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Dr. Peter Attia: Exercise, Nutrition, Hormones for Vitality & Longevity | Huberman Lab Podcast #85



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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman,
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and I'm a professor of neurobiology and ophthalmology
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at Stanford School of Medicine.
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Today, my guest is Dr. Peter Attia.
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Dr. Attia is a physician who's focused on nutritional,
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supplementation-based, behavioral, prescription drug,
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and other interventions that promote healthspan
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and lifespan.
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His expertise spans from exercise physiology
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to sleep physiology,
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emotional and mental health, and pharmacology.
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Today, we talk about all those areas of health,
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starting with the very basics,
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such as how to evaluate one's own health status
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and how to define one's health trajectory.
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We also talk about the various sorts of interventions
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that one can take in order to optimize vitality
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while also extending longevity, that is, lifespan.
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Dr. Attia is uniquely qualified
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to focus on the complete depth and breadth of topics
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that we cover.
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And indeed, these are the same topics
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that he works with his patients on in his clinic every day.
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Dr. Attia earned his bachelor of science
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in mechanical engineering and applied mathematics
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and his MD from Stanford University School of Medicine.
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He then went on to train at Johns Hopkins Hospital
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in general surgery,
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one of the premier hospitals in the world,
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where he was the recipient of several prestigious awards,
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including resident of the year.
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He's been an author on comprehensive reviews
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of general surgery.
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He spent two years at the National Institutes of Health
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as a surgical oncology fellow
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at the National Cancer Institute,
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where his work focused on immune-based therapies
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for melanoma.
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In the fields of science and medicine,
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it is well understood that we are much the product
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of our mentors and the mentoring we receive.
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Dr. Attia has trained with some of the best
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and most innovative lipidologists, endocrinologists,
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gynecologists, sleep physiologists,
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and longevity scientists in the United States and Canada.
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So the expertise that funnels through him
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and that he shares with us today
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is really harnessed from the best of the best
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and his extensive training and expertise.
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By the end of today's episode,
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you will have answers to important basic questions
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such as, should you have blood work?
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How often should you do blood work?
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What specific things should you be looking for
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on that blood work that are either counterintuitive
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or not often discussed and yet that immediately
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and in the long-term influence your lifespan
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and health span?
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We talk about hormone health and hormone therapies
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for both men and women.
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We talk about drug therapies that can influence the mind
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as well as the body.
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And of course, we talk about supplementation, nutrition,
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exercise, and predictors of lifespan and health span.
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It is an episode rich with information.
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For some of you, you may want to get out a pen and paper
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in order to take notes.
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For others of you that learn better simply by listening,
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just want to remind you that we have timestamped
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all this information so that you can go back
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to the specific topics most of interest to you.
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I'm pleased to announce that the Huberman Lab Podcast
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is now partnered with Momentous Supplements.
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We partnered with Momentous for several important reasons.
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First of all, they ship internationally
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because we know that many of you are located
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outside of the United States.
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Second of all, and perhaps most important,
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the quality of their supplements is second to none,
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both in terms of purity and precision
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of the amounts of the ingredients.
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Third, we've really emphasized supplements
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that are single ingredient supplements
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and that are supplied in dosages that allow you
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to build a supplementation protocol that's optimized
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for cost, that's optimized for effectiveness,
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and that you can add things and remove things
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from your protocol in a way that's really systematic
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and scientific.
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If you'd like to see the supplements
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that we partner with Momentous on,
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you can go to livemomentous.com slash Huberman.
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There you'll see those supplements and just keep in mind
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that we are constantly expanding the library
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of supplements available through Momentous
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on a regular basis.
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Again, that's livemomentous.com slash Huberman.
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Before we begin, I'd like to emphasize that this podcast
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is separate from my teaching and research roles at Stanford.
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It is, however, part of my desire and effort
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to bring zero cost to consumer information about science
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and science-related tools to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Our first sponsor is Thesus.
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00:04:04.320
Thesus makes custom nootropics that are designed
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for your unique needs.
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because nootropics means smart drugs.
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And to be honest, there is no such thing as a smart drug
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because there's no neural circuit for being smart.
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There are neural circuits rather for being creative
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or for task switching or for focus.
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As we all know, different sorts of demands,
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whether or not they are cognitive or physical,
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Today's episode is also brought to us by InsideTracker.
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InsideTracker is a personalized nutrition platform
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that analyzes data from your blood and DNA
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to help you better understand your body
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and help you reach your health goals.
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I've long been a believer in getting regular blood work done
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for the simple reason that many of the factors
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that impact your immediate and long-term health
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can only be assessed from a quality blood test.
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And nowadays with the advent of modern DNA tests,
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you can also analyze, for instance,
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what your biological age is and compare it
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to your chronological age.
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And obviously it's your biological age that really matters.
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The challenge with a lot of blood tests and DNA tests,
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however, is that you get information back
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about metabolic factors, hormones, and so forth,
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but you don't know what to do with that information.
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InsideTracker makes it very easy to know what to do
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with that information to optimize your health.
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They have a personalized platform.
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It's a dashboard that you go to.
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You can click on the level of any hormone,
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metabolic factor, lipid, et cetera,
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and it will tell you the various sorts of interventions
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based on nutrition, supplementation, et cetera,
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that you can use to bring those numbers
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into the ranges that are ideal for you.
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If you'd like to try InsideTracker,
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Today's episode is also brought to us by Helix Sleep.
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Helix Sleep makes mattresses and pillows
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that are of the absolute highest quality.
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because they are customized to your unique sleep needs.
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I've talked over and over again on this podcast
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and on another podcast about the fact
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that sleep is the foundation of mental health,
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physical health, and performance.
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There's just simply no other substitute
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I've been sleeping on a Helix mattress
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for well over a year now,
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and it's the best sleep that I've ever had.
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And that's in large part
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because the mattress was designed for me.
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What you need to know, however,
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do you sleep on your side, your back, your stomach,
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That's not necessarily what you need
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in order to get your best night's sleep.
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But if you're interested in upgrading your mattress,
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you go to helixsleep.com slash Huberman
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for up to $200 off your mattress order and two free pillows.
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And now for my discussion with Dr. Peter Attia.
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Peter, thanks for joining me today.
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Thanks for having me, man.
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I've been looking forward to this for a very long time.
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That's fine.
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I'm a huge fan of your podcast.
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I know that you went to Stanford
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and worked with a number of people
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that are colleagues of mine.
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So for me, this is already a thrill just to be doing this.
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Yeah, well, likewise.
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I have a ton of questions,
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but I want to start off with something
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that I wonder a lot about
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and that I know many other people wonder about,
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which is how to assess their current health
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and their trajectory in terms of health and wellbeing,
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specifically as it relates to blood work.
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So what are your thoughts on blood work?
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Is it necessary for the typical person?
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So this is somebody who's not dealing
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with some acute syndrome or illness.
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And at what age would you suggest
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people start getting blood work?
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How frequently should they get blood work?
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How often do you get blood work done, et cetera?
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Yeah, there's a lot there.
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I mean, the way I talk about this with patients
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is first taking everything back to the objective.
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So what's the thing we're trying to optimize?
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So if a person says,
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look, I'm trying to break 10 hours for an Ironman,
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I don't know that blood work is going to be
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a game-changing aspect of their trajectory
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and their training.
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They're going to benefit much more
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from sort of functional analysis of performance.
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So I'm assuming based on the question
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that you're really coming at this through the lens
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of living longer and living better
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through the lifespan, healthspan lens?
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Yeah, and just, I think most people have some sense
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of their vitality or lack of vitality,
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but I think everyone wonders
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whether or not they could feel better
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and whether or not blood work will give them a window
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into how they might go about feeling better.
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Yeah, I think it does to some extent,
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but I also think that it has a lot of blind spots.
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So I kind of break things down into the two vectors
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that make up longevity, which are lifespan and healthspan.
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So lifespan is the easiest of those vectors to understand
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because it's pretty binary, right?
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You're alive or you're not alive,
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you're respiring or you're not,
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you make ATP or you don't, end of story.
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So what gets in the way of lifespan
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is essentially the four horsemen of disease, right?
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So atherosclerotic disease, cancer, neurodegenerative disease
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and metabolic disease,
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which directly isn't the cause of many deaths,
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but basically creates the foundation
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to all of those other diseases.
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So if you're a non-smoker, what I just rattled off
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is about 80% of your death.
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So how does blood work help address those?
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It varies.
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So on the atherosclerotic standpoint,
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it's a very good predictor of risk
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if you know what to look for.
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So primarily ApoB would be the single most important
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lipoprotein that we care about.
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I gotta explain what that means in a second.
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And then also other markers of inflammation,
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endothelial health and metabolic health.
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When it comes to cancer, blood testing
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in the sense of biomarkers is not particularly helpful
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outside of knowing that the second leading environmental
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or modifiable cause of cancer
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is metabolic ill health after smoking.
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So we don't actually know a lot about cancer
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in the sense of what causes it.
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It's really stochastic and it's a lot of bad luck.
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So we know that smoking drives it
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and we know that even though epidemiologically
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we say obesity drives it,
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what it really means is metabolic poor health.
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It's probably the hyperinsulinemia
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that comes with obesity that drives it.
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So biomarkers help with that,
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but there's still an enormous blind spot to cancer.
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We could talk about liquid biopsies aside
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because those aren't really biomarker studies,
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but put that away.
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On the neurodegenerative side,
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I don't think we have a lot of insight
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that comes to understanding Parkinson's disease,
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but when it comes to dementia,
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particularly the Alzheimer's disease,
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which is the most prevalent form of dementia,
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I think the biomarkers can be quite helpful.
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They overlap a lot with the atherosclerotic diseases.
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So the same things that drive the risk of heart disease
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are driving the risk of dementia.
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And then there's some novel stuff as well.
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If you include genetic testing,
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which you can get out of a blood test,
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we get a whole suite of genes, not just APOE,
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but far more nuanced stuff than that
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that can also play a role.
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So you can stratify risk in that sense.
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So in aggregate, I would say blood testing of biomarkers
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provides pretty good insight into lifespan.
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When you get into healthspan,
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you have kind of the cognitive, physical, emotional domains.
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I think here the biomarkers are far less helpful,
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and here we kind of rely more on functional testing.
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So when it comes to sort of the cognitive piece,
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you can do cognitive testing.
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In terms of long-term risk,
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a lot of the things that imply good cognitive health
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as you age are in line with the same things
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that you would do to reduce the risk of dementia.
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So all the biomarkers that you would look to improve
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through dementia risk reduction,
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you would be improving through cognitive health.
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On the physical side, I mean,
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outside of looking at hormone levels and things,
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which we look at extensively,
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and understanding how those might aid in
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or prevent some of the metrics that matter,
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it really is, this is a biomarker aside thing.
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I mean, I'd be much more interested
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in a person's DEXA, CPET testing, VO2 max testing,
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zone two lactate testing, fat oxidation,
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those what I would consider more functional tests
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00:12:51.040
that give me far more insight into that.
link |
00:12:53.320
And then of course the emotional piece,
link |
00:12:54.560
which depending on who you are,
link |
00:12:56.920
might be the single most important piece
link |
00:12:58.360
without which none of this other stuff matters,
link |
00:12:59.800
right, if you're a totally miserable human being,
link |
00:13:01.940
your relationships suck.
link |
00:13:03.800
I don't think any of this other stuff matters.
link |
00:13:05.460
And certainly there's nothing that I'm looking at
link |
00:13:07.800
in biomarkers that's giving me great insight into that.
link |
00:13:10.820
Do you ask about emotional state
link |
00:13:12.480
or do you try and assess emotional state indirectly
link |
00:13:14.640
when you do an intake with one of your patients?
link |
00:13:17.920
Probably not so much in the intake
link |
00:13:19.420
because I think it takes a while
link |
00:13:20.760
to form a relationship with a patient
link |
00:13:22.220
before that starts to become something
link |
00:13:24.920
that they're necessarily gonna wanna talk with you about.
link |
00:13:27.400
But I definitely think of it
link |
00:13:29.360
as an important part of what we do.
link |
00:13:31.760
And I think without it,
link |
00:13:33.820
none of this other stuff really matters.
link |
00:13:35.560
Again, the irony of thinking about
link |
00:13:38.200
how many years I spent sort of in pursuit
link |
00:13:39.960
of fully optimizing every detail of everything
link |
00:13:43.640
without any attention being paid to that dimension
link |
00:13:46.580
is not lost on me.
link |
00:13:48.000
And look, there are some patients who,
link |
00:13:50.680
that's just not something that,
link |
00:13:51.760
that's something that's compartmentalized.
link |
00:13:53.240
Maybe they're doing well in that department
link |
00:13:55.120
or maybe they aren't,
link |
00:13:55.960
but they just aren't willing to engage on that yet.
link |
00:13:58.840
In terms of frequency of blood testing,
link |
00:14:01.840
if somebody feels pretty good
link |
00:14:03.200
and is taking a number of steps,
link |
00:14:05.340
exercise, nutrition, et cetera,
link |
00:14:07.240
to try and extend lifespan and improve health span,
link |
00:14:13.640
is once a year frequent enough?
link |
00:14:16.720
And should a 20-year-old start getting blood work done
link |
00:14:20.000
just to get a window into what's going on,
link |
00:14:21.720
assuming that they can afford it
link |
00:14:22.780
or their insurance can cover it?
link |
00:14:24.240
Yeah, I mean, look,
link |
00:14:25.080
I certainly think everybody should be screened early in life
link |
00:14:27.560
because if you look at like what's the single most prevalent
link |
00:14:31.200
genetic driver of atherosclerosis is Lp little a.
link |
00:14:34.520
So unfortunately, most physicians don't know
link |
00:14:36.100
what Lp little a is,
link |
00:14:37.080
and yet somewhere between 8 and 12% of the population
link |
00:14:40.020
has a high enough,
link |
00:14:40.880
and depending on who you,
link |
00:14:43.200
I had a recent guest on my podcast
link |
00:14:44.640
who suggested it could be as high as 20%
link |
00:14:46.760
have a high enough Lp little a
link |
00:14:48.120
that it is contributing to atherosclerosis.
link |
00:14:51.080
So to not want to know that
link |
00:14:52.920
when it's genetically determined, right?
link |
00:14:54.300
This is something that you're born with this
link |
00:14:56.680
and you only need to really check it once.
link |
00:14:59.240
Why we wouldn't want to know that in a 20-year-old
link |
00:15:01.480
when it can contribute
link |
00:15:02.680
to a lot of the early atherosclerosis we see in people.
link |
00:15:08.200
It's leaving money on the table, in my opinion.
link |
00:15:10.440
The frequency with which you need to test
link |
00:15:11.960
really comes down to the state of interventions.
link |
00:15:16.120
I don't think it makes sense to just do blood tests
link |
00:15:18.080
for the sake of doing blood tests.
link |
00:15:19.200
There has to be kind of a reason.
link |
00:15:20.400
Is something changing?
link |
00:15:21.560
A blood test is, for the most part, a static intervention.
link |
00:15:26.080
It's a look at a window in time,
link |
00:15:28.840
and there's benefit in having a few of those
link |
00:15:32.680
over the course of a year if you're unsure about a level.
link |
00:15:36.200
So if something comes back and it doesn't look great,
link |
00:15:38.600
yeah, it might make sense just to recheck it
link |
00:15:40.200
without reacting to it.
link |
00:15:41.800
But typically, in patients,
link |
00:15:43.320
we might check blood two to four times a year,
link |
00:15:45.580
but we're also probably doing things in there
link |
00:15:47.620
to now check, like, hey, we gave this drug.
link |
00:15:52.160
Did it have the desired outcome?
link |
00:15:54.760
You put on three pounds of muscle
link |
00:15:56.600
and lost three pounds of fat.
link |
00:15:57.880
Did it have the desired outcome?
link |
00:16:01.240
Speaking of tracking weight and fat lean mass percentages,
link |
00:16:06.200
is that something that you recommend
link |
00:16:07.960
your patients do pretty often?
link |
00:16:09.460
I know people that step on the scale every day.
link |
00:16:10.960
I know people like myself that, frankly,
link |
00:16:13.000
I might step on the scale three times a year.
link |
00:16:14.680
I don't really care.
link |
00:16:16.240
I pay attention to other things
link |
00:16:17.600
that are far more subjective.
link |
00:16:19.600
Maybe I'm making a huge mistake.
link |
00:16:20.920
What are your thoughts about quantitative measurements
link |
00:16:24.160
of weight BMI for the typical person?
link |
00:16:29.320
I think they're pretty crude.
link |
00:16:31.720
I think a DEXA, I'd rather take a DEXA annually
link |
00:16:37.120
and then maybe follow weight a little bit more closely
link |
00:16:40.380
to get a sense of it.
link |
00:16:41.380
And so with a DEXA, you're getting,
link |
00:16:43.920
at least the way we look at the data,
link |
00:16:45.480
four pieces of information.
link |
00:16:47.520
Now, most people, when they do a DEXA,
link |
00:16:49.520
should I explain what that is?
link |
00:16:50.800
Yeah, I think some people might not know what DEXA is.
link |
00:16:53.080
In fact, I confess I have a crude understanding
link |
00:16:55.660
of what it is.
link |
00:16:57.640
Tell me where I'm wrong
link |
00:16:58.800
and hopefully where I'm at least partially right.
link |
00:17:02.040
My understanding is that there are a number of different ways
link |
00:17:03.760
to measure lean mass to non-lean mass ratio.
link |
00:17:07.080
And there's one where they put you underwater.
link |
00:17:09.520
There's one where they put you
link |
00:17:10.340
into some sort of non-underwater chamber.
link |
00:17:12.880
There's calipering.
link |
00:17:14.340
And then there's the looking in the mirror
link |
00:17:16.680
and pinching and changing the lighting.
link |
00:17:20.800
It's funny, if you've done it enough,
link |
00:17:23.440
I can sort of tell my body fat by my abs, right?
link |
00:17:26.720
So I can sort of tell by how good the six pack
link |
00:17:29.440
or how bad the six pack is, what the leanness is.
link |
00:17:31.620
And that's actually not a terrible way to do it.
link |
00:17:34.440
A bodybuilder, for example, which I've never been,
link |
00:17:37.040
can tell you the difference between being 6%, 7%, 8%, 10%,
link |
00:17:41.480
just based on the degree of visibility within the abs.
link |
00:17:46.760
But basically a DEXA scan is an X-ray.
link |
00:17:50.720
So it's the same principle as just getting a chest X-ray
link |
00:17:53.740
where ionizing radiation is passed through the body
link |
00:17:56.600
and there's a plate behind the body
link |
00:17:58.080
that collects what comes through.
link |
00:17:59.820
And the denser the medium
link |
00:18:02.720
that the electrons are trying to go through,
link |
00:18:05.420
the less of them that are collected.
link |
00:18:06.840
So when you look at an X-ray,
link |
00:18:08.000
as everybody's probably seen an X-ray,
link |
00:18:09.760
that which is white is most dense.
link |
00:18:11.780
So if you had a piece of metal in your pocket,
link |
00:18:14.280
it would show up as a bright white thing.
link |
00:18:16.760
That's why ribs and bones show up as white.
link |
00:18:19.560
And the things that are the least dense,
link |
00:18:21.960
like the lungs where it's just air, are the blackest.
link |
00:18:25.320
And everything is a shade of gray in between.
link |
00:18:27.600
So a DEXA is just doing that effectively,
link |
00:18:30.560
but it's a moving X-ray.
link |
00:18:31.800
So you lay down on a bed and it takes maybe 10 minutes
link |
00:18:34.840
and this little very low power X-ray
link |
00:18:37.360
kind of goes over your body.
link |
00:18:39.160
And the plate beneath it is collecting information
link |
00:18:43.460
that is basically allowing it to differentiate
link |
00:18:45.960
between three things.
link |
00:18:47.760
Bone mineral content, fat, other.
link |
00:18:52.440
And the other is quantified as lean body mass.
link |
00:18:55.480
So that's organs, muscles, everything else.
link |
00:18:58.620
So when most people do a DEXA,
link |
00:19:00.680
they get the report back and the reports are horrible.
link |
00:19:02.800
I've yet to see one company that can do this
link |
00:19:04.700
in a way that isn't abjectly horrible.
link |
00:19:06.840
We've created our own templates.
link |
00:19:08.320
We have our own dashboard for how we do this
link |
00:19:09.940
because we've just given up on trying to use theirs.
link |
00:19:12.340
But the first thing most people look at
link |
00:19:13.520
is what's my body fat?
link |
00:19:14.800
And this is the gold standard outside of like MRI
link |
00:19:17.960
or something that's only used for research purposes.
link |
00:19:20.000
So a DEXA is going to produce a far better estimate
link |
00:19:23.000
of body fat than calipers or buoyancy testing
link |
00:19:27.460
or things like that, provided the machinery
link |
00:19:29.760
is well calibrated and the operator knows how to use it.
link |
00:19:34.220
I've heard some people argue that in the hands
link |
00:19:36.200
of the guy who's been doing calipers his whole life,
link |
00:19:40.600
it could probably be comparable with calipers.
link |
00:19:42.440
But nevertheless, for an off the shelf tech,
link |
00:19:45.720
DEXA is amazing.
link |
00:19:47.840
Of the four things that get spit out of the DEXA,
link |
00:19:50.560
we think that the body fat is the least interesting.
link |
00:19:53.380
And so I would rank that as fourth on the list
link |
00:19:56.120
of what's germane to your health.
link |
00:19:58.020
The other three things that you get spit out
link |
00:19:59.920
are bone mineral density, visceral fat,
link |
00:20:03.960
and then the metrics that allow you to basically compute
link |
00:20:09.160
what's called appendicular lean mass index
link |
00:20:11.180
and fat free mass index.
link |
00:20:12.920
And so those three metrics are significantly
link |
00:20:15.320
more important than body fat.
link |
00:20:17.440
And the reason is as follows, right?
link |
00:20:19.440
So bone mineral density basically speaks
link |
00:20:22.340
to your risk of osteoporosis and osteopenia.
link |
00:20:26.280
And that doesn't sound very sexy to people our age,
link |
00:20:29.840
you know, 50 year old guys listening to this,
link |
00:20:31.740
it's like, yeah, big deal.
link |
00:20:32.720
But for a 50 year old woman, this is a huge deal, right?
link |
00:20:35.800
A woman who's just about to go through menopause
link |
00:20:37.640
or has just gone through menopause is at an enormous risk
link |
00:20:40.740
for osteopenia and then ultimately osteoporosis.
