WEBVTT - Ep 157 Retinoids Part 2: …how it’s going 0:00:00.880 --> 0:00:04.040 From the moment of birth you begin to age. The 0:00:04.160 --> 0:00:08.720 changes are almost entirely internal and imperceptible, but by your 0:00:08.760 --> 0:00:12.760 twenties the sun has probably left its first telltale marks 0:00:12.800 --> 0:00:16.279 on your most prominent feature, your face. You start to 0:00:16.280 --> 0:00:20.080 get tiny lines or wrinkles, or, as dermatologists put it, 0:00:20.440 --> 0:00:25.040 you experience photo aging, usually by your early thirties, and 0:00:25.120 --> 0:00:29.159 with each passing year, those first fine furrows begin to 0:00:29.240 --> 0:00:33.600 deepen and multiply. To some, the lines are signs of 0:00:33.720 --> 0:00:37.040 character or a merry disposition to be neither fretted over 0:00:37.159 --> 0:00:41.080 nor fought against. To many others, though, they are scars, 0:00:41.600 --> 0:00:47.440 reminders of the disappearance of youth. Not surprisingly, then, eliminating 0:00:47.479 --> 0:00:51.720 wrinkles is a roughly three billion dollar business in youth 0:00:51.760 --> 0:00:56.040 conscious America. In the past fifteen months, however, we have 0:00:56.120 --> 0:00:58.840 been told that much of this energy and enterprise may 0:00:58.840 --> 0:01:02.360 have been rendered obsene elite by a drug that purports 0:01:02.400 --> 0:01:06.959 to improve skin tone and erase wrinkles. Its scientific name 0:01:07.160 --> 0:01:10.520 is all trans retinoic acid, but most of us know 0:01:10.600 --> 0:01:14.520 it by its brand name retine Once, a popular acne 0:01:14.560 --> 0:01:18.160 cream marketed by Orthopharmaceutical, a six hundred million dollar a 0:01:18.240 --> 0:01:23.399 year subsidiary of nine billion dollar Johnson and Johnson. Retine 0:01:23.440 --> 0:01:25.880 has been hailed by doctors and the press as the 0:01:25.920 --> 0:01:29.680 first drug as opposed to a cosmetic that shows promise 0:01:29.760 --> 0:01:33.120 not only in treating the symptoms of aging, but also 0:01:33.360 --> 0:02:26.680 in actually reversing part of the process itself. She liked 0:02:26.680 --> 0:02:28.119 my dramatic rendition there. 0:02:28.160 --> 0:02:31.919 I loved the dramatic rendition. I do want to know 0:02:32.160 --> 0:02:35.240 how big the industry is today because I can't say 0:02:35.600 --> 0:02:37.320 Money magazine right, okay? 0:02:37.760 --> 0:02:38.519 Eighty wait? 0:02:38.800 --> 0:02:40.600 Three billion dollars in nineteen eighty eight. 0:02:41.600 --> 0:02:46.720 Wow. Yeah. So that quote was excerpted from the article 0:02:46.720 --> 0:02:49.120 that you quoted erin thank you for sending me this 0:02:49.520 --> 0:02:52.560 last episode, which was the selling of retinee by Leslie 0:02:52.680 --> 0:02:57.480 Freeland in CNN Money Magazine, published April first, nineteen eighty nine. 0:02:57.760 --> 0:03:02.239 Nineteen eighty nine. Got it. Oh, I'm so excited for 0:03:02.280 --> 0:03:02.840 this episode. 0:03:02.919 --> 0:03:03.880 It's going to be a good one. 0:03:04.639 --> 0:03:07.840 Hi. I'm Aaron Welsh and I'm Aaron Alman Updike and 0:03:08.000 --> 0:03:09.800 this is this podcast will kill. 0:03:09.639 --> 0:03:12.760 You so last week. If you haven't listened to last 0:03:12.800 --> 0:03:17.040 week's episode, I recommend it must you before today, not necessarily, 0:03:17.080 --> 0:03:18.399 but it's a good primer. 0:03:18.760 --> 0:03:19.720 Yeah. 0:03:19.760 --> 0:03:25.840 No, makeup term intended. Get it sit of one, because 0:03:25.919 --> 0:03:29.400 last week we focused all about how retine came to 0:03:29.440 --> 0:03:34.200 be and really the horrific backstory of the person Albert Kligman, 0:03:34.240 --> 0:03:36.840 who was very much at the forefront of the development 0:03:36.880 --> 0:03:40.840 of retine and all of the horribly unethical experiments that 0:03:40.920 --> 0:03:43.960 went down in order to create this product that now 0:03:44.080 --> 0:03:48.320 is so ubiquitous. And today we are going to talk 0:03:48.360 --> 