How To Replace Exercise, Heat, Cold & Fasting With Pharmaceuticals WARNING: Proceed At Your Own Risk

If you are getting older and your visceral fat is building up, that's actually extremely bad for you. It's a bad sign of near death. So what pioglitazone does is it mobilizes your visceral fat and moves it into subcutaneous compartments where, number one, you look more youthful, but in fact, you're reducing cause of death. So pioglitazone is just an amazing, amazing drug.

Is it a new drug? Do a lot of people know about this?

No, it's not a new drug at all.

It has been five years since I've interviewed today's podcast guests, and I'm very surprised I took this long to get her back on because the first show that we did was epic. She. She broke my podcast Internet talking about her book, the Kaufman Protocol. It's Sandy Kaufman. And she is not just a physician and an anesthesiologist, but as you'll learn if you heard our first interview or today's interview, she's kind of like this relentless, you know, almost like biohacker who comes up with unique pharmaceutical solutions for solving different problems and kind of blends medicine with natural living and also is a real expert in anti aging and longevity. She has a master's degree from UConn, and then she got her medical degree at University of Maryland. She did a residency fellowship at Johns Hopkins. And I run into Sandy here and there at different places across the globe, including some fantastic conferences. And she's always somebody who people listen to because she's got some really unique takes on a lot of the stuff that we love to talk about on this show. So, by the way, her book is called the Kaufman Protocol. It is fully updated. I'll link to it in the show notes. And the shownotes are going to be at BenGreenfieldLife.com Pharma hacks. Pharma hacks. Sandy, welcome to the show.

Great to be here. This is going to be fun.

I know. Remember we were at that conference in the mountains, nosebleed country somewhere. Where were we? I forget, where were we? We were at Colorado.

Sundance.

Oh, yeah, Sundance. Sundance. We're at this, like, private longevity conference, and you and I were sitting at dinner and we were talking about exercise and sauna and cold and red light therapy and all these things that people do. And you said, well, you know, I travel a lot and I've got a hack for a lot of that stuff that saves me a lot of time. And you basically think the way you phrase it was, you said something like, there's a Drug for just about everything that people do to optimize health with those type of methods these days.

I think that's exactly what I said. Yeah.

And then I think what I said, not to rehash our entire conversation, was we should do a podcast about that.

And here we are.

Yeah, here we are. Okay, so what actually got you thinking about this in the first place? Was it just, hey, I'm busy. I don't have time to sit for 40 minutes in a sauna or go to the gym for an hour or I hate cold plunges, or. What actually got you down this path of pharmaceutical alternatives to popular biohacks?

Well, as you said in the intro, I'm a physician. I'm an anesthesiologist. So what I do mostly all day is deal with pharmaceuticals. And pharmaceuticals are very clean molecules. We know who made them. We know exactly what they do. And so when you start studying these molecules, you figure out, like, what they actually do for your cells. So if you trace everything back to cellular optimization, you'll find that the behaviors of these molecules trigger the exact same things that a lot of these very popular activities do. So, whereas I'm not against sitting in a sauna, it feels great. When you boil it down, it's the same mechanism. So if you're busy, it's just easier.

Yeah. And I know you have kind of a whole list of things that you do, but before we even dive into that, I just know a lot of people right off the bat are thinking, well, wait, there's a difference between climbing Mount Everest and getting dropped off by a helicopter on the top of Mount Everest. And if you're going to tell me some drug simulates me, you know, focusing and meditating and breathing my way and counting my way through a sauna session, surely I'm going to miss out on some of the character development.

Well, in no way can I develop anyone's character. If you have poor character, that I can't help you, What I can do is recommend systems to, again, cellular optimization.

Are you saying that there is a substitute for hard work, that there's a shortcut, or that there is a time and a place when you could use something to simulate what you might be getting through the hard work, Blood, sweat, and tears.

I. I think they're just very complimentary. Sometimes you have time for these things, and sometimes you don't. And.

There has to be a way to sort of replicate things. You know, I love exercise. I'm a junkie. Just like, you know, probably most of your followers, I run I lift, I swim, I rock climb, but I travel a ton, so I just can't always get to those things. And I'm certainly not going to pull a sauna out of my suitcase in a hotel room.

So, you know, I think they're going to work hand in hand, especially for people that are on the road a bit or just, you know, it's just easier sometimes people have busy jobs, busy lives. It's just going to augment what people are doing already.

Okay, got it. And then, by the way, I'm going to buy the website, suitcasesana.com you just give me a great business idea. The other thing, just to get a lot of these, these precursors out of the way is I know you're going to describe a lot of these pharmaceuticals and drugs. And I also know that people are likely going to wonder, well, my doctor's never going to prescribe me this stuff. Like, like my doctor is not going to give me, you know, whatever, you know, pigalatazone or whatever that one is for autophagy and prescribe that to me just because I can't get in the sauna or exercise or something like that.

That, that is true. So it depends on the physician to which you are going. Typical primary care folks are going to look at this stuff and go, yeah, that, that's ridiculous. It's, it's, it's, you know, unclear, unheard of, whatever. However, there are some physicians that will do it. For example, I do, and I see patients in Hollywood, Florida, and, and I will prescribe it as well. There are, you know, ways to get it on the Internet and I don't want to be seen as suggesting that people do things illegally and. But there are absolute ways to get medications easily, safely, as long as people do it sort of in a safe way. And some of the drugs I talk about are completely and utterly safe. And some of the other ones need a little bit of guidance.

