The Melanie Avalon Biohacking Podcast Episode #354 - Daniel Tawfik 

TRANSCRIPT

Daniel Tawfik
There's levers that we have at our disposal to mitigate against the changes that we have at age-related chronic disease. It's like these are players in the symphony and you can't dial one up to 11 in the spinal tap world and just dial without any consequences to the other members of the symphony.

A lot of folks are calling it the most important longevity tissue. That's probably true.

Melanie Avalon
Welcome to the Melanie Avalon biohacking podcast where we meet the world's top experts to explore the secrets of health, mindset, longevity, and so much more. Are you ready to take charge of your existence and biohack your life? This show is for you. Please keep in mind we're not dispensing medical advice and are not responsible for any outcomes you may experience from implementing the tactics lying herein.

So friends, are you ready to join me? Let's do this. Welcome back to the Melanie Avalon biohacking podcast. Oh my goodness, friends. What a fascinating and helpful episode we have for you today. We talk all the time on these shows about things like metformin, rapamycin, lotosnaltrexone, methylene blue, all of these really fascinating and interesting longevity related supplements and medications. And today's episode is a deep, deep dive into how to actually use these compounds for the utmost when it comes to health and longevity. I cannot recommend healthspan enough and you can get 10% off with the coupon code Melanie10 at Melanie Avalon.com slash healthspan. I think in the episode I said ifpodcast.com slash healthspan, but both of those links will work. I currently use healthspan to get my prescription for lotosnaltrexone, which we talk about in this show. And I am so excited because I'm going to start a rapamycin protocol as well. So stay tuned for that. By the way, we didn't even touch on this in today's show, but healthspan also provides access to prescriptions for hormones, things like estrogen, progesterone, and testosterone, including for women. Yes, topical testosterone for women. They also have GLP1 inhibitors. I am just so thankful to Daniel Toffik for what he's doing with healthspan. And I can't wait to hear what you guys think. And by the way, I have had the best experience with healthspan. They make the whole process so easy to get these prescriptions. The customer service is amazing and I truly cannot recommend them enough. The show notes for today's episode will be at Melanie Avalon.com slash get healthspan. Those show notes will have a full transcript as well as links to everything that we talked about. So definitely check that out. I can't wait to hear what you guys think. Definitely let me know in my Facebook group, I have biohackers, intermittent fasting plus real foods plus life, comment something you learned or something that resonated with you on the pinned post to enter to win something that I love. And then check out my Instagram, find the Friday announcement post. And again, comments there to enter to win something that I love. All right. I think that's all the things as a brief reminder, you can get 10% off site wide for all of these incredible longevity medications and supplements. When you go to Melanie Avalon.com slash healthspan and use the coupon code Melanie 10. Without further ado, please enjoy this fabulous conversation with Daniel Tofik. Hi friends. Welcome back to the show.

Melanie Avalon
I am so incredibly excited about the conversation I'm about to have. It's kind of crazy because in the history of this show, which has been like half a decade, we talk about various supplements and medications related to longevity all the time. So things like metformin and rapamycin and methylene blue and LDN and all these different things. And I don't think I've ever had anybody on the show who actually provides direct access to all of these things to consumers because as you guys know, and I even got a question about this in my Facebook group when I was asking for questions about longevity medications is some of these things you need a certain diagnosis to get them if you can even get them, but we'll talk about things like rapamycin. So the question is how do you get these different things if you really want to support your utmost longevity? So I was so excited when my dear friend who I've had on the show in the past, Andrew McConnell, he wrote a book called get out of my head, which is a modern approach to stoicism. Actually he introduced, after I met him, he introduced me to his friend Daniel Tofik who is the founder and CEO of a company called health span. And so friends, first of all, I went and looked at the website when Andrew told me about it. And I was so excited because it was literally all the things I, the aforementioned medications and such that I talk about all in a place that is accessible to consumers. So that was really exciting.

Oh, and then there were some things I hadn't even heard of and some things I hadn't even knew were things like an oxytocin nasal spray, which I have so many questions about, but in any case, so it was very exciting. I did a call with Daniel and he is just the best. And he's here with me today on the show. I heard all about his personal story and what led him to founding health span. And this guy knows his stuff. He studied at UCLA where he actually did research aimed at addressing Alzheimer's pathology by improving glucose metabolism and targeting mTOR dysfunction. And we talk about mTOR a lot on this show as well. And he has a personal story, which I will let him tell for why he founded health span. But in any case, I have now been using health span, I guess, for, I don't know when it was that we got me set up, maybe like a year or so. And it's been, I've been using it to order low dose naltrexone. It's been absolutely incredible. It's so easy to use, so user friendly. The customer support is really amazing, especially because I'm a little bit neurotic with what I order. So I wanted like clear capsules and when the pharmacy sent the wrong thing, they just completely took care of it and have been so, so amazing. So I have so many questions about all these things. Daniel, thank you so much for all that you're doing and for your time and for, thank you for being here.

Daniel Tawfik
Oh, thank you for having me, Molly. That was a very generous and very thoughtful introduction. So I'm really excited to be here.

Melanie Avalon
I am too. I've been looking forward to this ever since our phone call, like I said, and, you know, using HelpSpan. So I, okay, I have a lot of like foundational questions to start off with.

Actually just really quickly because I mentioned that your research at UCLA with Alzheimer's disease, this is a little bit of a tangent question, but I, a few months ago, I interviewed Charles Pillar. He's the investigative journalist from Science Magazine that actually discovered the fraud that was happening in Alzheimer's research. I don't know if you remember when that, like that whole thing came out. So he wrote, he wrote a book called Doctor where he talks all about it and literally that book blew my mind when it comes to lab work and fraud that happens in like just the scientific community. That's an intro question for a way to say I'm dying to hear a little bit more about the work that you did surrounding Alzheimer's. And also did you run across anything like that or do you remember like when that became a whole thing, that, that whole story?

Daniel Tawfik
Yeah, I mean, so this is dating back almost 20 years for me. No fraud in the extent that we were dealing with a mouse model exclusively. So only to the extent that we were just investigating this idea that Alzheimer's dementia is downstream of some metabolic dysfunction, meaning specifically when mitochondrial function diminishes in the capacity of the neuron to uptake glucose and utilize it for energy. When that diminishes, you see the subsequent diminishment of the neuronal function and you get the atrophy of the neuron itself.

And so we were looking at these genetically designed mice who had this receptor, a deficiency in a way that we engineered them to be less adept at utilizing glucose. We were looking at whether or not the use of metformin could restore that by using GLUT4 channels to get glucose into the membrane and then better allow access of the nutrient itself and restore the function of the neuron. And we had a lot of success there, but there was always some confounding factor with whether or not the metformin was targeting the access to the glucose or if it was more of a function of mTOR activity because metformin is a stimulant of AMPK and downstream of that it inhibits mTOR, this cellular switch that makes a decision whether the cell has a sufficient amount of nutrients available to be in a growth stage or in a more of a quality control restorative phase where we're going to use cellular components for energy. So when people are fasting, they're essentially inhibiting mTOR in the same way that taking metformin does.

So we were looking into utilizing rapamycin, this kind of geroprotective compound in the context of a mouse model for AD and we saw these very interesting effects where we saw less of the inflammatory pathology that we would associate with with AD pathology. So time goes on. I'm familiar with this research and I start hearing about kind of in the influencer worlds of Peter Tias and Matt Gaberlin talking about the use case of metformin and rapamycin in humans and they're doing it kind of on these end of one experiments kind of biohacker but very analytical people too. So they had access to the diagnostic tools to determine in themselves if things are going awry or things to look out for from a side effect profile. So in the popular discourse, you saw a lot of people interested in these molecules that kind of target this metabolic overdrive that happens as we get older. And when I went to go talk to my PCP, it was just like, no, you're in your mid 30s. Why would you want to take metformin? You're perfectly healthy.

