#161 - AMA #23 [sneak peek]: All Things Nicotine: benefits, risks, and mechanisms of action

1. 0:00 – 0:10

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey, everyone. Welcome to The Drive podcast. I'm your host, Peter Attia.

2. 0:10 – 6:00

   How Peter first became interested in the potential benefits of nicotine

   1. BOBob0:10

      Hey, Peter.

   2. PAPeter Attia0:12

      Hey, man. How are you?

   3. BOBob0:13

      I'm doing well. How are you?

   4. PAPeter Attia0:16

      Um, good, except for the fact that my shin is on fire. It is killing me at the moment. I, uh, uh, I think you know I've discovered recently the use of long, high socks for sumo deadlifts, which has been a game changer. Um, and then today when I was doing my warmup set, I just forgot to put the socks on, so I literally had 135 pounds on the bar, and two reps into it ripped a hole in my shins, uh, that, like, by the time I put the bar down, there was blood down to the floor, and I was like, "Dude, how could you forget to put your socks on? Like, your magic favorite socks."

   5. BOBob0:56

      [chuckles]

   6. PAPeter Attia0:57

      So anyway, I'm, I'm lamenting my, my, my badness there, but other than that, I'm good.

   7. BOBob1:04

      That's good. I don't think we have any questions around that, but I do have a question. Do you do... You do sumo deadlift. Do you do a standard as well? Are you still using your hex bar?

   8. PAPeter Attia1:11

      Um, I go back and forth. So, uh, I, I used to love to deadlift twice a week, alternating two of the three between a sumo, a standard, and a hex bar, and I go in phases. Like, right now I'm really loving sumo, and I've fallen out of love with s- with trap bar. I don't know why. I just was having trouble kind of finding it again, and whereas I feel really good in the sumo. Um, and I actually haven't done straight bar in probably, like, six months. I mean, uh, like a traditional narrow, narrow stance straight bar. Um, but I, I like mixing them up. I mean, I just... You know, I, I sort of think deadlift is... I, I, I think it's probably the... If you could only... So this, the sort of silly, unrealistic question of if you'd only do one exercise, what would it be? Uh, it would definitely be variations of deadlifts for me.

   9. BOBob2:03

      Mm.

   10. PAPeter Attia2:04

       Hey, that rhymed. Hmm.

   11. BOBob2:07

       That's very nice.

   12. PAPeter Attia2:08

       Yeah.

   13. BOBob2:08

       It's poetic.

   14. PAPeter Attia2:09

       I'm good like that.

   15. BOBob2:09

       [laughs]

   16. PAPeter Attia2:11

       Um, so we have a, we have an interesting episode today.

   17. BOBob2:14

       We do. We do. We, uh, we consolidated a bunch of questions around nicotine. Um, we've got... We've, uh, we've received a bunch of questions, and, uh, you know, typically people will just, I think, would say that... I, I don't even think people would ask, you know, "Is smoking bad for you?" But there actually are a lot of thing, a lot of questions around nicotine and are there benefits to nicotine. And in particular, we got questions around, um, that people have heard about it, it improving cognition, and if that's possible. Is there any literature on that? Uh, there's also a question about nicotine improving fat oxidation, and can it actually help with weight loss? And another one, which is really interesting, that I think we'll get to is, is it possible that smoking is protective against COVID-19?

   18. PAPeter Attia3:03

       Yeah, this is where I think the AMAs are fun because it, that turned into a really interesting, uh, deep dive, and I would have never even thought of that, so it was nice to see a whole bunch of people had asked that question. And then, of course, we got to, we got to look into it. Um, y- you know, I say before we jump into this, I will just say from a personal standpoint, I became interested in nicotine about, uh, maybe 11 years ago, um, and realized that if you could strip away the addictive nature of nicotine, and we'll get into that a little bit more, the actual molecule was quite interesting, um, and started chewing nicotine gum intermittently. Um, and obviously the... if anybody's ever chewed nicotine gum who's not a smoker, you realize you gotta go really easy because, um, it can make you quite nauseous and things like that. Um, and so I would, you know, for the next three or four years, I was on and off nicotine gum, uh, you know, somewhere between four and eight milligrams a day, uh, and, and, and, and found it to be quite beneficial as far as sort of sharpening, uh, my sword, so to speak, and, and, and just got me a little focused. And I, I was fortunate in that I never really felt even the s- the slightest semblance of addiction to it, so I could chew it for 10 days in a row and then stop it for a month and didn't even really notice I was not taking it. So, um, uh, I don't know that that's necessarily something that everyone can experience. Um, recently I have discovered these little pouches, nicotine-containing pouches, which you can sort of put in your, in your mouth. Uh, they also have lozenges and things like that, that I much prefer 'cause then you don't get the... There was always some... I always thought the gum tasted kinda gross. It also had a little sugar in it. It was a little too sweet. Um, and these pouches are, um, you know, they're, they're mostly flavorless. They have a bit of an aroma. Um, and to be clear, they're not, they're not like dip or chew, you know, and we'll get into what that difference is. So you're just basically just getting a pretty high dose of nicotine, and it's bypassing the liver, so it actually hits you quicker.

