Speaker 1: Emily. We're talking about cortisol today, which people say is
Speaker 1: a stress hormone, and yeah, we'll get there. But I've
Speaker 1: been thinking a lot about stress this week, and one
Speaker 1: thing I wanted to tell you is that my fitness
Speaker 1: tracking watch, which is a Samsung watch, periodically pings me
Speaker 1: just to be like, hey, you're feeling very stressed right now,
Speaker 1: and this.
Speaker 2: Is that sounds so annoying.
Speaker 1: Not helpful, Samsung. I have no idea why. Like, it'll
Speaker 1: come up and I as a doctor, you know, I'll
Speaker 1: take my pulse and be like, it's something weird happening,
Speaker 1: and I think I feel fine, But then of course
Speaker 1: it gets in your head it's like, what, well am
Speaker 1: I stressed? And then I decide, well, I must be stressed,
Speaker 1: and then I'm stressed. Does this happened to you?
Speaker 3: No, because my fitness tracker, of which I have two,
Speaker 3: give me different kinds of inputs. But I will say
Speaker 3: at the end of the day, every day I get
Speaker 3: a message that's like, today you spent blah blah blah
Speaker 3: minutes in the high stress zone. And then it tells
Speaker 3: me whether those are like part of my actual exercise
Speaker 3: or other things sort of like today you spent two
Speaker 3: hours and nine minutes in the high stress zone, the
Speaker 3: majority of which came from activities outside of strain. And
Speaker 3: then it's like, oh, well, what else was I what
Speaker 3: else was I doing? And then it's usually like usually
Speaker 3: this came from sleep, and then I'll be like.
Speaker 2: Why did you drink alcohol?
Speaker 3: That's like it's like, so it gets a little more judgmental,
Speaker 3: but yeah, people don't like the judgment aspects of watches.
Speaker 3: It's like, I, do you ever do you run with
Speaker 3: a watch?
Speaker 2: I do exercise. Do you notice that when you start.
Speaker 3: Running it beeps a number like plus one, plus two,
Speaker 3: negative one?
Speaker 2: Does your watch do this?
Speaker 1: My watch doesn't do that.
Speaker 2: This is the worst thing.
Speaker 3: You're like running along and you're like I feel pretty
Speaker 3: good and then your watch beeps and it's like negative
Speaker 3: six and that you suck it, your bad And so
Speaker 3: I think they should dial down the amount of information
Speaker 3: our watches are pushing at us.
Speaker 1: I think telling someone, hey, you your stressed man is
Speaker 1: more or less the equivalent of me telling my sixteen
Speaker 1: year old daughter, like, you seem like you're in a
Speaker 1: bad mood, Like it's just just it's not going to
Speaker 1: go well.
Speaker 3: One step up from like are you getting your period?
Speaker 3: But like it still pretty bad?
Speaker 1: Okay, having three older sisters, I know not to ask
Speaker 1: that question. You'll learn that. You learn that maybe we
Speaker 1: need a more objective readout of stress. Maybe that objective
Speaker 1: readout is cortisol. Maybe not. Let's figure it out, find out.
Speaker 3: I'm Emily Aster, I'm an economist and a data expert.
Speaker 1: And I'm Perry Wilson, I'm a medical doctor.
Speaker 3: It's Thursday, July ninth, twenty twenty six. And this is wellness.
Speaker 1: Actually, because you're getting a staggering amount of health and
Speaker 1: wellness information nowadays from every source imaginable, and some of
Speaker 1: it is awesome and some.
Speaker 3: Of it is well actually both Fortunately we are both
Speaker 3: people who know how to read studies, how to parse
Speaker 3: the data, and can tell you what's worth thinking about
Speaker 3: and what you can safely ignore.
Speaker 1: But before we dig in, a note that this podcast
Speaker 1: is for educational purposes and should not be construed as
Speaker 1: medical advice. We don't know your unique situation, so talk
Speaker 1: to your doctor for personal health decisions.
Speaker 2: This week we're asking what's the deal with cortisol?
Speaker 3: Perry and I will give the official smasher pass and
Speaker 3: then we'll get to your question of the week, but
Speaker 3: first let's do the health news roundup after the break.
Speaker 1: And we are back with the health news of the week, Emily.
Speaker 1: The FDA is allowing Zin pouches to market their relative
Speaker 1: health benefits compared to other tobacco products like cigarettes. What's
Speaker 1: going on here? What's up with zin?
Speaker 2: So Zin is a tobacco product.
Speaker 3: It is a nicotine product particular, and people like it
Speaker 3: a lot of people like it a lot. It's become
Speaker 3: very popular with like tech bros. Because there's this sense
Speaker 3: that nicotine increases your focus, and people like Andrew Huberman
Speaker 3: are kind of into the health benefits of nicotine, but
Speaker 3: they also understand this smoking is bad for you, and
Speaker 3: so this is like a way to get your nicotine
Speaker 3: without smoking. And Okay, so the FDA has now allowed
Speaker 3: Zin to make help what I would describe as health statements.
Speaker 3: So the claim things like using Zin instead of cigarettes
Speaker 3: puts you at a lower risk of mouth cancer, heart disease,
Speaker 3: lung cancer, stroke emphasem, and chronic broncholitis that statement is.
Speaker 2: I would say broadly true.
Speaker 3: So these products are definitely safer than cigarettes. I think
Speaker 3: what many people are concerned about is that children will
Speaker 3: see this and be like, hey, Zen's a health food
Speaker 3: and like I can do and this is like not
Speaker 3: bad for me at all. And on top of an
Speaker 3: app atmosphere in which you can also get as we
Speaker 3: talked about an earlier episode, like fruit flavored vapes, we're
Speaker 3: kind of entering a place where somehow we've come up
Speaker 3: with this idea that there's health benefit opportunities to things
Speaker 3: that are not cigarettes but still have this nicotine. And
Speaker 3: I think that's pretty dangerous in part because if you
Speaker 3: get addicted to nicotine and then there's no zin around,
Speaker 3: you got to move to something else, like cigarettes, which
Speaker 3: are bad for you.
Speaker 1: Yeah, or just zin, I mean this is or just zin.
Speaker 2: Is bad for you. We don't really.
Speaker 1: I mean this is true that smoking, like lighting something
Speaker 1: on fire and inhaling the smoke that comes out of it,
Speaker 1: is worse for your lungs than sucking on a nicotine pouch.
Speaker 1: This is, Yes, you're at less risk of lung cancer,
Speaker 1: but nicotine is a highly addictive substance. It binds to
Speaker 1: a receptor in your brain called the NMDA receptor. It
Speaker 1: makes you feel certain good things and like all physically
Speaker 1: addictive substances. When it's taken away from you, you feel
Speaker 1: much worse you did at baseline. The psychological impact of
Speaker 1: that may be substantial. Certainly the economic impact is substantial
Speaker 1: because these things cost money. And being addicted to something
Speaker 1: that you need to take, even if it had like
Speaker 1: absolutely no ill health effects, if it's just like, oh man,
Speaker 1: I've got to buy this every day and keep sucking
Speaker 1: on it, imposes a cost. So it's an interesting shift
Speaker 1: at the FDA where they're kind of being accurate, but
Speaker 1: I think from a public health standpoint, they're not doing
Speaker 1: a great job telegraphing that, like this still isn't a
Speaker 1: good idea.
Speaker 3: Yeah, I also think we're we're actually in terms of
Speaker 3: the health benefits or costs of nicotine. You know, there's
Speaker 3: some research that nicotine kind of increases focus, but I
Speaker 3: don't know that we have anything that would tell us
Speaker 3: about the health potential health costs of consuming quite a
Speaker 3: lot of nicotine, which is effectively what people are doing
Speaker 3: when they're consuming many many zinn pouches in a day.
