Dr Rhonda Patrick’s Interview on The Diary Of A CEO Podcast (Transcript)

So imagine that’s person A, that’s Steve A.

And then there’s Steve B. I do the exact opposite. Based on what you know about the science and about outcomes and expected outcomes, how would Steve A that followed your advice live his life as he ages? And how would Steve B, how would his outcomes be as he ages?

Obviously this is super, you’re forecasting here and it’s hypothetical, but what do you think the variance in these two people’s lives would be?

DR RHONDA PATRICK: Well, if you’re talking about the extreme ends, like if Steve B was eating sugar and smoking and drinking and just obese and sedentary, everything that you don’t want to…

STEVEN BARTLETT: Which is like a lot of the population.

DR RHONDA PATRICK: I mean, then you’re talking like a 14 year difference in life expectancy, which is pretty big. But not just life expectancy, the way your independence. Right. Your mind. So you’d be forgetful and I mean, it would be a terrible quality of life, right? So it’s not only are you going to die earlier, you’re just not going to live a good quality of life.

So Steve A might be into his 90s and out surfing, you know, because you’ve exercised, you’ve given your body the right nutrients that it needs, you’ve gotten good sleep, you’re not overweight, you’re not eating a lot of refined sugar. All these things that sort of accelerate the aging process. And we can talk about different components of this and how they do affect the way we age and our disease risk.

But I mean, there’s studies that show even a 14 year difference in life expectancy for someone who’s morbidly obese versus lean.

STEVEN BARTLETT: So Steve A could be out surfing at 90 and Steve B would be potentially dying at 75. But also his quality of life would, his health span would diminish probably in his 40s and 50s, right? So it’s really, it’s a 14 year reduction in lifespan, but potentially a 30, 40 year reduction in health span.

DR RHONDA PATRICK: And quality of life and health span. Being able to be functionally independent, being able to be cognitively sharp, feel good, right? And your mood, I mean, all these things are affected.

The Future of Aging Research

STEVEN BARTLETT: You must be sitting on some crazy ideas because as a biomedical scientist, you can see some of the research and technology that’s coming down the pipe. So I’m wondering, before we get into the conversation, are there any big ideas about the future of aging and longevity that are in your mind that you think about that are actually really important to know? Because as Brian Johnson has often said to me, you want to live to see these breakthroughs.

DR RHONDA PATRICK: Yes, yes. I am excited about some gene therapies and being able to sort of reprogram our cells to be more youthful. So, you know, this is something that was pioneered back in 2006 by Shinya Yamanaka from Japan, and he actually won the Nobel Prize.

Why his research was so important for the field of aging wasn’t really known at that time, when what he had shown is that you could take a cell that’s old and it could be any cell. It could be from an 85 year old person with Parkinson’s disease, for example. And you get it. You know, we’re constantly getting skin cells and sloughing them off.

Every day you can take one of those cells and add four different proteins to them. They’re called transcription factors. Essentially, all that means is they’re kind of like master orchestrators of many different genes in your body. And how genes are activated and turned on and doing what they’re supposed to, or they’re turned off and quiet for the time that they’re supposed to be quiet.

And you add those four proteins and you can take that 85 year old cell, skin cell, from a person with Parkinson’s disease, and you can make it into what’s called an embryonic stem cell. And it does that by sort of wiping out the, what’s called epigenome.

So people are familiar with their DNA, right? Well, the epigenome is something that sort of sits on top of your DNA and it regulates how your genes are being expressed or turned on and off. Right. And it sort of brings it back, reprograms it to this youthful state where it becomes an embryonic stem cell.

And then that embryonic stem cell can then form any type of cell in the body. It can form a heart cell or a liver cell or a brain cell or a cell from your eye. And so this is called induced pluripotent stem cells.

And this was a breakthrough at the time because it was so important. It’s important for cell regenerative therapies. Okay, let’s say someone does have Parkinson’s disease and you want, you know, Parkinson’s disease, people are losing dopaminergic neurons, and they’re substantia nigra. So these are dopamine producing neurons.

And dopamine is important for motivation, and it plays a role in our, you know, cognitive function, but it’s also important for movement. Right. So people with Parkinson’s disease are losing those at a rapid rate, and they lose control of their motor capabilities.

And so you want to be able to take an old skin cell from someone, reprogram it to become a dopamine neuron, and then inject it into that person. Right. It’s their own cell, so they’re not going to reject it. Right. So that was the big thought at the time.

Fast forward, you know, a decade or so, and a whole handful of brilliant aging scientists have discovered that instead of taking these old cells and putting these four proteins on it to become this sort of stem cell, they can pulse it. Just a quick little pulse.

STEVEN BARTLETT: What is a pulse? Like an electronic shock?

DR RHONDA PATRICK: No, what I mean is it’s just not incubated for as long of a time period. So it’s a shorter time interval that you’re putting these four different transcription factors on top of the cell that reprogram it. Right.

And the reason for the shorter time is that you don’t want it to lose its cellular identity. So let’s say it was a skin cell. You want it to stay a skin cell, not become an embryonic stem cell, but you want it to be a skin cell from a 1 year old, not an 85 year old.

So the way to do that is what’s called partial reprogramming. And so they basically, researchers have found that you can just sort of what I call pulse. It’s partial reprogramming. You’re kind of putting it on for a shorter period of time.

And then that cell keeps its identity, but it’s youthful, it wipes out all the damage, everything that’s accumulated over those 85 years. And this has been shown in animal studies, in rodents, that if you add these four different transcription factors and you give them to mice, you can rejuvenate many of the different organs.

So essentially turning back the aging clock in different organs in these mice. Now, this obviously has to be translated to humans, but I think it’s super exciting, and I do think it’s the future in terms of solving aging and rejuvenation, rejuvenating our organs. And so it’s something that I’m pretty excited about and following closely.

STEVEN BARTLETT: And are they then living longer?

DR RHONDA PATRICK: Some of these studies were done in animals that are what’s called accelerated aging. So, yes, they were living longer in that background of accelerated aging. The question is, you know, can they live longer if it’s just a normal mouse? That’s not an accelerated aging model. And these are things that are all being done right now. These sorts of studies are in progress.

Where to Begin

STEVEN BARTLETT: Where do you think is the most important place for us to start this conversation? Based on everything, you know, and maybe some of the. Presumably there’s some foundational stuff, right?

DR RHONDA PATRICK: I do. I think the important place to start would be. We’re talking about. We were talking about aging as a disease, and I think being sedentary is a disease, and I think that’s a good place to start. What I mean by being sedentary is not physically active, someone who doesn’t engage in any type of physical activity.

The Sedentary Lifestyle Crisis

STEVEN BARTLETT: And what is the spectrum there of someone who doesn’t move at all for 24 hours a day versus someone that’s constantly running marathons and doing crazy stuff. But where are most of us on that scale, and are we moving enough?

DR RHONDA PATRICK: Most of us are not moving enough. If you’re talking about globally, we’re on that sedentary scale where we’re just not physically active. We sit at our computer or a desk or a cubicle all day, and we’re not actually moving around a lot.

I say sedentaryism is a disease because it’s actually been shown to increase the risk of early mortality even more than diseases that we know of, like type 2 diabetes, cardiovascular disease, or even terrible habits like smoking. So being sedentary actually could predict early mortality even more than those diseases.

The Dallas Bed Rest Study: A Groundbreaking Discovery

But let’s take a step back. It’s even bigger than that. There’s this amazing study called the Dallas Bed Rest Study. The study started back in the 1960s, and this is done by probably the world’s most talented cardiovascular exercise physiologist. Ben Levine and Jere Mitchell were involved in this early study in the 1960s.

What they did was they took five men – they were college students – and they put them on bed rest. This is like three weeks of legitimate bed rest. They couldn’t get up to go to the bathroom, so they had a catheter in them. They did not move for three weeks. The researchers wanted to find out what happens to your cardiovascular system if you are not moving around for three weeks.

If you think about it, there’s a lot of people that are undergoing surgery or they have some sort of bad illness, influenza or something, that keeps them bedridden. It’s not unusual to be three weeks, to be honest. So it’s not completely irrelevant.

What was found is after that three weeks, their cardiovascular system was just tanked. They were probably some of the most well studied men at the time. One of the biggest factors that was measured was their cardiorespiratory fitness. This is often called VO2 max. Essentially it’s the maximum amount of oxygen that you can breathe in, and your lungs then breathe that oxygen to your muscles. It’s measured during maximal exercise when you’re putting in a maximal effort. That’s called your cardiorespiratory fitness.

Their cardiorespiratory fitness tanked. Now I mentioned this was in the 1960s. About 30 years later – and this is where Ben Levine came into the study. He’s at the UT Southwestern in Dallas. He’s also one of the most famous cardiovascular exercise physiologists out there right now. They found these five men from 30 years earlier, and they measured their cardiorespiratory fitness and a variety of other parameters that they had measured at the time.

What they found was that three weeks of bed rest was worse on their cardiorespiratory fitness than 30 years of aging. So essentially, their cardiorespiratory fitness was no worse 30 years later than it was after their three weeks of bed rest, which is kind of amazing because you would think that the 30 years of aging would be worse on your cardiorespiratory fitness than the three weeks of bed rest.

STEVEN BARTLETT: And it’s the same.

DR RHONDA PATRICK: The same individuals, the same five men. Now, after the three weeks of bed rest back in the 1960s, they were able to get their cardiorespiratory fitness back up again once they started exercising and moving around. It took a while, but when you look at their baseline levels, their baseline cardiorespiratory fitness, and you compare it to their cardiorespiratory fitness baseline 30 years later, it wasn’t worse than what happened when they compared it to the three weeks of bed rest.

Why Cardiorespiratory Fitness Matters for Longevity

You might go, “Well, why is that so significant, the cardiorespiratory fitness dropping?” We know that cardiorespiratory fitness is one of the best predictors of longevity. There are studies that have shown that people with a high cardiorespiratory fitness live five years longer than people with a low cardiorespiratory fitness. That’s pretty big difference. They’re basically 80% less likely to die of many different causes of death – cardiovascular disease, cancer, respiratory disease, things like that – than people with a low cardiorespiratory fitness.

So you’re really getting a five year increased life expectancy. You’re sort of pushing and delaying those age related diseases like cardiovascular disease, like cancer, for example. You’re pushing them down later in life so you’re not dying from them sooner.

We do know that really just getting anywhere out of that low cardiorespiratory fitness – so people with the low cardiorespiratory fitness are people that are sedentary – and if you just move anywhere above that, even if you’re going from low bad to like low normal, you’re gaining about two years increase in life expectancy. And that’s not really that hard to do.

But if you think about cardiorespiratory fitness, like right here, just having this conversation, actually even just sitting quietly, it takes about 3 milliliters of oxygen per minute per kilogram body weight to do that. To carry groceries to your car, it takes about 11 milliliters of oxygen per minute per kilogram body weight.

As you’re aging, you’re kind of heading towards this cliff, right? Because your cardiorespiratory fitness goes down with age. That’s what happens naturally. If you’re at the point where you don’t work on your cardiorespiratory fitness, if you’re not being physically active – and there are certain exercises that are better at improving cardiorespiratory fitness than others – if you’re not trying to improve it, you’re going to be heading towards that cliff faster.

Then everything becomes a maximal effort. You’re out of breath just talking, you’re out of breath carrying groceries to your car. Everything is a maximal effort and you don’t want to be there. That quality of life is not good. On top of that, you’re also going to die sooner. So you’re talking about two things here – talking about decreased health span and decreased lifespan.

STEVEN BARTLETT: So we should be moving more.

DR RHONDA PATRICK: Right. And the question is, well, how do you improve your cardiorespiratory fitness?

STEVEN BARTLETT: Yeah.

The Science of Improving Cardiorespiratory Fitness

DR RHONDA PATRICK: Do you lift weights? Do you go for runs, do you bike? What is it that is really good at improving cardiorespiratory fitness? That’s the question that a lot of exercise physiologists have answered over the last couple of decades.

You want to engage in what’s called vigorous intensity exercise. This is the kind of exercise where you’re not able to have a conversation when you’re engaged in it. Your heart rate is going up to about 80% your max heart rate, you’re not able to really talk. I would say it’s something that can be done in intervals. So you can do high intensity interval training. You have these intervals where you’re getting your heart rate up, you’re doing vigorous exercise, and then you have recovery periods where you’re kind of resting, you’re lowering your heart rate, you’re not doing that maximal sort of exercise.

I say this because there have been studies, multiple studies that have shown people that engage in moderate intensity exercise – so this is the kind of exercise when you’re breathy, but you can still kind of have somewhat of a conversation while you’re doing it.

STEVEN BARTLETT: Like the StairMaster.

DR RHONDA PATRICK: Like the StairMaster, yeah, exactly. Even people that are engaging in that type of exercise for two and a half hours a week – so this is following the physical activity guidelines – 40% of those people can’t improve their cardiorespiratory fitness. It’s like, well, I don’t know about you, but I don’t want it to be a coin toss in terms of if I’m doing that kind of exercise. If I have a 50% chance of not improving my cardiorespiratory fitness, if I’m doing this, I want the sure thing.

The sure thing is you take those people and then you have them engage in high intensity interval training and they’re able to improve their cardiorespiratory fitness. That’s because you’re putting a stronger stress on your cardiovascular system. So the adaptations are greater. Part of the adaptations are you’re able to bring in more oxygen, carry it to your muscles, carry it to your other tissues better. That’s your cardiorespiratory fitness.

The Norwegian 4×4 Protocol

That’s really, I would say the bottom line here is engaging in even just once or twice a week. I would say that the most well researched protocol for that would be something called the Norwegian 4×4. That is where you’re doing a longer interval. It’s a four minute interval and it’s best done on either a stationary bike or maybe a rowing machine. You’re going as hard as you can and maintain that intensity for four minutes and then you’re going to go down to light exercise and recover for four minutes and let your heart rate go down and you do that four times. So it’s a four by four.

That is probably one of the most robust ways to improve cardiorespiratory fitness. But there are other ways. Even doing one minute on, one minute off. So you do one minute as hard as you can go again for that entire minute. You’re not going all out, but as hard as you can and maintain that for the entire minute. Then you rest a minute and you do that 10 times. So it’s a 20 minute workout.

The Minimum Effective Dose

STEVEN BARTLETT: So for the several million people that are listening right now, if you had to prescribe them all something to do and it was the minimum they had to do, tell me what exactly the workout would look like and how frequent it would be on a weekly basis.

DR RHONDA PATRICK: I would say the minimum effective dose would be once a week.

STEVEN BARTLETT: Okay.

DR RHONDA PATRICK: And it would probably be the one minute on, one minute off. If you want the upper end robust effects of improving cardiorespiratory fitness, you can still improve it with something like a tabata.

STEVEN BARTLETT: What’s a tabata?

The Norwegian 4×4 Protocol and Heart Health

DR RHONDA PATRICK: Where you’re doing a 20 second interval and you’re going more all out because it’s shorter time and then you’re recovering for 10 seconds. So it’s a 22 second on, 10 second off. You do that eight times and if you repeat that twice, so it’s essentially a 10 minute workout. That’s also something that can improve cardiorespiratory fitness.

But I would say, and I’ll tell you why, there’s the minimum, right? So the one minute on, one minute off. But I would say the Norwegian 4×4 is the gold standard. And that’s because it’s not only improving cardiorespiratory fitness. This is probably one of the most exciting pieces of evidence I’ve seen with respect to exercise and aging.

And that is that being part of an exercise protocol was shown to reverse the structural changes that occur with age in the heart by 20 years. So what do I mean by that? I mean, people that were 50 years old, that were sedentary, so they weren’t really going to the gym, they weren’t engaging in any sort of physical activity, but they weren’t, you know, they didn’t have diseases, they didn’t have type 2 diabetes. They didn’t have cardiovascular disease. I would argue sedentary. Being sedentary is a disease.

But putting that aside, they didn’t have any diseases. Right. And they’re 50, so they’re midlife. And this was again, this was done by Ben Levine out of UT Southwest in Dallas. He took these 50 year olds and put them on a pretty intense exercise routine for two years or a stretching routine. This was like the control.

And this type of exercise routine was progressive. So they started out lighter and sort of worked their way up. Right. Like, you don’t want to just start with a Norwegian 4×4. People that never exercise. I mean, that’s going to be tough. So it was a progressive sort of building up to that.

But towards the end of about the first six months, these people were exercising about five to six hours a week. And that included one to two sessions of the Norwegian 4×4. And it also included a lot of, you know, they’re doing moderate to vigorous intensity cycling or running and some strength training as well. And they did this for two years. Their hearts were looked at.

And so as we age, our hearts shrink and they get stiffer. And that plays a role in causing cardiovascular disease. I mean, that’s the number one killer in the United States. It also affects cardiorespiratory fitness. Right. Why does the heart stiffen with time? Well, it has a lot to do with actually being exposed to a lot of glucose.

When you’re eating a lot of refined sugar and refined carbohydrates, you’re having a lot of glucose around in your system. This causes a chemical reaction called glycation. So you get these advanced glycation end products that sort of react with your collagen that’s lining your heart and your myocardium and it causes it to stiffen.