Right, right. No, I've never bought laboratory research chemicals not safe for human consumption off Sigma Aldrich, but people do that, I hear. So when we're talking about, let's say, autophagy. Right. One common thing that people do to enhance autophagy is fast. You know, it modulates the MK and the MTOR pathways, and it's one of the ways that we see potential increases in longevity in yeast, fruit fly, other organisms. Some would argue that a big part of it is the calorie restriction, not the compressed feeding window. But nonetheless, there's some autophagy that takes place via that and some of these other things that people do that are hormetic stressors, what would you use as some type of agonist for something like that?

That's actually really funny. I thought we were going to do it the other way around. From top to bottom. You're starting at the bottom. So in order to activate autophagy, you need to tell your body that you have fewer calories available. So you need to activate AMP kinase. Right. Or deactivate mtor. There are several medications that do this. The most infamous, of course, is metformin. A lot of longevity folks are on metformin, so that's an easy one to start with. But several other ones do it too. Pigletazone does it. Lithium does it. So autophagy is actually a pretty easy category to hit.

What was that? Pigletazone. Describe that one to me.

So. So Pioglitazone is a really interesting drug. It is sold as a diabetic drug. What it is is a Parr gamma activator. What is that, we ask. So it basically controls glucose metabolism, but it also has some. Some alpha activity. And what it does is several things. So number one, it lowers your glucose levels. Number two, in your mitochondria, it activates your PCG1 alpha, which is really quite useful. One of the most important things I think that it does is it actually mobilizes your visceral fat. So if you are getting older and your visceral fat is building up, that's actually extremely bad for you. It's a bad sign of, you know, near death. So what Pigletasone does is it mobilizes your visceral fat and moves it into subcutaneous compartments where, number one, you look more youthful, but in fact, you're reducing cause of death. So Pioglitazone is just an amazing, amazing drug.

Would you say that Pioglitazone would trump metformin when it comes to a lot of these autophagy and MTOR modulating mechanisms?

I would actually, yeah.

Is it a new drug? Do a lot of people know about this?

No, it's not a new drug at all. Some people don't like it because it will put an extra pound on you. So if you're fat, you get a whiff fatter. But if you are thin, it doesn't really do that. It has a few other cool things up its. Up its. Up its sleeve, for example, it activates Clotho. Very few things do that. And that. That's sort of like a cool thing that it does. And because one of the other things is because it reduces glucose. It actually also inhibits age formation. So advanced glycation end production. So it hits many, many reasons or categories of aging.

What's the mechanism of action via which you would gain fat?

Because it's sort of mucking around you with your P A R R alpha activity.

So basically, your body has a choice. Am I going to use fats or am I going to use glucose?

Oh, I see. So you're burning more glucose and thus you're dipping into less of your fat stores.

That is correct. But what it does do to the fat is it redistributes it.

Okay. You also mentioned that with pioglitazone, it can upregulate the Clotho pathways. I've talked about Cloth a little bit on the show, but can you explain why that would be beneficial?

So, to be perfectly honest, we don't exactly know what Clotho does, but it's demonstrated that at least in kidney cells, if you have a plethora of it around your cells, you do significantly better. A lot of people are trying to figure out exactly why that is. Everyone's trying to upregulate your Clotho, but in terms of actual specific cellular mechanisms, we don't really know yet.

It has an effect on cognition, too, doesn't it?

It does. It has positive effects everywhere. The highest levels are in your kidney, but it does. It gets everywhere. And there's an absolute correlation between higher levels and just cellular health. But again, in terms of absolute specific mechanisms of action, we don't know.

Yeah. When I interviewed Dr. Adil Khan a few months ago, he was even looking into gene therapy, I think, by the company Mini Circle for Clotho, that I. I don't know if it's been approved or even released yet, but apparently that's one of the gene therapy targets that should be rolling out, I would imagine, in the next year for Clotho. What do you think about that, that whole realm of gene therapy?

I have to say I'm a little skeptical. I like the idea that we can titrate medications or titrate the input of things, because we don't actually know if you know. Sometimes too much of a good thing is not necessarily good. And once you put something in your genetic makeup, there's no taking it back.

Yeah. Unless you use the reversible antibiotic, which apparently can do it.

Well, so they say. Right. But, you know, Liz Parrish is very much into gene therapy, and I think it does have a lot of good things about it. As for myself and as for patients that I speak with, I Think we're not quite ready for that yet. Which is why I look pharmaceuticals that we're known, they're trusted, we know what the half life is. You can either give it or not give it, titrate accordingly. I think it's a little bit safer.

Right. The difficulty of the approval process automatically or introduces a bit of a gating and vetting mechanism with a pharmaceutical, that's for sure. Okay, so, so your sauna in a suitcase, you can't pack your sauna in a suitcase. You get to a hotel or you're traveling and you want to get the benefits of, let's say, you know, the heat shock proteins and you know the things that sauna does for you. What's your drug of choice?

Oh, so this is a great one. I love this one. So this is a drug called cell backs S E L B E X and it's been FDA approved in Japan for drug induced gastritis.

And oddly enough it up, it upregulates heat shock proteins and that's pretty much all it does. So it's, it's really remarkable because there have been some studies in early Alzheimer's demonstrating that if you are on Celvax, you just do significantly better. Because Alzheimer's is a disease of misfolding of proteins and if you can refold them, are you just going to do significantly better? Therefore, on top of not getting drug induced gastritis from all the drugs that I'm on, I am readily up regulating all of my heat shock proteins.

