[00:00:00] Carl Lanore: [00:00:00] welcome back to another episode of super human radio. Today is, uh, let's see. April 6th, 2020, we're deep into the self quarantine, social dis distancing,

[00:00:11] Dr. Michael Lisanti, MD - PhD: [00:00:11] uh,

[00:00:11] Carl Lanore: [00:00:11] of this current pandemic. Uh, we are making history all around the world and, uh, today's show is very important. You know, we've done quite a few really good shows about, uh, coronavirus covert 19 that you don't hear anywhere else.

[00:00:26] And this one is really an important one. I learned about this particular research from Charles Grashow. And, uh, it fits nicely, uh, in the context of what the show was about. anti-Asian cause many of us already do things, uh, that, uh, and take things out of considered Sena Lytics and there may be a value, uh, a protective, a prophylactic value in those, uh, in dealing with and treating even a covert 19.

[00:00:52] Before we do that, I have to thank. Our title sponsor, uh, legendary foods. Uh, they are an amazing company that makes nut [00:01:00] butters, that have no sugar in them. But they taste sweet and delicious, and they also make an alternative to the pop tart, which is the tasty pastry, which I love. I actually take the nut butters and make sandwiches with the, with the tasty pastry.

[00:01:15] Uh, but I'm a govern. I eat a lot. But anyway, so they have, uh, a tasty pastry, which is, uh, supposed to be like a pop tart, but it actually has nine grams of high quality protein, uh, less than one gram of sugar and three to four impact carbohydrates. You can get them This email address is being protected from spambots. You need JavaScript enabled to view it. let them know that Carl sent you, of course.

[00:01:36] And now we bring my guest on today and he is Dr. Michael a Santhi. How you doing ductless Santi?

[00:01:43] Dr. Michael Lisanti, MD - PhD: [00:01:43] Good. Good. Is as good as could be expected under lockdown, but very positive. Yeah.

[00:01:48] Carl Lanore: [00:01:48] And we have to be right. Hey, look it up. Parents, what they went through. I mean, this is nothing, right? We, if you told my father, Oh, you're gonna have to stay home for a month, and you could do that on his head, he'd say, you know, as opposed to going into [00:02:00] actual war or something like that.

[00:02:01] Anyway, um. We freeze once in a while. I think dr Liz Santhi. There you go. You're back. Okay. Yeah. We should have mentioned that we're talking to you all the way from the UK and I'm going to give you a little, uh, information about dr lasantha. He began his education at NYU at graduated Magna cum LATI and chemistry.

[00:02:19] He obtained an MD and a PhD degree at Cornell university medical college. In cellular biology and genetics. Uh, he's also a fellow of the Whitehead Institute at MIT. After, uh, let's see what else he was at Albert Einstein school of college, uh, college of medicine. Uh, and, uh, now you are actually the chairperson in translational medicine at the university of Salford in Manchester.

[00:02:45] Is that, is that correct? That I get it right?

[00:02:48] Dr. Michael Lisanti, MD - PhD: [00:02:48] That's absolutely right.

[00:02:49] Carl Lanore: [00:02:49] Dude, when do you sleep?

[00:02:53] Dr. Michael Lisanti, MD - PhD: [00:02:53] I mean, really? That's amazing. Well, eight hours a day, so, uh, yeah. Well, I'm actually, [00:03:00] uh, always energetic. Always thinking about anti aging. Anticancer cures. So it keeps me going. Keeps us all going.

[00:03:09] Carl Lanore: [00:03:09] Inquisitiveness.

[00:03:10] That's a wonderful gift. It really is. So let's talk about this. Why, why this study on looking at  as a treatment or prevention for coronavirus, what research was done before this that kinda gave you a glimpse, like, we should look at this?

[00:03:24] Dr. Michael Lisanti, MD - PhD: [00:03:24] Well, we actually identified  as a new center lytic drug. And what we saw.

[00:03:30] Is that it to selectively target senescent cells with an efficiency of 97% and we published that in 2018 and if you go back in the literature, you can see that also the drug was used to treat patients with cystic fibrosis and it dramatically extended their lifespan. And it did that by preventing the inflammation and fibrosis that is characteristic of the disease.

[00:03:58] And also it's been shown that. [00:04:00] A Zithromycin can extend lifespan and survival in patients with, uh, idiopathic pulmonary fibrosis or IPF. So it's actually a very under-recognized, anti-fibrotic anti inflammatory drug that inhibits the production of . It reduces fibrosis. And if you look in the literature, and it's also been shown to inhibit viral replication.

[00:04:30] Now, the reason that all those things come together as they all require protein synthesis, you need protein synthesis to make . You need protein synthesis to make collagen for the fibrosis, and you need protein synthesis for the virus to replicate. So this drug actually would be ideal potentially for treating patients with Kovac 19 and in fact, that would explain why.

[00:04:58] The French had [00:05:00] such good luck with the combination between hydroxy chloroquine and as the , but surprisingly, they didn't test the Zithromycin alone. I think potentially is that through myosin alone would be actually sufficient. And, uh, and you could think of the COBIT 19 almost like a very acute case of cystic fibrosis in the sense that it creates this very acute inflammation.

[00:05:27] Huge levels of aisle six, which other groups have shown is a predictor for being intubated and put on a respirator in the case of coven 19. So anything you could do to reduce the inflammation and fibrosis would be something that you could prevent, uh, the disease becoming very cute and deadly. So I think, you know, the French clinical trials are right on target with.

