[00:00:00] Carl Lanore: [00:00:00] Hey, Hey, welcome back to another episode of super human radio at the beginning of a new week, January 11th, it's a Monday. Uh, we have a fascinating show planned for you today. Uh, during the first day we're going to be talking about ketamine. Ketamine is being used, uh, to treat major depressive disorder, to learn what ketamine is.

[00:00:21] And we're gonna learn about a new study that shows. A protein that may be the key to making ketamine work better later in the show, we're going to be joined by, uh, Alex leaf. Who's been on the show before he actually worked for Superman radio many years ago, um, discussing, uh, the potential implications of, uh, a COVID vaccine during pregnancy.

[00:00:46] Uh, obviously there's no data to show that it's dangerous, but there's no data to show that it's safe. And we're going to explore this concept, uh, with him later in the show. Of course, before we do anything else, we have to thank our title sponsor and [00:01:00] that's legendary foods and they have their new tasty pastry, which is birthday cake flavored.

[00:01:05] If you haven't tried it, you're missing out zero sugar. It's flaky, like the crust that you'd find on an Apple turnover, it's delicious, uh, 20 grams of high leucine, high quality protein, not overloaded with fiber, like so many healthy snacks are today. It's just as a period snack. And I'll tell you, you better buy a couple extra boxes.

[00:01:27] Of course, it's fine. Them. They're going to want to eat them and don't tell them that they're good for them. Go to sh SHR network.biz/legendary. Use the code SHR 10 to save 10% off all of your products from legendary foods. Now we'll bring my guest on and I'll just get some banner things set up here. Uh, Dr.

[00:01:50] Velez, uh, is with the university in Canada. Tell, talk about your university. First of all, let's plug, uh, the institution first.

[00:02:00] [00:02:00] Professor Argel Aguilar-Valles, PhD: [00:02:00] Hi, Carl, thank you very much for this opportunity. Uh, I'm in Ottawa and university school, uh, Carlton Carlton university, and, uh, it's a, uh, research intensive, comprehensive university here in the Capitol.

[00:02:15] Okay.

[00:02:16] Carl Lanore: [00:02:16] Um, so before we even talk about ketamine and what research there has been before this research. Uh, we've already getting questions from listeners. Let's see if I can get one up here. Well, for some reason it's not showing up, but I'll read it from the internet. Um, it's from Josh Bruner. He says, what does ketamine effect?

[00:02:36] Does it affect serotonin or something else? What, what is ketamine? Actually, it, it it's a, it wasn't an anesthesia or something like that at one time.

[00:02:45] Professor Argel Aguilar-Valles, PhD: [00:02:45] Yes, it is still youth as an anesthetic. So it was, uh, it was, uh, created in the lab in the 1950s. And then in the 1970s, we started to use as an anesthetic for, uh, for general surgery.

[00:02:58] And [00:03:00] even currently it's one of the anesthetics that supply for children when they go into pediatric surgeries. So it's still uses stock. But, uh, after it discovery was also the realization that ketamine causes, this can cause these hallucination effects and dissociative effects this sort of like a detachment from reality sensations that can be appealing for particularly for some party goers.

[00:03:25] So it, we started to use this, a recreational drug, uh, and, uh, that's, that's the main reason why it was, um, It was classified as a controlled substance in practically everywhere in the world. And, uh, it was much later, uh, in the, uh, in the nineties when the potential for treating depression was, uh,

[00:03:45] Carl Lanore: [00:03:45] was discovered.

[00:03:47] I mean, anything that would make you detach sounds like it could also be beneficial, uh, to be administered immediately after. A traumatic event because we know that benzodiazepines are used periodically when someone [00:04:00] undergoes a, a horrific event and it helps make you more distant from the memory over time.

[00:04:05] And you, you don't have the traumatic effects. Long-term do they use ketamine that way as well?

[00:04:11] Professor Argel Aguilar-Valles, PhD: [00:04:11] No, it hasn't been used that it's been, it's been tested to as a potential treatment for PTSD or post-traumatic stress disorder. And it actually has these very important effect that it reduces suicidal ideation very rapidly and very effectively.

[00:04:29] So it does that in PTSD patients, as well as major depressive disorder patients, but it's usually administer after, uh, not immediately after the, uh, traumatic event. It's actually the only, uh, approved, uh, by the FDA and other health agencies around the world. The only approved use that we have is for what they call treatment resistant depression.

[00:04:51] So when you've been diagnosed with major depressive disorder, uh, and you've been through a couple of rounds of, uh, typical [00:05:00] antidepressants SSRI, uh, the serotonin re-uptake inhibitors, uh, and you don't improve your state. And usually these. These trials and in a patient will go on for six months just to see if the patient responds or not.

[00:05:14] And, uh, after going to a couple of these medications, if you don't, you haven't responding, you might be allegeable for, for Academy and treatment. And it has to be a minister in a, in a clinical setting because they need to, you know, monitor that you don't have any excessive, uh, Uh, uh, the, the sausage or hollow synergenic responses that can put you in, in some sort of danger.

[00:05:35] So it's really in these specific circumstances that is being used, but there are several clinical trials indicating that it's effective for, uh, for, you know, for PTSD and other psychiatric disorders. The problem is that because of the, no, no, no.

[00:05:51] Carl Lanore: [00:05:51] Goku. You may be going to mention what I was going to ask that.

[00:05:53] Professor Argel Aguilar-Valles, PhD: [00:05:53] Okay. No, that the problem, uh, it's not, it's not recommended for, you know, when you're first [00:06:00] diagnosed with an ad with a depressive episode is not the first, uh, a first-line medication. It, uh, the, your physician or your therapies will go usually first with an SSRI. And if that works, then you will stick to that.

[00:06:13] It's up to this point because this potential of abuse, it's really only recommended to those cases where there's really no, nothing else has worked so far. So I want to talk

[00:06:22] Carl Lanore: [00:06:22] about the abuse first. So, so first of all, Um, it's a very, it's widely used in the penitentiaries and prison systems because the prisoners want to escape being prisoners.

[00:06:35] And there's a phenomenon. When you take an effective dose of ketamine, you go into a K hole, they call it and the K hole is almost a catatonic state. Is it not? It's like you, you become like a zombie, right? Hmm. Yeah,

[00:06:49] Professor Argel Aguilar-Valles, PhD: [00:06:49] that's correct. Uh, you know, it's, it's sort of like, uh, You perhaps can see it as a preamble to anesthesia, right?

[00:06:54] Anesthesia is putting you in this deep state sleep is not analogous to any of our [00:07:00] normal or typical sleep States. Uh, but it it's an anesthetic state. So when you are abusing it, you can reach certain, you know, like some sort of in-between state or something close to anesthesia that, uh, yeah, indeed it helps you awake.

[00:07:14] Uh, the reality for the moment. Uh, it is unclear where, well, the doses that are used for depression are what we call super vanish sub anesthetic. So they're really much lower than it would normally take to induce these, uh, these, you know, these dissociative or these hollow synergenic States. So, uh, the doses are considered in that regard safer.

[00:07:38] Because they, you don't reach that obviously, but if you, you know, if you give it, uh, if you will prescribe it for people to take at home, there's always a risk of abuse. Uh, so that's why there's still a lot of regulations in

[00:07:49] Carl Lanore: [00:07:49] place. Yeah. Is it, is it habit for me? Is that why he like, so I, I know people, I know people who have used ketamine in.

[00:08:00] [00:08:00] Uh, clinic setting clinical settings for depression, and they all say the same thing. You feel horrible. It's a, it's a, it's a weird feeling. They can't really explain it, but they don't feel, it's not like you feel, um, salvation or, or re or relax or yeah, they, they, they make it sound like it's a very uncomfortable.

[00:08:21] Hi, if you will. So it does. How do they, why would someone develop a, uh, device? It's a stupid question because I did a lot of drugs when I was a kid that didn't make me feel cool. I just answered my own question.

[00:08:36] Professor Argel Aguilar-Valles, PhD: [00:08:36] It's true. I mean, you know, when you are, uh, you know, your first experience with, uh, a lot of the drugs of abuse, it could be either, uh, you know, very.

[00:08:47] Good. And then you want to pursue that, or it could be really bad because you're naive to it and you're not really know what to expect. And a lot of these house intergenic trucks, uh, not only, uh, uh, [00:09:00] um, ketamine, but I'm thinking, you know, more typical, uh, hallucinogenics like LSD and psilocybin. Yeah. The reaction, the even, even, you know, even a Canab is the reaction that you have to, it can depend a lot on the context.

[00:09:14] So if you are in a context that for some reason next you feel stress, uh, you reaction can be quite bad, but if you are in a context that can be safe. Uh, uh, the reaction can be different. Um, and yeah, so, you know, there's also sort of all sorts of people out there and all sorts of experiences. So, uh, for some people just taking certain doses may cost something more, uh, you know, more pleasant or more, even if it's not pleasant, it might be just interesting or, or, you know, If it's helping you awake something that is really, uh, haunting you.

[00:09:48] I mean, uh,

[00:09:51] Carl Lanore: [00:09:51] people will go for that. Yeah. That becomes the reward. So, uh, and, and, and lastly, about ketamine, before we talk about your research, cause I [00:10:00] have a feeling that what your research has discovered will create more effective dosing. Uh, then this kind of, uh, we'll try this. We'll try that. So, um, are there, are there unwanted effects of ketamine, a short or long-term.

