Speaker 1: From the moment of birth you begin to age. The
Speaker 1: changes are almost entirely internal and imperceptible, but by your
Speaker 1: twenties the sun has probably left its first telltale marks
Speaker 1: on your most prominent feature, your face. You start to
Speaker 1: get tiny lines or wrinkles, or, as dermatologists put it,
Speaker 1: you experience photo aging, usually by your early thirties, and
Speaker 1: with each passing year, those first fine furrows begin to
Speaker 1: deepen and multiply. To some, the lines are signs of
Speaker 1: character or a merry disposition to be neither fretted over
Speaker 1: nor fought against. To many others, though, they are scars,
Speaker 1: reminders of the disappearance of youth. Not surprisingly, then, eliminating
Speaker 1: wrinkles is a roughly three billion dollar business in youth
Speaker 1: conscious America. In the past fifteen months, however, we have
Speaker 1: been told that much of this energy and enterprise may
Speaker 1: have been rendered obsene elite by a drug that purports
Speaker 1: to improve skin tone and erase wrinkles. Its scientific name
Speaker 1: is all trans retinoic acid, but most of us know
Speaker 1: it by its brand name retine Once, a popular acne
Speaker 1: cream marketed by Orthopharmaceutical, a six hundred million dollar a
Speaker 1: year subsidiary of nine billion dollar Johnson and Johnson. Retine
Speaker 1: has been hailed by doctors and the press as the
Speaker 1: first drug as opposed to a cosmetic that shows promise
Speaker 1: not only in treating the symptoms of aging, but also
Speaker 1: in actually reversing part of the process itself. She liked
Speaker 1: my dramatic rendition there.
Speaker 2: I loved the dramatic rendition. I do want to know
Speaker 2: how big the industry is today because I can't say
Speaker 2: Money magazine right, okay?
Speaker 1: Eighty wait?
Speaker 2: Three billion dollars in nineteen eighty eight.
Speaker 1: Wow. Yeah. So that quote was excerpted from the article
Speaker 1: that you quoted erin thank you for sending me this
Speaker 1: last episode, which was the selling of retinee by Leslie
Speaker 1: Freeland in CNN Money Magazine, published April first, nineteen eighty nine.
Speaker 2: Nineteen eighty nine. Got it. Oh, I'm so excited for
Speaker 2: this episode.
Speaker 1: It's going to be a good one.
Speaker 2: Hi. I'm Aaron Welsh and I'm Aaron Alman Updike and
Speaker 2: this is this podcast will kill.
Speaker 1: You so last week. If you haven't listened to last
Speaker 1: week's episode, I recommend it must you before today, not necessarily,
Speaker 1: but it's a good primer.
Speaker 2: Yeah.
Speaker 1: No, makeup term intended. Get it sit of one, because
Speaker 1: last week we focused all about how retine came to
Speaker 1: be and really the horrific backstory of the person Albert Kligman,
Speaker 1: who was very much at the forefront of the development
Speaker 1: of retine and all of the horribly unethical experiments that
Speaker 1: went down in order to create this product that now
Speaker 1: is so ubiquitous. And today we are going to talk
Speaker 1: about what retine even is, what are all of the
Speaker 1: other retinoyans that are out there, and what do they
Speaker 1: do and do they actually work? And how and why?
Speaker 2: How and why? Love it so excited because I that's
Speaker 2: definitely something I didn't come across in any bit of
Speaker 2: my research. I was like, I don't I don't know
Speaker 2: if retinol works for anti aging or whatever. And I
Speaker 2: know that I have my biases in terms of disbelieving
Speaker 2: any claim that any skin care products makes in general.
Speaker 1: But yeah, yeah, yeah, it's gonna be fun. We're gonna
Speaker 1: get all into it. But first first, we're drinking the
Speaker 1: same thing as last week we are.
Speaker 2: Quarantiny is skin deep and it has carrot juice again,
Speaker 2: Vitamin A blah blah blah, beta carrote. I remember that
Speaker 2: made a caroteen to vitamin A to trettonoen. Yeah, that's
Speaker 2: the pathway. So we got carrot juice in there, we
Speaker 2: got ginger lemon vodka. You know, it's a it's a hit.
Speaker 1: It's a hit. And the full recipe is up on
Speaker 1: our website, this podcast with kit you dot com, and
Speaker 1: our social media channels. If you're not following us, you
Speaker 1: should be. And we've always got a non alcoholic Plussy
Speaker 1: Berita version as well.
Speaker 2: On our website, you can find great things. You can
Speaker 2: find transcripts, you can find the sources for each and
Speaker 2: every one of our episodes. You can find a contact
Speaker 2: us form if you want to hear a certain topic,
Speaker 2: or you just want to say hi, or if you
Speaker 2: say hey, come say hi to us, come to my
Speaker 2: organization and give a talk. We've got a submit your
Speaker 2: first hand account for and we've got links to merch
Speaker 2: to Patreon, to music by Bloodmobile, to our bookshop dot
Speaker 2: org affiliate account, our Goodreads list.
Speaker 1: Wow, I think so many things on that one little website.
Speaker 1: Who can believe it? Oh also rate, review and subscribe. Okay,
Speaker 1: shall we get into this is going to be a
Speaker 1: big one, So I let's just take a break and
Speaker 1: get started.
Speaker 2: That sounds great.
Speaker 1: Retinoids, retinoids. So how I'm going to try and break
Speaker 1: down or organize this episode is we'll first talk about
Speaker 1: what the heck is a retinoid and what is like
Speaker 1: vitamin a and again not a ton of detail, because
Speaker 1: we're really going to focus on the uses of vitamin
Speaker 1: A or retinoids in skin and skincare, and then how
Speaker 1: and what the evidence is to actually support that, And
Speaker 1: then finally we'll get into how that evidence has perhaps
Speaker 1: been extrapolated by the cosmetic industry to sell us all
Speaker 1: anti aging products and whether or not there's any data
Speaker 1: to support such extrapolations.
Speaker 2: Love it, Oh my gosh, I'm so excited.
Speaker 1: It's going to be really, really fun. I'm excited about it.
Speaker 1: So the term retinoid encompasses a pretty wide range of chemicals.
Speaker 1: Retinoids as a large group, are essentially all either vitamin
Speaker 1: A derivatives or they function like vitamin A in our
Speaker 1: bodies or in our skin. So whatever their chemical structure
Speaker 1: may be, because especially with the development of more synthetic retinoids,
Speaker 1: they don't look the same as vitamin A looks. Whatever
Speaker 1: their chemical structure the things that we classify as retinoids
Speaker 1: are binding to specific receptors, retinoid receptors and acting in
Speaker 1: a similar way to vitamin A and vitamin a's other
Speaker 1: name is retinol or all trans retinol. And again there
Speaker 1: are a bunch of different types or a bunch of
Speaker 1: different forms, and you might be familiar with some of
Speaker 1: these names. Retinol, retinal esters, retinal the hide, tretonoen isotretonoen adapolene.
Speaker 1: There is a whole range of these chemicals and they
Speaker 1: all again function at these retinoid receptors, and we're gonna
Speaker 1: lump them for the purposes of this episode into two
Speaker 1: major buckets, prescription retinoids and over the counter retinoids. Cool. Cool,
Speaker 1: So what the heck do any of these retinoids actually do?
Speaker 1: Vitamin A, which vitamin A is, just call it like
Speaker 1: equivalent to all of these for the purposes of this Okay,
Speaker 1: we're lumping it all.
Speaker 2: That's fine.