[00:05:54] Using as , but there are other drugs also like rapamycin [00:06:00] and also doxycyclin, which are both anti-aging drugs, and they both also behave as inhibitors of protein synthesis, both reduced aisle six and both also reduce fibrosis, and they also reduce viral replication. So I don't know why people aren't to trialing these.

[00:06:23] But they should be.

[00:06:25] Carl Lanore: [00:06:25] I agree. Now is that the minus and falls into the class of drugs as an antibiotic, correct,

[00:06:30] Dr. Michael Lisanti, MD - PhD: [00:06:30] yes. Also doxycyclin and I think Lyson is also considered or was originally considered an antibiotic because the name rapamycin is, is really. The same name you would give to an antibiotic, the Mycenae

[00:06:46] Carl Lanore: [00:06:46] Mycenae.

[00:06:47] Right, right. And, and, and, and that makes sense cause it was used as an anti-rejection drug. Um, so that makes a lot of sense. Now you're not a fan for turning off M tore all the time, right? Yeah.  [00:07:00] so are you not a fan of  inhibition continuously around the clock, right. You're, you're, you're, you're afforded for short periods of time to do, to a job.

[00:07:08] Right.

[00:07:08] Dr. Michael Lisanti, MD - PhD: [00:07:08] Well, I think what you need is you need a dominion because you also need protein synthesis to maintain your body to, for. Repair, wounds, healing, et cetera. So you can't shut it off forever.

[00:07:23] Carl Lanore: [00:07:23] Right, exactly. I'm glad to hear you say that. Cause a lot of people out there that are talking about shutting it off forever in an effort to live longer.

[00:07:29] Um, so, okay, so now that that means drugs or molecules like quercetin, resveratrol, even , which was originally a chemo, they all have found their way into the realm of being sent Alytics. Would these also be effective?

[00:07:47] Dr. Michael Lisanti, MD - PhD: [00:07:47] I think anything that would inhibit protein sentences would probably be effective. And there's good evidence in the literature that different drugs that inhibit protein synthesis also inhibit [00:08:00] viral replication.

[00:08:00] So I think any one of them individually would be sufficient for both treatment and prophylaxis. It's just a question of get getting those drugs trials. There's been anecdotal evidence, I think, but, uh. You know, it depends on the toxicity of the drug. Doxycyclin is actually not very toxic. It's used for acne worldwide.

[00:08:25] It's one of the number one drugs prescribed worldwide. As this remixing is also considered a very safe drug. So I think both of them individually would be potentially sufficient.

[00:08:40] Carl Lanore: [00:08:40] Now for treating someone who has the virus and is displaying the symptoms, um, would cause usually we get the, is it from eyes and then like a five day, you know, hammer, you take his Z-Pak five days or six days in your, you're done.

[00:08:57] Would you give the same doses for [00:09:00] longer periods of time until the patient was out of the woods or would you approach it differently? You think.

[00:09:06] Dr. Michael Lisanti, MD - PhD: [00:09:06] I think the regular dose of is that their Mycenae should be sufficient. And we have seen that, uh, in time lapse photography of the cells and culture, that it only takes five hours for the azithromycin to kill all of the senescent cells, nearly all of them.

[00:09:22] So I think regular dose of Z-Pak should be fine. Obviously you need to talk to your doctor and, uh, see if you can find somebody. Who's sympathetic, but it may not be well known, but in the United States, 25% of all prescriptions are called off label. That means, or another use. So it's perfectly legal in the United States to prescribe an FDA approved drug for another use.

[00:09:50] So any doctor could prescribe any FDA approved drug for any use. So I think that gives people in the U S [00:10:00] the wide latitude. That's not true in the UK and Europe, but in the United States there's wide latitude and I think that helps people identify and repurpose FDA approved drugs. If they have a hunch and they see that there's a anecdotal effect, then they can put that drug into a clinical trial and ultimately get FDA approval for that indication.

[00:10:23] Carl Lanore: [00:10:23] So do you really think the mechanism of action here is the eradication of senescent cells? And the only reason why I asked that ended the reduction of protein synthesis, because I'm sure you saw a study that was published earlier this year or late last year that showed that a single bout of resistance training, uh, eliminated.

[00:10:45] 60% of senescent cells in muscle tissue. But we have to understand that that also triggers an increase in  following that exercise routine. So is it possible that it's, it's, [00:11:00] it's, it's, it's just about eliminating senescent cells and not turning off 

[00:11:07] Dr. Michael Lisanti, MD - PhD: [00:11:07] I think, you know, there's plus and minuses to both approaches, but I think that.

[00:11:14] You know, if you look at the literature on , you know, they've done experiments in mice and they've used believe Mycenae to induce fibrosis. Bleomycin is an anticancer drug and it's one of its major side effects as lung fibrosis. But if they give it in combination with azithromycin or shortly afterwards, then there's no fibrosis.

[00:11:36] And that's because there are cells that generate the fibrotic material. The collagen. They're called myofibroblasts. And, uh, if you look at the published studies in our work, you can see that as if through mice and eliminates all the myofiber blows. So essentially it's an anti-fibrotic that has wide implications potentially for many other [00:12:00] my Brodick diseases.

[00:12:00] The number one fibrotic disease actually is postop adhesions. A lot of people who have surgery develop fibrosis. And their abdomen. And that can lead to torsion and obstruction of the bowel. So, and also there is scar tissue, you know, from surgery on the skin. So that forms keloids. So essentially also, you know, as the three mice that may have a role there in removing fibrotic tissue, both internally and also on the skin.

[00:12:35] So I think. All of this is related again to senescence in modifier Blas.

