Nicotine CRACKDOWN (One of My Guests Got ZYN Banned?!), Cancer-Fighting Fruits, Ozempic® Alternatives (Minus the Life-Altering Side Effects) & More! Solosode 476

Ben Greenfield [00:00:00]: In this episode of the Ben Greenfield Life podcast, the ban on nicotine pouches, which fruits are best for cancer prevention? A Q and A on Ozempic alternatives and much more, fitness, nutrition, biohacking, longevity, life optimization, spirituality, and a whole lot more. Welcome to the Ben Greenfield Life Show. Are you ready to hack your life? Let's do this. Well, folks, welcome once again to another solo -sode. I am sore as a chimpanzee with rhabdomyolysis. It's crazy. What happened was, you may have heard me interview this guy who has done all this research on the ancient spartan training programs and Chinese training programs and ancient Indian warrior programs and wrestlers and all the American presidents, and he's put together all these crazy fitness routines. His name is James Purad.

Ben Greenfield [00:01:09]: I'll put a link to the show notes. The show notes for this episode, by the way, are BenGreenfieldlife.com/476. It's BenGreenfieldlife.com/476. Anyway, after I interviewed James, he sent me a few sample protocols, everything from a tar Mahara crazy running program all the way down to these secret soviet kettlebell training routines that he had researched and developed. Well, I convinced my twin 16-year-old sons to join me in an eight-week soviet kettlebell training program. I'm three days in and holy cow, I've got muscles sore that I don't think I've ever used before in my life. It's been a, been a rough morning. Lots of saunas and cold plunging this morning, I can tell you that.

Ben Greenfield [00:01:56]: Got a great show for you today, a little special announcement towards the end related to my relocation to the beautiful woods of Idaho. But we'll save that for the end. And today we're just going to jump right into some news flashes. Got some great questions. If you have a question for the podcast, you can surf on over to BenGreenfieldlife.com/476 and leave your question over there. But anyway, I had another podcast guest who I interviewed, and I figured I'd bring this up right away, just basically get this elephant out of the room. You may have heard me interview the mass spec guy, Ben Katz. The mass spec guy, Ben Katz.

Ben Greenfield [00:02:36]: In our interview, he talked about how some of these nicotine pouches, Zyn in particular, were the ones that he talked about, using synthetic cooling agents. Unfortunately, it turns out that these cooling agents also enhance the flavor of the nicotine pouches as a result of some of Ben's work, on his Instagram channel. I don't know if our podcast had anything to do with this or not. I'm not going to narcissistically pretend that it did, but I think this is interesting. It happened shortly after our podcast was released, Zyn got banned. I'm sure the person most pissed off about this is Tucker Carlson, who I think goes through probably four or five zins during the average interview that he does. But anyway, Zyn nicotine pouches got banned. So the idea here is that Philip Morris International, who just so happens to own and produce Zyn, came under the regulatory eye of regulatory authorities and the Senate.

Ben Greenfield [00:03:35]: Because though vaping and cigarettes, I would say, are far less healthy than something like a Zyn nicotine pouch, the problem is that you're not supposed to flavor tobacco. You're not supposed to make tobacco even more of a vice than it already is, even more addictive than it already is, by adding a bunch of flavoring agents. The way that I understand this ban is that even though Zyn isn't using flavoring agents, some of the other chemicals or molecules that they're adding to Zyn have resulted in them stepping over the boundaries of a 2022 ban on all sales of flavored tobacco that was actually in DC in the District of Columbia. So anyways, the idea here is that apparently they are recalling and removing zin from shelves, and you can't get your nicotine patches as easily now. And it's actually a really, really interesting development in the realm of nicotine, a stimulating, addictive product that I will admit doesn't prove focus and I probably chew on. I probably go through about a pack of Lucy nicotine gum a week, just chewing on nicotine gum here and there. I'm pretty careful and cognizant about how I use it and how often I use it. I know some people who literally go through a whole pouch of Zyn, one of these entire pouches designed for maybe a week or two weeks of use in a single morning.

Ben Greenfield [00:05:04]: But anyways, Zyn has yet to be authorized by the FDA in the similar way that nicotine gum and lozenges are authorized by the FDA. Isn't that funny? A pouch is something that is banned as far as a flavoring agent, but companies that are producing gum and lozenges can get away from it. So if the FDA decides to ban Zyn altogether, it will become illegal in the states. Right now, as far as I know, they're undergoing a lawsuit for faults and what is called malicious advertising. And as far as the actual ban goes, I think the idea is that it's happening in multiple states I don't think it's nationwide, but it is going to be more and more difficult to get your hands on these Zyn pouches. So I suppose stock up if you're a Zyn fan or switch to gum or lozenges or, I don't know, just maybe grab a pipe or a cigar. Either way, I think you do need to proceed with caution with nicotine, but you would actually really enjoy this podcast that I did with Ben Katz, the guy who used mass spectrometer equipment to test all sorts of things, energy drinks and chocolate and candy and kratom and nicotine and all these common vices that we use. I'll link to that one in the show notes at BenGreenfieldlife.com/476.

Ben Greenfield [00:06:24]: But if you're a Zyn user, be careful, you might not be around much longer. The next thing is, a lot of people are sleeping less this time of year. A lot of people are sleeping less this time of year. And the BBC did a pretty interesting review on why that might be why many of us are familiar with this struggle to muster the energy to leave bed in the morning during winter. But sometimes we often have difficulty staying in bed during the summer and the warmer months. Well, new research suggests that humans may need more sleep during the dark, cold winter months than we do during the summer. And this seems to even occur in people living in cities where artificial lights would be expected to interfere with the natural influence of daylight on our sleeping patterns, right? You'd think that we could just artificially create summer, which I think in some cases we kind of do, with constant exposure to bright, blaring overhead LED fluorescent lights and malls and indoor areas and cars and the like. But yet still, even while living in an urban environment, this latest study found that with artificial light included, humans still experience seasonal sleep.

