Latest / Gladden Longevity Podcast / Fatty15: A Deep Dive Into Cellular Benefits, A Breakthrough in Longevity - Episode 260

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Fatty15: A Deep Dive Into Cellular Benefits, A Breakthrough in Longevity - Episode 260 · Gladden Longevity Podcast

• 0:47
  today.
• 0:48
  She has a fascinating story.
• 0:51
  We've actually had done a podcast together previously and we were talking about Fatty 15.
• 0:58
  which is a 15 carbon saturated fat that is the first essential fatty acid I guess has been discovered in the last 95 years or with something close to that.
• 1:10
  So pretty, really fascinating stuff.
• 1:12
  And I know they've been doing research and some other things.
• 1:14
  So with that introduction, Stephanie, welcome to the show.
• 1:16
  Great.
• 1:17
  Dr.
• 1:17
  Gladden it's wonderful to be here.
• 1:19
  Yeah, it's good to see you in person.
• 1:21
  So just to refresh the audience's memory, give them a little bit of the backdrop, a little bit of your
• 1:28
  background in terms of being a marine biologist, the dolphins in Coronado and some of that story.
• 1:33
  Yeah, absolutely.
• 1:35
  So yeah, I'm a veterinary epidemiologist by training and work for a World Health Organization, CDC, was recruited by the Navy about 20 years ago, maybe a little longer
• 1:46
  than that now.
• 1:48
  And how do they recruit?
• 1:50
  They were, you know, they were, they had accumulated so much data on their dolphins over 60 year period, Navy has dolphins.
• 1:57
  And they really wanted to, to their credit, dive deeper into the long -term health of dolphins.
• 2:04
  And they said, we're sitting on all this data.
• 2:06
  It would be great to get a veterinary effort to make this.
• 2:09
  It actually was a connection of a friend from veterinary school who was working for the veterinary for the Navy.
• 2:15
  And she said, I think I might know the right person to bring it to the stop.
• 2:19
  That's not the usual thing that shows up on Indeed, right?
• 2:21
  That's right.
• 2:22
  That's right.
• 2:23
  Exactly.
• 2:24
  So, yeah, so I joined the Navy team there, Navy's Green Mammal Program.
• 2:30
  They have cared for a population of bottlenose dolphins for over 60 years and assisting population of about a hundred bottlenose dolphins.
• 2:38
  Because they get such great care, they live a lot longer than they do in the wild.
• 2:43
  In the wild, yeah, you said almost twice as long.
• 2:45
  so they live like in the wild, so they lived in their 20s, Navy routinely live into their 40s and 50s.
• 2:50
  So with that, we had...
• 2:53
  geriatric dolphins and started seeing that some, but not all of the older dolphins were developing aging associated diseases like chronic inflammation, high cholesterol, fatty
• 3:03
  liver disease, and even Alzheimer's.
• 3:06
  Okay.
• 3:07
  Actual Alzheimer's.
• 3:08
  Really?
• 3:09
  Okay.
• 3:10
  Well, that's fascinating.
• 3:11
  But do they have the genes for Alzheimer's disease?
• 3:13
  Have you looked at that?
• 3:14
  Yes, we don't know yet about the genes, but what's been fascinating is when you look at the histopathologies of the changes in the brain, consistent with Alzheimer's, that we
• 3:24
  were seeing it in the Navy dolphins, as well as it's now been reported in numerous wild bottlenose dolphins too.
• 3:30
  So it does appear to be a naturally occurring disease and a long live large brain mammal.
• 3:35
  Okay, interesting.
• 3:37
  I wonder if whales have it.
• 3:38
  I would be surprised if they didn't.
• 3:40
  Yeah, there's some long -lived whales, right?
• 3:42
  I think beluga whales live a long time.
• 3:44
  They live a long time.
• 3:45
  Yeah, there are some whales that lived in, they think, about 200 years.
• 3:48
  That's right.
• 3:50
  Amazing.
• 3:50
  Yeah, amazing.
• 3:51
  So in that population, I think there was a subpopulation, right?
• 3:55
  Even though you have these dolphins that are living 40 years, 50 years, inside that group, there were differences.
• 4:02
  Do you want to talk a little bit about that?
• 4:04
  Yeah, absolutely.
• 4:05
  So as we saw these changes, some were aging.
• 4:08
  healthier than others.
• 4:09
  And we actually identified a measurement of aging rate in dolphins.
• 4:12
  And we found - What was that?
• 4:14
  What did you use?
• 4:15
  It was hemoglobin.
• 4:16
  Okay.
• 4:17
  Was one of the names.
• 4:18
  So declining hemoglobin over time was predicted and increased red blood cell distribution width.
• 4:24
  So RDW.
• 4:25
  Right.
• 4:25
  So - Let's define that for the audience.
• 4:27
  Cause not everybody knows what RDW is.
• 4:30
  No, go ahead.
• 4:32
  Okay.
• 4:32
  So red blood cell distribution width, it's a measurement of basically how
• 4:37
  different size, the variability in red blood cell size.
• 4:41
  And it can tell you a couple things, doctor.
• 4:43
  Okay.
• 4:43
  Right.
• 4:44
  Yeah, no, it's just so the audience understands.
• 4:46
  So your bone marrow is making red blood cells and they can come out in different sizes, but the healthier you are, the more uniform in size they are.
• 4:55
  Right.
• 4:55
  And so that's the healthier membranes, the healthier the cells are, et cetera.
• 4:59
  So this RDW is really a measure of how much
• 5:03
  variability is there in the size of the red blood cells, right?
• 5:06
  And so a lower number is better in that situation.
• 5:09
  And that's something we measure in all of our clients here.
• 5:11
  Also at Gladden Longevity.
• 5:12
  It was always in our labs, but we didn't know exactly what to do with it.
• 5:15
  Now when we heard about it's an aging metric for dolphins, it's like, well, maybe it's an aging metric for mammals.
• 5:21
  And I guess it's been shown to be an aging metric for mammals.
• 5:23
  That's exactly right.
• 5:25
  It's been a fascinating index for things like chronic diseases.
• 5:29
  aging rates.
• 5:31
  And so, and it's, you know, it's as we look and we know more now it's making sense because red blood cells become representative, the longevity and the health of our red blood
• 5:39
  cells.
• 5:39
  Now we're realizing directly reflects the health of all of ourselves and therefore us.