And so now the heart can’t really respond to stress well, it’s stiff. And that plays a role in, like heart attacks, for example. So exercise is one of the best things you can do to move glucose out of your vascular system and get it to your muscles. And so that’s one of the things that it does and helps with not causing that stiffening of the heart.

And so essentially these 50 year olds had their heart, the structure, so it was bigger and less stiff. After two years of this exercise protocol, it essentially made their hearts look like 30 year olds. And I mentioned they were 50 year olds. I mean, that’s amazing. That’s incredible that you can take someone midlife, put them on a two year training protocol and reverse the aging of their heart by 20 years.

How to Perform the Norwegian 4×4

STEVEN BARTLETT: So on this Norwegian 4×4, you’ve convinced me to give it a shot. But specifically how I do that. So I do my warm up and then I do four minutes of hard exercise, I take a break. And the exercise I’m doing in those four minutes can be any number of things, but I just have to get up to 85, 80% of my exertion levels, 80% difficulty.

DR RHONDA PATRICK: So the way it works is, as I mentioned, it’s best if you’re doing a cardiovascular type of exercise. So like the assault bike, you could do assault bike? Yep, assault bike. You can do a rowing machine. You could do a stationary cycling machine as well.

STEVEN BARTLETT: Could I run?

DR RHONDA PATRICK: You can, but that is, it’s definitely, I think it’s better on doing like maybe a bike or assault bike or something. But you can run like whatever it is that you like to do and you are going as hard as you can for that four minutes and maintain within that four minutes. So it’s not an all out or it’s far from all out. Right. But you’re not really having a conversation while you’re doing it.

And then the four minutes of recovery, if you’re running, you kind of go down to walking. If you’re on the rowing machine or the assault bike, you’re just going very slow. You’re just really going slow and you’re letting your heart rate come down, you’re letting your muscles kind of recover. Your cardiorespiratory fitness, you know, your cardiorespiratory fitness system recover somewhat.

And then after that four minute recovery, you go back to the four minutes of like intense again. And you’re doing that four times. It’s not easy. But you know, people can start out, they don’t. I mean, even if you start out with not going super, super hard in those four minutes where you just maybe you can have a conversation, but you’re still going hard, harder than you’re used to pushing yourself.

And I think for people that haven’t really engaged in any type of high intensity training before, that’s a good idea where you kind of, you got, you can’t just start doing it right out the gate. You want to kind of work your way up that. So doing the four minutes, just try to put in as much effort as you can right during those four minutes and then you do your recovery and you repeat that four times, but then work your way up as you do it. One week, two weeks, a month, later, two months later, and really try then to get to that point where during those four minutes, you’re pushing yourself hard, where you’re not really able to have that conversation.

The Science of Lactate: Your Body’s Miracle Molecule

STEVEN BARTLETT: And physiologically, what is going on in my body when I get to that 85, 90% effort range and I stay there for a couple of minutes, that doesn’t occur when I’m doing my Stairmaster.

DR RHONDA PATRICK: I mean, so many things are happening. There’s a lot of different, I would say, physiological responses that are.

STEVEN BARTLETT: You’ve got a big smile on your face when I ask.

DR RHONDA PATRICK: Yes, I do, because it’s one of my favorite things to talk about. And it has to do with when you’re pushing yourself really hard. You need to make energy, right? And the way that most of our cells make energy, like our muscles, is by using our mitochondria. These are tiny organelles inside of our cells that produce energy, but they need oxygen to do it.

So that’s where the oxygen comes into play when you start to push yourself really hard. You can’t get the oxygen to your muscles quick enough, but you need to make the energy. And so your body decides to make energy in the form of ATP without the mitochondria, and it uses glucose to do that. And you’re not making as many of those ATP energy molecules, but you’re still making them, and you’re making them quick. And that’s what your body wants to do.

And so it’s using glucose to do that without the mitochondria, but as a byproduct, it’s making something called lactate. And this is what gets me so excited, because for the longest time, lactate was thought to be this just metabolic byproduct of glucose metabolism. You know, when you’re pushing yourself really hard. Anaerobic. It’s called anaerobic, by the way. You’re not only anaerobic, you’re just somewhat anaerobic. You’re still producing energy with your mitochondria. It’s just you’re also producing without the mitochondria. It’s not like a sort of black and white sort of thing, right? It’s a little bit gray.

But the reality is you’re producing something called lactate. For the longest time, I always thought this lactate. Oh, it’s just. It’s bad because, you know, it can form lactic acid, and that burns. Forms that burn in your muscles. And, you know, this was, you know, decades ago, and we now know from the work of George Brooks out of UC Berkeley that lactate itself isn’t causing the burn.

And not only is it not causing the burn, it’s like a miracle molecule that’s being made. This metabolite, lactate gets into your circulation and it gets consumed by your heart, by your brain, by your liver, and it’s used for energy. It’s very much similar to beta hydroxybutyrate, that ketone body that you always hear about, People talk about when they’re fasting or doing a ketogenic diet. It’s actually very similar to that. It gets used, it gets transported through the same transporter and it’s used like energy, very similar to that.

But what’s more exciting is that lactate is a way for your muscles to communicate with other organs like the brain. And it’s called the signaling molecule. So your muscles are going, “I’m working really hard. This is really hard. We have to respond to this work, we have to adapt.” And so your body goes, “Okay, I got to like turn on all this awesome stuff that I have because I’m working so hard. I need to respond to that so that like, I’m good, right?”

Lactate’s Impact on Brain Function

And so what happens is the lactate, this has been shown, it gets consumed a lot by the brain. And in the brain it activates something called brain derived neurotrophic factor BDNF. And this is kind of like a miracle grow for your brain. So essentially it’s able to increase the growth of new neurons, which is amazing. It’s called neurogenesis. It increases the connections between neurons, so it improves memory, cognition, and then it’s involved in what’s called neuroplasticity. So the ability of your brain to adapt to a changing environment, this is all from lactate.

And it also increases neurotransmitters like norepinephrine. So focus and attention, serotonin, your mood, you’re feeling better, you’re motivated. All these things are happening because of lactate. And there’s been studies in humans showing that people that are compared, working hard, working out hard, vigorous exercise versus sort of moderate to light exercise, they make more lactate and that lactate, it’s been shown that high levels of lactate are correlated with improved cognition scores, improved impulse control.

So serotonin plays a role in impulse control. So you’re able to not just go on your impulse, right? You’re able to kind of like, which is great if you want more focus and attention, right? So this is all really exciting stuff because it all comes down to just, it’s like your muscles are these little chemical, pharmaceutical factories and the way to make them, make these pharmaceuticals is to work them, to challenge them.

And that can be done with an easy high intensity interval training protocol. A variety of them at Norwegian 4×4 can increase brain derived neurotrophic factor. That’s been shown. The one minute on, one minute off protocol also has been shown to increase that again through the lactate. So that’s one of the big sort of, I would say, differences between vigorous intensity exercise and more of that moderate intensity or like low intensity exercise.

And I honestly think, you know, I think the guidelines, you know, everyone’s sort of obsessed with steps. “I need to get my 10,000 steps in my 10,000 steps.” And they have wearable devices and I think that’s great. But I think we need to change the 10,000 steps to at least 10 minutes of vigorous intensity exercise. Like you could do 10 minutes of, you know, any type of exercise that’s really going to get your heart rate up and it’s going to be so much better.

Can You Just Drink Lactate?

STEVEN BARTLETT: So this is a really dumb question, but it’s the question that I had in my mind, which is, if lactate is such a miracle drug, why can’t I just drink it? Why can’t I just get a shot of lactate versus having to go through vigorous interval training?

DR RHONDA PATRICK: It’s a great question, Steven, because there have been studies that have been done looking at, for example, traumatic brain injury patients. So people that have undergone some sort of head trauma and they’ve infused sodium lactate through like an IV into their, you know, system, and the lactate immediately gets consumed by the brain and it’s been shown to improve their recovery.

So it’s called the Glasgow Score. You may have heard of it, but it’s kind of essentially this battery of tests that’s done to sort of assess how someone’s recovering from traumatic brain injury. And the sodium lactate does improve that. So there are, you can find out there, different types of lactate that you can consume and theoretically it should help. But what happens is when you consume the lactate, lactate actually gets used by the gut. So a lot of it’s going into the gut cells before it gets into your circulation.

STEVEN BARTLETT: There’s always a trade off with these bloody things. Whenever you try and trick the system or shortcut the system by like drinking something. I feel like there’s a trade off which people don’t talk about a lot.

The Benefits of Lactate for Gut Health

DR RHONDA PATRICK: Well, the thing is, it is good for the gut. In fact, a former colleague of mine, Mark Chikunaga, has shown that lactate is really beneficial for the gut epithelial cells. In fact, if you think about it, all these sort of beneficial probiotic bacteria like Bifidobacterium, for example, they’re producing lactic acid. And that lactic acid does get converted into lactate. It’s sort of like this physiological homeostasis where you have the difference of just a hydrogen atom. So you’re having lactic acid and lactate sort of in this equilibrium, so to speak.

But those bacteria in your gut are making lactate, essentially. And the reason it’s so good is because it is a very easily utilizable source of energy for the gut cells. So not to go off on a tangent here, yes, there is always a trade off, especially for doing something orally.

But when it comes to exercise, there’s so many things. Like I mentioned when we first started talking about exercise, if you could pill up what exercise does, I mean, it’s so many things, right? It’s not just the lactate, so many different things, so many different adaptations that occur. I mean, it would be a miracle drug.

So you’re not just getting the lactate, you’re getting the improvement in cardiorespiratory fitness. You’re getting the muscular response, right? The adaptations to your muscle. You’re increasing stress response genes like heat shock proteins that are important for preventing neurodegenerative disease. You’re making antioxidants because the inflammation that you’re generating while you’re exercising, there’s hundreds and hundreds of things that are happening all in concert from exercise. And you just can’t pill it up.

Why the Body Doesn’t Make More of These Beneficial Compounds

STEVEN BARTLETT: I have another really silly question, which is if lactate and these other things even like creatine and all these other things are so good for me, why doesn’t my body just make more of it?

DR RHONDA PATRICK: I mean, your body does make it. The problem is that as we’re aging, everything becomes less efficient. Everything doesn’t do what it used to do as well as it did when it was younger. And also in the case of creatine, which we can talk about later if you’re interested, then your body only makes so much of it.

STEVEN BARTLETT: Why doesn’t it make more? Maybe I’m not giving it the minerals or the environment it needs naturally to make more. I don’t know.

DR RHONDA PATRICK: You get it from your food, too. Creatine is found in meat, in poultry, in fish. So probably that’s why your body doesn’t make more of it, because it knows you’re going to be getting it from your diet as well. And so that is another way to get creatine.

Of course, the vegans and the vegetarians, that’s a whole other ball game because they aren’t eating meat. And so they’re really essentially only relying on what their body can make.

Protecting Cognitive Function for the Future

STEVEN BARTLETT: We’ll definitely talk about that later on this point of the brain then. I don’t want to be an older person who can’t remember things and stutters over my words and falls into cognitive decline. And I’m 30, so I feel like I’m at a moment in time where I can really make decisions now that have a really big impact on my 90 year old brain and my ability to think straight and clearly and remember things. Are there things that I can be doing now that will have a profound impact on my cognitive performance at 90?

DR RHONDA PATRICK: Yes.

STEVEN BARTLETT: And what are those things?

Exercise and Brain Growth: The Hippocampus Study

DR RHONDA PATRICK: Absolutely. Well, first of all, just to kind of wrap up the exercise story, because I think this study is so profound and in fact, it wasn’t done in 32 year olds, it was done in older adults. So we’re talking 60 year olds or a little bit older. And these individuals were put on a aerobic exercise training program for one year that was more of like a 70 to 75% max heart rate. So it wasn’t so vigorous, but it was pretty vigorous for them. Right.

And the basis of this study was to look at brain aging as we age. I mentioned our heart aging. Right. It gets stiffer and shrinks with age. Our brain also shrinks with age. It’s called atrophy. And as we age, especially starting in midlife, so around the age of 50, your brain and certain areas of the brain, like the hippocampus, which is involved in learning and memory, starts to shrink by about 1 to 2% per year.

STEVEN BARTLETT: I don’t want that to happen.

DR RHONDA PATRICK: Same same. The good news is in this study, after a year of this sort of aerobic exercise training program, they were doing three times a week, about 30 minutes a day. Really not even that intense, these individuals. And then there was a control group that was kind of the stretching. They like to use the stretching as the control group.

So let’s talk about the control group, the stretching group. They did lose about 1 to 2% in terms of the size of their hippocampus. It shrunk 1 to 2% after that year, which is what you would expect normally. However, the group that was training, not only did they not have their hippocampus shrink by 1 to 2%. It actually grew by 1 to 2%, which comes down to that neurogenesis, that growth of new neurons, the brain drive neurotrophic factor that’s able to do that.

You’re actually able to grow new neurons even when you’re in the age of 50, which is amazing. It’s incredible. So that study I love because a couple of reasons. One, it shows that it’s possible to not only stave off some of the components of brain aging, but to reverse it and increase it right through exercise. And number two, I love it because it’s never too late. You can start this in your 60s and still have a benefit. Right. You’re talking about being in your 30s. But some people watching this show, listening to the show, may already be in their 50s or 60s. Right? So it’s never too late.

Likewise, we’re talking about being cognitively sharp and not getting dementia. There’s also studies showing that people like women that were brought into the lab, they had their cardiorespiratory fitness measured. Those women with the highest cardiorespiratory fitness were 80% less likely to come down with dementia over the follow up period of time.

So again, I think exercise is one of the big ones when it comes to brain aging. But you asked an important question. You say, “What can I be doing now that’s going to affect the way my brain ages for the subsequent decades of my life?” And there are other things that can also be done that don’t even require as much effort as exercise. Exercise is the gold standard because being able to not only stave off atrophy of the brain, but to regrow some of it is incredible. Right? I mean, that’s just mind blowing.

Exercise and Existing Dementia

STEVEN BARTLETT: Have they ever taken people with dementia, Alzheimer’s, and put them on an exercise program and monitored the decline of their cognitive abilities on an exercise program?

DR RHONDA PATRICK: Yes. I mean, it’s much harder when you already have someone who is in that pathological state, because things just really snowball and accelerate. And there are some benefits. I mean, but it’s not. Prevention’s always the best. Prevention’s always the best. And so, I think that if there’s any sort of take home here, it’s that let’s try to do what we can now so that we don’t get to that point before.

Understanding the Causes of Dementia and Alzheimer’s

STEVEN BARTLETT: We get into the easier ways of staving off cognitive decline. Do we know what causes dementia and Alzheimer’s yet? Do we have any ideas? Cause we can. When they do the brain imaging, they can kind of see these plaques on the brain, they say.

DR RHONDA PATRICK: But, I mean, there’s a lot of different. It’s multifactorial, which means there’s a lot of different causes of dementia and Alzheimer’s disease. So I would say you mentioned plaques, amyloid beta plaques. What happens is that’s the aggregation of a protein in our brain called amyloid that typically is cleared from our brain.

And what happens is this abnormal thing happens where you’re not clearing the amyloid, and so it starts to kind of form these clumps and aggregates with the amyloid proteins that are not being cleared. And that essentially is happening outside of your neurons, but it’s happening where the synapses are formed between neurons. And so what happens is it kind of disrupts the synaptic connection between neurons, which is essentially forming a memory.

And so when you start to disrupt that connection, you lose. Not only the memories start to go away, but the whole purpose of the neuron is to kind of. I mean, one of the purposes is to form a memory. And so you start to, neurons start to die, right when they start to lose their purpose.

The Role of Sleep in Brain Health

Amyloid aggregation is linked to a lot of things. So, for example, I mentioned it being cleared when we sleep, particularly when we’re in our deep sleep stage, slow wave sleep. That is, something happens that’s kind of incredible. It’s called activation of the glymphatic system. So you’ve heard of the lymphatic system? Well, the glymphatic system is essentially this series of networks and almost these highways and essentially roads and stuff, all throughout the brain, where you’re squirting this cerebral spinal fluid throughout the brain, and it’s clearing away all the garbage, things like proteins that didn’t get cleared, and it’s sort of squirting them out and clearing them out through this glymphatic system.

That glymphatic system is activated during sleep. And it’s one of the reasons why people that don’t get good sleep over the course of decades have a higher risk of Alzheimer’s disease is because they’re getting these amyloid plaques built up in their brains.

Glucose Metabolism and Brain Function

But there’s other causes as well. So, for example, glucose metabolism is disrupted in the brains of Alzheimer’s disease. You need glucose, your neurons need glucose. And so essentially your brain isn’t able to make energy correctly without the glucose getting into your brain. And so that’s another sort of metabolic underlying cause of Alzheimer’s disease, where you’re essentially, I mean, it’s thought to be where you’re eating a lot of refined carbohydrates, refined sugars, and you’re not exercising. And essentially you’re disrupting the glucose metabolism in the brain as well as the whole body. Right. So the brain and body are connected.