Oh, so so these other drug. Well explain what drug induced gastritis is, because you make a good point. If you're using all these things, there might be effects on your gastrointestinal system that you want to avoid.

No. Correct. So anyone that takes a variety of medications knows that sometimes people say, oh, it just doesn't sit in my stomach. Well, right, because it does. It goes to a stomach, sits on the lining where it has to sort of have these drugs absorbed and sometimes that causes a bit of inflammation which we call gastritis. Right. Because it's in the gastric area and that just can be extremely annoying. You know, people perceive it as heartburn, abdominal pain, etc. So this drug is specifically for drug induced gastritis, which I find horribly ironic. Right. So I get to pop it into my pill stack and it helps me in two regards.

So is, is the mechanism of action by which it would inhibit gastritis based on the actual production of heat shock proteins or is that just kind of a bonus side effect that gives you the the sauna without a sauna, it's.

The same effect based in two different tissues. So but because heat shock protein is going to help with protein creation and proteostasis, which is basically getting destroyed by the inflammatory process of drugs sitting in your stomach. So it's the same process in a different organ system.

So when you see these studies out of Finland that show that regular use of asana four to five times a week results in, particularly in men who are studied there, remarkable decrease in risk of dementia and Alzheimer's. Is that via this same heat shock protein like effect that Celbex is simulating?

Absolutely, absolutely. Because Alzheimer's is, as I said, it's a protein misfolding disease. That's what amyloid is. And if you can refold these proteins, then you don't get as much cell dysfunction and therefore the dementia is less pronounced or even reversed.

So if you had a high genetic risk for something like Alzheimer's or dementia, maybe you didn't have access to a sauna, you couldn't afford a sauna, you're traveling and can't use a sauna or you're even intolerant to a sauna, maybe you're claustrophobic or you freak out or you can't stand the heat or whatever. Cellbecks could be a good choice.

Oh, it absolutely is. And there are zero side effects. Zero side effects. It is an incredible, incredible medication and I would, I would even say use it in addition to the sauna because there, there's no ramification of over upregulating your heat shock proteins.

Have you ever used it? And because of the upregulation of these heat shock proteins, found that a sauna becomes more intense or uncomfortable or does it not cause anything like that?

No, you would never know because it's not affecting the temperature of your body at all. Obviously heat shock proteins are being upregulated because you are in an area that is hot. Right. By definition, that's what happens. Why does that happen? Because if you think about the molecular basis of proteins, when you heat them up, they lose their three dimensional structure, right. They fall apart and then a chaperone has to come and put the molecule back together so that the protein does what it's supposed to do. But it's based on the stress of temperature. Right? Cellbex isn't based on the stress of temperature. There's no temperature elevation whatsoever. It just upregulates the chaperones. So you're not going to see any interaction between the two systems. Physically, you're only going to see it on a molecular basis.

And arguably if you had upregulated heat shock protein density due to cellbex use, you would be able to withstand heat a little bit better. Like if your friends had challenged you to see who can last the longest time in a sweat lodge, that might be your illegal performance enhancing drug of choice.

I don't know if that's true. Feel free to try it because I.

Don'T think that you proceed at your own risk.

I don't think you can perceive that your proteins are unfolding.

Well, I was more referring to the fact that I believe one effect of higher number of heat shock proteins would be increased ability to be able to withstand temperature stress.

I don't know why people get up and leave the sauna. Is it dehydration? Is it electrolyte deficiency? Is it just an elevated temperature that's causing an inflammatory process? I actually don't know what causes people to get up and leave. I don't think that you can actually physically sense your proteins unfolding because that would be pretty damn impressive.

Yeah, yeah, that's a good point. You don't have to have some Jedi skills I would imagine.

You know, put an IV and be hydrated, drink a lot of electrolytes, take an anti inflammatory and then I bet you can do it.

Yeah, yeah, I bet. One of the reasons people get out of the sauna is very similar to the so called central governor mechanism that causes people in say an ironman triathlon or a marathon to bonk. Even when adequate carbohydrates are present, the body kind of, or the brain kind of shuts down the body because it perceives stress that could in some way become pretty deleterious. Right. Like you've been going for eight hours now, you better just stop and you get central nervous system fatigue due to that. Central governor Tim Noakes I think has done some writing on this. So I think probably that's, that's one of the reasons people tap out in the sauna. But anyway, so, so cellbacks. That's an interesting one. You just mentioned inflammation. I know there's a lot of anti inflammatories out there. There's also a lot of protocols that people do to lower inflammation such as cold therapy or red light therapy or something like that. What would you say from a recovery or an anti inflammatory or even like an oxidative stress reduction type of strategy would be pharmaceutical?

Oh, that's a good question. So the best one is going to be one that no one's ever going to take.

Well, I take it. So hydralazine.

Hydralazine.

Okay, you're gonna love this one. So hydralazine is a medication that people would give you if you walked into the emergency room with very elevated blood pressure. Okay. So it is an arterial vasodilator. So basically it will emergently drop your blood pressure.

Therefore, it takes a while to build up into your system to actually be able to take it safely. A lot of people are.

So are we talking about, like, more powerful than something like Viagra or sildenafil?

