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Understanding Barrier Repair with Dr. Carl Thornfeldt of Epionce · Skin Anarchy

• 0:00
  SPEAKER_00: Hey guys, welcome back to Skin Anarchy.
• 0:02
  SPEAKER_00: It's a very, very special episode today because we're going to be interviewing a true pioneer in the skin health space.
• 0:07
  SPEAKER_00: He has brought a brand to us that has been paving the way for so long.
• 0:10
  SPEAKER_00: Epions has been around, I think, long before any of the skincare brands that we see right now that are now focusing on barrier health.
• 0:17
  SPEAKER_00: They were doing this way before.
• 0:18
  SPEAKER_00: And, you know, it's just one of those trail-blazing brands that has really paved the way for so many.
• 0:23
  SPEAKER_00: So without further ado, please welcome Dr.
• 0:25
  SPEAKER_00: Carl Thornfeld.
• 0:26
  SPEAKER_00: Welcome, Dr.
• 0:27
  SPEAKER_00: Thornfeld.
• 0:27
  SPEAKER_00: I'm so honored to host you.
• 0:28
  SPEAKER_01: Thank you very much.
• 0:29
  SPEAKER_01: And uh it's a pleasure to be here.
• 0:31
  SPEAKER_01: And thank you for inviting me.
• 0:32
  SPEAKER_00: Yeah, I know it's a pleasure to to host you and to learn from you today.
• 0:35
  SPEAKER_00: I can't wait to dive in.
• 0:36
  SPEAKER_00: You know, I know that your journey has been, you know, long before the brand even started.
• 0:40
  SPEAKER_00: You know, it was really in rooted in innovation, rooted in trying to understand the science of the skin.
• 0:46
  SPEAKER_00: And I'd love for you to walk us down memory lane and tell us where did the science really begin and how did that evolve into the brand.
• 0:53
  SPEAKER_01: I was afflicted, unfortunately, with significant atopic dermatitis when I was a child.
• 0:57
  SPEAKER_01: And even though my dad was chief of pediatrics at Oregon Health Sciences Center and the second board-certified allergist in the state of Oregon, I was still in and out of treatments and really suffered uh significantly from this time.
• 1:12
  SPEAKER_01: So I always had this interest of being able to understand what actually happened to me and why was that occurring.
• 1:19
  SPEAKER_01: So I was called to rural America and after I did my training at my undergraduate at Oregon State and then my medical school and Oregon Health Sciences Center, or I should say I trained in family practice because I felt I could be a better specialist if I truly understood the whole human body.
• 1:34
  SPEAKER_01: But when I got out into practice in the high desert area of eastern Oregon, where I was the only dermatologist, full-time dermatologist for 30,000 square miles, 140,000 people scattered over 10 counties.
• 1:46
  SPEAKER_01: Um what was interesting about that is I really got to see the extremes of skin insults.
• 1:53
  SPEAKER_01: It's an agribusiness type uh area.
• 1:55
  SPEAKER_01: So there was uh ranching, farming, as well as uh lumber and mining and so on, with big variations in temperature uh from 20 below in the wintertime to 115 in the summer, you'd really get to see how many of the skin reactions would occur.
• 2:12
  SPEAKER_01: And by that, what I mean meant was that when I went into training, um, I thought, you know, if I trained at the top programs, I'm gonna really know how to fix people.
• 2:20
  SPEAKER_01: And um, when I got out into practice, I thought the reason people didn't get well, the doctor wasn't quite smart enough.
• 2:27
  SPEAKER_01: Well, when I was in San Diego, UC San Diego, I'd see patients like 15 times for a disease, and then I didn't see them anymore.
• 2:33
  SPEAKER_01: I thought I had cured them.
• 2:34
  SPEAKER_01: Well, I came out to this rural area and realized after I'd see a patient 15 times and I didn't see them, I'd see their families at the one hospital or at one of the high school football games, where we had one mall serving all that area, and all the major roads to go to Boise all went through our town.
• 2:50
  SPEAKER_01: And so I'd see the family members and I would ask, Oh, how's such and such doing now that he's cured?
• 2:54
  SPEAKER_01: Well, you know, doctor, he isn't really cured.
• 2:56
  SPEAKER_01: He's really not doing very well.
• 2:58
  SPEAKER_01: And I'll tell you, after 18 months, I was just like, How come people aren't responding?
• 3:03
  SPEAKER_01: Now, you have to go back to what it was like.
• 3:05
  SPEAKER_01: In those days in the early 80s, most effective agent for inflammatory skin diseases had a 56% cure rate, okay?
• 3:13
  SPEAKER_01: Or clearance rate, I should say.
• 3:14
  SPEAKER_01: But I never had a patient come in and say, Hey, can I get 56% better?
• 3:18
  SPEAKER_01: And I never wanted that.
• 3:19
  SPEAKER_01: I wanted to completely get clear and stay clear and not have recurrence.
• 3:24
  SPEAKER_01: I was actually on top of a mountain.
• 3:26
  SPEAKER_01: I relaxed by punishing my body with physical things, climbing mountains, open water swimming, things like that.
• 3:32
  SPEAKER_01: And it really struck me, going up over 9,000 feet, how the sun felt stronger, the wind was stronger, and so on.
• 3:39
  SPEAKER_01: And it struck me that, you know, what the major purpose of skin is protection.
• 3:44
  SPEAKER_01: Everything we were doing, all the research we were doing in the retinoids and the work I was seeing done on others with hydroxy acids and all the pioneering work we were doing with steroids and other topicals that resulted in some of my 22 US patents anyway.
• 3:59
  SPEAKER_01: I really realized that all of those were really destroying the barrier more.
• 4:03
  SPEAKER_01: And could that be the real issue?
• 4:05
  SPEAKER_01: And there were particularly two diseases that I thought were important.
• 4:09
  SPEAKER_01: So I'll let you hang on that for a minute.
• 4:11
  SPEAKER_00: Yeah, no, I'm very curious because you know, it's interesting what you're saying, because we don't talk about extreme environments to study anything.
• 4:20
  SPEAKER_00: We have to understand the extreme.
• 4:22
  SPEAKER_00: So it's very, very interesting what you're explaining here because the skin is usually discussed in a way of like, okay, you know, we're all living in the same place, but we're not, you know, and we don't have the same conditions, we don't have the same exposures, environmental, whatever that might be.
• 4:34
  SPEAKER_00: So that's very fascinating.
• 4:36
  SPEAKER_00: But what were those two conditions?
• 4:37
  SPEAKER_00: I'm I'm very curious.
• 4:39
  SPEAKER_01: Okay, so the first one was winter itch.
• 4:41
  SPEAKER_01: And what we would see then, that's also known as eczema estivali.
• 4:44
  SPEAKER_01: And about right after Thanksgiving, when we get our first really hard freezes, usually early November, about a month later, people would start getting itching, particularly starting on their lower legs, hands, and feet, and could become quite widespread.
• 4:58
  SPEAKER_01: But what was interesting about that condition, it really didn't matter what we did for treatment, it always burned out about spring vacation time, about mid-March, it would go away.
• 5:07
  SPEAKER_01: And then the other condition was another disease that also afflicted me, which is called polymorphous light eruption.
• 5:13
  SPEAKER_01: And that's that true sun allergy that people talk about.
• 5:16
  SPEAKER_01: It's triggered by ultraviolet A, and that would start about mid-March and would burn out about the 4th of July.
• 5:22
  SPEAKER_01: And I often wondered, oh, how does that do it?
• 5:24
  SPEAKER_01: How is the skin regulating itself and what's actually going on there?
• 5:27
  SPEAKER_01: Well, at this time, no research had really been done on the epidermis itself.
• 5:31
  SPEAKER_01: And so I started looking at that and biopsying and uh found that in fact there was, they moved into winter itch, the skin barrier, the epidermis, and the stratum corneum, where the berrier resides, uh, became thinner and more disrupted.
• 5:44
  SPEAKER_01: Uh, and the amount of sebum being produced, which provides key barrier oils, was also diminished.
• 5:50
  SPEAKER_01: And then in the spring, under the auspices with the uh UV light uh particularly and more activity, you would see the epidermis thicken, the stratum corneum thicken and repair, the sebum production increased, and that accounted for the spontaneous resolution.
• 6:06
  SPEAKER_01: So then the question, because I had the mind of an investigator, how does that happen?
• 6:11
  SPEAKER_01: What are the regulatory pathways that actually regulate the epidermis and the sebum production?
• 6:18
  SPEAKER_01: And so that's started uh a nine-year odyssey for me in understanding the molecular and cellular biology of how the epidermis really regulated itself.
• 6:28
  SPEAKER_01: And so, as you know, the vast majority of inventions are not done by just a single person.
• 6:33
  SPEAKER_01: It's usually a team.
• 6:35
  SPEAKER_01: And there was one other individual, true Renaissance man, Dr.
• 6:38
  SPEAKER_01: Peter Elias, who is working in skin lipids as well.
