[00:00:00] Carl Lanore: [00:00:00] Welcome back to another episode of super human radio. Today's Monday, the beginning of the week, it's a. March 30th just a couple more days and it'll be April and we'll be out playing in the sun. Oh, no, we won't because we're quarantine. That's right. I forgot about that. A deep into the coronavirus quarantine right now, we're making history.

[00:00:21] If you're listening to this show a hundred years from now, and, uh, we have a great show plan today talking about something that everybody loves, and that's coffee. And, uh. I want to thank our title sponsor legendary foods for making the goodies that they make that allow us to snack without guilt. They're nut butters are amazing.

[00:00:44] The flavors are ridiculous. And the introduction of their new tasty pastry, which is basically a pop tart, but it's been upgraded. It's got nine grams of high quality high leucine protein, [00:01:00] less than one gram of sugar. Uh, actually three to four grams of impact carbohydrates. The flavors are amazing, and you can get This email address is being protected from spambots. You need JavaScript enabled to view it. and they've got some new flavors coming out I know about, but I'm not saying just yet.

[00:01:16] So check those out. I'd like to welcome my guest to the show. And that is dr Detlev Boysen. How you doing? Duck?

[00:01:26] Dr. Detlev Boison, PhD: [00:01:26] Yeah. Doing fine. Thank you very much.

[00:01:28] Carl Lanore: [00:01:28] Thanks for being here. Um, you ha you have just published a very, very fascinating, uh, uh, article about, uh, coffee and, uh, traumatic brain injury. But before we get into the study, what, what led you to even want to do this study?

[00:01:42] Was there previous research that pointed you in a direction that made you think, gee, we need to look further at this in this particular situation?

[00:01:50] Dr. Detlev Boison, PhD: [00:01:50] Yeah. So this, this research is basically based on my passion and interest in one molecule called a dentist. And, uh, I've built [00:02:00] an entire research program around this one molecule, which involves research and traumatic brain injury, epilepsy, and even cancel.

[00:02:09] Uh, so the reason why I'm testing etic Denison is if you're looking at conventional, um. No pharmacological treatment options in taking drugs for the treatment of neurological conditions. Those drugs are highly target centric. They block a receptor or a channel, and in the best case, they are able to suppress the symptom, but those drugs cannot affect the entire network, which is implicated in a complex neurological disease such as epilepsy.

[00:02:42] And therefore, it's not as surprised that. 35% of all patients with epilepsy today are completely resistant to any of those, uh, so-called antiepileptic drugs. So we need something else. And, uh, I'm a biochemist by training and I, [00:03:00] uh, use a different, um, philosophy to approach, uh, understanding disease and finding treatments for disease.

[00:03:08] And this brought me to the molecule. Denizen. Which was in fact, one of the first molecules that came up in chemical evolution. So a long, long time ago, we had a primordial soup on, or a planet where the first living systems from and smart scientists from the 1960s found out that five molecules of hydrogen cyanide can spontaneously from the Porin base adenine.

[00:03:35] So I didn't even, it's chemically H five five and five. And it's the core molecule for dentists. And so at Denison has been there from the beginning of life. And that's important because if you think about how would you construct the first living set, the first living system, what's the most important thing that needs to be done.

[00:03:57] Exactly. It's an edge. [00:04:00] And you need the very simple self regulate resistance. So if you'll add three phosphate groups to a dentist, and then you get ATP, which is the energy currency of all cells. So you have ATP with represents NRG. So if you have an energy crisis. Uh, ATP degrades and releases a Denison.

[00:04:21] So the simplest system that you can construct is to have a feedback. This system that whenever you have an energy challenge and energy crisis, you get a drop in ATP. You get an increase in a Denison, and then select a dentist and as a global inhibitor to just prevent everything that consumes NRG.

[00:04:41] Interesting.

[00:04:42] Carl Lanore: [00:04:42] So I could see how that would affect cancer too. I mean, uh, the whole, uh, uh, key tone discussion, uh, alternative substrates of energy. You know, it's all based on energy. Everything is, everything is based on energy. You take the energy away and things just, they stop working.

[00:05:01] [00:05:00] Dr. Detlev Boison, PhD: [00:05:01] Exactly. Yeah. Yeah.

[00:05:02] And of course, a Denison is way known. Uh, is this sleeping user.

[00:05:08] Carl Lanore: [00:05:08] I was just, I just, I wrote that down. Sleep pressure. When, when a dentist and accumulate you get tired. In fact, I brought some good why we haven't come out with a nasal spray of adenosine. It's a drug apparently where people can just take a couple of blasts and all of a sudden they get sleepy and they go to sleep.

[00:05:24] Yeah. That

[00:05:24] Dr. Detlev Boison, PhD: [00:05:24] would be amazing.

[00:05:25] Carl Lanore: [00:05:25] Well, let's work on that uni another time. Okay.

[00:05:30] Dr. Detlev Boison, PhD: [00:05:30] Yeah, but this is again, the evolution of a principal. So during the day you can see, consume a lot of energy. You produce a Denison, which induces sleep, which helps you to save energy. For example, an epileptic seizure is an excessive consumption of NRG.

[00:05:49] Um, uh, to produce all the firing of the neurons and the conversions and epileptic seizures induce a massive release of a Denison, which X S [00:06:00] the endogenous agent to stop a seizure. And Albany stopped because a Denison is, is released as a way to conserve energy. Okay.

[00:06:12] Carl Lanore: [00:06:12] Hold on a second. Just one second. So, because you're saying things that I want, I want to talk about your research, but I also want to ask you, it's obvious to people who are listening.

