How To Reap The Anti-Inflammatory and Longevity Benefits Of Astaxanthin with David M. Watumull

Coming up on this episode of the Doctor's Pharmacy. Importantly, Astaxanthin actually crosses the blood-brain barrier. So it gets to the brain, gets into the cells and helps through reduce.

Oxidative stress and inflammation. Hey everyone, it's Dr. Mark. To all the healthcare practitioners out there, let me ask you a question. Would you like to make your life a little easier? I'm sure the answer is yes. As a functional medicine doctor, I know you can relate about how complicated and time consuming ordering lab tests can be. Thankfully, with Rupa Health, you can easily order lab tests from more than 30 different lab companies such as Dutch, Great Plains, Genova, Access, Medical Laboratories, and many more, all from one convenient location. This is really a much needed option in functional medicine. Rupa Health has saved me a ton of time in ordering labs and helped me provide better service for my patients. Lab ordering is quick and painless with Rupa Health, and best of all, it's free for practitioners. So sign up for free today. You can find out more information by going to rupahealth.com, that's R-U-P-A-Health.com As I've dug into the research on aging while writing my book, one thing has become super clear. We need to take care of our mitochondria. These are our cellular energy factories. Now, as we age and we eat too much and we sit our desks and are exposed to too many toxins, our mitochondria deteriorate and our bodies suffer. And that is why I'm happy to recommend Mitopure from Timeline Nutrition, a product that specifically regenerates mitochondria and supports cellular energy production. Mitopure clears away the damaged mitochondria from ourselves and supports the growth of new healthy mitochondria. And as an added bonus, the latest research shows that healthy mitochondria improves immune function too. Now I've been using Mitopure for almost a year now and at 63, I feel stronger and more energized than ever. Right now, a timeline nutrition is offering my community 10% off Mitopure, which you can get in a capsule powder or protein blend at timeline nutrition.com forward slash Dr. Hyman. That's D-R-H-Y-M-A-N. That's T-I-M-E-L-I-N-E.com slash Dr. Hyman. D-R-H-Y-M-A-N and use the code Dr. Hyman 10. and now let's get back to this week's episode of the Doctor's Pharmacy. Welcome to the Doctor's Pharmacy. I'm Dr. Mark Hyman, that's the Nourish Place for Conversations that Matter. And if you're interested in longevity and natural molecules and how they interact with their biology to activate ancient longevity pathways, I think you're gonna find this conversation interesting because it's about a particular molecule widely found in nature that has remarkable properties called astaxanthin. You might've heard about it, or maybe you haven't, but you certainly have eaten salmon, which is orange, and that's what you're eating. So that's what's in there. And today we have as our guest, David Guadalupe, who's had more than 20 years of experience in developing this product and this product development in understanding Astaxanthin as a powerful and safe, naturally occurring anti-inflammatory compound that can upgrade our health. He's the co-founder and CEO of AAX3 Life, which is a consumer longevity company that's formed to help people be their best selves. And A-X3 Life targets inflammaging, one of the core hallmarks of aging. You've heard me talk about on the podcast that I've written about in Young Forever. And the core of that product is Astaxanthin, Biopure Astaxanthin. He's also the CEO of Cardax, a life sciences business focused on advancing pharmaceutical and nutraceutical applications of Astaxanthin.

Well, welcome, David. Thanks, Mark.

Great to see you again. Pleasure to be here. All right, great. Well, it was great to have you on it because I think, you know, obviously our audience is really interested in longevity and some of the biology of what goes on underneath the hood. And a couple of things seem to be pretty universal as we get older. One is inflammation, and that is one of the hallmarks of aging or inflammaging. And oxidative stress, which isn't actually a hallmark of aging, but it kind of indirectly is because a lot of it is about mitochondria and mitochondrial function and how that plays a role with the development of reactive oxygen species and oxidative stress that gets out of control. And oxidative stress, when it's too much, will actually cause downstream cascade of damaging cells, tissues, organs, and accelerating aging. So can you talk a little bit about how oxidative stress and inflammation impact health and age? And what can we do on a practical level daily to unlock our key to longevities by addressing these two key components of aging?

As you've outlined, oxidative stress and inflammation drive a lot of issues as we age with our health outcomes. And as you've advocated in your book and on your podcast and everything, Diet is a foundational role, exercise, lifestyle modifications, but supplements do play an important role in managing health. And we've been really focused on astaxanthin as a naturally occurring supplement that can help you safely address oxidative stress and inflammation at the source. Because as you've talked about, if you have oxidative stress and inflammation that's kind of left to go awry, It can manifest itself into different types of things that may downstream appear to be different types of issues. But if you can really focus on the root causes and restore health at that kind of basic cellular level, that's something that really is worth pursuing. Yeah.

