Ray Cronise on Cold Thermogenesis, Intermittent Fasting, Weight Loss & Healthspan
Posted on May 4th 2016 (about 3 years)
Dr. Rhonda Patrick speaks with Ray Cronise, a former NASA material scientist and co-founder of zero gravity, a company that offers weightless parabolic flights to consumers and researchers. In this episode, coming at the tail end of a rather extreme 23-day water fast for Ray, we discuss, perhaps unsurprisingly, some of the benefits that are associated with fasting! Ray talks about shifting one's perspective from looking at nutrition only through the lens of meeting day-to-day nutritional needs, and instead, also considering optimizing metabolism for longer-term effects as well, the importance of thinking about longevity in the context of functional healthspan, some of the similarities between the body’s physiological response to heat stress, cold stress, and exercise and so much more."We used to eat to support our activity because food was rare. And today, we're active to support our eating. And the more simple thing is you can't out exercise your mouth. It's impossible. You can swallow way more than you can move." - Ray Cronise Click To Tweet
- Bruce Ames - episode with Dr. Ames
- Luigi Fontana
- Penn Jillette
- Richard Ross
- Scott Parazynski
- Tim Ferriss - episode with Tim Ferriss
- Valter Longo - episode with Valter Longo
Learn more about Ray Cronise
Rhonda: Hello, everyone, today I'm sitting with my friend Ray Cronise. Ray is a former NASA scientist and he is the co-founder of Zero Gravity. Ray is known for popularizing using mild cold stress as a tool for weight loss. And he recently did something completely crazy. He has just completed a 21-day medically-supervised water fast. So, what's up, Ray? How's it going?
Ray: Well, technically, I'm not done because I still haven't eaten. This is day 23. I did some other tests at the end, but hopefully tomorrow or maybe the next day. So I feel so good. I don't know if I ever have to eat again, right? This is dietary restriction, right?
Rhonda: Like, to the extreme, I mean, this is...
Ray: To the extreme... Yeah, and you know, there's a lot of misconceptions. People believe that it's much more draconian than it is. And it is socially extreme but it's probably not biologically extreme. You know, we can imagine that in our evolutionary past, there are periods of days or weeks that we didn't have food and the fact that I feel perfectly normal, that we had some conversations earlier there are some things that slowed down a little bit. It's not like you can do everything and words don't come exactly as quickly, but for the most part, it doesn't feel any different than day 1.
And I think one of the reasons I adapt so quickly is because I mostly lived a dietary restriction lifestyle when I'm not doing this. But, anyway, it's interesting that you don't feel hunger, I don't have headaches, I don't feel tired, you know. I just feel like normal me. It's just that food just isn't on the thing to do. So, for us Type As that love to do stuff, you just work and do your thing and you don't have to stop to eat.
Rhonda: What instigated you just to try out not eating for 21 days and what's your...
Ray: Yeah. So, going back part of my own personal problems was I had gained 80 pounds during the time period of when I was at NASA and leaving NASA and the company I had between there for about eight years. And, yeah, I was type 2 diabetic, basically, I had high cholesterol, I had issues.
I lost my weight doing the cold stress and everybody has read my story on that. You know, it's in Tim Ferriss' 4-Hour Body and TedMed Talk out there. But even when I lost weight, all those things still didn't fit. So, I actually had to start looking into diet and I was exercising and I was doing the sort of a body-life plan, six meals a day, cardio alternating with upper and lower body six workouts a week. So, it wasn't like I wasn't doing what they said, but it didn't fix the problems I had.
So, as I started digging deeper, about that time the bow wave of press came with Tim's book and, of course, everybody looked at ice baths because Tim, in a chapter, his self-limits that he put in are all about ice baths. And of course, that's not what I was doing. I did some extreme stuff in the beginning to sort of understand, but I wasn't focused on the ice baths. I was focused on just exposing body to mild cold all the time. You know, I used to say, "Gloves before sweater makes you look better." You know, just always making your body burn just a little bit more calories.
And so, in doing that and getting out there, everybody threw the BS flag. They're like, "You really didn't lose weight that way. The cold you burn more calories." They used to say, and you can find these articles, they used to say, "You burn more calories getting hot." And that's just simply not true. But then, it was said. And so, then started the myths.
And because of the blog and people having questions, and I constantly get inundated with protein, carbs and fat, I want to know how the calorie works. So, fast forward a couple of years, I bought an indirect calorimeter. I had it in the lab, built next to my kitchen. And I just started repeating all the classical experiments. Well, there's this whole body of literature that was done on fasting and it's fascinating.
And, not only as a medical modality that they were actually getting better. Things that get better at the facility on here. People are lowering their blood pressure dramatically, dealing with diabetes, dealing with eczema. You know, I had a guy who is a sweet mate, Hunro [SP], from South Africa that was with me for couple... You know, he was fasting. He was there for a couple of days. He's gone back, but fixed his eczema completely. So, the idea that there's something there that the body when it gets in this really restrictive mode, starts to repair things. That's not so farfetched.
Rhonda: No, it's been shown.
Ray: But it's so long ago. And how do you sell it? Like, people say, "Well how do you sell sitting in a room drinking water?" You know, it sounds crazy. But I think it's something we really need to be ranked at science. I think we need to look at the intersection of this.
So, starting last year, I did a series of experiments where I was changing my diet over a 6-week period. And what I was able to demonstrate is that I was actually able to lose body fat at about the same rate as when I was water fasting, which to me is pretty neat. You know, by just doing some simple changes, that's the kind of thing I used when Penn Jillette lost his weight.
But the point is that in seeing that I could function on so little, it seems like the basis where we start, where your stuff then picks up, which is, "Okay, we get down to this, basically, we're not overly nourished now, what things do we need to deal with? What other kinds of supplements? What kind of things we need so that we don't get the the dietary restriction without malnutrition? How do we add that back? And now, having experienced it, it seems like something that I think will be a part of my lifestyle for the rest of my life.
Rhonda: So, you getting to this dietary restriction without malnutrition, we have a lot to talk about with dietary restriction and its effects on the human physiology. But did you supplement with anything? Was this like, so this 21-day fast were there any vitamin, mineral supplements, like, along with that?
Ray: No, and that's the surprising thing. I'll show you my nutrient panel. Even lasting with 14 days, my vitamin D went up, it didn't go down because I was in sunny California, lying in the sun, that was beautiful. I wasn't deficient in anything. All my blood panels turned out normal. On day 7, I did around the clock amino acid panel, where I did all the amino acids in there, several metabolites that are in there. And of course, they tracked with the circadian day, just like you've talked about. They're not something that are fixed. This idea that we're eating protein and it's pumping in our bloods. It's always there. But they do cycle with the day.
Of course, things like alanine, which is mainly used for the gluconeogenesis, it went through the roof, lipids go through the roof. So, there's some changes, certainly some physiological changes, but I wasn't deficient in anything.
The idea that we have to have nutrition every day and this balanced meal, that's one of the things that I really want to challenge because I do think we need a comprehensive nutrient adequacy across the spectrum. It is probably measured in days or weeks, not every single day.
Rhonda: Yeah. So, in terms of, like, the micronutrients and certain micronutrients that are needed you're talking about B vitamins, vitamin K, selenium, zinc, magnesium, the question still remains, like, what is an adequate level because a lot of the RDAs that are set are set on, based off of animal studies that have been that have shown that deficiency can cause death. And so, like, the couple standard deviations above that are what are considered what you need.
But the question is, and this something that my mentor Bruce Ames has proposed and put out there and I know that you're familiar with, it's something that he calls Triage Theory. And that is, well, there's all these enzymes and proteins that require some of these micronutrients as cofactors that are not essential for short-term survival. So, if you're deficient in it, it doesn't matter right now because it's not needed right now. It's needed for a long-term survival, it's needed to repair damage that's constantly happening. It's needed to prevent things like cancer, Alzheimer's disease.
So, the question of deficiency in and of itself, I think, needs to be challenged. I think we don't really know how much of these certain micronutrients we need to make sure DNA repair enzymes are still working, to make sure our tumor-suppressor genes are working, to make sure that all our antioxidants are... You know all these pathways that need these micronutrients are getting their cofactors that they need to work optimally or to at least be working as we're aging. So, I think that's... If we look at something like a blood panel, I mean, "Well, we're not deficient." Based on what? Based on the short-term functions because we don't know, right?
Ray: Well, yeah, but at the same time, we also don't the consequences of over nutrition. You know, we get a massive excess of a biologically active compound in levels that we would never would have seen in nature. And we've seen it with vitamin E, we've seen it in vitamin D, we've seen it in some of the other ones. So, the question is here first if we stop thinking about our diet as a daily thing and start thinking it as a lifetime thing, then things change because there may be things that are very much something you do. I mean, you guys are in prime reproduction time.
So, to get fecundity to go up and be more fecund, we want to increase essential amino acids. We know that things like methionine, whatever, increase fecundity. At the same time, where I am, which I'm done with that process at 51 that I want to make sure that have longevity. And they're also negatively associated with longevity.
So what I feel like where we are right now, the science and things we can be doing in the next decade, is taking this body of knowledge and yes, we can start peeling the onion more and more and more mechanistically. And now, we've spread that to all the blogs and they're peeling the onion. But every now and then, they cut off and forget half of it. They just sort of put these technical words out there. But how do we bring it back that look at something more comprehensive? How do we look at healthspan, you know?
Before we lengthen life, we need to lengthen healthspan. And I'm saying that if we look at...if I'm not deficient... The average person thinks if they go without a meal, their metabolism is going to to crush, for example, right? And this will be... We'll finish with the micronutrients but we'll go to the macro level. But if they think that by skipping a meal something's going to happen or by somehow not including some food group or something in every single meal that somehow, they're going to be deficient. You know, the ubiquitous the evil words I've told you before: protein, carb, and fat. I hate them. If you get on my blog, you'll see why.
But no one's going to be deficient in protein, really. And if they're going to be deficient, it's going to be one of nine essential amino acids. We know what they are. We've studied them quite a bit. And the fact of the matter is that for the average person out there, we also know that those nine happen to be connected to longevity too. And no one is looking at that part.
So, my point is looking at this as a spectrum. So, originally, we looked at diet because of the economics of food and the scarcity of food. If you don't have enough, it's great that every single thing meets a certain minimum, right? So, when these rules of eating were developed, and we can look at some of those later because I have all of those USDA guidelines from the turn of the century, which are just fascinating. Because they actually said why they did it and today, they have different reasons but they say the same thing. And that's kind of spooky to think about. We've made up new reasons for the same explanations.
But anyway, if you look at what they said, if you think about the average person is spending 60% of their income on food. And when you're at a situation where you have a limited, if you look at this as a budget thing, more people may relate to it. If you're in a budget, and you're barely making off each month, every dollar counts. But the value of $100 to me and a billionaire, it's still a $100. So, the point is that every dollar counts the closer you get to what you're meeting your needs are.
So, this idea of balanced meals, and balanced diets, and balanced nutrition, always being deficient came at a time when people really were deficient. Deficient, deficient, deficient...enough to see the diseases that we've identified. Now, what you're saying...
Rhonda: Their gums were falling out because they're getting scurvy.
Ray: Right. Yeah, and where you're at and I am too is... Okay, now, in addition to that, not necessarily what we are deficient in, if I change the language and say, "What more can we get at the micronutrient types, the..."
Rhonda: What do you need?
Ray: ...all the phytochemicals to maximize and optimize our longevity. You know, there isn't any perfect diet. We're not designed to eat anything. We can eat everything and that's why we're spread everywhere. But I think, somehow, this construct of food, and the construct of the balanced meal, and the construct that it happens in a single setting versus spread out over days or weeks, where I think the body is... It's much more rational to me to think that the body deals with it several days and weeks and doesn't become deficient instantly. I think that's where the attention needs to focus.
And there's really no money right now to be made in that. I can't sell somebody something. I can't sell them more supplements. I can't sell them more trainings. I can't sell them more exercise. And so, it's kind of a trap. But I think there's people like you and I, and some of the collaborators I'm working with and yours too, that's just intellectually curious about it. But we need to bring it back to whole food, we got to bring it back to foods that... What can we get out of what we have? And then, what's leftover to supplement.
Rhonda: Right. So, you were eluding a little bit to some of the studies on dietary restriction and I think it's important a lot... In science, dietary restriction doesn't refer to the extreme type of restriction that you just underwent.
Ray: Yeah. Can I make...real quick... Let me explain how I tell people about this because before I started doing this research, the way I saw it was overnutrition, too much, normal diet, deficient, undernutrition. That's what was in my head. As I began to read, a lot of that dietary restriction without malnutrition work and I'm now always at the end, what I realize is probably, what's more a thing is there's overnutrition, which is actually a small bar because in nature, it's really hard to do that.
Rhonda: But how do you separate overnutrition from giving people getting too much of your amino acids, too much of fatty acids, too much glucose without getting the micronutrients.
Ray: Right, but let me talk the big... At the big block level first, overnutrition is a sort of a small little thing because in nature you don't really have it. Normal nutrition is what we would normally, in a normal healthy person would eat there. But then there's this all diet restricted without malnourishment, which I would say is a big block because that's human survival. We have to be able to survive periods of this up and down with nutrition. And that's a big block.
And interestingly, the things you and I are most interested in, the micronutrients, which are all coming from these leafy green plants, are actually abundant. You don't get much calories from them, but you can find them all the time. And then when they're stressed, xenohormesis, they may be actually given us even more. So, you got that... And there's undernutrition.
When I added this extra block and said, "You know, I call it the survival block." That block is a place where we likely lived and we likely survived, not optimally we don't have parasites. We don't have infectious disease. We don't have the things they were battling. So, we can, maybe, leverage that to live longer.
So, now, back to what you were saying. I think we that we don't know. I don't know that we know where that upper limit is. But I know that, from a calorie perspective, and I hate to use that word too, because it's misused a lot... And then there's people that even question and we can talk about that in a minute. But we certainly are overnourished from just the calorie-density perspective. You know, we are.
And this is disease of affluence. We have so much disease of affluence. You can go to countries that don't have access and they don't get the same disease. They get the wealth in China, India, and then, they come with it.
Rhonda: What's so interesting is that, and ironic, is that at the same time that we're overnourished, we are, according to a lot these NHANES studies coming out, we are getting inadequate levels of many of these micronutrients. Think, if you're over nourishing yourself that you would then would have adequate levels of these micronutrients. But the thing is, people are eating the wrong food. They're eating the wrong foods and so they're not getting all their folates, vitamin K, selenium. They're not getting all these important micronutrients and yet, they're getting, a lot of fatty acids, amino acids. They're getting a lot of the macronutrients that people like to call them.
Ray: Macro, that's right. yeah.
Rhonda: And it is a big problem, you know...
