Geoff

Siim, great to have you on the program.

Siim L.

Yeah. Great that you're having me on. Been watching your show for quite a while and I enjoy the episodes.

Geoff

Yeah, awesome. Thank you. Where are you dialing in from? I know that we're in different time zones. It'd be helpful to give our listeners here a context of where you're based and your background there.

Siim L.

Yeah. I am from the cold, wintery regions of Estonia, calling in from home. I live on this one island called Saaremaa, which translates into basically an island, and that's where I was born, and that's where I live most of the time. I recently came from the Los Angeles as well, from the Metabolic Health Summit, so I do travel around quite often.

Geoff

Yeah. So folks that aren't familiar with Siim, you've become quite a biohacking experimenter, looking at things like intermittent fasting, different hardware interventions and wearables to things like cryotherapy and all of that. I thought that, given that we're both fairly N=1, guinea pig biohackers, that it'd be fun to just kick off the conversation with going down the list of different things we've all experimented with and give our thoughts about them, whether we think they're great, where we think the science is good, where we felt personal subjective or quantitative improvements from those biohacks, and also what are interventions we think are over hyped, less legitimate, maybe on the side of quackery or pseudo science. That could be a first thing to start. I noticed that we both are wearing Oura Rings. These are sleep-tracking, heart rate variability rings. Give us your thoughts, and then I'll give you my thoughts.

Siim L.

Well, I think that I got the first-generation Oura Ring as well, so I would say that it is one of my favorite biohacking technology devices that I use, just because it's very practical. It's not like some sort of woohoo thing that doesn't have real science behind it. It's simply a means of improving your sleep quality, so that itself can have a compounding effect on everything else you do as well like your productivity, or your mental focus, and even the emotions you feel during the day. I would say that even simply having the ring puts you in this sort of a mood where you're being mindful about your sleep quality, whereas in other cases, you may be simply going into this paths. You may go down the path of not being that careful with your sleep quality, and you don't really know how well you sleep during the night. The Oura Ring simply gives you really good quantifiable feedback about how well you sleep at all and how much deep sleep are you particularly getting. Yeah, a lot of people who maybe pick up the ring in the first place, initially they definitely see, "Oh, I'm not actually getting any REM sleep," or "I'm not getting any kind of deep sleep at all."

Siim L.

I personally have found that, just the fact of having it, that's going to give you more responsibility over your sleep quality.

Geoff

Yeah. No, I think I would agree with you on that. I think even just on a practical matter, I think there's a lot of wearables one can wear these days, whether that's a Apple watch, or a Fitbit. I just found that the ring form factor just much more convenient. I like sleeping and rolling around a little bit, and having a big watch that you're wearing that you need to charge every single day is a little bit cumbersome. Just even aside from the data side around heart rate variability, projecting out deep sleep, deep sleep, what you mentioned. I think just the practicality of the ring is just a nice little device.

Siim L.

Yeah, you're right. You don't really even notice it when you're wearing it. The ring looks cool as well. If you have the black ring, then it may also turn some eyes or turn some heads, and people are going to ask, "What kind of a thing is that?" A quite funny thing, a few years ago, one of my friends and I were thinking of yeah, maybe we're going to intercept the market, and we're going to create a toe ring as well that can now track your sleep. That would be like the Torah. But I don't know that has been put into practice.

Geoff

Yeah. That's funny. I've seen that you've experimented with a hyperbaric chamber, hyperbaric oxygen chamber. We had Dr. Scott Sherr on our program talking about hyperbaric oxygen chambers, so I had some experiences with that as well. Curious to hear about your thoughts on hyperbaric oxygen and your subjective thoughts on it.

Siim L.

I would say that yeah, it has a bunch of research that supports the benefits of hyperbaric oxygen chamber, but I still haven't done it that much to see any kind of significant difference. I've only done it a few times, because there isn't a chamber in Estonia. The near ones would probably be in London or Stockholm or somewhere. I would say that how effective it's going to be is going to depend upon only your personal levels of oxidative stress and inflammation and such. Even personally, I don't really experience a lot of chronic inflammation or chronic stress, so I'm living in a quite clean environment already with fresh air and sunlight, so I haven't noticed that much difference from that.

Geoff

Yeah. I think it's funny. I think we are matching up on our subjective experiences from this as well. I think there are actual, billable medical indications for hyperbaric oxygen chamber. There's different diseases and injury states that hyperbaric oxygen chambers are in the medical handbook for standard of care. But in terms of a healthy person like you or I going in there for enhancement or longevity benefits, it was not immediately obvious. I personally didn't measure that many biomarkers before or after. We did do some finger sticks for blood glucose and blood ketones. Then I think it got a mild elevation of blood ketones, but that might just be because I was fasting inside the oxygen chamber for an hour or so, and I'm fairly fat adapted. It went from something like .3 to .4 or something mild. I think that might just be noise.

