151: Does Astaxanthin Increase Longevity?

In this episode, Dave Watumull joins Dr. Buck Joffrey to discuss the benefits and mechanisms of astaxanthin, a powerful antioxidant and anti-inflammatory compound.

He explains its role in longevity, particularly through the Interventions Testing Program (ITP), where astaxanthin was shown to extend lifespan in male mice by 12%.

The discussion also covers the safety profile, bioavailability, and clinical studies demonstrating cardiovascular benefits.

Gender differences in efficacy are explored, along with practical advice on dosage and where to find astaxanthin products.

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Transcript

Disclaimer: This transcript was generated by AI and may not be 100% accurate. If you notice any errors or corrections, please email us at phil@longevityroadmap.com.

 Lo and behold, it did increase the activation of Fox oh three in particular in heart tissue. And so that was the first time that ACE Anthem was demonstrated to activate Fox oh three in a mammal.

Welcome everybody. This is Buck Joffrey with the Longevity Roadmap, and uh, today we're gonna talk about an interesting. Um, an interesting, uh, nutraceutical, I guess an interesting, uh, substance, uh, that, uh, the reason I wanted to have it on is because there's, we've, we've talked about it before, but there's a, uh, program called the intervention testing Program, uh, that's very rigorous, um, multi university thing.

Basically, their focus is on trying to figure out, you know, which drugs actually show some longevity benefit and stuff. In the past, um, you know, a lot of the medications that you think of would be on there have shown benefit, big one being rapamycin. Um. 23% benefit in, uh, male, uh, mice compared to, you know, the, uh, 26% with females.

So significant longevity benefits ized and across the board has always been pretty dominant. There. Other stuff, a carbo, um, which is, you know, basically kinda, you just take a little bit of that before a meal and you can decrease your blood sugar. Um, there's 17 alpha estradiol canagliflozin, which is another, um.

Another type of diabetes medication, which basically makes you pee out extra sugar. It's an SGL two inhibitor, and there's, uh, there's others too. But those were sort of the, the big ones. And the reason I wanted to talk to our guest today is because he's a, I saw a study about astaxanthin, and as it turns out, particularly in males, uh, this, uh, this particular.

Compound does seem to have a, a statistically, uh, uh, beneficial, uh, impact on, particularly in male, uh, male rodents. This is, uh, it's kind of a hard, it's, it's kind of hard to get numbers that are like 10% increase in longevity and statistically significant. So I felt like it was something that we ought to talk about.

And so, um, we're gonna talk about that with our guest today. Again, you know, not telling you what to take, what not to take. Uh, but I think, you know, part of the issue out there in the whole longevity space is trying to, Hey, you hear a million of these substances left and right, you know, this is supposed to be beneficial.

That's supposed to be beneficial, but the reality is that most of them don't have any real science behind them, at least with the interventions testing. Program is this ITP. You actually have, you know, multiple universities. Doing these very rigorous studies helps you kind of figure out like, okay, this is beneficial in rodents.

I mean, it may or may not be beneficial in humans. Who knows? But at least you're basing some of what you're putting in your body on science rather than, you know, what? Some influencer says, so, uh, obviously have no connection with this company or anything like that, but we, we will have all the information on astaxanthin after these messages.

Hey, longevity enthusiast. It's time to take you to the next level. I've been fine tuning my longevity regimen for years, and I look better and feel better than I did a decade ago. In fact, my blood work is even better than it was back then, and it's all because of my data-driven regimen. And it's inspired me to create a course and community just for you.

It's called the Longevity Roadmap, and I urge you to check it out. If you're tired of your belly fat, tired of being tired, or just wanna optimize yourself for the next 50 years, visit longevity roadmap.com. That's longevity roadmap.com. Welcome back to Show Everyone. My guest today is David Watumull, chief operating and financial Officer at cardax and co-founder of a X three Life.

He's, uh, has more than 20 years of experience in the life sciences industry, overseeing areas ranging from product development and regulatory strategy to finance and operations. His career is focused on translating advances in biology into scalable health solutions with a particular interest in the role of oxidative stress and, and inflammation, uh, in aging.

Welcome, David. How are you? I'm great. Thanks for having me on. So, you know, I was trying to, um. Figure out, like, you know, I, I think I pinged my producer about this a while ago, and I, and I was trying to figure out what was about Xanthin that I was interested in, and I realized that there was a study in the, uh, interventions, trading protocol.

First of all, tell us, uh, folks, maybe you could summarize for people, listeners what the intervention, uh, training protocol is, uh, and then maybe kind of, uh, explain, uh, what. Astaxanthin, uh, actually did their. Yeah, so the, the ITP, uh, which is the Interventions testing program, is um, a program that's funded by the National Institutes of Health, and specifically the National Institute on Aging.

And it is conducted at three independent institutions. The University of Michigan, the University of Texas, San Antonio, um, and the Jackson Labs in in Maine. And, uh, there are several principal investigators, um, you know, primarily at each of those, uh, institutions, um, that have been running this program for the last 20 plus years.