• 5:44
  Right.
• 5:44
  Exactly.
• 5:45
  And easy to test.
• 5:46
  Yeah, that's that's really interesting.
• 5:48
  So in the in the dolphins, you would start to notice that as they age, there was the RDW went up.
• 5:57
  OK.
• 5:58
  And then, but there must have been some disparity there between these populations because there was some group that liked a fish that was high in C15.
• 6:06
  That's right.
• 6:07
  Exactly.
• 6:07
  So as we started seeing differences, even among individuals within the same population, some had slow aging rates and some had fast.
• 6:15
  Right.
• 6:16
  This was fascinating because like you're saying, it's the same population of dolphins did this advanced technology called metabolomics to look at.
• 6:23
  bunch of small molecules and they're all fish diet and they're blood.
• 6:26
  And like you just shared, yeah, C15 was the leading predictor of slow aging.
• 6:31
  And when you're measuring C15, because we actually C15, we went back and started to look at our at some of our testing that we do and actually C15 shows up in one of our Genova
• 6:41
  NeutraVal tests.
• 6:43
  But I'm curious with the metabolomics, how is it?
• 6:46
  What's the best way to measure C15?
• 6:48
  Is it in the red blood cell membrane?
• 6:50
  Is it is it in the plasma or?
• 6:52
  What's your take on all that and what were you doing with the metabolomics?
• 6:56
  Yeah.
• 6:56
  So we, so with the C15 measurement, probably the red blood cell membrane.
• 7:01
  So what you're getting from Genova is probably the best measurement, especially with regard to longevity and our long -term health.
• 7:11
  So you're already doing the right measurement.
• 7:15
  And then is there, you know, with most things in biology,
• 7:20
  It's what I consider an economy of balance like you can get too little of something you can also get too much of something So do we know what the sweet spot is or we have a sense
• 7:29
  for what the sweet spot is?
• 7:30
  You know C15 we do it's a really interesting Phenomenon with c15 that it does there does seem to be an ideal level that we're now recognizing as there's almost three levels that
• 7:41
  were recognized if we have a paper in review currently at metabolites
• 7:46
  talk a little bit about what's in that paper, but what we're identifying, and this is also leaning upon lots of studies on humans with C15 levels, that there's low C15, and that's
• 7:57
  where we're heading toward the potential definition of a nutritional deficiency syndrome.
• 8:02
  And that's less than 0 .2 % of all fatty acids in red blood cells.
• 8:06
  And then there's not deficient, so healthy.
• 8:11
  And that's...
• 8:12
  really the sweet spot as far as optimal, the broadest health benefits come in this around between 0 .2 and 0 .4 % equal to 20 micromolars, or I think what your readings you make it
• 8:24
  as five micrograms per mil.
• 8:27
  And it appears that we need that amount to be able to best have anti -inflammatory activities, metabolic balancing, all these activation of P -PARS and AMPK and inhibiting
• 8:39
  mTOR.
• 8:40
  wonderfully, it's all around that same level.
• 8:42
  So it's telling us this is what we need.
• 8:44
  There may actually be optimal levels that we're just learning now that goes beyond, above and beyond us being healthy.
• 8:50
  The normal levels, yeah.
• 8:52
  Yeah, and we're, that's based upon a study that was done in Sardinia looking at the blue zone, folks, high longevity and low longevity, folks.
• 9:01
  showing that the high longevity people had C15 values as high as 0 .4 to 0 .6.
• 9:06
  wow.
• 9:07
  Okay.
• 9:07
  So, triple, double to triple what we're used to having in most of the world.
• 9:12
  Well, that's really fascinating because it kind of makes you wonder if there's, and I've wondered about this, if there's kind of a linear effect, both in terms of longevity, but
• 9:23
  also with regards to measuring RDW.
• 9:26
  Is it kind of a linear thing?
• 9:28
  Like, do the people that have...
• 9:29
  levels of 0 .6, let's say, or 0 .5, are there RDWs, are there red blood cell sizes are more tightly clustered in terms of being uniform or how does that work?
• 9:39
  It's a great question.
• 9:40
  We don't know yet.
• 9:41
  So it's going to be a great thing to be able to look at.
• 9:43
  I mean, even probably here at the Gladden Longevity Inst- Institute.
• 9:48
  we're looking at it.
• 9:49
  Yeah.
• 9:49
  But that would be a great thing.
• 9:51
  We do know at these lower levels that, you know, when you get to below 0 .2 % and above,
• 9:56
  that there is this linear relationship between the two.
• 9:59
  So then the more it's like as we get beyond normal to optimal, do we see that tighten up even more?
• 10:04
  Yeah, no, it's pretty interesting.
• 10:08
  You know, one of the metrics that we've started measuring here is whole body phase angle, right?
• 10:15
  So whole body phase angle is a measure of, it's for the audience, it's basically a measure of cellular health.
• 10:22
  And it has to do with resistance and reductance and...
• 10:26
  Basically, the higher the number, typically, there are some things that will falsely elevate it.
• 10:32
  But if you know the individual and they start at one point and you can raise it, and they haven't put on weight -developed cancer or something else that would artificially raise
• 10:40
  it, it could be a sign of increasing cellular health.
• 10:45
  And that's basically the cell's ability, as I think about it, to hold a charge, if you will.
• 10:50
  How robust can it hold a charge?
• 10:52
  And the more integrity you have in the cell membrane, the
• 10:56
  greater the charge it can hold, the more energy in a sense it has to work with.
• 11:01
  And so we're measuring the RDW on all of our clients as well.
• 11:04
  In fact, we just collected data on everybody that's been on Fatty 15, looking at RDW and also whole body phase angles.
• 11:14
  So yeah, and we don't have enough, this term it is, we don't have enough data yet to be able to make any conclusions, but I will tell you that we were...
• 11:23
  Dosing everybody at a particular dose of 100 milligrams a day.
• 11:27
  And that may not be what we need to go for in the longevity space.
• 11:32
  Before we get to dosing though, let me have you delineate a little bit about what you see this doing to the cell membrane and then also the impact that it has on some of the other
• 11:43
  longevity metrics, but maybe start with the cell membrane.
• 11:46
  Absolutely.
• 11:47
  And that's really the heart of C15, right?
• 11:49
  So it is a...
• 11:50
  you know, a promiscuous molecule that does a lot of good things.