Ray: Yeah. And what we try to do to address it and we've got a series of papers coming out, but the metabolic winter hypothesis is already there. And the food triangle, one of the reason we do it... Because first of all, ideology aside, this sort of eat meat, don't eat meat debate is boring to me and I never even go there. You know, we've talked about it that night, it's just gets to be old. So, this isn't a...it's not that.
But it turns out, animals are biologically very similar from a...that's why we use them for models. They've everything. And plants, are very fundamentally simple. And it just so happens, mostly, the energy that you get from animals is mostly fat. And the energy you get from plants is mostly dietary carbohydrate, and I won't say carbohydrate again, except for nuts, and seeds, and avocados, and things like that, that have significant amount fats.
But when we look at it and draw this food triangle, what we put at the top were the leafy greens, the cruciferous vegetables, stems like celery and asparagus, mushrooms, and bulbs, which is what? The vast majority of what you eat every day should come from the top of this thing. If you eat the majority of this food, the volume of food, if you just eat the volume of food...
Now, you have a choice. If you eat on the left side, which will be kind of a Paleo Diet, you can maintain your weight but you won't get as much fiber, you won't get the extra phytonutrients, the extra things that are over here because you end up calorie displacing, energy displacing. If you start adding all these stuff, because as soon as you start adding this part over there, you start going over your energy limit and now you still haven't gotten to where you and I want to get, which is enough of the micronutrients.
On the other hand, when you add on the plant side, what's interesting is, you get great things in fruits and berries, nuts and seeds, I mean, every single issue of "American Journal of Clinical Nutrition" just about has a study on nuts and seeds, and the flavonoids, the carotenoids, all the those that are in nuts and seeds. You get...
Ray: ...legumes and big one I mean, that's a huge life of...you look at the, what is it, the book? "The Blue Zones"
Rhonda: "The Blue Zones"
Ray: You know, legumes are big part of that.
Rhonda: So, this part of it, is it the right side of your...
Ray: The right side of...
Rhonda: ...of your triangle? So, it's a lot of plants, nuts and legumes, right?
Ray: Yeah. Basically, the bottom of that side is cereals, pulses, which are legumes, starchy vegetables, fruits, and then to a small thing, which is nuts and seeds, which we separate just to distinguish the fat content.
Rhonda: From an aging perspective, so a lot of people have different goals. My goal is to have a healthy and extend my healthspan. You mentioned healthspan. And what that really means is to...you're not necessarily going to live to be 200, but you when you are 90 years old, you're going to be physically active, fit. You're going to be biologically 20, 30 years younger, 40, 50 years younger. You have a brain...
Ray: Most people don't guess me at 51.
Rhonda: Right. So, the thing is that there's a chronological age and there's a biological age. And you want to be biologically younger, like, who cares what your chronological age is? And the thing, to bring it back to the legumes and plants and the nuts and seeds is that if you...
Recent study has been published by this Japanese group where they looked at a variety of different biomarkers that are age-related. So, these scientists looked at telomere length markers of senescence. They looked at hematopoiesis. They looked at glycated hemoglobin, blood glucose levels, insulin sensitivity. They looked at inflammatory cytokines biomarkers of inflammation, biomarkers of all the inflammatory pathways.
And they looked at it in three different populations of people: the elderly, which are about 85 to 90 years old; centenarians, which were 100 years old; and then, semi-supercentenarians, which are like 105; and then supercentenarians, which are 110 up to 115. And to me, if you look at the average lifespan in the U.S., it's 79. So, it's close to 80. Well, if we know right now that humans are physically capable of living to be 115 years old, that's almost, you can round up, 40 years longer lifespan. That's like a 50% increase in lifespan. That is huge that we're doing... Right now, no science fiction, no nanobots involved, no CRSPR, nothing. It's already designed in our biology. That's possible, right?
Ray: And in some of those populations, some of them just are sort of outliers, where they just live long. Some of them are fully functional.
Rhonda: Exactly, healthspan, yes.
Ray: Yes, they're fully functional.
Rhonda: Fully functional with cognitive...I mean, they're... So, my point is that the only biomarker that was identified to drive the aging process in all three categories, the elderly, the centenarians, semi...or all four, was inflammation. Inflammation was inversely related to age. It's the longevity. And when you think about the human body and biology and physiology, the number one driver of inflammation in humans, in our bodies, is the gut. The gut is where we have the highest concentration of immune cells, it's where we have the highest concentration of bacteria. And when those two combine, you get war firing away of cytokines. And that's the major source of all inflammation in our body right there.
And what has been shown in countless studies, particularly over the last five years is that the gut likes fiber. These it...
Ray: And not only that, but the gram-negative bacteria, the fat-loving ones, those are the ones that are usually the most inflammatory. And I did a post on this a couple of years ago. And I think there are two really big things that are going to end up coming out of it. First of all, fecal transplants, in our lifetime, will actually, I think, be a part of aging. I think we would end up that just basically, that microbiome, keeping it ripe because of antibiotics, because of the things that we do in life that destruct.
You know, I usually tell people, "You know, you send 12 Amish men to a rock concert, they can have a great message, get up on stage. But the environment is not conducive." And in that microbiome, they are what we eat. Their waste products go in our absorption organ. And this is critical.
And it's not just because we've seen all the transplant studies we've done in mice. It's not just eating the food, but it's also having the right distribution down there. And all it takes is a little bit of wrong things and then you get an explosion of something. And so, again, what's socially extreme may not be biologically extreme. The kinds of solutions we need to have for that and the kind of fiber in the food. And what we need to do, on the right side of the food triangle, I guess, I should just say right, for the audience. On the right side of the food triangle, all of those food we're going higher and higher in fiber.
Rhonda: Right and it's interesting that these different types of fiber, like with different types of beans and nuts, they're fueling different types of bacteria. And they make these byproducts that are literally regulating our immune system, they're regulating hematopoiesis, they're increasing the amount of t-regulatory cells to regulate autoimmunity. They're decreasing all these immune cells that are firing away... So, they're regulatory the inflammatory process. And gut, that's point on...
Ray: And all these, well, oligosaccharides...
Rhonda: All those, exactly...
Ray: ...that you feed them. And that's just crazy, all the things that are going on there and yet, if you think about what we're doing is we're, first of all, we're deluging that from the time we wake up in the morning until the time we go to bed, we're just always in the chronically fed state. We weren't in the chronologically fed state.
And in our next paper, one of the next papers that we're having, it will talk about the implications of the chronically fed state. So these brings up, what you talked early about, is intermittent fasting. And when I was looking at a lot of these, again, my first twist of this was to look at the metabolic thing.
So, let's get metabolism out of the way because this other stuff is a lot more interesting to me. But this, in terms of metabolism, everybody wants to think, "I need to increase my metabolism." "I'm going to eat this meal, it's gonna..." "I'm eating this protein shake, my metabolism is going to rise." Well, it turns out, I've not measured a single broken metabolism in three years of my life. In a 100 people, no one has a broken metabolism. Your metabolism scales with your mass, pretty much, you know?
Inside, whatever size you are, is your thin lean self. You have that thin lean self to steal a cloth on what you lost and carry it out all day, and that is what happens. But, what's really interesting, now on the extreme side. So, I could say all these in terms of food, but when I was dieting, even doing extreme dieting, by everybody else's...just a very low-calorie diet.
Rhonda: Your 21-day is extreme.
Ray: What I'm saying is, before even that, just in the things that I do, where people lose weight rapidly, with most people that I work with lose weight, 0.6 to 0.8 pounds of fat a day. And that's without exercise. The exercise...
Rhonda: is that with cold?
Rhonda: No cold?
Ray: No. Cold is part of it, but it's not part of it in the way you're thinking of it. So, I use it as adjunct therapy, but it's not to increase the metabolism.
Rhonda: We'll talk about cold later.
Ray: Yeah. So, basically, though, what's interesting is that in all the different regimes, my metabolism always tracks with the Francis Benedict equation. And when we go back later, I'll show you. I've got the 1918 study. I'll show you. I've all their data. The point is those guys did this research and what they did is right and what we've done today is we have popularized these words. And I literally have debates with people about metabolism...
Rhonda: Can you define what you mean by metabolism?
Ray: Yeah. So, what I'm talking about is the net sum of respiration of all your cells. So, the way we measure metabolism is we measure the carbon dioxide, exhale, breath by breath, and the oxygen that goes in and then oxygen that comes out. So, we know the delta oxygen. We know the carbon dioxide. And so, the ratio of carbon dioxide to oxygen is called the respiratory quotient or RQ. It tells us like a thumbprint what fuel we're burning.
So, if you look at this general stoichiometry, like the combustion of ethanol. Ethanol plus oxygen equals CO2 plus water. And you do the balance equation like you did, you'll see that you get a three on one side, two on the other or two on the one side, three on the other...no, two and then three, and you get the respiratory quotient of 0.67. So that's a number. So, if I'm mainly metabolizing alcohol, my respiratory quotient will push down. Carbohydrates of all kinds, it doesn't matter what kind they are, all of the glucose, anything that's dropping in there, those have a respiratory quotient about 1. And then fats or lipids, are around between 0.69 and 0.7.
So, what's really interesting is that...and amino acids, they average 0.84, if I average all of them. So, proteins are kind of mixture. One protein might be slightly lower, slightly high, but they average 0.84, which is great because the only way we measure protein is not through the carbohydrate because by that time, the deaminations happen. You've lost all that energy through urea and it looks like sugar coming out otherwise, right?
But what we can do with protein is we collect the urine, which is why I'm carrying an orange jug around all day. Too much information but it's science, right? So, we get the nitrogen from the urine and then we can back out. But by knowing the carbon dioxide produced and the oxygen, we can see the ratio of glycogen to fat burn, real time.
Rhonda: And you're saying that you have not seen someone's metabolism that's been broken?
Ray: Meaning they're at their... Their metabolic rate, which will be like speed of the car, is what all of the industry is focused on. Everybody wants to increase their metabolic rate. What I'm saying is how fast you're going only matters if you're headed in the right direction. You need a compass too. And RQ is kind of a compass. It is the indicator. Am I burning mainly carbohydrate or am I burning mainly fat? You can run your ass off for hours, and if you're only burning carbohydrate, you just get on the glycogen treadmill. And so then, what people do to counter that is they say, "Oh, I'm going to remove all the carbohydrate and shift my body into ketosis so I'm burning fat all the time. So that when they're running, they are burning fat.
But, again, it's not necessary because it turns out, when we become more restrictive, your body is smart. And when we become more restricted, you naturally start shifting to more and more and more fat because your body knows to reserve glucose...conserve it. It wants to. So, where I'm going with metabolism is that all the discussions we have about metabolism, about boosting metabolism, about all these things, even cold stress, a lot of them fall into that simple thing I said earlier, which is we use to eat to support our activity because food was rare. And today, we're active to support our eating. And the more simple thing is you can't out exercise your mouth. It's impossible. It's thermodynamically impossible. You can swallow way more than you can move. It's just not...
So, while I was talking about metabolism, what I'm saying about not being broken is, you don't have a slow metabolism. That's not your problem. It's not that you have a slow metabolism. Now, you got to get hormones to speed up your metabolism that nobody, by the way, ever measure. Isn't it amazing? All these people talk about metabolism and they don't measure in.
So that's what I started to say earlier was, I have these debates. And I say, "You know, how metabolism do you measure? Do you know anybody who's measured a metabolism? Have you ever touched anybody that measured...?" And the answer is most people never made it. And I hadn't. I was talking about metabolism. I was guilty of all the same stuff. I'm, you know...
But once I started measuring it every day, when we measure yours later, you're going to find, it's way more dynamic than you think it is. It's way... And then, I mean, because you are very precise about the things you want to know. This one is really going to mess with you because it's not what we think. So, this boosting the metabolism, we're going to boost metabolism.
Now, cold stress, we'll come back to it when we talk about cold stress because there's some really specific things on cold stress and really some specific numbers that I can give you or I can show some things that I've done with cold stress, which is kind of interesting because it turns out mild cold stress, naturally tends to lower RQ, meaning shifting towards fat. So, and we'll talk about that when we get to that.
But to sum up metabolism, we're not broken. And that's one of the things I'm going to try to talk about in our book in more common language. I say, "Well, we're not broken. Let's not start with that let's start with the food we're eating and the social environment of how why we eat."
And then, superimpose on top of that my benign conspiracy or I could say our benign conspiracy, which is I really wanted people to shift more to healthspanning. I want to shift more towards to a kind of a diet that will promote healthspan because it's really embarrassing that the community we run with, and we know all the people we're talking about, the community we run with that are talking longevity and talking about all of those stuff, and they aren't eating well. And if we can't, like, we know this stuff works. Like, you said earlier, we know it works now. We don't even... We just have to do it.
Rhonda: Well, who doesn't want to live a healthier life and be younger when they're older? I mean, who doesn't want to not be crippled and degenerated and...?
Rhonda: Yeah. Who wants any of that...
Ray: Heart disease...
Rhonda: ...suffering. I mean, all that, yeah. It's like, I think that eating to increase your healthspan, I think, it is my goal and I think that it is a lot of people's goals even if they don't realize it. Even if they don't realize it.
Ray: And so, the one twist, what I would say, the pause that I think we should do now, to think about just a little bit, is I think my vision of doing what we're talking about before was about slugging how much stuff that I could get in my body that was helpful. And now, I'm not so sure that's right. Now, I'm not so sure that that...in doing so, I might unintentionally over nourishing things that I really don't need to.
So, let me talk. In my specific diet. Since for me animal products are rare and appropriate. So, what do I mean by area and appropriate is its people and places. It's not how often I eat something. So, I'm not the person that says, "You know, I'm going to have sushi every two weeks. Or I'm going to have...whatever." It's people and places.
So, for example, with sushi. It's something that I absolutely love before. Now, if I eat it too often now, my diabetes comes back, you know. I hate to ruin everybody's party. It may not happen for everybody but I know because I have a glucose monitor.
Rhonda: I've seen...
Ray: I know exactly what it is.
Rhonda: ...your data.
Ray: Yeah it's like right here. I know exactly what my blood glucose is at any minute. And so, I know what it is and I know that it comes back. And so but my son really loves to eat sushi. So, for me, if he wants to go and we'll go do that because I don't tell my kids how to eat, they mostly eat like me, but they eat whatever they want. And we'll go. I'll have a big bowl of rice or I'll have something before that fills me up. And then, maybe, I'll have a couple of pieces. We're having fun when we're doing that stuff.
I don't go pig out on sushi. I just don't do that anymore. Or we make our own. So, I make all the sushi that I do with mushrooms and lots of other things, which they love just as much, especially because you can eat as much as you want. You know, it feels great. You know, so it's inexpensive. I shop at the Asian store.
