Feeling stressed out? Your metabolism may be sharing the burden.
This episode, featuring returning favorite Dr. Molly Maloof, revolves around stress. An essential facet of human function, how we perceive and respond to the stressors in our lives is key for our well-being. It’s not all simply in your mind, and even if the source of a stress IS mental, there can be physical and metabolic downstream effects.
Intermittent fasting is an example of direct physical and metabolic stress. Yes, while we are huge advocates of fasting & its many benefits, it is important to understand this nuance. That teases out a question...should you still fast if you’re under heavy stress?
Speaking from personal experience, Dr. Maloof provides interesting insight into when it may be time to take a stress break from fasting. In addition, Geoff & Dr. Maloof chat about nutritional periodization to train your metabolism, continuous glucose monitoring and how to interpret different glucose spikes, and the importance of mitochondrial function.
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Molly, really good to have you back on the program. It's always fun to catch up.
Thanks. I'm so glad to be here.
Yeah, you're in our new studio now, and our first couple episodes that we spoke were some of our most popular episodes. Obviously you're a well-known thought leader in personalized medicine and intermittent fasting, and I know our last conversations, which really focused on intermittent fasting broadly but also specific for women, was a very helpful resource, so really excited to have you back on the program.
So, a lot of ways to jump in the conversation here, but perhaps it might be most interesting to get some updates on what you've been working on over the last year.
You started a new class at Stanford as a visiting lecturer. You've been working on some new concepts and ideas. I've also been following your personal Instagram and seeing all the experiments you've been doing with different protocols, so can we just get the update over the last year?
Oh my gosh, so much has changed. I can't remember the last time I was here, but it was definitely last year at some point. I was asked to speak at Stanford and become a lecturer there, and essentially design a course around whatever topic I wanted to talk about, which was broadly health span. The course was called "Living Better Longer, Extended Health Span for Longer Lifespan." It really was this sort of treatise on, everyone's trying to ask, "How do we get to 100?", "How do we get everybody healthier so that they live longer?" I think that the real answer is compressing morbidity to the very end of life. You look at the centenarians of the world, most of them do get some chronic disease but it's like the last three years of their life, so they're really healthy for longer. That is, to me, the strategy we all need to be focusing on, on how do we take our lives forward. How do we do that? A lot of it has to do with breaking down fitness, metabolism, stress, and relationships into its own components and even nature, and figuring out what are the biggest actionable steps that we can take to improve our health.
One of the things that I discovered in the research of the course was just how important relationships are. It's kind of an overlooked area, but it's really important that you maintain healthy relationships because it causes a lot of stress. That was kind of an interesting discovery that I got, but a large percentage of the course, I'd say a good 30% of it was all about metabolism, all about blood sugar management, all about the importance of fasting, how to implement fasting into your life without losing your mind, because a lot of people are still afraid of it. Then essentially, all the different things that we can do to monitor our health in real time, to enhance our health, different things like hormesis, optimizing our fitness regimens to optimize our metabolic flexibility. I did design an entire lecture on metabolic flexibility that I didn't actually end up giving because it was so complex that I was like, "This might be only for doctors right now and for people who are super nerds." I was afraid it was going to be over students' heads, but I think that metabolic flexibility is going to be a really important facet of metabolism that everyone's going to be talking about. So that was with the course, and I have one more lecture left next week. It's been so much fun teaching students and seeing how they've responded to all the content, but then I've also been working on a company.
Yeah, I've been trying to figure out for the last few years, "How do I take health optimization to the masses, and what's the most scalable product that can be brought to people?" I really have come to the conclusion that it's CGM. I started building out some decks, sort of co-founder dating, and randomly there was a point, and actually just talking to VCs that I'm friends with, and I got enough positive signals that this was the right move to take, but then my VC friends were like, "You've got to find a CTO and you've got to find someone to help you build your business model." So randomly, when that was my intention I was sending out, a few days later I literally got emails from these two guys in Chicago who are working on the exact same thing I was working on. They were working on a business model and working on a deck and working on this technology, and I was like, "Wow, you guys are"-
How did they find you? I mean that's pretty fortuitous.
It was really fortuitous. It was very much a weird synchronicity, but I think the fact that if you search name on the internet and you search for CGM or doctors who are interested in this, I'm pretty out there about how much I'm passionate about this, and then also the fact that I worked at Sano for the last year. Sano's still trying to pull their product together and they're still fundraising, but they did have to downsize dramatically, which opened an opportunity for me to think about, "Well, I want to keep doing, and I really, really am passionate about this," so I decided that maybe building a software company for CGM would be the right play because I thought really hard about how other companies have come to be, like 23andMe and Alumina, and how 23andMe was like one of the first consumer-facing genetics companies. I said, "You know, there's totally room to be the first consumer-facing CGM company."
Sano really could've been that, but I think the conclusion that Ashwin has come to and what a lot of people have come to-
The CEO of Sano.
CEO of Sano, is that Sano may have been better off just being a straight hardware play with an API for helping companies build upon it. I'm really thinking that that's the right strategy to take this company. The company that I'm working on is called NutriSense. We're kind of exiting stealth this summer, which is exciting, but yeah. I think the time to start a company is when you think that you may know something that can give you an advantage over everyone else, and I feel like I have a lot of experience and knowledge at this point where I've read more white papers on CGM than anyone I know. I listen to Peter Attia's podcast and I'm like, "This guy's arguably one of the experts in CGM, and I still feel like I can teach him things." So I feel really confident that I'm one of the few people who can do this.
I think when we got to know each other a couple years ago, I think we were in a very different social, cultural understanding of CGM, continuous glucose monitoring. I remember when we started implanting these things, it was very-
Cyborg-y, very fringe. We were using diabetic medical devices for human optimization or biohacking use cases, and now fast-forward two years, it's been a lot more in the public consumption and much more in public dialog now, so I think the timing is good. I'm curious; over the last couple years, as you've been personally studying, using CGMs, continuous glucose monitors, have you updated your thinking, or what are some of the most interesting insights as you've gotten much more experience on this?