[00:10:15] Professor Argel Aguilar-Valles, PhD: [00:10:15] Well, it has apart from the, uh, these, uh, these dissociative States, it has, as we discussed the, uh, the potential of abuse, uh that's, that's another effect that is not desirable. It can also interfere with memory formation because it's a its primary target. It's one of these neurotransmitter receptors, uh, that, uh, are very important for the formation of memories.

[00:10:43] So acutely, uh, when you administer ketamine, it can have these, uh, these, uh, effect where, uh, Uh, interferes with whatever is happening. Maybe you won't be able to remember it. Some sort of like a short term, um, honesty, uh, how Misha.

[00:10:59] Carl Lanore: [00:10:59] Yeah. [00:11:00] Yeah.

[00:11:01] Professor Argel Aguilar-Valles, PhD: [00:11:01] So, uh, that's why it's, it's not, uh, it's, it's, uh, it's an, it's a strong, it's a powerful treatment, but it has, uh, you know, many psychiatry is still considering some sort of dirty drug.

[00:11:14] Like something that, yeah, we might use it in case we don't have any more options. But if we can find a better alternative that does the same without all of these side effects, that will be the, uh, that will be, that will be great.

[00:11:26] Carl Lanore: [00:11:26] We can go for that. Talk about your research. So you, you, you, your group set out to better understand how and why ketamine works, and this could actually unlock better dosing and better protocols.

[00:11:40] So talk about, talk about your study. Uh, what, what was the desired end point of your study? First of all, what were you trying to find out?

[00:11:48] Professor Argel Aguilar-Valles, PhD: [00:11:48] So, uh, you know, from a, a more, uh, like pure research perspective, we want to understand how it works and obviously the more, uh, application or, um, [00:12:00] uh, recent to pursue this is because understanding how some of these, uh, new treatments for something like depression, uh, work.

[00:12:09] Then you can, as you mentioned, you can envision, or you can try to decide something that might be safe, but I may be devoided of all of these on the terrible side effects of many of these, uh, well, ketamine has on people. So the idea is what is to identify what's the requirement in the brain in terms of, of what cells, what molecules are really essential.

[00:12:32] For the antidepressant effect. If we can pinpoint all of these, these basic, uh, mechanisms, these molecules, then maybe we can try to, uh, use that information. So, yeah, as you said, either use a weather dosage that stimulates these antidepressant responses without triggering the other undesirable effects, or you send an alternative, a similar molecule that has more specific [00:13:00] effects that can, I mean, those.

[00:13:01] So that was sort of like the, the big idea behind, uh, motivating us to do that.

[00:13:07] Carl Lanore: [00:13:07] Okay. So how was your study design?

[00:13:11] Professor Argel Aguilar-Valles, PhD: [00:13:11] So we, we work, we are basic research lab. That means we don't work directly with patients. We work, uh, in animal models. So we use animal models. In this particular case, we use mice. They are a great tool for research because we can do, uh, genetic manipulations on them in order to, you know, prove that something that, uh, that's something that you suspect is involved in the effect of ketamine it's involved in it.

[00:13:39] So you can take it out. Like this is what we call a mutant  it sounds like very  and very, uh, Perhaps scary, but they will. What it just means is that you go in and take a little bit of their DNA out and basically they are no longer, um, expressing or, um, um, you know, producing certain elements in the, [00:14:00] uh, in their body.

[00:14:01] So when you remove some of these, uh, genes, uh, They may not have a big effect in the miles and miles can, you know, be born, grow, reproduce, and die almost normally. So, uh, in this case, we were using a certain type of mice that have a protein missing. A I can explain a little bit more what it is, what this protein is, but that's sort of the model.

[00:14:26] And then how do you measure depression in a mouse? That's the

[00:14:30] Carl Lanore: [00:14:30] million dollar question, right? I bet I can get right. They, they don't move. They don't want to have sex. They go sit in the corner and they, they, they, they just stay there. That's it.

[00:14:40] Professor Argel Aguilar-Valles, PhD: [00:14:40] Exactly. A lot of, uh, what you will call a passive responses to any stimulus that you give them.

[00:14:47] So indeed, um, uh, and sort of like an easier way to, um, to elicit these things will be for example, to stress semis, you stress them for several weeks in a row, and then [00:15:00] all your mice or most of your minds will become these, this really, uh, You know, fragile looking, uh, passive, uh, um, uh, animals, because basically you are, uh, you are, uh, Trying to mimic what happens to many people.

[00:15:13] Like they face a lot of chronic stress. Chronic stress is really a major factor in developing his disorder. So, yeah, well, we mentioned at the end is several, uh, behaviors of the mouse. You put them in challenging circumstances. Like, uh, there's a couple of tests where you, for example, put them to swim. My certain natural swimmers.

[00:15:32] They, they have no problem swimming, even if they never encountered water in their lives. So we put them where they will swim. But at the press miles, we'll swim less in a, in a, in a confined area, in a confined container that they know they, they realize they can't escape and, uh, uh, uh, chronically stress mouse will just be more passive and just sort of float there.

[00:15:53] And you, if you are administered on ketamine or ordered on to the presence, you will then trigger more active behaviors. The [00:16:00] mouse will start again. Sniffing around trying, moving around, trying to find the escape route. So this is some of the, uh, uh, uh, behavioral tests that we use in broadens to sort of screen for potential antidepressants and also to see what, what, what, um, you know, what components of the animal's brain would be important for the responses.

[00:16:19] And then, um, so we knew before that there was a protein called, um,  it's a, it's an acronym that basically means mammalian target of

[00:16:32] Carl Lanore: [00:16:32] rapamycin. We talk a lot about Mtwara on the show because well, all about all, about muscle, but also when you sh you know, we, we talk about senescent cells and how M Tor affects senescent cells.

[00:16:45] And, and so w my audience is very well versed in an tour. Oh, fantastic.

[00:16:50] Professor Argel Aguilar-Valles, PhD: [00:16:50] So, uh, so mTOR is, as you mentioned, it's actually involved in a lot of metabolic responses. So it's, it's, it's activated by, uh, several [00:17:00] stimulators that has to do with, you know, uh, uh, energy, uh, Uh, management in the cell, in a cell. So in the brain, it also happens.

[00:17:09] And, uh, one of, uh, but as you may know, and you audience may know, and to regulate a lot of, uh, of functions in a cell or in an animal. So you can, uh, it's more than a dose and different, uh, Functions, if you will. And the molecular targets, the different proteins that are affected by MTRR, you can, there there's many of them there's probably close to a hundred, if not more, obviously.

[00:17:33] Um, it was the most traded a while ago by the group of Ron Dunham in, at Yale university. That if you block mTOR using rapamycin, which is, this is this blocker of mTOR, uh, it basically kills the function of mTOR, so to speak, um, Then you wouldn't be able to, uh, elicit this antidepressant effects of ketamine.

[00:17:55] So what they demonstrated was that mTOR in the brain, it was required for [00:18:00] the role of ketamine. Now what we in the lab, I was, I was working as a research associate with, uh, Dr. Nan Sonnenberg and McGill university. When we started this, uh, this study, um, uh, here also in Canada. And he's been working with one of them, uh, one of the targets of mTOR, one that controls a process called protein synthesis.

[00:18:21] So all the factory in the brain that produces proteins that are important for every function of a new, even in the most sense, even

[00:18:28] Carl Lanore: [00:18:28] in the muscles. Yeah. Yeah,

[00:18:30] Professor Argel Aguilar-Valles, PhD: [00:18:30] exactly. So it's, it's everywhere in the body. And in the brain, it has, it's really important for, for example, again, for formation of memory. So every time you form a new memory, these, this pathway is activated the mTOR and the proteins that are important for that are called 40 VPs.

[00:18:46] Again, it's another acronym. It just means, uh, 40, yeah, 40 binding protein. And , it's, it's something that controls, uh, protein synthesis in the brain. So these 40 VPs are, are blockers of proteins into disease. And [00:19:00] when mTOR activates them, Uh, you remove the brake and you can, uh, have pertains indices. Go ahead.

[00:19:07] So we suspected, okay. This is a really key, uh, effector of Amtrak, a really key factor that is controlled by mTOR, and that controls are really important function for learning and memory in, for induction of, of something that we call synaptic plasticity, which is the ability of the brain to sort of, uh, change the connections between neurons when it's needed.

[00:19:29] For example, when you learn something new, But, uh, it also seems to be important for your mood regulation. So if you're chronically stressed and you're feeling the press, most likely the mTOR activation it's decreased. So what ketamine, while we suspected that ketamine was doing is increasing the activation of mTOR and increasing protein synthesis and allow them, all of these plasticity events that occur normally in the brain.

[00:19:53] Right, exactly. Right. Right. So then how do we prove this? Well, we take one of these new termites, their [00:20:00] miser lacked the four MVP. So may we remove the four MVPs from the brain and we treat them in ketamine.

[00:20:05] Carl Lanore: [00:20:05] Well, I want to ask you a question. So, so these, these transgenic mice. They have no for ADP from birth or do you then once they're born, you administer a drug that, that turns the for ADP off.

