Is This the Missing Longevity Nutrient?

When we first made this link in the Dolphins, we did eight studies over three years. We showed that C15 is not only a beneficial and active saturated fat, but that it was meeting these rare criteria of being an essential fatty acid. And importantly, this is critical that over the last 24 months and really 12 months, four independent teams have now looked at the criteria of C15 being an essential fatty acid. It's including gold standard studies that were used back in 1929 and 1930. One really important follow up from independent teams that have nothing to do with us all concluding that yes, C15 meets the criteria of an essential fatty acid. So lots of exciting work on that frontier.

My guest on today's podcast is a veterinary epidemiologist. That might be the longest multisyllable phrase I've used in quite a while on my show. Veterinary epidemiologist Dr. Stephanie Van Watson. Welcome to the show, Ben.

It's great to be here. I'm glad to challenge you right out of the gate.

Right out of the gate. You wrote this book, the Longevity Nutrient. This thing was intriguing for me because I'm always looking around for things that haven't been talked about yet in the whole nutrition and supplementation world. This definitely fit into that category and we'll talk about it. It's a fascinating book by the way. If you guys want to check it out, go to BenGreenfieldLife.com C15. That's C15. And I'll put all the show notes over there which promise to be juicy for this one or should I say fatty. Stephanie, what's a veterinary epidemiologist?

It's a nerd who loves animals about as a short answer there. So our job is to basically find patterns related animal populations, remembering that humans are also animals. So veterinary epidemiologists tend to help not only in large population studies with non human animals, but actually most of us are working for public health and other groups. So looking at human trends over time.

You mean you're studying humans or you're studying animals and figuring out if what you find in animals could be translated.

Yeah, both. But the latter is obviously is a good reason why we're chatting today because, you know, it's like as a veterinarian you really come to understand there's so many more similarities between animals than there are differences. So that whole comparative approach has, you know, we're always thinking with regard to, you know, when we go to veterinary school, we learn about 12 species instead of one. So it helps you understand the links between all of us.

Well, I was walking out to actually record this podcast out of the kitchen. My wife's like, have fun talking to the dolphins. Because I told her last night I was going to be interviewing this dolphin researcher. And she's like, why the heck are you interviewing someone about dolphins on your health podcast? So I should let you answer that question, Stephanie, because you. I mean, this whole story of how this book came to be started with, if I'm not mistaken, dolphins.

Yeah. So there I was. I mean, this whole discovery bend was an accident, which is wonderful and gifted to us by dolphins. So, again, veterinary epidemiologist, I was recruited by the Navy about 24 years ago to help better understand health and wellness of aging. Navy dolphins. The Navy has cared for this sustained population of about 100 bottlenose dolphins for over 66.0years. They live in the open ocean here in San Diego Bay, go out into the open ocean every day. Every day they choose to come back. So it's a really amazing population. They get such good care, Ben, that while dolphins in the wild live to about 20 years old, dolphins at the Navy are now living in, routinely living into their 40s, 50s. And I just learned last week when I was stopped by for a visit, two of the dolphins are turning 60 years old this year. So much older. Dolphins at the Navy.

No dolphins could even live that long. That's interesting that they come back. So a dolphin is released into kind of like its native habitat from this Navy base or whatever, and they go out into the ocean, but then eventually just like, show back up at the front door.

They do. And they live, you know, they live in the bay there. So they kind of have a home base in San Diego Bay. And so they'll go out in the bay, do their work, which is easy peasy, and then. Yeah, yeah, Come back.

Do you guys count them? Is there ever, like, a rope? Probably not that high up on people's priority list. But thinking back to biochemistry. So when you're saying C15, 15 refers to the number of double bonds, number of carbons.

So it'll tell you carbons.

Okay, so there's 15 carbons. But because it's a saturated fat, every single bond between each of those 15 carbons is a double bond.

So is not a double bond. So it's.

It's not a double bond.

Exactly, Exactly.

And when you say not a double bond, what does that mean?

So that's a good point. So it's a single bond. So if you, like, we think back to our biochemistry days, right? See two bars go across Almost like an equal sign versus a single bar. So a single bar means it's super sturdy. It means it can't bend. So if you think about in a fatty acid structure, if it's a double bond, think of it as a hinge. So it allows the bond, allows that fatty acid to bend, which makes it flexible, which is why unsaturated fats that have double bonds are oils at room temperature, so they're able to be flexible. But those double bonds can also be attacked by oxygen, which then leads to risk of lipid peroxidation and other things. So think about saturated and unsaturated fats as kind of like a yin and yang of the fatty acid world. Saturated fats are sturdy. Unsaturated fats are flexible. And we need both to maintain a balanced cell membrane. But specifically, we're learning that our cell membranes need C15. This odd chain, saturated fatt, plays a very special role with regard to improving the integrity of our cells.

Yeah, it's a little bit counterintuitive, isn't it? Because you hear double bond, and you think that a double bond would be, like, more rigid, less flexible, twice as strong and unable to bend and more solid at room temp, right?

That's right, yeah. So it goes against, again, where all these things where it's like, wait, a saturated fat that's good for us, and double bonds are weaker. So we're all learning together.

Okay, so 15 carbons long, this fatty acid that you find in dolphins, and you're saying that's the first essential fatty acid to be. How many years do you say? 90.

90 years since 1929. 1930.

Okay, walk me through that. What's that mean? That it's essential.

Right. So this is a big deal, right? So an essential fatty acid is a nutrient that our bodies must have in order to maintain our baseline physiological health. If we don't have enough of it, we will see a deficiency syndrome. So our health will fall apart. Importantly, our bodies can't make enough of this nutrient of this fatty acid. Therefore, we have to get certain amounts routinely from our diet. So prior to our discovery with C15, there are two known essential fatty acids. One's an omega 3 alpha linolenic acid, and one's an omega 6 linoleic acid, which were discovered way back when by George and Mildred Burr, back in 1929 and 1931.