[00:06:22] So the whole fascination with the ketone diet ketosis, we know that it works for epilepsy as well. Yes. So what, what do, what do ketones do that affects a Denison? Cause obviously they must have an effect on a Denison right.

[00:06:35] Dr. Detlev Boison, PhD: [00:06:35] Yes, they do. Yeah. So, so keto or ketogenic diet has a large number of different effects, and that's the power of the diet because it exerts beneficial mechanisms through, uh, dif, different ways of operation.

[00:06:50] And one of those mechanisms is an increase of a dentist in the brain. Yeah. Which we have demonstrated in our research, and we found that a [00:07:00] ketogenic diet leads to downregulation of the major Denison removing enzyme Adams in kindness.

[00:07:07] Carl Lanore: [00:07:07] Wow. Fascinating. That is interesting.

[00:07:11] Dr. Detlev Boison, PhD: [00:07:11] So, so

[00:07:12] Carl Lanore: [00:07:12] good.

[00:07:13] Dr. Detlev Boison, PhD: [00:07:13] I'm sorry. Yeah. So, so one way that ketogenic diet X is, is by actually increasing a dentist in the brain.

[00:07:20] Carl Lanore: [00:07:20] And now to segue to caffeine. Since we know that the people who, uh, like I am fast right now, I haven't eaten since 6:00 PM last night and I, I, I do a time restricted feeding and then sometimes I don't, there's periods of time where I eat breakfast. Um, but I'm doing time restricted feeding right now. And, uh, one of the things that we know is that, uh, drinking a cup of coffee will actually increase ketone production in the liver.

[00:07:46] Is there some sort of mechanism, this, uh, this, uh, friendship between ketones, adenosine and caffeine?

[00:07:55] Dr. Detlev Boison, PhD: [00:07:55] Yeah, this is, this is obviously all related. And so at dentist an [00:08:00] X by binding to a dentist and receptors and caffeine is an antagonist of a dentist and receptors. So if you get snippy in the evening.

[00:08:08] Because you have more identities in the brain, and if you drink a cup of coffee, it makes you a note and a release. We moved to a steep drive.

[00:08:18] Carl Lanore: [00:08:18] Okay, so let's talk about coffee now. And something that I learned. I'm writing a note for myself. Uh, something that I learned from your study was that when someone suffers a traumatic brain injury, let's say a concussion or they bomb blast or something like that, they hold their breath, don't they?

[00:08:37] Dr. Detlev Boison, PhD: [00:08:37] Right? Yeah. So, um, and it's again, the, um, the ancient mechanism to increase a Denison to conserve energy. So when you have a traumatic brain injury. Um, you run into an energy crisis. You also have excessive energy consumption in the brain because the injury triggers neuronal firing. So this region [00:09:00] is a massive search and a Denison.

[00:09:02] And now Jen Dennison is very beneficial initially because it exes in Europe protected. Uh, it, it prevents neurons from dying. But, uh, this excessive surgeon at Denison, um. It can also be detrimental if a dentist and concentrations are high enough or if the endogenous metabolism of a Denison is compromised, and if high levels of a dentist and reached the brainstem, it can induce a respiratory arrest, um, are called apnea.

[00:09:36] So I love it so far, dentist and have been shown to block respiration. And this is thought to be one of the major reasons for acute mortality after severe traumatic brain injuries.

[00:09:51] Carl Lanore: [00:09:51] That's fascinating. I never realized that that was why PR people who suffered a traumatic brain injuries often that's [00:10:00] why they die.

[00:10:00] Right? Because of the apnea. They stopped breathing.

[00:10:03] Dr. Detlev Boison, PhD: [00:10:03] Yes. This is one of the reasons for acute mortality within the first 10 minutes after a traumatic brain injury.

[00:10:11] Carl Lanore: [00:10:11] Now. Now you designed a study, discard that. Describe the study model that you did with the rodents and, and how you performed this research.

[00:10:21] Dr. Detlev Boison, PhD: [00:10:21] Yes, so I want to, our hypothesis was that, um, uh, traumatic brain injury cooking cause acute death. Um, within minutes after the injury because of excessive levels of a Denison. So therefore, it was an obvious rationale to use caffeine to prevent that. Um, so we used a rat model of a severe traumatic brain injury.

[00:10:47] Which causes a lethal outcome in, um, uh, a little over 40% of all rats. Um, so what, what basically happens in those studies is [00:11:00] after the injury, the NMS immediately stop breathing and die. Um, so what we then did is, uh, we had those, those dying rats and injected the single dose of 25 milligram per kilogram caffeine into those reds, uh, 10 seconds after the traumatic brain injury.

[00:11:20] And after doing that, the rats immediately started breathing again and also obliged. Wow. Enema treated acute, those of caffeine survived.

[00:11:33] Carl Lanore: [00:11:33] Is this exclusively, it's result in, in Denison, or we also know caffeine seems to upregulate dopamine and dopamine kind of is a, an energetic neurotransmitter. Does dope play a role in that survival, you think?

[00:11:48] Dr. Detlev Boison, PhD: [00:11:48] Um, no. I don't think so because the interactions, dopamine takes longer. Okay. Um, so the effect of caffeine on Denison receptors is, is immediate and can be used [00:12:00] for immediate rescue offs, those animals.

[00:12:02] Carl Lanore: [00:12:02] So the reality is that to use this as a rescue therapy, you would have to inject it. W you could, obviously, if the person's unconscious, they're not going to swallow.

[00:12:12] So you would inject and, and I, I don't know if you said this, I was writing a note, but the, the dosage was 20 milligrams, a kilogram equivalent in human right.