   19. BOBob5:16

       Yeah, I've tried the gum and the, and the lozenges, and I found with the gum, uh, same as you. And also, I think on the instructions that part of it is you chew it a little bit, get a little bit of nicotine out of it, and then you're, you're supposed to park it, which sounds like what you're probably doing with that pouch or what you do with a lozenge 'cause otherwise I think it, if you're just chewing it like regular gum and chewing it a lot, it, it made me nauseous.

   20. PAPeter Attia5:37

       Yeah. Um, so by the way, I'm just gonna, I'm gonna just take one of my patches now and just stick it in here for a minute, so yeah.

   21. BOBob5:46

       Flavor country.

   22. PAPeter Attia5:48

       Yeah. Yeah, exactly. I don't normally do this, uh, during a podcast. In fact, I've never put one in during a podcast, but it, I sure do like it when I'm writing, when I'm, um, sitting there trying to focus a little bit. So,

3. 6:00 – 9:50

   Untangling nicotine from tobacco

   1. PAPeter Attia6:00

      um, all right. So Let's, uh, let's help people understand a little bit why nicotine isn't dangerous. Let's start with that, right? 'Cause I- as you alluded to at the outset, you would not be blamed for having a knee-jerk reaction to the notion that nicotine is a bad thing. Um, so you wanna talk for a second, Bob, about the difference between nicotine and tobacco?

   2. BOBob6:26

      Yes. So the... When you're looking at nicotine and tobacco, and you're looking at... Well, when you're looking at tobacco, obviously cigarettes contain leaves from tobacco plants, um, and tobacco also contains nicotine, so you've got that, you've got that connection there. And something that I didn't realize is that tobacco is actually, it's in the nightshade family of plants. And so when you look at potatoes and tomatoes and eggplants, there's actually, there's nicotine in there, but the nic- the level of nicotine in those, uh, plants are nowhere near, uh, tobacco. So nicotine makes up, uh, it says about 1% to 3% of the dry weight of tobacco, whereas these nightshades, it's like millionths of a percent, very trace amounts. Um, but interestingly, even the, the US Surgeon General said there's, there's not enough evi- evidence or inadequate evidence, um, to infer a causal relationship between nicotine exposure and risk for cancer. So I think like a lot of other people, when... So I, I have you beat Peter by [chuckles] maybe a decade or two as far as my interest in nicotine, but it, it was more about, uh, I smoked in high school a little bit, smoked cigarettes, and I can certainly speak to the, the addictive nature of cigarettes. But at that time, and probably years after that, I would just think, you know, when people would talk about nicotine being bad for you, I'd say, sure, the, it's, it's in cigarettes, and it's probably one of the many carcinogens in tobacco smoke. And if you go to the, I think it's like, uh, they got the WHO where they've got their long list of potential and known carcinogens, and I think they, it says they have at least 69 chemicals, um, that is con- that, that are contained in tobacco smoke that are carcinogens, but nicotine is actually not one of them.

   3. PAPeter Attia8:08

      Yeah. That, that, that's an important point, right? This is, this is something really worth reiterating, right? So the, the US Department of Health and Human Services says they've identified at least 69 chemicals contained within the tobacco plant, i.e. things that make it into cigarettes, that are carcinogens, and nicotine's not one of those things. So it's interesting in that nicotine is the thing that I think we're gonna talk about has some benefits. It also unfortunately has that addictive part of it, so it brings you back to the tobacco. But in and of itself, it doesn't cause cancer.

   4. BOBob8:42

      Right. And, and if you look at the WHO, this could be an, you know, an entirely different podcast, but, uh, red meat and processed meat are, I think it's, you know, uh, processed meat is a, I think it's a Class 1, and then there's the, the next class down, which is red meat. So I figured I'd go to the list on the WHO, and if there's anything, you know, on nicotine being carcinogenic, I would think that the WHO would have it listed there, but it's, it's not, so.

   5. PAPeter Attia9:05

      So what you're basically saying is the WHO will go so far as to claim that red meat is a carcinogen, and we've written so much about this topic and basically said, [clears throat] the evidence suggesting that red meat is carcinogenic is so weak, um, that it's, it's very difficult to take it seriously. And if there's any, uh, carcinogenic properties of meat, it's, it's really low signal. Um, and you're saying if they, if they can't even recognize nicotine as carcinogenic given their sensitivity for identifying carcinogens, the, the likelihood that it has any cancer-causing properties is, is approaching epsilon if not zero.