Oh my gosh, my insights have changed a lot. First of all, I spent a large amount of time last year doing research; I spent like a whole year just dedicating myself to research to this, and so that time at Sano was epically valuable for my career in understanding of metabolic health. I hate to keep coming back to the same topic, but fasting was the big question mark I had in my book around, "Well how do we lower fasting glucose?" Fasting was like fundamentally the silver bullet answer to that. The research that I did kind of backed up my mental model of how the body works around metabolism, so fundamentally, we have this design in our genetics to be well-adapted to fasting, but we've lost it because of our culture, and because over the last hundred years, we've been selling people this idea that people need to eat breakfast and snack all day. Those weren't really part of the human diet until like the last hundred years, which people don't realize. People weren't eating that much. People were eating maybe twice a day. Eating snacks was just not a part of the culture.
So when human cultures develop western eating habits, they typically adopt snack foods, and where do snack foods come from, right? They come from packaged, processed, highly refined carbohydrates, and lots of vegetable oils, and lots of sugars. These are metabolic toxins, right? The food industry has been doing their best to sell people these things that they don't need in order to get them to spend their money on nonsense. The problem is the side effect of all this snacking and breakfast-eating, I think, and particularly breakfast eating that involves cereals and sugar and refined carbs, we have a really sick country. Essentially, fasting and intermittent fasting and time-restricted eating, what that's doing for people is it's tightening up that window, and it's doing this thing called "flipping the metabolic switch," which is moving someone from carbohydrate-dominant metabolism to fat metabolism. It's actually training your mitochondria to actually effectively burn fat more efficiently.
That has massive downstream effects because it's almost like our bodies want this, and yet we've forgotten this. What I love about CGM is you can literally quantify the time you have in carb metabolism. Now if you go keto, you're going to see your body flat line your glucose, right, but what's really interesting is is that there's a lot of people who are doing keto or doing low-carb but they're occasionally cheating with really high-carb foods. You can actually see the damaging effects of that.
You see a crazy spike.
You see spikes, right? I have a friend who's a cancer patient, and he eats a super high-carb vegan diet, but his blood sugar is like below 120 postprandial pretty much consistently. I was actually surprised to see how healthy his blood sugar looked despite the fact that he doesn't do intermittent fasting and he eats carbs all day long. There were maybe a few meals that were problematic that he had eaten out that were involving large amounts of potatoes and he had some ice cream that day, but as long as he eats his healthy vegan diet, like he was able to eat flour-based foods, which I cannot touch because if I eat flour, I get a blood sugar spike, but I'm also adapted to lower carb eating right now, right? What I've learned is that-
So when you say "spike," are you looking at 150 migs per deciliter?
Looking above 140 really. What I've learned is that my range, I feel best when my range is below 120, and I don't go above 120. That's my optimal range, and I also feel best when my fasting is around 80. This has taken me years to accomplish this, like a few years of learning how to tone my metabolism through different behavioral changes. For me personally, eliminating flour and sugar, like I am so much better off, but there are people who do fine with flour and sugar. It's amazing that different people have different metabolisms and different responses. So, CGM is this beautiful window into your health and into what's going on in your body. If I eat that same diet that my friend who's a vegan eats, I cannot do well on that. We all need to realize that there's going to be different strategies to get to optimal blood sugar, and you may have to try different protocols and different behavioral programs to get to that place, but what works for one person may be different for someone else. What I want to do is provide people with the tool that can help them understand what's going to work for them.
I think that that's something that I talk a lot about, which is that you and I have different starting points and we potentially have different goals of what we want to optimize for, whether you want to optimize for health span or if I'm trying to win an Olympic gold medal. For either weightlifting or marathons, there's just very, very different nutritional protocols and training protocols for that, but having a tool like a CGM where you can actually personalize and dial it in for yourself, that is, I think, really the future. I think that's what you're looking to work on.
Especially for performance as well, right? Anyone who's exercising regularly knows that they need different fuels for different things they want to achieve, and there is still this general carbohydrate dominant mantra of how people need to fuel athleticism, and I think that's true for performance; I think if you really need to go perform, eating some carbs is going to be really fast energy. It's going to give you this sort of power boost, but if you're training, what I've learned is that nutritional periodization can boost metabolic flexibility. You can do different training protocols where you might train keto one day, and that's literally like wearing a weighted vest, versus training with-
Or a fasted exercise.
Or a fasted exercise, right, which is also a very efficient way of burning fat because you're going to burn up your glycogen stores. It's taken me a few months to really get into the habit, but high intensity interval training, if I do it three days a week, I see my weight change really fast.
Yeah, let's talk about exercise, but I want to go back to the CGM and the fasted blood glucose a little bit because I think you're the right person to ask. I mean, I think folks that are listening probably are aware of fasted blood glucose insulin, but I think it's interesting to actually get into your number. You're trying to minimize spikes to be below 120, and you're trying to target a 80 milligram spike.
That's optimal, I think.
Yeah, so I'm curious. As you recommend it to your clients or your patients-
So when I first started, it was below 100 for fasting, below 140 for postprandial because above that is pre-diabetic, right? I was like, "Well as long as you're not pre-diabetic, you must be fine," but that's not the case actually. I started doing even more research into this and discovered that in fact, there is this idea of being pre-pre-diabetic where you're not pre-diabetic yet but you're also maybe partially insulin-resistant or metabolically inflexible meaning that, let's say you have a family history of diabetes. There's literally six different tests you can do, but fundamentally, going fasting to a carb stimulus, you'll see a person more likely raise their blood sugar to borderline pre-diabetic levels versus somebody who doesn't have that family history. You'll also see, I wish I had my presentation in front of me to go over this because it's pretty cutting-edge stuff, but essentially what you'll find is somebody who goes into fasting is not going to drop into fat metabolism as fast, so they're not going to fast as easily, which means that they're going to feel like their fuel supplies are low when they're trying to implement these behavioral changes.
So, what that is telling us is that they're metabolically inflexible, which means that they're not easily shifting back and forth. A really healthy body is able to take whatever fuel that it has available to it, generally speaking one fuel source being fat or carbs. Most of the time people basically taking whatever fuel source that they have available to them and efficiently starting to burn that fat or burn that carbohydrate. The problem comes in when people basically eat high-fat, high-carb foods together because that causes metabolic gridlock. That's kind of like a traffic jam in your mitochondria. It's like-
That's a standard western diet.
