PUSHING THE LIMITS PODCAST

Dr Sandra Kaufmann — The 7 Reasons Your Cells Age (And How to Stop It)

Full Transcript

[0:00]

SANDRA: So now they are using these things to treat people with heart failure because you can actually get rid of the senescent cells in your heart, grow back new healthy heart cells.

[0:20]

LISA: Well, hey everyone. Welcome into Pushing the Limits. Today I have the absolute amazing Dr Sandra Kaufmann with me as a guest. Welcome back. You're back on the show. It's been a little bit of a while, but fabulous to have you.

SANDRA: It is. It's one of my favourite podcasts to be on. You are awesome and I appreciate the revisit.

LISA: Oh, no. Yeah, it's been too long actually. And you've got two books out now. You had The Kaufmann Protocol number one and number two with the Why We Age and How Not To and then The Aging Solutions is your second book that you've brought out. And for those who don't know you, you are really famous in the world of longevity and anti-aging and you have such an incredible background like being a paediatric anaesthesiologist. I got that. I remember in the first podcast I got that all twisted and came out wrong and you laughed. But you've also had as a doctor other amazing experiences like doing brain surgery and things like that. Can you just give the listeners who didn't see the first podcast a little bit of a brief as to what your history is and then how that set you up for what you do now in the longevity and anti-aging space? Sort of give that background.

[1:38]

SANDRA: Sure. So I started out as a cell biologist. I have a master's in cell biology. And the joke is always that my father pointed out that cells don't pay bills, so I'd better figure out how to get a real job. So I went to med school. I did a year of general surgery. I did a year of neurosurgery. So yes, I have operated on people's brains which is incredibly fun. But you know outcomes are not so great. So I migrated to the world of anaesthesia. And I ended up doing a fellowship in paediatric anaesthesia at Hopkins. And now I feel like that was a lifetime ago. So I've been a practising anaesthesiologist. I'm now a regional medical director, transitional director. So I get flown around the country to fix anaesthesia departments. So that's sort of my pseudo day job. But about 15 years ago, I decided to figure out why we aged and to try to stop aging and I developed the Kaufmann Protocol and then a rating system. And now I have an entire longevity pyramid as to what we do every day, every week, every month, so on and so forth to try to decelerate the process as much as possible from a cellular perspective.

[2:52]

LISA: And your background really set you up for that because when you're doing things like anaesthesiology, you have to understand the breakdown of drugs and stuff. You understand pathways very very well and intricately. And you are also the type of nerd that spent, you know, I remember you saying you had post-it notes all over your office and people used to come in and go like, what the hell's going on here?

SANDRA: Well, you were trying to piece this all together and it was a bit of a lofty goal like I'm going to cure aging. Like nobody's ever done that before.

No, I mean it was honestly rather absurd. You know, I got a whole lot of Don Quixote chasing windmill jokes going on and, you know, like who do you think you are and you're not a Nobel Prize winner. But you know what, it's amazing what one person can do if they're just determined, right? And it's like, and I'm a mountain climber as well and it's like you don't just jump up the mountain and you're done, right? It is step by step, moment by moment and then you chunk it. So this is what I did. Like every day that I sat in the hospital, I just read a little bit more and a little bit more and a little bit more. And over the course of time, you figure it out or at least to a certain degree. And then you start piecing it together and once you understand that this is a big giant puzzle and I feel like I've got the corners and I've got some of the edges and a lot of the insides, but maybe I'm still missing some. There's still bits and pieces that aren't quite there. But I think that we're really really getting a handle on aging and I don't want to take all the credit because that would be ridiculous. Like I am not a researcher per se. Like I don't sit there in labs and stare at cells and count chromosomes and that kind of thing. I just read everybody else's work and then try to synthesise it and understand it and then apply it sort of clinically to what I know as an anaesthesiologist and a physician.

[4:40]

LISA: But I think that's where the gold lies, right? Because everybody who's in the research field is so far down their own rabbit hole that they know their thing, but they don't know the thing next door or the thing that the other guy's doing down the road. And so when you have this overview and you're obviously very humble, but you are a genius. You have a brain that's able to take all that in and then put it through the lens of your experience as a doctor, as an anaesthesiologist, with all the stuff that you have to know there. And then be able to — not everybody could do this. Not everybody could synthesise this sort of data and put it together in a way. And what I love about your protocol is that you brought it across in a way that the lay person can really get a handle on which is not easy because it's very complex science behind it. But actually, your books were so — your book was one of the ones that came around in my handbag for six months. I read it in every cafe and repeated things over to myself because there's a lot in there, but it was also brought across in a way that was structured and that I could sort of get a bit of a grip on some of it. And I think you and I are a little bit alike. We're both athletes. We both like pushing the limits physically. Both in our 50s and wanting — the worst thing in the world is to age. It is horrific. And I've been a caregiver for my mum for the last 10 years and just watched the horrificness of what's coming at us all and wishing that a lot of the stuff that I know now I had known a decade ago and it could have saved her a lot of suffering and my dad a lot of suffering. And then looking at it from me and like hurry up researchers, get the stuff together because I don't want to experience all of that. And so I think you and I are both very similar in the fact that we're very obsessed with trying things on our own bodies, testing things out, experimenting, and having some control over our destiny. And we don't always get things right. But can you just tell us a little bit about, you know, you put this protocol together? Let's start there with the seven tenets of aging and then what you've been discovering and then we can go through some of the key ingredients, the supplements, the things that we can do to really help ourselves. So yeah, over to you.

[7:13]

SANDRA: Yeah but before I do that I just do want to comment. So what's interesting, so you watched your parents sort of have issues. My mother was the same. My mother was the first victim of toxic shock. And as a kid, I watched her lose both of her legs and all of her fingers fell off. And she was very ill and then she had aspiration issues. And I watched her just go from a reasonably very active woman to just this horrible 40 years of a downhill slide. And it was miserable to watch. And it's true. Like it puts it in your head, I don't want that to happen to me. Right.

LISA: Exactly.

SANDRA: Now, the flip side of that, which I think is amazingly ironic, is my father is a physician. And when I started coming out with all of this stuff, he just told me that, isn't that sweet? Isn't that cute? But he never actually read it or paid attention. But now that I have a bit of notoriety and he's 85 now, he calls me with suggestions.

LISA: Well, you must be doing it right.

SANDRA: He does. Well, but it's really funny. He goes, have you thought about exercise? He goes, because I run laps around the tennis court now every week. And he goes, I think it's keeping me young. He goes, you should look into that. And it's funny and it's adorable, but it's like, dude, you could have done this like 20 years ago. But anyway, so everyone has a different perspective.

[8:33]

SANDRA: But anyway, so back to your question. Okay. So the seven tenets of aging and what's interesting about these is the categories have stayed exactly the same but over the course of the years I've added subcategories. So I'll try to do this without boring anyone to tears because it does get a little annoying. All right.