At the time, the metformin was kind of the thought to be to have the safest profile just because of the ubiquity of the usage of it and just observational data, kind of the side effect profiles, very little. So when I went to talk to my primary care physician, it was just like, no, you don't have diabetes. It's indicated for diabetes. You don't have diabetes. There's no reason someone with your health status would be on metformin.

Daniel Tawfik
And that was something that I kind of that brick wall that I saw kind of across the spectrum. I'm surrounded by physicians and my family. My wife is a physician. My brother is a physician. It was clear that what was happening from the academic standpoint in the research community wasn't getting to the clinical front lines where someone who's I spent almost five years studying these molecules and it was just like the way that I was, my understanding of the molecules was very different than my primary care physician. That was the brick wall that I faced my own personal journey.

When my wife had lymphoma and her cancer relapse and she had to get a stem cell transplant at City of Hope Hospital and she was put on rapamycin so we were pretty intimate with how this molecule works from just kind of a research perspective but she was taking from the indicated use of a stem cell transplant. I got to re-emerge myself with all the research on rapamycin and kind of the anti-tumorgenic effects that it has outside of just the indicated chronic use for immunosuppression. I wanted to get her into the practice of someone who was kind of familiar with these kind of who had a strong metabolic oncology perspective and you know all the clinical team was great and they're really dedicated to dealing with acute issues of a person in the throes of the disease. But I wanted to, I was like post-stem cell transplant, I wanted to see if there was a practice that I would feel comfortable that we had a physician that can manage kind of all the lifestyle factors, make sure that the metabolic components of this disease was really honed in on it and I tried to get her into Peter Attia's practice.

Daniel Tawfik
He had written an article on the use of metformin as a kind of prophylactic against tumor growth because of like the metabolic quirks of cancer cells and their kind of voracious capacity to use glucose as an energy source and I was like I wonder if we can get her and this is 2019 before Peter Attia was 60 minutes Peter Attia and it just wasn't possible for sort of many reasons but like the thought dawned on me like why couldn't we just create our own practice you know like why with my background you know my wife was very sick at the time so it was just she wasn't the propelling force and she was dealing with her own issues but like with her understanding of these things and kind of that that backstory of trying to make sure that people don't end up in the state that she was in right there's lovers that we have in our disposal to mitigate against the chances of you having age-related chronic disease and if we could use one of the kind of core foundational pieces would be like we would be analyzing all those coming out of the research community and creating protocols for people that may include some of these these what we call JARO protective novel molecules like myosinin and metformin and you know what would turn into sGLT2 inhibitors which were really there's a lot of interesting data on if we could offer those for their off-label use because of their kind of multi-pathway upstream capacity to target these these metabolic pathways that go awry as we get older that would be meaningful for us and that's what healthspan turned into and it's involved a bit from just distributing the medications to working more intimately with with patients so that's kind of like the the genesis of the company i think it's five years in the making so we're progressing every every day and trying to really kind of push the field forward and have as much scale as possible to have as much impact so that folks no matter what state they're in they can they can have access to a longevity scientist that they can connect with to discuss their issues

Melanie Avalon
Oh my goodness. Okay, so many things. I think listeners can see now why I'm so excited about all of this. How is your wife now doing?

Daniel Tawfik
She's doing great. At this point, it's seven years. Her cancer relapsed in 2019 in August, so six and a half years removed from her stem cell transplant. She still has a lot of residual issues from the stem cell transplant.

Essentially, she was given a new immune system. And some of that immune system, particularly when she just got it, had some graft-first autoimmunity issues with this baby naive immune system attacking her own tissue. So there's some residual effects of that. But she is actually prescribed the majority of the medication that we prescribe to manage those rapid bias and SGLT2 inhibitors. And it just coincides with our broader philosophy of prescribing those for the off-label use for a more broad use case outside of just kidney issues or managing diabetes. So overall, she's doing really great.

There is some kind of... She has to be way more on top of things that your average person is, but it's just like that's who she is. And as a physician, she has the tools to do that. But overall, she's doing great.

Melanie Avalon
So to that point, because you're saying that she's, you know, on a lot of these things. And two, so two of the big ones that you mentioned just now is the rapamycin and metformin. And something that's so intriguing to me is, because I've been following kind of a similar timeline, it's probably around like 2019, like you said, when I first started really learning more about these things for me, and like learning about Peter T and all that stuff. It's interesting to me, metformin, for example, I feel like most people know about it now, and they know about its longevity potential. Like I can mention metformin and feel like I don't have to, at least if I'm like talking with my audience and stuff, I don't have to give like a lot of background about it.

Like people pretty much know the use case for it, both for like diabetes and also for longevity. And I feel like it's a little bit more accessible. But rapamycin, I would have thought by now, I think I would have thought by now it would be more accessible, but like I don't even, until I met you, I was like, I don't even know how I would go about getting this. The dosing for it seems to be so controversial or debated, like the, you know, the amount to do and is it an immunosuppressant or immunostimulator? Like, yeah, so I'm just curious, the evolving science surrounding it, what do you think are the barriers to it becoming more used? And also how, how tricky is that dosing? And how do you guys handle that on, on your site?

Daniel Tawfik
All the points you brought up are totally spot on. So one of the issues is because it's, rheumatosin has been around, it's a generic medication. It's been tested, it's indication is immunosuppression. So that in itself is a very scary thing, right? We don't want to suppress your immune system because it's so frontline against all sorts of pathogens. And so we, from cancer to everything else, right? This is something we need to really make robust as particularly as we get older. So that's a pretty scary label.

And the incentive structure to do a clinical trial to get FDA approval for health span promotion, it just will never happen because the things are costly and how do you measure health span? And you probably should choose in what we call an indication, something to an end point with a system. It becomes really hard to finance that type of thing. I think because of that, there's not with GLP ones, there's gonna be a gazillion indications it's studied for because everyone's looking for insurance to profit off of it, right? Which is totally fine. For the generic medication, that's not like targeting such a, it's targeting a nebulous thing, which is health span. It's just, it's gonna be almost impossible to do it. With that being said, they're in the process. A woman named Joan Manik is her company called Tornado Therapeutics. And they're coming out with something called, what we call a Rapalogue, a more targeted version of rapamycin that seems to not have any affinity to the complex mTOR has two complexes, one that manages cell growth and autophagy, the things that we want to kind of modulate here and there cyclically. And then at higher doses, the way that my wife was taking rapamycin on a daily basis, the concentrations of rapamycin go up to a point where it inhibits the second complex, which has some capacity to regulate. metabolic health lipid. Someone who's taking too high of a dose will have elevated lipids, elevated glucose levels, and would see some diminishment of immune capacity. What John Maddox Group is doing is making a molecule that has no sensitivity to the Complex 2, all of the side effect profile, and that can specifically target Complex 1. So that's an interesting piece of what we have to look forward to and the incentive structure to get that. They can bring that to the market and they can make money off of it. That doesn't exist for the generic rapidly that is commercially available and is something that most consumers can afford. So there's that dynamic. I think in terms of there's so much in the discourses, particularly in the influencer community, there's just a lot of opinions that are end of one self biohacking that put a lot of confusion into this. Not confusion, but it just makes everything very murky on dosing in particular and whether the extent to which rapamycin is delivering is the holy grail of longevity medication. So we're constantly dealing with that.

Daniel Tawfik
There are three studies that I was so excited about, which kind of break through the noise of all of these influencers with opining about this medication that they may or may not be taking. But there's three studies that are really, really interesting and they hone in on the dosing question because they could target a therapeutic dose and then they measured autophagy levels. They measured side effect profiles and all the safety considerations. There was a therapeutic range that didn't really elevate any of the side effects that we would really be worried about.