And, uh, this was a program that was put in place to see if there was a way to, um, better research, um, lifespan, um, in mammals, uh, and to, uh, test various interventions that could be, uh, pharmaceutical agents, it could be, uh, supplements, herbs, vitamins, you know, any type of molecule, uh, or intervention of interest that has, um, valid.

Preliminary data in the field of longevity is something that can be proposed to the ITP. Um, and then there is a, a committee that will review, uh, the proposals and each year select a cohort of new agents to test. And so they've been doing this every year since, um, you know, the early two thousands and over the last 20 years, there's only been maybe 10 or so agents that have statistically significantly extended lifespan and maybe only five that have extended lifespan more than 10%.

And, uh, with astaxanthin, we were invited to, uh, supply the material to the program back in 2019 based on preliminary data in several model organisms demonstrating that astaxanthin extended lifespan, which included round worms, fruit flies, and yeast. Um, but then also several of, uh, astaxanthin mechanisms related to longevity on key age-related pathways and hallmarks of aging, if you will.

Um, this was also a coupled with research that we conducted with our collaborators at the University of Hawaii, um, that are experts in the space of general science and experts with, uh, exploring the role of Fox oh three, the anti-aging gene. We studied whether astaxanthin could help to activate FOX oh three in their mammalian model.

And lo and behold, it did increase the activation of Fox oh three in particular in heart tissue. And so that was the first time that astaxanthin was demonstrated to activate Fox oh three in a mammal. So that data together with everything else was proposed to the ITP, uh, by our collaborators at the University of Hawaii and the ITP selected us for inclusion in their program back in 2019.

And then after following, um, the, the cohort of animals for, uh, several years. Uh, and this is a, a highly, highly rigorous program. Like I mentioned, three separate institutions running, uh, this study in parallel in triplicate. They have hundreds of, of mice each year that are especially bred, uh, for this model.

That are genetically heterogeneous, which is much better for being relevant to human aging than the typical inbred laboratory strains of mice that are used for, for most research purposes. And so these are mice that, um, are probably the best that you could use for exploring mammalian lifespan. Ideally, you would test in humans, um, or even non-human primates.

Um, but uh, it, it's difficult because humans obviously live much longer than mice and as do non-human primates and other larger, um, mammals. And so the, the mouse model is the, uh, most practical for research purposes, but hopefully still being translatable, uh, to humans based on the, uh, kind of fundamental mechanisms of aging.

So with, with our, uh, study with ITP after, you know, three or so years, uh, they, they follow all the mice, uh, with all the various interventions and I see how long they live. Uh, and they compare them to the, the controls. And there are several hundred male and female control animals and a couple hundred male and female tests, uh, you know, kind of treatment animals.

And, um, in our case, it was demonstrated that astaxanthin extended the lifespan of the male mice by. 12% with very high statistical significance. Uh, and this was the first time in the 20 year history that a supplement had extended, uh, lifespan by more than 10%. And it's really special because this is a supplement that's extraordinarily safe, well tolerated, broadly accessible.

And so previously things like rapamycin, you know, had been proven to work. And that's really what put rapamycin on the map as a longevity agent was, um, efficacy. In this ITP program, and there's been a handful of other agents since, but, uh, none of them have the, the same combination of benefits like astaxanthin.

So this was especially, uh, exciting for us. Um, and so we, we were really glad to see those results. And we are co-authors on the paper along with the investigators, um, that in this. This paper was published at the very end of, of 2023. And so I think this is something that is starting to make waves in the longevity space, uh, and should be there in the conversation with any of the other leading longevity agents given its efficacy, uh, in all of these models, including the gold standard mammalian model, the ITP.

Yeah. Uh, interesting stuff. The ITP, you know, we sort of mentioned that a few times on the show. Uh, you're right. Rapamycin is, uh, certainly one of the, uh, winners there. Then there's others that you would think, uh, given what we've, uh, you know, what, what the human studies are like, Metformin, that actually didn't show a whole lot of longevity, uh, benefit.

Obviously we're talking about mice, so, you know, somewhat limited that way, but it's meaningful information for people who are looking for that. But let's, let's back up a little bit just in terms of, so, um, astaxanthin, right? Uh, and what exactly is it? Where does it come from? So astaxanthin is a xanthe, carotenoid and carotinoids are the family of compounds that include, uh, the better known molecules like beta carotene, for example.

Um, and so these are naturally occurring pigments that co-evolved with photosynthesis, um, you know, millions, billions of years ago to help protect plants, uh, from oxidative stress. And there's a whole family of these retinoids. Um, and they, you know, evolved over time for various purposes. And in the case of, of astaxanthin, it's one of the more optimized carotinoids.

Uh, if you look at the evolutionary tree of the retinoids, um, that, um, you know, were developed over time. With astaxanthin, um, it is oxygenated, uh, which means that on its terminal end rings of the molecule, it has, uh, hydroxyl and ketone groups, uh, which make it very different than betacarotene, which to the untrained eye, if you look at the molecular structure, they look very similar.