link |
00:20:43.900
Because estrogen is the single most important hormone
link |
00:20:47.140
in regulating bone mineral density.
link |
00:20:50.060
And we can come back and talk about why that's the case,
link |
00:20:51.960
but it's very interesting how the biomechanics
link |
00:20:55.080
of bones work and why estrogen specifically is so important.
link |
00:21:00.260
And this is a huge cause of morbidity, right?
link |
00:21:02.440
So, you know, if you're over the age of 65
link |
00:21:05.120
and you fall and break your hip,
link |
00:21:07.480
your one year morbidity is about 30 to 40%.
link |
00:21:12.760
Which again, just to put that in English,
link |
00:21:14.800
if you're 65 or older, you fall and break your hip,
link |
00:21:17.120
there's a 30 to 40% chance you're dead in a year.
link |
00:21:20.420
Wow.
link |
00:21:21.260
Bones matter.
link |
00:21:24.600
So we want to really get a sense of where you stack up
link |
00:21:27.960
for your age, for your sex, and if you're anywhere
link |
00:21:31.440
off the pace, we have to ramp up our strategy
link |
00:21:34.880
and be super aggressive about how to increase that
link |
00:21:37.440
or at a minimum, prevent any further decay.
link |
00:21:41.360
And are there age related charts for these sorts of things?
link |
00:21:44.040
Yeah, this all gets spit out into what's called a z-score.
link |
00:21:47.140
So when you're looking at your BMD,
link |
00:21:49.440
it's gonna give you a z-score.
link |
00:21:50.560
So a z-score of zero means, and you understand this,
link |
00:21:54.160
but it's z-score referring to a probability distribution
link |
00:21:56.760
in a standard mode.
link |
00:21:57.680
So z-score of zero means you're at the 50th percentile
link |
00:22:00.440
for your age and sex.
link |
00:22:01.480
A z-score of plus one, your one standard deviation above,
link |
00:22:04.200
minus one below, et cetera.
link |
00:22:06.320
There's also a t-score, which is doing the same thing,
link |
00:22:08.800
but comparing you to a young person.
link |
00:22:11.600
And so the t-score is technically used to make the diagnosis
link |
00:22:14.200
of osteopenia or osteoporosis.
link |
00:22:15.800
We tend to look more at the z-score and basically say,
link |
00:22:18.160
look, if your z-score right now is minus one in four years,
link |
00:22:22.560
I want your z-score to be zero.
link |
00:22:24.120
Not necessarily because you've increased that entire way,
link |
00:22:27.440
but maybe you've increased slightly
link |
00:22:29.160
while it's expected that you would have declined.
link |
00:22:31.960
I see.
link |
00:22:33.800
What are some things that we can do
link |
00:22:35.200
to improve bone mineral density at any age?
link |
00:22:38.920
So it turns out there's a real critical window
link |
00:22:41.440
in which we are malleable.
link |
00:22:43.080
So depending on the age at which someone's listening
link |
00:22:45.280
to us discuss this, if you're under 20, 25,
link |
00:22:50.400
you are still in that time of your life
link |
00:22:52.800
when you are able to reach your potential.
link |
00:22:55.560
So it turns out that strength training is probably
link |
00:23:00.040
the single best thing you can do.
link |
00:23:02.320
And this was a surprise to me,
link |
00:23:03.800
because we did an AMA on this topic a little while ago,
link |
00:23:07.400
and that's when I got really deep on this with our analysts.
link |
00:23:10.760
My assumption was running must be the best.
link |
00:23:13.280
Some sort of impact must be the best thing you can do.
link |
00:23:15.960
I assumed running would be better than swimming and cycling,
link |
00:23:18.680
but it turned out that powerlifting
link |
00:23:20.160
was probably the best thing you could do.
link |
00:23:22.800
And I think once you understand how bones work,
link |
00:23:25.240
it became more clear, which is,
link |
00:23:27.520
powerlifting is really putting more of a shear force
link |
00:23:30.480
from the muscle via the tendon onto the bone.
link |
00:23:33.160
And that's what the bones are really sensing.
link |
00:23:35.080
They're sensing that shear force that's being applied
link |
00:23:37.840
through the bone, in a compressive way,
link |
00:23:39.760
depending on the bone, of course.
link |
00:23:41.480
And that's what's basically activating the osteoblasts,
link |
00:23:44.360
which are the cells that are allowing bone to be built.
link |
00:23:49.360
So this turns out to be probably more important for females,
link |
00:23:56.040
because how high you can get
link |
00:23:59.280
during that period of development,
link |
00:24:00.720
say till you're 20 or 25,
link |
00:24:02.600
basically sets your trajectory for the rest of your life.
link |
00:24:05.640
So where we get into real trouble is with patients who,
link |
00:24:08.480
for example, used large amounts of inhaled steroids
link |
00:24:12.220
during that period of their life,
link |
00:24:13.120
because let's say they had really bad asthma.
link |
00:24:15.360
Or patients who needed large amounts of corticosteroids
link |
00:24:18.200
for some other immune-related condition.
link |
00:24:20.240
So during their critical window of development,
link |
00:24:22.140
they were taking a drug that was impairing this process.
link |
00:24:25.660
So we have some patients like that in our practice,
link |
00:24:27.960
and that's just an enormous liability
link |
00:24:30.200
that we're working really hard to overcome,
link |
00:24:31.840
with nutrition, with hormones, with drugs, with training.
link |
00:24:37.240
And it's just something you have to be aware of.
link |
00:24:41.000
I wasn't aware that inhalants for asthma
link |
00:24:45.640
and things of that sort can impair bone mineral density.
link |
00:24:48.480
Yeah, they're steroid-based.
link |
00:24:50.080
Some of them, of course, are just beta agonists,
link |
00:24:51.800
and they're fine.
link |
00:24:52.640
So anything corticosterone-like, interesting.
link |
00:24:55.720
And then I always get asked this question,
link |
00:24:57.400
and I always reflexively want to say no,
link |
00:25:00.120
but I don't really know the answer, so I don't reply.
link |
00:25:02.760
What about topical corticosterone?
link |
00:25:05.520
People will put cortisone cream.
link |
00:25:06.740
To me, it seems almost inconceivable
link |
00:25:08.520
that it would have a systemic effect,
link |
00:25:09.900
but then again, what do I know?
link |
00:25:11.480
It's all docent and time-related.
link |
00:25:14.320
So if you're talking about like,
link |
00:25:16.040
I've got a little rash under my skin,
link |
00:25:17.960
I'm gonna put corticosteroids on, probably not.
link |
00:25:21.400
But certainly with enough of it put on,
link |
00:25:23.620
I mean, it is absorbed, so it could be an issue.
link |
00:25:26.920
But that's not typically what we're concerned with.
link |
00:25:29.080
I mean, we're mostly concerned with people
link |
00:25:30.560
that are taking even modest amounts of prednisone
link |
00:25:33.440
for months, years at a time,
link |
00:25:36.100
or like I said, kids that are using steroid inhalers
link |
00:25:39.880
for years and years and years.
link |
00:25:42.520
Again, I'm not suggesting that if your kid's
link |
00:25:44.120
on a steroid inhaler, they shouldn't be.
link |
00:25:45.640
You have to solve the most important problem,
link |
00:25:47.660
and if asthma is the most important problem, so be it.
link |
00:25:49.760
I think you just want to turn that into,
link |
00:25:51.640
okay, well, how much more imperative is it
link |
00:25:54.760
that our kid is doing things that are putting
link |
00:25:57.480
a high amount of stress on their bones
link |
00:25:59.920
and via their muscles to make sure
link |
00:26:01.720
that they're in that maximal capacity to build?
link |
00:26:05.000
Do you think that somebody in their 30s or 40s or 50s
link |
00:26:08.200
could still benefit from strength training
link |
00:26:09.920
in terms of bone mineral density and longevity
link |
00:26:13.240
as it relates to bone mineral density,
link |
00:26:15.760
given that there was this key window earlier,
link |
00:26:18.320
they might've missed that window?
link |
00:26:19.160
Oh yeah, no, no, this is essential for the rest of life
link |
00:26:21.100
because you're now trying to prevent the fall off.
link |
00:26:23.320
So basically the way it works is you're sort of,
link |
00:26:25.720
from birth to say 20, you're in growth.
link |
00:26:28.880
From 20 to 50, you plateau.
link |
00:26:31.200
At 50, men start to decline, but it's really small.
link |
00:26:34.780
Women start to decline, and it's precipitous.
link |
00:26:36.880
And it's related to the drop in estrogen
link |
00:26:38.760
associated with menopause or pre-menopause?
link |
00:26:40.880
Correct.
link |
00:26:41.720
And can we get into any of the broad contours
link |
00:26:46.120
of what that strength training looks like?
link |
00:26:47.840
We had Dr. Andy Galpin on the show.
link |
00:26:49.720
He talked a lot about ways to build strength
link |
00:26:51.320
versus hypertrophy versus endurance, et cetera.
link |
00:26:53.640
I think there's pretty good agreement across the fields
link |
00:26:56.100
of physiotherapy, et cetera, of physiology and medicine
link |
00:27:00.680
in terms of how to do that.
link |
00:27:01.500
But my understanding is fairly low repetition ranges.
link |
00:27:04.620
So this is anywhere from one to six repetitions,
link |
00:27:07.680
typically not aiming for a pump hypertrophy,
link |
00:27:11.960
that sort of thing, but heavy loads that are hard to move.
link |
00:27:14.640
80% of one repetition maximum or more
link |
00:27:18.020
done with long rest periods,
link |
00:27:21.840
two to three times a week type thing.
link |
00:27:24.000
Is that about right?
link |
00:27:24.840
Yeah, if you look at the literature on this,
link |
00:27:26.760
it's going to tell you,
link |
00:27:28.080
it's going to differentiate powerlifting from weightlifting.
link |
00:27:31.440
In other words, yeah, you do need to be kind of moving
link |
00:27:34.360
against a very heavy load.
link |
00:27:36.480
Now, again, that can look very different
link |
00:27:37.820
depending on your level of experience.
link |
00:27:40.480
I really like deadlifting.
link |
00:27:42.280
Now, I can count the number of days left in my life
link |
00:27:45.280
when I'm going to want to do sets over 400 pounds,
link |
00:27:48.300
but I'll pick and choose the days that I do.
link |
00:27:51.280
But I grew up doing those things.
link |
00:27:54.000
I'm comfortable with those movements.
link |
00:27:55.560
If I had a 60-year-old woman who's never lifted weights
link |
00:27:58.600
in her life who we now have to get lifting,
link |
00:28:02.400
we could get her to deadlift,
link |
00:28:03.700
but I think I wouldn't make perfect the enemy of good.
link |
00:28:07.800
I'd be happy to put her on a leg press machine
link |
00:28:09.760
and just get her doing that.
link |
00:28:13.200
It's not as pure a movement as a deadlift, but who cares?
link |
00:28:16.000
We can still put her at a heavy load for her
link |
00:28:18.560
and do so safely.
link |
00:28:21.680
Now, that said, there was a study that was done in Australia
link |
00:28:24.520
and hopefully we can find a link to it.
link |
00:28:27.600
There's a video on YouTube that actually kind of has the PI
link |
00:28:30.120
sort of walking through the results.
link |
00:28:31.480
I could send it to you.
link |
00:28:32.520
And it's just amazing.
link |
00:28:34.360
They took a group of older women.
link |
00:28:36.040
They looked like they were in their 60s or 70s
link |
00:28:37.640
who had never lifted weights in their life,
link |
00:28:39.320
who had osteopenia,
link |
00:28:41.040
and some probably already had osteoporosis.
link |
00:28:43.120
And they basically just put them
link |
00:28:44.120
on a strength training protocol.
link |
00:28:45.680
And it is remarkable to watch these women.
link |
00:28:47.720
They're doing good mornings.
link |
00:28:48.980
They're doing deadlifts.
link |
00:28:49.820
They're picking heavy things up off the ground.
link |
00:28:51.920
I think one woman was picking up,
link |
00:28:54.640
God, I want to say she was picking like 50, 60 kilos up
link |
00:28:58.740
off the ground.
link |
00:28:59.840
I mean, just staggering sums of weight
link |
00:29:01.560
for these women who have never done anything.
link |
00:29:03.600
And their bone health is improving at this age.
link |
00:29:07.320
So the goal, frankly, is to just never get to the point
link |
00:29:12.600
where you have to do this for the first time.
link |
00:29:16.200
Strength training is such an essential part of our existence
link |
00:29:18.960
that it's never too late to start,
link |
00:29:22.420
but you should never stop.
link |
00:29:24.560
I love that advice.
link |
00:29:25.400
Is it a systemic effect or a local effect?
link |
00:29:27.480
So for instance, let's say that,
link |
00:29:30.660
well, my mother is in her late 70s.
link |
00:29:33.800
She actually used to be really strong when we were kids.
link |
00:29:35.760
She could move this fish tank that was in my room
link |
00:29:37.740
long before I could move it.
link |
00:29:39.000
And she's really strong.
link |
00:29:41.640
Over the years, I wouldn't call her frail by any means,
link |
00:29:44.920
but I certainly think she could benefit
link |
00:29:46.800
from some strength training.
link |
00:29:48.940
Let's say she were to start doing some leg presses
link |
00:29:51.200
or start even with air squats
link |
00:29:52.760
and maybe work up to some pushups.
link |
00:29:55.040
Are the effects all local?
link |
00:29:56.080
Meaning if she were to just train her legs
link |
00:29:58.360
or just do pushups, would it only be the loads
link |
00:30:01.600
applied to the limbs and muscles and tissues
link |
00:30:04.580
that were involved?
link |
00:30:05.420
I think that's where the bulk of it is, yeah.
link |
00:30:07.240
So you need to train the whole body, essentially.
link |
00:30:09.120
Yeah, now keep in mind,
link |
00:30:10.260
the diagnosis of osteopenia and osteoporosis
link |
00:30:12.960
is based on only three locations,
link |
00:30:15.640
the left hip, the right hip, and the lumbar spine.
link |
00:30:18.200
So that's just the convention
link |
00:30:22.000
by which we make the diagnosis.
link |
00:30:24.240
And I think part of that has to do with
link |
00:30:25.880
that's where the majority of the insults occur.
link |
00:30:27.960
Now, not all of the insults.
link |
00:30:29.400
I've seen people that have,
link |
00:30:31.460
because of horrible bone density,
link |
00:30:33.160
they're fracturing ankles and tibia, fibula,
link |
00:30:36.780
like they're having low-tib fib fractures just walking.
link |
00:30:39.960
So clearly bone density outside of those regions
link |
00:30:42.320
does matter, but much of it is really focused on,
link |
00:30:46.200
and by the way, you fall, you break a wrist.
link |
00:30:48.000
So this is a systemic issue,
link |
00:30:51.040
but the majority of the response is a local response
link |
00:30:54.160
because it really comes down to putting a load
link |
00:30:56.920
directly on that bone and then having that bone in kind
link |
00:31:00.080
respond by laying down more bone.
link |
00:31:03.100
Before we continue with today's discussion,
link |
00:31:05.320
I'd like to just briefly acknowledge our sponsor,
link |
00:31:07.420
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link |
00:31:10.640
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link |
00:31:12.880
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00:31:15.360
that also has adaptogens and digestive enzymes.
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00:31:18.400
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link |
00:31:21.120
so I'm delighted that they're sponsoring the podcast.
link |
00:31:23.560
The reason I started taking Athletic Greens
link |
00:31:25.160
and the reason I still drink Athletic Greens twice a day
link |
00:31:28.120
is that it supplies total foundational coverage
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00:31:31.020
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link |
00:31:32.420
and it supplies important nutrients that I need
link |
00:31:35.360
to support my gut microbiome.
link |
00:31:36.920
The gut microbiome, as many of you know,
link |
00:31:38.640
supports the immune system.
link |
00:31:39.760
It also supports the so-called gut-brain axis,
link |
00:31:41.800
which is vital for mood, for energy levels,
link |
00:31:44.160
for regulating focus, and many other features
link |
00:31:46.480
of our mental health and physical health
link |
00:31:47.960
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link |
00:31:50.480
in any endeavors we might be involved in.
link |
00:31:52.600
If you'd like to try Athletic Greens,
link |
00:31:54.000
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link |
00:31:56.680
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00:31:58.280
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link |
00:31:59.960
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link |
00:32:03.840
And of course, vitamin D3K2 are vital
link |
00:32:06.080
for all sorts of things like hormone health
link |
00:32:08.160
and metabolic health and K2 for cardiovascular health
link |
00:32:10.560
and calcium regulation.
link |
00:32:11.740
Again, you can go to athleticgreens.com slash Huberman
link |
00:32:14.960
to claim that special offer.
link |
00:32:16.680
You mentioned falling and the problems with falling
link |
00:32:18.840
and breaking things and mortality related to that.
link |
00:32:21.800
I wonder whether or not there are also
link |
00:32:24.060
health-related effects of just having weak bones
link |
00:32:26.920
that are not just about falling and breaking a bone
link |
00:32:29.480
and dying a year later.
link |
00:32:31.460
Even though that's obviously very severe,
link |
00:32:33.720
because I think when people hear about that,
link |
00:32:35.000
some people might think, well, I'll just be more careful.
link |
00:32:37.360
I'll just move more slowly.
link |
00:32:38.300
I'll sit in a wheelchair if I need to,
link |
00:32:40.880
even though I might be able to walk
link |
00:32:42.280
if it keeps me from falling.
link |
00:32:43.440
Some people, I think, adopt that mentality.
link |
00:32:46.640
What are some of the benefits of having
link |
00:32:49.040
high bone mineral density for men and women
link |
00:32:51.840
that are perhaps independent of risk of injury?
link |
00:32:55.880
Well, I think it's actually the inverse
link |
00:32:57.180
of what you just said, right?
link |
00:32:58.240
It's sort of like, you have to sort of
link |
00:33:01.900
be able to articulate what it is you want
link |
00:33:04.600
in your marginal decade.
link |
00:33:05.740
So we use this thing in our practice
link |
00:33:07.420
called the marginal decade.
link |
00:33:08.800
Marginal decade is the last decade of your life.
link |
00:33:10.880
So everyone will have a marginal decade.
link |
00:33:12.800
That's the only thing I can tell you
link |
00:33:14.000
with absolute certainty, right?
link |
00:33:16.420
I believe you.
link |
00:33:17.260
There's no immortality.
link |
00:33:18.600
There's no hidden elixir that's gonna help us live
link |
00:33:20.720
to be, you know, whatever.
link |
00:33:22.200
I mean, we're all gonna be in our last decade at some point.
link |
00:33:26.400
And outside of people who die suddenly
link |
00:33:28.280
or through an accident, most of us know
link |
00:33:31.320
when we're in that marginal decade.
link |
00:33:33.000
You might not know the day you enter it,
link |
00:33:34.520
but most people who are old enough,
link |
00:33:37.840
if you tell them, are you in the last decade of your life?
link |
00:33:39.800
They probably have a sense that they are.
link |
00:33:41.960
So I think the exercise that we like to go through
link |
00:33:44.940
with our patients very early on
link |
00:33:47.560
is have them in exquisite detail,
link |
00:33:51.700
more detail than they've ever considered.
link |
00:33:53.320
So we have to prompt them with like 50 questions,
link |
00:33:57.040
lay out what their marginal decade should look like.
link |
00:34:00.620
Wow.
link |
00:34:01.460
That's a serious exercise.
link |
00:34:02.720
It's a very serious exercise, right?
link |
00:34:04.220
Like what, tell me everything that is going to happen
link |
00:34:06.840
in your marginal decade.
link |
00:34:07.680
I don't know when it's gonna be, Andrew.
link |
00:34:08.760
It could be 87 to 97 if we're doing well, right?
link |
00:34:12.440
It might be 79 to 89.
link |
00:34:14.040
I don't know.
link |
00:34:14.880
But it would really be a very nuanced
link |
00:34:19.520
exploration of that topic.
link |
00:34:21.660
And I think until you do that,
link |
00:34:23.700
all of this other stuff is just abstract
link |
00:34:26.720
and kind of nonsense.
link |
00:34:28.680
You know, until a person can tell you
link |
00:34:30.760
what it is that they want to be doing in that last decade,
link |
00:34:34.760
you can't design a program to get them there.
link |
00:34:37.940
I mean, think about it.
link |
00:34:39.000
You know, someone wants to do an Ironman,
link |
00:34:41.800
we take it for granted that we know what the objective is.
link |
00:34:44.880
I have to be able to swim two and a half miles.
link |
00:34:46.520
I have to be able to get out, take my wetsuit off,
link |
00:34:48.480
hop on my bike, ride 112 miles, get off my bike,
link |
00:34:51.760
take the bike shoes off, put the run shoes on,
link |
00:34:53.520
run 26.2 miles, like we get it.
link |
00:34:55.120
We know what the objective is.
link |
00:34:56.480
And only by knowing that can you train.
link |
00:34:58.960
Can you imagine if I said to you,
link |
00:35:01.480
Andrew, I'm going to have you do an athletic event
link |
00:35:03.600
in a year, start training.
link |
00:35:05.580
I'm not gonna tell you what it is, just do it.
link |
00:35:08.440
It could be playing basketball.
link |
00:35:10.440
You know, it could be swimming to Catalina Island.
link |
00:35:12.840
It could be running a hundred miles.
link |
00:35:15.120
You wouldn't be able to do it.
link |
00:35:16.260
So similarly, if we don't know what our marginal decade
link |
00:35:18.760
is meant to be, there's no way to train for it.
link |
00:35:22.200
Do you think this is a good exercise for anyone
link |
00:35:24.440
and everyone to do on their own, regardless of age here?
link |
00:35:26.880
I'm hearing this and I'm thinking,
link |
00:35:28.600
I need to think about when my last decade might be
link |
00:35:31.320
and what I want that to look like.
link |
00:35:33.120
Absolutely.
link |
00:35:33.960
I mean, when I say we do it with our patients,
link |
00:35:34.920
that's only because that's the population I work with,
link |
00:35:36.620
but there's simply no reason
link |
00:35:37.880
everybody shouldn't be going through this exercise.
link |
00:35:40.120
And then you sort of back script from there,
link |
00:35:43.080
figure out what people should be doing
link |
00:35:44.200
given their current health status.
link |
00:35:45.560
Exactly right, we call it backcasting.
link |
00:35:47.280
So the first step we do is once we've really delineated
link |
00:35:50.580
what the objective function looks like, we then say,
link |
00:35:53.520
okay, how do you break down that
link |
00:35:56.220
into metrics that we can measure?