0:03:51.680 about what retine even is, what are all of the 0:03:51.720 --> 0:03:54.160 other retinoyans that are out there, and what do they 0:03:54.160 --> 0:03:56.440 do and do they actually work? And how and why? 0:03:57.080 --> 0:04:02.480 How and why? Love it so excited because I that's 0:04:02.480 --> 0:04:04.800 definitely something I didn't come across in any bit of 0:04:04.800 --> 0:04:07.320 my research. I was like, I don't I don't know 0:04:07.640 --> 0:04:13.280 if retinol works for anti aging or whatever. And I 0:04:13.640 --> 0:04:17.400 know that I have my biases in terms of disbelieving 0:04:17.440 --> 0:04:20.880 any claim that any skin care products makes in general. 0:04:21.160 --> 0:04:24.320 But yeah, yeah, yeah, it's gonna be fun. We're gonna 0:04:24.360 --> 0:04:27.320 get all into it. But first first, we're drinking the 0:04:27.360 --> 0:04:28.800 same thing as last week we are. 0:04:29.560 --> 0:04:36.040 Quarantiny is skin deep and it has carrot juice again, 0:04:36.680 --> 0:04:40.760 Vitamin A blah blah blah, beta carrote. I remember that 0:04:41.440 --> 0:04:45.200 made a caroteen to vitamin A to trettonoen. Yeah, that's 0:04:45.240 --> 0:04:47.840 the pathway. So we got carrot juice in there, we 0:04:47.920 --> 0:04:52.120 got ginger lemon vodka. You know, it's a it's a hit. 0:04:52.440 --> 0:04:54.840 It's a hit. And the full recipe is up on 0:04:54.880 --> 0:04:57.400 our website, this podcast with kit you dot com, and 0:04:57.600 --> 0:05:00.560 our social media channels. If you're not following us, you 0:05:00.600 --> 0:05:03.480 should be. And we've always got a non alcoholic Plussy 0:05:03.480 --> 0:05:05.599 Berita version as well. 0:05:05.640 --> 0:05:09.400 On our website, you can find great things. You can 0:05:09.400 --> 0:05:11.880 find transcripts, you can find the sources for each and 0:05:11.880 --> 0:05:14.720 every one of our episodes. You can find a contact 0:05:14.839 --> 0:05:17.360 us form if you want to hear a certain topic, 0:05:17.680 --> 0:05:19.640 or you just want to say hi, or if you 0:05:19.680 --> 0:05:21.919 say hey, come say hi to us, come to my 0:05:22.760 --> 0:05:26.039 organization and give a talk. We've got a submit your 0:05:26.040 --> 0:05:28.560 first hand account for and we've got links to merch 0:05:28.760 --> 0:05:32.200 to Patreon, to music by Bloodmobile, to our bookshop dot 0:05:32.320 --> 0:05:34.120 org affiliate account, our Goodreads list. 0:05:34.760 --> 0:05:37.880 Wow, I think so many things on that one little website. 0:05:37.920 --> 0:05:45.400 Who can believe it? Oh also rate, review and subscribe. Okay, 0:05:45.640 --> 0:05:48.720 shall we get into this is going to be a 0:05:48.760 --> 0:05:50.880 big one, So I let's just take a break and 0:05:50.920 --> 0:05:51.440 get started. 0:05:51.640 --> 0:05:52.360 That sounds great. 0:06:17.040 --> 0:06:22.280 Retinoids, retinoids. So how I'm going to try and break 0:06:22.279 --> 0:06:25.640 down or organize this episode is we'll first talk about 0:06:25.320 --> 0:06:28.719 what the heck is a retinoid and what is like 0:06:28.839 --> 0:06:31.960 vitamin a and again not a ton of detail, because 0:06:32.080 --> 0:06:35.560 we're really going to focus on the uses of vitamin 0:06:35.600 --> 0:06:41.000 A or retinoids in skin and skincare, and then how 0:06:41.040 --> 0:06:44.280 and what the evidence is to actually support that, And 0:06:44.360 --> 0:06:48.919 then finally we'll get into how that evidence has perhaps 0:06:49.000 --> 0:06:54.240 been extrapolated by the cosmetic industry to sell us all 0:06:54.279 --> 0:06:57.400 anti aging products and whether or not there's any data 0:06:57.440 --> 0:06:59.880 to support such extrapolations. 0:07:00.320 --> 0:07:02.360 Love it, Oh my gosh, I'm so excited. 0:07:02.440 --> 0:07:04.840 It's going to be really, really fun. I'm excited about it. 0:07:05.480 --> 0:07:10.440 So the term retinoid encompasses a pretty wide range of chemicals. 