Speaker 1: Vitamin A is an essential nutrient. It's a fat soluble vitamin,
Speaker 1: so it dissolves in fat and we can store it
Speaker 1: in our fat. And like all vitamins, this is something
Speaker 1: that we need in our diets. We don't make it ourselves,
Speaker 1: and it is essential for life and survival. We need
Speaker 1: vitamin A from the very earliest stages of embryonic development
Speaker 1: all the way until our death. Vitamin A is essential
Speaker 1: in the formation of our nervous system and the way
Speaker 1: that our bodies are built and patterned as an embryo,
Speaker 1: like the way that an embryo is literally built. And
Speaker 1: it's also essential for vision, and its role in vision
Speaker 1: is really well established and again worthy of its whole
Speaker 1: own episode. But that's not today.
Speaker 2: That's not today.
Speaker 1: We get vitamin A in our diet in the form
Speaker 1: of carotenoids like beta carotene in our carrots, and then
Speaker 1: also from eating ingesting like pre formed vitamin A in
Speaker 1: our foods, like if you're eating meat, it probably has
Speaker 1: some vitamin A in it as well. Okay, but today
Speaker 1: we're going to focus on how we use retinoids, specifically
Speaker 1: in our skin, because they have become such a seemingly
Speaker 1: ubiquitous and essential part of skin care. So to understand
Speaker 1: how these retinoids work in our skin, let us first
Speaker 1: understand our skin a little bit better love it. So.
Speaker 1: Our skin is composed of three major layers, starting from
Speaker 1: the bottom, aka the inside of our bodies, and going
Speaker 1: towards the outside, we have the subcutaneous tissue. It's also
Speaker 1: called the hypodermis, and that's mostly just like fat and stuff.
Speaker 1: It's like your fluff, right, okay. And then you have
Speaker 1: your dermis, which is like the bottom layer of what
Speaker 1: is really like skin, skin, and your dermis is made
Speaker 1: up of stuff like collagen and elastins, which are made
Speaker 1: by these cells that are called fibroblasts. Your dermis is
Speaker 1: also where all of the blood supply is to your skin.
Speaker 1: And your dermis is like the really strong part that
Speaker 1: really holds us together, like quite literally. And then on
Speaker 1: top of your dermis is your epidermis. And your epidermis
Speaker 1: is very very thin. It ranges like on the soles
Speaker 1: of your feet and the palms of your hands. It's
Speaker 1: the thickest, maybe the width of like two credit cards
Speaker 1: stacked together, all right, if you can imagine that. I
Speaker 1: don't know. Whenever I see those, I'm like, I don't know,
Speaker 1: is that the fancy credit cards now were like old
Speaker 1: school credit cards. I don't know. It pretty thin.
Speaker 2: One of mine is metal and very thick. But I'll
Speaker 2: just say one of that it's.
Speaker 1: That it's like that thick, I don't know. And then
Speaker 1: in other places, like the skin on your eyelids is
Speaker 1: incredibly thin, like the width of maybe a sheet of
Speaker 1: paper thick, okay, And our epidermis, like specifically, this teeny
Speaker 1: tiny little layer is the number one protection that we
Speaker 1: have from the outside world. And despite how relatively thin
Speaker 1: it is, just like in general and also compared to
Speaker 1: the other layers the dermis and our subcutaneous tissue, it
Speaker 1: still also has a whole bunch of layers within it.
Speaker 1: And we talked a little bit about the different layers
Speaker 1: of in our skin cancer episode. But it's I almost
Speaker 1: imagine it like one of those really really fancy cakes
Speaker 1: that they make on Great British Bake Off, where you
Speaker 1: have like a bunch of different layers that are like
Speaker 1: different compartments, but all together they're like delicious cake.
Speaker 2: Okay, Like the really thin layers. Like how many layers
Speaker 2: are we talking?
Speaker 1: So let's get into it. There's the basil cell layer,
Speaker 1: which is the bottom of our epidermis. This sits on
Speaker 1: top of a basement membrane that touches our dermis, and
Speaker 1: our basil cell layer is the cells that proliferate. So
Speaker 1: these are like stem cells. They proliferate, they replicate, and
Speaker 1: as they replicate, they also migrate upwards towards the outside world,
Speaker 1: like towards the top of your epidermis. And as they migrate,
Speaker 1: they also differentiate. And the major cell that we have
Speaker 1: in our epidermis are called keratinocytes. And they're called this
Speaker 1: because they make keratin, which is the protein that we
Speaker 1: make in our skin and our hair and our nails,
Speaker 1: et cetera. And so this basil cell layer is the first,
Speaker 1: like the bottom layer, and then you have a bunch
Speaker 1: of these keratinocytes. And then as they migrate upwards and
Speaker 1: continue to differentiate, they form from these like fat, chunky, juicy,
Speaker 1: I don't know, like a moose layer cake up into
Speaker 1: something more flat and squat, like say, I don't know,
Speaker 1: like a meringue layer, like something a little bit a
Speaker 1: little bit more firs like fluffy, right, yeah, but not
Speaker 1: like a cooked meringue, something like a somewhere between super
Speaker 1: jelly and more firm. I'm losing it on the baking reference.
Speaker 1: I'm here.
Speaker 2: My baking knowledge is much more limited than yours.
Speaker 1: Like a pudding layer, no, not a pudding layer. Anyways,
Speaker 1: we're just going to layer Okay, well it'll make sense
Speaker 1: again at the top, so then they get to be
Speaker 1: more squat and flat and stuck really close together. And
Speaker 1: then at the very top of our skin, the very
Speaker 1: first layer, like when you're touching right here, that layer
Speaker 1: is super keratinized. Basically, those cells no longer even really
Speaker 1: look like cells. They just look like layers of keratin
Speaker 1: because they're so smushed and stuck together. They no longer
Speaker 1: have a nucleus. Those are kind of like fondant that
Speaker 1: you put on top of the cake.
Speaker 2: Hah hah.
Speaker 1: Okay, all right, this is what we're trying. That very
Speaker 1: important outermost layer, the fondant is called the stratum corneum,
Speaker 1: and the stratum cornium is a really important part of
Speaker 1: our whole epidermis. It holds our water in like fondant
Speaker 1: holds the rest of this jello cake together. It protects
Speaker 1: us against UV damage and oxidative stress. It protects it
Speaker 1: against infections and other environmental toxins. Just below this stratum corneum,
Speaker 1: all those other cells they're still very keratinized like that
Speaker 1: the next layer down, but they have a little bit
Speaker 1: more room between them. There's a little bit more kind
Speaker 1: of like mortar holding the bricks together, more fatty stuff,
Speaker 1: and then you have just the rest of your kind
Speaker 1: of cell layers down to that basal layer. Throughout this,
Speaker 1: we also have other cells, right. We have melanocytes, which
Speaker 1: are pigment producing cells. We also have hair follicles, sebaceous
Speaker 1: glands that produce sebum, We have nerves, we have other
Speaker 1: immune cells. But most of your skin are these keratinocytes.
Speaker 1: So being our largest organ by surface area, a lot
Speaker 1: of different things can go wrong in our skin, especially
Speaker 1: as it is constantly being insulted from everything in our environment.
Speaker 1: And as it turns out, retinoids are used medically by
Speaker 1: prescription to treat a pretty wide variety of skin conditions.
