go over the evidence for its longevity benefits. What studies and animals and humans have shown so far

and the reasons to be skeptical, including potential risks and side effects.

I'll talk through why I'm considering it as a part of my own health journey, but also what my reservations are.

And by the end, we'll recap the key points. Basically, is rapamycin a true longevity silver bullet, or just another far out, chancy, experimental elixir? But remember, as always, this podcast is not a substitute for professional medical advice, diagnosis, or treatment. This show is for informational purposes only.

treatment and results may vary based on circumstances, situation, and medical judgment after appropriate discussion. Always seek the advice of your qualified health provider with any questions you may have regarding medical care, and never disregard professional medical advice or delay seeking advice because of [00:03:00] something in the show.

And to emphasize this point, don't decide what to do with rapamycin for yourself until you see your own physician. Okay, so whether you've never heard of rapamycin or you've already gone down the internet rabbit hole on it,

we'll keep this conversation approachable, just as if we were chatting over a post workout FitAid. See what I did there? About this intriguing drug that might help us stay youthful. So let's start with the background on rapamycin.

what exactly is it? Rapamycin, also known by the brand name Sirolimus, is a drug that has been around for a few decades.

Back in the 1960s and 70s, researchers were exploring the soil on Easter Island. The island's local name is Rapa Nui, which is where the name rapamycin comes from, and they discovered a new compound produced by bacteria in that soil.

and by 1972, scientists had isolated this compound from the soil and named it rapamycin, initially noting it had antifungal [00:04:00] properties.

Sam Rhee: So at first, scientists thought it might be a useful antifungal medication.

however, as they studied rapamycin more, they found it had some other remarkable effects. It turned out rapamycin could suppress the immune system. In medical terms, an immunosuppressant. This made it extremely useful for a completely different purpose, which is preventing organ transplant rejection.

in organ transplant patients, you want to dampen the immune system to a certain degree so it doesn't attack the newly transplanted organ, and rapamycin was found to be effective for this. And the FDA approved it in 1999 for use in kidney transplant patients.

Sam Rhee: And since then it's been given to millions of transplant patients to protect their organs.

it's also been used in drug eluding coronary stents to prevent those stents from getting clogged and for a rare lung disease.

But the main thing to know is that rapamycin has been a legit medicine for years, typically given daily to suppress immunity just enough to help transplant [00:05:00] patients.

Now, why are we even talking about this transplant drug in the context of longevity? The link became apparent when scientists unraveled how rapamycin works at the cellular level. Rapamycin's big trick is that it inhibits a protein in our cells called mTOR, m t o r.

that stands for mechanistic target of rapamycin.

Yes, this protein is literally named after rapamycin because rapamycin was key to discovering it. mTOR as a protein is basically a master controller for cell growth and metabolism. You can think of mTOR as a central nutrient sensor. It gauges if cells have enough nutrients like amino acids, growth factors, energy, and decides if the cell should grow Divide, or instead, hunker down and do maintenance.

When nutrients are plentiful, mTOR is active and it promotes cell growth and proliferation. When nutrients are scarce, like if you're fasting, mTOR activity drops, and the cell shifts into maintenance mode, [00:06:00] which includes things like autophagy, which is a cellular cleanup recycling process. Rapamycin turns down mTOR activity, essentially mimicking a low nutrient signal, and by inhibiting the mTOR pathway, rapamycin causes cells to act as if they're in a calorie restricted or low energy state.

So why does that matter for aging?

Well, you may know that decades of research have shown that caloric restriction, where you eat significantly fewer calories while still getting nutrients, can extend lifespan in many organisms.

One reason is that it enhances autophagy and reduces cellular growth signals, which seems to slow down aging processes. mTOR is a key player in that whole story. So scientists theorized, if we use rapamycin to inhibit mTOR, could we get similar longevity benefits without actually cutting calories?

It's like a fasting impersonator at the cellular signaling level,

and sure [00:07:00] enough, when researchers started testing rapamycin in various lab organisms, The results were striking. Rapamycin consistently extended lifespan in every species tested. Yeast, worms, fruit flies. Mice all lived longer when given rapamycin. This is a big deal. There are a lot of compounds that might extend life in a worm but do nothing in a mouse, for example.