They have these ring groups on the end and a long Pauline, uh, backbone, kind of, uh, like a pipe cleaner backbone. And so they look very similar. But the oxygenated head groups of astaxanthin, uh, give it polarity, which allows it to, uh, align favorably, uh, in cellular membranes, um, with the polar, uh, phospholipid, uh, heads.

Um, and then it's, um, you know, hydrophobic. Tail can integrate into the inner membrane. And so it really allows it to span and anchor into and stabilize the membranes and be well situated to, um, mitigate, um, you know, free radicals. And, um, in nature, astaxanthin is actually very prevalent. Most people have consumed it, even if they've never even heard of it before.

And this natural pigment is what makes. Salmon, pink lobsters, crab, shrimp, red. Um, and it's produced by, uh, microalgae. It's produced by, there's various, uh, you know, species, um, and organisms that, that produce. There's bacteria and yeast, um, as well that, that produce astaxanthin. But one of the most predominant, uh, sources of astaxanthin in nature is microalgae.

Um, and like I mentioned earlier, it's produced as a defense mechanism against UV light, uh, from the sun. And so a particular strain of microalgae, um, for instance, will start out life as a green algae or is a green algae. And then as it grows, when the sunlight stresses it, then it will actually produce assan and then turn bright red.

Um, and so it helps to protect, um, the, the microalgae. And then this is something that the microalgae are consumed and it works its way up the food chain. So, for instance, in the case of salmon, it's really interesting because it's what makes their salmon, you know, the beautiful pink and red color, but it also promotes their health and vitality as they swim upstream to reproduce.

And so when they turn bright red, as they're swimming upstream, that is the ashin, um, being, you know, transferred to their skin perhaps as a, uh, sign of being readiness, uh, to, to spawn. And then ultimately when they reproduce and lay their eggs, the astaxanthin is transferred to those eggs. And that's why the salmon eggs are bright red.

Because of the acid anthem and it helps to protect, uh, those eggs from the sunlight in the shallow waters, um, where the eggs are laid. And then it helps with the development, um, of the, of the salmon as they grow. And so it has a really profound role in nature and it's really exciting to see. Um, that it's, it's used in the marine environment.

It's even what makes flamingos pink, ubiquitous prevalence, um, natural pigment, but it has much more of a role than just providing color. It, it has these really important impacts on oxidative stress and inflammation and key cellular signaling pathways. So let's talk a little bit about that. Um, I think primarily you've, uh, it sounds like it's an antioxidant.

Is that the primary mechanism at play here? Yeah, so that's true, but it is important to distinguish that not all antioxidants are the same. And so in the case of astaxanthin, it has a lot of indirect effects on various pathways, but unlike certain, uh, other, you know, typical pharmaceutical agents or, or other, uh, molecules, it doesn't bind you into particular receptors and, you know, and, um, activate or inhibit, you know, certain pathways, um, rather it.

Integrates into cellular membranes. Um, like I mentioned, because of its polarity, it spans across the membrane. We've actually done research with a collaborator, um, that, uh, has an appointment at Harvard and also private, uh, research, uh, company that, that explores, you know, how these, uh, molecules behave in membranes and show that it perfectly spans the membrane without disrupting it.

Reduces lipid peroxidation. Um, and importantly it gets into all of the cellular membranes, the lipid bilar, so the plasma membrane, which is the outer membrane of the cell, but also the nuclear, uh, membrane. So it helps to protect DNA, and importantly the mitochondrial membranes and other membranes of other organelles in the cells.

Um, and so all of these locations are, are very important. In particular sites like the membrane of the mitochondria are, are privileged and, and hard to get to. And so, um, the fact that it gets there is really important. Um, and because of its structure, um, it can, uh, interact with, um, you know, with reactive oxygen species, for example, both inside and outside the membranes.

Um, and so. With that, it can have an effect on reducing general levels of oxidative stress. Um, but your cellular signaling pathways are also redox sensitive. And so when you impact that, you can impact inflammatory pathways, um, and other, you know, nutrient energy sensing pathways. Um, and there's also research showing that, um, in the membrane it can, um.

Integrate into the lipid RAFs where you have clusters of receptors and it can impact membrane, um, you know, fluidity and permeability and potentially, um, you know, the impacts of, of, you know, those receptors and other, uh, molecules on various signaling pathways. Um, and even potentially there's, there's potentially some proteins that it may directly interact with, which is kind of early stages of research that may further explain some of its efficacy as distinguished from other antioxidants.

Um, but what's really exciting is that, so. It gets into those membranes and can both, uh, fight off, you know, oxidative stress, um, that is inside the membrane, uh, but also outside the membrane. Um, and so that gives it a very favorable, uh, position to act. Um, and from there stems, you know, many of its, its effects on various pathways.

Uh, like I mentioned. O one of the questions I have, I think you mentioned, uh, in the ITP, that longevity, I think you, I think you said specifically in males, uh, it was, uh, what was it, 11 or 12% longer? 12%. Was it not as effective in females? Yeah, so it's a very interesting that the females, uh, it did not show a, a statistically significant increase in lifespan in the females.