Ben Greenfield [00:07:38]: Maybe it doesn't just have to do with the light, maybe it has to do with, for example, the temperature. Now, previous studies have found exposure to artificial light before bedtime, and I've talked about this on the podcast before, can suppress the secret of melatonin, which is the hormone produced by your pineal gland that regulates your circadian clock, that natural sleep-wake cycle that repeats every 24 hours and makes you feel sleepy. But this latest German study that I wanted to get out in today's news flashes used detailed sleep recordings of about almost 200 patients who lived in urban settings and yet suffered from disturbed sleeping patterns. They found that even when exposed primarily to artificial lights, these people experience seasonal variations in REM sleep, which is directly linked to circadian rhythm. These people slept, on average, an hour longer in December compared to June. And this REM, this rapid eye movement sleep, which is the most active stage of sleep during which you dream, during which your heart rate increases, it was 30 minutes longer. The REM sleep phase was in the winter than during the summer. And REM sleep is highly regulated by your circadian clock.

Ben Greenfield [00:08:48]: So the fact that it goes parallel with seasonality makes pretty good sense. But this study also had some other surprising results. They found that there were also seasonal changes when it came to slow wave sleep, also known as deep sleep or SWS slow wave sleep. And they found that specific changes in not just REM sleep, but also deep sleep, the two major stages in sleep, occurred during the year. Now, slow wave sleep, just so you know, deep sleep occurs during the final stage of non-rapid eye movement sleep. Of non-REM sleep. NREM sleep is when your body repairs and regrows tissues builds muscle and strengthens the immune system. It's important for the consolidation of long-term memory and processing newly acquired information.

Ben Greenfield [00:09:32]: It's very important that you get this non-rapid eye movement sleep. It's one of the reasons I'm not a fan of using, like, THC gummies prior to sleep, if you care about memory and learning consolidations because THC can suppress that non-rapid eye movement sleep. CBD, not quite so much THC. Marijuana. Yes. So the slow-wave sleep of the study participants was 30 minutes shorter in September than in February. So basically what they showed, there was a seasonality of deep sleep as well. So this means that basically, you need less deep sleep in the autumn than in the winter.

Ben Greenfield [00:10:10]: You need less REM sleep in the summer compared to the winter. And interestingly, and here's what I think is kind of fascinating, we also know that a good night's sleep is dependent on temperature. Your body requires a temperature between about 31 and 35 degrees Celsius, which is about 87, close to 88 to 95 degrees Fahrenheit, which is conducive to ideal sleep. Now, in the summer, when higher temperatures are more common, that can be harder to control, especially during heat waves. So this means that if you want to avoid the jet lag-esque symptoms that you can sometimes experience as the seasons change and as you experience temperature fluctuations, my number one tip for you is a be careful with artificial light, especially in the evening. I think most of you already know that, and it's something that's, you know unless you've been living in a rock, a lot of people know to avoid light at night now. And they're even now programming our TVs and our computer monitors and our phones to take advantage of that fact. But be engaged with cooling mechanisms also.

Ben Greenfield [00:11:22]: Like if you find yourself sleeping in in the winter, consider using something like a BedJet or a lot of people like this eight-sleep mattress, even though, from what I understand, it kicks off a little bit more EMF than what I'm comfortable with or for a long time, even though I think the company is now becoming defunct. Another company called Chilisleep had the ability to increase not just the cooling mechanism to help you to fall asleep, but can also produce heat to help you wake up. So you could use that in the winter, and then, of course, in the summer, you keep the bedroom environment as cool as possible. A lot of people ask me what I use now. My Chilisleep broke. I think they were having chip issues. They couldn't repair it. The chilly sleep is the one that circulates cold water underneath your top sheet at night.

Ben Greenfield [00:12:05]: And that can also, that water temperature can also be increased, for example, to help you wake up, alarm clock free in the morning. Now, I use one called a BedJet. It's pretty cool. I have a little remote control. I can set it for anywhere from 65 up to 80 degrees Fahrenheit. I can set it to switch to warmer air as the morning approaches. I can set it for cooler air during the night. It does a really good job cooling the bed.

Ben Greenfield [00:12:29]: It's like an air conditioning unit for my bed. It even has special sheets that allow the air to move more flowy or to move more freely underneath the sheets for your sleep. So what I use now is called the BedJet. And again, the eighth sleep is the one that I know a lot of people are comfortable with and have success with. But I thought this was just very interesting how much the seasons change your sleep. And if you are one of those people who, hey, year round, based on work life, etcetera, you know, you want to sleep 10:00 p.m. to 06:00 a.m. you don't want to sleep, you know, 09:00 p.m.

Ben Greenfield [00:12:56]: to 07:00 a.m. in the winter and 11:00 p.m. to 05:00 a.m. in the summer. And so you can tweak light and tweak temperature to take advantage of that fact. I should mention, by the way, when I'm talking about all these things, light, temperature, et cetera, these are called zett gebers or zeitgebers German word for timekeepers. And you can use this when you're traveling, you know, the same type of facts. For example, you can limit light exposure when you travel until the actual sun has risen in the area of the world that you happen to be in.

Ben Greenfield [00:13:26]: To allow yourself to adjust to that time zone more easily, you can, you know, I use for jet lag a lot, getting a cold body of water or take a cold shower, especially in the morning, to jumpstart that, that drop in adenosine or that, uh, that, that adjustment in adenosine. Maybe I'll get to adenosine later on. I think I will. In this podcast, uh, you can also use protein, a protein-rich meal to jumpstart the circadian rhythm. So light temperature, a protein-rich meal, and then physical movement. Those are the four best ways to beat jet lag. So get bright light in the morning, avoid bright light at night, get the body nice and cool in the morning if you can, and then repeat that in the evening. And then also get about 30 grams of protein with breakfast.

Ben Greenfield [00:14:07]: Don't skip breakfast those first few mornings when you're traveling to get over jet lag a little bit more easily. And then finally exercise. Exercise, preferably when the morning has come around, whatever area of the world that you happen to be in. So anyways, and I do want to talk about caffeine a little bit because a lot of people are under the impression that to not throw off your sleep, you're supposed to not drink caffeine for the first 60 to 90 minutes after awakening because it's going to shove your sleep, drive forward and make you feel tired earlier in the day. Not necessarily true. I'm going to get to caffeine later on this podcast, but I'm just going to leave that there as a teaser for you. All these studies I talk about, you can access if you go to BenGreenfieldlife.com/476 all right, next up, just published on my website a very interesting article, the unique anti-cancer strategies of one of Finland's healthiest and fittest 73-year-old men, a guy named Vessi.

