20 Burst results for "Metformin"
New Schizophrenia Guidelines
"Lot has changed since 2004 when the APA the last road practice guidelines on schizophrenia this September and twenty-twenty. They updated those guidelines and here's a few of the key changes. There's less emphasis on divorce pushing between the conventional or first generation antipsychotics and the second generation or a typical perhaps because the Katy Trail put an end to the notion that the newer ones are better tolerate or the older ones are more effective, but the guidelines do Place greater emphasis on clozapine. They recommend clozapine after a patient has failed to respond to two trials of a guy psychotics and they Define failure of response meaning less than a 20% response and unlike the 2004 guidelines. They don't require that one of those trucks. Else be with the first-generation antipsychotic. They also recommend clozapine first line for a number of patients, which when you think of it is a lot of people with schizophrenia, those are people with suicidality problematic aggression and potentially with tardive dyskinesia. That doesn't respond to other options. The guidelines do go into great detail on how to treat side effects to antipsychotics. They list metformin as first-line for weight gain and metabolic syndrome and they list the vmat2 Inhibitors two of which are like ft approved and one of which are not all is first line for tardive dyskinesia. That's one area where I might differ from the guidelines they seem to emphasize these FDA-approved treatments, which actually have a fairly poor number needed to treat and not-so-great tolerability and are extremely expensive at $80,000 a year and they give real short shrift wage. Other options for tardive dyskinesia things like ginkgo biloba extract Keppra and amantadine which were actually given more emphasis in the neurology guidelines wage in several places. The guidelines give Credence to the idea of checking blood levels on antipsychotics to see if the patient is actually taking them a lot of authors of advocated for this and the fact here is that you just don't know if the patient is taking it even though the blood levels of most antipsychotics don't correlate with any therapeutic level except for clozapine where the therapeutic effects are greater above blood levels of 350. It's still useful to check them before moving to clozapine because you don't know if the patient even took the medication that you gave them too often. They don't and perhaps the biggest and most welcome change here is the emphasis on psychosocial therapies while they were recommended in a more generic form in 2004 here they recognized A whole host of specific psychosocial programs for people with schizophrenia so they can get their lives back. Here's one that was striking to me. They recommend that all first episode page be treated and something called a coordinated Specialty Care Program. These are things that have been researched since 2004 and shown to improve outcomes. They are team based programs incorporate both medications along with education resiliency training family therapy and vocational rehab sounds like a full pallet of what people need when they're going through them first episode too bad. These programs are hard to find but they're starting to Institute the more public Mental Health Centers and some academic centers have them but helpfully the guidelines do give you a reference to free resources where you can train your staff to start one locally
"metformin" Discussed on Cardionerds
"He will also need pharmacotherapy for his diabetes hypertension in addition to lifestyle measures, really looking forward to our upcoming diabetes hypertension episodes to dive deeper into these topics. Let's get back to our patient K., A. After losing thirty pounds, his agency drops to five point six on Metformin. and. Blood pressure is controlled on single agent therapy with justice hearten..
Online pharmacy Valisure says tests show carcinogen in diabetes drug metformin
"Testing from online pharmacy value sure shows that many batches of the drug metformin used often by diabetes patients contain high levels of a carcinogen which can cause cancer David light is the CEO vouchers testing has shown that about half of the many factors that we tested we tested twenty two have failed for unacceptably high levels of the carcinogen and
"metformin" Discussed on Ben Greenfield Fitness
"And obviously, I forget at times, you know, like, we all do you don't always remember. But I always take that sixty milligrams. So my script is filled by my doctor, and it's I get a bottle of. Two months script. So I get one bottle of the sixties one bottle of the thirties thirties last a lot longer. Okay. And you're not concerned at all about that somehow down regulating your own thyroid production. No because I said when I look at my levels of three, and I look at my thyroid, stimulating hormone. I'm just a little bit out of the rain, but I'm obviously higher. So I would feel like if I was going to drop off, and I stopped and again, I probably should test this out. I have I have done in the past. You go back into normal. Most doctors who are really smart about this and understanding, you know, the optimization pathways or something like that. They want to see when you're just Ostra and your other hormones are optimized they also wanna see a slight uptick Enviro to just to keep up with that that whole, you know. How would I say like just just the whole circular pathway of like all of your hormones staying in balance? If you got one optimized you what the other one at the higher under the range too. And so that's why they give you a little bit of mild dose of that fire away. But again this thyroid medication versus Synthroid or site of. Mel is totally different. Because those hormones are medications can definitely affect your natural production in the primary effect that one would expect when they do something like this would be enhanced fat loss or higher metabolism or energy. I mean, all three for sure, you know, all three and again, I'm not willing ille- recommending this. I mean, obviously, you should go to a physician, you know, they'd need to obviously, do it intake on you and figure out what's going on get your bloodwork and your labs, and you know, see your symptoms and all that stuff. But I mean to me like, you know, the real protocol when you're hormonally optimizes to saucer own metformin. And when there's a need an arm or thyroid or thyroid which again same thing dusted. Okay. Got it got it. Now there there are ton of other things that you get into in your book, guaranteed shredded. In addition to metformin and thyroid you talk about and kind of educate people on everything from fentor mean and Buta role to to nicotine gum to a pretty hefty dose of vitamin d it's very interesting stack. And we don't have time to get into every element of it. You know beyond metformin in thyroid today, but Jay is indeed ripped and built and for those of you who are interested in in looking his protocol..