Genetic Risk Factors: The APOE4 Gene

But there’s also genetic causes as well. And some people have genes that can increase the risk of Alzheimer’s disease because they’re not able to clear amyloid as well, because they’re not able to repair damage as well. So the blood brain barrier, which is really important for filtering out toxic things from getting into the brain, it starts to break down. And that’s one of the, I would say early, early signs of Alzheimer’s disease is that breakdown of the blood brain barrier.

And that happens in people that have a genetic risk factor called APOE4. You may have heard of this, but this is probably one of the biggest genetic risk factors for Alzheimer’s disease. About 25% of the population has one copy of this gene that increases the risk of Alzheimer’s disease by twofold. If you have two copies of it, it increases the risk of Alzheimer’s disease by tenfold. So twofold being 200%, twofold being twice as much. Yeah, 200% and tenfold being 1,000%. Right. You’re basically. I mean, it’s pretty bad.

And it’s not your destiny to get the Alzheimer’s disease. If you have those genes, you can do things in your lifestyle that can sort of turn the table. So you’re not essentially going to be getting that Alzheimer’s disease. And a lot of different lifestyle factors like getting good sleep, like exercising, avoiding alcohol, avoiding smoking, not being overweight and obese, those affecting your Alzheimer’s disease risk. More importantly, if you have one of those genes, then you really have to be cognizant of those things, because if you have one of those APOE4 genes, then essentially your lifestyle matters even more than people that don’t.

Testing for Genetic Risk Factors

STEVEN BARTLETT: And you can do a test to figure out if you have those genes?

DR RHONDA PATRICK: Yes, yes. There’s a variety of genetic testing services that can be done. Pretty much all the ones that are out there on the market. Ancestry, DNA. I mean, depending on where and what. There’s so many out there right now that will test for that.

STEVEN BARTLETT: I’d be mortified if I found out I had two of those genes.

DR RHONDA PATRICK: Two of them is less common. When I mentioned the 25% of the population having it, it’s usually one allele. Alcohol essentially can really increase the risk of Alzheimer’s disease if you have one of those genes. And I think that there’s really no safe amount of alcohol that can be consumed for people that have APOE4, if you’re concerned about dementia and Alzheimer’s disease.

The other thing is contact sports and traumatic brain injury. People that have any one or two of the APOE4 genes, if they have that, then if they get a TBI, like if they’re playing American football or they’re playing soccer or MMA or boxing, whatever, then you talk about going up to a tenfold risk for Alzheimer’s disease when you get an injury, because people with those genes don’t repair damage as well, so it affects their brain’s ability to repair damage. And so that’s also really important to consider.

STEVEN BARTLETT: So moving back then to the simple things that we can do to improve our cognitive performance as we age, the things that are simpler than doing the.

The Power of Simple Supplements

DR RHONDA PATRICK: Vigorous HIIT training, there’s actually quite a few. And first and foremost, the one I love the most is a simple multivitamin. And the reason I love this is because, I don’t know. It was about 10 years ago, there was a huge study that was published, and it was published in the Annals of Internal Medicine. And it was called “Enough is Enough. Multivitamins are not only useless, they’re harmful.”

And it was essentially looking at a variety of studies and arguing that multivitamins are expensive urine. You’re just not really doing anything. And in fact, if you take a multivitamin, you might even be increasing the risk of disease. That study was terrible. And I, 10 years ago, went and just broke it down and pulled it apart piece by piece.

But here we are, 10 years later, three large clinical trials have been done. These are randomized controlled trials where older adults were given either a multivitamin, and this was just your standard run of the mill multivitamin centrum silver, or they were given a placebo and they were given this for a couple of years.

And what three different studies showed was that a multivitamin improved cognition, improved processing speed, it improved what’s called episodic memory. So the kind of memory where you’re remembering experiences and you can recall events, things like that. Not only did it improve it, it improved it so much that it was equivalent to reducing the aging of the episodic memory by five years. So a simple multivitamin.

And why is that important? Because multivitamins have a variety of these vitamins and minerals that we’re not getting from our diet that are important for everything, for metabolism, for the way our neurotransmitters are firing, for reducing damage that’s causing oxidative stress. So a simple multivitamin. How much easier can it be than taking a simple multivitamin?

And the fact of the matter is that we’re talking about a randomized controlled trial. This is showing cause. This isn’t just an association. This is showing that you took a multivitamin for a couple of years and improved your cognition more than a placebo. So I think that’s pretty incredible. And it’s one of the examples that I like.

Early Research on Aging and Nutrition

But diving deeper into some of the nutrients, this is an area I started out as a scientist. I started out as a chemist, actually. But when I first got into biology, I was working in an aging lab and studying aging. It was very interesting to me because I essentially, with my own experiments, with my own two hands, could manipulate these tiny little worms. They’re called C. Elegans, and their whole genome was sequenced at the time, and this was in the early 2000s.

And they have a lot of genes that are similar to humans. It’s called homology. And one of the genes is the insulin signaling pathway and the IGF1 pathway. So insulin signaling would be something that’s activated with glucose. You’re eating a lot of sugar. And I could take these worms and I could genetically decrease their insulin signaling. So it kind of, if you think about a parallel to that, that would be okay. We’re not going to be eating as much sugar. We’re not going to be activating that pathway so much.

And I could do that in this worm that has a life expectancy of about 15 days, and I could extend its life expectancy to 30 days. So you’re increasing its life expectancy by pretty much 100%. Well, not only did they live longer, they were healthier and youthful. And you could see that visually they’re moving around, and they were just youthful worms.

And so I was very excited about this in my 20s, because I was like, wow, this is very relevant. We have this gene and we know lifestyle factors that affect it. Sugar. So the take home for me was lifestyle matters. Yeah, genetics. Maybe that’ll be something one day where we’re decreasing the insulin signaling. But I was looking for the now, not the future technology.

And so the now to me was, wow, I don’t want to be constantly activating my insulin signaling pathway. Look what happens to these worms if you reduce it. I mean, it’s amazing. They’re youthful and they live longer. And so I started to kind of get into diet and lifestyle sort of just out of curiosity and sort of reading in the literature.

The DNA Damage Discovery

And I came across some studies from my mentor, Dr. Bruce Ames, where he was showing that not getting enough nutrients, like for example, folate. Folate is found in dark leafy greens like kale. Folate, if you decrease folate and make someone deficient in essentially causes double stranded breaks in your DNA. That essentially is like being under ionizing radiation.

And that experiment was done like you could take a mouse, make it like put low folate in the mouse’s food, and then take another mouse and put it under an ionizing radiation machine. And the amount of double stranded breaks in your DNA, which cause cancer, which accelerate aging, which affect how your cells are functioning, it was the same.

So it was like, wow. Not having a certain nutrient in your diet was like standing under an irradiating machine. Ionizing radiation. No one’s going to want to stand under an ionizing radiation machine, but no one’s thinking about how your diet can do the same thing. And that was kind of. I got into a lot of Bruce’s research at the time.

So Bruce, anyone in the science field knows Dr. Bruce Ames, he actually came up with the Ames carcinogen test. And that essentially was a way of cheaply looking at and identifying whether something’s a carcinogen. And he got into sort of nutrition as he started to figure things like folate, basically, lack of folate being a carcinogen, essentially. Like ionizing radiation is a carcinogen. And then he started to go on to other nutrients as well, like magnesium and B vitamins.

But I think for me, the aha moment was micronutrients. And these vitamins and minerals are affecting the way we age, are affecting our health on a similar level as these toxic things that we’re worried about, like ionizing radiation. And nobody’s thinking about it like that.

The Vitamin D Crisis

So I’ll give you an example. Vitamin D. You talked about dementia. What’s going to help prevent dementia? Vitamin D is. It’s actually more than a vitamin. Vitamin D gets converted into a steroid hormone. So a steroid hormone, essentially what it does is it goes into the nucleus of a cell where all your DNA is, and it’s activating genes and deactivating them. It’s affecting your genome. And it’s actually over 5% of your genome is being affected by vitamin D.

Why is that important? Because 70% of the US population has insufficient levels of vitamin D. The reason for that is because vitamin D3 is actually made in the skin from UVB radiation from the sun. And so if you’re not outside, then you’re not really making a lot of vitamin D3 in your skin. And vitamin D3 then gets converted into this steroid hormone that regulates everything.

And so modern day society, we’re inside all the time, we’re working, we’re not outside. And even if you were outside, there’s so many other factors that affect it. So anything that blocks out UVB radiation blocks out the availability of your body to make vitamin D3. So sunscreen. That’s a big one. Melanin, the darker pigmentation that acts as a natural sunscreen. And then latitude, depending on where you live also.

So a good number of months out of the year, if you’re in a more northern latitude, like England, like Wales, like Chicago or Sweden, UVB radiation’s not even hitting the atmosphere for several months out of the year. Combine that with sunscreen or melanin and you got this disaster.

In fact, there was a study out of the University of Chicago that looked at African Americans and Caucasians and their ability.

STEVEN BARTLETT: From white people.

DR RHONDA PATRICK: Yeah, exactly. Their ability to make vitamin D3 from UVB radiation from the sun. And as I mentioned, melanin is a natural sunscreen. And people that are from African origin or South American or Southeast Asian. People that are closer to the equator usually have more melanin. It’s an adaptation to prevent you from burning from the UV rays of the sun.

Well, this University of Chicago study found that people that are African American had to stay in the sun six to ten times longer than people with fair skin, the Caucasians, to make the same amount of vitamin D3. And so as a consequence, if you take someone who, like yourself. Well, you’ve got a little bit more melanin. A little bit, yeah, you’ve got a little bit more melanin. But let’s say you take someone who.

STEVEN BARTLETT: Has, like my mom, she’s Nigerian.

DR RHONDA PATRICK: Okay, your mom from. Yeah, Nigerian. And let’s say your mom moves to Chicago?

STEVEN BARTLETT: Well, she’s moved to bloody England.

DR RHONDA PATRICK: Or if she moved to England. Right, exactly. Then you’re talking about a recipe for disaster in terms of vitamin D. Because you’re not only not making it several months out of the year. I forgot how many months out of the year? Maybe four or five or something like that where the UVB radiation’s not even hitting the atmosphere, but you have this natural sunscreen.

STEVEN BARTLETT: What’s the consequences of that in terms of symptoms?

DR RHONDA PATRICK: Well, it’s not like an acute thing where you kind of just look in the mirror and you’re like, what is.

STEVEN BARTLETT: The causation then in terms of.

DR RHONDA PATRICK: Right, right, yeah. So the reason I say this is because people always think of like, well, I’m not getting enough vitamin C and I have scurvy and you can look in the mirror and your gums are falling apart. It’s easy to identify this Vitamin D deficiency or insufficiency is more insidious. It’s kind of this damage that accumulates over time. It’s something that isn’t quite noticeable or maybe you’re feeling, maybe you’re feeling lethargic or you don’t have enough energy, things like that, but you don’t really know quite why.

So vitamin D insufficiency and deficiency, there are acute effects where if it’s severe, it can cause rickets and bone malformations and stuff, especially if it’s happening early in life. But what we now know is that being deficient or insufficient in vitamin D can increase dementia risk by 80%. And that’s been shown in multiple studies.

The converse is also true. So people that supplement with vitamin D3 and this is where a simple solution comes in. So you’re not making it from your skin, but you can take a supplement. People that supplement with vitamin D3 have a 40% reduced risk of dementia. So in other words, they’re avoiding deficiency, which is very common, and avoiding that deficiency then is reducing their dementia risk.

And there’s actually even been studies in people with dementia, in people with Alzheimer’s disease that were giving a vitamin D supplement or a placebo control, and those individuals given the vitamin D supplement had improved cognition, they had lower markers of amyloid plaques. So those were also measured as well. So vitamin D is doing a lot of things. It’s regulating 5% of your protein coding human genome.

The Recipe for Dementia

STEVEN BARTLETT: If I want to increase my probability of getting dementia, then I’ve got to stay out of the sun. I’ve got to avoid vitamin D, I’ve got to drink alcohol, smoke, be sedentary and I’ve got to sleep really badly.

DR RHONDA PATRICK: Yes. And eat a lot of refined sugar. Yeah, yes, yes, exactly.

STEVEN BARTLETT: Okay.

DR RHONDA PATRICK: Exactly. Now you might go, well, how much vitamin D? I’m talking about deficiency and insufficiency and you really want to get a blood test to know what your levels are. There have been, I don’t know, 30 plus studies that have looked at vitamin D levels and all cause mortality. So that would be again, dying from a variety of different diseases, cardiovascular disease, respiratory disease, cancer.

And people that have blood levels of vitamin D between 40, 60, maybe 80 nanograms per milliliter have the lowest, all cause mortality. So these people are not deficient, not insufficient. Insufficiency happens at about 30 nanograms per milliliter, below that; deficiency is 20 nanograms per milliliter and below.

And so there have been a variety of studies that have looked at, for example, the brain and the aging brain and vitamin D levels. And it’s been shown that for every 10 nanomole per liter decrease in vitamin D blood levels, there’s an increase in brain damage. It’s called white matter hyperintensities. It’s basically damage to the white matter in your brain. And the white matter in your brain is myelin. That’s how your brain’s communicating and how electrical impulses are being moved so that you can think and talk and all that. Exactly, yeah.

STEVEN BARTLETT: I hadn’t had one today, so I feel like you’ve persuaded me.

DR RHONDA PATRICK: Most people that are deficient can increase their blood levels to a normal sufficient level by about 4000 IUs of vitamin D per day. So not. And that’s been done, that’s been shown in multiple studies. It’s not that hard to take. In fact, vitamin D supplements are probably the cheapest supplement out there. It’s like 10 cents per pill.

The Cancer-Fighting Power of Cruciferous Vegetables

STEVEN BARTLETT: When you talked about these, I was really surprised to hear that they have cancer preventing chemicals in them. And then I was looking at some of the research and it does say exactly as you said. Things like kale, broccoli, brussels sprouts are linked to a reduction in breast cancer risk, prostate, lungs and colorectal cancers. According to the World Cancer research fund and PubMed, most of us don’t eat enough of this stuff because it’s not the tastiest stuff.

And you talked about sugar as well. It makes me think about the diet that I’m currently on, which is the ketogenic diet, and whether that is an optimal diet in terms of all of the things we’ve discussed earlier. Dementia, longevity, aging. What is your views on the ketogenic diet?

The Benefits of Beta-Hydroxybutyrate

DR RHONDA PATRICK: I think there’s the extreme ketogenic diet, like the classical ketogenic diet, and then there’s modified sort of low carb ketogenic diets that do allow for – I mean there’s – yes, these are leafy greens that are carbohydrate, but they’re high in fiber and they’re low glycemic index. And so you can actually eat leafy greens on a ketogenic diet and still be in ketosis.

So the ketogenic diet is very – I’m very interested in it because I do think that beta hydroxybutyrate, which is the major circulating ketone body that’s produced when you’re in ketosis, is highly beneficial. Much like lactate, it can actually do a lot of what lactate can do. It gets into the brain and it’s an easily utilizable source of energy by neurons.

STEVEN BARTLETT: These are ketones, which is what your body makes when you abstain from carbohydrates and sugars. It eventually shifts into ketosis where you’re running on – you’re in ketosis and you’re running on ketones.

DR RHONDA PATRICK: Yes, it’s what you’re measuring when you’re doing your finger prick. It’s beta hydroxybutyrate, that’s the major circulating one that you’re measuring. And that’s actually a signaling molecule. It’s activating brain derived neurotrophic factor in the brain.

And so it’s very interesting because it’s almost like having lactate in your body but having it constantly. So I’m super interested in a ketogenic diet, particularly for people that respond well. I mean, some people, their triglycerides go really high, their cholesterol goes really high, and there’s sort of individual variation in terms of how you respond.

And so it’s good to always measure everything, right, to make sure that you’re responding well to ketogenic diet or to maybe cycle it. I’ve been very interested in cycling it for brain benefits as well because of the beta hydroxybutyrate, where it’s just so beneficial for the brain. It’s been shown that beta hydroxybutyrate – so what happens is when you have this ketone like beta hydroxybutyrate get into the brain, it’s able to be used as energy instead of glucose.

Understanding Ketosis: The Basics

STEVEN BARTLETT: I feel like we should take a step back and explain what keto is for the listener who maybe has never really heard or understood it before. And I know that there’s a large proportion of people that don’t know what it is because I spend a lot of time at dinner parties trying to talk about it. And it’s super surprising to me that the average person actually doesn’t really know what keto or ketosis is.

DR RHONDA PATRICK: So I think that’s great. Yeah, we can talk about ketosis essentially, if we kind of take a thousand mile high view of it. Without getting so technical, I would say the best way to think about being in ketosis is your body is using fatty acids as energy and not much glucose.

You’ll still use a little bit of glucose. You need to use glucose because your red blood cells, for example, don’t have any mitochondria, they need glucose. But you’re mostly using fatty acids as energy that are being produced from – they’re being released from fat stored in adipose tissue.

STEVEN BARTLETT: Which is like my belly.

DR RHONDA PATRICK: Which is like your belly, visceral fat, subcutaneous fat.

STEVEN BARTLETT: So this sounds great. My body’s going to burn the fat instead of burning glucose, which I’ve got from eating bread or something. So I’m going to get skinny.

DR RHONDA PATRICK: People do lose weight on a ketogenic diet.