Okay, so essential fatty acid doesn't mean you can't make it. It means you can't make enough of it.

Exactly.

Okay. All right. So when it comes to C15. 90 years is a long time. Why is it that you think this hasn't even been discovered before or looked into before? I mean, obviously you'd expect for science to find new things as time progresses, but it just does seem like a long time with what we know about fatty acids, for this not to have been identified as an essential fatty acid before this.

Yeah, you're exactly right. And then add on top of that, then that I'm a dolphin veterinarian, right? So it's like we have people who spend their whole lives working on fatty acids. And so how was this not discovered before? When we first made this link in the dolphins, we went to Dr. Ed Dennis, who is a global leader in fatty acids. He was the editor in chief for the Journal of lipid research for 15 years. So we're lucky that Ed was in San Diego close to us. So we went and met with him, and we said, hey, this is what we found in the dolphins. Do you think C15 might be beneficial? And he said, probably not, because we all know about C15. We've known about it since the 1950s. It's present at such low levels that it's a biomarker of how much dairy fat we eat. Chances are we didn't miss it stuff. But the dolphin component is interesting. So here are the studies we would need to do to figure out, is it bioactive? At what concentrations, is it bioavailable? What activities does it have? Like, a whole slew of core questions that would need to be answered. So we did eight studies over three years. And the culmination of those studies, we published in Scientific Reports, with Ed Dennis as the senior author on this paper, in which we showed that C15 is not only a beneficial and active saturated fat, but that it was meeting these rare criteria of being an essential fatty acid. So we published that in 2020. And importantly, this is critical that over the last 24 months, and really 12 months, four independent teams have now looked at the criteria of C15 being an essential fatty acid, including gold standard studies that were used back in 1929 and 1931, where you deprive a pregnant mouse of C15, you let her have the babies. So now the babies are C15 deficient. They demonstrated nutritional deficiency syndrome, so poor growth. And when they gave the babies C15, their growth restored. So another study was done in worms showing that you could remove every nutrient, not just fatty acids, but every nutrient from a baby worm. And if you give it just C15, its normal growth will restore. So really Important follow up from independent teams that have nothing to do with us all concluding that, yes, C15 meets the criteria of an essential fatty acid. So lots of exciting work on that frontier.

Well, I'm sure as a veterinary epidemiology ourselves, yeah, it's a little bit counterintuitive, isn't it, because you hear double bond and you think that a double bond would be like, more rigid, less flexible, twice as strong and unable to bend and more solid at room temp, right?

That's right, yeah. So it goes against again, where all these things where it's like, wait, a saturated fat that's good for us and double bonds are weaker. So we're all learning together.

Okay, so 15 carbons long, there's this fatty acid that you find in dolphins. And you're saying that's the first essential fatty acid to be. How many years do you say? 90.

90 years since 90.

Okay, walk me through that. What's that mean? That it's essential.

Right. So this is a big deal, right? So an essential fatty acid is a nutrient that our bodies must have in order to maintain our baseline physiological health. If we don't have enough of it, we will see a deficiency syndrome. So our health will fall apart. Importantly, our bodies can't make enough of this nutrient, of this fatty acid. Therefore, we have to get certain amounts routinely from our diet. So prior to our discovery with C15, there are two known essential fatty acids. One's an omega 3 alpha linolenic acid and one's an omega 6 linoleic acid, which were discovered way back when by George and Mildred Burr, back in 1929 and 1931.

Okay, so essential fatty acid doesn't mean you can't make it, it means you can't make enough of it.

Exactly.

Okay. All right. So when it comes to C15, 90 years is a long time. Why is it that you think this hasn't even been discovered before or looked into before? I mean, obviously you'd expect for science to find new things as time progresses, but it just does seem like a long time with what we know about fatty acids for this not to have been identified as an essential fatty acid before this.

Yeah, you're exactly right. And then add on top of that, then that I'm a dolphin veterinarian, right? So it's like we have people who spend their whole lives working on fatty acids. And so how is this not discovered before? When we first made this link in the dolphins, we went to Dr. Ed Dennis, who is a global leader in fatty acids. He was the Editor in chief for the Journal of lipid research for 15 years. So we're lucky that Ed was in San Diego close to us. So we went and met with him and we said, hey, this is what we found in the dolphins. Do you think C15 might be beneficial? And he said, probably not, because we all know about C15. We've known about it since the 1950s. It's present at such low levels that we. And it's a biomarker of how much dairy fat we eat is. Chances are we didn't miss this stuff. But the dolphin component is interesting. So here are the studies we would need to do to figure out, is it bioactive? At what concentrations? Is it bioavailable? What activities does it have? A whole slew of core questions that would need to be answered. We did eight studies over three years. And the culmination of those studies, we published in Scientific Reports with Ed Dennis as the senior author on this paper in which we showed that C15 is not only a beneficial and active saturated fat, but that it was meeting these rare criteria of being an essential fatty acid. So we published that in 2020. And importantly, this is critical that over the last 24 months and really 12 months, four independent teams have now looked at the criteria of C15 being an essential fatty acid, including gold standard studies that were used back in 1929 and 1931, where you deprive a pregnant mouse of C15, you let her have the babies. So now the babies are C15 deficient. They demonstrated nutritional deficiency syndrome, so poor growth. And when they gave the babies C15, their growth restored. So another study was done in worms showing that you could remove every nutrient, not just fatty acids, but every nutrient from a baby worm. And if you give it just C15, its normal growth will restore. So really important follow up from independent teams that have nothing to do with us all concluding that yes, C15 meets the criteria of an essential fatty acid. So lots of exciting work on that frontier.

