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Hormesis and the beneficial role of stress with Dr Michelle Woolhouse and Paul Taylor

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Hormesis and the beneficial role of stress with Dr Michelle Woolhouse and Paul Taylor

This week’s podcast episode is a fascinating conversation around the human genome evolution, and how stress plays a key role in our ability to adapt to modern day stressors. 

Exercise physiologist, nutritionist and neuroscientist Paul Taylor talks with fx Medicine ambassador Dr Michelle Woolhouse on the role of hormesis, and the intricate balance between stress and our ability as humans to adapt to and overcome modern day health challenges. 

Paul shares some thought-provoking ideas around evolution, hormesis, and today’s modern lifestyles.  

This podcast is beneficial for all interested in the evolution of the human genome, and the importance of nutrition and exercise in combatting chronic disease and withholding age-related disease, supporting the whole person, and promoting homeostasis to combat burnout.

Covered in this episode

(00:26) Welcoming Paul Taylor
(02:27) Paul’s background
(03:25) Evolution and its impact on health and wellbeing
(11:09) The new science of hormesis
(14:35) Diet and eating for your genome
(18:03) Paul’s definition of stress
(22:41) The power of recovery
(27:06) Resonant frequency for recovery
(30:54) Muscles and holistic health
(35:15) Myokines and age related disease
(37:24) Supporting your constitution
(40:24) Nutrition to support hormesis
(45:42) Harvesting discomfort
(50:04) Thanking Paul and final remarks

Key takeaways

  • Paul’s definition of hormesis: “sublethal exposure to stressors or toxins, which at high levels can kill you but at low to moderate levels induce stress resistance.” 

  • Heat shock proteins are a subclass of stress response genes that are activated during exercise according to exercise intensity. Heat shock proteins clean up cellular damage and activate over 300 metabolic priority genes that optimise our metabolism and brain function.  

  • Hormetins; stressors that are intricately dose dependant; improve stress resilience and increase our endogenous defences.  

  • Common hormetins include exercise, nutrition, fasting, emotional stress, and hot/cold exposure. 

  • Recovery vs relaxation: knowing the difference and practicing accordingly to improve psychological flexibility. 

  • Paul’s 3 key points for nutrition: 
    • Low HI diet (human interference) 
    • Gut-brain axis health (gut health maintained through a diverse diet) 
    • Nutritional hormesis (diversity, fasting, and the inclusion of nutritional hormetins) 

Resources discussed and further reading

Paul Taylor

Connect with Paul: Instagram | Facebook | LinkedIn
Paul's Website
Paul's Book: Death by Comfort

Hormesis and Hormetins

Journal: Nutritional Hormetins in Ageing and Longevity
Journal: Nutritional Hormesis in a Modern Environment
Article: Physiological hormesis and hormetins in biogerontology
Journal: Intermittent Fasting–Dietary Restriction as a Biological Hormetin for Health Benefits

Exercise as therapy

Research: Massive study uncovers how much exercise is needed to live longer
Journal: Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases
Article: Exercise and gene expression: physiological regulation of the human genome through physical activity

Journal: Lack of Exercise Is a Major Cause of Chronic Diseases


Michelle: Welcome to fx Medicine where we bring you the latest in evidence-based integrative, functional, and complementary medicine. I'm Dr Michelle Woolhouse. fx Medicine acknowledges the traditional custodians of country throughout Australia, where we live and work, and their connections to land, sea, and community. We pay our respects to the elders past and present, and extend this respect to all Aboriginal and Torres Strait Islander people today. 

Modern humans, as a general rule, are not doing well. Collectively, we are the most overweight, depressed, medicated, and addicted bunch that has ever roamed the planet. Yet the benefits and ease of modern-day life are all around us, behaviours such as eating ultra-processed foods to being sedentary to poor sleep habits and low stress tolerance are making us inflamed, sick, tired, and wired. But my guest today is going to show us how, by embracing discomfort, we can improve our physical, mental, and emotional well-being. 

Paul Taylor is a former British Royal Navy air crew officer, an exercise physiologist, a nutritionist and neuroscientist who is currently finishing his PhD in applied psychology. He is the director of the Mind Body Brain Performance Institute and delivers leadership and resilience workshops across Australia and beyond. Welcome to the show, Paul. 

Paul: Absolute pleasure to be on, Michelle. Thank you for having me. 

Michelle: Oh, goodness, Paul. What a treat to have you on the show. I wanted to start by firstly congratulating you about your book. It is a fantastically accessible read and really filled with relatable science that helps a reader come away with key holistic concepts for longevity and health. 

Paul: Oh, well, thank you. That's hit the mark then. 

Michelle: So, am I right in saying your first career was in the military? And did this experience infuse your passion for wellness? And how did that happen? 