Ben Greenfield [00:15:04]: I first met Vessi eight years ago at a biohacking summit in Finland. He turned out to be a very eccentric inventor, one of the most athletically talented old guys I've ever met in my life. Very smart. He had competed in several sports on a national and competitive level, including shooting, military, three-skill sports, diving, and sprinting. He rides horses and plays left-handed and right-handed tennis and swims and skis and skin dives and walks long distances and swing dances, and took us out on a giant Viking ship that he built to go camp on an island. Very interesting guy. When I met him, he could crank out 25 pull-ups, and speak multiple languages. He owns several multinational corporations and is an inventor.

Ben Greenfield [00:15:45]: And he looks remarkably well-preserved and young for 73 years old. Well, he wrote me an email a few weeks ago about some of the unique anti-cancer strategies that he has implemented with friends, and with people who he advises. Now, he's not a doctor, I don't want you to misconstrue any of this as medical advice, but one of the things that is in that article, which is very comprehensive, I'll link to it in the show notes. But he wrote me a super long email and I wound up editing it and turning it into an article, just getting into all of his anti-cancer strategies. And one of the things that he harps on is the idea of berry consumption. Specifically, there's a whole range of different berries that are used in northern European medicine, particularly in Finland, that have supposedly anti-cancer properties. And he gets into a lot of them, from black chokeberry for colon cancer, to blueberry for many cancers, to lingonberry for endocrine-based cancers, to grapes for different types of lung cancers. And so anyway, I dug into this a little bit because I have been seeing a few other articles that have come out lately about cancer, and specifically cancer and fruit consumption.

Ben Greenfield [00:16:57]: I would definitely put berries into the category of fruit consumption. So the first one was a paper that looked into whether fruit intake protects against colorectal cancer. It was what's called a Mendelian randomization study, a Mendelian randomization study. So what that means is they actually look at common genetic variations associated with fruit intake. So in this case, they looked at almost 65,000 participants. They looked at these specific genetic variations, and they were able to examine the relationship between genetically predicted fruit intake and colorectal cancer risk. Now, this is very interesting. I interviewed Dr. Matt Dawson recently about the idea of using genetic proxies.

Ben Greenfield [00:17:43]: This means if you have enough big data and you know that a certain gene or a certain blood marker is associated in a very large population with a certain lifestyle factor, like smoking or alcohol intake, or in this case, fruit consumption, or a certain amount of fitness or vo two max or grip strength or vitamin D levels, you can, using big data, produce some very accurate predictions about causal relationships between certain lifestyle or dietary or exercise factors and certain disease risks. And in this case, they use this Mendelian randomization tactic to look at the causal relationship between fruit consumption and colorectal cancer risk. Now, in a nutshell, or I guess I should say in a melon rind, higher genetically predicted fruit intake was indeed associated with reduced colorectal cancer risk. And this was specifically very, very significant when it came to men. So then I looked at another recent study that came out that actually dug into what kind of fruits could actually reduce colorectal cancer risk. And this is a big issue. I mean, we're even seeing children now coming down with colorectal cancer, which I think could be a combination of everything from herbicides to pesticides to toxins to ultra-processed foods, to a host of factors, including microbiome-based factors. And I think that my friend Dr. Mercola's new book coming up soon on cellular health gets deep into the colon and aerobic and anaerobic bacteria in the colon and a whole host of factors related to this.

Ben Greenfield [00:19:23]: But regardless, this is important. I think even if you're not some, you know, you know, a 70-year-old person who's at a high risk of colorectal cancer, this is important for your kids to know. So what this meta-analysis of observational studies looked at was what fruits were associated with reduced risk of colorectal cancer. Turns out that any citrus fruit, right? So lemon, orange, mango, etcetera, apples, watermelon and kiwi. So citrus fruits, apples, watermelon, and kiwi are the four that are the most associated with decreased risk of colorectal cancer. I think it's also interesting because if you look at kiwi in particular, a kiwi fruit extract, you can buy that on Amazon. It's fantastic for constipation as well. But this was a total of over a million participants under the age of 80 in this meta-analysis of observational studies.

Ben Greenfield [00:20:14]: And that's what it found. Citrus, apples, watermelon, and kiwi are the ones associated with the lower risk or the lowest risk of colorectal cancer. Now, I still think that based on data that I've seen, I'm going to link to a few papers in the show notes on the antioxidant and anti-cancer properties of berries, which is what got me talking about in the first place. I think that berries still are the most powerful when it comes to the lowest in fructose and sugar, but the highest in a lot of these cancer-fighting compounds. So as a matter of fact, one of these studies, and if you want to read the full paper, I'll link to it, it's called The Protective Role of Dietary Berries in Cancer. It's a pretty comprehensive 2016 paper. So it begins by highlighting the significant impact of colon cancer globally and specifically treating colorectal cancer. This is a topic near and dear to my heart because my father, several months ago, actually passed away from colorectal cancer.

Ben Greenfield [00:21:20]: And so I'm actually pretty motivated to get information out there to people about prevention, of course, because I'm genetically related to my father, this is also information that's near and dear to my heart. So, basically, berries are very rich in a lot of compounds. You're no doubt familiar with antioxidants, polyphenols, flavonoids, and a host of different vitamins that play a critical role in combating oxidative stress and inflammation, which are key contributors to cancer development. Oxidative stress and inflammation. Not just cancer, but a host of chronic diseases. You control oxidative stress and inflammation, and you are going to be well-equipped to fight a lot of diseases. And there is a Goldilocks effect, right? You want every single day to create oxidative stress in your body from herbs and plants and spices and sauna, exercise, cold and sunlight, radiation and grounding, etcetera. But there is a Goldilocks Zone to oxidative stress.

Ben Greenfield [00:22:10]: You know, the same can be said for inflammation. Exercise allows your body to mount an inflammatory response. Don't take a bunch of antioxidants after exercise. Don't go for a long, cold soak. But in general, rampant chronic oxidative stress and inflammation are definitely associated with cancer development. So the high antioxidant content in berries helps to neutralize those free radicals. While a lot of the plant defense compounds in berries produce this so-called xenohormetic effect, which allows your body to be able to better mount its own antioxidant response. So it's kind of operating on a one-two combo punch here.