Well, I'm sure as a veterinary epidemiologist, you probably get this all the time. You just talked about dolphins earlier and then rodents and then worms. But what about, like, you know, people, Right?

So there's that. So what's been important with people? Like, so, for example, in this, as far as infant development and growth, there are. There's a whole other team, there's are multiple teams working on the early stages of C15 in humans, showing that even from the level of the oocyte that the more C15 that's present, the better that Oocyte multiplies, so it's signs of a healthier embryo for in vitro fertilization. Studies have shown that the more C15 mom has as a human, right, that the more C15 baby gets, and the more C15 baby gets, the better the fetal body growth and head circumference, which is brain development. The better the baby once it's born and its growth and development. And there's a study done called the Eden Cohort study in France that has followed kids all the way up to six years old, showing the more C15 they got from mom during and after pregnancy, the better the cognitive development of these children. So, you know, when all of these add up, these pieces that you know, gets us to an essential fatty acid that you know is meeting the requirements and is relevant to humans.

Importantly, a lot of the research I've seen on dairy seems to indicate, and this surprises a lot of people, maybe it's because of our built in bias still about saturated fats being unhealthy, is that full fat dairy seems to be where you get more of the benefits of dairy compared to non fat or fat free dairy. And I've always wondered, is that because something about separating the fats from the proteins affects the dairy, Something about the extra protein processing FX the dairy?

I don't know if C15 could fit into the picture here, but is there any research that you know of on people eating full fat dairy products being healthier and maybe some of those health benefits coming from the C15 composition of full fat versus non fat or fat free dairy?

Right. So yes, and in part it's because C15 has been used as a biomarker of dairy fat. So it's almost like we were saying before, how did people not discover this before? It's been right in front of us. It's just been the interpretation of people with higher C15 have a lower risk of developing type 2 diabetes, heart disease, fatty liver disease. But the reason why, when you asked earlier, Ben, why hadn't this been discovered before? People were just seeing C15 as a biomarker of dairy fats benefits, not that the fact that C15 itself may be beneficial. So when we isolated C15, right. And we took a look at how does C15 do compared to whole dairy fat. Other folks have shown, like Bishop et al did that study in mouse model of type 2 diabetes and fatty liver disease and you know, we had shown that C15 improves health, so decreases glucose, insulin, weight, body, you know, body weight on a high fat diet, lower inflammation. When Bishop et Al gave the same model whole dairy fat, the mouse got worse. So, and it's because. And they attribute it to that whole dairy fat has much higher levels of C16 and C18 of these pro inflammatory saturated fats. So kind of getting to the point where like thorning it all Hedge talked about, how do we deal with whole dairy fat? It's kind of a mess. You do absolutely have studies saying whole dairy fat can be good for you. There's equal studies saying whole dairy fat or having these high levels of these pro inflammatory fats can be bad for you. It's super confusing. And I think what we're getting to is understanding, like you said, different forms of dairy fat have different amounts of beneficial nutrients, which is why the Navy had funded us to say, hey, can we just take C15 and if you're showing that it has these benefits, can we just put that to work absent kind of the confusion and you know, of dairy fat?

Well, before we close the loop on dairy, because I don't want to just leave people hanging and, you know, sitting there in front of their full fat Greek yogurt now asking themselves, eat this, do I not eat this? Like, what's, what's your take on the dairy fat thing? Like, would you eat or, you know, would you drink full fat milk? Would you eat full fat yogurt based on what?

You know, I do not shy away from whole dairy fat, but I do think it's in moderation. Like, we shouldn't make 90% of our diet dairy fat. You know, if we look at the Sardinian population and the high longevity zone, they have swapped out cheese so we can start cheese for meat. So eat a lot less meat. They eat a lot of cheese. And their cheese specifically has, has 50% more C15 in it compared to other dairy fats. And so with regard to understanding fats that are good for us, it's dairy fat that comes from animals that are grass fed have twice as much C15 in it than like cows, for example, that are fed corn. And so when I'm going for my whole dairy fat options, I go for cheeses that are from, if hopefully, you know, from grass fed animals. Animals.

Okay, that's actually super important to know. So. So in Sardinia, the cheese that they eat is special because that cheese is coming from grass fed animals.

Yeah. And even better, there's actually multiple studies showing not only is it about grass fed animals and they use sheeps and go sheep and goats. It doesn't really matter if it's a sheep, a goat or Cow. But if they are fed not only grass, but grass at high altitude, that has even more C15 in their milk. So the Sardinian high longevity zone is in a mountainous region in Sardinia. So they're really getting, they are hitting that sweet spot of grazing, you know, grass eating sheep and goats at high altitude. And that's resulting in their cheese. One of which is pecorino, which I love, has, you know, high C15. And it helps except explain why people in this high longevity zone have two to three times higher C15 levels than the rest of us.

Okay, we are rabbit holing big time. But, but why is it that like a hypoxic sherpa goat cheese would, you know, would, because of some type of oxygen limitation, produce a cheese that's better than a goat at normal altitude?

Yeah, I mean, I think you're heading down the right rabbit hole. I think it's, you know, C15's role is to be a slight sturdy fatty acid that helps make things, living things, more resilient to stressors. And so hypothesis Ben, but not yet been tested, is are these high altitude grasses and animals put at, you know, really having to leverage C15 to be able to make them more resilient? And again, in a hypoxic environment, kind.

Of makes me wonder if any type of stress might induce upregulation of C15. Because I have goats, but I don't live at altitude, but I do have cold tubs. So if I like cold thermogenesis my goats, maybe I could induce higher C15.

