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Speaker 1: I'm Tracy. Welcome to the podcast.

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Speaker 2: Thanks for having me on. Paul, it's great to be here.

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Speaker 3: I don't know whether I should call you doctor, professor, researcher,

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Speaker 3: ventor author.

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Speaker 1: I mean, can you make your mind up here? Kevin?

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Speaker 2: Kevin's fine, Kevin's perfect.

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Speaker 3: So you have a Bachelor of Science in chemistry, which

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Speaker 3: I remember is feeling miserably.

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Speaker 1: You also are trained in eurosurgery.

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Speaker 3: You've got seventy five typing patents, that's bonkers, and about

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Speaker 3: four hundred published papers.

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Speaker 1: When are you going to get your finger out and

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Speaker 1: do some work.

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Speaker 2: I'm a lucky guy, Paul. I really love what I do,

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Speaker 2: and I have been able to do medicine and science

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Speaker 2: in the hopes of helping people. And if you're going

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Speaker 2: to translate science into things that actually do help people,

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Speaker 2: that requires turning the science into an invention. And if

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Speaker 2: you're going to have that invention help people, that requires

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Speaker 2: navigating the path from the idea to the invention to

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Speaker 2: actually some sort of clinical product or clinical device or

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Speaker 2: clinical drug. And so I've over the years, I've been

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Speaker 2: doing this for forty years, and in that time I've

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Speaker 2: learned how to navigate the individual steps and I happen

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Speaker 2: to enjoy all of it. So I'm a lucky guy.

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Speaker 2: I'm a very lucky guy. You know. I choose what

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Speaker 2: I get to work on, what I want to work on,

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Speaker 2: and I've gotten to work with brilliant colleagues. But we're

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Speaker 2: doing this for patients, and the patients they don't choose

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Speaker 2: to have the condition they're confronting. They're the heroes and

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Speaker 2: the story, not the people who get to enjoy what

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Speaker 2: they do.

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Speaker 1: Like us.

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Speaker 3: A good point, and the guy, I have your book

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Speaker 3: here and really interesting what happened?

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Speaker 1: I saw your book on Amazon.

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Speaker 3: And I'm like, bye, I want to get that because

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Speaker 3: I'm very interested in the vegus nerve. And then I

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Speaker 3: got an email about you as a potential guest on

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Speaker 3: the podcast, and I hadn't done the connection right and

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Speaker 3: then they said, oh, we'll send your book and send

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Speaker 3: a book, and I'm like, hold on a minute, I'm

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Speaker 3: reading this book right now, and I hadn't done the connection.

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Speaker 3: So it's quite fortuitous, really, But tell us there's a

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Speaker 3: little bit of a story behind why you got into medicine,

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Speaker 3: involving your mom, So can you take the readers through

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Speaker 3: that story? Because I think it's always interesting why people

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Speaker 3: do what they do.

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Speaker 2: When I was five, my mother died suddenly of a

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Speaker 2: brain tumor, a brain tumor called a glioblastoma multiform.

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Speaker 3: End I'm sorry, it's pretty incurable. Shortening was back then

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Speaker 3: was yeah.

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Speaker 2: And unfortunately it was horrible, And unfortunately today for is

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Speaker 2: that we haven't we haven't made a lot of progress

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Speaker 2: in the in the cure of glioblastoma multiform and even today.

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Speaker 2: And that was what some sixty three years ago or something.

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Speaker 2: So at the time she died, her dad, my grandfather,

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Speaker 2: was a professor and pediatrics at Yale Medical School in

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Speaker 2: New Haven, Connecticut, and I remember climbing up on his

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Speaker 2: knee and asking him why didn't the neurosurgeon take the

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Speaker 2: tumor out and then she could come home, And he

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Speaker 2: said that there was no way that could be done

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Speaker 2: because the tumor was like a horseshoe crab and it

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Speaker 2: had tentacles or legs that went through the brain, and

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Speaker 2: if he had pulled on one part of the crab

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Speaker 2: or the tumor, the damage would have extended into my

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Speaker 2: mother's brain into other parts and she wouldn't been the

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Speaker 2: same person. Who she was and and so I said, well,

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Speaker 2: somebody should do something about that, and he said, well,

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Speaker 2: maybe you will. And so your question is a leading one,

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Speaker 2: of course. And now it's you know, three years later,

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Speaker 2: and I'm a neurosurgeon working on trying to invent cures.

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Speaker 2: As you know, Paul, when you're late in a career,

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Speaker 2: you can look back and connect the dots and make

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Speaker 2: a history into a story in it. And it looks

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Speaker 2: like it was a planned trajectory. Was there a plan

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Speaker 2: when I was five? No? Is it interesting that I

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Speaker 2: became a brain surgeon and then a brain surgeon doing

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Speaker 2: research to try to make cures after my grandfather said that, Yes,

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Speaker 2: it's it's it's memorable, it's unforgettable, but it's you know,

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Speaker 2: it's young people listening. Chase your dreams. That's that's the

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Speaker 2: that's the idea. Chase chase your dreams and and do

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Speaker 2: and and and dream that you can help help people

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Speaker 2: or help the world, because that's what we all need. Paul.

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Speaker 1: Yeah, yeah, look absolutely.

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Speaker 3: And so my my daughter's nineteen, my son's fifty, My

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Speaker 3: daughters at university, and she's studying bio medicine, right, and

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Speaker 3: she's at a minute. She's in her second year and

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Speaker 3: she's got one eye on medicine, one eye on a

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Speaker 3: PhD and being a researcher and is And the only

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Speaker 3: advice I've given her is follow whatever you're really curious about,

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Speaker 3: and you know what, what is it that really interests you,

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Speaker 3: because you're probably going to do this for many, many years,

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Speaker 3: and if you're not curious, then it's going to end

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Speaker 3: up being a millstone around your neck your career.

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Speaker 1: So be curious.

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Speaker 3: I take it by your nods and smiles that he

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Speaker 3: would also endorse that advice.

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Speaker 2: I would. And hopefully you're not paying all the tuition bills, Paul,

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Speaker 2: because what I what I what I would add, and

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Speaker 2: you might not like me for this if if you are,

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Speaker 2: But what I would add is that do both. No,

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Speaker 2: nothing's nothing's permanent till you're nothings. Nothing's permanent until you're thirty.

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Speaker 2: And and I don't think anyone should be in a

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Speaker 2: rush to finish their training. And if you need to

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Speaker 2: take more time to be trained in two things instead

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Speaker 2: of one, so be it. If that's you know, you

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Speaker 2: don't do it willy nilly, and you don't do it

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Speaker 2: to delay going into the to the workforce as a strategy.

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Speaker 2: But if you're curious about these things and you love

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Speaker 2: doing both, then do both until you have to only

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Speaker 2: do one. And and I will tell you, Paul, none

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Speaker 2: of her professors are going to tell her what I

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Speaker 2: just said. It's not gonna it's not gonna happen. Everybody says, Oh,

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Speaker 2: you can't do both, Oh you have to focus all this,

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Speaker 2: that and the other thing. No, you can do both,

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Speaker 2: and you should do both until you can, until until

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Speaker 2: the world dictates otherwise. Because it's when you're trained in

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Speaker 2: multiple areas as I have been over the years and

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Speaker 2: am that allows you to create bridges between fields that

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Speaker 2: don't exist. And that's where that's where pioneering advances come from,

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Speaker 2: not just in medicine and science, but pioneering advances in

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Speaker 2: the world come when people bridge fields and make connections

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Speaker 2: that didn't exist. And you know, we're living in an

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Speaker 2: era now where the coin of the realm is usefulness.

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Speaker 2: And if you can bridge fields, whether it's science and

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Speaker 2: medicine or something in something else, you're going to add

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Speaker 2: a value that other people can't because you've been trained

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Speaker 2: in two areas. So I would tell her to train.

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Speaker 3: In both, I fully endorse that, and I fully endorse

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Speaker 3: the you know train for a long time. I've just

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Speaker 3: finished my PhD in psychology at the age of fifty four.

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Speaker 3: But for me, as a long time exercise scientist, nutritionist,

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Speaker 3: it is the bridging the fields. And I call myself

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Speaker 3: a psychophysiologist, and I buying my head off the wall

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Speaker 3: at all these psychologists who think you can optimize for

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Speaker 3: mental health just with thinking skills and that the body's.

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Speaker 1: Got nothing to do with it. It drives me bunkers.

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Speaker 2: But anyway, well, you and Plato poll are on the

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Speaker 2: same page, right, didn't he say, to heal the brain,

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Speaker 2: you heal the body, and to heal the body, you

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Speaker 2: heal the brain. He said soul. But it's the same thing.

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Speaker 1: Yeah, you know, exactly when the Greek's talked about. So

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Speaker 1: they were really talking about that. So let's get back

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Speaker 1: to you.

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Speaker 3: With all of the stuff that you have been interested

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Speaker 3: in over the years, all the stuff that you've done,

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Speaker 3: why did you choose to write a book on one

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Speaker 3: nerve in the body?

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Speaker 2: My life's work culminated in the recently last August. First,

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Speaker 2: I believe with the FDA approval in the United States,

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Speaker 2: of using something that I had originally thought of and

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Speaker 2: improved and invented, using a vagus nerve stimulator to treat

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Speaker 2: rheumatoid arthritis, which is of course as an inflammatory condition. Now,

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Speaker 2: my life's work was bringing this connection to the fore,

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Speaker 2: this connection between the nervous system, the brain, and the

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Speaker 2: immune system. The immune system produces inflammation, and what we

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Speaker 2: discovered is that the brain can control that inflammation or

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Speaker 2: slow it down by sending signals through the vegus nerve.

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Speaker 2: And we can talk about what is the vegus nerve

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Speaker 2: and how it works. But it's a very great nerve,

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Speaker 2: which is the name of the book, and it's great

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Speaker 2: for many reasons, but let's start with a very simple one.

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Speaker 2: It's the only nerve in your body. If you cut

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Speaker 2: it on both sides that it's lethal. Oh wow, I

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Speaker 2: did not know that true. So if it travels from

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Speaker 2: about the it starts in your brain, and it travels

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Speaker 2: from about the level of your ears, down your neck

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Speaker 2: and chest into your abdomen, and along the way it

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Speaker 2: touches all the organs in your body that you don't

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Speaker 2: think about all day long, your heart, your lungs, your liver,

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Speaker 2: your pancras explain, and and we say vegas nerve. But

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Speaker 2: you have two of them, like two thumbs. You have

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Speaker 2: one on each side, and within each of these two

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Speaker 2: vegas nerves. And this is where it gets complicated and interesting.

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Speaker 2: You have one hundred thousand individual fibers, so people, so

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Speaker 2: you have two hundred thousand vegus nerve fibers, and and

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Speaker 2: each and every one of those fibers has has the origin,

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Speaker 2: a beginning, and an end. It begins in either the

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Speaker 2: body or the brain. Those are the ones that go

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Speaker 2: up their sensory where it begins in the brain and

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Speaker 2: goes down to the body. And those aremotor or epharantor

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Speaker 2: or outward traveling from the brain. That means because because

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Speaker 2: they've evolved over hundreds of millions of years, that means

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Speaker 2: that each and every individual fiber of the two hundred

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Speaker 2: thousand fibers has a specific function. Some go to the heart,

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Speaker 2: some go to the spleen, some go to the lungs,

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Speaker 2: and on and on and on down the list. So

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Speaker 2: people talk, you know, almost online anyways, you'll find billions,

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Speaker 2: not millions, billions of web impressions about the vegas nerve.

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Speaker 2: And people wave their arms, and they talk about it

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Speaker 2: like it's a solid copper wire. And someone says, oh,

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Speaker 2: I'm going to do this that or the other thing

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Speaker 2: and stimulate my vegas nerve. And I say, you have

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Speaker 2: two hundred thousand vegas nerves. They each have their own function.

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Speaker 2: Which one are you going to stimulate? And how?

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Speaker 1: And so did today? Are you saying ken that they

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Speaker 1: all act independently?

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Speaker 2: All those yeas?

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Speaker 3: Yes, So they are they all individual neurons essentially all.

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Speaker 1: Well let me ask, let me anatomically, yeah, well, I

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Speaker 1: mean let me.

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Speaker 2: Can you walk and chew gum? Can you chew gum

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Speaker 2: and play the piano? Of course you can, and so

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Speaker 2: can your listeners. And so that's how the nerve system works.

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Speaker 2: So it begins with some sort of a simple animal

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Speaker 2: and evolutionary history, right, a snail or a slug or

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Speaker 2: a jellyfish or something, and it has a few nerves,

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Speaker 2: a lot less than we have, and they and they

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Speaker 2: have reflex functions. So there is a predator on this side,

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Speaker 2: and there's an image of the predator comes in and

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Speaker 2: a nerve reacts to that and it instantly, not instantly,

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Speaker 2: but very quickly activates motor nerves that push the whatever,

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Speaker 2: the snail or the sorry, the slug or the worm

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Speaker 2: or the jelly, push it away from the predator or

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Speaker 2: towards food. These are all hardwired reflexes, and over time,

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Speaker 2: hundreds of millions of years that the nervous system of

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Speaker 2: these evolving animals collects more and more reflexes, until you

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Speaker 2: end up with a brain and a nervous system the

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Speaker 2: size of ours. And that's how evolution works. And each

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Speaker 2: individual nerve still has a simple function. Right, So you're

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Speaker 2: in your doctor's office and she thumps your knee with

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Speaker 2: a rubber hammer and your your leg pops up, and

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Speaker 2: you said, who you know who did that? Right? Well,

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Speaker 2: that was her hammer stretching the pateller tendon and your

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Speaker 2: knee sending a sensory signal up a few nerve fibers,

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Speaker 2: not millions, a few, a few hundred maybe into your

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Speaker 2: spinal cord, and that sends some signals up to your brain,

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Speaker 2: and some of the signals return from the spinal cord

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Speaker 2: to your quadriceps. From Morris, your muscle contracts and your

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Speaker 2: leg goes up. That's a reflex. Well, all your organs

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Speaker 2: are also operating under the reflex control systems. So in

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Speaker 2: the case of the heart, will do the heart first,

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Speaker 2: and then the immune system. The heart. Your heart's beating along,

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Speaker 2: your brain's keeping scores, keeping keeping the pace, and you

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Speaker 2: get startled and your heart rate skips or you think

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Speaker 2: of a stressful thought and your heart rate skips up.