[00:20:19] Professor Argel Aguilar-Valles, PhD: [00:20:19] So we had two, two different actually several version of solve the mute, and one that was completely from birth, not having the 40 BPS, uh, and others that were, uh, specifically knocked out, uh, from, uh, Specific populations of neurons. So we have different types of neurons in the brain. It's not only one general type, there's many, many different, but you can classify them roughly as excite that there are neurons neurons that activate our neurons or inhibitor in neurons, which are neurons that inhibit our neurons.

[00:20:50] So we targeted these two major populations. So we, we remove it from either of these populations and we look for the responses to ketamine. And we [00:21:00] always compare to what we call a wild type animal, an animal that has a 40 VPs intact. And that's the response in the way that we expect, uh, to respond to ketamine, which is increasing all of these active behavioral responses and increasing all of these synaptic plasticity events in the brain.

[00:21:16] So those were our major endpoints, the behavior and the synaptic events, plasticity events in the brain. So when we removed the 40 BPS, uh, as we had the, um, suspected, uh, the mice were completely resistant to ketamine. They no longer were responding. And that is strongly indicated that this protein was required.

[00:21:41] Now, as I mentioned, uh, what's important. It's where this is happening. The brain has many different cell types. I just mentioned, for example, neurons can be roughly classified into two types. So that's why we decided to look at where, where is this event happening, which cells that is happening. And maybe we can have a, you know, this will help us to [00:22:00] define better how ketamine is working.

[00:22:03] And, uh, we remove them from either excitatory or inhibitory neurons and to our surprise, uh, the major effect happened in healing during your own. Why was the surprising because inhibitor in euros are roughly, uh, only about account for only about 10% of the neurons in the brain, roughly. So it's a minority of the neurons, but their role in controlling the way our brain Brock is break it.

[00:22:29] Sorry, works. It's fundamental. So, if you have deficits in, in, in our province with some of your inhibitors in euros, you can have things major things like epilepsy, where the rest of the neurons that are excitatory, they don't have a co uh, sort of like a checkpoint by these inhibitor neurons and things go, you know, go out of control and you can have these, these, uh, these seizure events.

[00:22:52] That's an extreme case, obviously, but, uh, uh, um, when we knocked out the, uh, the 40 VPs from these [00:23:00] inhibitory neurons, Well, we basically, uh, ketamine was no longer able to work. So it really indicated that these protein in this neurons, um, uh, is, it was sort of like, uh, one of the essential components that you need in order to have a, an antidepressant effect by ketamine.

[00:23:19] And this is one of the major findings of the

[00:23:21] Carl Lanore: [00:23:21] study. This is so fascinating because you have traversed so many areas of interest of this show. Um, that, you know, that the fact that by, so I want to make sure I understand well things real quick. Yeah. So suppression of M Tor can affect memory formation. Yeah.

[00:23:40] Okay. I take, I take six milligrams of rap myosin once a week to, to rid my body of senescent cells, but the Dr. . The physician, who's done 30 years of research on senescent cells and, and mTOR and, and, and, and, uh, rap myosin. I [00:24:00] texted him one day about a year and a half ago. You know, I'm a, I'm a, I'm a, somebody who likes to build muscle.

[00:24:06] So I'm 230 pounds. I eat about 300 grams of protein, a day, high leucine protein, which turns mTOR on. And I said, has anyone done any research on taking rapamycin, but eating high quality protein? And what is the net effect? I have a funny feeling that M Tor is not being as suppressed in me as it is to a person who only eat 60 grams protein a day.

[00:24:31] But that's another discussion. Um, yeah. The other thing that I thought was interesting was the, uh, when you invoke the epilepsy discussion, We know that the ketogenic diet, which increases ketones, but suppresses the, by the brain's need for glucose can help, uh, suppress epileptic events, which leads me to question what nutritional roles.

[00:24:59] We see [00:25:00] in people with depression, because if you're not getting enough protein and you're not creating enough M tour, and you're eating a lot of glucose, uh, producing foods, and we know that there is now something called type three diabetes, where it's exclusively that insulin resistance of the brain, do these people also suffer from depression at a higher rate.

[00:25:22] Professor Argel Aguilar-Valles, PhD: [00:25:22] So, yeah. Yeah. A couple of things there, uh, first regarding your, uh, you know, rapamycin intake. It's always on the dose, right? Because you're taking it through your, uh, you know, to your digestive system. It has to be absorbed. So actually rapamycin can have a lot of effects in the gut itself and, and, uh, whether it reaches the brain, depending on how much you take that's, that's debatable, it, it might not add the concentration that you're taking.

[00:25:50] It might not be enough to reach the brain and maybe break that broken down before. And you don't have, uh, like, uh, an effect, a [00:26:00] direct effect on the brain. You can affect other things, obviously not affect, but you know, the tissue. Exactly. And now, uh, regarding the, uh, yes, there is a lot of links with, uh, obesity and, um, poor diet, like particularly, uh, you know, high carbohydrate, high, high, fat diets, uh, combined, um, uh, in, in eliciting depression.

[00:26:24] So, uh, there is a big link there now. Uh, one funny, not funny, but one thing that happens with, uh, depressed people is that good major depression disorder, uh, diagnosed people is that, uh, you can have both extremes people with, uh, increased appetite and increased body weight. But you can also have population of people that has decreased appetite identity, Chris' body weight, and all extremes are being associated with depression.

[00:26:52] This is where, uh, the, uh, the confusion comes and, and, and actually just indicate that what we call major [00:27:00] depressive disorder is probably a collection of different disorders that we lump together because they resemble somehow, but they may actually be different. And the cost is for each individual case may be different.

[00:27:12] And this is, uh, you know, there, the discovery of ketamine and its effect. It just emphasizes that different people respond differently to, to, uh, to treatments and, and that we should be reconsidering these more personalized approach when treating somebody with a disorder. So all our, our, our definitions are on, on all of these psychiatric disorders need to be refined to better reflect the reality, which is.

[00:27:37] That, uh, there is a great diversity of people out there that are all lumped together in the same diagnostic category, but yes, indeed like a poor diet, uh, um, Uh, it's, it's associated with increased, uh, depressed mood and it can be a risk factor for developing major depressive disorder.

[00:27:56] Carl Lanore: [00:27:56] I want, I want to take our first commercial break.

[00:27:58] Uh, I've got so many [00:28:00] questions now. It's just amazing. I want to talk about inflammation. I want to talk about the gut microbiome. You know, it's interesting because I'm one of those people that when I was young and I would get depressed, a girlfriend would break up with me. I would lose my appetite and I know other people who, when they get depressed, all they want to do is eat.

[00:28:16] So that's a fascinating. Dichotomy there that it's people are still depressed, but the it's there's gotta be, um, I don't know. It's just very, very intriguing to me. Very intriguing to me. I was going to take a quick commercial break. We've got lots more to discuss, stay tuned. You're watching and listening to superhuman radio.

[00:28:37] Hey, welcome back. Those of you. Who've been fans of. Wow. What happened to my camera? Look, my fingers are invisible. Those of you who've been fans of the show for a long time. Know that I am not a fan. Of the scale. I've complained about scales a lot. I say they really don't give you any information. You don't know.

[00:28:55] You can take two people and put them on a scale. They both work weigh 200 pounds, but one [00:29:00] person is very, very obese and has very little muscle. And the other person has a lot of muscle and is very, very lean, still 200 pounds. But there's a new scale that I'm crazy about. I've shared with you. If you're following me on Facebook, that the past couple of years have been.

[00:29:13] Pretty slow slide downhill, uh, in my health and training because of my two surgeries, uh, in 2019, well, I've made 2021 the year for me to get back to my all time, physical health and strength. And one of the things I've started using is something called the Darra scale and it's made by fit track. The reason I'm using this scale is because it tells you so much more than just your body weight, just the effects of gravity on your body.

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[00:30:41] Don't miss out on this. This is really, this is the first scale that I really like, because it gives you so much more information than just your body weight. Check it out. All right now, back to the discussion at hand. Give me a second here and let me bring back my guests. [00:31:00] We're talking about ketamine.

[00:31:03] We're talking about how it can be used to treat major depressive disorder. I'm going to adjust my camera as we talk. So, uh, one of the things that I wanted to ask was I've heard people say that when they use ketamine for major depressive disorder, it wears off. After a while there the beneficial effects wear off.

[00:31:22] Would your research help us understand how to make it last longer?

[00:31:30] Professor Argel Aguilar-Valles, PhD: [00:31:30] Uh, not directly, not yet, but that's where we think we're heading with this. Uh, um, the, yes, you're correct. The, uh, initially, uh, the, uh, the treatment was a single injection, a single intravenous injection for the mean, and people saw effects for about a week, which is remarkable because for example, SSRI is you have to take for, uh, several weeks or even months to, uh, to have, uh, I surf like a reach, a peak effect.

[00:31:57] So ketamine was talking really fast and [00:32:00] one single struggle was lasting. So what actually people are trying now in the clinic is several doses of ketamine. Uh, the, the, the version that's approved for a treatment resistant depression is actually intra a nasal spray. Uh, uh, so the, the it's it's much easier to administer than, than having to go intravenous, uh, but still, um, Uh, it's the same sort of like a effect that is for a few days.

[00:32:25] And then it sort of like wears off. Some people, uh, will remain sort of like in a better state for a longer time, but you, you need some sort of like a. Booster or reinforcement eventually. And what people have tried in the clinic is trying several doses that seems to still work. And again, we're talking about doses that are very low compared to what you will need to take in order to have on of these, uh, you know, more, uh, uh, vivid Alison nations or, or, um, Dissociative state.