So it's really sort of a ubiquitous process that we're constantly navigating. And it's not that all inflammation is bad or all oxidative stress is bad. It's when they get out of control, it's a problem. So, you know, as part of ongoing research and actually new research at NIH, science has been looking at how do we address this through various natural or synthetic compounds. And Astaxanthin is a powerfully occurring plant compound that is found in algae and oceans and essentially can have powerful effects in protecting us for many reasons. So, you know, we'll talk about some of the NIH research and some of their programs that they have around looking for molecules that are in either pharmaceutical stock or in nature that actually can activate many of these beneficial longevity pathways. But let's talk about Astaxanthin particularly and how it helps fight some of the key hallmarks of aging like mitochondrial dysfunction, inflammaging, cell signaling. So talk about, and just get into the weeds a little bit about how it works on some of these fundamental mechanisms that we now know underlie all aging. So we talked about this before in the podcast, but if you address, for example, heart disease and cancer and get rid of them from the planet, your life expectancy might increase five to seven years. If you address all the hallmarks of aging, which underlie all the chronic disease of aging, you could extend your life by 30 or 40 years, which means living to be 120. So there's a big difference. So can you talk about particularly how astaxanthin targets some of these key hallmarks of aging?

Yeah. So, in order to do that, we can really look at what astaxanthin does in cells. So, first of all, when you ingest it orally, it's distributed systemically. So, it is distributed throughout your body to all your tissues and gets into the cells. In particular, it gets into the cellular membranes. and including not just the plasma membrane, but importantly, the mitochondrial membranes, nuclear membrane. And given its structure with its polar head groups and polyene backbone, it perfectly spans and anchors into the membranes. And with that, it's a great scavenger of reactive oxygen species, free radicals, bullets inside and outside the membranes. And so as it's sitting there at that key site, say, at mitochondrial membrane, Mitochondria, of course, are our body's energy plants and as a byproduct of energy production, of course, you have oxygen free radicals that are created and need to be addressed. And so, astaxanthin is perfectly situated to sit there in the mitochondria and address the excess reactive oxygen species that can lead to oxidative stress and as you've talked about, trigger inflammatory pathways. And so, looking at, say, inflammaging, by reducing excess oxidative stress, you can prevent the pathological activation of inflammatory pathways like NF-kappa B and its downstream cytokines like TNF-alpha, COX-1, COX-2, IL-1, IL-6, prostaglandin E2, a lot of the targets of a lot of the anti-inflammatory drugs, but instead working upstream at the pathway activation level. In terms of inflammaging, working upstream to prevent the pathological activation of these inflammatory pathways, we think plays a major role in mitigating the effects of inflammaging. Then if you transition to, say, mitochondrial function, again, being situated in the mitochondrial membrane, as is adiponectin, has demonstrated impacts on membrane stability in the mitochondria. Reductions of oxidative stress, lipid peroxidation in the mitochondria. There's been studies showing increased ATP production, say, in young and geriatric dogs, for example. So it plays a fundamental role at the mitochondrial level. And in addition to impacting inflammatory pathways, it impacts other cell signaling pathways related to aging, such as AMPK. So we've seen impacts on AMPK and related age-related pathways. So, the sirtuins, FOXO3, even mTOR, target of rapamycin. So, with impacts on all of these pathways, you get impacts on autophagy and mitophagy and mitogenesis and all these critical roles that are part of the aging process. That's amazing. Okay, I'm going to unpack that because.

That was a lot and a lot of acronyms in there. I don't think people necessarily know what they are, but I'm going to help you unpack that. So, I think the question really was how does this molecule impact some of these ancient preserved longevity pathways, these receptors and mechanisms that are designed to keep us alive, to keep us alive longer, and our survival mechanisms. And I talk a lot about them in Young Forever, these key longevity switches, things like the nutrient sensing pathways, mTOR, which is basically regulating autophagy by being Fasting, when you fast, you basically inactivate mTOR, you inhibit mTOR, and that allows your cells to clean up and do self-cleaning and repair, which is autophagy, which is so important to clean up all parts and recycle things. It, you said, as Anthony also impacts AMPK, which is another regulatory pathway, is part of our nutrient sensing pathway that's very involved in blood sugar control and mitochondrial function in regulating inflammation, even activating sirtuin pathways. And then sirtuin pathways also you mentioned are involved in the interplay between Astaxanthin and aging. So as sirtuins are involved in DNA repair and inhibiting inflammation. You mentioned things like COX-2 and NF-kappa B. These are compounds in the body that are regulating inflammation. So when you have high levels of NF-kappa B or COX-2, basically you're driving inflammation. And Astaxanthin works on these mechanisms, for example, NF-kappa B is involved in regulating gene transcription for all these inflammatory cytokines, some of them which you mentioned. And so we have, you know, these, this really amazing interplay between these natural molecules in our biology to regulate these essential pathways. You mentioned FOXO, which is another really important I want to get into, but that is involved in regulating a lot of our antioxidant pathways and our antioxidant enzymes. So basically it's, we, we, we call these compounds pleomorphic. Pleomorphic means it has many, many, many activities. For example, if you take a blood pressure drug like an ACE inhibitor inhibits this angiotensin converting enzyme, which regulates your blood pressure. That's it, basically. Whereas these compounds work on multiple pathways across multiple receptors and multiple mechanisms that affect our aging process. So it's amazing to me how nature and humanity have co-evolved to help regulate these essential biological processes without any side effects, which is amazing because a lot of these drugs that we use like Advil, for example, which can cause all kinds of side effects or even Celebrex, which is a COX-2 inhibitor, has these side effects. But we don't want those side effects. We want effects that are beneficial. And that's what's really exciting. So whether it's regulating inflammation, regulating oxidative stress, regulating autophagy, regulating mitochondrial function, regulating DNA repair, Astaxanthin works across all these and that's why it has broad effects across across your health, from your brain to your heart to your immune system to your eyes across the board, it's beneficial. So I think it's kind of an amazing story. I mean, and there are many molecules in nature that do this, but astaxanthin is one of the, I think, superstars. So tell us, tell us about some of the benefits. I just sort of mentioned a few of them, but tell us about some of the research that's been done. This is a very, very, very well researched compound. Tell us about some of the health benefits. and we'll go through some of them and what do they do and what are the highlights of how Astaxanthin optimizes our health?

