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Dom D'Agostino

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2015-11-03
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2015-11-03
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  1. “Yeah, if you're ingesting it, the gut pretty much the gut in the liver, I think, probably are pretty greedy and take their share. I'm not sure how much glutamine you're actually getting to the muscles when you do that. But glutamine, I would say, is a conditionally essential amino acid. So under periods of high stress or catabolic physiological state, your body will use more glutamine. Glutamine is also an important amino acid for maintaining your immune system. So it plays I would say if you're deficient in glutamine, it can compromise your immune system. So you want to make sure that if your immune system is challenged, which it would be, you know, if you have cancer, if you're getting chemotherapy, if you're a burn patient, you're going to want, you might want glutamine. Although we want to work, we're testing a hypothesis.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  2. “A fairly high concentration relative to other amino acids, I guess I would say, by cancer cells. And we call that glutaminelysis. So cancer cells can use glucose, primarily glucose, but they can also use glutamine. And this is understood now and kind of well defined in the literature. But we know that glutamine I mean some formulas actually promote or hospitals will promote giving IV glutamine or oral glutamine to cancer patients that's not necessarily proven to be a bad thing but I think I was erring on the side of caution by removing the glutamine from the extend product at least for our studies. And we want to go back and do a parallel study with aglutamine actually to see and the IV glutamine.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  3. “Yeah, I should have described. So cancer cells kind of default to a metabolic phenotype called the Warburg effect, right? So they basically derive most of their energy from glucose metabolism and their biosynthetic processes as a tumor grows. It's using glucose for energy, but it's also using glucose to expand the biomass of the tumor. So it becomes the primary source of energy. And we knew this for some time, and that's sort of underlies the basis of using what's called a PET scan for imaging the location and the aggressiveness of a tumor in imaging, in FDG PET scan. So it basically shows sugar metabolism or glucose metabolism. Now investigators understand that the amino acid glutamine is also used”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  4. “Yes, it's short for science and innovation. So SCIVA TIN, right? Yeah, station. So been an incredible supporter of our cancer research program. So as you know, getting funding to do metabolic therapy research And it's actually the product that we're using in our cancer studies. So he asked me, he contacted me and wanted me to study this. And I looked at the formula and it had a high amount of glutamine in it. So I said, you know, I want to study this, but let's remove the glutamine and just do pure branch chain amino acids. I think he replaced the glutamine and put some taurine in it or whatever. And we started with that. And we added that because that's be”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  5. “My breakfast cooking. So that usually goes on in the morning. But yeah, my breakfast is always pretty much ketogenic. And if I have coffee, I do put butter in it and I put MCT powder in it on top of the butter. So it's very ketogenic. And the macronutrient ratio of my breakfast is always about 70 to 80% fat and with the balance being protein and a little bit of carbs from whatever green vegetables I have.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  6. “So that's what I had for breakfast. But before I eat breakfast, I always kind of drink water first and I take branch tea and amino acids with the ketone products that I just told you about. And that kind of gets energy to my brain like immediately. And I'm kind of really good to go after that. And usually, well, before that, I let my dog out and he just kind of goes crazy. So I kind of run around and watch him chase animals off our property. So it's always an entertaining thing while coffee's or I got water brewing for my coffee and I got my”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  7. “So, sardines are really good to travel with. They're my travel food too. So whenever my bag is packed, I usually have about a dozen cans of sardines packed in extra virgin olive oil. So I tend to just, I like them so much I eat them when I'm home too. So I have fish and eggs and some kind of green, usually asparagus, broccoli or spinach or kale. And if I make kale, I like to cook bacon and I cook the kale and the bacon grease. But I didn't do that this morning, but I'll probably do that tomorrow.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  8. “This morning I had eggs. I usually have four eggs and some kind of fish. I'm a big believer. I've kind of, I eat beef, but I've been phasing out beef and chicken and probably getting about two-thirds of my protein from fish. So I had eggs and fish in the form of sardines and a half of a can of oysters. I've been on this oyster kick for a while. Oysters, well, I mean, they're like a nutrition powerhouse, right? So are sardines. So I get the sardines packed in an olive oil. But they're really high in micronutrients like selenium, which are things that are maybe hard to get from other sources out there. But I think I just like the taste of them too.