[00:00:00] Carl Lanore: [00:00:00] welcome back to another episode of superhuman radio. We have a great show planned for you today. A very important topic. One that I've been talking about for over a decade now, and that is the sleep, sleep quality, the importance of sleep. Um, we know that. The majority of Americans don't sleep well, the ones who say they do, they lie a lot of times.

[00:00:21] The reality is that, uh, all around the world sleep is a problem today and it's leading to a variety of diseases. Um, extreme levels of sleep deprivation can actually take a person's life. I remember reading an article about a guy who just couldn't sleep and it killed him eventually. And so we're going to be talking about.

[00:00:41] Why that actually happens. And it intersects another topic that we love on this show. And that's the microbiome in the gut because you know, I'm all about the gut. I really do believe that a lot of diseases today begin in the gut. And if we could get those straightened out, we would be a lot better off before we get started.

[00:00:58] I have to thank. [00:01:00] Um, my title sponsor and that is legendary foods. Uh, legendary foods makes a generous contribution to this show to make it possible, and they have the best responsible snacks in the world. And what do I mean by that snacks that don't have sugar or much sugar at all in them purposefully high protein, low impact carbohydrates.

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[00:02:00] Go to eat legendary.com. Use the code SHR 10 to get 10% off your entire purchase. Show them some love, uh, because, and by the way, Ron Penna. The co founder, he and his wife, Shannon started legendary foods is the reason we're doing this show because he sent me this study and I thought, Oh, he knew that this was going to be fascinating.

[00:02:21] So I'm going to bring my guests on now and see if I can do this easily. There we go. And we will also introduce them also, um, to my left, I have dr. Alex Vaccaro. Beneath her dr. Yosef Kaplan door and then a professor and doctor, uh, Dragnet regalia. Welcome to the show. Uh, all three of you. Thank you for being here today.

[00:02:46] Prof. Dragana Rogulja: [00:02:46] Thank you so much.

[00:02:47] Dr. Alexandra Vaccaro: [00:02:47] Thank you.

[00:02:48] Prof. Dragana Rogulja: [00:02:48] So

[00:02:49] Carl Lanore: [00:02:49] I'm going to start with you, dr. Julia, because you are also the professor, uh, in this, uh, department of, uh, of medicine. And I want to put the brand up so we [00:03:00] can plug. Uh, this is from the Harvard school of medicine, uh, and their website is right there. So let's talk first about this, uh, this study.

[00:03:10] Why was this study even important? What preceded this work that led you to want to do this? Or I guess, uh, dr. Vaccaro was really the one who, who was the lead author on this, but why, why this study.

[00:03:23] Prof. Dragana Rogulja: [00:03:23] Yeah. So there's really a lot of evidence like you already alluded to that sleep loss is bad, right? There are a lot of diseases that can be directly or indirectly, uh, linked to poor sleep.

[00:03:37] So now we really think that. Having sleep problems can exacerbate a lot of diseases, but even cause some, and these are pretty serious things like including cancer, diabetes, depression, et cetera. So there's all this evidence there. And then you have sleep research, you know, people doing research on sleepy labs, et cetera.

[00:03:57] And. Most of this work, [00:04:00] not all, but most of it was focused on the brain, sort of what does sleep do for the brain. And that's not that surprising if you think about the fact that, of course the nervous system is needed to generate sleep. You dream during this time. And of course, if you don't sleep, you do feel.

[00:04:13] Pretty bad the next day. You can't really think straight and saw. Um, and so it's pretty clear that sleep is required for normal brain function. Uh, but we thought that this would not be all there is to it. Right? So we also know that animals that are a lot more simple than we are that have very simple, nervous system, have nothing resembling our brain.

[00:04:33] They do engage in these behaviors that resembles sleep and they seem to need, so many studies have been done where people would deprive various model organism and sleep longterm. And then what they would see is that normally this leads to death of the animal, but there was no explanation for this, so that there's never been any quality causal, causal cause of this, that, uh, found.

[00:04:54] And so when you put all of this together, we just thought that there's probably some more. [00:05:00] Fundamental or vital nature of sleep. The probably originated a long, long time ago. And then all of these, you know, fancy things to sleep is doing now probably evolved over the many millions, millions of years of animal level.

[00:05:13] Carl Lanore: [00:05:13] Okay. And so we simply ask them and yeah, yeah,

[00:05:17] Prof. Dragana Rogulja: [00:05:17] yeah, yeah. I, I think of humans as animals, so yes. Animals, including humans. Yes, exactly.

[00:05:23] Carl Lanore: [00:05:23] Um,

[00:05:25] Prof. Dragana Rogulja: [00:05:25] so, so, you know, so we, we definitely, we definitely think that, you know, all these things that people find there's a synaptic remodeling. There's. Flushing of things from the brain, et cetera, all of these things probably do happen, but that's not all there is.

[00:05:38] And again, memories, all of that are impacted, but that's not all. So we thought, okay, let's start from kind of first principles and just figure out for ourselves. What does it really do? Well, what happens when animals are sleep deprived? Can we really observe this kind of lifespan? You know, is it shortened in sort of predictable way or did things just fall apart [00:06:00] randomly?

[00:06:02] The main thing is that if the animal is dying, for example, when you really severely restricted sleep, there has to be some. Cellular damage. Right. And, and in the body somewhere. And so we just, that the most important thing is that we kind of rejected this notion that sleep has to be about the brain. You know, there's the same sleep is off the brain by the brain for the brain.

[00:06:22] It, we just thought it cannot be all about this. Maybe the reason why people can not figure out what's killing, what's killing animals when they're losing sleep is that they keep looking in the brain. And I just want to point out that. Studies before us, they have looked in sleep deprived brands and they just could not find any obvious signs of injury.

[00:06:39] So again, then we thought, okay, let's just start kind of from the bottom, build the story up exam and sleep deprived flies. It was shown by many, many labs that, uh, sleep in flies is very similar to our sleep, including the fact that they need. Sleep. So if you deprive them of sleep, they dire. So that's where we started from.

[00:06:57] And then we thought, okay, if we find something, [00:07:00] if we frequent figure out what's happening in these animals, we can then take it to other model organisms, including.

[00:07:06] Carl Lanore: [00:07:06] So the, the, uh, I'll go to dr. Vaccaro now. So the interesting thing about this was really, I have to believe that. So your approach was almost like metabolic comics, right?

[00:07:16] We do this and we look at everything that could happen and, and look for the one thing. That seems to be happening that then drives premature death. W you had to be surprised that it was the oxidative effects of reactive oxygen species. ROS is not all bad. ROS actually has been implicated in stopping solid tumors from growing.

[00:07:42] For instance, it causes apoptosis in tumor cells. So it's, you know, and, and we all want to find the bad thing and we always find out, well, it's not bad. It's only bad in these circumstances, but you had to be surprised when you saw this, uh, this causal effect in reactive oxygen species, [00:08:00] correct?