Sure. So, like you said, a lot of other agents and therapies are addressing downstream manifestations of problems. And so, like you've said, it's like whacK-A-Mole medicine. In the case of Astaxanthin, it's working at a more fundamental level. really restoring cellular function, homeostasis. And so when you're doing that, you can have this broad effect on all these things that appear to be different, you know, but in fact are very similar at the molecular level. And so, like you said, this results in a wide variety of health impacts. So we look at both, you know, like you've talked about, health span and lifespan types of applications. And so, Looking at lifespan, there's been a variety of studies in model organisms looking at lifespan. So we've seen extension of life in C. elegans, the roundworm models, also in yeast and fruit flies. And so that's led to research at the NIH-funded Interventions Testing Program, looking at lifespan in mice. we can talk a little bit more about that later as well. But this is something that has been demonstrated across species to impact lifespan, which makes sense given its impact on age-related pathways and mechanisms as we've talked about. And then in terms of healthspan, you don't just want to live longer, right? You want to live longer and feel better and be healthy throughout that lifespan. So healthspan is really important. And so things like joint and muscle health, you know, the things that you think about as you age, what happens, you know, your joints, you know, you slow down physically, mentally, etc. So with joint and muscle function, we've seen impacts certainly on the mechanisms of joint health. So if you look at, you know, what are the top selling rheumatoid arthritis drugs treating? They're going after TNF alpha. We've seen reductions of TNF alpha. And in fact, you know, we had a head-to-head study versus prednisolone, looking at reduction of TNF-alpha and reduce that to the same extent as prednisolone at the same dose. So it's very potent from an anti-inflammatory perspective, targets a lot of the same cytokines that, say, other agents may be addressing for, say, joint issues. Certainly in the community of individuals that have been taking AstraZeneca, there's been wide reports of improved joint and muscle function. But certainly if you also look at, say, animal studies, there's been an osteoarthritis model in rabbits and saw benefits in cartilage degradation, for example, or in the areas of like sarcopenia with muscle deterioration, obviously a major issue as people age. There's been studies in both humans and animals showing benefits there. So certainly from a physical standpoint, joint muscle function, you've seen a lot of benefits there. Then you look at the leading cause of death, cardiovascular issues. First of all, astaxanthin again gets to heart tissue and really helps prevent oxidative stress and inflammation, which a lot of people think of heart disease as too much cholesterol. But as everyone now knows, it's not just about the cholesterol or lipids, it's about the quality of those lipids, but it's also say inflammation, where studies like, say, like CANTOS from Novartis in recent years showed that even if you have no impact on LDL, but all you do is reduce inflammation, you can have a major impact on major adverse cardiovascular events. And so we've shown benefits on both reductions of inflammation as measured by, say, hs-CRP, but we've also shown benefits for lipids. So we've seen reductions in LDL cholesterol and importantly, oxidized LDL cholesterol. And so really the quality of the lipids reductions of triglycerides increases in HDL. And interestingly, In research that we worked on with our collaborators, we demonstrated in a mouse model that you could reduce the plaque buildup in the arteries. We had imaging we showed in the control versus the treated groups, the actual reduction of the plaque in the aortic arch, which was really cool to see. We also showed reduction of blood clots in multiple species in both dogs and rodents. Both thrombosis and re-thrombosis. types of settings. So pretty profound impacts on cardiovascular health, blood pressure has been reduced as well. So we think that's obviously a huge benefit for long-term health. And then if you transition, say, to brain health, cognitive health, the role of oxidative stress and inflammation is definitely demonstrated for your brain and mental health. And importantly, astaxanthin actually crosses the blood-brain barrier. So it gets to the brain, gets into the cells, and helps through reduce oxidative stress and inflammation. You can imagine all the benefits it could have there. There'd be a lot of great studies that could be done in terms of cognitive health. But say in humans, there have been studies looking at cognitive performance and maze tests and things showing benefits for memory and attention and information processing. In animals, there's been benefits showing neurogenesis, neuroplasticity, et cetera. There's been a lot of amazing research in the brain health space, which which again makes sense given its impacts on oxidative stress inflammation at that cellular level. And you can kind of go on and on, like you said, there's a lot of research and you know, you look at things like skin health, eye health, again, the same story, reducing oxidative stress and inflammation, you know, in those locations has really important benefits. And then if you say look at immune health, you think about, you know, anti-inflammatories, they're often, if you look at what are prescribed as anti-inflammatories, they're going to have immune issues. You may have immune suppression, and so you're kind of battling this, I'm reducing inflammation, but now my immune system is no longer functioning in a way that actually allows me to fight off infections and wound heal. And so with azasanthin, we've actually seen not only no immune suppression, but actually fewer infections, for example, in animals. So we really think it's the different mechanism of attacking inflammation by kind of working at the source, allowing normal functions. So, your immune system can function normally, but not in a pathological way in a chronic, long-term low-grade inflammation type of deciding, which is not what we want.