Speaker 3: So we're getting kind of a dose that's even a
Speaker 3: bit different probably than we've been tested and say mice. Yeah, Anyway,
Speaker 3: all right, something else that's going on is an outbreak
Speaker 3: of explosive diarrhea. Cyclospora outbreak is happening throughout the US,
Speaker 3: especially in places in the Midwest.
Speaker 2: Perry, what can you tell.
Speaker 3: Us about the explosive diarrhea and where it's coming next
Speaker 3: and why?
Speaker 1: Uh okay. Cyclospora is a parasitic amiba that causes a
Speaker 1: really bad gastro intestinal illness voluminous, watery, non bloody. For
Speaker 1: what it's worth, diarrhea people are going dozens of times
Speaker 1: per day, can lead to pretty severe dehydration, including the
Speaker 1: need for ivy fluids, et cetera. Current numbers, there are
Speaker 1: seven hundred reported cases. This is a one of the
Speaker 1: reportable outbreak, So like if you get a positive test,
Speaker 1: and if you run a clinical lab and a positive
Speaker 1: test comes through, you're required to report it, so we
Speaker 1: catch those, But there are likely people who are suffering
Speaker 1: in silence at home and their gatorade and not getting
Speaker 1: officially tested for this. It's predominantly in the Midwest. The
Speaker 1: concern is that we actually don't know the source. So
Speaker 1: it's clear that you know where a cyclist bora usually
Speaker 1: lives is on produce and particularly like mint and parsley,
Speaker 1: like the sort of garnishy produce, as well as berries,
Speaker 1: which gets into my head because the berries are so
Speaker 1: good right now, and I like am getting blueberries and
Speaker 1: strawberries and raspberries and blackberries all the time at my
Speaker 1: grocery store. But so far testing has not revealed a
Speaker 1: particular source. It is certainly out there.
Speaker 3: It's I should say, it's actually a hard thing to
Speaker 3: test exact sources for because it takes The incubation period
Speaker 3: is not immediate. So if there's something which makes you
Speaker 3: sick in you know, three hours, it's actually quite easy
Speaker 3: to say, Okay, you know a group of people got
Speaker 3: sick within three hours, we know exactly what they ate
Speaker 3: three hours ago. Okay it was spinach or whatever. Here
Speaker 3: it takes a while. People don't remember what they eight.
Speaker 3: They ate a lot of different things. It's been hard
Speaker 3: to pinpoint.
Speaker 2: Yeah.
Speaker 1: One thing I was looking into about this because my
Speaker 1: daughter gave me a hard time the other day because
Speaker 1: I made her a hamburger and she said it was
Speaker 1: undercooked and she's very afraid of gastrointestinal illnesses. And you sure,
Speaker 1: but you know, yes, I guess you should cook your
Speaker 1: meat adequately, but like, come on, a rare hamburger is
Speaker 1: just the best thing in July. So I did dig
Speaker 1: into this to see, like gastro intestinal illnesses in the
Speaker 1: United States, what percent come from meat and poultry versus produce?
Speaker 1: And actually forty six percent of the food born illnesses
Speaker 1: come from produce and thirty one percent from meat and poultry,
Speaker 1: which leaves I don't know whatever percent. I'm not sure
Speaker 1: what else, but more often, more often from produce. Yeah,
Speaker 1: could be things like that, but produce is the most
Speaker 1: common source for food born illnesses in the US. You
Speaker 1: should wash your produce, and guys, it's watermelon season, like
Speaker 1: you should be washing the outside of your watermelon. I
Speaker 1: know you think that you're cutting into it, but you
Speaker 1: know you cut through the skin and it goes through.
Speaker 1: That's my own that you can suffer.
Speaker 2: Your safety perries here for ruining everything.
Speaker 1: Washa, I'm not ruining it. Just wash it and then
Speaker 1: it's delicious. All right. Let's talk about a new secret
Speaker 1: shopper study of these GLP one websites. So, as you know,
Speaker 1: there are multiple websites online that market GLP ones, and
Speaker 1: a new study actually out of Yale. Although I wasn't
Speaker 1: affiliated with it, set up a fake persona and called
Speaker 1: forty nine of these websites and was able to get
Speaker 1: a prescription from forty five of the forty nine, and
Speaker 1: two of them issued a prescription in under five minutes. Emily,
Speaker 1: problem or solution, I.
Speaker 3: Would say problem. I mean, look, we've talked about this before.
Speaker 3: I'm a smashed broadly on GLP ones as a treatment
Speaker 3: for many things, and I think this is an incredible technology. However,
Speaker 3: it is a medication, injectable, medication or now oral, but
Speaker 3: like it's a medication that has significant effects on people
Speaker 3: and should ideally be prescribed by a doctor who has
Speaker 3: had some interaction with the patient. And I do worry
Speaker 3: about people who are really don't need this or for
Speaker 3: whom maybe it's even kind of damaging in the sense that,
Speaker 3: you know, we have seen some concerning at least anecdotal
Speaker 3: evidence about me people have suffered from meeting disorders in
Speaker 3: the past, this kind of this environment reupping those and
Speaker 3: I would worry about people in that category calling an
Speaker 3: online pharmacy and saying, hey, I feel like I need
Speaker 3: a JLP one similar to an article I saw come
Speaker 3: across my Instagram feeds. Just a clip of someone saying
Speaker 3: that the way that she got a JLP one was
Speaker 3: by wearing twenty pound ankle weights to the doctor so
Speaker 3: she could weigh the like required one hundred and sixtys
Speaker 3: to get on a GLP one, even though she was
Speaker 3: only one hundred and twenty pounds, which probably does not
Speaker 3: necesssitate needing a JLP one.
Speaker 2: So that feels bad to.
Speaker 1: Me, Yeah, that should feel bad. Just over fifty percent
Speaker 1: of the sites asked about eating disorders at all in
Speaker 1: their intake surveys, so there is some potential missed opportunities there.
Speaker 1: And I should say that almost all the sites are
Speaker 1: selling compounded GLP ones. They do this by making custom preparations.
Speaker 1: They take bulk amounts of like ozembic or munjaro, dissolve
Speaker 1: them in their own water, and then you have to
Speaker 1: add something to personalize it to the patients. They usually
Speaker 1: add like some B twelve or something so that it's
Speaker 1: not exactly the same as the branded pharmaceutical. So it's
Speaker 1: in this very regulatory gray zone. You got to be careful.
Speaker 1: I mean, you know. Again, there's a flip side of this,
Speaker 1: and I actually wrote about this this week, which is like,
Speaker 1: if it's this easy, then should there be prescriptions at all?
Speaker 1: Like this middle road of oh yeah, there are prescriptions,
Speaker 1: but everyone can fake it seem sort of dumb. So
Speaker 1: you either close these loopholes and you actually have to
Speaker 1: see a doctor and discuss it, or you don't and
Speaker 1: you just let people buy the things and the libertarians win.
Speaker 2: Right, Yeah, and I think we have either.
Speaker 3: Yeah, we haven't made that choice with most other medications.
Speaker 3: And I think most people would not make the argument
Speaker 3: that we should be allowing people to you know, take
Speaker 3: statins whenever or you know, just get on different But
Speaker 3: maybe maybe people would argue that.
Speaker 1: All right, that's in for the health news of the
Speaker 1: week after the break. What's the deal with cortisol?
Speaker 3: All right, Perry, I am delighted to talk about cortisol,
Speaker 3: something I've heard a lot about.
Speaker 2: As a woman in her let's say, mid to late forties.
Speaker 3: I'm aware that raising my cortisol too high will lead
Speaker 3: to the dreaded belly fat. And I'm sure we'll get
Speaker 3: later to the many ways in which my bones are
Speaker 3: attorney to dust due to my high cortisol. Belly fat combo.