Paul: Yes. So, my first career was in the military. I was spending eight years flying in helicopters and in the Royal Navy hunting submarines for a few years and then doing helicopter search and rescue. But before I had joined, I had done a master's degree in sports science, so I always had that. And then when I got through all my training and got to my squadrons, my secondary role was always a sports officer, and so, when I was doing helicopter search and rescue, I did another master's part time in nutrition. So, I was always interested in health and well-being, and the interest just grew from there. And I started doing a well-being newsletter and got some really good feedback from it, and that's when I thought, "Actually, when I leave the forces, this is what I want to do." 

(03:25) Michelle: As I've been researching this podcast, listening to some of your other podcasts, as you generously share your knowledge with the world basically, but I really loved your take on evolution and what we can learn from evolution and how does this impact our understanding of physiology and health and well-being. 

Paul: Yeah, I look at... One of the big things that... I think the favourite quote that I have from any research journal I've read was from Prof Frank Booth, who's a legendary exercise physiologist, and he said back in 2012 the human genome has not changed in over 45,000 years. The current human genome requires and expects us to be highly physically active for normal functioning. 

So, when you run everything off that principle, that we still have a hunter-gatherer genome and it is wired for that sort of lifestyle, of high physical activity, of eating real foods, of having intermittent stressors, about having good social support networks, then it becomes very clear why we're starting to have such levels of chronic disease both physical and mental because we don't move very much. Most of our diet is crap. We're digitally connected but socially disconnected. Sleep hygiene is all over the place. And all of these things, as you well know, Michelle, they have significant and additive impacts on your physical and mental health. 

Michelle: Absolutely. I've been reading your book, too. You talk so much sense around the modern-day exercise physiology basically. And I think there's still a lot of confusion out there in terms of... I mean, what I say to my patients is exercise science has come so far in the last decade, which I absolutely love, because when I was in medical school... I won't tell you how long ago, but quite more than one decade ago. Basically, it was, sort of, like walking is man's best medicine, which it is absolutely, but tell us about what we should be doing. Because in your book, you talk actually about some of the evolution like walking not just 10,000 steps a day but for hours and hours, 8 hours, 12 hours on our feet. And the functionality of the body and how we evolved into the humans that we are, what do we need to be doing? 

Paul: So, well, if you look... For me, the best evidence comes from studies of modern-day hunter gatherers. So, there's a tribe in Tanzania that is very, very well-studied called the Hadza, and at the time that these studies that were done by a bunch of Harvard researchers, they were still getting more than 90% of their food from hunting and gathering. So, this is the best snapshot of what our genome is designed for. And what these Harvard researchers did is they put physical activity trackers on them but also heart rate monitors, because they wanted to know not just how much they moved in terms of steps but what was the intensity of their physical activity. So, as a little bit of backdrop, I guess, for the listeners; No government agency talks about steps, and that's for a couple of reasons. Number one, not everybody has a way to measure their steps obviously, but also as important as that is it's the intensity of those steps are really, really important. So, walking is very different in terms of the physiological effects than sprinting. 

So, we talk about moderate to vigorous physical activity. So, let's have that in the background. So, at times like that, Hadza women and girls take about 10,500 steps a day on average, and that's double the amount of average people in 111 nations. So, we generally, in modern society, take about 5,000 steps a day on average. Obviously, there's lots of people who do more, but there's lots of people who do less. Hadza men and boys take 18,500 steps a day, 3 to 4 times the amount of men and boys in modern society, but it's when they looked at the moderate to vigorous physical activity that, for me, this was just astounding. 

Now, backed up for that, our recommended guidelines are 150 to 300 minutes of moderate activity or 75 to 150 minutes of vigorous activity, spread throughout the week and including at least two strength training sessions. Most Australians don't hit that bottom number of 150 minutes of moderate, and it's the same in most developed nations. The Hadza do 950 minutes, 945 minutes of moderate to vigorous physical activity every week. They move on average, in terms of intensity, 7 to 10 times the amount of the average Australian or average American. 

Michelle: That's incredible. 

Paul: But when you understand the impact of exercise on your health... So, there was a very famous journal article called Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. This is by Bente Pedersen, legendary exercise physiologist and Saltin. And what they actually showed is exercise can prevent and/or treat 26 of the most common chronic diseases, and we are just not moving anymore. Not very much at all. 

And so the key thing, I think, for people to understand is that exercise actually controls our gene expression, and I'm sure lots of your listeners will be aware of that, but for those who aren't, I just like to simplify things and go, think of your genes as lights on the ceiling, and gene expression is like the dimmer switch, turning on and off of those genes. And exercise is a very, very powerful regulator of it. 