Speaker 1: So let's get into some of this, focusing mostly on
Speaker 1: prescription retinoids here. We'll talk more about over the counter
Speaker 1: versions later. Prescription retinoids are often used to treat acne,
Speaker 1: which is again what you talked a lot about Aaron
Speaker 1: in last week's episode. One of the main first things
Speaker 1: that we figured out that retinoids can do so acne
Speaker 1: is what happens when pores and your hair follicles, which
Speaker 1: poors are kind of like hair follicles that no longer
Speaker 1: have a follicle in them. They're just little channels down
Speaker 1: to the lower layers of your skin. When these get
Speaker 1: stuffed with dead skin cells and bacteria that end up proliferating,
Speaker 1: they can eventually come to the surface and burst forth,
Speaker 1: and when that happens, you get a lot of inflammation,
Speaker 1: you get a lot of pain, and potentially a lot
Speaker 1: of scarring. We use retinoids very often to treat acne,
Speaker 1: especially to treat acne that can cause that kind of scarring,
Speaker 1: because not all acne does. Retinoids are also used to
Speaker 1: treat some kinds of psoriasis, and psoriasis is something that
Speaker 1: can result in what are called like hyper keratotic, meaning
Speaker 1: there's a lot of like thick, disorganized keratin production and
Speaker 1: it forms these plaques, and so retinoids can be used
Speaker 1: to help treat that.
Speaker 2: How do those plaques form?
Speaker 1: Oh, my gosh, soriasis is its whole own episode, I.
Speaker 2: Know, is there like a TLDR.
Speaker 1: TLDR is it's like disorganization of keratinization and like the
Speaker 1: sloughing of your skin, and it's an autoimmune disorder. So
Speaker 1: there's like a lot more detail to it.
Speaker 2: Did not read the instruction manual and we're just gonna
Speaker 2: throw carrotin everywhere.
Speaker 1: Right right, right, right?
Speaker 2: Okay? Is that?
Speaker 1: Yeah, it's like a lot more detailed than that, especially
Speaker 1: for psoriasis, because it's like autoimmune, so there's like your
Speaker 1: immune system in general not reading in the manual. So yeah,
Speaker 1: in general, not reading manuals zachar it, okay. Retinoids are
Speaker 1: also sometimes used to treat certain types of skin cancers,
Speaker 1: including caposi, sarcoma, and also other more rare forms of
Speaker 1: things that tend to be under this umbrella of like
Speaker 1: abnormal keratinization or what's called desquamation, which is basically when
Speaker 1: your cells are not adherent to each other in your
Speaker 1: skin the way that they should be, right, because they
Speaker 1: should be pretty well brick and mortared together, like enclosed
Speaker 1: by this fondant is like one tight nug right yeah.
Speaker 1: But disclamation means that things are not well connected, so
Speaker 1: then you get a lot of flaking, a lot of itching.
Speaker 1: So these are things like ichthiosis or Dernier's disease. There's
Speaker 1: a lot of different things that can potentially benefit from
Speaker 1: retinoid treatment, and of course the big elephant, the wrinkly
Speaker 1: elephant in the room. Retinoids are used for photoaging. Now
Speaker 1: let's take a minute here, shall we. Aging, of course,
Speaker 1: is a completely natural process. And I don't mean natural
Speaker 1: in quote unquotes the way that says the word natural.
Speaker 1: I mean that aging is not a disease state, but
Speaker 1: it is characterized by visible changes in the architecture of
Speaker 1: our skin. Aging skin is characterized by things like a
Speaker 1: loss of hydration and like an inability to regulate hydration
Speaker 1: as well because of damage to that kind of outer
Speaker 1: layer of skin. It's also characterized by reduced collagen production,
Speaker 1: a loss of elasticity, and a delay in recovery after
Speaker 1: injury to the skin. And there's probably more UV damage
Speaker 1: like exposure to the sun speeds up and exacerbates this
Speaker 1: aging process in a way. And that is the process
Speaker 1: that people are talking about when they say photoaging. And
Speaker 1: so photoaging looks like all of the things that I'm
Speaker 1: not going to say any brand names, but certain brand
Speaker 1: of skin care product commercials might tell you that you
Speaker 1: must avoid at all costs.
Speaker 3: Right.
Speaker 1: It manifests on your skin as things like fine lines, wrinkles, dispigmentation,
Speaker 1: things called solar linigenies, which are those like spots, sun spots,
Speaker 1: loss of elasticity, blah blah blah blah blah. Histologically, we
Speaker 1: see a thinning of your epidermis so that those cake
Speaker 1: layers all together are thinner, okay, and disorganization of some
Speaker 1: of the connective tissue. So it's not like laid down
Speaker 1: in really nice sheets the way that it is in
Speaker 1: non photo damage skin.
Speaker 2: Looks like a cake that I would make.
Speaker 1: Then I think you can make a great cake here,
Speaker 1: and don't sell yourself short.
Speaker 2: Thank you, But I beg to differ.
Speaker 1: It's a homemade cake, okay. Yes, And so all of
Speaker 1: these changes are going to vary not just with the
Speaker 1: amount of UV exposure that someone's exposed to, but also
Speaker 1: with things like the amount of melanin in your skin,
Speaker 1: because melanin, which is the pigment produced by our melanocytes,
Speaker 1: is protective against UV damage. And it's just going to
Speaker 1: vary based on straight up genetics in ways that we
Speaker 1: don't fully understand. But there's a lot of genetics involved
Speaker 1: in both aging and photo aging. So how do retinoids
Speaker 1: then fit into these drugs? I said that we use
Speaker 1: them for these things, how exactly like, what are they
Speaker 1: doing right?
Speaker 2: And how are they doing all of these different things
Speaker 2: because it sounds like the mechanisms of aging or the
Speaker 2: mechanisms of a condition like psoriasis, like acne are different.
Speaker 2: So what is it? What is the unifying thing that is?
Speaker 1: Yeah, excellent question, let's get into it.
Speaker 2: Okay.
Speaker 1: So retinoids, I already said, are this group of a
Speaker 1: variety of different chemicals with different chemical structures that act
Speaker 1: on this common ground of these retinoid receptors. We have
Speaker 1: a bunch of these throughout our body, like six different
Speaker 1: kinds of retinoid receptors. There's a few of them, like
Speaker 1: three or four at least that are present in pretty
Speaker 1: good numbers in our epidermis and our deermis. What retinoids
Speaker 1: do is they bind to these specific receptors which are
Speaker 1: on our DNA. And what they do then is they
Speaker 1: modulate the expression of other genes. So what does that mean?
Speaker 1: They are changing the way that our skin cells are
Speaker 1: interacting with our environment. So our skin, again is the
Speaker 1: major barrier between us and our outside world. So we
Speaker 1: might think of it as just like a thing that
Speaker 1: just sits there, but it's not. It's an organ and
Speaker 1: it's a very dynamic organ It's constantly responding to changes
Speaker 1: changes in light and temperature, humidity, responding to pathogens, trying
Speaker 1: to fix all of the damage that UV rays are
Speaker 1: imposing on it. So topical retinoids especially bind to these
Speaker 1: retinoid receptors. They turn some genes on and turn other
Speaker 1: genes off. And what it seems like they do is
Speaker 1: they turn on genes that produce things like growth factors,
Speaker 1: and they turn off genes that do stuff like chop
Speaker 1: up collagen into tiny little bits. And they also can
Speaker 1: turn on genes that help to induce that skin cell,
Speaker 1: those keratinocytes to differentiate from that basal cell layer and
Speaker 1: just increase turnover overall of cells. Okay, so that's a
Speaker 1: lot of different functions, right, And.
Speaker 2: This is both topical and oral retinoids, So yeah, this
Speaker 2: is all of them are going to work in the
Speaker 2: same way.
Speaker 1: Topical retinoids and oral retinoids. They're going to bind to
Speaker 1: the same receptors, They're binding to the same things. The
Speaker 1: oral ones are going to be much stronger, and they're
Speaker 1: going to be binding to additional receptors that are not
Speaker 1: only present in your skin, but other places as well.
Speaker 1: And reaching deeper down into your dermis that topical preparations
Speaker 1: are not going to reach as well, because your dermis
Speaker 1: is where the blood flow is, and it's actually really
Speaker 1: hard to get things that you have topically all the
Speaker 1: way down deep.
Speaker 2: Right, too many layers of defense in there.