You did not get that from me, but yeah, you're heading in the right direction.

I don't have mountains, but I have too many cold tubs around here. All right, well, we'll save that for another day. I'll let you guys know if I wind up cold plunging my goats. But back to the longevity piece, because Sardinia is obviously one of these longevity enhanced blue zones. Apparently. You talk about longevity a lot in the book. You talk about a lot of these other chronic diseases, but specifically you talk about longevity and you describe these longevity must haves that you've identified in terms of something that a molecule must cause for it to be a longevity must have. Can you get into that a little bit?

I can. So as we started learning about C15's role, its activities, how it works and what, what it's doing, Dr. Nicholas Schork, who's head of NIH's longevity consortium, and he's been playing that role for over 15 years, Nick came in and he's like I'm reading all these studies are now over 100 peer reviewed studies on C15 available@discoverc15.com for those who want to nerd out. And Nick said, Steph, like C15 is, the evidence I'm seeing is that C15 is emerging as a geroprotector. And, and I said, great, what's a geroprotector? So that's where Nick described that a geroprotector is the holy grail of a longevity molecule because it slows the rate at which we age to stem the onset of the diseases that kill us. Which means that if it's a true geroprotector, you're going to see clinically relevant benefits within months. Right. In a person who's already going through that process of aging. That's what excited Nick because he's like, we don't have that today. And this has the potential to have a meaningful effect. We worked with Nick and he came up with these five longevity molecule must haves. The molecule needs to show that it targets the human longevity regulating pathway. It needs to show that it targets key hallmarks of aging. There needs to be evidence it slows the rate at which we age, that there are clinically relevant benefits seen within months, and that there is strong evidence that the molecule can actually help prevent the onset of diseases. So what we do, we go through the book, is we show that C15 does all of that. It activates AMPK and inhibits MTOR. Right. This is what metformin and rapamycin do, respectively. It targets six hallmarks of aging, including improving mitochondrial function and decreasing senescent cells and decreasing inflammation. It has evidence of slowing the rate at which we age. There's a key biomarker aging rate called red blood cell distribution width or rdw. And C15 has been shown to reliably reverse that. So if it goes high, it's a faster aging rate. C15 has repeatedly shown to bring that down. And then we talked about, we'll talk about clinically relevant benefits through clinical studies, in vivo studies within months having to do with liver health, metabolic health, cholesterol. And the last is there are meta analyses. So studies of studies involving tens of thousands of people over decades repeatedly showing that people with higher C15 have a lower risk of developing type 2 diabetes, heart disease, fatty liver disease. Lee et al showed that for every 50% incremental increase in C15, the percentage that we have in our cell membranes and in our blood decreases our risk of type 2 diabetes by 8% and their risk of getting coronary heart disease by 17%. So when you bring all these pieces together, that's where you get to.

Checking off these must haves of a longevity nutrient.

Yeah, well, kind of back to like, you are what you eat type of idea. Or you are what you eat. 8. Is it because C15 is like comprising our cell membranes with this more stable fatty acid? Is it just that or is it doing other things? Like this is kind of like a mechanism of action question, you know?

Absolutely. And this is so important, Right. If you don't understand mechanism of action of something and what concentration. Right. You need to achieve that mechanism of action, it's kind of like game over. Right, Ben? It's like a lot of skepticism around, like, how does it really work? So you're spot on. That C15 as a stable fatty acid goes into our cell membrane and it makes it more st and resistant to lipid peroxidation, which is a major driver of chronic diseases and aging. It is such a simple thing that it does. And we'll talk about. It does more. But that is a core mechanism of action. In addition, you know, we and other groups have shown that C15 is a pleiotropic molecule, which means it does a lot of different things. And so I'm just going to name off some acronyms, but we're not going to go into detail. But it, you know, we know that it activates AMPK, AKT, MPAR, Alpha Delta. We know that inhibits MTOR, JAK, STAT, HX6, lots of stuff.

Okay, so by the way, those are all. I mean, interrupt you. You said ampk, ACT and ppar, those are all the same things that would get triggered via exercise. So it sounds to me like you're saying it might act as a little bit of an exercise memetic agent.

That is correct, yes. Especially that PPAR delta. Yeah. Ampk, don't. Not the fact that you're exercising while we're doing this. I'm incredibly impressed.

Yeah. In my opinion, most. Sorry to interrupt. Most exercise memetics and calorie restriction mimetics are best combined with, respectively, exercise and calorie restriction. If you're looking to maximize the benefits from those, you don't just like pop a pill and watch Netflix.

Nope, you don't get any of that. You got to do. And in fact, it helps like a lot of people, even for myself, it helps me exercise. Like I, you know, I'm able to exercise longer, so. And it makes it more enjoyable for me.

Okay, so I interrupted you as you were going down the Alphabet letters.

Yeah, so we've got. Yeah, inhibits, you know, when we talk about activates things, it inhibits things like MTOR, HDX, 6, JAK, STAT. And so it's like the core thing is if you look at all these different mechanisms and we just published last week that it inhibits these two things called FAAH and maob. And it does, by doing that, this is really critical to cognitive health. So super exciting. To help sustain higher healthier dopamine levels and endocannabinoids, which we'll touch on in a little bit. So the point being it's an essential fatty acid. Nature takes essential fatty acids and it has them do a lot of things, which is a big reason why we and dolphins and dogs have these receptors. It's because they're waiting for us to eat the right things and trigger these receptors and keep us balanced from a metabolic and immune standpoint. So it all makes sense given the fact again that this is an essential nutrient that every mammal gets from birth.