0:07:10.880 --> 0:07:15.520 Retinoids as a large group, are essentially all either vitamin 0:07:15.560 --> 0:07:20.600 A derivatives or they function like vitamin A in our 0:07:20.640 --> 0:07:24.440 bodies or in our skin. So whatever their chemical structure 0:07:24.480 --> 0:07:28.600 may be, because especially with the development of more synthetic retinoids, 0:07:28.600 --> 0:07:32.280 they don't look the same as vitamin A looks. Whatever 0:07:32.320 --> 0:07:35.840 their chemical structure the things that we classify as retinoids 0:07:36.240 --> 0:07:42.480 are binding to specific receptors, retinoid receptors and acting in 0:07:42.520 --> 0:07:46.680 a similar way to vitamin A and vitamin a's other 0:07:46.800 --> 0:07:50.840 name is retinol or all trans retinol. And again there 0:07:50.840 --> 0:07:53.440 are a bunch of different types or a bunch of 0:07:53.440 --> 0:07:56.280 different forms, and you might be familiar with some of 0:07:56.280 --> 0:08:05.360 these names. Retinol, retinal esters, retinal the hide, tretonoen isotretonoen adapolene. 0:08:05.760 --> 0:08:10.720 There is a whole range of these chemicals and they 0:08:10.760 --> 0:08:14.600 all again function at these retinoid receptors, and we're gonna 0:08:14.680 --> 0:08:17.640 lump them for the purposes of this episode into two 0:08:18.000 --> 0:08:26.200 major buckets, prescription retinoids and over the counter retinoids. Cool. Cool, 0:08:26.720 --> 0:08:29.360 So what the heck do any of these retinoids actually do? 0:08:30.280 --> 0:08:34.280 Vitamin A, which vitamin A is, just call it like 0:08:34.679 --> 0:08:37.560 equivalent to all of these for the purposes of this Okay, 0:08:37.880 --> 0:08:38.800 we're lumping it all. 0:08:39.000 --> 0:08:39.440 That's fine. 0:08:40.040 --> 0:08:43.680 Vitamin A is an essential nutrient. It's a fat soluble vitamin, 0:08:43.800 --> 0:08:46.360 so it dissolves in fat and we can store it 0:08:46.400 --> 0:08:49.439 in our fat. And like all vitamins, this is something 0:08:49.440 --> 0:08:52.480 that we need in our diets. We don't make it ourselves, 0:08:52.559 --> 0:08:56.840 and it is essential for life and survival. We need 0:08:56.920 --> 0:09:01.439 vitamin A from the very earliest stages of embryonic development 0:09:01.840 --> 0:09:05.560 all the way until our death. Vitamin A is essential 0:09:05.679 --> 0:09:09.320 in the formation of our nervous system and the way 0:09:09.360 --> 0:09:12.559 that our bodies are built and patterned as an embryo, 0:09:12.720 --> 0:09:15.560 like the way that an embryo is literally built. And 0:09:15.640 --> 0:09:18.680 it's also essential for vision, and its role in vision 0:09:18.800 --> 0:09:21.440 is really well established and again worthy of its whole 0:09:21.520 --> 0:09:24.560 own episode. But that's not today. 0:09:24.840 --> 0:09:26.960 That's not today. 0:09:27.000 --> 0:09:29.160 We get vitamin A in our diet in the form 0:09:29.240 --> 0:09:32.719 of carotenoids like beta carotene in our carrots, and then 0:09:32.760 --> 0:09:36.120 also from eating ingesting like pre formed vitamin A in 0:09:36.120 --> 0:09:38.720 our foods, like if you're eating meat, it probably has 0:09:38.760 --> 0:09:42.280 some vitamin A in it as well. Okay, but today 0:09:42.280 --> 0:09:45.679 we're going to focus on how we use retinoids, specifically 0:09:45.720 --> 0:09:48.800 in our skin, because they have become such a seemingly 0:09:49.000 --> 0:09:53.359 ubiquitous and essential part of skin care. So to understand 0:09:53.520 --> 0:09:57.160 how these retinoids work in our skin, let us first 0:09:57.280 --> 0:10:01.520 understand our skin a little bit better love it. So. 0:10:01.640 --> 0:10:06.120 Our skin is composed of three major layers, starting from 0:10:06.160 --> 0:10:09.240 the bottom, aka the inside of our bodies, and going 0:10:09.280 --> 0:10:12.400 towards the outside, we have the subcutaneous tissue. It's also 0:10:12.440 --> 0:10:15.920 called the hypodermis, and that's mostly just like fat and stuff. 