Speaker 1: Exactly, We've got such great skin. So all of this
Speaker 1: variety of functions, what does it end up doing? Like
Speaker 1: what do we see with retinoid application. We see a
Speaker 1: thickening of that epidermal layer, so the whole entire, from
Speaker 1: the basal layer to the top. We see a thickening
Speaker 1: of that, especially the moose section in the middle, those
Speaker 1: like healthy growing keratinocytes in the middle. We also see
Speaker 1: an increase in collagen and elastin production, and so this
Speaker 1: is sometimes called like a regeneration of the extracellular matrix.
Speaker 1: This is the stuff that holds our skin together. And
Speaker 1: because retinoids are turning off genes that are chopping up collagen,
Speaker 1: we see more collagen and elastin being made. And because
Speaker 1: it's also increasing cell turnover, what that means is that
Speaker 1: you're sloughing off skin. It's pushing from that basal layer
Speaker 1: up and up and up to that stratum corneum and
Speaker 1: being kicked off of our bodies into my carpet more rapidly. Okay,
Speaker 1: So that is one of the ways that it helps
Speaker 1: in acne because by pushing out cells more rapidly, you're
Speaker 1: also reducing the amount of sebum that's produced and sitting around,
Speaker 1: which helps to reduce the formation of those areas where
Speaker 1: you've got nuggets of dead skin cells that are being
Speaker 1: able to sit there, which means that you have less
Speaker 1: of a conducive environment for bacteria to grow and thrive. Yep.
Speaker 1: It's also why you often see if someone has acne
Speaker 1: or even doesn't have that much acne and starts using
Speaker 1: a retinoid, you can often see this. There's a lot
Speaker 1: of different terms for it, like purging is not a
Speaker 1: very medical term, but you can see a worsening of
Speaker 1: your acne when you initially start using it, and that's
Speaker 1: because it takes time for that epidermal turnover to push
Speaker 1: all of what's already deep in your skin out to
Speaker 1: the surface. Okay, and I'm not done. There's more. The
Speaker 1: reason that this then ends up helping in things like
Speaker 1: pigmentation changes like say sun spots, is because in increasing
Speaker 1: that cell turnover. You're reducing how much time the keratinocytes,
Speaker 1: those skin cells are in contact with the melanocytes, which
Speaker 1: is a fancy way of saying, you just have less
Speaker 1: pigment that's getting built up in random little cells. And
Speaker 1: in doing all of this, retinoids also seem to help
Speaker 1: protect against further UV damage. And I find this point
Speaker 1: especially interesting because retinoids can actually make people much more
Speaker 1: sensitive to the sun. They can heighten photosensitivity, they can
Speaker 1: make you have rashes or have more easy sunburns. But
Speaker 1: on a large scale, part of what they are doing
Speaker 1: is turning on and off genes that are also getting
Speaker 1: turned on and off in the opposite direction from UV damage,
Speaker 1: if that makes sense. So they're kind of counteracting what
Speaker 1: ultraviolet light is doing to our skin.
Speaker 2: Right, Okay, so if ultraviolet light says flips the switch
Speaker 2: to off, retinoids are flipping that on exactly.
Speaker 1: Okay. Yeah, So that is all of what we know,
Speaker 1: and again there's a lot more detail. I've got a
Speaker 1: bajillion papers if you want the real deep deats. But
Speaker 1: that is what we know about how these retinoids are
Speaker 1: working and why it is that they are used medically
Speaker 1: for the indications that they are often used for. Now,
Speaker 1: all of this data that we have is almost entirely
Speaker 1: exclusively from tretnoen aka retinoic acid aka the stuff you
Speaker 1: can only get with a prescription.
Speaker 2: So prescription only is that? Because like I want to
Speaker 2: know more about this, maybe this is a bigger question,
Speaker 2: but not because strength is that? Because application? Like why
Speaker 2: is it? Why is that prescription only?
Speaker 1: Oh? Erin we will get there, okay, okay, okay, okay, okay,
Speaker 1: but that is kind of like the big picture of
Speaker 1: retinoids in general. Okay, do you have any questions or
Speaker 1: I'm shocked.
Speaker 2: I mean I do, but I know that you're going
Speaker 2: to get into a lot of it, and so I'm like,
Speaker 2: I want to be like, but how does that this?
Speaker 2: And yeah, how does it increase cell proliferation? Is that
Speaker 2: thing all the time? Like is that something that we
Speaker 2: should aim for? Or is that have potential consequences?
Speaker 1: Like?
Speaker 2: Are there consequences to retinoid use? You?
Speaker 1: I mean absolutely yes, So there are definitely major side effects.
Speaker 1: The biggest side effect for topical preparations of any type
Speaker 1: of retinoid, but especially the prescription retinoids, so tretonoen and
Speaker 1: other similar retinoids, because there are other ones as well.
Speaker 1: The biggest side effect tends to be skin irritation, and
Speaker 1: that's because it is doing all of the things that
Speaker 1: we said that it's doing right, So it's increasing your
Speaker 1: cell turnover. It's like forcing your skin to be making
Speaker 1: a whole bunch more of what it's doing. And so,
Speaker 1: especially depending on your skin type, depending on what you've
Speaker 1: been using before, depending on your son exposure, some people
Speaker 1: have really strong negative reactions to various retinoids and really
Speaker 1: can't tolerate them. The other big thing to know about
Speaker 1: retinoids is that they are also to ratogenic, So teratogenic
Speaker 1: means potentially incredibly harmful to a developing fetus. Now this
Speaker 1: is very true for isotretinoin, which is the form of
Speaker 1: retinoid that is used orally in the US. There are
Speaker 1: other forms of retinoids that are used orally in other places.
Speaker 1: So this is true for oral forms of vitamin A.
Speaker 1: While vitamin A is like an absolutely necessary part of
Speaker 1: human embryotic development, like you can't make a brain or
Speaker 1: an embryo without vitamin A, it's concentration dependent, so if
Speaker 1: you have too much of it, you also are at
Speaker 1: risk for pretty severe developmental problems in a developing embryo.
Speaker 1: So with oral retinoids, we see very high rates of
Speaker 1: congenital defects, which can include anything from congenital heart malformations,
Speaker 1: neurologic malformations, so problems with your heart, problems with the nerves,
Speaker 1: problems with the way that the face is formed, and
Speaker 1: a whole range of like really really wide ranging developmental
Speaker 1: problems because it tends to affect really early stages of
Speaker 1: embryotic development, as well as a very high rate of
Speaker 1: spontaneous abortion when people are on oral retinoids and get pregnant.
Speaker 2: Okay, I have a couple of questions.
Speaker 1: Give it to me.
Speaker 2: Why would you go on oral retinoids versus topical Is
Speaker 2: it just to have more of these systemic or like
Speaker 2: deeper dermal effects.
Speaker 1: Great question. So the main indication medically for oral isotretinoin
Speaker 1: is severe acne that has been unrest responsive to everything else.
Speaker 2: Okay, and then question two. You said that high doses
Speaker 2: of vitamin A can lead to congenital defects. Is that
Speaker 2: something that you would encounter outside of oral tretonoen like
Speaker 2: eating a lot of care you know what I mean?
Speaker 2: Like yeah, does our body have a way of you know,
Speaker 2: excreting excess vitamin A that is taken like through dietary forms.