TENET 1 — DNA

[8:56]

SANDRA: So tenet one is what goes wrong with your DNA. And mostly it is telomeres that get shorter and epigenetics. And what I've added in the last year is something called heterochromatin distribution. So the way your DNA is clustered in your nucleus, it's either very tightly packed or not. And that distribution controls what you can make in terms of proteins or not. And it also traps things that are sort of toxic. Like we carry a lot of stuff from evolutionary baggage that if it gets loose causes transposons and then you can get different cancers. So controlling that is one of the essences that I've added. So those are the three basic reasons that your DNA ages. So that's tenet one.

TENET 2 — MITOCHONDRIA

[9:41]

SANDRA: Tenet two is mitochondria and we think of them as the powerhouse of the cell and energy production. They control calcium. They control whether your cell is essentially going to live or die at some point. And your mitochondria fail in seven different categories essentially, right? And I'm not going to go through all of these, but it's free radicals, it's NAD deficiency, it's you can't control — there's something called the mitochondrial permeability transition pore that fails, sirtuin 3 deficiency that controls all mitochondria actions. Anyway, the list goes on and on to seven essentially, but that's category two.

TENET 3 — PATHWAYS

[10:19]

SANDRA: Category three is what I call pathways. And these are things that start with your genes and then get translated down into proteins and it's just a pathway and they sort of intersect. There's four basic ones. I mean there's a gazillion if you really counted but I think there's four big ones. So the sirtuins are very important. You have seven mammalian. And they control most all of your homeostasis. Cellular homeostasis, one three and six are particularly crucial to aging. The other ones sort of flit around. We're not exactly sure — I mean they're important, but what do they do for aging? So 1, 3, and 6 are the keys. The AMP kinase pathway is very important. The mTOR pathway and then recently within the last year, I've added all the circadian rhythms to the pathway system.

LISA: Wow. Okay.

SANDRA: Because well, and this is really interesting. So people go, oh, you should sleep better. But no one actually tells you how to do it. Right. And it turns out that there are two proteins that put you to sleep and there are two proteins that wake you up. And they turn each other on and off, on and off, on and off over the 24-hour cycle. And then those two are controlled by two different proteins. There's ROR alpha and REV-ERB. And then there's a sort of a blanket of other things that control it as well. So NAD and sirtuin 6 and a whole bunch of things. But anyway, that's a pathway and it fails with time. So it's not like people can't sleep because they're concerned. People can't sleep because of cellular failure.

LISA: Anyway, so that's pathways. We'll dive into the circadian things. We'll come back to it.

TENET 4 — QUALITY CONTROL

[11:54]

SANDRA: All right. So four. Four is what I call quality control. Quality control is the idea that things go wrong over time. For example, you have 10 to the fifth DNA errors per cell per day. A ton. And as a consequence of that, your body knows it has to fix it. So we have five different mechanisms to fix your DNA. Unfortunately, those fail over time. Same thing happens with proteins. There's a whole science of proteostasis to keep the proteins doing exactly what they need to do. So you've got a whole system of chaperones that keeps them folded and you can upregulate them.

LISA: Those are heat shock protein activators. Exactly.

SANDRA: Or you can take medications to do that, which is what I do. And then when all else fails, then you recycle bits and pieces of your cell, and that's called autophagy, right? Because it's better to recycle pieces than just have them sitting around as a big junkyard. So that's four.

TENET 5 — IMMUNE SYSTEM

[12:54]

SANDRA: Five is your immune system that starts failing over time and becomes your inflammasome, right? That's huge. And I just spent four or five months obsessed with mast cells.

LISA: Oh, really?

SANDRA: And it started out to be like a three-pager and it turned into a 50-pager. So I ended up making it an e-chapter. I'm calling it an e-treatise and it's on Amazon. And it's really boring but man it is all inclusive.

LISA: Oh wow. Okay. Because we've got clients with mast cell activation, I need to get that book.

SANDRA: Well, over the course of time, we all have mast cell activation because the world does everything wrong as you get older. So things that are helpful, you don't have. Things that are harmful, you increase. So we actually have more mast cells as we get older. And when they degranulate, they release histamine, which everyone freaks out about. But I think even more importantly is they release proteases. There's tryptases and chymases and all of these chemicals dissolve you. They dissolve proteins. They dissolve your collagen. They dissolve your elastin. So as a consequence when you degranulate and you're destroying all of your own tissues, it's a problem. So it leads to — like if you have coronary disease, you're going to rupture the plaque because you're dissolving it and poof, you've had a heart attack.

LISA: Wow.

SANDRA: They're very prevalent in any sort of aneurysm. So if you have a brain aneurysm or if you have an abdominal aortic aneurysm, the proteases start dissolving the wall and then there's a 90% mortality.

LISA: I need to know that one. Remind me to come back because my mum had a brain aneurysm, my dad died of an aortic aneurysm, and we have — so then yeah.

SANDRA: So I bet you have some mast cell dysfunction in your family then.

LISA: Yeah, I mean I had asthma and hay fever and things all through my childhood as well. So, I don't know. There's the 9P21 gene that apparently makes us very prone to inflammation as a family. So that one, definitely come back to that one for me.

TENET 6 — INDIVIDUAL CELLS

[15:03]

SANDRA: So six is individual cell issues. It's the idea that stem cells we need to keep very happy and safe. Senescent cells we need to sort of eradicate. The idea that a red cell is different than a brain cell and so on.

TENET 7 — WASTE MANAGEMENT

[15:26]

SANDRA: And then waste management is basically the issues of sugars. And we all blame glucose, but fructose is seven to 10 times worse than glucose. And ribose is like 500 times as bad.

LISA: Really? Wow.

SANDRA: Oh my god, yes. And so everyone buys ribose. I'm thinking you might as well just have eaten a pile of nasty sugar. It's terrible. Anyway, the sugar is a six-carbon ring and it gets broken down into pieces and these pieces get stuck onto proteins and there's an intermediate thing and it's a six non-enzymatic step process and at the end you get something called an AGE, an advanced glycation end product. And that too lands on things and dissolves them. So if it's on collagen it causes cross-links and they break. It can activate a lot of inflammatory pathways. They're just evil. But I developed a six or seven stage process to sort of eradicate AGEs. So that's kind of cool.

LISA: Let's get into that as well because who doesn't like sugar? We're all fighting too much sugar.

SANDRA: Oh no, without a doubt. And so which is — I mean I try to do things for everything so as a consequence I take far too many supplements and far too many pharmaceuticals but there's a reason for all of it. Anyway, and the last thing in waste management is lipofuscin accumulation. Anyway so if you accept that those are the reasons that you age, then that's where we start.

THE MICROBIOME

[17:05]

SANDRA: And the one thing that people always say is, okay well what about your microbiota? And the answer is, granted, you have more bugs in you and on you than you have of your own self. So you are carrying around a lot of kind of childrenry kind of things because they get everything before you do. When you eat, they get to eat your nutrients before you get them. But as a consequence, you're really living off of their metabolites and the metabolites go to our cells and then we still have to deal with it. So I indirectly deal with it. So I don't want people to think I'm brushing it off.

