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Speaker 1: The first hand account for this episode features the story

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Speaker 1: involving the death of a family member. Some listeners might

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Speaker 1: find this upsetting, so please listen with discretion.

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Speaker 2: Hi. I'm Tori, and I have familial hypocholesterolemia. I think

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Speaker 2: growing up, I always knew my dad was different because

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Speaker 2: he walked with a limp and he spoke weirdly. He

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Speaker 2: couldn't like write or do anything, but I didn't know why.

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Speaker 2: And then I remember when I was ten years old,

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Speaker 2: my mom requesting that I get my cholesterol checked at

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Speaker 2: a doctor's appointment, and they're like, she's ten. I think

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Speaker 2: it was when they sat me down and told me

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Speaker 2: that my dad had had a heart attack which turned

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Speaker 2: into a stroke when I was a baby, and so

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Speaker 2: that's why things were a little different. And then that

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Speaker 2: the same thing happened to his father. His father was

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Speaker 2: forty five. My dad was forty seven when he had

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Speaker 2: his heart attack, and then they told me what causes

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Speaker 2: it and why they're worried that I could have it.

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Speaker 2: When I was fourteen, my cholesterol was two hundred and

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Speaker 2: thirty two, which not good, and they told me, like, oh,

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Speaker 2: died an exercise. Come back in a year and it

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Speaker 2: was two hundred and thirty one, and so we were like,

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Speaker 2: this is something more, it's not just lifestyle. But then

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Speaker 2: the pandemic happened and there was like so much going on.

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Speaker 2: But I finally got like tested again, and they were like,

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Speaker 2: we can't put you on statin unless you have a

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Speaker 2: geneticist prove that this is something. So I had to

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Speaker 2: go to a geneticist, and I have a fun little

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Speaker 2: chart that's like she's missing something. That's now what I

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Speaker 2: live with. I'm on statin for the past two years.

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Speaker 2: My cholesterol is one ninety seven, still a little high.

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Speaker 2: But last July, I was taking a nap and I

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Speaker 2: got like shook away by my brother in law and

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Speaker 2: I hear like sobbing in the background, and I remember

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Speaker 2: being told we have to go to the hospital right now.

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Speaker 2: And I check my phone and there's a text from

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Speaker 2: my mom that says your sister's heart stopped and the

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Speaker 2: name of the hospital that they were at. And so

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Speaker 2: we speed over there, and when we get there, the

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Speaker 2: chaplain tells us that there was nothing they could do.

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Speaker 2: She was only three weeks away from her twenty sixth birthday.

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Speaker 2: It was kind of a huge shock and kind of

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Speaker 2: be like.

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Speaker 3: Oh, this is real, This is like real real.

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Speaker 2: You know. So, yeah, that's something that I live with

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Speaker 2: and the constant back in my mind. I don't really

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Speaker 2: know how to talk about it unless it's like fun

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Speaker 2: fact my DNA's miss you know. But it always comes

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Speaker 2: up where I'm like, oh, I don't eat red meat.

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Speaker 3: Oh I can't have that.

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Speaker 2: I can't do this. I have to take my pills.

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Speaker 2: I have a plethora of pills that I take every

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Speaker 2: morning a night. For a bit, my twin had to

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Speaker 2: wear a heart monitor because they now have a FIB.

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Speaker 2: I've dazzled it for them. It is something that's discussed openly.

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Speaker 2: I think that fear has gotten really largely into my

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Speaker 2: mom's head and she's like, you have to take this,

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Speaker 2: this and this, and are you doing like your exercises

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Speaker 2: and stuff like that, and so I think it is

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Speaker 2: just very established that this is a fear. It's a

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Speaker 2: huge part of my life, and then it's a huge

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Speaker 2: part of my anxiety where it's like this could be it.

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Speaker 3: But I think just realizing that.

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Speaker 2: This is going to be the rest of my life

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Speaker 2: and it may not be as long as you know,

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Speaker 2: others and my dad was lucky to survive his heart attack.

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Speaker 3: His father and my sister were not.

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Speaker 2: So it's just kind of this like constant worry that

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Speaker 2: this might happen, and a lot sooner than you think.

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Speaker 1: Torri, thank you so much for taking the time to

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Speaker 1: chat with us and share your story. We deeply, deeply

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Speaker 1: appreciate it. Thank you so much. Hi, I'm Aaron Welsh

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Speaker 1: and I'm Erin Alman Updike, And this is this podcast

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Speaker 1: Will Kill You And.

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Speaker 4: Today we're talking about cholesterol today and next week.

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Speaker 3: Because it's kind of a big deal.

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Speaker 5: So it's going to take a while.

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Speaker 3: A pretty big deal. It's a pretty big deal.

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Speaker 2: Yeah.

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Speaker 1: We decided to divide this up into two different episodes

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Speaker 1: because the first is really about cholesterol, because you know,

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Speaker 1: LDL is one just one part of the cholesterol story.

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Speaker 1: Athos Gloves is just one part of the story. And

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Speaker 1: so that's the story that we're going to be talking

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Speaker 1: about this week, So the role of cholesterol in our

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Speaker 1: bodies overall and the role of cholesterol in disease. Yeah,

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Speaker 1: and then next week we're talking statins, we're.

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Speaker 5: Talking what do we do about it?

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Speaker 3: What do we do about it?

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Speaker 1: It won't it won't just be statins, but it will

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Speaker 1: be focused on like how do we lower cholesterol? And

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Speaker 1: why would we lower cholesterol?

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Speaker 5: Why? Yeah? How low can we go? Just kidding that

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Speaker 5: is like a very.

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Speaker 1: Small part, but yeah, say there is a low that

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Speaker 1: is too low?

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Speaker 3: Correct?

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Speaker 5: Yeah? Yes, yeah, do you eat it?

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Speaker 1: There's there's a lot of good material to cover, so

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Speaker 1: let's just get through the rest of this intro is necessary.

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Speaker 1: It's not exciting, but like you know, we want to

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Speaker 1: get to the media.

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Speaker 3: It's quarantine disaster. What are we drinking this week?

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Speaker 4: We're drinking plac attack black attack, black attack? Are we

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Speaker 4: attacking plaque? Is plaque attacking us?

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Speaker 5: A little bit of both?

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Speaker 3: Yeah. Plac Attack is a delicious bev.

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Speaker 1: It has blueberries and lemon juice and uh sparkling water

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Speaker 1: and a little bit of simple syrup and cement to

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Speaker 1: make it nice and refresh.

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Speaker 2: Yeah.

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Speaker 4: Has nothing to do with your cholesterol, but it is delicious.

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Speaker 1: Yeah.

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Speaker 4: We'll post the full recipe on our website, this podcast,

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Speaker 4: Akillia dot com and all of our social media channels too.

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Speaker 5: So are you following us there? Because then you could

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Speaker 5: see this.

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Speaker 3: You could see this, You could see this.

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Speaker 1: You also could see this if you go to our

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Speaker 1: website This podcast will Kill You dot com, which features

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Speaker 1: not just pictures of quarantine, eat recipes and still maybe

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Speaker 1: videos from past one's working on that still still, but

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Speaker 1: you can also find things like transcripts. You can find

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Speaker 1: our show notes. You can find links to bookshop dot org,

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Speaker 1: affiliate page, music by Bloodmobile, about us page, merch Patreon,

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Speaker 1: submit your first hand account form, contact us form.

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Speaker 3: I got there in the end, you did.

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Speaker 5: You really nailed it, are and I don't think you

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Speaker 5: missed a single thing.

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Speaker 3: Thanks for saying that. That's all we got, right.

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Speaker 1: We can just yeah, I think so, rate reviews, subscribe,

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Speaker 1: do those things, and also I'll just throw it out there,

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Speaker 1: you know. Thank you to everyone who has ever suggested

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Speaker 1: an episode topic.

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Speaker 3: It's really helpful.

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Speaker 1: We love getting topic ideas from you all and feedback

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Speaker 1: from you all, and so keep it up.

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Speaker 5: Yeah, I love it. Also, thank you to everyone who

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Speaker 5: has submitted first hand accounts too. We really do read

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Speaker 5: them all, and sometimes it might take us, like I

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Speaker 5: don't know, two or three years.

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Speaker 3: To reach out to you.

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Speaker 1: That doesn't even longer us what our record is, yeah,

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Speaker 1: more than three years, But.

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Speaker 4: Thank you, we really do appreciate it. And like being

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Speaker 4: able to hear all of your stories and share your stories.

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Speaker 4: It's what makes this podcast in our opinions, So thank you.

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Speaker 3: Absolutely.

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Speaker 1: Well, let's take a quick break and then get into

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Speaker 1: the story of cholesterol.

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Speaker 4: Let's my goal for you today is that in the

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Speaker 4: next I don't know twenty minutes or so, okay, you

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Speaker 4: will understand what on earth cholesterol actually is and what

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Speaker 4: our bodies are supposed to be using it for, and

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Speaker 4: then what your doctor actually means when they talk about

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Speaker 4: your quote unquote cholesterol and why those levels matter for

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Speaker 4: your health.

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Speaker 5: All right, love this, Okay.

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Speaker 4: So, cholesterol itself is a type of lipid molecule, and

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Speaker 4: we think of lipids as fats. Technically fats are just triglycerides,

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Speaker 4: but whatever think of them as fats. And it's specifically

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Speaker 4: a type of lipid called a sterol, like colsterolol.

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Speaker 5: Okay.

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Speaker 4: Cholesterol is just a string of carbons and hydrogens and

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Speaker 4: one oxygen that's formed in these little rings. There's like

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Speaker 4: four rings together, so it's a pretty rigid molecule. And

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Speaker 4: cholesterol is an essential molecule for all animal life and

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Speaker 4: really nearly all kinds of life on Earth need things

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Speaker 4: like cholesterol. So plants they don't make cholesterol, really, but

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Speaker 4: they do make a whole bunch of other very similar

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Speaker 4: compounds called phytosterols phytosterols phytosterols. Anyway, all except booth thank you,

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Speaker 4: and fungi make their cell membranes out of something called ergosterol. Okay,

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Speaker 4: sterol also, And one of the biggest things that sterols,

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Speaker 4: like cholesterol for us animals does is provide shape and

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Speaker 4: structure to our cell membranes. So cholesterol molecules are interspersed

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Speaker 4: throughout all of our cell membranes, like the outside of

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Speaker 4: our cells, which is called our plasma membrane, and then

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Speaker 4: also all of our organelles inside of our cells also

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Speaker 4: have membranes that also have cholesterol within them. And what

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Speaker 4: this does is provide just the right amount of rigidity

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Speaker 4: and structure without being.

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Speaker 5: Like too solid okay right.

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Speaker 4: Cholesterol molecules are also moved back and forth across these

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Speaker 4: cell membranes. They interact with proteins both inside and out

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Speaker 4: side side membranes, and they serve as signaling molecules that

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Speaker 4: helps our cells communicate like within the cells, like between organelles,

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Speaker 4: and then also between cells themselves.

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Speaker 2: Hmm.

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Speaker 3: It's petra a big deal does a lot of things.

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Speaker 4: It really does, because I'm not even done the backbone

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Speaker 4: of cholesterol. Those ring structures of carbons and hydrogens are

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Speaker 4: also the precursors to all of our steroid hormones. So

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Speaker 4: that's estrogen, testosterone, cortisol, all of them, and vitamin D

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Speaker 4: and our biol acids, which we learned in our gall

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Speaker 4: butter episodes.

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Speaker 5: Pretty freaking important.

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Speaker 4: So suffice to say, we need cholesterol in order to

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Speaker 4: be alive, right totally.

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Speaker 5: Where do we get it from? Let me tell you.

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Speaker 4: We make our own cholesterol, and most all of our

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Speaker 4: cells can make cholesterol, like all of our cells are

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Speaker 4: capable of it, but it's a pretty energy intensive process.

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Speaker 5: So the vast.

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Speaker 4: Majority of cholesterol that we actually use in our body

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Speaker 4: is made in our liver.

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Speaker 5: And then we also get.

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Speaker 4: Cholesterol and other fats and fatty acids that we also

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Speaker 4: need from our diet, so we absorb it through our

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Speaker 4: intestine and then that gets transported to our liver. So

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Speaker 4: while our cells can make their own cholesterol, they're generally

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Speaker 4: not making quite enough of it, which is why our

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Speaker 4: liver makes so much, something like more than fifty percent

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Speaker 4: of the cholesterol that our cells use, which means that

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Speaker 4: we have to be able to deliver cholesterol from our

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Speaker 4: liver and our intestine to everywhere else in our body. Yea,

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Speaker 4: and our body uses blood to transport stuff around, okay.

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Speaker 3: The super high ways of the body exact.