[00:08:01] Dr. Alexandra Vaccaro: [00:08:01] Yeah. Uh, definitely.

[00:08:03] I think we were all surprised. Um, and like you said, I think the key was really to look everywhere. And, um, I think I was expecting probably to see multiple arguments that will be affected, and that will be really hard to actually pin it down to one specific place in the body. Uh, I think that was the most surprising to me, uh, when I looked at all those tissues and that it was only the gut that had.

[00:08:30] It's increasing reactive oxygen species or ROS, like, like you described, uh, and that it was still clear, um, compared to, uh, non deprived flies. So that was definitely like the most surprising thing. Um, and then I think what was really interesting, like you said, is that. ROS are good. And we see that they start accumulating at the beginning of the deprivation and it's gradual.

[00:08:53] Right. So it's probably happening. I was kind of a protective response at the beginning, but then they reach really high levels, [00:09:00] uh, right before animals start dying.

[00:09:01] Carl Lanore: [00:09:01] Well, let's, let's talk about that. So the, the, uh, maybe, um, Um, we could, we could throw this question to your, your, your colleague, dr. Yosef, uh, DOR.

[00:09:11] So we, we, the study was designed in such a way where you took a group of control and a group of, uh, of, uh, fruit flies. And what did you do to actually increase the oxidative stress in, in the, in this, the subject fruit flies out.

[00:09:31] Dr. Yosef Kaplan Dor: [00:09:31] I mean, we didn't directly try to cause the distress. Right. What we tried was to prevent sleep and we used three different methods. So one, and that's the one we use the most, um, is where we specifically, um, activate neurons in the fly brain that prevents sleep and other two

[00:09:50] Carl Lanore: [00:09:50] methods. Yeah. No, no. And how did you do that?

[00:09:53] So, so you, you used the, you used a, a function of, of temperature sensation, right?

[00:09:58] Dr. Yosef Kaplan Dor: [00:09:58] Yeah. So, [00:10:00] um, basically we use it's a widely used method, so we have genetically modified flies and just, we can, um, make them to express the specific protein called trippy one, uh, in very specific small subset of neurons in the fly brain, uh, and what we do.

[00:10:16] So this protein is sensitive to temperature. So, and flies cannot control their own body's temperature. So it's very easy. You can take these flies and just put them from a low temperature to high

[00:10:25] Prof. Dragana Rogulja: [00:10:25] temperature

[00:10:26] Dr. Yosef Kaplan Dor: [00:10:26] and. Forgive. Yeah, I, so in salvage it will be moving from 20 pounds of resales is at 29 degrees Celsius and you have to help you do convert it to Fahrenheit, but it's, it's not, it's not a dangerous temperature.

[00:10:38] Definitely would have flies can be healthy and

[00:10:41] Carl Lanore: [00:10:41] they're just uncomfortable, right? Like, like, like I'm that way. If the temperature is too warm in my bedroom, I don't sleep well. I know that I like to keep my bedroom 67 degrees and I sleep better. So what you're saying is that this is just a more severe, uh, reaction in, in these flies.

[00:10:59] It's not [00:11:00] that they just don't sleep well. They just don't sleep. Right. Yeah.

[00:11:03] Dr. Yosef Kaplan Dor: [00:11:03] So I, yeah, so I need to specify it's not, uh, the fact that they don't feel comfortable because of temperature. So it's true that, uh, temperature affects sleep in animals, including and flies, but our control flies, uh, we're also getting the same higher temperature and they were waiting fine and they were healthy.

[00:11:19] So the temperature is used as a, as a trigger as are like a very specific trick to activate a very small number of neurons in the fly brain. And then the flies don't sleep. So it's not the temperature per se.

[00:11:32] Prof. Dragana Rogulja: [00:11:32] Can I add something? Sorry to interrupt. Have you heard of, well, have you heard of optogenetics where you use light to?

[00:11:39] Okay. So that's, a lot of people will have heard of that. It's basically a method where you expressed certain light-sensitive proteins in the cell and. Then, if you, if you shine light from those neurons, they can be activated. This is called up to genetics. And the method that we use is called Thermo genetics.

[00:11:56] So the protein that you expressed in neurons is the [00:12:00] channel that's temperature sensitive, and then the neurons get activated essentially. And those neurons that prevent sleep, get activated. So your animals are constantly in this aroused kind of a way.

[00:12:11] Carl Lanore: [00:12:11] And as you pointed out the control, the controls, they had normal sleep patterns, even though they were not as sensitive, let's say to that door, their neurons weren't as sensitive to that temperature,

[00:12:20] Prof. Dragana Rogulja: [00:12:20] we don't put that temperature sensitive channel into their neurons.

[00:12:28] From, let's say from temperature, but there's nothing in their neurons. That's allowing that temperature actually activate specific. Right.

[00:12:36] Carl Lanore: [00:12:36] So then I go, well, I was going to say so then, so then around the 10 day, Mark, you started to look at the markers for cell damage, right? In the end, the ones that did have the activated neurons for temperature, right.

[00:12:53] Dr. Yosef Kaplan Dor: [00:12:53] Yeah. Yeah. Yeah. But I just wanted to add that we also use other methods of sleep deprivation and which gave us the same results. [00:13:00] So, uh, another one was just, um, basically shaking the flies. So we have a device where we put the flies on it and we shake them randomly. So they don't get used to it. You know, it's like rocking a baby.

[00:13:09] Um, and it works very well for one night. If you do it for many days, they get used to it and managed to sleep. But we had a small number of lives that were sleep deprived. For several days. And then we can actually, that was really good because then we could separate between the effect of shaking itself and the stress that it could cause, and the actual loss of sleep.

[00:13:28] And also, uh, we used Newtons. So we have Newton's flies. We have mutations in specific genes that are known to control sleep, and we, and these flies are just continuously not working well, so they're not completely deprived, but there was a lot of sleep in the winter to various degrees. Uh, so those are those three very different methods and they all gave us the same result in terms of, uh, oxidative stress

[00:13:52] Carl Lanore: [00:13:52] in their gut.

[00:13:54] Interesting. So around 10 days you started to see a lot of a high rate of mortality, right?

[00:14:00] [00:14:00] Dr. Alexandra Vaccaro: [00:14:00] Yeah. That was, um, so that's with thermogenetic, uh, sleep deprivation when you use this, uh, heat sensitive protein in, um, flying rooms and, um, yeah, I think that was very striking when we started looking at it.

[00:14:13] Survival, um, uh, especially with jargon at the beginning, we would, we wouldn't be really, um, struck how like the survival curves, the pattern was the same every time when you would do the experiment and starting day 10 of civic relation. You would start seeing a lot of flies, um, being sick. And what I mean by that is they're very sick.

[00:14:35] They don't move a lot. And you can tell that, you know, there are definitely not healthy in my diversity, but also you start seeing dead flies and that would go then on for, uh, until they old dead.