It comports with the way we prescribe too. We think about it as 0.75 to 1 milligram per kilogram of body weight. It's typically how we would dose it. Let me go back to the studies, but let me tell you our way of doing it. We've had over roughly 7,500 patients on rapamycin. And they all go get their blood work while they're on the protocol itself. And some people are cycling it, doing it every, cycling from a monthly perspective, meaning they're taking it three months on, three months off. Some people, and they're all taking it on a weekly basis on that kind of, that dosing strength schedule once every seven days or once every 14 days, depending on what their lab results come back. So if we see any of the mTOR complex two stuff flaring up, we'll, we'll change the cadence of the dosing or lower the dosing. But typically we don't see that side effect profile. And now going back to the, the three studies that came out in 2025 that were really exciting, there was a group setting ovarian function in whether essentially we get around your mid thirties, fertility rates declined quite a bit. And what they did is they looked at kind of the, we call this kind of metabolic overdrive like cells were overproducing their over, there's some we call hyper functions. They were overly producing proteins that there wasn't a commensurate amount of quality control through which we typically get through autophagy. Basically, you know, think about from the neurons perspective go jumping from ovaries to neurons for a second, like in a neuron when we mTOR is overactive, you get the production of all these misfolded proteins, these tau proteins that cause an inflammatory landscape in, in the brain and the extracellular matrix. And the same thing was happening at around from 34 to 37 in women. And so when they looked at kind of the whole milieu of cells, they saw this metabolic overdrive, the overproduction of proteins without a commensurate around of quality control, degrading proteins that were kind of toxic to in degrading tissue function. And then they put these women on kind of the longevity that the same rapamycin dosage that we talked about that we do in our clinical practice, they put those women on rapamycin. They saw that that imbalance of overproduction of certain proteins causing tissue decline goes down and then autophagy increases such that the ovarian function gets preserved over time.

Daniel Tawfik
There was a study in heart failure patients as a very small study, but they were also able to, so heart in the cardiomyocyte, there's an overproduction production is hyper function overactivity of mTOR that's happening where the fibroblasts are laying down too much collagen and the tissue becomes really stiff when it should be really flexible to allow for the ejection of the fluid to be really agile. So they put these patients who had HCM cardiomyopathy on rapamycin and they saw greater flexibility, but the same dynamics. It was this over mTOR activity was too much. And if we could reset it by using rapamycin on a cyclical basis, there was not the overproduction of these, of these proteins. And there was a commensurate amount of autophagy. So clearing out of the misfolded proteins, that hyper, that too much function goes back to that overdrive that's really unhealthy, goes back to a more stable level and the tissue function gets restored.

The last one was there was a recent study on chronic fatigue syndrome, which is a really nebulous thing. Basically when a patient overexerts themselves and we're talking about doing really standard things, they feel really overexerted. They, there's something called the post-exertion malaise where they could be doing just work for 10 minutes and then just feel totally fatigued after. And they saw that in these patients, there was a inhibition of a top normal autophagy function. And of the patients that had the worst kind of the worst symptoms, rapamycin usage, increased autophagy, restored autophagy back to normal levels and healthy levels. And from a symptom perspective, patients were felt from this, this kind of exertion standpoint had more resilience than they had before.

I'm not speaking incredibly articulate about this particular study because there's a whole set of criteria that I can't really speak to from the symptom relief perspective, but it was just really interesting to see that outside of doing like an FDA clinical trial, researchers were kind of going back to these kind of these communities of people that are struggling and there's no matter what tissue type, there is this kind of this pathway that goes kind of that goes awry as we get older. And it's somewhat ubiquitous, universal. It doesn't matter if it's your brain or your muscle, across the board, there's this hyper function of a cell that leads to the diminishment of function and rapamycin can kind of make it such that they, it takes the, the hits the brake on it or the accelerator might be missing, mixing metaphors here, but and also increase the body's capacity to clear out debris through simulating autophagy and make it such these pathologies get in some meaningful way, somewhat reversed and having a meaningful impact and ensure outcome. So it's, it's a, it's pointing to kind of what aging is fundamentally and there's just so much overlap between this mTOR capacity and like metabolic health and the foods we consume and the way we move our bodies to that, you know, I talk about rapamycin quite a bit.

Daniel Tawfik
You can get that, that stimulation that mTOR inhibition through a myriad of ways without ingesting anything either. So that's always a possibility too.

It just means from the, from the individual's perspective, understanding what levers to tap into whether you're like, I want to be in a cellular growth phase for which serves a purpose as we age and or do I want to be in a phase where I'm kind of doing more clearance and maintenance kind of work, which we just need stimuli of both and there's molecules through that rapamycin reformin, SGLT2 inhibitors and there's just lifestyle mechanisms too. You can do that too. If you don't want to take a medication, that's also fine too. Like you shouldn't be just medication, medication, medication, but just under if people understood these mechanisms, then they could leverage the way to stimulate these, these levers and mechanisms in their life. And the operative thing too is you don't want to do chronically anything. You want to get like, you want the muscle growth in one phase of life or one phase of a year, one phase of a week with rapamycin, the converse of taking rapamycin. So like I take rapamycin once every seven days, but I get that kind of autophagy stimulation, but then I have my amino acids for the rest of the week so that I can have normal muscle growth, which serves the longevity purpose too. So when people understand the mechanisms, they can leverage these things, these stimuli throughout their week, throughout their month, throughout their year, throughout their season of life. So I think that's really important.

Melanie Avalon
First of all, going back to what you were saying at the beginning about just practically, there's probably never gonna be the studies we would want to see on longevity for these medications. It reminds me of, I had David Sinclair on the show a few times, also before, I mean, I guess he was popular at the time, but it was kind of like we were saying with Peter Tia before he was really, really, really huge. But I remember in his book Lifespan, a big part of that is advocating to make aging a disease primarily so that it can be a diagnosis criteria so that they can, you know, then they could actually do studies on these drugs for longevity purposes. Maybe someday, we shall see.

Okay, I think what you said at the very end kind of answered or pretty much did answer because Maris had a question. She wanted to know if the benefits, and this was just about longevity meds in general, but she wanted to know if the benefits outweigh the side effects. And she said, do they make things grow that we do not want growing in the body? And so I think you kind of spoke to that with the cyclical approach to things. Like, you know, you don't want to be on presumably any one thing all the time in like growth, growth, growth mode or, you know, anti-growth mode. It sounds like you need a balance of both.

Daniel Tawfik
I think that's precisely right. You can see certain populations of people that are, I mean, Americans are, unfortunately, we have this word, the standard American diet, this phrase, the standard American diet. And essentially, through nutrients, all that we consume, we're stimulating cell growth a lot. So particularly with folks that are obese, the stimulation of these growth pathways through the food that we ingest, the hormonal response to the foods we ingest, whether it's insulin, which is a huge stimulant of mTOR. If we're doing it all the time, we're growing a lot of tissue, and not all of our tissue is healthy, right?

So you see the propagation of dysfunctional cells, whether they're senescent cells or tumor genic cells, or cells that have this hyper function, they're kind of overdoing the thing that they were built for, leading to an imbalance of activity. There thereby, like through the constant simulation, from a caloric perspective, a nutrient perspective, they're driving the hyper functions of the cells of the tissue, which then drives the diminishment of function of that tissue. Another group that this is received as bodybuilders who are constantly stimulating muscle growth, but there's no that I'm aware of a no anabolic stimulus that just targets the muscle itself, it targets the growth of everything. So you see heart failure, all the that study of rapamycin for heart failure. The converse of that is you're driving the growth of these fibroblasts that are making the tissue more stiff across any tissue we have. If you see the overactivity of it, you're leading to growth and overactivity of the cells that's not in balance with cells that do something 180. An example of this that I always explain is osteoblasts and osteoclasts in people with osteoporosis. there's an mTOR component to osteoporosis, which is the osteoclasts, which is breaking down bone formation. It's supposed to remodel bone, so basically you layer it. Think of like layering down bricks or bricks in a property, and you've got to kind of sand it down to make it smoother. There's some material that's kind of laying down material, and then we're smoothing it down to give it shape and more formation to be formed to the architecture of the body better. In osteoporosis, the osteoclasts are overactive. Their mTOR activity, in some cases, is like very heightened, and in that it diminishes. In being overactive, they create this porosity to the bone itself. Across any system, there's a version of that story. In the bodybuilders, they're kind of always turning on the switch to let's be in growth phase, and that's not a good thing. Conversely, not that there's many people that actually fit this criteria because it's extremely hard to do, but folks that are in a caloric restricted state all of the time become feeble.