[00:12:41] Carl Lanore: [00:12:41] Okay. So, um, senescent cells accumulate in our bodies over time. Is there a linkage to blood sugar management and the synthesis of senescent cells?

[00:12:59] Dr. Michael Lisanti, MD - PhD: [00:12:59] I [00:13:00] think, you know, we're still in. The infancy of understanding metabolism and senescence because it may be different in different cell types.

[00:13:09] And, uh, when people talk about senescence, senescence in normal cells is more or less associated with an energy deficit. But those senescent cells still have to produce an awful lot of protein because they have the senescence associated secretory phenotype, which requires a lot of energy. To synthesize the inflammatory mediators.

[00:13:32] Whereas also in cancer cells, when they become senescent, they have a, a different metabolic phenotype, I believe, where there's increased potentially increased mitochondrial activity. So I think it depends on the cell type. What we're really talking about is I think the senescent fire Blas where there's an energy energy deficit, but they may be more glycolytic, but also that may be associated with inflammatory.

[00:14:00] [00:13:59] Phenotype. So it's really that laboratory phenotype, which is so deadly, and that production of the aisle six is, is also almost contagious because I all six is the inflammatory mediator that is secreted. And so then it makes the other surrounding cells also senescence. So it's almost like an infectious disease where senescence spreads from one part of the body to the other.

[00:14:26] Based on the secretion of a vial six so we really need to take  out of the equation. And is it through, my son and doxycyclin have both been shown to inhibit protein synthesis and  production. So either one of them would be a way to control a I all six levels to reduce  levels.

[00:14:52] Carl Lanore: [00:14:52] Is it practical to think of those if a doctor wanted to prescribe them as a prophylactic to take those, you don't have the virus now you're living in [00:15:00] Westchester, you know, someplace like that and you're like, I don't want to get the virus doc.

[00:15:03] And he goes, well, we'll put you on a, we'll put you on Zithromycin for a low dose every day, or just one T Z pack and you're good for a month or two. Any ideas. I

[00:15:14] Dr. Michael Lisanti, MD - PhD: [00:15:14] guess, you know, for the prophylaxis, could it be done weekly? Obviously it would have to be done under the supervision of your doctor, but people have shown that  and inhibits viral replication of a Zika virus and also a bowl of ours.

[00:15:31] So it's not specific to a particular virus. It's, it's because it's inhibiting protein synthesis. And also doc cycling has been shown. To inhibit a replication of the dang gay virus. Another retro virus has been shown to inhibit the replication of the HIV virus. All we think because of the inhibition of protein synthesis, so in viruses or just either [00:16:00] RNA or DNA in a protein coat, and without that protein coat, they can't leave the cell and they can't become infectious.

[00:16:09] So without protein synthesis, you cannot make a live virus. So if you can inhibit protein synthesis, you can block viral replication. And that's what we would need here as prophylaxis and also for therapy, because then you prevent the transmission internally of the virus from one cell to the other. So you would sort of nip the infection in the bud and you wouldn't get the fibrosis or inflammation.

[00:16:37] So. No, and is a through my son. You have a drug that would inhibit both inflammation. Fibrosis and viral replication, what more could you ask for?

[00:16:47] Carl Lanore: [00:16:47] Very exciting. I know. I mean, so I'm assuming that, uh, this fibrotic tissue, uh, that builds up from a variety of things. I mean, we have people who have a failing kidneys because, uh, the, [00:17:00] uh, the, the.

[00:17:00] The, what do they call the, uh, well, the glomerular filtration rate slows down because the kidney becomes fibrotic. And so there's lots of talk about how do you treat that? And most people who have a fibrotic kidneys, they are told, you know, that's, that's it. It's just a slow, I mean, couldn't Z Pat, is it, uh, is it from myosin be used even in that type of an incident?

[00:17:19] Do you think?

[00:17:20] Dr. Michael Lisanti, MD - PhD: [00:17:20] Exactly. It should remove fibrosis, uh, and prevent fibrosis systemically. And, uh, this would happen. Ton of benefits. Also, fibrosis is associated with aging, so we normally become more and more fibrotic with a time and also more and more inflammatory with time. So you could imagine that it could reverse the fibrosis and inflammation of aging, probably through its Sena lytic activity, but also through its ability to inhibit protein synthesis.

[00:17:53] In some ways it shares a lot of properties with and Meissen. Uh, but, uh, is it through my son is also [00:18:00] considered a very safe drug. And, uh, I think, you know, people use it for lung infections. There's no reason why we couldn't use it now. And I know that doctors often say that you can't use an antibiotic to cure or treat a viral infection.

[00:18:21] But they need to read the published literature where it's already been shown by many people. That inhibitors of protein synthesis specifically is it reminds and do inhibit viral replication. I think the problem is that a lot of doctors don't know about the literature, and so they have a kind of knee jerk response.

[00:18:42] They don't actually check their facts and they should read the published literature. Obviously we have to do clinical trials, but. Right now, since these are FDA approved drugs, they could be prescribed, uh, off label. And I think, you know, both [00:19:00] those drugs are very safe. Doxycyclin is one of the most prescribed drugs worldwide for any indication.

[00:19:08] It's also used for malaria, for acne, acne, rosacea, a urinary tract infection. The list goes on and on because it's such a broad spectrum antibiotic. But also it's been around, it's been FDA approved since 1967 so it's over 50 years old. And I think, you know, people trust a doxycycline and they know that people can take it for six months at a time without major side effects, except with a little stomach upset.