[00:32:55] So these are doses that are, are much lower than that. [00:33:00] So, but what we discovered is that these proteins were not only important for, for the initial effect, that the rapid effect that you see. Yeah. You observe within minutes, we have served the same in mice. As in humans, within minutes, you see a change in their behavior.

[00:33:15] And it lasts about the same about a week and this protein is important for both effects. So it's not only relevant for the rapid effects, but also for the sustained effects. So what, what we would need to do now is to identify. What, um, what's the, uh, regulate in by regulator? I mean, uh, these four VPs, they control the, uh, the levels of, uh, many other proteins.

[00:33:44] Like there, they control proteins seem to seize, but it's not a general effect. It's not protein CTCs, just like of every single protein that a neuron expresses. Right. It's a specific population and we haven't identified that population. Uh, so that's [00:34:00] where we need to, uh, to investigate what is this population of proteins, this specific group of proteins that is, uh, that is controlled by the 40 VPs that is necessary for the ketamine.

[00:34:11] And I think that will be key to be able to expand, um, for example, the effects of ketamine, something that recently was reported, however, in a clinical study, in a study with people with depression, Was that actually, uh, it was, it was somehow unexpected. Uh, so the idea of the study was to test with a rock.

[00:34:31] Am I seeing will block the effect of ketamine in the same in humus, in the same way that it happened in mice. And, um, these was in a group in, um, our university of Baltimore or no, sorry. University of Maryland in Baltimore. And they, so they, they gave, uh, rapamycin in, uh, actually they just dissolve it in orange juice.

[00:34:51] If I'm wrong, mistaken. And they gave it to people. Surprisingly, the acute effects didn't change. Like the effect of ketamine was still there. [00:35:00] And then when they looked at those people a week later, what they saw is the number of people that were still showing signs of improvement. What's much larger in the group that received the rapamycin.

[00:35:13] So contrary to what happened in mice, which we still don't understand how, why, why these, these massive difference, uh, rapamycin seems to be able to extend the effect

[00:35:24] Carl Lanore: [00:35:24] of, of Canada. I mean, I have, I have, I have, I ha I have, I have an idea. I want to share with you. Yes. So, um, rapid myosin, uh, changes the inflammatory landscape of tissue.

[00:35:38] That's right. And there's good research. I did a show probably six years ago, maybe seven years ago that linked major depressive disorder and chronic inflammation hand-in-hand that inflammation gets to the brain, not everybody's brain. Some people's blood brain barrier seems it's successful, but once the blood-brain barrier barrier is breachable, the inflammation gets to the [00:36:00] brain and the inflammation is what's causing the, and we know that.

[00:36:03] Reduction of senescent cells reduces cytokines and chemo kinds and all that sort of stuff. So maybe working better because at this wild, while the drug is doing its job, the inflammation landscape is dropping simultaneously.

[00:36:19] Professor Argel Aguilar-Valles, PhD: [00:36:19] That's you are you, you are correct. That, that was actually the first gap that many people suggested when they saw that study.

[00:36:25] And then the author authors. Unfortunately, they weren't able to measure the cytokine levels in these patients, which is unfortunate. But that is indeed a possibility that the periphery, when you administer rapamycin, is having us to set effects on, on your body systemic without necessarily reaching the brain because it's broken down before that happens.

[00:36:45] So, uh, it can reduce all of these inflammatory signals. That actually is one of the fields. Things that it seems to be more widely, uh, you know, characterize the major depressive people. We, we, we talk about [00:37:00] how many, some people eat more, some people less, some people slip, sleep more, some people sleep less and so on and so forth.

[00:37:06] But I'll a great amount of people. We've mentioned depressive disorder has these elevated cytokines and elevated inflammatory markers and actually chronic inflammatory, uh, diseases are linked to a higher risk of developing ah, uh, depression and so on and so forth. So yes, it is possible that they can have this effect there and it can extend by that means the, or facilitate somehow the effect of ketamine, the effect that ketamine is having in the brain.

[00:37:35] Carl Lanore: [00:37:35] So, so, uh, rapid myosin has a three-day life in the body. It's a pretty long lasting drug. How long does ketamine last? Once it sits administered,

[00:37:45] Professor Argel Aguilar-Valles, PhD: [00:37:45] it's a few hours. Like you mesh it. Yeah. You try to measure ketamine levels the next day in the blog, or even in, in, when in mice you can go and measure in the brain.

[00:37:56] Next day is already gone. So the peak is, uh, [00:38:00] two or three hours after injection, even shorter, perhaps the peak, I think it's fast. It's like half an hour, an hour after the injection, uh, in the blood and in the brain. And it starts to be broken down into, uh, into different metabolites. And actually some of the metabolites have been shown to also have onto the person effects.

[00:38:19] So, uh, and, uh, some of the metabolize last, a bit longer in the blot. That end in the brain that ketamine itself. So some of the longer lasting effects actually are thought to be, or have been proposed to be mediated by these, um, These metabolite called hydroxynorketamine or H and K for short. And we also tested that.

[00:38:40] We also decided, okay, is this H and K, which have been shown to be, uh, to have these antidepressant effects in mice? Does it also depend on the, on the proteins in disease? And we found them, yes. So both. Both, uh, both drugs are actually, uh, triggering the same type of effect in the brain, at least in terms of [00:39:00] protein synthesis and being mediated by the 40 week piece so that there was another exciting finding that, that we have.

[00:39:06] Carl Lanore: [00:39:06] Okay. So here's a question. So is, is ketamine processed through the liver, like many other drugs through the P four 50 cytochrome enzyme cascade? Yes. Okay. Okay. So what about methylating ketamine so that the liver has a harder time breaking it down and then when you methylated drug, quite often, it's metabolites and methylated and they last longer as well.

[00:39:31] Professor Argel Aguilar-Valles, PhD: [00:39:31] That's a, that's an interesting possibility. They, I'm not sure why it hasn't been done to be honest, but, uh, perhaps it's there, the, the, the, you know, the potential risk that you may also extend, uh, on, on the terrible effects. So maybe, um, maybe methylating the, uh, uh, well, if the, if the metabolite is proven to, to be effective in humans as well, which is something that we need, uh, it needs to be done.

[00:39:57] Uh, it's been shown in animal models, but not [00:40:00] in humans, as far as I know that will be the first step and maybe, uh, working on the stability of that, of that, of that animal, uh, metabolite will be, um, an important improvement. And the reason why I'm emphasizing in the metabolite is at least the. Data in animal models suggest that it doesn't have the, uh, um, the, uh, uh, addictive effects and potentially doesn't have either the Holocene as a housing eugenic effects because it doesn't block as effectively.

[00:40:29] These receptors that mediate the NMPA receptor, which is. So blockage, which is mediating.

[00:40:36] Carl Lanore: [00:40:36] It sounds like to me that you need to be making the metabolite a separate drug by itself. Methylating it? So it stays around longer and administering it through intra-nasal so that it gets to the brain right away.

[00:40:48] Professor Argel Aguilar-Valles, PhD: [00:40:48] Hmm. Yeah. Yeah. That, that's an exciting possibility that, that, and, and then what, what we shown is that basically in terms of proteins interest, they're doing pretty similar things. They're both, uh, triggering [00:41:00] and depend on the presence of 40 BP. So it might be that just working on the metabolite may be a safer way to go.

[00:41:07] But yeah, I have to say that we still need to show that it, it, it does have an antidepressant effect on the press. People, not only in my offer

[00:41:15] Carl Lanore: [00:41:15] now, what does the intro I'm rushing you to put before the next break? Does the intra-nasal administration of ketamine allow people to function? Like they can still keep their job, take it in the morning and go to work, or do they still have a period of time where they have to just kind of hang out and wait for the effects to kind of subside.

[00:41:35] They S they still

[00:41:35] Professor Argel Aguilar-Valles, PhD: [00:41:35] have to wait for the effects because there's, you know, different people react differently and you may have a, you know, someone that more specific people and, and, and, and start having some, maybe perhaps  or the social team responds that it needs to sort of wear off. And so you eat, it's always administered in a clinical setting and often with a, you know, a therapist present.

[00:41:57] And that is, and perhaps a nurse observing, uh, [00:42:00] the effect, but for potential

[00:42:01] Carl Lanore: [00:42:01] effects. I want to take our last commercial break. When we come back, we'll wrap up the interview. We're talking today with Dr. Ardell Aguilar Velez, and this is very fascinating. Uh, major depressive disorder is a big problem in the United States and around the world, it makes people unproductive.

[00:42:18] Uh, they become prisoners in their own bodies, so to speak, uh, and, and helping them free themselves from that. Self-induced prison is very, very important. Stay tuned. We'll be right back with more super human radio.

[00:42:36] Welcome back as a ghost in my computer. Every time I go to a break. Oh no, it didn't do it this time. It changes my camera. Um, we're talking today about ketamine for major depressive disorder. This research. Shows how ketamine works. This is fascinating research because this show, we love discussions about M tour, uh, am PK, uh, ketone [00:43:00] bodies, uh, inflammation, the microbiome.

[00:43:03] What role does the microbiome play do you think in, uh, in, in depression, obviously when we talk about inflammation, we're talking about the army of the immune system. When we talk about the army of the immune system, we're talking about the gut because 85% of the immune system resides in the gut. How many of these people that have major depressive disorder have horrible gut problems, too?