[00:12:23] Dr. Detlev Boison, PhD: [00:12:23] No, there's the dose for REITs is 25 milligram per kilogram. Um, and this is equivalent to four milligram per kilogram in humans.

[00:12:34] Carl Lanore: [00:12:34] Not much at all. So that

[00:12:36] Dr. Detlev Boison, PhD: [00:12:36] means it's human that weighs 80 kilograms.

[00:12:39] That would be 320 milligrams of caffeine. And that's equivalent to about, um, 26 ounces of standup coffee or. Oh, one of those big Starbucks coffees,

[00:12:55] Carl Lanore: [00:12:55] or for this audience, about a third of a pre-workout supplement, [00:13:00] because most pre-workout supplements have four to 600 milligrams of caffeine anhydrous. Uh, and this is very interesting.

[00:13:08] So, uh, that would then beg the question, well, if I'm an MMA fighter and I know that in the next couple hours, I'm going to get punched in the head a lot, should I just drink caffeine to pre-treat.

[00:13:23] Dr. Detlev Boison, PhD: [00:13:23] Yeah. So we know this was exactly the reason why, why we did this, a recently published study, because, um, um, every injury happens in a specific context.

[00:13:35] So first of all, we wanted to know, uh, if this effect also is maintained, if the caffeine, uh, if the brain is already pre caffeinated. No, because a lot of us, I think about 80% of the population regularly consumes caffeine. So it can be assumed that at the time point of the injury, um, uh, the victim is already a caffeine aid.

[00:14:01] [00:14:00] Carl Lanore: [00:14:01] It's a prophylactic at that point in time.

[00:14:03] Dr. Detlev Boison, PhD: [00:14:03] So we wanted to know if the acute rescue with, with, uh, with a singer caffeine, those will also work. Um, if the brand is pre caffeinated and we found, uh, the answer is yes. So it works. Also, if the brand is pre caffeinated, and it also works when the caffeine is given, um, uh, an acute dose of caffeine is given immediately before the injury.

[00:14:29] Um, but after the injury, it needs to be given within 10 seconds. If we delay the administration to 90 seconds, the effect was gone. Um, but we also looked at caffeine withdrawal. Um, because, um, if you have a chronically caffeinated and then suddenly you stop, uh, caffeine consumption, um, the outcome might be worse.

[00:14:55] So we introduced the group where we in caffeine [00:15:00] withdrawal 24 hours prior to the injury, um, and the outcome was worse. Um, we also, um, tested the effects of caffeine withdrawal after the injury. And again, the outcome was worse. So if you think about a traumatic, if you think about a chronically, um, caffeinated TBI victim, um, after the injury, once the patient is hospitalized, there is basically a default caffeine withdrawal.

[00:15:29] Understand that of care. Um, caffeine is not given. And, uh, in this study we found that continuing chronic caffeination actually helps with recovery of motor functions. Interesting, very related research in epilepsy models. And they found that any change in any sudden change in the caffeination paradigm, um, needs to be considered, [00:16:00] uh, with a lot of caution.

[00:16:01] So if, if you're chronically caffeinated and suddenly stop, um, uh, consuming caffeine, this mat. A make your brain move on, or, or on the other hand, if you have never any caffeine and suddenly you use high doses of caffeine, this can also be detrimental.

[00:16:19] Carl Lanore: [00:16:19] So does the Tennessee and play a role in, in, uh, in memory and memory consolidation.

[00:16:25] And then that's why when people like I had to give up caffeine for awhile. And I, I couldn't think straight. I couldn't remember things. And, you know, my brain was tired, let's say. Is that a function of the downregulation of a Denison? Yes.

[00:16:40] Dr. Detlev Boison, PhD: [00:16:40] Dennison place plays a large role for cognitive processes, for depression, for psychiatry problems.

[00:16:49] Um, but, but this again is because it's such a.  ancient master regulator. It's a regulates four types of a dentist and receptors, [00:17:00] which can have excitatory and inhibitory function. But we also discovered that a dentist has additional dentist receptor independent functions, uh, by regulating, uh, DNA methylation.

[00:17:14] Interesting. It's the regulator of epigenetic changes in the cell. So if, if meth, our groups are edit or remove to DNA, the entire gene expression program can be changed. And this is all regulated by a dentist, a dentist, and has direct interactions with the dopamine system. So it's doing so many different things at the same time.

[00:17:34] So we found that grew up in a dentist in the brain. Is actually a common pathological hallmarks font, not only in epilepsy, but also in Alzheimer's disease and Parkinson's disease. And that a reconstitution of a Denison is beneficial for a wide range of brain pathologies.

[00:17:57] Carl Lanore: [00:17:57] Supplementing with, uh, an [00:18:00] ergogenic that's been well studied for safety, uh, creatine, creatine monohydrate.

[00:18:06] Yeah, it increases the production of adenosine triphosphate. And obviously if you're working in, you're active, you're going to cleave more, but you're going to end up with more Denison. It does create team player. Could it be an interesting contributor to this whole discussion?

[00:18:24] Dr. Detlev Boison, PhD: [00:18:24] Uh, that's a very interesting thought because creatine increases ATP, which is the ma major souls for Denison.

[00:18:32] So therefore it's likely that, uh, creating also. Increases the availability of a Denison, but this hasn't been studied seriously

[00:18:42] Carl Lanore: [00:18:42] because the, uh, the, the U S army did a study about 10 years ago on creatine monohydrate. They gave it to. Uh, soldiers who were, were working overnight, you know, garden and so on.

