Transcript of Dominic D Agostino: Ketosis & Oxygen Toxicity - #187 Bulletproof Radio podcast #187 The Bulletproof Executive 2013
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Dave: Hey. It's Dave Asprey of Bulletproof Radio. Today's Cool Fact of the Day is that the ketogenic diet was actually developed to treat epilepsy in children. In 1997, Meryl Streep starred in a TV movie that promoted the ketogenic diet for pediatric epilepsy in an attempt to bring the treatment back into the mainstream. Today's guest has been in the show before and it was one of the most popular episodes we've ever had. This is none other than Dominic D'Agostino. He's a PhD and an assistant professor at the College of Medicine Molecular Pharmacology and Physiology at the University of South Florida. That is a very long title, Dominic. He worked to develop and test nutritional and metabolic therapies including things like the ketogenic diet and things that use oxygen. He's doing amazing things for seizures, epilepsy, metabolic disorders, Alzheimer's disease, ALS and cancer. Dominic talked to us at the conference about new research in ketosis and what happens in your central nervous system when you get oxygen toxicity. He's done some amazing work at the Office of Naval Research so you're going to learn a lot about why you want to be in ketosis some of the time, maybe all the time, maybe not all the time; and what supplements you can use for ketosis; and what ketosis is going to do for your performance. This is just a wealth of knowledge from a guy who's the biohackers' biohacker. I'm a big admirer of Dominic's work and this is an amazing podcast. Check it out. Dominic, thank you so much for being here with us today. You've been on Bulletproof Radio before to discuss metabolic ketosis and how to optimize fat burning of ketones. What are you speaking about at the 2014 Bulletproof Biohacking Conference? 3
Dominic D'Agostino: My topic will be mastering ketosis, nutritional ketosis. It will be about exploiting the benefits of exogenous ketones for performance enhancement, physical performance and cognitive performance and how this project evolved out of funding from the Office of Navy Research, specifically, the Navy SEAL Fighters, who can use this technique as a strategy to prevent oxygen toxicity. What are the areas of metabolic therapy research that you explore in your work at the University of South Florida? Dominic D'Agostino: The metabolic therapy research that we're currently doing as mentioned is supported by the Office of Navy Research for preventing oxygen toxicity seizures that divers can get and the ketone therapies that we develop from this project are being applied to a variety of disorders including neurodegenerative disorders, wound healing, even cancer. I have some preliminary data that I'd like to share today on the effects on performance, specifically resilience under hypoglycemia and enhancement of exercise efficiency as far as oxygen utilization. Well before we get to that, can you explain to us what is ketosis and what are some of the common terms used in ketosis research? Dominic D'Agostino: OK. I like to start off talking about ketosis in the context of starvation. If we stop eating or if we severely limit carbohydrates, our body mobilizes fat stores for energy. Fat from our diet, which can be a ketogenic diet, or mobilization of free fatty acids from adipose tissue are metabolize in the liver and convert it to water soluble breakdown products of fatty acids called ketone bodies, beta- Hydroxybutyrate and acetoacetate. The benefits of these ketone bodies are that they are alternative energy sources. Specifically, I think from an evolutionary perspective, they provide a form of high octane fuel for the brain. In the absence of food or carbohydrates, starvation allows us to... it gives us fuel for the brain so it continues to supply energy for the brain and this can provide resilience against the 4
hypoglycemia, which would occur. It also has a protein sparing effect. By feeding the brain ketones, it prevents the breakdown of skeletal muscle for glucose. As your brain becomes adapted to ketones, your thinking and other physiological processes are maintained well. From that context from starvation, nutritional ketosis is simply prolonged carbohydrate restriction that can mimic many of the metabolic states of fasting, but obviously you can maintain this indefinitely if you want to, unlike fasting of course. The ketogenic diet is used for drug- resistant epilepsy or drug- refractory epilepsy. It's the standard of care when drugs fail. It controls seizures in about 2/3 of the cases. What we bring to the table, I guess our lab, is takes about 24 to 48 hours to achieve nutritional ketosis but with ketone supplementation, you can do that within 10 to 15 minutes. With more potent forms of ketones like ketone esters, you could produce starvation level ketosis that would take one week's time and do that in about 10 minutes. This has practical applications for a Navy SEAL diver just prior to a mission, so it can potentially enhance the mission capabilities of a Navy SEAL diver by preventing scene as oxygen toxicity seizures, and also in the process enhancing their physical and cognitive performance. Can you define what CNS oxygen toxicity seizures are? Dominic D'Agostino: Oxygen is a stimulant to the brain. Oxygen is good but at hyperbaric pressure, we're breathing 20% oxygen now; Navy SEAL divers use a type of equipment where they're breathing 100% oxygen, so five times the amount of oxygen. If they go down, if they dive down to 132 feet of sea water, for example, they wouldn't but if they did, that would be five atmospheres of oxygen, so the brain oxygen level would probably go about 10 to 20 times. That level of oxygen will cause a seizure probably within five minutes and it would be fatal. 5