Dramatic Weight Loss Results

STEVEN BARTLETT: My dad has lost so much weight, it’s ridiculous. It’s like shocking.

DR RHONDA PATRICK: On a ketogenic diet.

STEVEN BARTLETT: Yeah, it’s crazy. He was quite a big man, if I say so myself. Very big belly. And he sent me this screenshot the other day after a couple of months on the ketogenic diet, and he’s like 13 – he’s just for the first time ever been 13 stone since he was in his teens. He’s now 13 stone.

So he’s lost the equivalent of about four or five stone in weight in a couple of months. And he just looks completely different. Now, I’m not necessarily saying to stay on that diet forever, but the speed in which one can lose weight on a ketogenic diet is remarkable.

How Ketosis Works

DR RHONDA PATRICK: Right. And so you’re basically – the food that you’re eating is predominantly fat, right? So you’re basically not only using the fat that your body already has stored, but you’re also fueling yourself. You’re feeding yourself more fat. Right? So you’re basically using the fat as energy, and through a whole bunch of biochemical reactions, you produce ketone bodies as a byproduct of that.

It doesn’t necessarily have to be just ketogenic diet – you can, when you’re fasting, you go into ketosis, right? Because if you think about it, you’re not giving yourself food. Instead, you’re relying on what your body already has as a source of energy. And you only have so much glucose stored as glycogen in your liver.

And that – I would say, after there’s individual variation, but after about 12 hours of not giving your body food, you sort of deplete all your glycogen stores and then so you start to shift to lipolysis, which means the breakdown of fat. So fasting is another way to get into ketosis.

Another way would be intense exercise. So like these endurance athletes that are doing long duration types of exercise also can go into ketosis. Right. Because they’re depleting their glycogen stores much quicker and they’re also using all this energy that they’ve fueled themselves with because it’s so intense. Long duration type of exercise. And you can combine these things as well. Right. You can do endurance exercise with a ketogenic diet and you really kind of can get into ketosis quicker.

Metabolic Flexibility

STEVEN BARTLETT: Is it like a switch?

DR RHONDA PATRICK: So there is something called metabolic flexibility, which essentially means that your body is able to switch between burning glucose and using glucose as energy, but also using fatty acids as making – as energy and then producing ketones as well.

And the more – I would say, the more if you’ve done ketosis or if you exercise a lot, like frequently or you do any form of fasting or what’s called time restricted eating. So let’s say you eat all your food within an eight hour window and then for 16 hours you’re not eating food. Your body is used to switching to fatty acid metabolism, to using fatty acids as energy. So you’re really metabolically flexible.

And not everyone’s able to do that because most people actually they think they eat within a 12 hour period. But there’s been studies that have been done that have shown that actually they eat more like within a 15 to 16 hour period. Not even a 12 hour period, certainly not a 10 or 8 hour period.

So there’s, as I mentioned, it takes about 12 hours on average to deplete all your glycogen levels. Now, you can accelerate that if you’re doing a lot of physical activity, but once you deplete that liver glycogen, that is when you shift into burning fatty acids and then eventually ketosis.

Longevity Studies on Ketogenic Diets

STEVEN BARTLETT: In terms of longevity, have they ever done any studies where they’ve put someone on the ketogenic diet or like a mouse or a rat on a ketogenic diet versus the average diet and then monitored how long they live?

DR RHONDA PATRICK: There have been studies by Dr. Eric Verdin out of the Buck Institute for Aging in Nevada, California, and I mean, this was several years ago. He’s done these studies probably almost 10 years ago, maybe about 2018 or 2017, these studies were published.

But he did do some of these studies with a ketogenic diet in rodents, and it did seem to extend life expectancy, but more importantly, the health span, so particularly in the brain. So it’s like their brain had aged much, much better. They had less of all of the pathological features of Alzheimer’s disease.

And again, I do think, like I mentioned, I’m super interested in beta hydroxybutyrate in particular. I mean, it’s multifactorial because on the one hand, you’re not eating as much glucose, right? And that in and of itself is important because glucose can be so damaging, particularly if you’re not physically active.

Because if you’re physically active and you’re eating some amount of glucose, it’s going into your muscle. It’s not damaging the vascular system. The vascular system is very much related to the brain, right? So when you start to stiffen your blood vessels and stiffen everything, I mean, that’s affecting blood flow to the brain. It’s causing hypertension. That all affects brain aging as well.

So I think just – and then the damage that the glucose does in and of itself, like, I mean, there’s studies. It was really interesting. There’s studies showing that people, even on the high end of normal in terms of their blood glucose levels, so they’re normal, but they’re kind of on the high end of normal. They had more brain atrophy than people on the low end of normal.

STEVEN BARTLETT: By brain atrophy, you mean their brain was shrinking.

The Multi-Level Brain Benefits of Ketosis

DR RHONDA PATRICK: Shrinking. And it was the hippocampus, by the way, again, that part of the brain that’s involved in learning and memory. So the glucose itself has this effect on causing damage and accelerating the aging process.

But then there’s this other very interesting effect of these chemicals that are made as a byproduct of being in ketosis. And that is the beta hydroxybutyrate, that ketone body gets into the brain. It’s transported across the brain through an MCT transporter. And when it gets into the brain, it can be used as energy. And your neurons don’t need to use glucose, and it can do that.

So your neurons can use glucose as energy, but it takes energy to use that glucose to make energy. When you use the ketone, the beta hydroxybutyrate, it takes less energy to make that energy. So it’s energetically favorable to actually use that ketone, that beta hydroxybutyrate on top of that.

This is what’s so interesting. It frees up glucose so the neurons aren’t using the glucose. Where does the glucose go? Right. Because it’s there. It sort of shunts it into this other pathway that’s called the pentose phosphate pathway. I don’t want to burden people with all those technical details, but let’s get to the important part of that is that it shunts glucose into this pathway that makes essentially its precursors that make what’s called glutathione, the major antioxidant in the brain.

And so you’re making more glutathione day after day after day. That is huge because oxidation in the brain, inflammation. This is a huge cause of brain aging and Alzheimer’s disease, dementia. We now know neuroinflammation is one of the major causes of it. And so if you have more glutathione in your brain, you are going to basically sequester that damage that’s causing – that’s aging the brain essentially.

And so the glucose now is not being used for energy, it’s being used to make an antioxidant in the brain. That’s also really cool. And there’s more.

So then the beta hydroxybutyrate itself is a signaling molecule like lactate, the ketone. The ketone itself is a signaling molecule where it’s basically – it’s a little bit of a stressed state, right? So when you’re in ketosis, you’re stressing the body, it’s either exercise or you’re fasting, or you’re on this ketogenic diet.

And so your body again is responding to that stress by making a bunch of awesome resilient stress response things that are basically going to improve the way you age. And so the ketone beta hydroxybutyrate then activates brain derived neurotrophic factor, this miracle growth for your brain, right? It’s involved in growing new neurons, it’s involved in increasing the connection between neurons, it’s involved in neuroplasticity, all those things.

And so you get this multi level benefit – not having the glucose causing the damage. You have basically the glucose now being used. Not only is it not causing damage, it’s being used to make an antioxidant. And then you have the whole ketone aspect where you’re essentially making and activating all these beneficial pathways in the brain that reduces aging.

Exogenous Ketones

STEVEN BARTLETT: And what’s going on when we take exogenous ketones, external ketones, via a drink or something like that.

DR RHONDA PATRICK: Yeah. So what’s happening is you’re essentially giving your body the beta hydroxybutyrate ketone that it would make normally if you were undergoing ketosis and using fatty acids only as energy, you’re giving your body a big boost of it. So you’re kind of bypassing the way that your body would make it itself and giving it to your body.

And it’s great for people that have a hard time with doing a ketogenic diet, for example, maybe they just can’t stick with it or maybe they don’t respond very well to it. In terms of other biomarkers, they’re going to get a lot of the benefit, but it’s only going to last one to three hours, right?

STEVEN BARTLETT: Yeah. Until it flushes out.

Exogenous Ketones and Cognitive Enhancement

DR RHONDA PATRICK: Until you use it up. Yeah. And so it’s in addition to just people that want to get that focus and attention, which is what both you and I have experienced when we’ve taken these supplements, this exogenous ketone, there’s also some potential therapeutic effects.

So people that have mild cognitive decline, maybe like the first stages of dementia or Alzheimer’s disease, can kind of perk up and perform better when they have, when they’re given an exogenous ketone, a supplemental ketone, beta hydroxybutyrate. There’s not a lot of studies on it, but there’s like a few case studies where case studies being like a single person is given it and they’re followed and looked at, and it’s very interesting.

STEVEN BARTLETT: I actually know that they’re doing studies on exactly that at the moment, because I’ve spoken to a few of these companies and a few scientists that are in this field over the last couple of weeks, in fact, and they were saying that we’re currently in the process of doing studies to see that if exogenous ketones, which are these ketone drinks or ketone shots, can repair your cognitive faculties. And is that via the process that you describe where glucose is pushed into this other pathway?

DR RHONDA PATRICK: Yes. So I think I’m aware of the same study. Because I’ve looked it up in the clinical trial and what’s being looked at after giving this exogenous beta hydroxybutyrate, this supplemental ketone, in people with Alzheimer’s disease, you can repair damage because again, you are activating brain derived neurotrophic factor which can, it can repair damage, it can grow new neurons, it can help with brain atrophy, it can strengthen connection between neurons, and then the glucose now is being shunted into that repair pathway, that glutathione’s being activated and that’s able to repair damage as well.

So I’m excited to see that study published. I would hypothesize that there’s going to be beneficial effects and it’s going to be pretty exciting, particularly because it is hard for older adults, some older adults, to do a ketogenic diet. It’s not the easiest thing to follow. I mean, you do have to be pretty disciplined. So this alternative to being able to supplement with something that can sort of, at least for the course of a couple of hours, do what being on a ketogenic diet can do is very exciting.

STEVEN BARTLETT: When you took the keto shot that you had at home, what did you experience? You said it was potent, it was powerful.

DR RHONDA PATRICK: Yeah, it was like a nootropic effect where. When I mean nootropic effect, it’s the kind of effect where you feel focused, your attention, your alertness is enhanced. You’re sort of filtering out all the background noise in your brain that sort of those little thoughts that pop in and distract you, and so you’re more productive. And that was very noticeable.

In fact, there was a time when I was like, before any podcast, I would take a shot of it, and it’s kind of expensive, but it is. There’s a lot of people that are using it now. And I think it’s. I think it’s a better alternative to some other nootropics that are common right now, like nicotine, for example, which can really have a negative trade off, but can do something similar. Whereas this is, like, not only gives you that sort of cognitive enhancement, that brain pump, it also has, like, benefits for brain aging.

Superfoods and Essential Nutrients

STEVEN BARTLETT: What are your superfoods? There must be foods of yours. Olive oil has become one of my superfoods. Just a food that I love to just put on as many things as I can. Because everybody tells me about these polyphenols, which are apparently amazing for you, but what are some of your sort of favorite superfoods that you try and consume that most people might not think of? So we talked about leafy greens. I guess that’s one of them.

DR RHONDA PATRICK: It is leafy greens. They have. They’re high in magnesium. And, you know, magnesium’s at the center of a chlorophyll molecule. Chlorophyll give plants a green color. Magnesium is very important for preventing damage to DNA and cancer. And half the US population doesn’t get enough of it. They’re high in a lot of different compounds. I mean, they’re folate, vitamin K1. So you’re getting a lot of these micronutrients that are important. So I do like dark leafy greens.

I particularly like kale broccoli because of something called sulforaphane, which is. Sulforaphane itself is not in them, but a precursor. When you break the plant or you chew it, it makes sulforaphane. So there’s an enzyme that gets activated that converts a precursor in these plants called glucoraphanin into sulforaphane. Sulforaphane also increases glutathione in the brain. It helps detoxify pollutants like benzene, bisphenol, a BPA as well. So I do like dark leafy greens of the cruciferous family of vegetables. Again, that would be kale broccoli. Those are the cruciferous family.

I also like blueberries. Blueberries are a source of polyphenols. You mentioned olive oil as a polyphenol. If you’re on a ketogenic diet, olive oil is like the great. Right. Because you need fat. And olive oil is so great because it also has those polyphenols that are beneficial. And it’s been shown even in studies to improve cognition and memory and lower even markers of bad cardiovascular disease, like apob, for example, lower that. So blueberries I like because blueberries have also been shown. Even a cup of blueberries a day has been shown to improve cognition. So I like the polyphenols. It increases blood flow to the brain.

I also like salmon and I think that would be something that most people would think is healthy. I like it because it’s high in the omega 3 fatty acids, which I’m very, very. I think it’s very, very important to get enough omega 3 fatty acids. I also supplement with them because there’s a lot of research out there. And if you want to get into that, we can. But the superfood would be the salmon because it is a fatty source of fish that is high in omega 3 fatty acids, EPA and DHA, which are found in marine sources, not plant sources of omega 3.

Omega-3 Fatty Acids and Mental Health

STEVEN BARTLETT: I found it really interesting when I was looking at Omega 3 that it has an impact on mental health and depression and things like that.

DR RHONDA PATRICK: Yeah, it does. It resolves inflammation. It’s sort of an anti inflammatory. And inflammation plays a role in depression. Big role. In fact, we know that people that are injected with inflammatory molecules, like something that’s made in our gut from the bacteria in our gut called lipopolysaccharide. If you inject them with that or a placebo control, which is saline, it causes depression. But if you give them an omega 3 fatty acid supplement, EPA, it blunts the depressive symptoms.

So in other words, if you’re causing the inflammation by injecting something that causes inflammation in people, it causes depression. But if you give those same people something that blunts that inflammation, omega 3 fatty acids, it doesn’t cause the depression, which is kind of amazing. And there’s a ton of other evidence out there, but omega 3 fatty acids are, they’re so important.

And what’s interesting was there’s a study out of Harvard that, that identified the marine source. So I talked about salmon, epa, dha, and then there’s the plant source, ala. And I say marine source because it’s really, those are the important ones that you really want from the ocean, from fish, seafood. So this Harvard study identified not eating enough seafood as one of the top six preventable causes of death up there with not having hypertension, not smoking. So essentially not getting enough Omega 3 from seafood was so important for preventing early death that it was comparable to people having high blood pressure, having cardiovascular disease, for example.

And again, it’s one of those things where people just don’t think about what they’re not eating, what they’re not getting. And there’s so much research that had been done even since that, that study that was published in like 2009, looking at omega 3 fatty acid levels in our blood cells, red blood cells. This is called the Omega 3 index. It’s really an important marker of our long term Omega 3 because our red blood cells stay around in our system for like 120 days. So it’s a long term marker of your omega 3 intake.

And there’s been a variety of studies done from Dr. Bill Harris out of the Fatty Acid Research Institute, so I’m an associate scientist there, showing that people with what’s called a high omega 3.

STEVEN BARTLETT: Index, which is a lot of omega.

DR RHONDA PATRICK: 3, a lot of omega 3, their omega 3 index would be 8% or higher. That’s considered high compared to a low omega 3 index, that would be 4% or lower. The average omega 3 index in the United States is about 5%. So it’s on the low, low range. People that had the high omega 3 index, in other words, they were either eating a lot of fish like salmon and or supplementing with fish oil or microalgae oil, which is another marine source of these omega 3 fatty acids. They had a five year increased life expectancy compared to People with a low omega 3 index. Pretty big difference there.

And all you have to do is essentially either eat enough seafood and or supplement with a fish oil supplement. But what was so fascinating about this study was that Bill and his colleagues not only looked at the omega 3 index, they looked at people that also smoked. And they said, okay, we know smoking is terrible for your heart. We know it causes early mortality, cancer and all that, right? What about people that smoke and their omega 3 index?

So there was four groups that were looked at, smokers that have either a high omega 3 index. So these smokers were either supplementing or they were eating a lot of seafood. And then there were smokers with a low omega 3 index. And they compared them to non smokers with a high omega 3 index versus a low omega 3 index.

And what was so fascinating about this study was that smoking was like as bad for you in terms of mortality as having a low omega 3 index. So the smokers with a high omega 3 index had the same mortality risk as non smokers with a low omega 3 index. Which is fascinating because everybody knows to avoid smoking smoking, if you want to take years off your life, if you want to decrease the quality of your life, start smoking right now. But the same mortality risk was found in non smokers who did not have a high omega 3 index.

Right now I say this, I’ll talk about this, and smokers will say, “oh, great, now all I have to do is take fish oil and I’ll have the same life expectancy as a non smoker with a low omega 3 index.” But of course, the take home here is that for those of us that are not smoking, but we’re not getting enough Omega 3 from our diet, that’s like smoking in terms of mortality risk. So super important, and I like talking about this because it really makes it again, really clear that not getting these essential nutrients can be very detrimental to our health.

And it’s easy to fix. You can take a fish oil supplement, you can increase the amount of salmon that you’re eating. And there have been studies from Bill’s group that have shown people that supplement with between 1 to 2 grams of fish oil per day can go from a low omega 3 index to a high omega 3 index, which is not hard to do.