And rapamycin is one of the few that seems to work in many different species suggesting it hits a fundamental aging mechanism. It, in fact, rapamycin was the first drug proven to extend lifespan in a mammal mice in a rigorous excellently constructed study. And that opened the floodgates of excitement that maybe just maybe.

Rapamycin could have an anti aging effect in humans too. So to sum up the background, rapamycin was discovered on an exotic island. became a drug to help transplant patients by suppressing immunity. And in the [00:08:00] process of studying it, we learned that it targets an aging related pathway called mTOR. And in lab animals, turning down mTOR with rapamycin makes them live longer, presumably by triggering cellular housecleaning autophagy and dialing back some of the age accelerating processes.

It went from an obscure compound to a potential longevity. Superstar in the eyes of scientists,

which is quite the winding road for this medication.

so what are the evidence for longevity benefits?

it's one thing to have a theory that a drug might slow aging, but it's another to show actual data that it does. So rapamycin's impact on lifespan and healthspan?

Healthspan meaning healthy years of life.

The strongest evidence come from animal studies.

The landmark study that everyone cites was published in Nature in 2009. In that study, rapamycin was fed to middle aged mice. The mice were equivalent to about 60 years [00:09:00] The mice were equivalent to about 60 year old humans in age.

And it still extended their lives. This was remarkable because it suggested that it's never too late to start, even starting rapamycin at a later life phase. The mice lived longer. How much longer? Well, the rapamycin treated mice saw about a 9 percent increase in lifespan for males and 14 percent for females on average.

Now, that might not sound huge, but think of it this way. That's like giving a 60 year old person a drug, and they end up living significantly longer than they otherwise would have.

The mice lived about six months longer than their non treated counterparts.

And six months for a mouse that usually lives three years at most in captivity is roughly equivalent to 15 to 20 extra years of life for a human whose average life expectancy is currently around 75 to 80 years. So in mouse terms, the life extending benefit of rapamycin was quite significant. And since 2009, there have been many [00:10:00] follow up studies on mice.

Consistently, rapamycin extends median lifespan, which is the age by which half the population has died, and often maximum lifespan as well, pushing the oldest age that some mice reach. And depending on the strain of mice, dosage, and timing, the effects vary. But increases of 10 to 30 percent in lifespan are commonly reported.

And not only do the mice live longer, but they often stay healthier longer. Delayed onset of cancers, improved heart function in aged mice. One study even showed that brief treatments with rapamycin in early adulthood could have lasting positive effects on lifespan.

the evidence has been so overwhelming that one scientist said rapamycin is a universal anti aging drug in animals, extending life in all animals tested from yeast to mammals. It's hard to overstate how unusual that is in anti aging research. So what about higher animals like primates?

We don't have [00:11:00] conclusive lifespan studies and primates yet. Those take a long time.

but there have been trials in marmoset monkeys and currently in pet dogs like the dog aging project, which I mentioned in a previous podcast

to see if rapamycin can improve health span.

Sam Rhee: Some preliminary results in monkeys showed rapamycin was well tolerated and affected some aging biomarkers, but it's too early to say if it extends their lives. The dog studies are ongoing and so we will stay tuned on that front.

It's being taken very seriously. So moving on to human studies, the big question is, is there any evidence in humans that rapamycin could positively affect our aging or health? We obviously don't have a definitive give rapamycin to people and see if they live longer study yet because those will take decades and a lot of funding, but we do have some intriguing early findings.

One key area researchers have studied is the immune system of older adults. And as we age, our immune system tends to decline, which is why vaccines don't tend to work as well in the elderly and [00:12:00] infections can hit harder. Rapamycin's immune effects are complex. It suppresses some immune functions, but paradoxically, it might boost immune function in certain contexts by reducing chronic inflammation and rejuvenating immune cells, so to speak.

In 2014, a controlled trial was done where people over 65 were given a rapamycin analog, which is a drug similar to rapamycin or a placebo for several weeks. Then they all got a flu vaccine. The group that had taken the rapamycin like drug had about a 20 percent better response to the flu vaccine than the placebo group.