Standard western diet, so it's not surprising we're all getting really sick, right, but it's also not surprising that a person with a family history of diabetes also has metabolic inflexibility because A, they were probably born to that person, so they were born with maybe a person with gestational diabetes, or they were also raised at a very young age to have a diet that was not adaptive to health. So it's not all genetics; a lot of it is the nature and the nurture combines. I think that these individuals with a family history of diabetes are set up for failure with metabolic health because they are in that environment with that genetics.
So the question is is how do we start measuring and monitoring sooner so that we don't end up with pre-diabetes or diabetes? I'm just curious; I'm sort of banking on this idea that people want to know about their health before they're sick. To me, pre-diabetes is a sickness state, and pre-diabetes, you've already lost a good percentage of your beta cell function, you've already demonstrated that you're not successfully metabolizing carbohydrates. I just don't want you to get to that point, and there's a lot of benefits to just avoiding insulin resistance. Insulin resistance is a huge problem for people because it can have all these downstream negative effects like acne. People don't realize that hyperinsulinemia contributes to acne. Where do you get hyperinsulinemia? You get it largely, like insulin spikes, from too much refined carbs and too much refined sugar. If you just eliminate those things from your diet, you see your skin improve. I was just looking at this very famous model on Instagram, she's got like 800,000 followers. She's this sort of famous Australian model. She was complaining about how bad her skin was and showed a photo of how bad her skin was without makeup.
Whenever I see someone with acne and I look at what they eat, inevitably it's refined flour and sugar. It's like, getting better blood sugar has better effects beyond just avoiding disease. It's like, I want to look better, I want to feel sexier, I want to have better hormones, better performance in my athleticism. I want all these things that go beyond just being not sick. I want to live longer. I want to maintain organ reserve. I want to be able to not have wrinkles. My skin has gotten actually younger-looking since I fasted more. I've notice that when I'm not fasting as often, my skin is not as good. I want all of these cool things that come from better blood sugar, and I think CGM is a pathway to get there.
Yeah. I want to touch on a couple points. You mentioned hormone health, and I think a lot of the conversations we've had with low carb advocates that touch around female health, mention PCOS. I know you have some ideas and concepts around PCOS-
Not to go too far away from here. I think the interesting thing you brought up is that you're really pushing this notion that pre-diabetes is already a sickness state, that even pre-diabetes is bad. You're trying to address the pre-pre-diabetes, which is kind of this cutting edge here. Your definition of that is trying to target 80 as opposed to 100 for fasting glucose and you try to keep your postprandial 120, or the rule of thumb is 140.
Say that, okay: you have a big carb-y meal. You spike above 140 or 160; it's like 200, but it comes down quite nicely after in a couple hours. What is really going on in that extra 50 milligrams deciliter for that one hour where it's really, really high?
Well what people don't realize is that when you have that level of blood sugar in your body, it's taxing your mitochondria, and your mitochondria are like, "Oh crap, I got to burn this." Mitochondria produce oxidative stress, and you get this burst of oxidative stress, which is essentially like exhaust fumes in your cells. Those exhaust fumes are getting into your blood stream and they're damaging your blood vessels. Basically your entire blood stream is your blood vessels. Damaged blood vessels sets you up for heart disease, sets you up for damaging blood vessels in your brain, contributing to things like vascular dementia, and damaging blood vessels in your kidney. The idea is that you don't want to damage your blood vessels while you're young. We know that diabetes damages blood vessels, but we also know that these oxidative stress bursts are damaging. If you want to avoid these chronic diseases, you got to make sure you don't do that to your body.
Basically, all the research is suggesting is that those postprandial spikes are significantly damaging to blood vessel health, and that's part of the reason why we want to keep people with lower blood sugar. We also want to have lower insulin levels because you have this beautiful organ called your pancreas, but it can only be tapped so much before it stops working. Every time you have hyperinsulinemia, which means you have to push out extra insulin to lower your blood sugar to maintain your health, it's like you're taxing your body's systems. You're taxing that pancreas and you're giving it more work that it needs to do, which means it's going to wear out sooner. I mean, a large percentage of diabetes is just age related. It just comes from being old. If you don't want to ruin your pancreas and have diabetes at 70, you have to keep it younger for longer, and the way to do that is to not give it the stimulus, give it the stimuli that cause it to wear out.
Yeah, I think that's a good practical tip in the sense that when you're drinking that soda or that OJ that's just 50, 60, 70 grams of sugar and you see that spike, yes, if you're young and healthy, you'll recover pretty quickly postprandially, but that spike and that extra 50 milligrams deciliter of sugar is actually damaging your vascular tissue, right? That leads down the line to atherosclerosis and all of that.
Exactly, exactly, and acne, right? Hyperinsulinemic states contribute to hormonal dysfunction and they contribute literally to acne formation. There's great research on this that's come out, and yet it hasn't made it to the mainstream yet, but what's a great stimulus for insulin as well is dairy. Dairy products are fabulous for growth if you want to build muscle and you want to drink a bunch of whey, but if you're not using the fuel in your body, all that insulin and all that sugar is still causing inflammation in your body as well, and that's contributing to poor skin health.
Yeah, so there's a bunch of different reasons, but getting back to the hormone topic, there's really sort of two states that women need to think about when they're thinking about fertility, and one is do they have enough hormones or do they have too many hormones? It's really a very simply way of describing it, but there are women that are sort of overweight or maybe not overweight but have hormonal dysfunction through polycystic ovarian disorder, and that's typically a hyperinsulinemic state. That's a high insulin state. For those women, they really want to lower their blood sugar. They really want to lower their insulin output. They really want to lower their dairy consumption and lower sugar consumption. These are women that I would not recommend Greek yogurt to; these are women that I would recommend very much more plant-based nutrition, lower carb. I mean, I'm not anti-meat or anti-fish, but I would definitely want them to be eating enough fiber to bind up those hormones, but really lowering their insulin output is key.
On the other hand, there's women who maybe are the kind of infertility where they're just underweight, where they actually need to put on a little bit of body fat or they actually maybe need to instigate some growth where actually dairy products are great. High-fat dairy products are actually great for them because maybe they have lower hormone levels because they've actually pushed their body fat levels too low. Those are the women that actually need to stimulate growth and need to eat more-
They shouldn't be fasting.
And need to gain weight, and shouldn't be fasting as much. So it's about a balance, and it's about asking, "What are the signals that you're sending your body?" In those women, if their body fat is too low, that means, "I'm going to prioritize survival over reproduction." If you want to send the survival signals, you need to send the signals that there's food availability in your environment. You want to send the signals that you need to eat more, and those are women that actually eat more calories and gain some weight.