So, anyway, back to the food triangle. You know, I eat on the right side of the food triangle and I get nuts, seeds and avocados often. And I eat lots of fruits so I have fruits around all the time. I'm not glucophobic like all these people think, "It's sugar." Well I don't eat refined sugars. But I eat that. If I want a sweet in something, I use a date. But what's really interesting is that as my diet has change, my palate and my taste acuity has changed immensely. And recently Penn Jillette's been posting on Facebook and he's says... First, he was saying I ruined him. And somebody corrected him and said I fixed him. But now, even in his eight months' time, he's eating these things, like making this big blow out for show and he's not enjoying it as much as it..."I just don't enjoy those things anymore as much as I did."
So, I get those things. But what I'm not doing is I'm not doing the all-day eating thing. So, I don't start with the smoothie and do this, and do this, and do this. I tend to compress my eating window so I'm kinda naturally doing alternate-day fasting, or every other day eating, or intermittent fasting because I'm just decreasing my meal frequency. And I eat a lot of food. You would not believe how much I'll eat. And that's why a lot of people say, "Oh, yeah, I went vegan and everything start happening." Well, most people just don't eat enough food. And clearly, we can live off this, if our primate cousins are fine. So, there's not a debate there.
And if you're eating junk food, the worst place to try eat healthy food is a vegan restaurant because they basically just shake sugar, salt and fats and put it on plants. Like the Western diet takes sugar, salt, fat and throw it on meat and stuff. You know meat is the delivery system for sauce when it really comes down to it.
Anyway, when I'm eating on that right side, what I try to do is decrease the frequency. And that's where I think it's kind of neat because I do think blending, for example, not juicing but blending... I know you're an advocate too.
Rhonda: Yeah, you need the fiber.
Ray: I think, well, I get tons of fiber in my diet because I eat an enormous, enormous amount. But I think blending certainly ruptures the cells, certainly get more access. There's some study on that. I think we do more on that. Where I'm excited is like this summer I did all hydroponics. I grew all my greens. And I'll show you some of the pictures, but two weeks from seeds to harvest. I use the vertical earth garden. It's an amazing thing. And I'm growing. But what I think, what if we start stressing these plants and go into that next level? You just go and beyond even that.
Rhonda: So, we need the, probably, explain a little bit about that. But first, I want to ask you with your intermittent fasting, do you usually eat in mornings, like, evenings? When do you actually take in most of your food?
Ray: I tend to...I'm not a morning person. I've never eaten in the morning. I get up early. My best thinking time is between, they say, 4:00 a.m. to 9:00 a.m. That's where I can really do. I taught myself a year and a half ago to sleep. I never could get back to sleep my whole life, so there's not very many times that I slept past 7:00 in my entire life. I'm like, even if I go to bed, like, my circadian it's hard to get up. But I taught myself how to go back to sleep. So, I've been trying to sleep so I can go get in [inaudible 00:39:20]. I'm averaging right now, I'm averaging eight, nine hours of sleep, so...
Rhonda: Are you tracking your sleep right now?
Ray: Yeah. I'm tracking my sleep, so...
Rhonda: Is this like your own thing or is this like an app?
Ray: This is the Withings app. This is the Withings Aura. So, I have a whole suite of Withings things. They have the Aura that measures your sleep, the Scale which...
Rhonda: Can you spell that?
Ray: Withings, W-I-T-H-I-N-G-S, and they have the Sleep. And this Activite, or whatever, the Pop. This guy measures sleep too. So, I have that. You know, they have the camera that measures the VOC, your scale measures CO2. So, it's sort of interesting because it matched your environment, what kind of environment you're in. But I'm now sleeping way better.
And we talked a little bit on you Facebook page about melatonin. We can get it at in second too, but, so, I tend to eat in the evening or in the afternoon. And because I'm working out of my house, it's just when. So, one of the things that I try to teach the people I work with is, don't name a meal. Technically, the first meal is "breakfast." You're going to "break-fast" tomorrow. And it's going to taste really good.
But, and then I don't...naming meals is convenient for restaurants so they know what they serve you, right? But there's not time of day eating and there's not time of day foods. It doesn't matter what you eat, where you are, whatever. This idea that you're fueling your body for the day, it's just not true.
Rhonda: Well, the one aspect that I think I think that is important and that has to do with the circadian rhythms. So, in the morning, you're the most insulin sensitive. In the morning so the way our metabolic enzymes, they're going on a rhythm. So, there is that component. And the reason I'm sort of interested in it is because I also will practice intermittent fasting and I'd like to talk about the aging aspects of that.
But it used to be that I was fasting the day and just eat at night. And that's mostly because my husband, Dan, can't sleep if he doesn't eat something before bed, which is like he can't sleep when he's hungry. And there's some truth to that, right?
Ray: There's several people that are like that. There's some people that are like that one.
Rhonda: Yeah. Well, recently, we were traveling in Europe for a while and we were doing Airbnb's and so, like, we wouldn't have any food, like, so if we were eating, we would eat mid to late afternoon, like, 3:00 or 4:00, the latest. And that was it. So, like, then, I was done and didn't eat anything until the next day. And what I found is that I really felt really good doing that, which is the opposite. So, I started not eating like right before bed, whereas that's what was, been doing originally.
Ray: So, to back that up, talk about glucose. if you're eating starches in the evening, instead getting those sharp peaks that you all saw today, the sharp peak like this, you'll get tailing. So, this is true. I mean, there's no doubt that you get tailing. Glucose doesn't clear as fast the later in the evening. So, I'm not talking about night. I'm talking about night I may eat at 2:00 or 3:00 in the afternoon, and then maybe I'll eat at 5:00, or 6:00, or 7:00, you know. I'm not a late...
Rhonda: Not like at 10:00 p.m.
Ray: I don't eat it like... No, I don't do that.
Rhonda: That's what's so dangerous about lot of people. And there were times when I'm working late and I don't get home until 8:00 p.m. or 8:30 and then it's like, then I have to cook and then dinner is not ready until 9:30. And it's like, that's too late.
Ray: And I have a weapon because I have this third option. Don't eat.
Rhonda: Don't eat.
Ray: And once I freed myself, I've been on a business trip for two days and came all the way home and the only thing I have from the time I left to the time I came home was water.
Rhonda: Yeah, I actually did...
Ray: And that seems radical, but having that option is a tool in our tool kit.
Rhonda: it is radical, but I agree with you. It doesn't have to be two days. It can just that night, for some people. And I do think that I know several people that are late-night eaters. They'll not eat in the morning because they're so busy and they'd work, work, work. But it's not until later in the evening, and then they end up eating around 10:00 at night. And you're the most insulin resistant at 10:00 at night. And it's like, they have problems with metabolism problems and weight loss and all these things.
And I think that it's just...it's not healthy just based on what we know from circadian rhythm, just based on that alone, we know that that's like the time that you're not supposed to eat. You're not supposed to get all these, like, glucose and fat and everything...
Ray: I can't wait until you see our paper because we've got some other explanations that will go right along with this. It will actually, it will superimpose well with this. And I completely agree. So, it's...
Rhonda: I'd love if you would like to talk a little bit about caloric restriction or dietary restriction, which is what we know call it, and intermittent fasting. And, like I've seen some studies comparing the two in terms of longevity and how there's similar effects in almost every respect in terms of the metabolic effects, glucose metabolism, in terms of brain atrophy, brain aging, multi-organ aging all being delayed. The one difference that was found in this paper, and I forgot which group it was that did this, and it's pretty recent was that when they challenge the brain with some sort of a neurotoxin that can cause neuronal cell death, the intermittent fasting was protected, but the caloric restrictive or dietary restrictive was not. And they hypothesized with the ketone body, whatever...
Ray: And I haven't got into that part. So, this is...what I'm doing right now is my lead-in. My point was, first, when we start with the idea of fasting and expand it beyond what you do to take a blood test. In other words, this idea that we're "fasting" every night, this is not where I'm going.
So, when we start the fact that here I am at 23 days and I'm fully functional, I don't feel bad. You guys have been with me, running upstairs doing this stuff.
Rhonda: We're having this conversation.
Ray: Yeah, it's fine. I mean, it is...you do get a little foggy at some point. So, you're not as on top of things. Like I told you earlier, words are more difficult just it's kind of interesting to certain things. But if we start from this basis that during this time we have these amazing healing processes that happen, which I was telling about blood pressure, 30-point drops in blood pressure in a matter of weeks people with eczema and all those things that are...
So, we have these amazing repair processes that are happening in the fasting state. And we fast forward...
Rhonda: Can we talk about why that is? I mean, that's been shown mechanistically in animal models and in monkeys. Mice, monkeys have been shown that when you fast, it is a mild stress on the body. You are deluded to the...
Rhonda: ...hormesis and that causes massive changes in gene expression. And many genes are increased that are involved in dealing with damage, repairing damage, anti-inflammatory. All that stuffs being turned on. Go, go, go, go.
Ray: And the body starts sequestering the things that it needs. You know, the popular myth is all your body's fasting is going to hold on to fat. No, it's not. That's your storage organ. It's going to use the fat.
But the point is, is the stuff we're interested in your body starts mobilizing. It starts cleaning house. You know, metabolically cleaning house. Going in saying, "Here's a dysfunction cell, I need these resources, need this, need this..." Just like what you do when you're trying to make things in... You rob around...
Rhonda: Which is really, really, really good because those dysfunctional cells, as you call them, they're often senescent, which means they're not dead, they're not alive, they're sitting around and what are they doing? They're secreting inflammatory...
Ray: ...your hormones.
Rhonda: Yeah, they're damaging cells in your body. So, if you can do something to get rid of that crap, you better do it. And fasting, intermittent fasting, has been shown to do it.
Ray: Right. So, if we would get rid of the fasting term, meaning the overnight thing. So, we lose that. We go to this extreme and say, "You know, look, the longest medically-supervised water fast was 382 days." And that 382 days, yeah, 382...276 pounds, 382 days, I'll send you the paper. Actually, I might have even posted the...on your thing.
But it's 382 days, medically, in the middle of...
Rhonda: Supplement or anything?
Rhonda: Just water?
Ray: Yes. They did the multivitamin. And then, in the middle of 49 days, they had to do some electrolytes. But other than that, he was fine. And he weighed 185 when he's done.
Rhonda: What did he start with? What was starting at?
Ray: Well, he lost 276 pounds.
Rhonda: Okay. So, he had a lot of fat to burn.
Ray: Yeah, absolutely. He had the energy.
Rhonda: Right. That's important, right?
Ray: No, he's not...
Rhonda: If I were to do 380, I think, I'd probably be dead.
Ray: I don't know. There's probably some breatharians down the street that would disagree with us, right? No, so the point is, is that... So, that is...but when you say it's extreme, what's interesting is, there's no reason I couldn't, other than I don't want to get much thinner other than that, there's no reason why I couldn't go on and on and on at this point. The idea that somehow fasting is miserable was because people are responding to regularly dosing their body with meals. And in the anticipatory habitual stuff that's going on, and what do they get? There's symptoms of hunger: headache, lethargy, lack of focus, irritability. What happens when you give up cigarettes? Lack of focus, irritability, headache, shaky... Heroin, alcohol, and I'm not saying that food is addictive in that way.
I'm saying the body only knows withdrawal when you're regularly dosing it all the time with stuff. So, all of what you feel, what you feel now is hunger really isn't hunger. Like, right now, I'm hungry and the only real symptom of hungry when I say that is that my mouth will water and right now, food will taste so freaking good, you wouldn't believe it.
Like, I go to cooking classes. They have cooking classes. He would say, "You go to those cooking classes while you're fasting?" Yes, because a lot of taste is smell. And surprisingly, my friend, Richard Ross, he was one of my clients. He's an amazing...He's a cephalopod...a scientist at the museum in San Francisco. What's amazing is you can just smell food and believe me, it's almost as if you ate it. It's crazy. I can't it's like I can't...
Rhonda: Smelling food is good. I like, I enjoy smelling...
Ray: Yeah, but I mean, it's really intense. It's like something you've not experienced before.
Rhonda: Like when you don't eat and you just smell it... I've not...
Ray: And it's almost like you taste it. It's whatever...but it doesn't send you into any crazy feeling because you're in a perfectly normal state. The body shouldn't... you know these symptoms are not a way a starving animal finds food. You got to be clear, you got to be lucid, you gotta find food. So, okay, getting back to that, the senescent...
Rhonda: Can I ask you a question? Did any of your friends join you? Like, was this like something that other people that are also starving also...
Ray: The people...all the fasting...
Rhonda: Has anyone ever just like gone crazy and start eating, like...?
Ray: No, you don't have those urges. That's the point. That's a myth about what it is because what people's idea of hunger and what's people idea of eating is based on the idea that their entire life, they've never been more than 10 to 15 hours without food. So, first, we had to dispel the myths that fasting, which is this overnight fasting, which is has it's point, as you say, hormonally, has it's point. But one of the reasons eating late is problem because then, you eat, you go all the way into night, and then you get up in the morning and you drink your shake right before you get a workout. Now, what? You got four-hour-a-day fasting. And if all important activities happen during this down state it's like taking amphetamines all the time and staying awake just because you can.
The brain needs that time. It doesn't shut down the... It doesn't go metabolic. Brain activity doesn't go away. It just changes. What I'm saying is our body is somewhat...I feel this body is somewhat the same way.
So now if I start from this basis. So, here I am at 23 days, I'm doing okay. Now, I start compressing that window and so, okay, now where do we get with those health benefits start kicking in, you know? You know, intermittent fasting is some of it, some of it dietary restrictions. So, you could dietary restrict and be chronically feed.
Rhonda: What do you mean by that?
Ray: You could be eating all day long, very small amounts, and by a calorie perspective, which is why I don't like calling it calorie restriction anymore. I'm going to start...
Rhonda: Right, dietary restriction.
Ray: You could be dietary restrictive, but in the chronically feed state because postprandial, metabolically, we change.
Rhonda: Yeah. And SIRT1 gets activated every time you're making... So, when you're eating anything when you're eating food, you're going to make NADH, which is which is going to shut off SIRT1, which is also part of the benefit of fasting.
Ray: So, feeding frequency, when we look at feeding less frequency, and that may be a reason that I... We can look at the study with that lens and say, "Okay. How did they feed them?" If they did the standard three meals a day, which was just made up, I'll show you the document of where it was talked about, in fact, we'll...
Rhonda: Wait. What are we talking about? Who?
Ray: I'm talking about what happened a hundred years ago, when we started, you know... Hippocrates questioned whether we should eat once or twice a day. He said “some was the habit, some was the season, some was the age, some was to country where you live”. In other words, people were eating once or twice a day. Literally, they just don't have a lot of food. They didn't shut down the pyramids three diet, three times a day to feed those guys, you know? They said, "Chisel, pull the rope, here are some water." And then, they give them some bread later, you know. And they managed to do something that we can't do today, right?