[00:43:28] Any idea?

[00:43:31] Professor Argel Aguilar-Valles, PhD: [00:43:31] I don't know the exact number, but it it's probably quite large. Uh, there is, there's quite a lot of evidence that, yeah, there's a lot of, uh, gut dysbiosis that is this alteration of the, a more healthy, uh, got microbiota, uh, in, in, in depressive disorder. And yeah, as you say it, all of these different bacteria, not only, uh, you know, control the way we are.

[00:43:57] On to, uh, two infections [00:44:00] or inflammations, but they also, uh, you know, say Cray secrete, psychoactive substances, substance, like metabolize of the bacteria that enter our bloodstream and then affect the way our brain works and, and, and, uh, are forums under. You know, stressful circumstances and so on and so forth.

[00:44:17] So it does have a major, a major role. Yeah. Yeah. Particularly in, in, you know, when you have people that, uh, uh, you know, one way to cope with stressful situations is usually go for a, you know, a bad diet, a high carbohydrate diet that will change, that will contribute to this. Uh, you know, it's a, it's a vicious circle that it's.

[00:44:38] It starts with something that maybe, uh, it seems that it's helping you to cope with eventually it might make things worse because he's altering, uh, your, your, your, uh, your body physiology and the way your body responds. Um,

[00:44:50] yeah.

[00:44:51] Carl Lanore: [00:44:51] I, I I'm, I'm convinced that boutique coffee. And we could thank, and we get thanked my Italian and Latin [00:45:00] ancestors for this because we love dark coffee.

[00:45:03] We love that black coffee, you know, uh, but I'm convinced 79% of Americans drink coffee every day. Over 70% of Americans complain about having digestive issues. Autoimmune disorders are on the rise diseases like Parkinson's disease and ALS and multiple sclerosis are now being tied to an autoimmunity.

[00:45:27] You know, when you, when you put all these things together, depression tied to inflammation. Inflammation starts from the gut because the inflammatory cytokine. So I recently given up coffee for good. I'll never drink another coffee. I'm 62 years old. I've drank coffee most of my life, but it's no good for me.

[00:45:45] It hurt. It hurts me. It hurts me, but I overlook the pain because every time, the morning when I drive down highway 42, my favorite Starbucks is there. And this is what I, now, this is what goes through my mind. Now I drive by, I look at [00:46:00] Starbucks. My brain tells my microbes. There's coffee. My, my microbes go feed me, feed me, feed me.

[00:46:05] They create chemicals that tell my body, why do I want coffee so bad? I don't it's because my gut is telling me my brain feed us, feed us. So now I go in my head F you die. And I drive by, I keep on going, because I'm convinced that coffee is causing problems in the population today, you know? My mother and father drank coffee, they drank four ounces of coffee and you could see through it.

[00:46:32] Today, the coffee is so dark. The turbidity of the it's like a liquor store and all of that stuff. It's like all those particles suspended in that coffee. And then what do people do? They drink it on an empty stomach. It erodes the mucosal barrier. It starts to cause erosion in the gut. And I'm going to tell you right now, 50 years from now, they're going to find out that coffee is destroying the guts and the guts is destroying our bodies.

[00:47:00] [00:47:00] Professor Argel Aguilar-Valles, PhD: [00:47:00] Yeah, no, it's yeah, you're right. Like, you know, as with everything, uh, the poison is on the dose. So the fact that is, is so you know, so, uh, taking so much all the time and, you know, as you said, you know, like past generations will take a coffee, but it was a cup, the size right. Where it was now, we take like,

[00:47:24] Carl Lanore: [00:47:24] Yeah, 20 ounces. It's huge. And it's,

[00:47:27] Professor Argel Aguilar-Valles, PhD: [00:47:27] as you said in, you know, mass production of anything, it, you know, it has risked mass production of coffee  and stuff like that. So you're consuming all of those things and it's, you know, as you said, it's not once in a while. It's every day, several times a day. So it's bound to have some effects and I will add to that, like, if I will be.

[00:47:49] Perhaps more. I dunno. Yeah. Coffee in excess is not great for sure. I, that, that, but also like a lot of people will take it with sugar, like, and just the amount of [00:48:00] sugar that, that, that goes with coffee. It just like, you know, it's, it's started swearing again. That's uh, that also has like major effects on fees through you guys that we have everywhere,

[00:48:12] Carl Lanore: [00:48:12] sugar, sugar feeds the pathogenic microbes in the gut.

[00:48:15] If you want to kill them, you have to stop them. Okay. So there are currently ketamine clinics out there right now, treating people with major depressive disorder in the United States and Canada and around and around the world. So what do you hope those clinicians take away from this research study?

[00:48:31] You've just performed.

[00:48:35] Professor Argel Aguilar-Valles, PhD: [00:48:35] Well, I think at this point we are these, this particular project it's still in an early stage. So I would, I would really hope that in the next few months we'll be able to take it to the next level and really identify, as I mentioned before, those. Uh, those essential, uh, targets of the four EVP that are mediating, like what we [00:49:00] can call perhaps the ultimate targets of ketamine that are responsible and that then these, these can be used, uh, actually to design better therapies.

[00:49:09] What I will also like to see more and which again is not, it's not very often. And again, our research is not necessarily. Focus on that, but it's this better recognition that, uh, different types of depression needs to be treated differently. So there is an effort out there obviously to, uh, you know, identify these markers, for example, the inflammatory markers.

[00:49:36] So you go, you will go for a profiling, uh, ideally, and then, um, Uh, uh, see if you have your inflammatory markers highly elevated or not, because as you said, there's people that aren't with that. Uh, but that's not part of our, you know, offer diagnostic process for depression. It's usually based, I still on the, on the questionnaire that therapies or a [00:50:00] psychiatrist may administer to you, or even a general physician and say, okay, yeah, you fit the criteria for depression.

[00:50:06] Take your medication, didn't work taking other medication. So it's still a guessing process that actually hurts people because you have to wait for months to these things to work. So that's not ideal. And that's why, um, the idea of improving ketamine. And making it safer. Uh, and perhaps then using it as a first line of therapy, it will actually, uh, be an Oh, another major improvement in the way we treat depression and also identify because there's probably people out there that won't respond to ketamine, so that that's important to identify as well.

[00:50:39] And, and then maybe that's, uh, those people actually are not necessarily the same as the people, in terms of the disease characteristics. They're not the same as the people. That respond to get, I mean, so it, all of these work in recognizing what individual factors lead to a person to be depressed, you will be fundamental to really have a [00:51:00] effective therapies for most people for, for a great majority, uh, which is a problem these days that a lot of people are breeding, not responding to typical

[00:51:08] Carl Lanore: [00:51:08] anteaters.

[00:51:09] Adam  says, uh, uh, apparently ketamine is great. Great for M E slash CFS. I don't know what those, those acronyms are. Do you know cerebral? No.

[00:51:23] Professor Argel Aguilar-Valles, PhD: [00:51:23] Yeah, I see it there. I'm not sure what he means.

[00:51:25] Carl Lanore: [00:51:25] Yeah. Adam, could you spell that out please? Also he asked if it would be good for people with autoimmune disease and chronic inflammation.

[00:51:31] Is there any anti-inflammatory benefits of, of ketamine that you're, you're aware of?

[00:51:37] Professor Argel Aguilar-Valles, PhD: [00:51:37] Uh, we have seen in our, in our, our, our, our own models, when you have a chronic stress in, in mice, it's, uh, um, you will, um, have elevated cytokine levels. And we have observed that ketamine is able to bring those down so it can have certain anti-inflammatory effects.

[00:51:58] So what I would like to see [00:52:00] is more data in patients as well, because. That's, you know, patients are much more diverse than, than our laboratory mice that are, they're basically clones from each other. So they all respond fairly similarly. But when you again, when you're working with people, uh it's uh it's um, It's a different story, but yes, there is some evidence that it can have some anti-inflammatory, it's not its main thing, but it can cause inflammation to be reduced at a

[00:52:25] Carl Lanore: [00:52:25] certain level.

[00:52:27] So my next guest is Alex leaf. He's he's a friend and he just typed that, uh, M E CFS stands for myalgic and separate, except for my, uh, my artists, my, uh, my lightest. Chronic fatigue syndrome due to any evidence that people with chronic fatigue syndrome, chronic fatigue, fatigue syndrome would benefit from ketamine.

[00:52:50] Professor Argel Aguilar-Valles, PhD: [00:52:50] That's a good question. I'm not aware of any study in that regard. That just means it probably in my not been tried already. [00:53:00] Uh, people have been focused a lot on, for example, these, these are rapid, uh, uh, effect of ketamine on, for example, suicidal ideation. So that's been a lot of the focus, but I haven't seen like chronic fatigue or more, uh, These type of, of depression.

[00:53:17] I mean the chronic fatigue in itself, I haven't seen, but you know, it's also beneficial for people with depression that have similar symptoms to chronic fatigue syndrome. So it may work. It's probably, it probably has some beneficial effects, but it will need to be proven in a clinical study.

[00:53:35] Carl Lanore: [00:53:35] Dr. Angela Velez.