Daniel Tawfik
Muscle is a really healthy tissue. A lot of folks are calling it the most important longevity tissue. I think that's probably true.

If you're always in a caloric restricted state, or you're always taking Raphomycin seven days a week, or you're taking Metformin all the time, so we saw an influencer taking these Megadoses and Raphomycin and Metformin and all these mTOR inhibiting molecules, you're also getting too much of mTOR in a mission because you're not going to get normal muscle growth. It's just like these things are very complex. These systems are pretty complex, and you just don't want more is not better. We see this with Raphomycin, particularly when we started, and particularly with the set influencer. You can read between the lines. Most people know who I'm talking about, but we're taking the Megadose, and all the folks that would come to healthspan would be like, I want to take the 13 milligrams per week. That's not really a good idea. That's not a good idea because you're over inhibiting mTOR, and you're getting levels of Raphomycin in your system that can potentially inhibit mTOR complex too, which is how you stimulate all that side effect profile. So mTOR is not always better. It's usually like you have seasons of life. You need to cycle through different stimuli or hormetic effects of lack of stimuli in the case of fasting. You can teach me more than I could ever... I can talk about the Raphomycin synthetic version of fasting, but I think going in and out of those phases makes a lot of sense.

Melanie Avalon
Speaking to the nuance of everything, my mind is kind of blown thinking about something you just said, which is how the example of excess mTOR overstimulating osteoclasts, which we think of as breaking down bone, it's so interesting that, you know, an excess growth signal could signal something that actually decreases growth, you know, like that's so complicated.

Daniel Tawfik
It took almost because these systems, like here you have two different cell types. If one is not in balance with the other, you get the, you get the overactivity of one cell type at the expense of another.

It's like, these are players in the symphony and they can't just, you can't dial one up to, you know, to 11 in the spinal tap mold and just dial in without any consequences to the other members of the symphony. So these, these pathways, it's like, okay, mTOR, mTOR is bad, right? It drives, it's kind of a simplified version. mTOR is bad. So I want to chronically inhibit mTOR all the time, or I want muscle. mTOR is great. Let's, let's just take amino acid, let's take leucine, which stimulates mTOR all the time. Well, how does that play with kind of like this metabolic overdrive dynamic? Like that's growing all sorts of bad tissue in the bodybuilder dynamic. So it's, it's just like, there needs to be some balance of how these, these pathways are, are working or, and any cell types are working with each other. I think they all serve a purpose may have a way to balance themselves pretty naturally through, you know, billions of years of evolution that we can't just hijack that those systems by hitting the, the break really hard or hitting the accelerator really hard.

Melanie Avalon
I have a related listener question, but before that one quick question for me, you mentioned that when people are on your Rapamycin protocol that you're testing their levels, their blood work, and you're looking at the mTOR complexes and things like that. So I'm really curious, because one of my good friends is James Clement, and he does a lot of research, and he did the largest study on the blood work of supercentenarians, but he does ongoing research on mTORs, like one of his things he studies all the time.

And he's often telling me about the timeline of how long these different compounds remain elevated. And so I'm really curious when you're testing somebody's blood work to see where they're at, what is the turnaround timeline of how the medication affects the mTOR complexes, and then how do you know it's not being affected by one of the other lifestyle things that they're doing?

Daniel Tawfik
We can give a patient a Raphomyosin bioavailability panel, which is the first question of like, how long is it in your system? And I think about it in terms of like three days. If I take it on Saturday, I'm not going to be doing weightlifting because it's kind of mixing signals of like anabolic versus catabolic signaling. So I'll just go for a hike or do cardio on Saturday. And then Sunday, there's going to be some bleeding over to Sunday, but I usually do kind of like a restorative day from my own kind of lifestyle regiment of exercise.

So we're looking at like three days it's in your system, inhibiting mTOR. There's a different question about whether it's like inhibiting mTOR Complex 2, which we can't... There's no test for that in the sense of there's tests in academic, there's tests that exist to see mTOR Complex 2 sensitivity in the lab, but it's not commercially available. All we have is proxies to see all of the things that mTOR Complex 2 regulates when it's inhibited to see if those levels are elevated. So you came in and you did baseline blood work with us and you had a lipid profile coming in that then three months later is elevated after we do it six weeks later after you have been on the protocol up to basically from week three to week six, you can go get your blood work with us and we can see if the dosing is incorrect. At this point, it doesn't really happen because we feel pretty comfortable with the dosing guidelines based off of body weight. But if someone has a certain Complex 2 sensitivity, we can pick it up in these proxies for metabolic health in serum chemistry testing. Basically, your lab core and quest accessible to the public test that anyone would have access to that we prescribe out at that cadence. Unfortunately, from a diagnostic perspective, there's nothing more granular than that that's commercially available. That would be in the price range of someone, something that is not under $1,500. But we have a pretty good sense from the lipid profile, the metabolic profile. So these are pretty cheap tests that anyone, like if a clinician wants to make this more accessible at their local practice, they can use a CMP, complete metabolic panel profile. They could make that accessible to monitor their patients to make sure they're not getting on either side of the profile. And then there'd be other things too, there'd be more drastic, which is like an infection arising. If you did the mega dose, the 13 milligrams per week, if you did the dose that my wife was taking for immunosuppression, were you getting infections more than you know you're dosing too high?

Melanie Avalon
Okay, gotcha. That completely makes sense.

And that was actually a perfect segue to the listener question I had because you were talking about how you do your protocol with rapamycin and then not doing strength training in that three-day window when it's in your system. And similarly, so not rapamycin but metformin, Kersey wanted to know how does metformin impact strength training and what is the best protocol to combine both? So is there a similar concern with metformin and strength training?

Daniel Tawfik
Yeah, absolutely. So I don't take metformin for this very reason. And it's not something that from a clinical perspective, we are as bullish on at this point in how the research has panned out on it for this particular reason. It has a use case. It absolutely has a use case. And for a subset of patients, it's going to make a lot of sense. It's very well studied from a safety perspective. It's very, from just a metabolic health perspective, it has a preponderance of data showing its effect on metabolic health outcomes that are great. That being said, for someone who exercises regularly, you're blunting some of the mitochondrial adaptions to exercise. And for resistance training too, because there's a go to the mitochondrial adaptions, you're basically tricking the cell. You're almost putting, you're blunting the mitochondrial. You're in fact poisoning the mitochondria to think that it's in a nutrient deprived state. And as such, you're putting a muzzle on the mitochondria to take one molecule of glucose and it's not creating the more energy rich version of cellular energy ATP. It's creating which has three phosphate groups. The phosphate groups are like the energy source. The mitochondria is then outputting something called AMP, which is a monophosphate, one phosphate group, and signaling to the cell that we're low on energy. But it does that by putting this muscle from a visual sample. You think about a muzzle. It's not really a muzzle. It's binding to one of the sites on mitochondria and it's diminishing its capacity to create energy. So it's also diminishing the mitochondria's capacity to, for mitochondrial biogenesis to become more efficient at creating energetic output, if you will. So for that reason, because exercise should be like the first thing before you even take medications or someone who doesn't have a metabolic disease, has diabetes or some other metabolic disease, they probably shouldn't be using metformin for that purpose.

They should probably make sure that exercise is the first thing that they're doing and diet is right up there with it in parallel. But if you're exercising, I just wouldn't recommend doing because you're still getting some adaptations, but you're not getting the full effect of the adaptations to exercise. So I think that's really important. For that reason, we've kind of downgraded metformin. From a metabolic perspective, we think the best GLT2 inhibitor is much more interesting. You still get the AMPK benefits, but it's not mediated. It's not delivered in the same way of flaunting the mitochondrial's capacity to sense, to output energy in the same way. And we can talk about SGLT2 inhibitors, but I think the listener's concern is super valid. From the perspective of resistance training, it's diminishing inflammation a little bit, which is a great thing, right? That's a really good thing. This is one of the the giroprotective... When we say giroprotective, it means that it's conferring a benefit that is really kind of root cause and affects multiple pathways that are systemic of aging.