Sam Rhee: In other words, their immune systems reacted more vigorously, producing more antibodies. That was a big hint that rapamycin was kind of dialing back the immune aging and making the immune system behave more youthfully. That same study also noted changes in immune cell markers consistent with improved immune cell function.

Building on that, another study published in 2018 tested a combination of rapamycin related [00:13:00] drugs in older adults and found that something even more striking. The people who took the drug combo had fewer infections over the year compared to those who took placebo. To put numbers on it, in that trial, the treated group had 1.

5 infections per year on average versus 2. 4 infections per year in the placebo group in the follow up period, which is a significant reduction in illness.

They also confirmed the improved response to vaccines in this study. So not only laboratory markers, but actual health outcomes, the catching of fewer colds or infections, were better in the rapamycin group. And that's a pretty encouraging sign that rapamycin is doing something beneficial in the aging immune system.

Beyond the immune system, we don't yet have clinical trials showing, say, improved lifespan or clear cut prevention of diseases due to rapamycin. These studies are just beginning. There are also studies being planned or started for seeing if rapamycin can help with Alzheimer's disease, heart aging, and other [00:14:00] conditions.

But what we do have right now is a growing crowd of self-experimenters and physicians who are trying rapamycin for longevity and tracking results. There was a recent survey published in 2023 that collected data from 333 individuals who were taking rapamycin off label for health and longevity reasons. And the results were interesting.

the people generally reported positive effects, with many saying they felt healthier on rapamycin.

In fact, a large portion agreed with the statement rapamycin had anti aging properties and that their health had improved since starting it. They noted things like feeling more energetic, improvements in mood, and better physical health. Now this is all self reported and not a controlled trial, so take it with a grain of salt.

But it shows why enthusiasm is high. A lot of users are convinced it's helping them.

Let's talk about the early adopters and longevity enthusiasts.

In the biohacking community, rapamycin has become a hot topic over the past few years. Big names have publicly talked about it.

[00:15:00] Dr. Peter Atiyah, a well known physician focused on longevity has discussed rapamycin at length. He actually classifies rapamycin as one of the most promising longevity interventions as opposed to others that he thinks are overhyped. He has mentioned that he personally has used rapamycin, albeit cautiously, and he explores the science on his podcast.

Then you have tech entrepreneurs like Brian Johnson, who's famous for spending millions on anti aging experiments on himself. He, for a time, included rapamycin in his routine as well. He, for a time, included rapamycin in his routine as well. He was taking rapamycin for almost five years as part of his ultra quantified self experiment.

And a number of other doctors, such as Dr. Alan Green, Dr. Matt Kaberlin, have been vocal about rapamycin. Some actively taking it, some prescribing it, some as researchers. And all of this attention has led to rapamycin sometimes being dubbed the fountain [00:16:00] of youth in a pill in media headlines. Now, we should all be cautious when it comes to fountain of youth claims, because there's a lot of hype.

But the reason rapamycin stands out is that it actually has more serious science behind it than most supposed anti aging supplements. It's multiple studies across species and some human data hinting at benefits. So in a, so in summary, the evidence for rapamycin as a longevity drug is compelling, but still incomplete.

In animals, it absolutely extends life robustly. In humans, it seems to improve some aging related functions, such as immune performance, and anecdotal reports are positive. That makes it very promising. But it's not a done deal, which is a perfect segue into our next part of our discussion. The skepticism and the risks.

It almost sounds too good to be true, right? An existing, inexpensive drug that could help us live longer and healthier? Sign me up, but as a physician [00:17:00] and as a rational human, I have to emphasize we are not 100 percent sure rapamycin will actually extend human lifespan or even health span in the long run.

All the excitement is based on indirect, all the excitement is based on indirect evidence. We are not the same as mice or worms and we live much longer lives. It's possible that what works to extend the mouse life may not have a big effect on a person's 80 year old lifespan, or it could even have unforeseen consequences.

The truth is we won't know for sure until we have more data and that could take many years. There's a lack of long, there is a lack of large long term clinical data proving rapamycin users live longer or healthier.