[00:53:37] I want to thank you for coming on the show today. It's been fascinating discussion. Thank you very much. Take care of yourself. You too. Bye. We're going to take one quick commercial break. And when we get back, we're going to be joined by Alex Lee. Who's. Uh, who's helping me behind the scenes here.

[00:53:52] Understand acronyms, uh, and we're going to have a fascinating discussion about the upcoming, uh, rush [00:54:00] or push, uh, to get pregnant women, to take the new COVID-19 vaccine. Uh, there is no evidence that it's dangerous. But there's also no evidence that it's safe. And last I checked. People always wanted to err, on the side of caution.

[00:54:15] Uh, so we're going to have a fascinating discussion. Stay tuned. You're watching and listening to super human radio. Bright back. There he is. He's in the background making me look smart. Hey, doing Alex. I'm

[00:54:30] Alex Leaf, MS, CISSN: [00:54:30] doing great.

[00:54:30] Carl Lanore: [00:54:30] How are you? Good. Good, good. Welcome back. So Alex leaf made an interesting post the other day, and Elisa said you have to have Alex on the show and it's actually, and I want to, I want to do something.

[00:54:44] I am not a virologist. I'm not a doctor. I'm a critical thinker. I consider myself fairly intelligent. Alex is probably a genius. Um, well you, you are. No, no, no, no. I'm being real. I'm not, I'm not, I'm not blowing smoke. You're a very highly intelligent individual. [00:55:00] Um, but also Alex is one of the more conservative people.

[00:55:03] I know Alex rarely says stuff. To get attention. Uh, he never says stuff that isn't founded in science and you made a post the other day. Um, you and your lovely bride, Brianna are wanting to have a baby. Uh, we are in the midst of COVID hysteria right now, a disease that if you're 75 years old or under your risk of dying from, uh, surviving is 99 point X.

[00:55:33] You can argue about the number after that. Um, so most of us, I feel like I don't need I'm 62 years old. Maybe I had it already. Maybe I didn't, I'm not worried about it. I'm not worried about vaccines or anything like that. Um, but invoking a vaccine on a pregnant woman is a completely different thing because it Chan transgenerational effects.

[00:55:55] And so on. Talk about the post that you made the other day.

[00:55:59] Alex Leaf, MS, CISSN: [00:55:59] Yeah. [00:56:00] So, um, I guess the posts really, I started just because, uh, certain news outlets, uh, the CDC specifically said that, you know, the vaccine should be offered to pregnant women and there's no reason for them to consult with their gynecologist or whoever their primary care physician is before they agreed to get it.

[00:56:20] And to me, it was just kind of like, wow, okay. Uh, the CDC followed it up by saying that, you know, experts said it's not an issue to get in pregnancy, and there's no reason to be concerned. And that, uh, I tweeted about that on Twitter, kind of what the tongue in cheek comment that, you know, um, expert opinion isn't as good as scientific data, unless it's the CDC saying so.

[00:56:46] Right. And it, it just, it. Led to me actually writing a post about it on Facebook. Uh, that essentially says, look, um, the fact of the matter is that we have three [00:57:00] clinical trials that have been done one by Pfizer, one by Moderna and one by AstraZeneca and every single one of those trials, as part of their exclusion criteria kicked out pregnant women, they said, we don't want you in our trial.

[00:57:13] And it's understandable why they would do that. The liability, right? Yeah. Um, So we don't have data on pregnant people like at all. And what that means is that forming any sort of conclusion about them, be it, you know, it's safe or it's dangerous falls under, what's called a fallacy of ignorance, which is when you form a conclusion when there's no evidence to be the basis of that conclusion.

[00:57:40] And so that was basically, my post was just a reminder to people that, Hey, You know, you have a right to get this vaccine if you want to get it. But you know, if you're like, if you are currently pregnant where you're intending on becoming pregnant soon, then you also have a right to not get the vaccine because of the unknown effects [00:58:00] it would have on both pregnancy outcomes and any fetal outcomes after, uh, the woman gives birth.

[00:58:07] So. You know, I'm not, I'm not the only one who shares this opinion. Either the world health organization has said that they don't recommend the vaccine be given to pregnant women due to the positive or the lack of data. And the, uh, the United Kingdom has also said that, um, Australia is still. Up in air Australia, hasn't decided whether they want to make that recommendation or not.

[00:58:32] And so, uh, they haven't said to give it or not to give it to pregnant women yet they haven't put their foot on the ground. The us has said, go ahead and give it. And so my whole post was just a reminder to people that we don't have any data available. None at all. And, you know, from a precautionary principle, you want to make sure it's safe in pregnancy for both yourself and for the baby.

[00:58:55] Carl Lanore: [00:58:55] So let, let, so let's stop there for a second. So let's talk about [00:59:00] this. Let's talk about the mother's life. First. You had statistics that you got, I think from the CDC, uh, the, uh, cases of pregnant women contracting COVID and surviving it. Yeah, there's a little, there's a little alien behind you. I didn't want to scare you.

[00:59:16] Um,

[00:59:16] Alex Leaf, MS, CISSN: [00:59:16] yeah, I know she likes to climb on the bookshelf,

[00:59:19] Carl Lanore: [00:59:19] so, so, um, maybe she wants to read a book. So, uh, what, what are the statistics look like? How is a pregnant woman at greater far greater risk of dying from COVID than a non-pregnant woman of the same age?

[00:59:33] Alex Leaf, MS, CISSN: [00:59:33] Yeah. So this is an excellent point because that's really, the question is, you know, When you decide if you want to get the vaccine or not, you're dealing with no data at all, but what's the, what's the alternative.

[00:59:45] The alternative is your risk of contracting. COVID right? Because, uh, the trials have shown that it reduces the risk of contracting COVID now, I mean, the studies have limitations, um, [01:00:00] but without a doubt, it does show that it reduces the risk of contracting COVID in. What would constitute the age range that women can become pregnant.

[01:00:09] So what's the risk if you're pregnant and you can track symptomatic COVID so a lot of people get COVID, they don't even have symptoms, right. Or they're very, very mild. Um, this is, if you look at the CDC did an analysis of 400,000 women that all had symptomatic. COVID like they were experiencing the respiratory.

[01:00:31] You know, symptoms of having this infection and what they found is that when they compared, when they corrected for, you know, underlying health conditions, age and race, and they found that being pregnant. For every 1000 women that contracted symptomatic, COVID your risk of being admitted to the intensive care unit was about 10 pregnant women per 1000 that became infected compared to four for every 1000 [01:01:00] non-pregnant women.

[01:01:00] Right? So, I mean, that's, you know, a 250% increased risk of being admitted to the ICU, but in absolute terms, it's literally an additional six people for every thousand. So, yes, your risk is higher, but

[01:01:16] Carl Lanore: [01:01:16] it's not that. Yeah, but how many of them got, but now here's the real important, how many of those pregnant women die?

[01:01:23] Alex Leaf, MS, CISSN: [01:01:23] Uh, pregnant women, one and a half for every thousand compared to 1.2 for every thousand non pregnant. So a three, so a third of a person difference. That means one more pregnant woman would die for every 3000 people that got symptomatic COVID, uh, compared to non-pregnant. And I mean, that number would manifest as four and a half versus three and a half.

[01:01:48] Right. Um, people

[01:01:50] Carl Lanore: [01:01:50] forever, so, okay. So, so the, the, the protection for the mother is negligible at best negligible at best. So it's [01:02:00] statistically significant because everything's statistically significant in a study when the numbers. Uh, are are different, but the reality is you're talking about one more woman per 3000 pregnant women versus non-pregnant women.

[01:02:13] So now let's talk about something that should really be considered. If you're a factory, excuse me. If you're a factory making a human being, then what it will do to the human being that you're making should be discussed. Number one. So let's look at the positive side. If a mother. Or a woman of childbearing age gets the measles or the mumps.

[01:02:42] Um, and she gets better from that. Is it not true that her office spring has the antibodies and is protected against that? Isn't that what herd immunity is all about?

[01:02:52] Alex Leaf, MS, CISSN: [01:02:52] Well, I wouldn't say that that's what herd immunity is about, but it's certainly, uh, you know, one of the benefits of having a [01:03:00] mother that's been exposed to these pathogens is the immune memory is able to cross the placenta and help protect the infant, uh, during the early stages of life, until their own immune system is able to take over.

[01:03:12] And what I mean by that is the immunity does not last forever. That's why everyone gets chicken pox, for example, right. Um, because the immunity is only short-lived while those immune cells are circulating in the, the baby's body before they die. Um, and that's actually one of the potential benefits of the vaccine as well.

[01:03:33] Is that the vaccine, what ends up happening is it just codes for a spike protein that exists on the virus that our immune system uses to identify this virus? Your cells start making it, they say, Hey, this is a foreign protein fragment. I'm going to put it on myself. Surface immune cells are going to come touch it and be like, wait, this is foreign.

[01:03:54] We need to alert our T cells. Our T-cells are going to come in and be like, yep, we, [01:04:00] uh, we need to start attacking this. And we need to make a specific antibodies that are structurally, uh, that can, um, Work with this protein basically to neutralize it. And so that's how you get immune memory from this vaccine.

[01:04:14] Uh, that immune memory, just as if you had a natural infection, that immune memory will go with you into the baby and help protect it. Theoretically, you know, during the first. However long those immune cells last and it's life,

[01:04:28] Carl Lanore: [01:04:28] there could be a potential benefit to the offspring in the early stages of its life, from the mother being vaccinated.