Daniel Tawfik
So inflammation is one of those. Metformin is reducing oxidative stress and inflammation. So on the day that you're doing resistance training, those both that oxidative stress and the inflammation are actually conferring the adaptation to exercise. You need an inflammatory response to get the muscle growth to happen.

That's one of the signals to repair an area. So for that reason, it diminishes some of the resistance training benefits. So I would say probably if you're doing everything right on the exercise or on the diet side, you probably don't need metformin. That's something you could talk to with your physician specifically, but that would be my recommendation.

Melanie Avalon
Didi wanted to know if berbering gives the same benefits as metformin.

Daniel Tawfik
Yeah, it's different. I can't speak to the exact biochemistry difference, but it's the same pathway. It's stimulating the AMPK. So it's kind of like the natural version of metformin. But just from that's my understanding of the molecule, but it's not super sophisticated.

So beyond just like what it's targeting from a metabolic pathway perspective. And what I would say is, yeah, they're doing a very similar thing. One is a supplement version, one is a medication. They're really targeting the same thing. So yeah, they're similar.

Melanie Avalon
So before we leave the world of rapamycin, while we're talking about the immune system regulation, so I have not, I have not done the protocol. I've never tried rapamycin ever.

I'm very, very curious by it. Would it interact with, because like I mentioned briefly in the beginning, how I take lotus naltrexone, LDN, from HealthSpan, would those interact since they're both playing on the immune system? Oh, I guess LDN is playing more with the endorphins.

Daniel Tawfik
Yeah, but it's also modulating neuroimmune function, which is really important. At best, they're additive.

They're not cross-talking in a way that creates a side effect, but I take both of them at the same time. And the LDN is really, from its immune modulation perspective, is targeting kind of errant cytokine signaling and sort of diminishing overall immune dysfunction in a way that's not mTOR dependent. So there are different pathways. And to the extent that hallmarks of aging is this inflammation, they're both targeting inflammation but not in not targeting the same pathway. So it's not like overdrive that same kind of dollop to 11 dynamic that I was talking about before. So we have patients taking both at the same time. There's no real issue there.

Melanie Avalon
I'm curious, how long have you been taking it and what dosage are you on? And the reason I'm asking is I started for lotus naltrexone. I started taking it in 2014. It was initially prescribed as a prokinetic by a GI doc, actually, like a conventional GI doc, but then I stayed on it long term for the holistic health effects, so like the sleep, the mood, the inflammation.

And I've tried different dosages in the past, but I actually have perpetually for a while been on 1.5, which I know is very low. But I actually had a doc suggest that A, that it be cycled, or B, that I go off of it temporarily because my CRP is always like a complete flat line, like it has been for years. And she was saying maybe I was too inflammation suppressed, but I like being inflammation suppressed. So I'm just curious your thoughts on like dosages and like cycling it.

Daniel Tawfik
Yeah. So the cycling is interesting. Here is where there could be some more academic research going on. And then it suffers from the same, it's a generic medication. It's a low dose version of generic medication naltrexone. So academics are setting, and there's a guy named Jared Younger, who's doing a study on LDN right now. I would highly recommend anyone who's dealing with long COVID or chronic fatigue syndrome or one of these autoimmune fibromyalgia, see if they can be enrolled in that trial just so we can measure some outcomes in symptom management with his protocol. But there again, we don't have a definitive answer and it becomes symptom management quite a bit.

I've been taking 4.5 for years and the only time I ever felt good was within the first month. I was like, wow, I feel great. This endorphin thing is real. And then I just take it like a vitamin now. But cycling makes sense in the context of that. Your body, we stand up receptors. It's a feedback loop of how much endogenous opioid, we could be increasing the endogenous opioid, but there's not a commensurate around. Our body adapts from the amount of endogenous opioid receptors that we have. So it stabilizes. That's what happened for me. So taking it in and out. Now I'm in the context, I don't have an autoimmune condition. And someone with IVS or IVD, they would probably take it continually, but there's no definitive answer. And this is where the murkiness of our field comes in. We think just from an endpoint perspective, these are good things like CRP going down and information going down is good. But it becomes really N of 1 for us. We're trying to measure as much as possible. So did this to patients protocol, saw this outcome and blood work. That's a lot of biostatistics that we have to do on our backend that there's no clear signal on it that we have arrived at yet. So it's completely theoretical at this point.

Melanie Avalon
I don't remember if I told you this story. Did I tell you the story about when I was on LDN in the hospital, like in 2017? No, no. Okay. So apologies to listeners who have heard this story before because I tell it quite a bit, but I find it so fascinating and eye opening and enlightening.

It really speaks to how, I don't know, how there's definitely a lack of education around a lot of this stuff just in the conventional medical system and also how you need to have patient advocacy to make sure that you're being heard and understood. And I just think it's funny. So I was in the hospital actually for anemia in 2017, I think. I was on LDN. And when I finally got discharged from the hospital, I of course asked for all the hospital notes. So I got my whole chart, all the notes they had taken about me. One part of it said, patient says she doesn't drink a lot, but she's on naltrexone. And so for listeners, naltrexone in the normal dose form is used to treat addiction, alcohol withdrawal, things like that. Low dose naltrexone is a very, very minute amount that temporarily blocks your endorphin receptors in the body. So then your body rebounds and naturally creates more endogenous endorphins. But I just remember being like, wow. So they're just assuming I'm lying. And I would have never known that unless I asked for the doctor's notes. Isn't that wild?

Daniel Tawfik
That is why I think you did tell me the story last year. As soon as you started saying I was in the hospital and I was like, I know where this is going. I was like, sometimes when they're doing the best they can, they're dealing with so many acute problems of the patients coming in with all sorts of really bad stuff. When I go talk to them, I had to get a health form filled out for some policy that I was getting filled out. They asked me about LDS. My primary care physician asked me about LDS. He's like, what's that? I said, it's like naltrexone but a very small dose. It was like a 30-minute conversation about why I was taking naltrexone. It's understandable why we have these conversations with physicians.

They're really doing God's work in terms of healing people. But that doesn't mean that they have need to know who Jared Younger is at doing an LDN study and stuff.

There's a bandwidth problem here. I think a lot of that's going to be resolved with some AI tools that they'll have the capacity to answer, go talk to an AI about what is the latest research on LDN for healthy people. Those will have it all at their fingertips on this at some reason. I think that's a good thing and that's something to look forward to.

But it definitely requires a lot of curiosity of the physician that you're talking to. I want to know about how this... There's a perplexity of... I don't know what's going on with this patient. I'm going to go look at a lot of research. Oftentimes, they don't have that luxury of the time.

But sometimes, you'll get a really curious physician who she or he wants to dive deep into the research. There's a doctor I was just looking... I'm totally lapsing on his name. But he solved his own autoimmune condition that they thought was cancer. You might be familiar with this. I'll send you after the recording his name. But he had to solve his own issue. So he was taking rapamycin in the immunosuppressive regiment. So I don't want people to have false hope of like, oh, I'll take rapamycin and cure my whatever the ailment is.

But he was taking it in the daily dosing. But he had to go through all the literature. And there's a lot. And there's the thing that's really perplexing. We're all very hopeful people. We want to know that there's things out there that can change the trajectory of our aging and maintain our function for as long as possible. So we can be active and do all the things we like to do for the longest period of time. There's always going to be a paper that's titled, this thing is solving this problem.

Because we're hopeful, optimistic people, we want to believe so much. And this is where the influencer community becomes like, everything is good. Everything is good. And dial it up to 11 again. So it requires some analytical skills to figure out. Like, OK, there's a data point that says it's good. But what was the p-value of this study? And how can you discern what's good information and what's a little more flimsy?