• 6:42
  SPEAKER_01: I went to him and said, you know, let's go ahead and form a research organization focused right on the epidermis.
• 6:48
  SPEAKER_01: And we were the first ones that did that.
• 6:50
  SPEAKER_01: So we found this group, we put together a whole team, including Dr.
• 6:54
  SPEAKER_01: Man Mao Guing, who I worked with very much, and then Ken Feindgold, and a whole really great group there at UC San Francisco.
• 7:01
  SPEAKER_01: And so working together, we made uh significant discoveries.
• 7:05
  SPEAKER_01: And I think one of the major points was that we then learned how the skin regulated itself and realized the stratum corneum was a regulatory tissue.
• 7:16
  SPEAKER_01: Profound concept.
• 7:17
  SPEAKER_01: So what we found that when the skin was injured for any cause, uh and the stratum corneum was disrupted, that would trigger not just a mild erythema and acute inflammation to increase blood flow to the skin, but it also within 10 minutes or so would trigger synthesis of cholesterol, uh, a number of the ceramides, there's 11 ceramides, and certain free fatty acids, especially linoleic acid.
• 7:41
  SPEAKER_01: And within 45 minutes, these were being synthesized by the epidermal cells.
• 7:45
  SPEAKER_01: And then that was also being deposited out in the uh stratum corneum barrier.
• 7:50
  SPEAKER_01: So that provided the mortar for the stratum corneum.
• 7:54
  SPEAKER_01: And then what we also found is that would increase basal cell proliferation and would also trigger an acceleration, a significant acceleration of the cellular differentiation to form the bricks in the outer layer.
• 8:07
  SPEAKER_01: Now, Peter Lyas is the one who came up with the uh phrase uh bricks and mortar, and that's really exactly what it is.
• 8:13
  SPEAKER_01: Is so you have the key protective barriers, the stratum corneum, and it has these protein bricks that are anucleate cells, but also hold water packets, as well as 97% of it being protein.
• 8:26
  SPEAKER_01: And then you had it embedded in these layers of these key lipids.
• 8:30
  SPEAKER_01: And it turned out it was those three key lipids were critical.
• 8:34
  SPEAKER_01: And so we did more research into that as well.
• 8:37
  SPEAKER_00: Yeah, that's you know, what's fascinating about what you're saying is I had this argument with somebody.
• 8:42
  SPEAKER_00: Like, I mean, you discovered this, but we're, you know, the students that have learned from this.
• 8:47
  SPEAKER_00: I mean, I was arguing with somebody.
• 8:48
  SPEAKER_00: I'm like, you need those three lipids, you know, you need them to be able to actually create the lipid architecture, you know, the actual three to one to one ratio, as many call it, you know, and people don't believe when you say that.
• 9:00
  SPEAKER_00: They don't believe that.
• 9:01
  SPEAKER_00: And I want you to go into that, like if you don't mind, like explaining the importance of this, because most of the time the stardum corneum is looked at as it's just the dead layers, you know, it's just the dead layers of the skin.
• 9:10
  SPEAKER_00: No one discusses exactly what you're talking about, which is that downstream signaling that happens and why the integrity matters so much.
• 9:17
  SPEAKER_00: Because can you dive a little bit more into those pathways, maybe?
• 9:20
  SPEAKER_01: Yeah, I'll gladly do that.
• 9:21
  SPEAKER_01: Thank you for that comment.
• 9:22
  SPEAKER_01: And also it's great to hear that you have have that uh interest as well.
• 9:27
  SPEAKER_01: And of course, with your background in uh medicine, I know that's uh very interesting for you as well.
• 9:32
  SPEAKER_01: So um, what we found is that normal baby skin has a one-to-one to one ratio of cholesterol, ceramide, and free fatty acid.
• 9:40
  SPEAKER_01: The question then was what triggers the repair process?
• 9:44
  SPEAKER_01: And so what we found was that when we looked at various ratios of the components, so the cholesterol, the ceramides, number of ceramides, and the free fatty acids, which we found that for optimum activity of barrier repair, 50% of those free fatty acids needed to be linoleic acid.
• 10:04
  SPEAKER_01: We found that there were two concentrations or two ratios, I should say, that actually triggered uh barrier repair.
• 10:11
  SPEAKER_01: And this was work that Dr.
• 10:13
  SPEAKER_01: Manmao Ging and I did.
• 10:14
  SPEAKER_01: We did many, many experiments looking at all the different ratios because the cardiologist several months previously had published about the ratio of the omega-3, omega-6 for cardiac function.
• 10:26
  SPEAKER_01: And I thought, okay, could that be actually the signal that was going on in the skin?
• 10:30
  SPEAKER_01: Because there's variations as people mature and get exposed to all these environmental insults.
• 10:36
  SPEAKER_01: There's got to be a protective mechanism.
• 10:38
  SPEAKER_01: And sure enough, we found that the three to one to one ratio triggered a dramatic epidermal proliferation and differentiation, and then it dramatically increased the production of the stratum corneum.
• 10:52
  SPEAKER_01: Instead of taking normally 28 days, we could get it produced in about three days.
• 10:56
  SPEAKER_01: And we also found that a two to one to one ratio also had some function, and there's a company now that sells a product, a 242, which is similar to that, but that was 40% less effective than the three to one to one.
• 11:09
  SPEAKER_01: And the three to one to one is still considered the gold standard.
• 11:12
  SPEAKER_01: I mean, we did a literature search just a month ago or so, and it's still considered the gold standard for buried repair as far as the amount of data proving its functionality and clinical studies and so on, um, documenting that.
• 11:25
  SPEAKER_01: So that was really critical.
• 11:27
  SPEAKER_01: But the fact that the problem then was all right, now that we have this ratio, how do we apply it to the skin to keep it going?
• 11:35
  SPEAKER_01: Not just put it on for temporary later, but we needed to upregulate the regulatory aspects of that.
• 11:41
  SPEAKER_01: So the regulatory lipids, uh, various protein signals, various elements that were important.
• 11:46
  SPEAKER_01: And so the formulas that we made really had not just the three to one to one, but also triggered all the metabolic pathways to make more.
• 11:55
  SPEAKER_01: So you continue to have benefit throughout the day when you're getting all these exposures to the expososomes, which is all the environmental insults.
• 12:04
  SPEAKER_01: And so that was also one of the big aspects.
• 12:07
  SPEAKER_01: At the time, keep in mind this was in the 80s, there was really no synthetics that we could formulate together that would actually trigger any of those aspects.
• 12:16
  SPEAKER_01: I mean, it's really complex.
• 12:18
  SPEAKER_01: I mean, there's eight inflammatory pathways of the chronic inflammation going on.
• 12:22
  SPEAKER_01: There's five barrier pair pathways.
• 12:24
  SPEAKER_01: So you have to activate those four, suppress those eight.
• 12:27
  SPEAKER_01: And so, having had experience with herbs and primarily growing up with my dad on a sheep farm, I said, well, let's go to the herbal arena and uh see what we could find.
• 12:38
  SPEAKER_01: So we screened um a number over a hundred different herbs that have been reported to have any benefit in skin diseases.
• 12:45
  SPEAKER_01: And we wanted to see, do they actually work?
• 12:47
  SPEAKER_01: How do they work?
• 12:48
  SPEAKER_01: Is it bury repair?
• 12:49
  SPEAKER_01: Do they work on the inflammation and uh what concentration is required to produce the effect?
• 12:54
  SPEAKER_01: Because as you know, as a physician, really anything you put on, there is a peak.
• 12:59
  SPEAKER_01: It's a bell-shaped curve, and you want to be in that therapeutic concentration.
• 13:03
  SPEAKER_01: And the fallacy, one of the fallacies in America is that more is better.
• 13:07
  SPEAKER_01: Well, it doesn't happen that way in the human bodies, you will know.
• 13:10
  SPEAKER_01: Okay.
• 13:10
  SPEAKER_01: So it was so we really wanted to find out what those therapeutic concentrations are, and and we were able to discover all of that and figure out the interaction of uh how barrier disruption played a role in triggering the chronic inflammation.
• 13:25
  SPEAKER_01: As a matter of fact, uh I first published that in 2005 in cosmetic dermatology, that the chronic inflammation was actually as as a result of the barrier damage, was actually the uh trigger for most of the damage that we see in photoaging.
• 13:40
  SPEAKER_01: So since that time, other people have now labeled it as inflammaging, but that was subject to one of my patents many years ago.
• 13:46
  SPEAKER_01: Does that answer your question pretty well?
• 13:48
  SPEAKER_00: Yeah, no, it does.
• 13:49
  SPEAKER_00: And it leads me to so many other questions because you know, you brought up, for example, linoleic acid.
• 13:53
  SPEAKER_00: And I really would love to learn more about linoleic acid because I know it's behind creating one of the ceramides that's an anchor for that orthorhombic formation of lipids.
• 14:02
  SPEAKER_00: And so can you talk to us a little bit more about linoleic, maybe?