You mentioned modulation of mtor, and then earlier, of course, you were talking about diabetes. I think two darlings of the anti aging industry as far as off label drugs are metformin and rapamycin. How do you think about the head to head comparison of something like C15 with. With something like those?

Right, so that's where Nick came in and he had the same question you did, Ben, which is, hey, if we test C15 head to head against rapamycin, metformin and then the third molecule called carbose, which is also in the kind of anti diabetic world, isn't that like.

A negative glycemic index sweetener?

Yeah, exactly. We don't use it here as much as in Asian countries is popular. And basically what it does, it prevents absorption of carbs.

Dr. Sandra Kaufman, she's big into all these different ways to block glucose absorption. I think acarbose is on her list of supplements. Okay, so you're testing C15 about against or at least comparing it against metformin, rapamycin and acarbose. And what are you guys finding?

So what we did is we used this panel that is industry standard for the pharmaceutical world and it's called Biomap. It's 12 human cell systems mimicking various disease states, heart disease, liver disease, lung disease. And what you do is and you treat these diseases in a dish with 10 concentrations. So no, let me take that back. Four concentrations of each molecule. It measures 148 different biomarkers and it Gives you a profile of how well does this molecule behave across many different human cell systems. So it's a great way to assess safety, but also efficacy. So we did that with C15, pure C15 against these other longevity leaders. And we were able to show that C15 had the most cell longevity enhancing cellular benefits than all of them, most closely mimicking rapamycin. And when you step back and you look at what we know rapamycin and C15 do, it's they're anti inflammatory, antioxidant, anti fibrotic, so anti scarring, antimicrobial and anti cancer. So it's this wonky set of tools that if you have these, you're going to live longer. And so the conclusion we came to in the paper that Dr. Shork and I, in this paper that we published in 2023 was, hey, maybe we didn't need to go to Easter island for this molecule. Right. That is grown in bacteria that grow in a faraway place. Maybe what we've needed to support Our longevity is C15 Again, what all mammals get and we've been taking out of our diets by reducing the amount of dairy fat we eat.

Yeah, this whole biomap measuring thing that you use, I hadn't come across it before, but it's kind of cool because yeah, it's not like a double blinded human clinical trial long term in living people, but it's almost like kind of a cool algorithmic way of comparing things head to head. I hadn't heard of it before, but I think. Let me find this section of the book. You actually say you start with a handful of different human cell types like lung cells, white blood cells, vascular cells and skin cells. Then you expose them to a variety of factors that replicate a multitude of diseases. And so you're getting a bunch of diseases in a dish that mimic things like heart disease, cancer, inflammation, arthritis, liver scarring, et cetera. And then it gives you a comparison of what's going on in that dish based on what you test against these diseases. Almost like a bunch of little miniature celebrity death matches in a petri dish.

I love that. Yeah, I think biomath's going to call you up and ask if they could use that.

It is really cool though, because again, I don't think you would say this either. This is not the same as a human trial, but it certainly gives you some pretty cool data to work with.

That's exactly right. And I tell you, Ben, as the years have gone on since we first started using biomap, I have become A huge believer in it. And it's because we've been able to see it move forward. Right. So it predicted, for example, that C15 would have anti cancer benefits in this dish. And then there's a group that then moved C15 forward in cancer studies in vivo and they were able to figure out what was the mechanism of action. So it was a JAK static and HDAC6 inhibitor, which are anti cancers. It mimicked gemcitabine and paclitaxan, which are two anti cancer drugs. And most importantly, when they moved in vivo to a mouse model that it decreased the tumor size of mice with breast cancer. So it's remarkably good at being a predictor of what activities it will have. And because these are human cell lines, it's a predictor of what's going to be useful in humans. Again, this is used by the pharmaceutical industry and they are not going to waste. This helps them be much more efficient at honing in on which molecules are most likely to make it across the line.

Yeah. A few minutes ago you mentioned the endocannabinoid system. Why are you talking about that?

Right, so this is a fun component that, you know, as people started, you know, taking pure C15 and supplementation, we had about half of the people within two weeks reporting deeper sleep, calmer mood and less joint pain.

Wait, I want to back up, interrupt you real quick. Were they like taking this right before bed or is this just kind of like chronic long term use effects?

Yeah, like it was more like. And it's within two weeks. And so, you know, it takes a few, maybe a few days to. But let's say pretty reliably at two weeks, half of the people, and we're like, you know, hey, we understand C15's mechanism of action, you know, from what we understand today, that doesn't really line up with what we know about C15. But then the science continued and we learned that C15, that our bodies use C15 not only for all the things I just talked about, but Our body uses C15 to make a second molecule, a metabolite called pentadecanoyl carnitine, which we'll just call pdc. And what we found was again, the first step is take the molecule, throw it against a bunch of receptors to understand is it active, is it activating relevant receptors? And so that's where we found that Pdc fully activated CB1 and CB2 receptors, where CB stands for cannabinoid. So these are the receptors throughout our brain and body that respond to cannabis. Right. And they're named that because of cannabis. But we don't have those receptors because our bodies were waiting for humans to find cannabis and start using it. Right. Like dogs have it and dolphins have these receptors.

So you're telling me weed is not an essential plant?

Weed is not. That was not the big discovery. So. But why are they there? Right, and so what we showed is there's a. Previously there is a one called an endocannabinoid. So it's a cannabinoid that our bodies make that are intended to activate these receptors. Prior to our discovery, there was only one known full acting endocannabinoid. This PDC was the second. So the second ever discovered. Which then helped explain. Aha. Deeper sleep, calmer mood, less joint pain, all of which I have experienced myself. And now it's like I get it, like I'm understanding why those benefits.

So the way that it's working on these receptors, you said it acts on CB1 and CB2 receptors or. Or it upregulates this PDA which acts on those receptors.