So that is a completely different drug class and, and we can get to those. But the interesting thing about hydralazine is the hydrazine molecule aspect of it. And the reason I take it is several fold. So, number one, it is a very potent free radical scavenger in terms of free radicalized oxygen, but it's also one of the most potent reactive nitrogen scavengers. And by blocking those pathways, you're going to block basically a lot of the inflammatory processes. So that's kind of really cool. The other thing the hydralazine or the hydroxy hydrazine molecule does, it's one of the most powerful transglycosylating agents. So if you eat glucose, and I'm sure you don't, but I'm a junk food junkie, when you eat glucose, it is attracted to very specific amino acids and nucleic acids. And when it sits on, becomes something called an age, which is an advanced glycation end product. So the glucose sits there and it's like six non enzymatic steps. The first three are reversible and the last three are not. And the idea is, during the period that it's reversible, if you put a molecule that's more attractive to the glucose, it'll jump ship. And then you're. You just rescued your tissues. So the hydrazine molecule is extremely attractive to a glucose molecule. So it falls under the transglycosylating sort of category. And it's been demonstrated that if you take hydralazine and you load up with glucose.

The hydralazine molecule bonds to the glucose and you can trace it out of your. Out of your urine. And you just sort of, you know, avoided a whole glucose load.

So why'd you say nobody's ever going to take it?

Because it takes a long time to build a tolerance up without killing your blood pressure.

Oh, so. So you're going to get dizzy, you're going to get all the things that would happen if you kind of open up the fire hoses. Too much.

So it's a bit like being able to build up toxins in your body. Sort of. So when I first started, I took 5 milligrams and thought I was going to die. My blood pressure was 60 over 40 and I thought, oh, this is the dumbest.

Oh my gosh.

So then I went down to two and a half milligrams, built up, and over the course of three years, I can now take 100 milligrams with no effect.

Wow.

So when I down 100 milligrams of hydrolazine, I take it now with meals. Um, it's a fantastic transglycosylating agent and reduces inflammatory processes.

You would take it with any meal that contains an appreciable amount of glucose.

Yep.

Okay. Interesting. Is there, is there a, like a brand name for hydralazine?

It's an. That's the generic name. It is so old and so dirt cheap. I'm sure there are a million names for it.

Okay, okay, got it. So that's super interesting because a lot of people talk about the buildup of advanced glycation end products, or ages, as a primary contributor to the aging process, to skin, hair, nail degradation, et cetera. And this is something that could potentially, especially for someone eating glucose and carbohydrates, put the brakes on that.

Oh, a hundred percent. In fact, I have a six to seven step methodology for blocking the effects of glucose. I mean, you can block the absorption, you can block gluconeogenesis, you can block the formation of sorbitol, you can block age production, you can sponge up extra age, you can pee out extra glucose. In fact, that's probably a good time to talk about the flozen category.

These are flozen. Okay.

So there's a group of drug, I call them the flozin family, and it's canagliflozin, D, pegliflozin, empangliflozin. There's a bunch of them. And they are sodium glucose reuptake inhibitors. And the way this works is that your body, your kidneys, filter out most of the glucose floating around in your vasculature. Right. I mean, it works backwards than what you would think. So the body takes the glucose out, it sits in your kidneys, and you re uptake it back into your vasculature. Right. So in effect, you're not usually dumping a whole lot of glucose, but if you block those receptors, you just pee out a ton of glucose.

I was gonna say if. If you did want to get insurance or wanted to get Screened for something. Some of these drugs would potentially raise an eyebrow. Someone might think you were pre diabetic or diabetic with that amount of glucose in your urine.

Well, I, I will tell you that, yeah, if you're going to take any lab studies for real, you got to be off this, all of this stuff, because it just, yeah, it'll, it'll, it'll look pretty damn funny. The other thing is, I don't get any of these drugs from the United States because if anyone saw that, what I was on, they would think I was 100-year-old, diabetic, hypertensive, someone dying of cancer. This, you know, these are serious drugs.

Yeah. Is that safe to order these drugs? Generic, overseas versions. Do you have some kind of a vetting mechanism that you use or something like that?

So. I do, I do. There's a particular website, I went through a variety of websites to test. And what you do is you see sort of what brands are on this particular website. You check for their authenticity, safety, who makes them, who, you know. Yeah, there's a whole series of, you know, sort of things that I look at to determine what's valid and what's not valid. I think in the United States we become very centric such that we think that only things made here are reasonable. And, and in fact, you know, there's a whole, you know, globe out there of, of, of people taking medications, and they are perfectly safe if you check them, you know, accordingly.

Yeah, well, obviously, since you're a licensed medical physician in the U.S. i don't know if you're able to share or not. But you said there's a website. Are you able to share the website or is that not allowed?

I can, but we have to have the warning that if people order this stuff and they use it, you know, I, I, I'm not their physician, so I don't want to be responsible for anyone killing themselves by accident because honestly, these are real guns. And someone that knows something should be keep keeping a watch out for these people.

Okay. All right, I'll put in the show notes@bengreenfieldlife.com Pharmahacks Sandy, Will, Will email me this hidden secret website where you can, you can get your hands on this kind of stuff you mentioned when we were talking about not hydralazine. Actually, I think it was hydralazine, the one that drops your blood pressure and can cause some vasodilation that acts differently than a phosphodiesterase inhibitor like sildenafil.

What did you mean when you were Talking about that, is there something else that you would use in that category that would be beneficial for something beyond, say, erectile dysfunction?

So the answer is yes, those are phosphodiesterase inhibitors. That's the class of medication that you're looking at. And I take something called pentoxifying.

Pentoxifying.

Pentoxifying.

Okay.