Oxygen is a stimulant to the brain and that's good for some people under certain circumstance; traumatic brain injury, for example, and there's a number of applications for that. But because oxygen is a drug, too much stimulation causes excitotoxicity. This excitotoxicity is the fundamental reason why seizures occur. Ketones preserve brain metabolism in the phase of an oxidative challenge, which would be an over abundance of molecular oxygen, because too much oxygen also contributes to the production of oxygen free radicals from the mitochondria. We know from our lab the mechanistic studies that we do at ketones is that they prevent the formation of oxygen free radicals and that's just one of the many mechanisms through which ketones can enhance brain energy metabolism, and protect it from oxidative stress. OK. You've just explained how starvation is a strategy to prevent CNS oxygen toxicity. With respect to regular people, how does starvation change brain metabolism and how does that actually help us? Dominic D'Agostino: Yeah. Studies down to early as scripture, even around the times of Hippocrates, 400 BC, there was reports of fasting preventing epilepsy. The science started to emerge around 1920s where this was validated. Shortly after that, the diet emerged, the ketogenic diet which mimicked the metabolic or physiological effects of fasting. We knew that fasting was a means to control seizures and from a medical perspective, doctors kind of put their heads together and realized that carbohydrate restriction can mimic, if you took a sample of the blood, the glucose would be low, insulin would be low and ketones would be elevated; and that physiological state mimicked starvation. It became in Johns Hopkins and Mayo Clinic did studies and now have a pretty active clinic and network of doctors through the Charlie Foundation actually that promote the use of the diet for the metabolic management of seizures. It all originated kind of out of the observations of not eating, fasting and fasting can be very 6
detrimental to a person's health if it's continued, prolonged. A way to get the benefits of fasting would be the ketogenic diet because it could elevate you... It prevents what lowers insulin, which triggers a lot of physiological processes including ketogenesis that is neuroprotective and good for disease management. How can we use ketogenic supplementation to produce instant ketosis? Dominic D'Agostino: That's really the thrust of our research right now. The data for the use of the ketogenic diet in seizures is very abundant and it's well recognized and accepted, but it's also underutilized. I'm trying to bring that to the forefront. A problem with the ketogenic diet and in using it in kids, especially for pediatric epilepsy, is compliance. In even for the metabolic management of cancer, it becomes difficult for most people to maintain, to comply with a macronutrient ratios that are needed to sustain ketosis. Exogenous ketones in the form of ketone esters that would be the most potent form of ketones. Ketone mineral salts and also MCT oil; the most effective would be Dave Asprey's Brain Octane, it's highest in caprylic acid. These are all strategies to elevate blood ketone levels independent of carbohydrate restriction. From a practical point of view, a person could follow a less restrictive ketogenic diet and still you have benefits of carbohydrate restriction for your body to naturally produce its own ketones. You could further elevate ketones using a number of ketogenic agents - esters, mineral salts or caprylic acids, all this brain octane. That would give you the benefits of a classical, medically, supervised ketogenic diet; eating something like a modified Atkins diet, which instead of a four to one ratio of fats to carbohydrates and proteins, you could a one to one or two to one. From a practical point of view and a quality of life point of view, for kids and adults using this for therapy, that makes a huge difference. That makes it from going to something that's strange 7
and very difficult to follow. I mean you would be essentially ostracized from your family because most families would not kind of buy into this. You'd have to eat separately to basically being able to even go out to restaurants. Last night, I had fish and salad with lots of olive oil and that could be part of a low carb ketogenic diet with supplementation. You mentioned the Bulletproof brain oil or even just MCT oil. Ideally, how much do we strive to have in our diet per day? Dominic D'Agostino: That needs to be done on an individual basis. I've met people that like myself, for example, I can tolerate up to probably eight tablespoonfuls of MCT per day. I think I've gone up as high as 150 milliliters, so around that range, a little bit over. Although I've met people that unfortunately some people who are trying to manage a disorder, one teaspoon since I'm running to the bathroom. What I've found though, fortunately, is