It's quite amazing. So, there's just such a vast array of research on all these various things. And, the reason it works across all these problems and diseases is because it works on some of these underlying mechanisms that have to do with all disease. so what we talk about in functional medicine is the fundamental physiological systems or the biological networks or the hallmarks of aging. And so it's like, it almost seems too good to be true, but actually, when you look at the data, it's pretty impressive. Hey everyone, it's Dr. Mark here. Optimizing your health and wellness is a lifelong journey, and we all know how important things like proper nutrition and exercise are to live better. But I want to talk with you about another foundational tool for optimizing wellness that often gets overlooked. infrared saunas. Infrared saunas are extremely effective at reducing the body's stress response and creating balance in the autonomic nervous system. They can improve circulation, help with weight loss, balance blood sugar, improve detoxification, each of which improves your brain function. When it comes to infrared saunas, my number one brand is sunlight. Whether you're craving relaxation or deep sleep or detoxification, sunlight infrared saunas will help you achieve your health and wellness goals from weight loss to muscle recovery and Skin Rejuvenation. Their patented infrared technology will restore your body and your mind. Right now you can save up to $600 on your purchase. Simply visit sunlighten.com/mark-hymen and mention my name, Dr. Hymen, to save. Are you tired of spending hours searching for healthy and eco-friendly products at your local grocery store? Do you find it frustrating that the available options are often limited and expensive? With Thrive Market you can order all your favorite healthy pantry staples, snacks, and household and body care goods and so much more and have it delivered right to your door. Thrive Market has made it their mission to bring you the best organic, non-GMO, sustainable, ethically sourced options at up to 30% off retail. They have thousands of carefully curated products to meet any diet and you can shop from the comfort of your home, meaning one less errand to run. They've got your whole house covered and offer brands you already know and love like Primal Kitchen, Sette, Dr. Bronner's, and so many more. And you can get a monthly or annual membership to find the perfect fit for your family. And right now, Thrive Market is offering all Doctors Pharmacy listeners a great deal. You can get 30% off your first order and a free gift up to $60 if you sign up now. All you have to do is head over to thrivemarket.com/hyman. That's thrivemarket.com/hyman. And now let's get back to this week's episode of the Doctor's Pharmacy. So talk about also how, you know, where we find this in nature, you know, what this is kind of one of the carotenoids, right? We've heard about carotenoids, the oranges and carrots, sweet potatoes, you know, beta carotene and all this stuff. Right.

And.

You know, it, it, it works as a, as a plant's defense system against environmental stresses. And, but, you know, talk to us about how it shows up in nature. Talk to us about, you know, how it plays a role in the marine food system and the chain and, and how even with salmon, why it's so important for salmon, which is, you know, when we see the orange color, why, why it's so important for them as opposed to other fish, for example.