• 14:05
  SPEAKER_00: Because we don't really see this a lot in the ingredient list anymore.
• 14:08
  SPEAKER_00: You know, it doesn't come up anymore for some reason, but it's so essential.
• 14:12
  SPEAKER_01: It is essential, and you're exactly right.
• 14:14
  SPEAKER_01: With the 11 uh ceramides, and that also includes phytosphignosine, which we used a lot of because that's the master one.
• 14:21
  SPEAKER_01: All the others come from uh phytosphignosine.
• 14:24
  SPEAKER_01: So that was our major ceramide that we used.
• 14:27
  SPEAKER_01: But back in the 80s, there weren't any really good sources of uh ceramides, and the the phyto ones had not really been well characterized.
• 14:36
  SPEAKER_01: There was an animal one that uh we had a lot of interest in.
• 14:40
  SPEAKER_01: But being a physician, I wondered, well, what about the safety of that particular organ extract?
• 14:46
  SPEAKER_01: And what do you know it had prions in it?
• 14:49
  SPEAKER_01: So we completely decided not to use that.
• 14:52
  SPEAKER_01: Now, as many of these ceramide products are coming out and many people are using different ceramides, I'm highly doubt that level of safety studies have been evaluated by other people.
• 15:02
  SPEAKER_01: But I you know you wonder what else is in there.
• 15:04
  SPEAKER_01: And so, anyway, but you're exactly right.
• 15:07
  SPEAKER_01: You have to have several different kinds of ceramides, they're basically broken into the five different groups, and the linoleic acid is important in creating the glucosyl ceramides and several of them.
• 15:17
  SPEAKER_01: So, but we found that the linoleic acid was necessary for the optimum barrier function as we reduced the concentration of the linoleic acid or just replaced it with the other bulk free fatty acids, which included steeric acid, palmatic acid, and those, and lauric acid.
• 15:34
  SPEAKER_01: We found that the barrier didn't completely form properly.
• 15:38
  SPEAKER_01: Now, was it just the deficiency of the linoleic acid, or was it because they could not create the right ratio of ceramides because they didn't have the linoleic acid attached to it?
• 15:48
  SPEAKER_01: And I think it's a combination of both.
• 15:49
  SPEAKER_01: So linoleic acid is really important, and of course it's been shown to have a number of other types of effects, it's been reported to have benefit for drug delivery.
• 15:57
  SPEAKER_01: It has anti-inflammatory effect, antimicrobial effect.
• 16:00
  SPEAKER_01: It's a fascinating molecule, it really is.
• 16:02
  SPEAKER_01: And the those complexity of the ceramides is really important, and you know, it's anywhere to 40 to 50 percent by weight of the uh stratum corneum lipids.
• 16:12
  SPEAKER_01: But the fact of the matter is the big problem with ceramides alone, and as I mentioned, we tested all these different ratios.
• 16:20
  SPEAKER_01: What we found is if we used each of those ingredients individually, the barrier was disrupted more.
• 16:25
  SPEAKER_01: What we found is if we combined two, so if we did like two ceramides and added uh linoleic acid or added cholesterol to it, it did not damage the barrier more, but it didn't allow repair of the barrier.
• 16:38
  SPEAKER_01: It wasn't until we had all three there that we could start seeing some benefit of barrier function.
• 16:45
  SPEAKER_01: And then when we found those ratios, as I said, we found that there were two ratios that really dramatically increased and triggered the whole repair process.
• 16:53
  SPEAKER_01: So that's the uh fallacy now of you know having ceramides as a hero product.
• 16:58
  SPEAKER_01: Yeah, ceramides that contribute to moisturization.
• 17:01
  SPEAKER_01: They've got some mild anti-inflammatory effects, some mild antimicrobial effect.
• 17:05
  SPEAKER_01: Um, but really within the barrier, they're critical as long as you have the different types, several different types of the ceramides combined with it.
• 17:14
  SPEAKER_00: Yeah, no, that makes a lot of sense.
• 17:16
  SPEAKER_00: Actually, you know, this is very interesting because we see so much marketing now around things like moisturization versus barrier repair, but then no one discusses this idea of your barrier has to be intact, it has to be healthy to be able to retain moisture.
• 17:31
  SPEAKER_00: And I would love for you to kind of speak on this topic because right now in the industry, what I'm saying is we have barrier creams and we have moisturizers.
• 17:38
  SPEAKER_00: And no one's talking about that interplay between them.
• 17:40
  SPEAKER_00: You know, it's like, where is the purpose of each one?
• 17:43
  SPEAKER_00: And how should we be understanding our skincare when it comes to actual solutions at the end of the day, you know?
• 17:50
  SPEAKER_01: Good point.
• 17:51
  SPEAKER_01: In addressing that issue, it's very important to understand that hydration or moisturization, increased water holding capacity of skin is not the same as barrier repair.
• 18:00
  SPEAKER_01: And one of the keys for barrier repair is not just all barrier repairs are not the same.
• 18:06
  SPEAKER_01: Okay.
• 18:06
  SPEAKER_01: So it's not just repairing the barrier, but it's the percentage of repair, but it's also the speed at which it occurs, because the longer that barrier is open, the greater the amount of expososomes will penetrate in and then trigger damage.
• 18:20
  SPEAKER_01: And with the skin being the largest organ in the body, that's a that's a huge aspect because we know that the chronic inflammation occurring in the skin that sends out signals throughout the body.
• 18:30
  SPEAKER_01: Good example, people who have uh atopic dermatitis.
• 18:33
  SPEAKER_01: In a twin study that was done, they took kids, twins that both had dermatitis.
• 18:38
  SPEAKER_01: One they treated the other, they did not.
• 18:40
  SPEAKER_01: Obviously, this was done in a foreign country because of ethical reasons.
• 18:43
  SPEAKER_01: Anyway, what they found was at 18 years old, the untreated kids had stunted growth, poor motor skills, less cognition, which meant that that those years of the chronic inflammation was destructive to that body, all right, which tells you it's important that we have that barrier intact to prevent and help control the chronic inflammation.
• 19:02
  SPEAKER_01: And I think that's one of the things that is so important with Epiance is we are optimizing barrier function, but we're also controlling that chronic inflammation.
• 19:10
  SPEAKER_01: And and that that's important to have that.
• 19:13
  SPEAKER_01: Now, back to your issue about moisturization and the amount of barrier.
• 19:17
  SPEAKER_01: So, for example, for speed of barrier, we closed the barrier with our three to one to one ratio in we had 89% barrier closure within 45 minutes.
• 19:27
  SPEAKER_01: 100% petrolotum had 43% barrier closure at two hours.
• 19:33
  SPEAKER_01: And at eight hours, it was only 65%.
• 19:36
  SPEAKER_01: Glycerin had a 32% barrier closure.
• 19:39
  SPEAKER_01: No other barrier products had greater than a 22% barrier closure.
• 19:44
  SPEAKER_01: So they're saying, oh yeah, we do this barrier repair.
• 19:46
  SPEAKER_01: Okay, but how much barrier repair are you doing?
• 19:49
  SPEAKER_01: And how fast is it actually occurring?
• 19:51
  SPEAKER_01: If you air dry something after you remove the stratum corneum, it takes 35 hours for a normal person to heal.
• 19:59
  SPEAKER_01: But people who have any of the underlying autoimmune diseases or prediabetes or other type of processes, it may take as long as 14 days for that barrier to repair.
• 20:09
  SPEAKER_01: So you want to slam the barrier shut.
• 20:11
  SPEAKER_01: And that's what our ratios do is they slam that barrier shut.
• 20:15
  SPEAKER_01: Now, a lot of these products that are out there claim, oh, well, we're high in ceramides.
• 20:19
  SPEAKER_01: If you actually look at the formulas there, you will see that a few of the other agents that have lower levels of barrier repair, such as squalene, beeswax, mineral oil, certain of the plant oils.
• 20:32
  SPEAKER_01: Now, not all plant oils improve the berrier.
• 20:34
  SPEAKER_01: There's only a few that do, only a handful that do, which I've published in one of the various chapters in a cosmaceutical book.
• 20:40
  SPEAKER_01: And so those other ingredients are in there at lower concentrations and they do contribute to it.
• 20:46
  SPEAKER_01: And also keep in mind the thing with the ceramides being the hero product, the pH that actually shows the optimum ceramide effect is 4.5.
• 20:55
  SPEAKER_01: A lot of people get burning and stinging with a 4.5 pH.
• 20:58
  SPEAKER_01: Yeah, that's very low.
• 20:59
  SPEAKER_01: That's very low.
• 21:01
  SPEAKER_01: And so there's some other aspects of it, and I think it's just that the marketing stories don't appreciate number one, the complexity of the skin.
• 21:10
  SPEAKER_01: Number two, that to prevent disease and to make your skin as healthy as possible, you have to make sure that you rapidly close the barrier, you rapidly heal the barrier, and then also uh manage that chronic inflammation.