The question therefore is, well, why, why would you do this? And I do it for several reasons. So the first reason is that it increases microvasculature, right? Blood flow to microvasculature. So it decreases the viscosity of your blood. It makes blood cells themselves more deformable. So as you get older and you get capillary death in the, in sort of like the distal aspects of your vascular tree, which is why people have, you know, dysfunction in various areas. This increases oxygenation to the tissues. So that's incredibly useful as well. It inhibits glycation. So this is yet another age inhibitor. So that's quite useful. And it's also really good for your mitochondria. It's a PCG1 alpha activator. It's. And it's an NRF2 activator. So good for microvasculature, great for your mitochondria and decreases glycation issues as far as I'm concerned. Like, that's a win win.

Now, if you're co consuming a phosphodiesterase inhibitor with something like hydralazine, I would imagine you'd be even more careful because you're going to have two different pathways for dropping blood pressure.

That is correct.

Okay, so you worked your way up with both.

So what I do is if you look at the recommended dose for any of these medications, it's based on people with pathology. Right. So as an example, this one will say 400 milligrams three times a day. Well, I don't actually have any pathology, so I'll take 400 milligrams once a day. Spaced out from the hydralazine. Right. Because the indications and the dose are just entirely highly different for pathology versus longevity.

And how much do you think pharmacogenetics plays a role in this as well? Because I know that now it's pretty easy to get a pharmacogenetic profile and it's often included with many of these DNA tests. But do you think there's a pretty high variation from person to person in terms of the CYP activity or anything else that would determine how hard something like this or soft it might hit someone?

So you can either, I mean, yes, those tests are extremely useful. On the other hand, you can do what we call the cheat test, right? So as an example, if you ask someone if they consumed alcohol and they go, oh, I can't do that, I don't metabolize it very well or I get hungover really easily, clearly you can look, you know what their genetics are, right?

Or coffee, make coffee makes me jittery. Yeah.

Or so, so all of the, all these enzymes and genetic pathways that you're talking about, we used to metabolize everything else as well. So you can sort of guess if you don't want to get the genetic testing. On the other hand, it's sort of fun and it's interesting to use. But I will tell you that most people, 90 some percent of the people are all the same.

Yeah. Yeah. Okay. I actually want to talk about the brain here for a second because if you look at a lot of these popular nootropics out there, you'll find lithium in many of them. Anywhere from, I noticed about 5 to a maximum of 25 milligrams of lithium in some of these compounds. For the research that's been done on lithium as far as brain optimization, delaying cognitive aging, et cetera. And I remember you brought up lithium when I was sitting with you at that conference one day and you mentioned doses of like I think 75 to 150 milligrams, which you know, is, is at least four times what you'll find in the highest dose of any of these popular nootropics out there. So what's the deal with lithium? And in particular using a higher dose via a pharmaceutical versus, you know, these almost like fairy dusted doses you'll find in many nootropics.

Excellent question, excellent question. So, so lithium is extremely interesting and it be it came to my attention because I was looking at telomeres and all the enzymes around telomeres, so telomerase and tert and terra and all of those things. And it turns out so most people that think about lithium think about people that are bipolar, right? And if you are bipolar and you are put on lithium, that's what most of the studies are. But let me back up. If you are bipolar, your telomeres are statistically significantly shorter than a standard person's telomeres are. If someone has been on lithium for greater than two years with bipolar disease, their telomeres are significantly longer than an average person. But you say to yourself, well, what's going on here? Right.

Unfortunately we don't have any studies of normal People on significant doses of lithium, because why would they? So we don't really know what the effects are. However, what we can know is that people in areas where there's higher lithium in foods or in water, et cetera, there is a decrease in all cause morbidity and mortality. All cause. Right. So it just demonstrates that it's a useful ion and it turns out that it's considered essential. Now at 1 milligram per day, which is pretty, pretty pathetic, it's very, very low. So what does lithium do? Well, it turns out it competes with the magnesium receptors.

So they sort of replace it. So if you had super high doses, 600 to 900 milligrams, you start seeing sort of pathological issues. Usually at 300, you don't. So that's a fairly safe dose. Right. So the idea is if you want to maximize your lithium with decreasing side effects. I decided on 75 to 150 just based on sort of pharmacodynamics. That's what a person can handle. They are emotionally stable with no side effect profile.

Do you think, do you think that if you were emotionally unstable or you dealt with anxiety even if you weren't bipolar, issues with maybe like OCD or AD like tendencies, et cetera, that a higher dose of lithium would be noticeable in terms of modulating some of that?

Oh, a hundred percent, 100% in fact. I mean, that sounds terrible. So. But I have two teenage daughters, one's 18 and one's 20, and they were going, bit of stress, going to college, you know, all sorts of family stresses, and they were really having challenges. I'm like, what the hell? So I gave them 75 milligrams of lithium a day. And I have to tell you, they each told me, that takes your stress and turns it down by like 25%. Wow. No cognitive change, just calmer, no rash decisions, very stable. And I will tell you that I tend to be a very calm person myself.

But I've had a lot of very sort of horrible things happen in my life over the last year. And I think that I have managed them better just being on a bit of lithium.