Fish Oil Supplements vs. Whole Fish

STEVEN BARTLETT: So I guess two questions, which is, is having these little Omega capsules the same as eating the salmon in terms of the Omega 3 that I’m getting, and how long do I have to take these little omega capsules for to move from having a low index to a high omega 3 index.

DR RHONDA PATRICK: Well, these are great questions, Stephen. So essentially this little capsule here is not the same as eating salmon. And there’s a few reasons why. So for one, when you’re eating a fish that’s high in omega 3, like salmon, you have this omega 3 in what’s called triglyceride form. So the omega 3 is bound to a glycerol backbone and that’s really important for the way you absorb it. Some fish oil supplements don’t have that. They’re. They’re basically molecular distilled and then they have an ethanol backbone. So it’s not quite as bioavailable.

But I think more importantly is that these fish oil supplements are purified. So you’re not getting mercury or microplastics or things that are also found in the whole fish.

STEVEN BARTLETT: So these are better?

DR RHONDA PATRICK: Unfortunately, I think so. I do, as much as I think it’s better. For the longest time I was always a whole foods first approach. But we do have this environmental pollution problem and fish have been contaminated with heavy metals, they’ve been contaminated with microplastics. I would say that salmon is one of the lowest fish that has the lowest amount of mercury compared to other fish. So on a per gram basis, you’re getting less mercury per gram with salmon than you would be with something like swordfish, for example.

But you also have microplastics, unfortunately that are now in fish. And it is something that enters our body when we eat the fish. And so I do think the fish oil supplements are a good alternative because you’re getting those omega 3 fatty acids and you’re not getting some of the other bad things that are in the fish.

STEVEN BARTLETT: That’s fascinating. I didn’t really think of Omega 3 as being that important, especially as it relates. I always thought about it as being something that would help my brain work better today, you know, cognitive performance now.

Omega-3 and Cardiovascular Disease

DR RHONDA PATRICK: Well, it does that and it also helps prevent the cognitive decline later. And also cardiovascular disease, that’s a big one. So there have been some really large randomized controlled trials that have actually given people with cardiovascular disease that are on some sort of standard of care treatment like a statin.

And they’ve given them 4 grams a day of a purified form of omega-3 called EPA versus a placebo. And the people given the omega-3 had 25% less cardiovascular related death or events like heart attacks and strokes.

So it’s not only like preventing, you know, we talked about all cause mortality and this association where you live longer, it’s also helping people that already have cardiovascular disease and reducing their risk of dying from it.

The Science Behind Creatine

STEVEN BARTLETT: When I asked you before this conversation started rolling, what you’re really excited about at the moment, your response to me was there was a few things, but one of them which lit up your face was creatine.

DR RHONDA PATRICK: Yes.

STEVEN BARTLETT: And it’s funny because it lit up your face again.

DR RHONDA PATRICK: Yeah, it’s funny because creatine has been around for, I mean, ever, for decades. And it’s always been in my mind. It was like one of those gym bro things. I’m like, “I don’t need to be swole. I don’t need creatine to get swole.” And, you know, this was the thought for many, many years.

And then over the last five years or so, the effects of creatine on the brain started to really get my interest. Anything that affects the brain, I really become interested in. And so that’s kind of what did get me the most excited about creatine.

But also I started doing a lot of resistance training. And so I was like, okay, here I am now. I’m like one of those gym guys. I’m doing the barbells, I’m doing the squats and the deadlifts and all that. And so why not give myself some of the creatine?

What Is Creatine and Why Is It Important?

Well, what is creatine? Right? Why is it important? You talked about earlier, you know, why doesn’t our body just make more of these things that are so beneficial. We do make creatine. We make about, I don’t know, our liver makes about 1 to 3 grams a day of creatine, and our brain also makes. And those are the two organs that make it.

Creatine gets consumed by other tissues, like the muscle’s probably the one that’s the greediest, because creatine is stored as phosphocreatine, but it’s used to make energy, essentially. So it can increase muscle mass, it can increase muscle strength in combination with resistance training because you’re able to regenerate and make energy faster.

So, for example, I became interested in it after reading studies where people that supplemented with creatine that were engaged in resistance training were able to gain more lean body mass. They were able to gain more strength. It was increasing their training volume. So you can do one to two more reps, right, of whatever exercise you’re doing, and it seems to decrease the recovery time between those sets as well.

So you’re able to increase your training volume. Well, anything that’s going to increase your training volume is going to then have the downstream effect of increasing the adaptations like increased muscle mass or increased muscle strength.

Personal Experience with Creatine

I started supplementing with creatine about a year ago, and I started supplementing with it for that reason, for my training. And I was doing about 5 grams a day because that was really what was shown to be beneficial for muscle health in combination with resistance training.

And it’s important for people to realize that supplementing with creatine by itself without any type of resistance training isn’t going to grow your muscle. It’s not going to make you stronger. You have to put in the effort. Because what creatine is doing, it’s helping you make the energy quicker, right?

And then being able to make that energy quicker means that you’re able to then do that exercise better, harder, more of it, right? So it’s sort of supercharging your exercise routine. And 5 grams a day was like, okay, perfect. That’s what I’m doing. I’m doing five grams a day, and definitely noticed an effect on my training volume where I was doing more reps.

Creatine’s Effects on the Brain

So that was like, okay, a year ago, I had already been aware of the effects on the brain. I thought maybe the five grams a day would do that. So what are the effects on the brain? Well, your brain also consumes a lot of energy, you know, needs a lot of energy. So it does make its own creatine.

But it turns out if you can give your brain more of that creatine, particularly under a period of anything that’s causing stress. So let’s say lack of sleep, or let’s say emotional psychological stress, or in my case, high cognitive load, where you’re just every day learning concepts, complex things, you’re trying to remember them, you’re putting ideas together and coming up with new hypotheses.

And, you know, you’re just studying a lot, and it’s very cognitively demanding. And it’s a type of stress on your brain. That’s like my life, right? Under this condition of stress, depression’s another one. That’s a stress on your brain or neurodegenerative disease. That’s a stress on your brain.

So any kind of stressful condition, that’s where creatine shines in the brain. I would argue that all of us. Who has the perfect amount of sleep never has stress. Nobody, right? There’s always some sort of stress in the background. So that’s when I was like, okay, so if you’re the perfect person, you have no stress, you get the perfect amount of sleep every night. Your brain makes enough creatine to kind of do what it needs to do.

I know that I’m constantly under stress, so I’m like, okay, well, I think I need a boost.

The German Study: 10 Grams vs 5 Grams

And this is where a lot of very interesting studies have come out of many different labs, some out of Germany, that looked at the dose of creatine and how it increases creatine levels in the brain. And this is why I now supplement with 10 grams a day.

So the study out of Germany found that 5 grams a day of creatine, if you’re supplementing with 5 grams a day, your muscles are greedily consuming it, particularly if you’re working out. They want it. They want it after about 5 grams a day, especially over a few months, like, you’re saturating your muscle and that’s enough, right?

Anything above that kind of spills over to the brain. And so what this German study found was that 10 grams of creatine increased creatine levels in several different regions of the brain. And that was probably the most exciting, I would say, evidence that supplementing higher than 5 grams a day was actually doing something in terms of getting creatine into the brain.

Research on Cognitive Function and Sleep Deprivation

There have now been a variety of studies that have looked at different outcomes. Right. So if you supplement with 10 grams of creatine or even go higher than that, like 20 grams of creatine, how does that affect cognitive function? Right.

And so some of these studies have been done by Dr. Darren Kandow, he’s at the University of Regina in Canada. And they’ve looked at things like sleep deprivation. And it’s been found that if you take someone and you sleep deprive them for 21 hours and give them about 25 to 30 grams of creatine, it completely negates the cognitive deficits of sleep deprivation.

Actually, not only does it negate the cognitive deficits of sleep deprivation, it makes people function better than if they were well rested. That’s where I was like, “Wait a minute, there’s many times when I’m traveling, I’m jet lagged, lots of times when I’m sleep deprived and I have to be doing a podcast or a presentation, whatever.”

And in those situations, I go up from my 10 grams to more like 20 grams. Like today, for example, I wasn’t really sleep deprived, but you know, there was a lot of high cognitive demand. This is a long podcast, there’s all that stuff. And so I went up to 20 grams today on my creatine.

Personal Benefits and Energy Levels

And, well, I will say, even at the 10 grams for me, we were talking about this with respect to being in ketosis. I don’t feel that mid afternoon crash when I have the creatine, not being on a ketogenic diet, not being in ketosis. It’s very clear for me.

And I have done this where sometimes I only do 5 grams and then if I do that, I’ll notice. I’m like, “Why am I tired right now?” So there’s something interesting and maybe it’s placebo, I’m going to throw that out there. Very possible. But I don’t know, maybe the creatine is again, it’s able to regenerate that energy quicker and so that’s also beneficial for the brain.

The Shift in Research Focus

And now I would say all these creatine researchers, a lot of them are shifting to the brain. It used to be all muscle focused and now people are super interested in what creatine is doing to the brain, especially if you’re supplementing with more of it.

And you know, this is important for people that are under a stressful situation, but also for vegans, because creatine is found in food, mostly in animal products like meat and poultry and fish, dairy. A lot of vegans don’t eat that.

And I’ve had so many of my vegan friends, I’ve got them on the creatine and it’s changed their lives. I mean, they’re like, “This is incredible.” You know, can you imagine someone who’s not getting any creatine from their diet because they eat no meat, and all of a sudden they start supplementing with 5, 10 grams of creatine and it’s like they have energy.

Some people say they require less sleep, which is kind of interesting. That’s kind of a comment I’ve heard many, many times from people, is that it’s like their brain doesn’t need as much sleep, they have more energy.

So I’ve been a big fan of the creatine, not only for the muscle especially because, you know, working out is something that’s very important, but for the brain as well.

Immediate vs Long-term Effects

STEVEN BARTLETT: I always thought of creatine as something that you took and you kind of had to load up on, and then over a couple of weeks or months, the effects would kick in. But you were telling me that if I had creatine in the morning, that same day, I would experience potentially improved cognition if I have a big enough dose.

DR RHONDA PATRICK: Yes. So, great question. A lot of studies that have been done that you’re referring to have been done in the context of exercise and muscular performance. And the reason why people have to load up on like they do a loading phase, let’s say 20 grams, and then they go down to this sort of maintenance phase of 5 grams is because it takes, I don’t know, I think it’s about a month or so before you can saturate your muscular stores of creatine.

STEVEN BARTLETT: What does that mean?

Creatine Saturation and Loading Phases

DR RHONDA PATRICK: It means that the creatine, which is actually stored in your muscle as phosphocreatine, is there and ready to be used to make energy. So it takes again, it takes about a month or so to do that, unless you are really giving your muscles a high dose. Right. So the five grams a day, it can only do it for so many days. And then finally you get saturated when you do this loading phase, you kind of just accelerate that whole process.

And so that’s why when people are doing these experiments where they want to test the effects of creatine, they want the participants to have really high levels of creatine in their muscles, quick. Because they don’t want to do a month long experiment, right? They want the experiment to be like a couple of weeks or a week. So that was kind of the whole concept behind this loading phase. If you’re not someone who’s going to some kind of competition, you know, like your CrossFit games or something, you don’t really need to do that loading phase. If you’ve already been supplementing with 5 grams a day for like a month.

Creatine’s Effects on Brain Function

When it comes to the brain, what’s happening if you get above that 5 grams, that’s pretty much all consumed by the muscle. You’re having some leftover in circulation and the brain takes it up and it takes it up, right? What it really shines is under that stressful condition, which again for me I feel like every day is, is like cognitively demanding for me. Because I’m constantly learning new material or learning new information or working on things, right? And so there’s a lot of cognitive stress on my brain.

And so I feel like I’m constantly under that stress. And that’s where getting the creatine in your brain helps you make that energy quicker. And so that’s why like I’ve done, I’ve had, you know, been jet lagged and have to give a talk at you know, like 5am in the morning, my biological time after not getting sleep. And I’ve done like 25 grams of creatine. And it’s insane how much it helps me. Again, it could be placebo because I’m anticipating that effect, which is fine. Placebo is a real thing. It’s great. I’m all about it. But there’s some evidence also that this works, right? That the creatine is helping with under that sleep deprivation and that stressful condition.

STEVEN BARTLETT: I was reading about a study in 2025 where they gave creatine to people that had sleep depressive symptoms alongside CBT training. And the people that had creatine and the cognitive behavioral therapy training experienced a greater improvement in their depression symptoms than those who just received the cognitive behavioral therapy. Which is incredible.

DR RHONDA PATRICK: It’s fascinating. I mean depression is a type of brain stress, right? I mean we know inflammation plays a role in depression, we know oxidative stress plays a role in depression. And there have now been some animal studies that have shown creatine is somehow having an anti inflammatory effect. That hasn’t all been worked out. So I don’t know if it’s all just the energy component of it. It could also be this other sort of newly identified role that creatine’s playing in sort of having an anti inflammatory effect. And I don’t know enough about that. I don’t know that there’s enough even known about that. But I do know that it exists.

And it’s fascinating because again I think where creatine really shines in the brain and it’s been shown study after study is under some kind of stressful condition, depression or sleep deprivation. Or there’s a new study that came out, it was published, I don’t know, a month ago or so showing that it was a very small pilot study. And I want to caveat this. There was no placebo control, but it did show that giving people with Alzheimer’s disease creatine, I believe it was 20 grams a day, did improve their cognition.

And so again, this is a whole new field where now we’re looking at creatine in the brain, not just the gym bros and not just the muscular effects, but in the brain and how it’s affecting the brain and being beneficial for cognition, for brain aging, for depression.

Creatine and Cancer Risk

STEVEN BARTLETT: Is there a link or an association with cancer outcomes in creatine? I was wondering because there was a study that I was looking at earlier. Yeah, this one, it says a 2025 study of 25,000 people each found that for each additional 0.09 grams of creatine over a two day average was linked to a 14% reduction in cancer risk.

DR RHONDA PATRICK: Right.

STEVEN BARTLETT: Which was in the Frontiers Journal and reported by the BBC.

DR RHONDA PATRICK: Yeah, it’s like a new unexplored, you know, association here where it’s like, I don’t know why creatine is doing it. Is it the anti inflammatory effect? Is it? Who knows? But again, I mean, I was aware of that study and it’s like a whole new area that needs to be explored where, you know, some people were worried about creatine actually causing cancer. I’ve actually had people ask me that question and it’s actually the opposite where it seems to be reducing cancer risk.

Debunking Creatine Myths

STEVEN BARTLETT: Some of the other sort of misconceptions around creatine are that it’s going to. I mean, there was this stereotype that people take it, they get massive muscles and they become bloated. So I think that put a lot of women off, in particular, according to some research that we actually did, just to understand perceptions of creatine in my investment fund. But the other one was hair loss. People think there’s some sort of association with hair loss. That is if you take creatine, you’re more likely to lose your hair.

DR RHONDA PATRICK: Right. So there was this one study that was published I don’t even know how many decades ago. Maybe you can pull it up. But it was in rugby players, I believe, and these rugby players that were given, I believe it was a high dose, maybe it was 20 grams. I can’t remember the exact dose. But they had increased levels of dihydrotestosterone DHT, which is something that is linked to androgenic alopecia.

So this would be, you know, basically your. The DHT can affect the hair follicle and keep it in this like stunted phase where it’s not growing. And so that can cause hair loss. And that one study didn’t measure hair loss. It just again looked at the DHT, the dihydrotestosterone levels. It’s never been replicated. There’s after so many decades, it’s never had any animal evidence showing that this actually causes hair loss. Nothing has really come up showing that this is something to be concerned about. So I take it as okay, it’s like a one off thing. Who knows what was going on here. But like you would think if it was real, it would be replicated after. When was it published?

STEVEN BARTLETT: 2009.

DR RHONDA PATRICK: 2009.

STEVEN BARTLETT: Yeah. So it was a group of rugby players, they were given 25 grams a day of creatine. But there was actually a study, a randomized control trial done in 2025 this year with 45 resistant trained men all given 5 grams a day of creatine over 12 weeks. And there was no significant difference found in their hair outcomes or DHT versus placebo.

DR RHONDA PATRICK: There we go. When was that published?

STEVEN BARTLETT: 2025.

DR RHONDA PATRICK: Oh, this year.

STEVEN BARTLETT: Randomized control trial.

DR RHONDA PATRICK: Amazing. Thank you. Well, I mean, to get also to your other point about the water weight gain, I know this is a real thing because also several of my girlfriends were concerned about this as well. And it’s funny, you know, creatine does bring water into the cell, but that’s actually, it’s not a bad thing. Right. And you’re really not going to get a big gain in weight. I mean, I can’t imagine there’s nothing more than like two pounds, you know, if anything at all. So I do think that is sort of something that’s. I don’t. It’s a fear that’s not justified in my opinion. I mean, you lose, you gain four pounds of water weight when you’re on your menstrual cycle.

The Science of Fasting

STEVEN BARTLETT: You mentioned fasting. There’s been lots of conversation around fasting, around whether it’s good, bad, how long to fast, or whether just restricting your calories is the same as fasting. A lot of people talk about autophagy. My girlfriend talks about water fasting. What is your perspective on the role of fasting? How we should do it, if we should do it, when we should do it, who should do it?