Acutely, in terms of mental clarity, some of the theoretical benefits, you get hyperoxygenated, because you're in 100% oxygen at one to two and a half atmospheres of pressure. The thought there, the mechanism action there is that you get more oxygen into your brain. I'm not sure if I felt acutely smarter or sharper. Maybe a little placebo, but it was just not as acute as some other interventions. I'm curious to hear if that seems consistent with your experience.

Siim L.

Yeah. I think the benefits are maybe like 1 to 5% or something along the lines for healthy people who are already quite optimized, so to say. Someone who maybe suffers from some sort of a disease like cancer or something else, they may definitely experience a much greater benefit from that. But yeah, I would say that if your pillar stones or the fundamentals aren't that well optimized, then you will definitely may benefit from it just because it's going to help you to reach the baseline, so to say. But if you're already functioning from the baseline on a consistent basis, then you're not going to go to a magnificent next level just because your fundamentals are already quite optimized.

Geoff

Yeah. I think to give the steel-man argument, or the best possible argument for the hyperbaric oxygen folks, Dr. Sherr and some of the advocates around hyperbaric oxygen chambers did mention that you need multiple sessions over a consistent period of time to really get hyperoxygenated. Maybe we just did it too few times and too inconsistently to really see that mark in measured improvement. But it seemed that he was citing towards some data, I believe, in China, where they're doing studies and did see improved test-taking performance in, I believe, a Chinese student population. It sounds like we didn't actually see an acute crazy benefit off of a one ad hoc use. But maybe it's possible that over consistent use, we might see a benefit there.

Siim L.

If I had a chamber at my home, then I would definitely-

Geoff

I'd be doing it. I'd be using it, yeah. Same. It's not cheap, so listeners out there, this is not something that ... do your homework if you want to experiment there, because it's not necessarily a cheap thing. These are pretty expensive serious medical devices that you got to be playing into. Although I believe I've seen people make home-brew different hyperbaric chambers, which may or might not have 100% oxygen, which is a fire hazard. Then too, they're plastic bags as opposed to steel containers. So definitely not something trivial to do yourself, because if you're doing 100% oxygen, again, that's a fire hazard. That things explosive. And then too, how do you contain increased atmosphere pressures? It's not trivial.

Siim L.

Yeah. It's much easier to make your own ice bath.

Geoff

Yeah. Yeah, yeah, exactly. I think that's a nice segue. Curious to hear about your thoughts of cryotherapy versus heat shock therapy like sauna, infrared saunas, steam rooms. Curious to hear your thoughts of cold versus hot. Do you use both? Do you use them strategically? How do you incorporate temperature deltas in your protocol?

Siim L.

Yeah. I would say the sauna and ice lake swimming are the origin of biohacks of the Nordic countries like Estonia, Finland, and Russia, and so on. I'm a huge fan of those, and I think that they are actually one of the most effective quote/unquote "biohacks," although they're simply traditional medicine or folk practice in these parts of the world. I usually maybe go to the sauna for two to three times a week, and I really think that the optimal range for the temperature is somewhere around 70 to 90 degrees celsius, which in Fahrenheit I would say is like 200 or something. That's the sweet spot where I tend to be.

Geoff

Yeah, 100 celsius is 212 Fahrenheit. Yeah. You're getting up there. That's hot. It's probably around 150 to 180 degrees Fahrenheit, for our folks in ... yeah.

Siim L.

Yeah. I would say that that's a good dose, because it's not going to be that stinging hot or burning hot, but at the same time it's still going to make you sweat a whole lot. It is mildly discomfortable. That's the main idea that I think that's where most of the benefits are also coming from. You have to actually make it slightly uncomfortable but at the same time you don't want to quote "trigger" a fight-or-flight response and become stressed out, because that's simply going to negate most of the benefits.

Geoff

Yeah. Yeah. What do you typically use heat for versus cold? How nuanced ... do you use them strategically, or do you just use them ad hoc?

Siim L.

Yeah. If I were to take a sauna, then I usually try to go expose myself to the cold as well in some form. At the moment, it's the winter, so there's snow around, and I can literally take a sauna for maybe 10 to 15 minutes and then go outside, sit in the snow for a few minutes as well, and that's going to be an amazing contrast effect where you're going from this heat into the very cold. It feels quite phenomenal, and I would say that the combination of those things is much better than doing them separately just because it stimulates the lymph flow much more effectively with that. After you go back into the sauna from outside from the cold, then you're going to feel this massive surge of blood flow and it feels really, really something different, and really, I'm a huge fan of that.

Geoff

Yeah. I actually did something. I'm more of a heat person than a cold person, mainly due to the fact that it's easier for me to get access to a steam room or a sauna. The gym I go to in San Francisco, there is a steam room in there, so I can get access to the heat. I guess I could do an ice bath, but I'm not in Estonia where there's ice for me to just plunge into. But I'm curious to get your thoughts on the literature. I think there's been studies on ice baths or cold alone and heat alone. I don't know. Have you seen studies on doing them together, where you just cycle hot, cold, hot, cold, hot, cold? I think if you look at some of the mechanisms of actions of cold versus what you expect from heat, they almost cancel each other out, where the cold is really designed for reducing inflammation, reducing adaptation to metabolic stress of exercise, for example, and heat really doubles down on the metabolic stresses of exercise. But I think you brought up an interesting point of, can you increase the lymph flow and the blood flow? I'm not sure if people have actually studied that as an actual intervention versus just heat alone or just cold alone. Just curious to hear, aside from I think the folk tradition, which I think is interesting, have you seen if there's data between cycling hot and cold versus hot alone or cold alone?