[00:19:37] So I think we should, we should do the clinical trials now, but we should also. Think about prescribing it off label for viral infections.

[00:19:48] Carl Lanore: [00:19:48] Douglas doxycyclin is not a fluoroquinolone, right?

[00:19:52] Dr. Michael Lisanti, MD - PhD: [00:19:52] No, no, no. What's recycling? Yeah,

[00:19:58] Carl Lanore: [00:19:58] it's a tetracycline for [00:20:00] acne. When we, when we were kids, she had to take it for acne.

[00:20:02] Tetracycline,

[00:20:03] Dr. Michael Lisanti, MD - PhD: [00:20:03] exactly. But now what's like the next generation? Tetracycline? It's got a very similar structure, but it has a longer half life. And a much better absorption has 100% absorption and half-life about 24 hours. So, you know, and I've heard anecdotal stories of patients in the UK that had been prescribed doxycyclin where it had benefit.

[00:20:31] So, and also patients in Italy that I'm aware of, that it had benefits. So these are anecdotal. Uh, stories, but, uh, they're from people I know, and trust.

[00:20:45] Carl Lanore: [00:20:45] So, you know, I keep, I keep saying to myself, and maybe I'm just trying to tell myself that I'm a better resistance to these types of things, then the average 62 year old.

[00:20:57] But I keep saying, what's the difference between an older person at a [00:21:00] young person? We know that this virus seems to vanquish older people, but isn't it because just in their, their, their hearts aren't as strong, you know, they're just, they're just not functioning well. And it's not about age. It's really about biological age, if you will.

[00:21:18] Um, that like I could go out and I could get on a treadmill and, and walk at a very high pace for an hour, no big deal. I could even run, uh, I can lift weights for an hour. And so isn't that indicative of your ability to resist these types of diseases that isn't it your heart that gives out when you're sitting there, you can't get oxygen, your lungs are inflamed and your breathing and your hearts run and run around and then boom, you just, you give up.

[00:21:48] Isn't that what kills people in these types of, uh, in this particular pandemic?

[00:21:53] Dr. Michael Lisanti, MD - PhD: [00:21:53] I guess it's the inflammation, but. You have to look at also what is the host receptor for COBIT 19 host receptor [00:22:00] means the virus binds to a cell, and that cell then internalizes the virus and then replicates the virus. The host receptor to had been proposed for coven 19 one is CD 26 which is a marker for senescent cells, and the other one is

[00:22:18] Andrea can roading enzyme to which has also increased in senescent cells. So the virus is almost selectively or preferentially targeting senescent cells. So if you think about it from a statistical point of view, it wouldn't be surprising that older people would be more effected and it might be more lethal in older people because, and also those cells that are senescent.

[00:22:46] Are already making inflammatory mediators because they have increased protein synthesis, better cell for a virus to target, where the machinery is already fine tuned for making a lot of protein like [00:23:00] the senescent cell. So the virus is actually quite smart in the sense that it's targeting the senescent cells, which make a lot of inflammation, and it's also targeting the cells that are already revved up for protein synthesis.

[00:23:14] All of this fits very nicely with the idea and the closest relative of the virus is actually the SARS virus or the SARS one virus. And people have shown in young mice that viruses. Relatively harmless, but in old mice that are 12 to 14 months, it's lethal. So the same age, a tendency towards people with high or advanced chronologically logical age is also seen in the SAR is a one virus.

[00:23:50] So it's very similar. So there's a clear association with aging

[00:23:56] Carl Lanore: [00:23:56] for sure. But what, but what did I have less? [00:24:00] I take a rap rap myosin once every two weeks, six milligram dose. I am a F and we're going to talk about time restricted feeding when we come out of this break. Um, but I do a lot of things that are supposed to reduce the accumulation of senescent cells.

[00:24:15] I train resistance training four to five days a week. Uh, I, I sleep well. I'm, I'm militant about getting good sleep. I track my sleep. Um, I stop eating at 6:00 PM, which is the requisite three, uh, three hours before bedtime that Dr. Dale Bredesen talks about, um, in aging better and reversing, uh, Alzheimers disease.

[00:24:39] I do all these things. Is it fair for me to think that, okay, I'm 62 on the outside, but on the inside I'm probably a little bit younger because I don't have that accumulation of senescent cells that my litter mate would have had they not done all the things I've done so far.

[00:24:56] Dr. Michael Lisanti, MD - PhD: [00:24:56] I think that's probably absolutely right, because you know what we're [00:25:00] talking about is, as you said, biological age, and there may be a disconnect between biological age and.

[00:25:08] And chronological age and people who have reduced their senescent cells. And also rapamycin has been shown to prevent the onset of senescence. So maybe you also had. Oh

[00:25:24] Carl Lanore: [00:25:24] gosh, we lost them on V rapid myosin. That's that wireless connection. That's okay. We're going to take a break now. Anyway, when we come back, we're going to talk about time restricted feeding because that plays into this because we know time restricted feeding or intimate and fasting affects the accumulation and eradication of senescent cells.

[00:25:41] Stay tuned for human channel evolution just got kicked up a notch.

[00:25:50] Dakota Santhi we'll pick up right where we left off in just a second. And I have to pay homage to a new sponsor, organic by. Um, [00:26:00] so a lot of my audience knows that I've had a love hate relationship with coffee and caffeine for a long time. And, uh, I have tried to give up coffee, but. Something is always missing in the morning.