link |
00:36:00.200
So, you know, you described doing a whole bunch of things.
link |
00:36:02.600
Okay, just to let you know, to do that will require
link |
00:36:05.440
a VO2 max of 30 milliliters of oxygen
link |
00:36:09.240
per minute per kilogram.
link |
00:36:11.160
And the person will say, okay, what does that mean?
link |
00:36:14.080
We'll say, well, that's a measure
link |
00:36:15.400
of your maximal uptake of oxygen.
link |
00:36:18.320
And that declines at about 8% to 10% per decade.
link |
00:36:22.840
So if you have to be at 30,
link |
00:36:24.960
and let's just assume you're gonna be doing that at 90,
link |
00:36:27.660
so what do you need to be at 80, 70, 60, 50?
link |
00:36:31.000
Okay, here's what it would need to be at 50.
link |
00:36:33.180
Okay, what are you now?
link |
00:36:34.520
Ah, there's a big gap.
link |
00:36:36.040
You're below where you need to be now.
link |
00:36:37.280
So you're obviously higher than 30 now,
link |
00:36:40.680
but if you're only at 42 now,
link |
00:36:42.900
and you need to be at 30 in 40 years,
link |
00:36:45.920
you're not gonna cut it.
link |
00:36:47.100
You have to be a lot fitter.
link |
00:36:48.680
Okay, now let's do the same exercise
link |
00:36:50.640
around strength and stability.
link |
00:36:52.880
And without exception, most people,
link |
00:36:54.840
when they do this exercise, will find out
link |
00:36:56.460
they're well below where they need to be.
link |
00:36:58.860
So the gravity of aging is more vicious than people realize,
link |
00:37:04.360
and therefore the height of your glider
link |
00:37:06.360
needs to be much higher than you think it is
link |
00:37:08.880
when you're our age if you wanna be able to do the things
link |
00:37:12.440
we probably wanna be able to do when we're 90.
link |
00:37:15.100
I absolutely love this approach.
link |
00:37:17.120
I've never done it in terms of my health.
link |
00:37:18.720
I've always thought about what I wanna accomplish
link |
00:37:20.200
in the next three to six months or next year or so.
link |
00:37:22.480
And by the way, that's a great approach.
link |
00:37:23.940
That's forecasting.
link |
00:37:24.880
Forecasting is fantastic.
link |
00:37:26.160
Forecasting is really good at short-term things.
link |
00:37:29.260
It doesn't work for long-term things.
link |
00:37:31.360
Long-term, you have to do backcasting.
link |
00:37:33.840
This backcasting approach really appeals to me
link |
00:37:35.720
because in my career, well, I never anticipate, excuse me,
link |
00:37:38.400
I never anticipated I'd be podcasting,
link |
00:37:41.320
but that's what I did.
link |
00:37:42.600
At some point as an undergraduate, I looked,
link |
00:37:44.480
professors, I'm like, that looks like a pretty good life.
link |
00:37:46.480
They seem pretty happy.
link |
00:37:47.320
I talked to a few of them and then I figured out
link |
00:37:49.400
what I need to do at each stage
link |
00:37:50.600
in order to get to that next rung on the ladder
link |
00:37:53.800
and just kind of figured it out
link |
00:37:56.280
in a backcasting kind of way, as you refer to it.
link |
00:37:59.280
I think this is incredibly useful
link |
00:38:00.960
because it puts all the questions about blood work
link |
00:38:03.380
and how often to get blood work
link |
00:38:04.480
and what to measure in a really nice context
link |
00:38:07.120
that's highly individualized.
link |
00:38:08.680
I've never heard of this before, so.
link |
00:38:10.960
And I should give a nod to Annie Duke.
link |
00:38:12.740
I used to always refer to this as reverse engineering,
link |
00:38:15.800
but in Annie Duke's book,
link |
00:38:17.200
she wrote about this exact thing and called it backcasting,
link |
00:38:19.760
and I was like, I like the term backcasting better.
link |
00:38:22.320
I think it's more intuitive than reverse engineering.
link |
00:38:24.480
Yeah, there's a real genius to it,
link |
00:38:25.960
and I think it, because it sets so many things
link |
00:38:28.000
into the appropriate bins and trajectories.
link |
00:38:30.800
I've heard you talk before about some of the prime movers
link |
00:38:33.920
for longevity and all-risk mortality.
link |
00:38:38.400
And I'd love for you to review a little bit of that for us.
link |
00:38:42.280
I think we all know that we shouldn't smoke
link |
00:38:44.040
because it's very likely that we'll die earlier
link |
00:38:46.520
if we smoke nicotine.
link |
00:38:48.520
I'm neither a marijuana nor a nicotine smoker,
link |
00:38:50.960
so I feel unstable ground there,
link |
00:38:52.920
but anytime we see smoking nowadays,
link |
00:38:54.800
people really want to distinguish
link |
00:38:56.400
between cannabis and nicotine.
link |
00:38:58.880
So I am curious about any differences there
link |
00:39:00.920
in terms of impact on longevity, but in that context,
link |
00:39:06.400
what are the things that anyone and everyone can do,
link |
00:39:09.960
should do to live longer, basically?
link |
00:39:13.800
How long you got?
link |
00:39:16.120
Well, you tell me.
link |
00:39:16.960
You tell me.
link |
00:39:19.560
I'd like to live to be,
link |
00:39:20.680
I'd like my final decade to be between 90 and 100.
link |
00:39:23.400
Oh, no, I meant how long do you, but yeah, yeah, yeah.
link |
00:39:25.720
And will we spend from now until you're 90
link |
00:39:27.480
talking about this?
link |
00:39:28.320
Well, there's a risk of that,
link |
00:39:29.240
but top contour is fine.
link |
00:39:30.960
I know you've done a lot of content on this
link |
00:39:32.440
and we will give people links
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00:39:33.760
to some of that more in-depth content,
link |
00:39:35.640
but let's say we were on a short flight
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00:39:38.360
from here to San Diego, we're in Los Angeles now,
link |
00:39:42.240
and we've got takeoff and landing,
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00:39:43.920
and we don't want to kink our neck too much
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00:39:45.640
by doing this thing.
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00:39:46.480
So if I just said, hey, give me the extended version
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00:39:50.200
of the three by five card, what does that look like?
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00:39:55.080
So let's start with a couple of the things
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00:39:56.840
that you've already highlighted, so smoking.
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00:39:58.400
How much does smoking increase your risk
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00:40:00.440
of all-cause mortality?
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00:40:01.840
And the reason we like to talk about what's called ACM
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00:40:04.160
or all-cause mortality is it's really agnostic
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00:40:07.480
to how you die, and that doesn't always make sense.
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00:40:10.680
I mean, if you're talking about a very specific intervention
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00:40:14.040
like an anti-cancer therapeutic,
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00:40:15.800
you really care about cancer-specific mortality
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00:40:17.800
or heart-specific mortality,
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00:40:19.840
but when we talk about these sort of broad things,
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00:40:21.440
we like to talk about ACM.
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00:40:22.800
So using smoking, smoking is approximately
link |
00:40:26.080
a 40% increase in the risk of ACM.
link |
00:40:29.280
And what does that translate to?
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00:40:30.560
And that means I'm shortening my life by 40%?
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00:40:35.080
No, it means at any point in time,
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00:40:36.680
there's a 40% greater risk that you're going to die
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00:40:39.720
relative to a non-smoker and a never-smoker.
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00:40:42.000
Yeah, yeah, so it's important to distinguish.
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00:40:43.440
It doesn't mean your lifespan is going to be 40% less.
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00:40:46.120
It means at any point in time standing there,
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00:40:47.720
your risk of death is 40% higher.
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00:40:50.560
And by the way, that'll catch up with you, right?
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00:40:52.340
At some point, that catches up.
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00:40:54.720
High blood pressure, it's about a 20 to 25% increase
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00:40:59.040
in all-cause mortality.
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00:41:01.160
You take something really extreme
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00:41:02.440
like end-stage kidney disease.
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00:41:04.200
So these are patients that are on dialysis
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00:41:06.520
waiting for an organ.
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00:41:08.240
And again, there's a confounder there
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00:41:09.400
because what's the underlying condition
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00:41:11.800
that leads you to that?
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00:41:12.620
It's profound hypertension, significant type 2 diabetes
link |
00:41:16.320
that's been uncontrolled.
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00:41:17.840
That's enormous.
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00:41:18.680
That's about 175% increase in ACM.
link |
00:41:23.060
So the hazard ratio is like 2.75.
link |
00:41:26.840
Type 2 diabetes is probably about a 1.25 as well.
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00:41:30.440
So 25% increase.
link |
00:41:32.240
So now the question is like, how do you improve?
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00:41:33.680
So what are the things that improve those?
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00:41:35.680
So now here we do this by comparing low to high achievers
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00:41:39.780
and other metrics.
link |
00:41:40.620
So if you look at low muscle mass versus high muscle mass,
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00:41:45.500
what is the improvement?
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00:41:47.800
And it's pretty significant.
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00:41:49.120
It's about 3x.
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00:41:50.580
So if you compare low muscle mass people to high muscle mass
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00:41:53.360
people as they age,
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00:41:54.760
the low muscle mass people have about a 3x hazard ratio
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00:41:58.080
or a 200% increase in all-cause mortality.
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00:42:01.140
Now, if you look at the data more carefully,
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00:42:03.280
you realize that it's probably less the muscle mass
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00:42:07.600
fully doing that,
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00:42:09.280
and it's more the high association with strength.
link |
00:42:12.200
And when you start to tease out strength,
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00:42:15.360
you can realize that strength could be probably 3.5x
link |
00:42:18.700
as a hazard ratio,
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00:42:19.620
meaning about 250% greater risk
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00:42:24.180
if you have low strength to high strength.
link |
00:42:26.640
And high strength is the ability to move loads
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00:42:29.200
at 80 to 90% of one repetition.
link |
00:42:31.400
It's all defined by given studies.
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00:42:32.920
So the most common things that are used are actually,
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00:42:36.720
they're used for the purposes of experiments
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00:42:39.260
that make it easy to do.
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00:42:40.360
And I don't even think they're the best metrics.
link |
00:42:42.120
So they're usually using like grip strength,
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00:42:45.320
leg extensions, and like wall sits, squats,
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00:42:49.380
things like that.
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00:42:50.360
So how long can you sit in a squatted position
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00:42:53.020
at 90 degrees without support
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00:42:54.640
would be a great demonstration of quad strength,
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00:42:56.840
a leg extension,
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00:42:59.080
how much weight can you hold for how long
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00:43:00.880
relative to body weight, things like that.
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00:43:03.320
We have a whole strength program
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00:43:04.980
that we do with our patients.
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00:43:06.160
We have something called the SMA.
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00:43:07.240
So it's the strength metrics assessment.
link |
00:43:08.840
And we put them through 11 tests that are really difficult,
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00:43:13.880
like a dead hang is one of them.
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00:43:14.960
Like how long can you dead hang your body weight,
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00:43:16.640
stuff like that.
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00:43:17.640
So we're trying to be more granular in that insight,
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00:43:20.840
but tie it back to these principles.
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00:43:23.340
If you look at cardio respiratory fitness,
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00:43:25.360
it's even more profound.
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00:43:26.880
So if you look at people who are in the bottom 25%
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00:43:30.680
for their age and sex in terms of VO2 max,
link |
00:43:33.640
and you compare them to the people
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00:43:36.240
that are just at the 50th to 75th percentile,
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00:43:40.640
you're talking about a two X difference roughly
link |
00:43:43.280
in the risk of ACM.
link |
00:43:45.920
If you compare the bottom 25% to the top 2.5%,
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00:43:50.040
so you're talking about bottom quarter to the elite
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00:43:53.160
for a given age, you're talking about five X,
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00:43:57.880
400% difference in all cause mortality.
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00:44:01.280
That's probably the single strongest association
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00:44:03.360
I've seen for any modifiable behavior.
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00:44:05.940
Incredible.
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00:44:06.780
So when you say elite, these are people
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00:44:08.960
that are running marathons at a pretty rapid clip?
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00:44:11.240
Not necessarily.
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00:44:12.080
It's just like what the VO2 max is for that.
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00:44:13.820
Like my VO2 max would be in the elite for my age group.
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00:44:17.480
My VO2 max, but again, I'm training very deliberately
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00:44:20.560
to make sure that it's in that.
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00:44:21.640
So I wouldn't consider myself elite at anything anymore,
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00:44:24.840
but I still maintain a VO2 max that is elite for my age.
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00:44:28.160
I consider you an elite physician
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00:44:30.280
and possibly an end guy all around.
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00:44:33.520
But true.
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00:44:36.440
But in terms of, okay, so for the-
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00:44:38.800
But the point is like you don't have to be
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00:44:40.000
a world-class athlete to be elite here, yeah.
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00:44:41.960
Got it.
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00:44:43.560
So maybe we could talk a little bit about the specifics
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00:44:45.440
around the training to get into the top two tiers there,
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00:44:49.740
because it seems that those are enormous positive effects
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00:44:52.700
of cardiovascular exercise,
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00:44:54.560
far greater than the sorts of numbers that I see around,
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00:44:58.280
let's just say supplement A or supplement B.
link |
00:45:00.520
And that's, you know,
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00:45:01.560
like this is my whole pet peeve in life, right?
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00:45:03.900
It's like, I just can't get enough of the machinating
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00:45:07.640
and arguing about this supplement versus that supplement.
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00:45:11.400
And I feel like you shouldn't be having those arguments
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00:45:15.320
until you have your exercise house in order.
link |
00:45:18.600
You know, you shouldn't be arguing about
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00:45:22.040
this nuance of your carnivore diet
link |
00:45:24.060
versus this nuance of your paleo diet
link |
00:45:25.960
versus this nuance of your vegan diet,
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00:45:28.440
like until you can deadlift your body weight for 10 reps.
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00:45:31.860
Like then you can come and talk about those things
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00:45:33.700
or something like, let's just go up with some metrics.
link |
00:45:35.280
Like until your VO2 max is at least to the 75th percentile
link |
00:45:39.760
and you're able to dead hang for at least a minute
link |
00:45:42.280
and you're able to wall sit for at least two,
link |
00:45:44.160
like we could rattle off
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00:45:45.000
a bunch of relatively low-hanging fruit.
link |
00:45:48.840
I wish there was a rule that said,
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00:45:49.840
like you couldn't talk about anything else, health related.
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00:45:52.480
We can make that rule.
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00:45:53.880
No one will listen to it.
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00:45:54.840
I don't know about that.
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00:45:55.680
We can make whatever rules we want.
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00:45:56.840
We can call it Atiyah's rule.
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00:45:58.600
One thing I've done before in this podcast
link |
00:46:00.160
and on social media is just borrowing
link |
00:46:02.000
from the tradition in science,
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00:46:03.240
which is it's inappropriate to name something
link |
00:46:05.080
after yourself unless you were a scientist before 1950.
link |
00:46:08.820
But it's totally appropriate to name things
link |
00:46:10.320
after other people's.
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00:46:11.160
I'm going to call it Atiyah's rule
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00:46:12.480
until you can do the following things.
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00:46:15.360
Don't talk about supplements.
link |
00:46:16.200
Please refrain from talking about supplements and nutrition.
link |
00:46:18.200
There it is.
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00:46:19.040
Hereafter, thought of, referred to,
link |
00:46:21.000
and referenced as Atiyah's rule.
link |
00:46:23.320
I coined the phrase, not him.
link |
00:46:24.640
So there's no ego involved, but it is now Atiyah's rule.
link |
00:46:28.000
Watch out, hashtag Atiyah's rule.
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00:46:30.160
Oh God.
link |
00:46:31.360
Wikipedia entered Atiyah's rule.
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00:46:33.360
In all seriousness, and I am serious about that,
link |
00:46:36.280
dead hang for about a minute.
link |
00:46:37.840
Seems like a really good goal for a lot of people,
link |
00:46:40.440
at least.
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00:46:41.280
That's our goal.
link |
00:46:42.120
I think we have a minute and a half
link |
00:46:43.320
is the goal for a 40-year-old woman.
link |
00:46:45.000
Two minutes is the goal for a 40-year-old man.
link |
00:46:46.820
So we adjust them up and down based on age and gender.
link |
00:46:51.460
Great.
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00:46:52.300
And then the wall sit, what are some numbers?
link |
00:46:53.800
We don't use a wall sit.
link |
00:46:54.720
We do just a straight squat, air squat, at 90 degrees.
link |
00:46:58.820
And I believe two minutes is the standard
link |
00:47:01.040
for both men and women at 40.
link |
00:47:02.640
Great.
link |
00:47:03.480
And then, because for some people,
link |
00:47:05.120
thinking in terms of EO2 max is a little more complicated.
link |
00:47:07.360
They might not have access to the equipment
link |
00:47:08.760
or to measure it, et cetera.
link |
00:47:12.000
What can we talk about, think about
link |
00:47:13.520
in terms of cardiovascular?
link |
00:47:14.560
So run a mile at seven minutes or less,
link |
00:47:17.200
eight minutes or less?
link |
00:47:18.020
That's a good question.
link |
00:47:18.860
So there are really good VO2 max estimators online,
link |
00:47:22.660
and you can plug in your activity du jour.
link |
00:47:26.200
So be it a bike, run, or rowing machine,
link |
00:47:29.320
and it can give you a sense of that.
link |
00:47:31.440
And I used to know all of those,
link |
00:47:34.440
but now that I just actually do the testing,
link |
00:47:36.300
I don't recall them, but it's exactly that line of thinking.
link |
00:47:39.400
Like, can you run a mile in this time?
link |
00:47:41.320
If you can, your VO2 max is approximately this.
link |
00:47:44.200
Great.
link |
00:47:45.040
And I think somewhere in my podcast realm,
link |
00:47:49.440
I've got all those charts posted of like,
link |
00:47:52.740
this is by age, by sex.
link |
00:47:56.200
This is what the VO2 max is in each of those buckets.
link |
00:47:59.000
Terrific.
link |
00:47:59.840
We'll provide links to those.
link |
00:48:01.080
We'll have our people find those links.
link |
00:48:02.880
And then you mentioned deadlifting body weight 10 times.
link |
00:48:05.680
I just made that one up.
link |
00:48:06.880
That's not one that we include, but something like that.
link |
00:48:10.960
We use farmer carries.
link |
00:48:12.400
So we'll say for a male,
link |
00:48:14.200
you should be able to farmer carry your body weight for,
link |
00:48:17.480
I think we have two minutes.
link |
00:48:19.280
So that's half your body weight in each hand.
link |
00:48:21.920
You should be able to walk with that for two minutes.
link |
00:48:24.880
For women, I think we're doing 75% of body weight
link |
00:48:27.240
or something like that, yeah.
link |
00:48:28.440
Great, I love it.
link |
00:48:30.500
As indirect measures of how healthy we are
link |
00:48:33.880
and how long we're going to live.
link |
00:48:34.920
It's basically grip strength, it's mobility.
link |
00:48:37.420
I mean, again, walking with that much weight
link |
00:48:39.120
for some people initially is really hard.
link |
00:48:42.280
We use different things like vertical jump,
link |
00:48:43.960
ground contact time if you're jumping off a box,
link |
00:48:45.980
things like that.
link |
00:48:46.820
So it's really trying to capture,
link |
00:48:48.800
and it's an evolution, right?
link |
00:48:50.040
I think the test is going to get only more and more involved
link |
00:48:53.160
as we get involved, because it took us about a year.
link |
00:48:56.440
Beth Lewis did the majority of the work to develop this.
link |
00:48:59.720
Beth runs our strength and stability program in the practice
link |
00:49:02.920
and basically I just tasked her with like,
link |
00:49:04.680
hey, go out to the literature and come up with
link |
00:49:07.120
all of the best movements that we think are proxies
link |
00:49:09.480
for what you need to be like the most kick-ass,
link |
00:49:12.800
you know, what we call centenarian decathlete,
link |
00:49:14.520
which is the person living in their marginal decade
link |
00:49:16.420
at the best.