0:10:15.960 --> 0:10:18.960 It's like your fluff, right, okay. And then you have 0:10:19.080 --> 0:10:22.120 your dermis, which is like the bottom layer of what 0:10:22.240 --> 0:10:25.439 is really like skin, skin, and your dermis is made 0:10:25.520 --> 0:10:29.120 up of stuff like collagen and elastins, which are made 0:10:29.160 --> 0:10:32.520 by these cells that are called fibroblasts. Your dermis is 0:10:32.520 --> 0:10:35.280 also where all of the blood supply is to your skin. 0:10:36.640 --> 0:10:40.080 And your dermis is like the really strong part that 0:10:40.160 --> 0:10:44.080 really holds us together, like quite literally. And then on 0:10:44.200 --> 0:10:48.040 top of your dermis is your epidermis. And your epidermis 0:10:48.280 --> 0:10:51.360 is very very thin. It ranges like on the soles 0:10:51.360 --> 0:10:53.120 of your feet and the palms of your hands. It's 0:10:53.160 --> 0:10:56.240 the thickest, maybe the width of like two credit cards 0:10:56.280 --> 0:10:58.720 stacked together, all right, if you can imagine that. I 0:10:58.720 --> 0:11:00.840 don't know. Whenever I see those, I'm like, I don't know, 0:11:00.880 --> 0:11:03.080 is that the fancy credit cards now were like old 0:11:03.080 --> 0:11:05.400 school credit cards. I don't know. It pretty thin. 0:11:05.640 --> 0:11:07.680 One of mine is metal and very thick. But I'll 0:11:07.720 --> 0:11:09.000 just say one of that it's. 0:11:08.880 --> 0:11:25.480 That it's like that thick, I don't know. And then 0:11:25.559 --> 0:11:28.360 in other places, like the skin on your eyelids is 0:11:28.400 --> 0:11:30.680 incredibly thin, like the width of maybe a sheet of 0:11:30.720 --> 0:11:36.440 paper thick, okay, And our epidermis, like specifically, this teeny 0:11:36.600 --> 0:11:40.400 tiny little layer is the number one protection that we 0:11:40.520 --> 0:11:44.360 have from the outside world. And despite how relatively thin 0:11:44.559 --> 0:11:48.000 it is, just like in general and also compared to 0:11:48.080 --> 0:11:52.960 the other layers the dermis and our subcutaneous tissue, it 0:11:53.160 --> 0:11:56.600 still also has a whole bunch of layers within it. 0:11:57.840 --> 0:11:59.760 And we talked a little bit about the different layers 0:11:59.760 --> 0:12:04.400 of in our skin cancer episode. But it's I almost 0:12:04.400 --> 0:12:08.200 imagine it like one of those really really fancy cakes 0:12:08.200 --> 0:12:11.760 that they make on Great British Bake Off, where you 0:12:11.840 --> 0:12:14.120 have like a bunch of different layers that are like 0:12:14.200 --> 0:12:17.200 different compartments, but all together they're like delicious cake. 0:12:17.679 --> 0:12:20.480 Okay, Like the really thin layers. Like how many layers 0:12:20.520 --> 0:12:21.040 are we talking? 0:12:21.280 --> 0:12:23.679 So let's get into it. There's the basil cell layer, 0:12:23.880 --> 0:12:26.720 which is the bottom of our epidermis. This sits on 0:12:26.840 --> 0:12:30.440 top of a basement membrane that touches our dermis, and 0:12:30.520 --> 0:12:34.560 our basil cell layer is the cells that proliferate. So 0:12:34.679 --> 0:12:39.760 these are like stem cells. They proliferate, they replicate, and 0:12:40.000 --> 0:12:45.280 as they replicate, they also migrate upwards towards the outside world, 0:12:45.360 --> 0:12:49.400 like towards the top of your epidermis. And as they migrate, 0:12:49.440 --> 0:12:53.600 they also differentiate. And the major cell that we have 0:12:53.840 --> 0:12:58.280 in our epidermis are called keratinocytes. And they're called this 0:12:58.320 --> 0:13:01.600 because they make keratin, which is the protein that we 0:13:01.679 --> 0:13:03.440 make in our skin and our hair and our nails, 0:13:03.480 --> 0:13:07.680 et cetera. And so this basil cell layer is the first, 0:13:07.760 --> 0:13:09.840 like the bottom layer, and then you have a bunch 0:13:09.920 --> 0:13:14.040 of these keratinocytes. And then as they migrate upwards and 0:13:14.080 --> 0:13:19.440 continue to differentiate, they form from these like fat, chunky, juicy, 0:13:19.880 --> 0:13:25.520 I don't know, like a moose layer cake up into 0:13:25.559 --> 0:13:30.120 something more flat and squat, like say, I don't know, 0:13:30.200 --> 0:13:32.120 like a meringue layer, like something a little bit a 0:13:32.160 --> 0:13:35.760 little bit more firs like fluffy, right, yeah, but not 0:13:35.800 --> 0:13:39.080 like a cooked meringue, something like a somewhere between super 0:13:39.160 --> 0:13:43.120 jelly and more firm. I'm losing it on the baking reference. 