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  9. “Than you could otherwise get with any kind of MCT oil out there or anything out there. So I will bring that with me when I travel. So I'll be in Budapest and Belgium and a few other places along the way. And I will probably not be eating keto. I'll be eating low carb, but not keto. But I'll be cruising around at probably two to three millimolar, more or less off of a ketogenic diet, low carb, but not ketogenic.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  10. “Basically, I mean, you're approaching the potency of a ketone ester. The ketone esters will probably always be the most potent molecules out there. It'll be hard to touch that. But some of the more palatable ketone salt products that are being developed and tested now. We're working really hard to make them tolerable and palatable will be able to approach the potency of the esters that are developed for military applications, which I think is really exciting because they're going to taste, they're actually, you'll look forward to tasting them. They're that good. And they can put you into that mild ketosis range, that one to three millimolar independent of carbohydrate restriction or fasting. So you will have the ability to derive a lot of the benefits, whether it be health, longevity performance, of ketosis, of higher levels of ketosis.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  11. “And has some interesting properties in and of itself. But it allows you the powder increases tolerability, at least double or triples it. And so it allows you to kind of cruise along at an extra 2 millimolar and stay there. And then you could take that powder and then add some cana to it or some other ketone salt products that we're developing.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  12. “I do sometimes not all the time, sometimes I'll just take this straight MCT powder. It just kind of depends on my mood or whatever. But I always take MCTs are so versatile and they're so cheap and so readily available. Traveling with MCT oil is not really that good. So the powder is something that I've been testing and I really love it. powder the huge advantage of an MCT powder especially caprylic triglyceride is that with straight mct oil i'm running to the bathroom you know when i on an empty stomach or if i try to get my levels up to above one millimolar above whatever baseline i'm at whereas the mct powder that i'm working you know that's being formulated and tested is sort of spray dried with a probiotic fiber that's healthy for your micro”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  13. “Well, there's two that I kind of bring with me. One would be a MCT powder, and it's basically caprilic triglyceride, like a brain-octane, but a powdered form of it. And it's not on the market yet, but I just kind of have it. And I use the ketoquena product that's put out by keto sports. It's kind of the first thing I take when I get up. I drink a glass of water and then I take a small amount of ketones to bump me up to about one millimolar. And then I eat a ketogenic breakfast.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  14. “Be in that state because I just feel better generally in a moderate state of ketosis. But I think it's probably good too to have metabolic flexibility for your body to be able to use all sorts of food for energy. So going in and out of ketosis may be optimal, like to get your body in and out. And I do that from time to time depending on I'll be traveling, I'll be in Europe the next two or three weeks actually. So trying different foods. So I'll probably get out of ketosis. But I actually travel with ketone supplements too. I kind of cheat along the way.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  15. “Yeah, anecdotally, I would say yes. I mean, there's some memory going on here. Yeah, if you use ketone levels as kind of an index for this, like your body's ability to make ketones, it's definitely better. Like if you're on a ketogenic diet and you break ketosis and go eat sushi for a couple days and come back, I can get into ketosis real quick relative to the big learning curve I had when I started doing this. So I would say, yeah, I'm not sure we've studied it to that extent. I think you're referring to, but that brings up a good question, you know, because a lot of people want to go in and out of ketosis. Like, can I just use this intermittently? Can I eat ketogenic, but just throwing carbs during my workout? And people say, well, should I be on a ketogenic diet all the time? Should I always be in nutritional ketosis? And I tend to...”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  16. “during exercise. And I think that's what happened. So I think resting and just kind of being in a calm state and letting your sympathetic nervous system kind of chill out and having a good diving is a lot of mental preparation goes into diving. But I found that if I could just kind of calm my body down and if I'm in the state of nutritional ketosis, fasting ketosis, I could increase my breath hold time by like three times, like 300%. And that blows my mind. So I need to study this.