Yeah, exactly. It's this metabolite that then activates these receptors.

Okay, so if you're binding to those receptors, would you, and this is just like a total thought experiment and you like smoked weed or had an edible, would you need more of it to actually work with those receptors? Because the receptor side is already occupied.

Yeah, that is an interesting question. If there's what we don't know is competition. That. If, let's say. Yeah, that the, the phytocannabinoids. Right. The non ones that our body.

Cannabinoids.

Yeah, yeah. If they're stickier right to the receptor, then there may be a competition component. The neat thing about endocannabinoids, which is fascinating, is that our bodies make it on demand. So we store C15. And then when our bodies need less pain, calmer mood, better sleep, our bodies will actually then make.

The endocannabinoid versus if you take an edible, it just goes up at that time and then goes down based upon how long when you had eaten it. So maybe they'll do a one, two punch that you can store it in your tissues, your tissues will use it when you need it, and then you have your edible which will have its immediate effect at that time.

Yeah, interesting. You said you store it in your tissues. What do you mean?

So C15. So as we eat C15, it goes into our cell membranes. This includes cells in all of our tissues. So we want to have C15 stored in our tissues because of all the things we Talked about anti inflammatory antioxidant that keeps our liver, our heart, our brains healthy. But it also means we've got a store of C15 waiting so that when our body needs endocannabinoids, when it needs to deal with pain, when it needs to deal with sleep, it's able to make those endocannabinoids and increase the levels upon demand. Which again is something I learned while writing the book about endocannabinoids and just fascinating.

Yeah. It kind of makes me wonder too if you're kind of a pothead or you're too reliant on CBD or THC, if you could kind of use some form of C15 to wean yourself off that or kind of taper off.

Yeah, that's the hypothesis. It helps. Yeah, exactly.

Interesting. So if it's stored, is there a way to actually get a blood test or some kind of tissue sample or something that the average person could do to see how much C15 they actually have in their bodies?

Yes. And so the good news is, because C15 has been used as a biomarker for how much dairy fat we eat, the test has been used for decades reliably. So fatty acid panels, if you just, you can ask your doctor to do a fatty acid panel, just make sure that they check and that C15 is included. Another reason why C15 wasn't discovered until recently is that fatty acid panels before the 1990s for the most part didn't include C15. So if we had done that dolphin study, Ben, three years earlier, we would have missed the entire discovery because there were C15 wasn't on the panel. So a bit of luck came into play here.

Yeah, but if I ask my doctor for a fatty acid panel, I mean, I know doctors are smart, but maybe they're not trained in this specific type of panel. Usually even a smart doctor is going to give me an Omega 3, they'll order an Omega quant or something like that. Is there an actual test you could ask for or an at home panel? Or do you literally just need to go to your doctor and say, hey, C15 is the one I want you to test for.

Yeah, so you can do the latter first. And if they don't have it, or they're like, what are you? I don't even know what C15 is. And then you're going to give them the fuck. But what we know is, so what? We worked with Genova Diagnostics to develop an at home blood spot test. So if people don't have an option, and that's what I used. Then you can get this at home. Blood spot test and then turn it in, you mail it in and they send you your results.

Oh, easy. So if I go, if I have like an account of Direct labs or whatever, would it be on there?

Yeah, it should be on there.

Okay, easy. And it's just at home.

Yeah.

Oh, most people are, I mean most of my listeners are going to do that because they just like to take it into their own hands and I know it's good. That would be that expensive.

It's not. Yeah. I mean for people who are used to ordering, you know, tests and to be able to get results, you know that it's, it's in the same realm as other tests. And so I use that one and that's why I was able to show that my C15 levels in that test. Right. That uses this ref, you know, a different reference range than maybe other tests. But this one showed from the concentration that I have this Sardinian level. So 0.46% and over 5 micrograms per mil.

Yeah, you're going to start talking like an Italian biohypoxic goat.

Yes, exactly. C is easy.

So dolphins, you mentioned eat fish. They don't eat yogurt, but at least I don't think they do. I don't know what you're doing in the Navy if you guys have a Ben and Jerry's there. But the thing about fish oil, because fish oil is often called a source of some of these essential fatty acids that you named earlier, I think how do you compare C15 to fish oil supplementation? Do you still use fish oil or what's your take on the fish oil?

I love fish. There's so much, there's so many studies been showing that the more fish we eat, if we eat two to four servings a week, that the better our health. So dolphins are onto something. So we know that fish are good for us. They contain a lot of important nutrients, including the omegas. So with regard to fish oil, you know, fish oil goes back to the 1800s industrial revolution of that was our cod liver oil was our main source of vitamin D and it helped to get rid of, to cure rickets. I mean so fish oils played a really important role in supporting our health. When we talk about, again I think we talked about earlier the yin and Yang, that Omega 3, Omega 3s are important to keep our cell membranes flexible. They have some anti inflammatory benefits. The purer this EPA, the omega 3.

In that supplement or even better the pharmaceutical, the better the outcomes in the longer term studies because you just have more control over what was in that fish. Every fish has a different life and that dictates the fatty acids that are in that fish's oil. So in comparison, C15, again, we talked about getting it from dairy fat, but that becomes complicated. So again, that's why the Navy funded US to isolate C15 and create a pure bioavailable form that you can control. And again, this was for the dolphins, to control and supplement the dolphins diets so they could get exactly the amount of C15 they needed. So it's a stable powder at room temperature versus an oil. So again, complementing each other.

Yeah, I'll leave it at that.

Okay, so they can complement each other. So, so DHA and epa. If I look at a fish oil label, what is it? Dose of hexaenoic acid and ecosapentanoic acid. Am I even close?