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Speaker 2: That skipping up of your heart activates sensory nerves which

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Speaker 2: tell your heart the heart's beating a lot faster now,

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Speaker 2: which activates a reflex response in your vegus nerve to

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Speaker 2: slow the heart down.

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Speaker 1: Yeah.

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Speaker 2: Well, we discovered. Our basic discovery was that the same

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Speaker 2: thing happens in inflammation. When inflammation raises up to a

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Speaker 2: point that's too high or higher, that is detected by

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Speaker 2: the vagus nerve and other nerves in the nervous system,

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Speaker 2: and the signals from the brain to the immune system

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Speaker 2: in the spleen traveled down the breath the vegus nerve

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Speaker 2: and it works like the breaks on your car. That's

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Speaker 2: the basic discovery.

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Speaker 1: That's pretty cold stuff. I want to return to the

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Speaker 1: immune because I want to spend a little bit of

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Speaker 1: time on the heart.

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Speaker 3: Just because you mentioned the heart first. Heart red variability

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Speaker 3: as a measure of veagal tone talk us through. Is

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Speaker 3: that a perfect measure of legal tone? Are there any limitations?

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Speaker 3: How do you think it is useful? So so I'll

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Speaker 3: give you I kind of am my idea on this

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Speaker 3: with with with my limited knowledge compared to yours, is

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Speaker 3: that and the your HRV can be the canary and

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Speaker 3: the coal mine about how you're dealing with stress in

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Speaker 3: your life and cumulative stress. So kind of commentary on

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Speaker 3: all of that give give us the overview of it.

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Speaker 2: So you asked some very simple questions in the beginning,

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Speaker 2: and then you end it on a very complex point.

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Speaker 2: So I think the simple answers to the simple questions are, No,

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Speaker 2: it's not a perfect measure of vegel tone. Yes, it

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Speaker 2: is widely used. And there's the rub. And I do

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Speaker 2: spend some time on this in the book, And so

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Speaker 2: you're readers who are interested in this discussion may find

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Speaker 2: the book clarifying. But let's break it down because it's

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Speaker 2: actually really important to talk in simple terms on complicated things.

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Speaker 2: So what is heart reveriability? Heart reveriability is a mathematically

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Speaker 2: derived calculation using very complicated math and statistics things like

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Speaker 2: fast foury transformations and things like that, to look at

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Speaker 2: a very simple measure. The simple measure is that is

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Speaker 2: the time in milliseconds, usually between individual heartbeats. So how

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Speaker 2: does that work? Well, I already said that some fibers,

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Speaker 2: not two hundred thousand, but some of the fibers in

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Speaker 2: the vegus nerve going to the heart, maybe a few dozen,

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Speaker 2: maybe a few hundred. When they are activated, the electrical

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Speaker 2: signals traveling down those fibers are converted to chemical signals

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Speaker 2: in the heart and the result is a complex series

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Speaker 2: of steps that causes the heart to beat slower. What

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Speaker 2: does that mean. It means that the vagus nerve is

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Speaker 2: prolonging the time to the next heartbeat. That's how your

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Speaker 2: pulse slows. So what does that mean? Well, what these

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Speaker 2: statistical or mathematical transformations do is they simply count the

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Speaker 2: distance in time, the amount of time between each and

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Speaker 2: every heartbeat for some period of time five minutes, twenty

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Speaker 2: minutes overnight, and that is the number that's applied to

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Speaker 2: which the statistical analysis is applied, whether it's a summation

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Speaker 2: of standard deviations, whether it's distributions around the frequency of

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Speaker 2: the events, and by consensus and by physiological experiments, mostly

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Speaker 2: in analysts animals, but some in human there's a consensus

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Speaker 2: that the that the power of under the curve in

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Speaker 2: the high frequency domain most closely reflects vegas nerve activity.

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Speaker 2: And people say that because if you block the vegas

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Speaker 2: nerve and experiments with drugs or surgery, that that the

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Speaker 2: area and that high frequency part dissipates, So it's controlled

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Speaker 2: by the vegas nerve. So does that mean that that's

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Speaker 2: all there is to it? No, Actually, unfortunately it's only

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Speaker 2: the beginning. And and here we can go through some caveats. First,

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Speaker 2: I said, the math is complicated and the statistics are complicated.

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Speaker 2: They're algorithms that people subject the data to and like

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Speaker 2: other algorithms in the social media universe, you don't know

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Speaker 2: what they are.

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Speaker 3: So and just on that, Kevin, sorry to interrupt that.

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Speaker 3: The different devices, so you're app a watch your garment,

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Speaker 3: they will use different ways of measuring it.

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Speaker 1: You talked about r M, S SD and and and

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Speaker 1: there's there's a whole mindful listener, are we looking at

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Speaker 1: high frequency par low frequency par like once you start

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Speaker 1: to look onto the hood, my god, it gets complicated.

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Speaker 2: Absolutely right, Paul, you took the words out of my mouth.

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Speaker 2: That is the point you cannot say I'm wearing this

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Speaker 2: device today and that device tomorrow and my heart rate variability,

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Speaker 2: no and so, and when you do the experiments yourself.

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Speaker 2: And I've done some of this with my colleague in

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Speaker 2: the lab, saying Gita Schavan. She and I run the

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Speaker 2: lab together here at the fine Stein Institute in New York.

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Speaker 2: Years ago, we built a heart rate variability software package

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Speaker 2: and hardware package on a laptop with some wearables. It

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Speaker 2: made a wearables meaning electrodes like EKG electrodes, because we

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Speaker 2: were doing it here in a clinical research center, and

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Speaker 2: what we found just totally confused me. So we found,

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Speaker 2: for instance, if a patient had periventricular contractions or extra

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Speaker 2: extra ventricular contractions, extra heartbeats or skip to heart beat,

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Speaker 2: you'd have to subtract that from the analysis because it's

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Speaker 2: not the same as everything else. And when you do that,

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Speaker 2: you get a completely different number for the heart rate variability,

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Speaker 2: even if you have thousands and thousands of data points.

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Speaker 2: So I didn't understand that, I said, Statisticians tell me, oh,

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Speaker 2: that's what you'd expect, But I don't understand that. The

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Speaker 2: second thing we observed is everything else also made a difference.

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Speaker 2: Were they sitting down or lying down when we made

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Speaker 2: the recordings. Had they had a cup of coffee or

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Speaker 2: a full breakfast two hours before or had they not

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Speaker 2: eaten at all? Did they Were they breathing that this

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Speaker 2: is really important. Were they breathing on a controlled respiratory

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Speaker 2: cycle or were they breathing randomly, sometimes breathing at eight breaths,

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Speaker 2: sometimes twelve, sometimes sixteen. Huge differences in, you know, and

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Speaker 2: a huge difference in whether you were making the recordings

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Speaker 2: for five minutes or twenty minutes or two or three hours.

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Speaker 2: So when you talk to you're a physiologist, so I

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Speaker 2: don't have to tell you all this, But when you

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Speaker 2: talk to physiologists about this, if you don't control for

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Speaker 2: all these variables, you can't compare it. You can't and

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Speaker 2: the age of the patient and everything else. Then you

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Speaker 2: can't make direct comparisons across And that's what you're seeing

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Speaker 2: online now on social media. You're seeing these generic recommendations

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Speaker 2: about HRV, which you know, for a population level measure

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Speaker 2: of thousands or hundreds of thousands of people, and may

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Speaker 2: have some truthfulness, but we all know you can't apply

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Speaker 2: a population statistic to an individual person or case anymore

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Speaker 2: than you can say somebody's going to win the lottery

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Speaker 2: and the odds of the winning or losing or x,

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Speaker 2: Y or z, and therefore I'm going to win or lose.

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Speaker 2: You don't know from a population.

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Speaker 3: So but if we then zero in on the individual,

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Speaker 3: my right, what is the utility or the usefulness of

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Speaker 3: having one device bocking it over time on one device,

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Speaker 3: And do you think that's useful for the individual? There's

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Speaker 3: a reflection of kind of high their bodies dealing globally

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Speaker 3: with stress.

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Speaker 2: Maybe. So again it's complicated. So let's let's talk about

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Speaker 2: the other thing we that one hundred percent influences is

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Speaker 2: that we haven't talked about yet. So we've said that

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Speaker 2: there's one part of the of the high free of

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Speaker 2: the analysis that gives you the high frequency curve, if

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Speaker 2: you will, or the high frequency domain which reflects vegas nerve.

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Speaker 2: But there's a couple of other ones that that give

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Speaker 2: that that that point to either the input from the

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Speaker 2: fight or flight, the sympathetic nervous system to the heart,

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Speaker 2: which tends to speed it up. And in the context

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Speaker 2: anyways of this specific thing we're talking about, you have

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Speaker 2: you have inputs that speed up the heart and inputs

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Speaker 2: that slow down the heart. Sympathetic comparison, I'm not saying

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Speaker 2: they act in opposition. I'm just saying they both have

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Speaker 2: inputs that pushing in different directions, and so people call

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Speaker 2: that sympathovagel balance and things like that. Well, I'm not

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Speaker 2: really sure. I'm not really sure how to break that

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Speaker 2: down into a recommendation for an individual person for the

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Speaker 2: for the very simple reason that we don't have enough

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Speaker 2: well controlled, randomized clinical trial data using as you said,

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Speaker 2: one device in a particular cohortic patience for a particular condition.

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Speaker 2: So you could have a you could have people with

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Speaker 2: with with very healthy if you will, heart rate variability

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Speaker 2: numbers with some condition or problem in their brain or

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Speaker 2: in their body that is not affecting heart rate, or.

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Speaker 1: Whether there's other conditions that very strongly affected.

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Speaker 2: Right well, and the one that comes top of mind

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Speaker 2: because we I think it's the best studied at this

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Speaker 2: point is COVID. So at the end of the COVID pandemic,

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Speaker 2: there was some very important work out of Spain. Autopsy

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Speaker 2: studies showed that a lot of people, a significant percentage

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Speaker 2: of people who in this relatively small study, but I

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Speaker 2: think it was eight out of twelve or something like

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Speaker 2: that had damage to their vegas nerve. And they looked

400
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Speaker 2: in the vegas nerve and they found that there was

401
00:24:32,840 --> 00:24:35,919
Speaker 2: virus there, the COVID for the SARS virus, and they

402
00:24:36,040 --> 00:24:39,440
Speaker 2: found inflammation and nerve damage. So now the question gets

403
00:24:39,480 --> 00:24:43,480
Speaker 2: turned around, right did the heart is the heartbreat variability

404
00:24:43,640 --> 00:24:46,920
Speaker 2: a problem of stress or caused by some sort of

405
00:24:47,119 --> 00:24:49,320
Speaker 2: stress imbalance, or is it a problem that their vegas

406
00:24:49,400 --> 00:24:53,280
Speaker 2: nerve was actually damaged and couldn't carry the signals? And

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00:24:54,560 --> 00:24:57,520
Speaker 2: you need both. You need vegas nerve input and you

408
00:24:57,600 --> 00:25:01,440
Speaker 2: need fight or flight or sympathetic input. And you're the physiologist,

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00:25:02,200 --> 00:25:04,800
Speaker 2: you probably know. The study of the of the sheep

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Speaker 2: in New Zealand on the treadmill studied by the exis.

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Speaker 1: Oh you don't, I don't know this study.

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Speaker 2: No, tell me, well, it sounds like a far sight cartoon, right,

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Speaker 2: You've got a bunch of sheep in the lab running

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Speaker 2: on a treadmill. So it was a study in New Zealand.

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Speaker 2: It published an extremely reputable journals just a few years ago.

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Speaker 2: And here's what they found. They found when the sheep

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Speaker 2: started running up a twenty percent incline that their cardiac

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00:25:35,920 --> 00:25:38,359
Speaker 2: output increase and their heart rate increase, and that was

419
00:25:39,160 --> 00:25:42,800
Speaker 2: in association with an increase in their fight or flight response,

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Speaker 2: exactly what you teach everybody in extra hise physiology. And

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Speaker 2: therefore that means that it must have turned off the

422
00:25:51,080 --> 00:25:56,280
Speaker 2: parasympathetic rest and digest because they act in opposition right, wrong. Wrong.

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Speaker 2: What they found is when they blocked well, first of all,

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00:25:59,800 --> 00:26:02,080
Speaker 2: they measured the vegus nerve in those sheep and it

425
00:26:02,200 --> 00:26:06,800
Speaker 2: was also turned on. And when they blocked it, cardiac output,

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00:26:06,920 --> 00:26:12,200
Speaker 2: coronary blood flow, and I believe VO two max all declined.

427
00:26:12,680 --> 00:26:18,719
Speaker 2: In other words, the collaboration, the dance between vegas input

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Speaker 2: and fight or flight input is the key. Now, every

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Speaker 2: physiologist knows that everything in organ system functioning is that

430
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Speaker 2: when you turn something on, you turn on the off

431
00:26:30,760 --> 00:26:34,480
Speaker 2: switch at the same time. You know, you turn on insulin,

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Speaker 2: you turn on glucagon, you turn on blood clotting, you

433
00:26:37,880 --> 00:26:41,480
Speaker 2: turn on fiber analysis, and you can go right down

434
00:26:41,560 --> 00:26:44,720
Speaker 2: the list. And that's exactly what's happening with the vaguel

435
00:26:44,800 --> 00:26:48,439
Speaker 2: input to the heart. Is that when you turn on sympathetic,

436
00:26:48,520 --> 00:26:54,280
Speaker 2: you also turn on parasympathetic. So to optimize function. So

437
00:26:54,600 --> 00:26:57,800
Speaker 2: how much of that is being captured in heart revariability?