Siim L.

Unfortunately, I haven't noticed anything like specific in terms of the contrast of hot and cold. But I do think that some of the benefits do coincide with each other like the inflammation reduction also happens in sauna just because of sweating out some of the toxins as well and boosting the growth hormone and such. But the metabolic side...maybe the cold itself wouldn't trigger the same metabolic response as the sauna. But at the same time, it still helps to convert the white fat into brown fat, which itself still mimics some of the physiology of exercise.

Geoff

Fair enough. I would just, I think, caution that, depending on what you want to do ... if you want to recover for a sports match the next day, you probably want to end up with cold. If you want to just maximally adapt to the exercise and how the growth hormone, as you said, you probably want to end up on heat. And maybe if you just do cold, hot, cold, hot, cold, hot, and then you end at the intervention that you want to optimize, whether that's for recovery or for adaptation, that might be just a little bit extra level of nuance as opposed to let's just do everything and not really understand how these things interact.

Siim L.

There is definitely a specific time where I would want to do this hot-and-cold thing. If I'm coming from a resistance training workout, then I definitely don't want to expose myself to the cold, because the cold will shut down the hypertrophy response.

Geoff

Exactly, exactly.

Siim L.

Usually if I do the hot and cold, and I'm doing it on a rest day just to do some metabolic exercise without causing actually any additional stress on the body and at the same time promote recovery from the cold. Yeah. Usually if I'm working out, then I'm only taking some sort of a warmer steam room or a sauna. And if I'm having a rest day, and if I want to promote recovery, then I will take the cold as well.

Geoff

That's exactly how I use hot and cold. You hit it spot on for how I use that as well. Anytime I'm trying to maximize adaptation, maximize growth hormone, I'm just going into the heat.

Siim L.

Throwing everything into the frying pan, so to say, doesn't really give you the results.

Geoff

Yeah. Very opposite adaptations. But I think you're right. I've done this cycling. I was at this retreat center down in ... where is it? It's near Pebble Beach, basically just south of San Francisco area. I was just doing cycles of hot and cold, hot and cold. And it just feels subjectively nice, I think, just from the contrast. I think it would be interesting if we actually did some randomized control trials on exactly the biomarker effects of hot-cold cycles versus just cold alone or heat alone. You just came back from the Metabolic Health Summit, which is very much into ketogenic diet, low-carb diets, intermittent fasting. Tell me about your experimentations. What's your protocol of fasting, dietary restriction, all things that you put through your digestive system?

Siim L.

Well, I've been doing some form of intermittent fasting for like seven years, since high school, so that's my favorite nutritional hacks and ways of eating. I haven't really gone back to a regular three square meals a day ever since that.

Geoff

How'd you get started? Your high school, or how'd you decide to just eat weird?

Siim L.

Yeah. I started losing weight as well at that time. I simply wanted to know how to get shredded faster, so that's when YouTube was also starting to become more popular. Lots of posted videos that talked about the 16 and 8 type of Leangains method, where you fast for 16 hours and eat within 8 hours. You basically maybe have two meals or something. Yeah, that's what I was doing for several years actually and was really, really effective in terms of I noticed a huge difference in mental clarity throughout the day and lower inflammation and everything. Probably the best benefit is that you don't become so attached to food, and there's more mental capacity to focus on other stuff.

Geoff

Then moving into ketogenic diet.

Siim L.

I started it off as simply an experiment to try it out, because I heard some amazing benefits from anti-cancer and such. I don't have cancer or any disease, but I simply was curious about, "Okay, I'll try it out, and we'll see what happens." The first weeks were somewhat like different. I did notice, again, some of the similar benefits in terms of mental clarity and more cognition, but I didn't even lose any strength or physical performance during the time either, so I stuck with it. I just enjoyed the foods. I enjoyed the reduced hunger and increased satiety, so for me, it goes back to maintaining productivity throughout the day, and not being so attached to food, and not being dependent of constantly frequently eating. Keto diets make fasting so much easier as well. The fat adaptation that occurs from keto, the same coincides with the fat adaptation you get from intermittent fasting, so that's one of my perfect combo, in my opinion.

After having gone through it for several years, then I don't really have to be worried about eating carbs either. I've built up the metabolic flexibility and fat-burning machinery so I can really easily dip in and out of ketosis. I can eat carbs. I'm not going to feel lethargic from it, and I'm not going to feel any performance droops or performance drop-offs if I don't eat the carbs at all, so my body's quite well adapted.