Scientists like to say mice are not men, meaning promising results in animals don't guarantee the same in humans.

And because of this, many experts urge caution. For example, you won't find the FDA or mainstream guidelines telling everyone to go take rapamycin to slow aging. Far from it.

in fact, the FDA currently [00:18:00] doesn't even consider aging itself to be a disease, so you can't market a drug for aging.

So let's talk about the risks and side effects because rapamycin is not a benign gummy vitamin. It's a potent drug. The very thing that makes rapamycin useful, its ability to modulate the immune system and cell growth, can also produce side effects.

Transplant patients who take rapamycin daily, known side effects include things such as elevated cholesterol and triglycerides, mouth ulcers, slowed wound healing, rash or acne, edema, swelling, and of course, increased risk of infections due to immune suppression.

The doses and schedules longevity users take are usually much lower, so we don't see all those heavy side effects commonly, but some do carry over. One of the most common side effects, even on low once weekly dosing, is mouth sores, also known as apthous ulcers or canker sores. These are usually small sores on the tongue or inside the mouth that can be annoyingly painful.

They're not dangerous, but definitely a nuisance. Usually, they go away on [00:19:00] their own and they can be managed by adjusting the dose or taking a break.

and in the survey of rapamycin users I mentioned, the only side effect that stood out statistically were the mouth sores.

Another potential issue are metabolic effects. Rapamycin can cause a slight insulin resistance, meaning it might raise your blood sugar or reduce how effectively your body handles carbohydrates.

Why? Because mTOR is involved in metabolism and rapamycin, by inhibiting mTOR, can interfere with some of the insulin signaling pathways. So in simple terms, some people on rapamycin can see their fasting blood glucose level creep up, or their glucose tolerance worsen. There's also often a slight increase in blood lipids, cholesterol, and triglycerides in patients on rapamycin.

So you could be trading a possible long term benefit for a mild hit on your metabolic health in the short term. Now interestingly, in mice, these side effects, like higher blood sugar, are actually associated with longevity. But in a person, you obviously don't want [00:20:00] to induce diabetes or other issues related to increased blood sugar.

In practice, many doctors prescribing rapamycin for longevity will monitor these markers and, if needed, adjust diet, or add something like metformin, which is another drug, to counteract any blood sugar rise.

But it is a factor to be aware of. And now there's the big elephant in the room, immune suppression.

Sam Rhee: Rapamycin's whole job in transplant patients is to dampen the immune system so it doesn't reject a new organ.

When intermittently used at low doses, rapamycin seems to actually enhance some aspects of immune function like we saw with vaccines, but it's a fine line.

Too much rapamycin or too frequent dosing, and you could absolutely increase your risk of infections. There are anecdotal reports of rapamycin getting things like zoster or shingles, or slower recovery from viral illnesses, which could be due to the drug. Brian Johnson, who I mentioned earlier, actually stopped taking rapamycin after he experienced repeated infections that he and his doctors [00:21:00] felt might be linked to rapamycin.

He decided that risk wasn't worth it for him, and that's a cautionary tale. If your immune system gets a bit too suppressed, you might start catching every cold that goes around, or have minor infections more often. That risk likely varies person to person. Some people on low dose rapamycin report no issues with infections at all, but others might.

Another risk that's been discussed is effects on fertility or hormone sensitive pathways. Rapamycin can inhibit a lot of cell growth signals.

So there are concerns about, for example, reproductive cells or glands.

In animal studies, high doses of rapamycin can reduce sperm function or ovarian function, which makes sense, since it slows cell growth.

This might not be an issue at low doses, but if a young person who is still planning on a family, it's still something to consider.

We just don't have data on fertility impact in humans at the doses [00:22:00] used for longevity. Similarly, because mTOR is important for wound healing and muscle building, taking rapamycin might slow your wound healing a bit. And some people have noted that if they get injured or have surgery, they pause the rapamycin treatment to allow full healing, which seems prudent.