"metformin" Discussed on Ben Greenfield Fitness
"Then also use the code, Ben. That's enough. We got huge. This is a monster. So we should get started. Let's do it. So before we jump into today's episode with j Campbell. I realize that as you're about to find out this particular podcast may generate some amounts of confusion. We discuss metformin something that I have vilified in the past. We also discussed testosterone replacement therapy something that I've also questioned the wisdom of in the past. And I've been doing since I interviewed Jay quite a bit of research on all the different studies that he has been sending me, and you know, the the question that I get after I release a podcast like this is Ben what are you going to change? What would you do what what your plan and? All summarize it as follows. And then listen into the episode to understand what I'm about to say here a regarding mitt foreman. And what we discuss when it comes to the safety of metformin. I still do not plan on beginning to supplement with the fifteen hundred to two thousand milligrams of metformin that the appears to be so popular in the anti-ageing circles and primarily that is because Mike urrent habit of using things like bitter melon extract Salen cinnamon, apple cider vinegar. It cetera seemed to be managing my my blood glucose levels, just fine. And I do wear a continuous blood glucose monitor and have no concerns about my blood sugar. If I did have concerns about my blood sugar. However, or if I wanted to use metformin froze of the some of the other benefits, Jay. Discuss in this episode like muscle gain or fat loss. I I'm I'm no longer opposed to the idea of using metformin. I thoroughly went through all the research studies that Jay sent to me and for the reasons that Jay alludes to in what you're about to hear. I think metformin is. Okay. And I know people also say, we'll bended you, right? One of the big articles on the internet that says the dark side of mitt foreman. I did and one of the things that you will find if you go in listen to my podcasts over the past ten years is I will readily admit when I find new research or new research comes to light that what I've said before was not fully informed or more research has come out on it. And therefore, I will I will change my stance. I will change my position. I am not so dogmatic and myopic that I'm not willing to look at research. And listen, what people are saying in this case it turns out. That most of the research done on the deleterious effects of metformin were done on compromised patient populations with liver issues kidney issues, or in people who were using..
"metformin" Discussed on The Peter Attia Drive
"I I would say professionally I am really really obsessed with the question of what is the appropriate dose of caloric restriction and the frequency and of the molecules that mimic that so when you start to think about metformin rapamycin, especially and complete caloric restriction. So I've really lost interest in much of the junior stuff that gets close to there. So I sort of you that as filler when you're not fasting. Okay. Let me interrupt for second for my medical audience. A lot of them are gonna have no fucking clue. What you just said. So rapamycin metformin caloric restriction operating on the principle that a lot of studies in animals mammals show that some form of. Caloric restriction increases longevity through a series of mechanisms and there are molecules and receptors that might mimic or be at least partially responsible for the action of this caloric restriction in terms of promoting longevity. Rapamycin his one metformin might be another this. Sorry. I just wanted to make sure I understood I am dumb about this stuff. No. Thank you for clarifying that so molecules like metformin, which have Annetta -ffective activating, an enzyme called AMP, which is a nutrient sensing enzyme, it mimics something that you see when you're being deprived of calories. Conversely, rapamycin inhibits something called the mechanistic target of rapamycin. They very creative on the naming 'em tool m toward a great superhero. Sounds like a man Bagai skeletal should have been an excellent it should have been so rapamycin inhibits that tour, which is the central nutrient sensor for me, no acids. So again, when you inhibitory you were mimicking deprivation of amino acids, and then of course. There's just the old fashioned way to do it..
The good and bad of rapamycin
"Current obsession of the anti-ageing industry is rapamycin in the sixties group of Canadian researchers from Gil university set sail for Easter Island, especially inhabited speck of land two thousand miles off the coast of Chile the team collected hundreds of plant samples thousands of animal specimens and blood and saliva from the nine hundred forty nine residents of the island, but what they found buried in the dirt of Easter Island turned out to be the biggest fine of all us soil based bacteria that mystified scientists for the next fifty years, but is now known to create a special chemical known as rapamycin named after Easter island's native name Rapa Nui a growing body of research now shows that rapamycin can actually extend not just the average lifespan of mice as many drugs have already been shown to do. But also the maximum life span by up to thirty percent. But as with metformin, there's a dark side. To rapamycin part of the way it works by inhibiting excess activation of immune cells via pathway called 'em tour and up regulation of cellular cleanup mechanisms called a tough Aji. Now in addition of the tour pathway activated autocracy can indeed slow ageing and control issues like neurological diseases and genetic disorders, but as an immune system suppressor rapamycin his also able to increase risk of infectious diseases, diabetes and produce side effects, like impaired, wound healing, long talk city, an increased risk of cancer. But in the same way that there are natural compounds that can be used as alternative cement Forman. They're also natural compounds mimic rapamycin is able to do for health and longevity. One example is spurting sperm has been shown to induce similar benefits as rapamycin with no known side effects and also promotes longevity in yeast worms and mice wall sperm. Yes. Sperm is the most concentrated form of sperm being and guys stop in your wives. It also exists in high concentrations in foods, like wheat germ. Dark leafy greens, mushrooms, and smelly firm it to cheeses and of swallowing sperm or eating, stinky cheese. Just isn't your thing. Then you can simply also tap into the benefits of rapamycin by adopting a habit of intermittent fasting or regular periods of mild Cala restriction.