There's a legendary professor that I talked about earlier, Frank Booth. He showed 15 years ago that, every time you exercise, there are three waves of gene expression that are activated. And the first and most important are these stress response genes. A subclass of them are called heat shock proteins. I'm sure you're familiar with them, Michelle, but they're so important in helping us to adapt to stress. So, for me, these are the things that no psychologist talks about. 

All psychologists, they talk about self-care and self-compassion when it comes to resilience, but you need a biological response and that comes from heat shock proteins. They're activated every time you exercise in proportion to exercise intensity, but they're also activated in cold and heat exposure. And they actually go into your cells, and they clean up the damage, but then they trigger the activation of another 300 metabolic priority genes that just make our metabolism function better in our body and our brain. And then we have this other third wave of gene expression called your mitochondrial enzyme genes. And I'm sure your listeners, Michelle, are very familiar with the importance of your mitochondria. 

Michelle: Wow. And so this is... I mean, there's a lot of talk I think over the last, kind of, five years about this new science of hormesis. Can we break that down a little bit? You talk about gene expression. What's actually happening on a cellular level? And why do we need hormesis so much? And can we have too much of a good thing? 

Paul: Yeah, great question. So, hormesis. Let me summarise hormesis as sublethal exposure to stressors or toxins, which at high levels can kill you but at low to moderate levels induce stress resistance. So, it turns out now that there are over 600 known hormetins in our environment. So, exercise is one obvious one, right? If you don't do any... 

Michelle: Yeah, and easy to get. 

Paul: Yeah, if you don't do any, it's bad for you. Then if you do some, it's good. You do more, it's better. But you get to really high amounts and then it becomes bad again. Sunlight's another hormetic stressor. No exposure to sunlight, you're going to have vitamin D deficiency and all sorts of trouble. Then you get exposure to sunlight, it's good for you. More is better, but then there becomes a point where it starts to become damaging to you. But we even know, Michelle, like radiation, I'm sure when you studied medical school, they said any exposure to radiation and nuclear radiation is bad. 

Now, we actually know there can be beneficial effects from small intermittent doses of radiation. I'm not suggesting anybody goes out and does this deliberately. But British medical radiologists in the '50s who they thought were exposed to unhealthy levels of radiation actually ended up getting less cancer than their peers. Chernobyl accident workers, the recovery ones who went in to recover the guys who had been exposed and were still exposed to levels, although not anywhere near as much as those who were around when the leak happened, but they were exposed to levels and they thought these guys are going to be in trouble as well. They had less cancer than other workers who weren't exposed to any, right? 

So, it's all about the dose response, and it's all about the interaction with your individual genome as well. And for instance, food. Everybody talks about broccoli being really good for you because it's got sulforaphane, and they talk about it as an antioxidant and resveratrol as an antioxidant. They're not antioxidants. They're toxins, but they just produce an antioxidant effect in the body. So, these are small doses of poison that are invented by plants or created by plants to protect them against insects, and they create an aversion response in insects. But because we are so much bigger, when we eat things like broccoli, or grapes, or resveratrol, it creates a very mild stressor at a cellular level, and our cells react by upregulating protective genes. 

So, for instance, superoxide dismutase, catalase, glutathione, perioxidase. And I say to people, these are the special forces of your antioxidant defence system. So, by moderate intermittent exposure to these stressors, we actually increase our endogenous defences, and we get a net benefit from it. 

Michelle: And that just makes so much sense. This is what I loved about your book, too, is coming back to those general principles, so that once you know a general principle, you can, kind of, lead with it with intelligence. And this is why I love this science of hormesis. And because you hear a lot on Instagram or any of those social media platforms or whatever, it's so polarising. 

So, there's a group of people that are carnivores and say all plants are dangerous because of what you've just said. So, what would you say to that? Because I, sort of, see... I always come back to basic principles. And what I love about nutrition is diversity. So, when you have diversity within your diet, you're taking, in your mind's eye, those small doses of multiple different chemicals that are sublethal, that are then creating multiple different effects. So, you're, kind of, hedging your bets in many ways. What would you say to the carnivores? 

Paul: Yeah. For me, I always say, Michelle, anybody who tells you that there's one diet that we should all be eating is either demented, or they're trying to sell you something, or they're a member of a cult, right? It's one of those three things. So, for me, it just doesn't make any sense that stuff that we have evolved in eating for hundreds of thousands of years, animals and plants, that would have any damage in their natural forms, right? And that's the key in their natural forms is the key. 

I think, for those purists, if you like saying that these things are toxins and therefore it's bad, it's a misunderstanding of these pathways, and it's a misunderstanding of hormesis. And we know now, for instance, the Nrf2 pathway which involves HIF-1, and all of these cascade down in terms of cellular adaptations. That's what they don't understand, right? To just go, "This has some toxins in it, therefore it's bad for you," is a massive misunderstanding of human biology. And not just human biology but all species. 