   6. BOBob9:47

      Yeah. That's right.

   7. PAPeter Attia9:49

      Okay. So,

4. 9:50 – 16:40

   Nicotine replacement therapy (NRT) for quitting smoking: products, protocols, and a review of the literature

   1. PAPeter Attia9:50

      so where, where, where do, where do all these nicotine replacement products come from? So, so, uh, I, I, I mean, is it safe to say that this entire industry of gums and patches and lozenges, inhalers, nasal sprays, little pouch that I'm sucking on right now, these are basically tools to get people to stop smoking, right?

   2. BOBob10:09

      Yeah. So if you, yeah, you look at the literature and there's this, you know, NRT, they call it nicotine replacement therapy. So you've got nicotine which is addictive, and so you, you could implicate that in getting people to smoke and stay smoking and make it hard for them to stop. But they're actually exploiting this, uh... They're exploiting nicotine, in fact, to help people quit smoking. So you've got all these products that are f- some of them, uh, most, the ones that we'll talk about for the most part I think are FDA approved, uh, for nicotine replacement therapy to get people to help, uh, quit smoking. And there's, there's some reviews, and, uh, probably a lot of people are familiar with the Cochrane collaboration. They put together a review and found high-quality evidence that this NRT increases the chances of successfully quitting smoking by about 50% to 60%. And I think anybody who smokes knows how, how hard it is to quit.

   3. PAPeter Attia11:01

      But, but hang on, Bob. We're gonna have to make sure we make sure people know we're talking relative success increase. Can you put that in absolute terms please?

   4. BOBob11:11

      Yes.

   5. PAPeter Attia11:11

      [chuckles]

   6. BOBob11:11

      So the, [chuckles] for the six months, the absolute quit rate, this is, uh, just in general, at six months, so you try to quit, and they look at people after six months and see if they're, if they've gone back to smoking. And the people who have, who have quit and, uh, for six months and haven't returned to smoking, the absolute, uh, rate is about 3% to 5%, which is pretty depressing. Um, and so in that case, that means that NRT may increase the rate from an absolute perspective by a couple of percentage points, maybe 2% to 3%.

   7. PAPeter Attia11:42

      Yeah. So a- again, I, I... [clears throat] Another great teaching point here, which is you could read the headline and say, "Wow, nicotine replacement therapy increases your odds of quitting by 50% to 60%," and that sounds like an awfully big number, but you have to always ask the question, what does that mean at an absolute level? And if the absolute rate, the absolute success rate of people quitting, uh, nicotine, uh, sorry, quitting tobacco at six months is 2% to 3% and you increase that by 50% to 60% Well, look, it's, you know, it's, it's an improvement, but in the big picture, it tells us that it is very hard to quit smoking using NRT. And I gotta be honest with you, I don't know why it's not higher, Bob. Like, I don't know why the relative improvement d- with, with NRT isn't, like, 1,000%, uh, or, you know, like, 500%. Like, why... Do you have a, do you have a sense of why, maybe as a former smoker, why when you, if you, if you take someone who smokes and you give them NRT, you can't get 50% absolute, uh, quit rate at six months?

   8. BOBob12:49

      You know, it's hard for me to say. It's been so long since I smoked. Um, it would be... I, I think it'd be interesting to look into. I, I wonder if people think that, like, they, you know, they go to a lozenge or they go... And, and the, the lozenges that I've tried and the gum that I've tried, I usually just try the smallest dose. So the, like the, um, the lozenges that I have, I think are, they come in, for the most part, two milligram and four milligram, and I take the two milligram one. And I, and I think we'll get to this, but it, a cigarette supposedly has about, uh, one milligram of nicotine contained within the, the, the cigarette. But I think it's a different route of ad- administration, and I think that people might think that it, it's... They probably say something to the effect of, "It's just not the same," and they go back to the smoking. And I think some people think it's like, well, maybe it's the oral fixation or things like that, and, and-

   9. PAPeter Attia13:36

      Or, or do you think it's just that, that when you're smoking, the inhalation is the fastest route of administration, so the rush and the buzz from the nicotine when you inhale it in, you know, across that entire alveolar surface area, nothing can compete with that, and so all of these little piddly NRT therapies are just, you know, insufficient to, to, to reach the same level?

   10. BOBob14:01

       I think that plays a role. I think that they're working on, if not, if they haven't already developed this, but patches, and maybe some of the, the sprays, the nasal sprays and things like that, that they're, part of why they're, you know, you have these different routes of administration is they're trying to mimic, you know, getting a, a speedier delivery to it. So maybe those will be more efficacious in the future.