Speaker 3: Oh it's terrible. But before we get into this just
Speaker 3: for people who are getting all their information about cortisol
Speaker 3: from the same Instagram that I'm getting it from. Let's
Speaker 3: start by defining what is cortisol and what are we
Speaker 3: actually talking about here overall.
Speaker 2: So you're a doctor, tell.
Speaker 1: Me, yeah, oh man, cortisol gets such a bad rap
Speaker 1: online and it's such a critical hormone, it's so important.
Speaker 1: So cortisol is a steroid hormone. We've talked about these
Speaker 1: several times before and wellness. Actually, steroid hormones are really
Speaker 1: interesting because the site that they act on is in
Speaker 1: the nucleus, is with the DNA of a cell. So
Speaker 1: all the steroid hormones, including things like testosterone and estrogen,
Speaker 1: get into the nucleus and change how DNA is transcribed,
Speaker 1: so it can fundamentally change what cells are doing, which
Speaker 1: means all these things can do a million different things.
Speaker 1: It's not like you know this one protein is responsible
Speaker 1: for or you know, increasing your sugar level or decreasing
Speaker 1: your sugar level. It does a million things. And I
Speaker 1: think the best way to sort of think about cortisol
Speaker 1: is that it is there primarily to save your life
Speaker 1: in the next ten minutes at the expense of the
Speaker 1: next ten years. So cortisol is a hormone that's present
Speaker 1: to keep you moving and alive after something really bad
Speaker 1: has happened to you, like you got mauled by a
Speaker 1: saber toothed tiger, or you are, you know, running from
Speaker 1: something that is trying to eat.
Speaker 3: You can I'm gonna pause you there because I think
Speaker 3: for most people the thing they think is driving that
Speaker 3: is adrenaline.
Speaker 2: So when you tell me you were chasing by a tiger,
Speaker 2: I think adrenaline. Yeah, they're not the same.
Speaker 1: They're not the same. And cortisol is secreted by the
Speaker 1: adrenal glands, which is where adrenaline comes from. Two and
Speaker 1: they are by all means related and evolutionarily followed kind
Speaker 1: of similar. But adrenaline is much more cardiovascularly active in
Speaker 1: terms of like flogging your heart and whatnot, whereas cortisol
Speaker 1: is more focused on sugar levels. So when you're being
Speaker 1: chased by a tiger, you want there to be plenty
Speaker 1: of sugar in your blood for your muscles to use
Speaker 1: and for your brain to use. And you really don't
Speaker 1: care about whether there's energy for your gut or your
Speaker 1: liver or like your bones, or for your immune system even,
Speaker 1: which is a very energetic, energy intensive thing. So you're
Speaker 1: kind of like shutting everything down and focusing all that
Speaker 1: glucose into muscle and brain. And so when you give
Speaker 1: someone cortisol or when they're indogenous, when their own cortisol
Speaker 1: goes up, their blood sugar goes up, their immune system
Speaker 1: ramps down. That's why glucocorticoids, which are cortisol derivatives, are immunosuppressants,
Speaker 1: things like prednozone. Many people have used hydro cortizone cream
Speaker 1: like for itches and stuff like that. So hydro cortizone
Speaker 1: is cortisol, the exact same molecule. There's no difference between
Speaker 1: hydro cortizone and the cortisol that you're adrenal land secretes.
Speaker 1: I mean they put it in a cream obviously, But
Speaker 1: that's what it is. The problem that people attribute to cortisol,
Speaker 1: and sometimes incorrectly, as we'll go into, is like, what
Speaker 1: if that stressor lasts longer than twenty minutes, Right, you're
Speaker 1: running away from the tiger. Oh, you made it away
Speaker 1: from the tiger. Great, you're good, everything's safe, everything can
Speaker 1: go back to normal. What if your whole what if
Speaker 1: your whole life is stressor what if you're constantly feeling
Speaker 1: like you're being chased by a tiger and your cortisol
Speaker 1: levels are high all the time, and it tells a
Speaker 1: really nice story that like, ooh, that would do a
Speaker 1: lot of bad things. But as I said, cortisol gets
Speaker 1: a bad rap, and it might not be as bad
Speaker 1: as you think.
Speaker 3: So in terms of just sort of people thinking about
Speaker 3: like the way that their quarter so moves throughout the day,
Speaker 3: because cortisol is a it is a hormone, and it
Speaker 3: would be a mistake to think of it as just
Speaker 3: always flat except when you're chased by a tiger. It
Speaker 3: is something which is fluctuating through the day. It's highest
Speaker 3: in the morning, so when you sort of first wake
Speaker 3: up in the morning, your cortisol tends to be tends
Speaker 3: to be higher, and it's lowest sort of in the
Speaker 3: middle of when you are asleep, is my sense, like
Speaker 3: on average for most people, and then it will spike
Speaker 3: at times during the day. This is something that's quite
Speaker 3: hard to measure, but in principle it would spike when
Speaker 3: you are doing either physically or emotionally stressful activities like
Speaker 3: running from a tiger is that true.
Speaker 1: Yeah, yeah, yeah. The morning cortisol spike is well described.
Speaker 1: It is one of the reasons why heart attacks are
Speaker 1: more common in the early hours of the morning, for example,
Speaker 1: because your body's sort of revving up to get ready
Speaker 1: to wake up the day. And we will get to
Speaker 1: this is a circadian rhythm, like one of our fundamental
Speaker 1: circadian rhythms. It's about five times higher in the morning
Speaker 1: than it is at night. I mean, it's a real
Speaker 1: it's a real shift over time. And if you really
Speaker 1: dig into the data, you'll find that the level of
Speaker 1: cortisol might not be as important as the circadian rhythm
Speaker 1: of cortisol. So one of the things we see in
Speaker 1: the truly chronically stressed are actually not high cortisol levels.
Speaker 1: It's a loss of that fluctuation. It's flat cortisol levels. Yeah.
Speaker 3: So I think that's a good that's a good pivot
Speaker 3: into what I the first piece of what's tough about
Speaker 3: this entire discussion is going to be really hard about
Speaker 3: the data, which is like what are we measuring and
Speaker 3: when are we measuring?
Speaker 2: So this is not there are some things we measure in.
Speaker 3: People where I think we can say, you know, maybe
Speaker 3: you want to do some repeat measurements, but like we
Speaker 3: have a good sense like something like you know like
Speaker 3: a one C levels for like a diabetic. You know
Speaker 3: you test me we you test it fasting not fasting.
Speaker 3: But we have a good sense, we have a stable
Speaker 3: sense of like how we test that, and we could
Speaker 3: use to say, you know you're a diabetic, you're not
Speaker 3: a diabetic. Measurements of cortisol which are done typically through
Speaker 3: your blood, although actually they can also do saliva, you
Speaker 3: can also do hair. You have many different ways to
Speaker 3: test this. They don't all test the same thing.
Speaker 2: And because there's this fluctuation, it's actually a really really
Speaker 2: hard thing to hit.
Speaker 3: If you wanted to say, what's the number that's going
Speaker 3: to tell me I'm chronically stressed in some dangerous way,
Speaker 3: there's sort of no number like that.
Speaker 1: Yeah, and actually it's a lab test that's pretty bad.