And so it just requires a lot of time. It really does. It really just requires a lot of time.

Daniel Tawfik
So I think that should be a foundational piece of what people building towards the future are doing, is they're really just grokking as much of what's in the research community, taking data points from preclinical animal studies all the way to human studies. And then the folks that are the most fortunate among us can help fund some of these human studies that don't have a clear commercial outcome associated with it.

Melanie Avalon
Yeah, and also a quick comment on the AI stuff. I was a little worried for a bit because earlier versions of like chat GPT and the different AI bots, they, well, at least with chat, it would just make up stuff. Like it would like make up studies. I would like ask it to read studies and tell me, and it would just make up stuff. And I was like, this isn't very concerning because I started using it to help prep for different shows. And then I would like go look at the links it gave me. And I was like, this is not at all, but it seems to be getting a lot better now, thankfully. But I was like, Oh, we are on a slippery slope right now.

Daniel Tawfik
we had to let go of someone who was overusing it. And I was like, these are not real links you provided, but if you can just prompt it with something of tell me, can you give me like all of this, just tell me the studies, just point me in the direction of the studies. So it's kind of acting like a search engine more, but it's giving you kind of a summary of what the study. So in like, in that capacity, it could help the physician. And if you're also providing a good data set of like, if someone's really focused on providing it, the studies to that, that's another way to like, make it a little more accurate as well.

So it's it is overall getting better in the sense that you're like, it's not hallucinating as much. But I do think it could be a powerful tool for my brothers. The hospital is set at Kaiser. He's seeing an issue that's like an outlier. He's never seen it. He can give it, you know, it could be a good diagnostic tool for these outlier things that doctors might not immediately understand.

I think because it can it essentially has all the data points, you know, that exists in digital form. And that's powerful. That's more than like the human brain can really capture. So I think there's a lot of things we have to be wary about. In like the hallucinating sense of things, but also just know that it could be a powerful tool in the future.

Melanie Avalon
I totally agree. I got a lot of questions about methylene blue, but also you're mentioning the SGLT2 inhibitors. Which path do you want to go down?

Daniel Tawfik
either one's fine. I think like methylene blue, I'd be more cautious about like telling everyone to take it.

I can just give people like the the my honest assessment of it. And SGLT2, I'm just like less cautious about like this is what this is like metformin 10 years ago. So either way, you want to you want to go I can do both too. I'm totally fine on a time perspective.

Melanie Avalon
Two brief questions about methylene blue. The first one is so easy. It's fun. It's Kena. She wants to know, is it really, really blue? Like dye your teeth blue? Yes, it is.

Daniel Tawfik
No, if you take it in a pill form, it's not going to dye your teeth.

Melanie Avalon
And isn't it a pill that comes to your health line?

Daniel Tawfik
Yeah, yeah, we we we prescribe a pill form that your urine will be blue is the thing. So that's it's everything's blue. I would be like, I don't we did a subsample of patients who are on it. And we use this diagnostic tool called me screen that measured mitochondrial output from a different a different bunch of parameters. And it was we did not do a good job in the study for a lot of reasons. It was like, we couldn't control a lot of things that the patients were doing. But we, we put, I think it was eight, eight to 10 people on methylene blue. And it was not clear that it like, it made a huge impact on mitochondrial function.

We're we're doing a podcast with one of the researchers Francisco Gonzales Lima, who is a huge proponent of it. And the way that his diagnostic tools in kind of meta neuronal metabolic function, the how mitochondria function in the brain, he's having a ton of really powerful data that he's he has a lot of more diagnostic tools that he's measuring. And he's super bullish on it. My my what I would say is probably like, if you're doing all the things for mitochondrial function, right now, like you're exercising, you're doing maybe you're doing intermittent fasting, you're getting like that hormetic effect through for your, for your mitochondria. You probably don't need to take methylene blue. I took methylene blue and I felt really good. The thing about methylene blue is the one of the reasons why you might be feeling really good. It's an MAL I inhibitors. It's basically this enzyme that breaks down serotonin and, and dopamine. And my, my neurobiology is my voice in psychiatry. So I keep I'm not the most eloquent person talking about the subject, but it basically inhibits that enzyme. So you feel good. And it could just be that you have a lot of neurotransmitters flooding your brain to make you feel really good, too. So there's that dynamic. And my sense of how these medications work, is it's probably that that made me feel good while I was taking it. And I still take it. I just don't take it every day. I think in people that take it, who have some mitochondrial deficit, it does seem to from Dr. Francisco Gonzalez Lima's work, he it's really strong evidence that it does seem to resuscitate mitochondrial function in that, that patient population. So we're talking about people with Alzheimer's dementia, these neurological deficits that, that could really be improved. But we didn't see this, like, oh, this is everyone should be on it type thing. And so we offer it and we, someone could sign up for a week, like, we have a policy, we don't actually charge patients until we approve it. So we will talk to them about the, they have a desire to use it, but at least we'll give them some feedback on whether it may or may not be appropriate for them. So methylene blue may not be appropriate for for everyone.

Melanie Avalon
That was, because I've been, I listened to a podcast recently, it might have been a Peter T1. That was the takeaway that I took away was that if you are struggling with mitochondrial issues, it could help.

But otherwise, maybe not. It's funny.

Daniel Tawfik
I think I stuck on it because I was feeling good. And then it was like, I think it's the neurotransmitter thing, but I was like, it was giving me a little pepper. My job is very, very difficult sometimes. So I needed a little more pep in my step, like a cup of coffee, but that's what I would make an analogous to.

It's like more like a cup of coffee for me, but then there's people that feel like they're more active. They got more pep in their steps. So potentially there's some mitochondrial benefits, but what I can do is I ensure you to Dr. Gonzalez-Nima and he is like, he's the man when it comes to this subject. He really can speak more eloquently to it, but my own kind of end of one in our small study that we did in the diagnostic tool is not like we were using it, we feel really strong about it, but it's not like clinically it, you know, there's some questions about it. So we didn't have clear signal on its capacity, but there's a lot of confounding factors with the way that we, we took this patient population was monitoring them.

Melanie Avalon
Methylene blue was definitely out of all of the biohacking things that I adopted earliest when it would have been the most controversial and rogue. It was definitely methylene blue.

I just remember ordering fish tank cleaner off of Amazon and you had to like dilute it. And I just remember being like, I might kill myself with this. I don't know.

Daniel Tawfik
doing it for science. I think we could recommend that people don't do that.

Try to find a clinician that can over see it a little bit for you. But the body is very resilient. You can introduce all sorts of things and you'll revert back to homeostasis at some point. I hope people don't clip that and be like, yeah, you just take whatever.

Melanie Avalon
Take all the things.

Daniel Tawfik
Yeah, it's you're not you like, be careful about what you ingest and everything and have a doctor oversee things. I would say that's kind of like the the mode of operating we should all adopt.

Melanie Avalon
Yeah, I agree. And actually, Nydia had a question about it that is, I think, actually just a good question in general about all of these things. Well, she wanted to know what it does in the body. We talked about that.

Who should or shouldn't take this? We talked about that. But then she said, is this replacing a deficiency or forcing an effect? Which I think is a really great general question. So everything we've been talking about so far, nobody has a deficiency of metformin. It's not like a nutrient that you're taking. It's creating an effect.

Daniel Tawfik
It's creating an effect in, but actually the way I was going to answer was the deficiency. It's not the like your body doesn't produce enough methylene blue. No one, we don't have like endogenous methylene blue in Dr. Francisco Gonzales Lima's perspective. It's a deficiency in the mitochondrial electron transport chain to efficiently like propagate energy across the mitochondria. So it's acting as like a donor. It's passing the electron more efficiently. It's making the mitochondria more effective. That's deficiency in the sense of like there's a process that's deficient, but not like your body's capacity to make methylene blue. It's not in that sense of the word deficiency.