DR RHONDA PATRICK: I think it depends on what your goal is. So you mentioned people talk about calorie restriction. And really is the fasting just about the calorie restriction? And I think when it comes to weight loss, losing weight predominantly, hopefully fat, not muscle, then calorie restriction is the main thing to do here. And intermittent fasting is sort of a tool to get you there.

In other words, people that are doing intermittent fasting tend to eat fewer calories, and that’s been shown in several studies. Even if they aren’t counting their calories because they are limited in the amount of time they’re eating, and then they’re fasting for a longer period of time, they end up just consuming naturally fewer calories.

STEVEN BARTLETT: Being in a calorie deficit, is that going to put you into the ketogenic state that you get from not fasting?

DR RHONDA PATRICK: No, not if. Not necessarily. No, it’s not. So you can be in a calorie deficit, but it depends, right? So when you’re in the fasted state, what’s important here is you’re activating a bunch of pathways that don’t become active when you’re in a fed state. And there’s a lot of biochemical reactions that sort of dictate all that. But you mentioned autophagy, right? And that’s the big one. That’s happening only when you’re really in a fasted state.

STEVEN BARTLETT: What is it?

Understanding Autophagy

DR RHONDA PATRICK: There’s different types of it. So generally speaking, it’s the clearing out of damaged stuff within your cell. So what is damaged stuff? It can be protein aggregates, for example, if we think about in neurons, amyloid beta protein aggregates. So autophagy could play a role in clearing that out.

STEVEN BARTLETT: The plaques and stuff you get in your brain.

DR RHONDA PATRICK: Exactly. But you also get plaques in your cardiovascular system. So autophagy can play a role in clearing that out, but it also can be fragments of DNA, it can be all sorts of gunk and stuff that just can accumulate inside of your cell. And so you’re kind of getting rid of that also.

It can be even on the level of, let’s say it’s the organelle level. So you can actually have your mitochondria. We talked about mitochondria being the major source of energy inside of our cells. Mitochondria are very important for the health of all of our cells, our neurons, our muscle, because they produce energy. But mitochondria also accumulate a lot of damage quite easily because they produce energy and they use oxygen to do that. They make a lot of what’s called reactive oxygen species.

So these are things that can really react with our DNA, with proteins inside of our cells with lipids, so the cell membranes. So your mitochondria don’t really have a repair system like our DNA does. So we have DNA repair enzymes that can repair damage to our DNA. Right? That’s where magnesium comes in. Magnesium’s required for these enzymes to be activated to repair damage to our DNA, to prevent cancer.

Our mitochondria don’t have that kind of repair system. They have another repair system, and one of it is what’s called mitophagy, which is kind of a sub part of autophagy. And it’s where the mitochondria, they accumulate damage. You can essentially take that mitochondria and get rid of it or a piece of that mitochondria damage and get rid of it through this sort of autophagy type of thing. But it’s called mitophagy, and that happens with other types of what are called organelles within our cells.

So this autophagy process. This autophagy is sort of a general term, but it’s essentially the cleaning out of damage. It’s the repair process for damage. And it’s something that happens most of the time when we’re in a fasted state, which typically happens when we’re sleeping.

Optimal Fasting Duration

STEVEN BARTLETT: How long do I have to be in a fasted state for?

DR RHONDA PATRICK: I mean, it depends. I would say that we haven’t really worked that out great in humans because people aren’t measuring biomarkers of autophagy in humans. There have been some studies that have looked at being in a fasted state for like 16 hours. And essentially once you break through that part of depleting all your liver glycogen, that’s an important precursor for activating autophagy. So I mentioned earlier, that happens after about 12 hours, right? So as you get to 12, 13, 14, 15, 16 hours, then you’re probably getting to that state of autophagy.

However, there’s such limited evidence on that in humans, a lot of it comes from animal studies. With that caveat, I will say that you can get a lot of benefits. So some of the metabolic benefits for fasting include improved glucose levels, improved blood pressure regulation, metabolic effects, improved, for example, weight loss. Right.

Now, can you get all of that from just doing caloric restriction versus doing like this intermittent fasting? Right. You can get a lot of it. But there have been studies showing that doing this sort of intermittent fasting is beneficial for some of these metabolic parameters outside of the caloric, being in a caloric deficit.

STEVEN BARTLETT: What does that mean, metabolic parameters?

Intermittent Fasting Benefits

DR RHONDA PATRICK: Again, glucose regulation, blood pressure, your blood pressure control as well. So these things have been shown in people that are doing time restricted eating. So they’re basically doing a type of intermittent fasting where especially if they’re doing a really compressed window, so they’re eating all their food within six hours and then fasting for like 18 hours, that’s really beneficial, right?

And even if they have the same amount of calories as people that are calorically restricted, they’ve compared those head to head. People that are doing the fasting have better improvements in their glucose regulation, better improvements in their blood pressure than people that are even still eating fewer calories but not doing the fasting component.

STEVEN BARTLETT: So what would you recommend for the average person? I asked you earlier on to give me sort of a perfect prescription of what I should do in terms of fasting on a daily basis. You think I should have eating sort of fasted windows of 12 to 20 hours?

DR RHONDA PATRICK: You know, I think it really depends on what you’re looking for. And personally, if you are wanting to have this more autophagy kind of potentially autophagy activation where you’re clearing away stuff within your cells. Again, we don’t really know the hard number yet, but I would say yeah, you probably want to be around a 16 hour window of not eating.

STEVEN BARTLETT: What do you do?

DR RHONDA PATRICK: I mean, it depends on the day.

STEVEN BARTLETT: On an optimal day, most of the time I’m probably eating all of my food within a 10 hour window. And so I’m fasted for 14 hours. But optimally it all depends on my family and eating dinner with my family and what’s going on.

STEVEN BARTLETT: Do you ever do longer fasts?

DR RHONDA PATRICK: I don’t do. I mean, I would say a day is like the longest that I do, but I do a lot of exercise on top of that. And so you can kind of kick yourself into that autophagy state a little bit more because it’s kind of like we talked about this, it’s a way of sort of supercharging your ketosis.

And so if you’re exercising and fasting, that kind of supercharges that whole autophagy system as well. But I do think it’s kind of an interesting idea to do some longer fasts, maybe once a year, once a quarter, depending.

STEVEN BARTLETT: Why?

DR RHONDA PATRICK: Because you are activating that repair process. Now you have to do resistance training. Because you don’t want to lose muscle mass. Protein is important. It’s one of the signals for muscle protein synthesis, which is essential for gaining muscle mass and maintaining muscle mass.

Breaking Fasts and Protein Requirements

STEVEN BARTLETT: So after a fast, you want to break the fast with something protein rich.

DR RHONDA PATRICK: Absolutely. Definitely protein rich for sure. But I think also during a fast, if you can do some kind of, you want to stimulate your muscles with mechanical force because that’s the other signal to stimulate muscle protein synthesis.

And so I think one of the biggest concerns people had with fasting, and this was over the last five years or so, is that studies have shown people that undergo intermittent fasting tend to lose muscle mass because they’re eating fewer meals, they’re not getting as much protein, and perhaps they’re not doing resistance training.

Now there have been other studies that have looked at people doing intermittent fasting and resistance training and they don’t lose muscle mass because they are doing, they’re getting that mechanical stimulation of their muscles which is preventing the loss of muscle mass.

And so I think the take home here is if you are doing intermittent fasting, you want to make sure you’re getting all your protein, 1.2 to 1.6 grams of protein per kg body weight per day, depending on how much you’re resistance training. And you also, you want to make sure you’re getting your protein in that small window that you’re eating and you want to make sure that you’re doing resistance training as well. Those are two really important things if you are going to do intermittent fasting.

Sleep and Meal Timing

STEVEN BARTLETT: There was a study I read which is linked to that, which said. Linked to that but sort of adjacent, that says in nine human trials they found that 23% of people enjoyed better sleep after intermittent fasting, which I thought was interesting.

DR RHONDA PATRICK: Yeah.

STEVEN BARTLETT: Causation is obviously hard to establish there, but.

DR RHONDA PATRICK: Right. I think, and that brings us to this other sort of aspect of intermittent fasting, which is time restricted eating. Essentially. What’s the best thing to do is really you want to eat within an earlier time window. And there’s a lot of reasons for that.

One of them is that when you eat later in the day, let’s say 8 o’clock at night, 9 o’clock at night, your body’s starting to naturally make melatonin. That’s a hormone that’s involved in helping you get sleepy, while melatonin also inhibits the production of insulin. And so you basically will have elevated blood glucose levels when you’re eating later in the day because you’re basically less, your glucose regulation is impaired somewhat.

So it’s better to try to eat your food earlier in the day. But then there’s also this area of you want to probably stop eating like three hours before your natural bedtime. And that does affect sleep. So if you think about it, when you’re sleeping, you don’t want to be digesting. There’s all these things that are activated during digestion and that’s going to affect the way you sleep.

And so there are some interesting studies that have found that people sleep better if they stop eating at least three hours before bed. That is something that I do try to do almost daily. And it’s also something that was very interesting. I think a friend of mine, Dr. Sachin Panda at the Salk Institute, was one of the first people to observe that.

He’s got this app that he has called myCircadianclock. And he’s used this app over the years for clinical trials where people will take a picture of their food and it timestamps the food so that he knows what time they’re eating and when they stop eating. And people that are part of this trial started to send him comments going, “Oh, I stopped eating earlier, and all of a sudden my sleep is better.”

And after you start to get about 10, 20, 30 people making the same comment, you start to go, “Wait a minute, there’s something here.” And so I think he was one of the first people to actually observe that correlation between stop eating earlier and sleeping better.

Protein Timing and the Anabolic Window

STEVEN BARTLETT: Well, you talked about protein earlier when we were talking about resistance training and fasting. When should I. Someone told me that you’re supposed to take protein straight after you do a resistance training workout, straight after you lift the weights, like 30 minutes after. Does it matter?

DR RHONDA PATRICK: Well, that’s what was thought, I think, previously for I don’t know how many years it was thought this was. There was an anabolic window, right, where you want to take in this protein within 30 minutes to an hour of doing your resistance training. And that way the amino acids that are anabolic, like leucine, are going into the muscle and building muscle, essentially.

We now know that it’s not really an anabolic window. It’s about your daily protein intake. Because what exercise is doing, what the resistance training is doing, is it’s sensitizing all your transporters and your muscle to amino acids. And that’s happening over the course of 24 hours.

So you can take that protein in within that day, and it really still do the same thing. So I don’t think you have to slam your protein shake within 30 minutes to an hour. Maybe if you’re a bodybuilder and you’re really trying to get that little, tiny, tiny, tiny percentage, maybe you’ll have a little bit of a benefit. But generally speaking, most people, what you want to look at is your daily protein intake, because that’s essentially the most important thing.

And the exercise itself is sensitizing all these transporters on your muscle that are allowing the amino acids to come in and build protein, increase muscle protein synthesis.

Understanding Insulin Resistance

STEVEN BARTLETT: There’s a term that you’ve used a few times which I’m not super well educated on, which is insulin resistance. What is insulin resistance? And is that something associated with diabetes? And therefore, does someone like me need to care? I don’t have diabetes.

DR RHONDA PATRICK: Okay, let’s take a step back. When you are eating something that is going to raise your blood glucose levels, right?

STEVEN BARTLETT: So like a piece of bread or some sugar or whatever, right?

DR RHONDA PATRICK: So essentially, if you’re increasing that glucose spike in your bloodstream, you want to have that glucose go somewhere. You want it to go to your muscle, or sometimes it goes to your adipose tissue. But in order to do that, you have to activate. And insulin then causes these transporters that usually aren’t active to kind of come up and take in the glucose.

So insulin resistance is when you’re basically constantly, constantly activating that pathway such that your cells don’t respond to the insulin like they used to. And so the insulin isn’t doing its job as well. And so essentially your blood glucose levels stay elevated, and that causes all sorts of damage, the glycation and things like that we’ve talked about.

STEVEN BARTLETT: So it’s really insulin failure. Insulin’s failing to do its job.

DR RHONDA PATRICK: Well, it depends because you’re still making the insulin, but it’s essentially not. The insulin receptor isn’t responding to that insulin. And so it’s not doing its job. Yes, it’s not doing its job, but it’s different from type 1 diabetes in the sense where type 1 diabetes, you’re actually not even making the insulin. So that’s very different.

So, yeah, insulin is not able to do its job, but insulin resistance and I mean, there’s so many different diseases that’s been linked to, but everything, I think everything is so complicated. So I don’t know that everything’s due to insulin resistance, but it’s one component of something that’s accelerating the way you age.

Red Light Therapy and Skin Health

STEVEN BARTLETT: I had a light doctor in here the other day, a sunlight doctor the other day. And we spent a lot of time talking about light and sunlight. And one of the things that I’ve been really fascinated by is red light therapy over the last couple of months. Do you have a sort of red light therapy routine?

DR RHONDA PATRICK: It’s interesting that you ask. So, red light therapy in the scientific literature called photobiomodulation. I know that’s a complicated word, but, you know, there’s essentially a variety of different wavelengths that can be used to stimulate physiological processes like mitochondria inside of your cells to do stuff.

I now am convinced that red light therapy plays a role in helping with skin aging. So I do have a mask. It helps with skin aging and wrinkles. There have been enough studies now that is pretty convincing that it does seem to improve the way skin ages.

I do think the important thing here is the parameters that are done. It’s not just wavelength, but it’s also the energy, so irradiance. And so you have to kind of look at all those parameters and make sure you can replicate that with whatever product that you’re using.

STEVEN BARTLETT: What about infrared saunas?

DR RHONDA PATRICK: Infrared saunas or traditional saunas?

STEVEN BARTLETT: The infrared ones.

DR RHONDA PATRICK: Infrared. So infrared saunas are a type of sauna that is using infrared radiation, infrared wavelengths to heat up the body. And so they’re not very hot. So if you look at the ambient temperature in an infrared sauna, it goes up to like 140 degrees Fahrenheit, which is very different from a traditional sauna.

So infrared saunas don’t have all the same benefits as a traditional hot sauna, something that maybe goes up to 175, 180 degrees Fahrenheit. Unless you are staying in that infrared sauna for a very long time, perhaps even twice as long as you would or more in a traditional sauna.

Infrared Saunas and Depression Research

The interesting thing about infrared saunas, I would say so a colleague of mine, a collaborator of mine, Dr. Ashley Mason, she’s at UCSF and she’s been doing what’s called the heat bed study. And it’s an infrared sauna that is essentially a head out heat bed. So your whole body is in this infrared sort of bed, but your head is out of it, your head’s not in it.

And people, she’s now done a couple of studies and the most recent study has been done in people with major depressive disorder. So they have depression. And these people are doing an infrared sauna to a pretty extreme degree. So she’s elevating their core body temperature by around 2 degrees. So they’re essentially getting in a somewhat feverish state.

And in order to do that, I mean, these people are in this infrared sauna for well over an hour. So not like most people that are doing infrared saunas, they’re probably staying there for like 20, 30 minutes. Right? So people are getting very, very hot to the point where their core body temperature is going up to, you know, increasing to like one and a half to two degrees. Right. And she’s looking at the effects on depression.

And so what she has found is kind of amazing is that people that are doing this infrared sauna, this heat bed, and doing cognitive behavioral therapy, CBT, they are experiencing massive antidepressant effects. So there’s something called the Hamilton Scale, which is like a battery of tests that are done to assess depression and just to give you some sort of basis of like, if there’s something considered clinically significant, then you have like a three point change on that scale.

Well, essentially this infrared sauna plus the cognitive behavioral therapy improved the Hamilton scale assessment by 16 points. And these are people that did four or eight rounds of it. So it was over the course of either one month or two months. Some people just couldn’t finish it because it is pretty intense. Like you’re heating your body quite a lot and you’re sitting in this infrared sauna for over an hour and it’s pretty intense. But the magnitude of effect on the antidepressant effect was it’s stunning.

And this kind of all stems back from her mentor, Dr. Charles Raison, his research that was essentially like an infrared sauna. So he did something, this was back in 2016, he did this study where he put people in this sort of infrared sauna like thing, and it elevated their core body temperature again by about 2 degrees. There are people with major depressive disorder or he gave them a sham control. So it was kind of hot. And people were thinking they were getting the treatment, but it was actually a placebo.

Okay. It was enough for them to think they were getting the treatment, but it wasn’t elevating their core body temperature enough. And they did one treatment of this. Okay. And he showed that the people that did one treatment of this had an antidepressant effect that lasted six weeks later after one treatment, sham control, didn’t get this beautiful study. You know, Ashley kind of followed on that study and showed multiple sessions of it really had an even more robust effect.

But I say this because I don’t want to say infrared saunas aren’t great. However, there’s a lot of benefits that have been related to more hot, traditional types of saunas. Finnish saunas, for example, traditional saunas that are hotter, right. And so you’re staying in these 175, 180 degree sauna for like 20 minutes, and it’s associated with, you know, lower cardiovascular rated mortality. So if you’re doing it four to seven times a week. That’s associated with a 60 sorry, 50% lower cardiovascular related mortality versus doing it one time a week or all cause mortality. It’s associated with 40% lower all cause mortality versus doing it one time a week.