• 21:25
  SPEAKER_00: That makes so much sense.
• 21:26
  SPEAKER_00: That I mean, I cannot tell you how much clarity this adds to this entire conversation that I've been trying to have on this podcast because there are so many, I mean, so many moving pieces right now in skin health, you know, and we have so many like bio-engineered ingredients now that are kind of claiming to do what you're explaining here has already been proven, you know, and that's where I get very lost as both a consumer as well as a healthcare professional, is that, you know, we understand the skin enough to where we should be focusing on this, but we're now just trying to introduce new things for no reason.
• 21:57
  SPEAKER_00: So I'd love to kind of get your take on that as well.
• 22:00
  SPEAKER_00: Because you understand what it takes to actually cause signaling in the skin in a meaningful way that's physiologically compatible.
• 22:07
  SPEAKER_00: What is your take on all of these like more emerging ingredients?
• 22:12
  SPEAKER_00: Like, for example, exosomes are very buzzy right now.
• 22:14
  SPEAKER_00: You know, a lot of regenerative skincare is very buzzy right now.
• 22:17
  SPEAKER_00: How do you feel about that?
• 22:18
  SPEAKER_00: Do you think we even need those ingredients?
• 22:20
  SPEAKER_00: Or I mean, where should we be looking to?
• 22:22
  SPEAKER_01: Well, the exosomes and other vesicles, microvesicles, there's three groups.
• 22:27
  SPEAKER_01: They're there actually are made and they are and they are necessary.
• 22:30
  SPEAKER_01: I think the one of the biggest problems, though, is people assume that the exosomes that are being made from aged or damaged skin or unhealthy skin are going to be normal in structure and function.
• 22:44
  SPEAKER_01: No, you can't assume that.
• 22:46
  SPEAKER_01: Because for those exosomes to work, they have to be able to, the molecules have to bind to the receptor site in a key and lock type of motif.
• 22:57
  SPEAKER_01: In other words, the architecture of the molecules is really important.
• 23:02
  SPEAKER_01: And that's not appreciated very well.
• 23:04
  SPEAKER_01: And so many of these products out there, they say, well, it does this and does that.
• 23:09
  SPEAKER_01: And again, it gets back to my foundation is that, all right, if you're claiming that, prove it.
• 23:15
  SPEAKER_01: Okay.
• 23:16
  SPEAKER_01: Do the clinical studies.
• 23:17
  SPEAKER_01: But at the other hand, you also better do the safety studies as well.
• 23:20
  SPEAKER_01: I mean, as a physician, I'm first and foremost a physician.
• 23:24
  SPEAKER_01: And that is, I wanted to make sure that as I was working on preventing and treating my disease and treating other patients, that I did what patients expect.
• 23:34
  SPEAKER_01: And that is they come to the skincare professional expecting you to be the clearinghouse as far as what's safe and effective.
• 23:41
  SPEAKER_01: And how can you provide safe and effective ingredients if they actually have not been studied in a final formulation in living, breathing patients by trained investigators and using devices that can actually measure the skin parameters?
• 23:55
  SPEAKER_01: Okay.
• 23:56
  SPEAKER_01: So that's why I keep pushing that it's important to do clinical studies with the finished product because what happens in formulation, many of these individual regulatory molecules are actually modified during the formulation process, either by the heat, by the way they're mixing, the different kinds of emulsifiers, the other things that give it a nice aroma.
• 24:16
  SPEAKER_01: All those aspects can have an adverse effect on the functionality of the exosome function, of the transcription factors, of all these different aspects that you need in totality.
• 24:29
  SPEAKER_01: And so I think kind of an example to think of that we hear a lot about are antioxidants.
• 24:34
  SPEAKER_01: Well, there's 15 antioxidants used in the skin, but you know what?
• 24:38
  SPEAKER_01: None of them occur individually.
• 24:40
  SPEAKER_01: Okay.
• 24:40
  SPEAKER_01: All 15 of them, they're split into three different regulatory cycles so they can continue to regenerate themselves because the major source of reactive oxygen species is in fact normal cell metabolism.
• 24:53
  SPEAKER_01: So you have to have your antioxidant system working.
• 24:55
  SPEAKER_01: And people say, well, you know, this is the most potent antioxidant, or I'm doing 20% vitamin C.
• 25:00
  SPEAKER_01: So what?
• 25:01
  SPEAKER_01: The body only uses a certain concentration, and you have to deliver that concentration to the specific strata you're trying to modulate.
• 25:10
  SPEAKER_01: There's six strata in skin.
• 25:12
  SPEAKER_01: You've got to get it to that site at that right concentration in a stable form so it can actually bind to the cell and trigger the processes.
• 25:20
  SPEAKER_00: Yes, yes.
• 25:22
  SPEAKER_00: That's, I mean, I cannot tell you how refreshing it is to hear this.
• 25:25
  SPEAKER_00: And speaking of antioxidants, I'd love for you to kind of debunk this a little bit more because vitamin C has been going crazy, you know, for the past few years.
• 25:33
  SPEAKER_00: People have been formulating with like 30% vitamin C, 20% vitamin C.
• 25:37
  SPEAKER_00: And I always wonder, because I'm like exactly what you're explaining, the vitamin C has to get inside of the cells to actually work.
• 25:43
  SPEAKER_00: You know, whether it's uh working as a cofactor, whether it's working to mop up for your like whatever it's doing, you have to get it inside.
• 25:50
  SPEAKER_00: So, what is your advice to consumers that are buying these products and they're just saying, like, yeah, you know, this is gonna really help me with the damage, with the photo damage that I'm getting, you know, they apply their vitamin C religiously every day.
• 26:02
  SPEAKER_00: Do you think that that matters after a certain point?
• 26:05
  SPEAKER_00: Or do you think that we need to have like more, I don't know, balanced formulations or like, you know, more holistic formulations?
• 26:11
  SPEAKER_01: Yeah, I absolutely believe in that the holistic is formulations are really important because what our goal and trying to understand all this was going on is I said we didn't set out for it to develop an anti-aging product.
• 26:25
  SPEAKER_01: We set out to understand how the skin operates optimally and how it repairs itself from injury, how it prevents the diseases that occurred and occur as we age, which means that the skin, when it is insulted, it doesn't just strip itself off, do this massive exfoliation or anything like that.
• 26:44
  SPEAKER_01: No, it starts triggering production of the three key barrier oils.
• 26:48
  SPEAKER_01: It starts activating or inhibiting the chronic inflammation pathways with other signaling molecules, and it's it repairs itself gently and quietly, and then you uh end up with the uh supple skin and soft skin.
• 27:02
  SPEAKER_01: So one of the fallacies is people think that, as I've mentioned, more is better, and that's not really the case.
• 27:07
  SPEAKER_01: Okay, so you need to have the optimum concentration, and as I said, there's no place in the body where a single antioxidant works.
• 27:15
  SPEAKER_01: No, all the microenvironments, there's the combination of the multiple antioxidants.
• 27:20
  SPEAKER_01: As a matter of fact, five clinical studies with looking at different diseases, different types of cancers and heart disease, they found that high dose of a single antioxidant, including a study that was done with vitamin C, actually triggered increased uh heart disease, and they stopped the clinical study over a year earlier because the increased incidence of the heart attacks that occurred.
• 27:40
  SPEAKER_01: They stopped the study on prostate cancer with selenium because the increased incidence of prostate cancer.
• 27:46
  SPEAKER_01: They stopped the high dose vitamin A on colon cancer because the colon cancer rates went up.
• 27:50
  SPEAKER_01: In other words, we have examples in the human body that have been published in not just dermatology literature, but in other literature clearly showing that high concentrations of a single antioxidant is in fact damaging.
• 28:03
  SPEAKER_01: And that's not how they occur in your body.
• 28:05
  SPEAKER_01: I mean, there's over 8,000 compounds that in the laboratory have shown to be antioxidant effects.
• 28:11
  SPEAKER_01: About 150 have actually been studied in humans.
• 28:16
  SPEAKER_01: Okay.
• 28:16
  SPEAKER_01: Of those, half of those showed minimal to mild benefit.
• 28:21
  SPEAKER_01: The others, half showed no benefit at all.
• 28:23
  SPEAKER_01: They actually showed increased toxicity.
• 28:25
  SPEAKER_01: So that's the antioxidant story, but it's a kind of a dirty little secret that people don't want to talk about in the molecular arena.
• 28:32
  SPEAKER_01: Although there have been a number of functional medicine doctors that have been reporting about how you know high dose antioxidants in and of themselves are disease causing and so on.
• 28:40
  SPEAKER_01: And that's absolutely been demonstrated in the scientific literature.
• 28:44
  SPEAKER_00: Yeah, that's that's fascinating.
• 28:46
  SPEAKER_00: I didn't know that.
• 28:47
  SPEAKER_00: I mean, honestly, that's it's interesting now then to look at what is actually being marketed because we, I mean, we went from like, for example, vitamin C to glutathione, which glutathione just never even made sense to me, you know, like topically applying glutathione didn't make any sense.