So it's trying to target, it's confer an effect in that sense of things. But the therapeutic use case is to deal with a energy gap, a energy deficiency that stems from dysfunctional mitochondria, inability to take a nutrient and turn it into ATP because there's some kind of mechanical issue with the mitochondria. In this case, it's very energetic mechanically to transfer electrons across the the electronic transport chain of the mitochondria.

Melanie Avalon
Exactly. Thank you. Fun fact for listeners, I think methylene blue was the first synthetic drug, maybe?

Daniel Tawfik
I can't answer. I don't know. I don't know if that's true.

Melanie Avalon
Yes, widely considered the first fully synthetic drug, 1876.

Daniel Tawfik
from Malaria?

Melanie Avalon
Yeah. Very cool. Briefly, it's interesting. I don't think I have had on this show a conversation dedicated to SGLT2 inhibitors.

Daniel Tawfik
Yeah. So there's a group of drugs. Their SGLT2 is sodium glucose transporter 2. That's what it stands for. And then their inhibitors. So basically what it does is binds to this transporter in your kidney that's like swashing back and forth glucose. It's basically kind of filtering out glucose and sodium. And it's putting a stopper on the back into basically reabsorbing the glucose to go into the bloodstream. And it's making you pee out this excess glucose. So I think about it as like, I think it's like 65 grams of glucose that you would pee out.

And so it's having this kind of osmotic effect on your kidney where there's less pressure. And the same is true for heart failure folks who are having high blood pressure. So those are two indications that indications being the intended use case for this class of medications and for people who have diabetes. Nowhere in there did we talk about like it binds to the mitochondria and it makes it less efficient in producing energy and touching the mitochondria. any mitochondrial benefit seem to be downstream of the fact that there's less glucose available in your bodies using fatty acids and all the benefit of the metabolic effects, but independent of messing around targeting the mitochondria. It doesn't bind to the mitochondria the way that metformin does and has some consequences to that. So there is a question of does the SGLT2, in the same way all of these class of medications have this kind of caloric restriction, when I say all these metabolic drugs, whether GLP1s or SGLT2s, they seem to be having these healthspan benefits of prolonging the healthy state that you're in for as long as possible. So there specifically for SGLT2, there was a study on lifespan in a clinical model using the drug Canagua Flosin that increased lifespan by some not like double digit, like it's just eluding me the exact number, but in the teens are low 20% increase in life extension in mice that were given this medication.

There's also like all these these hallmarks of aging benefits like lower senescent burden, there's telomere attrition is seems to be blunted. So there's all these benefits. The question is like and I imagine he did the same studies with GLP1s that'd be pretty similar. Is it because you're kind of forcing a caloric restricted state? That's what I would probably, I would assume is what's going on. Or is there something intrinsic about the molecule in the way that it interacts with your brain? So like GLP1 specifically, is there something there that there's some intrinsic thing about the molecule outside of like you are more calorically restricted, you have less glucose availability, you're using alternative energy sources, less glucose means you have less insulin spikes. Insulin is really pernicious and chronically elevated. Insulin is really pernicious to overall health. It stimulates mTOR. You want to have lower baseline insulin levels. So is it the metabolic effect of these drugs, SGLT2 inhibitors or GLP1s or is there something about the medication itself?

Daniel Tawfik
And it's there's some studies on that that say like they're independent of this caloric restriction and the metabolic effects, there seems to be some other benefits with both of the SGLT2 and the GLP1s. But I couldn't like give you an honest answer at this point.

I think it's still unknown and what the research community is trying to solve for that or figure those questions out. But SGLT2 inhibitors from a systems perspective of all of the, it doesn't have a huge side effect. The side effect profiles is pretty minimal, but it also has this kind of cross systems benefit. That's what I'm excited about.

That's one I take. And I'm pretty judicious about what things that supplements I take. It's probably five to seven things that I take, not like 40 things because of all the noise that introduces into delineating what's bringing the effect. It's just a lot of confounding variables that you're introducing.

So that's one of them. I think it's interesting.

Melanie Avalon
That is fascinating. And wow, 60 grams of glucose, like the equivalent of excreting that. So if you were on like a keto diet, is there any changes there?

Daniel Tawfik
I don't think so. I see. I don't think I wouldn't. I would assume now these are the patient population that they were studying are diabetics, right? Or someone with heart failure. People who have some kidney issues. These are folks that have some comorbidities that are, they're not the healthiest folks.

So the question would be like, is it excess glucose? That is like, I'll tell you, I'll take it on Thanksgiving. When I give myself like, I'm like, okay, I'm going to take this and I'm going to be peeing quite a bit. So it's an excess. And my assumption is like, if you're on a ketogenic diet, that because I am more leading to the side of things that it's having this metabolic health benefit, this caloric restriction by siphoning off this glucose, which is like 250 calories a day that you're siphoning.

Melanie Avalon
Yeah, I was thinking how many calories it would be.

Daniel Tawfik
Yes. So I think it's without that glucose like readily available to siphon off.

I don't think for someone on a ketogenic diet, it's going to confer much benefit unless there's some additional benefit from the molecule binding to a receptor in a way that we don't currently know. So I would say probably not for someone on a ketogenic diet.

Melanie Avalon
Have you worn a CGM and started taking it and tested?

Daniel Tawfik
Yeah, it definitely blunted the like I saw I was in it was a more stressful time when I was wearing the CGM. And I was like, I got to get things back in order.

So I was doing a little stress eating to, to, you know, like even someone super health conscious is, you know, has our fallible human traits that are human nature. But I did see it just be blunt my default, the latent kind of glucose levels. And then it definitely blunted. If I, you know, I did these kind of experiments eating like white rice, and it was it was less taking that SGLT2 inhibitor than it was before.

Melanie Avalon
Awesome. And for all of these, and listeners, we haven't even remotely touched on everything that you guys offer. So everybody, I'll go ahead and give a link. So if people go to ifpodcast.com slash healthspan, that will redirect to their website, which if listeners go to ifpodcast.com slash healthspan, that will redirect to this website, which is get healthspan.com. And the code Melanie 10 will get you 10% off. So definitely take advantage of that.

Thank you so much for that, Danielle, by the way. And like I said, we only touched on some of them. There are so many more things that you offer. You offer lab work, you offer supplements, you have these different blends, like an AMPK blend and a topology blend, other GLP ones. I just have to ask you, I think we talked about on the phone, and I'm still super curious, the oxytocin spray, do you use that? And is that something that you just, like, do you spray it and then like feel happy?

Daniel Tawfik
So there's definitely like a cortisol diminishment. And so you've got to be careful with that because you don't want to blunt cortisol too much because it serves a purpose, right?

So I take it that the research around it was not in the stress modulation specifically. It was there's, I think they're husband and wife or brother and sister. Arena, Michael Conboy out of UC Berkeley found that oxytocin was as oxytocin levels decline as you age, that association, they thought that was the blood serum factor that was driving less muscle growth, so sarcopenia. So in a mouse model where they would do these kind of bind a young mouse to a old mouse and kind of share the same blood transcription factors and all of that, all kind of the same serum factors, that they would restore a muscle deficient mouse back to a more robust, more resilient, more lean body mouse. I didn't say that particularly, but hopefully people understand that. And then when you supplemented oxytocin, it would do the same thing. So their thought was like oxytocin was the serum factor that was driving muscle growth. And because it diminishes as you age, you get more sarcopenia.

And so that was the research that drove kind of our interest in it. That being said, no, like the 95% of people take it for the stress modulation. I take it for stress modulation. When I don't take it every day, I'll take it on an as need basis, but I wouldn't put it in the five to seven things that is like, this is a longevity hack. You could probably get this from staring into your pet's adorable eyes or... It's not something that I would say, like, you need this for as your, but if you need it for, if a lot of people like it for its mood enhancement and all dealing with stress, but it's not like a core driver of touching kind of the hallmarks of aging.

Melanie Avalon
Okay, gotcha. I imagine it would help with sleep, maybe?