[01:04:34] Okay. So that's, that's a plus, that's a plus. Now, what do we know about M RNA type vaccines at this point in time, he said, this is the very new, uh, type of vaccine that has the ability to modulate the immune system, correct?

[01:04:48] Alex Leaf, MS, CISSN: [01:04:48] Yes and no. So M R and a. M RNA. Um, how do I want to say it? Like M RNA, uh, drugs [01:05:00] have been researched for at least 30 years.

[01:05:03] So we have a lot of research behind them figuring out how they work, how we can make them as efficient as possible safety data. Um, I mean, we have studies in rodents, for example, showing that MRI and a, this vaccine doesn't effect any pregnancy or fertility outcomes. The question is, does that apply to humans?

[01:05:20] Uh, A lot. There's been a lot of, of misinformation perpetuated about MRN vaccines, uh, due to people misunderstanding kind of how they work. And so we have decades of data with them. It's just the question is that, you know, in those decades, why hasn't ever been used in humans for anything up until this point and there's two potential answers.

[01:05:47] One answer is more cynical. And it says that while we really, uh, this vaccine, you know, had emergency use authorization before proper safety testing, uh, the previous data in some [01:06:00] cases did show that it had harms. For example, using we've used MRNs vaccines against Corona viruses in cats, because cats are especially prone to Corona viruses for things like eye colds, and they've been shown to have harmful effects on cats.

[01:06:14] Or I shouldn't say harmful effects, but they've been shown to have adverse effects. Yeah. And we're humans. Right? So that's a cynical view. Uh, the more kind of, uh, beneficial view or optimistic view is that we literally poured billions and billions of dollars into research and development and, uh, demonstrated what can be achieved if the entire nation and the entire world, in fact, agrees that something needs to be researched and brought to market.

[01:06:42] And this is how quickly it can happen in a safe and effective manner. So there's two views. I don't know which one's correct. I don't think anyone does because it's just a matter of opinion. Um, but I, my position, as far as pregnancy goes is [01:07:00] that I have not seen any data at all to suggest that there is a reason to not get the vaccine and pregnancy, nothing, but.

[01:07:11] There is no human data at all. And so the precautionary principle for

[01:07:17] Carl Lanore: [01:07:17] me

[01:07:19] Alex Leaf, MS, CISSN: [01:07:19] that I want to be abundantly cautious, and I want to wait. Until future safety data in pregnant women is available. And it will,

[01:07:31] Carl Lanore: [01:07:31] it seems, that seems reasonable. That doesn't seem over the top. It doesn't seem like 10 hat wearing idea.

[01:07:39] I mean, it just, it seems very reasonable. You know, the last interview we talked about ketamine and how ketamine affects M tour. It depends on mTOR tour for it to work and its antidepressive effects and that. Taking rapamycin and ketamine at the same time in rodents mitigated its effects, but it [01:08:00] worked in humans.

[01:08:01] So there you have an example where just because something happened in rodents doesn't mean it's going to happen that way in humans.

[01:08:08] Alex Leaf, MS, CISSN: [01:08:08] Well, there's a lot of examples about that. I mean, countless, um, and a lot of it fundamentally comes down to, for example, different just differences in metabolism, rodents, have a.

[01:08:21] Body specific metabolic rates, seven times faster than humans, which means that they're going to metabolize compounds and detoxify certain drugs in the such differently than they are humans. Um, now again, safety data in rodents seems optimistic. My only concern is that we don't have any data in humans.

[01:08:41] And so when I made this post, I specifically said at the end of it, I said, look, the whole purpose of me thing, this. Is not, that is not to instill fear. I'm not saying, Hey, you shouldn't get the vaccine because there's a lack of data. What I'm saying is that there is a lack of [01:09:00] data. And now you can, you need to contrast this lack of data with the risks of COVID pregnancy, which we discussed earlier.

[01:09:10] Um, basically an additional six people per 1000 can expect to get severe COVID statistically. So, if you are willing to accept that risk, then I think it's, it's a smart move to wait until more safety data is available to get the backseat. If that risk is too great for you, then I fully support your decision to get the vaccine.

[01:09:33] My position is I want to support the position that people take, and I want to support the, the, uh, data or ability to make that choice for themselves. I don't want anything forced upon them.

[01:09:46] Carl Lanore: [01:09:46] But more importantly, we have, we have a population out there that's saying trust the science, trust, the science trust, the science, that, those science for this.

[01:09:55] So that seems population should be going well, there's no science for this. So we really don't know what you [01:10:00] should do, but instead they're saying, Oh, it's safe. Go ahead and use it. So it's trust the science when, when the science favors our position, but when there's no science at all, just listen to us.

[01:10:12] Alex Leaf, MS, CISSN: [01:10:12] Yeah. We're experts. It's it's fine. Yeah. Yeah, exactly.

[01:10:17] Carl Lanore: [01:10:17] Well, I want to invoke something else that we didn't plan on talking about, but it's fascinating to me cause I know Alyssa and I are going to talk about this on the first casual Friday at the end of the month. And I think that you may have had some discussions about this on social media and gotten some backlash.

[01:10:33] Um, recently cosmopolitan put some really overweight women on their cover and said healthy or the new healthy or something like that. And first of all, You can't look at somebody and tell if they're healthy or not. Right. If we could, man, we wouldn't need all that diagnostic stuff in the hospital. We just look at and say, Oh, you got cancer.

[01:10:52] You better go. So that's first of all, silly, but more so is it? Well, no, no.  what [01:11:00] is, what is silly about this whole discussion is, and something I've talked about on this show for years, you know, you can buy. For those of you old enough for Chevy Vega, you could buy, you could buy a, uh, what's that little Cooper and you can pull a fifth wheel with it.

[01:11:17] And you'll probably be able to get across the country one time, but you may not be able to get across the country the second time, because even though that car looked like it could do the job. It starts to wear out and break down. And so this idea that really obese people are healthy is only if you take a snapshot in time of them.

[01:11:38] If you continue on that path over five years, six years now, you see the cumulative damaging effects of their metabolic system under that weight. So sure. The gal who's 22 years old and she's carrying 200 pounds of body fat and she goes and gets blood work done. And the doctor goes, you're healthy. Yeah, you're [01:12:00] healthy today, but you can't stay like that and be healthy.

[01:12:03] And we know that already. So I think you may have commented something like that on Facebook. And the reason I'm setting this table is I want to talk about pregnancy for a second. So pregnant women. By and large in the United States think that when they're pregnant, it doesn't matter. In fact, we have, we have pediatricians and the pediatrician, we have obstetricians telling their patients, don't worry, eat whatever you want.

[01:12:26] Don't and these people gained women gain 150 pounds during pregnancy when really all they needed to gain was maybe 40 or 50 pounds tops to deliver a healthy baby and not destroy their own. Uh, body, but what are, what are we talking about here? When we talk about pregnant women, given the state of what women think pregnancy, weight looks like, how about those women that are so heavy?

[01:12:54] So they put on so much body fat that they're actually more susceptible from dying from COVID. [01:13:00] Am I, am I being a jerk here by imposing that question?

[01:13:04] Alex Leaf, MS, CISSN: [01:13:04] I don't think so. I think that it's well-established that. Obesity. Um, if you take, let me, let me put it this way. So, uh, probably a couple months ago, I did an entire article on how obesity affects immune function.

[01:13:18] And if you take the immune system of a 24 year old person who is obese with a BMI of around 33 34, so not even morbid obesity, this is literally grade one obesity, right? Then you compare their immune system functionality to someone who is of a normal weight. Their immune system is equivalent to that of a 55 year old.

[01:13:43] And so, and then there's a bazillion different, uh, mechanistic explanations to explain how obesity causes immunosenescence. And this is why obesity is such a huge risk factor for respiratory diseases. Like COVID it's because it [01:14:00] causes your immune system to be dysfunctional. Uh, it causes immunosenescence.

[01:14:04] So you're not able to Mount as robust of an immune response when you encounter pathogens. Uh, it, and that's well-established in the scientific literature. Obesity is a huge risk factor for,

[01:14:15] Carl Lanore: [01:14:15] uh, mortality from this virus and mortality from this virus.

[01:14:20] Alex Leaf, MS, CISSN: [01:14:20] Yes, exactly. And that's been observed with COVID that's been observed with like everything that every, uh, pathogen that we're aware of, including COVID.

[01:14:29] Some of the earliest data we had was showing that people with obesity were at like a threefold increased risk of mortality. Um, now, and this is also exactly why older adults are at an increased risk is because your immune system becomes less functional. As you get older. It's a normal part of aging.

[01:14:47] That's why P that's why people over age 75 in the U S make up 60% of all deaths in, in the U S right. And people below age, what is it? A [01:15:00] 45 make-up 0.8% of all deaths. Right. And in between there, you have, you know, an exponential curve. Where the older you get it, exponentially more deaths because of immune system dysregulation, and also other factors like malnutrition, having low amounts of muscle mass, typical things that happen with aging, uh, comorbidities.

[01:15:22] People just tend to become more metabolically dysfunctional as they age as well. And so, yeah, with pregnancy, you it's, it's used as an yeah. Excuse for a lot of women to kind of pig out, eat whatever they want gained a bunch of weight. Uh, and this might not necessarily be a problem depending on what your starting weight is.