Speaker 1: So there's some lab tests like sodium level that's just
Speaker 1: it's been figured out and we can do it really
Speaker 1: quickly and it's highly accurate, and you test the same
Speaker 1: blood sample twice and you get the same number, and
Speaker 1: like it's really nice, and cortisol just isn't one of
Speaker 1: those things. I mean One of the major issues is
Speaker 1: that ninety five percent of cortisol in your blood is
Speaker 1: bound to proteins and is inactive, so these are just
Speaker 1: chaperone proteins that carry it around. And then the free fraction,
Speaker 1: the five percent, is the thing that does stuff in
Speaker 1: your cells. But almost all the lab tests out there
Speaker 1: are measuring the total, so you know that's is it
Speaker 1: correlated with the free Yeah, but not great and it's
Speaker 1: hard to know. There's obviously the timing of measurement that's
Speaker 1: really important, so you know, you really want to get
Speaker 1: if you actually needed to measure cortisol, for example, to
Speaker 1: tell if you have a disease of excessive cortisol production.
Speaker 1: And these diseases exists called Cushing syndrome or Cushing's disease,
Speaker 1: you get a test early in the morning when you've
Speaker 1: got the best chance of capturing things high. The assays
Speaker 1: that they use for cortisol have a lot of false positives,
Speaker 1: so there's cross reactivity with a bunch of other hormones
Speaker 1: and other substances that people are taking in It's just
Speaker 1: like I mean, I'll say right now, like getting your
Speaker 1: cortisol measured if you don't have symptoms of a cortisol
Speaker 1: excess disease is you're unlikely to get any useful information.
Speaker 3: So I think, okay, So when we talk about the
Speaker 3: way to measure cortisol, actually measuring blood has both the
Speaker 3: total and free fraction issue. It also has the issue
Speaker 3: that when you take someone's blood, it raises their cortisol.
Speaker 1: Yeah, because stressful.
Speaker 3: It's like, it's stressful, like somebody's sticking a needle in
Speaker 3: your arm and you're like, and it's a tiger, Like
Speaker 3: I better get ready to run away.
Speaker 2: It's not a tiger. You ask for that.
Speaker 3: But as a result, like saliva is in some sense
Speaker 3: the sort of best metric of this at a moment,
Speaker 3: because it's not stressful to take someone's saliva. But the
Speaker 3: thing that I wonder is why, you know we have
Speaker 3: continuous glucose monitors. Why has someone not made something that
Speaker 3: I stick in my You could put it on his
Speaker 3: zin pouch, something I stick in my mouth and leave
Speaker 3: in my mouth all the time, on like the side
Speaker 3: of my cheek, and then it constantly measures my quarter cel.
Speaker 3: Don't you think Brian Johnson would buy that in like
Speaker 3: one hot second, Like why is the market not delivering
Speaker 3: that Perry.
Speaker 1: What's the problem, No doubt people are pitching that in
Speaker 1: Silicon Valley right now.
Speaker 3: Call me, call me VC funds. We're gonna measure the
Speaker 3: cortisol with our mouths stick stick.
Speaker 1: I think two things. One, cortisol is complicated to measure.
Speaker 1: It's you know, it's a it's a hormone. It's it's
Speaker 1: it's a bigger molecule than something like glucose, which is
Speaker 1: small and easy to measure. And then the second thing
Speaker 1: is that nobody knows what to do with the answer.
Speaker 1: I could tell you what your cortisol is.
Speaker 3: That's not the answer. I'm sorry, that's not the answer
Speaker 3: to why they're constantly met. People love to measure stuff
Speaker 3: or something to do it. The first answer was right, Scott,
Speaker 3: you should have stopped at that one.
Speaker 1: Okay, we will erase the second. Now it's fine. I
Speaker 1: can be wrong sometimes.
Speaker 3: Okay, So this is very hard to measure, and we'll
Speaker 3: get into like why that probably means you shouldn't you
Speaker 3: shouldn't measure it. But despite its difficulty in measuring, there
Speaker 3: is actually a fair amount of research on the relationship
Speaker 3: between cortisol measured in some way. We will get to
Speaker 3: and various health outcomes, and I will just like spoiler,
Speaker 3: I think most of this literature is really bad and
Speaker 3: it is observational and not causal, and I have a
Speaker 3: lot of complaints about it, and I've been practicing my complaints.
Speaker 3: But before we get into them, I do think it's
Speaker 3: worth talking like a little bit more. You alluded to
Speaker 3: Cushings disease, but a little bit more about the places
Speaker 3: where high cortisol can actually be very damaging.
Speaker 2: Or we know that this is a this is a problem.
Speaker 1: Yeah, we should talk about Cushing's disease because actually a
Speaker 1: lot of the influencer work is taking what people see
Speaker 1: in Cushions disease where cortisol levels are through the roof
Speaker 1: and saying therefore, mildly elevated cortisol levels and normal people
Speaker 1: also do this thing. And so so what Cushing's disease
Speaker 1: is is a benign tumor, typically on the adrenal gland
Speaker 1: that secretes cortisol. It is unregulated, so it's sitting there
Speaker 1: and it's just secreting cortisols, secreting cortisols, secreting cortisol, and
Speaker 1: that is quite bad for you. The syndrome of Cushing
Speaker 1: syndrome is characterized by pretty dramatic moon faces. What they
Speaker 1: call it the very round face that you may be
Speaker 1: familiar with if you see people on very high dose
Speaker 1: of other cotquot steroids like predmozone. Sorry about these terms,
Speaker 1: but this is what the medical terms are. A buffalo hump,
Speaker 1: which is like a collection of fat on the upper
Speaker 1: part of the back at the bottom of the neck,
Speaker 1: strea which are really violacious, like deep purple stretch marks
Speaker 1: in the abdomen, a lot of accumulation of visceral fat, diabetes,
Speaker 1: high blood sugar, and so on and so forth. The
Speaker 1: treatment is removal of the cortisol secreting tumor, and.
Speaker 3: I think it is it's actually very important to note
Speaker 3: because some of the things we see in the sort
Speaker 3: of wellness influencer claim space are things that seem like, well,
Speaker 3: if you have this cushions disease, you will have this,
Speaker 3: and therefore, if you have a mildly elevated level of
Speaker 3: cortisol in the normal range, you also get less maybe less.
Speaker 1: Belly fat, but still some belly fat, right right, And
Speaker 1: that has that nice sort of like step by step
Speaker 1: ring to it. But if you've been listening to Onelm's actually,
Speaker 1: you know, you actually have to prove these things with data.
Speaker 1: So let's talk about data. I mean, I you know,
Speaker 1: there are clearly cases where cortisol high cortisol levels are
Speaker 1: bad for you. I mean maybe the most dramatic one
Speaker 1: is in sepsis in septic shock, where it is fairly
Speaker 1: well established that if people are coming in with very
Speaker 1: high cortisol levels in the setting of sepsis, they're more
Speaker 1: likely to die. It's a nice study in PLUS one
Speaker 1: in twenty nineteen that took one hundred and thirty nine
Speaker 1: patients with severe sepsis or septic shock, and those who
Speaker 1: had cortisol levels that were high by their definition had
Speaker 1: a tenfold higher mortality risk. It's a pretty large effects size. Now, Emily,
Speaker 1: that's not a causal step, as you said, that's observational.
Speaker 1: So walk me through like why, yeah, is it the
Speaker 1: cortisol that's bad or what are you thinking when you
Speaker 1: hear Okay, high cortisol tenfold risk of death in septic shock.
Speaker 3: Yeah, So I I think sort of two things in
Speaker 3: that case, which will come up again later. So one
Speaker 3: is that, yeah, this is not a randomized the cortisol
Speaker 3: some people came in with a higher level of cortisol
Speaker 3: than others. It seems plausible to me that that is
Speaker 3: measuring something else about, you know, how stressful, like what
Speaker 3: else is going on in your life? Or even like
Speaker 3: how bad is this sepsis? I realize all sepsis is bad.
Speaker 3: Sepsis is not good, but sort of like, could you
Speaker 3: read this as this is is kind of a metric
Speaker 3: itself of how much is the body struggling in other ways?