[00:14:48] Prof. Dragana Rogulja: [00:14:48] Yes, this was a really cool,

[00:14:50] Carl Lanore: [00:14:50] I'm sorry, go ahead.

[00:14:51] Prof. Dragana Rogulja: [00:14:51] Sorry. I was just going to say that, that this was the first, like Alex alluded to, this was the first kind of encouraging moment for us, because to be honest, you know, [00:15:00] we were really excited about this, but.

[00:15:03] You know, I don't know how much faith we had that we would really find something specific, you know? Cause it was like, okay, this is a, a big problem. A lot of people have looked before. It's probably a lot of, a lot of things are falling apart. You can imagine that a lot of things go bad when you don't sleep.

[00:15:17] So finding a specific. A specific cause of that scene seemed unlikely. And yeah. So then if you, if you look at these curves and you see that it's very predictable, when the animals would start dying, that kind of tells you that there may be a really specific reason. It's not like just all over the place,

[00:15:33] Carl Lanore: [00:15:33] things are falling.

[00:15:34] What would it be safe to assume that in the absence of Frank sleep deprivation. But just the subtleties of having really crappy sleep for decades would maybe not kill you as quickly and predictably in this timeframe, but clearly would kind of where the lie years off of your life.

[00:16:00] [00:15:59] Dr. Alexandra Vaccaro: [00:15:59] Yeah. I mean, and we have evidence in, in flies because, uh, what is nice with this, uh, thermogenetic tools?

[00:16:06] Um, is that you can like use, he set target small group of neurons, um, and, uh, you can use different flight, um, transgenic lines by targeting different group of neurons. And then we actually could find. Um, uh, activation of new that would lead to different levels of different degrees of sleep deprivation.

[00:16:25] So the one that we show in the, in the paper, uh, leads to about 90% sleep loss. There were two different lines, but they produce the same amount of sleep deprivation and very consistently give the same survival pattern. But now if we only 60% sleep loss, Or even, um, less, um, 45%, for example, you will see the exact same events, but it will be shifted, right?

[00:16:51] So they will die, um, after the 90% sleep loss wise, because they didn't lose as much sleep as the 90% sleep loss, [00:17:00] uh, flies. Uh, and they will accumulate, uh, reactive oxygen species and oxidative stress, but it will occur later. So you can, I mean, I think it's still only, um, Um, plausible that in humans, the same thing happens.

[00:17:11] You're constantly sleep deprived or you have insomnia or sleep like poor quality of sleep for years, and it will eventually have

[00:17:23] Prof. Dragana Rogulja: [00:17:23] that outcome.

[00:17:24] Carl Lanore: [00:17:24] I wonder, I wonder what would happen if you go good. I'm sorry, drag. The please go.

[00:17:29] Prof. Dragana Rogulja: [00:17:29] I'm so bad. I'm

[00:17:29] Carl Lanore: [00:17:29] sorry. No, it's okay. Listen, if you don't do that, you won't get a word in edgewise with me.

[00:17:34] Go ahead.

[00:17:36] Prof. Dragana Rogulja: [00:17:36] I'm just going to say that there's probably a certain amount of sleep. That can be tolerated without these kinds of effects. We did see some manipulations, like in insomnia, cardiac flies, like where, where some people that would lose, I don't know, like 15 to 20% of sleep and they were okay. They were not dying earlier, but it's hard to say and apply, spend a lot of climb in [00:18:00] this.

[00:18:00] There's not that much for them to do so they probably spent more time kind of inactive. They've ended ended this sleepy state, so to speak that then necessarily need for survival. So there probably is a certain threshold, you know, below what you don't want to fall for these kind of life threatening effects.

[00:18:16] And then everything that there could be like more sleep than you need for, you know, some kind of mental function or whatever, but there is a certain amount they need for like proper. Um, you know, for survival and that, and we don't know yet what that is.

[00:18:30] Carl Lanore: [00:18:30] So, so what do you, what do you think about, what do you think?

[00:18:32] I'm sorry, go ahead. Go, go.

[00:18:35] Dr. Yosef Kaplan Dor: [00:18:35] Yeah. I just wanted to add quickly that, um, we, so we do think that what we found in flies and mice may apply to humans, but it doesn't mean that that's the only function of sleep. There's also drug on a set and it could be, it's very likely that some other bad effects on health of insufficient sleep could be unrelated to what we found.

[00:18:51] So, you know, there's a lot of things. And if it's very important.

[00:18:56] Carl Lanore: [00:18:56] Well, what do you

[00:18:57] Dr. Yosef Kaplan Dor: [00:18:57] think? Does it have to be all about the God and ROS,

[00:19:00] [00:19:00] Carl Lanore: [00:19:00] but do you, do you think that, uh, if, uh, circadian rhythm wasn't observed, but sleep duration was so in fact that if you, if you, if let's say flies, fruit flies, sleep at night, like humans, if you disrupted nighttime sleep, but let them sleep during the day, would you see a reversal of these conditions?

[00:19:22] Prof. Dragana Rogulja: [00:19:22] That's a great question. Yeah, I think we don't, that's a really good question. We haven't done those experiments yet. Where are you actually allow the same amount of sleep, but at a different time, and this is actually super important because probably what you're thinking on when you're a lot of people that work weird.

[00:19:38] Yeah, exactly. And there is evidence that those people have higher incidence of certain cancers and colon cancer is actually. One that comes up high. And so I do have a feeling that, you know, those people probably also sleep less than they should because you probably never really get the same amount of sleep and, you know, your clock doesn't.

[00:19:58] Yeah. Yeah, it's not the same. So [00:20:00] we all know that, but it's exactly something that we could do in flies. So, you know, we can do those kinds of experiments, which has gone though, yet. I might, my gut feeling would be that, uh, no pun intended my feeling would be that probably that's important. That's also important.

[00:20:15] Like what my new sleep, I do think. Yeah.

[00:20:17] Carl Lanore: [00:20:17] Yeah. From an evolutionary perspective, I believe in that, in fact, we can thank a 1987 film called, um, Wall street with Charlie sheen and Michael Douglas, uh, for the, uh, switch in observance, observance of, of good sleep. When, when bud Fox is talking to Gordon gecko and Gordon's on the beach in California, and he's just bragging that he's been up all night trading, uh, in the stock exchange in China.

[00:20:44] And he says to bud, nobody makes money when they sleep and thousands and thousands of Americans went. Oh, so maybe I should stop sleeping if I want to be successful. And everything went crazy after that people thought, Oh, sleep's not important. I've had so many people tell me that over the years. And then I [00:21:00] watched them and I watch how their lives hit the wall eventually.

[00:21:03] But anyway. Okay. So you also did additional experiments in mice and you found this same hyper cumulation of reactive oxygen species in their guts. Did you see higher levels of ROS in any other areas or any other tissue?

[00:21:21] Dr. Alexandra Vaccaro: [00:21:21] No, I'm similar to the flies. When we looked pretty much everywhere in mice, uh, the only tissue and the only organ where we could see elevated reactive oxygen species and oxidative stress was, um, the small and the large intestines.