Ben Greenfield [00:22:46]: So the anti-cancer properties of berries this paper gets into are attributed to their ability to modulate some signaling pathways associated with cancer progression. These signaling pathways have very long, complex names like NF-κB, the Wnt pathway, the Akt mTOR pathway, and the ERK/MAPK pathway. But basically, the long story short is that these are pathways critical in regulating cellular proliferation, programmed cell death, aka apoptosis and angiogenesis, or the formation of new blood vessels. By influencing each of these pathways, berries can inhibit tumor growth and tumor spread. There's actually a great book by a guy I interviewed named Dr. William Li called Eat to Beat Disease. If you want to get more, and especially the anti or pro-angiogenesis properties of different foods. Check that book out. Eat to beat the disease.

Ben Greenfield [00:23:38]: You may start eating black squid ink pasta after reading that book. I'm just going to warn you or listen to the podcast interview that I did with him. Fantastic book, eat to beat disease. Anyways, so this study concludes that incorporating berries into the diet is a powerful strategy in cancer prevention and treatment, particularly for colorectal cancer. You know, backing up a lot of what Vessi wrote in this article on my website about the anti-cancer effects of some of these northern European approaches to managing cancer, both preventively and then also treating it acutely with high berry intake. So I don't necessarily expect you to go out and hunt down sea buckthorn berries and cloudberries and lingonberries and some of the berries that, you know, I've had a chance to personally forage for in Finland. They have a biohacking summit in Helsinki, Finland every year. Shout out to my friends from the Biohacker summit, and usually we go foraging for berries during this summit.

Ben Greenfield [00:24:34]: But just the average berries that you can find in the average, say, the American grocery store or European grocery store work just fine. Now remember, berries are included among the dirty dozen fruits that tend to be sprayed, that contain edible skin, or the ones you need to be more careful with avocados and bananas. You don't necessarily have to break the bank to buy organic berries. Absolutely. Apples, lettuce, etcetera. So some of the best ones, are blueberries. Yay. Anthocyanins resveratrol blueberries are fantastic.

Ben Greenfield [00:25:04]: Always have a few frozen ones for making my morning smoothies. I like to toss a few in there. Strawberries are very rich in vitamin C and antioxidants. Strawberries can also help lower the risk of esophageal cancer. Raspberries are high in fiber and something called ellagic acid. Also talked about in that book, eating to beat the disease is linked to a wide variety of cancer preventions. And then blackberries, which also have a very, very high amount of anthocyanins in them. So anyway, the idea of fruits and fructose being poisoned is something that I know somebody is going to mention or bring up.

Ben Greenfield [00:25:38]: And here's the deal. Yes, excess fructose consumption in fruit can increase triglycerides. It can increase your risk of non-alcoholic fatty liver disease. It can cause accumulation of visceral fat, which can churn out inflammatory cytokines. But any study that has shown fructose or high fruit intake or high fructose corn syrup intake to be able to do that has only demonstrated that that's the case in the state of caloric excess. And what I mean by that is if I'm burning 2000 calories a day, I can comfortably tell you that I could drink 2000 calories of Coca-Cola a day and my liver would be just fine. Now, I might experience micronutrient deficiencies and vitamin deficiencies, etcetera. I could also eat a couple of pounds of apples a day.

Ben Greenfield [00:26:22]: And as long as I'm not exceeding my total calorie burn, that excess fructose is not going to spill over and create any kind of issues in my body. Now, yes, some people have things like fructose intolerance and fructose allergies and get bloating. Some people are sensitive to FODMAPs which are found in things like apples, these fermentable carbohydrates that can cause bloating and gas. But those issues aside, fructose is not a problem at all unless you're overeating. The problem is most people who are eating a lot of, let's say, dried apple chips and sodas and coke and high fructose corn syrup, etcetera, they're also eating to excess. But put me on a desert island with a bunch of blueberries, I'll sit there and eat them all day long. You know, as long, as long as I'm not exceeding the number of calories that I'm burning and have no issues or concerns about, you know, about high triglycerides or non-alcoholic fatty liver disease or anything of the like. So just understand the actual caloric dose of the fructose is the issue, not the fructose in and of itself.

Ben Greenfield [00:27:20]: And yes, I know there are some, there are some exceptions to this fact, like the harsh toxins or chemicals that might be used for extractions, used to create say high fructose corn syrup. I don't think that a Coca-Cola, 2000 calories of Coke is the same as 2000 calories of blueberries. I'm not a total calorie-in, calorie-out kind of guy. I think the quality of the food does matter. But nonetheless, the major takeaway that I want to give you here is that eating fruit is a good idea for cancer prevention. Berries are probably at the top of the totem pole. And then secondarily, apples, kiwis, citrus fruits. And gosh darn it if I'm not forgetting what the last one was.

Ben Greenfield [00:27:58]: Anyways, though, eat your fruits. All right. So let's go ahead and move on to the next topic that I want to discuss. The world's most popular drug, you guessed it, caffeine, aka 1,3,7-trimethylxanthine. And I'm drinking paraxanthine right now in this updated energy drink. But caffeine is 1,3,7-trimethylxanthine, one of the most widely consumed substances in the world, and the Journal of the International Society of Sports Nutrition. I love this journal. Their most recent edition got into common questions and misconceptions about caffeine supplementation.

Ben Greenfield [00:28:37]: So. So let's get into what they looked at and what they found. So, first of all, a little bit of a background here. Let's talk a little bit about what caffeine does when you consume it. So caffeine in most people is 99% absorbed within 45 minutes of ingesting it. Peak plasma concentrations occur between about 15 minutes and 2 hours after ingestion. That can depend on genetics, whether or not you're a fast caffeine metabolizer or a slow caffeine metabolizer. If you're a slow caffeine metabolizer, it's going to take a longer time to show up in your bloodstream.

Ben Greenfield [00:29:19]: And this is why people who are slow caffeine metabolizers if they have an Affogato espresso with ice cream after dinner at the Italian restaurant, can be up until 02:00 a.m. while a fast caffeine oxidizer can be slumbering peacefully by 10:00 p.m. so caffeine's elimination, half-life can range between one and a half and nine and a half hours, and again, ranges from individual to individual. And this is why some people can have a cup of coffee at 04:00 p.m. in the afternoon. And other people are totally screwed by that. So anyways, once caffeine is absorbed, your body converts about 70% to 80% of it into actually what I'm drinking right now, paraxanthine. The formation of paraxanthine and the subsequent excretion in the urine is the major pathway for caffeine metabolism and clearance.