Geoff

Nice. That's interesting to hear. I cycle in and out of keto, and when I am coming into carbs after a period of keto, the carbs hit me pretty hard. I feel pretty lethargic after a heavy dose of carbs. You don't feel like a carb slow-down when you're on keto, when you have-

Siim L.

Not necessarily. If I'm eating whole-food carbs like potatoes, rice, and some tubers, and some fruit or something, then I don't feel any different at all. The only potential danger to that may be that if I'm eating some processed carbs like pizzas or ice cream or such, then I may definitely feel lethargic. But I think that kind of mental fatigue and slowness doesn't come from the carbs, it comes from the processed foods and the gluten or whatever else that I may have been consuming.

Geoff

Fair enough. Fair enough.

Siim L.

For instance, if I started doing it the first times a few years ago, then at that time, I did notice the first times I did it, the next few days I was kind of brain fogged and really, really slowed down. But after having done it several times in a row and maintaining this sort of flexibility, then I would say that it goes away, and you will definitely overcome that.

Geoff

Yeah. Fair enough. I think the times where I usually just am on keto, and I'll just haphazardly break keto ... for example, yesterday one of my colleagues had a birthday, and I just felt like I had to have a slice of cake just to celebrate with her. Then after that slice of cake, I was like, "Oh, man. I want to take a nap for 30 minutes." That is real, if you are on keto, and you take a big lump of sugary carbs, very refined carbs there, you're going to get that insulin spike and crash, which will make you probably pretty lethargic.

Siim L.

You do notice if you're on keto, then you become more intuitive and more mindful about your blood sugar levels by default as well. You're not going to even need a glucometer to measure your ketones or measure your glucose. You're going to feel intuitively, okay, based upon your mental state and the focus, like, "Okay, what kind of fuel am I burning at the moment?" And yeah, from the past I can say, for instance, if I in some sort of a restaurant, I'm eating some sort of a soup, then I can taste. "Okay, my blood sugar is going to be jacked up a little bit just because there may be some potatoes inside the soup or something, and I'm going to feel slightly different."

Geoff

I agree. I feel like five years ago, or seven years ago when I was just a computer science student at Stanford ... this was like 10 years ago at this patient now ... I would've felt like you're talking nonsense. How do you intuitively feel your blood sugar? You know what I mean? I'm a skeptic by nature, but now after actually being in tune with your subjective performance and being thoughtful around diet and really being thoughtful about it, you can actually tell. I think a lot of people, I think, from the other side are like, "Oh, you guys are just talking woo-woo," or "You guys are kind of guessing here," or maybe not, but there's something that you can actually feel. It's a real sense of, "I feel a sugar crash coming," versus "I feel really, really sharp. I'm in ketosis. I'm in flow."

But talking more quantitative or something that is more measurable, I'm curious to hear about different biomarkers you've measured while intermittent fasting or on keto and then just from a body composition perspective. I think the most obvious thing that I've found in my own body comp is that it's so much easier to be lean and cut on keto intermittent fasting. I'm visibly just more fit looking than I was two, three years ago. Curious to hear about all the different interventions, aside from the subjective mental state, that you've had from intermittent fasting and/or keto.

Siim L.

From the basics of biomarkers, I would say that my blood glucose is definitely more stable throughout the day, and it tends to be even slightly lower than normally so to say. I do notice that most people who do keto and fasting, their baseline blood glucose for them is going to be slightly lower. They're not going to feel like hypoglycemic from that either, so their body is burning ketones, and the demand for glucose gets lowered, and they don't feel hypoglycemic whenever they skip a meal or they don't get dizziness.

Geoff

You don't get hangry.

Siim L.

Exactly. In the past, during high school or something, I may have had this short episode where you stand up too fast from the ground while laying down, and you start to feel dizzy a little bit if you haven't eaten anything for a few hours. But nowadays, that never happens. I never feel hypoglycemic, or I don't ever feel dizzy, or I don't feel lethargic during the day. My brain is always running on ketones, and it's really amazing for that. What I do think as well is that yeah, the baseline for hypoglycemia will also be lower after you keto adapt and even on my longer extended fasts, my blood sugar is really low, in the 50s or something, and that's going to be medically categorized as hypoglycemic and I should be hospitalized. But because my ketones are going to be elevated, I don't feel any difference, and it's an amazing feeling.

Geoff

100%. And when I did longer fasts, my blood sugar would be down to like 60 mg/dL. For a doctor to see someone walking up with 60 mg/dL, you're probably like, "Oh, yeah. You're hypoglycemic. Something's wrong with you. We got to pump you full of sugar." And it is kind of funny to realize that hey, doctors have, I think, again, very well trained in what they're supposed to do, but if you're deviating from the standard western diet, which is engineered to destroy your metabolism, they're almost at a loss of how to characterize you, which is something that hopefully biohackers, folks in our communities, can start shifting the culture, shifting the education around what does even a healthy metabolism look like.

Siim L.

Most of the ranges for all the biomarkers are also established on the western diet, so to say, and they're going to be drastically different for some people who are doing a low-carb diet or something.