that people can increase their tolerance over time and that if the MCT is taken with a meal with some protein, with some fiber to slow down gastric transit time and the gastric emptying that it can be tolerated. I've seen people not be able to tolerate 20 milliliters or a little over one tablespoon and now can tolerate four over time. The benefits that they're getting from that are really remarkable. MCT, like ketone esters and ketone mineral salts, not only does it elevate blood ketone levels but it also for reason we don't fully understand, it can lower blood glucose levels and keep glucose levels low. Most people are familiar with Glucophage or Metformin. It's a widely prescribed type 2 diabetic drug. Ketone supplementation in our hands, in the feedback that I'm getting shows that it has remarkable effects at preventing hyperglycemia. From therapeutic perspective and general health perspective, that's a huge benefit. I don't think most people are talking about that but our research is really kind of exploring that and we would like to make that public. We're actually going to have a paper on that pretty soon, showing the effects on glycemia. 8
With the ketone supplementation, is there a certain time in day that it's best to do it? Or is it best to spread it out throughout the day? Dominic D'Agostino: Yeah, I think it's a good question. It depends on what you're using it to, for example, put your metabolic biomarkers, glucose and ketones within a particular range and try to maintain it there to metabolically manage seizures or cancer, diabetes. I would recommend spreading it out at least three doses per day. If you are the kind of person who's using it for performance enhancement, I would kind of take more of it just prior to an event or a period of time if you're using it for cognitive resilience or maybe more. I was traveling recently and I tend to travel with my MCT or ketone supplements and find it very helpful as I am now chronically sleep deprived. Hopefully, in the next day or two I can catch up on sleep, but when I can't, when I don't have the opportunity because I'm traveling, staying in ketosis gives me cognitive resilience under periods of sleep deprivation, if I'm not eating like I should be. It's a good equalizer in that regard that it's a way to compensate if I'm not following through with other aspects of my life. You mentioned performance. Can you talk about how feeding ketones enhances performance? Dominic D'Agostino: In our animal models, we see that exogenous ketones essentially will cause rodent, mice or rats to run longer on a treadmill- like apparatus. They can run faster and they can run longer and this had been shown in other labs too, that are developing ketones for military applications. When I became aware of that... I have an interest in ergogenic supplements; supplements that enhance performance and that really caught my attention. Even though I'm a neuroscientist and was really studying its effects on the brain, the performance effects were real and I just saw an added benefit to the cognitive or seizure protecting effects. 9
In our animal models there's a clear indication that you can run farther and faster. There's work that has been funded by the National Institutes of Health and are funded by DARPA, I would say, at the National Institutes of Health, NIH, and also at Oxford University. In human subjects, advance athletes, they pretty much nine out of ten performed better and most of them set their personal records, one set a world record using exogenous ketones. That caught my attention too, as I got into this research. We developed our own forms of supplementation and found that we can mimic these effects that others have shown. With a form of ketone supplementation that's naturally derived, a ketone mineral salt, which is essentially a ketone body combined with sodium, potassium and calcium and that's in a solution that you can take. I did a project with a friend and a colleague of mine, Dr. Peter Attia, and he has a well- known blog on ketosis. We did an experiment where the work output on a bicycle was maintained at 180 watts and we looked at oxygen consumption, measured ketones and blood, and showed that mild ketosis, something that could be achieved with Brain Octane, maybe not quite at that level but we used a ketone mineral salt, was able to essentially maintain the same level of performance with a decreased oxygen utilization. Essentially, showing that your muscles are more metabolically efficient under a predetermined load over time and up to 68%. That can translate into an advanced athlete a pretty significant performance advantage. To my knowledge, I don't know if anything else said they can achieve that. Now, I guess the question that we have is would it happen under high intensity exercise? We did relatively lower intensity exercise and we did it for a 20- minute experiment, so it left us with very exciting preliminary data and a number of questions that we need to follow up on. We're pretty motivated to do that but we want to do it in a very scientifically rigorous manner and with a number of subjects, who some of them adapted to carbohydrates and some of them keto- adapted. Also women; I think it's important to do this in women. 10