Yeah, yeah. So the whole story of carotenoids and Astaxanthin is really interesting. Carotenoids actually co-evolved with photosynthesis. So they're a key component of photosynthesis and help to protect plants from photo-oxidative damage. So it played a fundamental role in evolution there. And in the marine environment, Astaxanthin is produced by microalgae. Like you said, it has a defense mechanism against UV light from the sun. And so these are green algae that when stressed by the sunlight produce astaxanthin as a defense mechanism and then turn bright red. And so it plays this vital role in dealing with severe environmental stress. And then microalgae then consumed up the food chain. So into crustaceans, krill, crab, lobsters, shrimp, you know, up through salmon, other fish, whales, obviously a huge part of their diet is krill. so it's been this really important nutrient throughout the marine environment. And to take one example with salmon, salmon of course are not just swimming around in the ocean. They also, you know, migrate, they swim upstream to reproduce. And it's amazing feats of endurance and strength to do that. But the way they are able to do that is because of astaxanthin. They are loaded up on astaxanthin, you know, in their flesh. and that really helps them deal with the consequences of that upstream journey. And so without Astaxanthin, salmon would not only be gray instead of the beautiful pink color that we all know, but they would be smaller, they'd be weaker, they're prone to infections, but they wouldn't be able to swim upstream. So it's a really amazing role that Astaxanthin plays in nature. And so, like you said, we've all consumed it through salmon or crustaceans, shrimp, et cetera. But certainly it's hard to get a high enough level on a consistent basis. And so, you know, just like the salmon, we would like to benefit in the same way. And certainly nature has come up with something that has really worked to have really important, you know, protections against environmental stresses. And with carotenoids, if you look at the evolution, they kind of went through a series of steps and ultimately went through different carotenoids. Like you said, beta carotene is an example of a commonly known carotenoid. But astaxanthin is a particular type of carotenoid called a xanthophyll carotenoid that was later in the evolutionary process that was optimized in the apex or king of the carotenoids. Importantly, it has oxygenated head groups. It has a hydroxyl group on each end of the molecule and a ketone group. That gives the molecule polarity so that when it spans the membrane, and we've actually done studies with our collaborator at Harvard, showing that azasaxanthin spans the membrane and doesn't disrupt the membrane. In the same study, you would look at say beta-carotene, which can also get into the membrane but is not polarized, doesn't have the hydroxyl groups for example, and then it just sits and kind of perturbs or disturbs the membrane. And so not every antioxidant is the same, not every carotenoid is the same, and so we think nature came up with acetyl-L-carnitine is kind of the optimal a carotenoid and certainly been demonstrated throughout the natural environment and certainly with humans in the last 20 years.

That's amazing. And how is it different than other antioxidants? We have vitamin C or vitamin E or other ones. So how does it compare?

So there's a few different things. One, you can look at its antioxidant, you know, capacity of performance. You can look at things like singlet oxygen quenching. And in those types of studies, we've seen that it's 6000 times stronger than vitamin C or 550 times stronger than vitamin E or 40 times stronger than beta-carotene. And so you can have a performance benefit in terms of scavenging free radicals, for example. But as in real estate, location, location, location, that really matters. And so the fact that astaxanthin gets to your cells but actually gets into the membrane of the cells, and like I just said, the fact that it spans and stabilizes the membranes, distinguishes it from other antioxidants and that it gets to not only the plasma or outer membrane of the cell, but gets to the mitochondrial membranes. And so getting to those privileged locations is something that not every antioxidant does. So you want to get to the cells, you want to get to the mitochondria, you want to get into the membranes, not disturb the membranes, and sit there and protect the membranes from oxidative stress. And so that's something that really sets.

Acetyl-L-Carnitine apart from other antioxidants. Interesting. Let's talk a little bit about now the FOXO gene, FOXO3, which is a really important gene. So maybe you can explain what it is, what a role is in the body, and how it plays a role in longevity, and what astaxanthin does to FOXO3 pathways.

Yeah, so the FOXO3 gene is really interesting and our collaborators here in Hawaii helped to actually uncover the link between FOXO3 and human longevity. you may be familiar with the Han Wu Li Heart Program, which was started in the 1960s with 8,000 Japanese American men. And this amazing program followed these men for decades with doctors' visits and blood tests and looked at all the reasons that their health declined or why they died. And it created this amazing database of of, you know, doctors visits records, but also biological specimens. And so our team in Hawaii here looked at that and discovered that FOXO3 was something that when assayed in these individuals was associated with those that lived the longest and the healthiest. And so if you have the right version of the FOXO3 gene, which would be the GG allele, that you would actually have the best chances of living to 100 healthy. And if you don't have that version, you know, if you have the TT or the GT versions, then you are less likely to live that long healthy. And so, and the difference between those different versions of the FOXO3 gene is how active they are. And with Astaxanthin, with the same group in Hawaii, we did a study in mice and we showed that Astaxanthin actually increased activation of the Foxo3 gene as measured by the mRNA expression and our mRNA levels. And so, this was actually in the heart tissue of the mice. And so, we demonstrated that you could increase Foxo3 activation in the heart tissue of the mice. And so, this was really amazing. And it also confirmed that in the roundworms, in the C. elegans where we saw life extension results, if you knocked out the roundworms version of the Foxo3 gene, the ortholog daf-16, the lifespan benefit went away. And so it looks like in the roundworms that the mechanism of extending life was via their version of Foxo3. We know in humans that Foxo3 is associated is one of the key anti-aging genes associated with longevity. And we demonstrated in mice that we have activated FOXO3. This was really amazing research that actually led to the National Institutes of Health or National Institute on Aging. They have a program that they fund called the Interventions Testing Program. And they actually selected Astaxanthin to be included in this program to look at lifespan in mice. Prior to this, lifespan was just, like I said, examined in model organisms. but not yet in mammals. And so the ITP, as it's called, the Interventions Testing Program, an NIA-funded program, has been running for the last 20 or so years. Every year they take a cohort of a few promising longevity agents, and there's a lot of well-known agents that have been tested in this program. Rapamycin is probably the agent that has been tested the most and demonstrated efficacy. in multiple cohorts. But obviously, rapamycin has side effects and has prompted people to look at different types of dosing and rapalogs or analogs of rapamycin. But even things like resveratrol, there was a lot of hype around resveratrol in 2006, 2007. It was included in the cohort back then. It actually did not extend lifespan in this model. Metformin has been tested. It also did not show benefit. The NAD precursor NR was tested, did not show benefit. There's only been a handful of agents that have shown benefit in this model. Interestingly, it's highly, highly rigorous. It's conducted at three different sites, the University of Michigan, the Jackson Lab, and the University of Texas Health Sciences. They have specially bred mice that are designed to not have confounding variables that you might find in typical laboratory in bred mice. They have specially bred mice they run it at three different sites in parallel, literally thousands of mice in each cohort. And so we were fortunate to be selected to supply the axi-Sapentin to this study.