Um, if you do look at the survival curves, it did look to extend, uh, the lifespan, if you look at the overlay of the curves of the treated versus control females. But it wasn't a statistically significant increase. And what's also interesting is that the female controls, and this is typical in ITP.

Historically live longer than the males. And so the, the female controls already, um, lived in this cohort about 9% longer than the male controls. Um, and in the case of the astaxanthin treated, um, mice, the males had that 12% extension. The females had. Like a 3% extension, but not statistically significant, but just numerically, if you look at the median lifespan, there was that 3%, not statistically significant, but also if you compared, um, the difference between the male and females.

The females still live slightly longer than the males, but just not as much longer as they did in the controls. And so it appears like, um, it allowed the males to catch up. To the females in a sense, but not quite, but almost. Um, and so is there a, is there a mechanism that, uh, that Yeah, so what comes to mind is there was another drug in the ITP uh, 17 alpha estradiol, which is actually non feminizing estrogen, and it showed a, you know, like 12 to 19% is what I have here.

In males, but little no effect in females. But I suspect that has something to do with, you know, the fact that, you know, it's an estradiol, so you could probably, you know, you'd probably figure out something around sex hormones and stuff like that. But, um, any thoughts or any theories on why it might be more beneficial in, in males?

Yeah, it, it would just be, um, you know, conjecture, you know, hypothesis, uh, just based on, you know, hormonal differences that, you know, that are, uh, influencing males to live shorter lives compared to females generally. And if you're mitigating that with astaxanthin, then you can counteract that and, and, uh, help to, uh, prolong lifespan.

But you may not have that same effect in the females, uh, via that mechanism. And so, but this is something that, uh, we and others have not. You know, fully researched and explored. And so it would be interesting to better understand, uh, why, uh, there was that difference. But again, there was still, uh, a positive trend in terms of if you looked at it, uh, visually and numerically, and perhaps if you had a larger number of animals, you might see a difference, but just not as much and see would've needed more animals to show statistical significance potentially.

Um, but with that said, uh, there are, you know, many, many studies in humans and animals. Demonstrating efficacy in females, um, for various areas of health. You know, cardiovascular and cognitive, you know, skin, um, you know, joint muscle, et cetera. And so it's not something that doesn't help females, but in this particular assessment of lifespan, it might be more beneficial to males.

So you've got some, so you're citing some preclinical studies. Preclinical and clinical. Uh, for example, um, we did conduct a cardiovascular, uh, human clinical study, um, like a pilot size study in about 40 to 60 subjects. And, uh, this included real world cardiovascular, uh, subjects that had risk factors, uh, for cardiovascular disease or history of heart disease.

And, uh, we partnered with a local, uh, clinic here in Hawaii and, uh, you know, had a, you know, kinda strict inclusion exclusion criteria to, to screen for the cardiovascular risk factors or history of disease, but also, uh, increased CRP, so systemic inflammation. Um, but it, you know, excluded, um, you know, other factors to try to have a, a good, you know, relevant sample.

So, so you, you excluded elevated high sensitivity CRP in this No. Included, we included for Elevated. You included it, right? Yeah. Yeah. Okay. And so this was on the heels? Yeah. Oh yeah. So go ahead. Just, just wanna explain. Um, it's a reminder, and I've talked about this before, but, you know, high sensitivity CRP is a inflammatory marker.

That's, that's really helpful, especially for cardiovascular disease and. Um, you know, some studies have suggested, and at least in patients who've already had, uh, cardiovascular events that it's more important, uh. To suppress than even LDL cholesterol, so our various, you know, uh, AOBs and stuff like that.

So that's a big deal. That's why I was pointing that out. So, so sorry to interrupt you. Go ahead. No, that's a great point. And, and yeah, just to add onto that, uh, CRP is something that whether you say it's more important or, or inflammation, whether it's more important or as important as lipids, uh, it's something that def.

Definitely is relevant in the cardiovascular space because, um, a lot of people with managed lipids still have heart attacks and other cardiovascular events. And we believe, and others believe, of course, that it's, uh, inflammation is a major driver, uh, of cardiovascular events beyond just you lipids. Um, and, and certainly can be involved in plaque buildup and rupture and all of these things.

And, um, in the case of, for example, Cantos, which was a, um, major clinical study. Conducted by Novartis with an anti-inflammatory agent, um, that, uh, specifically targeted, um, a particular type of inflammation, um, and did not have any effect on lipids, um, but just reduced inflammation, uh, and, and is measured by reduction of CRP.

Um, there was a. Um, if you had a reduction of CRP, you would have a reduction of major adverse cardiovascular events. And this was a major, major clinical trial outcomes trial over, um, several years, um, in thousands of subjects. And so this really underscored and validated the role of inflammation and, uh, H-S-R-C-R-P in cardiovascular events.

Um, and so on the heels of that. As well as, as other major studies in the space. Uh, you know, we thought it, it would be great to explore a cardiovascular, um, population with elevated CRP, um, that was on standard of care. So they were taking, um, you know, statins and other medications for. Um, uh, cholesterol and for blood pressure.