[01:15:40] Right. Um, but if you're someone who's already overweight or obese, you're only, you only need to gain about 15 to 20 pounds during your pregnancy. And yet your weight just continues to go up because you already have poor eating behaviors and habits in place. And you're just [01:16:00] capitalizing on those now. And that does.

[01:16:02] Damage the baby you're at a greater risk of gestational diabetes, which is harmful to the fetus you're and can cause premature births. Uh, you are literally starting to program the epigenetic changes in their DNA that can make them more susceptible to obesity later on in their life. Even if you don't care anything about yourself, I'm fundamentally, you need, you should probably care about your kid.

[01:16:28] Right? Right. Like we know that what you do when you're pregnant. Is going to impact your child's life way into adulthood. That's not good.

[01:16:38] Carl Lanore: [01:16:38] You know, what's really funny on the side of a jug of a claustrum it says it's not recommended for pregnant women on just about every dietary supplement in the world.

[01:16:50] It's called a CYA, cover your ass. Every supplement manufacturer in the world puts if you're pregnant or lactating, [01:17:00] Talk to your doctor before taking the supplement as a minimum and as a maximum, it says not recommended for pregnant women or lactating women. Now they haven't done the research to prove that it's harmful for pregnant women or their babies that they're breastfeeding, but because they haven't done the research, they say don't take it because they don't want the liability of somebody taking it.

[01:17:25] And having a child on the spectrum and saying, Oh, it was that supplement I was taking during pregnancy. But yet the CDC, the master controller of disease and research in this country has no problem telling you. We have no research to prove that it's safe, but we say it is we're experts. You take it. Think about the difference.

[01:17:47] Think about the balls, the balls on the scientists at the CDC who said. Yeah, no, that's okay. It's take no, don't take colostrum. Cause we don't know what that'll do to you while you're pregnant, but [01:18:00] yeah, you can have this vaccine. No problem. And I'm going to say something else real quick. I believe in vaccines, people think I don't, I believe in hormesis, the earliest vaccines were during the black plague where they actually scraped the push tools from people who survived the black plague.

[01:18:19] And they took that and they scratched the person's arm open and they rubbed that puss in and the person got mildly sick for two or three days. And then they were immune to the black plague. This is where vaccines came from. Vaccines work by hormesis. If you take just a little bit of the poison. You become strong enough to resist it over time, but what happened was AstraZeneca and Senator Jenica and all these other pharmaceutical companies thought, wait, how do we, how do we put that into a multi injection vile that's that's shelf stable for five years.

[01:18:53] Oh, well, we got to add all these other things that have nothing to do with making the vaccine work [01:19:00] better, but making it. Marketable and profitable. And that's the stuff that I don't like in there. And the last thing I'm going to say is vaccines work, but the vaccines that were being forced upon you today that you don't even have a choice.

[01:19:20] That's not, that's not good science. I don't care what it is. That's not good science.

[01:19:24] Alex Leaf, MS, CISSN: [01:19:24] Carl,

[01:19:25] Carl Lanore: [01:19:25] can I say one more thing we have all the time you want?

[01:19:28] Alex Leaf, MS, CISSN: [01:19:28] Yeah. I just, I also want to mention too, because. With the everything that's going on right now, people are very divided. People are tribalistic. They like to make enemies out of others.

[01:19:39] And the really the message I want to stress is, um, don't shame people for their decisions, right? I, you know, people are allowed to look at situations and decide what is best for them and their body. And especially with the vaccine, I, you know, it's really easy to throw [01:20:00] around claims of selfishness. Like, Oh, you won't get vaccinated because you're selfish.

[01:20:04] You don't care about the community or whatever. And the reality is that it's selfish for you to think that you're, you are allowed to impose your desires on another human. I mean, the fact of the matter is that every single clinical trial we have on this COVID vaccine, they all excluded children. They excluded pregnant and breastfeeding women.

[01:20:26] They excluded people with immune disorders and they excluded people who have allergies to it. Um, in particular, P someone with an allergy, are you going to shame someone who decided not to get the vaccine? Because it would cause an anaphylactic shock in them? Like that just seems so absurd when you put it that way, but it's like, you have no idea why someone decided not to get the vaccine.

[01:20:47] Who are you to believe they're a lesser human because of their decision. Like it's, it's harmful in people who are allergic to it. First of all, and that's every single government [01:21:00] organizations does know these people have a medical exemption. They should not get it because I mean, they could die. Uh, we have zero data in pregnant and breastfeeding women.

[01:21:09] Why not be cautious? We have zero data and people who are immunocompromised like an HIV patient. Why not be cautious? What

[01:21:16] Carl Lanore: [01:21:16] about root? What about, what about rheumatoid arthritis? What about. Clear autoimmune disorders, rheumatoid arthritis, Hashimoto's disease, uh, Addison's disease. These people have compromised immune systems that are attacking their tissue.

[01:21:29] Now shouldn't they be allowed to opt out if they want to opt out of a vaccine?

[01:21:34] Alex Leaf, MS, CISSN: [01:21:34] I would think so. The vaccines led some of those people in one of the studies, I think Pfizer had 40 out of their 30,000 peoples had rheumatoid arthritis. So, I mean, they were included in the study, but not in, in numbers that would allow for any meaningful analysis of that specific subgroup.

[01:21:51] And even if, and I mean, you know, there was, there was 240 adverse events in the vaccine group. It could have been all of them [01:22:00] involved people through maternity. Yeah. We don't know.

[01:22:02] Carl Lanore: [01:22:02] Yeah. Because it was blinded. Yeah. Right.

[01:22:04] Professor Argel Aguilar-Valles, PhD: [01:22:04] All right. Um,

[01:22:06] Alex Leaf, MS, CISSN: [01:22:06] and then we, and then all these studies excluded children. Uh, two of them involved people over 18.

[01:22:12] Uh, I believe the Pfizer trial went down to allowed people that were 16 and older to get the vaccine with human concern or with parental consent, but in children, uh, zero data on how the vaccine might affect them too. So, I mean, God forbid, people want to start vaccinating their kids with it with zero data on how it impacts anything, especially because there's such a low risk group.

[01:22:37] Right. And that's another thing is. My position from the start of this vaccine is that we should really be prioritizing the people that are dying from COVID like, if you are over 75 years old, you should probably get the vaccine because you're making up over 60% of deaths. Yes. And that's actually another concern with the studies is every single trial [01:23:00] in each one of them, less than 5% of the study participants were over 75 years of age.

[01:23:06] And we know that again, elderly people are less responsive to vaccines because of the immunosenescence. They do not develop immunity as well as a younger, healthier person does. So the question arises will the vaccine even be effective in them? Do they need a different dosing schedule, et cetera, et cetera.

[01:23:23] We can't figure any of that out from the data we do have. Right. Now that being said, even though there is no data, if I was over 75, hell yeah, I would be getting the vaccine. Why? Because my risk of dying is so great that going and assuming the vaccine is going to work is worth it. It really is. But when you have such a low risk, such as being, you know, a healthy young to middle-aged adult, or even if you're a pregnant woman, your risk is, is so.

[01:23:52] Well that I think there's enough room to just take a step back and be like, I just want to wait until there's a little more safety data [01:24:00] and those decisions shouldn't be

[01:24:01] Carl Lanore: [01:24:01] shamed. I agree with you. So we're coming to the end of the interview. I want to send people to your website. Your website is Alex leaf.com, correct?

[01:24:08] Yup. You've got some great blog posts there. You've got a blueprint for fat loss there. Um, but also you, do you still do nutritional counseling?

[01:24:18] Alex Leaf, MS, CISSN: [01:24:18] Yeah. Well, I do consult if people just want to talk to me then. Yeah, I do consults

[01:24:22] Carl Lanore: [01:24:22] for sure. Way to get in touch with you is through the website, Alex leaf.com. Yep.

[01:24:26] Just on my contact page, Alex is worth talking to because Alex. Lives the life that he promotes and he knows what works and what doesn't. And as you can see, Alex is very, uh, very centered about his opinions. Uh, if science provides insights into a specific direction, Alex is, is not going to discount it.

[01:24:50] And so he's the kind of guy that if you are trying to. Get your body in shape for 2021. And you want to talk to someone sensible who isn't going to tell you, well, you got to eat keto [01:25:00] or you got to eat carnivore or no, you know, you gotta, you gotta eat only cardboard. Uh, Alex we'll have you eating a diet that you enjoy eating because the diet that you enjoy you will most likely stick to and you'll get results from.

[01:25:12] Uh, he has, uh, you graduated from Bastyr with a degree in nutrition, right?

[01:25:17] Alex Leaf, MS, CISSN: [01:25:17] Yeah, my master's in 2016.

[01:25:20] Carl Lanore: [01:25:20] No. So he's not just some guy who took a course at, uh, some health club and is calling himself a nutritional counselor. Go to Alex leaf.com. Check them out, Alex. Thanks for being here today, brother.

[01:25:31] Alex Leaf, MS, CISSN: [01:25:31] Thank you for having me, Carl.

[01:25:32] It was fun. Talk

[01:25:33] Carl Lanore: [01:25:33] to you again soon. Okay. All right, bye. And that's it for today, we have great shows all week long. Uh, please share the show, help the show, blow up, share the show. I will see you tomorrow with more supreme-a radio. Thank you for watching and listening today. [01:26:00]