"metformin" Discussed on KTOK
"And I also am able to enjoy every aspect of what I do if I'm suing the FDA and going to court I enjoy that. If I'm looking at scientific research, I can three medical research papers all day long. If I'm looking to talk to our group at the church bet your life about new way. As that they may be able to slow the rate of aging, we do emphasize calorie restriction intermittent fasting. Most of what we advocate has nothing to do with commercial sale of anything. Which is why these accusations that drug companies like to make against our nonprofit group. It is ridiculous. We're out there. Trying to save lives. They're trying to sell them patented medicines. Some some people in this arena. This field have a problem with the term immortality. They don't like it. They prefer to talk about life extension. How do you feel about the term immortality? Will they don't understand it yet? They don't feel that you can go on indefinitely that there's some upper limit threshold. However, the journal nature two thousand seventeen published an article in what your group of highly respected scientists got together. And they said there is no upper limit to how long humans could look can live. In other words, we understand enough about why we age and why we generate all we have to do now is identify the solutions. What about the keep hearing about the length of the telomeres and how they are short. And every time cells divide, isn't that major? Isn't that the obstacle the ultimate obstacle? It's one obstacle. It's not the entire solution. But if we can identify way, we don't have that yet to lengthen telomeres, we could theoretically and able people to live a very long time. So since we don't know how yet no one really does some pretend to they're selling expensive product. But there is no validated way to lengthen telomeres. You can reduce your rate of telomere shortening by living healthy eating healthy foods. Fish oil can help a little bit calorie restriction that can all reduce the love it the amount of shortening. But actually, lengthen your telomeres, we need new technology. So in lieu of that we're looking at different medications. One of them's called metformin anti diabetic drug. It also happened to have anti aging properties. And most of our followers of the church perpetual life. They ask their doctor to prescribe the metformin whether they're a diabetic or not the data is compelling as far as adding healthy. Years to one's lifespan. So is idea that you want to extend your life long enough to the point where some of this technology. That's on the horizon, we'll catch up and and will arrive in time. You may be eighty five ninety by the time it arrives. But you'll go back. They would our strategy is stay alive long enough to benefit from what we believe are inevitable advances in the biomedical sciences were aging will be viewed as a relic of the past. Just what we look at the smallpox epidemics used to kill millions of people will they don't occur anymore. That disease has been eradicated men. Most other diseases, by the way, they used to kill people aren't around anymore. What we're suffering? Most drama is the genitive illnesses caused by us simply living too long. Let me get back to the church of perpetual life for a moment. And you have it's sort of nondenominational, you have Christians you have Jews you have Buddhists. Oh, absolutely. We have Thursday night services. Once a month where we have a respected scientists come in and talk, and I normally follow up with updates in our various human age reversal research projects at any given time. We have several studies going where we're trying drugs like metformin, another drug called data to nab drug called rapamycin, many many medications that you wouldn't want to take the way the FDA tell you to take them..
"metformin" Discussed on The Peter Attia Drive
"From prescription to usage to mortality exactly, and they're probably they don't need to d- to be the identify after mortality when you're dead. You're not prime. Any more K? So they did this study. So what they've done their four arms to the study. They came and took patients who are on Sufen Lereah twelve thousand patients. Okay. And they matched them to twelve thousand people without the Beatty's. Okay. Same pharmacies same doctors controlling for some other things. And of course, the people in sulfonate Maria had higher mortality than their control. You know? Right. Doubles. Of course, they had to be taking this oftener diabetes. So that's okay. Then they took seventy eight thousand people on myth for me and seventy eight thousand people who were non diabetic again matching them and the seventy eight thousand on metformin was met form in mono therapy monotherapy first line, right? And they watch their mortality so just to. Underline again, the people on metformin had diabetes control didn't have there are more bee's than the control. They also have more diseases than the control, but they had significant less mortality seventeen percent less mortality. In the mid forming group, and you know, the sulphonate Maria group was okay. So if you get less mortality with metformin when the setup is diabetes that really shows that mitt forming has a very important affect in Newman's as far as aging. What was the median dose of metformin in those populations? They were over thousand milligrams. That's it just a thousand milligrams. They intended more, but the average was about fifty meter about you know, I don't just fifteen hundred. Yeah. No thousand Manhattan story. They. This is a discussion there. I don't think they really could volley date the dose because an elegant thing to do if you have seventy eight thousand in your database is now stratified does. Absolutely. They taking five hundred thousand fifteen hundred two thousand they couldn't do that. And I really cannot answer you if you can get back to the data or not, I really don't know. The does the does which came from other studies. But you know, that's not the only thing we know about mid form that what was the what was the time course of that. By the way, do you know how years five years more tougher five years exposure to metformin or five years of prospective mortality following? No. It's will it's all it was all prospective study. Okay. It was all perspective study when they started. Okay. They went back. They looked at everybody on it for me. I'm asking is do we know how long the needed to be on metformin to achieve the Begnaud? We don't know. Okay. So we followed them for five years of mortality in a prospective cohort. But they could have been on metformin for five years or twenty five years. We don't know. No. It's newly it's newly prescribed for me. They were not more though. So we have normalized by duration. Lutely, absolutely, no. They haven't been on. It's forming before those are newly diagnosed type two diabetes so to near that's a pretty to be blunt goddamn staggering result. So my metformin moment nowhere near as dramatic as yours. Be basically came out of a research project. I did with two analysts in two thousand thirteen and I don't even remember what prompted the question. But there is a question we had internally about what was the benefit of metformin. Oh, now, I remember the quest. The question was was the relationship between hyperinsulinemia and breast cancer. This was the question we wanted to ask and as we dug and Doug, and Doug, and Doug and Doug something kept hitting us over the head over and over and over and over again, which was with or without diabetes with or without obesity with or without hyperinsulinemia any way you slice and dice the data of.