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00:49:17.600
Well, what I'm about to say is certainly a mechanistic leap,
link |
00:49:20.420
but if you look at the literature on
link |
00:49:22.920
exercise-related neurogenesis in mice
link |
00:49:26.240
or brain atrophy or brain hypertrophy, et cetera,
link |
00:49:30.840
in animal models, it's very clear that the best way
link |
00:49:33.300
to get a nervous system to atrophy, to lose neurons,
link |
00:49:36.240
shrink neurons, or lose connections between neurons,
link |
00:49:39.820
is to stop that animal from moving
link |
00:49:42.040
or to de-enrich its environment,
link |
00:49:44.560
deprive it of some sensory input or multiple sensory inputs,
link |
00:49:47.460
and the best way to enhance the size of neurons,
link |
00:49:50.880
the number of connections between neurons,
link |
00:49:52.120
and maybe even the number of neurons
link |
00:49:53.360
is to enrich its environment and get it moving
link |
00:49:55.200
while enriching that environment.
link |
00:49:56.800
You know, Andrew, I think it's very difficult for me
link |
00:49:59.160
to say that the same is not true in humans.
link |
00:50:00.840
And so the first time this became clear to me
link |
00:50:02.560
was in 2014, I had an analyst, Dan Pelletier,
link |
00:50:07.000
and I said, Dan, I'm gonna give you a project
link |
00:50:10.400
that is vexing me to no end, which is
link |
00:50:13.240
I want you to look at all of the literature that we have,
link |
00:50:17.640
both mechanistic and clinical trial data,
link |
00:50:21.240
that talks about Alzheimer's prevention.
link |
00:50:24.520
And I wanna know every single type of input,
link |
00:50:28.000
and I wanna have a clear sense of via what mechanism
link |
00:50:31.440
does it offer, what mode of protection.
link |
00:50:33.840
And it took Dan, and this was obviously,
link |
00:50:36.240
we iterated a lot on this together,
link |
00:50:39.640
and he came back with kind of an amazing presentation
link |
00:50:42.940
that took, I don't know, nine months to a year of work.
link |
00:50:46.920
And what amazed me was when he came back to it,
link |
00:50:49.560
he said, the single greatest efficacy
link |
00:50:51.880
we can point to is exercise.
link |
00:50:53.920
And I was like, Dan, that's gotta be nonsense, dude.
link |
00:50:56.540
There's no way exercise is the single best thing
link |
00:50:59.300
you can do for the brain.
link |
00:51:00.320
There has to be some drug you've missed.
link |
00:51:02.480
There has to be some other thing that you've missed.
link |
00:51:06.380
And he's like, no, this is hands down the best thing,
link |
00:51:10.000
because it's not just what it's doing to BDNF,
link |
00:51:12.680
it's not just what it's doing to vascular endothelium,
link |
00:51:15.060
it's not just what it's doing to glucose disposal
link |
00:51:16.720
and insulin signaling, all these things.
link |
00:51:18.200
It's just touching every aspect of the brain.
link |
00:51:22.240
And I was very skeptical for about six months,
link |
00:51:24.500
kind of really pushed on him, and I was like,
link |
00:51:26.880
I think you're missing something, Dan,
link |
00:51:28.120
I think you're missing something.
link |
00:51:29.320
And then finally, in the end, looped in Richard Isaacson,
link |
00:51:31.480
who's a neurologist that we work with really closely
link |
00:51:33.360
on Alzheimer's prevention, and ultimately,
link |
00:51:35.880
it turned into a paper that we wrote, basically,
link |
00:51:38.520
about this topic, and a few others.
link |
00:51:41.400
Because again, I thought, are you sure it's not EPA and DHA?
link |
00:51:44.600
That's gotta have a bigger impact.
link |
00:51:46.000
And again, there are a lot of things that I think do matter,
link |
00:51:49.040
and there's a whole host of things that we do
link |
00:51:50.800
for Alzheimer's prevention,
link |
00:51:52.480
but I think you're absolutely right.
link |
00:51:53.960
There's not one thing that I'll tell patients
link |
00:51:55.960
is more important than exercising.
link |
00:51:58.240
And by the way, it's not the sort of
link |
00:52:01.440
pathetic recommendations that are made.
link |
00:52:03.520
Like, you have to exercise a lot more
link |
00:52:06.200
if you wanna get this maximum benefit.
link |
00:52:07.700
You will get, you know, the maximum benefit
link |
00:52:10.020
comes going from nothing to something.
link |
00:52:12.120
So if you go from being completely sedentary
link |
00:52:14.800
to doing 15 met hours per week,
link |
00:52:18.000
you'll get probably a 50% reduction in risk.
link |
00:52:22.440
So a met hour, a met, just for people who don't know,
link |
00:52:25.160
is a metabolic equivalent.
link |
00:52:26.560
So we're exerting about 1.3 mets sitting here talking.
link |
00:52:29.920
If we were sitting here being quiet,
link |
00:52:31.180
it would be about one met.
link |
00:52:33.080
You know, walking really briskly would be about five mets.
link |
00:52:36.820
So 15 met hours per week would be
link |
00:52:40.200
three one-hour really brisk walks.
link |
00:52:42.520
That's not a lot of work.
link |
00:52:44.440
But just going from doing nothing to doing that
link |
00:52:47.600
would give you 50% of the benefit
link |
00:52:50.320
that you would get from going all the way.
link |
00:52:53.040
Now, again, I think I'm personally a little skeptical
link |
00:52:56.920
of how much that's,
link |
00:52:58.800
I think it's probably a bit less than that.
link |
00:52:59.980
I think there's more upside than people appreciate.
link |
00:53:02.720
But the studies, I don't think, can truly capture that.
link |
00:53:05.160
But look, you know, there's no reason
link |
00:53:09.260
to not be exercising more than that
link |
00:53:11.160
and capture more benefit,
link |
00:53:13.040
even though the rate at which you accrue it is less.
link |
00:53:15.600
And it also speaks to the healthspan side of this,
link |
00:53:17.760
which is not necessarily captured in those data.
link |
00:53:19.840
The healthspan gets back to the functional piece
link |
00:53:21.600
we opened with, which is what do you want to be doing
link |
00:53:23.880
in your marginal decade?
link |
00:53:24.920
Do you want to be able to pick up a great grandkid
link |
00:53:26.840
if they come running at you?
link |
00:53:28.160
Do you want to be able to get up off the floor?
link |
00:53:29.880
Do you want to be able to play on the floor with a kid
link |
00:53:31.520
and then get up on your own?
link |
00:53:33.800
And I think most people are thinking final years of life,
link |
00:53:36.800
they're trying to think, you know,
link |
00:53:37.620
how can they take themselves to the bathroom?
link |
00:53:40.080
They're thinking, how can they sit up off the toilet?
link |
00:53:43.040
I mean, you've got really basic,
link |
00:53:44.880
vegetative-type functions, right, at some level.
link |
00:53:48.760
I love this, again, this idea of marginal decade
link |
00:53:51.280
and using that as a way to backcast
link |
00:53:53.680
to actual methods and behaviors and protocols
link |
00:53:59.160
that one should be doing on a daily basis.
link |
00:54:02.120
I'll use ANIC data, as it's now called,
link |
00:54:05.160
to cite just, I know, three Nobel Prize winners,
link |
00:54:08.280
which doesn't mean anything
link |
00:54:09.520
except that they did beautiful work,
link |
00:54:10.800
but the point is that they're all in their 90s.
link |
00:54:12.880
So I'll name them
link |
00:54:14.120
because I'm complimenting them for what they've done,
link |
00:54:16.880
not just their work, but what I'm about to describe.
link |
00:54:18.620
So Eric Kandel at Columbia,
link |
00:54:21.360
Nobel Prize-winning for work on memory,
link |
00:54:23.380
Torrance and Wiesel, work on neuroplasticity,
link |
00:54:25.380
and then Richard Axel, who's also at Columbia,
link |
00:54:28.620
Nobel Prize-winning work for molecular biology of smell
link |
00:54:30.800
and molecular biology generally.
link |
00:54:33.440
All three of them still alive.
link |
00:54:35.780
Richard's younger compared to the other two.
link |
00:54:38.160
All three of them either swim, jog, or play tennis,
link |
00:54:41.480
or racquetball, I think is Richard's thing,
link |
00:54:43.780
multiple times per week.
link |
00:54:45.160
Eric was, they're all cognitively still extremely sharp,
link |
00:54:48.880
still interested in the arts, doing science,
link |
00:54:50.860
curious about science, running laboratories,
link |
00:54:52.740
writing books, going on podcasts.
link |
00:54:54.240
I mean, it's incredible.
link |
00:54:55.420
Again, that's ANIC data,
link |
00:54:57.000
but I was kind of surprised to learn that colleagues
link |
00:55:00.180
that were so intellectually strong
link |
00:55:01.940
were also so obsessed with exercise.
link |
00:55:04.000
I mean, they really are obsessed with their exercise routine
link |
00:55:06.500
and early on linked that
link |
00:55:08.040
to some of their intellectual vigor over time.
link |
00:55:12.780
I want to just also use it as a jumping off point
link |
00:55:14.720
to ask about one kind of niche thing, but it comes up.
link |
00:55:17.960
I don't think I'm going to out which one of those
link |
00:55:19.360
told me this, but one of those three individuals
link |
00:55:21.960
choose an excessive amount of Nicorette.
link |
00:55:24.840
Used to be a smoker and I asked him why.
link |
00:55:27.360
And he said, because in his estimation,
link |
00:55:31.040
it's protective against Parkinson's and Alzheimer's,
link |
00:55:33.520
or at least the nicotinic acetylcholine augmentation
link |
00:55:39.020
of nicotine, because nicotine is an acetylcholine receptor,
link |
00:55:41.280
obviously, is known to create a state of focus
link |
00:55:45.440
and neural enhancement.
link |
00:55:47.060
What are your thoughts about not smoking?
link |
00:55:49.720
Let's just, I want to be really clear.
link |
00:55:51.080
People don't smoke nicotine, vape nicotine.
link |
00:55:53.840
It's going to shorten your life.
link |
00:55:54.680
Just terrible idea, addictive, et cetera, in my opinion.
link |
00:55:57.840
But what are your thoughts about augmenting acetylcholine
link |
00:56:02.520
through the use of nicotine
link |
00:56:03.760
in order to keep the brain healthy and focused?
link |
00:56:06.080
Again, this is one Nobel Prize winner,
link |
00:56:07.780
so it's truly N of one,
link |
00:56:09.560
but he's so convinced that this matches up
link |
00:56:11.760
with the mechanistic data on acetylcholine and cognition
link |
00:56:14.400
that I'd love to get your thoughts on it.
link |
00:56:16.240
So I can't speak to the AD prevention component of it.
link |
00:56:19.320
I'd have to run that by a couple of my colleagues
link |
00:56:21.960
who I collaborate with on that,
link |
00:56:24.240
but I can definitely speak
link |
00:56:25.520
to the cognitive enhancement piece of it.
link |
00:56:27.900
And I actually did an AMA on this probably a year ago
link |
00:56:31.800
where I went into all of the gory details of it
link |
00:56:34.400
and talked about my own use of nicotine,
link |
00:56:37.100
which I'll cycle on and off.
link |
00:56:38.680
I've been doing it for the last 10 years.
link |
00:56:40.400
What form do you take it in?
link |
00:56:41.980
I used to use the gum.
link |
00:56:43.320
I don't like the gum anymore,
link |
00:56:44.360
so now I like these little lozenges.
link |
00:56:49.240
I'll tell you a funny story about this.
link |
00:56:51.200
So our mutual acquaintance, David Sinclair,
link |
00:56:55.460
mentioned a company to me a year ago.
link |
00:56:59.720
He's like, hey, have you heard of this company?
link |
00:57:02.120
And I forget the name of the company,
link |
00:57:03.440
but he gave me some name.
link |
00:57:04.920
So I go online,
link |
00:57:06.000
and it's like this company selling nicotine.
link |
00:57:08.800
And I'm like, I wonder why he's asking me to do this.
link |
00:57:10.480
Well, I'll just order a bunch,
link |
00:57:12.300
and then we'll figure out why,
link |
00:57:13.840
because there was some reason
link |
00:57:15.840
we were doing this potentially through investment.
link |
00:57:19.200
So I literally ordered a lifetime supply of this stuff,
link |
00:57:22.920
and it's pretty good.
link |
00:57:23.760
It's a really nice little patch,
link |
00:57:25.120
because the thing I didn't like about the gum
link |
00:57:26.600
was I hated just the taste of it.
link |
00:57:31.120
So then the next week I'm talking to David,
link |
00:57:32.800
and I'm like, by the way,
link |
00:57:33.640
I ordered all that nicotine stuff you told me about.
link |
00:57:35.400
He's like, what?
link |
00:57:36.880
And he goes, oh, oh, the company's name was something else.
link |
00:57:39.920
It was totally unrelated.
link |
00:57:41.680
I was like, oh, God.
link |
00:57:43.380
So the short answer is I think this stuff
link |
00:57:47.480
is absolutely a concentration-enhancing substance.
link |
00:57:53.040
It is addictive, and people need to be wary of that.
link |
00:57:55.040
Now, it's not addictive to everybody.
link |
00:57:56.440
I personally experience no addiction to it whatsoever.
link |
00:58:00.600
So I could do it every day for 30 days
link |
00:58:04.280
and stop and experience no withdrawal.
link |
00:58:06.400
I could forget about it.
link |
00:58:07.400
It doesn't really seem to matter.
link |
00:58:10.560
You have to be careful with the dose, truthfully.
link |
00:58:12.440
I mean, remember, one cigarette
link |
00:58:14.240
is about one milligram of nicotine,
link |
00:58:16.640
and a lot of these lozenges will plow
link |
00:58:20.240
four to eight milligrams into you in one shot.
link |
00:58:23.420
And for someone who is naive to that like I am,
link |
00:58:28.520
four milligrams is a lot of nicotine in one bolus.
link |
00:58:31.400
So you just have to be very mindful of it.
link |
00:58:34.440
I got a lot of flack when I did this AMA
link |
00:58:38.600
for obvious reasons, but people were like,
link |
00:58:40.640
how can you, as a doctor, encourage people to use nicotine?
link |
00:58:43.880
And I was like, first of all,
link |
00:58:44.920
I'm not encouraging anybody to use it.
link |
00:58:46.160
I just wanna be able to talk about the biochemistry of it.
link |
00:58:49.720
And if disclosing that I use it from time to time
link |
00:58:52.040
is an endorsement, then I apologize for that.
link |
00:58:55.920
But on the list of things that you can do
link |
00:58:58.280
to make your brain a little more focused,
link |
00:59:01.120
I would consider this infinitely safer
link |
00:59:03.300
than what a lot of people are doing,
link |
00:59:04.540
which is using stimulants.
link |
00:59:06.340
I mean, to me, I just tell patients outright,
link |
00:59:10.440
we are under no circumstance prescribing stimulants.
link |
00:59:13.520
I mean, we're not giving anybody Adderall.
link |
00:59:16.400
We're not giving anybody Vyvanse or any of these things.
link |
00:59:20.020
Not to say they don't have an appropriate clinical use,
link |
00:59:22.040
but they should be prescribed under the care
link |
00:59:24.360
of somebody who's really monitoring the use case for it.
link |
00:59:27.360
And using that as a tool to enhance concentration
link |
00:59:31.520
and cognitive performance
link |
00:59:32.360
is not something we're comfortable doing.
link |
00:59:33.760
Yeah, it's rampant on college campuses.
link |
00:59:36.480
I can only imagine.
link |
00:59:37.800
Our modafinil, modafinil,
link |
00:59:39.000
which are slightly different, of course,
link |
00:59:41.000
so non-clinical use, not prescribed for ADHD,
link |
00:59:44.640
but just it's rampant, recreational use, study-based use.
link |
00:59:48.400
But the data I've seen on modafinil suggests
link |
00:59:51.120
that it only really provides a nootropic benefit
link |
00:59:53.560
in someone who is deprived of sleep.
link |
00:59:55.480
Is there data that in a totally well-rested person,
link |
00:59:59.360
there is a nootropic benefit of modafinil?
link |
01:00:01.400
I don't know.
link |
01:00:02.240
I have one experience with R-modafinil
link |
01:00:04.000
where I took a half a recommended dose.
link |
01:00:06.200
This was prescribed by a doctor.
link |
01:00:08.400
I went to give a talk.
link |
01:00:09.600
This is in Hawaii.
link |
01:00:10.820
And four hours into the talk,
link |
01:00:13.140
my co-speaker came up to me and just said,
link |
01:00:16.040
well, first of all, you got a little bit of a spit
link |
01:00:17.880
in the corner of your mouth.
link |
01:00:18.760
And second of all, you haven't blinked in three minutes.
link |
01:00:20.840
And third, there's only two people left in the audience.
link |
01:00:23.880
I was so lasered in that I kind of forgot the context.
link |
01:00:27.800
I'm a little bit of a kind of a tunnel vision OCD type
link |
01:00:31.360
anyway, but that was all it took.
link |
01:00:33.580
I never took any more of it.
link |
01:00:35.120
It was a powerful stimulant.
link |
01:00:37.200
I take 300 milligrams of alpha-GPC now and again
link |
01:00:41.360
before some cognitive work, sometimes before workouts.
link |
01:00:43.840
And I do subjectively feel that it narrows my focus
link |
01:00:47.260
in a nice way, but I don't take it more
link |
01:00:50.480
than once or twice a day and more than once or twice a week.
link |
01:00:53.160
So this is an example of where,
link |
01:00:54.920
you know how we're talking about exercise
link |
01:00:56.360
versus sort of nutrition and supplements for longevity.
link |
01:01:00.040
I think there may be a whole bunch of things
link |
01:01:01.600
that are kind of interesting around focus,
link |
01:01:03.640
but nothing would compare to changing our environment.
link |
01:01:06.200
Like I think that if I compare my focus today
link |
01:01:09.560
to my focus when I was in college, there's no comparison.
link |
01:01:12.680
Like in college, I was truly a robot,
link |
01:01:16.120
but I think a large part of it was there was no distraction.
link |
01:01:19.400
There was no email, there was no social media,
link |
01:01:21.880
there was no internet.
link |
01:01:22.880
I mean, I was in college when Mosaic launched
link |
01:01:25.800
in the early 90s, and you had to walk like a mile
link |
01:01:29.880
to get to the computer lab on a big sun workstation
link |
01:01:32.600
to do anything in some computer code language.
link |
01:01:36.360
So when you're sitting in your room studying,
link |
01:01:39.920
there was no distraction.
link |
01:01:41.300
And I think that's a far greater component
link |
01:01:43.720
of what it means to be focused
link |
01:01:45.480
than the challenges we have today.
link |
01:01:46.600
So my thoughts on this would be if we really wanted
link |
01:01:50.600
to return to a state of focus,
link |
01:01:52.160
we're gonna have to individually do something
link |
01:01:54.560
about our environment.
link |
01:01:56.200
And I don't know what the answer is.
link |
01:01:58.080
Like I've tried every little trick I can think of,
link |
01:02:00.960
like closing my browsers when I'm writing and stuff,
link |
01:02:03.600
but I'm just not strong enough willed.
link |
01:02:05.720
Like I'll pick up my phone every 20 minutes
link |
01:02:08.040
to look and see if I miss the text message
link |
01:02:09.800
or something stupid.
link |
01:02:10.880
That's pretty infrequent.
link |
01:02:12.080
I did a episode on habits and looking at the data.
link |
01:02:15.600
It seems that people are getting interrupted
link |
01:02:19.040
or interrupting themselves about once every three minutes
link |
01:02:22.560
in the typical workplace.
link |
01:02:23.880
Now that typical has changed
link |
01:02:25.200
with a lot more people working at home.
link |
01:02:27.060
I do put my phone away when I try and work,
link |
01:02:29.040
that nothing focuses me like a deadline,
link |
01:02:31.640
a little bit of a fear-based urgency.
link |
01:02:33.880
That's it.
link |
01:02:34.720
Grant deadlines, drop deadlines as I call them,
link |
01:02:36.840
or podcasts we're gonna record today
link |
01:02:38.720
that nothing works quite like it,
link |
01:02:40.640
but such as life.
link |
01:02:42.940
Well, thanks for that offshoot about nicotine.
link |
01:02:47.000
Again, you're not recommending it.
link |
01:02:49.440
I'm not recommending it,
link |
01:02:50.400
but it's clear that augmenting the acetylcholine system,
link |
01:02:54.320
which is what nicotine does in its various forms
link |
01:02:57.100
and some related type pharmacology does enhance focus
link |
01:03:00.800
and pretty potently.
link |
01:03:01.800
So I think it's gonna be an interesting area
link |
01:03:03.260
for real clinical trials and things of that sort.
link |
01:03:07.520
Love to chat about hormone therapies and hormones generally.
link |
01:03:11.920
When Robert Sapolsky came on the podcast,
link |
01:03:14.000
we talked a little bit about menopause
link |
01:03:16.000
and the data around menopause.
link |
01:03:17.040
He's very interested in these findings that,
link |
01:03:20.600
I think I'm gonna get this right,
link |
01:03:22.140
that whether or not women benefit from estrogen therapy
link |
01:03:26.920
to offset menopause really depends
link |
01:03:28.620
on when that therapy is initiated.
link |
01:03:30.900
I don't know if you're aware of those data,
link |
01:03:32.240
but he claimed that if they begin estrogen therapy
link |
01:03:36.680
in the middle to tail end of menopause,
link |
01:03:40.040
the outcomes can be quite bad.
link |
01:03:43.040
Whereas if they initiate those estrogen therapies
link |
01:03:45.760
as they enter menopause or even before menopause,
link |
01:03:48.640
then the outcomes can be quite good.
link |
01:03:50.640
I don't know what percentage of the patients you treat
link |
01:03:52.620
are male versus female
link |
01:03:53.820
and what ages those patients are, of course,
link |
01:03:55.900
but what are your thoughts about estrogen therapy
link |
01:03:58.600
for women, menopause, and hormone therapies
link |
01:04:01.640
generally for women, maybe even testosterone therapy.
link |
01:04:03.560
You hear about that these days.
link |
01:04:04.600
And then we'll talk about men.
link |
01:04:05.880
So our practice is probably 70, 30 male, female.
link |
01:04:10.800
So we have lots of women and this is a very important topic.
link |
01:04:15.200
It's also probably, let me think.
link |
01:04:19.320
I just want to make sure I'm not being hyperbolic
link |
01:04:20.920
when I say this.
link |
01:04:22.720
Yeah, I don't think I am.
link |
01:04:24.060
It's hands down the biggest screw up
link |
01:04:26.280
of the entire medical field in the last 25 years.
link |
01:04:30.320
Now again, it's possible in the next hour,
link |
01:04:32.200
I'll think of, there's a bigger screw up.
link |
01:04:34.840
Another giant screw up.
link |
01:04:35.680
Yeah, but I don't think I will.
link |
01:04:37.360
I'm pretty confident that I won't be able to think
link |
01:04:41.240
of a bigger act of incompetence than what happened
link |
01:04:49.160
with the Women's Health Initiative in the late 90s
link |
01:04:51.960
and early 2000s, which is effectively the study
link |
01:04:55.800
that turned the entire medical field
link |
01:04:58.240
off hormone replacement therapy for women.
link |
01:05:00.880
So it's important, I think, to explain
link |
01:05:02.980
what the study looked at.
link |
01:05:04.360
So this was a study that was conducted in response
link |
01:05:08.080
to the widely held belief in the 70s and 80s
link |
01:05:14.000
that women should be placed on hormones
link |
01:05:17.000
as they're going through menopause, right?
link |
01:05:19.560
Menopause is, I guess maybe I'll even take a step back.
link |
01:05:22.480
I don't know how much your audience is familiar
link |
01:05:23.840
with how estrogen and progesterone work.
link |
01:05:25.360
Is it worth going into that stuff?
link |
01:05:26.840
Yeah, probably worth mentioning a bit of the top contour.
link |
01:05:29.080
Some of them might be familiar with it.
link |
01:05:30.400
We've done episodes on estrogen and testosterone,
link |
01:05:32.120
but frankly, as I think back to those,
link |
01:05:34.080
we didn't really go into the biology
link |
01:05:35.340
of estrogen, testosterone, you know.
link |
01:05:38.120
Yeah, so, I mean, actually an interesting aside
link |
01:05:40.360
that I always tell my female patients
link |
01:05:41.800
who get a kick out of this,
link |
01:05:44.140
when you look at a woman's labs,
link |
01:05:45.800
you'll see her estrogen, her progesterone, her FSH, her LH,
link |
01:05:50.080
her testosterone, her sex hormone binding globulin,
link |
01:05:51.860
all these things, but based on the units they're reported in
link |
01:05:55.320
it's a very distorting picture
link |
01:05:57.440
of what the most common androgen is in her body.
link |
01:06:00.920
If you actually convert them to the same units,
link |
01:06:02.960
she has much more testosterone in her body than estrogen.