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[00:26:38] It takes like 30 seconds to make it. You put a scoop hot water, let it cool off and you drink it. But it actually, so when I stopped drinking coffee, I lost my ability to focus. I lost my ability to recall things. It was like all of a sudden I felt like I had dementia all of a sudden real fast. And. Pure has eliminated that for me because it has 11 different [00:27:00] ingredients that are considered super foods.

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[00:27:55] For those of you who are trying to stay on the vegan path, this is a great, [00:28:00] great product. Check it out. Go to organifi.com O R, G, a, N, I F, i.com/shr so we got disconnected. Right when we were talking still about rapid myosin and, uh, I, we can either go back there or we can say we covered it because

[00:28:17] Dr. Michael Lisanti, MD - PhD: [00:28:17] I'm happy to talk about it.

[00:28:19] Carl Lanore: [00:28:19] Go ahead. So let's talk more about rap myosin for a second. Um,

[00:28:25] Dr. Michael Lisanti, MD - PhD: [00:28:25] shown to inhibit the onset of senescence by a doctor blog is Colone. So I think, you know, there's good evidence that it could also reduce aisle six production by preventing the SAS. Okay.

[00:28:40] Carl Lanore: [00:28:40] Now, there are other things that seem to have an effect on a senescent cell accumulation, inflammation, um, and a variety of other things that now have become in Vogue when we talk about reducing our biological age.

[00:28:56] And one of those things is time restricted feeding or intimate and fasting. [00:29:00] Is, do you think since these, uh, these eating strategies,

[00:29:06] Dr. Michael Lisanti, MD - PhD: [00:29:06] and this could be full blown Quito,

[00:29:08] Carl Lanore: [00:29:08] which I'm not a big proponent of eating all that fat, I just don't want to, uh, but I, you know, I say anything, any diet that produces ketones is a ketogenic diet.

[00:29:18] It doesn't have to produce four millimoles. It can produce one millimole. But do you think that these approaches to time restricted feeding have a potential impact? Maybe as a prophylaxis to. This particular virus?

[00:29:32] Dr. Michael Lisanti, MD - PhD: [00:29:32] Well, I wouldn't doubt it. We'd have to do the clinical trials, but I think, you know, I'm a big fan of ketones in the sense that, uh, they can be used to prevent human disease.

[00:29:45] For example, studies have been done with mice where they artificially induced a heart attack or a stroke, and they gave a ketone bodies and they could prevent. The heart attack or the stroke. [00:30:00] Uh, there are other drugs that you can take, not drugs, but supplements that you can take to mimic the effect of the ketogenesis, which, uh, also have been shown to have some anti aging effects, like a subtle carnitine, lipoic acid.

[00:30:19] Uh, those also have been shown to, uh, prevent heart attack and stroke. When they're give, given as a supplement, they don't behave as say, analytics, but they can potentially reduce the inflammation associated with aging and they can provide additional nutrients to mitochondria under hypoxia. So I think that's part of it is that ketone bodies will allow cells to undergo mitochondrial metabolism under.

[00:30:52] Hypoxia. Also, ketone bodies have been shown, as has a subtle carnitine in the poke acid to increase [00:31:00] the ability of sperm to swim faster. And berm have a lot of mitochondria. They have a color of mitochondria around their tail, and that's what allows them to swim fast

[00:31:15] Carl Lanore: [00:31:15] and interesting.

[00:31:16] Dr. Michael Lisanti, MD - PhD: [00:31:16] So, you know, anything that.

[00:31:20] Would boost the mitochondria, but reduce oxidative stress at the same time. And that's what you have with ketone bodies. The problem is also, some cancer cells can use ketone bodies, but you know, I think by and large, uh, you know, if you're in a situation where you have hypoxia. Like that's a sclerosis, or you have a heart attack or, or a stroke.

[00:31:46] You know, I'm, I'm surprised that that information has never been put into clinical practice because it could save also a lot of people.

[00:31:56] Carl Lanore: [00:31:56] Dr Dominic D'Agostino at the university of Southern Florida. I [00:32:00] don't know if you're familiar with him, but he's been a big proponent of the Quito, ketones and ketogenic diet and treating different disorders.

[00:32:07] And he did an amazing, it wasn't a study, it was just a, him and a couple of guys in the lab. But, um, they, uh, used insulin to bring down circulating blood glucose levels and then, uh, use ketones. Uh, simultaneously. And I think, uh, one of the guys who did it, his blood sugar level was down in the forties, and he was not feeling any.

[00:32:33] Uh, issues with, uh, hypoglycemia, no shakes, no memory, no blackout, nothing. He was just like, nothing happened. And at that point in time, I said to dr D'Agostino, I said, why don't we use that for people in diabetic Homer instead of. And instead of giving them glucose, which you know, like  worked faster, it hits the brain faster, and you know, it's amazing.

[00:32:56] There's so many things, like you're saying, I don't understand why more people aren't paying attention to [00:33:00] this. It's that there's so many things out there that people aren't paying attention to at this point in time. And it's really sad.

[00:33:08] Dr. Michael Lisanti, MD - PhD: [00:33:08] It could alleviate so much human suffering if we just were able to incorporate this knowledge.

[00:33:14] Into clinical therapies. The problem is that I guess there's no incentive for clinical trials, but somebody has to put the money into the clinical trials and, uh, we could reap a huge benefit. And, and ketone bodies, as you know, from fasting, are what the brain survives on during fasting. So that they're also an, and, uh, there's a certain clarity of thinking that is associated with fasting, that's thought to be from a ketone bodies.