"metformin" Discussed on Ben Greenfield Fitness
"I don't take a lot of cleansing supplements per se for me, it's it's more wholefoods in then the coffee enema when I'm traveling. I use a suppository called cold glide men, and I'll use that one or two times a week long, traveling when I'm calling it's kind of like a suppository version of a coffee enema, you know, it's it's caffeine. I believe there's some glue dominion there. There's a few other compounds that will increase bio flow and they're expensive like eighty dollars for packet of ten or. Twelve or something like that. But you know, it's just you know, is expensive compared to you know, nickel coffee enema. But that's what I do wanna travel, and those are really the main things red sauna and coffee enema, and then just food. I mean, if you what in your house? That's beijing. There's a lot of sauna places coming popping up nowadays and AD right now, we're just glancing. I was just glancing NA DVD home doing you still running there. Yeah. Looks like your daddy. Very good. Yeah. Speaking of NASD, second eighty over here next. You've had. Toby Toby like all taking a step back before we talk on eighty. What are your we talk about a few things about increasing density, increasing, you know, longevity getting on the topic of longevity talked about rapamycin. I'm we haven't talked taken any rapamycin yet. No. I haven't taken it. I do eat some things that would be considered too. So have you heard of sperm dean before? Yes. Oh, sperm dean is found in a lot of fermented cheeses, some whole grain some from entered soy product, some dark leafy greens a few different seeds in knots. And it actually it's like almost like a food version of rapamycin. So all do things like that. Sometimes I do not drink my own sperm. No, I don't drink anyone sperm for that matter, nor do I have a whale that I- milk. But. Well, you know, I do have a whale that I milk. Just not know what you're thinking that joke fell flat. Anyways, though, the thing is that I do not use rapamycin. Like, I mentioned I'm I feel like I get enough off G M towards fasting. So absolutely taking metformin. No, I do not take metformin. I I like some of the data on foreman particularly with its ability to be able to reduce a little bit of the activity, the electron transport chain. So it kind of down regulate some metal conductivity, which is good for longevity. Not so good during athlete. Honestly. I don't like, I don't I don't think athletes benefit from Norman. So there's kind of a paradox there. The the other issues with with metformin would be some of the data that I've seen on increased risk for diabetes. I believe it may have been I don't of the studies in front of me, Alzheimer's or dementia or something like that. In patients were taking for a long time like twelve plus years regularly. There's there's some Japanese studies that just kinda kinda make me question. Whether or not I should be using that versus some of the natural ways to increase insulin sensitivity or to control glycemic variability, particularly one that you've just named bear Breen bitter melon extract, say lawn cinnamon apple cider vinegar, croq- Mun, Jen saying there's a lot of compounds that I just kind of work into my smoothies or my diet naturally. Probably the one I use the most bitter melon extract. I take two capsules of that every night before dinner before I eat those carbohydrates. So I get better partitioning in muscle and liver tissue. And so that my blood sugar lowers pretty quickly and kind of back into Kito says pretty quickly by the time. I go to bed after that evening carbohydrate read. So I use use things that are like mitt Forman. But not meant Forman. Right. Absolute. No that Japanese study that you're talking about, you know, there's a lot of studies starring kind of the opposite that metformin prevents. Yeah. There are prevents dementia. So all of these to be worked out NHL funded like one hundred million dollars to really study mid form. And the other one they need to look at is be twelve. There's some studies on twelve deficiencies, which of course, you can just be twelve. But yeah, it's yeah. It's just like I don't same Rapa might like mid form rapamycin. I know there's a lot of kind of people in the anti-ageing and longevity industry obsessing over those right now..
"metformin" Discussed on The Peter Attia Drive
"And then you know, there may be some benefit to that. So then one other place, you might wanna do it is if you live in Beijing or in Delhi pollution, increases inflammation. That's well known. It increases I'll six right? So those sort of places taking something that might decrease inflammation might might be helpful and how robust or the data on the immune modulating or inflammatory modulating benefits of metformin is that relatively than five strong as the other stuff. We've talked about his though, I think I think it's not damaging. There's not that many papers on it. It's you know to be determined. But it's something that we're thinking a lot about. As a mechanism of wide might have anti-aging properties. Well, look, speaking of anti-aging, let's go back to an idea because we sorta skirted around a little bit, obviously, one of the most popular types of supplements being offered on the market today. And there several of them are supplements that are aimed at delivering precursors to an e production. So again, the logic here is it's generally, well, regarded that sells can't take up free AD they have to make their own NASD. Josh and Rabinowitz and colleagues actually published a paper in June of this year, the demonstrated that the must be made in the site applause him not in the mitochondria, and it's actually transported from the site of plaza to the mighty Qendra and disarmament's mainly went to the liver for well. Even before that. But just to explain the logic. The logic is you can make an AD from our or an amend an existing equilibrium. If I'm not mistaken D-I-N-O-V-I-T-E pathway, which is from trip to fan. That's right as well. So by giving these precursors the cells can take those up and presumably make any D there and get more of that any d into the mitochondria where presumably it, I think the main argument if I'm not mistaken is actually not around the ET see the open transport chain, but more around having them as cofactors for the Cirta wins because the ser- to ins, of course, play these two roles of a settling DEA settling as Jean regulators. They're basically turning on and off chain. So I think the thinking is and again, I don't wanna speak out of turn. This is not my expertise, but more NASD should be a an important cofactor for cer- tunes, which are A N D dependent histone deacetylases aged X is at doing. Okay. I mean, that's the simplest hypothesis any levels decline in aging you lose chewing activity declines, which is not good, right? Because you lose the ability to. Control, easy to control, gene expression, either on boost the NFC as declining and you get a little bit increase such an activity, right, right? Which totally makes sense. Concisely Joshu is a great experiment, basically asked when you take these supplements where do they go and lot of it goes to the lever mentioning it makes its way into other tissues because there was a simple idea like is going to get into the brain easily. It's gonna go to your heart is going to go everywhere. And it's going to do exactly what you said, and therefore have all these magical properties. I think the place where any supplements admit form and start to cross talk is to places the first is it goes to deliver said might be having some metabolic health effects on the lever. Like metformin and similar to what metformin does potentially a hypothesis, by the way, the second one is I think he gets into immune cells. You think that N are let's just make it simple and talk about NRA because that's the preparation. That's more commercial value that NRA is being taken up. Immune cells attention, but wouldn't Josh his paper contradict that. I don't remember..
