The Peter Attia Drive - #344 - AMA #70： Nicotine： impact on cognitive function, performance, and mood, health risks, delivery modalities, and smoking cessation strategies

00:00:00.000 Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the drive podcast.

00:00:15.820 I'm your host, Peter Atiyah. At the end of this short episode, I'll explain how you can access

00:00:20.280 the AMA episodes in full, along with a ton of other membership benefits we've created,

00:00:24.900 or you can learn more now by going to peteratiyahmd.com forward slash subscribe.

00:00:30.600 So without further delay, here's today's sneak peek of the ask me anything episode.

00:00:38.900 Welcome to ask me anything AMA episode number 70. For today's AMA, we're discussing a topic that has

00:00:45.160 been gaining significant attention in both the scientific community and among the public,

00:00:49.560 and that is nicotine. This is a topic that we get a lot of questions about, not only from our

00:00:55.220 audience, but also from my patients. In this episode, we discuss the distinction between

00:00:59.440 nicotine and tobacco, understanding why nicotine itself is not the primary driver of the major

00:01:04.740 health risks associated with smoking. We discuss the risks of nicotine use, including addiction,

00:01:09.980 sleep disturbances, cardiovascular effects, and its impact on mood and anxiety. We talk about the

00:01:15.400 various delivery methods of nicotine from traditional cigarettes, which I think everybody would agree are

00:01:20.260 bad, to pouches, gums, and synthetic options, ranking them from least to most harmful. The role

00:01:25.960 of nicotine in physical performance, cognitive enhancement, fertility, and its interaction with

00:01:30.800 other stimulants, such as caffeine. We touch on the guidance for those interested in minimizing the

00:01:35.960 risks while still using nicotine. And we end this podcast by looking at smoking cessation

00:01:41.920 and considerations for those trying to quit smoking, which often involves using nicotine replacement.

00:01:47.840 If you're a subscriber and you want to watch the full video of this podcast, you can find it on the

00:01:52.140 show notes page. And if you're not a subscriber, you can watch the sneak peek of this video on our

00:01:56.740 YouTube page. So without further delay, I hope you enjoy AMA number 70.

00:02:06.500 Peter, welcome to another AMA. How are you doing?

00:02:09.300 I'm doing really well. Thank you for having me back.

00:02:11.940 I mean, we're always happy to have you whenever you would like. And again, it'd be very awkward if

00:02:16.840 you weren't here. I think we do need to follow up based on one of our recent AMAs is, do you still

00:02:22.680 have a liquid of some form in front of you? I do. What kind of cup is that in?

00:02:28.540 You know, I'm actually drinking it in a glass.

00:02:31.900 Did you listen to our micro plastics AMA? And that's why you made that change?

00:02:36.200 Nick, I have made several changes following the AMA on microplastics. I believe that they

00:02:43.040 are all in the spirit of 80-20. So I'm really low on the sigmoidal curve of cost and energy

00:02:50.740 with one exception. And yeah, I think I'm just taking what I think are the relatively easy

00:02:57.320 steps to hopefully mitigate 80% of my exposure. And I'm going to spend no more time worrying about

00:03:04.220 the last 20%, which A, I have no idea if it matters. And even if it does, I don't think I

00:03:09.700 could live my life and be concerned with it. That's great to hear. Two things. First is,

00:03:15.840 by the time this comes out, we'll most likely have a short video on what those changes were.

00:03:20.660 So we'll link to that. If we don't have that video, something terribly went wrong. So we should

00:03:25.360 have it. The second is, are you just so happy that you continue to join us for these AMAs? Otherwise,

00:03:31.220 you would still be living so foolishly in your microplastic life. 0.90

00:03:37.460 I am looking forward to the day when someone else hosts an AMA for me. 0.85

00:03:41.160 Maybe an avatar.

00:03:42.520 That would be awesome.

00:03:43.620 We could just have AI Peter and it's just an ongoing AMA that never ends.

00:03:49.960 Well, today's AMA is not going to be that. It will be you live and it is on a single topic.

00:03:56.960 We get asked a lot about, there's so much more use of it. We initially did an AMA on it,

00:04:03.380 I think like four years ago. And at the time you didn't see as much use as you do now. And that's

00:04:09.080 nicotine. So we are going to talk all things nicotine today. This is going to look at benefits,

00:04:15.040 short-term, long-term around everything from cognition, exercise, whatever it may be,

00:04:21.160 risks of nicotine and things that people need to be aware of.