No, I think that's well-said, especially in terms of the conversation around intermittent fasting. I think especially as it's geared towards women, there's always the question, I'm sure you've heard this question, I've heard this question many times: "Is fasting for everyone if you're underweight?" If you have previous histories of eating disorders, that might not necessarily be for you. It sounds like what you're saying here is, again, if you start from an underweight position and you're looking to improve your hormone profile, fasting is not necessarily for you at that time.
Right, yeah. Well he's a really good example I got from someone on Instagram today who messaged me. She was like, "I've tried intermittent fasting but I just can't do it because I'm just ravenously hungry." I was like, "Well tell me about your stress levels." She goes, "Oh, I'm pretty much always on edge all the time. I have a super high-stress job. I take Vyvanse, and I drink four cups of coffee a day." I was like, "Well ..." What people don't realize about stimulants is that Vyvanse is synthetic stress. You are literally sending out more epinephrine and norepinephrine in your body when you take an amphetamine. You're doubling your stress levels through that, and then you're actually just taxing your body more when drinking four cups of coffee, so you're in a super fight or flight state constantly. That is a signal to your body that you are unsafe, that there is danger in your environment. You body does not know where it comes from. All it knows is that it's getting these signals. Your cells are dumb; they're actually like, "I don't know where it's coming from but I feel like there's a danger sign."
Funny thing about our bodies is that we don't realize where our stress comes from. Yes, of course a high-stress job is one thing, but there are millions of people on stimulants. There are millions of people that are abusing coffee. I mean, I drink about two to three cups a day. I know when I'm drinking too much coffee because I know that it's a coping mechanism, right? People who are running out of steam are using coffee to replace their energy levels. I've been working, arguably this is not healthy, six days a week, maybe 12-hour days since January, so I am fully aware that this is not a lifestyle that I need to sustain, but I also took on an extra job as a teacher and I'm a perfectionist, so I was working very hard to make these lectures literally perfect. Do I think that this healthy for me long-term? Absolutely not, but I'm going to take some time off in June and July and actually recalibrate, and then start fundraising.
So, I've learned a lot in that process. I'm going to tell you a story about my own personal experience. I started fasting while I was under a little bit less stress in February and March, and I was doing three 36-hour fasts a week. I lost 10 pounds, and I've actually kept most of it off. Actually, no; I lost like 13 pounds and then I've kept about 10 of it off back and forth, depending on the week. Generally speaking, those months were like, I was sort of heads down in work and I didn't have nearly as much stress as I did when I started teaching and started actually adding that new job. What I found is that during those two months, I felt very resilient. I felt very much in control of my eating habits. I didn't feel like I was over-consuming when I was re-feeding. I felt really good, my skin looked incredible, and I really felt like I had mastered the 36-hour fast. I didn't feel like it was actually a problem, but then, basically I came back from Japan and there was a bunch of stuff that was going on in my life and a bunch of change started happening over the course of a month.
Then, I consider your allostatic burden, which is basically your stress cup. It's like the cup that you can fill with stressors. I started filling it with new stressors, which was like new patients wanting to come to see me, starting to teach, having a breakup, having a business breakup, and then before I knew it, my stress load was overflowing and I could not do a 36-hour fast without losing my mind. I was like, "Wow. This is literally a signal. My body's asking me to reduce my stress levels." So I started cutting back on the weightlifting, I started cutting back on the fasting. I started doing regular meal-timing, and I started taking some adaptogens, and I started really listening to my body, realizing like, you cannot absolutely do every stressor that you want." I did add back in cardio and I started doing just low/moderate intensity cardio, and then I just started doing intermittent fasting instead of extended fasting. I would do like a couple intermittent fasts a week, because that was all my body could actually handle-
Like a 16/8 type thing?
Yeah, and I could only do that a few days a week. It was like, my body was literally sending me the signal that like, "You need to tell me that I'm safe or you're not going to be able to handle the stress." It was a really good learning experience for me because I think a lot of people who are hyper-ambitious Type As want to say, "I can do all these things. I can do keto, I can do low carb, I can do fasting, I can do weightlifting," and then you see these people burn out. I didn't want to burn out, so what I said is like, "Okay, what would be the right lifestyle for me right now to handle the stress burden that I've got?", and a lot of it was just changing the dose of things. Not completely eliminating weightlifting but doing it maybe less often, doing a little bit more yoga, doing a few high intensity interval trainings per week, but only 20 minutes at a time. Nothing too crazy. For me, I can't do a crossfit-type workout during that level of stress.
For me, it was like, I haven't gotten sick yet, knock on wood. I've actually felt like I've been able to bounce back from the high stress period time I had, and I've gained a few pounds, but then they come off. So it's like, weight to me is basically your body's defense mechanism for stress. People gaining weight, it's typically related to their bodies being like, "I need to protect myself. I need to make sure that I have fuel if there is a famine." It's a very logical response to your body's wanting to always protect you in a time of stress. So what I've really learned about health is that your body's always trying to take care of you, and the question is, are you listening to the signals it's sending you and are you actually responding to it effectively?
Yeah, I've just been nodding along for the last couple minutes as you've been explaining, I think, really clearly some of these concepts, which is that stress, in terms of how your cells process it, they don't know if it's a saber-toothed tiger chasing you or if it's a job stress. Obviously if you stack more and more of these things and you're trying to do keto, long fasts, heavy exercise, I mean you're overloading your system. I think that's where you have to understand the nuance of how to apply these things.
And also understanding your baseline-
Because some people, like you've probably noticed this: when you start to exercise more, you honestly have a larger container of stress that you can hold because you have more capacity. Where does that capacity come from? It comes from more capacitors. Where do capacitors come from? Literally your mitochondria are capacitors. They create membrane potential. They store charge. The more mitochondria you have, the more batteries you have to fuel your life. The thing that I've been really trying to figure out is what do you do to generate mitochondrial biogenesis? It really comes down to the right kind off exercise, avoiding allostatic overload, avoiding the stressors that are literally damaging your mitochondria, which is largely our psychological stress. Dealing with your stress, right, like figuring out how to not just reduce it but also, how do you bounce back from it? How do you build your mental fortitude around it? How do basically exercise your mind so that you can reframe shitty situations that could really cause you to fall apart, and instead, you've changed the frame around it? You've cognitively reappraised the situations in your life that are challenging for you and you turn it into a positive. Then also, how do you use your metabolism to generate this metabolic flexibility, which theoretically does generate more mitochondrial biogenesis?