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Speaker 4: And so while cholesterol is integral to life, when it

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Speaker 4: ends up causing problems, which is obviously what we're going

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Speaker 4: to focus on for this episode, is when that cholesterol

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Speaker 4: starts building up in high amounts in places that it shouldn't.

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Speaker 4: That is where we can end up seeing cholesterol cause disease.

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Speaker 4: And so to understand how that happens, we have to

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Speaker 4: understand how it is that our body is moving cholesterol

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Speaker 4: around from our liver to our cells, et cetera, and

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Speaker 4: how our cells are cycling that cholesterol, because then we

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Speaker 4: can understand how this might build up in places.

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Speaker 5: That it shouldn't.

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Speaker 4: Now, lipids, a key thing to understand about them, including

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Speaker 4: cholesterol and all of our other fatty acids, is that

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Speaker 4: they are not water soluble. Right, everyone who's tried to

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Speaker 4: make salad dressing knows this, and what that means is

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Speaker 4: that in order to move cholesterol around our bloodstream, it's

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Speaker 4: not just going to be free floating because it won't

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Speaker 4: do that well. Yes, So we actually move our cholesterol

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Speaker 4: around our body in little packages called lipoproteins.

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Speaker 3: Okay.

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Speaker 4: Now we have a bunch of different kinds of LiPo proteins,

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Speaker 4: lipofat protein, protein, and they all serve different functions. Most

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Speaker 4: of our cholesterol is made in our liver, right, So

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Speaker 4: our liver takes the cholesterol that it makes along with

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Speaker 4: other fatty acids, and connects it to a protein and

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Speaker 4: sends it out in a box that we call vl DL,

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Speaker 4: or very low density lipoprotein. Right, So it sends that

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Speaker 4: package out, and that is the type of cholesterol package

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Speaker 4: that our cells are going to end up using. Along

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Speaker 4: the way in our bloodstream. This VLDL gets broken down

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Speaker 4: a bit and eventually becomes a smaller box of cholesterol

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Speaker 4: and other fats that we call LDL or low density lipoproteink.

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Speaker 4: So VLDL and LDL these are the lipoproteins. These are

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Speaker 4: the packages of cholesterol that our cells are taking up

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Speaker 4: and using for cholesterol.

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Speaker 1: Okay, So these are the things that our liver is

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Speaker 1: making to say, here you go. Here's you said you

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Speaker 1: needed some cholesterol. To make your cell membranes or make

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Speaker 1: some hormones or whatever. Here's this package starts out VLDL

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Speaker 1: turns into LDL R.

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Speaker 3: Cells take that up.

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Speaker 4: Our cells are like, awesome, I got this. They grab

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Speaker 4: onto it, They bring it inside of them, protein, cholesterol,

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Speaker 4: fatty acids, and all in a little package right now.

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Speaker 4: Once it's in our cells, our cells can either use

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Speaker 4: it or they can store it for later if they're

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Speaker 4: like I want to have a little extra, or they

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Speaker 4: might get way too much of it, and then they

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Speaker 4: have to send it back out into our bloodstream. When

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Speaker 4: our cells are going to export extra cholesterol, they do

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Speaker 4: it in a package called HDL or high density lipoprotein. Okay,

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Speaker 4: And that is the cholesterol that's being transported from our

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Speaker 4: cells back to our liver so that our liver can

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Speaker 4: recycle it or excrete it into bile acids or whatever

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Speaker 4: our liver's going to do with it.

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Speaker 3: That makes sense.

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Speaker 1: So this is LDL being the you know, quote unquote bad.

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Speaker 4: Cholesterol unquote bad because this is what's going from our

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Speaker 4: liver out to our cells floating around in our bloodstream.

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Speaker 4: And it's small and it is sticky, so it can

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Speaker 4: get stuck in places in our bloodstream, but it's also

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Speaker 4: what our cells need to take it up and use it.

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Speaker 4: And then HDL is what's going from ourselves back to

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Speaker 4: our liver to be recycled.

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Speaker 1: Okay, what's the relationship between maybe this is jumping ahead,

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Speaker 1: give it, like the relationship between VLDL and LDL. What

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Speaker 1: decides how much your liver is making? If high LDL

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Speaker 1: is the problem, how does that? What's that feedback cycle?

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Speaker 2: Like?

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Speaker 4: Oh, this is really really good question, Aaron. The balance

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Speaker 4: between how much of the different types of cholesterol packages

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Speaker 4: that we have VLDL, LDL, HDL, whatever it is, It

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Speaker 4: depends on a lot of different things. It depends on

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Speaker 4: how much your liver is making, and some of that

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Speaker 4: is just genetic. Some of that might have to do

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Speaker 4: with your dietary factors. We know that like diets that

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Speaker 4: are high in fat, especially saturated fat, increase the total

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Speaker 4: amount of all these types of cholesterol in your bloodstream,

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Speaker 4: all these different cholesterol packages. We don't know why, though.

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Speaker 4: It also is going to depend on how good your

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Speaker 4: cells are at taking this cholesterol out of your bloodstream.

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Speaker 4: And one of the main things that determines that is

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Speaker 4: how many what are called LDL receptors you have on

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Speaker 4: your cells. These are like velcro myths that grab on

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Speaker 4: to those LDL packages of cholesterol really efficiently and pull

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Speaker 4: them into the cells so that those cells can use them.

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Speaker 4: But if you don't have as many LDL receptors, or

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Speaker 4: your LDL receptors are not as functional as someone else is,

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Speaker 4: or they just get saturated because you end up with

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Speaker 4: so much of that LDL cholesterol package floating around that

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Speaker 4: all your receptors are full, then you're gonna have more

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Speaker 4: of that LDL cholesterol in your body. And what determines

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Speaker 4: how much HDL cholesterol you have is even more unknown

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Speaker 4: because there's definitely like a big genetic factor there, but

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Speaker 4: we don't know, like why is it that some people's

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Speaker 4: cells are exporting more HDL and others aren't.

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Speaker 1: And the VLDL LDL is just sort of like that's

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Speaker 1: just a natural progression.

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Speaker 3: It's a progression.

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Speaker 4: Yeah, And again it is going to vary person to person,

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Speaker 4: like how quickly that VLDL breaks down into LDL within

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Speaker 4: your bloodstream while it's like bumping around. But it's all

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Speaker 4: very like person dependent. There's not like a lot of.

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Speaker 1: Hsiic is so it's so tricky because yeah, there are

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Speaker 1: so many different drivers of LDL.

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Speaker 3: Like why why?

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Speaker 1: Okay, this is getting in a little bit to the

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Speaker 1: evolution question of this, but like why would it be

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Speaker 1: more beneficial to have more LDL receptors or fewer receptors?

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Speaker 1: Why would it be better to store cholesterol rather than

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Speaker 1: utilize it?

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Speaker 5: Such great questions. I don't have answers.

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Speaker 4: I had a feeling you were going to say, yeah,

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Speaker 4: you know, I never do, but no, those are those

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Speaker 4: are all really good questions because that is really the

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Speaker 4: the determinant of whether cholesterol is going to become a

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Speaker 4: problem is if it is building up in the wrong

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Speaker 4: places or at the wrong times. And there are actually

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Speaker 4: a whole bunch of diseases that I'm not going to

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Speaker 4: get into any detail on today that are where cholesterol

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Speaker 4: is building up not outside of ourselves, not in our

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Speaker 4: bloods stream, but actually inside of our cells.

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Speaker 5: So you can.

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Speaker 4: Get build up of fats and cholesterol after that cholesterol

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Speaker 4: has been taken up into our cells if you can't

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Speaker 4: export it right. So for example, there's a genetic disorder

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Speaker 4: called Niemen Pick disease. Okay, and this is where you

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00:20:19,280 --> 00:20:23,720
Speaker 4: have a defective basically exporter molecule, and so you would

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Speaker 4: have really low HDL levels, low HDL levels and just

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00:20:27,840 --> 00:20:31,080
Speaker 4: low cholesterol levels overall because you're still taking up cholesterol

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Speaker 4: from your bloodstream, but then you can't get rid of it,

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Speaker 4: and now your cells are too full of cholesterol, right,

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Speaker 4: so that's going to be really detrimental.

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Speaker 3: There are other.

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Speaker 4: Ones as well, and I'm not going to get into

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Speaker 4: deep detail, because the way that we tend to worry

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Speaker 4: about the build up of cholesterol for most people is

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Speaker 4: when it builds up in our bloodstream, because that is

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Speaker 4: when we see increased risk of a number of different diseases,

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Speaker 4: but especially atherosclerosis, which is the fancy name for when

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00:21:02,400 --> 00:21:05,040
Speaker 4: cholesterol builds up in your blood vessels.

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Speaker 1: Okay, so cholesterol meaning these packages, these LDL packages specifically.

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Speaker 4: Well, yes, so here's what happens when you have high

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Speaker 4: levels of these LDL packages, or not just LDL packages

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Speaker 4: but other like VLDL, like other cholesterol packages that are

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Speaker 4: not HDL. Okay, okay, non HDL cholesterol. If that's high

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00:21:33,960 --> 00:21:40,320
Speaker 4: levels in your bloodstream, then sometimes because many of those particles,

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Speaker 4: especially LDL packages, are small and sticky in our blood vessels,

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Speaker 4: especially maybe at say bifurcations, like somewhere where your blood

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Speaker 4: vessels split or a curvature, or a place where you

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00:21:53,320 --> 00:21:57,520
Speaker 4: got damage for some reason or another. Those molecules can

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Speaker 4: get stuck along the walls of our blood vessels and

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Speaker 4: they get just underneath the first layer of cells into

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Speaker 4: the wall of our blood vessel, and once they are there,

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Speaker 4: those packages kind of disintegrate, and then you do have

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Speaker 4: just free cholesterol molecules in the wall of our blood vessel,

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Speaker 4: and our immune system is like, whoa dude, You're not

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Speaker 4: supposed to be here. You're only supposed to be inside

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Speaker 4: of cells or attached to your little protein package. What

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00:22:29,680 --> 00:22:32,159
Speaker 4: the heck are you doing here? So our immune system

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00:22:32,160 --> 00:22:37,760
Speaker 4: triggers a huge inflammatory response, and then that cycle basically

379
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Speaker 4: can kind of continue. More cholesterol gets stuck because there's

380
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Speaker 4: inflammation in the wall of your blood vessel. That triggers

381
00:22:46,760 --> 00:22:50,440
Speaker 4: more inflammatory markers to come in, and then over time

382
00:22:50,480 --> 00:22:53,919
Speaker 4: you get this build up of actual free cholesterol, not

383
00:22:54,040 --> 00:22:57,960
Speaker 4: just these packages, but like cholesterol floating underneath the wall

384
00:22:58,000 --> 00:23:01,400
Speaker 4: of your blood vessel. Okay, and then as these plaques

385
00:23:01,440 --> 00:23:03,959
Speaker 4: build up and our body is trying to respond to it,

386
00:23:04,040 --> 00:23:07,600
Speaker 4: eventually we build this kind of fibrous cap over it,

387
00:23:08,000 --> 00:23:12,240
Speaker 4: our smooth muscle cells build a cap and eventually they calcify,

388
00:23:12,800 --> 00:23:16,280
Speaker 4: and that's all our bodies response to try and stop

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00:23:16,359 --> 00:23:19,720
Speaker 4: this thing that's in the walls of our blood vessels

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Speaker 4: from taking over essentially.

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Speaker 1: Okay, so it's essentially a numbers game in that, you know,

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Speaker 1: we can throw things like the LDAL receptors in there,

393
00:23:32,440 --> 00:23:35,440
Speaker 1: we can throw, but ultimately it comes down to how

394
00:23:35,560 --> 00:23:38,760
Speaker 1: much LDL is in your bloodstream that is not being

395
00:23:38,800 --> 00:23:43,040
Speaker 1: taken up by cells for whatever reason, and that just

396
00:23:43,359 --> 00:23:48,880
Speaker 1: is associated with more of these little clogs, these sort

397
00:23:48,880 --> 00:23:51,240
Speaker 1: of sticking to the walls of your arteries, and then

398
00:23:51,720 --> 00:23:57,240
Speaker 1: that cholesterol leaking out into the actual lining, causing inflammation

399
00:23:57,600 --> 00:24:01,120
Speaker 1: and an immune response, which then leads to hard and plaques,

400
00:24:01,160 --> 00:24:04,280
Speaker 1: et cetera, and problems down the line.