link |
01:06:07.300
Interesting. Yeah.
link |
01:06:08.840
I did not know that. Yeah.
link |
01:06:10.000
Then again, I've never been a woman
link |
01:06:11.480
getting my hormone profile done.
link |
01:06:13.080
Yeah, so even though a woman's testosterone
link |
01:06:14.920
is much less than a man's level,
link |
01:06:18.720
it's still more than she has estrogen in her body.
link |
01:06:21.840
So phenotypically, right, estrogen is the hormone
link |
01:06:24.640
that's dominating and so it's the, you know,
link |
01:06:26.680
she has much higher estrogen than a man
link |
01:06:28.360
and much lower testosterone than a man,
link |
01:06:30.320
but in absolute amounts,
link |
01:06:31.840
she has more testosterone than estrogen.
link |
01:06:33.440
Just worth pointing that out.
link |
01:06:34.520
Incredible.
link |
01:06:35.360
So, you know, what's happening to a woman
link |
01:06:38.560
from the age she starts menstruating
link |
01:06:40.120
until she goes through menopause,
link |
01:06:41.840
outside of pregnancy and birth control and stuff like that,
link |
01:06:44.260
is she has this cycle, you know,
link |
01:06:45.760
roughly every 28 days, but it can vary,
link |
01:06:47.980
where at the beginning of her period,
link |
01:06:50.140
we call that day zero,
link |
01:06:51.600
her estrogen and progesterone are very low.
link |
01:06:55.040
You can't measure them.
link |
01:06:56.440
And then what happens is the estrogen level starts to rise
link |
01:07:00.960
and it rises in response to a hormone
link |
01:07:04.240
called follicle stimulating hormone, FSH,
link |
01:07:07.820
that is getting her ready to ovulate
link |
01:07:09.560
and she ovulates at about the midpoint of her cycle.
link |
01:07:11.660
So if we're just gonna make the math easy,
link |
01:07:13.440
on day 14, she's going to release a follicle
link |
01:07:16.040
from one of her ovaries.
link |
01:07:17.840
And the estrogen level is sort of rising, rising, rising.
link |
01:07:20.920
We love to measure hormones on day five
link |
01:07:24.140
because I wanna have a standardized way
link |
01:07:26.260
in which I measure her hormones.
link |
01:07:27.880
So our women know if we're in the business
link |
01:07:30.800
of trying to understand her hormones,
link |
01:07:32.080
the day her period starts,
link |
01:07:33.340
even if it's just a day of spotting,
link |
01:07:34.680
that becomes our benchmark.
link |
01:07:35.900
And then day five, I wanna see every hormone on that day.
link |
01:07:39.240
And if everything is going well,
link |
01:07:41.020
I know what her FSH, LH, estradiol,
link |
01:07:43.200
and progesterone should be on that day.
link |
01:07:45.380
So the estrogen rises,
link |
01:07:47.000
starts to come down a little bit as she ovulates,
link |
01:07:49.660
and then the luteinizing hormone kicks on
link |
01:07:51.560
because it's now going to prepare her uterus
link |
01:07:54.760
for the lining to accommodate a pregnancy.
link |
01:07:59.160
So now you start to see estradiol go back,
link |
01:08:01.440
but now for the first time, progesterone goes up.
link |
01:08:03.300
So progesterone has been doing nothing for 14 days,
link |
01:08:06.440
and now it starts to rise.
link |
01:08:07.700
And actually, progesterone is the hormone
link |
01:08:09.320
that's dominating the second half,
link |
01:08:11.040
which is called her luteal cycle.
link |
01:08:13.280
So the first 14 days is the follicular cycle,
link |
01:08:15.600
second is the luteal cycle.
link |
01:08:17.520
So once you get to about the halfway point of that,
link |
01:08:20.040
which is now, just to do the math, 21 days in,
link |
01:08:23.040
the body has figured out if she's pregnant or not.
link |
01:08:25.360
And again, most of the time she's not gonna be pregnant,
link |
01:08:27.760
so the body says, oh, I don't need this lining
link |
01:08:29.960
that I've been preparing, I'm going to shed it.
link |
01:08:32.240
So now progesterone and estrogen start crashing,
link |
01:08:35.840
and the lining is what is being shed,
link |
01:08:37.560
and that is the menses.
link |
01:08:39.640
By the way, it's that last seven days of that cycle
link |
01:08:42.620
that in a susceptible woman
link |
01:08:44.260
is what creates those PMS symptoms.
link |
01:08:47.280
So it's the, actually, this is something
link |
01:08:48.720
that you would probably have
link |
01:08:49.600
a better understanding of than me.
link |
01:08:51.340
There is something about this in a susceptible woman
link |
01:08:54.760
where the enormous reduction of progesterone so quickly
link |
01:08:59.080
is probably impacting something in her brain.
link |
01:09:01.880
So I think this is a legitimate thing, right?
link |
01:09:04.020
I mean, it's not like, oh, she's crazy
link |
01:09:05.960
because she's having all these PMS symptoms, no.
link |
01:09:09.320
We know that that's the case
link |
01:09:10.440
because if you put women on progesterone
link |
01:09:12.240
for those seven days, those symptoms go away.
link |
01:09:14.680
So if you can stabilize their progesterone
link |
01:09:16.640
during the last half of their luteal phase,
link |
01:09:19.640
and sometimes we would just do it
link |
01:09:20.680
for the entire luteal phase,
link |
01:09:21.840
just put them on a low dose of progesterone,
link |
01:09:24.100
all PMS symptoms vanish.
link |
01:09:25.460
Very interesting.
link |
01:09:26.300
I'll have to look up where the progesterone receptors
link |
01:09:28.700
are located in the brain.
link |
01:09:29.540
The Allen Brain Institute now has beautiful data
link |
01:09:33.240
of in situ hyperization,
link |
01:09:34.500
which for folks that don't understand
link |
01:09:35.880
is looking at RNA and sort of where genes
link |
01:09:38.600
and proteins ought to be expressed in the human brain
link |
01:09:41.320
by using actual human brain tissue sections
link |
01:09:43.380
as opposed to just mice.
link |
01:09:44.320
So I'll take a look.
link |
01:09:45.160
I think some insight into what that
link |
01:09:48.160
progesterone emotionality link might be
link |
01:09:50.300
and where it might exist neural circuit-wise.
link |
01:09:52.920
So then when the estrogen and progesterone
link |
01:09:55.480
reach their nadir again, that starts the cycle.
link |
01:09:58.500
So that cycle is happening over and over and over again.
link |
01:10:02.100
Okay, so it became well known in the 50s
link |
01:10:06.640
that okay, a woman's gonna stop menstruating at some point.
link |
01:10:09.480
Her estrogen goes down.
link |
01:10:10.540
Why don't we just give her estrogen?
link |
01:10:12.560
Because that's clearly gonna help
link |
01:10:13.920
with some of the symptoms of menopause.
link |
01:10:15.480
So what do women experience when they go through menopause?
link |
01:10:18.080
The first symptoms are what are called vasomotor symptoms.
link |
01:10:20.480
So this is usually in the form of night sweats,
link |
01:10:24.000
hot flashes, and depending on the woman,
link |
01:10:26.980
this can be really significant, right?
link |
01:10:28.680
These are women who can have a hard time sleeping.
link |
01:10:31.740
They can be having hot flashes during the middle of the day.
link |
01:10:33.540
They can wake up soaked in a pool of sweat.
link |
01:10:37.320
Those tend to pass after a couple of years,
link |
01:10:40.760
and then they get into sort of the more
link |
01:10:43.120
long-term complications of menopause.
link |
01:10:45.280
So what we call vaginal atrophy, vaginal dryness,
link |
01:10:48.680
and then the stuff that we talked about a while ago,
link |
01:10:50.800
which is the osteopenia, osteoporosis.
link |
01:10:54.160
A lot of women will complain of brain fog.
link |
01:10:57.920
So I mean, clearly this was an issue,
link |
01:11:01.800
and it was recognized 70 years ago.
link |
01:11:04.720
Why don't we give women estrogen back
link |
01:11:06.800
to replace that hormone?
link |
01:11:08.840
And so that went on for a couple of decades,
link |
01:11:12.200
maybe less, maybe a decade, and then it was realized,
link |
01:11:14.380
wait a minute, we were driving up the risk of uterine cancer.
link |
01:11:20.200
And the reason for that is if you just give estrogen
link |
01:11:23.440
with no progesterone to antagonize it,
link |
01:11:26.700
you will thicken the endometrium endlessly,
link |
01:11:29.960
and you will increase the risk of hyperplasia.
link |
01:11:33.220
Well, you'll definitely undergo hyperplasia,
link |
01:11:35.160
and then ultimately dysplasia.
link |
01:11:36.560
Dysplasia is precancerous,
link |
01:11:38.000
and ultimately we were seeing that.
link |
01:11:39.740
So people figured out, well, actually,
link |
01:11:42.120
if you want to give estrogen to a woman
link |
01:11:44.440
who still has her uterus,
link |
01:11:45.480
you have to give her progesterone as well.
link |
01:11:47.560
You have to be able to have a hormone
link |
01:11:49.360
to oppose the estrogen.
link |
01:11:50.920
And then that became effectively, call it the 1970s-ish,
link |
01:11:55.820
the standard for HRT.
link |
01:12:00.860
So in the early 1990s, the NIH said,
link |
01:12:04.560
look, we haven't really studied this.
link |
01:12:06.840
We have a ton of epidemiology that says
link |
01:12:10.440
giving women hormones seems to be doing really good things.
link |
01:12:14.160
They feel better, so all their symptoms go away.
link |
01:12:17.760
They seem to have lower risk of heart disease,
link |
01:12:20.200
lower risk of cardiovascular disease,
link |
01:12:24.800
lower risk of bone fractures.
link |
01:12:28.560
Everything seems to get better, lower risk of diabetes.
link |
01:12:30.420
But we haven't tested this
link |
01:12:31.620
in a randomized prospective trial, so let's do this.
link |
01:12:34.600
So that became the WHI.
link |
01:12:36.560
And it randomized, it had two parallel arms.
link |
01:12:39.240
So it had a group for women who did not have a uterus.
link |
01:12:44.580
So these are women that had undergone hysterectomy
link |
01:12:46.160
for some other reason.
link |
01:12:47.060
And then it had a group for women
link |
01:12:48.500
that did have their uterus.
link |
01:12:50.080
In the first group, there was a placebo arm
link |
01:12:53.240
and then an estrogen-only arm.
link |
01:12:55.200
And in the other group, there was a progesterone
link |
01:12:57.240
plus estrogen versus a placebo.
link |
01:13:02.160
Everything about the way this study was done
link |
01:13:04.480
is a bit wonky.
link |
01:13:05.380
Some of it is justifiable,
link |
01:13:06.880
but it's important to understand.
link |
01:13:08.840
First, the women were all way outside of menopause.
link |
01:13:13.400
So none of these women were started
link |
01:13:16.460
when you would normally start HRT.
link |
01:13:19.520
And there were probably several reasons for that,
link |
01:13:23.040
but one of them is, and I think this is a legitimate reason,
link |
01:13:26.860
they wanted hard outcomes.
link |
01:13:28.920
They wanted to know death rates.
link |
01:13:31.160
And if you're doing this on women in their 50s,
link |
01:13:33.880
you just weren't gonna get it, right?
link |
01:13:35.520
You couldn't-
link |
01:13:36.360
You gotta wait too long.
link |
01:13:37.180
Yeah, you gotta wait too long.
link |
01:13:38.020
There was only gonna be like a seven to 10-year study.
link |
01:13:40.280
So they had to do this on women who were much older.
link |
01:13:43.160
They also disproportionately took much sicker women.
link |
01:13:47.040
I believe the prevalence,
link |
01:13:48.720
and again, I'm gonna get some of these numbers wrong
link |
01:13:50.240
and people are gonna get all phosphorylated,
link |
01:13:51.760
but I mean, I'm in the ballpark, right?
link |
01:13:54.400
Something like 30, 40% of these women were smokers.
link |
01:13:57.220
The prevalence of obesity, diabetes was enormous.
link |
01:14:00.480
So they really disproportionately picked
link |
01:14:02.720
the most unhealthy population they could
link |
01:14:04.580
that was pretty advanced in age.
link |
01:14:06.360
And again, I think part of that was to say,
link |
01:14:08.200
look, we wanna make sure that after seven years,
link |
01:14:10.440
we really know if there's a difference
link |
01:14:12.160
in these causes of death.
link |
01:14:15.640
The other thing is, this is kind of weird,
link |
01:14:18.880
although again, I understand their rationale for it,
link |
01:14:21.320
but this is a great example of be very careful
link |
01:14:25.060
when you look at a clinical trial
link |
01:14:27.300
that it remotely represents the patients
link |
01:14:29.380
you're interested in treating.
link |
01:14:30.900
So they also treated no patients who were symptomatic.
link |
01:14:33.780
The rationale being, if we include in the study
link |
01:14:38.220
patients who are symptomatic,
link |
01:14:39.740
those who are randomized to placebo will drop out.
link |
01:14:45.180
Okay, it makes sense in terms of study design,
link |
01:14:47.420
makes no sense if the study design
link |
01:14:49.260
is intended to mimic the real world.
link |
01:14:52.140
That's right.
link |
01:14:52.980
So now let's just keep track of the three issues.
link |
01:14:54.500
We have a disproportionately unhealthy patient population
link |
01:14:58.180
who are not symptomatic,
link |
01:14:59.940
and we're starting them more than 10 years after menopause.
link |
01:15:05.680
The next thing that they did,
link |
01:15:06.960
which again, I understand why they did it,
link |
01:15:09.440
but it's now the fourth strike against this study is,
link |
01:15:13.640
and I've spoken with the PI of the study
link |
01:15:16.100
and asked this question point blank.
link |
01:15:17.720
I'm actually gonna have her on my podcast
link |
01:15:19.540
at some point soon to go over this in more detail,
link |
01:15:22.640
is why did you use conjugated equine estrogen and MPA,
link |
01:15:26.960
which is a synthetic form of progesterone?
link |
01:15:29.320
A horse?
link |
01:15:30.340
Yes.
link |
01:15:31.180
Estrogen?
link |
01:15:32.020
It's horse urine, they collect horse urine.
link |
01:15:34.300
So they're getting the-
link |
01:15:35.640
Horses do urinate a lot, or at least when they urinate,
link |
01:15:38.960
it seems like a large volume of urine
link |
01:15:40.520
from what I've observed.
link |
01:15:42.080
You have a lot of experience with this?
link |
01:15:43.320
No, but you know, my sister rode horses for a little while.
link |
01:15:46.400
My high school girlfriend had a horse and that thing,
link |
01:15:49.360
I mean, the peas were legendary.
link |
01:15:53.840
It's a male horse.
link |
01:15:54.840
Yeah. Yeah.
link |
01:15:56.080
So yeah, so the conjugated equine estrogen
link |
01:15:58.720
is the estrogen that's collected from female horses,
link |
01:16:02.280
and then it's a synthetic progesterone.
link |
01:16:05.080
And I said to the person, I said,
link |
01:16:07.920
well, why didn't you use what we use today,
link |
01:16:10.160
which is bioidentical estrogen and progesterone?
link |
01:16:12.520
Like today, when we put women on estrogen,
link |
01:16:15.080
we use a, it's an FDA product called the Vivel Dot.
link |
01:16:18.040
So it's a patch that you just put on and it's estradiol,
link |
01:16:21.120
but it's bioidentical estradiol,
link |
01:16:22.480
and we use what's called micronized progesterone,
link |
01:16:24.360
so bioidentical progesterone.
link |
01:16:26.600
And she said, well, at the time,
link |
01:16:29.480
we just wanted to test what was currently being used.
link |
01:16:31.640
I said, totally makes sense.
link |
01:16:33.000
But again, now you have four considerations
link |
01:16:35.720
that you have to keep in mind.
link |
01:16:37.680
Okay, so despite those four considerations,
link |
01:16:40.320
and I'm gonna make a case for you
link |
01:16:41.520
why I think the MPA created a real problem in that study,
link |
01:16:45.920
the synthetic progesterone.
link |
01:16:47.960
When the preliminary results were first made available,
link |
01:16:52.960
but not yet peer reviewed and not yet published,
link |
01:16:55.600
there was a huge fiasco, huge press announcement about it,
link |
01:16:59.600
suggesting that the women receiving the CEE plus MPA
link |
01:17:06.520
in the group with the uterus
link |
01:17:09.440
had a higher incidence of breast cancer.
link |
01:17:12.120
And that basically became the headline that never went away,
link |
01:17:15.440
though it turned out not to be true.
link |
01:17:18.120
Let's talk about the numbers.
link |
01:17:19.480
What was the increase in the risk of breast cancer
link |
01:17:23.080
in that group?
link |
01:17:23.920
Which gets to my, if you've ever listened to me
link |
01:17:25.960
on the podcast, rail on something.
link |
01:17:27.840
Listen, I have about 3,800 pet peeves and counting.
link |
01:17:31.280
My laboratory staff know these, know a good number of them.
link |
01:17:34.680
So you do not have to apologize for having many pet peeves,
link |
01:17:38.000
because as long as they have experience
link |
01:17:40.120
and data to support them, it provides a better life.
link |
01:17:42.240
So one of my biggest pet peeves is,
link |
01:17:44.800
and my team knows this,
link |
01:17:46.200
because sometimes they'll occasionally,
link |
01:17:48.080
they'll do this and I'll have to remind them.
link |
01:17:50.600
You never talk about a relative risk change
link |
01:17:52.860
without an absolute risk accommodating it, right?
link |
01:17:55.120
So what does that look like?
link |
01:17:56.760
So the relative risk increase of breast cancer
link |
01:18:00.320
in the estrogen plus MPA group versus the placebo
link |
01:18:04.360
was 25, 27%, and that became the only headline.
link |
01:18:11.160
HRT increases risk of breast cancer by 27%.
link |
01:18:15.400
Now, I don't think that's true at all today,
link |
01:18:19.840
but let's even look at the data.
link |
01:18:21.280
What was the ARR?
link |
01:18:22.960
What was the absolute risk increase?
link |
01:18:25.760
It was a difference between five cases per thousand
link |
01:18:29.480
and four cases per thousand.
link |
01:18:31.980
So the ARR was 0.1%, one case in a thousand.
link |
01:18:39.160
And it's true, going from four in a thousand
link |
01:18:41.560
to five in a thousand is a 25% increase,
link |
01:18:45.640
but it's a completely inappropriate context.
link |
01:18:48.320
I agree, and I feel like headlines of that sort,
link |
01:18:51.920
which have come up recently
link |
01:18:52.920
around various dietary interventions,
link |
01:18:54.680
we won't go there, at least not for the time being,
link |
01:18:57.900
are nothing short of criminal
link |
01:18:59.400
because they really distort people's thinking,
link |
01:19:03.000
but also they steer the course of science and medicine
link |
01:19:06.200
for, as you pointed out, for decades, if not longer.
link |
01:19:09.760
And they can really take us off our health track
link |
01:19:12.120
in serious ways.
link |
01:19:13.700
So I'll bring this meandering to a close,
link |
01:19:15.760
which is to say, even though I could spend the next hour
link |
01:19:18.440
talking about all of the ways in which this study was flawed
link |
01:19:21.800
and all of the very unethical things
link |
01:19:24.000
that were done by a number of the investigators
link |
01:19:26.120
who went out of their way to mask the truth of this study
link |
01:19:30.280
from the world, I'll tell a woman today,
link |
01:19:34.760
we're gonna start you on this
link |
01:19:35.960
when you're going through menopause,
link |
01:19:37.400
we're using bioidentical hormones,
link |
01:19:41.520
and if your upper bound risk of breast cancer
link |
01:19:45.920
is one case in 1,000, you should at least weigh that
link |
01:19:49.920
against all of the other benefits, which I'll talk about.
link |
01:19:51.960
Now there's something else I wanna say,
link |
01:19:53.400
because a moment ago I alluded to the fact
link |
01:19:54.720
that I think the MPA might have been the biggest issue
link |
01:19:57.120
in that study.
link |
01:19:57.960
So there were two findings in that study that were negative.
link |
01:20:01.420
One was the small increase in the risk of heart disease
link |
01:20:04.920
and the small increase in the risk of breast cancer.
link |
01:20:07.760
But consider the other group.
link |
01:20:09.860
We forgot about the group that didn't have a uterus,
link |
01:20:12.600
because remember, those women got estrogen only
link |
01:20:16.240
versus placebo.
link |
01:20:18.000
What was the difference in breast cancer there?
link |
01:20:20.800
Well, this is interesting
link |
01:20:21.620
because it didn't reach statistical significance,
link |
01:20:24.120
but its P value was 0.06 or 0.07.
link |
01:20:27.040
So it came very close, but it was in the opposite direction.
link |
01:20:30.260
It was a 24% risk reduction, about one in 1,000 as well.
link |
01:20:36.780
So when you had estrogen plus MPA,
link |
01:20:39.580
you had a barely statistically significant,
link |
01:20:42.400
the P value was 0.05,
link |
01:20:43.900
so it just hit statistical significance,
link |
01:20:45.900
one in 1,000 cases for breast cancer,
link |
01:20:49.060
and then you had one in 1,000 cases,
link |
01:20:51.760
but P value of 0.07 for reduction of risk of breast cancer,
link |
01:20:56.480
which to me suggests that the MPA,
link |
01:20:58.320
the synthetic progesterone, was playing more of a role
link |
01:21:01.020
than anything else.
link |
01:21:02.800
The second thing I point out is oral estrogen,
link |
01:21:06.180
which we no longer use, does increase coagulability.
link |
01:21:10.580
It does increase the ability of the blood
link |
01:21:12.880
to clot a little bit.
link |
01:21:14.300
And when we look at the more recent data on HRT
link |
01:21:17.820
using topical estrogen or patches of estrogen,
link |
01:21:21.980
we don't see that at all.
link |
01:21:22.900
In fact, we see the opposite now.
link |
01:21:24.060
So now we see the risk of heart disease
link |
01:21:25.340
going down in women with estradiol.
link |
01:21:27.740
And some women will be arriving to those treatments
link |
01:21:30.060
with mutations and things like factor V Leiden
link |
01:21:32.620
and other clotting factors.
link |
01:21:34.420
Is it appropriate to say that everyone,
link |
01:21:37.500
both male and female, should know whether or not
link |
01:21:39.420
they have mutant forms of factor V Leiden?