Lithium in the lunchbox for the teenage college students. You know, after you recognize it's the. Lithium is the only thing of these pharmaceuticals we've discussed that I actually implemented. After talking with you, I was, I was actually waiting to kind of experiment, you know, as a, a little bit of a relentless biohacker myself with some of these others until after I'd picked your brain a bit more. We talked Enough about lithium at that conference to where I actually ordered it from the source you recommended and started on 75 to 150. Actually upped my dosage about two weeks ago. Now. I noticed nothing, I think. And I also have a very low stress life. Um, very low stress. Right. I'm in charge of my own schedule. I work from home, I live out in the forest, I've got access to nature, I got a wonderful family, I have an amazing team around me and you know, maybe if I were more stressed and, and I also haven't had a hefty travel bout or anything like that, during which I could potentially try it in a more stressful scenario. But I, I did, I did try it. Not only due to the potential for stress modulation and again I just didn't notice much, but also because it just seems to have a lot of other benefits for just long term cognitive health.

Oh, absolutely. And just briefly. Right. So other little side things that it does, which I think is really cool. So in your mitochondria it actually controls your mitochondrial permeability transition.

For people that don't know what that is, there's little pores in your mitochondria and they go from the outside of the mitochondria all the way to the inside. And this pores, pore flickers when you are young like a little pop off valve. And when you are older it opens more regularly and toxic items from your mitochondria, especially cytochrome C go out into the cell and it actually sort of precipitates cell death. And lithium is one of the things that controls that pore. So that's really amazing. It's also extremely good for autophagy, which, which we know and love. And the last thing is we've found that it's extremely good for stem cell health as well as osteoblastic health. So better bones, better stem cells all over, especially neurogenesis. Nerves love it and gets to the blood brain barrier obviously, which is why it's sort of a neurotropic. So a lot of positive aspects without a whole lot of negative stuff.

I'm actually going to mention that to my wife because I actually have a crap ton of lithium. My assistant, who I had at order seemed to think I need to distort in a bunker for a while. But my wife actually has a high risk for osteoporosis. So I may, may talk with my life wife later on about the osteoblastic activity and see if, see if she wants to try it. Now you mentioned that it might interfere with magnesium in some manner. I think you said it might block receptors. Would you make a case for increasing magnesium consumption if you were on lithium?

Well, you don't want a full war, right? So so basically you would think that if you look at the molecules themselves, you're like they're not going to compete. That's ridiculous. But they actually do. So that this is why higher doses of lithium will cause issues, right? Because then you have a magnesium deficiency. That being said is most people are magnesium deficient to start with, which is why the magnesium.

Supplement companies are doing so well. What I would recommend however, is if you are low in magnesium and you want to supplement, go with something that crosses the blood brain barrier so that you know, your, your neurons and such will not become magnesium deficient. Plus magnesium threonate is demonstrated to increase, you know, plasticity of the hippocampus. So theoretically it'll make you smarter and give you better memories.

Right? So magnesium three and eight would be the choice. I use the stuff by optimizers, the magnesium breakthrough. It's like seven different forms including three and eight. So that, that's a good one I think. Good brand if you want to cover your bases with magnesium. So we mentioned 1, 2, 3, 4, 5, 6 different pharmaceuticals at this point and, and I will take notes for everybody who's trying to furiously write and figure out how to spell these things. I'll put it all@bengreenfieldlife.com pharmahacks but it also begs the question, Sandy, what about the liver processing all this stuff? We talked about the gastrointestinal system and, and some of the things that could help with gastritis. But what about just like overall hepatotoxicity, increased liver enzymes, you know, fibrosis, any of these issues that you might see when consuming a high number of pharmaceuticals.

So excellent question. So again, this goes back to see your doctor. If you have normal liver enzymes, normal liver activity, you should be absolutely fine. If you do not, then that's another question.

And then by the way, see your doctor after you've had about 48 hours of non difficult exercise because exercise will fabricate high liver enzymes on a lab test. So you want to kind of have a washout period from exercise, particularly eccentric muscle damaging exercise before that test, right?

Oh, absolutely, absolutely. The other thing is that, I mean I've tested mine over and over and everything is always absolutely fine. But this also goes back to dose.

If you are on a full therapeutic dose of all of these things, you may take a liver Hit. Which again is why I used decreased doses and then a very timed out schedule of when do I want to take what, how much. But then again, see, this falls into the how I'm an anesthesiologist and what I do for a living. So, you know, just recommending these as a blanket suggestion for folks is a little bit dangerous. You know, a true medical person needs to actually help plan what someone's going to take, when and why and how much.

Right. Big fat warning label on this podcast, a lot of people, and this is even a popular ingredient now. And in plenty of hangover remedies will say that something called DHM dihydromyricetin can help to lower liver enzymes and, and assist with liver health, especially when taking pharmaceuticals, drinking alcohol, et cetera. Is that one that you've ever heard of? It's not a pharmaceutical, it's. It's just like a over the counter supplement.

I love dihydromyricetin. Oh, it's one of my favorite. So. So dihydromyris. So I went through this whole, like how to activate each of the sirtuins independently and we all take Sirtuin 1 activators. And so I was on this kick to find the threes and of course the two that are decent are hinokial and dihydromyricidin. Dihydromyrisidine works because it, so it basically it's cert 3 only. But what that does is it upregulates all of your mitochondrial activities. So especially if you, you know, it's sold as a hangover remedy essentially. So alcohol will destroy your liver mitochondria and by upregulating them more quickly or having them be in a healthier state, you're just going to do better. So I'm a huge fan of dihydromyricidin. The caveat being, of course, is that all sirtuin activators need enough NAD to be efficient because it's a necessary CO factor.