I mean, hormesis is an evolutionarily conserved mechanism that you see across a whole host of different species. And it's about helping us to adapt to our environment. And to your point, Michelle, we can adapt to lots of different environments in terms of temperature but also in terms of food environments. That is one of our benefits is the ability to adapt to eating a wide range of foods. 

And so, for me, we have co-evolved with all of these nutrients that we get from plants, from meat, from nuts, from seeds and all of these things that our body has actually used and adapted to over time to get these health benefits to actually make us function really, really well. And what's happened is we've moved away from that. 

Michelle: You talk a lot about stress, which I've been talking a lot about stress for 25 odd years too, and this concept of good stress and bad stress. And I want to weave in that exercise stressor as well. What's your working definition of stress? What's your favourite one that has, kind of, informed you over the years? And in your opinion, how can we get it right? 

Paul: Yeah, the thing about stress... So, I've actually created... What I'm doing in my PhD is I'm talking all about stress fitness now, right? So, I think that that definition of that, kind of, gives you an insight into how I view stress generally. Now, it's an academic definition, so let people just run with this and then we'll pick it apart, right? 

Michelle: Yeah. 

Paul: So, I call it the malleable ability to engage, maintain, and extinguish the stress response and flexibly adapt to physical and mental challenges and/or advantages to enhance tolerance and/or performance. So, if we pick that apart a bit, you see that there's a physiological response, and there's a psychological response. So, that's one of the key things about stress is that it can be physical or psychological. It activates the same stress response pathways. And from a psychological perspective, it can be real or imaginary. That's the thing. 

Michelle: Absolutely. 

Paul: So, we can sit and have our audience members think about some boost that happened 20 years ago. And if they really get into that, they'll create a stress response as if they're being chased by a lion. And they can also catastrophise about something that might happen next week or whether they're going to have a job in six months or whether their kids are going to turn out all right or be basket cases, and they will create a stress response as if they're being chased by a lion. 

So, if we come back to my definition, the malleable—that means it's trainable, and that's key—ability to engage, maintain and extinguish the stress response. That's the physiological bit. And this research came out of a very interesting research paper on special forces, or soldiers going through special forces selection process. And it turns out the elite of the elite, at a resting state, they had high parasympathetic tone. I know you know what that is, but we'll explain that for our listeners in a second. So, they were more relaxed but then, as soon as they knew something was about to happen, their sympathetic nervous system switched on, that fight or flight response switched on, the parasympathetic, that rest and digest got suppressed. They were able to maintain high levels of the stress response throughout, but as soon as that stressor was gone, they switched. So, they have the ability to turn the stress response system on quickly, maintain it for as long as it's required, and then switch it off quickly. 

Michelle: It's almost like sprint training for stress, isn't it? 

Paul: Yep. 

Paul: Yeah, yeah. So, that ability to switch it off. So, anxious people, they can switch on their stress response system super fast as fast as these special forces guys. But when the stressor's gone, it stays on, right? And that's when people have had a stressful day. They come back, they go to bed, and they can't switch off. That ability to switch off is key. 

And then the next part is flexibly adapted to physical and mental challenges or advantages, right? And so that's about psychological flexibility, right? Can I change my thinking? Do I have the ability to switch to reappraise things and stuff like that? And all of this together then enhances your tolerance and performance. And as I say to people, I want you to think about every time you're exercising, you're training your stress response system globally to switch on and then switch off. So, like you said, it's that sprint training, switch on, switch off, switch on, switch off, which is what we need for the modern world. 

So, for me, there's the Goldilocks effect in stress. It can't be too little, can't be too much. It got to be just right. And avoiding stress is not the right idea and coddling, this mollycoddling that we have of our kids and trying to keep them free from any stressor just is actually doing them a misservice in the long-term. 

Michelle: Yeah. Well, stress will get you... I mean, events and stressful events in your life from where I sit as a GP for 25 years, nobody ever, ever gets away scot-free in life, so whether you have stress as a kid or have stress as an adult. And I think the ones that have the stress as a kid tend to do better. And there's some research to suggest that's actually a fair point. And the ones that don't get that in their childhood actually find it quite difficult emotionally to adapt to that. 

But one of the things that I loved about your work and something that I've been really interested in, in terms of burnout lately, because, I mean, obviously since COVID, we've spoken so much about burnout, is the power of recovery. And so one of the things that I talk about often in my book and my work is measuring the success of, say, anxiety management. You measure it through how well you recover from, say, a triggering or an anxiety, sort of event where those obsessive thoughts start to come down. And if that's getting quicker and quicker, your brain's getting better and better. So, that's obviously what we're talking about and the rest and recovery kind of response. But you talk about recovery incredibly, specifically in terms of your exercise training. Tell us about the power of recovery and what the research is telling us about that. 

