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Dom D'Agostino

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181
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2015-11-03
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2015-11-03
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  1. “I think that's not really being studied much. There's not a whole lot of investigators out there studying this. And I've been in touch with a lot of patients. And I realized that this is key. I think a lot of patients would be alive today if we had effective ways to mitigate. Because once they lose their mobility, once they get weak enough where they just can't move around, I mean, their whole psychology just deteriorates. Yeah, so there's a lot of reasons that we should be looking into keeping patients as strong and preserving their muscle as much 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

  2. “Destructive agent to lean body mass on top of inactivity, so being immobilized. So you have age-related sarcopenia, cancer gaxia, chemoinduced gexia, and this typically you have a patient that's bedridden, so they're not stimulating their muscle with activity. So you have four factors coming together that cause a perfect storm for you to just kind of waste away. And patients can go down so fast when they're put in that situation. So I think, so we're developing protocols to nutritional, you know, nutritional ketosis. We're looking at branch chain amino acid formulas, and we want to do some work with to define specifically what types of exercise can mitigate all these factors and maybe some drugs and stuff too we're interested in testing. So, yeah.”

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

  3. “Oh no, that's great. So you're in a state where you're basically wasting lean body mass. You're wasting tissue. And a lot of cancer patients succumb to cancer cachexia and its mortality is closely, intimately related to that. So as you lose lean body mass from being in a state, say for example, if someone has advanced metastatic cancer, that they will, their survival will be tightly correlated with that, the ability to preserve their lean body mass and maintain their function. In a lot of situations you get this situation where you have an older patient that gets cancer, like 70 year old and you have age-related sarcopenia, right? They're already losing muscle, compounded with cancer. which increases lean body mass loss due to the pathology on top of chemo induced kakexia. So chemotherapy is a pretty powerful”

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

  4. “Yeah, so Kexia would be defined as actually investigators are trying to get a clear definition of it and understanding of it, which our lab, I have one of my students who just studies cancer cachia. Kakexia is defined as in cancer as you're in a physiological state where your body is releasing factors like tumor necrosis factor alpha and inflammatory cytokines that inflammatory mediators that are catabolizing your muscle tissue, your lean body mass.”

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

  5. “Wasting, you'd want to do it in a very cautious way. But I definitely think this is something that should be implemented in our oncology wards, that fasting before chemo definitely has some real benefits that we should be utilizing.”

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

  6. “Body mass index Yeah, that would make her kind of a little pudgy, I guess, and have some extra weight to lose. We know that getting chemo in a fasted state, there's a couple reports out there showing that it could sensitizes. It can sensitize the tumor to the therapeutic fests of the agents and also there's some evidence showing that it could prevent some of the side effects associated with chemotherapeutic agents, specifically things that cause cell damage. So being in a state of fasting ketosis can sensitize the tumor to the damaging effects of the chemo and enhance your healthy cells resistance against the toxic effects of the chemotherapeutic agent. So that's, and you'd want to do it. I think, you know, the majority of patients could probably do it, but if you have someone with severe cancer cachexia, muscle”

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

  7. “Yeah, and you know, fasting has to be done under, you have to know your body, right? And fasting should probably be done under a pretty strict medical supervision to some extent. Yeah, so someone would have to do a little research on it. And it would depend on the particular person. So if you have a cancer patient that it's a woman with breast cancer, say, and she has a BMI of 28, you know, and going in for chemo, I think it's a good idea for them to fast before they go in.”

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

  8. “Yeah, histone deacetylase inhibitor. So HDAC would be HDAC And then there's class one, two, three, I think four. So class one and two HSTAC inhibitors are a big, big are of big interest to the pharmaceutical industry. So there are many, for example, we do a lot of cancer research. There's a lot of pharmaceutical companies focusing on histone diacetylase inhibitors for as targeting specific pathways for cancer therapy. So you have an endogenous HDAC inhibitor with beta hydroxyrates.”

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

  9. “Actually, did it at Yale, I developed the diet for them and sent it up to them as exogenous ketone. But the paper demonstrated that it activated or prevented the activation of a particular inflammasome that's linked to age-related chronic diseases. So it inhibited a specific inflammatory pathway that is really associated with all chronic age-related diseases. And it was independent of the ketone's effect on metabolism. So they teased out, they did a lot of studies to tease out the mechanism and demonstrated that the effect of it suppressing inflammatory pathway was completely independent of its metabolic effect. So we understand that When I got into this, I just knew that ketones were an energy metabolite. So now we know it's much more than a metabolite. It's an HDAC inhibitor.”

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

  10. “Well, there was a science paper showing that beta hydroxybutyrate is an HDAC, class one and class two inhibitor and can activate genes that play a role in enhancing endogenous antioxidant mechanisms, specifically superoxide dismutase and catalase. So these mechanisms, when they're upregulated, it confers protection against the environment. It sort of enhances our cellular defense mechanisms. It enhances the robust kind of protective mechanisms that the cell has that can preserve the genome stability. So maybe being in a state of ketosis and maintaining that can protect your DNA from damage. So that's the implications. Also anti-inflammatory. So we published a paper, our”

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

  11. “Yeah, yeah. And maybe ketones could be the fourth macronutrient, maybe, if you talk about exogenous ketones. So a ketogenic diet has a macronutrient ratio that mimics the metabolic physiology that you have when you're fasting. So if you were to take the blood out of someone, you know, do a blood sample of someone on a strict ketogenic diet, it would look like they're fasting. They've been fasting a few days. And it's that allows you to get some, that changes your physiology incredibly.”