MASTERING THE MAST CELL

[17:43]

LISA: Now that sets the stage beautifully because I've got so many questions now because there's so many areas that I want to dive into. So selfishly, I'm going to dive into that one about the proteases and the histamine a little bit deeper. So what's the name of the book for starters that's on Amazon or the treatise that we can go and geek out on?

SANDRA: Yeah. So it's — I tried to be clever and it's really not. It's just Mastering the Mast Cell.

LISA: Mastering the Mast Cell. That's a good one.

SANDRA: It's just electronic. And the idea is I'm going to write a series of these and at some point it'll get turned into a book. But rather than wait four to five years to have all this, I thought I'll just release them a chapter at a time. So at the moment I mean it just seems more reasonable.

LISA: Start a Substack. Put it on Substack and then release a chapter every now and again and make it paid and people will follow you on Substack. There's another idea for you.

SANDRA: Yeah. Well, right now it's on Amazon and it's like two bucks or something that covers the cost of being on Amazon. And everyone that reads it says, you know what, it's not funny. And I like — I either I'm just not in a funny mood these days or I couldn't find anything fun in mast cells, but it was just so important. I just pitched it out there.

LISA: And for people who are dealing with mast cell problems, which there are a lot, especially post-COVID and everything, this is maybe something that you want to dive into. Or if you're like me and you've got a genetic problem in the family where we have all these aneurysms that have impacted us massively, I'm always looking for ways and I had no idea of that connection from the mast cells to the aneurysms. That was a new one on me. So I'm very keen to go and read that now. That's a real big tip.

WHAT IS A MAST CELL?

[19:30]

LISA: So just explain what is a mast cell and what does it degranulate into? What are we talking about here?

SANDRA: Yeah. So it is called a mast cell because in the 1800s it was a Mastzellen or something like that. It was named — it just meant well-fed. I think that's what it is in German because Paul Ehrlich who was a med student at the time saw one under a microscope and it looks like a blob and it has a gazillion little granules in it. Somewhere between 50 to 200 granules and then a nucleus. And so these cells just sit around and when they get triggered they sort of release a lot of these granules.

So they're clearly immune cells. They're supposed to respond to and get rid of things that are trying to hurt you. The receptors on them, there's probably 20-some receptors. The standard ones respond to IgE and antigens. So if you have an allergic reaction to whatever it is, it's going to affect your mast cell. The mast cell is going to release histamine and a variety of other things and you're going to have an allergic reaction. All right? But that is a stereotypical thing. There are probably at least 10 to 15 different receptor types on this. For example, there is a corticotropin-releasing hormone receptor on your mast cell, which essentially means that if you are under stress and you release CRH, it's going to go to your mast cell and it's going to degranulate. So you can technically have a pseudo-allergic reaction to stress. And then there's cold receptors. You can actually — people have things where they turn red if they're cold or if they're hot. And this is actually where snake venom and bee stuff sort of occurs. Anyway, so there are many many receptors on this thing.

And then the question is what exactly is it releasing? And there's probably at least 30 to 50 things that are possibly in these granules. And as I said, the most common one is histamine. We all know that. So we've got histamine blockers and a variety of other things that help with allergies. But it's not just the histamine that causes problems. There are whole classes and subdivisions of enzymes. They're tryptases and chymases and a lot of them, but they all fall into the category of protease. Meaning breaking down proteins.

LISA: "Ase" is always something that breaks something down.

SANDRA: Exactly. So they tend to aim at collagen and elastin and all of these things that hold your body together. Right. So the more you have these reactions, the more you're going to disintegrate yourself. So I became obsessed with the idea. Now granted, there are other things in these cells and some of them are okay and some of them are not. But in general, having a little bit of a mast cell reaction, of course, it's helpful. You don't want them not to exist, but we don't want to have too many of them. And at the moment, we can't get rid of them. So the only way to do anything about it is to block the release of the granules.

LISA: Right. So they're called mast cell stabilisers. Yeah. So zinc, that type of thing.

MAST CELL STABILISERS

[23:10]

SANDRA: Right. So I came up with — again this took me like months to do — a whole list of over-the-counter supplements, natural agents, how well they blocked mast cell degranulation, which receptor they interfered with, where in the mechanism they blocked it. There aren't that many head-to-head studies to say this is better than that. But what I do is I go through and say there's probably four or five different mechanisms by which you can do this. You can pick either one agent or five if you want to hit it at different points. So there's a whole over-the-counter thing and then I did this whole deep dive into what pharmaceuticals are there. If you just want histamine, then you go back to the over-the-counter antihistamines that we get from the chemist.

In terms of true pharmaceuticals, cromolyn is technically the best one except it doesn't work orally. So you have to breathe it in. So it's really good for asthma but it doesn't really get around the rest of your body. And the half-life is very short. So it's a great agent, but it doesn't really work well in the longevity perspective. So the only one that really kind of works at the moment in longevity is something called ketotifen.

LISA: Ketotifen.

SANDRA: If you look at it, it's going to say ketotifen. And I said that for the longest time and then I googled it and it's like ka-FET-in. The problem with it is it makes you very very sleepy. And it gives you the munchies.

LISA: Not good.

SANDRA: Well, I will tell you that I experimented with this up and down. If you have mast cell activation syndrome, the dose is 1 milligram twice a day. So two milligrams in total. So I cut that in half for this and I was still zonked to no end. So I decided that a third to a half a milligram before bed was probably very reasonable. You can function during the day and you're fine. The munchies are still a bit of a problem and I ate my way through far too much stuff and I'm like, all right, I got to do something about this. So I'm trying to sort of balance it out at the moment.

But there are women that call me and they say, you know what? I can't gain weight and I can't sleep and I itch. I'm like, man, have I got the drug for you. And this poor woman in Switzerland was really funny. She's just absolutely lovely. And she goes, when am I going to stop eating? And I go, I don't know.

So there will be downsides. On the supplement side, besides saying there's lots, PEA helps, butyric acid helps. There's a lot of them. There really are. I don't remember all of the ins and outs because now I've moved on to another obnoxious subject. But they're in the publication and it's all of two bucks. So it's not expensive.

LISA: But this is something worth looking into if you have mast cell activation, which is a big portion of the population that have either genetic stuff going on or post-viral stuff or hay fevers, hives, all of those sorts of things. And as you say, probably most of us are going to get it at some point. And does this have anything to do with autoimmune? Is that part of that whole autoimmune picture or is that separate?

SANDRA: Well, I mean it all has to do with immune failure to a certain degree. But specifically, not really. No.