Paul: Yeah, look, recovery is absolutely critical. I think we need stress exposure and recovery. And I'm going to give you a quote from one of my favourite stoic philosophers, Epictetus. He said we must all undergo a hard winter training and not enter into lightly that for which we have not prepared. And he was actually talking about life, right? 

Michelle: Oh, I've got goosebumps. I've got goosebumps. 

Paul: Yeah, I just love that quote. And that goes back to your thing that, as a kid, if kids are brought up and their parents are trying to bring them up in a stress-free environment, they're not doing that winter training. They're not preparing for life. Now, obviously there can be too much, so I think our role as parents is to be around, let them fall down, and then help them to learn the lessons to become better as they go. 

But part of this whole thing is this recovery. And actually we get our best insights from the world of elite sport, because most of the performance improvements in the last decade in the world of athletics or elite sports have not been through training methods. It's been through recovery. So, these guys, you look at elite sports people around the world. They're having their heart rate variability monitored every day. And all the executives I work with, I get them to monitor their heart rate variability. And that is the best indicator of the cumulative stress load for me. But these guys are also doing personalised nutrition, and their nutrition is absolutely on point. They're making sure they're very well-hydrated. They're doing contrast therapies, cold and heat, right, to flush out the body and to build in stressors. And they're doing breath work. They're doing meditation. They're very, very serious around their sleep hygiene. 

And what I find in the corporate world is that people have a hard week, and, like these athletes, doing a hard tournament and they've got to get back up for next week. And the athletes come back and they're doing all the stuff I mentioned. Whereas people come home on a Friday night and go, "Jesus, that was a hard week. I need a drink." And having one or two, look, that's fine to unwind, but remember that's relaxation. That's not recovery. There's a fundamental difference. But when you have more than that, and then it starts to affect your sleep, and then if your sleep is affected, that affects how much you move the next day because of impacts on leptin in the brain. It also affects how much you eat the next day. You'll have higher levels of cortisol the next day. You'd be less able to handle the stresses of the day's events. So, this all plays in. All of it interacts with each other. 

And so for me, a lot of the recovery is around doing that breath work. I'm a massive fan of resonant frequency breathing. You can use box breathing. You can use any... 

Michelle: What's the definition of resonant...? 

Paul: Resonant frequency? 

Michelle: Yeah. 

Paul: Yeah, so for most people... So, this is a breathing frequency that connects the brain, the heart and the lungs through the activation of the vagus nerve and the phrenic nerve. And it tends to be...for most people, it is six breaths a minute. Now, everybody varies between four and a half and seven, but six breaths a minute seems to be the sweet spot where anybody without having anything measured can get 90% of the benefits. 

And so you can either do five seconds in five seconds out, but my preference is four seconds in, six seconds out, because I think the... 

Michelle: Yeah, activating that heart rate variability. 

Paul: Yeah, it optimises your heart rate variability. When you breathe in, you temporarily activate the sympathetic nervous system. When you breathe out, you activate the parasympathetic nervous system. So, having a longer breath out is even more effective than... But, look, even research... I talked about a research paper on my podcast a couple of weeks ago where they had people doing a 5-5 breathing rate and actually cleared amyloid beta from their blood, which was pretty amazing, right? 

Michelle: That's really amazing. 

Paul: Yeah, that is pretty good... 

Michelle: It's really amazing. 

Paul: ...particularly when you see how much hundreds of millions of dollars in failed drugs to try and achieve that, that there's been, and so... 

Michelle: And also like... I mean, to draw people to that exercise, even 5 to 10 minutes of simple breathing exercises every day, I mean, I can't tell you how many times I've said this. You and I are kindred spirits, Paul, and we've only just met, but breathing is probably the most powerful intervention that is cheap, simple, and it is so unsexy that knowing that beta-amyloid blood levels are going to get less, that's getting it sexier, I think, in my opinion. 

Paul: That's going to get very, very sexy. And I think a lot of the benefits that you see in meditation, you see in breath work as well. 

Michelle: Absolutely. 

Paul: And it's that ability to control your physiology and to switch off the stress response. So, the way I get people to do it, Michelle, is I say, at work, ideally every half an hour, if you can do it. Worst case scenario, every hour. Get off your arse and move, right? We need to activate our genes. Again, get off your arse. Move. Ideally 30 seconds of vigorous exercise, drink some water, and then sit down and do 1 to 2 minutes of resonant frequency breathing. That is like taking your brain out and plugging it into the wall to get a recharge. And then I say, at the end of the day, just before you're going to sleep, turn all your devices off and just do 5 to 10 minutes of breath work. And that will prepare your brain for sleep. 