00:04:24.080 We're going to look at different ways and vehicles that people can use nicotine and what are the pros

00:04:30.720 and cons. And then we're also going to end this with something that we've been asked a lot about

00:04:35.680 every now and then when it comes to smoking cessation. And I think we often say a lot of

00:04:40.880 people in our audience most likely are not smoking because if you are, you're probably not opting into

00:04:46.060 this deep content, but some people are. But also we hear from people where it's, hey, my parents,

00:04:53.360 significant other, children, friends, whatever it may be, are still doing this. How can I talk to

00:04:58.700 them about quitting? So we'll cover that as well. So all that said, anything you want to say before we

00:05:05.440 get rolling? Nope.

00:05:07.040 This is a great insight that you added right there. So thank you for that. All right, start out. Can you

00:05:13.920 explain just where the field of nicotine research currently stands and what's new and distinct from

00:05:20.900 when we talked about this four years ago? One of the things that we appreciated, meaning the team

00:05:26.260 and I, as we were preparing for this was trying to appreciate how much of the research on nicotine

00:05:32.060 is based on tobacco and its first application through obviously cigarettes, but then also the

00:05:40.040 idea of using tobacco to extract nicotine for non-smoke but tobacco-derived nicotine versus synthetic

00:05:48.640 nicotine, which is honestly what a lot of people are thinking about in that context. And so I think that's

00:05:54.120 important to understand that it is not always easy to tease out the impact of nicotine. And I'll

00:06:00.660 foreshadow one example that we're going to talk about, which is infertility. You would think we

00:06:05.260 would have legions of data that would explain the effect of nicotine on fertility, both for males and 0.70

00:06:11.740 females. It turns out that if you want to talk about it through the lens of smoking, that's true. 1.00

00:06:17.220 But if you want to talk about it through the lens of vaping or nicotine pouches, that's not true.

00:06:22.420 And so I think that's one of the issues that I think makes this difficult to talk about with

00:06:26.740 complete clarity. So anyway, I guess that's the first thing I would say. I think the second thing

00:06:31.560 I would say is, and you alluded to this four years ago, we did an AMA on nicotine. Don't worry,

00:06:36.700 those of you that listened to that, there's very little overlap. I spent way more time talking about

00:06:41.580 how nicotine worked, mechanisms of action. Today, we're probably going to, I think, answer a lot more

00:06:46.360 of the practical questions that people have. And I will also say that four years later, there's frankly

00:06:50.880 more research on some of the benefits of nicotine. And to be sure, we're going to talk about both the

00:06:57.240 risks and benefits of nicotine today. So anyway, I would say that's probably a good place to start.

00:07:03.380 It'd be really helpful for people double-clicking on kind of one thing you hinted at there, which is

00:07:06.960 for a lot of people, when they hear nicotine, there's just a negative connotation. And usually

00:07:11.600 it's because they associate it with tobacco, cigarettes. And so their mind initially goes to

00:07:16.740 nicotine as maybe a negative, harmful thing. So do you want to maybe quickly disentangle for people

00:07:22.760 the health risks of tobacco from the effects of nicotine specifically?

00:07:29.640 Yeah, this is something I think I, maybe I didn't do a good job of this four years ago, or maybe I did.

00:07:35.120 And at the end of the day, people just don't appreciate nuance. But I remember being very

00:07:41.140 surprised at how A, people thought that the takeaway from the podcast four years ago was we should all

00:07:48.640 be using nicotine. And B, people were like, how can you advocate for this as a doctor? So my hope is to

00:07:55.900 untangle all of that for people. Nicotine is one of many compounds found within the leaves of the

00:08:03.000 tobacco plant. As such, it is in tobacco-based products. But the major health concerns that are

00:08:10.040 associated with tobacco, which are primarily cancer and cardiovascular disease, for reasons we can

00:08:16.840 talk about another time and we're not going to talk about today, are not caused by nicotine per se,

00:08:23.200 but instead they are caused by several other components of tobacco itself and tobacco smoke,

00:08:31.520 such as everything from toxic metals, formaldehyde, things called polycyclic aromic hydrocarbons.

00:08:38.260 These are actually the things that are causing the harm. Now, there are byproducts of nicotine

00:08:44.460 that are produced in processing tobacco and they can be carcinogenic. So that means, and this is a

00:08:52.080 very important point, I want to make sure if you're trying to pay attention to the key points, this is

00:08:56.120 one of them. This means that any tobacco-derived nicotine product may contain carcinogens. This was

00:09:04.640 actually something I did not appreciate prior. I thought that you could extract nicotine from

00:09:12.200 tobacco and be completely free and clear of carcinogens. That is not the case. I want to be

00:09:18.540 clear. It might be that, and it likely is, in fact, it almost undoubtedly is, that smoking tobacco

00:09:24.400 is a much higher level of risk. But I want to make sure people understand that if your nicotine is

00:09:30.560 tobacco-derived as opposed to synthetic, you are still probably assuming risk. So the level of

00:09:37.320 these compounds depends on the processing technique and the tobacco variety, of course. So they're found

00:09:44.500 in the highest concentrations in products that actually still look like tobacco. So I think

00:09:49.840 that's kind of a nice way to think about it. Everybody can imagine what a cigarette looks like.