[00:18:53] And they gave a one group of placebo and one group, they gave them just five grams of creatine monohydrate. And the group that [00:19:00] got the creatine monohydrate had no problem staying awake all night long. So it, it had an interesting effect on, on brain activity. There's no doubt about it. It would be interesting to see if you.

[00:19:10] If you pre-treat with creatine and caffeine, if the outcome in a, at a traumatic brain injury is actually more improved or less improved, they're just, just a thought. Just a thought.

[00:19:20] Dr. Detlev Boison, PhD: [00:19:20] It would be interesting to study. Yeah.

[00:19:22] Carl Lanore: [00:19:22] Yeah. Um, I, I want to take our first commercial break when we come back, I want to dig deeper into the research.

[00:19:28] I want to find out if there was anything that really surprised you. Uh, about the outcome of the study and, uh, we'll discuss this, uh, to a greater degree. Stay tuned. You're listening to and watching super radio. If you're here on Facebook, we'll be right back. You are listening to the superhuman channel.

[00:19:43] Don't hate us because we feel good.

[00:19:50] Welcome back to the superhuman radio. We're talking with dr Detlev Boysen. He is from Rutgers university. I've been on the air for doing this show for, I'm in my 15th year right now. [00:20:00] And some of the best scientists I've spoken to come from Rutgers university. Um, I'm being sincere. I've, I've had some groundbreaking discussions about how glucose signaling, uh, is the trigger for cellular senescence.

[00:20:14] I did that show back in 2006. It was a, uh, Rutgers scientist that I spoke to then. Um, yeah, it's a, it's a great learning facility. It really, really is. Okay. So, uh, in the case of epilepsy and seizures. How would someone leverage this science? And then we'll get back into the whole discussion about traumatic brain injury.

[00:20:36] Dr. Detlev Boison, PhD: [00:20:36] Yeah. So, so we've shown in our own rodent models of epilepsy that, um, giving a drug that increases the activation of identity in a one receptors can compete the block. Seizures that are resistant to conventional antiepileptic drugs used in humans and that don't work. Um, we have also shown that [00:21:00] an inhibitor of the dentist and removing enzyme  completely blocks those seizures that are resistant to antiepileptic Rux.

[00:21:10] Um, that looks fantastic, but it has a catch because if you increase a dentist in two high levels globally. Uh, you get major side effects like sedation because I, Denison is asleep and user, so the animals no longer had seizures, but they will also sleep. So there's no way, uh, to, to just, uh, boost a dentist in a systemically up to very high levels.

[00:21:37] So therefore, we spent many years in developing local dentist and augmentation therapies to increase, uh, Denison directly. In the vicinity of an epileptogenic brain area, uh, to limit systemic side effects. So we've engineered, um, as STEM cell based, uh, brain implants. [00:22:00] Uh, we tested gene therapies and, um, use, uh, bio engineered silk, uh, for the local delivery for dentists, and have shown that a local source of a dentist in directly in the brain can, uh, completely suppress epileptic seizures.

[00:22:16] Wow. Um, but our most recent work is, uh, actually a lot more exciting because, uh, after our discovery that a dentist in X on DNA methylation, uh, we found out that a transient dose of a Denison is sufficient to prevent the development of epilepsy. Uh, so we have shown this in the total of five published studies that just the trends in those of a dentist and giving after an epilepsy triggering brain injury for just a few days, uh, can completely prevent the development of epilepsy.

[00:22:56] Wow. Because of that, we have now [00:23:00] launched a drug discovery and development program. To develop a novel adenosine kinase inhibitor that can be used to block the enzyme, just transiently, uh, in order to prevent epilepsy.

[00:23:17] So we've shown in the mouse model of, of epilepsy that, uh, using, um, a similar compound for only five days, um, can completely prevent epilepsy. And, uh, this is a highly attractive setup you'd, because even if those drugs have, uh, sedative side effects, but if they're just given trends in D, could have a long lasting therapeutic benefit

[00:23:45] Carl Lanore: [00:23:45] is it said Dennis being at the center of a central.

[00:23:50] Sleep apnea. There's a lot of people out there who have central sleep apnea that has nothing to do with the mechanical function of their throat or their palette. They just stop there, stopped breathing. They just [00:24:00] hold their breath.

[00:24:00] Dr. Detlev Boison, PhD: [00:24:00] Yeah. That's the reason for central central apnea. Yeah, and Dennison also plays a major role in a phenomenon called sudden unexpected death in epilepsy.

[00:24:14] Patients with epilepsy are the highlight likelihood of sudden death because they stopped briefly.

[00:24:21] Carl Lanore: [00:24:21] Wow.

[00:24:22] Dr. Detlev Boison, PhD: [00:24:22] And again, it's the same principle fades.

[00:24:25] Carl Lanore: [00:24:25] What about SIDS? With with babies?

[00:24:27] Dr. Devlet Boison, PhD: [00:24:27] Exactly. Sits is exactly the same thing. Sudden infant death syndrome is also based on excessive activation of adenosine receptors in the brainstem.

[00:24:37] Carl Lanore: [00:24:37] So theoretically, people at risk of those, if they had, uh, if they increase the enzyme that metabolizes adenosine, that could be protective for them.

[00:24:49] Dr. Devlet Boison, PhD: [00:24:49] Yes.

[00:24:49] Carl Lanore: [00:24:49] Does exercise increase this enzyme? How does exercise, we know that exercise influences a Denison CMP, you know, and all these other [00:25:00] interesting molecules does, does, does exercise increase the enzyme kinase?