STEVEN BARTLETT: So what’s going on there?

Heat Exposure Mimics Exercise

DR RHONDA PATRICK: Right, exactly what’s going on there. And so the really fascinating thing to me about this deliberate heat exposure from a sauna is that it is sort of mimicking moderate intensity aerobic exercise. And this has actually been shown, it’s been compared head to head to moderate intensity, like cycling on a stationary bike. A lot of the physiological responses.

So your core body temperature goes up, your heart rate goes up. Right. When you’re exercising, your heart rate goes up. Same thing happens when you’re in a hot sauna. Your heart rate goes up, your cardiac output is increased. Right. Your blood flow is increasing. All these things are happening and they’re very similar. Exercise, heat stress, you’re sweating, right, to cool down your body. So it’s a way of sort of mimicking this moderate intensity exercise that doesn’t really happen in an infrared sauna. If you do the same amount of time as you’re doing in a hot sauna now, perhaps if you increase that time, it would happen.

But there’s all these benefits that are happening with just doing a deliberate heat exposure from a sauna that seem to not only sort of mimic cardiovascular exercise, but they add on to it. So we were talking about cardiorespiratory fitness and how important that is for longevity, right. Where there have been studies that have looked at people that exercise on a stationary bike, or they exercise on a stationary bike and then follow that up with a 15 minute sauna.

And it’s been shown that those people that do the 15 minute sauna on top of the exercise have a more, a higher improvement in their cardiorespiratory fitness. They have more improved levels of their, their cholesterol and lipids, their blood pressure improvements were greater. So there’s this additive effect of adding on the deliberate heat exposure with the exercise that isn’t happening with exercise alone.

So again, that’s sort of just more evidence of why doing a deliberate heat exposure like a sauna, in fact, hot tubs, that’s something that’s also been shown to improve blood pressure. In fact, a study just came out a couple of weeks ago showing that a hot tub is very beneficial for improving blood pressure, for doing all the same things that a sauna does, which is kind of exciting because not everyone has a sauna.

STEVEN BARTLETT: I heard that you sometimes rehearse important talks and studies in saunas.

Using Saunas for Memory and Learning

DR RHONDA PATRICK: Yeah, I mean, this started back when I was in graduate school. I used to go to this. I lived across the street from a YMCA, and I used to go to this sauna and use the sauna before I would go into my lab and do experiments. And there’s a couple things I noticed. One, I was able to handle stress better. My stress of, you know, failed experiments, mentors putting all this pressure on me, all that stuff. Right. If I went to the sauna beforehand, I was very much. It’s like I was more resilient to the stress. And that was when I started to look into the effects on the brain. And that’s where I also am very interested in depression research as well. Right. Cause you’re causing, like, brain resilience.

But once I started to realize, like, this is affecting my mood, this is affecting my ability to handle stress, I was using the sauna, like, every day. I mean, I was, like, religious about it. It was crazy. I mean, it was like six to seven days a week. I was going in that sauna. And because it was like, using it every day, you have to multitask. You only have so much time in the day. Right.

And so I’d start rehearsing my presentations, like, going through them in my mind while I’m sitting in the sauna with these other people from the YMCA who probably think I’m crazy. Cause I’m sitting here, like, saying things. But I noticed that I was able to remember things better if I had gone through them in my head with the heat.

And it wasn’t till many, many years later. I mean, I kept doing that. Like, even sometimes when I travel and I’m giving a presentation or a talk, I’ll get in the hot bath in my hotel room and I’ll just lay in the hot bath. And I just go through my talk in my head. Or I’ll, like, look at my notes and like, if I forget something, I’ll go through it in my head.

And it wasn’t until several years later that I started looking into the science behind that. Like, there’s something going on here. What is going on? And I found that actually when you go into the sauna, so there’s a lot of physiological changes that happen. Growth hormone goes up. In fact, depending on the temperature and duration, growth hormone can go up anywhere between twofold to like, 16 fold. Like insane levels of growth hormone.

But there’s something else that goes up called IGF 2. And that is associated with improving memory and learning. So there have been animal studies that have done this. And so I’ve kind of connected the dots here and go, maybe that’s why. I don’t really know why. I mean, sometimes just like a very strong emotional response can sort of help you remember something. And you are, at the end of the day, causing a very strong stress response when you’re getting in the heat.

So I like to use the sauna for a lot of things. I do it. It depends on the day. Sometimes I do it. I like to do it before bed. So I’ll do like the hot tub or the sauna. It improves sleep. It improves my sleep. And that has to do with the growth hormone. It has to do with what are called somnogenic cytokines. These are inflammatory molecules that are made that cause sleepiness.

So if you think about when you’re sick and you have inflammation going on, when you have an illness, you’re very tired, you’re sleepy, you’re producing a lot of what are called somnogenic cytokines. These are cytokines that are involved inflammation molecules that are involved in making you sleepy. Those are also produced when you are undergoing deliberate heat exposure, like a hot tub. And that’s been shown as well as a sauna.

So sometimes I like to do the sauna at night, like to relax and help my sleep. Sometimes I like to do it after a workout to extend my workout. Like the study I talked about where you’re improving your cardio respiratory fitness as well.

STEVEN BARTLETT: Would you like some tea? My team can make you some tea if you’d like some tea.

DR RHONDA PATRICK: I would love some loose leaf tea in a metal cup.

STEVEN BARTLETT: Why don’t you want this tea?

The Microplastics Problem

DR RHONDA PATRICK: What you’re doing here is tapping into my. Sometimes my friends don’t want to talk to me because I’m like, the bearer of bad news, you know, where it’s like, “What is Rhonda going to tell me now that I shouldn’t be doing that I love doing?” Right.

Another obsession of mine of late has been microplastic exposure. And I know you’ve talked about this on the podcast before and it’s in the news now. A lot of people are sort of familiar with microplastics, right? Breakdown of plastic particles that are tiny, depending on the size and getting into our circulation, right?

And when you think of microplastics, you think of plastic. When you think of plastic, you think, “Oh, that plastic water bottle. Yeah, well, I’ll just avoid that plastic water bottle,” right? What you don’t realize is that everything, everything has plastic.

So you have here this to go coffee cup, which I don’t know how many coffees I had and teas I’ve had in a to go coffee cup, but it’s hundreds, hundreds and hundreds. And the thing that’s so disturbing is I learned that, you know, these many, most all of these plastic, I mean, sorry, these paper looking coffee cups are actually lined with plastic. They’re lined with a plastic liner to prevent the liquid to leaching into the paper.

And that plastic lining, when you add heat to it, that is boiling water for tea or hot coffee, it accelerates the breakdown of the plastic lining. So you’re drinking microplastic beverages and also the chemicals associated with them.

So there was this classic study that was done that showed heating up plastic essentially causes these toxic plastic associated chemicals like BPA, bisphenol A, which is an endocrine disruptor. It disrupts hormones, it sort of mimics estrogen. So it’s sometimes called an estrogen mimetic. It causes that to leach into your beverage 55 times more. 55 times, 55 fold. Yes.

STEVEN BARTLETT: Which is 5500%.

Microplastics in Beverages and Food Containers

DR RHONDA PATRICK: It’s a lot. Yes. And so you’re talking about drinking plastic chemicals and microplastics. So that was like, okay, well fine, I’m going to bring my mug in anytime I’m traveling and ask them to put my coffee in that. So I see so many people with these to go paper cups and they’re drinking coffee in it. And it’s so hard for me because I realize it’s like this plastic soup that you’re drinking now you have a tea bag on top of that.

And that is something that there’ve been over the course of the last seven or eight years, there have been studies that have come out that these teabags are composed made of, you know, there’s plastic polymers in them. And so there’s thousands of microplastics that are released in every milliliter of tea from these teabags. And there’s a variety of different tea bags. Essentially all of them release microplastics, the ones that look like they won’t release them.

So now, while I used to drink a lot of tea, when I’m on the go, I bring my own with me. I bring my own loose leaf tea with a little, you know, one of those little steepers that can steep the tea. And I use that because, mostly because of the heat, you know, it’s just accelerating that breakdown.

Yes, I’ll drink plastic. I mean, I’ll drink water out of a plastic bottle sometimes when I’m traveling because there’s no other options. And actually, there was a study that just came out. I’m sure you saw it. Did you see the study that showed glass had higher levels? So water that was in glass had higher levels of microplastic than water that was in plastic containers? This was a study that came out of France.

STEVEN BARTLETT: Oh, come on.

DR RHONDA PATRICK: You didn’t see the study?

STEVEN BARTLETT: No.

DR RHONDA PATRICK: Oh, my gosh. This is, like, everywhere. Everywhere. I mean, it came out, I don’t know, in the last two weeks or so. The study came out of France, and it was essentially showing that glass bottles had more microplastics in the liquid that they contained than plastic bottles, which contained liquid. And you might go, “What? That makes no sense, right?” I mean, why would the glass have plastic particles at a higher level than a plastic bottle?

Well, it turns out that the paint on top of the lid of the glass bottle has plastic polymers in it. And so the paint is flaking off and getting into the water that is contained in the glass bottle. There is, I think, a silver lining here. And that is, well, okay, there might be more microplastics in the beverages that are in the glass bottle compared to the plastic bottle, but the size matters.

So it was shown that the size is larger in the glass bottles compared to the plastic bottles. The size of the plastic, the size of the microplastic. And there’s a reason why this is important, because microplastics and nanoplastics, as you get smaller in size, they get smaller. They’re called nanoplastics. Those are the most dangerous because it can be more easily absorbed in the gut and get into the circulation. If it gets into circulation, it can more easily bypass the blood brain barrier and get into the brain.

Size matters. And so the larger size flaking off from the paint is less likely to be absorbed by the gut and to get into circulation. Now, this has to be shown. I’m sure that’s going to. This study is going to be done next. Like, this is going to be the next study. It hasn’t been shown yet.

The Role of Fiber in Microplastic Elimination

STEVEN BARTLETT: I’ve heard you talk about fiber as well, playing a role in getting microplastics out of our body.

DR RHONDA PATRICK: Okay, so, yes, fiber is interesting. This all comes from animal studies. And fiber seems to play a role in the absorption of microplastics and nanoplastics in your gut cells. And that’s really important because if you don’t absorb them, it’s excreted through feces. Right. And it’s been shown we only absorb about 1 to 2% of these microplastics that we’re ingesting fiber.

What it does is two things. One, it moves the microplastics through the intestines quicker, right? Which is what fiber does. But I think the more important thing is the type of fiber. So you want this fermentable type of fiber, soluble fiber. That’s the kind of fiber that’s really good for your gut microbiome.

And what that does is it’s essentially creating this viscous gel, like, sort of gel, like, you know, mucusy stuff inside of your gut that encapsulates the microplastic so that it can’t be absorbed by the gut, you know, what are called the gut epithelial cells. And so if you’re essentially not able to absorb those microplastics, then they’re not getting into circulation. And that’s like the biggest thing that you can do, right, is not get them into circulation.

Now, this is all based on animal evidence. I did speak with a microplastics researcher at Harvard, Dr. Carrie Nadao, and she wasn’t even aware of this, and now she’s, like, on it. So I’m hoping that there’ll be some human evidence coming soon looking at whether or not microplastics, if you’re eating fiber, if that can basically blunt the absorption of the microplastics into the system. I think people that are eating more fiber in their diet probably are getting less of that microplastics into their system. But that hasn’t been shown in humans. It’s only been shown in animals.

BPA and Endocrine Disruptors in Canned Foods

STEVEN BARTLETT: I’m guessing you don’t eat canned soup either.

DR RHONDA PATRICK: Yes. Yeah. So the canned soup is interesting. You know, again, aluminum cans are lined with this plastic lining, and that prevents the sort of breakdown of the aluminum, the metal. Unfortunately, it also causes these chemicals like BPA that are in the plastic lining to leach into the. In this case, the soup or the beverage or the liquid that they’re contained in. Right. There was this study that showed, I think it was. Was it 1000% increase of BPA after drinking soup out of a can versus a soup out of a glass. A thousand percent increase in bisphenol A levels.

STEVEN BARTLETT: I mean, that is bisphenol A levels being BPA, which is the bad thing in microplastics.

DR RHONDA PATRICK: It’s one of the bad chemicals in plastics that is an endocrine disruptor, so it’s disrupting hormones. And that can play a role in a lot of different things depending on what we’re looking at. So it’s hugely important for obviously, neurodevelopment in children, so pregnant women, but even disrupting hormones in general, like mimicking estrogen. I mean, that’s not something that guys want to do either. Right. So it is something to be aware of.

But the thing is, is that, you know, BPA, there was this beautiful marketing strategy that came out I don’t know how many years ago, but all this BPA was replaced with something else that wasn’t BPA, it was BPS. And so now everything is marketed as “BPA free.” And people think that is like, “Oh, oh, it’s not dangerous, it’s BPA free.”

However, what it’s replaced with is doing the same thing as BPA, if not worse. And that’s been now shown in multiple studies. So it’s also an endocrine disruptor. It’s doing the same thing. And yet people think that it’s safe because it’s “BPA free.”

Golf Courses and Parkinson’s Disease Risk

STEVEN BARTLETT: Did you hear about this study of people that live close to a golf course?

DR RHONDA PATRICK: Yes. Yeah, there’s a study that came out. I don’t know how it was very recent.

STEVEN BARTLETT: Maybe a month, 2025.

DR RHONDA PATRICK: Yeah. So maybe I think it was a couple months ago. And the study showed that people that lived near within a mile or so of golf courses had a much higher incidence of Parkinson’s disease. Right.

STEVEN BARTLETT: It says 126% higher risk.

DR RHONDA PATRICK: Right. Okay, so then why is that? Right. And this is where I want to get into the pesticides issue. Because it’s known, like any scientist that’s done research in neurodegenerative disease, it’s one of the ways that you induce Parkinson’s disease in animals is you give them insect, you give them essentially a pesticide. So rotenone being one paraquat.

And what that does is a mitochondrial toxin. So it’s basically causing your mitochondria to die. And then essentially when the mitochondrias are dying or apoptosing, you know, the cell undergoes apoptosis and dying. So you’re essentially, you can induce Parkinson’s disease in mice by giving them these types of essentially, you know, these types of insecticides and herbicides. So it’s well known that that can cause, you know, Parkinson’s disease.

It’s important to know that it’s mostly the ingestion of it and not the inhalation of it. And that was a big concern because it gets into the water source, and that’s what’s thought to be the underlying cause. People that are living close to a golf course is getting into. It’s contaminating the water source, essentially. And so people are drinking these, basically these pesticides, insecticides and herbicides. Right?

So a water filter, like a reverse osmosis water filter or something like that, that can filter out some of these molecules and hugely important. And I think that’s the solution to people that are living near a golf course or people that are living near any sort of agricultural place where they’re using a high volume of these types of herbicides.

The Critical Importance of Magnesium

STEVEN BARTLETT: What is the most important thing we haven’t talked about that we should have talked about? Rhonda?

DR RHONDA PATRICK: I think we talked a little bit about magnesium, but I don’t know that we talked enough about magnesium. And it is important because it’s something that is required for, gosh, over 300 different enzymes in your body need it to function properly. So it’s what’s called a cofactor. And I mentioned DNA repair enzymes. So it’s also used to make energy. So you need magnesium to make energy. And to use energy, you need magnesium to repair damage. That’s happening all the time.

And close to 50% of the population in the United States does not have adequate levels of magnesium because they’re not eating the foods that they need to to get the magnesium. Dark leafy greens I mentioned. It’s at the center of a chlorophyll molecule. There have been studies that have shown that for every hundred milligram decrease in magnesium intake, there’s a 24% increase in pancreatic cancer incidence. And that’s in a dose dependent manner. So you keep going up and up.

I think that people don’t realize that they’re not getting enough magnesium. Magnesium’s required to make, to turn vitamin D3 into the steroid hormone. So some people have a magnesium, you know, insufficient amount of magnesium they’re taking in and they’re actually not able to make enough vitamin D into that steroid hormone. Again, magnesium is controlling 300 enzymes. Some of those enzymes are actually the ones that are converting vitamin D3 into the steroid hormone.

So magnesium is hugely important. It’s something that can be easily corrected. The deficiency could be easily corrected by taking a supplement, but also eating more leafy greens, which is the best source of magnesium. The question is, what do supplements do? What kind of supplement do you take? How much should you take? All these things are, I think, questions that people are interested in.

STEVEN BARTLETT: So I’ve got some magnesium here. Is taking magnesium going to have a positive role then? On my speed of aging?

DR RHONDA PATRICK: I do think so. I think so, yes. We talked about cancer incidence, right? Magnesium. So I think magnesium is one of those sort of minerals that is when you don’t have enough of it, it’s causing that insidious damage over time that accumulates and then rears its ugly head, you know, in the fifth, sixth, seventh decade of life. And that ugly head happens to be cancer. So I do think that if you are able to avoid magnesium deficiency and insufficiency, then you are going to be able to basically make sure there’s enough magnesium around for everything in your body to use it with what it needs it for.

STEVEN BARTLETT: So, and I’ve heard you say that 50% of people are deficient in the United States in magnesium, right?