Speaker 1: Excellent question. It's not. It's a fat soluble vitamins, We're
Speaker 1: not excreting it, so it absolutely can build up in
Speaker 1: our tissues. It would be very difficult to get vitamin
Speaker 1: A toxicity just from eating something like carrots, because again,
Speaker 1: those are precursor vitamins that you're getting in the form
Speaker 1: of like carotenoids and things like that. So in that way,
Speaker 1: it's not impossible, but very difficult. Certainly, if you're taking
Speaker 1: a bunch of supplements that aren't isotretonoen but are other
Speaker 1: vitamin A supplements, then yes, you definitely could see similar effects. Okay,
Speaker 1: So what I want to mention, because I do think
Speaker 1: that this is an important part of the story, is
Speaker 1: that because of the risk of birth defects and spontaneous abortion,
Speaker 1: but mostly because of the risk of birth defects when
Speaker 1: someone is on something like isotretonoin or Acutane is one
Speaker 1: of the brand names for it, there are very extensive
Speaker 1: restrictions on the prescribing of this medication in the US
Speaker 1: and in most other countries. In a lot of places
Speaker 1: it's only dermatologists or other specialists that can prescribe it
Speaker 1: at all, and almost universally, anyone with a uterus who
Speaker 1: is considered of child bearing age has to read through
Speaker 1: a really extensive document that outlines the risks and guidelines
Speaker 1: of use. They have to sign a pledge committing to
Speaker 1: using two forms of contraceptive therapy, starting one month prior
Speaker 1: to the medication and continuing for at least one to
Speaker 1: three months after using isodrete NOE, and in some cases
Speaker 1: they have to take monthly pregnancy tests before they can
Speaker 1: get each prescription, which also means you can only get
Speaker 1: your prescriptions thirty days at a time. And despite all
Speaker 1: of this rigmarole, from what I have read, there is
Speaker 1: no real evidence that this has actually decreased the risk
Speaker 1: of fetal exposure to isotrete and no one why though,
Speaker 1: because I mean, I think because there are so many
Speaker 1: layers to this, right, like A, not all birth control
Speaker 1: is perfect. B. Signing a pledge is not the same
Speaker 1: thing as doing it. See how much are these risks
Speaker 1: actually being explained versus Oh, just sign here and do
Speaker 1: this and then you'll get your medicine right, Like, there's
Speaker 1: there's a lot, a lot, a lot of different layers
Speaker 1: to it. Okay, there's also a registry in the US
Speaker 1: that you have to sign up for, and like every
Speaker 1: person involved has to sign the prescribing provider, the the
Speaker 1: pharmacist who's dispensing it, the patient, and so it's all
Speaker 1: on a registry in the US, which is a country
Speaker 1: that has restrictions on access to birth control and is
Speaker 1: banning abortions and criminalizing pregnancy. Ah Okay, anyway, yeah, yep, yep, yep.
Speaker 1: So it's important to know it is. It can be
Speaker 1: a very effective medication for severe scarring like cystic acne
Speaker 1: that has it responded to things like topical preparations. It
Speaker 1: has the potential for serious side effects like birth defects.
Speaker 1: It also has some other side effects. It can increase
Speaker 1: your liver enzymes, It can increase your cholesterol. Most of
Speaker 1: those are transient and so they tend to get better
Speaker 1: as soon as somebody stops the medication. And in some cases,
Speaker 1: this medicine also can make people feel really bad, like
Speaker 1: cause things like depression, to worsen anxiety and things like that.
Speaker 1: And we don't really understand the mechanisms of any of that,
Speaker 1: but it's not a medication that is easily prescribed, just
Speaker 1: like bloop mm hm. But anyways, let's get back to wrinkles, yeah,
Speaker 1: shall we? All right? So I told you everything about
Speaker 1: what we know about something like retine, yeah, or even
Speaker 1: a dapoline, which I will say is now over the counter.
Speaker 1: You can get a dapolne It's different. Is one of
Speaker 1: the brand names in the US, and that used to
Speaker 1: be only available with a prescription, but now some concentrations
Speaker 1: of it are available without a prescription.
Speaker 2: H just real quick, because I feel like maybe you'll
Speaker 2: go down this road. But the different formations of this
Speaker 2: do they have just like different effects? Are they target
Speaker 2: different genes or what's the deal? Yeah, I'm so glad
Speaker 2: you asked, Darin.
Speaker 1: So the prescription strength retinoids are all either retinoic acid,
Speaker 1: which is thretonoen retine, or they are synthetic versions of
Speaker 1: a retinoid that are active when you put them on.
Speaker 1: That is the biggest difference between over the counter retinols
Speaker 1: that you can buy at CBS or wherever, Target Costco,
Speaker 1: anywhere sacks if you want to buy expensive versions. Right,
Speaker 1: all of those types which have names like retinol, retinaldehyde,
Speaker 1: and a whole bunch of these retinal esters. All of
Speaker 1: those types of retinols are not the active form retinoic acid.
Speaker 1: Thretonoen Retine is the active form of a retinoid. That's
Speaker 1: what's binding to your receptors. That's what's doing the thing.
Speaker 2: Okay.
Speaker 1: The other ones that are available through prescription, like adapolene.
Speaker 1: There's also like I mentioned already, isotretonoen There's a newer
Speaker 1: one called tazerotine. There's a whole variety of these. These
Speaker 1: are synthetic versions. They look different than retinoic acid, but
Speaker 1: they are binding to the receptors themselves, so they again,
Speaker 1: they work when you put them on. Everything that you
Speaker 1: can buy over the counter has to be converted. It
Speaker 1: is a derivative and isn't the thing that is binding
Speaker 1: to the receptor.
Speaker 2: Okay.
Speaker 1: So if you put on an over the counter retinl
Speaker 1: it says retinyl on the bottle, it has to be
Speaker 1: converted through a two step process before it becomes retinoic
Speaker 1: acid and is doing a thing to your skin.
Speaker 2: Okay, So like what then is that process or like
Speaker 2: how is it?
Speaker 1: It's oxidation by enzymes in your skin. You're basically your
Speaker 1: skin has to see it and be like, oh, I
Speaker 1: know what this thing is. It's like a vitamin A.
Speaker 1: I'm gonna use it. Boo buto boop. Then it converts
Speaker 1: it and then it uses it.
Speaker 2: But like ultimately, then how is it? Like is it
Speaker 2: just like the strength, the power, like the concentration?
Speaker 1: Okay, Okay, yeah, So here's the bottom line, because I
Speaker 1: feel like one of the big questions that I had
Speaker 1: in doing this episode is like, there's these prescription strength
Speaker 1: versions and there's these over the counter versions. We use
Speaker 1: the prescription strength for a lot of stuff. We have
Speaker 1: good data for Trenton Owen that it's doing most of
Speaker 1: the things that we're prescribing it for. There's less data
Speaker 1: for the photo aging effects of the other ones. Okay,
Speaker 1: because they don't need to do that study. We'll get there.
Speaker 2: Yeah, I'm excited for that, But what.
Speaker 1: About all of these other ones? Right, because you can
Speaker 1: get so many else And the bottom line is that
Speaker 1: while we have evidence that some of these might work,
Speaker 1: we don't have the type of evidence that you would
Speaker 1: expect from a drug and we will probably never have
Speaker 1: that kind of evidence. So what it ends up being
Speaker 1: is that all of the over the counter retinoids are
Speaker 1: substantially less potent than tretnoen. So it's often like the
Speaker 1: number that cited is that retinol, which is one of
Speaker 1: the most common over the counter versions, is about ten
Speaker 1: times less potent than tretnoen the prescription strength.
Speaker 2: Okay, so they put it in.
Speaker 1: Your bottle in theory at ten times higher concentration, right.
Speaker 2: I feel like, Okay, tell me that's not right.
Speaker 1: Well, Aaron, when I tell you how many papers I
Speaker 1: read for this to try and really get a sense
Speaker 1: of all of these other types of retinoids, do they
Speaker 1: work or do they not? I still don't have a
Speaker 1: clear answer. All of the data that exists for these
Speaker 1: over the counter versions of retinoids are subject to major
Speaker 1: industry bias because nearly every study is funded by industry.