link |
01:21:41.940
You know, we don't typically test people for factor V.
link |
01:21:44.380
My wife actually has it,
link |
01:21:45.340
but we didn't learn it until she had help syndrome,
link |
01:21:47.780
giving birth to our first daughter.
link |
01:21:50.340
But we kind of look for more family history reason
link |
01:21:54.300
to be testing things like that.
link |
01:21:56.080
We take a pretty detailed family history,
link |
01:21:57.420
so we'll kind of look for clotting issues there.
link |
01:21:59.900
What about, so your reflex nowadays is to put women
link |
01:22:05.700
on these topical estrogen therapies.
link |
01:22:08.700
Well, it's to basically have the discussion, right?
link |
01:22:10.780
So here's where we still struggle, right?
link |
01:22:12.740
Is, you know, we, if it were up to me,
link |
01:22:15.820
I'd prefer for a woman's HRT to be provided by her GYN
link |
01:22:20.820
because we want to be able to work in partnership
link |
01:22:22.660
with the GYN who we would like to see
link |
01:22:24.580
an endometrial ultrasound done every year.
link |
01:22:27.500
That's, you know, some would argue that's overkill,
link |
01:22:29.380
but you know, we think she'd be shoving
link |
01:22:30.820
a pap smear every year as well.
link |
01:22:32.460
So if we're looking at the cervix,
link |
01:22:34.020
we want to look at the endometrium.
link |
01:22:35.100
We want to make sure the lining isn't too thick.
link |
01:22:37.100
The other thing I should say, Andrew,
link |
01:22:38.020
is today we now realize that not all women
link |
01:22:41.660
can tolerate, pardon me, progesterone.
link |
01:22:44.780
So you have to be careful.
link |
01:22:45.820
So assuming, again, a woman still has her uterus,
link |
01:22:48.580
the estrogen solves most of the problems,
link |
01:22:51.160
but then you have to decide,
link |
01:22:52.320
can she tolerate the progesterone?
link |
01:22:54.340
And it needs to be, if given systemically,
link |
01:22:56.340
like 100 to 200 milligrams.
link |
01:22:58.500
And for some women, that is a life-saving intervention.
link |
01:23:01.180
I mean, they start sleeping better,
link |
01:23:02.540
their hair gets thicker, they feel better,
link |
01:23:04.700
but for some women, it literally drives them crazy.
link |
01:23:07.500
It's probably the reciprocal of what we were seeing
link |
01:23:09.980
in the case of women with PMS.
link |
01:23:12.060
So in those situations, we say, great,
link |
01:23:15.260
we're done with oral progesterone.
link |
01:23:16.740
We just use a progesterone-coated IUD.
link |
01:23:19.300
So then you get the local progesterone in the uterus
link |
01:23:22.740
for protection in the systemic estrogen.
link |
01:23:25.980
Fascinating.
link |
01:23:26.860
What about oral contraception in women?
link |
01:23:33.460
So the use of estrogen chronically through college years
link |
01:23:37.180
or 20s, 30s, maybe even teens, who knows?
link |
01:23:41.020
What's known about the long-term effects, if any?
link |
01:23:44.360
I got to be honest with you.
link |
01:23:45.200
I don't think I know enough to comment on it.
link |
01:23:47.100
It's not something that really impacts
link |
01:23:48.820
my patient population.
link |
01:23:50.260
You know, at least in what I see,
link |
01:23:53.540
more women are using IUDs for contraception than OCs.
link |
01:23:58.340
I mean, we use OCs sometimes in women
link |
01:24:01.900
who are premenopausal for symptomatic control,
link |
01:24:05.340
but we'll typically use like a low, low estrogen,
link |
01:24:08.420
so a very low synthetic estrogen,
link |
01:24:11.420
which I don't like using these very much,
link |
01:24:13.180
but if it's the only thing that we can get
link |
01:24:14.140
to control certain symptoms,
link |
01:24:15.480
and we'll use it like half her cycle.
link |
01:24:17.700
But it's typically not something we're that experienced with.
link |
01:24:23.280
What about testosterone?
link |
01:24:24.680
Because you mentioned that nanogram per mil,
link |
01:24:30.240
when you set everything to the same,
link |
01:24:33.280
I guess it's nanogram per deciliter,
link |
01:24:34.880
as it would be to kind of normalize everything.
link |
01:24:37.160
First picogram per mole.
link |
01:24:38.000
Right, yeah, and so what Peter was pointing out before
link |
01:24:41.400
is that you look at your charts
link |
01:24:42.640
and they're all in these different measures,
link |
01:24:43.960
and so when you normalize,
link |
01:24:45.160
testosterone is actually higher than estrogen
link |
01:24:47.400
in women, that's a surprise to me.
link |
01:24:50.680
Do you prescribe testosterone therapy to women ever?
link |
01:24:53.480
We do sometimes, but I do it with much more caution
link |
01:24:56.700
because I don't have the data, right?
link |
01:24:58.600
So what we'll say is, look,
link |
01:25:02.520
I mean, we're now really outside of an area
link |
01:25:04.740
where I can point to a lot of data.
link |
01:25:06.440
Like when it comes to estrogen and progesterone,
link |
01:25:09.320
I'll happily go toe to toe with anybody
link |
01:25:11.820
who wants to make the case that it's dangerous.
link |
01:25:14.160
Similarly, when it comes to using testosterone in men,
link |
01:25:16.720
I'll spend all day, and I can go through that literature
link |
01:25:20.120
until the other person cries
link |
01:25:21.840
and wants to just call uncle, right?
link |
01:25:24.280
When it comes to-
link |
01:25:25.100
And then you prescribe them testosterone.
link |
01:25:26.000
When it comes to estrogen in,
link |
01:25:27.800
testosterone in women don't have that data,
link |
01:25:30.460
and I'd love to see that trial done.
link |
01:25:32.760
So what's the sweet spot?
link |
01:25:35.560
How do we reconcile that?
link |
01:25:37.120
So it's not something I consider standard,
link |
01:25:39.820
and basically, if a woman is,
link |
01:25:41.720
if her testosterone, first of all, is staggeringly low,
link |
01:25:44.960
and again, even though her testosterone is low
link |
01:25:46.680
compared to a male, we still have a range.
link |
01:25:48.740
So if it's really at the bottom of that range,
link |
01:25:50.700
she's really having difficulty putting on muscle mass
link |
01:25:53.080
and really complaining of low libido,
link |
01:25:55.520
I think in that situation,
link |
01:25:56.900
we'll go ahead and use topical testosterone
link |
01:26:00.200
and replace her to a level
link |
01:26:03.320
that is still physiologically normal.
link |
01:26:05.820
Yeah, that's key, because when people hear HRT,
link |
01:26:08.080
they think about super physiological,
link |
01:26:10.320
seems to be the term-
link |
01:26:11.240
Yeah, like I've never seen a single symptom
link |
01:26:14.080
in a single woman that I've put testosterone on
link |
01:26:16.160
in terms of acne, body hair, things like that.
link |
01:26:18.480
Those are real symptoms that you have to be aware of,
link |
01:26:20.880
but clitoral enlargement and things like that,
link |
01:26:24.720
that doesn't happen under physiologic normal conditions.
link |
01:26:29.440
I'd love to talk a little bit
link |
01:26:30.360
about hormone replacement therapy in men.
link |
01:26:34.440
When one looks on social media and the internet,
link |
01:26:36.240
there seems to be a younger and younger cohort of guys,
link |
01:26:40.280
people in their teens and 20s, showing up to the table,
link |
01:26:43.160
thinking that injecting testosterone,
link |
01:26:45.840
sapienate or taking Anavar or whatever it is,
link |
01:26:48.100
is going to be the right idea.
link |
01:26:49.580
They mainly seem to be focused on cosmetic effects.
link |
01:26:52.720
I'm not a physician, so I can't say whether or not
link |
01:26:55.120
they were actually hypogonadal, et cetera,
link |
01:26:56.860
but it seems to me, again, correct me if I'm wrong,
link |
01:27:00.000
but it seems to me that similar to the Atiyah's rule
link |
01:27:03.600
as it relates to longevity,
link |
01:27:05.300
that we could come up with a broad contour rule
link |
01:27:08.480
in which if a male of any age
link |
01:27:11.640
is not trying to get decent sleep, exercise appropriately,
link |
01:27:16.640
appropriate nutrition, minding their social connections,
link |
01:27:18.960
et cetera, et cetera,
link |
01:27:20.120
the idea of going straight to testosterone
link |
01:27:22.980
seems like a bad idea.
link |
01:27:24.420
That said, just like with depression and antidepressants,
link |
01:27:28.160
there is a kind of a cliff after which
link |
01:27:32.720
low enough testosterone or low enough serotonin
link |
01:27:35.240
prevents people from sleeping, exercise,
link |
01:27:37.240
social connection, et cetera.
link |
01:27:38.420
So I do want to acknowledge that.
link |
01:27:39.940
But with that in mind, how do you think about,
link |
01:27:43.660
and perhaps occasionally prescribe and direct your patients
link |
01:27:47.760
in terms of hormone replacement therapy in men,
link |
01:27:50.400
person in their thirties, person in their forties,
link |
01:27:52.080
who's doing almost all the other things correctly?
link |
01:27:55.680
What sorts of levels do you think are meaningful?
link |
01:27:58.980
Because the range is tremendous in terms of blood tests,
link |
01:28:01.400
300 nanograms per deciliter,
link |
01:28:03.040
I think on the low end now in the US,
link |
01:28:04.420
all the way up to 900 or 1200, that's an enormous range.
link |
01:28:07.840
What are some of the other hormones you like to look at?
link |
01:28:09.740
Estrogen, DHT, and so on.
link |
01:28:12.480
So a lot to unpack there.
link |
01:28:15.780
So let's start with the ranges, right?
link |
01:28:18.440
So the ranges you gave are for total testosterone,
link |
01:28:23.060
of course, and we don't spend a lot of time looking at that.
link |
01:28:29.000
I used to spend more time looking at total and free
link |
01:28:31.840
when I used more tricks to modulate it.
link |
01:28:35.000
So I'm actually far more simple in my manipulation
link |
01:28:38.160
of testosterone today than I was six or seven years ago.
link |
01:28:41.200
Six or seven years ago, I mean, we were,
link |
01:28:44.680
we would use a microdose of Anovar to lower SHBG
link |
01:28:49.120
in a person who had normal testosterone,
link |
01:28:51.040
but low free testosterone.
link |
01:28:52.480
What was a low dose of Anovar in that context?
link |
01:28:55.640
10 milligrams, subling, two to three times a week.
link |
01:29:00.120
Anovar basically being DHT.
link |
01:29:03.320
Oxandrolone.
link |
01:29:04.160
Oxandrolone, yeah, exactly.
link |
01:29:05.000
And again, we're not recommending this.
link |
01:29:06.660
This is actually, if you're playing a competitive sport,
link |
01:29:08.360
can get you banned from that sport.
link |
01:29:09.800
It can also get you banned from having children
link |
01:29:13.080
if you do it incorrectly.
link |
01:29:14.080
Yeah, so a microdose of this has to be small enough
link |
01:29:18.160
that it doesn't impair your body's ability
link |
01:29:20.240
to make testosterone, but Anovar has such a high affinity
link |
01:29:24.360
for SHBG that it basically distracts your SHBG
link |
01:29:28.240
from binding your testosterone.
link |
01:29:30.080
Freeing up testosterone.
link |
01:29:31.080
That's exactly right.
link |
01:29:31.920
So the goal was how do I just give you more free testosterone?
link |
01:29:34.600
So if a patient shows up and they've got a total
link |
01:29:37.640
testosterone of 900 nanograms per deciliter,
link |
01:29:39.960
which would place them at, depending on the scale
link |
01:29:42.320
you look at, the scale we look at,
link |
01:29:43.640
that would place you at about the 70th percentile,
link |
01:29:47.000
but your free testosterone is eight nanograms
link |
01:29:51.100
per deciliter.
link |
01:29:52.440
So that's pretty bad.
link |
01:29:53.280
That means you're less than 1% free.
link |
01:29:56.000
A guy should be about 2% free T.
link |
01:29:59.000
So that dude should be closer to 16 to 18 nanograms
link |
01:30:02.940
per deciliter.
link |
01:30:04.640
So in that situation that I just gave you,
link |
01:30:06.560
his SHBG is really high.
link |
01:30:08.400
His SHBG is probably in the 80 to 90 range.
link |
01:30:11.880
That's very high.
link |
01:30:12.720
Because I think the upper range is somewhere around 55, 56.
link |
01:30:15.240
Exactly.
link |
01:30:16.580
So we would first back stall for what's driving his SHBG.
link |
01:30:21.040
So there's basically three hormones.
link |
01:30:22.720
So genetics plays a huge role in this.
link |
01:30:24.380
There's no question that just out of the box,
link |
01:30:27.380
people have a different set point for SHBG.
link |
01:30:30.440
Mine is incredibly low.
link |
01:30:31.720
My SHBG is like kind of in the 30s, 20s to 30s.
link |
01:30:35.880
But from a hormone perspective, there's
link |
01:30:37.480
basically three hormones that run it.
link |
01:30:39.400
So estradiol being probably the most important,
link |
01:30:42.960
insulin, and thyroxine.
link |
01:30:45.620
So we're going to look at all of those
link |
01:30:47.400
and decide if any of those are playing a role.
link |
01:30:49.280
So insulin suppresses it.
link |
01:30:50.880
So this is actually the great irony
link |
01:30:53.360
of helping a person get metabolically healthy,
link |
01:30:55.380
is in the short run, you can actually
link |
01:30:56.920
lower their free testosterone, all things equal.
link |
01:31:00.300
Because as insulin comes down, SHBG goes up.
link |
01:31:03.440
And if testosterone hasn't gone up with it,
link |
01:31:05.160
you're lowering free testosterone.
link |
01:31:06.960
So somebody who goes on a very low carbohydrate diet
link |
01:31:10.000
in an attempt to drop some water and drop some weight
link |
01:31:12.700
is going to increase their SHBG.
link |
01:31:14.480
Yeah, if their insulin goes down, they're tough.
link |
01:31:15.320
Bind up testosterone, less free testosterone.
link |
01:31:18.600
I can tell the carnivore diet people
link |
01:31:20.640
are going to be coming after me with bone marrow in hand.
link |
01:31:24.020
But then again, after this discussion
link |
01:31:25.940
extends a little further, I'm sure the vegans
link |
01:31:27.540
will be coming after me with celery stalks.
link |
01:31:29.320
So it's, so then the same as with estradiol.
link |
01:31:32.360
So except in the opposite direction.
link |
01:31:33.600
So higher estradiol is higher SHBG.
link |
01:31:37.760
So again, occasionally you'll see a guy
link |
01:31:39.600
with incredible, normal testosterone,
link |
01:31:41.520
but he's a very high aromatase activity person.
link |
01:31:45.760
So he has a lot of the enzyme
link |
01:31:47.400
that converts testosterone into estradiol.
link |
01:31:50.920
You can lower estradiol a bit with an aromatase inhibitor,
link |
01:31:53.880
and that can bring down SHBG.
link |
01:31:55.260
Now again, these things individually
link |
01:31:57.140
are rarely enough to move the needle.
link |
01:31:59.840
The last is thyroxine.
link |
01:32:01.120
So if you have a person whose thyroid is out of whack,
link |
01:32:03.380
you have to fix that before you,
link |
01:32:05.360
if their T4 is out of whack,
link |
01:32:06.640
you're going to interfere with SHBG.
link |
01:32:09.160
There are also some supplements,
link |
01:32:10.220
which I think you've probably talked about these
link |
01:32:11.700
on the podcast.
link |
01:32:12.540
I feel like I've heard you talk about these on the podcast.
link |
01:32:14.060
Yeah, there are a few that will adjust.
link |
01:32:15.680
You know, there is this idea.
link |
01:32:16.900
Now there's a much better review that just came out.
link |
01:32:19.640
I'll send it to you.
link |
01:32:20.480
I'd love your thoughts on it.
link |
01:32:21.300
And I've been perusing it line by line,
link |
01:32:24.040
but I love input from experts like you
link |
01:32:26.760
on the use of Tonga Ali for reducing SHBG.
link |
01:32:31.480
In my experience, it does free up some testosterone
link |
01:32:34.960
by which mechanism it isn't exactly clear,
link |
01:32:37.560
and the effects aren't that dramatic, right?
link |
01:32:39.760
There are probably multiple effects.
link |
01:32:41.480
For all we know, it increases libido,
link |
01:32:43.380
and it does generally by way of increasing estrogens slightly
link |
01:32:46.660
which can also increase libido in some individuals.
link |
01:32:48.700
So we don't know the exact mode of action.
link |
01:32:51.060
So we've talked about a few.
link |
01:32:51.920
The one that a few years back people were claiming
link |
01:32:54.120
could reduce SHBG was stinging nettles.
link |
01:32:58.720
Stinging nettle, well, urine seems to be,
link |
01:33:01.360
urinating seems to be coming up multiple times
link |
01:33:03.040
on this podcast for whatever reason.
link |
01:33:05.560
Stinging nettle extract,
link |
01:33:06.580
I took the most pronounced effect of that
link |
01:33:09.360
was you could basically urinate over a car
link |
01:33:11.960
when taking SHBG.
link |
01:33:13.000
What the underlying mechanism of that was, I do not know.
link |
01:33:16.560
I took it for a short while.
link |
01:33:17.520
It didn't drop my SHBG very much,
link |
01:33:20.320
but it did drop by DHT sufficiently
link |
01:33:23.360
so that I stopped taking it.
link |
01:33:25.040
I do not like anything that impedes DHT.
link |
01:33:28.060
I don't care if my hairline retreats.
link |
01:33:30.280
I don't care about any of that.
link |
01:33:31.560
DHT to me is something to be hoveted and held onto
link |
01:33:36.560
because you feel so much better
link |
01:33:38.460
when your DHT is in the appropriate range.
link |
01:33:40.720
And I'd love your thoughts on that at some point.
link |
01:33:42.200
Yeah, again, it really depends on the guy
link |
01:33:44.520
and it depends on what risk you're trying to manage, right?
link |
01:33:46.840
So prostate size starts to become
link |
01:33:49.020
one of the issues with DHT.
link |
01:33:50.600
Luckily, my prostate-specific antigen is low, and DHT,
link |
01:33:55.600
the things that I know can reduce it
link |
01:33:56.920
are things like finasteride, Propecia, things like that.
link |
01:33:59.160
So things that people take to try and avoid hair loss
link |
01:34:02.600
can dramatically reduce DHT
link |
01:34:04.560
and lead to all sorts of terrible sexual side effects,
link |
01:34:07.060
mood-based side effects, et cetera.
link |
01:34:08.840
But yeah, so I'm not aware of anything
link |
01:34:11.080
that can be taken in supplement form
link |
01:34:12.600
that can really profoundly drop SHBG.
link |
01:34:14.680
Yeah, we don't spend much attention on it anymore.
link |
01:34:16.920
Basically, I used to have
link |
01:34:18.880
a much more complicated differential diagnosis
link |
01:34:20.960
eight years ago.
link |
01:34:23.200
I would drive patients nuts
link |
01:34:24.440
with the whiteboard diagrams I would draw for them,
link |
01:34:26.440
when in the end, I think they were just like,
link |
01:34:27.640
dude, just what do I need to take?
link |
01:34:29.900
Today, we take a much more simple approach.
link |
01:34:31.340
So the first question is,
link |
01:34:32.480
should you or should you
link |
01:34:33.760
have your free testosterone being higher?
link |
01:34:35.280
That's the metric I care about,
link |
01:34:36.800
is free testosterone is the first most important,
link |
01:34:38.880
the second most important is estradiol.
link |
01:34:40.440
And sorry to interrupt,
link |
01:34:41.280
but you said if you look at your total testosterone,
link |
01:34:43.280
you want the free T to be about 2% of your total.
link |
01:34:45.320
Well, it should be, right?
link |
01:34:46.880
Now, I might not change that anymore.
link |
01:34:48.360
So in other words, if a guy's at 1%,
link |
01:34:50.720
then I know I have to really boost his total testosterone.
link |
01:34:53.440
If he's only going to get
link |
01:34:54.280
one to one and a half percent of it converted to free,
link |
01:34:56.720
I need to boost him.
link |
01:34:57.880
And that's why I don't care if he's outside the range.
link |
01:34:59.840
Like I'll have a guy who's free T,
link |
01:35:02.360
I might have to get a guy's total T up to 1,500
link |
01:35:04.820
to get his free T to 18.
link |
01:35:06.640
I see, so free T is the target.
link |
01:35:08.040
I like this approach. Free T is what we treat.
link |
01:35:09.400
And do you still use Anavarix?
link |
01:35:13.020
I don't use Anavarix.
link |
01:35:13.860
Sorry, to try and lower SHBG?
link |
01:35:15.720
I don't, no.
link |
01:35:16.560
Because it's too potent?
link |
01:35:17.760
No, because it's just too complicated for patients.
link |
01:35:19.880
You know, it's a drug that can't be taken orally,
link |
01:35:23.480
so you have to take it under the tongue.
link |
01:35:24.880
Like a troche or something.
link |
01:35:25.800
Right, but I had one patient once who,
link |
01:35:28.080
even though we told him about 87 times that,
link |
01:35:30.920
he was like swallowing the Anavars and his liver function.
link |
01:35:33.320
And he was like, we're talking 10 milligrams
link |
01:35:35.000
three times a week is a tiny dose.
link |
01:35:37.500
And three months of him, or whatever,
link |
01:35:39.280
two months of him swallowing that every time
link |
01:35:41.600
tripled his liver function test.
link |
01:35:42.980
So it's like, I was like, you know,
link |
01:35:44.600
it's just not worth the hassle of doing this for perfection.
link |
01:35:50.200
In reality, we can fix this another way.
link |
01:35:52.120
So the first order question is,
link |
01:35:54.280
do we believe clinically you will benefit
link |
01:35:57.240
from normalizing your free testosterone?
link |
01:36:00.720
Or taking it to a level that's call it
link |
01:36:03.580
80th to 90th percentile.
link |
01:36:05.300
So upper normal limit of physiologic ranges.
link |
01:36:10.600
That's the first order question.
link |
01:36:12.000
And that's going to come down to symptoms,
link |
01:36:13.600
and that's going to come down to some biomarkers.