Yeah, that was it.

So we nerded out before. I want to nerd out again, just real quick, just so people kind of understand this. So C15 is 15 carbon atoms with a single bond. And then EPA and DHA. What do those look like? Like if I were to look at like a diagram or a picture of an EPA and DHA next to a C15.

Yeah. So they have, they're polyunsaturated fatty acids. So that means they have multiple. So poly unsaturated means double bonds. Polyunsaturated means multiple double bonds. So they're going to have, it's a longer, bigger, kind of more complicated molecule that has lots of hinges and lots of bending points, which is why they're oils at room temperature. It's why, you know, omega 3s are oils and why they're more susceptible to oxygen. So if you're like, leave the oil out of the fish oil supplements, they can get rancid.

It shipped via Amazon and sits out in the summer heat for 90 degrees on your doorstep for two days while you're on vacation. And you come back and put that in your fridge, it's still probably pretty damaged.

Yeah, exactly. And so that fishy smell you get is the oxidation of those fatty acids. So it's not the manufacturer's fault. Right. It's just they're just molecules that are naturally more susceptible to attack by oxygen. The nice thing with, you know, with C15 is that whether in the bottle or in our bodies, its job is the opposite. It's meant to protect us against lipid peroxidation and shore up those membranes, but also be incredibly stable in the Bottle.

Yeah. So it sounds to me like your take on fish oil is probably a little bit similar to mine. I love fish. On any day that I eat fish, I don't use fish oil. And so that's on, like, three days of the week. And then on the other days, I take about 1 to 2 grams of a DHA EPA blend.

That I keep in the refrigerator. And so I kind of go back and forth. And I recently added C15 into the mix. After reading your book, I decided to do like a. Well, so far, I think I'm two months into kind of trialing using C15 via this, a supplement called fatty 15. So I've been taking. I think the label says two. I've been taking four of those a day. Is that okay?

You know, three, maybe three.

Okay. All right. I'm an overachiever.

Well, you may be catching up. Maybe you're catching.

It's like getting bigger. I'm almost £200 now, and.

I get. I get a little bit of flak for this, but I don't purposefully keep my body fat low. But. But I'm 4% body fat and 200 pounds, so I have a lot of muscle, and I just feel like I need a little bit more than the average. I don't know if that's true.

Well, and also, it depends. I think it depends on a person's diet. Like, if you don't eat a lot.

Of dairy, then.

I'm pretty lactose intolerant. I forgot to mention that.

Yeah. So it might be like, again, maybe some ketchup. But we have have people tell people, start with one, work from there. And we have over 95% monthly retention rate. And it's not because people are just crossing their fingers and believing. It's that they're seeing and feeling benefits within months. And so those doses seem to be working for most people.

How many milligrams is in one capsule?

100 milligrams.

And in the studies that you've done, because I'm sure you're running this in the supplement industry, people will make a supplement, but it's nowhere near or the dosage that were. That was actually used in the study or extrapolated to humans. How does the fatty 15 match up?

Yeah, so it matches up. So there have been multiple clinical trials. One of them used 200 milligrams. The other one did use 300 milligrams. But, you know, what we'll cover is that these clinical trials were done in people who were likely C15. And then we saw C15 deficient. So again, kind of to your point, Ben, that if you're starting from a C15 deficient state, so people are purposely avoiding whole fat dairy then or have a condition consistent with C15 nutritional deficiency, there's some catch up that's needed. And I think there was a desire by the people who are running the study to say like we really want to kind of push it to a higher amount so that because it's only for 12 weeks, it's not for six months or a year, so they were pushing it higher to say can we see benefits within 12 weeks?

Okay, got it. Well, if people want to try the one I'm using, I'll put it in the show notes@bengreenfieldlife.com C15. So I want to kind of give you a little chance, maybe slightly lightning roundish here, but you've had some people try and take down your research. And I came across it, you know, I do a little bit of stalking, a little bit of my own research in anticipation of these interviews that I do. So there's a really popular podcast called the Proof and more or less like the summary of a YouTube video that they did was they said C15 is non essential for humans and lacks strong evidence for metabolic health benefits and shows inconsistent absorption and effects in studies. What say you?

Well, it's easy to say things on YouTube. I'll say that it's a lot harder to get things published in peer reviewed studies. So we'll cover a couple of those things. And I will say, Ben, my hope is that the intent of some of these takedown videos are not. It's because there's earned skepticism in the supplement industry. Right. There's a good reason for this. Right. And it's really hard to keep up with the latest C15 studies. Literally every three to four weeks there's a new paper coming out around the world. So it's real hard unless you're spending all of your life, like I do, looking at the latest studies, which is one reason for writing the book. To have one resource for all of these studies, it's hard to keep on top of things. So my hope is it's not nefarious. It was just an unintentional misinformation that was provided. When we talk about there's no evidence at all that it's essential. We already talked about, not only did we show that it's essential, but now multiple teams have done that, the gold standard studies to show even beyond what Omega 3 and Omega 6 had to do to get their criteria of essentiality. We have surpassed that thanks to multiple teams coming in and revalidating it. So there is absolutely strong evidence for C15 as an essential fatty acid. So with regard to metabolic health, when we talk about if we walk our way up from mechanism of action, we know C15, you know, activates AMPK and AKT. That was then showed and I should mention activating AMPK is the main mechanism of action of metformin which is the top leading diabetes drug. Right. For globally. When moved into cell lines, C15 at those concentrations of activating AMPK and AKT were shown to improve glucose uptake at the cells. And even interestingly Fu et al showed that C15 actually mimicked insulin. It not only improved insulin sensitivity then it actually did as well as insulin in these cell based studies. Then we moved to in vivo efficacy studies. So then you treat a mouse that has type 2 diabetes showing that it decreases insulin, I'm sorry, decreases glucose, the whole suite of components of type 2 diabetes. Then you move into the human studies with regard to these large scale human epidemiological studies. The higher C15, the lower the risk of developing type 2 diabetes. So we had a third party come in and actually review our claims for fatty 15 and review the science and to say are these substantiated? It's called cars process. And they absolutely said with regard to our claims that including metabolic health, that there's clear substantiated evidence that C15 plays a core role in supporting our metabolism.