So, we hinted at exercise earlier, and oftentimes on the program, we have Ironman world champions or Olympic athletes talking about their physical training, but I imagine for most of our listeners, and myself included, I'm not going to be a world champion athlete but I do care about exercise to max my health span. How do I maximize my longevity in this health biomarker? So, curious to hear about your journey and your understanding and your learnings around ho to best supply exercise. You talked a little bit about high intensity interval training, weightlifting, cardio. How do you structure this, and then from a high performance perspective, a lot of athletes talk about nutritional periodization? Can we take some of those concepts and apply that to everyday intellectual worker lifestyles?
Yeah. Well I think the first thing is to recognize that I, in fact, mostly work with knowledge workers, so I'm definitely not like a physician who works with sports teams yet, but eventually probably will when the CGM company comes along. The one scientist I would turn to, if anyone here is listening, who's like a coach or trainer wants to really dig into is Louise Burke. She's this phenomenal woman who's basically written everything on the topic, and I need to reach out to her and basically get her to advise my company because she's like the guru of this entire topic.
Yeah, Australian researcher. She's great.
Yeah, exactly. I kept on looking into using keto in training and using low-carb nutrition in fitness, and the conclusion that I kept on coming back to was that there are people who can succeed with low-carb diets and there are people who do well with it, but it does seem like with exercise that requires high intensities, you do need a certain amount of glycogen around to really perform. Like Olympic weightlifting, like sprinting, for example, I wouldn't guess that these people are going to do that well in their performance on race day or on competition day. I doubt that they're really going to really effectively do their very best work on a completely glycogen-depleted state. I just can't imagine that's going to work that way. Arguably, people who have super high intensity regimens like rowers, it would be challenging for me to imagine that on their race day, that they're going to well with no glycogen around.
On the other hand, people who are doing these ultra marathons or these marathons, there are people that are succeeding and doing well on keto nutrition, but they are highly fat adapted and they are highly adapted to training in that environment. There's also the argument that maybe carbs around that day would still give them like an extra power boost, but I think the real magic in this nutritional periodization really seems to be happening around taking people who seem to be metabolically inflexible athletes, like these cyclists that are carb-loaded constantly and are on carbs all the time every day, never flipping the metabolic switch, you look at them and you find they've got some visceral fat. You find that they don't have good blood sugar metabolism, and you take them you shift them into ketosis, and you shift them into fasting and you burn off that visceral fat. Now you're really improving someone's health because you're lowering their fasting glucose and you're actually training their mitochondria to better metabolize fat more effectively so that they're less likely to bonk during a performance or during a training session.
One of my friends had done no training for this triathlon that she went and decided to just randomly do, but the one thing she had been doing over the course of a month was I got her into CGM and fasting. I said, "I want you to start fasting regularly to see you can improve your health, and I want you to cut out all refined carbs, so no flour and no sugar." She literally just did this for a month, but she was kind of burned out from her company shutting down. She ran a startup for a year and she was a mom, and there was a lot going on in her life. I was like, "Look, I don't know if you should really go off and do a bunch of competition right now," but she's like, "No, no. I'm going to go do this triathlon." I was like, "Okay, fine. I can't promise you're going to do well, but see how you do." She went and she did it. She finished it and did great, but the funny thing is is that one of her friends that she did it with who had been training on carbs for months actually bonked in the triathlon because she ran out of fuel and she had nothing left.
This is a great example of someone who's metabolically inflexible.
Yeah. She was so inflexible, she couldn't fat adapt-
She couldn't fat adapt.
Instantly on race day.
Exactly. So here is my friend who got rapidly fat adapted over the course of a month to somebody who's been training on carbs, and I was like, this is a perfect example of where athletes can really maximize their ability to perform because if you are carb-adapted and you're never burning fat, you're going to be on race day and unless you've got your goos and your gels, which by the way, I met one of the doctors at a party recently who literally was the scientist behind the gels and the goos. He's like, "But we've shown that we can improve performance." I was like, "Look, anybody can show in a scientific study that giving someone carbs is going to make them run faster, but you're not improving health." There's a big difference between improving health and improving performance. There's plenty of performance-enhancing tools in the world that are terrible for health.
I mean, if you do cocaine before a race, I'm sure they'll help your performance, right?
Yeah, exactly. I think the real future of athleticism and health is how do we keep athletes performing well and living long? Because a lot of athletes do have side effects of their lifestyles. There is actually this J-shaped curve in athleticism where super high intensity exercise seven days a week over the years is going to shorten your lifespan. I have a lot of friends who are professional athletes, and I want them to live longer and feel healthier, and not get sick, and not get disease. I think it's paramount that we figure out this nutrition piece to athleticism and performance so that we can keep people not only really performing well but having really healthy lives.
Yeah, I think that's definitely a mind shift sense that I have with my conversations with elite athletes where if you talk to a lot of athletes, they'll be like, "Yeah, I don't care about living five years longer. I just want to win a gold medal."
Yeah, that's true. That's true.
So there's definitely that mindset in that level of population, but I think the mindset is turning as athletes' careers are getting longer. Yeah, you could peak for one year and get that gold medal for that one year, but you're not going to be able to continue performing over a career of three, four, ten years. I think it's, how do you find that balance? I think at some level, there is this orthogonality between longevity and performance, because as you're saying, if you exercise too, too much, you're going to be breaking down your body. It's hard when your goal is to be an Olympian versus your goal is to live to a hundred. Sometimes it counteracts, right?
Well this is where the intersection between HRV and CGM is really powerful, because I definitely noticed on days where I was the most stressed, and I've noticed this in patients, I've noticed this in clients, I can see that somebody who is under-stressed has higher glycemic variability. You can see it in the curve. Part of it's because they're eating more often throughout the day. You see people sort of scavenge food; you're like, "I need to find food," and so people are snacking and eating throughout a day when they're more stressed out because food is like the most easy thing you can reach towards when you're stressed. That's one thing. Then the other thing is, one of the things that got me off of fasting when when I was the most stressed out was that I was noticing my blood sugar rising as I was fasting. Right? You should see it drop, but it wasn't dropping; it was only going up. The reason why-
So your body's releasing more cortisol-
More cortisol. I now have like a censor within my brain of "this is what high cortisol feels like," but the cool thing is is that I've developed that sort of internal interoception, this concept of feeling the inside of your body, feeling the senses of your inside self versus exterception, which is like sight, vision, touch. It's like, "No, I can literally feel what blood sugar of 70 feels like." I can feel what a blood sugar of 140 feels like, and I also-
And you're confirming this with data-
I have confirmed it.