SIRTUINS

[27:17]

LISA: All right. So then let's back up a little bit and go talk about sirtuins. So we've got seven sirtuins. These are enzymes and the longevity pathway. As you said, number one, three, and six are probably the ones that we should be focusing on. These are NAD dependent. So part of that whole NAD story which I'm actually working on a formulation we're bringing out in a few weeks for my biotech company — I'd love your eyes on it actually — taking a quite a holistic view of the NAD pathway because I think it's been, from my understanding, and of course sitting in front of you who's the pathways expert makes me a bit nervous saying this, but from what I've studied the last five years on the NAD pathway, the approach of just putting NMN or NR or NAD infusions in is maybe a little bit of a simplified approach. If we have someone who has methylation defects, maybe MTHFR problems, because it can cause methyl donor depletion. We also need to be looking — I always use this bath tub analogy — we've got the tap on pouring more NMN or NAD in but we've also got drains on it. So we've got CD38 rampant going too high and there are other parts of the pathway where we could be losing our NAD if we're inflamed, if we're senescent, all of that sort of stuff. So I've taken a very holistic approach to that whole NAD pathway and one of the things that we have in there is resveratrol, or you could use pterostilbene, because the NAD is crucial for the sirtuins. So yeah, let's talk a little bit about how it feeds the sirtuins or activates the sirtuins and what are the sirtuins and why are they absolutely crucial and by the time you're 40 they're starting to not work.

[29:20]

SANDRA: Wow. So that's a lot. I'm dying to see your product now.

LISA: I'm going to send you the formulation for critiquing.

SANDRA: Yeah. So as I said — and you're going to already know most of this — but I'll just state it for your listeners. As you said, there are seven mammalian sirtuins. One, six, and seven are in the nucleus. Three, four, and five live in the mitochondria. Two sort of flits around the cell. We don't really know where it is all the time. And one, three, and six are the keys. So one basically is in charge of all of the other ones. So I always tell people if you're going to do anything, just start with one. Pterostilbene and resveratrol are the classics. And then there's Powerful Flora that's actually very good for sirtuin one as well.

And it's funny, everyone in the world always says, is resveratrol still okay after the whole issues with studies? And the answer is yes. One iffy scientist does not discredit an entire molecule that's really rather beneficial. Bioavailability, pterostilbene versus resveratrol — I think pterostilbene is actually a better molecule. That being said, some companies have seriously revved it up. There's a company, for example, and I don't get paid for any of this, but there's a company called Rev Genetics and they put all these things in lovely molecular packages.

And then three — three, four, five control your mitochondria. Three is obviously the one in charge. Three is actually interesting because most of the sirtuins fail around 40. There's evidence that three starts failing like around 35. So that's really crucial.

And the two things here — the one that I like the most is dihydromyricetin.

LISA: Oh, DHM. Yeah.

SANDRA: Which I use a lot for people who won't stop drinking.

LISA: Well, exactly. Right. Because it helps the liver's mitochondria.

SANDRA: Right. So it is not just for that though. It's actually for sirtuin 3 activation. I think it's incredibly potent for three. And the funny thing is I buy it on Amazon all the time and then I started getting these things that say, are you an alcoholic? Sort of, I'm a drug addict but I'm not sure if that counts. But anyway, dihydromyricetin — there are a few others but I think that's the winner in that category.

And then sirtuin six. Six is important because six lives in the nucleolus and it's crucial for DNA repair. And the winner here is fucoidan.

LISA: Yeah. So that's a seaweedy type of thing.

SANDRA: Yep. Japanese seaweed. And as you mentioned absolutely correctly, the co-factor for these is NAD. So they can't do it without it, which people have known about this for a very long time because one of the first kind of interesting longevity products out there was called Basis, right? They had all these Nobel Prize guys and they put out Basis and it was pterostilbene and NAD and they charged a fortune for it and they did really well until there were wars about whatever. But it was one of the really first thoughtful longevity products. So it's kind of now very commonplace.

THE NAD DEBATE

[32:52]

SANDRA: But okay, so NAD — and you're going to know all of this as well — but NAD is needed for four different reactions within your mitochondria to produce energy. You need it as a co-factor for 500 different enzymes around the rest of your cell. So it's extremely necessary.

PARPs — so we talked about sirtuins which are for all cellular homeostasis. PARPs identify and tag DNA errors so that your mechanisms can come in and fix it. It's a co-factor for that. So if you are NAD deficient, not only do you have no energy, you lose cellular homeostasis and you're more likely to get cancer.

LISA: Wow. So pretty important.

SANDRA: So it's extremely important. But then the question of course is, what do you do? As you get older and you need more — just in terms of the PARPs, you have more damage as you get older so your requirement is higher. And less because your enzymes that make it are failing.

LISA: So our little bathtub thing is going in the wrong direction.

SANDRA: So the answer that we've come to decide is, okay, we're going to supplement with something. What is that something? And everyone's been yelling about this for a few years now, and I don't even know if we have a real solution. But from a scientific point of view, if you look at cells, the only cells that actually have an NAD receptor on it — meaning NAD goes to the cell and goes, aha, here's my door and I'm going to go inside — are brain cells or neurons. All right? There's no NAD receptor on any other cell. So it means it has to get moved or altered to be one of the other things, either NR or NMN or NAM, and then it can get into the cell, reprocessed, and then it becomes NAD.

Question is always, does liposomal NAD or NADH get in? And the answer is I don't actually know because we're not just feeding us — as I mentioned we're feeding our microbiome. So it is certainly very likely that they're getting the NAD or whatever it is that we're taking and we are absorbing their metabolites. So the answer is so multifactorial it's really kind of hard to say.

[35:05]

LISA: Yeah, I interviewed Professor Joseph Baur who's a NAD researcher, deep deep deep in the weeds, looking at does the NMN actually get into the cell or is it NR that gets more directly, or does the NMN have to break down into the separate components, get into the cell, reassemble itself, is it the microbiome? And at the end of it he said we still don't 100% know but we do know that when we lift up our NAD levels that does provide more for the sirtuins and it does more for our energy and all those other things that you said. But he did say there's a lot more research that needs to be done. And because there are also other studies that have shown an increased risk for some people, as I said, with methylation defects or older populations or cancer populations, that have to be a little bit careful not to just chuck in especially massive doses. Like smaller doses of NMN, but if you go like NAD infusions every week, that might be too much for certain people.

SANDRA: Right. So I would actually argue, and this is where I get really adamant, is other than people with traumatic brain injury, no one should have an IV infusion of NAD.

LISA: Wow. Yes. I agree.

SANDRA: Because it is too much, too fast. The half-life is very fast. And as a consequence, you're stuck with a load of just straight up nicotinamide. And that is actually a negative feedback mechanism. It's actually toxic. So when you do these big non-physiological doses, too much, too fast.

[37:03]

LISA: So I'm a big student of Dr Elizabeth Yurth. She has a Boulder Longevity Institute and incredible cellular knowledge. She's been warning about NAD infusions and high levels of just straight NMN and NAD. She actually loves a molecule called 1-MNA which was out of Poland and I imported it for a while but it became just too expensive and too difficult to manage and so I make my own sort of holistic pathway. But that one bypasses all of these complicated steps that can cause all of these issues. But she also says danger, danger, danger. We don't want to be doing high-dose NAD infusions. In rare cases, yeah, things like traumatic brain injury perhaps, but we've got to be a little bit cautious in our approach and don't go over those physiological levels and be aware of balancing the books. However, there are different approaches and people have different ideas about how to balance it. I've got my own ideas after studying this for quite a long time, but there is more research to be done.