401
00:24:04,200 --> 00:24:07,920
Speaker 4: Exact immediately yeah or immediately yeah. So those problems could

402
00:24:07,960 --> 00:24:10,880
Speaker 4: be that the plaque gets so big that it actually

403
00:24:10,920 --> 00:24:14,719
Speaker 4: blocks the vessel entirely, or it could be that the

404
00:24:14,760 --> 00:24:18,120
Speaker 4: plaque gets big and then becomes unstable and a chunk

405
00:24:18,160 --> 00:24:26,159
Speaker 4: of it breaks off, travels farther down and blocks smaller arteries. Okay, Okay,

406
00:24:27,119 --> 00:24:30,880
Speaker 4: that's cholesterol and how it causes athrosclerosis as short as

407
00:24:30,880 --> 00:24:31,399
Speaker 4: I could make it.

408
00:24:31,480 --> 00:24:37,080
Speaker 1: Their tell me about the relationship between LDL and things

409
00:24:37,160 --> 00:24:41,879
Speaker 1: like age.

410
00:24:40,000 --> 00:24:41,439
Speaker 3: Things like diet.

411
00:24:41,480 --> 00:24:44,680
Speaker 1: I know you mentioned saturated fats, but like and you said,

412
00:24:44,680 --> 00:24:49,240
Speaker 1: we don't know the mechanism. And then also some hard

413
00:24:49,320 --> 00:24:53,120
Speaker 1: numbers here, like what levels are we talking about and

414
00:24:53,720 --> 00:24:57,719
Speaker 1: what is important to consider? Like what is that if

415
00:24:57,760 --> 00:25:02,320
Speaker 1: you have a high LDL is that a snapshot in time?

416
00:25:02,400 --> 00:25:03,160
Speaker 3: How long has.

417
00:25:03,080 --> 00:25:04,880
Speaker 5: It been high?

418
00:25:04,920 --> 00:25:05,080
Speaker 2: Oh?

419
00:25:05,119 --> 00:25:08,840
Speaker 4: These are really fun questions. So yeah, in general, your

420
00:25:09,040 --> 00:25:11,600
Speaker 4: total amount of cholesterol, and when we're measuring your total cholesterol,

421
00:25:11,640 --> 00:25:14,280
Speaker 4: we're measuring all these different types of packages. Right, We're

422
00:25:14,320 --> 00:25:17,040
Speaker 4: measuring the HDL packages, We're measuring the LDL packages, We're

423
00:25:17,040 --> 00:25:20,320
Speaker 4: measuring all the packages. It is going to go up

424
00:25:20,400 --> 00:25:21,200
Speaker 4: as we get older.

425
00:25:21,800 --> 00:25:23,119
Speaker 5: Why, I don't know.

426
00:25:24,680 --> 00:25:27,240
Speaker 4: Are is it because our LDL receptors that are taking

427
00:25:27,280 --> 00:25:31,480
Speaker 4: this up are getting less efficient or not being recycled

428
00:25:31,560 --> 00:25:34,080
Speaker 4: as easily. I don't have a perfect answer for you,

429
00:25:34,400 --> 00:25:38,520
Speaker 4: but cholesterol does go up as we get older. So

430
00:25:38,600 --> 00:25:42,439
Speaker 4: that is one of the biggest risk factors for atherosclerosis

431
00:25:42,440 --> 00:25:45,760
Speaker 4: in general, is just age, and we can't do anything

432
00:25:45,760 --> 00:25:51,080
Speaker 4: about that. You also asked about diet and other things

433
00:25:51,080 --> 00:25:54,640
Speaker 4: that are going to influence it. Diet can have and

434
00:25:54,640 --> 00:26:01,640
Speaker 4: not just diet, also like physical activity levels and what

435
00:26:01,920 --> 00:26:06,400
Speaker 4: types of especially fat, so saturated fat versus unsaturated fat,

436
00:26:06,440 --> 00:26:10,480
Speaker 4: versus dietary cholesterol versus how many carbohydrates you're getting. All

437
00:26:10,560 --> 00:26:15,639
Speaker 4: of that is going to affect your body's cholesterol levels

438
00:26:15,640 --> 00:26:19,679
Speaker 4: and all the different ratios of these different packages that

439
00:26:19,720 --> 00:26:25,080
Speaker 4: we have. And we don't fully understand the exact mechanisms

440
00:26:25,080 --> 00:26:28,280
Speaker 4: of how this happens, but what we do know is

441
00:26:28,320 --> 00:26:33,280
Speaker 4: that diets that are higher in saturated fats tend to

442
00:26:33,520 --> 00:26:37,960
Speaker 4: increase both your total amount of cholesterol and specifically your

443
00:26:38,080 --> 00:26:39,600
Speaker 4: LDL cholesterol levels.

444
00:26:40,920 --> 00:26:43,919
Speaker 5: Okay, but not your HDL cholesterol levels.

445
00:26:44,359 --> 00:26:49,320
Speaker 1: Your body maintains a fairly consistent ability to produce HDL,

446
00:26:50,560 --> 00:26:54,280
Speaker 1: and so HDL is independent of LDL levels.

447
00:26:55,840 --> 00:27:00,960
Speaker 4: Yeah, okay, Yeah, they're not directly connected. There are things

448
00:27:01,000 --> 00:27:05,240
Speaker 4: that you can do that will sort of shift their proportions, right.

449
00:27:06,000 --> 00:27:09,080
Speaker 4: Increasing physical activity is actually one of those that ends

450
00:27:09,160 --> 00:27:12,920
Speaker 4: up increasing the amount of HDL and lowering the amount

451
00:27:12,960 --> 00:27:16,040
Speaker 4: of LDL, But there are lots of other things that

452
00:27:16,160 --> 00:27:19,160
Speaker 4: might just affect one versus the other. HDL is one

453
00:27:19,160 --> 00:27:21,120
Speaker 4: of the harder ones, because it's just really we don't

454
00:27:21,160 --> 00:27:24,280
Speaker 4: fully understand, like how do we we know that having

455
00:27:24,560 --> 00:27:30,000
Speaker 4: higher levels of HDL is protective against heart disease, right,

456
00:27:30,320 --> 00:27:36,120
Speaker 4: but we don't know why exactly, We don't know exactly

457
00:27:36,160 --> 00:27:38,439
Speaker 4: what levels it's at, and we don't really have a

458
00:27:38,520 --> 00:27:43,400
Speaker 4: lot to do to try and increase somebody's HDL for example.

459
00:27:44,280 --> 00:27:46,119
Speaker 5: Okay, is that interesting?

460
00:27:46,400 --> 00:27:50,679
Speaker 4: And so go ahead, and you asked about hard numbers, yes, right, yes, yes, yes,

461
00:27:50,840 --> 00:27:53,200
Speaker 4: Now these are going to depend a little bit on

462
00:27:53,680 --> 00:27:55,920
Speaker 4: which guidelines that you're looking at and things like that.

463
00:27:56,200 --> 00:28:00,679
Speaker 4: But like right now, the general can censis is that

464
00:28:00,920 --> 00:28:05,280
Speaker 4: quote unquote ideal levels of LDL cholesterol would be less

465
00:28:05,280 --> 00:28:09,399
Speaker 4: than one hundred milligrams per deestolator in your blood. Okay,

466
00:28:09,680 --> 00:28:11,720
Speaker 4: does that mean that if you have more than one hundred,

467
00:28:11,760 --> 00:28:13,840
Speaker 4: you're going to have plaque build up and you're going

468
00:28:13,920 --> 00:28:16,719
Speaker 4: to have a high risk of heart attack? No, absolutely not.

469
00:28:17,680 --> 00:28:21,439
Speaker 4: But we know that levels above a hundred are associated

470
00:28:21,440 --> 00:28:24,399
Speaker 4: with higher risk than levels below one hundred, and we

471
00:28:24,520 --> 00:28:28,960
Speaker 4: know that it's not quite like a linear relationship, but

472
00:28:29,240 --> 00:28:34,240
Speaker 4: it is definitely an increasing risk with increasing LDL levels

473
00:28:34,440 --> 00:28:38,280
Speaker 4: above one hundred. Yes, okay, So especially as those levels

474
00:28:38,320 --> 00:28:40,959
Speaker 4: get to be above one hundred and sixty or one

475
00:28:41,080 --> 00:28:44,920
Speaker 4: hundred and ninety milligrams per deestolator, then we are looking

476
00:28:44,960 --> 00:28:48,200
Speaker 4: at that is considered a very high level of LDL

477
00:28:48,240 --> 00:28:49,160
Speaker 4: in the bloodstream.

478
00:28:49,360 --> 00:28:49,680
Speaker 3: Okay.

479
00:28:50,560 --> 00:28:53,320
Speaker 4: And total cholesterol again, it's going to vary. Usually under

480
00:28:53,360 --> 00:28:56,640
Speaker 4: two hundred or even under one hundred and sixty would

481
00:28:56,640 --> 00:29:00,800
Speaker 4: be considered ideal total cholesterol. That's going to be again

482
00:29:00,840 --> 00:29:03,520
Speaker 4: a measure of your LDLs, your HDLs, and all the

483
00:29:03,560 --> 00:29:05,880
Speaker 4: other types of lipoprotein cholesterol packages.

484
00:29:06,760 --> 00:29:07,640
Speaker 3: Okay, okay.

485
00:29:08,600 --> 00:29:12,320
Speaker 1: And so when people talk about lifestyle modifications for managing

486
00:29:12,360 --> 00:29:16,960
Speaker 1: cholesterol levels, is that mostly geared towards decreasing LDL with

487
00:29:17,280 --> 00:29:20,360
Speaker 1: the kind of beneficial side effect of also hopefully increasing

488
00:29:20,560 --> 00:29:24,360
Speaker 1: HDL if it's something like exercise or certain types of

489
00:29:24,360 --> 00:29:26,720
Speaker 1: food that have an impact on both.

490
00:29:26,560 --> 00:29:29,720
Speaker 4: That's exactly what it is. Yes, Yeah, it's all about

491
00:29:29,800 --> 00:29:34,360
Speaker 4: dietary interventions, so decreasing saturated fats, increasing whole grains and

492
00:29:34,440 --> 00:29:38,160
Speaker 4: plant based proteins that have higher amounts of unsaturated fats,

493
00:29:39,000 --> 00:29:41,000
Speaker 4: and then increasing physical activity.

494
00:29:42,160 --> 00:29:42,480
Speaker 2: Okay.

495
00:29:42,880 --> 00:29:48,360
Speaker 4: Now, atherosclerosis or heart disease, cardiovascular disease, which are not

496
00:29:48,440 --> 00:29:50,840
Speaker 4: all exactly the same thing, but I'm using them interchangeably.

497
00:29:52,600 --> 00:29:55,160
Speaker 4: That is not the only thing that's associated with high

498
00:29:55,280 --> 00:29:58,240
Speaker 4: levels of cholesterol or high levels of LDL cholesterol.

499
00:29:58,480 --> 00:29:58,600
Speaker 2: Right.

500
00:29:59,520 --> 00:30:01,800
Speaker 4: There are a lot of other things that are associated.

501
00:30:01,800 --> 00:30:04,160
Speaker 4: And even when we hear the term cardiovascular, you might

502
00:30:04,200 --> 00:30:07,240
Speaker 4: think that's only your heart, And yes, I'm talking about

503
00:30:07,240 --> 00:30:09,720
Speaker 4: heart attack, I'm talking about heart disease, but I'm also

504
00:30:09,760 --> 00:30:13,800
Speaker 4: talking about stroke. I'm also talking about chronic kidney disease,

505
00:30:14,320 --> 00:30:19,000
Speaker 4: peripheral artery disease, and there's a whole range of other

506
00:30:19,080 --> 00:30:23,440
Speaker 4: diseases that the more that we look for associations between

507
00:30:23,560 --> 00:30:27,040
Speaker 4: high levels of LDL and other diseases, we find them

508
00:30:27,320 --> 00:30:31,520
Speaker 4: liver disease. There's also strong associations between certain types of

509
00:30:31,560 --> 00:30:36,960
Speaker 4: lipoproteins and an increased risk of Alzheimer's disease. And even

510
00:30:37,040 --> 00:30:40,280
Speaker 4: though that's only like a strong association with one type

511
00:30:40,400 --> 00:30:44,600
Speaker 4: of this like lipoprotein cholesterol package, it does look like

512
00:30:44,880 --> 00:30:48,880
Speaker 4: lowering total amounts of LDL cholesterol can also lower the

513
00:30:49,000 --> 00:30:53,600
Speaker 4: risk of Alzheimer's disease. Right, So there are these other associations.

514
00:30:53,640 --> 00:30:56,200
Speaker 4: There's some thought that there's associations with cancer, and we

515
00:30:56,320 --> 00:30:58,479
Speaker 4: just don't know the exact mechanisms.

516
00:30:57,960 --> 00:30:58,440
Speaker 5: Of all of this.