• 11:54
  Promiscuous molecule.
• 11:55
  Okay.
• 11:56
  All right.
• 11:57
  It gets around in the receptor.
• 11:58
  Is it a pluripotent molecule or a promiscuous molecule?
• 12:01
  I don't know.
• 12:02
  One of the other.
• 12:02
  Okay.
• 12:02
  Consumer friendly version.
• 12:04
  Very consumer friendly.
• 12:06
  Okay.
• 12:06
  Pleiotropic.
• 12:08
  Exactly.
• 12:08
  And so, but as far as the heart of what C15 does that is truly unique to this Goldilocks that is that it is a stable.
• 12:18
  saturated, you know, as you shared an odd chain staple saturated fat.
• 12:22
  It has no double bonds in its structure, which means there's no weak points in the molecule that could get attacked by oxygen into lipid peroxidation.
• 12:31
  And it's that weakness.
• 12:33
  It's like, that's where we're used to like polyunsaturated fatty acids, our oils, right?
• 12:38
  Because of this, these double bonds.
• 12:40
  C15 is a stable saturated fat that its job is to go into our cell membranes.
• 12:47
  and really shore it up and armor ourselves up and literally protect them against lipid peroxidation.
• 12:53
  Okay.
• 12:54
  So that's an interesting point.
• 12:56
  We also can measure lipid peroxidation, which is interesting.
• 13:01
  And just so the audience understands, there is a reason to have saturated and unsaturated fats.
• 13:07
  And when you think about, well, we need omega -3s, omega -6s, omega -9s, et cetera.
• 13:12
  Those are unsaturated fats.
• 13:14
  And the thing
• 13:16
  to realize is that when you're eating fish and you think you're getting omega -3s, it's really the cold water fish because the saturated fat will be a solid, like butter's a
• 13:26
  solid sitting on your table, whereas the unsaturated fats are an oil.
• 13:30
  So if you're a fish in cold water and all you have is saturated fats, you're gonna freeze up, so to speak, right?
• 13:36
  You're not gonna be able to swim.
• 13:37
  But if you have these unsaturated fats, they'll be more liquidy and you can actually still move around.
• 13:43
  But that being said, we're all at...
• 13:46
  you know, homeostatically at about 97 or 99, whatever it is we are, 98 .6.
• 13:52
  And so at that temperature, you know, we don't really have to worry about whether it's saturated or unsaturated.
• 13:58
  We actually need both.
• 14:00
  So that's interesting.
• 14:02
  So you think it's really shoring up the structural integrity.
• 14:06
  Is it doing anything else besides the structural integrity?
• 14:08
  Because it seems like it might be.
• 14:10
  Yeah, it does a lot beyond that.
• 14:12
  So with regard to...
• 14:14
  receptors.
• 14:15
  You know some key ones are with regard to longevity, activates AMPK and inhibits mTOR.
• 14:22
  Right.
• 14:22
  So with regard to cellular signaling.
• 14:24
  So that's a big deal.
• 14:25
  That's a really big deal.
• 14:26
  So rapamycin is used to inhibit mTOR and then we have other things that will actually activate AMPK like cardiovascular exercise, right, fasting.
• 14:37
  Saunas will actually do it.
• 14:38
  Things like metformin, berberine, resveratrol.
• 14:41
  All those things can activate AMPK.
• 14:43
  So when you activate AMPK, you're actually activating a lot of your longevity genetics, DNA repair, kind of putting your body into more autophagy where you're recycling the old,
• 14:53
  throwing out the bad, recycling into good new stuff.
• 14:56
  So AMPK is like super important for longevity.
• 14:59
  And then mTOR is super important for building bone, building muscle, building skin cells, looking good, feeling strong.
• 15:06
  So you need them both.
• 15:07
  It's just, we have to go teeter tottering back and forth between them, right?
• 15:11
  So it sounds like fatty 15 in higher doses.
• 15:16
  What's the dose curve on that?
• 15:18
  Like if you're taking 100 milligrams versus 200 versus 300 versus 400, is there like a linear amount of AMP activation and mTOR inhibition, or how does that work exactly?
• 15:28
  So there's been limited of how far out they've stretched the dosing, but we do see a dose response within this, what would be equal to like 10 to 30 micromolars or 20 micromolars
• 15:42
  being that sweet spot.
• 15:43
  So when we talk about dosing for every hundred milligrams of C15 we take in.
• 15:49
  you go, it's a good rule of thumb to go, you can go up by 0 .1 % of your total fatuses or go up by 10 micromolars.
• 15:56
  So if our goal is to be 20 and above, then most people are around this point too.
• 16:03
  So that does suggest that whatever it is we're doing in our lives, we're right at that kind of breaking point of deficiency versus, so we just need a little bit more to get
• 16:12
  something off.
• 16:12
  And we do, we do get C9 or C15 rather from other sources, right?
• 16:17
  So we get it from,
• 16:18
  from dairy?
• 16:19
  Yeah, dairy fat is by far our primary source.
• 16:23
  So nonfat milk has no C15, but once you get to that whole fat milk, you can get your hundred milligrams of C15 from dairy fat, at least from milk fat, at least we used to.
• 16:34
  We now are learning that our C15 levels in whole dairy fat even is dependent upon what cows eat.
• 16:41
  wow.
• 16:41
  So we have about half as much C15 for cows, but all corn.
• 16:45
  versus twice as much in cows fed grass, so grass fed dairy.
• 16:49
  Okay, so grass fed dairy has higher C15.
• 16:52
  Interesting.
• 16:53
  Okay, interesting.
• 16:54
  Yeah, and it's interesting because we all got into low fat milk and all that kind of stuff.
• 16:58
  So we kind of were robbing ourselves of some of this things that we didn't even know were healthy.
• 17:02
  So the AMPK mTOR story is interesting, but it's actually doing more than that.
• 17:06
  It does other things with regards to the.
• 17:09
  Hallmarks of Aging.
• 17:10
  So tell us a little bit about that.
• 17:11
  So we're now up to six out of the 12 of Hallmarks of Aging.
• 17:15
  Well, it's actually we're up to 16 hallmarks.
• 17:17
  God.
• 17:18
  I'm still keeping up with all of this.
• 17:20
  I was at 12.
• 17:21
  So and this is things, you know, work that we've done, but now the world is working on C15.