SANDRA: There is more research to be done without a doubt. And I'm sure you do the same thing. We try to block CD38 with apigenin in the evenings. Take a little TMG.

LISA: Yes.

SANDRA: A whole lot of things. And it's actually sort of interesting, too. Different tissues prefer different makeups. For example — and I'm going to screw this up because I haven't given this lecture in a while — but muscle prefers one, retinas prefer another. And it just has to do with enzyme distribution. Some organs can produce different — anyway, so what I advise people to do is to rotate the precursors.

LISA: That's also a good approach.

SANDRA: So we put my people through some NMN and then some NR and then we throw in some NAM just because you also have a lot of NAD floating around in your vasculature that serves as biochemical messages. So I think that there is a balance to be had. Small amounts of different things on a regular basis I think is the answer.

LISA: I think that's not a bad approach and then putting in some TMG or some resveratrol, apigenin, quercetin, rutin. That's the sort of path that we've taken to support all those supporting players. But again, none of us should be arrogant to think that we've got it all sorted in that department. But we also do know 100% that the NAD pathway is absolutely crucial if you want to age well and that the sirtuins are very much affected by the levels of NAD. So it is worth us doing what we can with the science as it now stands and being a little bit cautious on doing massive doses. I'm not a fan of the NAD infusions. I think that's just not a good plan for most of us.

WHAT DO SIRTUINS ACTUALLY DO?

[40:18]

LISA: But coming back to the sirtuins, the one, three, and six. We've got some things there. Can you just briefly — so sirtuin one is sort of the orchestrator of the others. What are they actually doing? What's their role in life? What are they doing for the aging process?

SANDRA: Sure. So big picture, as you said, one controls pretty much everything. So it controls if you're going to make endogenous free radical scavenging mechanisms. So it can control your oxidative status. It can control where you store fat. And I call this the abdominal tyre syndrome. When people hit 40 and they're like, I exercise the same. I eat the same. My belly is fat. Why is my skin look whatever? And it's because that's your sirtuins. They tell your body where to put the fat. They control your circadian rhythms. They control the NAD balance of the entire sort of milieu of factors. The big one, it controls DNA repair mechanisms. That's a big one. One helps control six and the nucleolus. So again, this falls into — if you're not sleeping, you don't have sirtuins, you're not going to fix your DNA and therefore you're more prone to have cancer. So that's huge. But pretty much all of your biochemical reactions are controlled some way by sirtuins. It's really really remarkable. And you can pick them apart and there's always a sirtuin in there.

So for example, if you go to mitochondria and you look at sirtuin 3, it dictates if you open and close your mitochondrial transition pores. It dictates — granted that the mitochondrial DNA only controls like 13% of the proteins in your mitochondria — but sirtuins 2 and 3 control that. It controls the antioxidant state of your mitochondria. It controls fission and fusion. It controls the entire mitochondrial program soup to nuts. So without sirtuin 3, you don't have PGC-1 alpha and then the whole thing tanks. So people are like, I don't have any energy. Well, of course you don't. How could you possibly have energy if your entire mitochondria shut down?

PGC-1 ALPHA

[42:55]

LISA: The PGC-1 alpha, what is that? Because we hear that a lot.

SANDRA: So there are pathways that control all of these cellular processes and it's just a piece of the pathway. And it's really interesting because if you look at this from arrows, this goes to this and this goes to that. So PGC-1 alpha is sort of like a sub-factor for a lot of things. So for example, estrogen affects your mitochondria, but it only does it in conjunction with PGC-1 alpha. And PGC-1 alpha doesn't work if you don't have sirtuins 2 and 3. And they all control — do you make subunits of your electron transport chain? Which subunits are you making? What is the proton gradient? I mean, so it's all very interrelated. And what's really interesting is that people try to fix small parts of their mitochondria expecting this huge energy burst when in fact if you don't fix it soup to nuts, it just doesn't run right. It's like having an old motor on your Volkswagen Bug and you're like, I changed the spark plugs. Why is this not running well? Well, because everything else is still rusted.

LISA: Wow. And the mitochondria is at the basis of so many of our problems. When they're not working properly and they're not producing the energy, the ATP for our little cells to go and do their cell thing, then we're all basically in trouble. So mitochondria is everything and they really are.

NRF2, GLUTATHIONE, AND THE PRECURSOR APPROACH

[44:36]

SANDRA: And I think that people do things with great intentions, but maybe not the most education necessarily. And as an example, the pathway to get rid of free radicals — you activate something called NRF2 and that makes catalase and glutathione and your superoxide dismutases and the whole pathway. And what's — I'm very worried because people take daily amounts, large daily amounts of glutathione. Another one of my pet peeves. So glutathione then turns off NRF2. Which means you're not making catalase and you're not making superoxide dismutase. So it's well intended but with terrible outcomes. So my advice to people is if you're going to do it, do it for a short amount of time and then lay off.

So for example, when I have my exosome clubs or whatever, my patients, I will give them an IV dose like once a month or once a quarter, but no more.

LISA: Do you like the approach of the precursors? Like I've studied quite a lot into the NRF2 pathway. In one of my formulations, Re:juvenate Pro, which is going after immunosenescence and the aging of the immune system being at the foundation of a lot of the hallmarks of aging downstream. So we sort of went upstream and went immunosenescence and tried to attack that. So gut health, helping with growth factors, sialic acid, nucleotides, colostrum extract that has a lot of those things in it. But the NRF2 — so I was going to ask you about broccoli seed sprouts for example. Broccoli sprouts, really good detoxification, NRF2 activation. In the formulation that we have, we have carnosic acid and we also have a native plant to New Zealand called kawakawa. Both are NRF2 activators. If I'm having an NRF2 activator, do I need to separate it from my NAC to not cancel each other out? I interviewed a doctor who was a broccoli sprouts expert who uses sulforaphane to activate the NRF2 and she was like, never touch NAC, glutathione, anything, vitamin C, none of those things because they're going to block your endogenous antioxidant capacity. And I've interviewed other doctors and they were like, nah, you can probably use both. Separate them by a few hours. What's your take?

[47:18]

SANDRA: So what's interesting about this is you have to think about the process. You're taking building blocks with an enzyme to get an end product with a feedback loop. This is the process. And the question is, what part of the process is failing over time?

So if you have a deficiency of precursors and everything else is okay, adding a precursor has no negative feedback issues. You're not going to cancel out anything. If you have an enzyme deficiency, which is a protein that can get destroyed — we all have enzyme deficiencies as we get older because our enzymes just don't work as well — if you add extra precursor, it can theoretically drive the enzymatic reaction. So it will help.

The issue however is if you don't do the precursor and you don't muck with the enzyme and you just give glutathione, then you truly are mucking with the feedback loop.

LISA: Exactly.