So it's not just like you going crazy.
I've done enough feedback cycles.
You've developed your subjective feeling to numbers, yeah.
Yeah, I've now developed these senses. By the way, like when we were in the savanna and we were foraging food, we knew when our body was low blood sugar because we were going to go out and find food, but that was a heightened state of focus. This is one of the beauties of fasting, which no one ever talks about: you're getting free catecholamines. You don't need Adderall. I think a lot of people are taking Adderall for that boost of catecholamines, which you can get naturally through fasting. When I was doing fasting and I was doing research, it was in Japan and I was spending a lot of time in research, I found that the days when I was fasting were the days where I had the best focus. The days when I was eating, it was like, you really start feeling the feeling of "I can feel the blood flow going to my gut," "I can feel my body start to digest," "I can feel my brain literally reduce its capacity to think." You develop these really in-touch sensations, and I really hope that this is potentially humanity's future and that CGM is just a stepping stone to getting people to the point where they actually can develop this knowledge on their own.
The thing that I love about CGM and I love about fasting is when you get off of it, you can fall off the wagon a little bit, but then you start feeling like, for example, I ate some pie a few days ago that had no sugar in it, but it was flour. I fell asleep right after. I was like, "Oh, I know that that spiked my blood sugar." I know because I got so tired afterwards, and that's just not me. I'm never this tired after eating anymore, and being tired after meals is a really good signal that you've got some insulin resistance, or you've got some immune reaction to the food you're eating.
I hope that humanity can develop this understanding of their bodies, and then if they need to use technology to get back on the wagon, get back on their programs, great, but then eventually, if people don't need it, great as well.
Sounds like you've developed a lot of self-awareness and self-reflection. You mentioned something about mindset as part of overall experience and overall health span, and this might be a good transition into that topic. When I did a seven-day water fast, I think I had a lot of similar experiences as you described where you just really understand how you feel. You really understand the difference between bored hungry or stress hungry versus actual nutritional hunger.
Yeah. There's a lot of different hungers.
I actually went over this in my class, about how there's like true hunger, which is like, "I legitimately have low blood sugar below 85," and then there's all these hungers of hormonal hungers; there's the hunger of insulin spikes and drops that when your insulin spikes and it drops, then you actually get hungrier. That's versus like ghrelin, which ghrelin naturally peaks about three times a day. There's the ghrelin hunger that's circadian programmed, and then there's the cortisol hunger, which is like, "I need food because I need to be safe," and then there's the leptin-resistance hunger, which is, "I literally am never full because I have leptin resistance and I'm not getting the signals that I should be getting that are satiety signals. The byproduct of that is that I'm just hungry all the time." There's also the emotional hungers, right? The hunger of feeling lonely, there's the hunger of feeling sad. There's the hunger of feeling like, the funny thing about this woman whose pie that I eat, her pies are called "revenge pie." It's like the hunger of being pissed off and angry and just wanting to eat something. There's all these hungers that are associated with emotions, and yet we're always turning to food as our answer. What I've learned through managing stress and mastering stress is there's a bunch of different things that you can do to master your mindset and your stress that aren't related to food. Things like running, for example. Stress would've been typically a danger signal, and running away from something is actually a great way-
To modify your stress response.
So essentially channeling a psychological stress into a physical stress, and you kind of run it out.
So I think exercise is a great antidote for stress, as long as it's healthy and it's not becoming like exercise bulimia. Getting back to hunger, there's also the hunger that comes from your environment, right? Just smelling food and seeing food can instigate the hunger response. There's these gustatory pathways, the olfactory pathways. Just tasting something in your mouth can make you hungry. Then there's the social hunger, right? "I'm sitting in a group of people and everyone els is eating. I'm going to eat." That's the hardest thing to deal with with fasting, is the social interaction. Then there's the hunger of sitting with your parents and they're expecting you to finish your meal, right? You're literally home visiting family and like, "Why aren't you eating?" Stuff like that. There's all these different socially acceptably ways of eating that are cultural and are part of our daily lives that really, we may think were hungry because we're in these environments, but we're not actually hungry.
Yeah, so what's the antidote here? Is it just updating culture? Education? Making it okay to fast?
People need to get over the idea that just because one person is eating means everyone has to eat. That would make fasting much more socially acceptable. That is a hard challenge. It is really, really awkward to go to a dinner with someone and not eat and have them eat because if they're not cool about it, they can feel really awkward. A lot of people sort of feel like "if you're doing something different, then maybe I should be doing what you're doing right now, and now I feel guilty for doing what I'm doing." I basically, like a few years ago, discovered that there was an antidote to social anxiety. There was a switch I flipped in my brain which was like, "I don't have to feel awkward at all anymore, anytime. Everyone else can feel awkward, but I just don't have to feel that way."
It was like, "Oh wow, I can be in weird situations and everyone else can be socially awkward, but I don't care anymore to feel that way." It's funny because it's like, I don't even notice other people's awkwardness really that much; I just kind of feel like so much of social awkwardness just comes from people feeling like they have to behave a certain way because everyone else behaves a certain way, but when you become your own boss and you carve your own path, and you've basically been doing things differently than everyone else for so many years, you basically have to get really comfortable with having weird conversations with people. That's basically been the last eight years of my life, is like, "How are you a doctor that does what you do?", and, "Why do you it the way you do it?", and, "How do you do it?" I'm just like, "You just get used to it."
Do you think it's like an exercise that you just have flexed so much? "I just don't even care about social awkwardness anymore?"
Yeah. I actually had a boyfriend a few years ago who really taught me mental mastery skills, and one of the skills he taught me was that anything in your brain that you feel negative, you can literally reframe by just practice. He had this notebook that I adopted, which is my list of to-dos that you do every day, and in that list, there's my work list, checking my email twice a day, which is a great hack of avoiding anxiety. Just don't check your email more than twice a day. There's the things that I do for nutrition, the things that I track for fitness, the things that I track for relationships, the things that I track for motivation, the things that I track for mindfulness, and the things that I track for visioning and creative visualization, stuff like that. It changes every quarter for me, depending on what I'm feeling like I'm working on, but it's kind of like exercise of your mind.