And this is the NIH study?

Yeah, yeah. So this is an NIH-funded study. It's called the Interventions Testing Program. And the study for our cohort started back in 2019 and actually just wrapped up this year. And we've been working with the ITP team to get the manuscript drafted. It's in the process of being submitted for publication. And we're going to be really excited to be talking about those results as soon as they come out, hopefully in the next few months. And so the thing that we think is really important when looking at this is, first of all, can you demonstrate efficacy in a model like this? But what is the practical application of this? Something like I said, like rapamycin, which has demonstrated lifespan benefits in this model, doesn't really have the utility in humans that we would like because of its, you know, limitations on safety and tolerability. Whereas with the case of azasanthin, because of its mechanism and because of just all the data that we've demonstrated, it's exceptionally safe. And so both because we've consumed it in our diet, we've had decades of experience as a dietary supplement. But it turns out that azasanthin is actually a major component of the animal feed. so farm raised salmon, you know, despite, you know, having poor living conditions and other things, they're actually fed Astaxanthin to make them pink just like they would get it in the wild. So it's a really important nutrient in their, in their feed, but also other, you know, animal feed utilizes Astaxanthin. And in order for the FDA to allow Astaxanthin to be used as an additive for animal feed, there was a very extensive set of safety studies that were done the likes of which would be done for pharmaceutical development. So long-term toxicity studies, carcinogenicity studies, et cetera, and showed at very high levels and very long durations, literally thousands of milligrams per kilogram of body weight. So compared to what human dosing is, which is fractions of a milligram per kilogram, or a couple milligrams per kilogram depending on how high you want the dose, it's orders of magnitude difference between these animal studies and human studies. And we showed or a study, third parties showed that there were no side effects of clinical significance in any of those studies. And so that's something that when we look at- that's impressive. Longevity applications, you want to have something you can take every day for the rest of your life that's safe.

And that's what we think really sets Astaxanthin apart. That's impressive. And just to clarify for people, the NIH sort of was looking for screening molecules that may have potential for longevity, and it doesn't test very many. And it's just had a few, and so this is a big deal to get Astaxanthin tested in this way and to look at its effect on longevity and many of the longevity pathways. So very excited to see that study and the latest science around that. I mean, there's so much more data. I mean, in 1998, there were 200 papers. Now there's over 3, 000 papers on Astaxanthin. Are there any other interesting sort of.

New data that's coming out that you want to share with us? I mean, it's just, like you said, it's been an explosion of research. And so when we started with this back in the late 90s, there was less than 200 peer-reviewed papers. 15 years later, it was up to 1,000 peer-reviewed papers. 10 years further on now to present day, it's more than 3,000 papers. I think we'll see over the next few years just a further explosion in the research with as has happened. And so it's been well studied and well known in the scientific community and starting to get more and more traction, but it really has not been known in the general public setting. And so the research is something because it's a naturally occurring molecule, unlike a proprietary pharmaceutical, research can be conducted throughout the world by various academic institutions and others in the private sector. And so what we've seen in recent years is just further research looking at elucidating the mechanisms of action. So say we've seen impacts like we talked about on ANPK and other age-related pathways, but things like, well, you know, does Aspergillus impact autophagy? And you can find papers on autophagy. And so really further elucidating the ways it works because we know that it works, you know, through nature, through evolution, and through the studies that have been done in humans and animals. But further understanding how it works is something that a lot of research, you know, is taking place at this time. And also further, you know, clinical studies. There's been more than 50 or 60 human clinical studies. These are smaller pilot types of studies, but areas of cardiovascular health, metabolic, liver health. I think continuing to expand in those areas is what's really exciting and what we'll continue to see in the coming years.

