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Welcome to ask me anything. Am a episode number 74. Today's am a, we're discussing a topic that has been gaining significant attention in both the scientific community and among the public and that is nicotine. This is a topic that we get a lot of questions about not only from our audience, but also for my patients, in this episode, we discussed the distinction between nicotine
And tobacco understanding why nicotine itself is not the primary driver of the major health risks associated with smoking. We discussed the risks of nicotine use including addiction sleep, disturbances, cardiovascular effects, and its impact on mood and anxiety. We talk about the various delivery methods of nicotine from traditional cigarettes, which I think everybody would agree or bad two pouches gums and synthetic options ranking them from least to most harmful the role of nicotine and physical performance. Cognitive enhancement fertility and
It's interaction with other stimulants, such as caffeine, we touch on the guidance, for those interested in minimizing the risks while still using nicotine. And we end this podcast by looking at smoking cessation and considerations for those trying to quit smoking, which often involves using nicotine replacement. If you're a subscriber and you want to watch the full video of this podcast, you can find it on the show notes page and if you're not a subscriber, you can watch the sneak peek of this video on our YouTube page. So without further delay, I hope you enjoyed
A number 70
here. Welcome to another am a, how you
doing? I'm doing really well. Thank you for having me
back. I mean we're always happy to have you whenever you would like. And again, it'd be very awkward if you weren't here. I think we do need to follow up based on one of our recent amas is, do you still have a liquid of some form in front of you? I do, what kind of cup is that it,
you know, I'm actually drinking it in,
In a glass,
did you listen to our micro Plastics AMA? And that's why you made that change
Nick. I have made several changes following the AMA on microplastics. I believe that they are all in the spirit of 80/20. So I'm really low on the sigmoid 'l, curve of cost and energy with one exception. And yeah, I think I'm just taking what I think are the relatively easy steps to hopefully mitigate
80% of my exposure and I'm going to spend no more time worrying about the last 20%, Which a, I have no idea if it matters. And even if it does, I don't think I could live my life and be concerned with
it. That's great to hear two things. First is, by the time this comes out will most likely have a short video on what those changes were. So we'll link to that. If we don't have that video, something terribly went wrong. So we should have it. The second is our you just so happy that you continue to join.
Join us for these amas otherwise you would still be living. So foolishly in your microplastic
life. I am looking forward to the day, when someone else hosts an AMA for me,
maybe an avatar. That would be awesome. We could just have a i Peter and it's just an ongoing AMA that never ends. Well, today's am a is not going to be that it will be you live and it is on a single topic. We get asked a lot about, there's so much.
More use of it, we initially did an AMA on it, I think like four years ago and at the time you didn't see as much use as you do now and that's nicotine. So we are going to talk all things nicotine today. This is going to look at benefits short-term long-term around everything from cognition exercise, whatever it may be risks of nicotine and things that people need to be aware of. We're going to look at different ways and vehicles that people can use nicotine.
And what are the pros and cons and then we're also going to end this with something that we've get asked a lot about every now. And then when it comes to smoking cessation and I think we often say a lot of people in our audience, most likely are not smoking because if you are, you're probably not opting into this deep content, but some people are. But also we hear from people where it's, hey, my parents significant other children friends, whatever it may be, are still doing this. How can I talk to them about quitting?
So we'll cover that as well. So all that said, anything you want to say before we get rolling? Nope, the great Insight that you added right there. So thank you for that. Alright, start out. Can you explain just where the field of nicotine research currently stands? And what's new and distinct from? When we talked about this for years ago,
one of the things that we appreciated, meaning the team and I as we were preparing for this was trying to appreciate
She ate how much of the research on nicotine is based on Tobacco and its first application through obviously cigarettes but then also the idea of using tobacco to extract nicotine for non smoke but tobacco derive nicotine versus synthetic nicotine which is honestly what a lot of people are thinking about in that context. And so I think that's important to understand that it is not always easy to tease out the impact of nicotine
And I'll foreshadow one example that we're going to talk about which is infertility, you would think we would have Legions of data that would explain the effect of nicotine on fertility, both for males and females, it turns out that if you want to talk about it through the lens of smoking, that's true. But if you want to talk about it, through the lens of vaping or nicotine, pouches, that's not true. And so, I think that's one of the issues that I think, makes this difficult to talk about with complete Clarity. So, anyway, I
I guess that's the first thing I would say, I think the second thing I would say is and you alluded to this for years ago, we did an AMA on nicotine, don't worry those of you that listen to that, there's very little overlap. I spent way more time talking about how nicotine worked mechanisms of action today. We're probably going to, I think answer a lot more of the Practical questions that people have. And I will also say that for years later, there is frankly more research on some of the benefits of nicotine and to be sure we're going to talk about both the risks and benefits of nicotine today.
So anyway, I would say that's probably a good place to
start would be really helpful for people double-clicking on kind of one thing you hinted at their which is for a lot of people when they hear nicotine there's just a negative connotation and usually it's because they associated with tobacco cigarettes and so their mind initially goes to nicotine is maybe a - harmful thing. So do you want to maybe quickly disentangle for people? The health risks of tobacco from the effects of nicotine? Specifically.
Yeah.
Yeah this is something I think I maybe I didn't do a good job of this for years ago or maybe I did and at the end of the day people just don't appreciate new ones. But I remember being very surprised at how a people thought that the takeaway from the podcast. Four years ago was we should all be using nicotine and be people were like how can you advocate for this as a doctor? So my hope is to untangle all of that for people. Nicotine is one of many.