"metformin" Discussed on The Peter Attia Drive
"You can capitulate that. So why why is that is not clear? So I personally don't take any of these supplements. I think I've got a reasonable diets of like us. Why don't you take metformin? I will not take anything unless it's done any drug unless gone through a rigorous clinical trial. That's just my own bias now. Some people would say, okay, you're aging of or you're going to by the time. They do a trial. You may not be around. So why not take a chance, right? Other people argue this about any debugging pills. Right. That you should just any boost Bill by the time people do clinical trial and all of that will take years and years and years and for those people who are already. Later in life. You know, go ahead and take metformin. And so so putting your bias aside because inherent in your bias is an assumption, which is the risk of taking it is greater than the benefit of not taking it. So either you don't think the benefit is that much or you think the risk is may be greater than some do. And you're certainly somebody who's in a position to evaluate both. So tell me where it fails. Is it a not enough benefit or a too much risk problem? Probably not convinced about the how much benefit for someone like me who exercises, especially right. I mean, the best effect of metformin and still it's antibiotic affect and you, and I both know you lift weights, you run your active, you sort of mimic, the FEC some at form, and in many ways active his an PK you get the muscle benefits at. So why should I take the now you could say, well, maybe as anticancer prevent. Agent. Maybe the data as an anti-cancer will see where that pans added a large scale trial. It's gonna come out where you're not talking about tame. Are you not not tame his the anti-ageing Trump won't be done for another five years? Done. Yeah. I think so I think so, but if you're healthy and your active it's hard to see why you would take now. Of course, you could argue that as you age you've gotten some indication that things aren't working as well. And therefore, you should help take it as as a complement whatever loss you had may be your little diabetic. Maybe the one place. I I'm rethinking about metformin. A lot is whether it's so mild anti inflammatory agent. So in other words, it sort of keeps inflammation down all the time. And whether the fact of that over twenty thirty years, if you're an ir sort of in our forties, and that would have benefit twenty thirty years later, what's the mechanism by which we I'm glad you brought that up because I forgot to revisit and you know, one of my favorite trials the Cantos trial where they basically targeted. I'll one beta of pro inflammatory agent directly in. Didn't change the lipid profile, but it reduced cardio exactly's. Which tells you that inflammation is? Oh, yeah. When there's going to be another trial announced very soon that I think will show similar results using load of methotrexate. Of course, I could be proved wrong. And maybe that's not I don't know what the trial's gonna show, but that's hypothesis. Let's take a fact just for the sake of time that lowering inflammation has wonderful benefits. What's the mechanism by which metformin will reduce inflammation? So we think that reactive oxygen species is the free radicals can serve a signaling molecules to activate side kinds and metformin by inhibiting the respiratory chain. Which is a major site of those reactive oxygen species. Decreases reactive oxygen species and decreases side kind and production and again a little bit right? It's not it's a week and hit of the respiratory chain. So if you not got the respiratory chain completely. You can never turn on the bigger probably. A bigger bomb you get bacterial infection cetera. So this is just again dampening it enough that if you get an infection can still respond, but describing the set point where you're at a little bit lower, and whether that has good effects over thirty years twenty years of keeping inflammation down..