Geoff

There is this viral photo on Twitter where the mannequins at this mall are fat people. Not to fat shame, but I think it is important to realize that would've been a morbidly obese model in 1800s, 1850s, and it is somewhat concerning for me to see that that is just the norm of how to sell clothes now. There's no reason for us to shame or not shame anyone, but it's just, I think, concerning from a population health level to just say that, "Okay, we've just shifted our standards of what we expect to be normal to be someone that is morbidly obese." I think that's problematic as a society and as a healthcare system.

Siim L.

I think the biggest danger to that as well that the people who justify being fat or something, they may not be operating from the perspective of their truer self, so to say, that they may be simply addicted to food, and they rationalize it away, that it's okay, it's who I am. Whereas in reality, their brain might be hijacked from the processed food, or the microbiome may be telling them lies, which may sounds like woo-hoo as well, but there is some truth to it, that processed food is addictive, and it can definitely change the mental powers and the decisions of a lot of people.

Geoff

The processed foods are engineered to be addictive and yummy and get you to keep buying. There's very smart people in the food industry. As you know, H.V.M.N. makes consumables, and we have smart people. It's just trying to sell you stuff, and hopefully there's folks that realize that that's not something that makes you proud at the end of the day, and can we help make people better and healthier as opposed to just getting them addicted to your product.

And I think one thing that's interesting that you touched upon is that the synergy of intermittent fasting and ketogenic diet, most of the conversations I've had with people really keep them separate, but I think it's a point worth underlining that these are very much related techniques. Intermittent fasting's essentially eating your own body fat, or fasting's basically eating your own body fat. And a ketogenic diet is essential, instead of eating your own body fat, you eat exogenous fat as your primary metabolic substrate. I think it's a point worth doubling down for our audience here, where intermittent fasting or fasting stacks really well with a ketogenic diet. I think if you really want to double down on the metabolic pathways that are triggered through either fasting or keto, it's really synergistic to stack them both together.

Siim L.

Yeah. I would say that the reason you would want to combine them is that the physiology of fasting is really therapeutic for the body, and it helps to heal it from the inside out, and it also has many other longevity-boosting benefits. One of the main trendy topics is autophagy, and it is very ramped up during the fasted state or doing energy deprivation. If you're already doing keto, then you will naturally potentially, you will be eating less frequently, and that's going to help you to gain more of the autophagy benefits. And you're going to be able to fast for longer and much more easily without suffering from the sugar cravings or not suffering from hunger, so you would naturally be adopting more of a fasting-focused lifestyle, and it's going to be much more easier for you. In so doing, you will indirectly gain the longevity-boosting benefits from fasting and autophagy and those sorts of things.

Geoff

I think one of the longevity pathways like mTOR, right? They sense protein, and when you're fasting, you're obviously not ingesting any protein. You're mitigating mTOR activation. And the same thing is mimicked on a ketogenic diet. Yeah, as you're talking, you're hitting the same pathways.

Siim L.

A keto diet is like a moderate protein type of diet. You're not consuming a bunch of carbs. You're not consuming a bunch of protein, and that itself is also going to help you to keep your mTOR moderate, so to say. They say that meat and protein are going to stimulate mTOR, and that's going to accelerate aging. But at the same time, there are other things that activate mTOR as well like glucose and insulin.

Geoff

Yeah. Carbs. Yeah, yeah, yeah.

Siim L.

Those are another one of those things that actually activate mTOR a whole lot. Especially if you combine the glucose with protein together, then that's going to spike insulin even more than just eating protein alone in a low-carb setting. On a keto diet, you're actually experiencing much lower levels of IGF-1 and much lower levels of mTOR just because you're already eating less frequently, and you don't have excess insulin and excess glucose floating around in the bloodstream.

Geoff

Yeah. No, I'm a huge fan of fasting and keto, but I can also see that it's not necessarily for everyone. I think it's always worthwhile to just give the parameters here. Have you seen people go too far down the line of keto or fasting? What have you seen in your practice and your community around what goes too far?

Siim L.

I would say that the biggest mistake people tend to make is that they become catabolic for too long, and catabolism refers to breaking down. That's what you're doing essentially when you're fasting or if you restrict your carbs too long or too often, so to say. That's simply going to eventually degrade the body to certain extent. I would say if you're starting to lose lean muscle mass from doing too much fasting too often or being on a keto diet for too long, then it's not going to be worth it, so to say, because muscle is also very invaluable and vital for longevity. It's going to help stave off a lot of the age-related diseases, and it's going to make you more insulin sensitive, so to say.

So mTOR isn't a bad thing. You would want to have mTOR for maintaining lean muscle mass and actually building muscle, so I would say that if you are practicing intermittent fasting and keto, then you should never be afraid of properly refeeding and becoming so scared of eating protein, or so scared of eating meat, and scared of getting kicked out of ketosis, because those things may actually have a beneficial effect on your longevity by making you more insulin sensitive for a period of time and helping you to increase your physical performance, build muscle, build strength. You have to simply know when to stimulate mTOR at the right time and make sure that you actually feed yourself every once in a while, because the body will function best when it's in homeostasis.