SANDRA: So I don't give glutathione except once in a blue moon. Because it's useful if you've been really sick or something. I tend to stick with the precursors because they can't really hurt you. If your enzymes are working, you'll make the right amount. If they're not working as well, you can force the chemical reaction a little. But you can't force it too much because it just has feedback loops. So precursors are fine.

But NRF2 has so many inputs. This is just one of them. And I still think that sulforaphane is fantastic. But I will tell you that I use smaller doses than anything people recommend. Because all of the studies on these things, at least 90% of them, are about one agent in a high dose looking for measurable change within a short period of time.

LISA: Which is always a problematic sort of framing for a start.

SANDRA: So if you go back to the cell and instead of having one input, you're having four inputs — because that's what you are, NRF2 — so if you're hitting all of them, you don't need to hit it over the head with a sledgehammer. You can titrate things in because they're synergistic and get the same effect.

LISA: So don't take massive doses of one thing.

SANDRA: So I take — I mean I take 70 supplements and 13 medications a day, but I take significantly smaller doses of everything because I think they're synergistic in the pathways.

LISA: And you've balanced it out to the best of your knowledge for your particular genetics. And I'm not saying you're right. You could be completely wrong but you're experimenting. You're using yourself.

SANDRA: A thousand percent.

LISA: Look at how functioning you are, how beautiful you are, how your skin looks like a 25-year-old. So something is going in the right direction. But it is about experimentation. We are not at the point yet. Hopefully we will get there with AI and all this magic stuff that's happening in the world, but right now we're doing the best we can with what we have.

LISA'S MUM AND THE POWER OF THROWING EVERYTHING AT IT

[50:56]

LISA: And I've had a situation with my mum where she had — not only the aneurysm, but she had a terminal brain cancer four and a half years ago, nearly 5 years ago. Given weeks to live, nothing you can do. So I'm going to experiment and I'm going to chuck the bus at it. And I did. And I went full bore. And I used over 150 supplements. I used a dozen drugs. I used a whole lot of peptides. I used stuff that would be way too long for this episode to talk about. But she survived a terminal cancer diagnosis. She's now 5 years in. Touch wood. She's 84. A lot of stuff is still going sideways. So we don't know how long and the cancer metabolism can change. So I'm on my toes all of the time. And I was talking to a colleague yesterday and I said, how much money it costs to run my mum. It costs me thousands a month. And he said, well, can't you drop some? And I'm like, which do I drop? It's worked so far. And so it's like, I can't tell you which one to drop.

SANDRA: Right. So I would argue you don't drop the number of things she's taking. My argument would be drop the dose. So you don't have to be at the full — and I did that press pulse sort of stuff and at the beginning it was attack and attack and attack, kill everything, use everything on both sides, because we had weeks to live and massive tumours and go hard. And then there was some downstream effects from the chemotherapy which I picked a chemotherapy that was not made for her cancer but I did advanced genetic testing and it was the one that would work with her genetics and her cancer. So that was the one that I had to chase around half the world to get and I got it. Had to pay for it privately and this would never have ever happened if I wasn't, like you, a dog with a bone and trying to save my mum's life.

And now I've heard of cases like there's a guy called Sid who was a billionaire who runs GitLab and he had a terminal cancer diagnosis about two years ago. He quit his job, hired a team of scientists. They made different vaccines that were based on his particular cancer that went specifically using these protocols and other things that they put in to attack his cancer. And he had no chance of living. Nothing they could do. They'd done all the standard of care stuff. He was dying. Not so dying now. He's fine. Amazing. And that was using AI. But when I did it, it was like 5 years ago. It was before AI. And just throwing the bus at everything with some very clever doctors. I had 15 doctors on her team. And I made the CEO decisions of what we were doing according to the amount of resources I also had.

OFF-LABEL DRUG USE

[54:10]

LISA: So there are solutions out there that we have now and this is another thing that Dr Elizabeth Yurth taught me, about the off-label drug use. We've gone through all the safety clinical trials, stage ones, stage twos, all of that stuff that takes like 15, 20 years for a lot of these drugs. Can we take some of those drugs and use them off label to actually fix a lot of these other problems and pathways and things? And that's what you're doing. That's exactly what you're doing.

SANDRA: Got it. Absolutely. Which is why I take 13 pharmaceuticals a day.

LISA: Yeah. Which sounds like a lot to the average person because most of the people that are in health are into the natural stuff, right? But for me it's like, what works? And yeah, if there's a natural thing — and that's the other thing, a lot of the natural stuff is pooh-poohed as being powerless and I think that is completely wrong as well because some of the natural things are more powerful than the drugs that are on the market. But they don't let you say that. You can't go, oh, curcumin could be good for XYZ because you'll get your head shot off and you'll be banned on certain platforms. So you've got to be open-minded and go research yourself and do these things.

A MOLECULE IS A MOLECULE

[55:20]

SANDRA: I just want to tag on to that idea and say that from an anaesthesiologist's point of view, I think about anything we put in our body as a molecule. It's a molecule. And molecules work by three-dimensional activity. And it does not matter to the body where this molecule came from. Did it come from a fish? Did it come from a plant? Or did it come from a lab? Our bodies don't care. There's no "this is good and this is bad." I used to have this argument with my sister all the time because she thought Botox was terrible and I'm like, well, it's all natural. Botulism is natural. Cyanide is natural. All things that are natural are not good. All things that are medical are not bad. You just have to figure out what the molecule is and what it's doing to you. And the benefit of pharmaceuticals is that yeah, they've had 20 years of testing. So we may know that it has some bad side effects. We may know that it has some great side effects. And the cool thing about it is it's also dose dependent. If I had diseases, I would have a higher dose requirement. But as a prophylactic, I can take smaller doses of something to prevent problems.

RAPAMYCIN, METFORMIN, AND LDN

[56:40]

LISA: That makes sense. Because there's some common drugs that people in the longevity and anti-aging world regularly use. Like metformin, like rapamycin, low-dose naltrexone. What are your takes on those specifically because they are used a lot? I think you're against rapamycin from what I've heard.

SANDRA: Yeah. I do not like rapamycin. I think it's a really bad idea to turn your mTOR system off so aggressively. And they go, oh, well, it's like two milligrams every other week on a Monday. I just think they're playing with fire. When you look at models, you lose hippocampal turnover. You lose a lot of things. You become sarcopenic. I think it's just dangerous. The good news, however, is mTOR and AMP kinase are backwards. So metformin, which is an AMP kinase activator, therefore makes it an mTOR inhibitor, just not as strong. So I think that we can get away with edging towards things without hitting them over the hammer.

So I like metformin. I think people went off the metformin deep end. People were taking 2,000 milligrams a day and that's nuts. 250 to 500 is a great dose and it's fantastic. Especially in a sugar-laden world. Helps your microbiota, helps your glucose, helps a lot of things. But too much can actually harm your electron transport chain. There's a lot of downsides at high dose.

LISA: Yeah. Exactly. So smaller dose and that's not unreasonable.