Given all these unknowns and side effects, many doctors take a cautious stance. For example, Dr. Andrew Huberman, a neuroscientist who talks a lot about health optimization, said publicly that while rapamycin is intriguing, as far as I know, he's not taking it for longevity right now because of the side effect profile and the lack of long term data.

His view, which I respect, is that it's a drug that can be taken relatively safely, but it has enough possible downsides that he'd rather wait until we know more, or until he has a clearer use of it, or until he has a clearer, or until he has a clearer reason to use it, and that's a totally valid approach.

In essence, the skepticism boils down to promising but unproven, and the [00:23:00] risks are you might be causing some harm in the short term for a benefit that isn't guaranteed.

If someone is otherwise healthy, do you really want them to mess with their pathways with a drug without certainty that it helps? That's the debate. Some people are comfortable with that risk reward ratio, and others want to see more evidence first.

We should also remember that everyone is different. A dose that might be fine for me might cause my friend to feel he A dose that might be fine for me might cause my friend to be lousy or get sick, depending on genetics, diet, or other medical issues. This isn't a one size fits all.

What about dosing and cost considerations? Let's say someone after doing their research and consulting a doctor is interested in trying rapamycin for potential longevity benefits. How do people actually take it in this context?

And what is the cost and what does it involve logistically?

these are obviously common practical questions.

Let's start with dosing. Dosing for longevity obviously is not the same as dosing for organ transplant.

In transplant medicine, rapamycin might be given every [00:24:00] day at 2 to 5 mg per day, or even sometimes after a higher initial loading dose. That daily regimen is what tends to cause more side effects than immune suppression. For longevity, nearly all experts and users favor an intermittent dosing cycle. For longevity, nearly all experts and users favor an intermittent dosing schedule, most commonly once a week.

A typical dose is in the ballpark of 5 to 6 milligrams weekly.

and some people will start lower like 1 to 2 milligrams weekly and then increase. Others might go higher if they tolerate it. There are folks out there taking 10 milligrams once a week, for example.

But surveys have found that most are using 5 to 6 milligrams weekly, which is the sweet spot that people settle on. The reason for once weekly dosing is to get a periodic knockdown of the mTOR pathway to trigger the good effects, but then to allow the mTOR pathway to come back to normal in between doses.

This intermittent approach seems to minimize side [00:25:00] effects while still providing benefit.

in fact, one paper noted that this weekly schedule is generally well tolerated with minimal issues aside from rare mouth sores. It does depend on the individual, however.

For example, one of my colleagues who has been taking rapamycin for six months adjusted his dose to seven milligrams every ten days because he was having a lot of GI upset.

So a higher dose spaced out longer seemed to work better for him. And he still gets those mouth sores, but he says that's not a big deal for him.

There is an ongoing debate about best dosing strategy, 10 days, 2 weeks, others have experimented with rapid mice in vacations, taking it for a few months, then pausing. Since we don't have definitive data, people are basically experimenting based on animal studies and theory.

We do know from mice that higher doses tend to produce bigger lifespan gains up to a point, but of course higher doses risk more side effects, so it's a balancing act.

One more thing on dosing, because rapamycin has a long half life, around two to three days in humans. [00:26:00] It's mostly out of your system by the next dose, but not entirely. That's why some choose, say, once every ten days, like my colleague, to be extra sure there's no continuous accumulation of drug. Again, these fine details are still being worked out.

If I were to start it, it seems reasonable to start at a once a week schedule to keep it simple, unless there's a reason to adjust. What about getting a prescription? Rapamycin is a prescription drug and you can't just buy it as a supplement at GNC. So how are people obtaining it for off label use? Well, there are a few ways.

There are an increasing number of doctors in the field of longevity medicine or integrative medicine who will prescribe rapamycin off label for patients who want to use it for healthspan. And one review mentioned there were more than 20 medical practices in the U. S. that were already prescribing rapamycin as an anti aging treatment.

There are also telemedicine services and longevity clinics that specifically cater to this. You can do a consultation, and if you're an appropriate candidate, they might prescribe it.

Additionally, because rapamycin is an FDA [00:27:00] approved medication, any licensed physician can prescribe it off label if they judge it's appropriate. Some patients have had luck talking to their regular medical doctors by presenting research, especially if they're older or have some condition that it might benefit.