[00:21:41] Dr. Yosef Kaplan Dor: [00:21:41] So, you know, I went to Pinterest because I wrote the provision protocol in mice was only for five days. That's pretty short timeframe. And there was at least one study where we know of that did the longer the probation. I forgot how many days exactly. In rats, um, by the lab of Carol Everson. And they did see some oxidative damage [00:22:00] in the gut like we did, but also in some other tissues, I think it was the long and, um, and deliver.

[00:22:06] Carl Lanore: [00:22:06] So

[00:22:08] Prof. Dragana Rogulja: [00:22:08] we're the only ones that were dying actually in those experiments. So we don't know.

[00:22:14] Dr. Yosef Kaplan Dor: [00:22:14] So we, we don't, we don't know what will happen in our hands. And we did it for a longer time period, but it definitely looks like the first thing that goes wrong is the gut.

[00:22:22] Carl Lanore: [00:22:22] And I can tell you what goes wrong. So, so my audience is going to go, Oh, call.

[00:22:26] We know we know, but anytime we talk about the gut, we're talking about the immune system. And anytime we're talking about the immune system, we're talking about inflammation because inflammation is the army of the immune system. So once you screw the gut up, everything else goes bad. It's inevitable. But with that, with that being said, Were you able to identify, um, the, where the production of ROS was coming from?

[00:22:50] Was it a particular group of microbes, for instance, like bacteria died, deets or Firmicutes or anything like that? Why are you [00:23:00] smiling?

[00:23:01] Prof. Dragana Rogulja: [00:23:01] I think, yeah, because like you're getting right. No, we ha we think we know what produces Ross. We're just not ready to talk about it because we need to check it like many more ways.

[00:23:10] But yeah, we think, we think we're. Actually pretty close to putting down the exact mechanisms

[00:23:20] Dr. Yosef Kaplan Dor: [00:23:20] in terms of, uh, at least on the fly. We know, uh, the main kind of cells where these roles accumulates because, um, what we did in the paper, we genetically I can use genetically modified flies that produce very high levels of antioxidant enzymes, uh, in the main cell type in the gut. So God, the guts has many kinds of cells.

[00:23:40] Uh, and in the fly gut, there is one kind of cells that the in parasites, you also have these, uh, cells in mammalian and the humans gut. These are the cells that absorb absorb nutrients. And these cells are known also to be able to produce ROS, for example, to, uh, kill bacteria or to control bacteria or to regulate how much proliferation you have in the gut.

[00:24:00] [00:24:00] So when we neutralize Raul specifically in these cells, then the flies can survive. Normally, despite the fact that they don't sleep. So we, we know that these are always the probably coming from those cells, but again, we need to, um, look into it more and study it more carefully.

[00:24:16] Carl Lanore: [00:24:16] Um, I want to take a commercial break and when we come back, I want to talk about preventing deaths using antioxidants.

[00:24:23] So your group experimented with the, was it, was it 51 or 53? Uh, dr. Vaccaro different antioxidants. And you discovered that some of them actually mitigated this damage? Well, I guess before we go there, what is the, what is the reactive oxygen species doing specifically? That speeds death? Is it increasing the accumulation of senescent cells?

[00:24:49] Is it damaging the nervous system? Is it, uh, is it, uh, modifying or, or mutating DNA? Do we know.

[00:24:59] Dr. Alexandra Vaccaro: [00:24:59] Yeah. So, [00:25:00] um, Ross can, uh, at high levels, cause as you mentioned in immediately, uh, earlier, um, at low levels, physiological levels of ROS are important and good. Um, uh, they have good, important, uh, signaling functions, but at high levels, They become harmful because they oxidized DNA, lipids, and proteins.

[00:25:23] And so by doing that, it will lead to, um, oxidative stress and the tissue, and then eventually can lead to cell death. Um, and so on. And

[00:25:35] Prof. Dragana Rogulja: [00:25:35] that we can't say, yeah, what's actually killing yet, but the guts is messed up, but we don't know yet what kills the animals. We do think that inflammation will play a role, for example,

[00:25:45] Carl Lanore: [00:25:45] I, yeah.

[00:25:46] And there was a couple of other nice things I want to talk about. Cause you also looked at, uh, ad libitum feeding and restricted feeding because obviously we all know that when you don't sleep well, the next day you crave. Carbohydrates and you just want to eat everything in sight. [00:26:00] So I know that you examined that as well.

[00:26:01] We're going to take a quick commercial break. When we come back, we're going to pick it up on the other side. Stay tuned. This is going to be fascinating because we're going to tell you about antioxidants that actually saved some of these fruit, fruit flies. So stay tuned. You are listening to the superhuman channel we're ripped and we're ready.

[00:26:23] Welcome back. Welcome back. We're talking with dr. Alex Vaccaro, dr. Yosef Kaplan, DOR, and dr. Dragnet regalia. We're talking about how sleep affects your lifespan. Quite frankly, really w that's what it comes down to. We already know that, um, sleep deprivation and impaired sleep quality is tied very closely to the development of type two diabetes.

[00:26:46] Um, so many of us wear blue light. Uh, blocking glasses at night when we work on our computers or watch television, because we don't want to stop that pulse of melatonin so that we can get to sleep. And then many of us like [00:27:00] myself, I take anywhere from six to nine milligrams of melatonin at night and have done so for the better part of 20 years now.

[00:27:06] Um, so let's talk about the antioxidant. And before we do that, I have to put up a comment because we have someone in the audience that's already on this. So, um, Chris Fox says without sleep, there is no melatonin, which is one of the most powerful antioxidants, no runaway train of ROS leading to death. You, you, you looked at 53 different antioxidants.

[00:27:31] One of them was melatonin. Wasn't not,

[00:27:34] Dr. Alexandra Vaccaro: [00:27:34] yeah, exactly. One was melatonin. Um, and I mean, I actually didn't know that before I. Went to the literature, looking for potential and talk students to try on my slippery flies, but melatonin is a very potent antioxidant. Um, and so that's why it was included in the list of, uh, compound that we originally tested.

[00:27:57] So, as you mentioned earlier, we tested, uh, [00:28:00] 53 of them and we selected them based on previous literature. Either on, uh, uh, uh, fruit flies, but other organism models. Um, and, uh, we added, um, the compounds to the fly food, um, and, uh, looked at survival and solidify flies also in control flies, uh, and looked at it so survival, but also.

[00:28:24] Uh, they're asleep, um, because we wanted to make sure that whatever effect that we will find with his entire concern, taxing and compounds was not, uh, due to, um, those slides should be more right. And so 53 compounds and we identified, uh, 11 that can, uh, extend survival instinct, defy flies.

[00:28:45] Carl Lanore: [00:28:45] And so what were the, what were the top 11 most effective?