So all alien theories aside, right? So, basically, what I'm saying is that we have this template that fits around, first the agricultural cycle, which I grew up on a farm. So, eat a small little something before you got out. Stop, early 11:00, have the biggest meal then while the sun's out. And then, it's a long day. You go there and there's a light meal towards the evening. And that's where this thing, three meals a day.
Now, for the workforce, its eat before you go to work. Have a break, have something to eat then. Go eat lunch. You know, now have a break, go have happy hour. Go home eat again. And then, you're...late nighters are obviously even worse. Go grab a round of ice cream before you go to bed or whatever. That's a chronically fed state.
What I'm saying is, you can be in a chronically fed state and still have just a little bit of calories, you know. You might lose body fat, and I'm not saying you won't be at a deficit, what I'm saying is this idea that you're always slugging... Every time we slug, we activate a whole set of hormones and react to it. And so, we talk about fasting and we talk about intermittent fasting, the idea that you're really going long periods. But even in the popular media, because everyone is terrified to say, "Don't eat." You know, you'll be anorexic or whatever, you'll have an eating disorder.
But the idea that you can last a day or two, I mean, really, I mean anybody tells me, it's like they're experts. And I say, "You can't use fat for metabolism, like, how many days have you been without food?" Like, exactly...
Rhonda: Well, this is a question I've been trying to answer for myself and that is what's the minimal time that I need to fast to get the autophagy benefits? Autophagy is clearing away those damaged cells we're talking about. And there's other benefits. So, there's lowering IGF-1 there's SIRT activation. That stuff, SIRT, can happen quickly and I mean, as soon as NAD...
Ray: So, just to give you an idea of my last fast, although it was...I did it over my IGF-1 went down to 69, at the end, I was at 69. This one, I was really interesting. I started 200. So, gaining the weight and eating...and I ate healthful things to gain the weight. But I did stuff to get up there, and I was massively eating two or three days before I really want to have a negative experience with fasting. I really wanted to really set off the hunger pangs that I've seen people have dealt with that. Most of them don't eat my diet before they fast and that the people that don't eat like me, they're really sick. I mean, they don't do so well.
So, I wanted to try to do that. So, for about four or five days before, and I didn't really gain weight during that period because I was eating...my food is really hard to gain weight on. But, so I was done with the weight loss, I'd already gotten up to my weight at the start, and I held it for about a month or so. And then, two or three days before I started the fast I just started eating three meals a day healthy food but just really eating a lot of volume of it. And my IGF was surprisingly...
Rhonda: Do you eat a lot of meat?
Ray: No, I don't eat any meat.
Rhonda: Your IGF went up.
Ray: Yes, it went up. Yeah. So zero I had none. I mean, I just had, it's just dull, whatever. And it was up at 200. And then, by the midpoint, it was already down to 100. So, it dropped 100 points in 7 days or 10 days. And we'll see what it is. I already did the last one, results will be back soon, we'll see what the ending is. Last time, like I said, I ended at 69.
So, but anyway, why I'm saying that is because I haven’t seen a lot of work out there on this, but I think there might be data that we could tease out of papers that exist. This is something I want to think about as sort of a next step, which is this meal frequency. You know, how often we're eating could be a huge problem. I mean, just frequency. Unfortunately, it's the social. You and I, as scientists, are able to sort of ignore the social... If we think we're wanting to do something, we get headstrong we're going to do it. Right? And you just don't care what people say and neither do I.
But a lot of people out there, they're eating primarily for social entertainment. That's the only reason, right? They think they're eating for health. But even the ones in a lot of fitness thing, they're socially doing what all of their crowd is doing, right? And even with us, I don't think we know enough yet, to really optimize. I think we did a relatively good job of creating a simple roadmap with the food triangle.
So, I think it helps from that perspective. We can say, "eat right." We can say if you're a bottom feeder, which would be meat and potatoes, pasta and meat sauce, fish and chips, burger and fries. That's the most energy dense diet you have and it isn't surprising everybody gains weight. Now, the fat people will blame the carbs, and the carb people will blame the fat. And they're both right for the wrong reason, which that'll be explained on the paper.
But, that food triangle becomes a roadmap and then the question is, how can we optimize eating frequency? Because I want to maximize my body's chance to do this and obviously, I could have fasted, and supplemented. There's no reason why you couldn't do that. Although, at what level of supplementation do you interfere with one of those other systems, right? So, we don't know that. But I think there are things that we should be doing, but because there isn't an economic endpoint, it's a health endpoint, us getting the funding to do that sort of thing becomes problematic.
Rhonda: That would be an interesting study. I like this. They're good, the meal frequency. I've seen I've looked at a lot of studies on intermittent fasting, dietary restriction in humans and finally figuring out like why a lot of the data wasn't being replicated in humans that was found in monkeys and mice. And then, they figured out humans, when they're dietary restricted tend to eat more protein because it's more satiating. And then, they're like, "Oh, so then their IGF-1 levels are going high." You know, eventually those things will sort of teased out...
Ray: right, but even down the satiation. Okay, so that's a made-up word. And the entire context to that word is used in talking to people in a chronically veg state. I'm satiated.
Rhonda: Yes, you are.
Ray: Right. So, what I'm saying is if we're going to change the language, we have to fundamentally...as scientists, especially, we have to disengage from all of those studies. They're all polluted. It's like, today, if I'm going to do a cholesterol study, I can't because there's nobody out there that has the issues that aren't on statins. The once we did before, are about the best we're going to do because we can't do a randomized control and put someone and say, "Just don't do what you're doing." And the other guys, "Do this."
So, we've polluted the data set. All the studies are varying proteins, carb, and fat. A thing that I want to get rid of. Well, okay, so I'm going to hold protein constant at 12% and so in order to do that, what am I going to do? I'm going to study sugar versus oil. Okay. What have you just learned? Nothing. Because if I add a whole food, starch, I screw up my protein number. If I add legumes, I screw up my protein number. If I add any of the things that I would actually really eat, I screwed it up in the fat side. Okay, you add lots of meat. You're screwing up your protein number, whatever.
So, what everyone's arguing about, the sugar versus fat crowd, the whole crowd, if you really look at the papers, it's pretty easy to see. They're basically arguing of that. And you can look at any arm of the study, it's really a simple thing to just look at the study and say, "You know what? I'm not even going to think about this."
Look at the carbohydrate arm, and you need to see two things. First, did the fat go down? Not this goofy study, where a low-fat diet is 40%. And say, "Oh, well, yeah, that's what they ended up eating." Well, no, if you're going to control it, control it. You and I can't say, "Well we're aiming to get 4 millimolar. But the lab tech just couldn't get it right and got it at 20 millimolar, and so therefore, we're just going go with that." And still call it a study. It's just ridiculous what gets out there and published.
But, if we look at it, on the carbohydrate arm, always, you'll see a rise in the carbohydrate arm and you won't see an increase in fiber. And if you don't see an increase in fiber, that means they added refined sugars...
Rhonda: Yeah, that's what it means.
Ray: It means it's just...compared to what you and I eat, it's an irrelevant study, I don't really... I mean, we don't need to debate sugar versus fat anymore. It's irrelevant because I don't eat oils nor I eat sugars because I don't use the energy without the food.
Rhonda: So, you can get whole foods, real food.
Ray: So, all of my foods, all of my dietary sugars, all dietary starches, all of my dietary fats are all come from whole foods. For example, if I didn't have the word... If we could eradicate the word carbohydrate from the diet, just that one. Think about it for a second. If I don't have the word carbohydrate, I can't equate a whole food starch with the refined sugar. There's no way to connect them. I can't equate a carbohydrate to this cotton, also a carbohydrate.
Rhonda: I always say refined carbohydrates.
Ray: Yeah, but even if you say that, you're still not saying specifically. This is a carbohydrate, the wood floor is carbohydrate, termites eat wood, moths eat shirt, cotton, linens, you know. What I'm saying is these are all carb. Chitin in crab shells, carbohydrate...
Rhonda: That's a vague term. Yeah, it's not very specific.
Ray: So, it doesn't mean really anything. Then we got to start saying complex carbohydrates. What the hell? Now, we're just making the language. This is nutritionism.
Rhonda: We're confusing it.
Ray: We're confusing it and yet, when, if you do a study and say, " I added potatoes and this is what happened. I added beef and this is what happened.:" You know, instead of a protein source because for most...
Rhonda: I added Twinkies and this is what happened.
Ray: Yeah, this is what happened. Exactly. So, the point I'm making is, is that it makes more sense because the labels are just confused. We have the eat more, eat less policy in the United States. It came out after the McGovern report, which basically is when we're going to say something good about food, from a government's perspective. "Eat more fruits. Eat more vegetables." If it's something that's bad, we're not allowed to name the food. "Eat less saturated fat. Eat less oils. Eat less refined sugars." We're not allowed to say the food. And from a government policy level, that's really what we do. And that's what happens in the messaging to the public. And you look at all across the agencies, they all use that message.
Rhonda: Do you know why that is? What was...?
Ray: Because they devastated the beef industry when they said don't eat red meat. To this day, everybody says red meat. And there's really not that much difference between any of the meat. They're all right about the same. We're all animals. Now, if you report the calories per weight, yes. I mean, I'm sorry, the fat per weight, it's the same. But if you report fat per calorie on all the different cuts of meat, we're all between 25%, 30%. We're all really...there's no lean meat. They're all about the same. I mean, they're very, very close.
And so, that again, we have 26, 27 national institutes for health, but nutrition is controlled by the USDA. Do I need to say anymore? I left NASA because I knew they weren't getting us into space. You know, that wasn't going to happen. NASA is a great organization, a lot of smart people there, everybody wants to do stuff. But in a mature bureaucracy, there's a rule against everything.
So, getting back to our stuff, what I'm saying is that if we would change the language and talk about food like all the things that you talk about on some of your videos that you do, the short videos like your smoothie or whatever. Yet, you're talking about what's in it, but you're always putting foods in it, you know. I don't see you dumping powder in anything you're doing. And I don't either. I know we've talked about this that night we talked.
So, if we start it with the whole food diet, and we say, "Okay, we got a whole food diet. Now, how much do I need to meet my minimum energy needs." I mean it, if I'm active, I'm going to have to eat more. If you're in the baby producing time, and that's what you guys are trying to get pregnant, you're going to have to definitely eat a different diet. But then, how do we deal with that whole meal frequency and eat in a smaller window to address this fasting? Or do we need to go a couple of days? You know, I mean, I don't think anybody can answer these questions right now.
Rhonda: Well, that's what I was wanting to get to with the, what time frame do you need to fast to get specific benefits? And the specific benefits that I really am interested in is the increase in the autophagy, which then increases hematopoiesis, you know. These processes are very important for long-term health and something that I'd like to sort of tap into. And from the Valter Longo's research at UCLA, at least in animals, in mice, he's shown that it takes 48 hours of intermittent fasting to activate that whole autophagy system robustly and to increase hematopoiesis.
So, now, whether or not that's applicable to humans or if there's, you know... I don't know and I'm trying to get in contact with him to figure that out because I'd like to know. Do I need to do, incorporate 48-hour fast to get those autophagy benefits that I want?
Ray: Yeah. And this is my goal post book. I'll get my book out there just because I want to get sort of the language change, how we're talking about food. To be able to get more people like us that can extract the social paradigm which is, "I don't care if you think what I'm doing is radical. It's not biologically extreme and there's a lot of different benefits." And studies that are starting to be... I want to see studies that are done that don't use the template of three meals a day, you're going into starvation mode, we're gotta make sure you get every single thing, you know.
We got shot down by an IRB, it was embarrassing. But we got shot down by IRB, I won't say where, for me to eat potatoes for two weeks in a metabolic lab. Because the IRB said it wouldn't be nutritionally sound.
Rhonda: Based off of?
Ray: Nothing. Okay, now, never mind. I had a better calorimeter than this major Ivy League school. Their IRB didn't want me to do it. You know, we were going to some full comprehensive blood work, something that we could, at least, write up as a case, something that could be a seed to get some funding. But that's how polluted it all is.
Rhonda: It really is.
Ray: And you talk to your average dietician and now, the protein, carb, and fat. I mean it just becomes just jabberwocky.
Rhonda: I personally just want to like figure out the best diet that...what I can do right now to extend my healthspan. And right now, I've been turning to what's known. I've been looking at these supercentenarians, which I know there are individuals out there that are 115 years old and are cognizant and are healthy and are still active. They're not like this crippled and you know.
And so, I want to look at these individuals and understand what it is about their genetics because we know that things like intermittent fasting, dietary restriction. We know that hormesis, different plant compounds that are present in a variety of plants, can activate a variety of genes that maybe activated in these individuals. We know for example FOX03 is one that's well known to be associated with...
Ray: And that's Luigi Fontana, I mean, he's big in [crosstalk].
Rhonda: Right, exactly. And so what can we do with our diet, with our lifestyle that can activate these different pathways to help us to live longer. But to get on that, sort of on that note...
Ray: So, temperature...cold
Rhonda: Yes. So, temperature, so there's a whole like...
Ray: Tell me about Wim, first of all. So, I know you've interviewed him...
Rhonda: It was fun.
Ray: ...but tell me all that. Isn't he an amazing man?
Interview: He's full of energy and passion. We had really a fun time hanging out.
Ray: A couple years ago, I went over for...and we spent a week together just to get...before everything was on a rush, he was like in a what-is-he-gonna-do-next phase. And we just spent every day just talking all day and night, that we're lying in beds and we're in the same room, we're just having these conversations. It felt like at camp when you were a kid, you know. You're lying there in the dark talking about stuff, hearing all these stories. What was really fun about the whole thing is that as I was...
You know, I went out, I usually carry just the gloves. I use these the Agloves. They're really Agloves but there's silver on them because you use it for iPhone and they're just little cotton gloves and I use these little ear bags. If I have those, if I cover those two symptoms up, I can tolerate cold really well. So, I have my gloves on and I'm out walking and then...
Rhonda: Where are you guys?
Ray: We're in Amsterdam.
Rhonda: Amsterdam, in winter?
Ray: Yeah, it was like February and we're walking to the grocery store and we walked down and he walked down. And he wants to strip down and get into the water, cold. He's just this way. It's just fun. We had a great time.
So, we're walking back and he's looking, he was, "Ho, ho." I think actually, "Look at this. The Ice Man has a coat and you have a short-sleeved shirt. This look crazy." Then, like, he took his jacket, he's "I need to..." And when we got home, he opened all the windows. He said, "You know, I've been trapped in this apartment all summer." But it was really interesting that people think of him and you see this. People think of him as an extreme and what Wim's actually trying to say is not extreme. He's saying, "Humans can do this." We can. A normal human can do it.