"metformin" Discussed on The Peter Attia Drive
"So do we believe that that is the vehicle through which that transaction is becoming clinically relevant. Right. Or do we believe that somehow inhibiting complex one in a cancer cell is dilatory is to a cancer? So I think both mechanisms. Ends are are working in concert. And so clearly metformin as you pointed out Laura glucose, insulin. I Jeff and insulin and idea in certain tumors can be a mighty John something that promotes cancer proliferated seems that about two-thirds of cancer seem sensitive insulin idea. So so that mechanism is still in play. But what we showed is equally plausible for cancers that have transporters of metformin, and they're called organic cat and transporters not every tumor has it. And that's what metformin dozen were clinically as a great anticancer agent because lots of tumors don't have them. But if they do have them, they'll take him up inhibit complex one and that will have anticancer facts right into the cancer cell. The reason that's important. Again, is our work genetically shown when we knock out complex one or three tumors don't grow if we give form and we can show his anticancer affects. Complex in addition. So that's right. Then could we design complex when inhibitors? Let me ask you a question sorted eruption of when you and what you just a moment ago when you inhibit complex three and tumors, don't grow. That's you have to inhibit complex three in a tumor cell or in a hypothesis introduce mysel- and the have had a sites are normal. Well, the way we these genetically engineered where the complex threes are one is only lost in the cancer cell. So this is the next experiment. You have to do you have to be able to separate. Listen to me telling you, the experiment. You have to do. It's important. I think to separate out how much of this tumor specific verses global metabolic, and the reason is the -plication are profound not just for other therapeutics. But frankly for a more fundamental question was what the hell should people be eating, right? If in as much as you believe that nutrition can impact cancer therapy. The answer to this question is relevant. So we have now generated a m- unpublished Orrick can talk about unpublished worked on the podcast. I don't know. It depends. When's that gonna be public? I feel but it doesn't matter. So we we've generated a mouse that contains the yeast complex one in the liver. Okay. So that this is this is where you'll be able to do the experiment because there's really a two by two that needs to be done here. I think they're both working in concert. But the major thing is and then metformin may have some anticancer affects but what is led to? Of because of our work another's is the idea that maybe we should target might Qendra. In addition for cancer therapy. Now, that's a little counter intuitive. Yeah. So this is again, you know, I mean, I'm sure the audience is like everything this guy says contrary, and so let's just turn them off now, but you know, our data's very clear might Conrail are necessary might condo function is necessary for tumor, Janice. All right. So let's take a step back. And explain to the listener who hasn't heard what you just said why that is gonna rock some people's world at think you've talked about some other podcasts. So there was a observation made in the nineteen twenties by gentlemen, name auto Warburg, one of the giants and active trained, Hans crabs for example. He won a Nobel prize in nineteen thirty one or thirty two basically for discovering the an enzyme for us ration-. And so he loved measuring respiration. But he did it in cancer. Did it in normal cells any notice a cancer cells? Those at least on the benchtop not in vivo, not in a real tumor not in humans just taking an tissues out that they made a lot of lactate it and they consume much oxygen. And it is this didn't make sense to him because he's like there's plenty of oxygen. Why should do that? And let him to think about perhaps that may be the mighty conjure being suppressed and cancer are and this led to this long long long dogma that very elegant sympathy normal cells use a lot of MIDA Condron might Akon delete t p very little glycolysis..
"metformin" Discussed on The Peter Attia Drive
"Did you assess the effect in that setting on AM PK how much? Was an PK act activity up regulated ESO. We don't think the anticancer affects do an PK fair. But do you have an answer to the question? Do you know what happened setting? So we they should go down a little bit. But not off. Yeah. Yeah. So we didn't we didn't think about that. We looked at other properties. Like any h ratios, which we think is the more than how much did the Aideed. So we could show clearly shut it down. Yeah. Yeah. Would metformin you could decrease it when the yeast complex, you can recover that ratio the AD two any ratio and all the metabolism IX that go with it. So when you inhibit complex one by metformin, the T cycle slows down, and you can capture that by mass spec. Classic. What's called metabolism? Which is basically looking at metabolite profiling, and and what's cool about that is there's a very good scientist give him a shot. Jason look acelle Duke University. Again, kind of a younger version of Joshua lists. And what Jason? Hooked up with the university of Chicago Varian cancer, very famous ovarian cancer, doctor slang land, fellow Irish from that point, and they were giving that form into patients, and then they gave these biopsies to Jason and Jason could detect t- cycle. He could he could ask two questions did them at form and get actually do the tumor. Yes. Yes. And the second one was if our mechanism of complex one that we showed is correct. Then the T cycle metabolites should be altered. And they wore in those human cancer cell metabolism paper. You can people can licking your is that our. So we published our metformin paper and fourteen I think Jason's papers in oh sixteen. I think we did the simple elegant experiment, which shows the necessity of complex one innovation. But I think Jason did the as close as you can of that mechanism is correct and the humans. He did the best. The next best thing you could do which is show that t- cycles. Capitalistic -ly. It begs a question is that working because paddock glucose output is going down and insulin is going down and presumably is going down. If insulin is going down. Jeff be three should go up. Insulin should go down, even if there's no change in amino acids, those things should all if you had a little like on off. Switch more glucose or less less as better more insulin or less less as better more, more or less less for all for cancer. All of those things would move in the right direction. If it had glucose output went down..
"metformin" Discussed on The Peter Attia Drive
"Complex one? In addition. So how would you test that will? It's hard to have a complex one knockout exacerbates incompatible with life. So that would be the obvious answer that doubts. Well, so I would argue for any drug the best experiment is to make a mutant of that particular complex. That doesn't bind metformin bingo. So I'm not a good structural biologist. But we did something really clever. We noticed that the yeast has a protein single protein, which will catalyze any to any. Okay. What complex one does exactly it doesn't proton pump which means it doesn't contribute to ATP generation, but we have engineered cells and mice to get rid of complex one and put back this yeast. Complex one which is refractory to metformin, but asked this question, but the FINA type of that cell is what how what is it? What is its electron transport teen doing if it's basically losing anything accomplishable, basically complex two through five still can't work, not Ana? So what this protein is yeast complex one home along a single poll. It does everything except the electron transport. So does the electron transport or it doesn't do the proton pump? Yeah. Okay. Got it. So you basically reduced your battery charge a little bit a little you have an interrupted the electron transport. Oh, that's elegant. Thank you, very elegant clever. Yeah. This the geeky ass- moment right now is like that is. As one of those things clever, very clever. Right. So you put the so the first experiment. We did is we did the cancer experiment. So people had noticed at least in laboratory settings if you give it Forman you can reduce tumor burden in mice. You know, the classic sort of experiments, so we'll be did is we took those cancer cells and put back the yeast version, but I wanna say something out before you say, you tell us what happened which is in fairness. Yeah. And we did a lit review of this in two thousand fourteen so it's very dated. I know what's going to happen. A bunch of people are going to say Peter, can you please link to it to internal document. I may link to what I gotta go back, and look and see how ridiculous it is. But to now four years old, but it was not clear at the time of this review if the anti-cancer benefits, which seemed real were either due to the inhibition of complex one or do some other mechanism by which AM PK was activated. And to my knowledge that is still not clear. It's clear you're gonna sell me. It's clear for cancer. Okay. Keep going, so I'll tell you the experiment and cancers, and then I'll tell you for diabetes as main effect ended. I think that's still up in the air. Okay. For inflammation. I think there's some strong evidence complex as well. So the simple experiment. We did was we said let's put back. In cancer cells that human cancer cells, we put in a mouse and mid grows rapidly. Right. And you can do it and colon cancer, breast cancer, lung cancer cells typical cancer, biology experiments, and we put the yeast complex one in and okay. So when the yeast complex one is not their metformin decreases tumor burden if the yeast complex one is there it does metformin can bind to eight. So the mighty congress still continues to work and Walla the tumors. Don't go down. So what you demonstrated through that experiment? Assuming were not being fooled by some other artifact, which is always possible is that when you prevent metformin from this one particular issue, which is binding complex one in hibbing that it's anti cancer properties cease to exist. Yeah..