Ben Greenfield [00:30:09]: Now, the way that caffeine actually keeps you awake is mechanistically, it binds to adenosine receptors. It blocks the binding of adenosine to its receptor, and that directly affects the release of neurotransmitters like norepinephrine dopamine serotonin, and gamma-aminobutyric acid and bye binding to those receptors. It keeps adenosine from causing sleep drive to be enhanced, thus keeping you awake for longer periods of time. It's blocking the effects of adenosine. Now another mechanism of action lesser known for caffeine is that it inhibits something called phosphodiesterase and that prevents another molecule called cAMP from being enzymatically degraded. Now, the accumulation of cAMP, because it's not getting broken down as much when you are consuming caffeine then stimulates the release of dopamine, epinephrine, and norepinephrine. That can cause not only wakefulness but also this kind of cool adipose tissue lipolysis, breaking down of fat, and subsequent fatty acid oxidation. That's why in some studies, caffeine has been shown to increase metabolism and cause you to burn more fat.

Ben Greenfield [00:31:21]: But there are lots of questions about caffeine, like can it dehydrate you? Can it actually burn an appreciable amount of fat? How much caffeine could kill you, etcetera? And that's what this great paper from the Journal of the International Society of Sports Nutrition got into. I'll link to the whole thing in the show notes at BenGreenfieldlife.com/476. But I wanted to get into some of the highlights for you today. So first of all, can caffeine dehydrate you if you are not exercising, just at rest, drinking caffeine at the office during the day, some people say it's such a profound diuretic that it can dehydrate you. Now, the most up-to-date research shows that habitual drinkers who are used to caffeine, not someone who's having their first cup of coffee for the first time anywhere up to around 300 milligrams do not produce a significant enough amount of diuresis to dehydrate you. Now, that means that you're not going to start to experience the dehydrating effects of caffeine until you're exceeding about three cups or more. And even then, some of the volume of the fluid associated with your caffeine intake is going to affect this.

Ben Greenfield [00:32:37]: Meaning if you're drinking a grande iced Americano with a shot of espresso that's maybe slightly less than 100 milligrams, the amount of fluid that you're getting in a grande, what is that, like 2020 4oz? That's more than enough to offset the diuretic, pee-inducing, or so-called dehydrating effects of caffeine. But then if you're having, like, I don't know, four espresso shots that are just the tiny one-and-a-half espresso shots without much fluid volume in them, it's a different story altogether. So kind of depends. But you gotta drink at least three servings of coffee or, you know, 300 milligrams plus of caffeine to start to get to the dehydrating effects. Now, when they look at the potential for caffeine to dehydrate you during exercise, it's a little bit similar if you're drinking caffeine and it's part of some kind of a fluid substance that you're consuming during exercise. As long as hydration is managed, it does not appear that caffeine intake during exercise results in any significant differences in things like fluid retention or urine output. If you're using concentrated sources of caffeine like no-dose tablets or caffeine tablets or some pre-workout that doesn't have fluid in it, but that is a high amount of concentrated caffeine, that is where there could be some diuretic dehydrating effects of caffeine during exercises. I mean, so I talked about this on the podcast recently.

Ben Greenfield [00:34:08]: I recently formulated a pre-workout. It's got about 80 milligrams of caffeine in it for a company called Vitaboom. You can check it out at Vitaboom V-I-T-A Vitaboom.com/ben, me, and my sons all had that pre-workout before our kettlebell training session yesterday. And we were sweating buckets way more than we had the other days when we hadn't had the pre-workout. And I know it was because of caffeine and some of the blood flow enhancers in that pre-workout, but if we hadn't been paying attention to fluid balance, our bodies would be more dehydrated from that versus having an energy drink that contained 80 milligrams of caffeine because the energy drink includes sometimes 16 20 24oz of fluid with it, whereas a pill does not. So it kind of depends on the delivery mechanism when it comes to caffeine during exercise. So the next question is, does caffeine significantly or appreciably decrease body weight and fat mass? Now, I already explained to you how caffeine can enhance fat oxidation both at rest and during exercise, but the question is, is that appreciable enough that the so-called thermogenic effect actually causes meaningful body fat reduction? Well, it turns out that if you are an untrained person just starting to drink caffeine or energy drinks pre-exercise, there is a big enough effect, a big enough thermogenic effect of caffeine to cause a significant amount of fat oxidation that would allow you to burn more fat and lose more weight caffeinated and exercising than if you weren't caffeinated.

Ben Greenfield [00:35:48]: However, if you are trained and you're also habituated to caffeine intake, then in that case, you're not going to see a huge impact of caffeine on weight loss energy. Yes. This could indirectly result in more weight loss because you're more likely to hit the gym or hit the gym harder because you have more energy. But if you're used to drinking caffeine and you're already a pretty trained person, you're not going to see a huge amount of fat loss. Now, I should note that in many of the clients I coach, I actually have them do fasted workouts with caffeine in their system. And anecdotally, I see better weight loss than everyone from Hollywood celebs who I train to athletes, to executives who are trying to burn a few extra pounds for swimsuit season, one of the protocols I have them do is go out in the morning, facet exercise post cup of coffee or green tea without calories and creamer added to it. And then we finish that up with two to five minutes of cold. And I can literally just see the fat melt off a body when I'm using that approach.

Ben Greenfield [00:36:48]: But I haven't seen any studies that have actually looked into the fat-oxidizing or weight-loss-inducing effects of caffeine when it's combined with facet exercise versus, say, fed exercise. So that's not something that's been studied. But I can say anecdotally, I think there's something to the idea of consuming a thermogenic agent fasting in the morning, doing aerobic exercise, and then preferably even chasing that with a cold. So you get some white adipose to metabolically brown active fat conversion. But anyway, might be getting into the weeds there. But it is an interesting strategy that I think works really well. Another question that they looked at in this study was how much caffeine could kill you. How much caffeine could kill you? Now, this might seem like a ridiculous question, but if you go to Amazon, you can buy caffeine powder, and like, you can buy a 10,000-plus milligram canister of caffeine powder.