Speaker 2: And this is just one measure of that.
Speaker 3: I will say in this particular case, the fact that
Speaker 3: the odds ratio is ten, which means like the mortality
Speaker 3: risk is ten times as high, that's actually a quite
Speaker 3: that's a very big effect. It is Therefore, the kinds
Speaker 3: of biases I have in my mind, like differences in
Speaker 3: other things that could be going on in people's lives
Speaker 3: and so on, probably aren't driving a tenfold increase in mortality.
Speaker 3: So the comp nation here of the particular outcome which
Speaker 3: is so extreme and how large the effect size is,
Speaker 3: would makes me more confident in that result, even though
Speaker 3: I think it would be better to have a randomization.
Speaker 3: Although this is a case in which I cannot imagine
Speaker 3: how you would randomize people to different cortosol levels. That's
Speaker 3: not really an available randomization, which is why we're going
Speaker 3: to generally nature rely on observational data.
Speaker 1: Yeah. Yeah. And for the medical people listening who trained
Speaker 1: back when I did, there was a time when we
Speaker 1: gave people cortisol or other gluca cortoicoids when they had
Speaker 1: sepsis because we thought, oh, all this inflammation is the
Speaker 1: bat like, their immune system's going crazy. We need to
Speaker 1: suppress their immune system a little bit. That was standard
Speaker 1: of care for a while. No longer really do that
Speaker 1: except in rare circumstances, and so it is quite complicated.
Speaker 1: And I think, you know, it's certainly possible that a
Speaker 1: large amount of that observed effects size is just due
Speaker 1: to the fact that really sick people have really high
Speaker 1: cortosol potentially, but most people who are listening to us
Speaker 1: are not current lead.
Speaker 2: Shop. Yeah, stop listening. If that's you are hanging.
Speaker 4: There, and.
Speaker 1: Maybe we're the one thing keeping them, you know, seeing
Speaker 1: in the hospital bed. We're not all right, we believe
Speaker 1: in you.
Speaker 3: Most people are worried about the idea that a chronically
Speaker 3: elevated or frequently elevated level of cortisol or just having
Speaker 3: high cortisol whatever people seem to mean by that, is
Speaker 3: bad for some health outcome, like heart disease being the
Speaker 3: sort of the one you should start with.
Speaker 2: It's the one that comes up the most. And so
Speaker 2: this is a place where there is some.
Speaker 3: Data, and i want you to describe the data, and
Speaker 3: then I'm going to tell you my feelings on it,
Speaker 3: why it's wrong.
Speaker 1: I'll set you up in the best way I know how. Okay,
Speaker 1: I'm going to give you two studies here. One is
Speaker 1: sort of a prototypical. There's other studies in this space
Speaker 1: looking at urinary cortisol. Gosh, we didn't even mention that's
Speaker 1: there's yet another place you can measure cortisol. You can
Speaker 1: measure it in the urine and then the risk of
Speaker 1: cardiovascular mortality. This was from the Journal of Clinical Endocritinology
Speaker 1: and Metabolism. That's a good journal. Twenty ten, eight hundred
Speaker 1: and sixty one participants above age sixty five. They got
Speaker 1: twenty four hour urine cortisol levels at baseline, followed them
Speaker 1: for six years. Over the course of that time, people
Speaker 1: in the highest turtile, so the highest third of urinary
Speaker 1: cortisol levels had five times the risk of dying in
Speaker 1: cardiovascular disease, but there's no difference in depths from other causes.
Speaker 1: So there's a big effect size fivefold from higher cortisol levels.
Speaker 1: I told you I'd give you one other study just
Speaker 1: to give you something to talk about. So nope, I'm not.
Speaker 1: I'm going to wait on the Mendelian randomization because it's
Speaker 1: going to require some explanations. So let's start with this.
Speaker 1: My urinary cortisol is in the top third of people's
Speaker 1: urinary cortisol. I have fivefold the risk of dying from
Speaker 1: cardiovascular disease in the next six years. Sounds pretty bad.
Speaker 1: Got to get my cortisol down, okay, I mean.
Speaker 3: Look, here are some things that raise people's cortisol. Being poor,
Speaker 3: working at night, having few resources, having a stressful family life,
Speaker 3: having other diseases, things like that. All of those things
Speaker 3: are independently associated with death from heart disease. We know
Speaker 3: that like a million different ways, exercise causes you to
Speaker 3: be less dying rate lowers your cortisol. Overall, all of
Speaker 3: these things are going on in the background. And if
Speaker 3: you look at the people in this study and you
Speaker 3: look at the tersiles, they differ in a bunch of
Speaker 3: different ways from each other, and it is therefore extremely
Speaker 3: difficult to imagine that we are attributing this difference in
Speaker 3: the risk of death to these levels of cortisol as
Speaker 3: opposed to attributing them to these other things. Now, this
Speaker 3: is a case in which actually the whole thing is
Speaker 3: very complicated, because, well, maybe it's these other things raising
Speaker 3: your cortisol, which is then causing you to you know,
Speaker 3: have a higher risk of death.
Speaker 2: That's an interesting mechanism.
Speaker 3: But if you ask, like, what's the act like, what's
Speaker 3: the action item here, what's the like thing that would
Speaker 3: it's changing these other things.
Speaker 2: It's not like if you gave someone.
Speaker 3: A shot that magically lowered their cortisol that would have
Speaker 3: this positive impact on them. These results are also this
Speaker 3: sample is quite small, not that many people died, which
Speaker 3: is good, and the therefore this sort of hazard ratio
Speaker 3: of five is like incredibly noisy. It's consistent with an
Speaker 3: effect that's two, it's consistent with an effect of thirteen times,
Speaker 3: which is definitely not true. It's just this is a
Speaker 3: statistically noisy, very potentially biased effect.
Speaker 2: I just I don't think we learn anything from studies
Speaker 2: like this. I just think we learned nothing.
Speaker 1: So I completely agree that there's all this stuff that
Speaker 1: can affect your cortisol that might also independently affect your
Speaker 1: risk of death. Right we know in America at least
Speaker 1: being poor dramatically increases your risk of dying from Christ and.
Speaker 2: Also dramatically increases so yeah.
Speaker 1: So so okay, that's classic confounding. The problem is, you know,
Speaker 1: we all love a randomized trial, but no one's going
Speaker 1: to do a randomized trial of like supplemental cortisol on
Speaker 1: people that's not going to happen. Probably would be considered unethical.
Speaker 1: So we're left with some other options, and I think
Speaker 1: I think we need to talk about Mendelian randomization. Okay,
Speaker 1: so let's put on our genetic hats for a second.
Speaker 1: I sort of believe in Mendelian randomization as an approach,
Speaker 1: and Emily, I think you are more skeptical of it.
Speaker 1: So I'm gonna let me tell you how I view it,
Speaker 1: and then you tell me why I'm wrong. Okay, here's
Speaker 1: the idea. There are certain genes that increase the amount
Speaker 1: of cortisol you make independent of other things. Genes that
Speaker 1: have to do with hormone synthesis and stuff, and everyone
Speaker 1: has little variations in their genes, and some are just
Speaker 1: a bit more active than others, and so all else
Speaker 1: being equal, there are people who genetically live at a
Speaker 1: higher cortisol level than a similar person who had a
Speaker 1: different genetic background, so you know, and this is true
Speaker 1: of everything, not just cortisol. Right, Like, there's some people
Speaker 1: just genetically have a higher LDL than other people, and
Speaker 1: some people have genetically lower LDL. Okay, because your genetics
Speaker 1: are assigned at birth, not no, at conception. That exposure
Speaker 1: happens before you know that you're poor, before you know
Speaker 1: you have stress in your life, before anything else, it
Speaker 1: cannot be related to that. The genetics are not related
Speaker 1: to those things. Being poor doesn't change your DNA, right,
Speaker 1: And therefore we can use those genetic signals and say, Okay,
Speaker 1: here's a person whose genes have them exposed to a
Speaker 1: higher level of cortisol than they otherwise would have been
Speaker 1: given everything that's going on in their life. And here's
Speaker 1: a person whose genes have their cortisol lower than they
Speaker 1: otherwise would have been, giving everything that's going on in
Speaker 1: our life. And if the person with the genes that
Speaker 1: predispose them to high cortisol has a higher risk of
Speaker 1: cardiovascular disease. Then the person whose genes predisposed them to
Speaker 1: low cortisol. I conclude, therefore, there is a causal link
Speaker 1: between cortisol level and cardiovascular disease.