So, what most people don't realise is that a normal operating, we're around low beta. When we get stressed, we're in high beta waves. And when you're anxious, you're in super high beta waves. A lot of people, they've had stressful days. They're trying to go to sleep. They're still in high beta. And to get to sleep, you have to come out of beta. You have to go through alpha into theta. Well, that breath work and many other types of breath work puts your brain in alpha state after just a few minutes. So, it is the best way to segway into sleep is doing a few minutes of breath work before you get into bed. And it just calms the whole form right down and prepares your body for sleep. 

Michelle: The other thing about your book and your work and even through my reading over the last couple of years in terms of metabolic health and the function of the muscles, so you talk about the muscle system in a really specific and very different way and how the muscular system interacts with the nervous system, and with the metabolic system, and with the immune system. Can you take us through that, of your understanding of how the muscles, and the strength of the muscles, and the different functions of them support whole person health and health span? 

Paul: Yeah, this is I think the most important discovery in physiology in the last couple of decades is the identification of a whole host of myokines. Some people call them exokines, but basically they're a form of cytokine. So, a cytokine is a messenger molecule. I'm sure a lot of your listeners will be familiar. Particularly post-COVID, we're all familiar with cytokines, right? But these myokines are...they're messenger molecules that are produced in contracting muscle. And we identified the first one maybe 50 years ago. And I've known for years that myokines produced will have impacts inside the muscle. So, they'll help the muscle to use glucose and fat, and they'll also help the muscle to remodel, to grow bigger, faster, stronger. 

But what we now know is that these myokines get out of our muscles, and they get into the circulation. And some of them are carried on other molecules called exokines. It gets a bit confusing. But anyway, they basically affect every single organ and every organ system in your body. They improve the health of your immune system. They improve your whole gastrointestinal tract and even influence your microbiome. They help your liver to dispose of glucose. They help your pancreas to secrete insulin. They help you to remodel bone and muscle throughout your life. 

And then myokines actually get into the brain. And one of the myokines in the brain is BDNF, brain-derived neurotrophic factor, that protects your brain cells against damage and can even help you grow new brain cells, even in your 90s. Now, for me, the exciting thing about myokines is we've identified about 600. We only know what 60 of them do so far, and this is the new frontier. 

And this is why I say to people, every time you're contracting your muscles, it doesn't matter whether you're walking, running, lifting weights, dancing, gardening, doing housework. Anytime you're contracting your muscles, you are producing these magical myokines, and they're going through your body. Now, we know they're released in proportion to exercise intent or the contraction intensity of the muscle. And that's why stuff that induces a stronger contraction, such as running, sprinting or lifting weights actually produces more myokines. 

Now, here's one of the things, Michelle. This is like you start off in your 20s and 30s with a full dose of the world's best medicine with these myokines. And then you lose it over your decades. So, people tend to lose muscle at the rate of 3% to 8% per decade. And it is not unusual for somebody at the age of 75 to have lost 50% of their muscle mass. This is like you've had all the world's best medicine, and you're now down to a half dose. 

Michelle: I know because sarcopenia is such a big problem, such a big problem for falls but such a big problem for frailty, confidence, mental health, all of these other kinds of factors. But it must have implications on this myokine system, and you kind of have to ask the question about the connection between sarcopenia and things like cognitive decline and late age depression and all of these kind of other factors as well. 

So, this connection between our muscular health and our brain health really needs to be... I guess we need to really inform people of this because the basic physiology teaches so much about why we've got all of these chronic diseases, which people are really scared of because we've, kind of, been told that we're going to live to 80 or 90. So, we know quality of life goes down when we get chronic diseases for which many of us, by the age of 50, have at least 1. Fifty percent of us has at least one. The myokines is, is there good ones and bad ones? How does that work? 

Paul: Yeah, the myokines, they're generally all good. There's one bad one called myostatin, and that basically...we think that's there to stop you growing unregulated, right? So, because if you didn't have myostatin and you're doing lots of exercise, you just become bigger, and bigger, and bigger, and become absolutely massive. 

Michelle: Some people would like that though. 

Paul: Yeah, so there's a bit of a balance that needs to be played, and sometimes people, their myostatin is a bit too high and that's not a good thing, right? But all of these other myokines are beneficial, at least the ones that we have described so far are very, very beneficial. 

And so it is use it or lose it in terms of your muscle. People have heard that before, but I think it now plays into health, both physical and mental. And I often say to people... And I want to say this without any judgement, right? But if you do not currently engage in regular physical activity, at least some of which is vigorous, there's not a snowball's chance in hell that your brain is functioning optimally, there's not a snowball's chance in hell that your nervous system is functioning optimally, and there's not a snowball's chance in hell that your ecosystem is functioning optimally, because we are built to move. It is wired into our genome. 