link |
01:36:15.800
I think there's two years ago, was it two years ago,
link |
01:36:18.280
or maybe a year ago, a very good study came out
link |
01:36:20.580
that looked at prediabetic men,
link |
01:36:23.920
you've probably talked about this study,
link |
01:36:25.520
and looking at insulin resistance and glucose disposal
link |
01:36:29.480
with and without testosterone.
link |
01:36:30.680
And the evidence was overwhelmingly clear.
link |
01:36:33.120
Testosterone improves glycemic control.
link |
01:36:36.560
Testosterone improves insulin signaling.
link |
01:36:37.920
This shouldn't be surprising, by the way,
link |
01:36:39.720
given the role muscles play as a glucose reservoir
link |
01:36:42.420
in a glucose sink.
link |
01:36:43.720
So now I include that as one of the things
link |
01:36:45.700
that we will consider as a factor for using testosterone.
link |
01:36:49.300
Now, again, it's not the only one,
link |
01:36:50.800
so you can accomplish that with exercise,
link |
01:36:52.780
you can accomplish that with these other things,
link |
01:36:53.880
but then you get into a little bit of the vicious cycle
link |
01:36:55.760
of will having a normalized testosterone
link |
01:36:58.240
facilitate you doing those things better?
link |
01:37:00.800
So let's just assume we come to the decision
link |
01:37:03.700
that this person is a good candidate
link |
01:37:06.880
for testosterone replacement therapy.
link |
01:37:09.200
The next question is what's the method
link |
01:37:12.200
that we're going to do it?
link |
01:37:13.040
Are we going to do it indirectly or directly?
link |
01:37:15.440
Now, we used to use a lot of Clomid in our practice,
link |
01:37:20.480
and have you talked about Clomid on the podcast?
link |
01:37:22.320
I haven't talked too much about it.
link |
01:37:23.720
No, we've talked a little bit about the fact
link |
01:37:26.120
that some people taking things like anastrozole
link |
01:37:28.400
to reduce aromatase activity can potentially run
link |
01:37:32.480
into trouble because they think,
link |
01:37:34.720
oh, well, more testosterone good, lower estrogen bad,
link |
01:37:37.720
and then they end up with issues like joint pain,
link |
01:37:40.080
memory issues, and severe drops in libido,
link |
01:37:42.880
and I think a lot of the reason why.
link |
01:37:43.720
And even fat accumulation.
link |
01:37:45.440
So if estrogen is too low, you can develop adiposity
link |
01:37:49.160
in a way that you wouldn't otherwise.
link |
01:37:50.240
There's a great New England Journal paper,
link |
01:37:52.240
it's probably 10 years old now,
link |
01:37:53.360
that looked at, I believe it was five different doses
link |
01:37:56.920
of testosterone siponate.
link |
01:37:58.040
So these men were chemically castrated
link |
01:37:59.640
and divided into 10 groups.
link |
01:38:01.200
It's pretty remarkable.
link |
01:38:02.240
Somebody signed up for this study.
link |
01:38:03.480
Yeah, so you were with and without anastrozole
link |
01:38:07.080
and five doses of testosterone.
link |
01:38:09.080
So now you basically had five testosterone levels,
link |
01:38:12.480
plus or minus high or low estradiol.
link |
01:38:15.400
And the results were really clear
link |
01:38:17.120
that the higher your testosterone
link |
01:38:19.320
and the more your estradiol was in kind of
link |
01:38:21.200
that 30 to 50 range, the better you were.
link |
01:38:24.280
So if estrogen was too low,
link |
01:38:26.080
even in the presence of high testosterone,
link |
01:38:28.160
the outcomes were less significant.
link |
01:38:30.800
And this is 30 to 50 nanograms per deciliter,
link |
01:38:32.920
not 30 to 50% of one's testosterone.
link |
01:38:35.720
Okay, great.
link |
01:38:36.560
Okay, so we haven't talked, but Clomid is,
link |
01:38:39.320
no, we have not talked a lot about Clomid.
link |
01:38:41.000
I'd love to get your thoughts on Clomid.
link |
01:38:42.560
So Clomiphene is a fertility drug.
link |
01:38:45.160
It's a synthetic hormone.
link |
01:38:46.720
It's actually two drugs, M-Clomiphene
link |
01:38:48.920
and I forget the other one.
link |
01:38:50.840
And it tells the pituitary to secrete FSH and LH.
link |
01:38:58.680
So the advantage of Clomid is it's oral
link |
01:39:04.040
and it's meant to be taken orally.
link |
01:39:06.120
So a typical starting dose would be like 50 milligrams
link |
01:39:09.560
three times a week.
link |
01:39:11.600
And if you do that, you'll notice in most men,
link |
01:39:15.240
especially young men, FSH, LH goes up.
link |
01:39:17.720
In any man, the FSH and LH go up.
link |
01:39:19.560
But if a man still has testicular reserve,
link |
01:39:21.760
he'll make lots of testosterone in response to that.
link |
01:39:26.080
Because that's the first order question
link |
01:39:27.600
we're trying to answer is do you,
link |
01:39:30.140
is your failure to make testosterone central or peripheral?
link |
01:39:34.080
Yeah, and I think just one point out again,
link |
01:39:36.440
correct me if I'm wrong, but my understanding
link |
01:39:37.840
is that a lot of the drugs that we're talking about,
link |
01:39:41.560
the synthetic compounds, testosterone, estrogen,
link |
01:39:43.760
things related to growth hormone, et cetera,
link |
01:39:46.400
were discovered and designed in order to treat
link |
01:39:49.840
and excuse me, in order to isolate and treat
link |
01:39:52.100
exactly these kinds of syndromes,
link |
01:39:53.440
whether or not it was the hypothalamus, the pituitary
link |
01:39:56.160
or the target tissue, the ovaries or the testes, correct?
link |
01:39:59.680
Correct, yeah.
link |
01:40:00.520
I mean, I think the easiest way to go about doing this
link |
01:40:02.400
is just give the hormone that's missing
link |
01:40:04.600
without attention to where the deficiency is.
link |
01:40:07.640
Why this becomes relevant is if you have a 35-year-old guy
link |
01:40:12.200
whose testosterone is low, but you can demonstrate
link |
01:40:15.680
that it's low because he's not getting enough
link |
01:40:17.960
of a signal from the pituitary,
link |
01:40:19.800
why would you bother giving him more testosterone
link |
01:40:22.040
when he has the, he has the Leydig cells
link |
01:40:24.080
and the Sertuli cells to make testosterone,
link |
01:40:25.780
he just needs the signal.
link |
01:40:28.320
Sometimes, though not always,
link |
01:40:29.780
just a course of Clomid can wake him up
link |
01:40:32.800
and he's back to making normal testosterone.
link |
01:40:35.160
So he'll do this three times a week,
link |
01:40:36.800
50 milligrams three times a week for a short course
link |
01:40:39.980
and then- Yeah, we would do it
link |
01:40:40.820
for eight to 12 weeks and then we reevaluate.
link |
01:40:43.080
And estrogen and testosterone will increase in parallel.
link |
01:40:46.760
Yes, and again, it depends.
link |
01:40:49.040
Aromatase activity is dependent on how much body fat
link |
01:40:51.560
you have and genetics and if estradiol gets too high,
link |
01:40:56.060
we think if it gets over about 55, 60,
link |
01:40:58.620
we will give microdoses of an estradiol.
link |
01:41:01.360
But it has to be real microdoses.
link |
01:41:03.120
I mean, you cannot pound people with an estradiol.
link |
01:41:05.600
To give you perspective, the sort of on-label use,
link |
01:41:10.520
like if you just go to a pharmacy and order an estradiol,
link |
01:41:12.960
you're gonna get one milligram tablets.
link |
01:41:15.200
Like we can't give anybody a milligram.
link |
01:41:16.840
They'll feel like garbage.
link |
01:41:18.200
We have to have it compounded at 0.1 milligrams
link |
01:41:21.080
and we might give a patient 0.1 two to three times a week.
link |
01:41:24.100
That would be a big dose of an estradiol.
link |
01:41:26.720
Yeah, I think that the typical TRT clinic out there
link |
01:41:30.160
is giving 200 milligrams per mil,
link |
01:41:33.680
one mil, 200 milligrams of testosterone once every two weeks
link |
01:41:36.280
and then hitting people with multiple milligrams
link |
01:41:39.780
of an estradiol and they're all over the place.
link |
01:41:42.320
I've never really understood.
link |
01:41:43.700
I mean, I guess I shouldn't be surprised,
link |
01:41:45.360
but it kind of blows my mind that these TRT clinics
link |
01:41:47.840
are up all over the place given how bad,
link |
01:41:49.560
I mean, I see the results
link |
01:41:50.800
because I have patients that come from them
link |
01:41:53.440
and I don't understand like why they're so incompetent.
link |
01:41:56.280
I actually think it's worse than that.
link |
01:41:57.800
I think that they simply don't understand
link |
01:41:59.840
and don't care because it's a pill mill
link |
01:42:03.760
and it's a money mill.
link |
01:42:04.860
I think that nowadays it seems almost everybody
link |
01:42:07.160
who's doing TRT is taking lower doses more frequently
link |
01:42:09.820
every other day or twice a week dividing the dose
link |
01:42:12.240
and being very, very careful with these estrogen
link |
01:42:14.640
or aromatase blockers.
link |
01:42:17.340
Most of our patients do not take aromatase inhibitors.
link |
01:42:20.160
It's not needed.
link |
01:42:21.000
It's really only the high aromatizers that need it.
link |
01:42:23.760
And so, yeah, when we'll talk about testosterone,
link |
01:42:27.260
we'll talk about dosing there because I agree,
link |
01:42:28.900
the more frequently you can take it, the better.
link |
01:42:30.620
And frankly, you don't need to go more frequently
link |
01:42:32.880
than twice a week.
link |
01:42:34.460
Because it's so slow.
link |
01:42:35.700
Yeah, the half-life of the drug is,
link |
01:42:37.300
I think it's about three and a half days
link |
01:42:38.580
is the plasma half-life or something like that.
link |
01:42:39.940
It could be off a little bit,
link |
01:42:41.300
but twice week dosing is really nice.
link |
01:42:45.020
So if you go to like a testosterone clinic
link |
01:42:49.380
that's giving you 200 every two weeks,
link |
01:42:51.540
50 twice a week is the same total dose,
link |
01:42:54.520
which by the way, is a physiologic dose.
link |
01:42:56.240
That's not going to give somebody
link |
01:42:58.660
any of the side effects you would see.
link |
01:42:59.980
You're not gonna get acne with that.
link |
01:43:01.560
You're not gonna get gynecomastia.
link |
01:43:03.580
You're not gonna get any things.
link |
01:43:04.500
The only real side effect you get from that
link |
01:43:06.220
is you will get testicular atrophy.
link |
01:43:08.340
That is enough to suppress.
link |
01:43:09.780
Yeah, to maintain fertility,
link |
01:43:12.120
what do you typically do for them?
link |
01:43:13.620
Well, so this is where,
link |
01:43:14.780
so I'll finish the story on Clomid
link |
01:43:16.340
because we currently do not use Clomid.
link |
01:43:18.180
And that's due to a really interesting observation
link |
01:43:22.460
that we made that I don't think has been reported
link |
01:43:25.860
in the literature yet,
link |
01:43:27.300
which is that Clomid was increasing levels of a sterol
link |
01:43:31.460
that we also happen to measure called desmosterol.
link |
01:43:34.580
I'm not familiar with that.
link |
01:43:36.020
So in the way that cholesterol is made,
link |
01:43:39.580
it's made by, there's two pathways that make cholesterol.
link |
01:43:43.360
So it starts like with two carbon subunits,
link |
01:43:45.860
like acetyl-CoA, and it kind of marches down a pathway,
link |
01:43:48.300
bifurcates, and cholesterol is the finished product of both.
link |
01:43:52.620
But in one of those pathways,
link |
01:43:54.740
the molecule right before cholesterol is called desmosterol.
link |
01:43:58.500
In the other pathway, it's called lithosterol.
link |
01:44:00.740
So we constantly measure lithosterol and desmosterol
link |
01:44:04.820
because we want to know how much cholesterol
link |
01:44:06.820
is being synthesized in the body,
link |
01:44:08.620
not just what your cholesterol is.
link |
01:44:10.820
We wanna know how much cholesterol you reabsorb.
link |
01:44:13.820
And those markers are really important to us
link |
01:44:15.660
when we're looking at cardiovascular disease risk.
link |
01:44:19.040
So when we gave patients Clomid,
link |
01:44:22.300
we were noticing a almost universal rise
link |
01:44:26.840
in their desmosterol levels.
link |
01:44:30.020
Now, the most obvious explanation for that,
link |
01:44:31.840
though the last time I looked,
link |
01:44:33.740
I couldn't find clear explanation for this
link |
01:44:35.980
in any of the clinical trials
link |
01:44:38.580
that led to the approval of Clomid.
link |
01:44:40.260
So I don't know if it was described.
link |
01:44:41.700
In fact, maybe it wasn't known.
link |
01:44:43.340
I suspect it is inhibiting the enzyme,
link |
01:44:46.100
which I think is called Delta 24 desaturase,
link |
01:44:48.520
that turns desmosterol into cholesterol.
link |
01:44:51.480
Makes sense if you inhibit that enzyme,
link |
01:44:53.180
you're gonna see a rise in desmosterol.
link |
01:44:56.440
This wouldn't have been a concern to me
link |
01:44:58.420
if not for the fact that Tom Dayspring,
link |
01:45:00.160
who's one of the physicians we work with,
link |
01:45:01.420
who's one of the world's experts in lipids,
link |
01:45:02.880
pointed out a very obscure story,
link |
01:45:06.220
which was that the very first drug ever approved
link |
01:45:09.760
to treat cardiovascular disease,
link |
01:45:12.580
at least to treat hypercholesterolemia,
link |
01:45:14.860
was a drug that attacked the same enzyme.
link |
01:45:19.140
So this was in the early 1960s, I believe,
link |
01:45:21.740
maybe the mid-60s, this drug was approved
link |
01:45:23.640
and it lowered cholesterol.
link |
01:45:26.540
And it was approved on the basis of lowering cholesterol.
link |
01:45:28.780
Now, today, no drug for ASCVD is approved
link |
01:45:32.140
on the basis of it lowering cholesterol.
link |
01:45:34.140
That's not a high enough bar.
link |
01:45:35.420
You have to reduce events.
link |
01:45:36.980
They actually have to show that you're preventing
link |
01:45:38.440
heart attacks and death.
link |
01:45:40.740
But at the time, it was like, hey, it lowers cholesterol,
link |
01:45:42.500
it's gotta be good.
link |
01:45:43.700
Well, in the late 60s, it was pulled from the market
link |
01:45:45.860
because events were going up.
link |
01:45:47.860
So cholesterol was coming down, events were going up.
link |
01:45:50.780
How could that be?
link |
01:45:52.460
We don't know.
link |
01:45:53.600
What we are suspecting is that desmostrol,
link |
01:45:58.220
which is still a sterol, was potentially more damaging
link |
01:46:02.900
and created more oxidative stress in the endothelium,
link |
01:46:05.940
in the subendothelial space than cholesterol.
link |
01:46:07.780
I see.
link |
01:46:08.600
Which would at least suggest to us,
link |
01:46:10.860
and again, we're taking a lot of leaps here,
link |
01:46:13.020
that maybe having high desmostrol,
link |
01:46:15.140
very high desmostrol, is not a good thing.
link |
01:46:18.340
And so once we kind of pieced all that together
link |
01:46:20.980
a few years ago, we were like, yeah,
link |
01:46:22.620
we're just not gonna prescribe Clomid anymore.
link |
01:46:26.380
And we then switched to HCG,
link |
01:46:30.740
which we used to use sometimes instead of Clomid,
link |
01:46:33.340
but it's more cumbersome to work with.
link |
01:46:35.100
It needs to be refrigerated.
link |
01:46:36.260
It's a much more fragile molecule.
link |
01:46:38.100
Yeah, I think we talked about this once.
link |
01:46:39.300
It's almost like if you accidentally knock over
link |
01:46:42.220
the little bottle, it's basically gone bad.
link |
01:46:45.580
Travel with it is very challenging.
link |
01:46:47.140
Can't travel with it.
link |
01:46:48.820
It's a needle.
link |
01:46:49.660
It's an injection, sub-Q.
link |
01:46:51.300
So easy to administer.
link |
01:46:52.540
It's not IM or anything like that,
link |
01:46:53.940
but it's just more of a hassle factor.
link |
01:46:56.860
But that said, it has the benefit that Clomid does,
link |
01:47:00.140
which is it preserves testicular function.
link |
01:47:02.580
It preserves testicular volume.
link |
01:47:05.180
So bodybuilders will often use this
link |
01:47:07.700
in their post-cycle therapy
link |
01:47:09.500
as a way to kind of recover function.
link |
01:47:11.780
And we would just use it now as ongoing therapy
link |
01:47:15.180
for a guy who still has testicular reserve.
link |
01:47:17.940
So on its own, no testosterone,
link |
01:47:19.680
no aromatase inhibitor, nothing,
link |
01:47:21.520
just a way to crank out a bit more testosterone
link |
01:47:23.900
from the testes, maybe some additional estrogen also.
link |
01:47:26.380
And HCG is a different model.
link |
01:47:28.140
HCG is just an analog of luteinizing hormone.
link |
01:47:30.900
So it's basically like giving them luteinizing hormone.
link |
01:47:33.280
So it's gonna crush endogenous luteinizing hormone levels,
link |
01:47:36.160
right, because it's-
link |
01:47:37.000
It's really, yeah, and it,
link |
01:47:39.780
you don't really see much of an impact on LH,
link |
01:47:41.980
but you do see endogenous testosterone production go down.
link |
01:47:45.420
Actually, no, I correct that.
link |
01:47:46.340
Both FSH and LH will go down on a high enough dose, yep.
link |
01:47:49.940
Just as a mention, and here I'm not making recommendations,
link |
01:47:52.500
but one supplement I've talked a lot about publicly
link |
01:47:55.580
is Fidogia agrestis, which is this weird Nigerian shrub
link |
01:47:58.700
that does- You're talking about this
link |
01:48:00.380
on Tim's podcast.
link |
01:48:01.220
On Tim's podcast and Joe's podcast,
link |
01:48:03.100
and there was a bit of a backlash
link |
01:48:05.600
because it does turn out that at high doses
link |
01:48:07.980
in rodent studies, it can cause some toxicity to the testes,
link |
01:48:12.340
but at lower doses,
link |
01:48:14.500
it does seem to increase luteinizing hormone.
link |
01:48:16.620
And after talking about this,
link |
01:48:17.520
a number of people went out there,
link |
01:48:18.380
did pre and post blood work,
link |
01:48:19.620
and the consistent effect seems to be an increase
link |
01:48:21.940
in luteinizing hormone.
link |
01:48:23.060
There's a noticeable effect on testicular size and volume.
link |
01:48:26.680
So a lot of people will take this and be like,
link |
01:48:27.740
oh, you know, their balls are getting bigger,
link |
01:48:29.740
and so they get all excited
link |
01:48:30.780
that something good is happening.
link |
01:48:32.700
But we don't know the long-term safety and efficacy
link |
01:48:35.500
of something like Fidogia,
link |
01:48:36.660
whether or not it needs to be cycled.
link |
01:48:37.780
Yeah, this is why I'm also very leery
link |
01:48:40.060
of the supplements in this space,
link |
01:48:41.580
because at least when we're using HCG or testosterone,
link |
01:48:46.060
like we have so many years of data.
link |
01:48:48.560
You have to remember how many women are using this stuff
link |
01:48:51.020
for reproductive medicine.
link |
01:48:53.060
So, you know, I think the FDA has a lot of faults.
link |
01:48:58.260
I think I have an entire podcast devoted
link |
01:49:00.480
to the corruption of the FDA
link |
01:49:02.300
and all of the mistakes that have been made
link |
01:49:03.900
with respect to their oversight in especially generic drugs,
link |
01:49:08.620
but it's way more regulated than the wild, wild west
link |
01:49:11.660
of nutty supplement land.
link |
01:49:13.280
Absolutely.
link |
01:49:14.120
I think that the reason for talking about things
link |
01:49:16.260
like Tonga and Fidogia was
link |
01:49:17.720
to provide some intermediate discussion
link |
01:49:19.980
between doing all the correct things,
link |
01:49:22.160
but no supplementation or hormone therapy,
link |
01:49:24.260
and then going straight to hormone therapy.
link |
01:49:25.900
It's sort of like the leap from,
link |
01:49:27.440
I can't focus very well to Ritalin, right,
link |
01:49:30.360
without a real diagnosis of ADHD,
link |
01:49:33.320
to, oh, well, maybe some things like alpha-GPC
link |
01:49:36.300
low doses of nicotine, right?
link |
01:49:38.020
But I agree entirely.
link |
01:49:39.740
I mean, the sourcing is important.
link |
01:49:41.440
The dosages are worked out empirically on an individual basis
link |
01:49:45.680
and there aren't randomized control trials.
link |
01:49:47.820
There just aren't.
link |
01:49:49.260
Yeah, and, you know, have kind of like a seven,
link |
01:49:54.480
this is another Peter principle, right?
link |
01:49:56.360
So I've got a lot of patients that come into the practice
link |
01:49:58.540
and, you know, during our intake, we go through,
link |
01:50:01.160
what drugs and supplements are you taking right now?
link |
01:50:03.360
And, you know, a lot of people come in,
link |
01:50:04.520
I'm not taking anything, Peter.
link |
01:50:05.680
I just, you're in charge now.
link |
01:50:07.320
Like, tell me what you think.
link |
01:50:08.800
And then you get a lot of people that come in
link |
01:50:09.960
and they're like, we're gonna need an extra few pages
link |
01:50:12.640
for this part of the documentation.
link |
01:50:13.480
Right, the people who travel with a suitcase
link |
01:50:15.120
that you can hear as they walk through the airport
link |
01:50:16.720
from all the pills that I like.
link |
01:50:17.560
Right, and so I give these patients
link |
01:50:19.400
a little homework exercise,
link |
01:50:20.520
which is you have to answer these seven questions
link |
01:50:22.680
for every supplement you take.
link |
01:50:23.940
And here's the spreadsheet and let's talk about it.
link |
01:50:26.100
And it basically just runs through,
link |
01:50:28.160
like, you know, it's basically walking you through
link |
01:50:31.280
the logic of why do you take this molecule?
link |
01:50:34.360
And I think for many people,
link |
01:50:38.000
when they do that, it's very sobering, right?