This is what I'm saying now about fasting. A normal human, I'm not a superhuman to go without food. This is normal. And normal humans experience it. And what's interesting is, just like this time with that and what we have in our metabolic winter hypothesis paper is this the fact that these two traits, cold stress and dietary restrictions, hit the same genes, hit the same UCP1. Hit the same PGC1 alpha, you know.
Rhonda: There's overlap, yeah.
Ray: Yeah, there's overlap and you know that winter never comes. There's never time of cold stress, there's never time of dietary restrictions, scarcity, and we're in a chronically-lighted environment because of modern lights.
So, if we think about this the idea, unfortunately gets, you know...the cryotherapy. And you know, I got to be...and it's all get sold as extreme. But what you found, like in your sauna thing, I don't know if you've talked about on another blog or whatever, but the idea that suddenly you get this amazing sleep, like, amazing sleep...
Rhonda: Well, I didn't. So, recently I had this experience where I had done some very extreme temperature contrast therapy where I was sitting in a very hot sauna, at its peak it was 220 degrees Fahrenheit, which is very hot. And then, transitioning once... I mean, I was bearing the pain, I was sitting on this hot sauna and really pushing it. Like, I wanted to get out but I stayed in.
And then, finally, I got to the point where I'm like, "Okay, I'm going to get out." And then I went straight into an ice bath, a very cold ice bath. I mean, it was just lots of ice. And that was also a very difficult because it was cold. So, I was going from, like, hot as a hell to, like, really cold. And that was the first time I've ever done that.
Ray: Did you notice the pain sensation on both sides was the same?
Rhonda: Yeah, it was burning.
Ray: Yeah, it's interesting. We only have one sense.
Rhonda: Well, what's interesting, I met with this... Okay, let me get to the sleep thing. I'm going to get sidetracked like I always do. But, so, I did this, like, four rounds and I had a variety...I mean, I noticed I felt really good, really relaxed there's a lot of things going on the brain. And I've done the sauna for years. And the sauna also makes me feel really good and I talked about some of the mechanisms why that occurs.
But the way I felt with the contrast therapy was a little different. I felt extremely just very relaxed and very, very happy and pleasant. And I've done cryotherapy. And cryotherapy also, where I was standing in a chamber with liquid nitrogen, I also felt really good, like, after doing that for two or three minutes, if we're at home, and I did for a bit. And I got a...and it felt good. And I know that's norepinephrine is being released. It's been shown with cryo and cold-water immersion.
But anyways, back to the contrast therapy, the thing that was so surprising to me was the fact that it completely reset both mine and Dan's circadian rhythm, where it usually, like, him more than me, we're kind of night people. Like, I go to bed before midnight, but he struggles to go to bed before midnight. And so, we were a bed at 9:30 p.m., so we did this in the evening. So, we started at like around 6:00 p.m., I think. But by 9:30 p.m. we were in bed and asleep by 10:00. And we woke up the next morning at 7:30. And that is not our typical schedule and certainly not his typical schedule. And that was very surprising to me, the contrast therapy, resetting my circadian rhythm.
Ray: So, one of the things you asked earlier about cold stress and weight loss with people I work with, that's actually one of the things I do. I want them to get a lot of sleep. So, I talk...I have sort of more of a metaphor, I guess, I use to sort of simplify things. But metabolic winter, I think of dark, cool, still and scarce. Metabolic summer is bright, warm, active and abundant.
One of the things that I want them to do is get a lot of rest, Like seasonal affective disorder. Is it a dysfunction or is it a feature? Because if you're...don't have a lot of food, it's really not worth to die. The idea that we're running through the spears and getting stuff is a bunch of cartoon stuff. I mean, the idea was we would just hunger down, we would wait. And interestingly, the first plants that we see, the first green that comes up to the ground are all attached to bulbs, starch, underground storage organs, which is kind of an interesting, easy way to find them.
But the contrast therapy, so I have them do 10 seconds of warm, 20 seconds of cold. I have them repeat that 10 times. And then, end on cold. Now, at first, it shocks...
Rhonda: This is the shower?
Ray: Yeah. It's a contrast shower. And it sucks at first.
Rhonda: How hot is the water?
Ray: Just your...you just need to get warm.
Rhonda: Just warm, okay.
Ray: So you get either a Gymboss timer or get the app on your phone and set it up for, like, a tap app would be. You know, 10 seconds, 20 seconds, and repeat 10 times, end on cold.
Rhonda: So, 10 seconds warm, 20 seconds cold, end on cold.
Ray: And Wim and I, we developed this, literally in his apartment. We were talking because we were talking about the benefits and we were talking about the saunas. We were talking about that. But what we do in a concise amount of time that would get us going. As a complete coincidence, just like you, I was doing something, I don't know, we are...or whatever, it was late and I was still going. My mind was still going. And I went and did that and I realized I'm really getting sleepy. And so then, I started repeating it and it's like, "Wow, I get sleepy really fast." I hit the bed and I go to sleep really quick.
So, at first, because our our skin can't sense absolute temperature. We sense differences, in fact, Wim did a little finger, one little finger task and they made them with ice water, he passed out, which is kind of funny because he said, "Did I die?" You know, the Ice Man passes out, submerged my body in ice and they did this little test. And there's this strong, I don't know what they...I haven't looked it up, but there's some strong react...something they do with your hand and it has a strong response and it can make people pass out.
So, anyway, but the point is, our body sense differences. And I wrote a blog about this online. It's called, Ch-Ch-Changes. And the body really, like, if you're out working in the fall, and when you go out, it's cool and start raking leaves or you start doing something physical and then you take off layers, and now you're fine or whatever. And then you walk in the house, "Ah, it feels hot." Right? And you say, "It feels hot in here." And everybody else says, "It feels normal in here." You're turning down the thermostat and vice versa walking.
So, we sense these changes and so what we try to do is make it practical where we can do it. And what I've found with myself and with hundred or so people I worked with is that, do it again in the morning, it just lights you up like a Christmas tree. You just feel ready to go. You get out and go,whooooo , you know. You're ready to go. Not a cold shower, but the cool...
Rhonda: The contrast.
Ray: And then, there, you can go as cold as you want. You have to have a big contrast. At first you might not go as far, but eventually, you're going to full cold because it's not... I mean, it's like 50, 55 degrees. You're can handle it.
Everybody has a part, their belly, their back, their face, something about them really makes them, like tighten up. But you'll figure that out. And what's paradoxical about it, and I saw this on my blog and people reporting back, this is all a couple of years ago, was that you start tolerating heat better too. And it was kind of weird, you start sweating less. Your body starts getting sort of more adapted to this contrast so that when you go from one environment to the other, you just doesn't seem to be as much as stressed, which means, when you go out walking, when you go outside, I always have people do the reserve of skiing. So instead of layering and taking them off as the day goes on, I say, carry it with you. And only put it on if you really need it.
You know, cover your symptoms first. You know, we don't get a frostbite of the head. We get it of the nose, ears, toes, fingers, the extremities, right? Basal constriction happens and when basal constriction happens, we start to losing the circulation, if it's cold. But if you cover those symptoms first and that was my very first experiment I did, before the first weight loss, I say, "Why am I cold?" And just sitting out in my back porch with a notebook trying to say, "Okay, how do I stay out here until I can't stay out here anymore? What makes me go back?" And what I found was my ears and face will send me into, "I can't stand it anymore," way more than my body.
So back to the contrast showers, what doing this contrast does is it slowly elevates your tolerance for cold, like, right now, I have zero cold tolerance because of the fast. And I opened my windows last night, and it's even at 66 degrees, which my house is normally colder than that, it's starts really feeling really cool. You know, that's just a temporary thing. And last time, I took about a month and a half or something to where my normal cold tolerance came back, I know it pretty well.
But as you do this contrast therapy, and you end on that cold for two minutes, again, in the morning, it gets you alert. And at night, because of that, I think, where you are in your circadian day, it makes you asleep. And I did the same thing in Australia that you did from your term, to reset. And then I tried it. Now, I didn't get completely over jet-lagged, so it wasn't really a complete success. But I used a combination of melatonin and those mild cold stress, and light, you know. And it still took a day or two. It's worse coming back, for me. It was much worse coming back. And I didn't completely fix it, so there's obviously a time function that we sort of can't avoid. But, I think something is simple as that has benefit.
Rhonda: Yeah, I'm definitely going to try to dig into some of the mechanisms there because it's...and it's hard to find, but I'm planning on trying to understand just because it's profound for me.
Ray: And there's really good data. Maybe I could find a Dropbox folder and send you. I'll send it, like...
Rhonda: Please send me anything. Yeah.
Ray: I'll send it, like, but, like, on clinically depressed patients. We're doing 5 minutes cold showers with 60 degrees F. And they were having as good of results with medications with their depression.
Rhonda: Please send me that because I've been theorizing that that would be the case based on the fact that cold, if you're, I think it's around 60, anything below 62 or 63 degrees Fahrenheit, 17 degrees Celsius, whatever that is. It increases norepinephrine and that's...
Ray: So, mild cold stress, when I talk to people, first of all, I don't think people really don't need to be doing ice stuff right now. I mean, it's just, there's way more risk and you can get a lot of benefits above it. So, what I always tell people, because I think everybody goes to the extreme and the fitness industry is the worse about this. But basically, the guidelines I give to people is this, it's that mild cold stress begins at 80F in water, okay. And it begins at 60F in air. So, that's where you start seeing a change. You start seeing a metabolic response, you start seeing a hormonal response at about those temperatures.
Water is really easy to deal with, all the way down to 60F, when you get a little bit below that, it starts hypothermia and walking hypothermia is a real problem and you can become hypothermic and not really know it. Because that shivering response shuts down and you go into your non-shivering thermogenesis. And, yes, you boost up, you can get 300% to 500% increase in metabolic rate, and you can measure this, which I can show you some stuff later that you can actually measure it, and a shift in respiratory quotient towards what we want to do, which is fat burn. But, it also, the risk of injuring yourself goes up greatly. So, my caution to everybody is to play in the mild places first and then go down. With air, if you're above...
Rhonda: Can you send me the studies on the risk of injury as well? Because I didn't...
Ray: Well, hypothermia is all of the device. There's basically a chart. But if you look at the chart, and I'll show you what it is. If you just put water in hypothermia, you can get a chart and there's an exposure time. And now, obviously, I can exceed that by far. And Wim can exceed it by far. You can train yourself to do it. What I'm saying is, you get the person out there. They get all excited. They start extreme and then they wind up having a problem.
So, and the air one is below 32. Below 32, you start having a big risk. If you work in the range of that, of 60 to 32, or 60 to 80, you pretty much, for a normal person, you're going to do just fine. Now, for swimming, because one of the things I want to do, this is the last time I'm ever doing weight loss stuff. I'm done with this forever. So, I'm actually going to start exercising and I haven't exercised for five years now, only cold stress. Yeah, so all of this kept, even after five years. You know, all of my muscles actually shrunk now, which is kind of weird to look because the volume of water that leaves your muscles when you're fasting. It really freaked me out last time. I was like, I just was sure that I was just atrophying like crazy. I was really, like, "I'd really screwed this one up."
When I get back the DEXA scans, as soon as you start eating and getting minerals in your diet again, sodium and other stuff, the water comes back up. You know, like, for example, when you pump up in a gym, you're not adding protein or amino acids, you're just adding fluid. So, anyway, but my point is, it's that, I stayed fit. I kept muscular and I did it all through cold stress. I just did cold stress.
Rhonda: Okay. So, what was your protocol?
Ray: So, the contrast shower is one of them. I also have a 8 by 16 swim spa that I put in backyard. And I have 110,000 BTU heat pump on it. So I can take it to 45F, all the way up to a hot tub. My kids love it they have a his or have a party, it's at 102 whatever. And so, a regular cold exposure in there, and I would just lounge. I mean for example...
Rhonda: Shoulders under?
Ray: Right, up to face. In fact, I did a thing with Steven Leckart from "WIRED." When he came, we did all kinds. I've got great data from him, but we did feet, I think, knees, waist, shoulder and head, when we're he was always submerged. So, I was doing metabolic rate the whole time.
Rhonda: What temperature was the water?
Ray: Sixty, I did him at 60. I did him at 70. I did him at 80.
Rhonda: And those were essentially the same between all three temperatures?
Ray: No, there is some differences. And then also, I did...and a lot of this is on a blog. I think it's called... What did I call it? If they just go to the metabolism tag, I came up some stupid name for it, but it's something metabolism, Mastering Metabolism or something.
Anyway, I'd do it in the third part. I talked about Steven's results. And then down at the comments section, I posted even more data because people became interested. I don't want too much of it up there just because it gets boring.
But the swimming, getting back to swimming, I want to take up swimming. No, I've always been able to swim so I've never been afraid of water. I scuba dive, I was a water skier, I love swimming. But I never learn to, like, swim laps, you know. And I really want that graceful, to be able to swim. So to me, the only exercise you can start at age at any level of fitness, and you can do it till the end of your life. So, I want to introduce...and what's interesting about resistive swimming, which means if you're swimming on a tether and you're swimming in a swim spa or a tether and a pool, where you just have a mount, so you have like a fiberglass rod and a rope that goes through a band.
When you're swimming, it's really glide left, glide right. You know, you're basically cutting through the water. It's not really a power move. You know, it's really about the hydrodynamics of the water streaming over you, you know. But when you're swimming on a tether and you're not moving, it's like slugging through water. So, it's actually physically more difficult to swim on a tether. It's the same activity, the same feel, but when you move, you start moving that fiberglass rod and you start bending it down some. And if you let off a little bit, you start going back. So, you actually, it becomes... even swimmers, really good swimmers, have told me, I had Olympic athlete in my pool, and she said "It really definitely gives you work out." If you want the workout part.
But what's really amazing about Steven's data is that when he got out of the water, instead of doing what everybody does and jumping in the sauna, we just had him sitting there. We were measuring his metabolism the whole time. And his respiratory quotient went from 1.0, which is most activities are burning glycogen, almost to 0.7, almost pure fat. And for over an hour, he was still burning fat.
Rhonda: And that's after what temperature being on the water?
Ray: That was 70.
Ray: So, for swimming, the optimal temperature of comfort and impact is about 75F, with all the stuff I've looked at, not to study, the stuff I've looked at my pool. Right around there, it's too much of a shot. Now, 70-degree water, for someone who lives on the West Coast are like, "What?" You know, right?
Rhonda: Right, that's what I'm thinking. I sort of...
Ray: If you live in the South the Gulf of Mexico is like 80, you're in the tropics, and down at 60, it starts becoming something, right?
Rhonda: What do you mean by becoming something? Like your metabolism really speeds or you're like burning fat?