• 17:27
  So it's been fun watching that the story continue to grow.
• 17:31
  So we know that it helps it with.
• 17:34
  with regard to the mTOR inhibition with cellular senescence, it decreases over 18 pro -inflammatory cytokines, again, in that sweet spot, including inflammaging, with regard to
• 17:44
  mitochondrial dysfunction.
• 17:46
  C15 actually has a rescue function to help repair mitochondria.
• 17:50
  They're often broken in this one spot.
• 17:53
  Mitochondria use basically this stepwise way to make energy.
• 17:57
  It's usually that first step that's broken.
• 17:59
  C15 can skip that, skips that.
• 18:01
  First up so it allows mitochondria to really yeah, so the respiratory transport chain one it actually can skip that to two Yeah, okay.
• 18:10
  That's interesting.
• 18:11
  I was not aware of that because you need NAD for one to work as I believe so yeah, that's interesting So when you're increasing C15 in the cell you're getting more cellular
• 18:22
  integrity you're balancing them to an AMPK and you're also improving
• 18:26
  Energy production?
• 18:28
  Exactly, we're repairing those mitochondria, getting the energy production up.
• 18:32
  With regard to, and we talked about cellular signaling, because off cellular signaling is a part of the homework of aging.
• 18:39
  We've talked about the AMPK and mTORS, and it also inhibits JAK -STAT and HDAC6.
• 18:47
  So talk to us about JAK -STAT.
• 18:48
  Yeah, it's fascinating receptor, I guess if we're nerdy enough.
• 18:51
  here.
• 18:52
  What's that?
• 18:53
  If we're nerdy enough, it's fascinating.
• 18:55
  Yeah, it is interesting.
• 18:56
  I came across it in a context of another peptide that somebody was developing, I don't know, a decade ago.
• 19:02
  But it's not something we're using consciously all the time.
• 19:06
  So tell us a little bit more about that.
• 19:08
  Yeah, absolutely.
• 19:08
  So this pathway is responsible for inflammation.
• 19:12
  It's also responsible for cancer cell proliferation.
• 19:15
  OK.
• 19:16
  And so it's become a really exciting target in the pharmaceutical field.
• 19:21
  to help with autoimmune diseases to calm down.
• 19:24
  So you hear a lot of the injectable options for autoimmune diseases.
• 19:27
  A lot of those are JAK -STAT inhibitors.
• 19:30
  Things like rheumatoid arthritis and other autoimmune diseases are everywhere now.
• 19:35
  I have it myself.
• 19:38
  And then with regard to cancer proliferation, helping to calm that down on the JAK -STAT.
• 19:44
  So the fact that we saw C15 was ineffective, actually others showed that it was a JAK -STAT inhibitor.
• 19:51
  made a lot of sense, especially when we see our customers reporting back in myself with an autoimmune disease, really seeing that being able to calm down.
• 20:00
  It's like, we understand why.
• 20:01
  Yeah, that's amazing.
• 20:02
  That's really, really interesting, both in the cancer cells and also in the autoimmunity.
• 20:07
  So is that also a linear dose dependent kind of effect?
• 20:12
  That one is.
• 20:12
  Yeah, both of those are linear dose response.
• 20:14
  So I imagine you could be taking C15, fatty 15 for general health.
• 20:20
  and then every hundred milligrams you're gonna bump yourself up 0 .1%.
• 20:25
  But if you're dealing with something like autoimmunity or cancer or another issue that's related to inflammation, let's say, going higher seems to have a linear effect in
• 20:37
  decreasing the inflammation based on the JAK -STAT inhibition.
• 20:41
  Is that the story?
• 20:42
  That's right, yeah.
• 20:42
  And we're seeing that same linear effect on, there was a study by True It All and they showed,
• 20:47
  that the higher the C15 levels, again, getting to this 0 .4 to 0 .6 % level, the lower the risk of developing cardiovascular disease over time.
• 20:56
  And so it may be, and that is linear.
• 20:58
  Well, we know that cardiovascular disease is inflammatory driven, right?
• 21:02
  Events, at least, are inflammatory driven.
• 21:04
  So there's more of a story than just inflammation, but of course, that's really kind of a driving element of it.
• 21:10
  Right, interesting.
• 21:13
  That's intriguing.
• 21:14
  So have you done any studies?
• 21:16
  Or maybe in the dolphins, the ones that had higher C15 levels, did they have better cardiovascular systems?
• 21:23
  Was any of that looked at?
• 21:24
  Better brains, better cardiovascular systems, whatever?
• 21:27
  Yeah, they had a lower cholesterol.
• 21:29
  Lower cholesterol.
• 21:30
  Total cholesterol.
• 21:31
  They do have a little bit wacky HDL versus LDL.
• 21:34
  Ratios.
• 21:35
  That's different than ours.
• 21:37
  But if you looked at total cholesterol, they had lower levels of that, lower inflammation.
• 21:43
  Dolphins are pretty good at being protected against
• 21:46
  cardiovascular disease.
• 21:48
  What we tend to see with them are for us, which are precursors for cardiovascular disease, which is this metabolic syndrome.
• 21:54
  We identified this dysmetabolic iron overload syndrome, or DIOS in the dolphins, which is now emerging in people as well.
• 22:02
  And it's been a really intriguing part of the story.
• 22:06
  So yeah, tell us more about that.
• 22:07
  Yeah.
• 22:08
  So, you know, dolphins, a big advantage of the Navy dolphins is it's a very clean population.
• 22:13
  So in people,
• 22:14
  you're going to have a bunch of different risk factors, a bunch of different phenotypes being driven by our environment, by our different genes, right?
• 22:20
  The dolphins was a pretty clean population to work with.
• 22:24
  So they really have a...
• 22:25
  By clean, you mean it's a fairly uniform population in a fairly uniform environment.
• 22:29
  That's right.
• 22:30
  Exactly.
• 22:31
  And so they really developed one phenotype of this metabolic syndrome, which was a combination of high cholesterol,
• 22:40
  elevated liver enzymes, ALT and AST and GGT, and then this mysterious hyperferritinemia.
• 22:47
  High ferritin, so it's like indicative of there's iron overload.
• 22:51
  Yes, and also ferritin is an acute phase reactant.
• 22:55
  That's right.
• 22:55
  So it'll go up with inflammation.