When I reframe something negatively, this is in psychological literature; I discovered it's called "cognitive reappraisal." I learned about this actually through reading about love and reading about how to, I could literally do a whole podcast on love because this is a fascinating topic, but when you're in love with someone and you want to maintain your love feelings for that person, you can literally just focus on the positive of that person and idealize them and ignore the negative. If you do that, you're literally going to up-regulate your love feelings for that person-
But the downside is that if you're breaking up with someone and you want to not think about them anymore or you want to get over your breakup faster, you have to basically constantly flip the switch of, instead of focusing on the great things about the relationship, you have to focus on all the things and all the reasons why you're to supposed to be with them. If you do that, it makes the breakup so much easier because focusing on the positive makes you love them more. Focusing on the negative makes you love them less. It's like, you can literally change your relationship to reality by just focusing your attention on positive or negative facets of reality that you want for yourself. For fasting, focusing on the fact that you focus better, focusing on the fact that you are mastering your mind, focusing on willpower. For me, it's wanting to avoid chronic disease, wanting to be the example for all my patients, wanting to not get Alzheimer's, not get cancer. I have a lot of different reasons why I focus on implementing things that are difficult into my life as daily practices and making them positive.
Yeah. It sounds like as you get more in tune with how your brain works, I mean that sounds like a very good practical tip.
It's really just programming.
Like if you want to gauge your reality, a lot of it is how you perceive things, and if you focus that attention on certain aspects of reality, you really create that reality around you.
Well exactly. I have friends who struggle with depression, and I notice when I'm talking to them that, like I had a conversation with a friend and I was like, "Have you noticed that almost every answer that you've made to any suggestion that I've given you has been a negative response?" He's like, "Okay, fair comment." I was just like, "Have you noticed that whenever you talk about your kids, you focus on the stress that they cause you and not on the joy that they bring you?" Sometimes you have to remind people that they're spiraling, right? Like people tend to spiral when they're under chronic stress, and the key is that you've got reign in your brain and you've got to realize that we have natural inclinations to go down these pathways of negative self-thought and negative patterning. If we don't actually notice our thoughts and notice the ways that our mind is working in real time, then we can end up with chronic stress bubbling over that stress cup, and then you have an infection, and then you end up with a serious health breakdown.
I've noticed this in a lot of patients lately because I've gotten some chronic fatigue patients coming to me. Their story is always the same: it's that they had a lot of stress in a high-stress job and a high-stress life. They weren't taking great care of themselves, and then they got hit with a really bad infection. Then for some reason, they just completely crumbled after that, or they got hit with an infection and a divorce. It's almost like their body's immune system was set up for failure because of that chronic stressor, and then a lot of these infections that people get that cause chronic fatigue are known to effect the mitochondria, which I just discovered. Spirochetes, for example, Lyme encephalitis are known to affect mitochondria and produce anti-mitochondrial antibodies, and a bunch of other viral infections can produce anti-mitochondrial antibodies. Then there's also just a bunch of research coming out around viral infections in the mitochondrial functions themselves. I think that there's a really big area of research that needs to be dug into more relating to this idea of energy fatigue and mitochondrial function. I actually feel like I'm opening up a Pandora's box of like, "Holy crap. There's literally unending things that I could do research on right now," and the question is, is this time?
I think you unpacked a good conversation around just traditional healthcare practices because I think you talk to a standard doctor and they're trying to do their job the best they can, but they're very focused on the physical aspect of health, like just the physical symptoms and the pharmaceutical that will treat that exact physical symptom, but I think what you're addressing is that there's oftentimes a mental psychological, almost the executive coaching side of health-
And how do you intertwine the mental psychology side with the physical physiological side of things? I think that seems to be the direction that the world needs to go in because there's so much psychological stress that our population is facing every single day, and it sounds like a lot of your clients are successful on the outside but just taking a lot of mental stress and it's breaking down their body.
Yeah. There's a researcher at Columbia, Dr. [Card 00:54:58]. He is just the guru, and the man has basically shown the connection between psychological stress and mitochondrial health. It wasn't until I started reading his research where I feel like everything crystallized for me. When I realized that our thoughts and our stress levels are physically damaging on a molecular level, like chronic stress, chronic hypercortisolemia, chronic activation of the catecholamine system without adequate recovery is actually going to damage your mitochondria directly, and then downstream from that are the markers of chronic disease. Also downstream of that, theoretically, are the markers of aging. There's this idea that there's these nine hallmarks of aging, but a lot of the people in the mitochondrial camp, the mitochondrial theory of aging, believe that all of those are downstream, and that fundamentally, you need enough power and enough energy to maintain the integrity of your structure, and that the physical self will break down when the energy deficiency begins, and that typically happens around midlife when people start losing that much capacity.
So, this changed my entire world view, when I started doing this research, reading this research. I was like, "Okay, so here's literally this clear pathway of how overeating, inactivity, chronic stress contribute to damage mitochondria, contributing to the markers of aging, contributing to the markers of chronic disease." So when that switch flipped, I was like, "Okay. Maybe all the emphasis really does need to be on lifestyle, and the real emphasis has got to be on using these drivers to optimize health and mitochondrial health rather than just focusing on giving people drugs to prop themselves up."
Right. It's almost too late.
It's too late, because your building's already broken down. It's like, you can only renovate a building so many times, right? There's going to be a point where Venice is underwater and they're not going to be able to save those buildings potentially. I mean they're going to keep trying, but largely this is an ancient city that people are trying to prop up with modern technology, and that to me is basically modern health. It's like giving people drugs for cholesterol and for diabetes is like taking a weeble-wobble and it's literally broken and it's fallen over, and it's trying to prop it up. Really what we're supposed to be doing when we're young is bouncing back and bouncing back, but we're not doing that anymore. We've lost that weight that's keeping us centered, and now we're falling over. We're using these primitive tools to prop ourselves up, and it looks like we're healthier, but we're not really healthier. The really, really screwed up thing that drives me fricking insane is statins increase risk of diabetes. High blood sugar damages blood vessels. Cholesterol has to go in and repair damaged blood vessels. I actually think we've gotten the entire theory on heart disease wrong, and I think that there's a lot of researchers that are basically saying, "Look, cholesterol's protective for a reason." The question is, what is it trying to protect you from? What is it trying to fix? Why is it there? Is it actually dangerous?" Peter Attia always says that it's necessary but not sufficient for causing heart disease. The real thing that I think we need to think about is, what's causing inflammation of blood vessels? Where's lipopolysaccharide coming from? Is it coming from oral health being disordered? Is it from your gut being disordered?