Speaker 3: The term Mendilion randomization implies that something is being randomized,
Speaker 3: and so I think when we think about this technique,
Speaker 3: we want to think about the word random. So what
Speaker 3: you are suggesting is that the genes are allocated randomly,
Speaker 3: that when you are given genes are there's a piece
Speaker 3: of the genetics that are coming randomly to you. That
Speaker 3: is not true when comparing across people in the population overall.
Speaker 3: So let me give you a more like direct example
Speaker 3: of this. Imagine that instead of cortisol, we were thinking
Speaker 3: about eye color and you said, there's a gene that
Speaker 3: determines your that determines your eye color. In fact, there
Speaker 3: is a gene that determines your eye color. There's a
Speaker 3: set of genes. We understand about how those work, but
Speaker 3: it is not when we look across the population, those
Speaker 3: genes are not randomly distributed. It's not like randomly when
Speaker 3: you're conceived you are given one of the eye color genes.
Speaker 3: It's random only conditional on the genes.
Speaker 2: That your parents have.
Speaker 3: So you have a set of parents, and you have
Speaker 3: your mom has a set of twenty three chromosomes. She
Speaker 3: has two copies of each, and at conception in the egg,
Speaker 3: you get one of those and which one you get
Speaker 3: is random. But who your mother is, the genetics that
Speaker 3: she starts with is not random. So when we talk
Speaker 3: about Mendolian randomization, there's something cool, a cool idea in here.
Speaker 3: I want you to imagine two children born to the
Speaker 3: same set of parents, and mom has two copies of
Speaker 3: each chromosome, and on one of those chromosomes she's got
Speaker 3: like the high cortisol gene, and on the other copy
Speaker 3: she's got the low cortisol gene. And her children, let's
Speaker 3: say one of them gets the high cortisol, one of
Speaker 3: them gets the low cortisol. That's random, and so then
Speaker 3: we have two siblings who are effectively everything is, you know,
Speaker 3: the same, except that in this case this particular thing
Speaker 3: is randomly allocated. Wait, and so you could then get
Speaker 3: many sibling pairs like that, and say, conditional on your family,
Speaker 3: controlling for your parentage. Comparing you to your siblings. We're
Speaker 3: going to see whether the sibling who was randomly allocated
Speaker 3: the high cortisol gene has worse outcomes than the sibling
Speaker 3: that was not randomly allocated. That's a really cool idea
Speaker 3: that uses genetics and randomizes.
Speaker 1: Do you agree? Yeah? All I wanted to say was
Speaker 1: that in my mind, one of these kids is named
Speaker 1: Gene and the other is named.
Speaker 2: I love that so much. Okay, but what okay?
Speaker 3: So that technique, that technique works like, that works sort
Speaker 3: of in concept the way I've described it, and there
Speaker 3: are some actually some issues with using that technique in practice,
Speaker 3: but at least in principle, there is a real randomization there.
Speaker 2: Here is the problem.
Speaker 3: The studies that are being done that are using a
Speaker 3: technique they are referring to as Mendillion randomization do not
Speaker 3: actually do what I just described. Instead, what they do
Speaker 3: is they don't look within sibling pairs. They look just
Speaker 3: across people in the population. And that is ridiculous because
Speaker 3: genetics are not randomly allocated across people in the population.
Speaker 3: I mean, an equivalent thing is if you said, well,
Speaker 3: I'm interested in the impact of race on something, and
Speaker 3: I don't think I can just look at people's race,
Speaker 3: because that's confounded with all kinds of other things. But
Speaker 3: I'm going to look at a gene for skin color
Speaker 3: and I'm going to relate that to the out Well,
Speaker 3: that's stupid, that's not like.
Speaker 2: Doesn't make any sense. It doesn't work.
Speaker 3: And so this this technique is not being it's not
Speaker 3: that it's conceptually poor, it's being used in a way
Speaker 3: that makes no sense.
Speaker 1: Well, so the there is a caveat to Mendelian randomization.
Speaker 1: So to take your skin color example, which says that
Speaker 1: in order to use this technique, you have to show
Speaker 1: that the gene is associated with the phenotype. Right, So
Speaker 1: the gene is associated with skin color, let's say, and
Speaker 1: the gene is associated with the outcome, but the gene
Speaker 1: is not associated with the outcome through any plausible path
Speaker 1: outside of the phenotype. So there is like some statistical
Speaker 1: testing you can may for that.
Speaker 2: Yeah, that's called the exclusion restriction.
Speaker 3: And in the cases that you've described, where we're comparing,
Speaker 3: say to people with different genetics across different families, where
Speaker 3: for example, one of them is born to a set
Speaker 3: of parents who have high cortisol and one of them
Speaker 3: is born to a set of parents with low cortisol.
Speaker 3: Now your exclusion restriction is failed, and so that just
Speaker 3: doesn't work. So I think you're right, there is a
Speaker 3: thing and it's totally failing, and these guys don't seem
Speaker 3: to understand that.
Speaker 2: I just don't understand. I fundamentally perry.
Speaker 3: This is like drives me crazy because people in medicine
Speaker 3: use this technique all the time, and I just think
Speaker 3: they don't understand what they're doing, and I can't understand
Speaker 3: why they don't understand.
Speaker 1: Let me give you the results of the cortisol Mendelian
Speaker 1: randomization because maybe this is a moot point. Okay, So
Speaker 1: in the observational framework, we've seen that a high level
Speaker 1: of cortisol increases your risk of cardiovascular death by five
Speaker 1: hundred percent. Okay. In the Mendelian randomization analysis, genes predisposing
Speaker 1: high cortisol increase the risk of cardiovascular death by eight percent.
Speaker 2: Right, I mean, okay.
Speaker 3: So one thing is if you think what Mendelian randomization
Speaker 3: is doing is fixing your causality problem, then I think
Speaker 3: what you would say, Okay, now we've got a better result,
Speaker 3: and it's basically zero like it's it does basically doesn't.
Speaker 1: Matter, does not suggest causality.
Speaker 3: I will say, I think counter counter example, as I've noted,
Speaker 3: I don't think the Mendelian randomization really makes any sense
Speaker 3: at all.
Speaker 2: And part of the reason that the effect I think
Speaker 2: is much.
Speaker 3: Smaller is because the genes are identifying have very little
Speaker 3: predictive power on actually having high cortisol, and so like
Speaker 3: just these these genes are not have very high penetrants,
Speaker 3: and so this may be failing and giving you a
Speaker 3: very small number for reasons that kind of have nothing
Speaker 3: to do with getting rid of bias. They may just
Speaker 3: be generating noise. I hate this technique.
Speaker 2: I understand that I'm being like and talking about I hate.
Speaker 1: I just that's fine. We can't randomize people to high cortisol.
Speaker 1: We can't supplement them with cortisol or placebo, so we're stuck.
Speaker 1: We have to make some inferences. But I will say
Speaker 1: that based on this data, it's there's not a compelling
Speaker 1: argument high cortisol level in and of itself is causal
Speaker 1: of cardiovascular disease.