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  17. “Weeks. So that's a pretty remarkable increase in the potential of utilizing ketones as an energy source. And I think some of the work by Jeff Bollock Just had an opportunity to visit him at Ohio State just last week, and he's done some remarkable work just showing between fat adapted athletes and carb adapted athletes. And they're both at elite levels. If you look at substrate utilization between these two groups, it's like night and day. I mean, even that the best carb adapted athletes, they're the ones that are using fat at the highest level are using much less fat than the fat adapted athletes, than the guys that are on the ketogenic diet. I mean, they're literally using about two to three times more fat.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  18. “And I think we build our transport and mechanisms of ketones with time. So it's called the monocarboxyl acid transporter, sort of the protein that gets the ketones across the membrane and allows cells to use it is upregulated over time. So the longer you're on a ketogenic diet, the more benefits you could potentially derive from it because your body is adapting to that state of ketosis by upregulating transporter mechanisms. And a few of my colleagues study this. And at least in a rodent model, in about takes about four weeks, and you could actually double the protein level, which the actual subunits of the proteins that are part of the transporter goes up about 50% when you transition an animal to a ketogenic diet for four.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  19. “But I'm a good ketone user too. So I would be if I'm sitting at my desk, so that's what I would kind of be registering. But if I got up and took a brisk walk around campus around my place or something, that would drop down to like two because I think their peripheral uptake of ketones would be higher. But I think you also have.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  20. “Yeah. So, yeah, if you look at his blog there, yeah, and I think the title is Jet Fuel, and you look at the oxygen consumption for a given work output. In his case, it was on a bike at 180 watts. He had roughly, you know, five to eight percent decrease in oxygen consumption for a given work output. So showing that your oxygen utilization was lower. And so your oxygen, your metabolic efficiency. So that's kind of the take home is that you can enhance, potentially enhance metabolic efficiency. So I can tell you that when I fasted for one week, I do a lot of snorkeling and a lot of diving and just kind of water sports. And out of curiosity, I was swimming around in the pool at my house, and I noticed I could stay under. Pretty intense ketosis allowed me to withstand levels of hypoxia.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  21. “Yeah, that's a really good question. And so our lab, in addition to looking at oxygen, we also look at what's called hypercapnia, which is high CO2 levels, because if you're in a spaceship that's headed to Mars or you're in a submarine, the level of CO2 that you're experiencing is about on an order of 10 times higher. So that's something that we're looking at. But when it comes to oxygen utilization, I guess one of the studies you could refer to is Peter Atia's blog, where we look at, we've kind of set the work. Peter took a ketone salt that we had and kind of a crude version of it. And I commend Peter for his bravery and downing this.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  22. “Two more animals for this group. And then it's like, oh, they could set you back a year and a half. Published study. So you always want to do that up front”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  23. “Yeah, it depends on your sample population, what kind of statistical power you have or the likelihood to that the study will detect an effect is the statistical power. And that you really have to sit down with a statistician and look at the probability of making a type 2 error or concluding that there's no effect. And I know just I took the basic stats class, but I still consult with a statistician when we're designing a study for a proposal or something like that. And you kind of, you need to run it by it. Because if you don't do it beforehand, the reviewers that are reviewing your paper, there's always that statistician that's part of the review committee who will ding you on it and be like, nope, we're not passing it. You got to go back and do.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  24. “The chemist that I got to make the product for me. So I had little tiny vials of it. And I was like, well, I was just kind of impatient. I was like, instead of getting enough to feed it for a week, I was like, let's just try to give it one dose and see what happens. And when it worked, it was just, we were just blown away. So we did like three or four rats and I was like, okay, I'm convinced completely unscientific, right? I mean, usually you got to do like in, you know, 12 and do stats and everything and do controls. But I was complete because we dove like four rats and they all went way beyond any other rat we've ever seen. So I was like, I have to move on this fast or someone's going to kind of take this idea or something. I was like, we got it. We got to move on this finding as fast as possible.