Speaker 1: Most of them are pretty small studies. None of them
Speaker 1: are really great studies. But there is a really big
Speaker 1: amount of data out there that is a conglomeration of
Speaker 1: data on histologic samples. So like you cut skin, you
Speaker 1: apply stuff, you look at it under a microscope. Animal studies,
Speaker 1: so you put it on a mouse and see what
Speaker 1: happens to their cute little wrinkles, and human studies, which
Speaker 1: some of them are well designed and some of them
Speaker 1: are really not well designed, but they're human studies on
Speaker 1: face skin, on armskin, on butt skin, on a whole
Speaker 1: bunch of different kinds of skin. And overall, the conclusion
Speaker 1: that I come to is that there is a preponderance
Speaker 1: of evidence that some of these retinols work in a
Speaker 1: similar way to trettonoen mostly retinaldehyde. There's maybe stronger evidence
Speaker 1: for and this is a type of retinol that only
Speaker 1: has to be converted one time in your skin before
Speaker 1: it's active, okay, And to a lesser extent retinol, which
Speaker 1: is one of the more common kinds and has to
Speaker 1: be converted twice at certain concentrations. These seem to be
Speaker 1: effective for treating photo aging, which is the only thing
Speaker 1: that people are studying them for. So I just that's
Speaker 1: what they're studying them for, Okay. Effective meaning what effective?
Speaker 1: Meaning when you test them. They reduce the appearance I'm
Speaker 1: putting all of this in air quotes. They reduce the
Speaker 1: appearance of fine lines, they reduce the appearance of sunspots,
Speaker 1: solar lintigenies, and in some cases might improve things like
Speaker 1: skin roughness or brightness or evenness or things like that. Again,
Speaker 1: these are not well designed studies, and I want to
Speaker 1: now remind ourselves of a really important part, because what
Speaker 1: I said is that there is evidence for some of
Speaker 1: these types of retinoids that at certain concentrations they may
Speaker 1: be similarly effective to trettonoen. So let's remind ourselves of
Speaker 1: our supplements episode. If you haven't listened, please do. It's
Speaker 1: one of my favorites. So cosmetics or cosmaceuticals, which is
Speaker 1: when a cosmetic product is actually supposed to be doing
Speaker 1: something to your skin, anything that you're buying over the counter,
Speaker 1: are regulated entirely differently than drugs that you get from
Speaker 1: the pharmacy, And much like supplements, which are also not regulated,
Speaker 1: cosmaceuticals are not regulated essentially at all, which means that,
Speaker 1: just like for supplements, skincare companies can make a huge
Speaker 1: variety of claims about what their products can or can't do,
Speaker 1: but they do not have to do any research to
Speaker 1: prove these claims. They do not have to get any
Speaker 1: kind of approval from the FDA, and they don't have
Speaker 1: to even tell the FDA what's in any of their
Speaker 1: bottles of anything before it comes to market.
Speaker 2: Like there's no even an ingredient quantity list.
Speaker 1: You have to have ingredients on your bottle. You don't
Speaker 1: have to tell the FDA anything about what it is
Speaker 1: before you sell it to consumers. Uh huh yep mm hmm.
Speaker 1: Which also means that these companies have absolutely no reason
Speaker 1: to waste their money doing how much work it would
Speaker 1: take and spending how much money it would require to
Speaker 1: do good, well researched, well designed, side by side randomized
Speaker 1: control trials where you're actually testing things the way that
Speaker 1: you need to.
Speaker 2: To get something approved as drug, rather than insure like
Speaker 2: an actual double blind or like, instead of just ensuring
Speaker 2: that the data will fall the way you want it
Speaker 2: to fall. Because exactly just going back to all of
Speaker 2: the different measures that you said, reduce the appearance of wrinkles,
Speaker 2: reduce the appearance of solar lintigenies, increase skin elasticity. I
Speaker 2: know that you said some of this was histologic changes,
Speaker 2: but I feel like two things are important to remember.
Speaker 2: One is that some of those observations seem to be
Speaker 2: just that like subjective, does it look less wrinkly?
Speaker 1: Like?
Speaker 2: How do you measure that quantitatively. But then number two,
Speaker 2: even if you do measure it quantitatively in some capacity,
Speaker 2: you could say reduce the appearance, even if it's the
Speaker 2: most minor reduction. And so is there actually meaning in
Speaker 2: that reduction?
Speaker 1: Oh my gosh, Aaron, that's I mean, that's even like
Speaker 1: a whole nother level, because drugs don't even necessarily have
Speaker 1: to show that, right, Like, if you have statistical significance,
Speaker 1: that's not the same as clinical significance. That's something that's
Speaker 1: true in all of medicine, and not just definitely not
Speaker 1: just skincare products, but like especially in skincare products, And
Speaker 1: like I mean, yeah, bottom line is not at any
Speaker 1: single cream or anything prescription or otherwise that you rub
Speaker 1: on your face is going to make you look like,
Speaker 1: I don't know, who doesn't have any wrinkles?
Speaker 2: A baby?
Speaker 1: A baby, Yeah, a baby. There you go. It's gonna
Speaker 1: try and say a famous person. I can't think of any.
Speaker 1: But yeah, so one hundred percent that is definitely true.
Speaker 1: I will say there are ways to quantify things like
Speaker 1: hyperpigmentation or the depth of wrinkles and things like that,
Speaker 1: and some studies do that, but a lot of studies don't.
Speaker 1: And that's the point. I have so many sources that
Speaker 1: you guys can go and read through. And some of
Speaker 1: these studies are fine. Some of these studies are halfway decent,
Speaker 1: but a lot of them aren't. And so it's really
Speaker 1: like you have to look at all of the evidence, right,
Speaker 1: and there isn't an incentive to do better studies right.
Speaker 1: And so here's the other thing that becomes so problematic
Speaker 1: with the way that these cosmetics and cosmaceuticals are regulated.
Speaker 1: There is no good way as a consumer to sort
Speaker 1: through these thousands of products that are available. And because
Speaker 1: labeling laws are essentially non existent, you have no idea
Speaker 1: what it is that you're actually getting, much less what
Speaker 1: percentage of these various retinols that you're getting. As an example,
Speaker 1: I did a Google search. I googled best over the
Speaker 1: counter retinoid. That's what I googled. I found a bunch
Speaker 1: of these top ten lists, you know, like US World
Speaker 1: News Is, like best Ones, and like health dot Com
Speaker 1: click on my affiliate link, Allure. I looked at all
Speaker 1: of these. I went through every single one of these
Speaker 1: top ten. By the way, they're all different, which tells
Speaker 1: you something, Yeah, it does. I read through the ingredients
Speaker 1: on every single one of these bottles that they recommended
Speaker 1: as top ten. Most of them had absolutely no concentration listed.
Speaker 1: Most of these used retinol, which again has some data
Speaker 1: to support its use. A lot of them used retinal palmitate,
Speaker 1: which is a type of retinal ester that actually has
Speaker 1: data that shows it doesn't work, it doesn't do anything.
Speaker 1: In fact, very few of them use retinow the hide,
Speaker 1: which again is another one that has some data, and
Speaker 1: I will say it's the one that people are the
Speaker 1: most hyped up out, which you just again have to
Speaker 1: take with grains of salt.
Speaker 2: This is the newest iteration or like.
Speaker 1: Exactly, yeah, And all of these products that you're buying
Speaker 1: are also chalk full of things like a bunch of
Speaker 1: other be vitamins, hyaluronic acids, all of these other things
Speaker 1: that skincare companies are claiming are also going to help
Speaker 1: your skin, whether or not it's true, whether or not
Speaker 1: they have any data to show for it. And by
Speaker 1: putting all of these products in combination, you have no
Speaker 1: idea if any effect that you're seeing is from the
Speaker 1: retinoid that's in there or from anything else in that formulation. Right,
Speaker 1: And and I just keep going arian because it's ridiculous.