438
00:26:57,880 --> 00:27:00,680
Speaker 2: I would say it depends. Can you take a heart

439
00:27:00,760 --> 00:27:04,119
Speaker 2: rate variability number and draw all kinds of specific conclusions

440
00:27:04,200 --> 00:27:07,760
Speaker 2: for a specific patient? I would say probably not. Can

441
00:27:07,840 --> 00:27:11,080
Speaker 2: we as you as you framed it before? Can we

442
00:27:12,320 --> 00:27:15,560
Speaker 2: can we using consistent measures in a patient about which

443
00:27:15,600 --> 00:27:17,960
Speaker 2: we know a lot of other things? You know, maybe

444
00:27:18,000 --> 00:27:20,080
Speaker 2: we know they're physically fit, Maybe we know they have

445
00:27:20,160 --> 00:27:22,720
Speaker 2: a low heart rate at rest, which is another that's

446
00:27:22,760 --> 00:27:25,760
Speaker 2: a very good sign of vegas nerve tone or a

447
00:27:25,840 --> 00:27:28,639
Speaker 2: low resting heart rate, and we know their.

448
00:27:28,520 --> 00:27:30,800
Speaker 3: Hearts a lot of Sorry, that's what a lot of

449
00:27:30,880 --> 00:27:34,800
Speaker 3: athletes use to use as a measure of their training status,

450
00:27:34,880 --> 00:27:38,960
Speaker 3: that when they were going into overtraining, their resting heart

451
00:27:39,040 --> 00:27:42,159
Speaker 3: rate would change by a few bits either one way or.

452
00:27:42,160 --> 00:27:44,080
Speaker 1: The other, and that was a kind of an early

453
00:27:44,200 --> 00:27:45,120
Speaker 1: warning sign.

454
00:27:45,040 --> 00:27:48,160
Speaker 2: Right absolutely. I think in a highly trained athlete under

455
00:27:48,520 --> 00:27:52,840
Speaker 2: under regular physiological monitoring, where you know where you're starting

456
00:27:52,880 --> 00:27:54,639
Speaker 2: with your restern heart rate, you know where you're starting

457
00:27:54,680 --> 00:27:56,560
Speaker 2: with your diet, you know what drugs they're on, you

458
00:27:56,720 --> 00:27:59,680
Speaker 2: know what their baseline, as you said before, their baseline.

459
00:27:59,800 --> 00:28:04,119
Speaker 2: HIV is using a consistent machine with data collected at

460
00:28:04,160 --> 00:28:07,360
Speaker 2: the same respiratory rate in the same body position. Yes,

461
00:28:07,480 --> 00:28:10,360
Speaker 2: I think, I think. I think that's great. I see

462
00:28:10,400 --> 00:28:12,680
Speaker 2: a problem and and uh, you know, I've done a

463
00:28:12,720 --> 00:28:16,160
Speaker 2: few podcasts lately talking about the book, and a number

464
00:28:16,280 --> 00:28:20,360
Speaker 2: of doctors and clinicians have said that they they see

465
00:28:20,440 --> 00:28:24,680
Speaker 2: in their patients, you know, these these wide variable swings

466
00:28:24,800 --> 00:28:27,399
Speaker 2: in the patient's heart rate variability and could it be

467
00:28:27,480 --> 00:28:29,520
Speaker 2: stressed And I'm like, well, it could be, but it

468
00:28:29,560 --> 00:28:32,399
Speaker 2: could also be changing the measurement, change in the breathing,

469
00:28:32,560 --> 00:28:34,240
Speaker 2: change in the time of day, so.

470
00:28:34,680 --> 00:28:36,840
Speaker 3: And whether whether or not they had a skin full

471
00:28:36,920 --> 00:28:40,080
Speaker 3: of alcohol, how their sleep was right, because I find

472
00:28:40,400 --> 00:28:43,480
Speaker 3: looking at mine, I tell you, when I drink alcohol, boom,

473
00:28:43,680 --> 00:28:45,400
Speaker 3: my HRV dropped significantly.

474
00:28:46,000 --> 00:28:48,640
Speaker 1: If I've been exercise, So I think it's quite useful

475
00:28:48,680 --> 00:28:53,160
Speaker 1: on that global level. If you know your own behaviors right.

476
00:28:53,400 --> 00:28:56,000
Speaker 2: Your own behaviors and your own baseline, you'll love this boss.

477
00:28:56,160 --> 00:29:00,000
Speaker 2: So there's a there's a there's a really important physiology

478
00:29:00,240 --> 00:29:03,120
Speaker 2: reason for heart revariability, and that is too.

479
00:29:04,040 --> 00:29:04,160
Speaker 1: Uh.

480
00:29:04,280 --> 00:29:07,640
Speaker 2: It's the it's the nervous system's way, the brain's way,

481
00:29:07,720 --> 00:29:11,160
Speaker 2: if you will. In the autonomic nervous system's way of

482
00:29:11,360 --> 00:29:15,920
Speaker 2: optimizing blood flowing to and through the heart with air

483
00:29:16,040 --> 00:29:19,640
Speaker 2: flowing to and through the lungs. And I talk about

484
00:29:19,680 --> 00:29:23,840
Speaker 2: this at length with a sort of self experimentation from

485
00:29:23,880 --> 00:29:28,280
Speaker 2: my dear friend and colleague in Stockholm hulf Anderson, who

486
00:29:28,440 --> 00:29:36,360
Speaker 2: who actually published his own data from showing the synchronization

487
00:29:37,240 --> 00:29:44,400
Speaker 2: of the heart rate variability tracings with the respiratory tracings

488
00:29:44,840 --> 00:29:50,360
Speaker 2: when breathing at a at a fixed pace as guided. Yes, yes,

489
00:29:50,840 --> 00:29:53,320
Speaker 2: and so you can you can you can say maybe

490
00:29:53,600 --> 00:29:57,600
Speaker 2: the whole thing about heart reveriability is nowhere near as important.

491
00:29:57,680 --> 00:30:00,400
Speaker 2: You may have very good heart revariability, but if it's

492
00:30:00,440 --> 00:30:04,880
Speaker 2: not synchronized with your respiratory variability, then you're not You're

493
00:30:04,960 --> 00:30:08,560
Speaker 2: not in a good physiological state. And that to me

494
00:30:08,760 --> 00:30:12,720
Speaker 2: is really interesting and and with with some with some

495
00:30:12,960 --> 00:30:18,040
Speaker 2: very rare exceptions, almost nobody's measuring that there's a device

496
00:30:18,120 --> 00:30:20,200
Speaker 2: out there that does that. I think it started in

497
00:30:20,400 --> 00:30:25,920
Speaker 2: heart heart hearts, heart mass that maybe maybe I don't

498
00:30:25,960 --> 00:30:29,320
Speaker 2: know what happened to the technology from Finland that was

499
00:30:29,680 --> 00:30:36,120
Speaker 2: showing the the overlap between the respiratory rate variability and

500
00:30:36,480 --> 00:30:39,560
Speaker 2: heart rate variability, you know, as a function of respiratory

501
00:30:39,600 --> 00:30:44,240
Speaker 2: sinus arrhythmia. But when those when those peaks coincide, that

502
00:30:44,800 --> 00:30:48,400
Speaker 2: that was a sign of complete health, and any amount

503
00:30:48,440 --> 00:30:53,040
Speaker 2: of alcohol the night before disrupts that synchrony even more,

504
00:30:53,160 --> 00:30:55,360
Speaker 2: even more than it disrupts heart rate variability.

505
00:30:56,160 --> 00:30:58,960
Speaker 3: Right, That's interesting, And look, we might come back to

506
00:30:59,040 --> 00:31:01,920
Speaker 3: that around briefing, but I do want to come back

507
00:31:01,960 --> 00:31:08,000
Speaker 3: to inflammation and the inflammatory reflex and the road of

508
00:31:08,240 --> 00:31:11,720
Speaker 3: the big star. So bring us down this pathway and

509
00:31:12,040 --> 00:31:18,760
Speaker 3: just twe then vegus nerve is playing a role or

510
00:31:19,120 --> 00:31:22,320
Speaker 3: reflective or whatever it may be in terms of inflammatory conditions,

511
00:31:22,480 --> 00:31:25,800
Speaker 3: and then we can get into the modulation stuff, which

512
00:31:25,880 --> 00:31:26,760
Speaker 3: is pretty exciting.

513
00:31:26,800 --> 00:31:28,840
Speaker 1: Shit, it's it's.

514
00:31:28,720 --> 00:31:31,680
Speaker 2: Been it's been an amazing it's been an amazing ride.

515
00:31:31,720 --> 00:31:33,920
Speaker 2: I mean, we've been working on this for twenty five years.

516
00:31:34,040 --> 00:31:36,880
Speaker 2: We can talk about it till till tomorrow morning if

517
00:31:36,920 --> 00:31:40,200
Speaker 2: you want that. We know as much about how this works,

518
00:31:41,240 --> 00:31:44,560
Speaker 2: how the vegus nerve turns off inflammation. We know as much,

519
00:31:44,680 --> 00:31:47,600
Speaker 2: probably more actually than we know about how most anti

520
00:31:47,640 --> 00:31:50,920
Speaker 2: inflammatory drugs actually work. I can Yeah, we can go

521
00:31:51,000 --> 00:31:53,760
Speaker 2: in the brain of a mouse and we can activate

522
00:31:53,840 --> 00:31:59,440
Speaker 2: a few pulsations, spikes, neural spikes using a method called

523
00:31:59,520 --> 00:32:03,520
Speaker 2: opto genetics, where you make individual neurons sensitive to a

524
00:32:03,640 --> 00:32:06,280
Speaker 2: laser light and we can shine the laser light on

525
00:32:06,400 --> 00:32:10,360
Speaker 2: those specific neurons at the origin of the brain of

526
00:32:10,440 --> 00:32:12,480
Speaker 2: the vegus nerve in the brain of a mouse, and

527
00:32:12,600 --> 00:32:16,200
Speaker 2: we can follow the electrical activity down the vegus nerve

528
00:32:16,280 --> 00:32:18,360
Speaker 2: through the neck of the mouse down into the abdomen.

529
00:32:18,800 --> 00:32:21,960
Speaker 2: We can show where the signals are converted from electrical

530
00:32:22,000 --> 00:32:25,560
Speaker 2: signals to chemical signals at a structure in the abdomen

531
00:32:25,600 --> 00:32:29,480
Speaker 2: of the mouse called the ganglia, which is a home

532
00:32:29,600 --> 00:32:33,040
Speaker 2: for nerves. So the vegus nerve ends there and it

533
00:32:33,160 --> 00:32:36,680
Speaker 2: activates another nerve down the chain. That nerve we can

534
00:32:36,760 --> 00:32:41,040
Speaker 2: show gets electrically activated and carry signals into the spleen.

535
00:32:41,520 --> 00:32:44,480
Speaker 2: We can show that inside the spleen the electrical signals

536
00:32:44,520 --> 00:32:47,680
Speaker 2: converted to another chemical one. This chemical now, the first

537
00:32:47,760 --> 00:32:53,719
Speaker 2: chemical was acetylcholine. The second chemicals norpinephrin. The nouropaephyrin activates

538
00:32:54,560 --> 00:32:58,120
Speaker 2: T cells, not all of them, but some and the

539
00:32:58,280 --> 00:33:01,640
Speaker 2: ones that express coaling as Setel transphrase, which means they

540
00:33:01,760 --> 00:33:04,800
Speaker 2: make a setyl coline. They now get turned on. And

541
00:33:04,960 --> 00:33:07,760
Speaker 2: so what you end up with is remarkable. From a

542
00:33:07,880 --> 00:33:11,720
Speaker 2: few flashes of a laser light in the brain of

543
00:33:11,760 --> 00:33:15,719
Speaker 2: a mouse, you get acetyl coline and no open ephron

544
00:33:15,840 --> 00:33:18,880
Speaker 2: cranking through the spleen to the point. And this goes

545
00:33:18,920 --> 00:33:22,480
Speaker 2: for hours, even from a few From a few, yes,

546
00:33:22,600 --> 00:33:24,960
Speaker 2: it goes for hours and hours because once these cells

547
00:33:25,040 --> 00:33:28,760
Speaker 2: downstream get turned on, they crank and they make lots

548
00:33:28,840 --> 00:33:33,080
Speaker 2: of neurotransmitters. Even though the electrical signal stops, they keep

549
00:33:33,200 --> 00:33:36,120
Speaker 2: pushing out the acetyl coline in the neuroper ephrin that

550
00:33:36,280 --> 00:33:39,320
Speaker 2: comes you get. There's so much of these neurotransmitters being

551
00:33:39,400 --> 00:33:41,920
Speaker 2: made in the spleen of a mouse you can actually

552
00:33:42,080 --> 00:33:45,080
Speaker 2: measure them coming out the splenetic vein. And it's those

553
00:33:45,240 --> 00:33:49,920
Speaker 2: neurotransmitters that slow down the inflammation in your body's white

554
00:33:49,960 --> 00:33:53,480
Speaker 2: blood cells as they pass through the spleen. And nobody

555
00:33:53,520 --> 00:33:55,520
Speaker 2: saw it as coming not when we started back in

556
00:33:55,600 --> 00:33:58,600
Speaker 2: the nineteen nineties, and even when we had worked out

557
00:33:58,880 --> 00:34:02,600
Speaker 2: all the science I just explained people still kind of were.

558
00:34:03,320 --> 00:34:06,560
Speaker 2: Scientists said Okay, well this is scientifically interesting, but doctors

559
00:34:06,600 --> 00:34:09,240
Speaker 2: were like this, how can this can't work in people?

560
00:34:09,320 --> 00:34:09,600
Speaker 2: Can it?

561
00:34:12,280 --> 00:34:15,800
Speaker 1: And now it was just so little diversion, Kevin, and

562
00:34:15,880 --> 00:34:16,640
Speaker 1: we will come back.

563
00:34:16,520 --> 00:34:21,440
Speaker 3: To this, But is this why in the study of

564
00:34:22,239 --> 00:34:24,640
Speaker 3: and I think it was in Penas in twenty fourteen

565
00:34:24,719 --> 00:34:27,960
Speaker 3: of the guys doing the vim Hoff breathing and then

566
00:34:28,719 --> 00:34:34,120
Speaker 3: and injected with an endotoxin, how they suppressed information?