That's amazing. In terms of the next steps for Astaxanthin as a molecule of interest in longevity, Where do you see this going?

Well, I see a couple of things. I do think that I think AstraZeneca will become part of the dialogue around longevity. There's a lot of talk around various other agents that have a lot of promise, NAD precursors, et cetera, et cetera. And we think AstraZeneca should be right there in that conversation and at the forefront of it because it has these profound impacts on aging. healthspan, lifespan, it's super safe, it's commercially available, you know, so it's accessible. So this is something that, you know, if you can imagine, snap your fingers, everyone taking Astaxanthin, you would have a much healthier society. And so this is something that, why wouldn't you do it? You know, if it's safe, it reduces oxidative stress and inflammation at this, you know, core cellular level. It's something that we frankly believe everyone, you know, should be taking. And so we think that that's going to be the next steps is really making astaxanthin a household name and something that is associated with longevity. That's really the next step is building this public dialogue, this community around astaxanthin and healthy aging. Then on the flip side, there's also pharmaceutical applications. You could look at, for instance, higher doses for disease states, which hopefully through diet, exercise, lifestyle supplementation with with compounds such as azasanthin, you're healthy. But the reality is people will develop issues. And so if you can have agents like azasanthin that are put through the FDA clinical trial process and approved as a pharmaceutical for certain disease applications, analogous to say the Omega-3s or the fish oils where you have prescription versions and you have supplement versions and we could see that as well. a pharmaceutical version of the molecule that we've developed and would look to advance in future years as well. Yeah.

What's interesting is, you know, when you think about, okay, this would be great. It's going to be a great molecule. It's, you know, maybe going to be good for a billion people. Right. And it affects, you know, joint pain and muscle function and cognitive health and heart health and lifespan and many, many things. So the problem is Supply. Right. So if you're looking at where it comes from, it comes from algae in the ocean and and doesn't seem like a really sustainable way to get that much astaxanthin. So, can you talk about the difference between the synthetic versions, the kind that are synthesized in the lab versus the natural astaxanthin and how they're different and why maybe even the synthetic might be better? Because typically people think, oh, synthetic, that's not good.

I want the natural form. Can you kind of explain that a little bit? Sure. So, we've actually worked with both forms. And so, my father and I, who I've worked for the last 25 years here with Astaxanthin, both started with a company that was producing microalgae. And so it was on the big island of Hawaii. It was literally in the lava fields. So you dig out ponds in the lava fields and grow microalgae, which it's a great environment for growing the microalgae and stressing them with the sunlight to produce Astaxanthin. But like you said, it's a very difficult process to scale. takes a lot of land, but also it's not the most pure. You have contamination issues in the case of that location, you're next to the volcano, so you could have bog, you're next to the airport, so you could have jet vapor from the fuel, you can have just other elements externally, it's essentially farming, and so you're going to have potential contamination. It also takes a lot of energy, a lot of water, so in terms of impact on the environment, you know, it's something that is not optimal. And so we thought that, like you said, if you want to bring this, you know, to the world, to the mass market, you need something that's scalable, that's sustainable, that's pure, that's consistent. And so we transitioned to natural product total synthesis. And so that is where you are in the laboratory, you know, taking chemical building blocks and constructing the molecule step by step and arriving at the exact molecule you find in nature, but without any other components. With the microalgae form, you not only have to grow the microalgae in the first place, but then you have to extract the astaxanthin from the microalgae, and you can't get just the astaxanthin out. You're gonna have maybe five or 10% astaxanthin, and the rest is other microalgae matter, which is probably, it doesn't hurt you, but you don't need that. That's not the active ingredient. and actually gives it kind of a fishy smell and aftertaste, which is not the astaxanthin, it's the other content from the algae. And so with the synthetic form, we have something where it is just the naturally occurring molecule, the exact same chemical formula, exact same chemical structure. So whether the algae synthesize it internally or we synthesize it in the lab, you're arriving at the same place, but in our case, we're doing it now with very high purity, very high consistency, you know, and something that in studies has been shown to actually be much more environmentally sustainable because it uses less land, less water, less energy. And so we think that is a huge, huge, you know, benefit for the synthetic form. And like you said, there's been some, you know, obviously there are some negative views on, you know, synthetic types of products, but in this case, we believe you have the best of both worlds. You know, synthesis is what's used to produce most of your small molecule drugs. and the manufacturing rigor of drugs is not what's in question, it's how they act biologically and their side effects. And so if you can produce a naturally occurring molecule, make a nature identical form, you have the pharmaceutical like manufacturing purity and control, but you have the benefits of this natural product. And so those are some of the key benefits. And the final benefit is we have a special formulation of the synthetic ascorbic acid, which if you don't formulate it or AsteraPhy in the case of the pharmaceutical form, it's not bioavailable. And so we specially formulate the Astaxanthin and we actually conducted a head-to-head study versus a leading microalgae Astaxanthin product on the market. It was a human study crossover design and we gave a group of human volunteers the microalgae Astaxanthin product and then measured their blood levels over the course of 24 hours had them washed out for an entire week without any AstraZeneca supplements or food, and then provided them with the synthetic form with our special formulation and demonstrated over the course of that same 24-hour period, both a maximum concentration or C max, as well as the total concentration, the total area under the curve over the full 24 hours of three times the blood levels of AstraZeneca. So there's a very significant bioavailability difference A lot of people don't realize, you know, you swallow a capsule, you think it all goes in your body, but it doesn't necessarily, you know, some can pass right through you, which is, which is a shame. And so in this case, having the, you know, superior, you know, three times bioavailability, you know, is kind of the third key component in addition to the environmental sustainability and the increased purity.