For example, if a patient had a history of cancer, their doctor might be more open to it given rapamycin's anti cancer possible benefits.

Then there's the gray market route. Some people order rapamycin from international pharmacies since generics are made in countries such as India or even online I don't recommend going around prescribing practices without a doctor's oversight, but it does happen.

And one survey found about 20 percent of rapamycin users were taking it without physician supervision. Essentially self medicating. That just shows you how eager some people are to get their hands on it. But of course, ideally one should do it with medical guidance. Because you need that monitoring for safety.

What about cost? So here's a pleasant surprise. It's [00:28:00] not very expensive. It's a generic drug. The brand name Rapamune can be pricey. But the generic Sirolimus is relatively affordable.

Pricing can vary, but the cost for a typical weekly dose is usually about five to ten dollars a week.

Some of the U. S., some compounding pharmacies in the U. S. might charge a bit more. Or if you go through a longevity clinic, it might be marked up. But compared to many other medications or supplements, it's not a budget breaker.

Uh, one thing to watch out for if you're working with a clinic that provides a whole package of anti aging services, they might bundle the cost or charge a premium. But since rapamycin itself is a generic, you do have the option to shop around.

What about regulatory considerations? As I mentioned, rapamycin for longevity is an off label use.

That means it's legally allowed, but it's not an FDA recognized indication. As I mentioned, the FDA is not [00:29:00] evaluating rapamycin for aging because aging isn't classified as a disease. And there's no company that would spend the money to get that indication anyway because the drug is off patent.

Practically, it means you can't just go into your regular pharmacy and say, Hey, I want rapamycin for aging and get a prescription. It means we don't have official dosing guidelines and it's all community driven.

In terms of accessibility, because it's prescription only, the main hurdle is just finding a doctor or service willing to prescribe it.

And now my own personal reflection. I want to shift gears a little bit, talk about my own personal take, why I'm even considering taking rapamycin for myself, and how I would approach it.

I'll admit the whole idea of longevity and extending one's healthy years fascinates me as a medical professional and on a personal level.

I've dedicated my career to plastic surgery and wellness, helping people not only look better, but feel better.

As a CrossFit coach and someone involved in fitness Our goal is to be able to function [00:30:00] at the highest level for as long as possible.

I mean, who wouldn't want to be that 80 year old who's still crushing it in the gym or playing with their grandkids without getting winded? So rapamycin caught my attention because it's one of the first interventions that has shown real promise in actually slowing markers of aging, not just masking them.

Unlike Botox, which is a great drug, but just works on the wrinkles on the surface, or even exercise, which is fantastic for health, but has its limits. Trust me, I feel that at a 5 a. m. class.

Rapamycin works at a cellular level on a pathway we know is tied to aging. And that's profound.

is amazing that we might be able to influence the biology of aging with a simple pill.

So why would anyone consider taking rapamycin? I think the biggest reason would be prevention. I'm 55 years old and I certainly try to optimize my life to a reasonable degree. I try to do all the healthy recommended lifestyle things, exercise regularly, keep my [00:31:00] diet relatively clean. I wish I could manage my stress better and get more sleep, but I'm still working on that.

I don't have any major health issues and I want to keep it that way for as long as I can.

. So if rapamycin could even add a few extra healthy years, keep me healthier into my seventies, eighties, or longer, that's something I think anyone would be interested in,

especially if rapamycin can reduce the risk of big killers such as cancer, heart disease, or neurodegenerative diseases.

In animal studies, rapamycin has been shown to delay the onset of cancers and other age related disease.

For example, in the studies, all mice got the same diseases as they got old, but the ones on rapamycin got them later and sometimes less severely. This suggests that rapamycin isn't just making them live longer in a frail state, it's actually extending their health span.

And I find that really appealing. Our goal isn't to live to 120 if those extra years are bedridden.

Our goal is to compress the period of [00:32:00] decline and stay vibrant for longer. And rapamycin theoretically could help achieve that by slowing down the accumulation of cellular damage.