Speaker 2: I totally that. I think we totally agree.
Speaker 3: I think your question about give me a better technique
Speaker 3: is an interesting one. I mean, I do think a
Speaker 3: true Mendelian randomization with a sort of a sibling pairastudy
Speaker 3: would be an interesting thing to explore. It could have
Speaker 3: some other problems, but I think that would be something
Speaker 3: interesting to explore. I agree this is a very difficult problem.
Speaker 3: I think one thing you could imagine randomizing if you
Speaker 3: sort of at least in a short term way, is
Speaker 3: you know, some of the kind of like behavioral techniques
Speaker 3: that might lower people's cortisol, like meditation. You can imagine
Speaker 3: running a study where you're like one group gets like
Speaker 3: a lot of meditation support or some other you know,
Speaker 3: therapy something that would lower their cortisol.
Speaker 2: It probably have other effects, so.
Speaker 3: It's not like a great study, but I you know,
Speaker 3: like it's something like that to try to affect people's cortisol.
Speaker 2: I agree, we're not going to find anything, but doesn't
Speaker 2: mean it's not interesting to.
Speaker 1: Try to at least.
Speaker 3: Luck. All right, let's get so sorry, I got so
Speaker 3: exercise guy. I feel like people are going to be like,
Speaker 3: why are you so exercised about this? But it's like,
Speaker 3: this is my job, This is like a thing, this
Speaker 3: is like the core of my of my like professional
Speaker 3: life other than parenting. Writing is like statistical methods.
Speaker 1: What you guys don't know is that Emily, Emily's first
Speaker 1: boyfriend was a Mendelian randomization study.
Speaker 4: So okay, I want to move rather quickly through the
Speaker 4: other basically true stuff that the other stuff.
Speaker 1: That people say that high cortisol does. If we're going
Speaker 1: to write off cardiovascular disease, and again, guys, we're not
Speaker 1: saying that there's no association between higher cortisol levels and
Speaker 1: these things. We're asking is it the cortisol not the
Speaker 1: like life stress and the other stuff. So I think
Speaker 1: you know a big one is diabetes metabolic disease, right, Like,
Speaker 1: we we certainly know that people with cushions syndrome much
Speaker 1: high risk of diabetes. We know that when you put
Speaker 1: people on steroids like prednozone or hyd you courtizona, their
Speaker 1: blood sugar goes up. I was surprised here, Emily, Like,
Speaker 1: there's a nice meta analysis of twenty one studies. This
Speaker 1: is appearing in psycho Neeuroendrochronology. In twenty eighteen, eleven thousand
Speaker 1: people or almost twelve thousand people, no significant difference in
Speaker 1: basil cortisol levels between subjects with and without the metabolic syndrome,
Speaker 1: which I just wouldn't have. And that's like, that's not
Speaker 1: even a causal study. It's just I mean, I think
Speaker 1: there's no link.
Speaker 2: What's so interesting there is?
Speaker 3: I might have I would have thought that that we
Speaker 3: would see an association there just because of all these
Speaker 3: other factors.
Speaker 2: Totally, But it seems like even you know.
Speaker 1: Even the confounding can't and the confounding can't.
Speaker 2: Get you there somehow. Yeah, maybe that's that's hard to measure.
Speaker 1: Let's do stubborn belly fat?
Speaker 2: Yes, so much of it? Okay, how do I.
Speaker 1: Have so much stubborn belly fat? I don't think you too.
Speaker 2: It's so stubborn. I am always arguing with it. It's
Speaker 2: always making these terrible points.
Speaker 1: Are Producer Tamar just rolled her eyes like Emily's saying
Speaker 1: she has belly fat.
Speaker 3: Enoise describe stubborn Well, okay, anyway, I as a middle
Speaker 3: aged man, stubborn belly fat is I get it.
Speaker 1: It's stubborn because it's like I work out, I try
Speaker 1: to eat right, and it's still there and that's annoying.
Speaker 1: So I did look into this for us once again
Speaker 1: in Cushing syndrome and Cushing's disease, there is a substantial
Speaker 1: increase in visceral outipost tissue. That's what belly fat is,
Speaker 1: as opposed to subcutaneous fat, which is kind of all
Speaker 1: over your body. Belly fat is visceral fat, and it's
Speaker 1: not good for you. Higher amounts of visceral fat are
Speaker 1: associated and potentially causally with cardiovascular disease. But in a
Speaker 1: study pering clinical endochronology in twenty twenty four, they looked
Speaker 1: at visceral fat and subcutaneous fat among people just regular
Speaker 1: joes with varying cortisol levels, and there was no association
Speaker 1: between higher cortisol level in the non pathologic range, in
Speaker 1: the non Cushing's disease range, and belly fat. So that's
Speaker 1: not it, folks.
Speaker 3: I also think it's worth saying, like when people are
Speaker 3: chronically stressed, it actually isn't.
Speaker 2: We said this at the topics.
Speaker 3: We're saying again, it's not that chronic stress means you
Speaker 3: always have a high cortisol level. It actually means your
Speaker 3: cortisol is very flat, as opposed to moving up and
Speaker 3: down like it's sort of supposed to typically, And so
Speaker 3: like your cortisol is supposed to be responsive to like
Speaker 3: events and to the day, which of course is evolutionary
Speaker 3: valuable because you want to really be able to respond
Speaker 3: when the tiger.
Speaker 2: When the tiger comes.
Speaker 3: When people are chronically stressed, they can get a sort
Speaker 3: of flattening of the cortosol, but it's not that it's higher,
Speaker 3: and so this sort of whole narrative is kind of
Speaker 3: con Yeah, it.
Speaker 1: Can even burn out. So there's some nice studies in PTSD,
Speaker 1: in patients with PTSD that actually shows your typical patient
Speaker 1: with PTSD has lower cortisol levels than controls who don't
Speaker 1: have trauma. So yeah, this whole idea that like, your
Speaker 1: cortisol is so high and because you're so stressed, if anything,
Speaker 1: it's blunting the cortisol response, or your cortosol might even
Speaker 1: be low.
Speaker 3: So you don't need to detox your cortisol, not that
Speaker 3: we have any Like people will sell you a lot
Speaker 3: of stuff gum ease.
Speaker 1: Yeah, n well, yeah, I mean I did, I did
Speaker 1: look into it in case people want to make their cortisol.
Speaker 1: You know what, there are some things that will make
Speaker 1: your cortisol lower that I think are good for you anyway,
Speaker 1: So there's a pretty large meta analysis of randomized control
Speaker 1: trials you talked about, you know, randomizing people to interventions
Speaker 1: to lower cortisol, which of course have off target effects.
Speaker 1: This is once again psycho Neeurontochronology twenty twenty four or
Speaker 1: fifty eight randomized trials just about thirty five hundred patients
Speaker 1: looking at different ways to reduce cortisol levels, and mindfulness,
Speaker 1: meditation relaxation techniques both reduce cortisol levels by about a
Speaker 1: third or so, not bad. Interestingly, the studies of yoga
Speaker 1: and tai chiet didn't have a significant effect, and the
Speaker 1: talk therapies like cognitive behavioral therapy and counseling did not
Speaker 1: have a significant effect.
Speaker 3: So meditation, Yeah, exercise is good for your cortisol lowers
Speaker 3: your cortisol.
Speaker 2: We also see that in randomized control trials.
Speaker 1: Yep, absolutely exercise and we've hit on the several times.
Speaker 1: But sleep, you guys, especially especially if you want to
Speaker 1: maintain that diurnal variation, which does appear to be an
Speaker 1: important thing for your overall health. Getting adequate amounts of
Speaker 1: sleep gets the cortisol into the right place at the
Speaker 1: right time.