SANDRA: You mentioned low-dose naltrexone. It's really interesting because it's an opioid antagonist and as such it is also an anti-inflammatory and people like it. I'm always just a little bit concerned — and this may sound super stupid and paranoid — but if you're in some sort of a horrible accident and you need painkillers, opioids aren't going to do anything for you because you're on an antagonistic drug. So there are many many anti-inflammatories that you can take. I just don't like that one.

LISA: I take that one. I take it to sort of downregulate Epstein-Barr, the autoimmune aspect of it. And I have mum on it from the cancer side of the story. But I'm always open to both sides of the story. Like I want to know what are the downsides because there is always a downside. And like you say, if we have an accident, can we get painkillers that are going to actually work? That could be problematic. So you've got to weigh all of this stuff up for you personally.

SANDRA: No, exactly. So I've kind of pooh-poohed two out of your three, but you know, more that I take.

THE FLOZINS (SGLT2 INHIBITORS)

[1:00:01]

LISA: So what do you take on the drug side? These are prescription drugs, so you're not going to be able to go everybody and grab some of these. But it's just interesting to know what you think works on the longevity side.

SANDRA: Yeah. So I love — there's a thing I call them the Flozins. They're sodium-glucose reuptake inhibitors. And there's canagliflozin, empagliflozin — there's just everything that ends in "-flozin." There's five or six of them on the market. And what they do — we have to back up a little bit and look at a kidney. So what a kidney does, a kidney basically cleans out your blood. All the blood goes through it and the kidney removes the glucose, filters it out, but then it puts it back.

LISA: Which is a little bit backwards, right?

SANDRA: Why does the kidney do that? I don't know. Probably about osmotic stuff and whatever. But a sodium-glucose reuptake inhibitor prevents the kidney from putting the glucose back. So you pee it out.

LISA: So you pee it out. Isn't that amazing?

SANDRA: And what's cool about it is your body has already taken out all the glucose it needs. This is just the extra. So you're not going to go hypoglycaemic. And more recently they've demonstrated that all of the Flozins have senolytic activity.

LISA: Oh wow.

SANDRA: So now they are using these things to treat people with heart failure because you can actually get rid of the senescent cells in your heart, grow back new healthy heart cells. And have lower glucose levels. And the only real risk is if you're incontinent and then you leak a little pee around your private parts and you get an infection. So for any normal human being that's reasonably healthy, that's not going to be a problem. So there's no real downside.

LISA: Wow. Doesn't cause candida or anything like that when you're peeing out lots of sugar?

SANDRA: I mean, as long as you're clean. Wouldn't recommend doing it when you're camping and maybe you don't have a lot of toilet paper available. But that's really the only downside.

LISA: And it's really good for people with heart problems.

SANDRA: Off label. Yes.

EPALRESTAT

[1:02:32]

LISA: Any other ones that come to mind?

SANDRA: Oh god. Yeah. So I take something called epalrestat. It is an aldose reductase inhibitor.

LISA: What's that?

SANDRA: So back to our glucose. Glucose is not so great. But what's worse about glucose is that it gets transported into cells, especially neurons, and it becomes sorbitol. And then sorbitol turns into fructose. Sorbitol is bad because it has a very high osmotic index and it sucks water in. And fructose is bad because it's seven to ten times more glycosylating than glucose. So if you had your choice, you'd stick with the glucose. So how do you do that? Well, there's an enzyme that converts inside of a cell glucose to sorbitol and that's aldose reductase. So by taking an aldose reductase inhibitor, you're blocking all of that.

So this drug is designed to give to diabetics that have neuropathy and by that point it's too damn late.

LISA: Exactly. We want to use it prophylactically because we're all going to head towards metabolic dysregulation and too high blood sugars and pre-diabetes and diabetes if we live a long time.

SANDRA: It's funny. I gave this to a friend of mine who swears cataracts got way better.

LISA: Oh wow. Well, because cataracts are caused by the advanced glycation end products.

SANDRA: Well, it's glycation. It's an oxidation problem, but it's also an osmotic problem. If you get a lot of glucose stuck in there, you get cell swelling. Anyway, so his vision got better.

EYE HEALTH PROTOCOL

[1:04:27]

LISA: Your eyesight good? Because by our age most people are shortsighted.

SANDRA: So, more interesting stuff. I am 57. I do not need reading glasses, but I use like four — actually, that's not true — five different types of eye drops every day. I use carnosine eye drops. I use visomitin eye drops. I use B12. I use methylene blue. And I just started using ketotifen eye drops.

LISA: Wow. Okay. Methylene blue eye drops. I use methylene blue orally, for mum mostly. UTIs were a major problem for her and it's very beneficial. It was sort of like the original antibiotic before we had antibiotics. And then got sort of sideswiped by antibiotics and put on the shelf. I've got blue-stained fingers right now because I've just been dealing with it every day. I go around looking like a Smurf. But I did not know about methylene blue eye drops. So what is it doing? Mitochondrial support for the eyes?

SANDRA: Yeah, it's a free radical scavenger and it boosts vision. Where do you get it? Online. There's companies that make it.

LISA: I'm going to have a look at that one. And your other eye drops are carnosine. What does carnosine do in the eyes?

SANDRA: It's a transglycosylating agent. And you take carnosine orally as well. So I take carnosine 400 milligrams daily. Any more than that and you just start buzzing which is annoying. The thing about carnosine though is there's an enzyme called carnosinase and it dissolves carnosine. And the more carnosine you take, the more enzyme you make to get rid of it. And you get this escalating cycle — you take it, you dissolve it, you take it, you dissolve it. So I always recommend that people rotate that to allow the enzymes to sort of turn back off. So I'll take it like two weeks in a row and then take a week off and then two more weeks and take a week off.

LISA: Is that the same as zinc carnosine?

SANDRA: Well, carnosine — lots of things are just complexed to things. So zinc carnosine tends to be taken because it's good for the stomach.

LISA: Yeah. And you can take the carnosine in the eyes and that will help with cataracts and things like that. Brilliant.

SANDRA: Well, and not just the cataracts. It keeps the lens more flexible so that you don't get presbyopia.

LISA: We don't want that. I'm 57 as well and I don't need glasses. Must be doing something right there.

THE KAUFMANN RATING SYSTEM AND KEY SUPPLEMENTS

[1:07:22]

LISA: Okay, now what haven't we talked about? Oh, I actually — I can give you more drugs.

SANDRA: Yeah, a couple more of those and then I want to hit a couple of the stuff that was on the list because I printed out your whole table.

LISA: Your because you've got this brilliant rating system. For those people, they must go and buy the books, The Kaufmann Protocol, the two books. Go and check them both out. And you've got a rating system that checks how it works in DNA, mitochondria, pathways, quality control, immune, individual cell, and waste management. And then you've given it a total at the end. So I went through yesterday and went yep, yep, tick, tick, tick, tick, tick. But there was a couple that I wasn't on and that was naringenin.

NARINGENIN

[1:08:13]

SANDRA: So naringenin. I love it because it is an osteoblastic activator. It also activates NRF2 and does a whole lot of other things. But I love it because it's great for your bones.