Speaker 1: The formulation really matters for retinoids because retinoids are not
Speaker 1: stable in light and in oxygen, they break down very easily.
Speaker 1: So if you don't know how long your bottle has
Speaker 1: been sitting on the shelf, you don't know if it's
Speaker 1: still active. Drugs. Pharmaceuticals are tested in their entirety, right,
Speaker 1: Drugs are tested by the entirety of the formulation. So
Speaker 1: no matter what brand, whether it's generic, whether it's brand
Speaker 1: name retine, if you're getting something that says it's zero
Speaker 1: point one percent tretnoen, then you are getting a formulation
Speaker 1: that has been tested to at least be non inferior
Speaker 1: to every other version of tretnoen that's available with a prescription.
Speaker 1: There is robust studies, at least now because they've been
Speaker 1: forced to do it after that lawsuit apparently, and there's
Speaker 1: safety data to back all of this up. With cosmetics,
Speaker 1: sure they can do a bunch of tinkering and add
Speaker 1: a bunch of stuff in that makes it go on smooth,
Speaker 1: makes it feel nice, right, but that doesn't mean that
Speaker 1: it's doing anything. And just like with supplements, when independent
Speaker 1: organizations have gone through and actually tested off the shelf
Speaker 1: a whole bunch of different retinoids. That's exactly what they
Speaker 1: found is that they either don't contain what they claim
Speaker 1: they do, or they don't contain it at the concentrations
Speaker 1: they claim or at like ridiculous concentrations that were nothing
Speaker 1: like the randomized control trials that the company funded to
Speaker 1: do anyways, or when they put them on their shelves,
Speaker 1: they degrade far more rapidly than they should. Therefore they're
Speaker 1: not effective by the time your bottle's gone. So would
Speaker 1: robust randomized control trials be really helpful? Yeah, they would.
Speaker 1: Where's the incentive? It doesn't exist, you asked, Aaron, what
Speaker 1: is the anti aging market? Let me tell you. In
Speaker 1: twenty twenty one, it was estimated to be valued at
Speaker 1: sixty three billion dollars.
Speaker 2: Did the article on from nineteen to eighty nine, say
Speaker 2: three billion, three.
Speaker 1: Billion in nineteen eighty nine, sixty three billion in twenty
Speaker 1: twenty one, And most numbers that I saw, and this
Speaker 1: was from a number of different like websites, because this
Speaker 1: information is not like conglomerated into studies. Yet most numbers
Speaker 1: said between sixty eight and seventy two billion dollars today
Speaker 1: and it is rapidly going like it just keeps growing.
Speaker 1: Who needs research? You've got marketing?
Speaker 2: I mean okay, and I just like here's the little
Speaker 2: devil's advocate here where I'm thinking, Okay, Well, if the
Speaker 2: pharmaceutical companies aren't going to do this research, then who
Speaker 2: would do the research? Universities, researchers, research organizations. Is that
Speaker 2: the best use of funding?
Speaker 1: No, it absolutely isn't right. So we can never try
Speaker 1: to get wrinkles on your skin now, I will say
Speaker 1: acne is a totally different thing, and that is part
Speaker 1: of why we should do a whole episode. But that
Speaker 1: is part of why the FDA agreed to make a
Speaker 1: dapoline or like what is different gel as the brand
Speaker 1: name in the US over the counter in the US
Speaker 1: in twenty sixteen is because it was so restrictive to
Speaker 1: be able to get it and it really works. And
Speaker 1: acne can be very problematic. It can cause a lot
Speaker 1: of scarring, It can cause a lot of psychosocial distress,
Speaker 1: it can cause like it's painful, Like acne is a
Speaker 1: very big deal, but we're talking about our wrinkles on
Speaker 1: your skin.
Speaker 2: Photoaging, Yeah, photo aging.
Speaker 1: Like I'm I'm sorry. It's not the same thing. So, no,
Speaker 1: it's not. And here's the other thing. It's not that
Speaker 1: this research is not being done.
Speaker 2: Right.
Speaker 1: These companies invest heavily in R and D, but they
Speaker 1: are absolutely not going to be incentivized to publish that
Speaker 1: and let everyone else get their formulations. Why would they
Speaker 1: write They're going to keep it in house. It's I mean,
Speaker 1: it's a it's it's of course it's capitalism. I mean,
Speaker 1: it's capitalism.
Speaker 2: I mean. So the answer to the question does it
Speaker 2: work for anti aging is so layered, right. You could
Speaker 2: say yes, and you could say yes, this study indicates
Speaker 2: that this, but you have to consider the effect size.
Speaker 2: How much does it actually reduce the appearance of wrinkles?
Speaker 2: You could consider how, oh, well, this study showed it,
Speaker 2: but it did a different test. You could show that yes,
Speaker 2: it was statistically significant, but the sample size was ten individuals.
Speaker 2: There are so many different challenges in getting to a
Speaker 2: answer that is not with a million different layers of qualifiers.
Speaker 1: One hundred percent, I will say, looking at all of
Speaker 1: the evidence, from all of the things, Trettonoen has evidence
Speaker 1: that has good evidence overall that it can reduce some
Speaker 1: signs of photoaging. But yes, the question of like, what
Speaker 1: does that mean to one person versus another? Right, does
Speaker 1: it matter to you? Does it not?
Speaker 2: Like you know? Well? And then a follow up question
Speaker 2: that I would have to trettonoen and yes, okay, if
Speaker 2: there is evidence that is in support of reducing the
Speaker 2: signs of photoaging, how long do those effects last if
Speaker 2: you use trettonoen, Like how long does it take for
Speaker 2: trettonoen to have that impact? And then if you stop
Speaker 2: using tretoen do the effects go away?
Speaker 1: It's a good question. Most of the evidence I saw
Speaker 1: is that it takes at least weeks, like there are
Speaker 1: some You also mentioned something about in the FDA put
Speaker 1: a caveat on there that there's no histological changes. So
Speaker 1: it is interesting the histologic changes that we see with
Speaker 1: trettonoen max out at a certain number of weeks and
Speaker 1: then seem to go back to being like less histologic changes.
Speaker 1: But the visible changes when they do like I forget
Speaker 1: the names of the fancy photographs and things where they
Speaker 1: take things and measure things, those changes, like the visible
Speaker 1: changes remain and continue to improve, but the histologic changes
Speaker 1: seem to be more transient. So people are still trying
Speaker 1: to figure out what does that mean? Does that mean
Speaker 1: that the histology is not necessarily like what is driving
Speaker 1: the visible changes? Anyways, that's a little bit too detailed.
Speaker 1: But what was your question?
Speaker 2: How long did the effects last?
Speaker 1: Oh? Yeah, so they take weeks to months to see
Speaker 1: an effect, but they do seem to last pretty long.
Speaker 1: And you all are also going to continue to age
Speaker 1: for your entire life. So like, if you stop using them,
Speaker 1: you will go back to photo aging after a few
Speaker 1: months to a year. It seems like they last for
Speaker 1: at least a little bit of time.
Speaker 2: But if you use them forever, you are also still
Speaker 2: going to photo age to some extent.
Speaker 1: Yeah, but significantly less than if you had ever used them.
Speaker 1: How significant, well, statistically significant? Aron, I know, clinically significant
Speaker 1: depends on the person.
Speaker 2: I mean it is.