[00:33:46] And part of that can be achieved also with the subtle carnitine, because essentially what you're doing is you're a subtle, carnitine is liquid with an acetyl group. So it's, you can't take a subtle [00:34:00] Colet. But you can take a subtle carnitine and it'll have the same effect that it would be activate your mitochondria without causing, uh, excess oxidative stress.

[00:34:16] In fact, that's what coupon bodies do. They get burned with less oxygens, so there's less oxidative stress.

[00:34:24] Carl Lanore: [00:34:24] So let's look at senescent cells for just a second. And as you pointed out, there's varying types of senescent cells. Do these strategies turn senescent cells into  cells, or do they allow the body to deal with them, uh, through the body's, you know, sanitation system and break them up and carry them out?

[00:34:47] Dr. Michael Lisanti, MD - PhD: [00:34:47] So  basically means to lice. Senescent cells. And so what is it through my son does, is it behaves as this analytic, it does [00:35:00] lice, senescent cells. Some other drugs that have been proposed to be some analytics, but they're not selective first announce themselves, whereas Zithromycin was selective for senescent cells.

[00:35:12] So I think you need two things. You need a drug that is a Sen alytic, but you also need to send a lytic that is. Not going to harm the normal cells. And I think is it through, my son fulfills both of those criteria because you could have a drug densest analytic, but also licensed normal cells and that could cause a lot of damage.

[00:35:37] So you want something that's fairly selective for the senescent cells, and we saw a huge subjectivity and all of that is backed up by existing. Clinical trials that were done on patients with cystic fibrosis and on patients with idiopathic pulmonary fibrosis, both of which extended their lifespan. [00:36:00] And both of those were previously considered to be, uh, you know, Le lethal diseases.

[00:36:06] But now people with cystic fibrosis, li live into their twenties, thirties, and forties. Because, and, and initially, initially they thought these are through, my son was behaving as an antibiotic, but in the end they saw it's behaving as an anti-fibrotic. And the same thing is happening today with the patients with Cova at 19 because in the end, the reason they can't get the patients off the respirator is because they can't breathe on their own because their lungs can no longer expand and contract because they don't have the flexibility.

[00:36:40] The fibrosis has. Basically turn the lungs into

[00:36:46] Carl Lanore: [00:36:46] petrified,

[00:36:47] Dr. Michael Lisanti, MD - PhD: [00:36:47] not flexible,

[00:36:49] Carl Lanore: [00:36:49] like petrified, petrified lungs.

[00:36:52] Dr. Michael Lisanti, MD - PhD: [00:36:52] The problem is that, you know, we're not treating the patients early enough, and [00:37:00] I believe that, uh, you know, if they were treated sooner, you know, it takes three to five days for them to get the results potentially from.

[00:37:10] The test, but they should really start right away because the drug is so inexpensive and so nontoxic, they could start right away and then in the end, if it's a bacterial pneumonia, it would have been the same treatment anyway, so it's not like knowing that the person was covered 19 positive is going to give you any additional information, so they should just treat the patients first.

[00:37:38] And then you know, if, if they turn out to be positive, fine, if they turn out to be negative, you treated a bacterial pneumonia. So it doesn't change your, it wouldn't change your treatment strategy. And in fact, having the test might actually do harm because the doctor might say, Oh, this patient has a viral infection.

[00:37:59] We're not going to [00:38:00] give them . So it might actually cloud. They were thinking because they don't know that the drug can behave as also an antiviral to inhibit viral replication. So I think people need to act quickly and they need to prevent people from getting on a respirator. They need to avoid. Because in the UK, for example, I think, you know, the rates are that, uh, the chances of coming off a respirator with covert 19 is about.

[00:38:33] One and two 50% but I think in the States it might even be lower. It might. I, I heard a number around 20 to 30% to recently. So you know that those are not good odds. So you don't want to get to the respirator stage, and that's all about the fibrosis. So you want to prevent the fibrosis as soon as possible.

[00:38:54] So we have to get the message out there any way we can.

[00:38:58] Carl Lanore: [00:38:58] It's interesting because [00:39:00] doctors are thinking of a azithromycin, I want to call it a Z-Pak, was it's easier for me. They want to, they want to look at it simply as an antibiotic. And they, and we've always heard, you know, well, you don't treat viruses with antibiotics, but it obviously has pleiotropic effects.

[00:39:17] And one of those effects is the inhibit the replication of a virus. And so they, they need to understand that this is a retro virus. It, it, it, um. It uses a reverse transcriptase enzyme, which builds our DNA and puts itself into our DNA and makes the cell a factory for producing the virus. So this is like, like SARS and HIV, and these are really nasty viruses.

[00:39:41] They are very small.

[00:39:42] Dr. Michael Lisanti, MD - PhD: [00:39:42] Then why you'd want to kill the cells that have the virus

[00:39:46] Carl Lanore: [00:39:46] and so now, yeah, I was going to say, so what you're telling me is they don't do this to all cells. They do it just to the senescent cells.

[00:39:53] Dr. Michael Lisanti, MD - PhD: [00:39:53] That's what we're thinking based on the receptors. We don't have experimental evidence for that.

[00:39:58] But, uh, [00:40:00] I've looked, you know, the literature is very sparse because, you know, all of this happened so quickly in December. And, uh, but if, but there have been some pathology papers on the morphology of the lung, what it looks like before and after and doesn't even look like a lung anymore. It's terrible.

[00:40:19] But I, I, what you said resonates with me about is that they're missing because. We've also shown that it's an antibiotic that can be repurposed as an anticancer agent to kill a cancer STEM cells that cause recurrence, metastasis and drug resistance. And there was a trial that was done for azithro in China, in lung cancer patients, and they gave just, I think a short course of five days.