Um, and we just wanted to see if on top of that, um, that, uh, taking axin from us at either a lower dose or a higher dose, uh, would, would have a benefit. And we also had a control group, a placebo group as well. We demonstrated, and this was males and females. Um, and we demonstrated in this study, which was conduct, which was started prior, uh, to, to COVID, and we actually had to suspend it during COVID, but we had an interim analysis when we were partway through with the study with the first 40 subjects.

And we actually had statistically significant, uh, reductions. In LDL, cholesterol, blood pressure, um, and importantly oxidized LDL, um, with the administration of astaxanthin. Um, and when you looked at subgroups, um, of people that had, uh, diabetes, um, there were reductions in triglycerides. Statistics signif significant and in hs, CRP.

Uh, so that was really exciting to demonstrate in our own hands in a clinical trial that we partnered with a local clinic on, uh, that ent to reduced, you know, these real world, uh, cardiovascular biomarkers in normal patients or normal subjects. It sounds like a. Really potent anti-inflammatory is what it sounds like.

Yeah. And it's, it's been demonstrated to reduce inflammation in human and, um, you know, non-human models, um, and cell culture. There's one particular study that, uh, is many, uh, was conducted many years ago in, uh, in animals that. Uh, compared, uh, prednisolone, uh, you know, sort of a gold standard steroid anti-inflammatory, um, in a either a mouse or a rat model, um, versus astaxanthin at various doses.

And they specifically measure TNF alpha, uh, so a major inflammatory cytokine that a lot of, um, you know, drugs target in the case of, for instance, like rheumatoid arthritis. Um, and. It turns out that astaxanthin reduced T NF alpha to the same extent as Prednisolone, uh, at the same dose, which was really interesting.

Uh, and so that's just one example of, of a study. But yeah, it is, like you said, a very potent anti-inflammatory. But it's like I mentioned before, in addition to being different than other antioxidants, it's also very different than other anti-inflammatories because it's not targeting a specific, uh, you know, cytokine, uh, you know, an inflammatory pathway like a TF Alpha.

Um, it's not. Completely inhibiting, uh, inflammatory pathways, but, um, it is, um, inhibiting the pathological activation of pathways like NF kappa B. And so you are, um, you know, preventing kind of the chronic activation of, um, inflammatory pathways, which of course you don't want over time, um, that leads to aging and or health outcomes, but you're not impacting the normal immune.

Inflammatory response when you need to fight off infections or heal wounds. Um, and this was, um, you know, proven in a variety of ways with, you know, increased, you know, health in various, um, you know, animal studies, uh, in, in terms of, uh, risk of infection. But also, uh, for instance, we've done studies looking at blood clots, uh, both primary and secondary occlusion of arteries in various animal species.

And a lot of times, for example, um, say in, in certain, uh, animal models like, like rodent models, um, they'll look at. Um, the blood thinning effect, um, and whether or not you can, you know, heal after, um, a wound. And so we were able to prevent blood clots in animal model, but not increase. Uh, it's like tail bleed.

They cut the tail and you see if it can clot, uh, and it, it normally clotted so you weren't impacting the normal, uh, type of response. And so. In general, this is a, a good way to think about astaxanthin is that it helps to restore or preserve normal function. And, and so you don't wanna have your inflammatory pathways, uh, chronically activated, but you want them to build to function normally when they need to.

Um, and so a lot of agents go in, um, and just, you know, uh, inhibit something or activate something all the time on all the time off. And that may help in that limited, you know, circumstance. But that's not something, that's not how your body was meant to function. And so that's how astaxanthin seems to function is kind of upstream, you know, with redox sensitive impacts on inflammatory pathways.

What's, um, um, side effect profiles? Uh, for Asto Santin, there's really no clinically meaningful side effects that have been demonstrated in human studies. Um, there are, you know, some people may report, um, you know, uh. Stomach a distress or, or upset stomach, uh, or impacts on energy levels or sleep. Um, it's hard though to pull apart whether it's related to the active ingredient, you know, astaxanthin itself or if it's one of the other agents in the formulation, um, that, for instance, make the astaxanthin bioavailable.

Um, but there have been no human clinical studies. Um, like for instance, when you do drug development, you have very large scale human clinical studies looking at efficacy, but also. Looking at side effects and, and then you'll have a better idea of what is actually, um, you know, uh, correlated to. The active ingredients, uh, or the, you know, the pharmaceutical agent.

And so in our case with, with astaxanthin, um, there, there haven't been any toxic effects demonstrated in human clinical studies, um, that, you know, with statistical significance or in animal studies. Um, there was one finding in a. Um, a rodent toxicity study, which, uh, I'll back up and mention that there's been a whole host of safety studies in animals, you know, toxicology toxicity studies that were conducted many years ago to actually support astaxanthin inclusion in animal feed because it's a really important ingredient in salmon feed and, and other, uh, animal feeds because of, um, imparting color, but also the health benefits.