[00:28:50] So

[00:28:51] Dr. Alexandra Vaccaro: [00:28:51] I would say like the three top ones are melatonin, which was definitely one of the best, um, um, in taxing the [00:29:00] compounds. Uh, it definitely applies to be more, um, we think because an Nettleton is intoxicated, but also because, and I didn't know that also, um, before working with it's Christmas, high levels in the guts.

[00:29:18] Uh, in lightly, that's why I might be more efficient at neutralizing ROS in the . Uh, another one that was very efficient, it's called liquid acid. Uh, and another one was, uh, NAD or, uh, Nico to the right

[00:29:38] and a D, which is also, I mean, that's been used in a number of studies. So,

[00:29:44] Carl Lanore: [00:29:44] so, so, so these, these compounds and all of them are in this study, right? Cause I have a link to the study itself so I can see what the other three 53 or 51 that these compounds did not help the fruit flies or [00:30:00] animals that they were tested on sleep better, but they mitigated the ROS accumulation in the stomach.

[00:30:06] Right.

[00:30:07] Dr. Alexandra Vaccaro: [00:30:07] Exactly. So none of those compounds, uh, actually extended sleep amount or mean increase the sleep amounts in the slipped by flies. It only extended survival. And it, I mean, it was doing that by clearing Ross, um, in the garden, slipper animals.

[00:30:28] Carl Lanore: [00:30:28] Did you look at glutosiome?

[00:30:31] Dr. Alexandra Vaccaro: [00:30:31] I did.

[00:30:35] Carl Lanore: [00:30:35] Well, I take, I take about two to three grams of glutathione a day as I age, and I I'm just a glutathione is a fantastic antioxidant. It's, uh, it's very good for the liver, the kidneys. And I'm just curious if it had an effect on mitigating the damage from, uh, from sleep poor sleep.

[00:30:54] Dr. Alexandra Vaccaro: [00:30:54] Yeah, actually we did end with the sign is, uh, was not able to extend survival and our flies.

[00:31:00] [00:31:00] Um, even though we tried different concentrations. Cause so I think that the key also here and I mean, it took us a while to figure out the right dose for each entire accident and the right time to administer and talk students to offline. Uh, so I can only say that for girls that I, and like we tried, I would say at least three concentrations for each compounds.

[00:31:23] We were not able to find the right concentration maybe, but. Um, I mean, if it's not part of the compounds that worked, um, I mean, we don't know exactly why. Um, but, um, yeah, that

[00:31:36] Prof. Dragana Rogulja: [00:31:36] would be that at some of those that would work, but so controversy is about a lot of these antioxidants, right? Where people there's some studies, uh, that showed that the thyroid can even be bad because it can help cancer cells survive.

[00:31:53] Right. Like. Like you said earlier that bras would kill cancer cells. So then these cancer cells can [00:32:00] use with the thigh and to defend themselves from, uh, from Ross, which would, which would kill. And that's what we kind of figured out. That's the super fascinating thing here is that, and that we really want to stress that.

[00:32:11] We're definitely not trying to say you can just pop a pill and any antioxidant and you don't need to sleep in. Okay. It's really. And this has been, this has been, I'm sure you're aware of it. The big controversy where people do all these studies on antioxidants, does it, you know, are they good? Are they bad?

[00:32:27] Did they extend life span? And they find really different results, even when they look at the same animal, you know, but in different labs. And so when we tried these antioxidants or non deprived flies, okay. We would not see any extension of lifespan, even in those students that were really good at. At rest in survival.

[00:32:49] In those animals that were not deprived, they didn't do anything. They did not extend the license. So that really tells you that there is a context specific need for antioxidants. It also tells you that you probably [00:33:00] should be mindful of what you're actually thinking, how much you're taking. And it could probably be different based on age, you know, of the.

[00:33:08] Subject and so on. Even the sex, we did our experiments on male animals, just for practical reasons that that probation worked better. But we've definitely interested in doing this from females because

[00:33:19] Carl Lanore: [00:33:19] I was going to ask you about hormones because we know that during sleep is when the hormonal symphony occurs.

[00:33:28] Uh, most of the hormones are made at night. The sex steroids are made at night growth. Growth factors are made at night. They pulse, uh, at night. And I was going to ask you, do you think there's, uh, a role in all of this? When we look at, we know that when people don't sleep well, their thyroids don't function, their ovaries don't function.

[00:33:49] I mean, all these hormones just go down. I'm wondering if there's a role for hormones and, and, and this discussion because. I've done shows. I did one show on [00:34:00] oxytocin and how it improves muscle quality in old rodents. Then shortly thereafter, I did a show on a gut microbe. Called El Rytary and El RO Terry thrives in the guts of animals with high oxytocin.

[00:34:16] So I said, well, does the oxytocin increase L Rytary or does the L Rytary increase oxytocin? And the scientist says we don't know yet. So, you know, there's this whole interplay with hormones and the gut as well.

[00:34:33] Dr. Yosef Kaplan Dor: [00:34:33] We don't know. I wish when you, and that's exactly what we wanted to find. Uh, we do think that, uh, it, it's very likely that there is some communication between the brain and the gut. And I mean, we know there is a lot of communication within the brain and the gut and the gut and the brain. So it could be that some signals that come from the brain when you're sleep deprived, affect your gut function, and that could lead to this accumulation of ROS.

[00:34:55] But we right now, we don't know.

[00:34:57] Prof. Dragana Rogulja: [00:34:57] But what's really cool. Here is also that because we have these [00:35:00] two quite different model systems. So flights in my survey, very similar in many ways, the flies are really similar to us. That's why we use them. Obviously we don't care about flies per se. I mean, we care about them deeply, but you know, we wouldn't be studying

[00:35:13] Carl Lanore: [00:35:13] them.

[00:35:15] You gotta be careful today saying you don't care about flies. You'll end

[00:35:18] Prof. Dragana Rogulja: [00:35:18] up not,

[00:35:18] Carl Lanore: [00:35:18] we care about them a lot. So let

[00:35:20] Prof. Dragana Rogulja: [00:35:20] me just say this actually want to address. We love right. We love flies. None at all. We love, I meant to say that nobody would be studying flies per se.

[00:35:32] Carl Lanore: [00:35:32] That's it?

[00:35:33] Prof. Dragana Rogulja: [00:35:33] That's what we're trying to say.

[00:35:34] Like, we, we studied them because they're similar. Plus don't get me wrong. They, they, they are amazing. We love them, uh, and, and really respect them. And, you know, but they're there. Um, Simpler than us in some ways. Right? So like they don't have, they have a lot of the molecules that we have, but they don't have all of the same hormones.

[00:35:52] You know, they're not exactly the same as us. Their lifespan is on a different scale, but that's why it's really cool that. We see [00:36:00] the same thing happening in their God and in the mouse. So it's a little bit more reductionist system in which we can come to kind of basic mechanisms more easily. So if I, if I may just address this for a second, like with animals, because I've seen, you know, people.