"metformin" Discussed on The Peter Attia Drive
"Because the the first thing is the one, I guess we would understand the most which is you've alluded to this. But I just want Oreo the listener a little bit. The mitochondria said of these five complexes each of them have multiple sub units. And what happens is these are basically the chains between the inner mitochondrial membrane in the inner part of the mitochondria where these reducing agents like an and D H an EP ADP are transferring the electrons and building up that gradient. So by the time, you get to the end of this thing, you've got so much potential energy and all of those electrons, and you run that transfer of phosphates from ADP ATP and everybody wins the game. So this is essential this electron transport chain like messing with that. Probably not a good idea metformin comes along, and it blocks complex one now doesn't block it completely blocks partially now complex one the chemical reaction that's occurring on the inner part of the mitochondria. I inner part of the mitochondria is that transfer of any D H two AD that we're gonna come back to any D. But for totally unrelated reasons, when you do that, what is that telling the cell by inhibiting that the cells readout is what physiologically three things I that battery that you're talking that generates to make ATP a less charge less charged. So then what happens ATP goes down ADP goes up. There's a kindness called aim PK kindness. Amp became his the MP kind Hase and him PK. It gets activated. And in part that enzyme is activated is a signal that says, I'm not fed enough, right mate. And one of the major things that does is it promotes Tuffy, my favorite your favorite Ord. Right. It's one of the dominant things at does. That's why when AMP K gets activated. We get another little benefit allow rapamycin affect on 'em tour. Which is it says, hey, man, I'm telling you from Gleich Olympic standpoint or an ox fos standpoint. Energy is low shut things down. Right nutrients are scarce, right? And this is happening in the liver. So for example, glucose production that happens in the liver starts to shutdown and part or Leiper Genesis making new lipids in the liver. And that's why like fatty leveraged might have some benefits. It's so that's one. The other thing is which alluded to any d to any h so any any right making a d so that ratio also gets. Admitted back to the cell, and what's that? How does the low end eat any D H, get transmitted? So the biggest one is lactate to pyre Vate. Right. It's a lactate to pyre Vate. It is a is a source of soldiers many ways you can feed pirates. We talked about glucose to pirate. Right. So glucose to pyre Vate uses any d to any h and usually pyre avait to lactate will go. Go ahead. And explain why during. So I have to tell you. And I think we're both because we're not on camera one of the difficulties of really getting into the nitty gritty of metabolism is. It's so much easier to write it in diagrams. Right. When you ride in the diagram simplistic ways is just like easier. It's just easier. Right. I mean, it's knobs laughing at me because I'm closing my eyes drawing, and as I'm saying it, you know, any Dino's the any. I mean, I'm getting confused. I promise you this. This'll be one of those episodes where the the show notes will be hand because we'll have all the diagrams. Well, they can actually you know, they can really do. Right. There's a book I've heard. Yeah. There's a book you wanna give plug this plot. So for all you metabolite lovers out there Naveh wrote a book called navigating metabolism. Want wa and I actually picked up a copy as soon as we got back from Easter Island..
"metformin" Discussed on The Peter Attia Drive
"We were joking around when we read Easter Island that our next trip. She needs to be to France, a Ducey the goats to suit the to see the lilac where from where was not in France where they were that metformin came from so two sentences on how metformin was discovered dead. They notice these. Goats that were eating pretty. I love this lovely stories. Let you know yesterday. I was talking to Ted Schafer goats as well. So I loved that the to northwestern guys only doesn't finalize goats are going to be these ones. So what's interesting on metformin? I think is it got approved as an antibiotic drug people went back and looked at people who are taking their for diabetes epidemiologically found that there was a lower rates of prostate cancer. So you probably talking to Ted shave about this. Right. So and Lauren breast cancer. So then people started investigating as an anticancer drug, then some people starting noticing. Wow, it has and flammability affects as I've talked to a friend David SABA, teeny. And that is an interesting the rapamycin and flam Metairie somewhat anticancer promotes metabolic health. So how does that all work? Well, he'll argue it's all an Tor as it. Well, I would argue Huck and metformin do three. Very disparate effects anti-diabetic anticancer anti-inflammatory, just like rapamycin. Would it must be hitting a node? That's very important for the cell. So metformin doesn't hit 'em Tor. Does though they PK does the AM PK, but that's due to I hitting my condo complex one. And then activating Ambi K, which can repress 'em Tor. But the analogy that I'm using basically MTA we knows a master of the universe. So might have gone, right? So if you inhibit might Qendra not to the point where he caused talk city just enough you can activate a variety of pathways which could promote have anticancer antibiotic and flam affects now metformin somewhat tissue specific, it seems to have a preference for the hypothesis so gets into the kidney and the liver. I think we've talked about this before about m-tall. Right. So m tower and rapamycin why would you use rapamycin on my getting everywhere? Think they've are getting you argued wouldn't it be great if you can get metformin to go to the liver to deliver. But not to the skeletal muscle. So metformin already has a little bit of that property. It only gets selectively into it doesn't get into the heart that well. Right. So it doesn't affect your heart function, not directly it affects your liver your kidney, it actually Cumulus quite a bit in the guts and some people get diarrhea with metformin. And so some people think metformin is affecting your micro by on. And there's a huge literature now thinking that some of how it's having its effects. So I think the liver citing there's three places that are important the liver and that can account for some of shutting down the glucose production and having the so-called anti-diabetic affect the colon and affecting your micro by on, and I think immune cells, that's the big one. We were missing. That's the one that. I'm very fascinated. Another was met form and getting into your macrophages, or you're probably maybe not your teeth cells. But at least your some of your. Immune cells that might be causing high levels of inflammation. And in a few look at three drugs that people like to use aspirin metformin and statins globally us combined. Maybe what a billion people probably more probably more the van diagram where they all overlap is inflammation. So let's talk a little bit about the anti-inflammatory properties of metformin..