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

  12. “But fasting is the fastest way to get into ketosis. And that's why if you have a child with drug resistant seizures and their administered or they're admitted into a place like Johns Hopkins, the old protocol was to fast them. They're not exactly sure if that's absolutely necessary with things like more with ketogenic diets have MCTs and stuff, but you can, fasting is classically been the fastest way to get into ketosis. So the ketogenic diet has a macronutrient ratio that's high in fat, typically 90 to 50, and by macronutrients.”

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

  13. “And get inside cells into the mitochondria. And as we fast within about 24 to 48 hours, we'll start registering ketones to the level that clinically is defined as being in ketosis. I was going to ask you about 0.5 millimolar typically. Yeah, so a person on a high carb diet would probably take about 24 to 48 hours to start even getting into mild ketosis.”

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

  14. “Mobilize and use up our stored glycogen, mostly in the liver. And our central nervous system more or less demands that we have a steady fuel supply to our brain. And in the absence of glucose availability, we'll be depleting our liver glycogen. The insulin levels will be suppressed and we'll start mobilizing fatty acids for fuel. Long chain fatty acids don't cross the blood brain barrier very efficiently. So the liver while you're suppressing the hormone insulin, you'll upregulate beta oxidation of fatty acids in the liver and an accumulation of products from fatty acid oxidation will start forming ketone bodies. And these ketone bodies are, they're more or less like water-soluble fat molecules, and they're small molecules that can readily cross the blood brain barrier.”

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

  15. “Your caloric intake. If you have a surplus amount of calories, you're more likely to push insulin up and drive anabolic processes. But a lot of times people, when they follow ketogenic diet, because ketones have a really good appetite suppressant effect that they will inadvertently restrict calories and may not even know it after a while and may be losing weight without even trying. And that's, I mean, that's one of the benefits, I guess you could say, of the Kijicheng diet. You can lose weight and you can alter your body composition without necessarily even trying. Just through the appetite suppressing effect.”

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

  16. “Be pretty hard. I mean, kids do it. Their growth rates are a little bit less with these kids that have drug-resistant seizures when they're put on the diet. But if you simply just do what's called a modified Atkins, and there's a lot of literature coming out now on the modified Atkins, Eric Kossoff at Johns Hopkins, he's a colleague of mine and more in the clinical realm, and he's done a lot of work showing that a modified Atkins, which is about 70% fat in like 20 or 30% protein, has the same sort of ability to metabolically manage seizures. And I think that sort of diet can be used pretty successfully in the performance world and specifically for bodybuilders. I think with that amount of protein, you would be able to grow muscle for sure. And it's calories too, right? I mean, calories are the driver.”

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

  17. “If you're trying to preserve or even increase your performance and strength and alter your body composition. So if I don't think the ketogenic diet is ideal if your goal is maximum a purely ketogenic diet. I think there's different, we have to kind of figure out what ketogenic diet we're talking about. But I don't think a purely ketogenic diet as it's kind of described in the literature, right? And 90 or 85% fat diet is an ideal diet for growth and repair. The diet that we use in our study is actually a little higher in protein, like 25% protein, which is really almost double that used by the Johns Hopkins group that developed the classical ketogenic diet. And it's really that protein level is important. So growing on a classic ketogenic diet would pretty...”

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

  18. “Going back to your question, as it relates to being on a ketogenic diet, we know that ketones are anticatabolic. That's why we can fast for 40 days. And the ketones have an anticatabolic protein sparing effect. And if our blood is flooded with ketones, we're less likely to liberate gluconiogenic amino acids from our skeletal muscle for fuel because the ketones can more or less replace glucose as the primary energy substrate to maintain your central nervous system, which is 3% of our body by weight but sucks up like 20 or 25% of the energy. It's a big metabolic engine. So the ketones kind of drive a lot of that substrate energy need. So in a situation where you're at a caloric deficit, I think that's where ketones can shine. If you're trying to make weight.”

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

  19. “Advanced lifters who've been at it for like 10 years may have a different response to a ketogenic diet than say a 15-year-old kid who's trying to bulk up for football. He would probably not be a good candidate for the ketogenic diet. Your sensitivity to things like IGF1 and insulin are much higher when you're younger and your teenage years especially. So you could compromise a lot of your potential development and strength if you're younger and doing that. But say guys the older we get, the less carbohydrate tolerant we get. So we lose our ability to kind of process carbs as we get older and our insulin sensitivity declines.”

    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 there's insulin and insulin signaling, right? Certain diet, like when you calorie restrict a rodent or even humans or any mammal, you will enhance insulin sensitivity, right? So you will be more sensitive to a given amount of insulin. And I think we're seeing...”