Compounds found within the leaves of the tobacco plant as such it is in tobacco based products but the major health concerns that are associated with tobacco which are primarily cancer and cardiovascular disease for reasons. We can talk about another time and we're not going to talk about today are not caused by nicotine per se, but instead they are caused by several other components of tobacco itself. And
Tobacco smoke such as everything, from toxic Metals, formaldehyde, things called polycyclic aromatic hydrocarbons. These are actually the things that are causing the harm. Now there are byproducts of nicotine that are produced in processing tobacco and they can be carcinogenic. So that means in, this is a very important point. I want to make sure if you're trying to pay attention to the key points, this is one of them. This means that any tobacco
Arrived. Nicotine product may contain carcinogens. This was actually something I did not appreciate prior. I thought that you could extract nicotine from tobacco and be completely free and clear of carcinogens. That is not the case I want to be clear, it might be that and it likely is in fact, it almost undoubtedly is that smoking tobacco is a much higher level of risk, but I want to make sure people understand that if
Your nicotine is tobacco derived. As opposed to synthetic you are still probably assuming risk. So the level of these compounds depends on the processing technique and the tobacco variety of course. So they're found in the highest concentrations in products that actually still look like tobacco. So I think that's kind of a nice way to think about it. Everybody can imagine what a cigarette looks like. If you take tobacco chewing leaves people Chew Tobacco. That's
To have a lot of the - properties. So, the more closely you are to Tobacco the worse things are. So obviously, if you're sticking it in a cigarette, or a cigar or pipe, yep, you're getting plenty of it there. If you're chewing it, or taking it in snooze. Also, a big problem. So, this is why I don't think I fully appreciated this for years ago. When you take nicotine out of tobacco directly, you're still assuming some of that risk that comes in curing and fermentation of the tobacco itself.
Before I move on, we should just
s-something because I forget sometimes people get confused by it. And even earlier this week, we got an email to the website, which is Peter for someone who cares so much about their health. Why did I see an Instagram or YouTube video of you wear on your hat or your T-shirt? There was the Marlboro logo do you support cigarette smoking. So while we have people just want to explain why, sometimes your clothing has that and how you
Not sponsored by big tobacco, and that is not a, you should be going in smoking, Marlboro Reds on the regular.
Yeah, boy. That's okay. This is a philosophical issue. But as some people listen to this podcast know, I am an enormous fan of Formula One and that goes way back for a long period of time. And up until 2005 tobacco was a major sponsor of Formula One. In fact, the largest
Sponsor would have been Marlboro, and they were in the early 2000s, all over the Ferraris, and in the era, that is my favorite era of Formula One in the 1980s. And the early 90s, they were all over the McLaren car. And so you are correct from time to time. You will see me wearing something or memorabilia that I have. That is a throwback to that era of Formula One. And I believe in the original Livery of those vehicles. In other words, I believe in era-appropriate.
Create nods to things that we pay attention to. And so yes, if you're looking at a hat or a shirt or a car that is replica or pays homage to something of that area, you're going to see The Livery of the sponsors of the time and that would have been Hugo Boss nacio now marburo. Anyway there's nothing else I can say about it other than it has nothing to do with a tacit or otherwise approval of these products. I want to be unambiguously clear I think smoking is an
Loot error, arguably the single biggest unforced error, you can make with respect to your health and fortunately, big tobacco does not sponsor Motorsport anymore and I think they're better for it.
Perfect back to the regularly scheduled program. Nicotine are there any harms associated with nicotine itself? Based on what we just talked about them?
Well, we're going to go into this in some detail, but I would say that clearly the biggest risk of pure nicotine, and now I'm just talking about it.
Lens of synthetically acquired nicotine. So you're getting rid of all the tobacco-related processing is in. It's addictive nature and make no mistake about it. Nicotine is highly addictive. There are some other areas where depending on the dose, there may actually be a harm. Again, I think this is very important to understand. There are some mechanistic insights, that suggests a negative impact on the endothelium. And it's certainly plausible that
Thing that negatively impacts the endothelium could increase the risk of cardiovascular disease. But these are not large studies. 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 a 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 atherosclerosis 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
Light 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 2020 for mendelian randomization. I know we talked 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.
We can assume are randomly assorted, that's the randomization part and let's ask the question. Will these jeans 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
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. Nevertheless so if you look at this mendelian randomization they wanted to look at
Relationship of nicotine by itself. On compromised, lung function, lung cancer, COPD chaseace5127 here. I don't think this was the world's best Mr. I think it was clever, though. What do 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 on 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 and what the authors of this study postulated, was people who are faster, nicotine, metabolizers are going to have lower levels of circulating nicotine and therefore less nicotine exposure.
Now, technically, you could also argue that maybe someone who's a faster nicotine metabolizer would smoke more or consume more nicotine. So put that aside for the moment, but nevertheless, the author has used these genetic variants associated with nicotine metabolism to adjust for basically smoking heaviness. And again, we're not interested in the role of smoking were interest in the role of nicotine, okay. Disease risk was increased with slower, nicotine metabolism, but the added risk was abolished when adjusted for smoking heaviness because of course, if you do this, you have to adjust for smoking.
And indicating that the main drivers of the outcomes are the non nicotinic components of cigarette smoke. Let me state that again, this is a complicated, Mr. But is the closest thing, I think we have to looking at humans and it's looking at how much people smoked, how quickly, they metabolize nicotine trying to do an overlay of that to appreciate the nicotine exposure. And it came away basically saying that the harm of
Smoking is due to the tobacco and tobacco related products, not due to the nicotine. I want to be clear, this is way way far away from what you would want to be able to say is Level 1 evidence. If you wanted to do this in a level one fashion, you would actually have to randomize people to a whole bunch of different tobacco free nicotine products and study the outcomes of Interest. Now of course nobody's going to do that for hard outcomes like mortality. But I certainly
Only think people could do that for softer outcomes and my hope is that somewhere. Along there people do
that, what do we know about potential side? Effects of nicotine.
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