I like to mention all the studies that we've done, most of the studies that we've done with ketosis are in males, male animals or male subjects because the estro cycle can influence your level of ketosis. It's hard for women to actually stay in... some of them to stay in ketosis when they're menstruating. That's a hot topic right now and I think one that we want to follow up on. We want to try to reproduce everything in females or see what the data shows on that because that's a big subset of population, the females. There tends to be even more interest in females because it's such an effective way to manage your weight and manage your life in general because a ketogenic diet is easier to follow I think, because your appetite is suppressed. When you go four or five hours without eating, it doesn't become a crisis and your appetite is suppressed and you're kind of okay. Whereas, if you're really adapted to sugars and carbs, and you go four or five hours without eating, it becomes a crisis like I got to eat now. It's what you typically observe and that's from a practical standpoint. That's an advantage that I like that I can eat breakfast in the morning and pretty much run all day. I might hit some Bulletproof coffee or tea even midday and just maybe some fats during the day and then I eat dinner at night. This is coming from someone who used to eat six meals a day when I was working out a lot and trying to power lift. I was eating as much as I could. I just feel so much better now and I feel my mental clarity is much better. I just feel healthier overall, eating this Bulletproof diet I would say. When you go the entire day without eating until dinner, do you ever snack? Dominic D'Agostino: Occasionally if I snack, it would be handful of macadamia nuts. I keep sardines that are packed in olive oil and lemon in my desk, so if I know my dinner's going to be late or if I had a really hard workout the previous day and I'm sore and I know my body needs some more nutrition, I will. I think what's important is that I feel like I don't need to eat. I feel that if I eat in the middle of the day, it's to just try to get in some extra calories to recover typically from a previous workout; or if I know the next day I'll be traveling 11
and won't get to eat as much, maybe I'll eat a little bit more. Maybe once or twice a week I'll eat in the middle of the day, but typically, I just rotate my meals about 12 hours apart, breakfast and dinner and that works really well. I didn't jump from that. I didn't jump from six meals to this. It was more of a gradual transition over time. Also with my schedule, sometimes it's kind of hard to eat during the day with meetings and being a scientist so it fits well with my lifestyle. Once someone puts their body into a state of ketosis, how long does it stay there without continuously feeding the ketones? Dominic D'Agostino: Yeah, that's a good question. It's a good question for kids and adults using it to manage seizures because if they go and have a candy bar, it can set them out of ketosis for 24 hours. Exogenous ketones could quickly put you right back in the ketosis in a matter of minutes. Therapeutically, that's a huge practical advantage. For someone using it just for performance advantage and they go out like I do occasionally, I'll just go out and have sushi; usually if I have sushi for dinner, my ketones will spike up because it starts using glucose and kind of sparing the ketones in a way like an hour or two after. Then ketones will quickly sharply fall down and in the morning, I'll be registering a zero. Either fasting or carbohydrate restriction the rest of the day will put me back in ketosis about 24 hours later. Obviously, you can just take some MCT or ketone supplementations the next day and stay right back into the 2- milliliter range, which I think is around ideal for the health benefits. Let's say I fall off the wagon and have a piece of cake during the day. Should I immediately go out and have some MCT oil to repair the damage and put myself right back into ketosis or what should I do? Dominic D'Agostino: It depends on why you're doing ketosis in the first place. I think you should assess how you feel. Each person is a unique 12
metabolic entity and I think they need to take it upon themselves through self- experimentation how they feel. In the beginning, if I had a little carbohydrates on a strict ketogenic diet, I actually felt better for hours after. Now, I think I may get a boost, but then my blood sugar gets rebounced back after it. My advice would be the meter is good; the blood glucose meter and the blood ketone meter is a good way. Try to take a measurement of your glucose and ketones when you feel great. Say, I feel great right now, so you look at your blood glucose and ketones and it's like where is that at. OK, my glucose is 72 and my ketones are 1.8. I'll repeatedly do that during times where I feel enhanced mental clarity or feel euphoric in some way. You'll find the numbers that are right for you and that's going to vary between certain individuals and that's kind of how I approached it. If I feel crummy and if I just feel hungry and irritable and there's other factors that can contribute to it, but I will have curiosity measure my glucose and ketones and it's usually far away from those numbers. The idea is to develop your own personalized strategy to get those numbers back. Essentially, it's taking a snapshot of the energy substrates that's in your blood and that plays a huge role in everything from appetite suppression to the way you think, to your motivation to want to go exercise. There's so many factors involved and we call that metabolomics. Our lab is actually doing more global metabolomics where we can take a sample of the blood or brain tissue in animals and look at 3,000 different metabolites. That gives us a snapshot of what's going on in our physiology at that point in time. We do it with and without ketones and whether the ketogenic diet or ketone supplementation. It also gives us some insight into metabolically how it's altering your physiology. That can be the future. If someone wants to biohack, metabolically biohack themselves, global metabolomics of your blood, you're looking at 3,000 different metabolites and then the analysis from 13