Ray: No. You're still going to burn carbohydrate as long as you're really active. And if you're shivering, you're burning carbohydrate, you're not burning fat. Shivering is exercise. So, here's where we are now, we talk about this little bit, the metabolic winter. Our body, which is... You know, I believe exercise is mimicking cold stress. I believe most of the benefits that we're seeing because here's what happens.
If I have people exercising and they start to shiver, I'm sorry, sort of exercising, not shivering, they start to exercise, they produce irisin. Irisin is known to up regulate and create more brown adipose tissue. We've seen these studies and it's come out in the last three years or four years. With shivering, shivering is the original exercise. I mean, we don't really have to go do something at the gym. I'm not talking about people that want to look better. I have no problem with people having it in as a sport or compete, competition or whatever. Our conversation is in the silo of longevity and healthfulness.
You know, this is metabolic. So, the first step of cold stress is that I'm shivering. Now, this is a very energetically expensive way to produce heat. Why? Because now 20% of it is being used to move the muscles and do that. So, then what happens? Little bit later, shivering stops, non shivering thermogenesis kicks in, up regulation happens, you see if you're 1. Now, I'm just using electron leaks through mitochondria and suddenly, I'm not producing my ATP, I'm just producing 100% heat. What's the cell used to do that? It's grabbing the most energy-dense fuel, and it's using lipids to do it. So that's a real good adaptive strategy. Because if you're keeping warm using glycogen, you'd run out, perishes quickly. Or if were using it and it was coming from gluconeogenesis, you would run out really quickly.
So, what's interesting is that if you think of exercise is a way that we mimic mild cold stress in the past or periods of mild cold stress. A lot of the benefits might actually be the same.
Rhonda: Yeah, I think there are definitely a lot overlapping benefits like the brown adipose tissue, PGC-1 alpha, increasing mitochondrial biogenesis all these, fat oxidation.
Ray: They all overlap.
Rhonda: But there are absolutely important benefits from exercise like... A study, just I was reading today, about on the brain how it's like doing aerobic exercise in midlife for a mouse, like, prevented the blood-brain barrier from breaking down, prevented, decrease the amount of activated microglial, all... So there's a lot of other benefits from exercise that did not related to...
Ray: The point is here, and this is about changing our conversation because it almost is impossible to talk about something other than exercise without someone saying, "Yes, but exercise..." Forget that. We all know there's benefits to exercise. Let's just put that aside for a second and let's say, "Okay, what specifically might be going on? What specifically..." The same people probably didn't study the same people that were in mild cold stress. And maybe some of the same benefits can happen with that.
So, all I'm saying is that it's possible. You can't prove right here. But it's possible that a lot of these benefits, of these excess moving, because in nature, all organisms are conserved or they conserve. They live a conserved life. We want to think of them all active and they're on the hunt. And they're more active than us and we live a sedentary, our lifestyle.
But the opposite of sedentary isn't exercise. The opposite of sedentary is active. And I didn't say I wasn't active. I never said I never got on a bike. I just didn't changed clothes to do it. I didn't say I didn't never got one of the kids for a walk, I didn't say that we don't go...I'm a skateboarder. So, I didn't say we didn't longboarding. I just said I don't, I didn't count it. I didn't write it down. I didn't do it.
Rhonda: You're not going to a gym. You're not like... You're not this...
Ray: So, what I'm trying to say disruptively is, "Wait. Let's stop talking about exercise for a minute." Because these all got started in around 1911, between 1900 and 1911. McFadden was the first one. I'll show you the books when all these got together. And the link of diet and exercise primarily through the calorie.
Now, we since learned there's a lot benefit. But the vast majority of people think it's energy. I'm outputting energy and I'm inputting energy and I'm trying to maintain that balance. And that's really not the way I'm thinking of exercise. I'm thinking of exercise the way we think of food differently. So, we are on the same side of that.
And I'm saying that there are things that exercise does that might likely mimic cold stress because exactly the same thing happens. It doesn't make sense for the body to create irisin that creates a tissue that burns fuel and just creates waste heat. Unless it was more energetically do it. It was more energetically to get up and move, to migrate the waste heat, to go get something. That would have probably been the pathway.
I'm saying there's a good argument to be made that maybe the benefits are that we evolve those sets of cold stress responses to happen to mimic the dietary restrictions as a survival mechanism for winter. And we've just engineered winter out of our life in the last century.
Rhonda: We do have temperature-controlled environments that are, you know... And I think that both temperature extremes are important. And if you're living somewhere, like, in the South, it's hot as hell in the summer and winter is cold maybe that's the way it was supposed to be. Maybe, your body is supposed to be shocked by the heat and shocked by the cold. But instead, we come into this heat and air-conditioned houses and, you know...
Ray: And what you said it, when we were talking to the party, we're sort of making our literal mind meld implosion in the center of the room, right? You know, I think we sort of forgotten everybody was there, we're... But the heat shock proteins, they're very similar to the cold. So, the point I'm saying is, if we could just entertain the thought Aristotle said it's a mark of the educated mind to to entertain the thought without embracing it.
And I'm saying, let's put exercise aside for a second. Just like I'm saying, as soon as I talk about calorie restriction, intermittent fasting, fasting, immediately, the dieticians go, "Yeah, but you got to have balance. You can't be deficient." It's like, "Okay. We understand that that's there. We don't want to talk about deficient. We're not talking about deficiency." But they don't even know the concept, they don't even know an idea behind how a person would possibly even live... They think you die in days without nutrition. They just, they do. And it's funny, right?
And yet, I'm having this is a pretty challenging conversation. And it's today, 23...
Rhonda: Yes. I have a question.
Ray: Go ahead.
Rhonda: On your 21-day fast, like, so what happen to your bowel movements, like...
Ray: They stop. I still haven't had one.
Rhonda: Like how long?
Ray: The last one had was Monday at a 7-11 on October the 12th.
Rhonda: And today's November 3rd.
Ray: I haven't, yeah. You just don't have them.
Rhonda: That's pretty wild.
Ray: Yeah. It's crazy. You don't have bowel movements.
Rhonda: Could you please do a uBiome, Like, I want to... Oh, you didn't do it before.
Ray: Dammit, I know. I wanted to...
Rhonda: Oh, Ray, what's wrong with you?
Ray: I just have so much to get...I just had so much other. I mean...
Rhonda: That would have been so interesting.
Ray: All the blood work I did was so expensive and I've used really donation on my blog. You know, there's plenty of opportunities to do this again. You're absolutely, well, I should have done it. I should have done it. And the last time, in the nitrogen, I forgot to do nitrogen. I didn't do nitrogen the last time. I had dexus. So this time I did nitrogen. So, I have that. But anyway, getting back to cold stress. The point I'm making is that this is what I mean about changing dialog. And what I'm trying to do in my book, "Our Broken Plate," is talk about how we can separate these. I got a chapter on exercise. Look, okay, I'm starting this all. Exercise has a lot of benefits. Okay, did we get that over with?
Okay, I don't want to talk about that anymore. I want to talk about were exercise overlaps with this really cool, really...pun intended, I guess...cool things in our biology that are connected with longevity. And it's like extreme. Okay, I know we can live in extreme environment. We can deal with all extreme stuff, but quite frankly, I don't have this testosterone rush. I don't have to beat my chest and say, "You know, I'm the he-man with the abs." I just really, really care a lot and I want to live long. You know, they can have the abs or whatever they want.
So, the point I'm making is what I want to do is look at this cold stress and say, "Okay, look, here are all the things that we know are up-related. Here are all the things that happen. Yes, they have an overlap with exercise. And then, over here, we've got nutrition. And there are things that we need to be nourished with and things we don't want to be deficient in, but here's where we have dietary restrictions." And I think that something can be put together. And then you add the third part of the trichotomy, which is sleep. It's clearly sleep is beneficial for both those.
So if we look at this little trichotomy. It's sleep, cold stress, and dietary restriction. To me, that's the axi we start with. And then, the exercise, again, just like we talked about with starches and sugars earlier with the studies, all the exercise stuff, a lot of it is done on people that are living in a normal world. So, if it makes you better in a normally overfed, overnourished kind of world, that doesn't mean people that have actually are approaching diets like you and I care about our diets and we're approaching something, at least the best we can figure out, approaching something that's optimal, if it's necessarily going to have the same benefit as us. It might drive overnutrition because there is a feedback loop. There is a point, there is a tipping point...
Rhonda: I'm just in my head, thinking there might be a temporal effect too because I'm just now, I'm recalling a study. So, this animal study I just told you that it was just published in FAS Journal, I believe...Maybe it was "Plus," it's one of the... I'm sorry I don't know which journal. But it was published like today where they showed that in midlife aerobic exercise had all these positive effects in your brain, delayed markers of Alzheimer's and all of those stuff.
There's another study, though, it's published, about last year in "Nature" that showed that cold stress, it was mild cold stress, actually, it's more than mild because it's more like standing in a refrigerator for 30 minutes, so it's cold.
Ray: Right. Every two hours.
Rhonda: Yeah. But it showed that mild cold stress protected against Alzheimer's disease in animal models that were genetically engineered to get Alzheimer's, human Alzheimer's. It showed that it protected against it but only if the cold stress was done in early life. So, if cold stress was done in midlife, and not in early life, it had no protective effect. So, it was kinda weird, and I'm not exactly sure why.
But, I do want to ask you on the cold stress. I would be interested in seeing the studies to see if there's synergistic effect on the brain. I'm also very interested in the brain and effects of exercise in the brain.
Ray: Most of the work that I did on cold stress, because where I was in that point in my life, I didn't understand calories. And so, I was really trying to understand how can we maximize calorie burn. I really believed the goal at that time was to create more metabolic output. And I hadn't quite found that I can control weight and everything perfectly with the dietary input. It's actually pretty trivial.
So, now that my goal has flipped, so a lot of the things that I know about these are ancillary to what I was looking at at that time. But I've aggregated a lot of studies on that. So, just, it would be a great day to dump, when we go back, I've got a lot of them. Unfortunately, I have to have paper when I'm reading a paper. I can't do it online. I can't do it electronically. Maybe with the new iPad.
Rhonda: Some people are physical, like, do you remember things by physical...
Ray: It was just because I did it that way for so long. I always had notebooks, I always wrote, whatever. Maybe, with the new iPad Pro, whatever, it's big enough and I can right on the paper. Maybe that will give me enough tactile input that I can do it.
So, the downside is I've got all these PDFs that are lost mentally... The upside is that I have lot of them organized because they are paper. I have a lot of them. They're in one place. We could just use data dump. But, I wasn't looking at what you were looking at. That's the point.
Rhonda: But I want to ask you about, like, a protocol. Let's say if someone wants to try to increase some of their brown adipose tissue, they want to ramp up their fat oxidation in using mild cold stress, is there some sort or general protocol where you say, "You know, spend..." in addition to your contrast that you've mentioned. You know, you spend 20 minutes in 60-degree water or something like that. Is there something that you think would work?
Ray: It's on my website. I actually have the data right there, you can see it. I mean, it doesn't burn a significant amount of fat. That's the downside. So, you're not going to really... The weight loss is minimal. It does in addition to dietary restriction, but you have to have some kind of deficit to start with. But it definitely shifts your RQ.
And what I have seen is that generally speaking, after a few weeks of cold stress and doing restrictive diet, where you're just running in a chronic deficit. You're going to see your RQ shift more towards 0.7, it lowers, it goes more towards fat burning. You know, you can get yourself easily into mode where you're about 75% of your day is fat, is burning fat, metabolizing fat, if you keep your activity low. As soon as you start doing things, it raise your activity, your respiratory quotient starts going back up and then you're on a glycogen treadmill, which is why all these people want to get to ketogenic because they want short, change this system.
But I'm talking about something that also benefits the microbiome, etc. And if I do that lifestyle, then the microbiome is like pushing a bubble on a bumper sticker, you know. They're just pushing the problem around, but nobody's worried about the microbiome. And that ends up being, I think, like, we said earlier, that's actually the most important place. That's where we need to start. Feeding it, and make sure we get that, but shifting it over to fat, you absolutely can with cold stress.
Most people just don't have access to cold water, you know.
Rhonda: What about just sitting in a cold bathtub, like if you just put cold water and...
Ray: Yeah, I think that. Again, what I do when I'm skiing, for example, is because since I was skiing every year, but I wasn't doing any activity or any training before. Normally, what that would mean is like on the second or third day, you will just be fatigued and your legs were wasted like noodles, right, everybody would think. Yet, it never happened to me. And the reason why is as soon as I come off the slopes, I go into the bathroom, I do a contrast shower, end on cold. The bathtub is already filled with cold water, as cold as it would come out the tap, just sit up to my waistline in cold water and all of that leaves. And you feel, when you get out, you've almost feel as if is you could go run and do anything again right then. It just does that. So that's like a little simple strategy that I use for that.
I moved past the calorie thing because in order to do the calorie balance, I needed to understand food. And so then, when I get the calorimeter... Yeah, I did some things with Steven on activity and all of a sudden it was like, "Wait a minute, it's all the food. It's the food. It's the food." Because no matter what I was doing, the numbers that I'm in... When you're really measuring your calories and you're really seeing exactly how much fat and carbohydrate you did in the session, you can't hide from it. And it's like over and over and I'm like, "Wait a minute. It's the food."
So, that got me off from four-year rabbit chase to figure out how that our relationship with food breaks. So to not answer your question, but address it at least to say is that I don't think I have it at that granularity. And I think, to me, where I am now, my interest is really in how much cold stress do we need to activate these things. That's where I want to go next with it. Next with, just like we were talking about earlier, with crowdfunding and potentially doing stuff with dietary intervention that we can measure these biomarkers, okay, then with and without cold stress, you know.
I live chronically in cold stress in the winter. So, I let my temperature fluctuate with the outside. My heat is set, maybe, at 50. So, it goes up sometimes because the day is warm and you get whatever.
Rhonda: Wow. That' what night is, it's get cold.
Ray: It's cool. Yeah, I don't sleep...
Ray: And I don't sleep with blankets.
Rhonda: At all?
Rhonda: You have sheet?
Ray: No, sometimes I, yeah...
Rhonda: At 50 degrees?
Ray: Yeah, I can sleep... Right now, I can't because of the fasting. But I conditioned myself. It's one of the things I did before, all of the stuff that came out in the "4-Hour Body." I started with blankets and I'm like we had blankets or we blanketed because we never use to heat bedrooms. That was blankets were for, the rest of the house was cold.
And now, we have blankets and we heat the bedroom. So, I started with the blanket and I folded it down. And then you'd have it back in the morning, right? And then you fold down. One night you wake up, it's "Huh, I didn't use the blanket tonight." You know, it was halfway. And I found that if it's just on my feet, just actually the weight on my feet, and it turns out, I have enough.