Speaker 3: So is it worth I think an interesting question is
Speaker 3: it worth measuring your cortisol at all? So we just
Speaker 3: gave you know there are these are recommendations too that
Speaker 3: will reduce your cortisol, but also things which you should
Speaker 3: probably be doing for a general like health maintenance regardless.
Speaker 3: Would you recommend someone measure their cortisol.
Speaker 1: If they had moon faces, a buffalo hump, or a
Speaker 1: violaceous strea, I would recommend that they have cortisol levels measured.
Speaker 2: Do you want to know what my cortosol level is?
Speaker 3: Because I looked it up while we were here, because
Speaker 3: I had it measured in the last time I had
Speaker 3: a blood test.
Speaker 1: What time of day was it.
Speaker 2: It was in the morning.
Speaker 1: It was fifteen micrograms pertest leader nineteen.
Speaker 2: It only got in in the sufficient range for.
Speaker 1: We should say, I can't believe yeah, sufficient, You know
Speaker 1: you die without enough cortisol, right, Like that's the other
Speaker 1: The flip side of this is that your adrenal glands
Speaker 1: can stop producing cortisol. This is called Addison's disease, which
Speaker 1: JFK had, and it causes like severe hypotension, sodium wasting death.
Speaker 1: You need to supplement that's bad too. So I think
Speaker 1: the cortisol is just like not something if you're into
Speaker 1: interested in your health and wellness, it's just not worth
Speaker 1: your time. It's like, don't you're not going to change
Speaker 1: your life based on it. And yes you should destress,
Speaker 1: but not because of cortisol.
Speaker 3: Look, I think every time we talk about hormones, I
Speaker 3: am more and more impressed with the endocrine system. I
Speaker 3: feel like, you know, the human endocrine system is so
Speaker 3: like tight, and it's so well thought out, and there's
Speaker 3: so much of the wellness space that's about like give
Speaker 3: yourself more of this hormone and more of that homer
Speaker 3: and do this, and most of the time, like your endocrinsism,
Speaker 3: like it's thinking about that, like it thought about when
Speaker 3: the cord sho should be, when it should be low,
Speaker 3: like how much you need. It's like estrogen, Like we're
Speaker 3: all kind of moving moving together, and I just I
Speaker 3: don't think it's a system we want to be messing
Speaker 3: with too much.
Speaker 1: With the exception of hormone replacement therapy and with the exceptional.
Speaker 3: Yeah, yeah, okay, there are some things, but like like
Speaker 3: our tendency to want to get inside the endocrine system
Speaker 3: and mess around with it, I think is over. I
Speaker 3: think we're doing we're doing too much of that outside
Speaker 3: of I agree hormone replacement.
Speaker 1: Yeah yeah. Cortisolt too high is bad, Cortisol too low
Speaker 1: is bad. It needs to have a specific pattern. You're
Speaker 1: not going to get this right with like ashwaganda, which
Speaker 1: does lower your cortisol a little bit, by the way,
Speaker 1: but like this is one. Trust your body a little
Speaker 1: bit and be zen.
Speaker 3: Trust your body, but don't trust Mendelian randomization because it's stupid.
Speaker 1: It can be done very well.
Speaker 2: It can be, but it's not okay. Enough of that
Speaker 2: for me, all right, Perry, smash your pass cortisol.
Speaker 1: I mean I'm a pass in terms of cortisol as
Speaker 1: a wellness metric. Obviously I love the hormone. I die
Speaker 1: without it, so do you. But I'm a past Emily
Speaker 1: Smasher pass.
Speaker 3: I am a pass on anything that involves detoxing, retoxing,
Speaker 3: changing gummies adapt to this and that. Just trust your
Speaker 3: endocrine system unless you have a buffalo and then get
Speaker 3: it looked at.
Speaker 1: All Right, that's it for cortisol. Your mail bag question
Speaker 1: of the Week after the break.
Speaker 2: Hi, Emily and Perry. This is celestin Detroit. My question
Speaker 2: is more personal to both of you.
Speaker 3: Is there anything that you felt certain about like ten
Speaker 3: years ago that now you look back on and cringe.
Speaker 2: We all have them, and I'm dying to know yours. Thanks.
Speaker 1: Oh, this is such a good question. I'm sure there
Speaker 1: are many things that I've suppressed, and I have convinced
Speaker 1: myself that I never believed that really I did. But
Speaker 1: the one I am quite sure I believed strongly. And
Speaker 1: I think I'm going to just cheat a little bit
Speaker 1: and say this was more like fifteen years ago, maybe
Speaker 1: even pushing twenty years ago. But I was a hardcore
Speaker 1: fluid resuscitation vigilante when I was in medical training. So
Speaker 1: when someone came into the ICU with sepsis, I was
Speaker 1: it was like a contest, like how much IVY fluid
Speaker 1: can I put into this person in the next twelve hours?
Speaker 1: And back then, we thought this was the right thing
Speaker 1: to do. This totally makes me cringe now, like there's
Speaker 1: been a lot of evidence in the past twenty years
Speaker 1: that suggests that overly aggressive fluid resuscitation can cause major
Speaker 1: problems down the road, and you know, people get volume
Speaker 1: overloaded and their lungs don't work anymore and stuff like that.
Speaker 1: But it was like it used to be a contest
Speaker 1: among the residents, like I gave that guy fifteen liders
Speaker 1: last night and like high five, like, yeah, that's how
Speaker 1: you treat sepsis. And I cringe a little bit thinking
Speaker 1: about that. Now, why you am.
Speaker 2: I that's amazing.
Speaker 3: Mine is more Mine is more personal. It actually vaguely
Speaker 3: relates to to cortosol. So I used to be very
Speaker 3: sure that you should exercise in the morning before you eat,
Speaker 3: and that you should like not eat anything before you
Speaker 3: you should like exercise fasted. But it turns out that's
Speaker 3: really stupid and it's really bad for your cortisol. I
Speaker 3: think it raises your cortisol a lot to exercise fasted,
Speaker 3: and I don't do that anymore. And I think it
Speaker 3: was part of this space of like, you know, like
Speaker 3: diet culture that I find now very cringey.
Speaker 1: It's okay, we're all entitled to change.
Speaker 3: I can't believe you guys were high fiving. That's like,
Speaker 3: that's so nerdy and weird. Oh yeah, it makes me Yeah, okay,
Speaker 3: I have feelings. I'm not going to comment.
Speaker 1: Thanks.
Speaker 2: All right, that's it for us today.
Speaker 3: Stick with us next week when we'll ask what's the
Speaker 3: deal with pregnancy brain and we'll have a special guest.
Speaker 3: Wellness Actually is produced in association with iHeartMedia. Our senior
Speaker 3: producer is Tamar Avisheid. Our executive producer at iHeart is
Speaker 3: Jennifer Bassett. Our theme music is by Eric Deutsch, and
Speaker 3: our content is for educational purposes only.
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Speaker 1: Head over to Wellness Action and leave us a question
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Speaker 2: We'll let the influencers have the last word.
Speaker 5: When your cortisol levels are elevated, you can hang on
Speaker 5: to a lot of fat around your middle and this
Speaker 5: can be really frustrating because it seems like you're doing
Speaker 5: everything right, but it's not budging. The first thing I
Speaker 5: want you to do is get rid of the high
Speaker 5: intensity interval training. The second thing is intermittent fasting.
Speaker 2: Get rid of it.
Speaker 5: Eat thirty grams of protein within thirty minutes of waking up.
Speaker 5: And the third one is the least fun, and that
Speaker 5: is to stop drinking coffee first thing in the morning
Speaker 5: on an empty stomach.
Speaker 2: This third one might piss you off.