that could really give you some deep insight into how your body is handling. Over time, a keto adaptation is something that should probably be discussed, too. Over time, the longer you follow a ketogenic diet, the easier it generally gets and the more benefits you derive from it because your body can transport and utilize ketones to a higher degree over time. I'm talking about not just days to weeks but months to even years. I think even after a year, your body is doing epigenetics mechanisms because ketones have effects on gene transcription that over time your body is an enhanced metabolic state from the level of the mitochondria over time. That needs to be appreciated. I'm just adding that in there because it needs to be appreciated and put in the context. When someone said they tried the ketogenic diet and didn't work for me and I ask, "How long did you try it?" "It was about two or three weeks. I gave it a good shot." It's like no, that's about when the time when you really even just start to get a little bit of the benefits after two or three weeks. If I ask them if they measured ketones, many of them didn't. To really give nutritional ketosis a legitimate shot, you have to do it for a minimum I think of six weeks and then that's when exercise performance really comes back to baseline and then you can start making some inroads to personal records, I think, by maintaining it; depending on the kind of exercise you do of course. What are the long- term side effects of living in a state of ketosis? Dominic D'Agostino: We don't know fully but the literature that I go back to are kids that have used the ketogenic diet for decades to manage their drug- resistant seizures. Many of them are coming off drugs that have horrible side effects. They are naturally just healthier once they get on a ketogenic diet. Many follow this for a decade or more and you generally see no side effects if it's managed correctly, especially, for ketone savvy and dietician is formulating the diet and the parents are knowledgeable. Some things that may pop up over time, there's a greater incidents of kidney stones, maybe elevated uric acid levels, which could 14
contribute to gout later on, but that's kind of debatable. Also, an elevation of low- density lipoprotein, LDL cholesterol. The implications of high LDL cholesterol over time are not fully known. What is known from a general perspective is that you get an elevation of the larger particle LDL and not the smaller atherogenic LDL particles with the ketogenic diet. The LDL that's elevated, I guess you could say, is relatively benign and not of concern. If there is an elevation of cholesterol... usually you have an elevation of your good cholesterol, you HDL, usually it stays the same or most people it's elevated; but an elevation of the LDL cholesterol may be perceived as problematic and alarming to a physician that's treating the patient. They will urgently try to get them off the diet. I would say that the person should look at the fractions of LDL molecules and determine specifically what size LDL particles are elevated. Besides that, maybe weight loss, but weight loss is usually a good thing for most people. Again, if you're a cancer patient using this diet to manage cancer and you have Cachexia that could be a concern, at least the calorie restriction. They would just need to ensure that they're getting enough calories from the ketogenic diet. Nutritional ketosis as you may know inadvertently causes some calorie restriction because it can suppress your appetite over time. I think you may have to compensate for that if your BMI is low like under 19 or 20, you need to almost force yourself to eat. I like fatty acids so for me it's relatively easy and most people they could be trained to eat more. You mentioned kidney stones. For stone formers, if they want to be in a state of ketosis, is there a way to counteract the risk of developing more stones? Dominic D'Agostino: Yeah. Hydration is key. Ketosis may actually decrease your thirst so you need to counter that with proper mineral supplementation, potassium, sodium. Potassium in the form of potassium citrate is what's recommended for kids with epilepsy that follow that ketogenic diet. A potassium citrate supplement 15