LISA: Osteoporosis. People listening. I need that for mum because she's got osteoporosis. So that would help with the osteoblasts, the building of the bone.

SANDRA: Yeah, there's osteoblasts that build and osteoclasts that dissolve. And as you get older you make less and you dissolve more so you get osteopenic. But by activating the osteoblasts you do better.

ASTAXANTHIN

[1:09:18]

LISA: And the ones that are top on your list are things like astaxanthin, which is a huge one that I've been taking since I met you and read your book. Very good for protection from sun.

SANDRA: I was revisiting some of these things and obviously astaxanthin as I said is my favourite molecule. But it's really cool because when you digest it, it travels around in your body in HDLs and LDLs.

LISA: Oh, I didn't know that.

SANDRA: Right. And I didn't realise this once upon a time. So by travelling in your lipids, it's preventing oxidation of your lipids.

LISA: The oxidised LDL, which are the dangerous thing that happens to cholesterol. You want your good cholesterol. Most people run their cholesterol too far down with statins and things.

SANDRA: So a macrophage will recognise an oxidised lipid as foreign and it engulfs it and takes it into the blood vessel and that becomes a foam cell, which is what atherosclerosis is. So I am convinced that astaxanthin intake at higher doses is going to reduce relative risk of vascular disease.

LISA: Wow. Another reason to take it, as if it needed another.

SANDRA: Isn't that cool? I was so excited when I learned that.

LISA: And you want the good cholesterol. You want it for your brain. You want it for your hormones. And a lot of people are running their cholesterol levels too far down with statins and not doing themselves any favours. Your all-cause mortality goes up when your cholesterol goes down too low. So there's a lot of nuance there but this is another thing that can help stabilise it. Excellent. Didn't know that.

SUPPLEMENT ROUNDUP

[1:11:20]

LISA: Then there's things like curcumin and resveratrol. We've covered quercetin, EGCG, alpha lipoic acid, sulforaphane, metformin, D3, CoQ10, omega-3s, berberine, melatonin.

MELATONIN

SANDRA: Melatonin is an interesting one. It helps you go to sleep, doesn't help you stay asleep. So people often confuse that.

LISA: But there is a genetic part to that story which I've only just become aware of in the last few months because I was a big fan of melatonin. Really good antioxidant. Very powerful for off-label use for cancer. But melatonin in certain genetic individuals — I've forgotten the name of the gene — can cause an increase in glucose levels. Have you come across that research?

SANDRA: I don't think I've ever heard that. No.

LISA: Yeah. I've only just become aware of it. In the genetic reports that I'm now getting because I do a lot of genetics in my practice, it's now picking up, hey, this person might not do so well on melatonin.

NOBILETIN

[1:12:35]

LISA: One of the other ones was nobiletin. I hadn't heard that one either.

SANDRA: Nobiletin. What's that? Nobiletin is an ROR alpha agonist.

LISA: Oh. Got it.

SANDRA: So it's part of the circadian rhythms. So there's two proteins that put you to sleep — BMAL1 and CLOCK. And then there's two that wake you up, which I'm blanking on. But there's two proteins that control the oscillation and they fail as you get older. And one of the more powerful ones is ROR alpha and I looked up and down to find things that would boost ROR alpha and nobiletin fell into that category. And conveniently, it comes from orange peel. And it turns out that naringenin also comes from orange peel. So now if you get a woman with osteoporosis who can't sleep, I just give them straight up orange peel.

LISA: Wow. Is it — you just eat the orange peel or you have it as a supplement?

SANDRA: It's a supplement. But I will tell you I tried making my own. I went to YouTube as we all do. How do you extract these things out of orange peel? So for a month I took orange peels and soaked them with vodka.

LISA: That's a good idea. Tell you what, it tasted damn good.

SANDRA: But hey, you got to enjoy yourself while you're getting healthy.

LISA: It looked kind of funny but it tasted great.

ROSMARINIC ACID AND OLEUROPEIN

[1:14:34]

LISA: Is naringenin and nobiletin quite hard to get as a readymade supplement?

SANDRA: They're a little esoteric. But you can certainly get them. I get them.

LISA: Okay. And then rosmarinic acid. I was glad to see that because that's what is in our Re:juvenate Pro formulation. So I'm a big fan of rosmarinic acid or carnosic acid. And oleuropein. That's another one that is very important.

SANDRA: Which one?

LISA: Oleuropein. So olive.

SANDRA: Oh, olive. Yeah. That comes up 10 on your list, which is quite high.

LISA: Yeah, there's a lot of good stuff. Go and get the list people. Go and download it. You can get the books, do your research, put together your own protocol, work with someone that can help you do that if you need to.

CLOSING

[1:15:16]

LISA: Dr Sandra, I don't want to take up any more time because I've gone over, but I just want to say you're amazing. I think you're amazing and I can't wait to have another more crazy nerdy conversation with you because I love nerding out with you. There's just so much to learn from you. You're an absolute genius.

Where can people connect with you? Do you have a website? The books obviously. Give us those titles again and how do people reach out to you? And you also have the Exosome Club for those. You're still doing that in Las Vegas.

SANDRA: Las Vegas. Yep. So the protocol, there's a website called Kaufmann Protocol, and it talks about all the numbers and the whole nine yards. My clinical practice is on kaufmannlongevity.com. So that's how you would find me in particular. I have a clinic in Miami that I see patients. I see patients now in Vegas in a regular clinic. I see patients online, so I do it globally.

And then Club Exosome, I run with Steve McCain in Vegas quarterly. Just so that people know that they can come and get whatever exosomes they want. And it's me, myself, and I. So you would be getting me. And the other funny thing is that whenever anyone flies in, they show up with their list of questions. And my general rule is you can ask me as many questions as you want until your therapy is done. So it usually takes between 5 to 10 minutes. And so they're always shooting questions at me like rapid fire. It's really rather funny.

LISA: And I got to have like over an hour's conversation with you. I'm just so privileged. Just an absolute amazing person. So I'm very very grateful to you. You're just putting out such great stuff into the world, helping so many people and I love your approach of self-experimentation and testing it all out on yourself.

SANDRA: Well, it's either really smart or really dumb.

LISA: We'll find out. Hey, you only live once and you want to live a long time. So we got to try to do it well. And at the end of the day, that's what it's all about. We're trying to protect ourselves, our loved ones from horrible decline, which you are guaranteed to have if you don't. And I'm scared of that. I've seen that. I'm living it day-to-day. It's ruined my life as well as my mum's life. So if I can help other people not go there, that's the mission I have in life. And you're adding to that mission. So thank you, Dr Sandra. You're just a wonderful, wonderful person. Thank you so much.

SANDRA: Oh, it is my pleasure. And right back at you. You are thoroughly impressive, astounding, knowledgeable, brilliant. And I thank you for letting me come on to your show.

LISA: Oh yeah. Anytime you want to come on the show, you just let me know if you've got something new to say. We'll just make it happen.

SANDRA: Deal.

LISA: It's a deal.