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  25. “Yeah, yeah, that was the original idea for this was I got turned on to the ketogenic diet because it was used for drug-resistant seizures. And my program officer, I ran the idea by him and he didn't really like the idea of a diet per se. I mean, his attitude of the diet for performance has changed over the years, but he was like, well, let's, you know, why don't you kind of look into developing a ketogenic diet in a pill and see if that's even possible? So I spent, and that was like 2008. And then that kind of started my journey into seeing if this was possible. And when we tested it in our rat model, So it made sense I was actually thinking that, well, the original study of design was to feed ketone esters for a week and then dive them. But my source was only making like a little bit at a time.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  26. “Yeah, they're developed originally with that application in mind with sort of a defense application in mind, a military application. And that's how my project originally got started.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  27. “Fire, or you gotta die down the plan of mine on a bridge or a ship that's not always easy to do. So we develop these things for providing resilience and safety and performance.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  28. “Yeah, so there's definitely a stealth component to a closed circuit rebreather. If you're using it and you're in the middle of a pond, in the middle of the jungle and it's perfectly quiet, like you would not know the person's under there. Whereas if you're using standard scuba, you would see a bubble trail coming across the pond at you, you know, and you could just sit there patiently and wait till they come out and shoot them. So with a rebreather, there's a big advantage, a stealth component. The disadvantage is obviously, you know, if you go down to just 50 feet of seawater, you're at the risk of getting what's called oxygen toxicity seizures within like 15, 10 to 15 minutes just at 50 feet. So you have to stay very shallow, which is not always hard to do during a mission if you have helicopters over you and they can see you in the water.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  29. “For six, eight, 12 hours is ideal. And it depends on the molecule you're talking about. So that's kind of what we're doing now. We're kind of screening various compounds to figure out which ones have a favorable pharmacokinetic profile in isolation. And then we start combining them together so we can get formulas where we hit the ideal formula for a particular application. So a ketone ester, yeah, is a ketone that is orally active. So you can take it and it can increase blood ketone levels in the rat study that I was describing. They are quickly put into ketosis and then in that particular study we would dive them in a hyperbaric chamber and increase the pressure and the level of oxygen within the chamber so it would be it would simulate a navy seal diving down to”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  30. “A ketone with a wide range of things. You could use glycerol. We use something called 1-3-butane diol. And you can attach ketone molecules to this with a trans esterification reaction. And when it's ingested in the body, there's various enzymes. We have hydrolytic enzymes that will esterase is that will break off the ketone and you'll get when you ingest it orally, you will start to liberate the ketones from the molecule that it's esterfied with and these will build up in your blood. And the idea, right, is to have a molecule that slowly releases the ketones in a very predictable fashion where you get a nice pharmacocinetic profile, you know, where you have, you can take it orally and then within 10 to 15 minutes, you're in starvation ketosis and then you stay in ketosis.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  31. “Okay, so your body makes primarily two ketones that it uses for fuel, one is acetylacetate and another is beta hydroxybutyrate. And they're both kind of interchangeable and they're converted to one another in the body. Beta-hydroxybuty actually has to break down to acetylacetate to be used for energy. But the beta hydroxybutyrate tends to be the primary, the highest level primary ketone in our body just because it's more stable, but it does need to break down to acetylacetate. So a ketone ester is taking one of these acetylacetate or beta hydroxybutyrate or both and taking those molecules and attaching it to something with an ester bond that functions is like more or less a carrier to it. So you can ester phy.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  32. “Yeah, it is in our animal models and we think it is in humans right now. So we have some studies approved where we're going to be looking at that in humans, looking at the metabolic effects. But the first study that we did is a rat study where we did an acute feeding, it's kind of a gavage. So we kind of give them a bolus dose. And these are rats that are maintained on a high carbohydrate standard rodent chow. And they've never been in a state of ketosis before, you know, unless they were deprived of food or something, which is they probably weren't. So they've never really seen ketones before. And in this study that we did, we acutely gave them a ketone ester and within about 15 minutes. To 30 minutes, they achieved a level of ketosis that would take about seven days of fasting for a human. They were in the four to five millimolar range.