• 29:01
  SPEAKER_00: But we have an entire industry that's snowballing on these like buzzwords that are coming from molecular biology and they keep doing it.
• 29:09
  SPEAKER_00: And I just wonder, like, you know, when it comes to cell signaling, I'd love for you to speak a little bit more to our listeners about cell signaling, because this is something I wish people spoke about in terms of what cells actually interact with and how they actually respond.
• 29:23
  SPEAKER_00: Because I don't think anyone really talks about that, you know, like in terms of like when you have a ligand binding to a receptor that elicits a response, what that means for all the other cells downstream, that's a whole conversation that never happens.
• 29:35
  SPEAKER_00: So, like when we're thinking about the skin, what are some things that we should understand in that arena?
• 29:40
  SPEAKER_01: First of all, with glutathione being an enzyme, um, when it's put on the skin topically, the various types of proteinases will usually destroy it.
• 29:47
  SPEAKER_01: So it doesn't really get down to actually have any benefit and goes back to the green tea stories where they showed some benefit on the forums of elderly man, but no other place in the body have they actually proven that high dose green tea extract actually works in reducing precancers and reversing photoaging.
• 30:05
  SPEAKER_01: So that's a similar situation with the uh glutathione.
• 30:08
  SPEAKER_01: And there are a lot of these ingredients out there that are people are talking about, but they're looking at it from a lens of just a particular molecule.
• 30:17
  SPEAKER_01: They don't seem to be thinking about how does it fit in the complex story.
• 30:22
  SPEAKER_01: And then if you're going to modulate all these different signals, how do you actually do that?
• 30:27
  SPEAKER_01: So I was excited to see the quorome type of technology being developed where that's how the cell interacts with the quorums.
• 30:34
  SPEAKER_01: And now that they're they're actually have discovered these, uh, that was a great breakthrough.
• 30:39
  SPEAKER_01: So there are some raw materials that you can get that have some ingredients with that.
• 30:43
  SPEAKER_01: But again, can you prove that it actually works and it works safely?
• 30:48
  SPEAKER_01: That's what patients want.
• 30:49
  SPEAKER_01: I mean, the problem with the with the whole vitamin C issue, one critical thing that people forget.
• 30:54
  SPEAKER_01: And I went to Oregon State.
• 30:56
  SPEAKER_01: Why is that important?
• 30:57
  SPEAKER_01: Linus Pauling, the uh Nobel Prize for Discovering Vitamin C in 1954, happened to be a professor there, okay?
• 31:03
  SPEAKER_01: And so I know a lot about that, okay?
• 31:06
  SPEAKER_01: And he in his original, when he would come back and give uh lectures to the chemistry department, he always talked about how the vitamin C, it's not just the L-ascorbic acid, you also have to have the ascorbate as well, which is very tranchitypal molecule.
• 31:21
  SPEAKER_01: But to actually trigger collagen synthesis, you also have to have iron.
• 31:26
  SPEAKER_01: And now we also know in the last few years, it's been shown, you also need to have some zinc as well to cause a synthesis of collagen.
• 31:33
  SPEAKER_01: So you can put high doses of vitamin C on, but unless you got the iron component there, you're not gonna get collagen synthesis.
• 31:39
  SPEAKER_01: But people say, well, my wrinkles are better.
• 31:41
  SPEAKER_01: Okay, why is that?
• 31:43
  SPEAKER_01: Oh, yeah, you're getting irritation.
• 31:44
  SPEAKER_01: You know, the original study that was published on vitamin C was published in the ENT literature.
• 31:49
  SPEAKER_01: And the problem was one-third of the patients dropped out because of visible contact dermatitis.
• 31:55
  SPEAKER_01: Well, if you have a contact dermatitis, the wrinkles are gonna look better, skin's gonna look more swollen.
• 31:59
  SPEAKER_01: But the fact of the matter is, of those patients who still completed the study, 65% had erythema and edema.
• 32:06
  SPEAKER_01: And they said, Oh, well, the vitamin C works in wrinkles.
• 32:09
  SPEAKER_01: Yeah, not really.
• 32:10
  SPEAKER_01: Okay, it produced an irritation reaction.
• 32:13
  SPEAKER_01: And what's gonna happen with that?
• 32:14
  SPEAKER_01: The chronic irritation reaction then triggers the matrix metalloproteinasis to produce destruction of the skin and trigger pre-malignant cells and destroy the collagen and elastin, prevent barrier repair, and a whole series of processes that occur from that triggering of the inflammation.
• 32:34
  SPEAKER_01: And so again, I think it's people are looking for a simplistic marketing piece of information rather than really saying, look, this is a complex organ system, and you need to understand how all these things work, and you need to understand how they work in formulation.
• 32:50
  SPEAKER_01: And the only way you can tell that is in fact with double-blind, prospective, controlled clinical trials with a finished formulation conducted by a third-party research after it's been institutional review board approved with a statistically significant number of patients.
• 33:06
  SPEAKER_01: Then you can tell whether or not it works because the odds are any type of herbal product or any other psych type of ingredient you put in 15 out of 16 times, it won't work.
• 33:15
  SPEAKER_00: That makes sense.
• 33:16
  SPEAKER_00: That makes sense.
• 33:17
  SPEAKER_00: And and this leads me to wonder because we had a movement of like natural-based skincare, you know, and plant-based skincare.
• 33:24
  SPEAKER_00: And we still see that, you know, like I brought up exosomes a little bit earlier about how we're making plant exosome products, you know, and it's like, what is the purpose of this?
• 33:33
  SPEAKER_00: Like, what is the skin is not going to react?
• 33:35
  SPEAKER_00: So I'd love for you to speak on this idea of biomimetic ingredients for the skin and why that matters, because that's where I feel like the marketing, it's a snowball at this point, you know, and it's like we just keep going down this road.
• 33:49
  SPEAKER_00: So can you speak to us about that in terms of true biomimetic ingredients?
• 33:53
  SPEAKER_01: Yeah, the biomimetic ingredients, they're they are claiming that because of certain structure and molecular makeup that in fact they work identically to the way the human body does.
• 34:04
  SPEAKER_01: And yes, it does depend on the specific molecule.
• 34:08
  SPEAKER_01: But the question is, do the plant-based ones in fact actually have the same functionality?
• 34:14
  SPEAKER_01: And the reason I bring that up is because one of the things that had always interested me was about the issue about why do basically plant extracts that are the tonics, why do they work better than the individual ingredients as you go down and fractionate it more normal?
• 34:28
  SPEAKER_01: I get it down to a couple of uh key hero ingredients, so to speak.
• 34:31
  SPEAKER_01: Why do the tonics work better?
• 34:33
  SPEAKER_01: Well, it turns out in plants, you have a group of compounds and elements that basically enhance the delivery and the stability of the active molecules.
• 34:43
  SPEAKER_01: And those are called the entourage components.
• 34:45
  SPEAKER_01: And as we did research in that, what we found is that the entourage components not only enhanced the functionality and the stability of the main secondary metabolite, which is what the active ingredients are primarily in plants, but it also even increased it enough that there were additional abnormalities that were modulated by the entourage ingredients.
• 35:08
  SPEAKER_01: And so I think one of the fallacies is that they're saying they're taking them from plants, but they are only using a particular molecule, which may have some variation in architecture enough that it's not going to be able to bind to the key, but certainly it does not have the entrage elements, molecules, and ions that are going to protect it and help maintain its stability.
• 35:30
  SPEAKER_01: Consequently, there's a very rapid breakdown of many of those biomimetics because the metabolic pathways are there and they destroy it.
• 35:38
  SPEAKER_01: But I don't see studies coming out actually looking at how are these molecules metabolized, because your body needs to have a way to catabolize so you don't get buildup molecules, particularly when you're looking at like fat-soluble vitamins and so on, because then like vitamin A and vitamin K, because you can end up with toxicity issues with that.
• 35:59
  SPEAKER_01: So the biomimetics in my mind, they're claiming that it has this same kind of benefit.
• 36:04
  SPEAKER_01: But from what our research showed in plants and what other very bright investigators have found, that in fact, it's not just the individual secondary metabolite, it's also the other components in there that allow it to provide that functionality.
• 36:18
  SPEAKER_01: And to my knowledge, I've not seen anything in the literature that these biomimetics actually have those additional molecules to improve their stability.
• 36:26
  SPEAKER_01: So you put them in, then you need to have a system to actually a delivery system to take it to the right strata.
• 36:33
  SPEAKER_01: It has to target the specific cell.
• 36:35
  SPEAKER_01: It has to be able to bind to the receptor in a proper way and sufficient enough to fully trigger functionality because that's the other problem.
• 36:43
  SPEAKER_01: A lot of these biomimetics will increase functionality, but these signaling molecules have multiple steps, like a tree that has the branches.
• 36:52
  SPEAKER_01: And so there's multiple aspects of functionality they modulate, and you've got oftentimes several different molecules are involved in producing a specific downstream pathway.