[00:40:44] It was a throw, and they nearly doubled survival at one year in patients. One cancer. So, you know, there is many, there's a lot of drugs like this where they're approved for one indication

[00:40:58] Carl Lanore: [00:40:58] and,

[00:40:58] Dr. Michael Lisanti, MD - PhD: [00:40:58] but they may have [00:41:00] benefits in many different indications. So we, the problem is that, uh, we have tunnel vision and we think one drug, one disease, but maybe the drug is already safe.

[00:41:12] It's already past a phase one clinical trial that says it's safe. That's where the off label prescribing comes in. That allows physicians with the FDA's approval to do a off label prescribing. So, and, and, and physicians in the States do take advantage of that. And that ultimately leads to additional clinical trials.

[00:41:36] You know, so if somebody sees anecdotal evidence that a drug works in another disease, then they'll do the clinical trial to, uh, to prove that. More thoroughly, but it all starts with a hunch and an anecdotal observation. And so I think that's why is it through my set eventually became [00:42:00] something that was so widely prescribed for patients with cystic fibrosis.

[00:42:04] It wasn't made for fish. And it's also not having an antibiotic effect in that case, but now it's, it's one of the standard treatments so of patients with cystic fibrosis, it's the number. I think it is the number one genetic disease in humans.

[00:42:20] Carl Lanore: [00:42:20] Really. I didn't know that.

[00:42:22] Dr. Michael Lisanti, MD - PhD: [00:42:22] Yeah. So some very unfortunate, but you know, it's good that we, that people have made the connections and now we need to make the connections further to, you know, to infectious disease because infectious disease also induces fibrosis.

[00:42:39] And in this case, it's a lethal fibrosis that's killing people.

[00:42:44] Carl Lanore: [00:42:44] We're going to take our last commercial break. When we come back, I've got a couple more questions. We'll wrap up the interview. We're talking with Dr. Michael Santi. He's all the way in the UK and, uh, sharing some really great information about how Lytics Alytics drugs that are being used right now to target, uh, [00:43:00] aging and help people stay more youthful.

[00:43:03] It's not about going out and getting a young girlfriend. It's not about even looking better. It's about staving off age-related disease. While those drugs may have a place. And treating viruses in general, especially the more aggressive ones like retroviruses. Stay tuned. We'll be right back. This is the superhuman channel where we use oxygen for the power of good.

[00:43:27] Welcome back.

[00:43:31] Santhi. You know, here in the United States, even though we have a lot more latitude to do off-label prescribing. Um, there is a big, big, big push right now and there's like a tug of war. I'm sure you're following some of the news here, even though you're in the UK, you know, the, the NIH says don't, uh, the FDA says don't, doctors are treating patients.

[00:43:52] They want to know what tools they can use. Um, what, what is your message to clinicians right now?

[00:44:00] [00:44:00] Dr. Michael Lisanti, MD - PhD: [00:44:00] I guess, uh, you know, obviously they need to be conservative, but, uh. I think the benefits outweigh the risks in this case, because you know, also the health care workers, you could imagine that, you know, these drugs could be given prophylactically to healthcare workers, doctors, nurses, anybody who works in the hospital.

[00:44:28] You know, many people are probably already taking them because they have acne, you know, uh, it's not that difficult. If you go to the dermatologist to get a prescription for acne, for doxycyclin. So it's not like, and also doc cyclin and is it through my center, not associated with tremendous antibiotic resistance.

[00:44:53] So I think the risks are small. If you were to take, for example, a probiotic as well, [00:45:00] I think that, you know, people take doxycycline for six months at a time. And then they take a break of a couple of weeks and they go right back on it. So, you know, we already have a lot of people taking doxycycline for acne.

[00:45:17] So I don't think the risks are that high. And the doctors can prescribe it because it's perfectly legal because it's already FDA approved. They just have to use that off label. Indications. So it's really at the discretion of the prescribing physician.

[00:45:36] Carl Lanore: [00:45:36] What about in the UK? They don't have that latitude, right.

[00:45:38] So what, what a doctor is doing, they know about this.

[00:45:41] Dr. Michael Lisanti, MD - PhD: [00:45:41] I don't think they're doing much. I mean, that's the problem. There is a, a piece of literature I read about it and, uh, you know, the way they've carved it out to, they're talking about. The treatment of [00:46:00] pneumonia in patients with advanced clinical, advanced chronological age, and they're recommending amoxicillin.

[00:46:08] But if the patient has an allergy to penicillin and therefore amoxicillin, then you can treat with doxycyclin, but only in the patients that are allergic to penicillin. So that doesn't leave. Much room and I don't think that the amoxicillin will be as beneficial. So I think, you know, doctors in the United States should take advantage of that, right.

[00:46:38] For them to prescribe off label. It's perfectly legal and, uh, and if the patient hasn't had the virus test, which is actually very, very difficult to combine, then also. How do you know it's not just pneumonia? So the legal justification, even though it would be [00:47:00] perfectly legal, another justification would be that you didn't have the virus test, and so you don't know that they're virus positive.

[00:47:07] And, uh, you just give it to them for the Monia.

[00:47:11] Carl Lanore: [00:47:11] We could kind of back into a study here. I was just thinking, cause my hay brain right now, there's a lot of people out there as you point out on doc cyclin, and it would be interesting when you get admitted to the hospital, they ask you what medications you're on.

[00:47:26] It would be interesting to see how many people are carriers of the virus. And have been on doxycycline at the same time. I bet that could be done in a week.