[00:25:07] Dr. Devlet Boison, PhD: [00:25:07] Um, that's not yawn. That's not known yet. So we know that exercise increases a Denison. So therefore it's like you, that exercise decreases the enzyme. Yeah,

[00:25:21] Carl Lanore: [00:25:21] I guess you're right. Yeah. Um, caffeine and coffee are spoken about as the same thing in today's day and age, however, they are very, very different compounds.

[00:25:34] And I've been doing some research, fascinating research on homocysteine and coffee and homocysteine and caffeine, and. Caffeine increases homocysteine, but coffee increases it more because it not only directly increases homocysteine statistic production, but it slows down metabolism and degradation of homocysteine.

[00:25:57] So it's a double whammy. So when we talk about this [00:26:00] research, was any of your research done actually on coffee, whole coffee with the caffeine attached, or was it all just caffeine and hydrous or something like that?

[00:26:10] Dr. Devlet Boison, PhD: [00:26:10] No, we exclusively use pure caffeine.

[00:26:13] Carl Lanore: [00:26:13] Yeah. Yeah. Um, what about the military? What work did you do with the military that was written up in the article?

[00:26:20] I think I actually have a picture of the article here. Let me just put it up here real quick while we, while we talk, we'll, we'll, we'll put this up. Yeah. So talk about this, this research more than just a cup of coffee.

[00:26:30] Dr. Devlet Boison, PhD: [00:26:30] Yeah. So the, the study that I described previously where we, uh, rescued those dying rats with the singer, acute dose of, uh, caffeine after the injury was funded by the U S army medical research and material, uh, commands, uh, telemedicine and advanced technology research center, also called Tetrick.

[00:26:54] Um, so they provided us with the research grants for, for two years to, to [00:27:00] study the effects of, um, uh, uh, caffeine on the outcome after traumatic brain injury, which is obviously of high significance for the U S military.

[00:27:13] Carl Lanore: [00:27:13] And what have, have there been any, any outcomes discussed already? Is there any new new information from this or is this just starting now?

[00:27:21] Dr. Devlet Boison, PhD: [00:27:21] Yeah, so this has been. So, so two, now, two, turns out the situation is a lot more complex, um, because there are a lot more variables that need to be considered. So, uh, in this, uh, published paper, we looked at, um, the pre caffeination standards of the brain, for example, because service members usually, um, are,

[00:27:47] Carl Lanore: [00:27:47] yeah.

[00:27:47] Drinking a lot of coffee. They do.

[00:27:49] Dr. Devlet Boison, PhD: [00:27:49] Yeah, exactly, exactly. And, um. But another effect of that we haven't considered yet, and that should be the focus of future research, is sleep. The prevention [00:28:00] service members who go into dangerous situations where they might be exposed to, uh, to a bomb, um, might be sleep deprived at the time point of the brain injury.

[00:28:12] Uh, and sleep deprivation also leads to an increase in a Denison. So we, we, we get into very complex in the actions between, uh. A sleep deprivation prior caffeination, uh, uh, the timing of the injury. Um, so this, uh, uh, probably needs a lot more research and, um,

[00:28:35] Carl Lanore: [00:28:35] yeah, that makes a lot of sense. So there's a, there's an interesting, uh, leaf that's becoming very popular around the world.

[00:28:45] It has a lot of use in, uh, in Vietnam, and, and we call it Cray. Tom. But it's a, its actual name is Mitra. Jeannine, specially Geosys, and it's actually in the coffee family, but it [00:29:00] doesn't contain any caffeine, but it contains other alkaloids that. Both affect the, uh, opioid receptor to some degree, but that also have some stimulatory effects.

[00:29:15] I, in fact, I took a gram of it this morning because I have a sponsor who sent me some and I'm trying and I'm going to see and you know, make you feel, it doesn't make you feel sleepy at all. Does it affect sleep? It doesn't make you feel hyper agitated like caffeine. It it, it's more like the, uh,  and, and, and agents in T they kind of make you awake.

[00:29:38] They make you more, more, more, uh, cognizant and focused. Uh, but they don't stimulate. And so just because this study was about coffee, and I know that they, these two plants are in the same family. I went and I, in fact, I found a study, and I'm going to see if I can put it up here real quick, but the study [00:30:00] is called.

[00:30:01] The, uh, uh, synthetic and receptor signaling exploration of Neutrogena alkaloids. And in fact, it affects the adenosine receptors, both one and two and two, a, I guess there's a, uh, uh, a two alpha and a and so on. And it does interact with them. And I thought, you know, if this interacts the same way caffeine does.

[00:30:25] But it also is a powerful analgesic. This may be even better for someone who's just suffered a traumatic brain injury because it, it'll help deaden the pain and it will affect the, uh, adenosine receptor as well that you're, that you're targeting here.

[00:30:43] Dr. Devlet Boison, PhD: [00:30:43] It's a very interesting compound, which has a dual mode of action.

[00:30:48] So. That binds both on opiate receptors as well as on  receptor, which is really interesting, and they're bright, combined. Some of the effects of caffeine. [00:31:00] Uh, with the stimulation of, um, uh, the opioid system. Uh, I'm not sure if this would be good idea for traumatic brain injury because increasing, um, the opiod receptors, uh, can also suppress recipe ratio.

[00:31:18] Carl Lanore: [00:31:18] Well, that's another study I found it the. This doesn't, because  it somehow affects the opioid receptor, but not the same way opioids do. And it doesn't, it does not affect the, I found another study. I didn't take the time to put it up there, but they looked at a, and it was a study on, um, various aspects of

[00:31:38] Dr. Devlet Boison, PhD: [00:31:38] this

[00:31:39] Carl Lanore: [00:31:39] leaf and how it interacts with the opioid receptor and what they, what they did point out in this one study is that doesn't, uh, doesn't slow down respiration like opioids.