Yeah, because of the number of supplements that I take, the amount of exercise that I do, the fact that I do have a glass of wine or a cocktail, usually about five days a week. And now I'm using pharmaceuticals like lithium. I actually take a little bit of DHM every morning. I take about three DHM capsules from Level Up Health. And then based on what you described about the sirtuins, I actually use a lot of NAD too. I'm usually NAD or NRIV once a month. Nad.

I went on this huge circadian rhythm binge okay. And what I discovered was absolutely astounding because everyone, every time you get a lecture on sleep, it's, you know, avoid external stresses, lights, food, exercise, etc before you go to sleep. But as it turns out, there are two proteins that put you to sleep, there are two proteins that wake you up and there are two proteins that increase the oscillation of those cycles. Right. And Nad and Sir 2 and 1 are, they sort of rule over all of your circadian rhythms, all of these. So nad, because it's circadian, has a very short half life. So it controls your circadian rhythms and it's created in a circadian rhythm. So it's extremely important for circadian rhythms. So if you do a giant IV bolus dose, you are going to screw up your circadian rhythms for several days. So I don't.

That is interesting.

The other interesting thing about it is if you take your NAD supplement at the wrong time, you can decrease the efficacy of your Sirtuin 1 supplement. So the best time to take it is actually mid afternoon, halfway between your light and dark cycle.

To take NAD mid afternoon, halfway between your light and dark cycle and then take your sirtuin at a separate time.

No, you can take those together. But there was a study that demonstrated like your sirtuins, you know, the half life is a little bit longer, but to activate them usually takes about an hour or so. But if you're going to do an NAD either in an iv, which I don't like because the dose is too big, I like the IM actually and then the orals are going to take half an hour or so to take effect. But if you want to sort of optimize both mid afternoon, mid light, mid light cycle.

Yeah, it's never actually disrupted my sleep. I mean I've done nadiv's like an hour before bed before, but I also tend to.

And I don't know if you could comment on this, maybe it's a CYP thing. I process stuff pretty quickly. Like even though I don't, I could drink five cups of coffee and be fine. For me to even feel something like psilocybin, I usually have to take two and a half to three grams to actually for it to really kick in at all with noticeable effects. I seems like I need a mega dose of just about anything I use.

Well, I think that you've upregulated all of your metabolic enzymes is, you know, pretty high and that. And then, and that's why, yeah, maybe.

All those pre workout stimulants I mainlined back in the bodybuilding days, 24, 7.

You never know. Well, the other thing you do is you can come off of everything for like a week. And then you can deregulate all of those enzymes because everything is on a feedback loop and see if doses are any different.

Yeah, that's true. For me, that's called camping or hunting. So the, the pharmaceuticals we've discussed so far, would you say those are kind of like the biggies? That's. That's the core range of items that you would use to simulate a lot of these things people are doing for cold, heat, exercise, fasting, et cetera?

Yeah, I mean, there's a few other things you can do, but those are the biggies.

Okay, I have a question about you. You talked about, for example, mitochondrial proliferation or mitochondrial health. People often use peptides, like, let's say Mot C or epitalon, as cycles throughout the year to assist with something like that. How, how equivocal would pharmaceuticals like this be to peptides? More powerful? Less powerful? Similar.

So I think that depends on several things. So, peptides, I'm sure your listeners are extremely educated, but I'll just put in my two cents worth here. Peptides work by sending messages to your DNA specifically to turn on the production of certain molecules. Right. It's like.

Asking for factory. I would like size X of this particular shoe. It's very specific. The problem is that the older you get, the cell may not be able to do that.

Less building blocks for the factory.

Exactly. So if you have a very good factory, if you're young, peptides are amazing. If you're old and you're not on the cellular optimization program, they are less effective because basically you're trying to get an old factory to make something that it just can't make. Right. So peptides are, I think, are a fantastic add on once your cells have been optimized. So again, so it just depends. So when you add a pharmaceutical to that, pharmaceuticals will work come hell or high water. Peptides will only work under certain conditions.

Are you still pretty into exosomes too? You gave me an exosome injection. No, you gave me an Exosome IV at that conference. I always feel amazing when I get those.

I love exosomes. I have what I call my longevity pyramid. There are things I do every day, things I do every week, and I inject exosomes every month. Come hell or high water.

You do inject or iv?

Both.

Okay. I didn't realize you could inject them. Is that like intramuscular?

You could put them anywhere you want. They're going to regenerate wherever you stick them. So I, you know, if I have an injury, I'll stick it there. If I, you know, have extra, I'll put it in my face. I've got some arthritic changes in my fingers, so I stab my fingers all the time, and otherwise I'll just do a big dump into my vein.

That's what you get for rock climbing. Have you ever tried an intranasal leak? The. The most I've ever felt out of exosomes, like, head clear as a bell for, like, two weeks was I did intranasal, a full vial over the course of a day. And I slept well. It wasn't like I was jittery, but every morning I woke up with just a head as clear as a bell.

So, yeah, so the key to intranasal is that you just can't have a cold or have extra goo or use a vasoconstrictor because you want to just make sure the mucous membrane is nice and clear and empty. You want to get it as far back as possible so it gets to the cribiform plate and through the mucous membrane into the vasculature. So it absolutely works. It just doesn't work for everybody because some people have sinus issues, you know, what have you, extra blah, blah, blah.

But, yeah, it's a no vasoconstrict. So no nicotine gum when you're doing your exosome spray.

Exactly.

What do you think about nicotine, by the way?

Oh, my gosh. So I'm not a huge fan. I've tried it several times and I have vomited my guts out. It's. It is damn ugly.