[00:36:15] Saying something like, you know, this is really cruel what we're doing and something like that. And I kind of want to address them that if, if you'll allow me for a second, the depriving animals of sleep and stuff. So I want to say that the reason we're doing these studies is because we genuinely believe that this is a, um, Health problem for humans because we know even from my own experience, look, I, I work on sleep.

[00:36:39] I'll still be a wheel silly, made email to each other at like two or three at night. Okay. Like we know that not sleeping is not good, but we still, you know, we all do it. Some people have trouble sleeping. As you said, as you get older. Even if you want to sleep, you just can, some people work shifts. Some people have babies that can't sleep.

[00:36:57] Some people are sick, some people this and that, right. You're just [00:37:00] worried. You'd also have been out there. We genuinely believe that this leads to a lot of health problems. That's why we're doing this. And we're definitely not into torturing animals. We care about them deeply. We tried to do meaningful experiments.

[00:37:11] This is something that I, because I struggled with this in the beginning, I don't like torturing animals. I don't like to see them suffer when you're working with .

[00:37:21] Carl Lanore: [00:37:21] You're not torturing animals by depriving them of sleep per se. You know, I mean, I don't think any, I don't think anybody in my, you know, my audience.

[00:37:29] Um,

[00:37:30] Prof. Dragana Rogulja: [00:37:30] we they're scientists scientifically minded or sort of, yeah, well, hopefully somebody at least sees this and like, thinks about it, you know, because we also do get some emails from people saying, how can you do that? And portrait animals. And I tried to explain to them, we really do care about that. We just think that this are our longterm goal is to come up with something that's going to help people in the longterm because I'm telling you it's not, not everybody.

[00:37:55] Needs a sleeping pill. Not everybody needs something to help them sleep better. [00:38:00] A lot of people need that, but a lot of other people, it's not that.

[00:38:06] Carl Lanore: [00:38:06] Um, various reasons you have the, the other thing that needs to be addressed is that sleeping pills like Ambien and Lunesta, just because you lay still for eight hours, doesn't mean you're sleeping in the clinical sense of what sleep is. You know, sleep is undulating. I have three different devices. I tracked my sleep with deep sleep REM sleep, light sleep.

[00:38:31] And these. These undulations are for a reason because hormones are produced every one and a half hours at night, testosterone is produced around 2:00 AM in the morning. You know, these things happen for a reason. We evolved to go to sleep when it got dark and be up and they called it the locomotive period in the daytime.

[00:38:54] And we have totally cast all of that aside in modernity. And we want to stay [00:39:00] up and watch Jimmy Kimmel and then eat right before bed. And all these things are antithetical to, to, to health. They, they, they don't improve health. So we have to do studies on sleep and we can't do them on humans. You know, quite often you can do shoes for you.

[00:39:16] Cause then you'll get, you know, Nobody's going to give you an IRB to torture humans do so you got to do to

[00:39:21] Prof. Dragana Rogulja: [00:39:21] fly. You can do it so you can get to the mechanism. And even mice would be really hard because how are you going to do these longevity studies really? And you need lots and lots of animals. So, you know, we found this, we found Ross within months of starting the project.

[00:39:36] It was actually extremely fast, but then we took. The following three years to make sure that there's no holes in our story. So really try to like poke holes any way that we could. And we couldn't find any, we just kept accumulating more and more data. And you just couldn't do that in another model organism, you could not do the, the level of study that we wanted to do.

[00:39:56] And we did do in the end using another model, but we do use [00:40:00] mice, you know, after kind of being. Led by flies. And then we like to see, right.

[00:40:04] Carl Lanore: [00:40:04] And you go, you go up the chain. So to speak until you can do actual human studies, what you probably can with this type of stuff, because there are plenty, there are plenty of insomniacs out there that are happy to be awake in a lab, as opposed to being awake in their living room.

[00:40:21] Yeah.

[00:40:21] Prof. Dragana Rogulja: [00:40:21] Or undergrads, you know, preparing for cramming for exams and stuff. So, you know, you can take some, just some stuff like take feces from people that have been sleep deprived, profile it, look for markers of inflammation, you know, look in the theater. There's all kinds of stuff that you can do, but you just cannot be.

[00:40:37] Really rigorous quantitative, like working with humans, it's just not possible to do the kind of thing that we wanted to do.

[00:40:45] Carl Lanore: [00:40:45] So I love this study for two reasons. Number one, you're getting to the root of some of the problems with sleep. We're starting to go. Okay. If we can. Do this, we can mitigate some of the damage of sleep, but you, you have solutions.

[00:40:59] I [00:41:00] love so often we do research papers and, and they point out diseases and conditions and people go, all I can do now is worry now, but you, you actually have some solutions. So when we come back, we're going to focus on those and we're going to, uh, Tie up the loose ends. So stay tuned. We'll be right back with more super human radio, brawn and brains.

[00:41:22] Finally meet.

[00:41:29] Welcome back to superhuman radio. So, uh, Chrissy's Fox ask a question. I'm going to put up here before we wrap up the discussion. How did ascorbic acid fare and the results of antioxidants?

[00:41:46] Dr. Alexandra Vaccaro: [00:41:46] Um, uh, sorry, I

[00:41:50] Carl Lanore: [00:41:50] couldn't vitamin C vitamin C.

[00:41:56] Dr. Alexandra Vaccaro: [00:41:56] Oh, I see it here now. Sorry. Yeah. So vitamin C's among the [00:42:00] compounds that, uh, work pretty well, um, in slipping fireflies, and you can actually, um, extend survival, um, absolutely by flies.

[00:42:10] If you feed them with vitamin C.

[00:42:13] Prof. Dragana Rogulja: [00:42:13] But he was on the lower end of effectiveness. If I remember, I think it was somewhere kind of at the bottom of our,

[00:42:19] Dr. Alexandra Vaccaro: [00:42:19] it's

[00:42:20] Prof. Dragana Rogulja: [00:42:20] not as good as the total issue.

[00:42:22] Carl Lanore: [00:42:22] You know, when my mother, my mother, my mother developed dementia and I insisted that she take three milligrams of melatonin every single night.

[00:42:32] And she actually started to become much more lucid and talkative. And, uh, melatonin is amazing. I am dr. Russell rider, who they call him the godfather of the Peniel guilt, Glen. He first came on my show in 2006 and we talked about melatonin. He teaches at, um, university of Texas at Dallas, I believe. And. I think he's in his eighties now [00:43:00] and he still teaches and he takes 60 milligrams of melatonin at night.

[00:43:03] Now I'm not suggesting people do that. He has graduated over the years to higher and higher doses. Um, but we've done shows that melatonin could potentially be the greatest anti-aging pill you could take for literally pennies a day. It has pleiotropic benefits to the body. And now we're talking about its antioxidant qualities as well.

[00:43:25] So, um, Ascorbic acid may help this may help. Is there a timing factor? Do you give it to the subjects right before bedtime, since the ROS is accumulating at night or does it matter?