• 37:02
  SPEAKER_01: And you need to have all those tour.
• 37:04
  SPEAKER_01: It's like for pigmentation.
• 37:05
  SPEAKER_01: There's 31 steps.
• 37:07
  SPEAKER_01: And if you want to have something that's truly hyperpigmentation, and that's why things just inhibit tyrosinase or block one of the other two or three steps, which is all we do today, why would you expect to get complete clearance?
• 37:19
  SPEAKER_00: 100%.
• 37:20
  SPEAKER_00: Yeah, it doesn't make sense.
• 37:22
  SPEAKER_00: And this is so fascinating because it really opens up that conversation of how the skin is a very, very dynamic arena.
• 37:29
  SPEAKER_00: Like you have to really understand all of the moving pieces.
• 37:32
  SPEAKER_00: And, you know, one of the biggest questions I think that comes up is in terms of like, for example, retinoids.
• 37:37
  SPEAKER_00: There's a lot of drugs in dermatology that I think they've been around for a long time, you know, and they're still being marketed and they're still being pushed as this is the one and done solution.
• 37:46
  SPEAKER_00: But I know for a fact, like, for example, hydroquinone or tretinoin, they don't work for a lot of people, you know, and they end up causing a lot of other downstream effects that are then you need to manage those.
• 37:56
  SPEAKER_00: So, what is your opinion on that in terms of people?
• 37:59
  SPEAKER_00: For example, if somebody is utilizing tretinoin, you know, for anti-aging benefits, photodamage, you know, control, how can we understand the true potential of this drug in our skincare routine versus, you know, just what we've been kind of marketed to for a long time?
• 38:13
  SPEAKER_01: So tretinoin, tretinoin was developed because they found that that was the final component of the vitamin A metabolic pathway that actually would trigger functionality within the skin and other membranes.
• 38:28
  SPEAKER_01: So that's why it's used in different parts of the body as well.
• 38:30
  SPEAKER_01: The thing is, though, that it only works on three of the eight pathways.
• 38:35
  SPEAKER_01: So you have five pathways that you have to upregulate.
• 38:38
  SPEAKER_01: Tretinoin doesn't really work in any of those, other than it has some effect in thickening the total epidermis, but doesn't improve barrier function at all.
• 38:46
  SPEAKER_01: And back 20 years ago, 30 years ago, 10 years ago, people understood that those agents, the tretinoids and their retinoids, are photosensitive, but that seemed to disappear from the literature about a dozen years ago.
• 39:00
  SPEAKER_01: And I've been surprised at how many young dermatologists were not aware that that was actually an issue.
• 39:05
  SPEAKER_01: Now, my background with that, we'd done work with that with Dr.
• 39:08
  SPEAKER_01: Stoughton at UC San Diego and some work for anti-cancer effect of the retinoids.
• 39:13
  SPEAKER_01: And the retinoids are powerful, but as I said, when you look at the skin pathways, you've got 13 pathways that need to be modulated, and it works on three of them.
• 39:20
  SPEAKER_01: And then the other problem is that how does it work?
• 39:24
  SPEAKER_01: Well, it increases uh proliferation.
• 39:26
  SPEAKER_01: And with doing that, you can speed up the proliferation enough you'll actually can have higher incidences of various types of uh abnormalities and precancers and so on occurring.
• 39:38
  SPEAKER_01: And I was at the meeting in Cannes, France, in February of 1985 when Dr.
• 39:43
  SPEAKER_01: Kligman presented the first information about anti-aging effect of tretinoid.
• 39:48
  SPEAKER_01: The speaker before him talked about how the uh use of the tretinoin increased the incidence of sun-induced precancers.
• 39:55
  SPEAKER_01: All the publicity went for the anti-wrinkling effect that Dr.
• 39:58
  SPEAKER_01: Kligman talked about.
• 40:00
  SPEAKER_01: And so I was a very big retinoid user.
• 40:03
  SPEAKER_01: Within a couple of years, I was the biggest retinoid user in Oregon.
• 40:06
  SPEAKER_01: And because I was trying to get rid of all these precancers, particularly in younger people, young adults, I was just stunned at how the frequency was.
• 40:13
  SPEAKER_01: And that was one reason why we did all the research.
• 40:16
  SPEAKER_01: I wanted to help reduce the incidence of precancers and skin cancers in young people.
• 40:20
  SPEAKER_01: Because I was taking melanomas off of six-year-olds, squamous cell carcinomas off 11-year-olds.
• 40:24
  SPEAKER_01: I mean, things that, you know, you just don't normally see in most of the population.
• 40:29
  SPEAKER_01: So anyway, it was uh then we started seeing that early on there would be benefit, but then there would be increased incidence over time.
• 40:38
  SPEAKER_01: And uh that was one of the issues that made me think about we need to look at this differently because we did know that it had an impact adversely on the stratum corneum and the photosensitivity.
• 40:49
  SPEAKER_01: And so the benefit uh walked a very fine therapeutic line or to true knife edge as far as producing too much activity.
• 40:57
  SPEAKER_01: And so I think there's a reason why, well, I know there's a reason why they are telling people now that use them for a certain period of time, six to twelve months, and you need to go to a maintenance dose of one to two times a week, and so on.
• 41:10
  SPEAKER_01: And the reason for that is is because adverse reactions started occurring, and you started seeing increased incidence of other aspects, like increased incidence of uh sun-induced precancers, increased incidence of skin sensitivity, increased reactions.
• 41:24
  SPEAKER_01: I mean, the incidence of contact reactions in the last 12 years to cosmetics is increased from 17% to 55%.
• 41:33
  SPEAKER_00: Oh my goodness.
• 41:34
  SPEAKER_01: Okay.
• 41:34
  SPEAKER_01: The incidence of sensitive skin is over 50% in several races, and all the races, it's at least 30%.
• 41:42
  SPEAKER_01: Okay.
• 41:43
  SPEAKER_01: So that tells you that there's abnormalities occurring.
• 41:47
  SPEAKER_01: So how much of that is actually related to the skin care regimens and that, and uh, which I think it clearly has, and I think the use of high-dose vitamin C and high dose vitamin A is a big contributor.
• 41:58
  SPEAKER_00: Yeah, no, that's that really, really clarifies a lot for me, actually, because tretinoin right now, there's just a lot of conversation around retinoids in general.
• 42:07
  SPEAKER_00: And I know a lot of companies are marketing, for example, retinol.
• 42:10
  SPEAKER_00: I know Bacuchiol became a thing.
• 42:12
  SPEAKER_00: You know, that's been one of my biggest questions is that, you know, we look at vitamin A, we look at it in, you know, leukemias, we look at it in actual very serious cancers.
• 42:22
  SPEAKER_00: And yes, we understand that it can repopulate an entire cell population, but do we want to be doing that every single day on our skin for years and years and years?
• 42:31
  SPEAKER_00: You know, so right.
• 42:33
  SPEAKER_01: And interesting about Bacuchiol, there was a Cochrane report just uh last year showing when they looked at the 15 clinical trials with Bacuciol, basically there was no benefit.
• 42:43
  SPEAKER_01: But even though people are comp are are saying, oh, it has this activity, the reality is it didn't.
• 42:48
  SPEAKER_01: Yeah.
• 42:49
  SPEAKER_01: And there were no randomized controlled trials done.
• 42:52
  SPEAKER_01: The trials were very poor quality, and the conclusion was no, acuceal doesn't work.
• 42:57
  SPEAKER_01: But again, that's an example of somebody discovering something of, hey, you know, what can we do for the marketing story?
• 43:03
  SPEAKER_01: And I think that's where I primarily diverge from many of the other thought leaders in the area of dermatology.
• 43:12
  SPEAKER_01: I am first and foremost a physician.
• 43:14
  SPEAKER_01: I want to make sure products are safe and effective.
• 43:17
  SPEAKER_01: That's why we were the first ones to do those RCTs against prescription products.
• 43:22
  SPEAKER_01: And we were also the first ones to start doing the repeat insult patch test safety study on all of our products.
• 43:28
  SPEAKER_01: And I know it was important because people, I got attacked for raising the bar and for changing how we look at cosmetics and so on.
• 43:37
  SPEAKER_01: And a cosmosceutical, the definition is it has impacts on structure and function temporarily like a drug, but it's got the elegance of a cosmetic.
• 43:48
  SPEAKER_01: But there's not really any federal regulation around that area.
• 43:52
  SPEAKER_01: You know, it's a lot, not like in Japan where you have quasi drugs that are well regulated and so on, and like our OTC FDA approved monograph to.
• 44:00
  SPEAKER_01: ingredients and that sort of thing.
• 44:01
  SPEAKER_00: So no, no, it's it's really, really fascinating.
• 44:03
  SPEAKER_00: And I think that's why I want you to speak about the way that you've built Epiance because I it hasn't, you haven't strayed from this idea of like, you know, focusing on what really the skin needs, you know, and I would love for you to speak on carrying that integrity forward.