517
00:30:59,600 --> 00:31:03,040
Speaker 4: But high levels of LDL cholesterol are associated with this

518
00:31:03,200 --> 00:31:08,760
Speaker 4: increased inflammatory response and this build up of cholesterol, especially

519
00:31:08,840 --> 00:31:14,480
Speaker 4: in the arteries in your blood vessels. So that's cholesterol, Aaron,

520
00:31:14,840 --> 00:31:17,520
Speaker 4: There's a lot more detail that I gotta be done.

521
00:31:17,600 --> 00:31:17,760
Speaker 5: You know.

522
00:31:22,040 --> 00:31:27,360
Speaker 3: It's a strange It's a strange beast. Yeah, yeah, yeah, So.

523
00:31:27,320 --> 00:31:30,080
Speaker 5: Can you tell me? You know, I don't even know.

524
00:31:30,160 --> 00:31:31,000
Speaker 5: I don't even know.

525
00:31:31,360 --> 00:31:35,520
Speaker 1: You don't even know. You know, We'll find somewhere again.

526
00:31:35,680 --> 00:31:57,120
Speaker 1: I think I can. I can make that happen. Cholesterol

527
00:31:57,400 --> 00:32:02,760
Speaker 1: is vital. It is an essential part of all animal life.

528
00:32:02,800 --> 00:32:08,360
Speaker 1: Without cholesterol, we wouldn't survive. Yet, these crucial functions have

529
00:32:08,480 --> 00:32:12,720
Speaker 1: been overshadowed by its role in the development of cardiovascular disease.

530
00:32:14,120 --> 00:32:18,920
Speaker 1: You could say that cholesterol is the Bill Buckner of

531
00:32:18,960 --> 00:32:19,760
Speaker 1: cell biology.

532
00:32:20,440 --> 00:32:21,320
Speaker 5: Bill Buckner.

533
00:32:21,640 --> 00:32:22,440
Speaker 3: Do you know who that is?

534
00:32:22,560 --> 00:32:24,280
Speaker 5: Why do I know that names?

535
00:32:24,560 --> 00:32:25,800
Speaker 3: I'm so embarrassed.

536
00:32:27,040 --> 00:32:32,120
Speaker 1: Okay, okay, okay, this basketball reference baseball. This might be

537
00:32:32,160 --> 00:32:36,560
Speaker 1: a stretch, yeah, okay, But once I landed on it,

538
00:32:36,640 --> 00:32:37,960
Speaker 1: I was like, I can't let this go.

539
00:32:38,080 --> 00:32:40,360
Speaker 3: I'm going to force this analogy.

540
00:32:40,800 --> 00:32:44,479
Speaker 1: Okay, So Buckner, Bill Buckner was a major League baseball player,

541
00:32:44,680 --> 00:32:48,120
Speaker 1: really a well rounded player, had over twenty seven hundred

542
00:32:48,200 --> 00:32:52,959
Speaker 1: hits in over his career, which spanned over twenty one seasons.

543
00:32:52,600 --> 00:32:54,080
Speaker 3: Which is huge.

544
00:32:54,360 --> 00:32:56,760
Speaker 1: Really, it was someone that you wanted on your team. Okay,

545
00:32:56,880 --> 00:33:01,080
Speaker 1: great player. But in the nineteen eighty six World Series,

546
00:33:01,360 --> 00:33:04,720
Speaker 1: while playing first base for the Red Sox, it was

547
00:33:04,760 --> 00:33:07,960
Speaker 1: the bottom of the tenth inning and in Game six,

548
00:33:08,560 --> 00:33:11,320
Speaker 1: and he missed a ground ball. It went right through

549
00:33:11,360 --> 00:33:16,320
Speaker 1: his legs, brutal right. The error clinched the game for

550
00:33:16,360 --> 00:33:18,880
Speaker 1: the Mets, and they went on to win the next game,

551
00:33:18,960 --> 00:33:22,840
Speaker 1: making them World Series champs. And this is like Boston, right,

552
00:33:22,920 --> 00:33:25,400
Speaker 1: So like Boston sports fans are known to be incredibly

553
00:33:25,400 --> 00:33:27,280
Speaker 1: forgiving and understanding.

554
00:33:28,720 --> 00:33:32,560
Speaker 3: They will never forget. Yeah. No, I think.

555
00:33:32,400 --> 00:33:36,160
Speaker 1: After the Red Sox won in the two thousands, there

556
00:33:36,240 --> 00:33:38,760
Speaker 1: was like, you know, okay, we forgive.

557
00:33:38,440 --> 00:33:41,560
Speaker 3: You Bill Buckner type of a thing. But it only

558
00:33:41,600 --> 00:33:42,720
Speaker 3: took almost twenty years.

559
00:33:42,880 --> 00:33:45,000
Speaker 4: I have to know, Aarin, did you like already know

560
00:33:45,080 --> 00:33:46,200
Speaker 4: this about Bill Buckner?

561
00:33:46,240 --> 00:33:52,520
Speaker 1: How did you I have like I have felt so compassion,

562
00:33:52,920 --> 00:33:55,239
Speaker 1: such compassion for Bill Buckner. I think I saw it

563
00:33:55,280 --> 00:33:57,320
Speaker 1: on some sports special when I was like in high

564
00:33:57,360 --> 00:33:59,920
Speaker 1: school or something, and I was just like, I was

565
00:34:00,080 --> 00:34:04,680
Speaker 1: heartbroken because he was so reviled after this happened, and

566
00:34:04,720 --> 00:34:06,320
Speaker 1: it was one mistake first of all, I mean, I

567
00:34:06,320 --> 00:34:08,280
Speaker 1: could go into this. It was also like the pitchers

568
00:34:08,320 --> 00:34:10,600
Speaker 1: had already blown the lead. It was game six, so

569
00:34:10,600 --> 00:34:12,799
Speaker 1: they still had one more game that they could have won.

570
00:34:13,120 --> 00:34:15,480
Speaker 1: But somehow all of this came down to Bill Buckner.

571
00:34:15,600 --> 00:34:17,839
Speaker 5: You need it, you need a guy do you need Yeah?

572
00:34:18,040 --> 00:34:19,239
Speaker 3: He was a scapegoat for sure.

573
00:34:21,080 --> 00:34:24,799
Speaker 1: That's so that that missed ball, the Buckner play, it

574
00:34:24,920 --> 00:34:29,040
Speaker 1: overshadowed his otherwise really impressive career, and it's mostly what

575
00:34:29,200 --> 00:34:34,400
Speaker 1: he's known for. So Bill Buckner Cholesterol, same thing.

576
00:34:34,560 --> 00:34:35,040
Speaker 2: Righting.

577
00:34:40,000 --> 00:34:44,120
Speaker 1: Both you know, admirable should be appreciated for more than

578
00:34:44,160 --> 00:34:48,600
Speaker 1: they are well rounded, but they're overshadowed by this bad reputation.

579
00:34:51,080 --> 00:34:53,840
Speaker 1: The only difference between the two that I could descern

580
00:34:54,280 --> 00:34:57,120
Speaker 1: is that Bill Buckner is undeserving of the hate that

581
00:34:57,160 --> 00:35:00,960
Speaker 1: he got, whereas cholesterol has earned it's bad reputation, at

582
00:35:01,040 --> 00:35:02,319
Speaker 1: least in certain contexts.

583
00:35:02,400 --> 00:35:05,920
Speaker 5: I love this. This is the I will never forget

584
00:35:06,360 --> 00:35:07,279
Speaker 5: this analogy is.

585
00:35:07,239 --> 00:35:09,360
Speaker 3: So glad cholesterol and Bill Buckner.

586
00:35:09,480 --> 00:35:11,360
Speaker 1: I don't think it's going to help anyone studying for

587
00:35:11,400 --> 00:35:19,160
Speaker 1: a test, but hopefully it'll bring more appreciation for Bill Buckner. Okay, so,

588
00:35:19,200 --> 00:35:20,839
Speaker 1: but today what I want to do is tell you

589
00:35:20,920 --> 00:35:26,520
Speaker 1: how cholesterol earned this bad reputation. Our story begins around

590
00:35:26,560 --> 00:35:29,280
Speaker 1: two and a half billion years ago with the Great

591
00:35:29,320 --> 00:35:30,560
Speaker 1: Oxygenation Event.

592
00:35:30,960 --> 00:35:33,160
Speaker 4: Oh, that's not the first time that we've gotten to

593
00:35:33,200 --> 00:35:35,920
Speaker 4: start this podcast this way, and I just love it.

594
00:35:35,920 --> 00:35:36,719
Speaker 3: It's it is.

595
00:35:36,800 --> 00:35:38,719
Speaker 1: I'm like, man, I really we should just do an

596
00:35:38,719 --> 00:35:43,600
Speaker 1: episode on that. I think it was our hemochromatosis episode

597
00:35:43,680 --> 00:35:45,520
Speaker 1: when I talked about it in the Importance of Iron.

598
00:35:46,200 --> 00:35:48,120
Speaker 3: Yeah, but it more recently.

599
00:35:48,440 --> 00:35:50,759
Speaker 5: Yeah, don't know.

600
00:35:50,880 --> 00:35:51,239
Speaker 2: Don't know.

601
00:35:52,080 --> 00:35:55,080
Speaker 1: But what happened during the Great Oxygenation Event? There was

602
00:35:55,120 --> 00:35:57,960
Speaker 1: a sharp sudden rise Booker.

603
00:35:58,120 --> 00:35:58,720
Speaker 5: Was it Boogers?

604
00:35:58,760 --> 00:35:58,880
Speaker 2: Oh?

605
00:35:59,239 --> 00:36:01,759
Speaker 3: I think it was me. Might have been that sounds right.

606
00:36:01,840 --> 00:36:02,440
Speaker 5: Yeah, I don't know.

607
00:36:02,960 --> 00:36:05,080
Speaker 3: Sorry, whatever however it happened.

608
00:36:05,080 --> 00:36:08,279
Speaker 1: But there was a sharp sudden rise in oxygen in

609
00:36:08,320 --> 00:36:12,279
Speaker 1: the atmosphere that was caused by photosynthesizing cyanobacteria, and it

610
00:36:12,320 --> 00:36:15,880
Speaker 1: had an enormous impact on life on this planet. Although

611
00:36:15,920 --> 00:36:19,359
Speaker 1: we air breathers don't think of oxygen as harmful, it's

612
00:36:19,360 --> 00:36:22,480
Speaker 1: actually quite toxic if you're not used to it, which

613
00:36:22,520 --> 00:36:25,400
Speaker 1: at the time of the event described most of the

614
00:36:25,440 --> 00:36:28,840
Speaker 1: anaerobes that were living on Earth, and so in response

615
00:36:28,880 --> 00:36:32,200
Speaker 1: to the accumulating oxygen, many organisms died out like it

616
00:36:32,239 --> 00:36:35,160
Speaker 1: was probably one of the greatest extinction events in our

617
00:36:35,200 --> 00:36:40,879
Speaker 1: planet's history. But other organisms evolved mechanisms that protected them

618
00:36:40,960 --> 00:36:45,560
Speaker 1: against oxidative damage, or they developed strategies to take advantage

619
00:36:45,600 --> 00:36:48,880
Speaker 1: of this molecule. This new molecule, like, for instance, aerobic

620
00:36:48,920 --> 00:36:55,160
Speaker 1: respiration cholesterol synthesis, which requires oxygen, evolved after the Great

621
00:36:55,160 --> 00:37:00,839
Speaker 1: Oxygenation Event, and it dramatically changed things. So you you

622
00:37:00,880 --> 00:37:04,120
Speaker 1: touched on this a bit, but in those early eukaryotes,

623
00:37:04,320 --> 00:37:08,320
Speaker 1: cholesterol was incorporated into cell membranes, which made for more

624
00:37:08,520 --> 00:37:13,120
Speaker 1: stable and less permeable barriers, protected them from oxydative stress,

625
00:37:13,680 --> 00:37:17,920
Speaker 1: It allowed them to signal across cells within cells, and

626
00:37:17,960 --> 00:37:22,000
Speaker 1: it just kind of helped to organize things, which ultimately

627
00:37:22,080 --> 00:37:26,839
Speaker 1: allowed for greater complexity, even multicellularity, because then you're having like, oh,

628
00:37:26,840 --> 00:37:28,719
Speaker 1: here's a little organelle that I can have, here's a

629
00:37:28,719 --> 00:37:32,080
Speaker 1: little whatever. You're not doing open floor concept anymore. We

630
00:37:32,160 --> 00:37:35,120
Speaker 1: are walling off, walling ourselves off.

631
00:37:36,400 --> 00:37:36,720
Speaker 3: Off.

632
00:37:37,560 --> 00:37:42,320
Speaker 1: So now establishing that so now fast forwarding to humans.