00:09:53.200 If you take tobacco-chewing leaves, people chew tobacco, that's going to have a lot of the

00:10:01.560 negative properties. So the more closely you are to tobacco, the worse things are. So obviously,

00:10:06.640 if you're sticking it in a cigarette or a cigar or pipe, yep, you're getting plenty of it there.

00:10:10.500 If you're chewing it or taking it in snooze, also a big problem. So this is why I don't think I fully

00:10:18.200 appreciated this four years ago. When you take nicotine out of tobacco directly, you're still

00:10:23.320 assuming some of that risk that comes in curing and fermentation of the tobacco itself.

00:10:28.040 Before we move on, we should just address something because I forget sometimes people

00:10:32.300 get confused by it. And even earlier this week, we got an email to the website, which is,

00:10:37.420 Peter, for someone who cares so much about their health, why did I see an Instagram or YouTube

00:10:44.880 video of you where on your hat or your t-shirt, there was the Marlboro logo? Do you support

00:10:52.240 cigarette smoking? So while we have people, do you just want to explain why sometimes your clothing

00:10:57.880 has that and how you're not sponsored by big tobacco and that is not a, you should be going

00:11:04.800 and smoking Marlboro Reds on the regular?

00:11:08.100 Yeah, boy, that's okay. This is a philosophical issue, but as some people listening to this podcast

00:11:13.840 know, I am an enormous fan of Formula One and that goes way back for a long period of time.

00:11:20.580 And up until 2005, tobacco was a major sponsor of Formula One. In fact, the largest sponsor would

00:11:30.860 have been Marlboro and they were in the early 2000s all over the Ferraris and in the era that

00:11:37.820 is my favorite era of Formula One in the 1980s and the early 90s, they were all over the McLaren

00:11:43.240 car. And so you are correct. From time to time, you will see me wearing something or memorabilia

00:11:50.300 that I have that is a throwback to that era of Formula One. And I believe in the original livery

00:11:56.940 of those vehicles. In other words, I believe in era appropriate nods to things that we pay attention

00:12:02.540 to. And so, yes, if you're looking at a hat or a shirt or a car that is a replica or pays homage to

00:12:10.540 something of that era, you're going to see the livery of the sponsors of the time. And that would

00:12:14.460 have been Hugo Boss, Nacional, Marlboro. Anyway, there's nothing else I can say about it other than

00:12:20.980 it has nothing to do with a tacit or otherwise approval of these products. I want to be unambiguously

00:12:26.100 clear. I think smoking is an absolute error, arguably the single biggest unforced error you can

00:12:33.460 make with respect to your health. And fortunately, Big Tobacco does not sponsor motorsport anymore.

00:12:38.980 And I think they're better for it. Perfect. Back to the regularly scheduled program.

00:12:43.980 Nicotine. Are there any harms associated with nicotine itself based on what we just talked

00:12:49.320 about then? Well, we're going to go into this in some detail, but I would say that clearly the biggest

00:12:56.280 risk of pure nicotine, and now I'm just talking about it through the lens of synthetically acquired

00:13:01.720 nicotine, so you're getting rid of all the tobacco-related processing, is in its addictive nature.

00:13:07.260 And make no mistake about it, nicotine is highly addictive. There are some other areas where,

00:13:15.080 depending on the dose, there may actually be a harm. Again, I think this is very important to

00:13:19.560 understand. There are some mechanistic insights that suggest a negative impact on the endothelium.

00:13:26.940 And it's certainly plausible that anything that negatively impacts the endothelium could increase

00:13:31.900 the risk of cardiovascular disease. But these are not large studies. These are not studies that have

00:13:36.280 been done in humans. And these are extrapolations typically from other animal models. So I guess

00:13:42.640 we should probably just maybe spend a minute kind of talking about nicotine again. If people want more

00:13:46.660 detail on this, I think it's covered four years ago. But nicotine activates, so nicotine is a molecule,

00:13:52.860 and it activates something called the nicotinic acetylcholine receptor. Now, these receptors are not just in

00:13:58.880 the brain where we most frequently talk about them, but they can actually exist throughout the body.