0:13:43.120 --> 0:13:43.480 I'm here. 0:13:44.040 --> 0:13:46.320 My baking knowledge is much more limited than yours. 0:13:48.000 --> 0:13:50.880 Like a pudding layer, no, not a pudding layer. Anyways, 0:13:50.960 --> 0:13:54.120 we're just going to layer Okay, well it'll make sense 0:13:54.160 --> 0:13:57.120 again at the top, so then they get to be 0:13:57.200 --> 0:14:01.080 more squat and flat and stuck really close together. And 0:14:01.120 --> 0:14:03.680 then at the very top of our skin, the very 0:14:03.679 --> 0:14:07.720 first layer, like when you're touching right here, that layer 0:14:07.880 --> 0:14:11.960 is super keratinized. Basically, those cells no longer even really 0:14:12.000 --> 0:14:14.480 look like cells. They just look like layers of keratin 0:14:14.520 --> 0:14:18.640 because they're so smushed and stuck together. They no longer 0:14:18.640 --> 0:14:21.680 have a nucleus. Those are kind of like fondant that 0:14:21.720 --> 0:14:23.240 you put on top of the cake. 0:14:24.320 --> 0:14:24.840 Hah hah. 0:14:26.000 --> 0:14:29.040 Okay, all right, this is what we're trying. That very 0:14:29.040 --> 0:14:33.160 important outermost layer, the fondant is called the stratum corneum, 0:14:33.760 --> 0:14:36.320 and the stratum cornium is a really important part of 0:14:36.360 --> 0:14:39.360 our whole epidermis. It holds our water in like fondant 0:14:39.400 --> 0:14:42.600 holds the rest of this jello cake together. It protects 0:14:42.680 --> 0:14:46.240 us against UV damage and oxidative stress. It protects it 0:14:46.240 --> 0:14:52.480 against infections and other environmental toxins. Just below this stratum corneum, 0:14:52.560 --> 0:14:56.960 all those other cells they're still very keratinized like that 0:14:57.160 --> 0:15:01.000 the next layer down, but they have a little bit 0:15:01.040 --> 0:15:03.960 more room between them. There's a little bit more kind 0:15:03.960 --> 0:15:09.040 of like mortar holding the bricks together, more fatty stuff, 0:15:09.840 --> 0:15:11.880 and then you have just the rest of your kind 0:15:11.880 --> 0:15:15.440 of cell layers down to that basal layer. Throughout this, 0:15:15.640 --> 0:15:18.880 we also have other cells, right. We have melanocytes, which 0:15:18.880 --> 0:15:23.960 are pigment producing cells. We also have hair follicles, sebaceous 0:15:24.000 --> 0:15:26.480 glands that produce sebum, We have nerves, we have other 0:15:26.520 --> 0:15:30.960 immune cells. But most of your skin are these keratinocytes. 0:15:32.000 --> 0:15:37.440 So being our largest organ by surface area, a lot 0:15:37.440 --> 0:15:41.320 of different things can go wrong in our skin, especially 0:15:41.360 --> 0:15:45.800 as it is constantly being insulted from everything in our environment. 0:15:46.800 --> 0:15:52.360 And as it turns out, retinoids are used medically by 0:15:52.400 --> 0:15:57.760 prescription to treat a pretty wide variety of skin conditions. 