633
00:37:42,800 --> 00:37:45,280
Speaker 1: By the time that our species came onto the scene,

634
00:37:45,400 --> 00:37:48,839
Speaker 1: cholesterol synthesis had been around for billions of years, and

635
00:37:48,960 --> 00:37:53,440
Speaker 1: the uses of cholesterol had expanded, became a precursor for

636
00:37:53,520 --> 00:37:57,920
Speaker 1: hormones involved in stress reproduction metabolism. It was essential for

637
00:37:57,960 --> 00:38:01,279
Speaker 1: staying warm as temperatures drop, and helped to provide enough

638
00:38:01,400 --> 00:38:04,760
Speaker 1: energy for foraging. It was involved a lot in energy balance,

639
00:38:05,680 --> 00:38:08,640
Speaker 1: and we weren't just making it ourselves. We were also

640
00:38:09,080 --> 00:38:11,359
Speaker 1: getting it from our diet, which helped to free up

641
00:38:11,440 --> 00:38:15,240
Speaker 1: energy that could be used for cognitive processing and social behavior.

642
00:38:16,560 --> 00:38:19,759
Speaker 1: Being able to hold on to cholesterol that we got

643
00:38:19,800 --> 00:38:23,520
Speaker 1: in our diets was really beneficial, particularly because food could

644
00:38:23,600 --> 00:38:28,000
Speaker 1: become scarce, and so in some populations living in certain

645
00:38:28,239 --> 00:38:33,600
Speaker 1: environments and under certain food availabilities, traits emerged that altered

646
00:38:33,640 --> 00:38:37,759
Speaker 1: the ways that our bodies dealt with cholesterol. So, for instance,

647
00:38:38,120 --> 00:38:41,360
Speaker 1: it's thought that like being able to utilize fats rapidly

648
00:38:41,400 --> 00:38:44,640
Speaker 1: and efficiently would have been really helpful in cold environments

649
00:38:44,680 --> 00:38:46,759
Speaker 1: when you needed to keep yourself warm and have enough

650
00:38:46,840 --> 00:38:49,560
Speaker 1: energy for foraging, and so there might have been a

651
00:38:49,600 --> 00:38:54,800
Speaker 1: particular pattern of cholesterol regulation that emerged in the people

652
00:38:54,840 --> 00:38:59,439
Speaker 1: living under these conditions interesting, right, And so it's sort

653
00:38:59,480 --> 00:39:03,200
Speaker 1: of thought that, like the way today that we regulate

654
00:39:03,280 --> 00:39:06,799
Speaker 1: cholesterol would have been very helpful in the past, but

655
00:39:07,600 --> 00:39:10,879
Speaker 1: in today's context, it's not really serving us well, right,

656
00:39:10,920 --> 00:39:13,359
Speaker 1: faced with these same challenges most of the time.

657
00:39:13,600 --> 00:39:16,280
Speaker 4: Well, and we just also have exposure to much higher

658
00:39:16,400 --> 00:39:20,120
Speaker 4: levels of dietary facts and things that we would not

659
00:39:20,160 --> 00:39:24,520
Speaker 4: have had exposure to thousands, hundreds of thousands of years ago, exactly.

660
00:39:24,640 --> 00:39:27,080
Speaker 1: Yeah, yeah, And so it's again sort of like this

661
00:39:27,280 --> 00:39:31,120
Speaker 1: context specific, something that evolved that was really beneficial under

662
00:39:31,120 --> 00:39:35,759
Speaker 1: one context in modern times maybe isn't as much, you know,

663
00:39:36,120 --> 00:39:39,040
Speaker 1: much much of the world lives a sedentary lifestyle and

664
00:39:39,120 --> 00:39:43,759
Speaker 1: consumes a diet rich in animal fats, saturated fats, and sugars,

665
00:39:43,840 --> 00:39:45,799
Speaker 1: where these types of foods are the ones that are

666
00:39:45,800 --> 00:39:49,319
Speaker 1: the most readily available. And so given that the most

667
00:39:49,400 --> 00:39:52,799
Speaker 1: damaging impacts of high cholesterol tend to happen later in

668
00:39:52,840 --> 00:39:55,759
Speaker 1: our life, things like heart attack and stroke, it's not

669
00:39:56,160 --> 00:39:59,160
Speaker 1: really surprising that high cholesterol seems to be a problem

670
00:39:59,320 --> 00:40:01,439
Speaker 1: for so many of us, right, It's just the sort

671
00:40:01,480 --> 00:40:06,720
Speaker 1: of constellation of different factors going on, right. But again,

672
00:40:07,000 --> 00:40:10,480
Speaker 1: our relationship with cholesterol. You can't really paint it with

673
00:40:10,520 --> 00:40:14,239
Speaker 1: a broad brush. It's super complicated, both at a population

674
00:40:14,440 --> 00:40:18,040
Speaker 1: level as well as an individual level. Context really does

675
00:40:18,120 --> 00:40:23,560
Speaker 1: matter with cholesterol, and this rich inner life of cholesterol

676
00:40:23,800 --> 00:40:26,960
Speaker 1: is what makes it so challenging to understand and to

677
00:40:27,040 --> 00:40:31,759
Speaker 1: communicate its health impacts. As important as cholesterol is in

678
00:40:31,880 --> 00:40:36,759
Speaker 1: maintaining healthy physiology, it's also responsible for some major issues

679
00:40:37,480 --> 00:40:41,719
Speaker 1: and scientists have suspected this darker side of cholesterol for

680
00:40:41,840 --> 00:40:47,319
Speaker 1: over a century. Wow yeah, So since its discovery in

681
00:40:47,560 --> 00:40:52,960
Speaker 1: the late seventeen hundreds and it's naming in eighteen fifteen cholesterol.

682
00:40:52,400 --> 00:40:54,840
Speaker 3: Yeah, quite a long time. Yeah yeah.

683
00:40:55,080 --> 00:40:58,759
Speaker 1: Cholesterol has inspired a great deal of fascination and over

684
00:40:58,840 --> 00:41:02,080
Speaker 1: a dozen scientists have been awarded a Nobel Prize for

685
00:41:02,160 --> 00:41:03,520
Speaker 1: their research on cholesterol.

686
00:41:04,000 --> 00:41:08,759
Speaker 3: Wow. Yeah, just for gold mine. It really is.

687
00:41:08,960 --> 00:41:13,360
Speaker 1: Yeah, In case you were curious, cholesterol comes from cholesterine,

688
00:41:13,520 --> 00:41:16,000
Speaker 1: which was the name given to it in eighteen fifteen

689
00:41:16,080 --> 00:41:20,279
Speaker 1: by Michelle Chevroule, who had isolated the stuff from human gallstones.

690
00:41:22,640 --> 00:41:27,600
Speaker 1: So coal, like chol e is bile and stereo solid

691
00:41:28,880 --> 00:41:34,000
Speaker 1: solid bile. Okaying, So when did people start to suspect

692
00:41:34,360 --> 00:41:39,000
Speaker 1: cholesterol's role in atherosclerosis? The first clue that we have

693
00:41:39,200 --> 00:41:43,440
Speaker 1: comes from nineteen ten, with a paper by German chemist A.

694
00:41:43,680 --> 00:41:49,000
Speaker 1: Windaus reporting that his patients with atherosclerosis in autopsies, he

695
00:41:49,120 --> 00:41:52,799
Speaker 1: found that their aortas were just chock full of cholesterol like,

696
00:41:52,960 --> 00:41:56,640
Speaker 1: much more so than his patients who did not have

697
00:41:56,719 --> 00:42:00,560
Speaker 1: the disease. The second clue arrives a few years later

698
00:42:00,680 --> 00:42:06,520
Speaker 1: in nineteen thirteen, when Russian experimental pathologist A. Nichkow showed

699
00:42:06,520 --> 00:42:10,279
Speaker 1: that when he fed rabbits basically pure cholesterol dissolved in

700
00:42:10,320 --> 00:42:14,480
Speaker 1: sunflower oil, they quickly developed lesions in their blood vessels

701
00:42:14,480 --> 00:42:19,000
Speaker 1: that looked a whole lot like human athrosclerosis. The rabbits

702
00:42:19,000 --> 00:42:21,520
Speaker 1: who were fed on a normal diet did not develop

703
00:42:21,640 --> 00:42:22,600
Speaker 1: those same lesions.

704
00:42:23,200 --> 00:42:25,480
Speaker 3: Curious, very curious.

705
00:42:25,800 --> 00:42:28,120
Speaker 1: And he was inspired to do this not because of

706
00:42:28,239 --> 00:42:32,839
Speaker 1: Windows's paper, but because of other previous work investigating whether

707
00:42:32,880 --> 00:42:38,080
Speaker 1: too much protein was toxic and caused premature aging. Interesting, yeah,

708
00:42:38,120 --> 00:42:40,840
Speaker 1: which was kind of the idea at the time. And

709
00:42:40,880 --> 00:42:44,719
Speaker 1: so there were these studies where rabbits were fed on

710
00:42:44,760 --> 00:42:49,319
Speaker 1: a super protein rich diet and the rabbits developed what

711
00:42:49,480 --> 00:42:54,440
Speaker 1: looked like human athrosclerosis, and so Innichkow wanted to know

712
00:42:54,760 --> 00:42:57,279
Speaker 1: what it was was it the protein? Was what is

713
00:42:57,320 --> 00:42:59,959
Speaker 1: it about the protein or that diet specifically that caused

714
00:43:00,120 --> 00:43:04,120
Speaker 1: a lesions? And so he narrowed it down to cholesterol.

715
00:43:04,520 --> 00:43:08,920
Speaker 1: H Yeah, fascinating. Yeah, and so on the surface and

716
00:43:08,960 --> 00:43:12,439
Speaker 1: Nichkow's results showing that a diet high in cholesterol led

717
00:43:12,480 --> 00:43:17,319
Speaker 1: to atherosclerosis like lesions, that's pretty compelling stuff to our

718
00:43:17,719 --> 00:43:21,560
Speaker 1: modern eyes. Yeah, in reality, it did not resonate with

719
00:43:21,600 --> 00:43:23,319
Speaker 1: the scientific community of the time.

720
00:43:23,520 --> 00:43:24,560
Speaker 5: It never does, does it.

721
00:43:24,560 --> 00:43:25,279
Speaker 3: It never does.

722
00:43:26,160 --> 00:43:29,799
Speaker 1: That's okay, you know, like there were three main reasons

723
00:43:29,880 --> 00:43:31,719
Speaker 1: for this hesitance.

724
00:43:32,000 --> 00:43:32,239
Speaker 5: Okay.

725
00:43:32,360 --> 00:43:34,400
Speaker 1: So the first was that when other people tried to

726
00:43:34,440 --> 00:43:38,560
Speaker 1: replicate his results in different animals, no, dice wasn't happening.

727
00:43:38,800 --> 00:43:39,520
Speaker 5: Okay.

728
00:43:39,560 --> 00:43:42,480
Speaker 1: Even when a Nichkow himself tried with a dog, he

729
00:43:42,560 --> 00:43:45,600
Speaker 1: could not produce a lesions, And so he reasoned that

730
00:43:45,680 --> 00:43:49,480
Speaker 1: it might be because dogs, as omnivores, are more accustomed

731
00:43:49,520 --> 00:43:52,480
Speaker 1: to eating cholesterol rich diets and so have evolved to

732
00:43:52,600 --> 00:43:55,440
Speaker 1: excrete or convert excess cholesterol. Oh.

733
00:43:55,600 --> 00:43:57,680
Speaker 3: Interesting, It turned out to be right about that way.

734
00:43:58,560 --> 00:44:02,440
Speaker 1: Rabbits, being herbivores, don't have that same cholesterol, right, They're.

735
00:44:02,360 --> 00:44:05,759
Speaker 4: Not usually eating cholesterol. So they're not equipped to manage it.

736
00:44:06,040 --> 00:44:08,400
Speaker 1: Yeah, but I don't think other people made this connection,

737
00:44:08,520 --> 00:44:10,560
Speaker 1: and so they were like, just I think it's just

738
00:44:10,600 --> 00:44:12,640
Speaker 1: something about these rabbits, because I think.

739
00:44:12,560 --> 00:44:15,000
Speaker 3: They also couldn't do it, and other animals like rats

740
00:44:15,040 --> 00:44:16,120
Speaker 3: maybe anyway, Okay.

741
00:44:17,040 --> 00:44:20,440
Speaker 1: What they were missing also was that this was a

742
00:44:20,480 --> 00:44:25,040
Speaker 1: two stage process. You had to have a high cholesterol

743
00:44:25,160 --> 00:44:29,480
Speaker 1: diet followed by a corresponding rise in blood cholesterol levels

744
00:44:29,640 --> 00:44:31,520
Speaker 1: to get athrosclerosis.

745
00:44:31,760 --> 00:44:32,560
Speaker 3: If you didn't have.