• 22:57
  Not to get too nerdy here, but we're talking about some different enzymes that when the liver is being irritated, let's say, or inflamed, either from excess fat that's being
• 23:07
  deposited in the liver from
• 23:09
  insulin resistance or metabolic syndrome as it's referred to or related to hepatitis or either chemical hepatitis or viral hepatitis or alcohol induced hepatitis.
• 23:20
  All those things will release these enzymes into the blood that can be measured.
• 23:23
  Those are signs of liver irritation slash damage, right?
• 23:27
  Yeah, that's right.
• 23:28
  And so we started seeing these elevations and so we worked down that exact list of rule outs.
• 23:33
  So all of a sudden we started seeing dolphins pop up with these elevated enzymes.
• 23:37
  They would come and go.
• 23:38
  They seemed fine.
• 23:39
  They might have been off, you know, eat a little bit less fish for a couple of days, but nothing major.
• 23:44
  And when we started looking into it, we said, gosh, is it a viral, a Titus, is it a Vecta?
• 23:50
  So we kind of worked down that rule out list and we got down to this looks metabolic because it was associated with this insulin resistance, high cholesterol.
• 23:59
  And then that's where then the iron picture came in.
• 24:01
  We're like, well, gosh, why are they have...
• 24:03
  You know, and when we look at.
• 24:04
  So you think it's an acute phase reactant for them, or do you think it's also something else metabolically going on with iron?
• 24:10
  We think it's going on with iron.
• 24:12
  So we have the good fortune of the Navy had saved all the tissues from mass dolphins.
• 24:17
  So we were able to actually look at dolphin liver tissues and lo and behold, iron deposited in their liver.
• 24:25
  Wow.
• 24:25
  An unusual amount.
• 24:26
  So we're able to basically find the single phenotype.
• 24:30
  And all of this then was associated with.
• 24:32
  low C15.
• 24:34
  So long story short, what we've gotten to with the dolphins, it appears to be that there's a set of people that this is happening to as well, where we have low C15 that makes our
• 24:45
  cell membranes fragile, including red blood cells.
• 24:49
  The red blood cells get weak.
• 24:51
  They get engulfed by the liver because the liver says, I'll take out any of those.
• 24:56
  So it's excess processing of the red blood cells, which is liberating the iron from the hemoglobin.
• 25:00
  So now you're getting more iron.
• 25:02
  That's it.
• 25:02
  Okay.
• 25:03
  So now the iron sitting in the liver gets that iron overload and then it really seems that everything else happens from there.
• 25:10
  So you have a combination of lipid peroxidation in the liver because of the membranes and then you have paired with iron and.
• 25:18
  at the time, this was 2012 when we published this paper and we said there's this iron overload, liver iron overload associated with metabolic syndrome.
• 25:26
  We didn't know it at the time, but in 2012 is the same year that Columbia University published a paper in which they discovered a whole new way cells were dying and it was
• 25:36
  called theroptosis.
• 25:37
  Yes, I've seen theroptosis.
• 25:39
  So that it was like, wait, this is what's happening in the dolphins.
• 25:42
  It's so much iron that it's toxic.
• 25:44
  And the interesting thing is that these people,
• 25:46
  in humans anyway, I think they can become anemic.
• 25:49
  And so the doctor wants to give them iron, right?
• 25:52
  Which is like, well, you need iron, right?
• 25:54
  But actually that's exactly the wrong thing for them, which is really fascinating.
• 25:59
  So, yeah, so looking at the high ferritin, so we do measure ferritin on everybody.
• 26:03
  And it's interesting, there are genes, as you know, in humans, hemochromatosis genes that can cause people to maintain or retain...
• 26:12
  or accumulate more iron, which can be damaging to tissues.
• 26:15
  So we do some things for those people because we test those genetics for everybody, like having them give away blood, basically, right?
• 26:23
  Donate blood or we just take it out and throw it in the trash.
• 26:26
  But that can be a good way to kind of get some of the iron out.
• 26:29
  But I wonder if in a hemochromatosis patient, if really boosting up their fatty 15 levels into this point,
• 26:38
  you know, 4 .5, .6 range would have a salutory effect on what's going on for them.
• 26:45
  Yeah, exactly.
• 26:46
  So when we gave Dolphins a higher C15 diet, we saw all the components of this whole syndrome be attenuated, so decreased in severity.
• 27:00
  So we actually, and mice, interestingly, mice don't behave this way.
• 27:04
  We behave this way.
• 27:05
  We respond this way, but mice...
• 27:07
  don't, they're just different metabolically.
• 27:10
  So, but there, we did, we were able, there are models that then repeat the same phenotype where the red blood cells get weak, you know, the results of over iron deposition.
• 27:20
  And then from there you get insulin resistance and type D, you know, all the downstream things from that.
• 27:26
  And we supplemented that model with C15 and it, every single component of it, there was no, the,
• 27:36
  anemia and the red blood cells were was alleviated it the iron deposition stopped in the liver the amount of fibrosis in the liver decreases a model of non -alcoholic
• 27:48
  steatohepatitis.
• 27:49
  Right.
• 27:49
  So do you think that it all leads back to increasing the integrity of the red blood cell?
• 27:54
  Right.
• 27:55
  So basically you're taking away the initiating factor of a weak red blood cell that's being gobbled by the liver depositing the iron and causing the issue.
• 28:03
  Right.
• 28:03
  You're so smart.
• 28:04
  Well, you're the one that figured it out.
• 28:07
  I'm just trying to follow along.
• 28:10
  Yeah.
• 28:10
  So that's exactly it.
• 28:12
  And back in this paper that we have in review in metabolites, we're proposing that this whole phenomenon is a C15 nutritional deficiency syndrome.
• 28:22
  Fascinating.
• 28:22
  That's really fascinating.
• 28:24
  Well, that's, I mean, that's like super exciting for anybody that's dealing with, and I think there's this trial that you've done on non -alcoholic fatty liver disease now too,
• 28:32
  which is not...
• 28:33
  not the iron accumulation, it's another metabolic syndrome that happens for humans.
• 28:37
  It sounds like maybe that's not true in dolphins, but it's an epidemic, of course, here with overeating, you know, high carb diets, saturated fats, all the different things that
• 28:48
  go into it, carrying excess obesity, not enough exercise, many, many things factor into it.
• 28:54
  But at the end of the day, these people are insulin resistant.