   11. PAPeter Attia14:22

       Mm-hmm. Well, well it'd be interesting actually to, at some point, um, do a podcast on smoking cessation, because we take this for granted that, um, gosh, I think at its peak, which would've been about 1964, 1965, I believe up to 59 if not 60% of Americans over the age of 18 smoked cigarettes. Um, which, you know, I don't know how to qualify that. I don't know what constituted smoking. You know, did that include people who just smoked socially, like, uh, at a bar, you know, a couple cigarettes a week, versus the pack-a-day smoker? But, but nevertheless, that's a pretty astonishing quantity.

   12. BOBob15:00

       Yeah.

   13. PAPeter Attia15:00

       I think the most recent numbers are about 18 to 19% of people over 18. Is that, sound about directionally right?

   14. BOBob15:07

       Yeah, I think so. I, I think... Yeah, we- we'll get to it with COVID, that they're, they looked at some prevalence numbers too, 'cause they were comparing, uh, rates of, uh, hospital admission compared to the general population, and I think it, it depends, but I think Americans might be like, like around 13% to 15%. It's definitely gone down, and it, it reminded me too, I think the podcast with Nir Barzilai, and he was talking about his centenarians-

   15. PAPeter Attia15:30

       Mm-hmm

   16. BOBob15:30

       ... and talking about, well, you know, uh, that, is it g- is it genes or the environment? And he would talk about a lot of the centenarians that he was studying and saying that it doesn't look so much like it's environment. And one of his, you know, one of the things that he pointed out was a lot of the centenarians had smoked. And I don't know if that was never smokers, but if you look at, if you look historically, you would think almost, like, how, how is it possible th- these people never smoked in their lifetime? It was so prevalent.

   17. PAPeter Attia15:58

       Mm-hmm.

   18. BOBob15:59

       Um, it was kind of amazing.

   19. PAPeter Attia16:01

       Yeah. I mean, we haven't had a lot of current smokers enter our practice. A few that have, obviously that's literally the first thing we address. If you're a smoker and you're interested in longevity, uh, there's harder to find a lower hanging piece of fruit than smoking cessation as you move to improve someone's health. Um, uh, we've used Wellbutrin, uh, which is an antidepressant. I, I, I used to know the numbers. In fact, I think we have a little white paper somewhere in the practice, um, that, that gave us a bit of a, an assessment on how to combine NRT with Wellbutrin. But this, this might be an interesting topic, but,

5. 16:40 – 20:29

   The cognitive benefits of nicotine: Overview of the literature

   1. PAPeter Attia16:40

      um... Okay. So what, what can we say about the cognitive benefits of nicotine? So here I am a few minutes after ingesting my little nicotine little patch. It's sitting in here. It's, again, it's bypassing my liver. It's getting into my system much quicker because it's being directly absorbed. Maybe it's placebo, but I gotta tell you, Bob, I've, I'm feeling pretty sharp right now.

   2. BOBob17:04

      [laughs]

   3. PAPeter Attia17:06

      I don't know what to say. I'm just feeling sharp. You got a differential equation for me to solve?

   4. BOBob17:11

      [laughs]

   5. PAPeter Attia17:12

      I can crack it.

   6. BOBob17:13

      Not offhand, but yeah. [laughs]

   7. PAPeter Attia17:14

      Yeah, just... I could recite Stokes' theorem like that. I'm, I'm ready to go.

   8. BOBob17:18

      It's gonna go entirely different AMA podcast.

   9. PAPeter Attia17:20

      [laughs] Um, okay, what... Y- you know, I, you looked into this. So how, how many studies have tried to ask this question directionally? [upbeat music] Thank you for listening to today's sneak peek AMA episode of The Drive. If you're interested in hearing the complete version of this AMA, you'll want to become a member. We created the membership program to bring you more in-depth exclusive content without relying on paid ads. Membership benefits are many, and beyond the complete episodes of the AMA each month, they include the following: ridiculously comprehensive podcast show notes that detail every topic, paper, person, and thing we discuss on each episode of The Drive. access to our private podcast feed; the Qualies, which are a super short podcast, typically less than five minutes, released every Tuesday through Friday, which highlight the best questions, topics, and tactics discussed on previous episodes of The Drive. This is particularly important for those of you who haven't heard all of the back episodes. It becomes a great way to go back and filter and decide which ones you want to listen to in detail. Really steep discount codes for products I use and believe in, but for which I don't get paid to endorse, and benefits that we continue to add over time. If you want to learn more and access these member only benefits, head over to peterattiamd.com/subscribe. Lastly, if you're already a member but you're hearing this, it means you haven't downloaded our member only podcast feed where you can get the full access to the AMA and you don't have to listen to this. You can download that at peterattiamd.com/members. You can find me on Twitter, Instagram, and Facebook all with the ID PeterAttiaMD. You can also leave us a review on Apple Podcasts or whatever podcast player you listen on. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit peterattiamd.com/about where I keep an up-to-date and active list of such companies. [outro jingle]

Episode duration: 20:29