Geoff

Yeah. It's fasting, not starving.

Siim L.

It's called intermittent fasting, so you're doing it intermittently, and then you feast in a sense. That's the perfect combo.

Geoff

It circles back to a topic that I've been underlining more recently, which is that longevity in of itself is sometimes orthogonal to performance. In the sense that if you're trying to win an Olympic gold medal, you're probably not doing things that are optimal for longevity and vice versa. Right? I think we all as individuals with our own baselines and our own goals, you understand what our individual goal is and then optimize our balance of longevity and performance. I think for me, I'm never going to be an Olympic champion in anything, but I do like functional strength, just being upper core tile in terms of fitness, and in terms of running, in terms of my calisthenics and all of that stuff. I like the performance aspect of being strong, but also I'm trying to optimize for proactivity in my cognitive performance and my longevity. It's finding that balance that works for my lifestyle, and I think that's going to be different for everyone.

For you, that might be more focused on longevity and more focused on performance. For someone training for an iron man, that might be more focused on performance and less on longevity. I think it would be a service to the broader discussion if we just had these two dimensions of this health space just more clearly defined. I think people are like, "Oh, you want better performance. Do you want to live longer, or do you want to perform better?" Obviously, if you're just jacking up steroids or testosterone growth hormone, that will make you perform better, but it will probably lower your health span, lifespan, right? That might be a trade-off that an individual might want to make, but it's probably a very slim portion of the audience. Someone that might want to be doing heavy caloric restriction, heavy dietary restriction for that chance the maximize their longevity, but then they'll be very low lean muscle tissue, somewhat emaciated, maybe not living a very happy life, that might be optimal for that specific person's lifestyle, but that probably is also a very small slice of the population. I think we need to have education or a culture to allow people to understand where they are, and what their goals are, and how do we help them get to their goals.

Siim L.

You pointed out very well that there's both ends of the spectrum. For instance, on one end, you have some pro body builder who takes steroids and eats too much protein, too many carbs all the time, and six to eight times a day. On the other hand, you have this starvation victim. They're always both on the extreme ends of the spectrum, and longevity, or the best of both worlds, is somewhere in the middle. You probably won't be winning the Olympia if your plan is to live long time, but you may still get at least 80% of the results if you do things right, and if you commit to it wholeheartedly so to say. And yeah, it's really important to educate people about how does this different biohacks or this different nutritional interventions, how do they affect their longevity in the long term? Because the conventional fitness otherwise is to eat six times a day with frequent snacks and make them all low fat and higher in protein and such. But what they don't tell you is that that may not have a pro-longevity benefit on them just because of stimulating mTOR frequently and maintaining this anabolism and not going into autophagy and such. So that's a really detrimental situation. It's going to be simply that people aren't aware what they're doing to their bodies completely, and that's simply quite unfortunate.

In terms of longevity and performance, then I would say it follows somewhat of a U-shaped curve. There are studies that show that the mortality risk of IGF-1 also follows a U-shaped curve, where too little IGF-1 is going to increase mortality and too much IGF-1 is going to increase mortality as well, so the best spot to be is somewhere in the middle, in the slope of the U-shaped curve.

Geoff

I think that's where it gets complicated and nuanced, because we all have our own genetic bio-signature in terms of what is that perfect spot for each of us, and exactly what are our goals, and what do we want to be dialing in? I know you've been studying, and you're working on a book around intermittent fasting autophagy. I think our audience here is relatively up to speed on the concept, on the practice and on some of the key biomarkers. But what do you think is the least understood in the fasting space?

Siim L.

One of the few things that I already mentioned, like making sure that you refeed properly and not being afraid of eating protein. That's one of the things that most people tend to be afraid of. It's also quite misunderstood how certain macronutrients affect the process of autophagy and being in a fasted state, so to say that it's very popular to be putting different flavorings and oils and butter into a coffee, and the idea that is it going to break a fast or is it going to maintain autophagy. Those are very complex, in my opinion, and whether they actually break a fast is going to depend upon how much calories you're actually consuming.

Geoff

Yeah. Maybe we should dive into that, because I think we get a lot of those questions, and I get a lot of those questions as well, because we run a big fast community called WEFAST. People ask about, "Can I put a little bit of sweetener in it? Can I put a little bit of cream in it? Can I put butter in it? Can I have caffeine? Can I have tea? Can I have amino acids? Can I have bone broth?" I think each of those have their own nuance, so perhaps we should go down some of the popular crutches and talk about the pros and cons.

Siim L.