• 44:18
  SPEAKER_00: As obviously, I mean you are a physician and the science is always first.
• 44:21
  SPEAKER_00: But even in the entrepreneurial space, I'd love for you to offer some advice in this industry because I don't understand why.
• 44:28
  SPEAKER_00: I don't want to sound mean when I say this to anyone listening, but there are a lot of physicians right now that I wonder where is your brain, you know, when you're making some of these products because they're not meant to do what they're claiming to do.
• 44:40
  SPEAKER_00: And you know, you're putting 18 ingredients into a bottle and claiming that this is going to fix like what we were talking about earlier, hyperpigmentation or wrinkles or whatever it might be.
• 44:49
  SPEAKER_00: It's just not plausible.
• 44:50
  SPEAKER_00: That's just not plausible, obviously in a formula, but also everything you've discussed here, your skin doesn't work like that.
• 44:56
  SPEAKER_00: You know, there are things like receptor saturation.
• 44:58
  SPEAKER_00: There are things like too much exposure to certain ingredients and factors.
• 45:02
  SPEAKER_00: And so I'd love for you to offer this advice on that entrepreneurial scale, you know, of like how can people still innovate but not lose sight of what's actually going to move the needle for the skin?
• 45:12
  SPEAKER_01: That's a very good question and a dilemma that I think all skin professionals wrestle with to some degree.
• 45:18
  SPEAKER_01: In my situation, because I was first and foremost a physician, my goal was to prevent, as I mentioned earlier, precancers in young people, to prevent the diseases that occur as we mature and the diseases that occur with activation from environmental insults.
• 45:34
  SPEAKER_01: And also I wanted to get clear from my dermatitis and stay clear and not have the reactions to the various medications that were being used.
• 45:44
  SPEAKER_01: So we really had that five foundation and having the investigator's mind, because I had done multiple phase three clinical trials when I was a resident and I had already patented azoleic acid for treatment of rosacea which became phanacea and as I mentioned 22 patents, but it was always looking at understanding the underlying biochemistry and the molecular level.
• 46:06
  SPEAKER_01: I used to think that all doctors thought like that.
• 46:09
  SPEAKER_01: I was so surprised when I found that's not the case.
• 46:12
  SPEAKER_01: A lot of them don't think like that.
• 46:14
  SPEAKER_01: And also because of variety of economic issues and so on, they may have a different desire for what they're trying to develop.
• 46:23
  SPEAKER_01: Our goal was to make products that were safe and effective and worked on the foundational problems.
• 46:28
  SPEAKER_01: So for example if we look at eczema patients and treated this is comparison with a megapotent topical cordosteroid clubetazole used twice a day, all the patients were cleared within three weeks.
• 46:40
  SPEAKER_01: Problem was when they stopped the treatment they all rebounded within four weeks.
• 46:43
  SPEAKER_01: Using the barrier repair technology it took seven weeks for them to completely clear even though they started noticing significant benefit within two days.
• 46:50
  SPEAKER_01: But there was no recurrence of any lesions for eight and a half months which tells you we were really working on the foundational problem.
• 46:59
  SPEAKER_01: Okay.
• 47:00
  SPEAKER_01: And that's what drives me is producing that that long-term benefit.
• 47:04
  SPEAKER_01: But because our goal was very different and because I came out of the pharmaceutical industry, I needed to start a company and do the research ourselves and then build upon that.
• 47:16
  SPEAKER_01: And if we could find things that would result in the products terrific.
• 47:20
  SPEAKER_01: But we needed to do the understanding research and as I mentioned the relationship with Peter Elias and his great team.
• 47:26
  SPEAKER_01: So we did that nine years of the basic research and then we needed to prove efficacy and safety.
• 47:32
  SPEAKER_01: So we did that with clinical studies.
• 47:35
  SPEAKER_01: And in 2003 we took on tretinoin.05% emollient combined with their lactic acid moisturizer and we were twice as good in rejuvenating the epidermis and the dermis and we had no irritation.
• 47:46
  SPEAKER_01: Oh yeah we got rid of 97% of the visible precancers as well.
• 47:50
  SPEAKER_01: Oh and 38% of the hyperpigmentation went away even though we had no depigmenters in our product line.
• 47:55
  SPEAKER_00: Wow.
• 47:56
  SPEAKER_01: Okay.
• 47:56
  SPEAKER_01: And so when other companies come out and say oh well we're a you know we've combined a retinoid and a hydroxy acid so you know this is a big breakthrough.
• 48:04
  SPEAKER_01: Yeah actually we showed over 20 years ago that that's not the case that we were better.
• 48:08
  SPEAKER_01: Okay.
• 48:09
  SPEAKER_01: But I think the differentiating point was I focused so much on the research early on rather than spending money on marketing because as I said I thought doctors thought like I did and realized that a lot of them didn't.
• 48:25
  SPEAKER_01: And so having been a uh lineman on championship teams in football, I knew the importance of having the team and so I went out and found a group of people that uh would buy off on the vision and had skill sets that I lacked.
• 48:38
  SPEAKER_01: I'm really good at a few things but I really suck at a lot of things.
• 48:42
  SPEAKER_01: Okay.
• 48:43
  SPEAKER_01: So I needed to bring people in that could overcome my deficiencies and together we were able to produce what we have as Epiance today.
• 48:52
  SPEAKER_01: Okay.
• 48:52
  SPEAKER_01: There was also a learning process for that and it took risk.
• 48:56
  SPEAKER_01: I mean twice I second mortgaged my house I completely exhausted all my retirement funds to finance the original research and all these sorts of things.
• 49:04
  SPEAKER_01: You know so I took big risks and fortunately my wife of almost 53 years agreed to do that.
• 49:09
  SPEAKER_01: And so we were able to be a successful company.
• 49:12
  SPEAKER_01: In other words from the very beginning our philosophy was different than others.
• 49:17
  SPEAKER_01: And having sat on scientific advisory boards for several cosmetic companies I had a pretty good idea what kind of products they would not be producing, but what kind of products I needed in my practice to help me be a better doctor.
• 49:30
  SPEAKER_01: Okay.
• 49:31
  SPEAKER_01: To reach the five goals.
• 49:32
  SPEAKER_01: And so I had a concept of 14 products.
• 49:35
  SPEAKER_01: We have completed 13 of those.
• 49:37
  SPEAKER_01: The 14th is in process now.
• 49:39
  SPEAKER_01: And so we've been successful in focusing in that particular area.
• 49:44
  SPEAKER_01: As we grew organically we were able to decrease cost of individual SKUs as we were able to increase volume of usage and we were also able to add more SKUs based on more research able to do more clinical trials.
• 49:58
  SPEAKER_01: We just finished our 37th clinical trial last year.
• 50:01
  SPEAKER_01: Okay.
• 50:01
  SPEAKER_01: And more than 15 of those have been RCTs.
• 50:04
  SPEAKER_01: And so that's what our our our major focus has been over the time and I'm very proud of how our marketing team and so on has been uh doing now and as we're building the company and spending more money and effort in the marketing arena.
• 50:19
  SPEAKER_01: But we were the first in so many aspects of it.
• 50:22
  SPEAKER_01: And as I said first for safety studies, first for blinded trials against prescription products.
• 50:27
  SPEAKER_01: And incidentally we've taken on 13 prescriptions we've beaten them all in efficacy and safety.
• 50:32
  SPEAKER_01: Okay?
• 50:32
  SPEAKER_01: 13 gold standard products.
• 50:34
  SPEAKER_01: So we've accomplished a lot and so I'm very gratified to be able to uh stand here and say yes we have been able to accomplish a lot.
• 50:43
  SPEAKER_01: I was hoping that this technology and the concepts would spread throughout the entire world but I realize that there's only a portion of people who absolutely are really driven by optimum skin health that they're willing to pay the price and their lifestyle and so on to make the changes to optimize their health.
• 51:02
  SPEAKER_01: That's really what we're trying to do.
• 51:03
  SPEAKER_01: You'll have maximum beauty with optimum skin health you're going to have the best health span.
• 51:08
  SPEAKER_01: In other words the years of quality living before you move into your terminal stages that's lengthened.
• 51:15
  SPEAKER_01: And Framingham study showed that people who were pleased with the appearance of their skin actually lived longer, had higher survival of heart surgeries had lower incidence of use of prescription medications than those that did not.
• 51:27
  SPEAKER_01: So we know there's tremendous health benefits for having healthy skin and that's what our major driver is optimized health.
• 51:34
  SPEAKER_01: And what that means is we have to look past what is the fad products.
• 51:39
  SPEAKER_01: We don't use fad ingredients because when we did studies looking at them they weren't that effective or we couldn't deliver them at the therapeutic concentration or they weren't stable when we mixed them with other ingredients.
• 51:51
  SPEAKER_01: So it's really been really science focused and I've just stuck with that.