[00:47:36] Dr. Michael Lisanti, MD - PhD: [00:47:36] Exactly. All you'd need to do. And you could even do studies in patients that were asymptomatic. You can take patients that are asymptomatic, that are positive for the virus.

[00:47:46] You just give them one of the antibiotics for a couple of days and you look at the virus tighter before and after treatment. And you would know in a very short period of time. There are so many patients that are available [00:48:00] for treatment. You could do almost instant clinical trials where the fact, you know, the fact is that this drug is already FDA approved.

[00:48:08] It can move right into a phase two clinical trial, and this is what they call a window trial. The window of opportunity study where you have the patient before and after the treatment with the drug. And it could be done in days and, uh, it wouldn't cost a lot of money because the drug is about 10 cents a day for the, uh, doxycyclin.

[00:48:33] Also, the azithromycin is off patent. It came off patent in 2017. So there are generic versions of, is the  as well? Not, you know, not just Z-Pak anymore. So I think, again, clinical trials could be done very quickly and they could just look at viral titers, but you know, retrospective studies, the data's [00:49:00] already probably, they're looking at, you know, what patients got doxycyclin and you know, you could look at hospital stay length of hospital stay, whether or not they were intubated and put on a respirator, clinical outcome.

[00:49:13] All of that data is probably there already. People just need to look at it.

[00:49:19] Carl Lanore: [00:49:19] Now. Well, I want to close the show with this last question. I just want to be clear. Both zipper, myosin and doc cyclin both have the anti-fibrotic effect or just the, is it the myosin?

[00:49:30] Dr. Michael Lisanti, MD - PhD: [00:49:30] Well, we have shown it for the, uh, as if they're Mason, but the literature shows that, uh, doxycyclin inhibit  production inhibits protein synthesis and show it.

[00:49:44] So it should also inhibit fibrosis. It doesn't behave in our hands as a , but it does reduce a viral replication of the dengue a virus. So, you know, for all intensive purposes, I think, you know, [00:50:00] inhibitors of protein synthesis would be sufficient in this case too. But you know, maybe  is better. Again, that's why you need to put these drugs into a clinical trial, but you might already have the data there.

[00:50:13] In patients that were recently treated. They just need to look at the

[00:50:16] Carl Lanore: [00:50:16] records

[00:50:18] Dr. Michael Lisanti, MD - PhD: [00:50:18] and the data's already there. They could draw conclusions pretty quickly, or you know, they could use the off label mechanism. They don't actually need FDA approval for a new indication because they can just use the drugs off label.

[00:50:34] So it's really at the discretion. I was sympathetic prescribing physician. And if they don't have a test that says the drug, the patient is virus positive, then there's no reason. I mean, even they can, they might think it's a bacterial infection. They don't know because they don't have a test. They didn't do the test because I think so few people qualify for the test.

[00:50:58] Right. So [00:51:00] in, you know, uh, we all take an oath. To do no harm. In the absence of that knowledge, they could all prescribe it as if it was a bacterial infection, but, but again, these antibiotics would take care of both. So, uh, you know, in some ways it might actually be better. You didn't have the test because then they wouldn't,

[00:51:22] Carl Lanore: [00:51:22] and they won't give it to you

[00:51:24] Dr. Michael Lisanti, MD - PhD: [00:51:24] withhold the antibiotic.

[00:51:25] But you know, but it's because they didn't read the literature and they don't know that these drugs behave as. Antiviral medications. It's that simple.

[00:51:35] Carl Lanore: [00:51:35] This is very, very interesting discussion. I want to thank you so much for coming on the show today. I, and I add you to my list of another reason why I'm proud to be from Brooklyn.

[00:51:44] Oh, there you go. Brooklyn.

[00:51:47] Dr. Michael Lisanti, MD - PhD: [00:51:47] I

[00:51:48] Carl Lanore: [00:51:48] thank you so much for being on the show today, dr Lasante. Great information and hopefully everybody got something good from it. You take care of yourself.

[00:51:55] Dr. Michael Lisanti, MD - PhD: [00:51:55] Thanks Carl. Take care. Thank

[00:51:57] Carl Lanore: [00:51:57] you. Hi, and that's it for today. Uh, we got [00:52:00] the blueprint Powell hour tomorrow, so Rob Regger, she'll be with us, and then we've got great shows all weekend, week long because of Elisa.

[00:52:05] Profumo. Thank her for this show. She saw child grass show, uh, posted this and she went out and got DACA. LA Santiago cause she's able to do the things I can't do while I'm doing all this other stuff. So thank you Alisa. And uh, you know what? Our Alexis go on. Our website broke 111,000 today, which is a landmark for us.

[00:52:25] We've never had that high of an, a low of an electric score, which means that traffic is up. Um, less than 1% of all global websites get below 100,000. We're heading there, thanks to your help and thanks to the help of my team. Who, Tom Saigon, Elisa Profumo, Michael Quantico, uh, Arbonne Bhagat and of course, Kirkland wore Leddy.

[00:52:47] Uh, all the people that helped me. Give the show a, the proper attention that it needs to produce good content. So thank you to all of you and here's to getting below a hundred thousand this year. And that's it for [00:53:00] today. Thank you for listening, pastor. Show around. This is a good show. I mean, I'm fast it from last night at six o'clock.

[00:53:05] I'm going to eat after the show, you know, intimate and fast and could protect you from getting this virus. Who knew? You wouldn't know if you didn't listen to superhuman radio. See you tomorrow.