567
00:34:34,280 --> 00:34:35,719
Speaker 1: Is that then was the no.

568
00:34:35,920 --> 00:34:42,280
Speaker 3: Epenephyrine basically driving that inflammatory response.

569
00:34:42,719 --> 00:34:45,000
Speaker 2: I'm impressed, Paul. We have openings in my lab if

570
00:34:45,000 --> 00:34:51,200
Speaker 2: you're looking for work in these states. That's that's a

571
00:34:51,280 --> 00:34:55,279
Speaker 2: really important point. So the simple answer is yes, that's

572
00:34:55,360 --> 00:34:59,040
Speaker 2: the answer. And the complicated answer is, and we could

573
00:34:59,080 --> 00:35:03,040
Speaker 2: talk about this a few different ways, but when fight

574
00:35:03,160 --> 00:35:09,239
Speaker 2: or flight happens, you have a measurable increase in epinephrine

575
00:35:09,239 --> 00:35:12,000
Speaker 2: and ripe and effron and depending on how long, also

576
00:35:12,480 --> 00:35:16,040
Speaker 2: glogle cortiicoids. And you can measure these things in the blood.

577
00:35:16,320 --> 00:35:18,440
Speaker 2: It's some of them, some of them are harder to

578
00:35:18,520 --> 00:35:20,640
Speaker 2: measure than others because they have short half lives. But

579
00:35:20,719 --> 00:35:23,719
Speaker 2: you can also measure the the metabolites of these things

580
00:35:23,800 --> 00:35:27,239
Speaker 2: in the urine. And so this has been studied for

581
00:35:27,320 --> 00:35:30,520
Speaker 2: a long time. I mean, I remember when I was

582
00:35:30,600 --> 00:35:34,239
Speaker 2: a post doc working at the New York Hospital and

583
00:35:34,360 --> 00:35:37,399
Speaker 2: Corno Medical Center and Rockefell University in New York City.

584
00:35:37,920 --> 00:36:12,040
Speaker 2: We used to we used to bring yeah occurs because

585
00:36:12,960 --> 00:36:17,160
Speaker 2: your white blood cells release. Back then we would we

586
00:36:17,280 --> 00:36:21,080
Speaker 2: were measuring individual cytokines like TNF and ile one. Today

587
00:36:21,160 --> 00:36:23,279
Speaker 2: we call that cytokine storm, and that's what it was

588
00:36:23,320 --> 00:36:26,040
Speaker 2: called all during COVID. But back then when we were

589
00:36:26,080 --> 00:36:28,480
Speaker 2: doing this, cytokines were new things. We were measuring them

590
00:36:28,480 --> 00:36:30,719
Speaker 2: one at a time. But that's what it was. What

591
00:36:30,880 --> 00:36:36,160
Speaker 2: we found is if we infused epinephrin or norepinephyrin into

592
00:36:36,280 --> 00:36:40,440
Speaker 2: the blood of these volunteers, they didn't get sick. So

593
00:36:40,960 --> 00:36:44,400
Speaker 2: so a chemical fight or flight, which is what that

594
00:36:44,560 --> 00:36:49,440
Speaker 2: really is, would prevent cytokine storm. And so that's what

595
00:36:49,560 --> 00:36:54,680
Speaker 2: wim Hoff is doing when when he and he and

596
00:36:54,760 --> 00:36:57,319
Speaker 2: this was proved. So I studied Whim down the hall

597
00:36:57,360 --> 00:36:59,399
Speaker 2: from here in your.

598
00:36:59,320 --> 00:37:03,680
Speaker 1: Birth actually had vim in and he was before, way before.

599
00:37:03,719 --> 00:37:06,120
Speaker 3: It was before that study was actually carried out in

600
00:37:06,120 --> 00:37:06,759
Speaker 3: two thousand and four.

601
00:37:06,840 --> 00:37:11,040
Speaker 2: So we did that study on Whim as an equals Won.

602
00:37:11,680 --> 00:37:16,120
Speaker 2: I think it was two thousand and seven before anyone,

603
00:37:16,480 --> 00:37:19,279
Speaker 2: you know, before he was famous as the iceman, and

604
00:37:19,719 --> 00:37:22,040
Speaker 2: we put him in saying gede, and I drew his

605
00:37:22,120 --> 00:37:24,319
Speaker 2: blood and put him in an exam room and shut

606
00:37:24,400 --> 00:37:26,920
Speaker 2: the door and we went and got coffee or something.

607
00:37:27,080 --> 00:37:29,439
Speaker 2: Came back two hours later and we drew his blood again,

608
00:37:30,320 --> 00:37:33,560
Speaker 2: and uh we said, okay, mister hop that's it. You know,

609
00:37:34,040 --> 00:37:35,440
Speaker 2: come back in a week and we'll see what all

610
00:37:35,480 --> 00:37:38,640
Speaker 2: these results are. He comes back in a week and

611
00:37:38,719 --> 00:37:40,520
Speaker 2: seeing ed and I looked at him. It's like, whim,

612
00:37:40,960 --> 00:37:43,880
Speaker 2: what did you do when we left? He goes. I

613
00:37:44,000 --> 00:37:53,160
Speaker 2: breathed like a motherfucker. Whose story? So he said why

614
00:37:53,520 --> 00:37:55,920
Speaker 2: and we said, because you turned off your side of

615
00:37:55,960 --> 00:37:58,719
Speaker 2: kind storm? And he said, are you going to publish me?

616
00:37:59,040 --> 00:38:01,160
Speaker 2: I said no, we're not going to publish. Why can't

617
00:38:01,160 --> 00:38:03,279
Speaker 2: you publish me? I said, because you're an equals one.

618
00:38:03,680 --> 00:38:06,759
Speaker 2: We don't have any controls. You know, what do we

619
00:38:06,800 --> 00:38:09,080
Speaker 2: have to do to publish me? Well, you should get

620
00:38:09,239 --> 00:38:11,520
Speaker 2: you know, ten or twelve people and ten or twelve

621
00:38:11,560 --> 00:38:14,800
Speaker 2: controls and do it again. And if that works, have

622
00:38:15,000 --> 00:38:19,120
Speaker 2: the trained people teach the controls to cross over and

623
00:38:19,239 --> 00:38:21,480
Speaker 2: do that. And that's the paper you read in the PNAS.

624
00:38:21,600 --> 00:38:24,880
Speaker 2: That was like five or eight years later, and on

625
00:38:25,000 --> 00:38:30,000
Speaker 2: a bunch of media events, Whim has acknowledged that what

626
00:38:30,080 --> 00:38:31,840
Speaker 2: I just told you is true, and thank me. But

627
00:38:32,160 --> 00:38:35,000
Speaker 2: I'm going to be on stage with him and Colonel

628
00:38:35,080 --> 00:38:39,840
Speaker 2: Jeff Lange at south By Southwest in March in Austin, Texas,

629
00:38:39,880 --> 00:38:42,560
Speaker 2: if anybody's in Texas. Yeah, yeah, that's.

630
00:38:43,239 --> 00:38:46,920
Speaker 3: Nice closing of the look. But so this brings it

631
00:38:47,000 --> 00:38:48,840
Speaker 3: to the point, and we will come back to the inflammation.

632
00:38:49,160 --> 00:38:53,839
Speaker 3: But that they and and it was really fascinating also

633
00:38:53,920 --> 00:38:59,080
Speaker 3: in your book that acute activation of the sympathetic nervous

634
00:38:59,080 --> 00:39:04,640
Speaker 3: system has different effects than chronic activation of the sympathetic

635
00:39:04,760 --> 00:39:05,480
Speaker 3: nervous system.

636
00:39:05,680 --> 00:39:07,880
Speaker 2: Right, absolutely, So I.

637
00:39:08,000 --> 00:39:12,799
Speaker 3: Think Kevin has huge implications overall health.

638
00:39:13,040 --> 00:39:15,319
Speaker 2: One hundred percent agree with you, Paul. It probably has

639
00:39:15,400 --> 00:39:18,440
Speaker 2: huge implications for heart revariability. It's just more difficult to

640
00:39:18,520 --> 00:39:22,040
Speaker 2: understand in the book. As you know, I split these

641
00:39:22,080 --> 00:39:25,200
Speaker 2: things into pieces, right, you know, whim hot breathing I

642
00:39:25,280 --> 00:39:28,640
Speaker 2: separated from cold exposure. Fighter flight I separated from rest

643
00:39:28,680 --> 00:39:32,480
Speaker 2: and digest acute from chronic because all these things have

644
00:39:32,600 --> 00:39:38,560
Speaker 2: different effects, you know. And so in the chronic fighter flight,

645
00:39:38,719 --> 00:39:42,920
Speaker 2: there's overwhelming evidence chronic low grade fighter flight as opposed

646
00:39:42,920 --> 00:39:47,759
Speaker 2: to this sort of massive voluntary acute fighter flight. The

647
00:39:48,160 --> 00:39:50,799
Speaker 2: holding your breath until you feel like you're gonna die,

648
00:39:51,040 --> 00:39:53,040
Speaker 2: and then take that big breath that you know that

649
00:39:53,200 --> 00:39:57,840
Speaker 2: induces a massive fighter flight. Turning the water in the

650
00:39:57,920 --> 00:40:02,520
Speaker 2: shower on a full cold or jumping in a cold bath,

651
00:40:02,840 --> 00:40:06,200
Speaker 2: that's fight or flight. It's instant. It's And tell your

652
00:40:06,360 --> 00:40:09,239
Speaker 2: listeners not to combine the breathing with the ice bath

653
00:40:09,360 --> 00:40:10,279
Speaker 2: unless I.

654
00:40:10,640 --> 00:40:11,480
Speaker 1: Always do that.

655
00:40:11,920 --> 00:40:15,600
Speaker 3: And I actually know somebody was in a session that

656
00:40:15,640 --> 00:40:17,040
Speaker 3: I was doing and I was telling them that, and

657
00:40:17,200 --> 00:40:19,320
Speaker 3: she came up to me after she was really interested

658
00:40:19,320 --> 00:40:22,800
Speaker 3: in her her boyfriend had actually died. Yeah, no, you

659
00:40:22,880 --> 00:40:26,520
Speaker 3: can't trying to do that, that that vim Hoff breathol

660
00:40:26,600 --> 00:40:28,400
Speaker 3: training and then trying to go onto what because you

661
00:40:28,440 --> 00:40:29,200
Speaker 3: can pass.

662
00:40:28,960 --> 00:40:33,680
Speaker 2: Out right, yeah, hyperventilate, Yeah, you hyperventilate, you lose the

663
00:40:33,840 --> 00:40:35,600
Speaker 2: urge to breathe. Then the cold water is to some

664
00:40:35,680 --> 00:40:37,840
Speaker 2: people faint. If you faint, don't have a urge to breathe,

665
00:40:37,840 --> 00:40:38,560
Speaker 2: it's a disaster.

666
00:40:39,080 --> 00:40:41,799
Speaker 1: I mean I do so, Kevin, sorry, can I go back?

667
00:40:41,840 --> 00:40:44,160
Speaker 3: So the with the vim Hoff style breathing with the

668
00:40:44,200 --> 00:40:49,600
Speaker 3: controlled hyperventilation and then the breath hold, So the breath

669
00:40:49,680 --> 00:40:54,040
Speaker 3: hold it gives an extra stimulus to the sympathetic nervous system.

670
00:40:54,320 --> 00:40:57,279
Speaker 2: Yeah, the hyperventilation, you're just blowing off CEO two. You

671
00:40:57,440 --> 00:41:00,720
Speaker 2: get the tingling in your lips and and and that's

672
00:41:00,920 --> 00:41:04,480
Speaker 2: that's that's very well known. And and it's the it's

673
00:41:04,560 --> 00:41:08,080
Speaker 2: the hold. It's the breath holding that induces the fight

674
00:41:08,160 --> 00:41:08,520
Speaker 2: or flight.

675
00:41:09,480 --> 00:41:13,239
Speaker 3: That's interesting, okay, because I thought the hyperventilation in and

676
00:41:13,360 --> 00:41:15,959
Speaker 3: of itself would activate the fighter flight.

677
00:41:17,080 --> 00:41:19,960
Speaker 2: It might, it might to a degree, But the hyperventilation,

678
00:41:20,160 --> 00:41:22,600
Speaker 2: what it's really doing is letting you hold your breath longer.

679
00:41:23,040 --> 00:41:24,680
Speaker 3: And so if you're going off seal to you and

680
00:41:24,800 --> 00:41:27,400
Speaker 3: it's not low oxygen and actually when people do it,

681
00:41:27,520 --> 00:41:29,040
Speaker 3: if you haven't done any vim.

682
00:41:28,920 --> 00:41:31,439
Speaker 1: Half stuff, and you know, you get to a third

683
00:41:31,520 --> 00:41:34,319
Speaker 1: and fourth round and and you know.

684
00:41:34,560 --> 00:41:37,520
Speaker 3: The breath hold is you can actually expel earlier out

685
00:41:37,560 --> 00:41:40,080
Speaker 3: of your lungs and not breathe, and you can get

686
00:41:40,160 --> 00:41:41,279
Speaker 3: up to it like two.

687
00:41:41,520 --> 00:41:44,160
Speaker 1: I've done over two minutes. I've seen somebody at four minutes.

688
00:41:44,360 --> 00:41:46,800
Speaker 2: I've done. I've done I've done three forty five. And

689
00:41:46,880 --> 00:41:49,400
Speaker 2: I'm not wow and I'm not a rage, but I

690
00:41:49,520 --> 00:41:51,560
Speaker 2: do it lying down on the floor of my gym.

691
00:41:52,480 --> 00:41:54,719
Speaker 1: Yeah yeah, yeah, yeah, yeah yeah.

692
00:41:55,600 --> 00:41:58,280
Speaker 3: And I think there are some Actually this is another

693
00:41:58,320 --> 00:42:00,640
Speaker 3: diversion we probably don't need to go down, but that

694
00:42:00,880 --> 00:42:04,560
Speaker 3: acute hypoxia in the Brian and the harmetic effect and

695
00:42:04,640 --> 00:42:07,279
Speaker 3: some of the benefits as well as well as hypercoptie

696
00:42:07,280 --> 00:42:10,280
Speaker 3: as well. There's so much interesting shit around the breath

697
00:42:10,960 --> 00:42:15,880
Speaker 3: and how it can can actually modulate our physiology.