00:14:02.760 And if you look at certain mouse models and rodent models, such as other rodents like rats,

00:14:09.520 it's been demonstrated that high doses of nicotine can actually increase tumor growth and even foster

00:14:16.980 metastases, in addition to increasing atherosclerotic plaques. Now, that sounds pretty devastating.

00:14:24.000 I just want to always point out, whenever we're talking about these rodent models,

00:14:28.280 there's lots of daylight typically between what happens in that model and what happens in humans.

00:14:33.160 And I think it's important to look at other ways to triangulate upon the answer. So we'll link to

00:14:40.000 those studies in the show notes. But the closest thing that we could find in humans was a 2024

00:14:46.920 Mendelian randomization. I know we talk about these a lot, but I always think it's worth explaining what

00:14:52.260 an MR is. So a Mendelian randomization says, let's look at genes in the population, which we can assume

00:15:00.360 are randomly assorted. That's the randomization part. And let's ask the question, will these genes

00:15:07.360 be a proxy for a behavior that I want to study or something that I want to study where I can now use

00:15:16.280 effectively observational tools to see if there's a difference? One example is Mendelian randomization

00:15:22.600 consistently shows that LDL cholesterol is causally associated with heart disease. Why? Because LDL

00:15:32.240 cholesterol is highly genetic and you can look across a population and see different levels of LDL,

00:15:38.840 even in people who are otherwise healthy. And you can examine the cardiovascular outcomes of these

00:15:45.280 people, which would be the dependent variable. And that's how you could infer causality. By extension,

00:15:50.700 by the way, HDL cholesterol turns out to be not causally related in the inverse. Nevertheless,

00:15:55.800 so if you look at this Mendelian randomization, they wanted to look at the relationship of nicotine

00:16:01.040 by itself on compromised lung function, lung cancer, COPD, CH, ASCBD, etc. Okay. I want to be clear.

00:16:08.220 I don't think this was the world's best MR. I think it was clever though. What did they look at?

00:16:13.360 Because like what genes would you try to parse out to understand how much tobacco someone is consuming,

00:16:18.700 which is what you actually want to be able to do. So what they looked at was they looked at genes

00:16:23.720 that spoke to nicotine metabolism. And so just as caffeine, we've talked about this in the past,

00:16:29.040 caffeine metabolism is highly genetic. So people like me are wickedly fast at metabolizing caffeine.

00:16:35.660 And therefore I seem to be able to drink it later in the day without a negative impact.

00:16:39.240 Someone who's a very slow metabolizer is going to feel it more. Similarly with nicotine,

00:16:44.040 you have high and low levels of nicotine metabolism. And what the authors of this study

00:16:48.760 postulated was people who are faster nicotine metabolizers are going to have lower levels

00:16:55.780 of circulating nicotine and therefore less nicotine exposure. Now, technically you could also

00:17:01.440 argue that maybe someone who's a faster nicotine metabolizer would smoke more or consume more nicotine.

00:17:05.880 So put that aside for the moment. But nevertheless, the authors used these genetic variants associated

00:17:11.400 with nicotine metabolism to adjust for basically smoking heaviness. And again, we're not interested

00:17:15.760 in the role of smoking. We're interested in the role of nicotine. Okay. Disease risk was increased

00:17:20.840 with slower nicotine metabolism, but the added risk was abolished when adjusted for smoking heaviness.

00:17:26.940 Because of course, if you do this, you have to adjust for smoking. Indicating that the main

00:17:32.080 drivers of the outcomes are the non-nicotinic components of cigarette smoke. Let me state

00:17:39.480 that again. This is a complicated MR, but it's the closest thing I think we have to looking at humans.

00:17:45.220 And it's looking at how much people smoked, how quickly they metabolize nicotine, trying to do an

00:17:51.380 overlay of that to appreciate the nicotine exposure. And it came away basically saying that the harm

00:17:59.080 of smoking is due to the tobacco and tobacco related products, not due to the nicotine. I want to be

00:18:05.820 clear, this is way, way far away from what you would want to be able to say is level one evidence.

00:18:13.500 If you wanted to do this in a level one fashion, you would actually have to randomize people to a

00:18:18.100 whole bunch of different tobacco-free nicotine products and study the outcomes of interest. Now,

00:18:24.480 of course, nobody's going to do that for hard outcomes like mortality, but I certainly think

00:18:29.820 people could do that for softer outcomes. And my hope is that somewhere along there, people do that.

00:18:35.260 What do we know about potential side effects of nicotine?

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The Peter Attia Drive - April 14, 2025

#344 - AMA #70： Nicotine： impact on cognitive function, performance, and mood, health risks, delivery modalities, and smoking cessation strategies

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