Daniel Tawfik
Yeah. Yeah. I think there's, I take it to get me through like mid-day lulls. So I find it to be energizing, but the paper that we did a research review on, it seems to like kind of whatever psychophysiological state you're in, if you're more in kind of a restorative phase, it will dry, it will heighten that. If you're more in an alert phase, it will drive your alertness. So that's kind of like, that's the double-edged sword of it.

Some people find it energetic. I think you'd have to just, what a lot of people like taking a night. There's a lot of individual variability with taking the oxytocin.

Melanie Avalon
Gotcha. Okay.

And so for people who would like to try some of these things, what is the process like as far as do they all require labs, working with a practitioner? Like what is the actual process like for getting these different medications and things that you offer?

Daniel Tawfik
The only ones that really require lab work baseline is the medications that have a side effect profile that we want to monitor. And then also that dosing is really a driver of outcome. So rapamycin is non-negotiable. You have to get the lab work while you're on it. So we can see outcomes and at the same time know that side effect profiles, we're not seeing anything pop up.

So we can continue at this. Things that we need to dial in dosing, rapamycin, we're delving into women's hormone therapy now, that requires lab work. For LDN, which is pretty innocuous in terms of side effect profile, we can get optional lab work, but it's not required for acarvos. It's not for metformin. It's our big two most gyroprotective bullish molecules that we have, rapamycin and SGLT2. We want to kind of follow the patient along while they're taking the medication and the women's hormone program that we're doing right now as well.

We want to dial in those levels. So it's kind of a supplement in a whole set of medications we do do not require. It's kind of an individual basis of which medication you're interested in. There may or may not be labs associated with it.

Melanie Avalon
Awesome. I'm just curious with rapamycin how how often are you getting blood work? I'm trying to look at this in my life and see how often I'll be getting blood work if I start it

Daniel Tawfik
Yeah. So it's, it's a baseline and then six weeks and then we move from three to six months optional after that. So we do baseline six weeks, three months. And then once we dialed in dosing, then it's, you can just, every six months we can get that dose.

Most people don't take rapamycin consistently over the course of two. I do, I do just because of my beliefs in the medication, but a lot of people cycle on and off of it to get kind of like that cyclical benefit that we were talking about. So it's not a hard, it's just like your clinician with the LDN. There's a lot of room to experiment with dosing here and how you're feeling and what your blood work is going back on and off of it. So even the biggest proponents of it will often cycle. It's Matt Kamerlein and Peter Attia. I haven't talked to James. I don't know if he's still on it or, but, you know, the biggest believers in the medication aren't necessarily even taking in all the time.

Melanie Avalon
Awesome. Okay.

Yeah, I might I might actually try increasing my dose because it's funny one of one of my practitioners was saying You know You have this flat line CRP Maybe should cycle off and then another one was saying oh you you're on that low of dose for that long Maybe you should try titrating up. So who knows going back to like the um, the self experimentation aspect

Daniel Tawfik
There's a test, I think, that we've been talking to this group quite a bit. And we've really, they have immunosynescence tests. It's just kind of like how there's multiple parameters of how youthful your immune is, how, how well you can bounce back, how well your stem cells are functioning and how kind of synest some of your that, I mean, that's kind of circular the way I described it, but like how dysfunctional your immune system is for lack of better words, that might be a good tool you could use in particular to get beyond the CRP as the marker.

I can, they're a company called Saper Bio. They have, they have a really interesting diagnostic tool and they will send you, they will send you a phlebotomist to your door so it's like, they can still do the analysis and you don't have to go to a clinician's office. So that's something I could recommend and even connect you to those folks.

Melanie Avalon
Oh, awesome. Yeah, that would be great.

Daniel Tawfik
It goes back to this question too. It's a very expensive test. It's like north of $600.

That's like these more novel tests that are done outside of like the big Boston Heart Lab Corps quest. The tools that are really peaking our interest in longevity, they also tend to be expensive, unfortunately.

Melanie Avalon
Okay, so I'll brace myself Well, thank you so much Daniel. So again listeners go to if podcast comm slash health span Use the coupon code Melanie 10 to use that site wide and um Daniel just thank you so much for this I am so so grateful to have met you and for everything that you're doing I can't I was gonna talk to you about this, but I can't even imagine The challenges and hurdles you probably had to go through and and go through to run a company like this I mean, I'm assuming there's probably a lot of challenges

Daniel Tawfik
There's a lot there's a lot but you know, like going back to the health stuff they've gone through a lot worse and it puts everything in perspective and so like just kind of marrying like how do we get it so that other people don't have to go through what our family went through kind of makes it easier to get Through like the the the issues with what we do are all sorts of regulatory and dealing with state laws and and all that so you need something to kind of buoy you through like some Mission to get you through and that's nice to have and had that experience with our family and trying to like, okay, we can Make it such that other people are not ending up in hospitals, you know, like Managing age-related chronic diseases so that makes work pretty meaningful

Melanie Avalon
I love that so much. That's how I feel about, I mean, not to the extent of like your wife and cancer and everything, but just like my own challenges in the past, like the anemia and the hospital and stuff. It's like made me very passionate about finding answers for things and then interviewing people, sharing information with people like yourself. So thank you, thank you, thank you.

So any other links to put out there besides the ones I gave listeners, which is I have podcast.com slash health span with the code Melanie 10. Can people follow your work or anything else you want to put out there?

Daniel Tawfik
Yeah, I mean, I think we do just, we have a mailing list, email list, and we do a research review every week, and then also follow us on YouTube, where we're going to be putting on a lot of content this year. We interviewed Dr. Francisco Gonzalez Lima, it should be out in the next couple weeks.

I'll also connect you to him, Melanie, because I think you're being great. If all your Methylene Blue questions, he will answer them in a really sophisticated way. But like, I think YouTube and our email list, where we do deep dives on things are our most, like, our kind of way to give back to the community of doing kind of doing some more education of how these molecules work and what to do outside of molecules. So I'm really proud of that work.

Melanie Avalon
Amazing. So can people when they go to the website, will the email list be there?

Daniel Tawfik
Yeah, they can just sign up for the email list and they can go to our research section of our website where we do. We also house all the research reviews that we do.

Melanie Avalon
Awesome. Well, the last question that I ask every single guest on this show, and it's just because I am so passionate about the power of mindset. So what is something that you're grateful for?

Daniel Tawfik
I do the gratitude for my family, and this is going to sound strange, but pets, health, because we have a lot and they're very dear to me, but all my little ones, I have a 10-month-old son now, just gratitude for their health because that's the scariest thing for me, just gratitude for everyone's health. This is paramount.

Melanie Avalon
Oh, I love that so much. And I imagine then when we talked on the phone, maybe your wife was about to have the baby probably 10 months ago.

Daniel Tawfik
We adopted, because of my wife's health issues, adoption is a very long process, so we were probably in the thick of it at that time, but we adopted our son 10 months. He's March 1st, so it's been a great year for us in that capacity.

We've expanded our family, so yeah, a lot going on personally for me.

Melanie Avalon
Oh my goodness. Congratulations.

That is so, so amazing. And I'm grateful that you adopted him and that he has such a loving, wonderful family and health knowledgeable parents to help him with all of that.

Daniel Tawfik
Yeah, no, it feels really good. It changes what you're prioritizing quite a bit, so I'm really grateful for that.

Melanie Avalon
I love it. Well, thank you so much, Daniel. I've just appreciated this so much. I can't wait to hear what listeners think of Healthspan, and I would love to have you on again in the future.

Daniel Tawfik
Thank you so much. It's been an absolute pleasure.

Melanie Avalon
have a good rest of your day. Bye.

Thank you so much for listening to the Melanie Avalon biohacking podcast. For more information and resources, you can check out my book, What Win Wine, as well as my supplement line Avalon X. Please visit Melanie Avalon.com to learn more about today's guests. And always feel free to contact me at contact at Melanie Avalon.com.

And always remember, you got this.