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  33. “Optimized the therapeutic effects of the ketogenic diet and probably further augment the therapeutic efficacy if we're talking about the clinical realm and maybe further augmented.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  34. “I see it as not one or the other. I think the ketogenic diet actually goes pretty well with exogenous ketones, and one would not have to be on such a strict ketogenic diet because it is very restrictive. It is. And you could do like a modified Atkins, which is kind of the way I think we should eat anyway. I mean, just eliminating all processed carbohydrates and just, you know, protein, fat, veggies is kind of how I eat. And I pretty much always stay in a state of ketosis just by using MCTs a little bit of exogenous ketones here and there. And I think it would allow us to”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  35. “Yeah, where in the case of NSADs, if you dose them right after your workout, maybe those inflammatory mediators are linked to activating the signaling cascades that are responsible for the hypertrophy effect. So you could be negating that effect. But we have not shown that to be the case. Actually, I think you could get a lot of benefit.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  36. “So if you fast, and subjects that just kind of go cold turkey and fast within the first 24 hours, it's a stress response or cortisol level spikes. Your sympathetic nervous system is activated. Their immune system could be suppressed. And I think that if you were to do the same thing but use exogenous ketones, you would cruise into a state of nutritional ketosis or sustain nutritional ketosis without some of the bumps along the way. And I think that you could probably reap some of the performance benefits. And I think it maybe be, and then, but then you could make the argument that that stress, that physiological stress that you're giving yourself is, you know, you're familiar with the hormetic effect, that that stress could be kicking on. Mechanisms that when activated can kind of be protective in and of itself.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  37. “Yeah, you have glucose withdrawal. I mean, your brain goes through glucose withdrawal and it uses glucose to not only for energy, but to make neurotransmitters to your brain homeostasis is your glucose levels are basically telling your brain that it's happy. It's in a homeostatic state. So if you feed your body, your brain ketones, it is preserving more or less that neurophysiological homeostasis, I think, and you're not going to have maybe a stress reaction.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  38. “Yeah. I think there are significant advantages to speeding up the process as far as how you feel. And I think that if you transition from a state of using glucose as your primary energy source to using ketones, that usually involves a gap in fuel flow to your brain. So your brain pushes.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  39. “Resilience. I think there's some real world benefits to staying in that range. And you'd be hard pressed to find any potential adverse effects that could be linked to having ketones in that range. But once you get into five, six millimolar range, that produces a metabolic, a mild metabolic acidosis that needs to be compensated for through your kidneys. And so it is putting a stress. It's a substrate load to your system and your body's got to deal with that. So I think that needs to be taken into account.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  40. “Yeah, there's that, you know, you have post-exercise ketosis where guys that are on a high carb diet after four or five, six hours of intense exercise, they're going to deplete their liver glycogen and ramp up fatty acid oxidation so high they're naturally just going to be in ketosis. Their body is used to seeing ketones, you know, because of the exercise that they do. But generally, yeah, I mean, like moderate to mild ketosis is kind of what I like to promote for health and longevity, and that's between one and three millimolar. If you're within that range, that's a range that you'll pretty much never get into if you're not on a ketogenic diet or not fasting. And I think staying in that range has some real world benefits as far as health benefits, longevity benefits, performance.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  41. “Yeah, I think it's pretty rare to see over five millimolar. In kids, you know, with kids that have a disorder called glucose transporter type 1 deficiency syndrome, I'm touching”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  42. “Maybe it's kind of telling the body you're in a fasted state, so why don't you conserve the glucose that you have? And also a big dose of ketones could potentially cause a small release of insulin. And that's kind of how we regulate our endogenous ketone production is that if our ketone levels get too high, that ketone will cause a very tiny release of insulin from the pancreas and that will signal delivered a kind of turn down or turn off hepaticetogenesis. And it's a, you know, we have, when we're in a state of ketosis, we lose ketones through our urine. We burn them up through peripheral tissues. And if they get really high, we stimulate a small amount of insulin release.