So there's benefits to the synthetic version.

That is what you're saying.

Yeah, it's great. Now, there's a lot of answers on the market.

How is this one different? Yeah, so almost every Astaxanthin product on the market comes from microalgae or some downstream version, say, like Krill, which ultimately consume Astaxanthin in nature derived from microalgae. And so the issues with these products are what I've described in terms of the supply to scale and serve the world is challenging. the purity, the consistency, the bioavailability, those are all the challenges with these products. Whereas our form, like we talked about, is the synthetic nature identical form. And we believe it's something that healthcare professionals, like yourself, would understand the benefits of the rigor of delivering this naturally occurring product but with the synthetic production. And so that's really the key difference that sets us apart. we also believe that, you know, no one has really created a conversation around Astaxanthin and so that's something that we're looking to do here is actually, you know, communicate the benefits of Astaxanthin, you know, to the world. And one important note I'd like to make is that, you know, there's a lot of research out there with both synthetic and natural forms of the product. You know, the safety studies I referenced, the very high dose long-term studies, those were with the synthetic form. A lot of the animal studies, a lot of the in vitro studies are done with the synthetic form, the human studies, most of them have been done with the microalgae forms because those have been the forms that have been on the market longer. But in recent years, you know, we, for example, have done clinical studies showing benefits in the cardiovascular, real world cardiovascular patient population that was on all the cardiovascular meds, you know, but we still showed benefits on top of that in terms of reductions of you know, lipids and oxidized LDL, blood pressure, Etc. So there's been, there will be more studies going forward with, with the synthetic form, but there's been a lot of research with both synthetic and natural. And biologically, astaxanthin is astaxanthin. And so you can look at the literature and, and the benefits of astaxanthin, you know, are applicable to both synthetic and natural.

But the real difference is how you make it, how you deliver it. And so that's really where we distinguish ourselves. that's amazing. Well, I, I mean, this was just such a great conversation. I think, you know, it's important for everybody to understand that, you know, living healthy and long requires the foundations, which is healthy eating, exercise, sleep, stress management, the right basic foundational social fabric that you're embedded in that keeps you healthy and connected and alive, and then supplements take a role. So I just want people to understand that they're part of, they're called supplements, not Replacements, but I think this is a very promising molecule, and I'm very excited to hear about the research on David, and particularly I want to see the data from the NIH trial because I think that's going to be a very compelling story. So thank you so much for your work over the years for bringing this product to market. I think people can learn more about it. They go to ax3.life and then learn more about it and how to look at the research and the data. It's all the studies are there. If you want to look at getting it, there's a great availability as well. So thank you so much for being on the podcast. I hope you've enjoyed this time and I hope you all listening have enjoyed the podcast. Please share with your friends and family. We'd love to hear comments on how you've learned to sort of regulate your lifestyle and inflammation in general and subscribe where you ever get your podcast and we'll see you next week on the Doctor's Pharmacy. Hey everybody, it's Dr. Hyman. Thanks for tuning into the Doctor's Pharmacy. I hope you're loving this podcast. It's one of my favorite things to do and introducing you all the experts that I know and I love and that I've learned so much from. and I want to tell you about something else I'm doing, which is called Mark's Picks. It's my weekly newsletter, and in it I share my favorite stuff, from foods to supplements to gadgets to tools to enhance your health. It's all the cool stuff that I use and that my team uses to optimize and enhance our health. And I'd love you to sign up for the weekly newsletter. I'll only send it to you once a week on Fridays. Nothing else, I promise. And all you have to do is go to Dr. Hyman.com/picks to sign up. That's Dr. Hyman.com/picks, P-I-C-K-S, and sign up for the newsletter and I'll share with you my favorite stuff that I use to enhance my health and get healthier and better and live younger longer.

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