Speaker 1: And because all of this is for cosmetics, right, it's
Speaker 1: for how you look, how you appear now is especially
Speaker 1: as women, is that something that we are judged on constantly? Absolutely,
Speaker 1: I have a lot of feelings. I think that's why
Speaker 1: I have so many resources and so for this episode,
Speaker 1: because I have a lot of feelings about this, but
Speaker 1: I'm trying to not dive into my feelings and just.
Speaker 2: Talk about the concealed don't feel thank you just kidding.
Speaker 2: Never take that advice. It was the villain song.
Speaker 1: It is, it is, It's true. But yeah, so, I
Speaker 1: mean it's it is a really really interesting, frustrating area.
Speaker 1: And it's also it is very very hard to get
Speaker 1: good data. There are so many people out there who
Speaker 1: are trying to break it down in ways that are
Speaker 1: understandable for people, which I appreciate, but almost always at
Speaker 1: the end of it, they are also being paid by
Speaker 1: skincare companies, and so it's very difficult to then take
Speaker 1: all of that information as non biased, right.
Speaker 2: Right, So, and we all have our biases, we did
Speaker 2: in general, but it is it is different when there's
Speaker 2: like money, terry support for those biases.
Speaker 1: I think, yeah, yeah, so I'm not gonna tell you
Speaker 1: any brands. I mean, I did mention the brand names
Speaker 1: of some things just so people know what I'm talking about.
Speaker 1: But yeah, you can get generic. But you do you
Speaker 1: use do you use retin eight? There?
Speaker 2: No, because it made me break out. I have like
Speaker 2: I had, Yeah, I had a little thing of retinal
Speaker 2: and I don't know what happened, but I started to
Speaker 2: use it and it made me break out.
Speaker 1: And I was like, yeah, I'm probably because it made
Speaker 1: you purge.
Speaker 2: Yeah, probably, And I just don't really, you know.
Speaker 1: That's fair. I have two different bottles. I just bought
Speaker 1: a new one during the episode. During researching for this episode,
Speaker 1: I was like, I'm gonna try it. I still have
Speaker 1: never used prescription strength, which I think is especially funny
Speaker 1: because I could have had a friend calling a prescription
Speaker 1: for me at any point. I mean, I still could,
Speaker 1: but I just I've never used the prescription, which is
Speaker 1: like the one that has the most evidence. It's all
Speaker 1: just you know, I don't know.
Speaker 2: I know, it's it's complicated, and I think I struggle
Speaker 2: a lot to articulate how I feel about aging and
Speaker 2: wrinkles and the freckles on my face and the fine
Speaker 2: lines and this and that, and I don't know.
Speaker 1: I will say all of the studies that I read,
Speaker 1: and I read a lot, they all look at like
Speaker 1: these areas, like you're near your eyes and near your mouth,
Speaker 1: and I'm like, I don't even care about those wrinkles.
Speaker 1: What about this one? There's nothing, there is nothing that
Speaker 1: will touch this between my eyebrows except botox, botos we
Speaker 1: already did that episode. But yeah, Aaron, that's I don't
Speaker 1: know what my conclusion is. There's some evidence for some things,
Speaker 1: but it is it is almost impossible to know if
Speaker 1: any of the things that you can buy over the
Speaker 1: counter are going to work. And so there are a
Speaker 1: lot of people whose stance is absolutely, don't waste your money.
Speaker 1: They're a complete waste of money. And I think that
Speaker 1: that might be a slightly unfairstance because for some people
Speaker 1: they might work, because again there is some evidence that
Speaker 1: they work in some cases, but it's also not okay
Speaker 1: to say, oh, these totally work because there's such a
Speaker 1: huge range, and it's just so difficult as a consumer,
Speaker 1: like nobody is looking out for us to help us
Speaker 1: sort through this essentially, so once again, the consumer just
Speaker 1: has to waste our money.
Speaker 2: It's it's it is. It is supplements reducts like it
Speaker 2: is doing the same thing where it's like, what's the harm, Well,
Speaker 2: you're spending your money on stuff that may or may
Speaker 2: not do anything.
Speaker 1: Yeah, and you might get a really bad reaction to it.
Speaker 1: Because even though over the counter retinals, because they're less potent,
Speaker 1: tend to be have less side effects of like the
Speaker 1: peeling and the irritation, the redness. They're not without side effect, right.
Speaker 2: Yeah, so and yeah, I don't know, it's a lot.
Speaker 1: Erin, it's a lot. It is a lot. You want
Speaker 1: to read more. I have I don't know, two and
Speaker 1: a half entire pages of citations. So let me tell
Speaker 1: you about some of my favorite ones. A couple of
Speaker 1: textbooks that I read on in cosmetic dermatology textbooks if
Speaker 1: you want some more detail on like the skin and
Speaker 1: just like big picture stuff. My two favorite review papers
Speaker 1: that looked at like the overall evidence for these over
Speaker 1: the counter versus prescription strength retinols were one by eleven
Speaker 1: at All from twenty ten that was titled how much
Speaker 1: do we really know about our favorite cosmeceutical ingredients? I
Speaker 1: liked that one. I also really liked one by Tatali
Speaker 1: at All from twenty twenty that was titled popular over
Speaker 1: the counter cosmeceutical ingredients and their Clinical Efficacy. I thought
Speaker 1: those were like pretty well balanced reviews. But I also
Speaker 1: have a whole bunch of actual data papers if you
Speaker 1: want to get real deep dive in. I've got some
Speaker 1: on the evidence just for tretnoen, and then also some
Speaker 1: on the tyatogenicity of retinols. One thing I should mention
Speaker 1: that I did not mention earlier is that when I
Speaker 1: was talking about the increased risk of birth defects and
Speaker 1: spontaneous abortion with the use of retinoids, that applies to
Speaker 1: oral retinoids. Recommendations from every single medical society are to
Speaker 1: not use any kind of retinoid, including over the counter,
Speaker 1: including topical, just for your skin products, at any time
Speaker 1: while you're pregnant, no matter what. All of the data
Speaker 1: that we have on the risks of birth defects is
Speaker 1: for oral medications of retinoids. We don't have strong data
Speaker 1: that shows that topical retinoids that you put on your
Speaker 1: skin increase the risk of birth defects, but out of
Speaker 1: an abundance of caution, the recommendation still stands to not
Speaker 1: use any kind of retinoid product. So, just to clarify
Speaker 1: if anyone was wondering, why, so, I got all those sources,
Speaker 1: and there's a whole bunch more, and we'll post the
Speaker 1: list of all of them on our website. This podcast
Speaker 1: will Kill You Do. Under the episode s Tap.
Speaker 2: We will thank you to Bloodmobile for providing the music
Speaker 2: for this episode and all of our episodes.
Speaker 1: Thank you to Tom Brayfogal and Leanna Skialacchi for the
Speaker 1: audio mixing.
Speaker 2: Thank you to everyone at Exactly Right.
Speaker 1: And thank you to you listeners. I hope you enjoyed
Speaker 1: this two part deep dive. Yeah, do you use retinals?
Speaker 1: Do you use prescription retinals? Do you not use any
Speaker 1: retinalds to use? Or the counter retinalds? I really want
Speaker 1: to know.
Speaker 2: Do you have feelings about retinals?
Speaker 1: Do you have feelings? I have a lot of feelings.
Speaker 2: Yeah.
Speaker 1: Should we do a whole episode about wrinkles?
Speaker 2: Oh? Yeah, I thought you were gonna say, should we
Speaker 2: do a whole episode about feelings? Yes?
Speaker 1: Yes?
Speaker 2: Yeah? And a big thank you, of course to our wonderful, lovely, generous,
Speaker 2: fantastic patrons. We appreciate your support. It means the world to.
Speaker 1: Us, it really does. Thank you so so much.
Speaker 2: Well, until next time, wash your hands you feel the animals?
Speaker 3: Ob Buba Buba, Buba Buba