• 28:57
  They end up depositing a lot of fat into their hepatocytes.
• 29:01
  which is called steatosis.
• 29:02
  And that's kind of the beginning of really a whole progression into a fibrotic liver and a serotic liver.
• 29:08
  And the next thing you know, you have liver failure, then you're on transplant list.
• 29:11
  So we've actually taken some people with, that were on transplant lists and actually reversed their whole liver situation using AMPK activation.
• 29:20
  That was the only tool that we could think of that might be super helpful.
• 29:23
  And it turned out that it was actually super useful.
• 29:26
  And I'm wondering if the fatty 15 is,
• 29:29
  is working primarily, it's magic in these non -alcoholic fatty liver disease people primarily through AMPK or are there other mechanisms that you've identified?
• 29:38
  It could be, for sure AMPK I think is playing a role.
• 29:41
  It's also a PPAR alpha delta activator.
• 29:45
  Okay.
• 29:45
  Which has been a target for candidate drugs for NAPLD.
• 29:48
  Well that's also amazing because PPAR gamma is associated with peroxisone function.
• 29:55
  Yeah.
• 29:55
  Right.
• 29:56
  So this is now we're getting super techie on this podcast.
• 29:59
  I apologize for this.
• 30:00
  But when you look at, when you look at neurodegenerative diseases, things like ALS and things like that, one of the things that we measure here is proxone proxosomal function,
• 30:12
  right?
• 30:12
  So a prodrome plasmalogen scan.
• 30:14
  And it turns out that when your proxosomes can't make these special fats called plasmalogens, you're at high risk for neurodegenerative diseases, right?
• 30:24
  And so I'll just leave it at that.
• 30:25
  There's more to it than that, but I'll leave it at that.
• 30:27
  So if there was a way to actually improve proxosomal function, you know, things like jumping in a cold plunge is one way to up regulate PPAR, right?
• 30:37
  But take, if you can take fatty 15, while you're jumping in your cold plunge, you get a one, two punch.
• 30:44
  That might be a really interesting thing to use in anybody that's, that's suffering or has a predisposition towards a neurodegenerative disease, whether it's Parkinson's.
• 30:54
  ALS, Alzheimer's, any of those would be really, really interesting.
• 30:58
  Yeah.
• 30:58
  And because dolphins can develop Alzheimer's, we have a whole other study that will be coming out published later this year.
• 31:07
  But we did like that, we did take, because we know that there's susceptible to C15 deficiencies, that we did take C15 and we ran it against a panel of targets for
• 31:17
  Alzheimer's disease and had some very exciting findings.
• 31:21
  So tell me about that.
• 31:22
  What did you find?
• 31:24
  It'll be coming out soon.
• 31:25
  Yeah, I know.
• 31:25
  But you can whisper it in my ear and I can repeat it.
• 31:29
  So one of them is interesting.
• 31:34
  I will share it.
• 31:34
  Actually, I'll share one because it's just too exciting to withhold.
• 31:37
  But it is an FAAH inhibitor.
• 31:41
  So these are enzymes in our blood that eat up cannabinoids.
• 31:46
  So let me step back for a second.
• 31:48
  that there are receptors in our brain throughout our body that are called cannabinoid one and two.
• 31:54
  They're named that because that's, the world discovered them because it's the targets that cannabis has.
• 32:00
  They aren't there for cannabis.
• 32:02
  But we have our own endocannabinoid system, right?
• 32:05
  Where we're making things that stimulate those receptors.
• 32:07
  Exactly, so those receptors are there for those natural molecules that we have.
• 32:11
  And so there's been a lot of research to try to figure out how can we get endocannabinoids.
• 32:16
  how can we leverage endocannabinoids to help support brain health?
• 32:20
  Because as we get older, those receptors tend to start slowing down and not doing their work.
• 32:27
  But the problem is that when we try to give endocannabinoids, we have these enzymes throughout our blood called FAAHs that just eat them up right away.
• 32:36
  They have no chance to even make it to our brain.
• 32:39
  And so it ends up that not only, I think we might've talked about this in the prior podcast,
• 32:45
  does C15 make, do our bodies use C15 to actually make an endocannabinoid?
• 32:51
  It also now, thanks to the study, shows that it also inhibits the enzyme that eats up the other endocannabinoids.
• 32:59
  So you've got a double, one-two you punch there too.
• 33:01
  Yeah.
• 33:01
  Really fascinating.
• 33:02
  That is fascinating.
• 33:03
  So now you're increasing the endocannabinoid system.
• 33:05
  So when you increase the endocannabinoid system's function in somebody that's struggling with neurodegeneration, let's say it.
• 33:13
  What's the net effect of that for them?
• 33:14
  Do they start to show cognitive improvement or they have fewer, you know, plaques or what happens for them?
• 33:21
  Less beta amyloid or less tau?
• 33:23
  It's mainly, I think, well, a lot of research is being done on that front.
• 33:27
  And I don't know with regard to like in the midst of disease, does it reverse or stop it?
• 33:32
  I think a lot of the work has been more done on on the early side of things and or prevention.
• 33:38
  And I think probably a big role of it is inflammation.
• 33:40
  neuroinflammation.
• 33:42
  So endocannabinoid system, even though we talk about more of a fluid.
• 33:45
  Anti -inflammatory system.
• 33:45
  Right.
• 33:46
  Anti -inflammatory.
• 33:46
  And right at the, you know, right in that core organ that we care about with the brain.
• 33:50
  So I wouldn't be surprised if a lot of that benefit is just coming from helping to calm the inflammation down in the brain.
• 33:58
  You know, one of the things that I've discovered is, and I think most brain fog comes from neuroinflammation.
• 34:05
  You know, it can happen for a variety of reasons.
• 34:08
  You can get hit on the head.
• 34:09
  You can...
• 34:10
  eat the wrong food, you can, you know, your sugar can spike, you can eat the wrong fat, you can eat whatever it is.
• 34:15
  But ultimately, it kind of comes down to neuroinflammation.
• 34:20
  And interestingly enough, we do plasmapheresis for people here, where we're actually removing inflammatory cytokines, right.
• 34:27
  And we could do that for several days and then put in young plasma and then put in rejuvenation factors and do all kinds of magical things.
• 34:33
  But it's interesting that, you know, if you can.
• 34:37
  do plasmapheresis for somebody that's complaining of brain fog, they'll wake up the next morning and say, I feel like crystal clear.