• 51:55
  SPEAKER_01: And as long as I'm in control of the company which I am you know we will continue focusing on that.
• 52:01
  SPEAKER_01: Now as new technologies come out because there's so many bright innovators out there that some of them are they're just incredible things.
• 52:08
  SPEAKER_01: The quorum issue the microbiome issue all these are really important that's cell signaling the exosomes but the key I think for the whole story with a lot of these signaling systems and including with like growth factors you know how are they actually working?
• 52:25
  SPEAKER_01: Well they're working by second messengers well how can you assume that that second messenger is going to have normal structure and function and go to the right receptor if the cell and the structure is damaged.
• 52:38
  SPEAKER_01: Aging skin is damaged skin you can't assume it's going to be able to create the right second messengers that are going to consistently produce the right signaling that they're the right message on the particular cells.
• 52:49
  SPEAKER_01: So there's a lot of other factors that people overlook because it's not amenable to short marketing bursts is my opinion on this.
• 52:56
  SPEAKER_01: And I'm not a marketeer and I have learned a lot about this whole aspect over the years.
• 53:02
  SPEAKER_01: But as you know and with all your different degrees you have to be a continual learner.
• 53:07
  SPEAKER_01: And if you don't have that attitude is that you know you can always learn from somebody else.
• 53:11
  SPEAKER_01: There's always bright people out there coming in you're going to go backwards.
• 53:14
  SPEAKER_01: You know you really need to continue to be a learner.
• 53:16
  SPEAKER_01: So I do evaluate new technologies are coming out.
• 53:19
  SPEAKER_01: We do a significant amount of literature searches and my research assistant actually been my senior nurse for 32 years.
• 53:26
  SPEAKER_01: And so she knows how I think that she's seen Ebbiance from the very beginning and so on.
• 53:31
  SPEAKER_01: So we're able to work very well and I I have a great team here and I'm just very thankful um for the group we have and uh we wouldn't be where we are without the whole team.
• 53:40
  SPEAKER_00: I love that.
• 53:41
  SPEAKER_00: And I I cannot truly like applaud you enough for sticking to your guns with the science.
• 53:46
  SPEAKER_00: Like I I really admire that.
• 53:47
  SPEAKER_00: And I I think that we can learn so much from your approach and what you've accomplished in this entire space of dermatology of skin health and I really hope that you know the future of skincare is going to be more of leaning into this direction that you've already established you know because I do wonder you know I've interviewed a lot of brands on this podcast and some of the technologies although they sound very interesting and you know exciting the physiologist in me is always like yeah you know this is very cool.
• 54:14
  SPEAKER_00: But the mechanism and the data and the proof it's just never there and I feel like we're putting that cart before the horse so many times you know in this space.
• 54:21
  SPEAKER_01: So I absolutely agree.
• 54:22
  SPEAKER_01: And so it's so refreshing to hear you share that there are other people like me that think along those same lines and how important it is.
• 54:30
  SPEAKER_01: And that's one reason why we do all of our own manufacturing as well.
• 54:33
  SPEAKER_01: We don't farm anything else because I want to make absolutely sure that we have all the ingredients and the formulations are made properly.
• 54:40
  SPEAKER_01: So it's an exciting world and I've been incredibly blessed and I've been in the industry long enough I've seen concepts come and go and failed for a lot of reasons and most of it is they could never prove that they actually worked with the finished products.
• 54:53
  SPEAKER_00: Yeah I think that's the biggest hurdle.
• 54:54
  SPEAKER_00: And you know it's funny because I started this I mean I'm just telling you off the books I started this seal.
• 54:59
  SPEAKER_00: It's like a validation seal you know it's like basically show me your data kind of thing.
• 55:03
  SPEAKER_00: Like show me the proof of the final product that you've shown you've proven that it works, you know, and I kid you not the amount of brands that have said yeah I'm interested in the seal but then you ask them for the data and they're just like no like I'm I'm not showing you anything.
• 55:16
  SPEAKER_00: It's disheartening because I align with what you've explained in this whole podcast.
• 55:21
  SPEAKER_00: You know, I really align with that as a scientist and also a consumer and it's sad to see that companies don't want to be more transparent about their science, you know, and say like we put in the time in the right place, you know, in the right research and we can prove that, you know, at the end of the day.
• 55:36
  SPEAKER_00: I hope that that shifts at some point, you know, and and and people start realizing like yeah you're selling a product but you're also selling an adjunct health solution for so many people.
• 55:44
  SPEAKER_00: Like there are people in rural parts of this country that have no access to dermatologists.
• 55:49
  SPEAKER_00: They have no access to proper health care and their only option is over-the-counter products, you know, consumer-based products.
• 55:55
  SPEAKER_00: And it's like where is that duty then at the end of the day on the behalf of these brands that you have to serve that consumer.
• 56:01
  SPEAKER_00: You have to serve that you know like in the same way that we learn in healthcare and in medicine um do no harm that kind of thing.
• 56:08
  SPEAKER_00: So yeah but no thank you so much doc.
• 56:10
  SPEAKER_00: This has been I can't tell you how much of a breath of fresh air this conversation has been for me.
• 56:15
  SPEAKER_00: I can't thank you enough for your time.
• 56:17
  SPEAKER_01: This is a amazing well thank you thank you so much uh for giving me this opportunity to share and it it is exciting and it's been a long road but it's been worth it the impact and the the patients that I have and are the people that tell me about how it's changed their lives.
• 56:31
  SPEAKER_01: I mean just the other day I had a person said oh you're you're the Dr.
• 56:35
  SPEAKER_01: Thornfeld that invented this product has changed the life of my family and myself.
• 56:41
  SPEAKER_01: It's incredible you know and just to have those kinds of positive results is just so gratifying.
• 56:47
  SPEAKER_00: I want to ask you one more thing though.
• 56:49
  SPEAKER_01: I want to ask you you mentioned azalic acid you patented azalic acid yeah I did the original research on that and uh the reason was that I was using it we were making ricin at the time to attach to uh monoclonal antibodies to treat terminal melanoma with a company called Hybridon.
• 57:04
  SPEAKER_01: So the first biotech company in San Diego.
• 57:06
  SPEAKER_01: And so I was extracting that from the castor bean and it had about a 70% prolongation of life for a year.
• 57:13
  SPEAKER_01: But I wondered why wasn't the castor bean destroyed because the ricin was such a potent weapon of mass destruction.
• 57:19
  SPEAKER_01: And it was because it was bound to the azoleic acid.
• 57:21
  SPEAKER_01: And so I really started looking at the azoleic acid and found that it had some very potent type of effects when I looked at veterin cellular biology all these different disciplines out there, but nobody really put it together for dermatology.
• 57:35
  SPEAKER_01: And because it was a lipid and we had done all this work with Dr.
• 57:38
  SPEAKER_01: Stoughton and was involved with the development of diperline and alkyl metazone those were a couple of those things projects I worked on and getting those invented, I had a very good basis uh in lipid biology already of the skin.
• 57:51
  SPEAKER_01: And so I found that the azolic acid not only was very potent for anti-inflammatory, but it was also broad spectrum anti-inflammatory also broad spectrum antimicrobial was also prevented metaplasia that occurred and even as a drug delivery agent for 5FU, we were able to turn down the incidence of contact reactions and improve the killing of actinkeratoses, particularly hypertrophic actinokeratoses using the aslaic acid as a carrier for 5FU.
• 58:19
  SPEAKER_01: So I had a number of patents with uh aslaic acid including the original patents for rosacea seboric dermatitis and ectino keratoses and so back in 1986.
• 58:30
  SPEAKER_00: Yeah so that's that's so impressive like I'm just so blown away with all of your discoveries.
• 58:35
  SPEAKER_00: That's that's amazing.
• 58:36
  SPEAKER_00: Yeah I as like I see it everywhere now you know everyone's trying to get behind you know using as like more and more and so it's interesting to see the the drug you know come up more in conversation now but that's that's profound.
• 58:48
  SPEAKER_01: Yeah the key with that more than anything is it's formulation system.
• 58:52
  SPEAKER_01: You've give there's very specific things that you need to do and that's why we have it in so many of our products because I know what it does and I know that it also transports some of these very difficult architecturally uh irregular molecules to deliver them to the right strata.
• 59:06
  SPEAKER_00: Wow well thank you so much.
• 59:08
  SPEAKER_00: This has been this is amazing.
• 59:09
  SPEAKER_00: I would love to have you back.
• 59:10
  SPEAKER_01: I was wondering I'd love to come back thank you.
• 59:12
  SPEAKER_01: There's so much more to talk about along so much once again thank you so much for taking the time this has been a real pleasure.
• 59:18
  SPEAKER_01: So this is my first true podcast so you did amazing this was this was wonderful.
• 59:22
  SPEAKER_00: I think this is one of my best podcasts I've recorded this year.
• 59:25
  SPEAKER_01: So great.
• 59:26
  SPEAKER_01: Well thank you so much.
• 59:28
  SPEAKER_01: Thank you so much.