[00:31:48] Do.

[00:31:49] Dr. Devlet Boison, PhD: [00:31:49] Yeah. Maybe because it also acts on the aid to a recent,

[00:31:53] Carl Lanore: [00:31:53] it's, I think it's an interesting compound. I think you might want to look at it just maybe, maybe as a, you know, as an a, another agent that does the [00:32:00] same thing as caffeine. Because, because I, I strongly believe we're on the verge right now of understanding that all the coffee we're consuming isn't the greatest thing in the world metabolically.

[00:32:13] You know, a coffee. So back in the day, there was a study done and they said, Oh, you know, coffee, um, that run that you put through a filter is better for you. Then, you know, the paper filter, the drip coffee is better for you than the other coffee. But now they're starting to figure out that they still do the same things.

[00:32:30] And, and coffee seems to have some, uh, pro-inflammatory effects that when used chronically longterm, the may outweigh the, the quote unquote. You know, boosts you, get in cognition and awareness and so on and so forth. I have a funny feeling that we're going to start seeing more information. Uh, but with that being said, you're, you're really, um, looking at it as a, uh, post traumatic brain injury therapy, and I can see this being [00:33:00] used like an EpiPen for people who have an allergic reaction.

[00:33:03] Boom, shoot it, and then, then they, then they're protected. Exactly.

[00:33:07] Dr. Devlet Boison, PhD: [00:33:07] Yeah. Yeah. The idea that we had because it's a Caseen pen would be available, could be given immediately after an injury. Yeah.

[00:33:18] Carl Lanore: [00:33:18] Yeah. Um, what was, was there anything that really surprised you about your research that you did not expect?

[00:33:24] Obviously when you do research, you have end points that you're looking for, but a lot of times there were things that happen while, wow, we didn't expect that. Did you have any of those moments in this research?

[00:33:34] Dr. Devlet Boison, PhD: [00:33:34] Yeah. One, one finding where that really stand out as was this complete rescue. Then when we started this research, we were hoping maybe to find some effects, but, but the fact that every single of those dying Rhett's started breathing again and survived, uh, was, was really festinating.

[00:33:56] Mmm. The one bothers to study that we don't understand yet [00:34:00] is, um. That if we doubled the caffeine dose, uh, we didn't find any effects. So there also seems to be some, uh, a certain, uh, yeah, those window of efficacy. So if we are above or below the optimal dose, will we lose those effects?

[00:34:21] Carl Lanore: [00:34:21] So I w I would assume that you've tried lots of different doses and found that one to be the sweet spot then.

[00:34:26] Right?

[00:34:27] Dr. Devlet Boison, PhD: [00:34:27] Right. Yeah. Yeah.

[00:34:29] Carl Lanore: [00:34:29] Interesting.

[00:34:30] Dr. Devlet Boison, PhD: [00:34:30] But we don't have an explanation yet for this phenomenon. Interesting.

[00:34:37] Carl Lanore: [00:34:37] Wow. That is fascinating. I'm thinking like what could it be? And uh, that, that is fascinating. Um, we're going to take our last commercial break and when we come back, I want you to tell people both lay people and, and clinicians what you hope they take away from this research and perhaps what we can look for in the future.

[00:34:55] Uh, in this, in this area. Stay tuned. We'll brother you are listening to the [00:35:00] superhuman channel where ripped and we're ready.

[00:35:05] Welcome back. We're talking about how caffeine could be a therapy and traumatic brain injury and even seizure with dr Detlev Boysen from Rutgers university. So Joel green for some reason, we usually have comments show right up on the screen, but I have to get with the it people cause nothing showing up.

[00:35:27] Joel green has an interesting question, doc. He says, I'm one of the SARS coven. Two treatment is REM deciview, which isn't a dentist seen analog. And there is some suggestion upregulating a Denison helps terminate RNA chains needed to replicate the virus. Could caffeine help? Hey, you're smiling already.

[00:35:52] This is, this is the audience that I attract it just for the record.

[00:35:58] Dr. Devlet Boison, PhD: [00:35:58] Very interesting question. [00:36:00] So REM doesn't via, um. Structurally, uh, and Dennis in analog, but, uh, does not act as a Denison. So it's like a lot of chemotherapeutic agents that are given for cancer therapy. The structure of motive of all those, uh, anticancer drugs is related to.

[00:36:24] Yeah. Basis of the DNA, uh, so that those compounds are incorporated into, um, into DNA and lead to double strength breaks and there by, um, uh, kill the cancer cells. So, uh, those smaller kids don't actually act like a dentist in. But, um, uh, of course, we did some research on our own, on our own, on. Possibly the possible interactions of a Denison with covet 19.

[00:36:55] And, um, so I published a paper, um, [00:37:00] a few years ago showing that inhibition of either missing kindness attenuates acute lung injury. Huh. So this might be interesting. Um, in light of, uh, um, the acute respiratory distress syndrome, which is at the end stage of the disease with excessive inflammation of lung tissue.

[00:37:25] Um, so, uh, so we think that Dennison could possibly be beneficial, um, um, during, uh, the end stage of, uh, covet 19 two. Okay.

[00:37:38] Carl Lanore: [00:37:38] Protecting the lung. So that, that, that leads to an interesting thought, right. So, uh, we know that a ski Mia, um, robs oxygen from the brain in the case of a stroke or from the heart,

[00:37:53] Dr. Devlet Boison, PhD: [00:37:53] but,

[00:37:54] Carl Lanore: [00:37:54] but they still want to work things want.