0:15:58.520 --> 0:16:01.640 So let's get into some of this, focusing mostly on 0:16:01.760 --> 0:16:04.720 prescription retinoids here. We'll talk more about over the counter 0:16:05.040 --> 0:16:09.360 versions later. Prescription retinoids are often used to treat acne, 0:16:09.440 --> 0:16:11.760 which is again what you talked a lot about Aaron 0:16:11.760 --> 0:16:14.600 in last week's episode. One of the main first things 0:16:14.600 --> 0:16:18.240 that we figured out that retinoids can do so acne 0:16:18.600 --> 0:16:22.520 is what happens when pores and your hair follicles, which 0:16:22.600 --> 0:16:24.600 poors are kind of like hair follicles that no longer 0:16:24.640 --> 0:16:27.520 have a follicle in them. They're just little channels down 0:16:27.560 --> 0:16:31.040 to the lower layers of your skin. When these get 0:16:31.160 --> 0:16:37.000 stuffed with dead skin cells and bacteria that end up proliferating, 0:16:38.040 --> 0:16:41.600 they can eventually come to the surface and burst forth, 0:16:41.760 --> 0:16:44.080 and when that happens, you get a lot of inflammation, 0:16:44.480 --> 0:16:46.840 you get a lot of pain, and potentially a lot 0:16:46.880 --> 0:16:51.440 of scarring. We use retinoids very often to treat acne, 0:16:51.720 --> 0:16:55.480 especially to treat acne that can cause that kind of scarring, 0:16:55.520 --> 0:16:59.480 because not all acne does. Retinoids are also used to 0:16:59.520 --> 0:17:03.960 treat some kinds of psoriasis, and psoriasis is something that 0:17:04.000 --> 0:17:07.400 can result in what are called like hyper keratotic, meaning 0:17:07.440 --> 0:17:12.760 there's a lot of like thick, disorganized keratin production and 0:17:12.800 --> 0:17:16.960 it forms these plaques, and so retinoids can be used 0:17:17.000 --> 0:17:18.080 to help treat that. 0:17:18.880 --> 0:17:20.399 How do those plaques form? 0:17:20.760 --> 0:17:23.880 Oh, my gosh, soriasis is its whole own episode, I. 0:17:23.800 --> 0:17:25.800 Know, is there like a TLDR. 0:17:26.400 --> 0:17:30.159 TLDR is it's like disorganization of keratinization and like the 0:17:30.200 --> 0:17:33.119 sloughing of your skin, and it's an autoimmune disorder. So 0:17:33.119 --> 0:17:34.560 there's like a lot more detail to it. 0:17:34.600 --> 0:17:37.359 Did not read the instruction manual and we're just gonna 0:17:37.400 --> 0:17:39.080 throw carrotin everywhere. 0:17:39.080 --> 0:17:39.920 Right right, right, right? 0:17:40.240 --> 0:17:40.920 Okay? Is that? 0:17:42.240 --> 0:17:44.520 Yeah, it's like a lot more detailed than that, especially 0:17:44.520 --> 0:17:47.840 for psoriasis, because it's like autoimmune, so there's like your 0:17:47.880 --> 0:17:50.720 immune system in general not reading in the manual. So yeah, 0:17:50.720 --> 0:17:56.719 in general, not reading manuals zachar it, okay. Retinoids are 0:17:56.720 --> 0:17:59.520 also sometimes used to treat certain types of skin cancers, 0:17:59.600 --> 0:18:05.440 including caposi, sarcoma, and also other more rare forms of 0:18:05.640 --> 0:18:08.960 things that tend to be under this umbrella of like 0:18:09.760 --> 0:18:14.200 abnormal keratinization or what's called desquamation, which is basically when 0:18:14.200 --> 0:18:17.560 your cells are not adherent to each other in your 0:18:17.560 --> 0:18:19.320 skin the way that they should be, right, because they 0:18:19.320 --> 0:18:23.560 should be pretty well brick and mortared together, like enclosed 0:18:23.560 --> 0:18:27.200 by this fondant is like one tight nug right yeah. 0:18:27.280 --> 0:18:30.119 But disclamation means that things are not well connected, so 0:18:30.119 --> 0:18:32.280 then you get a lot of flaking, a lot of itching. 0:18:32.680 --> 0:18:36.400 So these are things like ichthiosis or Dernier's disease. There's 0:18:36.400 --> 0:18:39.200 a lot of different things that can potentially benefit from 0:18:39.240 --> 0:18:44.560 retinoid treatment, and of course the big elephant, the wrinkly 0:18:44.600 --> 0:18:50.080 elephant in the room. Retinoids are used for photoaging. Now 0:18:50.359 --> 0:18:54.760 let's take a minute here, shall we. Aging, of course, 0:18:55.480 --> 0:18:58.640 is a completely natural process. And I don't mean natural 0:18:58.720 --> 0:19:01.439 in quote unquotes the way that says the word natural. 