#344 - AMA #70： Nicotine： impact on cognitive function, performance, and mood, health risks, delivery modalities, and smoking cessation strategies
Episode Stats
Words per Minute
170.6406
Summary
In this episode, we discuss the distinction between nicotine and tobacco, and why nicotine itself is not the primary driver of the major health risks associated with smoking. We discuss the risks of nicotine use, including addiction, sleep disturbances, cardiovascular effects, and its impact on mood and anxiety. And we end this episode by looking at smoking cessation and considerations for those trying to quit smoking, which often involves using nicotine replacement.
Transcript
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?
00:02:31.900
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.
00:03:37.460
I am looking forward to the day when someone else hosts an AMA for me.
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
00:05:07.040
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
00:06:11.740
females. It turns out that if you want to talk about it through the lens of smoking, that's true.
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
00:11:08.100
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?
00:18:38.900
Thank you for listening to today's sneak peek AMA episode of The Drive. If you're interested
00:18:44.020
in hearing the complete version of this AMA, you'll want to become a premium member. It's extremely
00:18:49.820
important to me to provide all of this content without relying on paid ads. To do this, our work
00:18:54.880
is made entirely possible by our members. And in return, we offer exclusive member-only content
00:19:00.640
and benefits above and beyond what is available for free. So if you want to take your knowledge of
00:19:05.740
this space to the next level, it's our goal to ensure members get back much more than the price
00:19:10.400
of the subscription. Premium membership includes several benefits. First, comprehensive podcast show
00:19:16.760
notes that detail every topic, paper, person, and thing that we discuss in each episode.
00:19:22.420
And the word on the street is nobody's show notes rival ours. Second, monthly ask me anything or AMA
00:19:29.680
episodes. These episodes are comprised of detailed responses to subscriber questions, typically focused
00:19:35.240
on a single topic and are designed to offer a great deal of clarity and detail on topics of special
00:19:40.920
interest to our members. You'll also get access to the show notes for these episodes. Of course,
00:19:45.280
third, delivery of our premium newsletter, which is put together by our dedicated team of research
00:19:51.400
analysts. This newsletter covers a wide range of topics related to longevity and provides much more
00:19:57.320
detail than our free weekly newsletter. Fourth, access to our private podcast feed that provides you
00:20:04.640
with access to every episode, including AMA's sans the spiel you're listening to now and in your
00:20:10.580
regular podcast feed. Fifth, the qualies, an additional member only podcast we put together
00:20:16.880
that serves as a highlight reel featuring the best excerpts from previous episodes of the drive.
00:20:22.620
This is a great way to catch up on previous episodes without having to go back and listen to each one of
00:20:27.280
them. And finally, other benefits that are added along the way. If you want to learn more and access
00:20:32.940
these member only benefits, you can head over to peteratiamd.com forward slash subscribe. You can
00:20:39.760
also find me on YouTube, Instagram, and Twitter, all with the handle peteratiamd. You can also leave
00:20:45.700
us review on Apple podcasts or whatever podcast player you use. This podcast is for general informational
00:20:52.480
purposes only and does not constitute the practice of medicine, nursing, or other professional
00:20:57.100
healthcare services, including the giving of medical advice. No doctor patient relationship is formed.
00:21:02.940
The use of this information and the materials linked to this podcast is at the user's own risk. The
00:21:09.300
content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or
00:21:14.680
treatment. Users should not disregard or delay in obtaining medical advice from any medical condition
00:21:20.080
they have, and they should seek the assistance of their healthcare professionals for any such conditions.
00:21:25.640
Finally, I take all conflicts of interest very seriously. For all of my disclosures and the
00:21:30.780
companies I invest in or advise, please visit peteratiamd.com forward slash about where I keep an up-to-date