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

  21. “In a human performance laboratory. And everything was recorded. The volume was controlled. All the parameters were controlled. Blood work was done. And the take-home on it was that strength, you know, body composition, or I would say strength and performance were maintained and increased, and there was muscle hypertrophy was seen with a ketogenic diet. And there was similar increases in power, in hypertrophy. And the big difference was kind of the overall body composition was more favorable in the ketogenic diet group, meaning they had similar increases in lean body mass, but they lost proportionally more fat. And that's the study that we completed. It's under review right now. The first journal kicked it back, so we went in for another journal. And did some follow up work with it.”

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

  22. “Yeah. So the gist of that is that we did a parallel, the control group was on a Western diet, which is pretty similar to kind of moderate protein higher in carbohydrates and moderate fat. And the ketogenic diet had roughly 75 to 80% fat restricted carbohydrates to about 20 to 20 grams per day. And the fat was also supplemented to some extent with MCT oil and coconut oil. And all the subjects, it was two weeks they had to be on the diet and had to confirm ketone levels by blood and urine. And once they did, we only did a two-week adaptation, which is kind of another subject we could talk about, but they adapted for two weeks and then kind of trained the heck out of them. And every workout was done in the lab.”

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

  23. “And yeah, I'll give you kind of like the synopsis of it. So we had 12 subjects, and these were advanced resistance trained individuals, meaning that they could squat in deadlift and bench a certain percentage of their body weight, which is kind of puts them in the range of, you know, the top 10% of lifters out there. I got to go back. It was some funky number, not like, you know, 185% or 75% of their body weight squatting for 7 reps or eight reps or something like that. So it would be like me, let me see, squatting for. 25 or something for a set of six or something like that. Yeah, these”

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

  24. “Very fast, yeah. Like two or three weeks, and other IRBs, I think I did one, a pharmacokinetic study for ketone esters, which I'll probably talk more about later, but that one, I think it's been rejected somewhere about seven or eight times. And I mean, it's just giving it as a single dose, kind of more or less a bioidentical molecule that our body makes and the committee is just because it's quote unquote first inhuman, you know, it's very difficult. And this is an outside IRB, which is less restrictive in many cases. So they can be a big hurdle to an investigator.”

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

  25. “Yes, the institutional review board that will review kind of the ethics and the safety of a study before signing off on it, essentially, and allowing. It's a committee of people that have kind of a broad range of expertise and they review the reason why the study is going to be done, the methodology, the ethics, the purpose and all that stuff, and approve whether or not the study can be conducted. And it really depends on what institute you're at. You can use an outside IRB that's outside of the institution and companies do that, industry does that, but they can be a big hurdle. And I found vastly different IRBs. You know, there's a small... College about 10, 15 minutes from here that ran a ketogenic diet study in advanced lifters for us. And the IRB was approven like two weeks at University of Fast.”

    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, that's good. You know, I serve on the university Institute for Animal Care and Use committee. It's called Aya Cook. It's like the animal IRB. And yeah, the committee has like a reactionary response to anything under a 25% calorie restriction. And if they lose more than 20, 25% of their weight for a fat rodent, really, that's not much you have to do that anymore. You got to refeed them. So yeah, I am amazed that some of the stuff got approved. I think the IRB was probably on vacation or something. The IRB is a little different now.”

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

  27. “This was two thousand ten. I think going into 2009 into 2010. So I'd been into this area of research for about a year or so in 2009. I really started getting research funding to do what I'm doing now.”

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

  28. “Research at Harvard Medical School, and he did a fascinating study that really, where he fasted people for 40 days, actually. And I've delved into the literature studying that. Well, I thought, well, I can do seven days if these study subjects were IRB approved in six months. So, yeah, I did that. And I found, you know, the first three days were a little tough. And then I started cruising along. But at day five and seven, I was feeling my energy level was taken a dip for sure, but I was amazingly resilient. being in a state of fasting ketosis and i was firmly convinced that uh and this is when i just started kind of studying this field so i was doing a lot of blood work on myself too to figure out what was happening”

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

  29. “I imagine you get a range of responses from that. Oh, okay. So you've talked to Peter Atia. He's filled you in on that. Yeah. So I guess going back when I really got interested in fasting, I did a seven-day fast and it just happened to conclude right before I had to give a lecture kind of on the topic. And I went into it with my glucose in the mid maybe 30s, low 40s and my ketones up there at about 5 millimolar or so. And then I did go to the gym. Yeah, I deadlifted 500 for 10 and I finished off with a one rep of 585 six blades. So that's, I haven't done that since. I haven't done anything that extreme since, but I just felt like I was inspired by George Cahill. He was a real”

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

  30. “I kind of go into describing how I study integrative metabolic regulation and how what we eat or certain supplements can change our metabolic physiology to treat, prevent disease, or enhance performance. It kind of sums up, yeah.”

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

  31. “Well, it depends on who it is, but I tell them I try to brief as possible. I just say I'm a scientist and I study nutritional neuroscience, I think is kind of how I like to phrase it as concisely 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