Ben Greenfield [00:37:44]: Well, it turns out that the potentially lethal dose of caffeine is about 5 grams. So if you weren't doing things right or if you were taking excess energy compounds, the so-called median lethal dose, the LD50 of caffeine, is actually not quite as high as what you would estimate, as a matter of fact, the toxic effects, like seizures, for example, not death, but seizures, heart palpitations, et cetera, can be observed with rapid consumption of around 1200 milligrams of caffeine. And there are some energy drinks that get pretty close to that. As a matter of fact, back to that mass spec guy who I interviewed, Ben Katz. He's even done mass spectrometry studies on energy drinks showing sometimes they're at two to three times higher the amount of caffeine than is actually advertised on the label. So it's important to think about. But, yeah, 5 grams of caffeine, you could die. And again, remember, the average cup of coffee has like 100 milligrams or so, depending on, you know, whether it's an orange milk of frappuccino or a double espresso or a triple red bull.

Ben Greenfield [00:38:45]: But, you know, that means you'd have to drink like 50 cups of coffee to get close to that lethal dose. Yet it can be done, especially with some of these concentrated caffeine extracts. So something to think about, something to think about. Don't miscalculate your caffeine dose. Sex differences regarding caffeine's effect, it also looked into, right? So there's literature showing that there are factors like your estrogen level or even the use of oral contraceptives, which can decrease the CYP activity that breaks down caffeine. So if you're on the pill, you're going to be more sensitive to caffeine, you're not going to metabolize it quite as quickly. Menstruation, time of month, periods. That can all influence your ability to metabolize caffeine more quickly or more slowly.

Ben Greenfield [00:39:32]: But it looks like overall, the most important thing when it comes to sex differences with caffeine is that males seem to respond much better to the ergogenic performance-enhancing effects of caffeine than females do. And that probably is due to some type of estrogen interplay in the female population. Therefore, that could also mean that a postmenopausal female might actually respond to caffeine just as well as a man might when it comes to the ability to be able to increase exercise performance. But it turns out caffeine helps men more than women, exercises harder, or improves performance. So the next question that they looked into was when it comes to performance. And this is something that's interesting because I'll tell you a story. When I used to do the Ironman triathlon, I would abstain from caffeine for two weeks leading up to the race, and then I would have caffeine before the race and during the race, in little energy gel packets. I would do the same thing with carbohydrates. I would go very, very low carb for about a week leading up to the race and then starting about four days prior to the race, I'd begin to carb load with the idea, very similar to what I used to do in my bodybuilding days, that if you restrict carbohydrates, you upregulate the enzymes responsible for taking carbohydrates in the muscle, and therefore you ramp up the amount of carbohydrate that you can store away as storage glycogen.

Ben Greenfield [00:40:54]: And there is something to that approach. But the idea behind the caffeine was that if you abstain from it, the notion is that you're going to be more sensitized to it, versus if you're a habitual caffeine drinker and you're consuming caffeine. I say drinker. Obviously, caffeine can be consumed in many delivery mechanisms beyond just coffee. I'm just going with the world's favorite way to consume caffeine. If you are habitually consuming caffeine, does it negatively impact the ability to be able to use caffeine as an ergogenic aid? Well, if you would have asked me a few years ago, I would have said yes. But more and more studies seem to indicate that unless you are on massive doses of caffeine, specifically six milligrams per kilogram per day. Right? So if I weigh 80 kg.

Ben Greenfield [00:41:45]: Rough math. So if I'm having 480 milligrams of caffeine per day, like almost five cups of coffee per day, then if I want to use caffeine as a performance-enhancing aid, I would indeed need to abstain from caffeine usage, or lower caffeine usage prior to whatever event or workout or performance for which I wanted the ergogenic effects of caffeine. But unless you're having a massive amount of caffeine, it turns out that you don't need to, like, restrict caffeine to be able to reintroduce it and see a performance-enhancing effect. That's kind of like old-school knowledge. But nowadays it appears that caffeine is ergogenic, irrespective of the user's typical caffeine consumption habits. I'll say that again. Caffeine is ergogenic, and performance-enhancing, irrespective of typical caffeine-consuming habits. Now, another question this paper looked into was whether or not, caffeine actually works for everyone.

Ben Greenfield [00:42:41]: For wakefulness, for exercise performance, muscular endurance, power, strength, sprinting, jumping, throwing, you name it. Well, this probably comes as no surprise to you that you can test your caffeine-metabolizing genetics. Caffeine is metabolized in your liver pretty rapidly, as we've already established via the cytochrome P450 enzyme pathway. And that's your CYP1A2 gene. It's responsible for about 90% of caffeine metabolism. Genetic variations in that gene can influence the rate of caffeine breakdown. For example, individuals who are homozygous alleles of that particular gene are fast caffeine metabolizers, whereas people who are heterozygous and AC, or actually a CC, are also known as slow metabolizers. So, yes, certain people can definitely have a large amount of variability when it comes to the ergogenic response to caffeine ingestion.

Ben Greenfield [00:43:36]: And it turns out that if you are a slow caffeine metabolizer, you're overall going to be more sensitive to caffeine and it's going to be more likely to induce a performance-enhancing effect. So it might not just be genetic factors, right? There could be other factors, such as how quickly you absorb it and your habitual usage, etcetera. But it turns out that in the majority of cases, slow metabolizers appear to be more responsive than fast metabolizers. As far as feeling the effects of caffeine more, although the research does go back and forth, there's some research that says fast metabolizers do better with caffeine. So I think we need more research on this. But all we can say is that, yes, different people will respond to caffeine differently. Next up, related to caffeine causing death. Some people wonder, well, could caffeine influence my cardiovascular health? We know that acute ingestion of caffeine has been consistently demonstrated to improve cognitive performance, particularly in the realms of attention and vigilance.

Ben Greenfield [00:44:44]: Improved cognitive function can indirectly contribute to cardiovascular well-being by promoting healthier lifestyle choices, like increasing spontaneous physical activity or the motivation to go to the gym. Now, we also know that caffeine can promote nitric oxide production, which can lead to improvements in your endothelial function. And that's important because endothelial dysfunction is a well-established precursor to atherosclerosis, one of the primary underlying causes of a variety of cardiovascular diseases. Now, many epidemiological studies have indicated long-term caffeine consumption can protect against specific cardiovascular conditions. Habitual caffeine use has been inversely related to the instance of stroke and heart failure. It's been associated with a lower risk of developing type 2 diabetes, a major cardiovascular risk factor. However, acute ingestion of caffeine, especially in people who aren't habituated to it. Like your, I don't know, eight-year-old son.