698
00:42:15,360 --> 00:42:18,480
Speaker 2: Right one hundred percent. I mean Andrew Huberman's podcast he

699
00:42:18,560 --> 00:42:21,640
Speaker 2: talked about this quite a bit. He talks about when

700
00:42:21,760 --> 00:42:28,239
Speaker 2: you take two breaths in like like like sniffs and

701
00:42:28,440 --> 00:42:32,799
Speaker 2: holds the physiological side and then maybe that takes two

702
00:42:32,920 --> 00:42:35,680
Speaker 2: or three seconds, and then hold it for a little

703
00:42:35,680 --> 00:42:40,120
Speaker 2: bit and then five or six or seven count on

704
00:42:40,600 --> 00:42:44,240
Speaker 2: an exhale through first lips. You know, now you're breathing

705
00:42:44,239 --> 00:42:46,920
Speaker 2: at a respiratory at six or something like that. And

706
00:42:47,440 --> 00:42:49,759
Speaker 2: when he walks through how that works, the first thing

707
00:42:49,840 --> 00:42:52,640
Speaker 2: he points out is that when you do that physiological side,

708
00:42:53,120 --> 00:42:57,560
Speaker 2: you're expanding your lung volume and that's active activating pressure

709
00:42:57,640 --> 00:43:01,439
Speaker 2: sensors in your lungs, which sends signals up your vegus nerve.

710
00:43:01,520 --> 00:43:06,600
Speaker 2: So right away you quote stimulated your vegus nerve. But

711
00:43:07,080 --> 00:43:10,120
Speaker 2: it's a few fibers in your lung that go up

712
00:43:10,200 --> 00:43:15,600
Speaker 2: to your brain. That's totally different than electrically stimulating, if

713
00:43:15,640 --> 00:43:18,479
Speaker 2: you will, the fibers that go down from your brain

714
00:43:18,560 --> 00:43:22,000
Speaker 2: to your heart or your immune system. Now, when you

715
00:43:22,640 --> 00:43:27,239
Speaker 2: stimulate those incoming fibers with the physiological sniffs, they activate

716
00:43:27,640 --> 00:43:30,920
Speaker 2: the locus ceruleus and the nucleus tractus solitarius. The locus

717
00:43:31,000 --> 00:43:33,480
Speaker 2: ceruleus is the origin of the fight or flight response.

718
00:43:34,000 --> 00:43:38,839
Speaker 2: So you have this signal coming in through your vegas nerve,

719
00:43:38,960 --> 00:43:45,080
Speaker 2: which is activating signals going out your sympathetic nerves. So

720
00:43:45,400 --> 00:43:50,440
Speaker 2: it's complicated. And and you know Charles Sherrington who has

721
00:43:50,680 --> 00:43:55,279
Speaker 2: won the Nobel Prize for being essentially the father of neuroscience.

722
00:43:55,360 --> 00:44:00,560
Speaker 2: With modern neuroscience with Ramoni Cahl, Sherrington knew everything. He

723
00:44:00,920 --> 00:44:05,040
Speaker 2: gave us the roadmap to understand everything about reflexes, and

724
00:44:05,600 --> 00:44:09,840
Speaker 2: his very famous treatise, The Integrative Action of the Nervous System,

725
00:44:09,880 --> 00:44:12,000
Speaker 2: he talks about the fact that you have to understand

726
00:44:12,040 --> 00:44:15,239
Speaker 2: a simple reflex signal in Everything starts with that in

727
00:44:16,600 --> 00:44:20,400
Speaker 2: simp uh, some sort of connection or inter neuron and

728
00:44:20,520 --> 00:44:23,240
Speaker 2: a signal out. And then he said, you can assemble

729
00:44:23,320 --> 00:44:26,440
Speaker 2: reflexes together and you can build a complex nervous system.

730
00:44:26,800 --> 00:44:29,719
Speaker 2: And then he said, having said all that, there's no

731
00:44:29,840 --> 00:44:32,719
Speaker 2: such thing as a simple reflex, because all the nerves

732
00:44:32,760 --> 00:44:34,759
Speaker 2: in your body are connected to all the other nerves

733
00:44:34,800 --> 00:44:38,000
Speaker 2: in your body one way or another, which is fascinating.

734
00:44:39,120 --> 00:44:43,719
Speaker 2: It's fascinating. So look, I understand why people say, do this,

735
00:44:43,840 --> 00:44:46,680
Speaker 2: that and the other thing. Stimulate your vegus nerve live along,

736
00:44:46,760 --> 00:44:50,440
Speaker 2: healthy life, and and and and and it's fine for

737
00:44:50,520 --> 00:44:54,040
Speaker 2: those people who who are you know, are under medical

738
00:44:54,080 --> 00:44:58,560
Speaker 2: supervision and enjoy self experimentation and and can afford to

739
00:44:58,680 --> 00:45:01,640
Speaker 2: try different devices. And that's all find and good. Where

740
00:45:01,800 --> 00:45:06,480
Speaker 2: where I where I say let the buyer beware is

741
00:45:06,560 --> 00:45:10,040
Speaker 2: when people are selling stuff, you know, buy this to

742
00:45:10,160 --> 00:45:12,239
Speaker 2: do this for your vegas nern Now I'm like, oh,

743
00:45:12,560 --> 00:45:16,799
Speaker 2: show me the data, where's your where's your clasical trial?

744
00:45:17,320 --> 00:45:20,000
Speaker 3: Yeah, and I bought one. It just start of interest

745
00:45:20,080 --> 00:45:22,520
Speaker 3: because of the of the area that I work in.

746
00:45:23,120 --> 00:45:24,840
Speaker 3: I think it was the greatest load of horseship, that

747
00:45:25,000 --> 00:45:26,680
Speaker 3: device that goes around your neck.

748
00:45:26,920 --> 00:45:30,520
Speaker 1: Right. So, but but we we will get into that.

749
00:45:30,719 --> 00:45:32,960
Speaker 3: I do want to bring the conversation now back to

750
00:45:33,480 --> 00:45:37,960
Speaker 3: inflammation and that inflammatory reflex, and let's talk about the

751
00:45:38,200 --> 00:45:42,359
Speaker 3: role and in certain conditions, and how the vegus nerve

752
00:45:42,480 --> 00:45:45,480
Speaker 3: and manipulation of the vegas nerve can be helpful.

753
00:45:46,719 --> 00:45:49,120
Speaker 2: We have, as I started to say before, we have

754
00:45:49,440 --> 00:45:54,239
Speaker 2: we have exquisite knowledge about the fibers that travel from

755
00:45:54,280 --> 00:45:56,239
Speaker 2: the brain to this plane to turn off side of

756
00:45:56,320 --> 00:46:00,400
Speaker 2: kind storm and in animal models of arthritis and lamatory

757
00:46:00,440 --> 00:46:06,920
Speaker 2: Biel disease, multiple sclerosis, diabetes, metabolic syndrome, obesity, stroke, and

758
00:46:07,840 --> 00:46:11,160
Speaker 2: I'm probably leaving out a couple all of these conditions,

759
00:46:11,600 --> 00:46:16,400
Speaker 2: there is data that activating that inflammatory reflex, those vagus

760
00:46:16,520 --> 00:46:22,080
Speaker 2: nerve fibers that stop inflammation. Activating that reflex gives a

761
00:46:22,520 --> 00:46:26,839
Speaker 2: significant advantage to the animal, either its survival or its

762
00:46:26,960 --> 00:46:29,839
Speaker 2: ability to fight off that disease because it slows down

763
00:46:30,239 --> 00:46:30,960
Speaker 2: the inflammation.

764
00:46:31,480 --> 00:46:35,120
Speaker 3: We also, now, does this disease have to be have

765
00:46:35,320 --> 00:46:37,440
Speaker 3: to have an autoimmune component?

766
00:46:37,960 --> 00:46:40,880
Speaker 2: Now we can note we can do it with animals

767
00:46:40,920 --> 00:46:45,640
Speaker 2: with sepsis and animals with cytokine storm from endotypesmetry. Yeah,

768
00:46:45,680 --> 00:46:48,560
Speaker 2: anything that activates what we call the innate immune system,

769
00:46:49,080 --> 00:46:54,360
Speaker 2: the cytokine produced by white blood cells like monocytes and macrophages.

770
00:46:54,920 --> 00:46:57,239
Speaker 2: And none of this wouldn't I wouldn't be on your

771
00:46:57,239 --> 00:46:59,200
Speaker 2: show right now. And I wouldn't have written the book

772
00:46:59,600 --> 00:47:02,720
Speaker 2: if it if this didn't all apply to human beings.

773
00:47:02,800 --> 00:47:05,759
Speaker 2: But it does. I mean, we've done clinical trials. The

774
00:47:05,880 --> 00:47:08,320
Speaker 2: company that did all the clinical trials in this is

775
00:47:08,360 --> 00:47:11,840
Speaker 2: a company I founded called set Point Medical. I co

776
00:47:12,040 --> 00:47:15,359
Speaker 2: founded it with my friend and colleague Shah Warren back

777
00:47:15,400 --> 00:47:18,279
Speaker 2: in two thousand and seven. And set Point Medical is

778
00:47:18,320 --> 00:47:22,920
Speaker 2: a California company now that has FDA approval because they

779
00:47:23,320 --> 00:47:27,480
Speaker 2: showed in a clinical trial of patients with severe rheumatoid

780
00:47:27,600 --> 00:47:32,040
Speaker 2: arthritis that implanting a device the size of a multi

781
00:47:32,160 --> 00:47:36,160
Speaker 2: vitamin on the left vegas nerve at about the level

782
00:47:36,200 --> 00:47:39,080
Speaker 2: of the Adams Apple and turning that device on for

783
00:47:39,280 --> 00:47:44,400
Speaker 2: one minute a day, that that is a therapy that

784
00:47:44,600 --> 00:47:49,160
Speaker 2: allowed patients with severe rheumatoid arthritis to enjoy significant improvement

785
00:47:49,239 --> 00:47:53,200
Speaker 2: in their symptoms eighty percent of the patients within one year. Now, Paul,

786
00:47:53,320 --> 00:47:58,319
Speaker 2: these patients were not getting improvement from all of these

787
00:47:58,480 --> 00:48:01,280
Speaker 2: powerful immunosuppressive drugs that are out there.

788
00:48:02,120 --> 00:48:04,200
Speaker 1: And those immune like drugs.

789
00:48:04,480 --> 00:48:06,680
Speaker 3: I think this is the thing for people to understand

790
00:48:07,080 --> 00:48:11,000
Speaker 3: drugs are not super targeted the way people think that

791
00:48:11,120 --> 00:48:14,239
Speaker 3: they are. Right, if you're taking an immuno suppressant to

792
00:48:14,360 --> 00:48:17,160
Speaker 3: try to manage your arthritis that is going to have

793
00:48:17,640 --> 00:48:19,440
Speaker 3: widespread knock on effects.

794
00:48:19,920 --> 00:48:23,920
Speaker 2: They have the most serious side effects that the FDA.

795
00:48:25,320 --> 00:48:25,920
Speaker 1: Will approve.

796
00:48:26,120 --> 00:48:29,160
Speaker 2: And because the side effects are so serious, these most

797
00:48:29,200 --> 00:48:31,440
Speaker 2: of these drugs, if not all of them for RA

798
00:48:32,120 --> 00:48:36,200
Speaker 2: have a black box warning, which means serious side effects

799
00:48:36,239 --> 00:48:42,040
Speaker 2: include things like cancer, sepsis, tuberculosis. So that's the thing.

800
00:48:42,480 --> 00:48:44,600
Speaker 2: There are people who've looked at this trial and said, oh,

801
00:48:44,640 --> 00:48:46,960
Speaker 2: I wish the effects size was bigger, And I'm like, well,

802
00:48:47,000 --> 00:48:49,680
Speaker 2: you haven't talked to the patients. Because the patients who

803
00:48:49,719 --> 00:48:52,600
Speaker 2: are having the effects from this vegas nerve stimulator, their

804
00:48:52,680 --> 00:48:55,399
Speaker 2: effects size before the vegas nerve stimulator was zero.

805
00:48:56,760 --> 00:48:57,800
Speaker 1: Yeah, exactly.

806
00:48:58,320 --> 00:49:02,279
Speaker 2: So that's the future. Oh, this this device goes in

807
00:49:02,800 --> 00:49:05,440
Speaker 2: through about a one inch incision. It's a same day surgery.

808
00:49:05,520 --> 00:49:07,400
Speaker 2: You're going in the morning, at home in the afternoon.

809
00:49:08,120 --> 00:49:10,600
Speaker 2: We know that it's not immunal suppressive. We have forty

810
00:49:10,719 --> 00:49:14,880
Speaker 2: years experience using other kinds of vegas nerve stimulation for

811
00:49:15,080 --> 00:49:19,840
Speaker 2: depression and epilepsy. We know that it's not going to

812
00:49:19,880 --> 00:49:22,880
Speaker 2: be a recurring cost because the battery in the device

813
00:49:23,520 --> 00:49:27,120
Speaker 2: is recharged with a collar the patient puts on like

814
00:49:27,160 --> 00:49:31,520
Speaker 2: a collar once a week to charge charges through the skin.

815
00:49:32,280 --> 00:49:36,719
Speaker 2: We know that on a cost basis that if you

816
00:49:36,760 --> 00:49:40,040
Speaker 2: look in the United States, the biologics for ra cost

817
00:49:40,160 --> 00:49:43,160
Speaker 2: upwards of fifty thousand dollars a year. So that means

818
00:49:43,200 --> 00:49:46,680
Speaker 2: for a fifty thousand dollars surgery that within two years,

819
00:49:47,000 --> 00:49:51,160
Speaker 2: everybody's saving money, the patients, the insurance companies, the hospitals, everybody.