Basically, when you get integrity breakdown of these barriers, you let the body let in things that shouldn't be let into the bloodstream, and then the body literally has to come and respond to that through activating the inflammatory response, through activating these responses to these problems that are actually root causes of disease rather than the modern medical system just saying like, "The disease itself is hypercholesterolemia," "The disease itself is diabetes." These are not diseases; these are organisms failing to adapt to the world that people are living in, and these systems that are set up in your body to protect you failing. That is chronic disease, and I'm so passionate about this because it just feels like the modern healthcare system, by design, it's the best we've got so far but it's not good enough, and it's not good enough to bring people into better health long-term. It's not good enough to save the millions of people that are trying to avoid chronic diseases from shortening their health span.
Right. I think doctors like yourself and conversations like this hopefully educate people, and hopefully more and more services that get people to shift their mindset. One of the things I always like to ask with folks that have a medical or technical background is what kind of study or what kind of technology to see exist? Obviously you're working on a CGM-based company, and as I listen to some of your thoughts around CGM, one of the core markers that glucose really is a downstream effect of is insulin. I wonder if there's a continuous insulin monitor that could be created or something. So, curious to hear your thoughts on, perhaps, the direction of how you think about taking your company or technology that you wish to see exists, whether that's a continuous insulin monitor, a better CGM-
I want a continuous ketone monitor, because if you had ketones and blood sugar at the same time, then you'd be able to literally see what your fuel supply is in real time, what you available to you. Generally speaking, the fuel available to you is your body fat, and then ideally you don't want to tap into your protein stores, but it's also your glycogen, your body fat, and your protein. So generally speaking, your glycogen stores last about a day, shorter if you exercise, which is the benefit of exercise, is you're burning off that glycogen quicker, but when we start to track your metabolism in real time, when you see your ketones available and when you see your blood sugar drop but your ketones are rising, you don't have to freak out because you know that you've got enough fuel. When you measure your blood sugar and your ketones and you see that they both go down or that they're both low, then you know that it's totally logical for you to feel really stressed out and freaked out.
This is where the magic happens when you start to learn to fast, because when you start seeing your ketones rise, you're like, "I've got this. I've got this available to me." Let's see, what else would I like? I really like the ketones and the blood sugar together, and then I think insulin would be awesome for sure, and cortisol would be really great. Real-time insulin and cortisol monitors, because insulin is basically the growth signaling, right, and if I could get real-time brain frequencies, that could be cool because I'm starting to think that for-
Like beyond just an EEG, or-
Kind of like EEG but like the theta state, alpha state, beta state. I listen to different theta and delta recordings when I want to drop my brain into different focus zones, and I kind of feel like for what HRV does for the stress response, these brain frequencies can do for your brain's response to stress or your brain's response to the environment around you. That would be cool. I definitely would like to marry CGM with movement and with HRV together, with that all being in one device. That would be optimal for me, and I may do it someday. It's possible that-
Yeah, hopefully you make it.
Yeah. I mean, some of these hardware companies, their patents are going to run out in the next few years, so open door to start making these things, but honestly hardware's so hard that I'd have to have a lot of money to build a hardware company. It's really hard to do, and it's just a pain in the ass. What else would I want? I mean, I really want to be able to prescribe food to people as drugs. I think food prescriptions, like I was saying this five, six years ago, and now everyone's like, "Yeah, that's obvious." I was like, "That wasn't obvious five years ago. Everybody thought I was nuts," so really personalized nutrition prescriptions. That's going to be great. I'm fortunate that a lot of cool companies are coming to me for personalized nutrition interventions, so I got to follow up with those guys.
Gosh, what else? Personalized supplementation is still really expensive, but it's like one of those products that all my clients love and they always come back to me for, so if I could make that more scalable, I would make that product for people because I'm a big believer that supplements can actually improve health, but they have to be really dosed appropriately to your body.
Tailored, right, because they're doing like blood panels to actually measure what they're doing.
Exactly, and most of the time, the consumer products that get to market just aren't big enough doses because you really do need some oversight to know if that's going to push someone in the unhealthy level and you need the feedback loops. There's a company called [Bays 01:04:01] that does a really good job. I'm actually just testing them out, but they theoretically are doing this. I'm going to see if there's a way to help them with more of a clinical play, because I think that this is really important, that people get enough vitamin D, enough magnesium, enough omega-3s, and enough B vitamins so that their bodies will function optimally. Especially with methylation, differences with genetics. So, I think we're actually heading into a really exciting time for personalization of health, and the consumerization of health.
Yeah. I mean, I think over the last couple years since we've been friends, I think we've seen the space move pretty quickly.
So I think there's a lot to be done. I'm sure we can go for another hour, another hour-and-a-half, so we'll have to have you back on, but we're really excited to follow the journey of NutriSense. How do our fans and listeners follow? I know you have Instagram, Twitter. What's the best way to get in touch?
Have them come to nutrisense.io and sign up for our email list, and if they're interested in being a participant, definitely sign up because we're going to be starting trials this summer. Then, come to my Instagram, drmolly.co. "D-R M-O-L-L-Y dot C-O." You can also email me at email@example.com for anyone who is interested in the company, and then if anyone wants to just Instagram me and send me questions, if anyone has any questions about metabolism, I'm always curious to know what people want to learn more about and what kind of things people want to hear about on podcasts. I've been astonished at how many women have come to me about fasting, and I honestly don't think if it hadn't been for you guys really showing me that fasting really is important to health, like I think it's just life-changing information. I think the more we can keep talking about this with people and time-restricted feeding really in particular, the more we can really get the country healthier. So, send us your questions and your comments and what you're looking for with CGM, and I'm happy to help.
All right, well said. We'll have you back on soon.
Thanks, it was great to be on again.
Thanks so much.
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