Also, I have to mention, as a plastic surgeon, I'm curious if rapamycin would have any noticeable effects on things such as skin aging. There's some evidence that it might improve skin quality. There have been some small studies of topical rapamycin on aging skin. Now I wouldn't bank on a fountain of youth for appearance specifically.

But you might think if it keeps you healthy, it would also reflect on the outside as well.

and anecdotally, my colleague has mentioned not only do their skin quality appear clearer, but their hair appears to be thicker, And their bald spot appears to be shrinking.

I don't know if that's a real effect or placebo,

but that would be great to have those side effects too. What are my concerns? Number one is safety. I'm wary of any longterm unknown effects. If I start taking rapamycin in my fifties and take it for decades,

what might happen that we haven't predicted? Could it be a rare side effect [00:33:00] that only shows up after 10 years of use? We just don't have long timelines and data yet. Now, for transplant patients, yes, some of them have been on it for long term, but they often take high doses, but they take high doses and they have other medical conditions in play.

I'm also concerned about the metabolic side effects. The last thing I want to do is induce pre diabetes in myself by taking a drug. That would be counterproductive. So, I'd have to monitor my blood sugar closely, and if I saw a trend upward, I might have to adjust my dose, or even take another drug, such as metformin.

I'm not terribly worried about day to day minor infections. Because I'm generally healthy, but if I started catching unusual infections or had trouble recovering from a flu, that would be a red flag. And I might stop the drug if that happened. Health always comes first. Longevity hacking comes second. I'm not going to risk serious illness now for potential benefit later.

And one other issue that we don't have [00:34:00] rapamycin could negatively affect muscle mass, and athletic performance. After all, rapamycin inhibits mTOR, and mTOR is a key driver of muscle protein synthesis. Some worry that it could impair muscle gains, or even accelerate muscle loss.

Now, right now, the available human data does not show a dramatic loss of muscle in people taking low intermittent doses.

Plus, there's anecdotal evidence of individuals who still maintain or can increase their muscle mass while on a once weekly regimen.

But this theoretical risk still exists, especially someone taking a higher or daily dose that inhibits the mTOR pathway more strongly.

So for bodybuilders or athletes who rely heavily on maximizing muscle protein synthesis, it may be prudent to proceed carefully, monitor strength and body composition,

Sam Rhee: and possibly adjust dosing if signs point to diminished muscle gains.

And I can already see a lot of people at my gym mentally crossing rapamycin off their list just with this issue, because they don't want to lose their gains, bro.

[00:35:00] So how do I plan to approach it? I haven't started it yet. I am rapamycin curious. I'll continue to talk to my doctor who has experience with rapamycin in patients. And even though I'm a physician myself. I value getting other experts, uh, opinions, especially those prescribing it. There are longevity clinics out there.

I might speak to some of my other local colleagues in geriatric medicine or endocrinology. And these discussions will help me weigh my personal risk factors and establish a baseline.

Before I start, I would get a baseline of various health metrics, blood work, including a complete blood count, uh, metabolic panel, glucose, liver, kidney function, lipids, inflammatory markers. Possibly a HB A1C, which is a three month average of a blood sugar level marker, possibly even immune function tests or an epigenetic age test.

I might also establish my exercise performance as a qualitative baseline. Maybe I'll [00:36:00] do FRAN, which is a popular CrossFit workout, before I start and then retest myself in six months.

I think the strategy is start low, go slow. I would probably start at a lower dose, maybe two milligrams weekly for a while, and then increase to five milligrams weekly if I felt that I was observing. And then I might increase to 5 mg weekly, uh, after observing if there were any possible effects. I would want to recheck my blood work, maybe every, I would want to recheck my blood work after several months to see if anything's changed.

Sam Rhee: Maybe my cholesterol spiked, or my blood sugar had increased. If my blood sugar went up, I'd consider adding metformin or adjusting my diet. And if my white blood cell count dropped significantly, that would certainly concern me about immune suppression.

I would want to continue all of my healthy habits. If anything, I might tighten them up even more to support my body. For example, rapamycin's benefits might depend on good nutrition and [00:37:00] not overeating. And maybe it might work best with synergy. And it might even work best in synergy with things such as exercise.