It's like with Bulletproof Coffee and putting butter into your coffee. I would say that whether it's going to break a fast is going to depend upon the general nutrient status of your body and how depleted your are from certain nutrients. If you're coming from a three-day fast, then taking like 100 calories of butter in a coffee, I would say that it's not going to have any significant effect on autophagy or the fasted state. But if you already ate the night before, and you've been fasting only for like 12 hours, then that same amount of calories from that same amount of butter would have a completely different metabolic response, just because your body has a reserve from the previous day. It's going to have a different effect, and it will probably break autophagy to a certain extent. But there's also different types of autophagy, like chaperone-mediated autophagy, which is more of a selective form of autophagy. It's been shown that ketone bodies stimulate that process of autophagy, and drinking that butter may raise your ketones and in turn, that can maintain some form of autophagy. So it's a very complex situation of how depleted your body is from certain nutrients.

Geoff

How would exogenous fat, and in what mechanism, would exogenous fat blunt autophagy?

Siim L.

Exogenous fat still can elevate mTOR to a certain extent, so to say, that mTOR is the main nutrient signal or nutrient detector what switches you over from a catabolic state into an anabolic state. The main nutrients that stimulate mTOR are glucose, insulin, and-

Geoff

Protein.

Siim L.

But at the same time, too much fat is still a source of energy that the body will detect, especially if it's higher in calories. But if it's like moderate amount of fat or moderate amount of calories, then that's not going to have that big of a difference. So there's a difference between taking 500 calories of butter or taking only 100 or 50 calories of butter. So the 50 calories may still maintain the autophagy to a certain extent, but if it's like 500 calories, then the body will simply-

Geoff

And then you're saying that the argument for you is that high amount of fat, they'll be some gluconeogenesis from that fat, and then that will trigger mTOR, and you're concerned about that?

Siim L.

Even high amounts of fat or high amounts of ketones, they may still raise insulin to a certain extent just because it's a nutrient that the body will try to store or try to mobilize in some form.

Geoff

I agree. I think the funniest thing when I hear people taking a Bulletproof Coffee is that they're like, "Yeah, I'm not hungry. I just drank a coffee." And it's like, "Well, you just drank 1000 calories of butter for your breakfast, so of course you're not hungry." I think it is easy to go fully into the absurd on the other side. I think the point of having a little bit of fat to start the day is sensible, and maybe you reduce a breakfast, a meal with carbs and protein. But when you're just replacing with 1000 calories of fat, and you think that's just like a free meal, that doesn't count as any calories, like "Look. You just ate 1000 calories of fat. Over you're not hungry."

Siim L.

Definitely. Less is more, and less is better in terms of the amount of butter or the amount of fats you use. But at the same time, if the Bulletproof Coffee helps you to fast for longer and helps you to skip breakfast, then I would say go for it. It's still a matter of your own choices and what kind of situation you find yourself in.

Geoff

Bulletproof or butter in coffee, I think that's one thing. What do you think of caffeine? Caffeine is a popular thing that people ask. Can I have a tea or a coffee with fasts? I can start off here. Usually we say that caffeine is not going to break a fast, but I think there is reasonable argument that you'd not want to have anything aside from water from a fast. But I think in terms of just general understanding of mTOR, some of the cycling pathways, caffeine doesn't affect those pathways, so in that sense, caffeine is okay for not breaking a fast.

Siim L.

Yeah. I agree that coffee's perfectly fine, whether that be caffeine from tea or coffee. It's actually shown that coffee stimulates some form of autophagy, and it does stimulate ketone body production as well through increasing lipolysis and such. Coffee's perfectly fine in my opinion. The only problem is that if you drink too much coffee, then it may simply raise cortisol too much, and that may raise blood sugar and insulin and such, so you'd have to make sure that you don't drink five cups of coffee or something. I myself tend to stick to only one to two cups of coffee a day, and that's perfectly fine.

Geoff

I think for me, when people just go cold turkey, they go from coffee, breakfast, everything, to just straight fasting, it's really, really hard, because you're not just addicted to insulin and carbs, you're also addicted to caffeine. So it's cutting all those things at once. It's going to give you a headache.

Siim L.

There's also the argument that coffee is going to stimulate some of the liver enzyme processes, and that's going to put you into a federal state. But I would say that it's not going to matter at all, because although you may stimulate the liver's enzymes, you're still going to maintain a catabolic state, so to say. You're still going to be in a fasted state, because you haven't consumed any real calories. It may actually be better from the circadian rhythm aspects, because if you do drink the caffeine in the morning, then you're going to offset the circadian rhythm properly, and you're not going to misalign yourself from it. Whereas if you skip it altogether, and you drink just water, then you may suspend your metabolism to a certain extent, and you keep your liver in this sort of a suspended state all up into the point where you're about to eat.

Geoff

Assuming they are used to having caffeine, right? Because if you don't have any caffeine, then you don't have the suspension state that you're probably referencing. How about amino acid bone broths? My opinion on amino acids or bone broth, amino acids, as we have discussed, trigger mTOR. I would refrain from too much bone broth and amino acids. Although Dr. Jason Fung, a well-known fasting doctor, will recommend bone broth. His argument there is that it's somewhat satiating and the benefits of helping someone sustain through a fast is better than having a little bit of amino acid. I think that's a fair point. I think it's the same argument with caffeine or a little bit of butter in your coffee. If it helps you stay on your fast, probably the net benefit of extending your fast longer is better than having that little bit of extra nutrient. But I think we should be clear to the listeners that yeah, bone broth has amino acids. Amino acids trigger mTOR. You're going to blunt some of the benefit of fasting, but that's an option. It is a trade-off that you have to make.