746
00:44:32,480 --> 00:44:34,560
Speaker 1: That second step, if your diet was super high in

747
00:44:34,600 --> 00:44:38,200
Speaker 1: cholesterol but you didn't actually have high circulating blood cholesterol,

748
00:44:38,960 --> 00:44:43,239
Speaker 1: then you athroschlorosis probably wasn't going to develop because you

749
00:44:43,280 --> 00:44:46,240
Speaker 1: were lacking the little the ability to make those platka.

750
00:44:46,360 --> 00:44:48,400
Speaker 5: You ate it, but then it didn't get stuck in

751
00:44:48,400 --> 00:44:48,800
Speaker 5: your blood.

752
00:44:48,800 --> 00:44:49,480
Speaker 3: Did you get stuck?

753
00:44:49,600 --> 00:44:52,040
Speaker 5: I never made it there for one reason, somehow.

754
00:44:51,680 --> 00:44:55,880
Speaker 1: Excreted or processed in a different way, never absorbed it whatever, whatever.

755
00:44:56,080 --> 00:44:59,359
Speaker 5: Just really groady poops, ye.

756
00:45:00,280 --> 00:45:02,640
Speaker 3: Real rough, real rough.

757
00:45:03,520 --> 00:45:06,560
Speaker 1: But the second reason that his results were met with

758
00:45:06,680 --> 00:45:10,920
Speaker 1: skepticism was the blood cholesterol levels that he was inducing

759
00:45:10,960 --> 00:45:15,320
Speaker 1: in these rabbits were staggering. It was like five hundred

760
00:45:15,440 --> 00:45:20,120
Speaker 1: to one thousand milligrams pertest leader and above of total

761
00:45:20,840 --> 00:45:23,960
Speaker 1: total cholesterol. Yeah, which is like way higher than it

762
00:45:24,080 --> 00:45:25,600
Speaker 1: then it gets for most humans.

763
00:45:25,800 --> 00:45:30,520
Speaker 4: Yeah, if I saw that, I would be when I

764
00:45:30,560 --> 00:45:32,120
Speaker 4: get to the three hundreds, I'm.

765
00:45:32,000 --> 00:45:34,400
Speaker 5: Like, we need to do something, thank you.

766
00:45:36,680 --> 00:45:37,879
Speaker 3: Oh just wait till later.

767
00:45:38,000 --> 00:45:39,840
Speaker 5: I don't know if it case episode or next.

768
00:45:39,600 --> 00:45:43,879
Speaker 1: But but so it was kind of like, uh, well, yeah,

769
00:45:44,040 --> 00:45:45,720
Speaker 1: enough of anything is deadly.

770
00:45:45,920 --> 00:45:48,640
Speaker 3: But like that's just not realistic. We're not this is

771
00:45:48,680 --> 00:45:49,440
Speaker 3: not what we're seeing.

772
00:45:50,440 --> 00:45:54,160
Speaker 1: Later, though, he showed that even small rises, so not

773
00:45:54,160 --> 00:45:56,399
Speaker 1: not five hundred to one thousand range, but like small

774
00:45:56,480 --> 00:45:59,640
Speaker 1: rises still led to athroosclerosis like lesions in these rabbits,

775
00:45:59,800 --> 00:46:02,680
Speaker 1: just longer to develop than like the couple of weeks

776
00:46:02,760 --> 00:46:03,600
Speaker 1: or whatever it was.

777
00:46:04,800 --> 00:46:07,279
Speaker 3: And then one last thing, the third.

778
00:46:07,000 --> 00:46:10,200
Speaker 1: Thing that held him back was the prevailing view of

779
00:46:10,280 --> 00:46:14,560
Speaker 1: athrosclerosis at the time when his work was being published.

780
00:46:14,880 --> 00:46:21,040
Speaker 1: Athrosclerosis was seen as an inevitable part of the aging process, interesting,

781
00:46:21,320 --> 00:46:24,319
Speaker 1: something that took decades to develop. And so how on

782
00:46:24,360 --> 00:46:29,480
Speaker 1: earth could these rabbits showing these atherosclerotic lesions within months

783
00:46:29,600 --> 00:46:32,480
Speaker 1: or weeks of eating lots of cholesterol. How could that

784
00:46:32,560 --> 00:46:35,680
Speaker 1: be a reasonable model for human disease. It just didn't

785
00:46:35,680 --> 00:46:36,800
Speaker 1: seem plausible.

786
00:46:36,440 --> 00:46:37,160
Speaker 5: Doesn't make sense.

787
00:46:37,520 --> 00:46:37,840
Speaker 2: Yeah.

788
00:46:37,880 --> 00:46:43,560
Speaker 1: Interesting that skeptical sentiment followed A. Nichkow for decades as

789
00:46:43,640 --> 00:46:49,080
Speaker 1: the sinescence hypothesis of athosclerosis proved particularly stubborn to dislodge

790
00:46:49,840 --> 00:46:52,760
Speaker 1: for his part, and Nichkow pursued this line of research

791
00:46:52,840 --> 00:46:56,080
Speaker 1: for fifty years. Like he was like singularly focused on,

792
00:46:56,200 --> 00:46:58,640
Speaker 1: like I want to understand cholesterol and what's going on

793
00:46:58,719 --> 00:47:00,720
Speaker 1: here till the end of his career.

794
00:47:01,560 --> 00:47:03,879
Speaker 3: And I just wrote this little comment here.

795
00:47:03,960 --> 00:47:08,120
Speaker 1: I wonder too, whether global politics came into play, because

796
00:47:08,600 --> 00:47:12,960
Speaker 1: there's like Cold War stuff. He was friends with Stalin apparently,

797
00:47:13,080 --> 00:47:14,759
Speaker 1: and so I'm wondering if there was just sort of

798
00:47:14,800 --> 00:47:17,680
Speaker 1: like a well, we're gonna distrust.

799
00:47:17,239 --> 00:47:19,880
Speaker 5: You, right, You're not a person that we want to

800
00:47:19,920 --> 00:47:20,319
Speaker 5: hear from.

801
00:47:20,760 --> 00:47:21,080
Speaker 3: Yeah.

802
00:47:21,560 --> 00:47:24,279
Speaker 1: Yeah, I don't know. I didn't see that anywhere. That

803
00:47:24,320 --> 00:47:27,040
Speaker 1: was just my own, my own little speculation. But in

804
00:47:27,080 --> 00:47:30,840
Speaker 1: any case, the next phase of the cholesterol athrosclerosis story

805
00:47:30,960 --> 00:47:33,760
Speaker 1: brings us to UC Berkeley in the mid twentieth century.

806
00:47:34,000 --> 00:47:35,560
Speaker 5: Oh wow, A long time later.

807
00:47:35,840 --> 00:47:38,520
Speaker 1: Yeah, yeah, about forty forty years or so.

808
00:47:38,680 --> 00:47:40,120
Speaker 3: Fifty years Okay.

809
00:47:40,000 --> 00:47:44,840
Speaker 1: Yeah, so there, young physician scientist John Goffman found himself

810
00:47:44,920 --> 00:47:49,880
Speaker 1: drawn to cardiovascular disease, in particular the relationship between diet

811
00:47:50,120 --> 00:47:54,279
Speaker 1: blood cholesterol and athrosclerosis, and he had come across in

812
00:47:54,360 --> 00:47:57,359
Speaker 1: Nichkow's work, but rather than dismissing it like so many

813
00:47:57,400 --> 00:48:00,719
Speaker 1: other people, he suspected that there might be something to

814
00:48:01,040 --> 00:48:04,719
Speaker 1: the cholesterol athrosculerosis link. God, it's so hard to say

815
00:48:04,719 --> 00:48:08,440
Speaker 1: that over and over again, but to get at the

816
00:48:08,480 --> 00:48:11,840
Speaker 1: heart of that link. But I'm pun intended, I literally

817
00:48:11,840 --> 00:48:16,760
Speaker 1: wrote pun intended. He nothing better than a planned joke.

818
00:48:18,120 --> 00:48:19,920
Speaker 1: But he he was like, well, I have to better

819
00:48:20,000 --> 00:48:23,759
Speaker 1: understand the dynamics of cholesterol in the blood, because by

820
00:48:23,800 --> 00:48:27,000
Speaker 1: this point in time, researchers had recognized that there were

821
00:48:27,000 --> 00:48:31,240
Speaker 1: these these compounds called lipoproteins that circulated in the blood.

822
00:48:31,280 --> 00:48:34,239
Speaker 1: They carried cholesterol, and they came in different forms. So

823
00:48:34,280 --> 00:48:37,160
Speaker 1: he was like, there might be like this, We can't

824
00:48:37,200 --> 00:48:40,160
Speaker 1: just say cholesterol. We have to be more detailed than

825
00:48:40,200 --> 00:48:41,680
Speaker 1: not to understand what's going on.

826
00:48:41,840 --> 00:48:43,680
Speaker 5: Which cholesterol package are we talking?

827
00:48:44,200 --> 00:48:45,080
Speaker 3: Yeah, exactly.

828
00:48:45,400 --> 00:48:48,560
Speaker 1: And so people had recognized different lipoproteins, but they didn't

829
00:48:48,600 --> 00:48:52,320
Speaker 1: know what they did and how their concentrations affected health.

830
00:48:52,719 --> 00:48:57,239
Speaker 1: Interesting unclear okay. Gosman was really the first to clarify

831
00:48:57,480 --> 00:49:00,799
Speaker 1: their role, and he did this through a complicated and

832
00:49:00,880 --> 00:49:04,000
Speaker 1: sophisticated technique. The long and the short of it is

833
00:49:04,040 --> 00:49:07,000
Speaker 1: that he was able to take a sample and reliably

834
00:49:07,120 --> 00:49:10,279
Speaker 1: sort and measure the different types of lipoproteins in a

835
00:49:10,320 --> 00:49:14,120
Speaker 1: blood And when he applied this technique to the question

836
00:49:14,280 --> 00:49:18,680
Speaker 1: that interested him the most, what caused atherosclerosis, he found

837
00:49:18,719 --> 00:49:23,319
Speaker 1: that not all lipoproteins had the same impact. And he

838
00:49:23,360 --> 00:49:27,520
Speaker 1: proposed that we shouldn't be looking at total cholesterol. That's

839
00:49:27,680 --> 00:49:31,120
Speaker 1: an incomplete picture. That's too broad of a picture. Really,

840
00:49:31,200 --> 00:49:34,600
Speaker 1: you need to give different weight to the different lipoproteins

841
00:49:34,640 --> 00:49:38,640
Speaker 1: in predicting the risk of cardiovascular disease. So, in other words,

842
00:49:38,680 --> 00:49:41,400
Speaker 1: he came up with the athrogenic index. He was like,

843
00:49:41,680 --> 00:49:44,120
Speaker 1: we need to we need to figure this out and

844
00:49:44,160 --> 00:49:48,960
Speaker 1: have these specific numbers. And he applied this index to

845
00:49:49,200 --> 00:49:52,000
Speaker 1: a small sample of patients and he showed that there

846
00:49:52,040 --> 00:49:55,840
Speaker 1: was a strong association between certain ratios of lipoproteins and

847
00:49:55,880 --> 00:50:00,880
Speaker 1: the risk of heart attack. As a fun little side here,

848
00:50:01,719 --> 00:50:05,160
Speaker 1: his wife, doctor Helen Goffman, published what was probably the

849
00:50:05,200 --> 00:50:09,640
Speaker 1: first heart healthy cookbook in nineteen fifty one, I think

850
00:50:09,640 --> 00:50:13,200
Speaker 1: because of this research was like, Wow, don't eat saturated vats.

851
00:50:13,239 --> 00:50:20,200
Speaker 1: Basically Goffman's research, though, really transformed the field. He bears

852
00:50:20,239 --> 00:50:22,960
Speaker 1: the title the father of clinical lipidology.

853
00:50:23,560 --> 00:50:25,680
Speaker 5: Wow, I know, gotta love it. Gotta love it when

854
00:50:25,680 --> 00:50:26,279
Speaker 5: we get a father.

855
00:50:27,080 --> 00:50:30,319
Speaker 1: Yeah, we have another father in the next episode, the

856
00:50:30,320 --> 00:50:37,800
Speaker 1: father of statn's. Yeah. But his central hypothesis, linking certain

857
00:50:37,920 --> 00:50:41,919
Speaker 1: cholesterol carrying lipoproteins with heart disease, once again, it met

858
00:50:41,960 --> 00:50:47,560
Speaker 1: with resistance, understandably so to a degree. So first of all,

859
00:50:47,600 --> 00:50:50,400
Speaker 1: he didn't have a mechanistic explanation as to why this

860
00:50:50,440 --> 00:50:53,080
Speaker 1: would cause disease. That would have to wait for a

861
00:50:53,120 --> 00:50:57,160
Speaker 1: few decades. And secondly, his sample sizes were fairly small.