And so, um, before the FDA would allow its inclusion, um, as this, uh, you know. Ingredient in the feeds for animals. Uh, there had to be a very extensive battery of, of safety testing conducted similar to what pharmaceutical companies would conduct prior to doing human clinical trials with, with various agents.

And so it was demonstrated that at high doses and over long durations that astaxanthin was, uh, very, very safe, uh, with no side effects of, of clinic clinical significance. Um, but there was one, um, rodent study where in a female. Rat, uh, or I think it was a female rat. It was demonstrated that there was a benign liver lesion.

Um, but it was, uh, sex specific species, uh, specific. Um, and it's something that, uh, female mice are known, uh, to develop and to not have clinical, uh, relevance. Uh, so this was the only. Finding from a true, um, you know, toxicity or toxicology standpoint. Um, that one may flag when looking at the toxicity studies.

But again, it doesn't appear to have any relevance to. Human studies. Um, but based on that finding, um, the European regulators, um, you know, said, okay, well just better safe than sorry, we'll use that as a dose limiting toxicity. And we'll say that the, the one dose lower than that from that toxicity study will inform our assessment of the safe level of vasin for human use.

And so they, many years ago, published that they thought a only a couple milligrams of astaxanthin would be a, a safe dose. Um, but I think with all the human studies. As well as all the ammo studies, it's been demonstrated that, um, you can certainly take much more than a couple milligrams of astaxanthin safely.

Um, and even, for instance, in ITP, you know, this was the equivalent of lifetime in the mice. They were started when they were middle age, uh, 12 months of age in our case, which was. Translating to maybe being someone being in their forties, uh, as a human. And, um, they consumed it every day for the rest of their lives, you know, and, and helped extend their lifespan.

And it's not specifically a toxicity study, um, but it, it adds to the mountain of evidence demonstrating that astaxanthin has, has excellent safety. So it doesn't have the typical side effects that most agents have. It's always, of course, prudent, you know, to closely monitor your health and work with a healthcare professional when integrating any new supplement or medication.

Um, but it appears to be something, um, that allows for a wide range of dosing and so people can, um, titrate their dose to effect, uh, because certain people find benefits. Um, you know, at lower doses, certain people find benefits at higher doses, and there's a variety of use cases and applications. And given its safety, uh, this is something that people have been able to, uh, kind of work and explore and find the right dose that works for them.

Um, the reason, one of the reasons I was curious about that is when I hear you talking about the cardiovascular effects, it reminds me a lot of colchicine. I dunno if you guys have looked at those papers. The research around Colchicine, especially again, in people who've had, um, cardiovascular events and, you know, I, I think the idea again is that Colchicine is this anti-inflammatory that seems to bring high sensitivity CRP down.

The big problem with, uh, colchicine in general is that it taken daily, it's, uh, for a lot of people don't tolerate it GI wise. That's the, the big issue. Have you guys looked at that data? Because it does sound to me like a very comparable effects of what you're seeing. Like, I mean, that's, that's kind of like what, you know, cardiologists, a lot of forward thinking, cardiologists now are putting, uh, patients on, uh, low dose colchicine if they have elevated, uh, high sense of ECRP.

Yeah, we haven't, uh, examined that, uh, combination. Um, or, or kind of the, the, the mechanistic, uh, similarities or differences, but certainly, um, yeah, I mean that, I think that would be worth exploring further. Um, but I'll mention that I, I say for the most part, most people, uh, do tolerate astaxanthin well and don't have GI issues.

Uh, if anything, uh, it can help to, in some cases mitigate GI issues given its effects on oxidative stress and inflammation and, uh, positive influences on the gut. Microbiome. Um, and so that's something where, um, you know, for instance, if you can tolerate salmon, for example, most people don't have an issue eating salmon.

Um, they're consuming astaxanthin, several milligrams per serving. Um, and uh, I think most people don't have an issue with that from a safety or tolerability, uh, standpoint. Um, but I think astaxanthin is pretty unique in getting into these cellular membranes and also being distributed throughout the body.

And so it's getting to your liver, it's getting to your heart. It's crossing the blood brain barrier, getting into the brain, uh, where oxidative stress and inflammation, you know, wreak major havoc over time. Um, so the fact that it's distributed systemically, uh, to all your key organs gets into the cellular membranes, uh, all the membranes, lipid, biers, uh, of the cells, um, and, and has these effects on oxidative stress and inflammation.

Other important, uh, you know, cellular signaling pathways. It's pretty unique in that sense and. From everything we've seen. It's something that can be integrated into existing, uh, regimens of, of, you know, supplements, medications, you know, diets, lifestyles. Uh, it, it can be incorporated well into those. And so I think it's something that could be a great compliment, uh, for most, uh, people, you know, almost in whatever they're trying to, to manage or, or to maintain in terms of their health and their longevity.

Very good. Well, um, tell us a little bit about, uh, well, first of all, what, what, um, when you're talking about the dosing. What? What doses were you used in those cardiovascular studies? The low dose was 24 milligrams or two capsules of our product. Um, and the high dose was 96 milligrams or eight capsules of our product per day.