Michelle: In terms of constitutional type, because there's some people...obviously, you know what I know about the elite athletes is that now the Institute of Exercise Science, whatever, are, kind of, looking at people that are much more kind of geared towards that elite athlete type. They recover well. They're naturally really good in that physical sort of domain. And obviously there's people that have got constitutional types that are less so. What do we know about that? And how do we support people that don't have that elite athlete, kind of, I guess, constitution? 

Paul: Yeah, look, for me, I say the elite is one thing, but here's the biggest thing. So, the American Medical Association produced a number of years ago this great paper that looked at the impact of cardiovascular fitness on your longevity. And it was absolutely monstrous, right? But the biggest impact on people's longevity went from being in the lowest 10% to 20% of fitness to going to below average. If you can get yourself from the lowest category to below average, you reduce your risk of death in the next 15 years by about 50%. 

Michelle: Wow. 

Paul: Now, you're a doctor, Michelle, do you know any medication that will do that? 

Michelle: Oh, no. I mean, I've always said, and I think you actually say this too, it's why I think we're kindreds, is if I could put exercise into a tablet, and it does 500-plus positive things for your body. It is the number one go-to. And if I could put it in a tablet and we could sell it, it's just phenomenal what exercise does for everything. It's a panacea essentially. 

Paul: It is a panacea, but the message needs to be, it has the biggest impact on the people who are doing nothing. 

Michelle: Yeah, absolutely. 

Paul: And it also has a dose response, which, again, you don't see in medicine in that if 10 minutes is good for you, 20 minutes is better. 30 minutes is better. We don't see that with pills. So, I think the message needs to be anything actually that you can do is a win and then just keep building and keep building and keep building, because you're just going to get more and more benefits. Now, some people, if they have injuries and things like that, they need to get creative and maybe they need to go and see an exercise physiologist who will help them deal with their injuries and still exercise. But there's very few people who cannot do anything, right? A lot of it is just because it's hard, and we've got to recognise that it's hard, but the benefits are just untold. 

Michelle: I mean, we're going to get into nutrition here, which is also part of your background. You have education in nutrition as well. It's such a confusing landscape for people, but you distil it. This is what I loved about your book. You distil it for your reader into three key points. What are they and why are they important? 

Paul: Yeah. So, look, the first one for me is to eat a low HI diet. And this is the most important one where HI stands for human interference, right? And here's how it works. It's basically you look at a piece of food and ask yourself, has it been alive recently and minimally interfered with by humans? And if the answer is yes, eat it. It's perfectly fine. 

But if you're looking at a piece of food and you're going, Mr. Krispy Kreme Doughnut, I don't remember seeing you running around on four legs. 

Michelle: Treat. 

Paul: Then, it's in your treat foods, right? So, I'm not saying don't eat it, but I use the 80/20 rule. And that's why my kids actually, they will self-monitor around the 80/20 rule. So, that's for me the most important rule. It doesn't matter whether you're carnivore, paleo, high fat, low carb, low fat, high carb, vegetarian, vegan, South Beach Diet, it's across the board. Has it been alive recently and minimally interfered with by humans? 

The second rule that I talk about is about feeding both your brains. And I know you know what I'm talking about here, Michelle, but for other people, this is about the enteric nervous system and the gut-brain axis. And we know that the health of your gut microbiome has a massive impact on your physical and your mental health. And it's been shown with animal studies that have now followed with human studies that you can manipulate the microbiome with faecal transplants. And you can either cause disease in a healthy animal by transplanting the microbiome of an unhealthy one or you can reverse disease as well. Now, you don't want to be going and sticking somebody else's poo up your jacksie. The best thing you can do is... 

Michelle: You really want to know... Yeah, really want to know what their health is like. 

Paul: That's right. And this is about feeding your good bugs. And what has become very clear from the research is that it is about eating a wide range of foods. And there's some people who eat a very healthy diet, but they eat the same thing week in, week out, and that's not good for you. It's certainly suboptimal. It's a wide range of foods. It's making sure you're having lots of resistant starch, that's a particular type of fibre. But what it turns out is really as important, if not more, is to have some fermented foods in your diet, because they basically fertilise the landscape, if you like. So, having fermented foods, a wide range of stuff with resistant starch, peas, beans, lentils, these sorts of things, and then also making sure you have a wide variety of foods and colours and stuff like that to give yourself good diversity, because that's pretty key. 

And then the third one I talk about is embracing nutritional hormesis. And we mentioned that earlier on a little bit about the certain compounds that you'll find in fruits and vegetables. So, having a wide range of those so you can benefit yourself from a cellular level, things like sulforaphane, resveratrol, curcumin. I mean, curcumin is just wonderful stuff. The stuff that some of the polyphenols and flavonoids in teas, ECG, EGC, EGCG, those sorts of things. There's a whole wide range of stuff that we get in these foods that are actually beneficial for us. 