Yeah, I think your tolerance builds up pretty quickly, but that's usually the reaction for most people who try it for the first time or try it after not having used it for a while. So, yeah, and definitely vasoconstrictive, which can be concerning for people if they've got things like high blood pressure or erectile dysfunction. For sure. You. You obviously have been doing a lot since our last podcast. I interviewed you about your book, the Kaufman Protocol. I think you rewrote or updated or revised it even in the past five years since our podcast. But what's going on right now with the whole Kaufman Protocol website or, you know, a new book on all the pharmaceuticals with the big red warning sign on them or anything like that, so.

You're right. So book one came out about five years ago. Book two came out about a Year and a half ago, two years. And it's called Aging Solutions. And it was the next 28 over the counter agents with updates in terms of cellular processes. Hopefully as equally as entertaining because it has a lot of bad jokes in it.

Yeah, thanks for not sending it to me, by the way. Jeez.

I promise I will mail you one. It's quite. I think it's entertaining. But the idea is science, humor, information good for everyone. I shied away from pharmaceuticals and I continue to only that I'm really concerned that someone's not going to understand that this stuff is really powerful. So there will be no bug on pharmaceuticals. What I am going to be doing, however, starting this year is there will be Kaufman Protocol seminars to teach physicians and honestly, anyone who wants to truly understand how the protocol works and then to be able to put it into clinics or into our own private use. We are working on protocol supplements based on the seven tenants of Aging, such that it's easier to target and people don't have to take, you know, 25, 30 different pills. Hopefully it'll just be sort of what I think is important, based in or sort of built into easy building blocks for people.

I've now built something called Club Exosome with Steve McCain where people can fly to Vegas quarterly and get Exosome therapies, which.

Which is a place where you often might need Exosomes.

Yeah, it's true. Well, we did, we did it there because he's an ex Olympic athlete and he had a lot of friends sort of that were beat up athletes. And then another good friend of ours is ex Circus Soleil and he's a big performer and he does a lot of breath work. He actually leads. Can hold his breath underwater for like 23 minutes or something. Ungodly.

Jeez. What's his name?

Brandon Burkow. Burkin. Yeah.

Interesting. Might be a good, good interview for the podcast.

He's truly remarkable. I can send you his information. But anyway, so they're based out of Vegas and we figure that people would love to come to Vegas. Cause it's an entertaining place to be. And so we do this thing quarterly and people fly in from around the globe, see a show, get their infusion and then off they go. And so this coming weekend is actually yet another club meeting. Because it's a club, it's not an intervention. I'm no one's physician. That's just because that's the way it sort of works since it's not FDA approved. Exactly. Or edible. So that's an interesting Ongoing thing and then, you know, a variety of side projects. So lots of stuff is going on.

Yeah. Okay. Million dollar question. The last time I interviewed you, I remember, I'm pretty sure that you said astaxanthin was your tippy top best choice for the anti aging supplement in your book that had the highest efficacy based on your ranking system, if I remember correctly. Would you still say astaxanthin is pretty high up there, or has it been beaten out by something else?

In terms of numbers, it's been beaten out, but in terms of how much I love it, it's still. It's still high up there. I couldn't live without it. I really couldn't.

What? Beat it out.

A few things. Fisetin is extremely amazing. Spermidine is. Is. Is up there. Um.

Ah, gosh, there's so many of them now, I think.

Are. Are they all. Are they all still kind of like, listed and updated at the Kaufman Protocol website?

Yes, they are. Everything is on there. So that's kaufmanprotocol.com, there's a master chart with all the numbers. And the other thing that we did is I had had an app once upon a time and it didn't work because I picked the wrong developers and they sort of screwed up the coding. So what my brilliant daughter did, it's been recoded and updated. And so for the low cost of 299, my. My algorithm, after you answer a few basic questions, will tell you what supplements you should be on.

That's what happens when you give your kids lithium, folks.

It's impressive. And now she's in college, you know, being whatever she is being. But she spent all summer creating merch, upgrading the website, doing the app. It's just been remarkable.

Incredible. Wow. Wow. Well, I'm going to link to our first podcast, which was equally as intriguing. If you're listening, go to BenGreenfieldLife.com Pharmahacks I'll link to all of the weird ways to spell all of these different hacks that Sandy mentioned. Proceed at your own risk. Medical disclaimer. Neither Sandy or I are giving out medical advice or prescriptive advice. This is all simply for informational purposes. So proceed at your own risk or benefit. So, Sandy, thank you so much for coming on. It's always just super interesting chatting with you.

Oh, it's fun. I. I can't tell you how much I enjoy this.

Awesome. All right, folks. BenGreenfieldLife.com Pharma hacks, check it out. I'm Ben along with Sandy Kaufman signing out from BenGreenfieldLife.com have an incredible week. Do you want free access to comprehensive show notes, My weekly roundup newsletter, cutting edge research and articles, top recommendations from me for everything that you need to hack your your life and a whole lot more. Check out BenGreenfieldLife.com it's all there. BenGreenfieldLife.com See you over there. Most of you who listen don't subscribe, like or rate this show. If you're one of those people who do, then huge thank you. But here's why it's important to subscribe, like and or rate this show. If you do that, that means we get more eyeballs, we get high rankings. And the bigger the Ben Greenfield Life show gets, the bigger and better the guests get and the better the content I'm able to deliver to you. So hit subscribe, leave a ranking, leave a review. If you got a little extra time, it means way more than you might think. Thank you so much.