And you know, a lot of my friends are astronauts, one of my friends is Scott Parazynski, and they talk about sleeping. A lot of astronauts can sleep free-tethered and float. And a lot of astronauts needed tethered to something because they need that feeling because they don't like the the mummy free float thing. So, I'm a little like that and my feet needs some kind of weight on them, and that's funny. So, then I start with the sheet the same way. Put it halfway down, sleep without it, and then you get it back up. And where you end up with is really an interesting place.
So, for me, the comfort you get from a blanket, that this is like sugar feels good and food gets good, and that sort of thing. The comfort you get from a blanket is sort of this warmness, womb-like feeling. That feeling for me is between me and the bed. And when this side gets cold, I turn over and that's the warm spot, you know.
Rhonda: But you acclimated yourself to the [crosstalk].
Ray: But I acclimated. Now, have you ever taken a nap on the sofa?
Ray: Did you need to use a blanket? No. You can just sleep on the sofa.
Rhonda: I don't remember.
Ray: But you know my point. People falls asleep on the couch all the time. You don't need to do all that. It's just conditioning. And so, you don't just like put all your blankets off and say, "I'm going to sleep without covers." That's crazy. That's just like you're not gonna... You got to do it slowly.
And there's a really simple test to see if your room is too warm or you're over blanketing. And that is if you stick your feet out from the covers at night or in the morning, or you have to stick your hands out. If you do those two things, that's a sign that you're sleeping with too much covers. Because that's a way to trick your brain into thinking that you're cooler than you really are. Because we actually have to go to cool.
So, on the melatonin, which is a natural place everybody knows about melatonin reset and that sort of thing. And we can talk about the sirtuin and that paper I sent you with the activation, which I think is good for the longevity stuff, but one of the rules of melatonin is to have you drop...
Rhonda: Core body temperature...
Ray: Temperature through your extremities.
Rhonda: You actually told me that. You're the first person who told me that when we met a couple of months ago. And I was completely fascinated and I looked up the studies and I found... Yeah, and it's strange, melatonin, it does make their core temperature drop.
Ray: So, what's needed is this is part of that, gotta drop the brain temperature. And what we do is we have this warm room, we get in our warm pajamas we get in our flannels, we put this blanket on. Everything is antithetical to what our body is trying to do.
Now, enter the contrast shower. You start out with the contrast shower. Say 30 minutes or 1 hour or so before you're going to go to bed, right? Out of the shower, lights go off. Now, I'm into the...all these people walking around, Blue Walker, Blue Walk... whatever, fuck, I don't do that. Just come out there, lights go off. I have a little red light that's...my bed light is red and I switch to paper. The screens go off, and now I'm with my old books. I love reading my old books, right? Okay. Thirty minutes I stay in the dark, and I do about 30 milligrams of melatonin at night.
Rhonda: That's a lot melatonin.
Ray: Yeah, it is. It's a lot of melatonin.
Rhonda: It's a lot of melatonin.
Ray: Yeah, it is. I do about 30 milligrams a night and there's a lot of really great stuff that was done in '90s: melatonin, the antioxidants side, and obviously, this longevity studies.
Rhonda: Seen some of those, yeah.
Ray: And I don't fear it. I don't think that it's a bad thing. I'm doing it exactly when my body would be producing it.
Rhonda: Let me ask you again. So, the contrast shower was 10 seconds warm, 20 seconds cold, how many times...?
Ray: End on cold.
Rhonda: End on cold for two minutes.
Ray: Ten times.
Rhonda: Ten times, end on cold for 2 minutes, right?
Ray: Yeah. You know, I want you to get used to it because that's the conditioning part...
Rhonda: I'm going to try this. Because I want to see if does my circadian rhythm.
Ray: And then dry off, get on bed, and at that point, it's...I don't do the dark or I do dark or I do red lights.
Rhonda: No blue lights.
Ray: So, I do that, I don't do screens. And then I wait 30 minutes and then I do the melatonin.
Rhonda: And then you do the melatonin.
Ray: Sometimes, it's a problem because it used to be, like, after contrast shower I told you I'd hit the pillow and I'd fall asleep in like seven minutes, you know. I mean, you get sleepy. And I usually like my melatonin, I use the fast dissolves. So, I used to have them just laying down there, ready to go. And I wake up in the morning, there they will still be. I forgot it.
But anyway, so the melatonin... And one of the things it did for me is it completely cured secondary insomnia. It just...
Rhonda: The contrast therapy and the melatonin?
Ray: The combination of the two, yeah.
Rhonda: And blocking it...
Ray: I tried time release, it never worked, I tried melatonin alone. I was doing the 1 milligram that did nothing. And if somebody just starts with 30 milligrams, you're going to feel hungover in the morning. So, you can't just start there. Because, do you know what... Have you played with melatonin?
Rhonda: I have. The largest dose I've done...I usually only take melatonin if I'm trying to get over jetlag. And I've done 3 milligrams or if I'm traveling somewhere I can't sleep...
Ray: So, for a normal person doing melatonin and, in that point, if they go over the dose, the symptom is in the morning, they feel groggy and they don't want to wake up.
Rhonda: I've heard about that, yeah.
Ray: So, in the beginning, it's just not possible to do that. So, it's just not possible to do that. But I built up a lot. And I'm getting all obviously at past 40, my melatonin is falling off precipitously at this point that's what all the studies say. I'm doing it at the circadian time. The time on my brain would be releasing it, probably is releasing it. And feel like at that point, I'm also I'm entering a fasted state as well. You know, the dietary restriction my meals were earlier in the day, so I'm so far past, I'm in the post-absorbed state at this point. And so, I just feel like it's going to be beneficial.
And then, this study just came out. And unfortunately, I haven't had time to dig into the one that I posted for you, which is the, basically, SIRT1 and melatonin and resveratrol all working together. So, they found a synergistic fact with melatonin, resveratrol, and SIRT1. So, again, I see this clue once again of this little trichotomy: sleep, dietary restriction, cold stress.
Rhonda: Well, melatonin is a hormone, regulates 500 different genes, I mean, it's 2.5% of the human genome. You know, it's, like you said, it's one of the most important hormones that regulate brain antioxidants activity. You know, those studies have been shown [crosstalk]
Ray: I mean, in '90s there are a lot of really, I know they were sort of fad diets books, but there are serious researchers too. They were all publishing all the little books that with the small print that used to come out the way diet books used to be, you know. Before it was big money. And then to glossy stuff we see today.
Rhonda: And you also mentioned that you know, you're at a point in your life where your melatonin is dropping precipitously. And that's at least from the studies that I've seen in like around 40 years, your pineal gland starts to make less and less melatonin.
The other interesting thing is that most of the melatonin made in the body is actually made in the gut.
Ray: Gut...right the serotonin.
Rhonda: Yeah, serotine gets converted into melatonin. And my question is, what is it doing in the gut? Like, what is it doing in the circulatory system? I'm kinda interested in that. Like, I'd like to know.
Ray: I think this is like...This paper really made me excited because I had hypothesized these connections. And ran them by David. And we actually, we touched on it. We had, because of editorial limits on that first paper, we had to sort of walk away a little bit from the sleep part. And we mainly focused on...
Rhonda: It sucks.
Ray: ...the other stuff. But what it's like. You know, it's like, okay we got...
Rhonda: Too many words, they make you trim it down.
Ray: Well, basically, but we've got it in there but we had to do... We just said that people can adapt to sleeping cool. These are like the aboriginal studies that were done. And I think in the '30s or whatever, where they took literally refrigerated trucks in Australia, took the natives, who by culture they sleep under 30-degree temperature. No covers, no blankets, they shiver all night. And they get perfect REM sleep.
And yet, the Caucasian control, those guys were just miserable and they were horrible. The same thing with the Lapps, you know. They could learn to sleep in these cold, just on a little cot above the floor. The ice hut, and they were getting amazing sleep even though it was cold. And they weren't all blanketed, you know.
So, what we know is we're highly adaptable. That's the point we're making in the paper. And in fact, we know that we've now some studies have come out in terms of metabolic rate and activity. The ones that were done in NIH, with [inaudible 01:55:27], people sleep better, I sleep better. Hospitals are cold not warm and there's a reason, you know.
Rhonda: What I like to understand is...one, I can't sleep in the heat. That's like, you know, I think a lot of people are like that. But what I like to understand is why core body temp... Core body temperature is absolutely under a circadian rhythm, obviously melatonin plays a role in that.
But I would like to understand why exactly. Why is it your body being cold, cooler make you sleep? Like, why? You know, I like to present a mechanism. I'm curious. I want to know. And I'm trying to figure it out. I just started looking into it...
Ray: I think it's tied to the fact that a drop in temp, half a degree, that the brain needs to see. You know, that's half degree. You know, it's really amazing...
Rhonda: Hibernation? You know, that's when a...in winter when they sleep.
Ray: Yeah. And if you think about it it's really amazing if you think about homeotherms versus poikilotherms. I mean, look at the difference in our regulatory mechanisms and you look at how in the hell our bodies stay in a certain temperature. And another big leader in the thermoregulation side, that's a whole another branch of people, really interesting colleague that I've met. He's been amazing, Ivanov, has done all those stuff in regulation.
Interestingly, our temperature is a result of energy flux. And we don't actually maintain body temperature. So, we're actually not maintaining 98.6. It's the net sum of what actually is going on. And that's actually kind of interesting. And he's done amazing studies. When I was doing all the stuff with the energetic stuff, his stuff was really, really incredible. But it just seems like this thing comes up over and over that these things get connected. And if you think about it, in the last century and that's the subtitle of my book How Our Mastery of Food and Environment May Have Led to Unintentionally Chronic Disease and Obesity.
Rhonda: Super cool, Ray. This has been a very interesting conversation we've had. We've covered a lot.
Ray: Yeah, we did.
Rhonda: We covered a lot. But...
Ray: The room didn't melt this time.
Rhonda: Yeah, right? If people wanted to learn more about the science you're doing and the books you're writing and the experiments you're doing, anything about Ray Cronise, where can they find you? What...
Ray: Well, Google is easy, just Ray Cronise. It's C-R-O-N-I-S-E. I guess you'll slug that. Right now, for a short period of time, when this is being... If you're looking later, I have a crowdsource. "Our Broken Plate" is the title. It's on Kickstarter. I love your support to try to do this. This is sort of proof that we can sort of do this.
And then, my regular website is hypothermics.com. But raycronise.com points to it. I probably be blogging a little less. I mean, literally, I blog once in the last year, twice. I'm not one of the people that has to put something up every week just to drive traffic because I don't care. I just want to have something that really to say that I put it up there. But go back and start and read, and you'll see actually where I was wrong. Because one of the things that you and I know, but a lot of people don't, science, you're only learning when you're wrong. And if your thoughts don't evolve and if you don't change along with time, you're probably not, like, pushing, hard enough.
So, you'll actually see my thinking evolve on this. Some of the things we talk about today, I go into more details. So that site. And then, sooner or later, I'll probably have "Our Broken Plate" and do a little work on there. So, I hope to use that as focus point to try to pull together some of the philanthropy money that's thrown and all the other stuff.
Rhonda: What about social media? Do you...?
Ray: Twitter. It's @raycronise. I have an Instagram. I think my Instagram is Mr. ZeroG. You know, you can link to all those YouTube channels all. And I'm not putting anything on there right now. But you can link to all those at my Hypothermics page.
Rhonda: Awesome. Cool. Thanks a lot Ray for this.
Ray: Great. It's been fun.
A nonessential amino acid that is able to be manufactured by the human body and not dietarily required. It is nevertheless found in a wide variety of foods, and is particularly concentrated in meats.
An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.
The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.VIEW AUTOPHAGY TOPIC
A laboratory analysis performed on a blood sample obtained either from a needle or finger prick. Blood panel tests are often used in healthcare to determine disease, mineral content, pharmaceutical drug effectiveness, or organ function. Typical blood panels include a basic metabolic panel, lipid panel, or a complete blood count.
A bow wave is the wave that forms at the bow or "forward part" of a ship when it moves through the water. As the bow wave spreads out, it defines the outer limits of a ship's wake.
The belief that it is possible for a person to live without consuming food. Breatharians claim that food, and in some cases water, are not necessary for survival, and that humans can be sustained soley by prana, the vital life force in Hinduism.
The practice of long-term restriction of dietary intake, typically characterized by a 20 to 50 percent reduction in energy intake below habitual levels. Caloric restriction has been shown to extend lifespan and delay the onset of age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast.
Organic pigments that are found mainly in the chloroplasts of plants and are responsible for absorbing light. Plants use carotenoids to create energy and protection from harmful UV rays and animals commonly use carotenoids as a precursor for vitamin A.
A member of the molluscan class Cephalopoda. The class now contains two, only distantly related, extant subclasses: Coleoidea, which includes octopuses, squid, and cuttlefish; and Nautiloidea, represented by Nautilus and Allonautilus. In the Coleoidea, the molluscan shell has been internalized or is absent, whereas in the Nautiloidea, the external shell remains.
The body’s 24-hour cycles of biological, hormonal, and behavioral patterns. Circadian rhythms modulate a wide array of physiological processes, including the body’s production of hormones that regulate sleep, hunger, metabolism, and others, ultimately influencing body weight, performance, and susceptibility to disease. As much as 20 percent of gene expression in the human body is under circadian control including genes in the brain, liver, and muscle. As such, circadian rhythmicity may have profound implications for human healthspan.
A substance whose presence is essential for the activity of an enzyme. Many minerals and vitamins are cofactors for enzymes.
Complex carbohydrate foods provide vitamins, minerals, and fiber that are important to the health of an individual. As opposed to simple or refined sugars, which do not have the vitamins, minerals, and fiber found in complex and natural carbohydrates. Simple sugars are often called "empty calories" because they have little to no nutritional value.
A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.
The process by which amino acids are broken down. The amino group is removed from the amino acid and converted to ammonia. The rest of the amino acid is made up of mostly carbon and hydrogen, and is recycled or oxidized for energy.
A medical condition in which patches of skin become rough and inflamed. with blisters that cause itching and bleeding, sometimes resulting from a reaction to irritation (eczematous dermatitis) but more typically having no obvious external cause.
Essential Amino Acids
Amino acids that cannot be synthesized from scratch by the organism, but must be supplied via diet. The nine amino acids humans cannot synthesize are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine.
A molecule composed of carboxylic acid with a long hydrocarbon chain that is either saturated or unsaturated. Fatty acids are important components of cell membranes and are key sources of fuel because they yield large quantities of ATP when metabolized. Most cells can use either glucose or fatty acids for this purpose.
Transfer of fecal material contain bacteria and natural antibacterials from a healthy individual into a diseased recipient.
Fecundity is similar to fertility. Representative of an organism's potential to create offspring.
