#161 – AMA #23: All Things Nicotine: deep dive into its cognitive and physical benefits, risks, and mechanisms of action

In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into nicotine, a complicated and interesting molecule that has effects on both the brain and the body. They analyze the results of the studies that describe nicotine’s cognitive benefits and potential for inducing weight loss. They talk about a smoking cessation technique called nicotine replacement therapy and give a full breakdown of the various routes of administration, dosing, and safety. Finally, they explore the fascinating and counterintuitive observation that cigarette smokers are less likely to get a severe case of COVID-19.

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AMA #23 Sneak Peak:

We discuss:

• How Peter first became interested in the potential benefits of nicotine [1:15];
• Untangling nicotine from tobacco [6:00];
• Nicotine replacement therapy (NRT) for quitting smoking: products, protocols, and a review of the literature [9:30];
• The cognitive benefits of nicotine: Overview of the literature [15:50];
• Where nicotine has the most positive impact on cognition [30:30];
• Possible mechanisms conferring the benefits of nicotine [37:00];
• How modafinil and other nootropics compare to nicotine [47:15];
• How nicotine may induce weight loss [54:00];
• Relationship between smoking and COVID-19: Analyzing the observation that smoking appears protective against COVID-19 [1:01:45];
• Breakdown of the various nicotine replacement therapies: route of administration, dosing, and safety [1:11:30];
• Concluding thoughts on nicotine: use cases, addictive properties, and more [1:19:45]; and
• More.

*WATCH A PREVIEW OF AMA #23 ON YOUTUBE*

How Peter first became interested in the potential benefits of nicotine [1:15]

Quick aside on Peter’s deadlift routine:

• Peter deadlifts in more the sumo (straight bar) and well as hex bar
• His current phase of deadlifting leans more sumo style rather than hex bar
• He’s using a traditional narrow stance straight bar
• But he goes in phases and likes to mix it up 

“This silly unrealistic question of, ‘If you’re going to do one exercise, what would it be?’ That would definitely be variations of deadlifts.” —Peter Attia

Nicotine questions for today:

• Does nicotine improve cognition?
• Does nicotine improve fat oxidation and can it actually help with weight loss? 
• Is it possible that smoking is protective against COVID-19?

When peter got interest in nicotine:

• From a personal standpoint, Peter became interested in nicotine about 11 years ago
• He realized that if you could strip away the addictive nature of nicotine, the actual molecule was quite interesting 
• He started chewing nicotine gum intermittently
• Note: If you’re not a smoker, go really easy with gum or lozenges because it can make you quite nauseous
• For about the next three or four years, he was on and off nicotine gum somewhere between four and eight milligrams a day and found it to be quite beneficial in terms of his mental focus
• And he never really felt even a slight bit of addiction (not the case for all people)
• More recently, Peter discovered nicotine containing pouches
• He always thought the gum tasted gross (too much sugar/sweetness) whereas the pouches are mostly flavorless
• With the pouches, you’re just basically just getting a pretty high dose of nicotine and it’s bypassing the liver so it actually hits you quicker

Untangling nicotine from tobacco [6:00]

Difference between nicotine and tobacco

Tobacco

• Obviously cigarettes contain leaves from tobacco plants and tobacco also contains nicotine
• Tobacco is actually in the nightshade family of plants, and when you look at potatoes and tomatoes and eggplants, there’s nicotine in there but at nowhere near tobacco
• Nicotine makes up about 1% to 3% of the dry weight of tobacco whereas these nightshades, it’s millions of a percent

Nicotine is not a carcinogen

• The US Surgeon General indicated that there’s inadequate evidence to infer a causal relationship between nicotine exposure and risk for cancer
• But this is counterintuitive when you think about how bad for you smoking is — since nicotine is in there, and it’s addictive, it’s normal to think that it’s one of the carcinogens in cigarettes
• But even the U.S. Department of Health’s list of 69 potential and known carcinogens in cigarettes, nicotine is not one of them
• In other words, nicotine—which has some benefits—unfortunately has that addictive part of it which keeps people coming back to smoking tobacco, but in and of itself it doesn’t cause cancer
• This is important to note because the U.S. Department of Health goes as far to say that processed meat is a class one carcinogen, and red meat is in the next class down as a carcinogen despite very little evidence 
  • See Peter’s many articles on the topic of red meat

“If they can’t even recognize nicotine is carcinogenic given their sensitivity for identifying carcinogens, the likelihood that it has any cancer causing properties is approaching…zero.” —Peter Attia

Nicotine replacement therapy (NRT) for quitting smoking: products, protocols, and a review of the literature [9:30]

NRT – Nicotine replacement therapy

• Nicotine is an addictive substance and so you could implicate that as getting people to smoke and stay smoking
• But now, they’re actually using nicotine to help people quit smoking
• There’s an entire industry of nicotine gum, lozenges, pouches, patches, etc.

A review by the Cochrane Collaboration

• Looked at people who have quit for six months and haven’t returned to smoking
• They found high quality evidence that this NRT increases the chances of successfully quitting smoking by about 50% to 60% (relatively)
• However, in absolute terms: Absolute quit rate at 6 months is ~ 3-5%, and therefore NRT may increase the rate by 2-3%
• “You have to always ask the question, ‘What does that mean at an absolute level?’” says Peter
• In the big picture, the small absolute increase tells us that it is very hard to quit smoking using NRT

Why doesn’t it work more?

• • Bob says the lozenges for the most part come in two milligram and four milligram
  • But a cigarette supposedly has about one milligram of nicotine contained within the cigarette
  • But… it’s a different route of administration and people probably say something to the effect of “it’s just not the same” and they go back to the smoking

• Is inhalation just the fastest route of administration making the rush and the buzz from the nicotine when you inhale it across that entire alveolar surface area?

• • I think that plays a role, says Bob
  • They’re working on patches and nasal sprays trying to mimic getting speedier delivery of it

Historical smoking data

• At its peak in the mid 1960s, close to 60% of Americans over the age of 18 smoked cigarettes 
• Now, Americans that smoke is around 15% 
• Interestingly, in the podcast with Nir Barzilai, he was talking about centenarians and discussing whether it is their genes or their environment causing them to live so long
• His basic conclusion is that it’s genes, not environment, citing that a lot of the centenarians had smoked

*One protocol that’s possibly more successful than just NRT for smokers trying to quit: Combining Wellbutrin, an antidepressant, with NRT

“If you’re a smoker and you’re interested in longevity, there’s harder to find a lower hanging piece of fruit than smoking cessation as you move to improve someone’s health.” —Peter Attia

The cognitive benefits of nicotine: Overview of the literature [15:50]

A meta-analysis from 2010

• They found 41 studies (48 experiments) where there were sufficient effect size data (i.e., a minimum of five effect sizes from independent studies were available) to conduct meta-analyses on nine performance domains, including motor abilities, alerting and orienting attention, and episodic and working memory. 
• When you do a meta-analysis, there’s usually an inclusion criteria and an exclusion criteria — In this case they only looked at the double-blind placebo-controlled trials on nicotine and smoking on human performance (i.e., attention and cognition) in healthy adult nonsmokers and smokers who were not tobacco deprived 
• Regarding the “not tobacco deprived” criteria — they are making sure that the smokers were not coming to the study already in a state of low cognition due to withdrawal symptoms 
  • For example, if you tell a heavy smoker to not smoke in the morning, their cognitive performance may actually decline just because of that, because they’re going through nicotine withdrawal

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