Dr. Peter Attia

These are not studies that have been done in humans. And these are extrapolations typically from other animal models. So I guess we should probably just maybe spend a minute kind of talking about nicotine again. If people want more detail on this, I think it's covered four years ago.

These are not studies that have been done in humans. And these are extrapolations typically from other animal models. So I guess we should probably just maybe spend a minute kind of talking about nicotine again. If people want more detail on this, I think it's covered four years ago.

But nicotine activates, so nicotine is a molecule, and it activates something called the nicotinic acetylcholine receptor. Now, these receptors are not just in the brain where we most frequently talk about them, but they can actually exist throughout the body.

But nicotine activates, so nicotine is a molecule, and it activates something called the nicotinic acetylcholine receptor. Now, these receptors are not just in the brain where we most frequently talk about them, but they can actually exist throughout the body.

And if you look at certain mouse models and rodent models, such as other rodents like rats, it's been demonstrated that high doses of nicotine can actually increase tumor growth and even foster metastases, in addition to increasing atherosclerotic plaques. Now, that sounds pretty devastating.

And if you look at certain mouse models and rodent models, such as other rodents like rats, it's been demonstrated that high doses of nicotine can actually increase tumor growth and even foster metastases, in addition to increasing atherosclerotic plaques. Now, that sounds pretty devastating.

I just want to always point out, whenever we're talking about these rodent models, there's lots of daylight typically between what happens in that model and what happens in humans. And I think it's important to look at other ways to triangulate upon the answer. So we'll link to those studies in the show notes. But the closest thing that we could find in humans was a 2024 Mendelian randomization.

I just want to always point out, whenever we're talking about these rodent models, there's lots of daylight typically between what happens in that model and what happens in humans. And I think it's important to look at other ways to triangulate upon the answer. So we'll link to those studies in the show notes. But the closest thing that we could find in humans was a 2024 Mendelian randomization.

I know we talk about these a lot, but I always think it's worth explaining what an MR is. So a Mendelian randomization says, let's look at genes in the population, which we can assume are randomly assorted. That's the randomization part. And let's ask the question, will these genes be a proxy

I know we talk about these a lot, but I always think it's worth explaining what an MR is. So a Mendelian randomization says, let's look at genes in the population, which we can assume are randomly assorted. That's the randomization part. And let's ask the question, will these genes be a proxy

for a behavior that I want to study or something that I want to study where I can now use effectively observational tools to see if there's a difference. One example is Mendelian randomization consistently shows that LDL cholesterol is causally associated with heart disease. Why?

for a behavior that I want to study or something that I want to study where I can now use effectively observational tools to see if there's a difference. One example is Mendelian randomization consistently shows that LDL cholesterol is causally associated with heart disease. Why?

Because LDL cholesterol is highly genetic, and you can look across a population and see different levels of LDL, even in people who are otherwise healthy, and you can examine the cardiovascular outcomes of these people, which would be the dependent variable, and that's how you can infer causality. By extension, by the way, HDL cholesterol turns out to be not causally related in the inverse.

Because LDL cholesterol is highly genetic, and you can look across a population and see different levels of LDL, even in people who are otherwise healthy, and you can examine the cardiovascular outcomes of these people, which would be the dependent variable, and that's how you can infer causality. By extension, by the way, HDL cholesterol turns out to be not causally related in the inverse.

So if you look at this Mendelian randomization, they wanted to look at the relationship of nicotine by itself on compromised lung function, lung cancer, COPD, CH, ASCVD, etc. Okay, I want to be clear. I don't think this was the world's best MR. I think it was clever, though. What did they look at?

So if you look at this Mendelian randomization, they wanted to look at the relationship of nicotine by itself on compromised lung function, lung cancer, COPD, CH, ASCVD, etc. Okay, I want to be clear. I don't think this was the world's best MR. I think it was clever, though. What did they look at?

Because like what genes would you try to parse out to understand how much tobacco someone is consuming, which is what you actually want to be able to do? So what they looked at was they looked at genes that spoke to nicotine metabolism. And so just as caffeine, we've talked about this in the past, caffeine metabolism is highly genetic.

Because like what genes would you try to parse out to understand how much tobacco someone is consuming, which is what you actually want to be able to do? So what they looked at was they looked at genes that spoke to nicotine metabolism. And so just as caffeine, we've talked about this in the past, caffeine metabolism is highly genetic.

So people like me are wickedly fast at metabolizing caffeine, and therefore I seem to be able to drink it later in the day without a negative impact. Someone who's a very slow metabolizer is going to feel it more. Similarly with nicotine, you have high and low levels of nicotine metabolism.

So people like me are wickedly fast at metabolizing caffeine, and therefore I seem to be able to drink it later in the day without a negative impact. Someone who's a very slow metabolizer is going to feel it more. Similarly with nicotine, you have high and low levels of nicotine metabolism.