Flavonoid are widely distributed in plants, fulfilling many functions. Flavonoids have been shown to have a wide range of biological and pharmacological activities in animal, human, and in-vitro studies. Examples include anti-allergic, anti-inflammatory, antioxidant, antimicrobial, anti-cancer, and anti-diarrheal activities.
A type of water-soluble B-vitamin, also called vitamin B9. Folate is critical in the metabolism of nucleic acid precursors and several amino acids, as well as in methylation reactions. Severe deficiency in folate can cause megaloblastic anemia, which causes fatigue, weakness, and shortness of breath. Certain genetic variations in folate metabolism, particularly those found in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene influences folate status. Inadequate folate status during early pregnancy increases the risk of certain birth defects called neural tube defects, or NTDs, such as spina bifida, anencephaly, and other similar conditions. Folate deficiency and elevated concentrations of homocysteine in the blood are associated with increased risk of cardiovascular disease. Low folate status and/or high homocysteine concentrations are associated with cognitive dysfunction in aging (from mild impairments to dementia). The synthetic form of folate is called folic acid. Sources of folate include most fruits and vegetables, especially green leafy vegetables.
A protein that provides the instructions for genes responsible for the regulation of cellular replication, resistance to oxidative stress, metabolism, and DNA repair. FOXO3 may play an integral part in both longevity and tumor suppression. Variants of FOXO3 are associated with longevity in humans. Humans with a more active version of this gene have a 2.7-fold increased chance of living to be a centenarian.VIEW FOXO TOPIC
The process in which information stored in DNA is converted into instructions for making proteins or other molecules. Gene expression is highly regulated. It allows a cell to respond to factors in its environment and involves two processes: transcription and translation. Gene expression can be turned on or off, or it can simply be increased or decreased.
A metabolic pathway in which the liver produces glucose from non-carbohydrate substrates including glycogenic amino acids (from protein) and glycerol (from lipids).
A highly branched chain of glucose molecules that serves as a reserve energy form in mammals. Glycogen is stored primarily in the liver and muscles, with smaller amounts stored in the kidneys, brain, and white blood cells. The amount stored is influenced by factors such as physical training, basal metabolic rate (BMR), and eating habits.
Gram negative Bacteria
Gram negative bacteria contain within their outer membrane lipopolysaccharides (LPS). This substance is known to elicit strong immune responses in animals and is also used experimentally to induce inflammation in the lab. These molecules are also referred to as endotoxin and bacteria that have been killed by the immune system in the gut are the major source of endotoxin.
Individual's basal metabolic rate (BMR) and daily kilocalorie requirements. The estimated BMR values is multiplied by a number that corresponds to the individual's activity level. The resulting number is the recommended daily kilocalorie intake to maintain current body weight.
The years of a person’s life spent free of disease.
The production of red bloods cells, white blood cells, and platelets from hematopoietic stem cells, which occurs in the bone marrow. Also called hematogenesis, or hematopoiesis.
Hemoglobin A1C (Glycated Hemoglobin)
A blood test that measures the amount of glycated hemoglobin in a person’s red blood cells. The hemoglobin A1c test is often used to assess long-term blood glucose control in people with diabetes. Glycation is a chemical process in which a sugar molecule bonds to a lipid or protein molecule, such as hemoglobin. As the average amount of plasma glucose increases, the fraction of glycated hemoglobin increases in a predictable way. In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, neuropathy, and retinopathy. Also known as HbA1c.
Warm-blooded animal species can maintain a body temperature higher than their environment. In particular, homeothermic species maintain a stable body temperature by regulating metabolic processes.
Biological responses to low-dose exposures to toxins or other stressors such as exercise, heat, cold, fasting, and xenohormetics. Hormetic responses are generally favorable and elicit a wide array of protective mechanisms. Examples of xenohormetic substances include plant polyphenols – molecules that plants produce in response to stress. Some evidence suggests plant polyphenols may have longevity-conferring effects when consumed in the diet.
the process of growing plants in sand, gravel, or liquid, with added nutrients but without soil.
Hypothermia is a medical emergency that occurs when your body loses heat faster than it can produce heat, causing a dangerously low body temperature. Normal body temperature is around 98.6 F (37 C). Hypothermia occurs as your body temperature passes below 95 F (35 C)
Indirect calorimetry calculates heat that living organisms produce by measuring either their production of carbon dioxide and nitrogen waste, or from their consumption of oxygen. This can be combined with other experimental methods to investigate numerous aspects of nutrient assimilation, thermogenesis, the energetics of physical exercise, and the pathogenesis of metabolic diseases.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
Insulin-like growth factor 1 (IGF-1)
One of the most potent natural activators of the AKT signaling pathway, stimulator of cell growth and proliferation, potent inhibitor of programmed cell death, primary mediator of the effects of growth hormone, and has been implicated in contributing to aging and enhancing the growth of cancer after it has been initiated. Similar in molecular structure to insulin, IGF-1 plays a role during childhood for growth and continues later in life to have anabolic, as well as neurotrophic effects. Protein intake increases IGF-1 levels in humans, independent of total caloric consumption.
A physiological condition in which cells fail to respond to the normal functions of the hormone insulin. During insulin resistance, the pancreas produces insulin, but the cells in the body become resistant to its actions and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level.
A broad term that describes periods of voluntary abstention from food and (non-water) drinks, lasting several hours to days. Depending on the length of the fasting period and a variety of other factors, intermittent fasting may promote certain beneficial metabolic processes, such as the increased production of ketones due to the use of stored fat as an energy source. The phrase “intermittent fasting” may refer to any of the following:
- Time-restricted eating
- Alternate-day fasting
- Periodic fasting (multi-day)
A protein secreted from muscle in response to exercise. Irisin may mediate some of the beneficial effects of exercise in humans. Some evidence suggests irisin may play a role in promoting weight loss, preventing diabetes, and slowing memory deficits associated with neurodegenerative disease.
A playful imitation of language consisting of invented, meaningless words; nonsense; gibberish. This term was coined by Lewis Carroll in Jabberwocky, a poem in Through the Looking Glass (1871).
The Sami people. An indigenous Finno-Ugric people inhabiting the Arctic area of Sapmi, which today encompasses parts of far northern Norway, Sweden, Finland, the Kola Peninsula of Russia, and the border area between south and middle Sweden and Norway.
A hormone that regulates the sleep-wake cycle in mammals. Melatonin is produced in the pineal gland of the brain and is involved in the expression of more than 500 genes. The greatest influence on melatonin secretion is light: Generally, melatonin levels are low during the day and high during the night. Interestingly, melatonin levels are elevated in blind people, potentially contributing to their decreased cancer risk.
 Feychting, Maria, Bill Österlund, and Anders Ahlbom. "Reduced cancer incidence among the blind."_ Epidemiology_ (1998): 490-494.
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
A sulfur-containing amino acid that is a constituent of most proteins. It is an essential nutrient in the diet of vertebrates. Methionine restriction in lower organisms has been shown to extend lifespan.
The collection of genomes of the microorganisms in a given niche. The human microbiome plays key roles in development, immunity, and nutrition. Dysfunction of the microbiome is associated with the pathology of several conditions, including obesity, depression, and autoimmune disorders such as type 1 diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, and fibromyalgia.
Vitamins and minerals that are required by organisms throughout life in small quantities to orchestrate a range of physiological functions. The term micronutrients encompasses vitamins, minerals, essential amino acids, essential fatty acids.
Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells used to transfer chemical energy from a food source to the electron transport chain. It exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively. NAD levels rise during a fasting state and activates the SIRT1 pathway. NADH levels rise during the fed state and serve as reducing equivalents to produce ATP.
A substance produced in the brain. Norepinephrine acts as a hormone and neurotransmitter and is best known for its role in the body’s “fight or flight” response to stress. Its role as a neurotransmitter has been exploited as a molecular target for a class of drugs known as norepinephrine reuptake inhibitors, which were developed for the purpose of treating disorders ranging from ADHD to narcolepsy and depression. Norepinephrine also plays a role in converting white adipose tissue into brown adipose tissue via an uncoupling protein 1 (UCP-1) mediated mechanism.
A carbohydrate polymer comprised of three to ten simple sugars connected through glycosidic bonds.
Surface of one's tongue. Used to describe a person's taste preferences.
A diet based mainly on foods presumed to be available to paleolithic humans. It includes vegetables, fruits, nuts, roots, meat, and organ meats while excluding foods such as dairy products, grains, refined sugar, legumes, and other processed foods.
PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha)
The master regulator of mitochondrial biogenesis. PGC-1α is activated in human skeletal muscle in response to endurance exercise. It is strongly induced by cold exposure, linking this environmental stimulus to adaptive thermogenesis. PGC-1a has been implicated as a potential therapy for Parkinson's disease by conferring protective effects on mitochondrial metabolism.
It is the opposite of a homeotherm. Organisms who do not use metabolism to maintain a certain body temperature. Often they can have variance in body temperature depending on the ambient temperature.
Relating to the period after eating. Postprandial biomarkers measures provide indicators of metabolic function. For example, postprandial hyperglycemia is an early sign of abnormal glucose homeostasis associated with type 2 diabetes and is markedly high in people with poorly controlled diabetes.
Highly processed grains, starches, or sugars. Refined foods are typically processed via industrial extraction, concentration/purification, or enzymatic transformation and often lack the vitamins, minerals, and dietary fiber of whole foods. Many refined foods have a high glycemic index, which can rapidly produce an elevated glucose response.
Regulatory T Cells
Also known as T regulatory cells or Tregs. A component of the immune system that suppress immune responses of other cells. This is an important "self-check" build into the immune system to prevent excessive reactions. Regulatory T cells come in many forms with the most well-understood being those that express CD4, CD25, and Foxp3 (CD4+CD25+ regulatory T cells).
Cellular respiration is the process by which oxygen is utilized to generate energy inside of the mitochondria.
A polyphenolic compound produced in plants in response to injury or pathogenic attack from bacteria or fungi. Resveratrol exerts a diverse array of biological effects, including antitumor, antioxidant, antiviral, and hormonal activities. It activates sirtuin 1 (SIRT1), an enzyme that deacetylates proteins and contributes to cellular regulation (including autophagy). Dietary sources of resveratrol include grapes, blueberries, raspberries, and mulberries.
Resveratrol Autophagy ↑ Deacetylases (especially SIRT1) → ↓ Protein Acetylation → Autophagy
Respiratory quotient. RQ=CO2 eliminated/O2 consumed. Used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. Such measurements, like measurements of oxygen uptake, are forms of indirect calorimetry. It is measured using a respirometer.
A disease caused by a deficiency of vitamin C. Humans and certain other animals require vitamin C from the diet in order to synthesize collagen. Scruvy can cause spongy gums, bleeding from the mucous membranes, and eventually, loss of teeth and open suppurating wounds form impaired wound healing.
The condition or process of deterioration that occurs with age. Cells that acquire enough damage can become senescent, which means they are not metabolically active and do not serve a function. Senescent cells often release inflammatory cytokines, which can then lead to the damage of neighboring healthy cells.
A member of the sirtuin protein family. SIRT1 is an enzyme that deacetylates proteins that contribute to cellular regulation (reaction to stressors, longevity). It is activated by the phytochemical resveratrol as well as fasting.
A class of enzymes that influence that influence aging and longevity through multiple molecular pathways. Sirtuins regulate a variety of metabolic processes, including release of insulin, mobilization of lipids, response to stress, and modulation of lifespan. They also influence circadian clocks and mitochondrial biogenesis. Sirtuins are activated when NAD+ levels rise. The dependence of sirtuins on NAD+ links their enzymatic activity directly to the energy status of the cell via the cellular NAD+:NADH ratio, the absolute levels of NAD+, NADH or nicotinamide or a combination of these variables. There are seven known sirtuins, designated as Sirt1 to Sirt7.
A type of polysaccharide – a large carbohydrate consisting of many glucose units joined by glycosidic bonds. Starch is produced by plants and is present in many staple foods, such as potatoes, wheat, maize (corn), rice, and cassava. It is the most common carbohydrate in human diets. Pure starch is a white, tasteless, and odorless powder.
A class of drugs that lower blood cholesterol levels by blocking the production of an enzyme in the liver called hydroxy-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). Taking statins may reduce the risk of cardiovascular disease in some people. Although statins are generally well tolerated, as many as 10 – 20 percent of people taking the drugs experience complications, including myopathy (muscle damage), liver damage, and cognitive problems, including issues with forgetfulness, memory loss, and confusion.
Distinctive structures comprised of short, repetitive sequences of DNA located on the ends of chromosomes. Telomeres form a protective “cap” – a sort of disposable buffer that gradually shortens with age – that prevents chromosomes from losing genes or sticking to other chromosomes during cell division. When the telomeres on a cell’s chromosomes get too short, the chromosome reaches a “critical length,” and the cell stops dividing (senescence) or dies (apoptosis). Telomeres are replenished by the enzyme telomerase, a reverse transcriptase.
Theory proposed by Dr. Bruce Ames which proposes that when the body is deficient in a micronutrient it will allocate its scarce supply to enzymes necessary for short-term survival and reproduction at the cost of long-term survival enzymes. This may result in the acceleration of the aging process.
Type 2 diabetes
A metabolic disorder characterized by high blood sugar and insulin resistance. Type 2 diabetes is a progressive condition and is typically associated with overweight and low physical activity. Common symptoms include increased thirst, frequent urination, unexplained weight loss, increased hunger, fatigue, and impaired healing. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, diabetic retinopathy (and subsequent blindness), kidney failure, and diminished peripheral blood flow which may lead to amputations.
Type A and Type B personality theory
Type A and Type B personality theory describes two contrasting personality types. In this theory, personalities that are more competitive, outgoing, ambitious, impatient and/or aggressive are labeled Type A, while more relaxed personalities are labeled Type B.
Uncoupling protein 1 (UCP1)
A protein found in the mitochondria of brown adipose tissue, previously known as thermogenin. UCP1 is expressed only in brown adipose tissue, a specialized tissue which functions to produce heat via non-shivering thermogenesis.
A compound, CO(NH2)2, occurring in urine and other body fluids as a product of protein metabolism.
Volatile organic compound. An organic chemical that has a high vapor pressure at ordinary room temperature.
An adaptive physiological response in which bioactive compounds, produced by environmentally stressed plants, induce beneficial stress response pathways in animals, including humans. Xenohormetic responses ultimately confer stress resistance and longevity and may explain some of the beneficial effects of plant-based foods. The term xenohormesis stems from two terms: xeno (stranger) and hormesis (a protective physiological response induced by mild stressors). Polyphenols, isothiocyanates, and other plant compounds are thought to exhibit some of their beneficial properties by inducing a type of xenohormesis.
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