And those were split into morning and evening, uh, dosing. Um, so in the case of the low dose, um. We had it massed with placebo. So everyone was taking four capsules in the morning, four capsules at night. And in the case of placebo, it was four placebo capsules, each administration. In the case of low dose, it was one active three placebo.

In the case of high dose, it was all four active capsules. Um, and so, um, we did that so that it could be, yeah, easily tolerated, see a statistical difference, uh, at the low dose as well as the high dose or just the high dose. It was just the, the high dose where we had the impacts, uh, that were statistically significant.

Um, but, um, there are many human clinical studies demonstrating, um, statistically significant, you know, uh, impacts on various you important markers of, of health, um, at lower doses as well. And interestingly, if we look at the. Blood levels of astaxanthin from the ITP study. They didn't measure them throughout the whole study, but they did a pilot study prior where they wanted to feed some mice and make sure that they could, that the chow was properly made and, uh, could deliver astaxanthin, uh, to the bloodstream, uh, of the mice.

And so in that pilot feeding study. The blood levels that were measured of, of Vasant and, um, when compared to our human, uh, study, um, but also to a, um, another human, uh, pk, you know, pharmacokinetic, bioavailability study that we conducted, um, seemed to, um, correlate to one to two capsules a day, or 12 to 24 milligrams a day of our form of estin.

So if you're trying to map to what the ITP dosed, um, there are some caveats where when they did some dose analysis, uh, throughout the, um, several years of the study, they got varying levels of, of astaxanthin in the chow, and that was reported in the published paper. It was unclear whether the chow was not properly formulated by the chow manufacturer, uh, you know, to whom we had sent the, um, or provided the astaxanthin or if the method of analysis, you know, had some flaws or, you know, whether it's handling, uh, of the samples or the actual methods themself for analysis.

So, um, there is some question around the exact dose that was used ultimately throughout the whole study in ITP. Um. But when, again, looking back at the pilot feeding study with the chow formulated as intended, um, the dose achieved, uh, blood levels there that were similar to what we've seen in that kind of one to two, uh, or, or say two capsule range.

Um. In humans, in our human studies with two capsules, we probably have slightly higher blood levels than what the ITP study, uh, demonstrated in that, in that pilot, um, you know, study. So I, so I think it's safe to say that one to two capsules would be our best estimate of what would correlate to the ITP program.

But if you look at some of the efficacy studies that we've conducted in various animal models. Um, that were higher dosing, that translates more to the higher dose of our human clinical study, that the eight capsules are nine, six milligrams a day. Um, which kind of supports, again, the, the fact that you can probably have benefits at a range of doses, um, and it just depends kinda what you're measuring in over what time period.

Um, so that kind of gives a, a nice range of, you know, one or two capsules or, you know, 12 to 24 milligrams on the low end and up to, you know, 96 milligrams, uh, say on the high end or more. In some cases. Some people take more than that. Um, oh, I'll just mention that in that human PK study that we conducted, um, we wanted to see how our form of vasant compared to other forms of astaxanthin on, on the market, other supplements.

And because back 20 plus years ago, uh, I was involved in a company that helped to bring one of the firsts and dietary supplements to the market. Um, and this was back in the 99, 2000 timeframe. Uh, this was a company on the big island of Hawaii that, uh, was growing micro-algae and then would extract the ASEs anthem.

Um, and um, you know, put that into a supplement form and, um. Thereafter, we actually were interested in exploring the pharmaceutical applications of astaxanthin and we realized that the micro algal extraction was not optimal in terms of production from an FDA standpoint for pharmaceutical development because it's not as pure and consistent.

And so we started doing, uh, natural product total synthesis. So laboratory production of the molecule nature identical with very high purity and consistency. Uh, and we made various, uh, derivatives of entin for pharmaceutical purposes and explored various formulations. And then ultimately after a decade or so of, of pharmaceutical development, uh, we pivoted back to the consumer space with a dietary supplement form of entin, but still bringing the laboratory produced, high purity pharmaceutical like rigor, you know, to the production.

And so we wanted to see how that compared, uh, to the existing forms on the market. Like we had launched many years prior, uh, that were extracted from the microalgae. And so we took the, one of the leading brands on the market from that utilizes microalgae, uh, just off the shelf, um, and gave the. Uh, got a, a group of human volunteers, um, and did a crossover design human clinical study.

So we, we brought the group in, gave them a dose of the, uh, commercially available micro algal astaxanthin product, and then measured, um, took their blood at multiple time points over 24 hours, and then measured that, uh, with, um, analytical methods that, um, you utilize, um. Labeled astaxanthin to really quantify very precisely the amount of astaxanthin in, in the blood or in the plasma.

And then we sent those, um, subjects home for a week so that the astaxanthin could wash out of their bloodstream and out of their body. Um, and so that'd be no longer detectable, and then brought the same group of people back in and then gave them the exact same dose of sahin, but from, from our product, um, and then again measured their blood levels.