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  43. “So the ability, and we're interested in doing this, the ability to elevate, to produce an artificial state of ketosis is possible with exogenous ketones. And it mimics many effects of therapeutic fasting, which would be an acute and sustained reduction in blood glucose. And we don't really know why there's a remarkable decrease in blood glucose that the dose-dependent decrease, but it seems to do seems to be related to the liver's output of glucose. So your liver is a master regulator of your blood glucose, really. So the drug metformin In type 2 diabetics will decrease hepatic gluconeogenesis so the liver's ability to make glucose and put into the bloodstream. We think that ketones are doing this Also, and I think.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  44. “Yeah, so I think we can view exogenous ketones in energy containing substance, right? So you could potentially take them as a source of energy. Their energy that your liver only produces under certain circumstances of what's considered kind of strange metabolic physiology, like a fast state.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  45. “Can have the advantage of potentially giving the protein sparing anabolic properties of the agents without the side effects. So there's research going on, but I don't think it's moving as fast as what we had initially anticipated as far as them being super potent agents that would make anabolic steroids obsolete got it. They're not at that level yet, but there's quite a few pharmaceutical companies working on it, and agents are, there's studies going on right now. And I think that data will probably come out in the next couple years.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  46. “Yeah, okay. So SARMs are designed with the intention in mind to minimize the androgenic component down to nothing. That's really the goal. And I think they're pretty close to doing that. The problem is in the real world when you read about guys taking this for muscle building, they have very kind of minimal anabolic properties compared to their anabolic steroid counterparts or cousins. But the advantage is that if you have a guy with prostate cancer or all males, you know, probably get prostate cancer in time. So you can high testosterone could drive the growth of your prostate and prostate cancer. And anabolic steroids could obviously have major side effects for women. I mean, we see this in women's bodybuilding, right? We see the side effects are pretty real and pretty non-reversible. A selective angrogen receptor module”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  47. “Wasting diseases. Yeah, I mean, they can just look at the literature and you talk, if you talk to the physicians and the doctors that treat their patients that are familiar with these agents and know how to intelligently prescribe them and administer them, they will tell you that they save lives. And I think that application may be useful in cancer. But I think the SARMs are kind of an interesting compound that's coming out. And I think there's definitely some potential for some drugs out there.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  48. “If you administer testosterone and the studies have been done up to a certain point, once you get to about 300 milligrams per week, say, you start to increase systemic IGF1 levels. And if you go up to about 600 milligrams per week, which would put you at a supraphysiological level about twice or three times that of a normal male, at least. causes deliver to increase IGF1 release. So systemic IGF1 will go up. But a dosage of say 100 to 200 milligrams a week does not increase to my knowledge factors, hormones, growth factors that would cause cancer to grow and spread. And I think at that dosage, especially with a lot of Male cancer patients, that would have a pretty remarkable protein sparing effect. And we know that anabolic agents can be life-saving drugs for HIV patients. Absolutely.”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  49. “Specific androgen receptor modulators out there. They're called SARMS. And there's a few SARMs that are out there. They basically have their designed to have the anabolic tissue building potency of testosterone and other anabolic steroids without the androgenic or the hormone effects. And they are actually developed specifically for cancer cacaxia. There's a few out there. There's actually a few out there. And I think we're kind of interested in studying them. We're looking at branch chain amino acids right now, which we think are pretty important too. But if you give so testosterone, for example, and a lot of males take testosterone to build muscle in the gym for hormone replacement therapy,”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT

  50. “Well, I think it's a little outside of mainstream cancer kind of world that I'm linked in with, but I think it should be. And I think we want to develop a pretty solid program here in our lab to look into this. When it comes to anabolic agents, I think you go to the literature and it shows that anabolic steroids do not promote within certain dosing levels. They do not promote the growth and the spread of cancer. Pretty sure the literature says that there are”

    2015-11-03 · The Tim Ferriss Show · #117: Dom D'Agostino on Fasting, Ketosis, and The End of Cancer · IDENTIFIED FROM THE TRANSCRIPT