There is some thought that exercise and rapamycin are complementary in improving health span. I'd also want to avoid any immunosuppressive things.

I certainly wouldn't want to be on rapamycin and another immune suppressing drug such as prednisone simultaneously.

And it would be interesting to repeat an epigenetic age marker, Um, to see if there's any change in trajectory after starting rapamycin.

Although these are experimental, they might give me some insight.

I think the big thing is to keep expectations realistic. I don't expect to feel 20 years younger overnight or anything dramatic. In fact, if repamycin is working, I might not feel anything at all. It might just be quietly cleaning up my cells in the background. And the payoff might be invisible in the short term, where no news is actually good news, and I'm just essentially betting my [00:38:00] future on it.

And if I keep those expectations, I think I would be okay with that mindset.

I would probably commit to taking rapamycin for a year or two and then re evaluate. one advantage is if you do stop rapamycin, its effects, both good or bad, will wear off. You can always restart it later, it's not permanent. Some people do cycle it, as I mentioned, a year on, a few months off.

We don't know if that's a better approach or not, but it is something some people are doing.

Emotionally and psychologically, it's interesting to take a drug that can potentially slow aging. It almost feels sci fi.

I'd be lying if I said I wasn't at least a little bit excited by that idea. But I check myself by saying, alright, this is still experimental.

And I have a responsibility to do it in an informed way, and share honestly about it.

In summary, I'm drawn to it because of its strong science backing and possibility of extending my healthy years. I am cautious for the unknowns, and I don't necessarily need it right now. It's just a choice to potentially enhance my [00:39:00] future health.

If I proceed, I would want to do it in a careful, monitored way. Almost like enrolling yourself in an experiment where n equals one, which is myself. And I would hope to share those insights in a future podcast if possible.

So we've covered a lot. So let's zoom out, recap some of the key takeaways.

Rapamycin is a drug with a really unique pedigree.

discovered on Easter Island. Used in transplant patients and now repurposed in the labs of aging researchers. It inhibits the mTOR pathway, telling cells to slow down growth and rev up maintenance mode like autophagy.

And in study after study with organisms from yeast to mice, it's extended lifespan. That makes it one of the most promising potential anti aging therapies we know of.

Early human trials have not shown people living longer yet, but show some improvement in immune function and other health markers.

And many early adopters claim it's helping them [00:40:00] feel healthier. But it's not a proven fountain of youth for humans at this point.

It's an exciting hypothesis backed by strong animal data and some suggestive human data, but it's not definitive.

There are trade offs and potential downsides, mouth sores, metabolic changes, lack of muscle growth. It's a real drug that deserves respect.

In terms of dosing and cost, A lot of people are taking 5mg once weekly, which tends to be well tolerated. The cost is on the order of tens of dollars a month, which is quite reasonable.

But, since it's off label, you'll need to find a willing provider to get it.

From my perspective, I think it's promising enough that it's on my radar to possibly use for myself.

And I hope that this discussion has been helpful and informative.

In conclusion, I just want to emphasize that no longevity approach works in isolation. It's not a magic pill that means you can ignore all the other basics. You'll still need to exercise. Is the [00:41:00] burpees part of this podcast? Eat well, sleep, reduce stress, have social connections and so on. Those are the foundations, and if rapamycin works, it would be icing on the cake, but if it doesn't pan out, those foundational healthy habits will still carry you far.

I'm really curious to hear your thoughts on rapamycin. Have you heard about it before? Would you consider taking a drug to potentially slow aging or is that a line you wouldn't wanna cross? Maybe some of you have even tried rapamycin. And if so, I'd like to know about your experiences. please feel free to reach out. Instagram handle is at Botox and Burpees podcast or our YouTube channel. Any comments or questions? This is a rapidly evolving field.

I'm sure there will be new studies and findings coming out very rapidly.

Until next time, take care of your body. Take care of your health.

And as always, keep chasing that best version of yourself, whether it's a better skincare routine, hitting that PR in a gym, or maybe someday a little pill that will keep [00:42:00] you younger at heart. Stay healthy and see you next episode. Thank you.