820
00:49:52,120 --> 00:49:54,839
Speaker 2: And we know that the drugs that people are using

821
00:49:54,880 --> 00:49:58,960
Speaker 2: today only work about half the time. And we know

822
00:49:59,400 --> 00:50:05,200
Speaker 2: that the set Points clinical trial, which needed about two

823
00:50:05,280 --> 00:50:08,479
Speaker 2: hundred and forty two patients, Guess how many people tried

824
00:50:08,480 --> 00:50:09,040
Speaker 2: to sign up.

825
00:50:10,200 --> 00:50:13,640
Speaker 1: I would imagine there's dogs and to sign up.

826
00:50:13,719 --> 00:50:19,640
Speaker 2: Thirty thousand, wow, thirty thousand people. Thirty thousand people, many

827
00:50:19,680 --> 00:50:22,480
Speaker 2: of them. If you asked the doctors of those patients,

828
00:50:22,560 --> 00:50:25,880
Speaker 2: the doctors like, oh, my patients are fine. Well, thirty

829
00:50:25,960 --> 00:50:28,879
Speaker 2: thousand patients tried to sign up for the clinical trial

830
00:50:28,920 --> 00:50:30,360
Speaker 2: of two hundred and forty two pass.

831
00:50:30,640 --> 00:50:30,759
Speaker 3: Now.

832
00:50:30,840 --> 00:50:33,680
Speaker 2: All of this work was led by the chief medical

833
00:50:33,760 --> 00:50:38,560
Speaker 2: officer at set Point, David Chernoff, and by a real

834
00:50:38,640 --> 00:50:41,800
Speaker 2: world class rooumatologist out of Arizona named John Tessa and

835
00:50:42,719 --> 00:50:47,360
Speaker 2: the papers published its open access for no paywall in

836
00:50:47,440 --> 00:50:50,640
Speaker 2: a very reputable journal called Nature Medicine, one of the

837
00:50:50,719 --> 00:50:53,719
Speaker 2: highest impact journals in your world. So that paper's out

838
00:50:53,760 --> 00:50:56,279
Speaker 2: there for any of your listeners with Ara who want to.

839
00:50:56,840 --> 00:51:01,600
Speaker 1: Read it, and my book keeper, I'll put it in

840
00:51:01,680 --> 00:51:07,480
Speaker 1: the show notes. And so then that what in the

841
00:51:07,560 --> 00:51:10,120
Speaker 1: year view, Kevin. Does that open the door to you?

842
00:51:11,160 --> 00:51:14,759
Speaker 2: It opens, Yeah, it opens the door to a new

843
00:51:14,840 --> 00:51:17,920
Speaker 2: world that is already happening. In the United States. We've

844
00:51:17,920 --> 00:51:22,399
Speaker 2: implanted down the hall from me. We enrolled the first

845
00:51:22,440 --> 00:51:25,160
Speaker 2: two patients in the United States under the FDA approval,

846
00:51:25,200 --> 00:51:28,600
Speaker 2: and that was in August or September, and since then,

847
00:51:28,640 --> 00:51:31,200
Speaker 2: I think we've implanted twelve more. I think they have

848
00:51:31,360 --> 00:51:34,360
Speaker 2: now the company has now implanted patients in Chicago and

849
00:51:34,440 --> 00:51:36,800
Speaker 2: a couple of other US centers. And this is just

850
00:51:36,880 --> 00:51:40,760
Speaker 2: the beginning poll. For a number of reasons, First, it works, Second,

851
00:51:40,840 --> 00:51:44,680
Speaker 2: patients want it. Third, it's cost effective. Fourth, it's safe.

852
00:51:45,280 --> 00:51:48,480
Speaker 2: And I think you're going to see because of the

853
00:51:48,520 --> 00:51:50,960
Speaker 2: way regulations work, it's going to be a year or

854
00:51:51,000 --> 00:51:54,640
Speaker 2: two in just our a patients who are not responding

855
00:51:54,680 --> 00:51:57,520
Speaker 2: to available therapies. But I think You're also going to

856
00:51:57,560 --> 00:52:01,880
Speaker 2: see very soon more clinical try and hopefully FDA approvals

857
00:52:02,239 --> 00:52:06,319
Speaker 2: for conditions like inflammatory bio disease, Crohn's disease, all sort

858
00:52:06,320 --> 00:52:08,960
Speaker 2: of colitis, and multiple sclerosis. I think will be the

859
00:52:09,000 --> 00:52:11,200
Speaker 2: ones that will come soonest, because we've already seen some

860
00:52:11,640 --> 00:52:13,040
Speaker 2: really interesting data on those.

861
00:52:13,400 --> 00:52:15,200
Speaker 3: Yeah, that was going to be My question is what

862
00:52:15,680 --> 00:52:18,000
Speaker 3: cops do you think are going to be off the

863
00:52:18,160 --> 00:52:18,880
Speaker 3: rank next?

864
00:52:20,040 --> 00:52:21,799
Speaker 1: And you've just mentioned.

865
00:52:21,480 --> 00:52:25,239
Speaker 2: Those, well, you know with for inflammatory biol disease, there

866
00:52:25,320 --> 00:52:29,520
Speaker 2: are published studies. Set Point, and I actually helped them

867
00:52:29,760 --> 00:52:33,200
Speaker 2: on a number of those studies, has published that in

868
00:52:33,400 --> 00:52:36,680
Speaker 2: open label pilot studies, which is how you have to start.

869
00:52:36,760 --> 00:52:40,279
Speaker 2: You can't do everything. You start with twenty people open

870
00:52:40,400 --> 00:52:42,719
Speaker 2: label and then you go to a large randomized clinical trial,

871
00:52:42,760 --> 00:52:45,439
Speaker 2: which is what happened for RA. But yes, we've seen

872
00:52:45,520 --> 00:52:49,359
Speaker 2: the open label trials for IBD work in the lab.

873
00:52:50,160 --> 00:52:54,800
Speaker 2: We've published that the multiple sclerosis mouse model works beautifully,

874
00:52:55,520 --> 00:52:58,560
Speaker 2: and so I think set Point will very soon be

875
00:52:58,680 --> 00:53:03,080
Speaker 2: doing clinical trials on multiple sclerosis patients. I think there

876
00:53:03,120 --> 00:53:06,120
Speaker 2: are clinical studies going on out there for conditions like

877
00:53:06,200 --> 00:53:10,839
Speaker 2: obesity and metabolic syndrome and diabetes, and there's always been

878
00:53:10,920 --> 00:53:15,880
Speaker 2: interest in is this vagus nerve connection between the brain,

879
00:53:16,160 --> 00:53:19,320
Speaker 2: the immune system and the gut. Is it's somehow involved

880
00:53:19,360 --> 00:53:22,120
Speaker 2: in conditions like Alzheimer's, in Parkinson's, And.

881
00:53:22,680 --> 00:53:29,000
Speaker 3: There's a very interesting lines of research Parkinson's first, right,

882
00:53:29,080 --> 00:53:31,920
Speaker 3: that seems to be originating in the gut. Now some

883
00:53:31,960 --> 00:53:36,000
Speaker 3: stuff about Alzheimer's as well. And you know that whole

884
00:53:36,120 --> 00:53:40,080
Speaker 3: gut bringing immune axis is a fascinating word, isn't it.

885
00:53:40,440 --> 00:53:42,080
Speaker 2: Well, if you want to if you want to get

886
00:53:42,160 --> 00:53:44,319
Speaker 2: a if you want to get a smile on your face,

887
00:53:44,400 --> 00:53:46,279
Speaker 2: go back you dig it out of the dig it

888
00:53:46,360 --> 00:53:49,320
Speaker 2: out of the out of the literature and find doctor

889
00:53:49,400 --> 00:53:55,440
Speaker 2: Parkinson's description of Parkinson's disease. And he said, he said

890
00:53:56,160 --> 00:53:59,000
Speaker 2: that the early signs and symptoms are things like constipation

891
00:53:59,200 --> 00:53:59,920
Speaker 2: involved this far.

892
00:54:00,719 --> 00:54:05,120
Speaker 1: There you go, There you go, Jesus, I think forgot

893
00:54:05,160 --> 00:54:06,800
Speaker 1: about for decades.

894
00:54:06,600 --> 00:54:09,160
Speaker 2: Yep, yep, until and now they're now they proved it

895
00:54:09,239 --> 00:54:14,040
Speaker 2: in animals. The clinical data are accumulating. You know that

896
00:54:14,520 --> 00:54:16,880
Speaker 2: for years when I was training to be a surgeon,

897
00:54:17,760 --> 00:54:22,719
Speaker 2: a routine operation for peptic ulcer disease was to cut

898
00:54:22,800 --> 00:54:27,320
Speaker 2: the vegas nerves to the stomach because that controls gastric

899
00:54:27,400 --> 00:54:29,920
Speaker 2: acid release, and so you would cut the vegas nerves

900
00:54:31,480 --> 00:54:34,319
Speaker 2: and the acid would go down and the patient would

901
00:54:34,320 --> 00:54:37,200
Speaker 2: feel better. That was before some Australians got the Nobel

902
00:54:37,280 --> 00:54:40,400
Speaker 2: Prize for proving peptic ulcer disease wasn't caused by acid,

903
00:54:40,440 --> 00:54:45,640
Speaker 2: it was caused by bacteria. Yeah, So that the reality

904
00:54:45,840 --> 00:54:49,400
Speaker 2: is that that there are there are thousands of people

905
00:54:49,640 --> 00:54:53,319
Speaker 2: on the planet Earth that have had their vegas nerves

906
00:54:53,360 --> 00:54:55,760
Speaker 2: cut below the diaphragm. Now I said it was lethal.

907
00:54:55,840 --> 00:54:57,719
Speaker 2: It's lethal if you cut it up high in the neck,

908
00:54:58,440 --> 00:55:01,560
Speaker 2: not down low. And so that gave an opportunity for

909
00:55:01,680 --> 00:55:04,080
Speaker 2: people recently in the last few years to go back

910
00:55:04,120 --> 00:55:07,759
Speaker 2: through medical records and ask a very simple question, did

911
00:55:07,840 --> 00:55:10,840
Speaker 2: your risk of Parkinson's go down if you had your

912
00:55:10,920 --> 00:55:14,240
Speaker 2: vagus nerves cut for peptic ulcer disease? And the answer

913
00:55:14,280 --> 00:55:14,560
Speaker 2: is yes.

914
00:55:15,440 --> 00:55:22,160
Speaker 1: Wow, Really, that's so cool? Does it? And you may

915
00:55:22,280 --> 00:55:23,799
Speaker 1: not know the answer to that question.

916
00:55:23,960 --> 00:55:27,480
Speaker 4: If you don't, then speculate, but does cutting it somewhere

917
00:55:27,640 --> 00:55:32,800
Speaker 4: somewhere dying, whether it's lung's, heart, spleen, whatever, does cutting

918
00:55:32,840 --> 00:55:36,200
Speaker 4: it there have knock on effects or is it just

919
00:55:36,400 --> 00:55:37,960
Speaker 4: purely or localized effect.

920
00:55:38,400 --> 00:55:41,719
Speaker 3: I'm thinking of because because it's two way. Yes, if

921
00:55:41,719 --> 00:55:45,200
Speaker 3: you cut it, you can you can stop something stimulating.

922
00:55:44,640 --> 00:55:45,479
Speaker 1: Something you don't want.

923
00:55:45,640 --> 00:55:51,600
Speaker 3: But is there any drawbacks or knock on effects on

924
00:55:51,680 --> 00:55:56,400
Speaker 3: intended consequences going back up the team, Well, we.

925
00:55:56,560 --> 00:56:03,080
Speaker 2: Know in animal experiments, we know that the signals are

926
00:56:03,080 --> 00:56:05,600
Speaker 2: traveling in both directions from the gut to the brain

927
00:56:05,680 --> 00:56:08,439
Speaker 2: and from the brain to the gut. And we could

928
00:56:08,480 --> 00:56:13,879
Speaker 2: talk about I was going to talk about brain development. Well,

929
00:56:14,120 --> 00:56:17,040
Speaker 2: can I give you two stories that are answers? Okay,

930
00:56:17,600 --> 00:56:19,400
Speaker 2: the first ones in mice and the second ones in

931
00:56:19,480 --> 00:56:23,400
Speaker 2: mice and people. So in mice, if you raise a

932
00:56:23,480 --> 00:56:26,239
Speaker 2: mouse in a germ free environment, so it doesn't have

933
00:56:26,640 --> 00:56:31,239
Speaker 2: an intestinal microbiome basically, or it may have a few bacteria,

934
00:56:31,320 --> 00:56:34,520
Speaker 2: but it's not a wild type microbiome full of bacteria

935
00:56:34,719 --> 00:56:37,160
Speaker 2: like will like would be found in the in the

936
00:56:37,200 --> 00:56:39,520
Speaker 2: wild germ free environment, like the boy in the bubble.

937
00:56:39,560 --> 00:56:42,640
Speaker 2: These are mice. If you let those mice live in

938
00:56:42,719 --> 00:56:46,600
Speaker 2: that germ free environment with no gut microbiome, their brains

939
00:56:46,640 --> 00:56:52,359
Speaker 2: develop abnormally. Wow, And they they don't have they don't

940
00:56:52,400 --> 00:56:55,920
Speaker 2: have good coordination, they fall off the rhodo rod, they

941
00:56:55,960 --> 00:56:59,240
Speaker 2: don't have good learning, and memory. They don't have normal

942
00:56:59,360 --> 00:57:03,959
Speaker 2: social behavior. It's not a subtle thing. It's a big deal.

943
00:57:04,520 --> 00:57:08,280
Speaker 2: If you then take those mice before it gets before

944
00:57:08,320 --> 00:57:11,000
Speaker 2: it gets to be too long. Early on, if you

945
00:57:11,160 --> 00:57:16,480
Speaker 2: intervene and put the microbiome from a normal mouse into

946
00:57:16,600 --> 00:57:20,800
Speaker 2: the germ free mouse and wait a week, the brain

947
00:57:20,880 --> 00:57:24,600
Speaker 2: will start to develop normally again, but not if you

948
00:57:24,680 --> 00:57:25,600
Speaker 2: cut the vegas nerve.