862
00:50:57,520 --> 00:51:02,000
Speaker 1: They weren't perspective, meaning you couldn't draw firm conclusions about causality,

863
00:51:02,080 --> 00:51:05,360
Speaker 1: like which came first? Was it cholesterol or heart disease?

864
00:51:05,400 --> 00:51:06,600
Speaker 5: Did you have heart disease and.

865
00:51:06,560 --> 00:51:10,760
Speaker 1: That is what caused your high cholesterol? Righte So doubt

866
00:51:10,800 --> 00:51:16,000
Speaker 1: lingered and things were getting heated. The quote unquote cholesterol

867
00:51:16,040 --> 00:51:19,680
Speaker 1: wars that began in the nineteen fifties reached new heights

868
00:51:19,719 --> 00:51:25,120
Speaker 1: in the nineteen seventies. Oh yeah, cholesterol Wars decades.

869
00:51:25,160 --> 00:51:26,719
Speaker 5: More than Salt Wars.

870
00:51:28,000 --> 00:51:31,920
Speaker 1: Honestly, very like, I would say, more contentious than Salt Wars.

871
00:51:32,200 --> 00:51:35,239
Speaker 1: Interesting in my reading of it. Yeah, tell me all

872
00:51:35,239 --> 00:51:36,280
Speaker 1: about it, Eric, Yeah.

873
00:51:36,640 --> 00:51:36,960
Speaker 3: Okay.

874
00:51:37,000 --> 00:51:41,160
Speaker 1: So, while some physicians and scientists had grown convinced.

875
00:51:40,640 --> 00:51:43,000
Speaker 3: That high blood cholesterol caused heart.

876
00:51:42,840 --> 00:51:45,960
Speaker 1: Disease, others argued that it was the other way around,

877
00:51:46,440 --> 00:51:50,400
Speaker 1: and they took issue with high Where do you draw

878
00:51:50,520 --> 00:51:51,000
Speaker 1: the line?

879
00:51:51,120 --> 00:51:52,279
Speaker 3: What does high mean?

880
00:51:52,960 --> 00:51:53,320
Speaker 5: Okay?

881
00:51:53,520 --> 00:51:54,400
Speaker 3: Yeah, yeah, okay.

882
00:51:54,680 --> 00:51:59,279
Speaker 1: So in medicine, one common cutoff for deciding this is

883
00:51:59,480 --> 00:52:03,400
Speaker 1: ninety five percent. So, for example, if ninety five percent

884
00:52:03,400 --> 00:52:07,160
Speaker 1: of people have cholesterol less than a particular value, anything

885
00:52:07,280 --> 00:52:12,160
Speaker 1: above that is considered abnormal. The problem with this is

886
00:52:12,160 --> 00:52:15,640
Speaker 1: that you're assuming any cholesterol value less than ninety five

887
00:52:15,719 --> 00:52:21,560
Speaker 1: percent is normal. It's non pathogenic. But average doesn't always

888
00:52:21,600 --> 00:52:26,160
Speaker 1: equate to normal. In the nineteen forties, ninety five percent

889
00:52:26,239 --> 00:52:29,680
Speaker 1: of the US population had blood cholesterol below.

890
00:52:29,400 --> 00:52:32,600
Speaker 5: To eighty to eighty to eighty ninety.

891
00:52:32,680 --> 00:52:36,040
Speaker 1: We know today that, yeah, that heart attacks occur with

892
00:52:36,200 --> 00:52:40,080
Speaker 1: levels much lower than that. In fact, most occur between

893
00:52:40,120 --> 00:52:43,320
Speaker 1: two hundred and to eighty, But since that was the

894
00:52:43,360 --> 00:52:46,000
Speaker 1: standard cut off at the time, doctors didn't consider a

895
00:52:46,040 --> 00:52:49,080
Speaker 1: cholesterol level of say two fifty to be worrisome because

896
00:52:49,080 --> 00:52:50,640
Speaker 1: it was considered normal.

897
00:52:50,400 --> 00:52:52,640
Speaker 3: And this is total cholesterol. There's still total cholesterol.

898
00:52:52,719 --> 00:52:56,840
Speaker 1: Yes, Yes, It took several strong epidemiological studies to turn

899
00:52:56,920 --> 00:53:00,400
Speaker 1: that thinking around and say, like, actually, average does always

900
00:53:00,440 --> 00:53:02,640
Speaker 1: equate to healthy.

901
00:53:02,840 --> 00:53:04,960
Speaker 5: Yeah.

902
00:53:05,000 --> 00:53:07,560
Speaker 1: So one of these studies I actually touched on in

903
00:53:07,600 --> 00:53:11,720
Speaker 1: a previous episode our Dietary Guidelines episode canceled Keys's seven

904
00:53:11,760 --> 00:53:12,560
Speaker 1: Countries study.

905
00:53:13,080 --> 00:53:14,760
Speaker 3: So in the nineteen fifties.

906
00:53:14,400 --> 00:53:17,640
Speaker 1: As a refresher, Keys and his colleagues conducted a wide

907
00:53:17,760 --> 00:53:22,680
Speaker 1: ranging study across seven countries examining relationships between diet, blood cholesterol,

908
00:53:22,800 --> 00:53:28,080
Speaker 1: and mortality due to coronary heart disease. The results were striking.

909
00:53:28,600 --> 00:53:31,440
Speaker 1: At one end of the spectrum, you had Japan with

910
00:53:31,560 --> 00:53:35,800
Speaker 1: an average blood cholesterol level of one sixty and less

911
00:53:35,800 --> 00:53:38,799
Speaker 1: than five fatal heart attacks per one thousand men.

912
00:53:39,160 --> 00:53:39,440
Speaker 3: Okay.

913
00:53:40,160 --> 00:53:44,600
Speaker 1: On the other end, you've got Finland with an average

914
00:53:44,640 --> 00:53:48,160
Speaker 1: blood cholesterol of two sixty and seventy fatal heart attacks

915
00:53:48,200 --> 00:53:53,600
Speaker 1: per one thousand. Yeah, and other countries kind of followed

916
00:53:53,600 --> 00:53:56,160
Speaker 1: the same trend, just like fell right on along that

917
00:53:56,200 --> 00:54:00,520
Speaker 1: plot line with blood cholesterol and saturated fat consumption. Positively

918
00:54:00,560 --> 00:54:05,320
Speaker 1: related to fatal heart attacks. Yep, again it was compelling stuff,

919
00:54:05,800 --> 00:54:09,520
Speaker 1: but again, like in many other studies, it showed correlation

920
00:54:09,680 --> 00:54:12,160
Speaker 1: and it didn't prove causation, and so a lot of

921
00:54:12,160 --> 00:54:16,600
Speaker 1: people remained unconvinced. The next study turned all but the

922
00:54:16,640 --> 00:54:19,080
Speaker 1: most stubborn skeptics into believers.

923
00:54:19,280 --> 00:54:19,600
Speaker 5: Okay.

924
00:54:20,200 --> 00:54:26,000
Speaker 1: In nineteen fifty researchers enrolled twenty eight thousand residents of Framingham, Massachusetts.

925
00:54:26,400 --> 00:54:28,920
Speaker 5: Love it framing Ham, Framingham.

926
00:54:29,320 --> 00:54:31,520
Speaker 1: The Framingham Study is one of the most It is

927
00:54:31,560 --> 00:54:35,440
Speaker 1: one of the most long term and valuable and informative

928
00:54:35,520 --> 00:54:37,960
Speaker 1: public health studies ever put together.

929
00:54:38,120 --> 00:54:39,680
Speaker 3: It's incredible. It's incredible.

930
00:54:40,719 --> 00:54:45,640
Speaker 1: They measured things like blood cholesterol, blood pressure, smoking, diabetes,

931
00:54:45,680 --> 00:54:48,640
Speaker 1: and family history of disease, and they follow these residents

932
00:54:48,680 --> 00:54:53,320
Speaker 1: for years. It is still ongoing, recording any disease events

933
00:54:53,360 --> 00:54:54,560
Speaker 1: as they occurred.

934
00:54:54,239 --> 00:54:58,480
Speaker 4: Including in offspring now the old offspring Like it's it

935
00:54:58,560 --> 00:55:01,560
Speaker 4: is a huge de type of study that's been on

936
00:55:01,680 --> 00:55:02,439
Speaker 4: going for so long.

937
00:55:02,680 --> 00:55:08,520
Speaker 1: The amount of information we've gained really cool, really yeah powerful, Okay,

938
00:55:08,840 --> 00:55:11,600
Speaker 1: But what this allowed them to do, what the study

939
00:55:11,640 --> 00:55:15,960
Speaker 1: allowed them to do was establish a sequence high cholesterol

940
00:55:16,160 --> 00:55:20,560
Speaker 1: preceded heart attack, and then they could also calculate risk.

941
00:55:21,080 --> 00:55:25,160
Speaker 1: What is high cholesterol? How much does smoking combined.

942
00:55:24,719 --> 00:55:27,120
Speaker 3: With high cholesterol impact risk? Things like that.

943
00:55:27,160 --> 00:55:30,200
Speaker 1: They could create these sort of calculations and say, what

944
00:55:30,280 --> 00:55:33,640
Speaker 1: are the factors that increases your risk of heart attack

945
00:55:33,800 --> 00:55:38,279
Speaker 1: or stroke. Where the Seven Country study showed the relationship

946
00:55:38,320 --> 00:55:42,120
Speaker 1: between blood cholesterol and heart disease at a population level,

947
00:55:42,400 --> 00:55:46,799
Speaker 1: the Framingham Heart study demonstrated it in the individual. So

948
00:55:46,880 --> 00:55:50,920
Speaker 1: this person had high cholesterol and then they experienced a

949
00:55:50,960 --> 00:55:54,560
Speaker 1: heart attack. That was sort of that directional relationship, right.

950
00:55:55,200 --> 00:55:59,000
Speaker 1: The link between high cholesterol and coronary heart disease could

951
00:55:59,000 --> 00:56:00,480
Speaker 1: not be ignored.

952
00:56:00,840 --> 00:56:05,600
Speaker 3: No no, which of course didn't prevent people from doing so.

953
00:56:05,719 --> 00:56:07,560
Speaker 3: The wars continued.

954
00:56:07,000 --> 00:56:12,160
Speaker 1: Aaron Wow, but increasingly those cholesterol doubters were becoming a

955
00:56:12,239 --> 00:56:17,160
Speaker 1: tiny but vocal minority. Other studies, such as dietary intervention

956
00:56:17,239 --> 00:56:20,439
Speaker 1: studies helped to build the case against cholesterol. But there

957
00:56:20,560 --> 00:56:25,040
Speaker 1: was still one important facet missing, and that was a mechanism.

958
00:56:25,560 --> 00:56:28,520
Speaker 1: So since at least the late eighteen hundreds, physicians had

959
00:56:28,600 --> 00:56:31,520
Speaker 1: noticed a condition that ran in some families where people

960
00:56:31,560 --> 00:56:35,520
Speaker 1: developed large deposits of lipids under their skin. Members of

961
00:56:35,560 --> 00:56:39,480
Speaker 1: these families were very prone to develop severe cardiovascular disease

962
00:56:39,600 --> 00:56:42,759
Speaker 1: at early ages, with some experiencing heart attacks in the

963
00:56:42,760 --> 00:56:47,759
Speaker 1: first ten years of life, and by the early nineteen seventies,

964
00:56:48,040 --> 00:56:51,440
Speaker 1: researchers had established that very high blood cholesterol was a

965
00:56:51,520 --> 00:56:56,360
Speaker 1: key feature of this, hence the name familial hypercholesterol aemia,

966
00:56:57,280 --> 00:57:00,160
Speaker 1: but they weren't sure what caused it or it it's

967
00:57:00,280 --> 00:57:03,200
Speaker 1: role in disease development. Particularly, they were like, Okay, there's

968
00:57:03,239 --> 00:57:05,719
Speaker 1: clearly a genetic link, but like, what's the mechanism here?

969
00:57:05,840 --> 00:57:09,919
Speaker 1: What is that mutation that leads to these high cholesterol levels?

970
00:57:09,960 --> 00:57:13,320
Speaker 4: Exactly what is going on that is causing this person's

971
00:57:13,360 --> 00:57:17,000
Speaker 4: cholesterol to be so high and then resulting in all

972
00:57:17,120 --> 00:57:18,440
Speaker 4: negative health outcomes?

973
00:57:18,520 --> 00:57:21,360
Speaker 3: Like what's why? Why? Why why?

974
00:57:22,080 --> 00:57:25,080
Speaker 1: In nineteen seventy three, the key to the puzzle was

975
00:57:25,200 --> 00:57:30,280
Speaker 1: unlocked by two researchers, Michael Brown and Joseph Goldstein, who,

976
00:57:30,400 --> 00:57:33,960
Speaker 1: over the course of their fifty year collaboration, would be

977
00:57:34,000 --> 00:57:38,480
Speaker 1: compared to Rogers and Hammerstein, which is, so I love.