Siim L.

Depending on how long you're fasting for, if you're fasting for several days, then having that bone broth is going to be probably a good idea, because it helps you to fast for longer and get some more electrolytes and actually get a little bit of more of the nutrients into yourself as well, so you're not going to go into the full-on starvation mode. But if you're fasting only for maybe less than a day or eating only-

Geoff

Yeah. Don't worry about it.

Siim L.

Yeah. It's not going to be that significant, and it's not going to be important. But in terms of breaking autophagy, then I would say that again, in the example of longer fasts, then that small amount of amino acids, they may inhibit autophagy for only a brief moment, only for that time duration where you're digesting those amino acids. After that, your body will probably go back into autophagy quite rapidly. So it's not going to take another additional three days to trigger autophagy after drinking a bone broth, because your body is already depleted from liver glycogen. Yeah, it's running low on those nutrients.

Geoff

Have you tried ketone esters? Have you tried exogenous ketones? I'm curious to get your thoughts on that. Obviously at H.V.M.N., we have a ketone ester that is popular. Curious to hear your thoughts. Do you think that breaks a fast? And also just opening up the discussion broadly, what do you think of applications of ketone esters?

Siim L.

I would say that the exogenous ketones in their pure form, they probably won't break a fast, and they won't significantly affect these things as well as long as you don't take several servings of them. But the problem is that most of these exogenous ketones, they're combined together with artificial sweeteners and other ingredients, so those in turn may spike insulin a little bit, and that's going to probably interfere with the fast a little bit. The ketone esters themselves, I would say that they don't really affect the autophagy process that much. They're simply a fuel source that the body will have to utilize in some form during the fast. But again, in the same example of maybe taking butter in your coffee, is going to burn through that source of energy, but it's not going to break a fast, so to say, technically.

Geoff

Yeah, obviously any sort of exogenous calories from fat or from a ketone ester is going to halt lipolysis for a little bit, because you have external energy that you're burning through. But is it triggering mTOR? Is it triggering some of these nutrient-sensing pathways? As far as we know, the fasting ketones do not, so you're not breaking those autophagy pathways.

Siim L.

The ketone bodies like beta hydroxybutyrate, they actually stimulate some form of autophagy, like the chaperone-mediated autophagy.

Geoff

Cool. I guess just broadly zooming out, have you played with exogenous ketones, ketone esters for performance use cases or anything in terms of just as a biohack broadly?

Siim L.

I use them sometimes before working out, and I do notice that they definitely help. The thing is that in most cases, I'm working out fasted, and those exogenous ketones simply give me an additional fuel source that help me to perform better. But if I have eaten anything before that, and I already have some nutrients in my system, then I would say that there isn't going to be a significant difference. Yeah. That's my go-to usage of those exogenous ketones. I like them for the electrolytes specifically, and they do increase at least the mental aspect of a workout, and they put you in the zone much more easily.

Geoff

You're talking about ketone salts versus ketone esters? I don't want to just disambiguate the two.

Siim L.

Yeah, I was talking about the ketone salts. I haven't used the ketone esters that much.

Geoff

We got to hook you up and then get your thoughts on that, because I think ... just to give you a sense ... a ketone salt will get you to 0.5, 1.0 millimole BHB, and then for a ketone ester, we get you up to 3 to 5 millimole BHB in that same period of time, which is a very material difference.

Siim L.

That would be interesting, yeah, to see.

Geoff

Wrapping up here, just last couple of questions. I know that you're working on a book. What are your big projects for the rest of 2019? Where are you traveling? I know you hit up different conferences. You were just at the Metabolic Health Summit, which my colleague Dr. Brianna Stubbs was there as well. Which conferences? What are your projects for '19?

Siim L.

My current plans as of now are, there's going to be a biohacking conference in Riga, which is in Latvia, in the end of April. That's where I'm going to be speaking. Then there's going to be another one called the Health Optimization Summit in summer, in August if I'm not mistaken. I'll be there as well. And in October, there's going to be the Biohacker's Summit in Helsinki, so I'll be speaking there as well. Those are my, at the moment, the go-to conferences that I'll be going to. I do have my own boot camps as well, planning to organize in Estonia where we're going to do some saunas and cold plunges and some lectures about fasting and all the other fun stuff.

Geoff

Obviously you're super passionate and knowledgeable of the space, and I think passionate about sharing your experiences and your learnings. Where do people follow you? Where do people find you?

Siim L.

Siim Land is my tag on all of the platforms, like on YouTube, Instagram, and my blog is also SiimLand.com, so people can find me there.

Geoff

Siim, awesome conversation. Thanks so much for taking the time.