949
00:57:27,240 --> 00:57:28,920
Speaker 1: There you go, there you go.

950
00:57:29,680 --> 00:57:35,120
Speaker 2: So so. Thinking along those kinds of lines, people wondered, well,

951
00:57:35,520 --> 00:57:40,200
Speaker 2: the golps that we inject to lose weight or control glucose,

952
00:57:40,720 --> 00:57:43,800
Speaker 2: what happens there? Well, it turns out that when you

953
00:57:43,920 --> 00:57:47,880
Speaker 2: inject GOLP in a mouse or a person, you have

954
00:57:48,160 --> 00:57:53,040
Speaker 2: decreased glucose, increased insulin sensitivity, and decreased body weight and

955
00:57:53,120 --> 00:57:56,840
Speaker 2: decrease food intake. That's why people take it. If you

956
00:57:56,920 --> 00:58:01,040
Speaker 2: cut the vegas nerve, it doesn't work. Really wow, So

957
00:58:01,640 --> 00:58:05,640
Speaker 2: the glps are sending signals up the vegas nerve, very

958
00:58:05,720 --> 00:58:09,040
Speaker 2: carefully done studies in mice. A surgeon in the UK

959
00:58:09,280 --> 00:58:10,880
Speaker 2: read this in mice that I've been to do that

960
00:58:10,960 --> 00:58:15,560
Speaker 2: in people. So he had cancer patients who were going

961
00:58:15,640 --> 00:58:18,120
Speaker 2: to have their stomachs operated on and had to have

962
00:58:18,280 --> 00:58:21,160
Speaker 2: their vegas nerves cut for part of the stomach surgery

963
00:58:21,200 --> 00:58:24,400
Speaker 2: for their gastric cancer. So he gave them golps as

964
00:58:24,480 --> 00:58:27,360
Speaker 2: a controlled experiment, and they had the normal GLP response.

965
00:58:27,400 --> 00:58:30,440
Speaker 2: I don't feel so hungry, Mike. Glucose went down, My

966
00:58:30,560 --> 00:58:34,000
Speaker 2: insulin sensitivity got better. Then he did the surgery and

967
00:58:34,080 --> 00:58:35,880
Speaker 2: repeated the golps. It didn't work.

968
00:58:37,760 --> 00:58:38,720
Speaker 1: Hit the bad.

969
00:58:41,480 --> 00:58:44,680
Speaker 2: Wild that is bunkers.

970
00:58:44,720 --> 00:58:47,080
Speaker 1: So it's mediated through vegas nerve activity.

971
00:58:47,440 --> 00:58:50,200
Speaker 2: Yeah, and once again, Paul, it's two hundred thousand vegas

972
00:58:50,240 --> 00:58:54,480
Speaker 2: nerve fibers. One hundred and sixty thousand of them are sensory,

973
00:58:55,200 --> 00:58:58,560
Speaker 2: forty thousand or motor. So when someone talks about well,

974
00:58:58,600 --> 00:59:02,640
Speaker 2: I'm humming, so I'm still simulating my vegus nerve. I

975
00:59:02,760 --> 00:59:06,320
Speaker 2: try to be polite and I'm like, yes, when you hum,

976
00:59:07,120 --> 00:59:10,040
Speaker 2: you have taken some kind of breath. You have stimulated

977
00:59:10,080 --> 00:59:12,360
Speaker 2: that part of your vegas nerve with the pressure in

978
00:59:12,400 --> 00:59:16,040
Speaker 2: your lungs, and when you exhale, that's done other kind

979
00:59:16,080 --> 00:59:18,600
Speaker 2: of breath. So you've stimulated that part of the vegas nerve.

980
00:59:19,080 --> 00:59:22,480
Speaker 2: And because you're humming and a branch is some branches

981
00:59:22,520 --> 00:59:25,040
Speaker 2: of the vegas nerve, go to your vocal cords that

982
00:59:25,200 --> 00:59:29,960
Speaker 2: control the the you know, your soundbox, your larynx. Yes,

983
00:59:30,080 --> 00:59:33,720
Speaker 2: you've stimulated that, But does that mean you've stimulated the

984
00:59:33,840 --> 00:59:36,400
Speaker 2: vegas dear to your pancreas. Does that mean you've stimulated

985
00:59:36,440 --> 00:59:39,560
Speaker 2: the vegas irve to your spleen? No, I don't know.

986
00:59:39,960 --> 00:59:43,360
Speaker 2: I mean you can walk into gum, so different different

987
00:59:43,480 --> 00:59:48,080
Speaker 2: fibers do different things, and your your brain is complicated

988
00:59:48,640 --> 00:59:51,440
Speaker 2: and somehow it coordinates it all. And I think it's

989
00:59:51,520 --> 00:59:56,000
Speaker 2: the inability to understand for all of us how sophisticated

990
00:59:56,040 --> 00:59:58,880
Speaker 2: and complicated this really is that makes it easy for

991
00:59:58,960 --> 01:00:01,840
Speaker 2: people to wave their hands and online and on social

992
01:00:01,960 --> 01:00:05,440
Speaker 2: media and say, you know, I've I've I've mastered everything

993
01:00:05,440 --> 01:00:08,720
Speaker 2: about my vegas nerve because I I hummed this morning.

994
01:00:14,320 --> 01:00:17,720
Speaker 1: So but author and I I am aware that you

995
01:00:17,880 --> 01:00:21,640
Speaker 1: have to go unfortunately. But are there is there anything

996
01:00:21,720 --> 01:00:24,080
Speaker 1: out there that you see in the internet that you go,

997
01:00:24,720 --> 01:00:27,560
Speaker 1: oh yeah, oh yeah, yeah, that's got some utility.

998
01:00:28,360 --> 01:00:31,720
Speaker 2: Well, I think the things that that have utility are

999
01:00:31,760 --> 01:00:33,840
Speaker 2: the things that I'm sure you use in your practice

1000
01:00:33,880 --> 01:00:36,520
Speaker 2: and your your doctor uses on you. You know, we

1001
01:00:36,600 --> 01:00:40,000
Speaker 2: should we should pay attention to healthy lifestyles. We should,

1002
01:00:40,400 --> 01:00:42,600
Speaker 2: you know, eat a balanced diet, get a good night's sleep.

1003
01:00:43,480 --> 01:00:45,520
Speaker 2: Focus on the things in life you can control, not

1004
01:00:45,640 --> 01:00:48,240
Speaker 2: the things you can't, you know, maintain some sort of

1005
01:00:48,840 --> 01:00:52,240
Speaker 2: a balance and harmony of work in life. Try to

1006
01:00:52,320 --> 01:00:55,160
Speaker 2: give back something to the world, to your community, to

1007
01:00:55,240 --> 01:00:59,680
Speaker 2: your family, Cherish those loving relationships, have a hobby, read

1008
01:00:59,680 --> 01:01:03,360
Speaker 2: a book, work out, and when you work out, you know,

1009
01:01:03,560 --> 01:01:08,840
Speaker 2: combine some some some yoga or stretching type workout with

1010
01:01:09,160 --> 01:01:14,480
Speaker 2: with VO two max exercises and strength training and these

1011
01:01:14,640 --> 01:01:17,720
Speaker 2: and and do I do cold exposure, Yeah, once or

1012
01:01:17,760 --> 01:01:19,760
Speaker 2: twice a week. I put the shower on full cold

1013
01:01:19,800 --> 01:01:22,480
Speaker 2: and and I get that fight or flight response. And

1014
01:01:22,600 --> 01:01:25,040
Speaker 2: do I do some breath work, Yeah, I do. I

1015
01:01:25,200 --> 01:01:28,600
Speaker 2: meditate because it makes me feel better. And the data

1016
01:01:28,720 --> 01:01:35,200
Speaker 2: are overwhelming that if these interventions are stimulating the vegus

1017
01:01:35,280 --> 01:01:38,040
Speaker 2: nerve to the inflammatory system, which they make, they might be.

1018
01:01:38,520 --> 01:01:40,760
Speaker 2: And we could talk about that for a minute if

1019
01:01:40,800 --> 01:01:44,720
Speaker 2: we have a few more minutes, but that if if

1020
01:01:44,800 --> 01:01:48,400
Speaker 2: they are doing that, and you are reducing your inflammatory burden,

1021
01:01:48,440 --> 01:01:51,080
Speaker 2: it's a Pascal's wager. It's probably a really good thing

1022
01:01:51,160 --> 01:01:54,080
Speaker 2: for you to to decrease the amount of inflammation on

1023
01:01:54,160 --> 01:01:56,360
Speaker 2: a day to day basis in your body. And if

1024
01:01:56,400 --> 01:01:58,280
Speaker 2: it doesn't work and you don't mind doing it, and

1025
01:01:58,400 --> 01:02:03,400
Speaker 2: you can afford to buy these interventions, then I don't

1026
01:02:03,440 --> 01:02:04,919
Speaker 2: see a harm in it. I do see a harm

1027
01:02:06,080 --> 01:02:09,440
Speaker 2: in practitioners who say, well, if I've got these patient

1028
01:02:09,520 --> 01:02:11,120
Speaker 2: and if I could just get her to breathe more,

1029
01:02:11,200 --> 01:02:14,480
Speaker 2: her rumatartar aarthritis would go away. No, that's not right.

1030
01:02:14,880 --> 01:02:16,960
Speaker 2: You know, if it was that easy, a lot of

1031
01:02:17,000 --> 01:02:19,720
Speaker 2: patients with rumatar aarthritis would take care of it. And

1032
01:02:19,960 --> 01:02:23,080
Speaker 2: maybe in rumatata arthritis their vagus nerve is actually damaged,

1033
01:02:23,560 --> 01:02:26,800
Speaker 2: or maybe in rumatar authritis it's not rumatori aarthritis, it's

1034
01:02:26,840 --> 01:02:30,760
Speaker 2: some undiagnosed infection that's affecting their joints that we haven't

1035
01:02:30,800 --> 01:02:33,520
Speaker 2: figured out yet. There's just lots of other things you

1036
01:02:33,600 --> 01:02:37,240
Speaker 2: can say and do. Before we blame the patient because

1037
01:02:37,280 --> 01:02:40,000
Speaker 2: the interventions don't work. It might be that we that

1038
01:02:40,160 --> 01:02:42,919
Speaker 2: we just don't have enough information. And so that's where

1039
01:02:43,000 --> 01:02:45,640
Speaker 2: that gets my dander up, because you know, we do

1040
01:02:46,120 --> 01:02:48,200
Speaker 2: have a lot of science behind a lot of these things,

1041
01:02:48,520 --> 01:02:51,480
Speaker 2: and we have people spending doing their life's work to

1042
01:02:51,560 --> 01:02:54,600
Speaker 2: try to figure these things out and we are making

1043
01:02:54,720 --> 01:02:58,160
Speaker 2: progress and advances, and you can't just wave your hands

1044
01:02:58,200 --> 01:03:02,840
Speaker 2: and say that you know, that doesn't mean anything because

1045
01:03:04,600 --> 01:03:07,960
Speaker 2: they figured this out in ancient China thousands of years ago,

1046
01:03:08,400 --> 01:03:11,440
Speaker 2: you know. So some we need a hybrid approach, right,

1047
01:03:11,760 --> 01:03:15,280
Speaker 2: We need a hybrid approach where people take responsibility when

1048
01:03:15,360 --> 01:03:18,080
Speaker 2: they can and do the best they can for healthy lifestyles.

1049
01:03:18,360 --> 01:03:21,120
Speaker 2: But we also have to acknowledge that doctors and caregivers

1050
01:03:21,360 --> 01:03:25,240
Speaker 2: are held accountable for the therapies they're giving. They're held

1051
01:03:25,280 --> 01:03:29,200
Speaker 2: accountable to make recommendations based on randomized clinical trials and

1052
01:03:29,800 --> 01:03:34,640
Speaker 2: large data sets and their experience and knowledge of what's first,

1053
01:03:34,720 --> 01:03:35,320
Speaker 2: do no harm?

1054
01:03:36,280 --> 01:03:39,480
Speaker 1: Yeah, yeah, totally agree, the first, no heart. It's got

1055
01:03:39,520 --> 01:03:42,720
Speaker 1: to be first. It's got to be the guiding principle. Right.

1056
01:03:45,360 --> 01:03:47,440
Speaker 1: My memory is a little bit sketchy on this. I

1057
01:03:47,560 --> 01:03:49,520
Speaker 1: need to find a paper and send it to you

1058
01:03:49,560 --> 01:03:51,800
Speaker 1: and maybe we have a conversation offline. But I remember

1059
01:03:51,920 --> 01:03:52,640
Speaker 1: reading a paper.

1060
01:03:53,200 --> 01:03:56,320
Speaker 3: It was in either rots or mice that had a mass,

1061
01:03:57,400 --> 01:04:02,680
Speaker 3: and they put them into old water and routinely, and

1062
01:04:03,200 --> 01:04:05,320
Speaker 3: I think they had another half that had that didn't

1063
01:04:05,320 --> 01:04:09,240
Speaker 3: have the mas, and what they found was regrowing on

1064
01:04:09,360 --> 01:04:12,120
Speaker 3: the of the mile and sheath on the ones that

1065
01:04:12,280 --> 01:04:16,400
Speaker 3: were exposed to the cold routinely, and they're I'm a

1066
01:04:16,440 --> 01:04:18,840
Speaker 3: bit sketchy about the theory, but it was basically that

1067
01:04:19,600 --> 01:04:23,400
Speaker 3: then the fire or flight like with that real cold,

1068
01:04:24,200 --> 01:04:27,360
Speaker 3: that is going to dominate everything else. So it was

1069
01:04:27,560 --> 01:04:32,560
Speaker 3: just basically it's about what was their theory about.

1070
01:04:33,000 --> 01:04:36,080
Speaker 1: Energy, and it was energy partitioning, and they were saying

1071
01:04:36,200 --> 01:04:37,400
Speaker 1: it was like, when.