978
00:57:38,280 --> 00:57:40,520
Speaker 5: That, yeah, Aaron, can we work together?

979
00:57:41,640 --> 00:57:44,480
Speaker 3: Yes? Yes? I was like, can that be us? I

980
00:57:44,520 --> 00:57:45,480
Speaker 3: want that to be us?

981
00:57:47,120 --> 00:57:47,480
Speaker 5: Yes.

982
00:57:49,280 --> 00:57:51,120
Speaker 4: I don't think we'll ever create something as good as

983
00:57:51,200 --> 00:57:55,479
Speaker 4: Rogers and Hammerstein, though let's be let's be the ld Goldstein. Yes.

984
00:57:55,560 --> 00:58:01,680
Speaker 1: Yeah. But Brown and Goldstein they were fascinated by the

985
00:58:01,720 --> 00:58:05,480
Speaker 1: mystery of familial hypercholesterolemia and they wanted to figure out

986
00:58:05,480 --> 00:58:08,800
Speaker 1: what caused such high levels of LDL and the blood

987
00:58:08,840 --> 00:58:11,880
Speaker 1: in affected individuals, because that was really one of the

988
00:58:11,960 --> 00:58:16,360
Speaker 1: key features of this was high LDL. As they discovered,

989
00:58:16,840 --> 00:58:20,200
Speaker 1: it wasn't that there was too much LDL being produced,

990
00:58:20,680 --> 00:58:23,640
Speaker 1: it was that too little LDL. It was being taken

991
00:58:23,720 --> 00:58:24,840
Speaker 1: up by the cells.

992
00:58:25,040 --> 00:58:27,120
Speaker 5: Ah, I love this so much, darn.

993
00:58:27,480 --> 00:58:32,440
Speaker 1: So the cells of people with familial hypercholesterolemia lacked receptors

994
00:58:32,480 --> 00:58:35,560
Speaker 1: that would allow them to scoop up the LDL from

995
00:58:35,600 --> 00:58:38,520
Speaker 1: the bloodstream. So they didn't have those little velcrow hands, right,

996
00:58:38,760 --> 00:58:41,720
Speaker 1: they didn't have enough felcrow hands, and so LDL just

997
00:58:41,840 --> 00:58:45,360
Speaker 1: kept piling up, piling up, circulating and circulating with nowhere

998
00:58:45,400 --> 00:58:47,800
Speaker 1: to go, and over time it just again it's a

999
00:58:47,880 --> 00:58:50,240
Speaker 1: numbers game. It's going to lodge into the blood vessel walls.

1000
00:58:50,360 --> 00:58:53,720
Speaker 1: It's going to cause a blockage, inflammation, plaques, et cetera,

1001
00:58:53,760 --> 00:58:54,240
Speaker 1: et cetera.

1002
00:58:54,680 --> 00:58:55,280
Speaker 3: Huh.

1003
00:58:55,560 --> 00:59:01,160
Speaker 1: Yeah, this discovery, Brown and Goldstein's discovery of the ld receptor.

1004
00:59:00,960 --> 00:59:04,040
Speaker 3: It transformed the field wow, so much so.

1005
00:59:04,000 --> 00:59:06,720
Speaker 1: That it earned them a Nobel Prize in nineteen eighty five,

1006
00:59:07,160 --> 00:59:10,720
Speaker 1: because not only did it explain why people with familial

1007
00:59:10,800 --> 00:59:17,520
Speaker 1: hypercholesterolmia develop cardiovascular disease, it clarified how our cells regulate cholesterol,

1008
00:59:17,600 --> 00:59:23,080
Speaker 1: specifically LDL, and why disease happens when that regulation goes awry.

1009
00:59:23,880 --> 00:59:27,000
Speaker 1: So it was a major major step forward in solidifying

1010
00:59:27,040 --> 00:59:30,160
Speaker 1: the cholesterol heart disease link, and it opened these different

1011
00:59:30,240 --> 00:59:34,960
Speaker 1: pathways to treatment. Can we do something about this receptor

1012
00:59:35,240 --> 00:59:35,960
Speaker 1: right instance?

1013
00:59:36,120 --> 00:59:36,520
Speaker 3: Yeaheah.

1014
00:59:37,760 --> 00:59:44,160
Speaker 1: Did it end the cholesterol wars? Not necessarily, It really didn't.

1015
00:59:44,640 --> 00:59:48,280
Speaker 1: The debate continued, but it had lost a lot of steam.

1016
00:59:48,800 --> 00:59:52,720
Speaker 1: The advent of cholesterol lowering drugs like statins changed the

1017
00:59:52,760 --> 00:59:58,080
Speaker 1: conversation by turning cardiovascular disease from a disease to manage

1018
00:59:58,160 --> 01:00:02,280
Speaker 1: into one to treat, even prevent potentially. But as we'll

1019
01:00:02,280 --> 01:00:05,000
Speaker 1: see next week, their use has also been met with

1020
01:00:05,080 --> 01:00:09,400
Speaker 1: a hefty amount of skepticism, and so the cholesterol wars

1021
01:00:09,480 --> 01:00:11,160
Speaker 1: really continue through today.

1022
01:00:12,040 --> 01:00:16,960
Speaker 4: It is so interesting, Aaron, how much like it. It

1023
01:00:17,040 --> 01:00:20,440
Speaker 4: is really hard, I think to find someone who doesn't

1024
01:00:20,480 --> 01:00:23,680
Speaker 4: at least agree that high levels of cholesterol puts you

1025
01:00:23,680 --> 01:00:27,720
Speaker 4: at high risk for heart disease. Yeah, and yet and

1026
01:00:27,800 --> 01:00:31,840
Speaker 4: there still is so much, like mama, about what you

1027
01:00:31,920 --> 01:00:33,840
Speaker 4: do about it or what we shouldn't do about it,

1028
01:00:33,960 --> 01:00:35,840
Speaker 4: or what your diet effect might be.

1029
01:00:36,360 --> 01:00:38,640
Speaker 5: Like it's oh, I can't wait for next week.

1030
01:00:38,800 --> 01:00:41,480
Speaker 1: Yeah, there's there's a lot more to cover next week

1031
01:00:41,520 --> 01:00:43,840
Speaker 1: when it comes to the story of statins and how

1032
01:00:44,560 --> 01:00:48,320
Speaker 1: the role that they have played in changing our approach

1033
01:00:48,400 --> 01:00:52,760
Speaker 1: to managing and preventing heart disease. Also how the HECTU

1034
01:00:52,760 --> 01:00:55,040
Speaker 1: statins work. Do you want to know the answers to

1035
01:00:55,080 --> 01:00:55,920
Speaker 1: these questions?

1036
01:00:56,200 --> 01:00:58,240
Speaker 3: I want to tell you to turn in next week.

1037
01:01:01,240 --> 01:01:02,919
Speaker 4: Shall we tell people if they want to just learn

1038
01:01:02,920 --> 01:01:04,480
Speaker 4: more about what we've already talked.

1039
01:01:04,240 --> 01:01:07,400
Speaker 3: About, Yes, absolutely we should. I have a lot of

1040
01:01:07,440 --> 01:01:08,400
Speaker 3: sources for.

1041
01:01:08,240 --> 01:01:09,520
Speaker 5: This that you do erin.

1042
01:01:09,720 --> 01:01:10,959
Speaker 3: I'm shouting out.

1043
01:01:11,400 --> 01:01:12,960
Speaker 1: So there was a if you wanted to learn more

1044
01:01:13,000 --> 01:01:17,680
Speaker 1: about sort of cholesterol in oxygen and the Great oxygenation

1045
01:01:17,720 --> 01:01:20,600
Speaker 1: event and why it plays a role. There's a paper

1046
01:01:20,640 --> 01:01:24,520
Speaker 1: called the evolution of cholesterol rich membrane as oxygen adaptation

1047
01:01:24,720 --> 01:01:28,800
Speaker 1: the respiratory system as a model by Zuniga, Hertz and Patel.

1048
01:01:28,480 --> 01:01:29,400
Speaker 3: From twenty nineteen.

1049
01:01:29,600 --> 01:01:32,800
Speaker 1: I liked that one, and then there's an excellent series

1050
01:01:32,880 --> 01:01:35,720
Speaker 1: by Steinberg from two thousand and four. It's a five

1051
01:01:35,800 --> 01:01:39,919
Speaker 1: part series called an Interpretive History of the Cholesterol Controversy

1052
01:01:40,560 --> 01:01:45,160
Speaker 1: Contra Controversy. I can't speak today erin. It's a five

1053
01:01:45,200 --> 01:01:45,720
Speaker 1: part series.

1054
01:01:45,800 --> 01:01:47,440
Speaker 3: Check it out, good good stuff.

1055
01:01:47,520 --> 01:01:49,160
Speaker 5: You did a good job, I think thanks.

1056
01:01:49,800 --> 01:01:50,840
Speaker 3: I also had a.

1057
01:01:50,800 --> 01:01:54,880
Speaker 4: Number of papers for this episode, I think probably my

1058
01:01:55,000 --> 01:01:59,120
Speaker 4: three favorites that cover a lot of ground. One was

1059
01:01:59,120 --> 01:02:03,040
Speaker 4: from twenty twenty by Luo at All from Nature Reviews

1060
01:02:03,160 --> 01:02:06,120
Speaker 4: Molecular Cell Biology. It was called Mechanisms and Regulation of

1061
01:02:06,200 --> 01:02:08,960
Speaker 4: Cholesterol Homeostasis, so this is just like how our bodies

1062
01:02:09,000 --> 01:02:12,120
Speaker 4: are using cholesterol. There was another older one by Maxfield

1063
01:02:12,160 --> 01:02:14,880
Speaker 4: and Tabas from two thousand and five in Nature called

1064
01:02:15,160 --> 01:02:18,640
Speaker 4: Roll of Cholesterol and Lipid Organization in Disease. And then

1065
01:02:18,800 --> 01:02:23,400
Speaker 4: one from twenty nineteen by Holmes and A. La Corpela

1066
01:02:23,640 --> 01:02:27,480
Speaker 4: from Nature Reviews Cardiology just titled what is LDL cholesterol?

1067
01:02:27,720 --> 01:02:29,280
Speaker 4: So that was a good one too. But they have

1068
01:02:29,320 --> 01:02:31,480
Speaker 4: a bunch more and you can check them all out

1069
01:02:31,760 --> 01:02:35,360
Speaker 4: from like these ones from this episode, but also from

1070
01:02:35,400 --> 01:02:37,720
Speaker 4: all of our other episodes on our website.

1071
01:02:37,720 --> 01:02:39,440
Speaker 5: This podcast with Killia dot Com I.

1072
01:02:39,520 --> 01:02:40,400
Speaker 3: Do the episodees tab.

1073
01:02:40,720 --> 01:02:44,280
Speaker 1: Indeed, thank you again so much, Tori for sharing your

1074
01:02:44,320 --> 01:02:47,080
Speaker 1: story with us. It means a lot, it really does.

1075
01:02:47,160 --> 01:02:47,520
Speaker 5: Thank you.

1076
01:02:48,400 --> 01:02:51,000
Speaker 1: Thank you also to Bloodmobile for providing the music for

1077
01:02:51,080 --> 01:02:53,120
Speaker 1: this episode and all of our episodes.

1078
01:02:53,440 --> 01:02:57,440
Speaker 4: Thank you to Leanna and Tom and Mark and Jessica

1079
01:02:57,520 --> 01:03:02,560
Speaker 4: and Christine, everyone, everyone exactly right. Yes, we really appreciate

1080
01:03:02,600 --> 01:03:03,680
Speaker 4: everything that you do for us.

1081
01:03:03,920 --> 01:03:07,560
Speaker 1: We do. Thank you to you listeners for listening, watchers

1082
01:03:07,560 --> 01:03:11,040
Speaker 1: for watching. Anyone who subscribes, participates, does anything with this

1083
01:03:11,080 --> 01:03:13,880
Speaker 1: podcast interacts in any way, We truly appreciate it.

1084
01:03:14,120 --> 01:03:16,520
Speaker 4: We do. Thank you, and as always, a special shout

1085
01:03:16,520 --> 01:03:19,040
Speaker 4: out to our patrons for your support over on Patreon.

1086
01:03:19,400 --> 01:03:23,880
Speaker 4: It means so much to us. Truly, thank you, truly.

1087
01:03:23,640 --> 01:03:24,000
Speaker 3: Thank you.

1088
01:03:24,840 --> 01:03:28,040
Speaker 1: Until next time, wash your hands, you filthy animals.