Ben Greenfield [00:45:42]: Who happened to sneak a few sips of your quad chocolate orange frappuccino? That can cause a transient increase in heart rate. And a systolic and diastolic blood pressure increase. And it can elevate what's called myocardial oxygen demand, which could trigger myocardial ischemia. And someone who has pre-existing cardiovascular conditions. Which your six-year-old son may not have, but which could be an issue for some people. And so, even high caffeine intake has been associated with increased arterial stiffness. Another risk factor for cardiovascular disease.

Ben Greenfield [00:46:18]: And atrial fibrillation. Cardiac arrhythmia. This has been reported amongst heavy caffeine users. However, if you actually step back and look at the research, you got to get, again, pretty high. For you to have heart problems from caffeine. More than 400 milligrams a day. This is where you start to see the Goldilocks zone jump in. And caffeine does not appear to improve heart health.

Ben Greenfield [00:46:41]: And may actually decrease heart health. Once you exceed about 400 milligrams daily. Okay, 400 milligrams daily. If you're exercising and using a bunch of energy drinks. And some of those compounds we talked about earlier, might exceed 400 milligrams. In this case, proceed with caution. Especially, since you have a high risk for cardiovascular disorders. But it's about 400 milligrams.

Ben Greenfield [00:47:00]: Where you do need to start getting concerned. About the potential effects on the heart. Next, the study looked at bone loss, right? Could caffeine actually cause you to lose bone or cause osteoporosis or osteopenia? Well, it turns out that high coffee consumption. Is actually associated with a lower risk of osteoporosis. And the overall consumption of coffee and fractures. Bone fractures are non-significant. However, there is a certain amount of coffee consumption. That can lead to a decrease in osteoblastic activity.

Ben Greenfield [00:47:34]: Which are the cells involved in bone formation? And high caffeine intake has also been shown to suppress vitamin D function. And alter the expression of vitamin D receptors. Which can also adversely affect bone mineral density. So when it comes to coffee and your bones, it's actually very close to coffee and your heart. It turns out that the threshold is also about 400 milligrams so if you're concerned about your bones or you're concerned about your heart, 400 milligrams is the. The amount of coffee to stop at. When it comes to how or the amount of caffeine to stop at, I keep using those terms synonymously.

Ben Greenfield [00:48:13]: I realize they're different, but no more than 400 milligrams of caffeine per day, preferably. I think in most cases, especially for bone and heart, is something that's important. Pregnancy, man. I mean, if you look at caffeine, it's lipophilic, it can transfer across the blood-brain barrier and the blood-placental barrier, right? And neither the fetus nor the placenta have enzymes for caffeine's metabolism. It can accumulate in the oviductal and uterine fluid environments, which means both pre and post-birth, your child could be absorbing caffeine. And multiple, multiple studies have shown that daily doses of even less than 300 milligrams of caffeine can increase the risk of pregnancy failure. Daily intake as low as 100 to 200 milligrams per day is associated with an increased risk of miscarriage and fetal growth restriction, low birth weight, and increased risk to the offspring, including cognitive impairments overweight, and obesity. Implications If I knew anyone in my life who was pregnant, I would highly recommend them, based on the cumulative scientific evidence, to avoid caffeine.

Ben Greenfield [00:49:19]: I'm sorry, but the Starbucks drive-thru is just not going to be an option for those nine months. And I think that's very important and something that could be one of the more important parts of what I'm telling you about caffeine. Don't have it if you are pregnant. Absolutely. So that's another thing that was discussed. Almost done. Going through this, I realize there's a lot of information on caffeine, but it's very, very interesting. Is caffeine addictive? Is caffeine addictive? There seems to be a common assumption that caffeine is an addictive substance.

Ben Greenfield [00:49:50]: Now, if you look at the diagnostic and statistical manual mental disorders, the DSM-5, caffeine withdrawal is an officially recognized diagnosis, as are caffeine-induced disorders and caffeine intoxication. But in order for something to be considered for criteria for caffeine use disorder, there has to be a persistent desire or unsuccessful effort to limit use, continued use despite knowledge of potential harm, and then withdrawal symptoms. This might sound like you after going one morning without a cup of joe. However, it actually is pretty weak when it comes to its addictive potential. Now, caffeine can have an impact on some neurotransmitters related to addiction. It does have the potential to be abused by some. There are some established withdrawal symptoms, but if you actually look at caffeine for the current mechanistic evidence and the criteria, according to the American Psychiatric Association, for something to be associated as addictive, caffeine is actually pretty weak on that. Believe it or not, I think it's pretty easy to stop caffeine.

Ben Greenfield [00:51:09]: I keep decaf on hand all the time. I have about two to three cups of coffee a week when I am at home. I have one to two cups of coffee a day when I travel, usually just because when I'm at home, I have all sorts of teas and mushroom teas and all sorts of fancy little things to try when I travel. It's just like a cup of coffee from the hotel lobby, you know, and I realize that's not mold and mycotoxin free and blah, blah, blah, but, you know, sometimes you just gotta take one for the team. So anyways, I drink a lot more coffee when I travel, but, if I get home from travel, even if I feel a higher urge for caffeine than I normally would, I find it's often just the taste and the black substance and the desire for something to induce some morning bowel movement. And I can literally just do decaf, and be fine. I think often it's the taste, it's the habit, it's the neural association with something in the morning that you do caffeine with, like reading a book or meditating or journaling that can result in it feeling addictive. But it's not as addictive as you would actually think.

Ben Greenfield [00:52:05]: So, one last thing this is important. Does waiting one and a half to 2 hours after waking to consume your first cup of coffee or any form of caffeine help you avoid the afternoon crash? And there's been a trend of a lot of podcasters and people on social media who recommend delaying your coffee ingestion in the morning by anywhere from 30 to 60 minutes to as much as 90 to 120 minutes after waking. The rationale is that you want to prevent prolonging your waking cortisol response because your adenosine levels are still going down during that time. And remember that adenosine is responsible for inducing the sleep drive. And so if you prolong that waking cortisol peak, then you would actually potentially produce an afternoon crash based on speeding up your sleep drive. Now here's the thing. Cortisol does have a circadian rhythm.