And then one other way of doing a bit of nutritional hormesis is some intermittent fasting. And I always say it's really about your goals, right? So, your bigger challenge is a metabolic challenge. I'm a big fan of doing regular intermittent fasting, at least 12, 13 hours overnight, nil by mouth. You can extend that out to 16. You know, people can, under supervision, do three, four, five-day water fast every now and then. And some people have said to me before, "Oh, you shouldn't be not eating for four or five days."  

But those intermittent fast, particularly if you're over 40, 50 and can be really beneficial as a metabolic spring clean, but just be aware about regular fasting as you get into your 50s and 60s because it can eat into your muscle. So, there's a bit of a... People have to walk their own journey here and go, "What is my biggest challenge right now?" So, I'm not very metabolically healthy. I'm in my 50s. I've stopped doing intermittent fasting because it was eating into my muscle. So, I was getting regular DEXA scans. So, that's the only rider that I would put on it. 

Michelle: Yeah. And I think you're right. I mean, we can't really give health advice that crosses the lifespan and the health span. It needs to, kind of, change as per... It's like women in menopause. There's different, kind of, health advice for that particular time of their life just like there's different health advice for teenagers in that adolescent phase, just like toddlers. So, it's really important, as we get old, that we have that change in health advice and to be comfortable with that. 

I love... This is one of my favourite things about your book was this concept of harvesting discomfort. Harvesting like as if you're kind of watching it as it, kind of, evolves. What do you mean by this? And how can we get our patients to start using this concept of harvesting discomfort? 

Paul: So, you look at the literature in psychology, and they talk about discomfort tolerance and how it predicts anxiety and all sorts of things. But I'm like, God, we need to go beyond tolerating to embracing and harvesting. So, harvesting, you're reaping it. You're reaping the benefits of it. And so this is deliberate hormesis. So, from exercise, particularly vigorous, which we've talked about, but also from cold exposure and heat exposure. And it turns out there are ludicrous amounts of benefits that, when you do regular cold water exposure and also from heat exposure, such as saunas. 

But what they all have in common, the exercise, the cold, the heat, is stress response proteins that then switch on hundreds of protective genes. And so that cold exposure can be 30 seconds of a cold shower at the end of your normal shower. That's the way I recommend that people start. 

And then you might, if you're feeling brave enough, get into an ice bath once a week or twice a week for some people or some people just every now and then to give yourself that cold shock. Did you know, Michelle, when you get into an ice bath at 4 degrees for 30 seconds, you get a 3% to 500% dopamine and noradrenaline that persists for hours, right? 

Michelle: Awesome. I mean, that's what we need. I found, when I did ice bathing... So, we did it nearly every day through COVID down in the bay, and we do five minutes submerged up into our neck. And it was just incredible the impact of that. A, I found I could manage my weight better by changing nothing at all and also just my mental health. But I found I just loved it. I would drive past the beach, and I'd want to be in there. I'd want to be in the water. And I've, sort of, lost it a little bit now because, I mean, we've kind of gone back to a little bit of a faster-paced life, but that was just really interesting this...this pull towards a discomfort was really quite an interesting observation. 

Paul: And it's because you feel so much better when you're doing it. Every time I have a shower, if I have a shower, then I must finish on cold for 30 seconds. And it doesn't matter what time of year or if I've been in the bed and I come back and I'm shivering. I have to warm up at the shower, and then I finish the shower with the cold. It's just the rule. But the metabolic benefits and benefits for mood are incredible. And some of the research coming out of saunas about longevity benefits from saunas, and it's a combination of the heat shock proteins and the impact of gene expression but also, when you get into saunas, it's like very mild cardiovascular exercise. And I find you do the two together, you do contrast people cold, it's a great workout for your cardiovascular system. The only rider I would say is, if you have unstable angina or had a recent heart issue, that's not for you because, when you're in heat, all your blood vessels dilate, and then you get into the cold and they shut super quickly. And then you get back in the heat, and they open. And it's just great training for your system. 

Michelle: I know. We've got to train. I mean, just there's been so much in this podcast that's just absolute gold. There's so much we can do that is cheap, accessible, available to everyone that really imposes the importance of things like recovery, of hormesis, of the basics of nutrition, of going from a completely sedentary lifestyle to one that is even only suboptimal makes a huge difference. So, thank you so much, Paul. 

Paul: Absolute pleasure. 

Michelle: Thank you, everyone, for listening today. Don't forget that you can find all the show notes, transcripts, and other resources from today's episode on the fx Medicine website. I'm Dr Michelle Woolhouse, and thanks for joining us. We'll see you next time. 


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