[00:37:56] And so the lack of energy, the lack of oxygen is what [00:38:00] really causes the. Collateral damage to tissue wood, wood modulating, or attenuating a dentist seen help ischemia leave less damage behind.

[00:38:12] Dr. Devlet Boison, PhD: [00:38:12] Yes, yes. No. We have shown this in a couple of studies where we induce a stroke in animal models. So we have shown that a Denison X as an endogenous neuroprotectant, and this comes back to the early evolutionary principle, if you have a stroke.

[00:38:29] You have an NRG crisis and, uh, what happens when you have an NRG crisis? You get in release of a dentist and so stroke, exactly like a traumatic brain injury leads to a massive increase of a dentist. The brain, which primarily has a protective function to prevent excessive injury to the brain.

[00:38:51] Carl Lanore: [00:38:51] You know, I have actually made intra-nasal melatonin.

[00:38:57] At home, I, I'm kind of like [00:39:00] a, uh, I have a hobby. It's called compounding pharmacy. And so I make things at home all the time. Transdermals and injectables and everything. And so I've experimented with intra-nasal melatonin and it works in fairly low doses. In fact, I've communicated with the doctor, um, Russell rider.

[00:39:19] Oh, from . He's been on the show numerous times over the years. And I, and he said it's a great idea, and I've made it, and it works. But the thing that it doesn't help with is sleep pressure, the onset of sleep. And I've thought if I could just add a dentist scene to it, have a Denison and melatonin in a nasal spray, spray it and you'd fall asleep and stay asleep.

[00:39:39] But the problem is a, Denison is a drug. It's a, it's a, it's a, a class. One, I think one or two drug a day can only be used by prescription, at least from the research I've done. I would just think that Dennis and intra-nasal and adenosine and melatonin spray could change sleep patterns for people [00:40:00] dramatically.

[00:40:00] Dr. Devlet Boison, PhD: [00:40:00] No, I don't think so because again, this is extremely short lasting. So in the, in the periphery, the, the half life of a Denison is in the range of, of seconds and in the brain. It's in the range of minutes. So the, the activities is too short. Last intra-nasal a dentist and might be useful for the emergency treatment, the stroke.

[00:40:24] How does epilepticus seizures that don't

[00:40:27] Carl Lanore: [00:40:27] stop or for that protective opportunity in a stroke, you start getting identity and into the brain to feed the energy shortage. And the brain, the brain would maybe would not suffer so much damage.

[00:40:41] Dr. Devlet Boison, PhD: [00:40:41] Yeah. Positively. It's given immediately,

[00:40:44] Carl Lanore: [00:40:44] but that's the key.

[00:40:45] Immediately, those, those types of injuries, traumatic brain injury, stroke, even heart attack, the window of opportunity to turn things around is, is, is very small. Very, very

[00:40:55] Dr. Devlet Boison, PhD: [00:40:55] small.

[00:40:57] Carl Lanore: [00:40:57] So, um, what would you like, uh, both clinicians [00:41:00] and lay people to take away from your research.

[00:41:03] Dr. Devlet Boison, PhD: [00:41:03] Yeah. I think, um, the most important, uh, you know, findings from 25 years of my research basically, is if we look into pathologies, we are faced with complex network problems.

[00:41:18] No matter which disease you look at, it's never one single pathway that is disrupted. It's always a complete network. And. Um, yeah, most drugs that you can give today don't affect the network. They infect isolated channels or receptors. Um, and this might not be the best possible approach. So I think. Uh, what we need is to move medicine, uh, along is to find smart strategies, uh, to, uh, develop network therapies, therapies that affect an entire network on many different levels, on the receptive level, on the biochemistry, on epigenetic levels.

[00:41:57] And, um, and that basically [00:42:00] means that, um. Treatments such as the ketogenic diet, which has multiple different effects, ideally suited to treat, uh, network dysfunction. Um, there are probably a lot of, uh, natural compounds out there that have not been utilized to the fullest extent. Um. Uh, and of course, molecules such as a dentist in which have so many different, uh, beneficial activities, uh, are highly suited to be developed as a, as network therapeutics.

[00:42:37] Carl Lanore: [00:42:37] Interesting. You know, when you said that I, I wanted to be sarcastic, I wanted to say, Oh wait, doc, you mean the human body is complex because really, because. We have been lulled into this idea that this pill will cure us, and it's not that way. [00:43:00] And you know, I've, um, uh, we've talked about Alzheimer's disease on this show, uh, numerous times over the years.

[00:43:07] And, uh, I've had, uh, Dr. Dale Bredesen on the show who wrote a fantastic book called the end of Alzheimer's. And when I tell people about it. And they buy the book. They do. They don't realize, Oh, I've got to change the way I sleep, the way I eat, the way I move. The way. Yeah. That's because the human body is complex and it just comes full circle.

[00:43:28] It's a network problem. Even though the symptoms may be coming from here, it's a network problem.

[00:43:34] Dr. Devlet Boison, PhD: [00:43:34] Yeah, yeah, exactly.

[00:43:35] Carl Lanore: [00:43:35] Yeah. Fascinating stuff. I think you've done some great work. I hope that you'll come back on what w what, what, what is your group looking forward to next? Uh, can you give us a peek behind the tent of what you're working on next?

[00:43:46] Dr. Devlet Boison, PhD: [00:43:46] Yeah, so a major focus right now is the prevention of epilepsy. I think that's really an absolutely major unmet clinical need to prevent, uh, [00:44:00] epilepsy, for example, after traumatic brain injury. And, uh, so we really hope that we can, um, come up with a solution for this problem.

[00:44:10] Carl Lanore: [00:44:10] Does not all epilepsy comes from TBI, right?