[00:43:42] Dr. Alexandra Vaccaro: [00:43:42] Yeah. So when we started the intoxicated feeding, um, I mean, we were, we had no idea, right. Um, how to give it one and what will work?

[00:43:51] Um, I kind of had the idea, you know, like, Oh, maybe if. The flies are pretreated, um, with the antioxidants

[00:43:59] Prof. Dragana Rogulja: [00:43:59] before those lived [00:44:00] your plaque, that will

[00:44:00] Dr. Alexandra Vaccaro: [00:44:00] be, you know, stronger and be able to deal with the deprivation, um, better. And it was actually the opposite because one, we pretreated flies. So even before there were sleep deprived or.

[00:44:13] Right. When we would start sleep, depriving them with antioxidant compounds. Uh, most of the time it would not extend initially would not expend survival, but it would actually be even worse than without the intoxicant compounds. And I mean, as we said, ROS are important for many things. So I think if you are deplete, um, Look up at probably not only the government, because you feed them with intoxicants and you don't know where it actually goes in the body, uh, with, um, those doses of and toxins.

[00:44:43] It probably is bad for them if they don't need it. And we think that, yeah, it's probably that because when we, um, started getting the toxin and starting day seven of 50 probation, which is exactly when we start seeing, um, uh, increasing Ross in the gods, then it [00:45:00] works. So you pretty much have to wait until they get to a point where they start getting sick and ROS levels sort of accumulating in the gut to feed them, to see the positive of, and talks to the feeding in.

[00:45:17] Carl Lanore: [00:45:17] So Yosef, this means that those of us who take antioxidants every day as part of our vitamin regimen, and then we become sleep deprived three weeks from now. It's not doing us any good.

[00:45:30] Dr. Yosef Kaplan Dor: [00:45:30] Well, I mean, I cannot tell, you know, uh, if it's good or bad for humans, but there is definitely, uh, this whole field of antioxidants.

[00:45:37] It's at least in basic research and longevity studies can quite controversial. Uh, and it's like we said, previously, it's really context dependent, uh, because Ross have so many important functions, physiological functions, and it also wanted to stress out. It's not only just intelligence, sorry that ROS are just some byproducts of metabolism.

[00:45:55] We have specific enzymes in ourselves in flies, mice and humans [00:46:00] and all those. And the only thing that those enzymes do is producing ROS and actually in humans, there are diseases that are associated with mutations in those genes. So if you don't produce, for example, a Ross in some immune cells, you develop disease.

[00:46:12] And also there are some gut disease, inflammatory disease associated with having not enough ROS. So, um, so it's really hard to say, for example, also, um, regards to cancer, right? On one hand you can think, okay. Roscoe's DNA damage that causes mutations that can contribute to cancer. But at least one study I know of it was done in Sweden, where they compared the rates of prostate cancer in men that were, um, with different diets or a take away without, uh, supplements.

[00:46:38] And actually, it seemed as if supplements and I think it was vitamin C, but I'm not completely sure, but one of the migraines, not only didn't help, but actually made increased incidents of, uh, cancer. So, um, so it's really hard to

[00:46:52] Carl Lanore: [00:46:52] tell. You know, um, so, uh, IGF one is implicated in [00:47:00] driving cancer, but in cancer cells leverage everything that is good for healthy cells.

[00:47:08] Cancer cells are probably one of the most evolution evolved cells designed to survive at all costs, and they make their own telomere race and repair their own DNA. Um, they leverage , but in the case of solid tumors, IGF one plays two roles in helping to promote the growth of tumor cells. And that is number one, it stimulates growth.

[00:47:36] But number two, it suppresses ROS. And so it not only increases growth, but it shuts off the suppressor of growth at the same time. So, you know, we, the truth of the matter is we really don't know a lot. We have to look as we go and things unfold. But as you point out, you know, antioxidants, ROS, [00:48:00] ROS is not a bad thing.

[00:48:01] It's a very, very important thing. And, and going out and, and, and, and, and I'm so glad you're on the show today because you know, that. Right now there's somebody at a newspaper that wants to write the article that says, skip sleep and take vitamin C. This study says the antioxidants will keep you from getting sick.

[00:48:20] And it's the, it's so much more complex than that. And it's insulting to tell the average people, something that dumbed down.

[00:48:29] Prof. Dragana Rogulja: [00:48:29] Exactly. People are not stupid. I think people can perfectly understand science. That's why we really appreciate this. And the other thing is if I can say that we put our paper, the PDF of our paper and our website, so people can go and look at the data.

[00:48:41] That's what we would really like is for people to actually try to read the paper. We think that it's pretty, you know, there's some technical stuff there, but we think it's pretty easy to follow. And the. Figures we hope are intuitive and you can kind of see the results that we see that the effects that we see are not subtle.

[00:48:57] It's, it's really, it's something you can see with your eyes. And [00:49:00] so I would encourage people to go and look, cause we tried to discuss the nuances of this, you know, what are the limitations of our study? What can we really say and what we don't feel comfortable saying yet? I think that that's really important.

[00:49:12] Thank you so much for inviting.

[00:49:14] Carl Lanore: [00:49:14] Oh, of course. This is fascinating stuff to me in the audience. I think it was funny because you guys were shocked every morning. You would go and look at the flies and they'd still be alive. Right?

[00:49:24] Prof. Dragana Rogulja: [00:49:24] That was amazing. Just, Oh my God. That was so crazy. I couldn't stop talking about that.

[00:49:29] Anybody who came into like 50 feet of me for those several years heard about this study, everybody knew, I was just like, wait, did I tell you what happened in the last two days, everybody, but people really cared. Everybody was so involved. It was super fun.

[00:49:45] Carl Lanore: [00:49:45] What is the enzyme that quenches ROS that our bodies make Yosef?

[00:49:51] Dr. Yosef Kaplan Dor: [00:49:51] Yeah. So, I mean, there's several of them, but the one that we used it's, uh, superoxide dismutase.

[00:49:56] Carl Lanore: [00:49:56] Yeah.

[00:49:56] Dr. Yosef Kaplan Dor: [00:49:56] It's converts, uh, one, one radical called [00:50:00] superoxide if converted to, um, peroxide. And another one that we used was catalyst, which degrades, um,

[00:50:05] Carl Lanore: [00:50:05] their oxide. Those are two very popular anti-aging products that take now sod and, and catalyst.

[00:50:12] They've both been implicated in extending human life. Isn't that interesting

[00:50:18] Prof. Dragana Rogulja: [00:50:18] you can't. So we did this genetically, you can actually, you know,

[00:50:23] Carl Lanore: [00:50:23] life extension, lifestyle, life, extension foundation cells, both superoxide dismutase. They sell sod and they started selling catalyst about five or six years ago after a couple of studies.

[00:50:37] Prof. Dragana Rogulja: [00:50:37] I didn't know this within all those that's really funny changed bacteria. I'll just say this. This is also fun to think about. There's some strains of bacteria that are filled with us so deep. And then if you in there in certain yogurts, a lack, this I guess, is a good strain and they pass. So a work for Wendy Garrett slab.