• 34:42
  It's like, I haven't felt this clear in years.
• 34:44
  And it's like, okay, I get it.
• 34:47
  It's really neuroinflammation.
• 34:48
  So if we have the ability to kind of go in and modify somebody's diet into a low inflammatory diet and get them doing the right exercise and cold plunge and other things
• 34:56
  that are activating all the right things.
• 34:57
  But if we could use fatty 15 to help modulate the entire system.
• 35:02
  not just be an anti -inflammatory, but to modulate and down -regulate the system, that would be pretty magical.
• 35:08
  Yeah.
• 35:09
  I mean, it's, and it, you know, it's, it does that word magical comes up a lot, right?
• 35:13
  And, and that it does a lot.
• 35:16
  We've talked about a lot on this talk and it's really, I think it's an essential fatty acid.
• 35:21
  And so it's just, nature has found a way for us to use this molecule, truly it being essential to help keep things balanced.
• 35:31
  Right.
• 35:31
  for as long as possible, which then helps with our longevity.
• 35:35
  With that neuroinflammation point, fascinating studies have come out showing where depression is they're calling it a neuroinflammatory disease.
• 35:43
  It is, right.
• 35:43
  It's an inflammatory disorder.
• 35:45
  That's right.
• 35:45
  So it's really incredible being able to look and see.
• 35:47
  So we do have a lot of customers who are improvement in mood.
• 35:53
  And again, I think you're right.
• 35:54
  I think that a lot of this for these people, it has to do with calming down that neuroinflammation.
• 35:59
  Yeah.
• 36:00
  No, that's fascinating.
• 36:02
  It can even, you know, when you have neuroinflammation, it can also show up as personality changes and right, increased aggression or anger or decreased resilience sort of to the
• 36:14
  environment of what's happening around you.
• 36:15
  Right.
• 36:16
  So it's not just cognitive.
• 36:18
  It's also sort of on the psychological side, which is kind of interesting.
• 36:22
  Yeah, absolutely.
• 36:23
  And so we work with a group called Gray Team and they're in Florida and they provide support for.
• 36:29
  post -deployment or post -warfare veterans who are at risk of suicide.
• 36:35
  And that's a massive problem.
• 36:37
  I would think all those guys should be not eating the dolphins, but taking a lot of fatty 15.
• 36:46
  It seems like it would help their brains.
• 36:48
  Does this help people recover from things like traumatic brain injury or brain surgery or concussion or any of that kind of, you probably, maybe you don't have that information,
• 36:56
  but it seems like it could theoretically.
• 36:58
  It would be a great study to do.
• 37:00
  I mean, certainly with regard to mechanisms that we know to help with brain injuries, with calming inflammation, being able to activate the right receptors, it is aligned.
• 37:11
  P par alpha delta has been a target for post -traumatic brain injury.
• 37:16
  So it would be consistent, but studies need to be done.
• 37:20
  But theoretical.
• 37:21
  What about autism?
• 37:23
  Any theoretical concepts there that, you know, those brains are kind of...
• 37:28
  working in a different mode.
• 37:29
  They've got gut biome issues, they've got vitamin D receptor issues, they've got lots of things going on that have been identified, but I just wonder if this could play a role
• 37:36
  there.
• 37:37
  It's possible.
• 37:38
  It's possible.
• 37:38
  No data on it yet.
• 37:39
  Yeah, but no data on autism yet.
• 37:42
  You know, a lot of factors have been looked at, but nothing's been found.
• 37:47
  So, you know, a big thing with us is timing of things that have been happening on the negative side of our health since, you know,
• 37:55
  as soon as you start looking at the 1980s, because that's really when C15 started dramatically coming out of our diet in the late 1970s.
• 38:03
  Congress came out with dietary recommendations telling us to stop eating saturated fats.
• 38:08
  So we've really been focusing on what trends, which can include autism, but what trends have been happening since that time, which coincided with the dolphins ended up getting
• 38:20
  less fatty fish in the 1990s, which is how they started developing.
• 38:25
  C -15 deficiencies by accident.
• 38:28
  Yeah.
• 38:28
  You know what's interesting when I think about it, if you're improving the integrity of red blood cells, I wonder if you're improving cardiovascular capacity, right?
• 38:39
  Which is another thing that we measure here is cardiopulmonary exercise tests on everyone.
• 38:42
  So we can look at VO2 max and anaerobic threshold and things like that and get a real feel for the cardiovascular system's physiologic function, right?
• 38:51
  But if you have, if...
• 38:54
  With these better, more integrity red blood cells, is there an increased oxygen carrying capacity on some level?
• 39:01
  There's, yeah, so there is a study that supports that.
• 39:05
  And that is, it was a study that was done to look at people with chronic obstructive pulmonary disease.
• 39:11
  So COPD.
• 39:13
  Right.
• 39:14
  These are typically people that either have a genetic predisposition.
• 39:17
  alpha -1 -nanotrypsin, I think, or they're smokers or they've been exposed to some toxin or whatever and it damages the lungs and the lungs don't, they can't move air efficiently
• 39:26
  up and down, particularly can't get it out.
• 39:28
  That's right, that's right.
• 39:29
  So they, and so they looked, they were looking at saturated fats in their diet and seeing if it had any change in their pulmonary, if it had any association, pulmonary function.
• 39:40
  And so what they showed was amazingly of all the different fatty acids, they actually looked at all fatty acids, not just saturated.
• 39:46
  of all the fatty acids that they measured that the higher amount of dietary C15 they ate, it was the only one that came out as significant.
• 39:54
  Had a linear association with improved.
• 39:59
  COPD symptoms.
• 40:00
  Yeah.
• 40:01
  that's fascinating.
• 40:02
  That's this is really fascinating.
• 40:04
  I know.
• 40:05
  I hesitate even saying all of these because it's just like, it's just too good to be true.
• 40:08
  I think again, it's just like essential.
• 40:10
  Yeah, it is interesting when you get when you get.
• 40:12
  when you come across something, and there are many things like this, quite honestly, right?
• 40:16
  But when you come across something that kind of works at a fundamental level in terms of cellular health, it just spawns itself across many, many different populations and many
• 40:27
  different activities in the body, which is either, you know, it can be either a negative, right?
• 40:31
  Like something that's bad for you or a positive like this, which is like amazing.