Ben Greenfield [00:53:02]: Circulating levels of cortisol are lowest at sleep onset. They begin to increase during sleep, and then they peak within about an hour of waking, and then they start to decline across the day. And that's all regulated by what's called your HPA axis. The fact is that the elevation in cortisol secretion when you have that first cup of coffee in the morning doesn't even occur if you're a habitual user of caffeine, even if your habitual use of caffeine is pretty low, like 200 milligrams a day, it's a moot point if you're a regular caffeine drinker. Anyways, this idea that caffeine could somehow upregulate the cortisol awakening response to the extent where you'll experience an afternoon crash later on in the day, and in people with high chronic intakes of caffeine, 300 to 600 milligrams a day, which many people get, the cortisol response is abolished completely. So, first of all, there's no issue if you're a habitual caffeine drinker, or just having your coffee within 30 to 60 minutes of waking. It's going to have barely an impact at all on your cortisol levels. Now, the idea here is that the other flaw, in my opinion, for delaying caffeine intake based on concerns with prolonging the peak secretion of cortisol is the same peak secretion of cortisol happens with your first exercise session of the day, or your first cold shower of the day or anything like that.

Ben Greenfield [00:54:21]: So based on that logic, you would avoid just stimulating your body, in general, all morning, and you just do whatever yoga and breath work and sip some non-caffeinated tea. Cause otherwise you're gonna die of a horrible afternoon crash at 02:00 p.m. It's just, it's not really the case. It doesn't work like that. There's not a significant enough impact on cortisol for that to be the factor. And then when you look at adenosine, well, when you wake, there's an immediate but gradual buildup of adenosine. Like your sleep drive starts, like, basically right when you wake. So suggests that adenosine levels, as many podcasters and social media people who are saying don't have your cup of coffee within 30, to 60 minutes of waking, they're saying that adenosine levels continue to decline upon waking.

Ben Greenfield [00:55:04]: And that's just the lack of understanding of the proper sleep-wake cycle influence on adenosine. Adenosine is actually rising as soon as you wake up. It's not declining and you're not going to contribute to further decline by having a cup of coffee in the morning. Your adenosine levels are already going up as soon as you wake up. And you don't have to delay caffeine intake in order to not have a crash later on in the day. And there's also no evidence to suggest that daily typical caffeine intake is associated with daytime sleepiness. If there were, the hack for that would just be as soon as you start to feel sleepy later on in the day, have another cup of coffee. And it would throw any concern like that out the window.

Ben Greenfield [00:55:48]: Anyways, another cup of coffee, another serving of caffeine. So in summary, though, there may be an upside to delaying your morning caffeine intake if you are already sufficiently slept. Cause you know why? You know, why dump something into your body if you're already awake? Really? The cortisol peak adenosine avoiding afternoon crash issue is a moot point. Like you are not going to throw off your body's sleep-driver circadian rhythm by having a cup of coffee right when you wake up. I suppose the only exception to that rule would be if you are trying to adjust to a new time zone and you've woken at like 04:00 a.m. because it's, you know, it's, it's 07:00 a.m. back home, but it's 04:00 a.m. you know, on the Pacific Time Zone where you're at.

Ben Greenfield [00:56:40]: And so you get up at 04:00 a.m. and you have a cup of coffee. Well, it's gonna be a lot harder for your body to adjust to your new time zone if you're doing that. In that case, it would make better sense to wait to have your cup of coffee until you do want to start waking up if that makes sense. Same thing with light-wear blue light blockers, don't have coffee, you know, don't get in a cold shower, don't do a hard exercise session until the time of morning has arrived, at which point you want to send your body awake from the signal. So hopefully that makes sense. Man. I'm going to link to this full article in the show notes at BenGreenfieldlife.com/476 I spent more time on that than I thought, so I'm not even going to get a chance to get into some of the questions that have come through for this week on Ozempic.

Ben Greenfield [00:57:22]: I'll answer the Ozempic real quick. And we'll leave it at that because I have two questions on this. Dave asked, would you recommend stacking Calocurb or the pendulum probiotic, which are two natural alternatives, with terzepatide, which is a GLP-1 agonist? And then another person says can you take Calocurb and Pendulum GLP-1 supplement at the same time? I'm going to give you my quick 32nd response to this and go listen to my podcast with Colleen Cutcliffe from Pendulum or my podcast from Calocurb, the doctor from New Zealand if you want to learn more about how those work as natural GLP-1 agonists without taking Ozempic. But here's the deal. Calocurb, the active ingredient in that is Amarasate, a highly bitter compound that when you swallow the Calocurb capsule an hour before a meal, triggers the bitter receptors in your small intestine to significantly reduce appetite by increasing not just GLP-1, but also two other appetite satiating hormones called CCK and PYY. They might be PPY PYY or PPY, it's not important. Anyways, the Pendulum GLP-1 probiotic operates on the microbiome level, increasing Ackermansia, butyricum, and bifidobacterium to increase your level of satiety and fullness via the microbiome pathway, a different pathway. And then finally my third method of controlling hunger.

Ben Greenfield [00:58:51]: Exogenous ketones, like drinkable ketones, can suppress ghrelin, the hormone that can cause you to become hungry. So if you don't want to use or terzepatide or anything like that or any GLP-1 injectable agonists, but you want the most amount of hunger suppression you can get naturally without the nausea and the muscle wasting, et cetera. Even though I realized that muscle wasting can be solved through adequate protein intake and weightlifting. You can wake up in the morning, you can take the pendulum GLP-1 probiotic before lunch. An hour before lunch you can take Calocurb. An hour before dinner, you can take Calocurb. Mid-afternoon, you can drink a shot of ketones and you can literally lose weight, and very effectively suppress hunger and cravings. And I want to have Cheetos or Doritos or Twinkies all day long hitting those hunger mechanisms on multiple pathways.

Ben Greenfield [00:59:48]: And it works beautifully. I have many clients who do this now. So again, the pendulum GLP-1 probiotic. When you first wake up Calocurb an hour before lunch, Calocurb an hour before dinner shot of ketones at some point during the day. And you will not even think about food, even if you're the most foodie food person on the planet. So yes, you can combine them. And that's how I would do it. If you're going to do it, I will link to those products in the show notes if you want to check them out.

Ben Greenfield [01:02:39]: Go to BenGreenfieldlife.com/476 for all the show notes. Until next time, I'm Ben Greenfield. Wish you an incredible week. Thanks so much for listening. Do you want free access to comprehensive show notes? My weekly Roundup newsletter, cutting-edge research and articles, top recommendations from me for everything that you need to hack your life, and a whole lot more, check out bengreenfieldlife.com. it's all there. Ben Greenfield Life see you over there. Most of you who listen don't subscribe like or rate this show.

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