Magnesium Triage Theory

DR RHONDA PATRICK: Close to 50%. And not to mention, you just talked about electrolytes, well, athletes, they actually require between 10 to 20% more magnesium than the general population because of their magnesium losses are so great and so they can be even more deficient. Magnesium’s needed for red blood cells and so people can have lower energy as well. So magnesium is so important for so many different things.

And like I said, I do think there’s a trade off here where whatever magnesium you are getting from your diet, if you’re not getting enough of it, it’s probably going to make energy instead of being used to repair damage. Because you need to make energy every day, right? That’s the most important thing. If you don’t make energy, you die. Like you can’t survive.

So whatever magnesium your body is getting, it’s not going to that process of repairing DNA, which doesn’t really matter until you’re in your fifth, sixth, seventh decade of life and cancer risk increases. Right. And so there’s this idea put out by my mentor, Dr. Bruce Ames, called triage theory. And he’s shown some evidence of it. Magnesium is one of them. Where magnesium seems to be triaged to energy production at the expense of repairing your DNA.

STEVEN BARTLETT: What does that mean?

DR RHONDA PATRICK: It means that if you’re not getting enough magnesium through your dietary intake and you’re not supplementing with it, whatever magnesium that you’re getting, there’s 300 different enzymes that need it to do their function. That your body is finding a way to triage it to the most essential functions that are going to basically help with.

STEVEN BARTLETT: Short term survival, Triage means it’s basically allocating.

DR RHONDA PATRICK: Yes, it’s allocating it to the processes inside your body that are essential for short term survival. Right now I get long term health diseases of aging like cancer that doesn’t matter as much.

STEVEN BARTLETT: If you’re deficient?

DR RHONDA PATRICK: Yeah. Your body basically says, “No, I’m not going to give whatever precious magnesium I have right now to prevent cancer because I need to live long enough to reproduce and pass on my genes.” And cancer doesn’t happen until I’m well past that. So this idea, it’s called the triage theory, and it’s been shown for several different micronutrients.

Another one is vitamin K. So vitamin K is really high in dark leafy greens. Well, what Bruce has shown is that vitamin K is important for a couple of things. One, it’s important for blood coagulation, blood clotting, and that all happens in the liver. You activate proteins in the liver for blood clotting. If you don’t have vitamin K, you can’t do that. It’s one of the reasons why when a baby’s first born, they give it a vitamin K shot so that they have blood coagulation.

The Shocking Link Between Magnesium and Cancer Risk

STEVEN BARTLETT: On your YouTube channel, you made a video about magnesium, which I recommend everybody goes and watches if you are interested in going deeper on this subject. And on your YouTube, I found a stat that said for every 100 milligram drop in magnesium intake is linked to a 24% higher risk of pancreatic cancer.

DR RHONDA PATRICK: Yes.

STEVEN BARTLETT: Which is shocking.

DR RHONDA PATRICK: It is. And again, it comes down to the DNA repair enzymes that require magnesium to be activated. And if over a lifetime, you’re part of that 50% of the population in the United States that doesn’t get enough magnesium, then you’re talking about not being able to repair damage to your DNA over decades.

And essentially what that means is at some point damage happens to your DNA in the right part of a gene that is what’s called oncogenic. It’s cancer causing. And so eventually it’s going to cause cancer if you’re not able to repair that damage. And so getting enough magnesium is important to make sure you’re repairing that damage.

And it’s not only important for cancer, but also all cause mortality. So there’s also studies showing that people with the highest magnesium levels have a 40% lower all cause mortality than people with the lowest magnesium levels. And they have a 50% lower cancer related mortality compared to people with the lowest levels. So again, cancer’s still in there.

And we’re seeing that magnesium intake is very important with respect to cancer. And that is something that people don’t realize when they’re not getting enough of magnesium in their diet. They’re not eating their leafy greens or they’re not taking a supplement that they’re sort of affecting their long term risk of cancer.

STEVEN BARTLETT: So people with high magnesium levels have a 50% lower risk of cancer death than those with low levels.

DR RHONDA PATRICK: Right.

STEVEN BARTLETT: And is that… You obviously can’t do a double blind placebo controlled test on that. So they’re really establishing causation. So it could be other things. It could be the other dietary factors that go into that. Maybe if we think about causation, people that eat a lot of hamburgers don’t have a lot of leafy greens.

DR RHONDA PATRICK: Exactly. You nailed it. Essentially, magnesium is packaged in these foods that are beneficial, like dark leafy greens. And there’s so many other benefits along with them that you can’t establish causation and say, “Aha, it’s just the magnesium.”

I would argue it’s probably not just the magnesium, but magnesium does play an important role. It’s just you can’t of course pinpoint it to just magnesium because you’re right, there are many other important healthy things in these micronutrients, in these plants that are beneficial for health as well.

The Nutrient That Makes Babies Smarter

STEVEN BARTLETT: There was a really random thing that I think parents might appreciate us talking about, which was when I was looking at your work, you mentioned this chemical that if parents take while their baby is inside them, mothers take. The baby is smarter.

DR RHONDA PATRICK: Yes. Choline.

STEVEN BARTLETT: Choline.

DR RHONDA PATRICK: Choline, yeah. Choline is an essential nutrient that is, it’s really concentrated in egg yolk. That’s a really good source of choline. But it’s important for, it’s a precursor for the neurotransmitter acetylcholine. It’s also important for producing all these epigenetic changes called methylation that regulates the way our genes are expressed. And it’s also important, very important for our cells, like the membranes of our cells. And it makes something called phosphatidylcholine.

It’s doing so many things is the point I’m getting to. I don’t want to get into all this nitty gritty cause people can get lost in that. But the point is that pregnant women that were given close to the RDA, it was like 500…

STEVEN BARTLETT: What’s the RDA?

DR RHONDA PATRICK: The recommended daily allowance. Actually, I think in this case it was the DRI, the Dietary recommended intake. So pregnant women were given close to what is the dietary recommended intake. So they were given 480 milligrams a day of choline, or they were given almost double that. So they were given 930 milligrams a day.

And I don’t remember what trimester they started in, but they were given this throughout a certain timeframe during pregnancy. And then a variety of cognitive tests were done after the child was born. And the children that were given… The mothers that had children that were given the really high choline intake, the 930 milligrams scored better on all these IQ tests.

And so essentially, their children were smarter if their mother had taken choline throughout pregnancy. And I think this is really interesting because it’s the one easy thing that people can do. They can supplement with choline or they can eat a lot of eggs with egg yolk, which is something I did both during pregnancy. I was eating probably six eggs a day and supplementing with choline, so I was doing both. And every mother wants to think… Every parent wants to think that their…

STEVEN BARTLETT: Child is smart, but I bet your child is smart.

DR RHONDA PATRICK: He’s a smart cookie. Yeah.

STEVEN BARTLETT: How old is he now? Almost 10.

DR RHONDA PATRICK: Seven.

The Final Question: Life’s Biggest Regret

STEVEN BARTLETT: Seven. Okay. We have a closing tradition on this podcast where the last guest leaves a question for the next guest, not knowing who they’re leaving it for, and the question left for you. Interesting. If you could go back and change one thing about your life, what would it be? And you cannot say nothing. That’s what it says.

DR RHONDA PATRICK: I would say the one thing that I would change. I’m 47 years old, just turned 47 last month. I have one child, and I think if I could go back in time, I would change my decision to only have one child, and I would have another child.

STEVEN BARTLETT: Why?

DR RHONDA PATRICK: Because I love being a mother. I love the joy that children bring to your life is… It’s unexplainable until you experience it, everything about it. Helping shape them, learning with them, going through hard times and experiences, but also experiencing the joys I regret, sort of.

You know, I had children later in life because I was really pursuing my career, and it is definitely challenging being an entrepreneur that’s a mother. I made this decision that I was going to have one child because I wouldn’t be able to do as much of what I love doing outside of being a mother if I had more than one child.

And now I realize that… Say that when I’m older and closer to dying. I know now that I’m not going to think about doing one more podcast when I’m on my deathbed. I’m going to think about all the experiences I’ve had with my family.

And I do have a pretty balanced, I would say balanced personal life and family life with my career. I don’t know that it was the easiest decision to make where I had to sort of give up some of my intellectual pursuits, some of my entrepreneurial, my productivity. Essentially, I had to give some of that up to be the best mother that I wanted to be, to be present with my husband and my son and enjoy everything that I enjoy, because that takes time.

And that time that I’m with them, I am not doing my podcasting or my research or any of that. And I’m happy with that decision. And in fact, I would even give up more of it for another child. And that’s a very personal thing that I’m discussing, so hopefully I’ll be okay with it.

STEVEN BARTLETT: It’s not the first time I’ve heard this.

DR RHONDA PATRICK: Really?

STEVEN BARTLETT: Yeah, no, yeah, it’s not the first time I hear this a lot, which is fascinating to me from high performance women.

DR RHONDA PATRICK: It is. It’s… You know, I say that it’s very hard to be a very high performing female and a mother at the same time. You either have to sacrifice being present with your family or your health because you don’t sleep as much. You know, you’re basically not going to be getting as much sleep because you’re going to be working rather than sleeping during some of those hours.

So I do think that it is very challenging. And I’m not saying that there aren’t really high performing mothers out there, but it is a very difficult thing to do.

STEVEN BARTLETT: When you say you made the choice to have one, was that an intentional choice? That is, you and your partner did family planning and said, “We want one,” or was it because you said your child is 7, you said you’re 47. So at 40, obviously it becomes a little bit more tricky than it does when you’re 30s to conceive.

DR RHONDA PATRICK: Right. So I think what… In my case, I got pregnant when I was 38 for the first time and I gave birth when I was 39. So I was pretty late already. And at that point I didn’t, you know, as I was, I was so overwhelmed and my productivity had gone down so much just from that event that I was worried that I wouldn’t be able to keep it up if I did another one right away, which I had to do because I had waited so long.

Now why did I wait so long? I was pursuing my career, you know, I mean, and I would argue now that I could have had a kid in graduate school, I could have had a child as a postdoctoral fellow. But again, it’s one of those things where you just, you keep, you want to get to this milestone and then this milestone and then you want everything to be perfect and you start to… This perfectionism can sometimes be a double edged sword, right?

Where your perfectionism then is like, “Okay, well, you’re going to have a trade off here.” And that trade off for me was my reproductive lifespan. You know, I was older when I started having children. Now there’s a lot of technologies out there now that can help with that. But at 47, it’s, I would say, not looking good, I think.

The Biological Clock and Family Planning

STEVEN BARTLETT: I ask about this, and I’m curious about this because me and my partner, I’m 32, she’s 30, turned 33 last week. We don’t have any kids. We’ve been together for almost seven years now, I think. And so you can imagine in my life how easy it would be to make excuses that I need to get through this year because this big thing’s happening or I’m moving to LA, so now’s not the right time. And then she’s got her business going on, so now’s not the right time for her. And she’s traveling and doing these retreats around the world. So that’s not perfect timing.

And then because of this podcast, I’ve played this scenario forward because I get to meet people who are a little bit further down the line than me, and I get to ask them about their regrets and the decisions they wish they’d made. And were they intentional about family planning, did they wish they’d done it earlier?

And the thing it’s changed in me is it’s made me realize that to start the process, if there’s something I want to do well before I’m ready, because there is a. Whether we like it or not, there is a biological clock. And the thing that I’ve observed in the guests, specifically high performance women, whether Ronda Rousey, the UFC champion, who I sat and interviewed and who was in tears talking about her failed IVF for the, I don’t know, the fifth, sixth, seventh time, or other women that I’ve sat here and interviewed and looked in their faces, is the regret of having that decision taken away from you is going to be much, much worse than the inconvenience of the choosing an imperfect time to have the kid.

So funnily enough, people don’t really know this. Because I don’t talk about this. But I walked away from this podcast after hearing this story over and over again. And I went to the women in my lives and I was like, it’s super annoying being that guy. Because especially as a guy saying it, I’m like, “By the way, family planning as early as possible is probably a good idea. And whether that means freezing your eggs or freezing your embryos or just giving yourself the option in the future is probably a good idea.”

And it was so interesting to actually see the reaction to me saying that to some of the women in my life that I care about, like my siblings or my partner, because upon saying, wasn’t incredibly well received, because I think it’s a confronting thing to say to somebody because there’s a bit of a stigma associated with freezing your eggs and IVF and freezing your embryos.

And even with my partner, the first time I said it to her, it was almost as if I was insulting a little bit. Insulting her. That’s almost how I thought she took it for the first three or four minutes. But then when I explained what I was saying by like, “Let’s give ourselves the option when we’re older. You know, let’s just give ourselves the option. And also, if you go through these procedures when you’re younger, you have higher quality yield from the eggs you freeze or the embryos you freeze. Let’s just give ourselves the option.”

And then she kind of turned five minutes into the conversation, and then she got super excited about it, 15 minutes in, and now we’re super excited. So we’re trying to conceive, but also we’re going to be freezing our eggs and freezing embryos in this year, in September, because. And I’ve just tried to be a really big influence to the women in my life to give yourself the option.

And I say this because I’ve seen the regret on this podcast, and that’s what I’m saying. And I think all people that can, and I know it’s expensive as early as you can, should consider the fact that we live in a world that is driving productivity, that is making us work later and later in life, that is making us more obsessed with our careers. And without us really knowing it, there is a clock, and it’s robbing us of the option to make family planning decisions.

The Regret of Not Having Options

DR RHONDA PATRICK: 100% agree. I can’t agree more! Everything you just said, I mean, if I had frozen my eggs or we had done IVF and frozen embryos that were viable and healthy, then we’d have the option, right? I mean, it’s so true. And I don’t know, I think I was just really blinded by and overwhelmed by how much work I have to do and thinking, “Oh, there’s no way I could do more than one.” Because, again, when I’m a mother, I go all in. Yeah, when I’m a podcaster, I go all in.

STEVEN BARTLETT: That’s exactly what you’re.

DR RHONDA PATRICK: You know, it’s not just, you know, when I have a guest on, I really need to be really interested in them and, you know, so there’s. It’s all in. But not giving myself that option is a big regret, you know, where at least if I had frozen my eggs down, then I would be at a point now. If I’d done this, you know, when I was 39 or 40 or even if I had done it the first time, you know, when I was earlier in my 30s, I should have done that, but I just didn’t have the foresight enough to do that, and I do regret it. So it’s great. It’s great that you talk about it to the women that are in your life. And even on the podcast, we’re really.

Forecasting Future Change

STEVEN BARTLETT: Bad at forecasting the fact that we will change. And I think this is really at the heart of it. We’re really bad at forecasting the fact that our current state of mind might not be our future state of mind. But you’ve only got to look backwards in your life and realize how different you are and how you think and what your priorities were. I was in nightclubs at 18 and 19. There’s nothing for me. Going to a nightclub now would be like a form of torture. I changed.

And so at 35, at 40, 45, there’s a high probability that I’m going to have a different perspective than the one I have now. So give myself the option at 45 to, you know. So that’s kind of how I think about it. And I say this out publicly. Because I just think I don’t like seeing that regret in people.

DR RHONDA PATRICK: It’s hard. Yeah, it’s definitely hard. Thankfully, I do have this joy in my life, and I’m so glad I have that. But.

Acknowledging Different Circumstances

STEVEN BARTLETT: And I have to acknowledge the fact that many people, even if they did want the option for fertility reasons, can’t have children. So it’s still not an option for everybody. Because there are, you know, people have certain health complications and other issues which prevent them from having kids, even if they wanted to, and even if they’re young. And I’ve got friends in my life that unfortunately, or in that situation.

But yeah, thank you so much for the work that you do. It’s really, really important work, in part because you’re so unbelievably engaging, but you’re so, because of your obsession, you’re so unbelievably rigorous and in the detail of the things you talk about. And as you said, there’s so many people around the world, and I know because we meet them wherever we go in the world that don’t have access to this information.

They’re not going to be on PubMed, reading through the journals and trying to distill these big words. And I think you do a brilliant job of educating many, many millions of people in every corner of the world through your YouTube channel and your Instagram, et cetera, and making these complicated things accessible.

And if you’re successful in that, which you very much are, you’re tilting the trajectory of their life, but also therefore their future and their kids lives and their kids kids lives. And that’s a really wonderful thing. And we need more public educators like you that have the talent of articulation and engagement that you do. Very, very rare and hard to come by.

I do a podcast where I look at all these people and you’re the very, very best at it and you’ve done it for so unbelievably long. And that’s why. So thank you so much for educating us and allowing us to live the future that would be most conducive with our health and happiness.

DR RHONDA PATRICK: Well, thank you so much, Steven, for the really engaging conversation and for asking the hard questions.

STEVEN BARTLETT: Thank you. This has always blown my mind a little bit. 53% of you that listen to this show regularly haven’t yet subscribed to this show. So could I ask you for a favor? If you like the show and you like what we do here and you want to support us, the free, simple way that you can do just that is by hitting the subscribe button. And my commitment to you is if you do that, then I’ll do everything in my power, me and my team, to make sure that this show is better for you every single week. We’ll listen to your feedback, we’ll find the guests that you want me to speak to and we’ll continue to do what we do. Thank you so much.

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