• 40:35
  So.
• 40:36
  Yeah, our team often says it fixes you where you're broken.
• 40:40
  At a cellular level.
• 40:42
  Yeah, that's what you have your priest for.
• 40:47
  I love it.
• 40:48
  So, okay, fun.
• 40:50
  Good.
• 40:50
  Well, it sounds like you guys are doing amazing work.
• 40:53
  So you must be incredibly excited about projects that you've got underway.
• 40:56
  What's underway for you from standpoint of research projects?
• 40:59
  Yeah, absolutely.
• 41:00
  So we have a couple of really exciting studies.
• 41:03
  in the works.
• 41:04
  One is focusing on anemia.
• 41:07
  So as we get older, as we've talked about the importance of red blood cells, we get older, higher risk of anemia.
• 41:12
  So it's basically the extreme phase of high RDW red blood cells are getting fragile at some point, you develop anemia.
• 41:19
  So use of C15, we've seen that work for dolphins and in relevant models.
• 41:24
  So we'd really like to do a formal study to see how that works with people.
• 41:29
  There's no treatment really for anemia long -term.
• 41:33
  if it's iron deficiency, but now we've, yeah, we've kind of shown that that may not be the actual, and then the other is this, the work with Alzheimer's, coming up.
• 41:43
  So really kind of diving into mechanisms of C -15 that are supportive of our cognitive and brain health.
• 41:49
  Yeah.
• 41:50
  That's pretty interesting.
• 41:52
  We do, we do brain testing on everybody here too, both computerized and also EEG testing.
• 41:59
  And we can look at brain activity.
• 42:01
  We actually look at it a couple of different ways, but we can look at brain activity and we can actually upregulate brain activity using transcranial magnetic stimulation, which
• 42:11
  is not the typical, you know, hammered into one section of the brain for depression.
• 42:15
  It's more of a lower level, but it actually is more also diffuse across the brain.
• 42:20
  It moves across four different areas of the brain and you can actually upregulate neuron activity and we can see the EEGs start to show.
• 42:27
  improved activity where you can like wake up the frontal lobes again and things like that.
• 42:32
  I'm really curious if adding this to that would be helpful.
• 42:36
  We're adding things that that improve brain derived neurotrophic factor because we want to get the neurons what they need to be able to, you know, grow more dendrites and and do
• 42:45
  things like that.
• 42:46
  So we're using things like Lion's mane and an inhaled peptide called C -Lanc, which is quite helpful.
• 42:54
  But I wonder if this would also have a really nice role there.
• 42:57
  Could be interesting.
• 42:59
  We could put it in our protocol.
• 43:00
  I'm ready to be a patient at your longevity institute.
• 43:03
  Come on in.
• 43:05
  Sure.
• 43:06
  That's great.
• 43:06
  No, it's good.
• 43:07
  Yeah, we try to leave no stone unturned because we're completely serious about making 100 to new 30.
• 43:13
  Yeah, and you've got to catch it early, so much earlier than what the traditional tests and medicine does.
• 43:21
  We're too late at that point.
• 43:22
  So being able to catch these things early and understand how we can impact them at the early stage is critical.
• 43:27
  You know, one of the other, I'll just bring this up and this will be a hypothetical question because you probably don't have the answer.
• 43:33
  But, you know, one of the other things that happens is people age as their immune system really starts to lose its potency, right?
• 43:39
  It becomes what we call senescent.
• 43:41
  It loses its ability to adapt to new challenges, if you will.
• 43:44
  I'm just curious if C15 has any impact on...
• 43:50
  the status slash function of the immune system, the youthfulness of the immune system.
• 43:54
  If you, you probably don't have any data on that, but I'm just wondering if in the dolphins, if you saw that their immune system was working better, their T lymphocytes,
• 44:02
  natural killer cells, any of that kind of stuff.
• 44:04
  Yeah.
• 44:05
  So we did see when we did this study to look for markers of aging rates in the dolphins, we saw declining hemoglobin, increasing RDW.
• 44:13
  We also saw decreasing lymphocytes, just like in humans.
• 44:17
  So more work needs to be done to see, we know for sure that we affected, C15 affected, helped to reverse that aging rate trend in hemoglobin and RDW.
• 44:27
  So next up, we'll be looking at this immune senescence to see if we can help on that side.
• 44:32
  Most of the work today, in fact all the work today has been focused on how do we calm an overactive immune system.
• 44:38
  But just as important is let's make sure that we've got those functioning parts up and working too.
• 44:43
  Yeah, exactly.
• 44:44
  And that's part of the reason that the immune system becomes senescent is it's overworked over here trying to take care of this old viral infection, old bacterial thing that's
• 44:52
  going on, right?
• 44:53
  And autoimmune disease, it burns itself out.
• 44:56
  So fascinating, really fascinating.
• 44:58
  Well, it was a pleasure chatting to you the first time.
• 45:01
  I think it may be even more of a pleasure chatting to you this time.
• 45:04
  We're chatting here in person but really wonderful conversation.
• 45:06
  Thank you for that.
• 45:07
  It's been wonderful.
• 45:08
  Thanks for having me.
• 45:09
  Yeah, thank you.
• 45:10
  So how do people learn more about what you're doing, your websites and all that stuff?
• 45:16
  I know you're, you know, fatty 15, you can go out and purchase it on the on the Internet, I believe.
• 45:21
  But why don't you just let people know how to do that?
• 45:23
  Sure.
• 45:24
  So they can go to fatty15 .com to learn more about the supplement and be able to purchase it there.
• 45:31
  And then all the science, great science that we're talking about is at discoverc15 .org.
• 45:36
  So we put all the peer reviews.
• 45:38
  So it's on two separate websites.
• 45:40
  Okay, discoverc15 .com and then fatty15.
• 45:44
  Okay, so if you're listening, if you want to get to science, discoverc15 .com.
• 45:49
  And it might help put you to sleep too.
• 45:52
  It's a whole lot of science.
• 45:54
  Okay, I thought maybe there's a sleep benefit to c15, but it's just reading the research.
• 45:58
  I got it.
• 45:59
  Okay, I got it.
• 46:00
  Good.
• 46:00
  Well, Stephanie, thank you so much.
• 46:02
  Appreciate it.
• 46:02
  Thank you, Dr.
• 46:03
  Gladden It's wonderful being here.
• 46:04
  My pleasure.