"metformin" Discussed on The World Transformed
"That as they as they looked at mortality rates for folks who had diabetes who took metformin versus those who didn't they said all these folks are doing a lot better than the people who didn't take the drug and in a turned out they weren't just doing better were diabetes was concerned they were doing better were almost everything is concerned right that right i mean they were they were doing better than people without diabetes or has he has i think that turkey reorganize that that really within tax they were yeah they were doing better than people without diabetes were comes to things like cardio cardiovascular disease numerous types of cancer glaucoma suddenly people who took metformin we're doing better than the general population on all of these to the point where people start wondering wall is this the fountain of youth is this the the miracle cure for everything probably not quite that right if if if it had turned out to be that i think we would have seen it sooner right it would have occurred to a sooner that that's what was happening with metformin but it's positive enough it's it's good enough that i think we will see people taking it for this reason in fact i believe that has already started and malia it's it started it started there are people that the and uh i mean i i'm i'm seriously considering talking to my doctor right i mean uh you know to say no i'm interested in this so you know for the dust to uh you know protect against pre dog prediabetes that sort of thing on a metre don't get don't become daughter and writer see of that'll pass muster with the uh with a doctor i will give it a truck i was actually thinking about one of my doctor and saying look i'm going to start taking this stuff you wanna prescriber tomato after by agree market off the internet.
"metformin" Discussed on The Healthy Moms Podcast
"With that we want to think about two things nutrition becomes hugely attrition becomes can of the thing that will really move the needle for you on the body changed exercises grade again exercise in and of itself as an metformin hit it is insulin sensitising it signalled your muscles to take in glucose during when you're exercising it actually can poll glucose into your muscle without insulin so it's a great way to kinda sidestepped this insulin resistance aspect and really get some good fuel into their but we do put on muscle a little bit easier so we can often tolerate a little bit more exercise so sometimes lots of walking in addition to good strength training and even some traditional like steadystate cardio which is not that effective for most people who are trying to lose weight more exercise them better if you are simona p c o s antidote me in you know running yourself into the ground but getting a lot of activity lots of walking lots of just being active throughout the day in a pretty regular training schedule in addition to the nutrition piece of it and again really honing what works for you in terms of your carbohydrate tolerance but also inflammation is a huge piece of the pc us and the insulin resistance problem but inflammation is a huge piece of this so inflammatory foods and poor fats in our diet is really really important for this group of women so looking at any food sensitivities obviously starting with a good paleo template is a great baseline place to start on because it gets out a lot of the most inflammatory egregious offenders you may have some issues beyond that making sure we don't need a lot of processed foods with bad fats which come in and processed foods salad dressings all of those sorts of things and getting lots of healthy omega3s from grassfed meat and fish and also.
"metformin" Discussed on Ben Greenfield Fitness
"And this article is about this metformin stuff which i did not know this comes from a plant known as french lilac and also goats ruehe and it it's been around since the sixteen hundreds as a treatment for diabetes and as like this know the this sort of longevity tonic and what this article goes into is this idea that that all of these folks you know from over a dozen of the people and tim ferriss his book tools of titans you know all the billionaires an icons in world class performance that book to craig venter who heads up you know the human longevity a project do and they're they're sequencing the entire human dna to rake kerr's while the guy of of singularity faymann ned david who cofounded a silicon valley start a called unity biotechnology which is basically like an antiageing drug creation facility they all altake metformin and it it perhaps one of the reasons for that is based on something that a dr peter attiyah has told me on on this podcast before and also what he's written about on the show before that and that is that one of the keys to longevity is keeping your blood sugar levels low and reducing rapid fluctuations in blood sugar levels but there's a whole lot more that metformin does in addition to lowering blood glucose and this article not necessarily good well i'm guessing well with this article goes into is a lot of good and the reason that's that it's the darling of the antiageing industry right now and why so many people are are either know purchasing it online which you can do pretty easily on online pharmacies or the dark web or whatever or you can just simply get a prescription from a physician or a net akhter friend or or whatever but um i am working and i'm going to publish this coming monday for those of you who are listening in on my own take on this because i've been taking an antiageing capsule that is very similar to metformin in terms of reducing postprandial blood glucose for the past three years ethic to capsules of it prior to dinner.