1072
01:04:37,280 --> 01:04:40,320
Speaker 3: It's cold, it's going to focus everything on that and

1073
01:04:40,560 --> 01:04:45,240
Speaker 3: dampen other things down. And now without reading the paper

1074
01:04:45,760 --> 01:04:50,680
Speaker 3: and just thinking that that mechanistically, do you think there

1075
01:04:51,160 --> 01:04:53,640
Speaker 3: is some sort of potential there?

1076
01:04:54,480 --> 01:04:56,680
Speaker 1: And this is without you actually reading the paper, right,

1077
01:04:56,760 --> 01:04:57,280
Speaker 1: So I get that.

1078
01:04:58,080 --> 01:05:01,479
Speaker 2: Well, it's okay because we talk about there are lots

1079
01:05:01,520 --> 01:05:06,240
Speaker 2: of papers actually that suggest that even in humans with

1080
01:05:06,600 --> 01:05:11,200
Speaker 2: with with MS, that intermittent cold exposure can help interrupt

1081
01:05:11,560 --> 01:05:14,720
Speaker 2: their clinical syndrome. And there are people who there are

1082
01:05:14,800 --> 01:05:17,720
Speaker 2: some MS patients who self treat when they lose some

1083
01:05:17,920 --> 01:05:21,840
Speaker 2: function of some body part, they get in the in

1084
01:05:22,000 --> 01:05:24,680
Speaker 2: cold water and they can restore that function. So this

1085
01:05:24,880 --> 01:05:27,240
Speaker 2: is a known thing. What we don't know the mechanism,

1086
01:05:27,760 --> 01:05:32,680
Speaker 2: and it is very possible to me that the acute

1087
01:05:32,760 --> 01:05:35,880
Speaker 2: exposure cold does activate fight or flight, and that does

1088
01:05:35,960 --> 01:05:39,600
Speaker 2: have anti inflammatory mechanisms, so that could contribute. That's a

1089
01:05:39,760 --> 01:05:43,040
Speaker 2: testable hypothesis. It's hard to test in people, but you

1090
01:05:43,120 --> 01:05:46,360
Speaker 2: can you can study it in people. What's equally interesting

1091
01:05:46,440 --> 01:05:49,000
Speaker 2: to me, And here's where I alluded to it a

1092
01:05:49,080 --> 01:05:51,439
Speaker 2: minute ago, But when you really try to find high

1093
01:05:51,520 --> 01:05:55,200
Speaker 2: quality physiology studies of cold exposure, there's not a lot

1094
01:05:55,240 --> 01:05:59,840
Speaker 2: of them. You'd yeah, okay, you've looked. So I did

1095
01:06:00,040 --> 01:06:01,800
Speaker 2: kind a couple. I talk about them in the book,

1096
01:06:01,840 --> 01:06:05,720
Speaker 2: and the book is fully referenced. You can find things

1097
01:06:05,960 --> 01:06:08,600
Speaker 2: like soldiers in in the in the Baltic States, or

1098
01:06:08,640 --> 01:06:11,919
Speaker 2: in Sweden or Finland. They douse them in cold water

1099
01:06:12,000 --> 01:06:13,760
Speaker 2: and put them in a cold room for hours at

1100
01:06:13,800 --> 01:06:17,080
Speaker 2: a time. And the key there is they let them

1101
01:06:17,120 --> 01:06:20,320
Speaker 2: get cold adapted. And then they ask questions, does that

1102
01:06:21,440 --> 01:06:26,040
Speaker 2: cause increased vegas nerve activity? Yes, because their heart rate

1103
01:06:26,120 --> 01:06:29,440
Speaker 2: will slow down once they get cold adapted, And does

1104
01:06:29,520 --> 01:06:34,240
Speaker 2: it cause decreased inflammation? And the best studies I found

1105
01:06:35,040 --> 01:06:39,600
Speaker 2: said yes. And the best studies I found used methods

1106
01:06:40,120 --> 01:06:42,680
Speaker 2: that are very similar to the ones we talked about before,

1107
01:06:43,200 --> 01:06:46,400
Speaker 2: from from the wim Hoff study and the Proceedings of

1108
01:06:46,400 --> 01:06:49,760
Speaker 2: the National Academy of Sciences by Peter Pickers from from

1109
01:06:50,880 --> 01:06:54,920
Speaker 2: from the from Holland, from the Netherlands. These studies they

1110
01:06:55,080 --> 01:06:59,520
Speaker 2: ask if I take white blood cells out of the body,

1111
01:07:00,040 --> 01:07:02,360
Speaker 2: and I put them in a test tube and I

1112
01:07:02,640 --> 01:07:06,240
Speaker 2: activate them with bacterial endotox and how much cytokines do

1113
01:07:06,320 --> 01:07:08,480
Speaker 2: they make? So we call that ex vivo out of

1114
01:07:08,520 --> 01:07:11,760
Speaker 2: the body stimulation, and it turns out in the cold

1115
01:07:11,920 --> 01:07:16,480
Speaker 2: adapted volunteers they make a lot less cytokines in those

1116
01:07:16,480 --> 01:07:18,840
Speaker 2: white blood cells that are cold adapted than the ones

1117
01:07:18,880 --> 01:07:21,840
Speaker 2: before they were cold adapt So I put that whole

1118
01:07:21,920 --> 01:07:26,480
Speaker 2: thing together, and really importantly the vegas nerve stimulation studies

1119
01:07:26,520 --> 01:07:29,280
Speaker 2: that we did again published in the Proceedings of the

1120
01:07:29,360 --> 01:07:32,560
Speaker 2: National Academy of Sciences with Yakov Lavigne and his team

1121
01:07:32,600 --> 01:07:36,000
Speaker 2: at set point, we showed that when we electrically stimulated

1122
01:07:36,040 --> 01:07:40,360
Speaker 2: the vegus nerve of the MS animals these this is

1123
01:07:40,400 --> 01:07:45,080
Speaker 2: called EAE, we saw decreased inflammation expected that, but we

1124
01:07:45,320 --> 01:07:50,080
Speaker 2: also saw increased myelination from the vegas nerve stimulation, which

1125
01:07:50,160 --> 01:07:52,720
Speaker 2: is what you said they saw in the cold rats.

1126
01:07:53,040 --> 01:07:55,360
Speaker 2: So wouldn't that be great if it works in people?

1127
01:07:55,440 --> 01:07:57,400
Speaker 2: We don't know yet. We have to do the clinical trial.

1128
01:07:58,480 --> 01:08:01,800
Speaker 1: Yeah, very interesting. She got Portsmouth University.

1129
01:08:01,800 --> 01:08:03,919
Speaker 3: I forget his blood me and I can't believe because

1130
01:08:03,920 --> 01:08:05,640
Speaker 3: I've had him on the podcast and talked to him

1131
01:08:05,680 --> 01:08:06,240
Speaker 3: several times.

1132
01:08:06,240 --> 01:08:07,200
Speaker 1: I'm having a brilliant fought.

1133
01:08:07,520 --> 01:08:11,040
Speaker 3: But he's done some really interesting cold exposure stuff where

1134
01:08:11,040 --> 01:08:15,200
Speaker 3: it's where people lie down on this kind of sort

1135
01:08:15,240 --> 01:08:18,000
Speaker 3: of teable on the water and then one leg gets

1136
01:08:18,080 --> 01:08:21,080
Speaker 3: submerged in the cold so they can look and do

1137
01:08:21,240 --> 01:08:22,800
Speaker 3: biopsies and stuff of one leg.

1138
01:08:23,200 --> 01:08:23,240
Speaker 2: Like.

1139
01:08:23,439 --> 01:08:25,799
Speaker 1: That's where we start to get into pretty code experiments,

1140
01:08:25,880 --> 01:08:26,120
Speaker 1: isn't it.

1141
01:08:26,640 --> 01:08:28,840
Speaker 2: Well, it is, but you know it's experiments like that.

1142
01:08:29,080 --> 01:08:34,040
Speaker 2: It wasn't It wasn't until fairly recently that that researchers

1143
01:08:34,120 --> 01:08:39,560
Speaker 2: actually proved that putting ice on a swollen joint decreases

1144
01:08:39,600 --> 01:08:42,519
Speaker 2: the inflammation in the in the knee and ankle. I mean,

1145
01:08:42,760 --> 01:08:45,560
Speaker 2: that kind of work is still our current, which is

1146
01:08:45,640 --> 01:08:48,920
Speaker 2: a riot. You would think somebody would have studied this

1147
01:08:49,200 --> 01:08:50,719
Speaker 2: thousand years ago, but they didn't.

1148
01:08:50,800 --> 01:08:54,640
Speaker 1: Yeah, and I'm very interesting now. I do know that

1149
01:08:55,080 --> 01:08:57,639
Speaker 1: you do have to go. What are you excited about

1150
01:08:57,760 --> 01:09:00,200
Speaker 1: for the future? Just before we let go.

1151
01:09:01,320 --> 01:09:05,400
Speaker 2: I'm excited that patients and doctors agree on a basic

1152
01:09:05,600 --> 01:09:10,040
Speaker 2: vegas nerve vocabulary, because that will be the fastest route

1153
01:09:10,479 --> 01:09:14,360
Speaker 2: to knock down barriers. Look, there's barriers to putting vagus

1154
01:09:14,400 --> 01:09:17,639
Speaker 2: nerve stimulators in people with an inflammatory or automune condition.

1155
01:09:18,080 --> 01:09:21,519
Speaker 2: A lot of the barriers are based on precedent. People

1156
01:09:21,600 --> 01:09:24,439
Speaker 2: aren't used to doctors and patients are used to taking

1157
01:09:24,520 --> 01:09:28,000
Speaker 2: pills and injections. They're not used to thinking about medical

1158
01:09:28,080 --> 01:09:32,240
Speaker 2: devices with rechargeable batteries to treat an inflammatory disease. We

1159
01:09:32,320 --> 01:09:35,639
Speaker 2: have to change, change the workflows. We have to change

1160
01:09:35,640 --> 01:09:37,840
Speaker 2: the way people think and talk about this, and my

1161
01:09:37,960 --> 01:09:39,680
Speaker 2: book tries to do that. It tries to give a

1162
01:09:39,760 --> 01:09:43,360
Speaker 2: common language, tries to give a series of stories that

1163
01:09:44,960 --> 01:09:48,080
Speaker 2: bring this whole thing to life. And my hope and

1164
01:09:49,479 --> 01:09:53,200
Speaker 2: my hope and dream is that many people start talking

1165
01:09:53,280 --> 01:09:56,839
Speaker 2: about this and that it shortens the path for patients

1166
01:09:56,880 --> 01:09:59,679
Speaker 2: who need new therapies to at least know that there's

1167
01:09:59,760 --> 01:10:02,040
Speaker 2: new options out there. It's not going to work in everybody.

1168
01:10:02,040 --> 01:10:05,400
Speaker 2: It's not snake oil. I'm not selling anything. I just

1169
01:10:05,479 --> 01:10:08,439
Speaker 2: want the idea to be on the tip of people's

1170
01:10:08,479 --> 01:10:11,920
Speaker 2: tongues so that those who can benefit from the therapy

1171
01:10:12,040 --> 01:10:16,320
Speaker 2: get benefit, and so that scientists and researchers, my colleagues

1172
01:10:16,600 --> 01:10:19,320
Speaker 2: are motivated to do more and go faster because there's

1173
01:10:19,320 --> 01:10:21,400
Speaker 2: a lot of people that can benefit from this. Millions

1174
01:10:21,439 --> 01:10:24,400
Speaker 2: and millions of people can benefit from this idea eventually.

1175
01:10:25,280 --> 01:10:25,479
Speaker 1: Yeah.

1176
01:10:25,560 --> 01:10:28,120
Speaker 5: Absolutely, And I think a big take home here for

1177
01:10:28,240 --> 01:10:31,439
Speaker 5: people is, before you go spending a shit lead load

1178
01:10:31,520 --> 01:10:34,759
Speaker 5: of money on these vegus nerve stimulators on the internet,

1179
01:10:35,240 --> 01:10:38,679
Speaker 5: make sure you're exercising well, make sure you're sleeping well,

1180
01:10:38,840 --> 01:10:40,959
Speaker 5: making sure you're doing a bit of breath work, particularly

1181
01:10:41,040 --> 01:10:45,120
Speaker 5: controlling your stress, do some bit of cold exposure, eat well.

1182
01:10:45,640 --> 01:10:48,840
Speaker 3: Do all those things first before you go spanding your

1183
01:10:48,880 --> 01:10:51,479
Speaker 3: money on all this expensive shit. And if you're doing

1184
01:10:51,600 --> 01:10:54,160
Speaker 3: all of that, then yes, go and spend some money

1185
01:10:54,240 --> 01:10:55,479
Speaker 3: and run a little experiment.

1186
01:10:58,760 --> 01:11:01,639
Speaker 1: Awesome, Kevin. That was a big thumbs up for people

1187
01:11:01,680 --> 01:11:06,000
Speaker 1: who are not watching and just listening. Kevin, listen, this

1188
01:11:06,200 --> 01:11:06,639
Speaker 1: is awesome.

1189
01:11:06,880 --> 01:11:11,679
Speaker 3: And thank you on behalf of mankind for you taking

1190
01:11:12,120 --> 01:11:15,360
Speaker 3: the time, which I know is pressive because I imagine

1191
01:11:15,360 --> 01:11:17,360
Speaker 3: where you are there's so much shit you can do

1192
01:11:17,520 --> 01:11:21,160
Speaker 3: with your time. But thank you for writing a book

1193
01:11:21,200 --> 01:11:23,200
Speaker 3: which I think is the best one that I have

1194
01:11:23,400 --> 01:11:26,800
Speaker 3: read yet in this area, although I haven't completely.

1195
01:11:26,439 --> 01:11:30,960
Speaker 1: Finished it, but so for the listeners. The great Nerve

1196
01:11:31,120 --> 01:11:35,320
Speaker 1: by Kevin J. Tracy MD and thank you for your work.

1197
01:11:35,400 --> 01:11:37,920
Speaker 2: Kevin, thank you and thanks for having me on. Paul.

1198
01:11:37,920 --> 01:11:38,640
Speaker 2: It's great to know you.

1199
01:11:39,479 --> 01:11:41,120
Speaker 1: Yeah, it's bloody awesome. Thanks mate,