Right. And I know that a lot of people will say, well you show that high levels of C15 in these models, whether animal or human models, is associated with all these benefits. But you haven't shown that taking your pill, your supplement, your fatty 15 causes those same benefits. I've heard that. What do you think about that?

Yeah. So when it comes to clinical trials, Right, So then you need a clinical trial in which people have the condition and so with supplements. We haven't that study. Absolutely to your point, haven't been done yet. The studies to date on clinical trials have focused on fatty liver disease. And that's because the hypothesis is that fatty liver disease, which didn't non alcoholic or it's now called mazzold, it's going through a rebrand, didn't exist before 1980. And so one of the hypotheses is that decreasing C15 levels that happened since the 1970s and especially since the 1990s have gone down population wide, that then these deficiencies may actually be causing fatty liver disease. So the clinical trials are being triaged based upon urgency. One in three people have fatty liver disease today. And so the two clinical TR trials that have been done with C15 have been on people with fatty liver disease, history of fatty liver disease. The first one, which was 200 milligrams per day, had people go on it. And this clinical trial then was a home run. And the reason for that is two out of three of the people in the study, they were 18 to 24 years old, had what we defined as a nutritional deficiency, right? So they had C15 levels lower than this, 5 micrograms per mil. So first of all, we're saying, like, okay, two out of three people with this condition have what's defined by, through cell based studies from the dolphins, from the epidemiological studies, all rally around, we need 5 micrograms per ML, at least to not be deficient. So it showed that two out of three people met this criteria of deficiency. Then among the people who took C15 supplementation and got their levels up and above that, 5 micrograms per mil, they had lower liver enzymes of ALT and ast, which is improved liver function. And again, these people had high liver enzymes at the start of the study. And it also increased their hemoglobin, which again, kind of going back to the whole aging rate and stability of cells, includes red blood cells. This is a marker of improved red blood cell health, which was not the intent of the study, but was really interesting. Which leaves you with why did half of the people who got C15 not have an increase in their C15 levels?

That's the other question I was going to ask you because like Dr. Bill Harris of Omegaquan, he came out with an article and said, well, half the people who took it didn't even see an increase. So there's questionable aspects of the absorption, you know, effectiveness of it.

Right. And fair enough. I mean, so what's important is that a couple of things. The first is that extensive clinical trials, pharmacokinetic studies have been done on this pure free fatty acid C15 ingredient. This was done by Mascarenus et al and Stallings et al. And they did lots of people, they did adults, they did kids, they did people with and without cystic fibrosis. And Ben, what they showed across two papers in extensive clinical trial trials were that this molecule is 100% bioavailable. So how much you ate reflects exactly how much was in your blood. So that leaves us with the question of what happened in this clinical trial. When you read more into the paper, what they showed was that the people who had the increase had a 95% adherence to the protocol. So they actually took the amount of C12.

Just basically not doing their homework.

Yeah. So if. And it's there and it doesn't explain all of it, but a good portion is that it def. It was significant. Of people who actually took the C15 had higher C15 levels. And importantly among that group that took, that adhered to the protocol, they had the increase and they increased their levels by 2 micrograms per mil, which exactly matches the 200 milligrams, which is what the prior study showed, that for every 100 milligrams you eat, you go up by one microgram per mil. So when you look at that group, it was spot on. So the big question is, well, if you don't take the supplement, you're not going to increase your C15. And they were 18 to 24 year olds and Jeff is like, it's kind of like the worst group for adherence.

Okay. So that was a 12 week study. So what I'm getting from what you're saying is that there's probably still a need for longer term human clinical trials of taking C15. But the way I think about this is if somebody's listening in, I'm a total kind of like N equals one guy guinea pig stuff on myself all the time. Somebody could theoretically start taking this, you said 100 to a maximum of 300 milligrams a day and then get pre and post bloods and maybe even this Genova Diagnostic C15 test to see what their absorption or what impact that has on the levels. Lots of people, especially my listeners who are smart cookies, know how to do that. They know how to get a pre blood test, take a supplement for X amount of time and then do a post test to see what the levels are and see how it changed their biomarkers. But the question I have for you is, is if somebody was going to do that, how long should they wait between the pre and post test for the C15 to build up or to have its effects based on what you know?

Yeah. So we do, just like you said, we strongly recommend that every person before they start fatty 15 the supplement to go get your blood work. C15 level is great to assess, to look at, but what's more important is are we seeing clinically relevant improvements? Right. So start and get your baseline blood work which includes and sometimes you might need to ask for things like ferritin levels and your full red blood cell indices. Because there are some special things like that RDW measurement that is kind of like bonus measurements of efficacy. But get your standard CBC and chem. Go back, we say we recommend between three to six months later. And that's where if you go to our reviews and that's where Ben, we're seeing again why people stay on fatty 15 retention is so high. People are doing exactly this and they're seeing the benefits. I mean, science works like this is, you know, it's what Nick, you know Schork, right. Dr. Shork, head of NIH's longevity consortium. It's why he has explained that there is no of all given the breadth of data across all these different aspects, he said there is no molecule that has more more support as its role as supporting a role as a Gerald protector. Our long term health and wellness.