0:19:02.960 --> 0:19:06.199 I mean that aging is not a disease state, but 0:19:06.880 --> 0:19:10.879 it is characterized by visible changes in the architecture of 0:19:10.920 --> 0:19:15.080 our skin. Aging skin is characterized by things like a 0:19:15.160 --> 0:19:19.080 loss of hydration and like an inability to regulate hydration 0:19:19.240 --> 0:19:22.440 as well because of damage to that kind of outer 0:19:22.560 --> 0:19:26.600 layer of skin. It's also characterized by reduced collagen production, 0:19:27.200 --> 0:19:30.920 a loss of elasticity, and a delay in recovery after 0:19:31.080 --> 0:19:36.440 injury to the skin. And there's probably more UV damage 0:19:36.480 --> 0:19:40.880 like exposure to the sun speeds up and exacerbates this 0:19:41.000 --> 0:19:44.560 aging process in a way. And that is the process 0:19:44.680 --> 0:19:48.199 that people are talking about when they say photoaging. And 0:19:48.280 --> 0:19:52.440 so photoaging looks like all of the things that I'm 0:19:52.440 --> 0:19:55.000 not going to say any brand names, but certain brand 0:19:55.240 --> 0:19:58.479 of skin care product commercials might tell you that you 0:19:58.600 --> 0:20:00.080 must avoid at all costs. 0:20:00.280 --> 0:20:00.399 Right. 0:20:00.920 --> 0:20:06.080 It manifests on your skin as things like fine lines, wrinkles, dispigmentation, 0:20:06.680 --> 0:20:10.920 things called solar linigenies, which are those like spots, sun spots, 0:20:11.400 --> 0:20:15.240 loss of elasticity, blah blah blah blah blah. Histologically, we 0:20:15.280 --> 0:20:19.320 see a thinning of your epidermis so that those cake 0:20:19.440 --> 0:20:24.600 layers all together are thinner, okay, and disorganization of some 0:20:24.640 --> 0:20:27.399 of the connective tissue. So it's not like laid down 0:20:27.520 --> 0:20:30.159 in really nice sheets the way that it is in 0:20:30.280 --> 0:20:31.520 non photo damage skin. 0:20:32.000 --> 0:20:33.520 Looks like a cake that I would make. 0:20:33.600 --> 0:20:39.320 Then I think you can make a great cake here, 0:20:39.359 --> 0:20:40.720 and don't sell yourself short. 0:20:40.720 --> 0:20:43.320 Thank you, But I beg to differ. 0:20:44.440 --> 0:20:49.000 It's a homemade cake, okay. Yes, And so all of 0:20:49.040 --> 0:20:52.040 these changes are going to vary not just with the 0:20:52.080 --> 0:20:55.560 amount of UV exposure that someone's exposed to, but also 0:20:55.680 --> 0:20:58.000 with things like the amount of melanin in your skin, 0:20:58.119 --> 0:21:01.640 because melanin, which is the pigment produced by our melanocytes, 0:21:01.800 --> 0:21:05.840 is protective against UV damage. And it's just going to 0:21:05.920 --> 0:21:08.600 vary based on straight up genetics in ways that we 0:21:08.680 --> 0:21:11.560 don't fully understand. But there's a lot of genetics involved 0:21:11.640 --> 0:21:17.040 in both aging and photo aging. So how do retinoids 0:21:17.040 --> 0:21:19.640 then fit into these drugs? I said that we use 0:21:19.680 --> 0:21:23.360 them for these things, how exactly like, what are they 0:21:23.960 --> 0:21:24.880 doing right? 0:21:25.119 --> 0:21:27.240 And how are they doing all of these different things 0:21:27.240 --> 0:21:30.000 because it sounds like the mechanisms of aging or the 0:21:30.040 --> 0:21:33.919 mechanisms of a condition like psoriasis, like acne are different. 0:21:34.520 --> 0:21:37.639 So what is it? What is the unifying thing that is? 0:21:38.240 --> 0:21:39.919 Yeah, excellent question, let's get into it. 0:21:40.040 --> 0:21:40.480 Okay. 0:21:40.600 --> 0:21:44.000 So retinoids, I already said, are this group of a 0:21:44.080 --> 0:21:47.240 variety of different chemicals with different chemical structures that act 0:21:47.400 --> 0:21:52.119 on this common ground of these retinoid receptors. We have 0:21:52.160 --> 0:21:54.240 a bunch of these throughout our body, like six different 0:21:54.320 --> 0:21:57.000 kinds of retinoid receptors. There's a few of them, like 0:21:57.320 --> 0:21:59.840 three or four at least that are present in pretty 0:21:59.880 --> 0:22:04.480 good numbers in our epidermis and our deermis. What retinoids 0:22:04.520 --> 0:22:08.440 do is they bind to these specific receptors which are 0:22:08.520 --> 0:22:12.240 on our DNA. And what they do then is they 