[00:50:57] A Harvard school of public health has a, [00:51:00] she's done some, some work with this. So these bacteria, if you eat them, if your God is fine, pass through, but there's inflammation, then your cells will lyse. The bacteria. Bacteria will release us. So D and that can, you know, I'm pro colitis and stop some stuff like this, all kinds of things.

[00:51:16] We're thinking

[00:51:16] Carl Lanore: [00:51:16] about if the lactic acid, uh, forms of bacteria, you're talking about.

[00:51:20] Prof. Dragana Rogulja: [00:51:20] It's called. I think it's called L laugh. This lactococcus like this. I think that's the name. And, uh, and you know, that, that might that's my understanding is that the bacteria are, have sod. They make us so D if your God is fine, you eat it.

[00:51:33] You know, pass this through. If your gut is inflamed, then you express what to pull the license design, that kind of license, the material sell

[00:51:39] Carl Lanore: [00:51:39] gut inflammation is so rampant in our population. I would challenge any of you. To walk into a Starbucks and look at a fairly lean person. They have a distended stomach.

[00:51:50] They look like there may be one or two months pregnant men and women. There's actually a study that was done about five or six years ago that looked at the girth size of the [00:52:00] average American waist and summarized that while the girth is increasing adipose tissue is not it's because our guts are literally becoming distended.

[00:52:09] Now. I have thought about this for a decade now, because if you have GERD, if you have obstructive sleep apnea, chances are you have gut issues that are causing the obstructive sleep apnea because of the dis the edema is narrowing the windpipe and causes the best soft tissue in the palate to fall down at night.

[00:52:28] I mean, I'm sure of what I'm saying. So. Yeah, I've looked at this for so long. The person who can figure out how to quench inflammation in the gut will save millions of people on this planet because something in our environment, something in our environment, I don't know if it's, if it's cell phones, because believe it or not.

[00:52:48] There's good studies coming out of Scandinavia that show that RF coming from cell phones, alter microbiome diversity, or is it the coffee we're drinking? [00:53:00] Is it, the pesticides were eating. I don't know, but I'm telling you the lack of

[00:53:03] Prof. Dragana Rogulja: [00:53:03] sleep

[00:53:04] Carl Lanore: [00:53:04] and the lack of sleep. I'm even finding caffeine. The more caffeine I drink, the worst, my gut gets not coffee, either.

[00:53:12] Bang energy drinks, the more caffeine I consumed, the worst. My gut guts

[00:53:18] Prof. Dragana Rogulja: [00:53:18] can get irritated. Yeah. I know.

[00:53:21] Carl Lanore: [00:53:21] Figuring out how to solve the inflammation in the gut. A conundrum is, is big, big, big for this America. Yeah. I

[00:53:29] Prof. Dragana Rogulja: [00:53:29] think a lot of people are probably working on this. A lot of people are interested in this. I think, I think that that's another thing we're just realizing in general inflammation is something we should really be thinking about more.

[00:53:39] Cause it's often not the, you know, it's not the bacteria that kill you. It's the inflammation. It's your body's response.

[00:53:46] Carl Lanore: [00:53:46] Yeah, that's a, that's a killed, you had COVID it was cytokines that were killing people during the lungs. It wasn't, the virus didn't kill them. It was their immune system response

[00:53:58] Prof. Dragana Rogulja: [00:53:58] going crazy.

[00:53:59] Yeah. So it [00:54:00] seems counterintuitive, but some things that can actually, the immune system can make it, make it better for you. Right. So I, so honestly I'm not the, after this thing that we saw, I'm saying like, you know, we know a tiny bit about biology. I'm not going to say that anything's possible anymore.

[00:54:18] Not going to rule anything out, but there needs to be a lot of evidence that needs to be a high bar to make a flames. You know, that, that,

[00:54:26] Carl Lanore: [00:54:26] and Serena kind of like, what would you, what would you like both clinicians and lay people to take away from your research? Who wants to answer?

[00:54:35] Prof. Dragana Rogulja: [00:54:35] Do you want to take it or,

[00:54:39] Dr. Alexandra Vaccaro: [00:54:39] Mmm.

[00:54:40] Dr. Yosef Kaplan Dor: [00:54:40] I definitely, I wouldn't encourage people. Just, you know, if you have a dependent of sleep, I wouldn't encourage people to just go and take supplements. Cause we really need to find a much more research is required. And then we also regarding inflammation and gut issues, there've been a lot of studies and people have been trying to cure some like inflammatory bowel disease with antioxidants and the results are mixed [00:55:00] and there are many explanations.

[00:55:01] One could be again, I mean, of course ROS are important. So it's really important to have like this perfect balance of Ross. Not too much, not too little, also. Actually, no, we need to have a specific concentration of the compounds in your guts to have an effect. And also some compounds have a pleiotropic effects, which means they are their antioxidant, that they do other things too.

[00:55:20] So sometimes effects are just because they reduce inflammation regardless of cross. But if it really, what we're trying now is trying to find the exact mechanism, how these rasa produced. Cause maybe then we could design more specific therapies, specifically target those roads that are made when you don't sleep.

[00:55:36] Again, much more studies are needed. Um,

[00:55:39] Carl Lanore: [00:55:39] no, I agree. Yeah, because too much of an antioxidant become, can become a pro oxidant. We've seen that in high dose vitamin C therapies, they actually becomes pro-oxidant. So you have to be careful with that. Look, I want to thank all three of you for coming on the show.

[00:55:52] This is fascinating. And please promise to come back when you know more, I want to know what tissue is making the ROS. Is it a [00:56:00] microbe? I want to know that. So you

[00:56:02] Prof. Dragana Rogulja: [00:56:02] come back.

[00:56:04] Carl Lanore: [00:56:04] Thank you so

[00:56:04] much.

[00:56:05] Prof. Dragana Rogulja: [00:56:05] Thank you. Thank you so much. It was awesome. Thank you.

[00:56:08] Carl Lanore: [00:56:08] Take care. And we are going to, uh, Say goodbye. Now we don't.

[00:56:13] Let me see. We have a show Friday. We do. We have a show Friday. We have a show tomorrow. Um, so we have some real good shows coming up. I hope you can tune in for those very soon. Let me see what's today. Today is actually Wednesday. Yeah, we have a, we have a good show tomorrow on C diff. If you know anybody who has C diff.

[00:56:32] And then, um, and then Friday we have BiOptimizers coming on. They're coming on to talk about a, uh, a magnet, their new magnesium supplement, which I've been using. I take it right before bed, believe it or not. And it definitely helped me sleep deeper. Talking about sleep quality. Uh, anything that helps you sleep deeper is, is a good one.

[00:56:50] Chrissy's Fox. Thank you so much. The paper will be linked in this show on my website. So you just have to go there. Okay. See everybody tomorrow. [00:57:00] Thank you for being here today and participating .