[00:44:13] There are people who are born with a predisposition to develop epilepsy, right?

[00:44:16] Dr. Devlet Boison, PhD: [00:44:16] Yes. Yes. Um, no, of course there are. Um, so most childhood epilepsies are genetic. You base, uh, but most dietary epilepsies, uh, I usually acquire, uh, this can be a traumatic brain injury or. Um, uh, February status epilepticus during childhood or a viral infection or a stroke.

[00:44:40] Uh, so basically any kind of injury to the brain, uh, can trigger, uh, uh, a process called epileptogenesis that basically turns a healthy brain into an epileptic brain over many months or even years. And, uh, this so called Leighton period is, uh, as a [00:45:00] time window for therapeutic intervention to prevent that from happen.

[00:45:06] Um, so another major research area we are interested in. So we've learned a lot, uh, about the role of identity in the brain, and we have translated what we learned in the brain, um, uh, to the area of cancer. So at Denison. Um, plays a major role in, in cancer biology. And we hope that seminar strategies that we developed for the treatment of brain conditions can also be used for the treatment of cancer.

[00:45:37] Carl Lanore: [00:45:37] You know, I want to clarify something. When we talk about the ketogenic diet, I want to be clear that people that just about any low carbohydrate diet can produce ketones, even if you're eating high protein. Now, if you're treating cancer, we know that. Cancer will is opportunistic. It's a highly evolved cell.

[00:45:57] It will use . It'll use [00:46:00] glutamine, it'll use other substrates to stay alive. But when we talk about the ketogenic diet, really what we're talking about here is any diet or eating strategy that produces ketones. When I wake up in the morning after a 12 hour fast overnight. I've got 1.1 1.2 millimoles of ketones in me already.

[00:46:20] So, you know, we, we don't, we don't need four millimoles. There's this, there's the people have turned the ketogenic diet into a competition. You're checking the ketones and they're putting, look, my ketones are four points. You don't have to go that deep into the cold ketone diet. Just the presence of ketones, the changes in insulin, uh, and, and the availability of blood sugar is where the magic is.

[00:46:43] Uh, you know, I, I just want people to understand that you don't have to eat 80% fat. And with that being said, I w since we've talked, we're talking about epilepsy here for a second. Epilepsy was once called hypoglycemic headaches back in [00:47:00] 18 hundreds. Some doctor discovered that when the brain became hypoglycemic, things started to malfunction.

[00:47:07] Do you think that epilepsy could be. Uh, when we talk about genetic predispositions, are we really talking about doing things that favor our, uh, our, our being versus don't? And some of us don't do well with some things and some foods as others. Could epilepsy actually be triggered by diet in the first place in childhood epilepsy.

[00:47:37] Dr. Devlet Boison, PhD: [00:47:37] No, I don't think so. Because most try to epilepsy Bay based on mutations in iron channels and receptors, and this is such an ingrade program. Um, uh. Which sometimes can be treated with the ketogenic diet, uh, uh, but, but in primarily the [00:48:00] genetic program drives, drives the development and, uh, of epilepsy and the expression of, of seizures.

[00:48:06] Okay.

[00:48:07] Carl Lanore: [00:48:07] And, and the other thing that I just want to mention is when children are diagnosed with epilepsy and they get on the ketogenic diet long, early enough. Sometimes just for a couple years, they can stop the ketogenic diet and the epigenetic effects take place and things change in the brain. Baby, the child isn't epileptic anymore.

[00:48:24] Have you seen those situations.

[00:48:26] Dr. Devlet Boison, PhD: [00:48:26] Yeah, that's correct. So in many cases, a ketogenic diet can be curative, REMS, genes, epigenetic mechanisms, and those effects are lasting. Fascinating

[00:48:38] Carl Lanore: [00:48:38] stuff. Will you come back on when you have new research? We do. We talk a lot about, uh. Ketosis, ketones, ketone esters, ketone salts, and the role that they play in metabolic diseases and so on.

[00:48:51] So if your next research is going to be in epilepsy, uh, and, and, and, and preventing it or, or curing it, I'd love to have you back on when that [00:49:00] stuff comes around.

[00:49:01] Dr. Devlet Boison, PhD: [00:49:01] Sure. My pleasure.

[00:49:03] Carl Lanore: [00:49:03] Thanks so much for being here. I know you had to set up a Facebook account just for today's show. Thank you so much for doing that.

[00:49:08] Okay, you have a great day. Take care.

[00:49:12] Dr. Devlet Boison, PhD: [00:49:12] Bye. Bye.

[00:49:13] Carl Lanore: [00:49:13] All right, so we're going to, uh, pretty much end the show here. I don't have anything else to talk about right this minute. Um, great show hitting it out of park on Monday and, Oh, why? Cause Elisa Profumo was working at superhuman radio again, and this is the quality of shows that she is responsible for.

[00:49:31] So you don't have to just listen to me drone on and on anymore. Thank her. Not me. I, tomorrow's Tuesday we got the a blueprint power hour. Elise has got the whole week booked with amazing, uh, uh, shows. And um, now that she's back. She's booking a week and two in advance. I'll start to pre-release the shows so people can know what's coming and be here in person.

[00:49:52] Oh. And also the live streaming player will be back this week. So those of you who can't watch this on Facebook. [00:50:00] But still want to be part of the live audience will be able to listen to it on your iPhone or to computer at work. So we'll bring that back and once that's done, you'll be able to go home and tell Alexa to play human radio, both the podcast and the live stream.

[00:50:15] We're going to get cool here. I will see everybody tomorrow. Thank you for watching today. And listen. [00:51:00]  .