0:22:12.480 --> 0:22:16.760 modulate the expression of other genes. So what does that mean? 0:22:17.400 --> 0:22:20.560 They are changing the way that our skin cells are 0:22:20.680 --> 0:22:25.359 interacting with our environment. So our skin, again is the 0:22:25.400 --> 0:22:28.600 major barrier between us and our outside world. So we 0:22:28.680 --> 0:22:31.239 might think of it as just like a thing that 0:22:31.560 --> 0:22:34.399 just sits there, but it's not. It's an organ and 0:22:34.440 --> 0:22:38.680 it's a very dynamic organ It's constantly responding to changes 0:22:38.760 --> 0:22:42.560 changes in light and temperature, humidity, responding to pathogens, trying 0:22:42.560 --> 0:22:45.199 to fix all of the damage that UV rays are 0:22:45.200 --> 0:22:50.920 imposing on it. So topical retinoids especially bind to these 0:22:50.960 --> 0:22:55.280 retinoid receptors. They turn some genes on and turn other 0:22:55.400 --> 0:22:58.199 genes off. And what it seems like they do is 0:22:58.240 --> 0:23:02.159 they turn on genes that produce things like growth factors, 0:23:02.760 --> 0:23:05.960 and they turn off genes that do stuff like chop 0:23:06.119 --> 0:23:11.360 up collagen into tiny little bits. And they also can 0:23:11.400 --> 0:23:14.680 turn on genes that help to induce that skin cell, 0:23:14.720 --> 0:23:19.240 those keratinocytes to differentiate from that basal cell layer and 0:23:19.560 --> 0:23:25.639 just increase turnover overall of cells. Okay, so that's a 0:23:25.640 --> 0:23:27.520 lot of different functions, right, And. 0:23:27.520 --> 0:23:32.560 This is both topical and oral retinoids, So yeah, this 0:23:32.600 --> 0:23:34.320 is all of them are going to work in the 0:23:34.359 --> 0:23:34.720 same way. 0:23:34.760 --> 0:23:37.760 Topical retinoids and oral retinoids. They're going to bind to 0:23:37.800 --> 0:23:40.320 the same receptors, They're binding to the same things. The 0:23:40.640 --> 0:23:44.520 oral ones are going to be much stronger, and they're 0:23:44.520 --> 0:23:47.040 going to be binding to additional receptors that are not 0:23:47.160 --> 0:23:49.600 only present in your skin, but other places as well. 0:23:50.040 --> 0:23:54.199 And reaching deeper down into your dermis that topical preparations 0:23:54.200 --> 0:23:56.320 are not going to reach as well, because your dermis 0:23:56.320 --> 0:23:58.760 is where the blood flow is, and it's actually really 0:23:58.800 --> 0:24:01.359 hard to get things that you have topically all the 0:24:01.400 --> 0:24:02.400 way down deep. 0:24:02.640 --> 0:24:04.400 Right, too many layers of defense in there. 0:24:04.560 --> 0:24:08.439 Exactly, We've got such great skin. So all of this 0:24:08.600 --> 0:24:12.080 variety of functions, what does it end up doing? Like 0:24:12.080 --> 0:24:16.479 what do we see with retinoid application. We see a 0:24:16.600 --> 0:24:20.520 thickening of that epidermal layer, so the whole entire, from 0:24:20.560 --> 0:24:22.840 the basal layer to the top. We see a thickening 0:24:23.080 --> 0:24:27.480 of that, especially the moose section in the middle, those 0:24:27.520 --> 0:24:32.680 like healthy growing keratinocytes in the middle. We also see 0:24:32.720 --> 0:24:36.919 an increase in collagen and elastin production, and so this 0:24:36.960 --> 0:24:40.920 is sometimes called like a regeneration of the extracellular matrix. 0:24:40.960 --> 0:24:43.919 This is the stuff that holds our skin together. And 0:24:44.000 --> 0:24:48.200 because retinoids are turning off genes that are chopping up collagen, 0:24:48.440 --> 0:24:53.080 we see more collagen and elastin being made. And because 0:24:53.119 --> 0:24:57.080 it's also increasing cell turnover, what that means is that 0:24:57.119 --> 0:25:01.080 you're sloughing off skin. It's pushing from that basal layer 0:25:01.160 --> 0:25:03.399 up and up and up to that stratum corneum and 0:25:03.440 --> 0:25:09.760 being kicked off of our bodies into my carpet more rapidly. Okay, 0:25:09.880 --> 0:25:12.280