ensuring that you get lots of sodium and minerals that helps you keep water in because it has a natriuretic effect so you will eliminate some excess sodium and a lot of people like that because you're not as bloated, your skin is tighter. Hydration and mineral supplementation and in particular, potassium citrate, especially if you're really deep in ketosis and you want to stay in ketosis. It'll offset the effects of the natriuretec and I guess mineral depleting effects of ketosis, especially initially. The first two weeks it's pretty significant and then your body adapts pretty incredibly over time to regulating its fluid and mineral balance, so this is more of a concern the first month or so and then over time you adapt naturally. Your physiology adapts. What does it mean to you personally to speak at the 2014 Bulletproof Biohacking Conference and to the work that you're doing? Dominic D'Agostino: That's a great question. Thank you for asking that. I'm really honored to be here and I'm really excited that Dave Asprey has an appreciation for nutritional ketosis. Not a lot of people do. Ketones are thought of as metabolic poison from the medical community. We know through our research and through self- experimentation and anecdotally that's not the case. I'm really thankful and grateful that I'm given a platform to talk about my research and to share this research with other people and to hear their feedback. I like to invite feedback on other things that I can do. It means a lot to me that I was invited to talk about my research here. I'm just excited to show everyone some preliminary data that I think will be very useful for the things that they're interested in, which is enhancing performance and cognitive resilience and performance. I just want to personally thank Dave for this opportunity and all the people behind the scenes who make it happen because I know it's more than one person behind this event. It's a lot of people working together to make this happen. I really appreciate that. 16
All right, Dominic, I know you've answered this before but we ask this of every guest. What are your top three recommendations for kicking ass at life and staying Bulletproof? Dominic D'Agostino: Yeah, that's right. He asks this question every time, right? I don't remember how I answered this before but I don't want to give the same answer. The top three... I think the first what I'm finding in my area of life is that you need balance. Above everything else, I know Dave is a go- go- go guy and all the people surrounding him are kind of go- go- go guys, that creative downtime is really important. I was just talking to some people that have achieved enormous things in their life and a number of them report back that they take an hour out of their time just to shut down. That creative downtime is extremely important. I think as you work your way up, the obligations and demand on your time becomes much more strained that even makes it more important to have that hour of creative downtown. I'm thinking like body, mind and spirit and that kind of gets to the heart of it, just that balance. Nutrition is that's what I study so I got to put that top of my list; that prioritized nutrition and if you're mind and your body are healthy, you can achieve greater things in life. One thing, I probably mentioned it before but it's becoming more important now is sleep. there's no way to biohack sleep. Maybe some are talking about here but you really need a good five to six hours of sleep at night. I've gone periods of time where I went two or three hours a night consecutively. I know in this world, people just try to get by less and less sleep. I think prioritizing not only the quantity of your sleep but also the quality. I think there's some technologies here that can help us do that. I think I'm really excited to see that so that's another enthusiastic reason why I'm here, I want to talk to people, so that would be my three, I think. Yeah. Creative downtime, nutrition and sleep. 17
Wonderful. Thank you so much, Dominic, for being here with us today. Dominic D'Agostino: Thanks for having me. I appreciate it. Dave: Have you heard about our new Brain Octane Oil? It goes far beyond upgraded MCT or any other coconut product for creating maximum cognitive function. This is about 4% of what's in coconut oil. It's 18 times stronger than coconut oil and it's what I put in my Bulletproof Coffee every single day. I use upgraded coffee beans, Brain Octane Oil. In my case, I can take two tablespoons of it but a lot of people would use much less than that and I put a couple of tablespoons of grass- fed butter in there, blend it, and have an amazing day. If you haven't felt the difference between upgraded MCT and Brain Octane Oil, you owe it to yourself to give it a shot. Featured Dominic D Agostino, Ph.D. Keto Nutrition University of South Florida, Molecular Pharmacology and Physiology Dominic D Agostino on Facebook Twitter @DominicDAgosti2 Resources Ketosis Ketone bodies What is a ketogenic diet? (The Charlie Foundation) Office of Navy Research 18
Oxygen toxicity Hypoglycemia (Mayo Clinic) beta- Hydroxybutyric acid Acetoacetate Refractory epilepsy (Johns Hopkins Medicine) Antioxidants and Free radicals (Rice University) Hippocrates The Father of Western Medicine The Charlie Foundation Caprylic acid Atkins diet Glucophage/Metformin National Institute of Health Defense Advanced Research Projects Agency (DARPA) Dr. Peter Attia Blood Glucose and Ketone Monitoring System Estrous cycle Metabolomics Epigenetics How Your Environment Hacks Your Genes For You Uric acid (Mayo Clinic) Gout (Mayo Clinic) Sizing Up LDL Cholesterol (Scientific American) HDL cholesterol (Mayo Clinic) Cachexia Natriuretic Bulletproof 2014 Bulletproof Biohackers Conference Dominic D Agostino is Mastering Ketosis Podcast #85 Brain Octane 19