And we saw a threefold increase in the, uh, maximum concentration, uh, as well as the total exposure of vasant in the bloodstream over those 24 hours. Uh, so that was, um, you know, something that we thought was really interesting to see the increased bioavailability. Um, and so again, all of those numbers I was discussing would take that into account that it was with the more highly bioavailable form.

So it may not be, um, you know. Exactly translatable to other forms of astaxanthin on the market. If you were just to swap, you know, milligram per milligram to see if it had the same effect. What's the issue with bioavailability? Is this some sort of lipid? Version of it or? Yeah, so the micro algal forum is esterified with fatty acids and um, primarily mono esterified.

So there's a fatty acid attached to one end of the acid anthem molecule in some cases. Um, it'll also be diaster with the fatty acid on both ends of the acid anthem molecule, and in some cases it'll be non as certified with. Just the acid molecule itself. Um, but it's primarily monos. Um, and with a, a variety of different fatty acids that it's ster with.

Um, and. That form is something that when the body brings it in, um, it doesn't necessarily easily get dispersed in the GI fluid. Um, but it, it ultimately, you know, will be incorporated in and then the, um, esters need to be cleaved and then the entin absorbed. Um, and, and that appears to, to impact, uh, the, the bioavailability.

And so in the case of our form, it's nonsteroid. Um, but if you just take non-steroid as stentin and just dose that directly, um, that the body won't absorb it because it's, uh, not water dispersable. And so it doesn't distribute or disperse well in the, the GI fluid, which is aqueous. Um, and so we, we have a formulation, um, that helps to.

Make the astaxanthin, even though it is lipophilic, it makes it water dispersable. And so, um, the theory is that it helps to disperse it really well into the GI fluid. And then from there it can be incorporated into, um, into the body, along with other fats as they're absorbed. Um, and so when those mechanisms of absorption are activated, when you consume a fatty meal, which is how it's recommended to take.

With a meal that contains fats, then it can kind of, uh, come along for the ride as the fats are absorbed. But when it's really well dispersed in the GI fluid, that appears to be a benefit in the case of our formulation. Interesting. Um, chili question I'll ask you about just why, why do salmon get, uh, their color and does this affect, uh, will this affect your skin in any sort of way?

Have you noticed any nice hue, a tan, or anything like that? Yeah, yeah, yeah. Fortunately we don't turn as, uh, bright pink or red as, as, as salmon or lobster. Um, but yeah, so, um, I think at a high enough dose it would be possible to, to turn that color. But I, I don't think that in our case, fortunately it doesn't get transferred to our skin as much, but whether it's astaxanthin or other OIDs, um, you know, certain people will find, uh, some, um, you know.

Um, coloration of their skin. Um, and in some cases it's, it's favorable. I mean, if you search online or look on TikTok, you'll find people that from a cosmetic standpoint are taking Carotinoids, uh, including astaxanthin because it gives them some more color. Um, and so that is something that has been demonstrated.

I think betacarotene has a more pronounced effect where if you eat too much of it, your palms can be, you know, colored orange, for example. Um, in our case, I think again, if you took enough of it, you would get some coloration of whether it's palms or, or, you know, face or o other skin. But it, it doesn't appear to be something that you turn bright pink or bright red.

We certainly haven't seen that with normal. Yeah. Administration. But, but that is something that if you look at the, um, the tissue of salmon or other, uh, you know, animals that consume ses anthem, you, you see those, um, deposits, you know, in, in the tissue. Got it. So tell us, uh, a little bit specifically about where to find your product.

Yeah, so Ax three Life is our website and, uh, ax three basically sends for astaxanthin with three times the bioavailability. Um, and so we are ax three life and so not.com, but do life is, is the domain. Um. For the website and also on, uh, social media, a3 life. And so, uh, we've really just been focused on creating awareness for astaxanthin and we believe we have, um, you know, an excellent form that's very pure and well absorbed and demonstrated, you know, to work in.

The ITP program, uh, for example, um, but ultimately, you know, we are supporters and believers in astaxanthin and, and so, um, you know, we hope that the general awareness for astaxanthin increases and, and are supportive of other products on the market as well. Um, but um, but yeah, I think it's just something where most people have not even heard of, of Assisant Anthem.

And, uh, it's something like omega threes where, you know, everyone has heard of it and knows that it supports, you know, cardiovascular health, you know, et cetera, uh, inflammation. And, and we think that this should be as well known as omega threes and, and other agents that are commonly used in day-to-day health.

And so we, we think it should be considered. You know, for your kind of daily stack of supplements for, for health, for longevity, as well as targeted use cases, whether it's cognitive, cardiovascular, joint, muscle, you know, endurance recovery. It has, uh, a lot of really important benefits in those areas.

Thanks so much for being on the show, Dave. Thank you. Pleasure. Thanks for listening. A quick reminder that while I am in fact a surgeon, nothing I say should be construed as medical advice. Now, make sure to include your physician in any medical decisions you make, and also, if you're enjoying the show, please make sure to show your support with the like, share, or subscribe.