link |
01:50:40.360
They kind of, a lot of them will come back and be like,
link |
01:50:42.220
you know what, I don't think I can come up with any reason
link |
01:50:45.800
along this really rigorous line of thinking
link |
01:50:47.940
as to why I'm taking 80% of this stuff.
link |
01:50:50.440
Well, I know people, and actually we know some
link |
01:50:51.900
of the same people were fanatic about like red light
link |
01:50:55.060
on the testes, sunning their testes,
link |
01:50:58.120
putting ice packs on their testes.
link |
01:50:59.680
It's kind of all over the place.
link |
01:51:00.960
The number of things that people are trying and doing
link |
01:51:03.480
in order to increase testosterone output
link |
01:51:05.800
from their testes is pretty remarkable.
link |
01:51:07.360
And that said, among some of the women I know,
link |
01:51:10.280
the number of things that they're doing
link |
01:51:11.320
to try and promote longevity and fertility,
link |
01:51:13.600
and in particular skin health, hair health,
link |
01:51:16.100
and nail health is also kind of outrageous.
link |
01:51:19.640
Everything from collagen to red light therapies,
link |
01:51:21.800
which may actually have some efficacy in certain cases.
link |
01:51:24.000
But there's a hunger there, right?
link |
01:51:26.960
Oh, for sure.
link |
01:51:27.880
One of the things that I hope gets a lot more attention
link |
01:51:29.800
is the use of rapamycin for preserving ovarian health.
link |
01:51:33.200
So the animal literature on this is pretty impressive, right?
link |
01:51:36.640
So in mouse models, rapamycin will preserve ovarian life.
link |
01:51:41.840
And so it makes sense, right?
link |
01:51:43.240
I mean, it totally makes sense
link |
01:51:44.320
why the most potent, zero protective molecule we have
link |
01:51:48.820
would also preserve and extend ovarian life, at least in mice.
link |
01:51:52.720
So I'd love to see the clinical trials done in women
link |
01:51:57.640
to test this hypothesis.
link |
01:51:59.240
I definitely want to come back to this
link |
01:52:00.480
because it's a key thing.
link |
01:52:01.600
I know that a lot of people are interested
link |
01:52:02.680
in female fertility out there,
link |
01:52:05.200
including their male partners.
link |
01:52:06.280
So going back to, so now I understand
link |
01:52:09.960
why you don't prescribe clomiphene
link |
01:52:11.160
because of this potential dysmosterol link.
link |
01:52:17.640
What about testosterone therapy?
link |
01:52:19.020
So less frequent, lower doses,
link |
01:52:22.100
less or no estrogen inhibition or aromatase inhibition?
link |
01:52:25.960
Yeah, we're only using an aromatase blocker,
link |
01:52:29.520
and we use Arimidex when we do.
link |
01:52:31.480
It's just to get that estradiol into the range we want.
link |
01:52:34.480
I like to see it between 30 and 50.
link |
01:52:36.720
That's the sweet spot.
link |
01:52:37.840
And I don't know, I would say like a third,
link |
01:52:41.320
maybe not even a third, I'd say probably 20% of men
link |
01:52:45.460
require a microdose of anastrozole to get into that range.
link |
01:52:49.740
Most do not.
link |
01:52:50.580
And I'd rather err on the side
link |
01:52:53.060
of being a little high than a little low.
link |
01:52:54.900
So I never really want to be below 25.
link |
01:52:57.840
If, unless, sometimes it's just below 25 and it is,
link |
01:53:00.940
it is what it is, that's fine.
link |
01:53:02.420
But if we're suppressing it to below 25,
link |
01:53:04.420
I never want to be in that zone.
link |
01:53:06.820
And then yes, so TRT is ultimately,
link |
01:53:09.520
giving testosterone, cipunate is usually what we use.
link |
01:53:12.620
Injectable, so as opposed to cream or pellet.
link |
01:53:15.020
Correct.
link |
01:53:16.480
I used to use pellets with women for some
link |
01:53:22.060
who were really adamant about the convenience of it.
link |
01:53:26.680
But for a bunch of reasons, I just,
link |
01:53:29.100
I'm mostly not doing that.
link |
01:53:31.220
And I've never been a fan of pellets in men.
link |
01:53:34.620
You can't control the dosage once it's in, right?
link |
01:53:36.820
Well, even if you know the dose,
link |
01:53:37.640
yeah, that's obviously a problem.
link |
01:53:38.740
But I don't think, there's a big difference
link |
01:53:40.660
between putting a pellet into a man and a woman.
link |
01:53:42.080
So when you're putting an estrogen pellet into a woman,
link |
01:53:44.180
it's like, it's that big.
link |
01:53:47.380
When you're putting enough pellets into a man
link |
01:53:49.780
for six months of testosterone,
link |
01:53:51.500
it's two sums of pellets that are longer than my finger.
link |
01:53:54.740
So you're putting like a V-shape,
link |
01:53:56.660
you're putting it into the gluteal fat.
link |
01:53:59.740
So it's just a more morbid procedure
link |
01:54:01.620
and I don't think it's necessary.
link |
01:54:02.800
I think if you know how to manage it,
link |
01:54:05.100
through sort of the injections and now,
link |
01:54:07.660
yeah, well, especially now if you're doing,
link |
01:54:09.540
we're having them do sub-Q injections anyway.
link |
01:54:11.580
So it's not IM, they're using a five eighths inch
link |
01:54:14.740
to a one inch 25 gauge needle,
link |
01:54:16.780
which is about the smallest needle
link |
01:54:17.700
you can push the oil through once to twice a week,
link |
01:54:21.380
depending on, and by the way,
link |
01:54:22.380
if they're real needle phobes,
link |
01:54:23.460
we use Zyosted, which is a preloaded pen.
link |
01:54:26.260
And are you having all men take HCG
link |
01:54:29.780
to maintain fertility and test their killer size?
link |
01:54:31.220
Only if they want to.
link |
01:54:32.260
Got it.
link |
01:54:33.100
Yeah.
link |
01:54:33.920
And by the way, we do not like to use TRT in men who,
link |
01:54:36.220
we don't like to use testosterone specifically
link |
01:54:37.840
in men who still want to maintain fertility.
link |
01:54:39.880
We just steer them away from that.
link |
01:54:41.020
Because total sperm count goes down.
link |
01:54:42.540
Yeah, we just say, why risk it?
link |
01:54:43.460
Like we'd rather use HCG.
link |
01:54:45.900
Just on its own.
link |
01:54:46.720
Yeah, just wait, just wait until you're done reproducing.
link |
01:54:48.540
Bank sperm, wait till you're done reproducing
link |
01:54:50.560
before we go to testosterone.
link |
01:54:53.120
What are some of the benefits
link |
01:54:54.900
and what are some of the cautionary notes
link |
01:54:57.660
with appropriate TRT, meaning of the kind of contour
link |
01:55:01.780
that we're talking about here,
link |
01:55:03.260
a lower dose with the yes or no low estrogen control?
link |
01:55:08.180
People, what generally people report, how do they feel?
link |
01:55:13.180
What does it allow them to do
link |
01:55:14.460
that they couldn't do or feel before?
link |
01:55:16.700
And then in terms of what are the markers to look for?
link |
01:55:19.840
Is it LDL, blood pressure, water retention, acne,
link |
01:55:24.020
those kinds of things?
link |
01:55:24.840
Are there some other things as well?
link |
01:55:25.680
Yeah, it depends on the doses, right?
link |
01:55:26.660
I mean, again, we're using these in really low doses.
link |
01:55:29.060
So it's pretty rare that we'd have a patient
link |
01:55:31.140
on more than 100 milligrams a week of testosterone.
link |
01:55:35.620
I think for comparison,
link |
01:55:36.940
like a bodybuilder could easily take 500 to 1,000
link |
01:55:40.300
during a high growth phase.
link |
01:55:41.900
I know some of these guys, they go ballistic
link |
01:55:43.980
or they're doing moderate levels of testosterone sibonate,
link |
01:55:47.420
but they're also taking dianabolic, sandralone,
link |
01:55:52.780
SARMs and a bunch of other things.
link |
01:55:54.500
I mean, their stacks are kind of ridiculous.
link |
01:55:56.180
I mean, no disrespect to that sport,
link |
01:55:58.340
but I mean, people are dying like crazy
link |
01:56:00.940
in that sport right now.
link |
01:56:01.760
It's outside of physiology.
link |
01:56:02.780
Yeah, and I think for 99% of people listening,
link |
01:56:04.840
they just, they look, they hear bodybuilder
link |
01:56:06.660
and they just go like, why would somebody do that anyway?
link |
01:56:09.620
I think that's the typical response.
link |
01:56:10.940
So the point is a lot of,
link |
01:56:12.860
but we owe those guys a great deal of gratitude
link |
01:56:15.420
because they've shown us the boundaries.
link |
01:56:17.100
Including the women.
link |
01:56:18.140
That's right, yeah.
link |
01:56:19.780
And so those bodybuilders have taught us a lot
link |
01:56:23.740
about like what happens.
link |
01:56:26.120
And so, yeah, the bloating, the water retention,
link |
01:56:30.900
acne, hair loss, hair growth, all of those things,
link |
01:56:34.020
we understand the truth of it is
link |
01:56:36.020
we just don't see those things in our patients.
link |
01:56:39.100
But 100 milligrams per week is a very low output.
link |
01:56:41.900
My understanding is-
link |
01:56:42.740
But it's a physiologic dose.
link |
01:56:43.560
I mean, the reality of it is it's enough for most people.
link |
01:56:44.940
I mean, there's probably the highest we've ever had to go
link |
01:56:47.060
is maybe 70 twice a week.
link |
01:56:49.500
What's the youngest patient you've ever had to put on TRT?
link |
01:56:52.780
Actual testosterone?
link |
01:56:53.940
Mm-hmm.
link |
01:56:58.180
Probably, that's a good question.
link |
01:56:59.020
I'm thinking about maybe 40.
link |
01:57:02.140
I think that's great for people to hear
link |
01:57:03.300
because I know that a lot of guys in their 20s
link |
01:57:04.960
are thinking TRT is the way to go, and I would argue,
link |
01:57:07.180
unless you're doing everything else right
link |
01:57:08.580
and you're still hypogonadal and you're really struggling,
link |
01:57:11.060
put that time off because also the fertility issue,
link |
01:57:14.020
you want to delay delay delay.
link |
01:57:14.940
Well, again, it depends if when we say TRT,
link |
01:57:17.100
if you're in your 20s and there's no other way,
link |
01:57:19.700
I would hope you would be steered toward HCG
link |
01:57:22.560
to at least preserve testicular function.
link |
01:57:24.340
Now, again, we don't actually know
link |
01:57:26.260
if after being on HCG for 10 years,
link |
01:57:29.820
your pituitary will still work.
link |
01:57:31.500
Right, you won't be able to make your own luteinizing.
link |
01:57:33.220
Exactly, so it might be the case
link |
01:57:35.260
that you're gonna need something upstream of that,
link |
01:57:37.660
like Clomid to kickstart it.
link |
01:57:39.620
But again, I don't want anybody who's listening to this
link |
01:57:42.500
who's using Clomid for fertility
link |
01:57:44.340
to think that there's anything wrong with it.
link |
01:57:46.220
My concern over this became like,
link |
01:57:47.940
if you're gonna be on this for 10 years, is it problematic?
link |
01:57:50.660
Not if you're using this for a course of IVF
link |
01:57:52.860
or something like that.
link |
01:57:54.340
So again, if we felt that someone's pituitary
link |
01:57:57.400
was not working, I would be happy to put three months
link |
01:57:59.820
of Clomid on them to kind of try to see
link |
01:58:01.480
if we could blast it back.
link |
01:58:02.860
Do you have men cycle on and off testosterone
link |
01:58:05.660
at these low dosages?
link |
01:58:06.660
Are they taking a month vacation from it every once in a while?
link |
01:58:08.740
Yeah, it totally depends.
link |
01:58:09.580
You know, I was talking to a patient yesterday
link |
01:58:10.880
where we just decided to change the cycle.
link |
01:58:13.680
Eight weeks on, then eight weeks on HCG.
link |
01:58:15.700
Eight weeks on, then eight weeks on HCG.
link |
01:58:17.380
So that's gonna be a cycle
link |
01:58:18.500
that maintains his testosterone level
link |
01:58:20.540
but fluctuates between endogenous, exogenous,
link |
01:58:22.840
endogenous, exogenous.
link |
01:58:23.980
Sometimes we'll just do testosterone on, off, on, off.
link |
01:58:27.620
And there it's like, how much can he replenish naturally
link |
01:58:30.720
but understanding his T will dip during those off cycles.
link |
01:58:34.340
It seems to me there's a tremendous incentive
link |
01:58:37.220
for somebody to develop a molecule
link |
01:58:40.780
that can directly target SHBG,
link |
01:58:43.440
besides oxyandryl and ANIMAR, right?
link |
01:58:46.380
If one could just drop SHBG just the tiniest bit,
link |
01:58:49.960
it seems like one could adjust the free T
link |
01:58:53.280
in a way that would be great.
link |
01:58:54.700
I don't know why that molecule is so hard to target
link |
01:58:56.620
but somebody ought to do it.
link |
01:58:57.700
The chemistry can't be that hard.
link |
01:58:59.140
I talked with Patrick Arnold about this
link |
01:59:01.140
many, many years ago.
link |
01:59:04.100
I wish I could remember what his ID,
link |
01:59:06.860
he had a comment about this that at the time made sense
link |
01:59:09.580
and I don't remember what it was.
link |
01:59:10.580
Cause I had that thought too, like, man,
link |
01:59:14.400
especially for that subset of guys
link |
01:59:15.840
who have normal testosterone
link |
01:59:17.620
but they're just overbinding it.
link |
01:59:19.660
I'm really glad that you brought up this issue
link |
01:59:21.380
of total testosterone versus free T.
link |
01:59:23.100
And the reason is ever since going on podcasts
link |
01:59:25.540
and talking about this stuff
link |
01:59:26.580
and talking about it on this podcast,
link |
01:59:28.580
people will send me their numbers,
link |
01:59:30.060
they'll send me their charts
link |
01:59:31.380
and then they'll send photos of themselves.
link |
01:59:33.020
And I can tell you, while I'm not a clinician
link |
01:59:34.860
and I haven't done fancy statistics on it,
link |
01:59:37.220
there's very little correlation
link |
01:59:38.620
between someone's absolute testosterone and how they appear.
link |
01:59:41.980
I mean, some of these guys look really lean, really strong
link |
01:59:46.060
and they'll say, oh, total testosterone is 550, 480, right?
link |
01:59:50.620
And then other people, you know, testosterone is 860
link |
01:59:53.900
but you look at them and you think,
link |
01:59:55.540
oh, they kind of have a kind of a doughy look to them.
link |
01:59:57.780
And so it's gotta be this free testosterone thing
link |
02:00:00.300
plus estrogen, et cetera.
link |
02:00:01.540
And so cosmetically-
link |
02:00:02.380
Well, but also training and nutrition too, right?
link |
02:00:04.060
I mean, I just think, I think for all this talk
link |
02:00:08.220
about testosterone, which I enjoy talking about
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02:00:10.380
and I enjoy talking about the data
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02:00:12.220
on long-term health consequences of testosterone
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02:00:15.020
because this is another controversial topic.
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02:00:17.460
I also think people kind of overstate its importance.
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02:00:19.980
I agree.
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02:00:20.820
And I think there's a group of people who think
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02:00:23.540
if I could just fix my testosterone,
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02:00:24.900
everything will be better.
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02:00:25.840
And it's sort of like, no, actually that's not true at all.
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02:00:29.620
Really, the only purpose in my mind of fixing testosterone
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02:00:32.580
is to give you the capacity to work harder.
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02:00:36.220
It's really going to help you recover more
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02:00:38.600
from your workouts.
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02:00:39.540
This should just give you a greater ability
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02:00:41.940
to experience muscle protein synthesis.
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02:00:44.980
So, you know, if I just give you a bunch of testosterone
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02:00:47.300
and you sit on the couch and your nutrition doesn't change
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02:00:49.460
and you're not exercising anymore,
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02:00:50.540
you're not gonna experience any benefits of this thing.
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02:00:53.540
I mean, my testosterone level has fluctuated quite a bit
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02:00:55.860
throughout my life.
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02:00:57.060
And when I think about as an adult,
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02:00:59.460
not sort of including when I was sort of
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02:01:01.420
a fanatical teenager, but as an adult,
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02:01:03.980
when was I at my absolute most insane physique?
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02:01:08.100
Like my best performance on a DEXA scan
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02:01:11.300
would have been 30, I was 38 years old.
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02:01:16.060
By DEXA, I was 7% body fat.
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02:01:18.260
My fat-free mass index was like 23.2,
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02:01:21.460
23.3 kilograms per meter squared.
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02:01:24.780
I mean, I was huge, strong, and totally ripped.
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02:01:30.420
My testosterone was in the toilet.
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02:01:32.160
I was over-training like crazy.
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02:01:34.740
I was exercising probably 26 hours a week,
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02:01:38.860
killing it in the gym, swimming like a banshee,
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02:01:41.420
cycling like my life depended on it,
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02:01:43.660
grossly over-trained, low T, but, you know,
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02:01:47.580
I mean, physically looked like twice the guy I am today.
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02:01:51.300
You know, today my T is probably
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02:01:52.460
twice as high as it was then.
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02:01:54.340
So, you know, now you could say, well, Peter,
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02:01:57.140
what if you took T back then?
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02:01:58.700
How much better could you have been?
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02:01:59.820
Sure.
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02:02:01.100
But again, I think the take home is
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02:02:03.820
just giving somebody T doesn't do much of anything.
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02:02:06.740
It probably helps on the insulin resistance front
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02:02:08.980
without any other thing, but to me, that's a waste.
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02:02:12.420
Like that's squandering the gift that it is giving you,
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02:02:15.300
which is the ability to do more work
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02:02:17.920
and, you know, capture the benefit of it via muscle protein
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02:02:21.540
synthesis.
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02:02:22.380
I agree, and I think that the psychological effect
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02:02:24.900
of testosterone, whether or not it's exogenous or endogenous
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02:02:27.860
is it makes effort feel good.
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02:02:30.640
Yeah.
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02:02:31.480
At some level, it really seems to do that.
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02:02:32.800
And Sapolsky tells me the main reason,
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02:02:34.940
or mechanistically the main reason that it can do that
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02:02:37.540
is by adjusting levels of activity in the amygdala.
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02:02:41.100
Interesting.
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02:02:41.940
And so there's some interesting imaging there.
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02:02:44.020
I'd love to chat more about the cholesterol pathway.
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02:02:47.500
And I know this is a huge landscape as well,
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02:02:49.480
but I think we're doing a good job of diving in deep,
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02:02:53.000
but not getting stuck in the underlying currents at all.
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02:02:58.640
There's tremendous debate about whether or not
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02:03:02.060
dietary cholesterol directly relates to,
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02:03:05.380
or does not relate to serum cholesterol, LDL and HDL.
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02:03:09.860
Here's my-
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02:03:10.700
Is there?
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02:03:11.780
Well, let me put it this way.
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02:03:14.580
There are people that argue, I'm certainly not arguing.
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02:03:17.220
There are people that argue that if one eats a ton
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02:03:22.640
of saturated fat, that LDL goes up and HDL goes down.
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02:03:27.580
Okay, but that's not dietary cholesterol per se.
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02:03:29.660
No, not dietary cholesterol per se.
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02:03:31.180
But, and then there are people that argue
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02:03:33.140
that any increase in saturated fat intake
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02:03:37.820
is going to be bad, that you already synthesize
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02:03:40.140
enough cholesterol for hormone production, et cetera.
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02:03:42.620
I'd like to talk about this in terms
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02:03:43.900
of how one should read their charts.
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02:03:45.860
My LDL is in what I'm told is healthy range.
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02:03:49.720
My HDL is in what I'm told is healthy range.
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02:03:52.340
I do try and not overeat things like butter, cheese,
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02:03:55.720
and red meat, but I do eat some of those things
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02:03:58.040
and I feel pretty good.
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02:03:59.440
But most people are operating under the assumption
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02:04:05.120
that eating saturated fat is bad
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02:04:07.440
and you only do it in so far as you want to taste it.
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02:04:10.940
And then of course, there's a small group of people
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02:04:13.120
that love to eat organs and meats and really pack
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02:04:16.760
cholesterol and would argue that it doesn't matter
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02:04:19.960
if your LDL is 870, it's not going to impact your health.
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02:04:24.440
What's the reality around LDL, HDL, dietary cholesterol,
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02:04:29.080
saturated fat, at least in your view?
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02:04:33.400
So first, let's differentiate between cholesterol and fat,
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02:04:35.720
just for the listener, because we use them,
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02:04:38.920
I don't want to make sure people understand.
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02:04:40.080
So cholesterol is a really complicated molecule.
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02:04:43.620
So it's a ringed molecule.
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02:04:47.240
I used to know exactly what its structure was,
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02:04:49.200
but it could have 36 carbons for all I remember.
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02:04:53.040
It is a lipid, so it is a hydrophobic molecule
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02:04:56.720
that is synthesized by every cell in the human body.
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02:05:01.000
It is so important that without it,
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02:05:04.040
if you look at sort of genetic conditions
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02:05:07.720
that impair cholesterol synthesis,
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02:05:10.560
depending on their severity, they can be fatal in utero.
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02:05:14.260
So in other words, anything that really interferes
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02:05:16.760
with our ability to produce cholesterol
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02:05:20.360
is a threat to us as a species.
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02:05:23.000
And the reason for that is cholesterol makes up
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02:05:26.400
the cell membrane of every cell in our body.
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02:05:29.440
So as you know, but maybe the listeners don't,
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02:05:32.980
even though a cell is a spherical thing,
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02:05:35.200
it has to be fluid, right?
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02:05:36.920
It's not just a rigid like sphere,
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02:05:39.800
like a blow up ball, right?
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02:05:41.360
It's gotta be able to kind of move in this way
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02:05:44.960
to mesh with other cells.
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02:05:47.440
It also has to accommodate having porous structures
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02:05:50.680
that traverse its membrane to allow ions
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02:05:54.400
and things like that to go across.
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02:05:56.740
And it's cholesterol that gives the fluidity
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02:05:59.440
to that membrane.
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02:06:01.180
It's also, as you're alluding to, the backbone
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02:06:04.040
of some of the most important hormones in our body,
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02:06:07.120
estrogen, progesterone, testosterone, cortisol.
link |
02:06:12.500
So we have this thing, super important.
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02:06:14.560
Okay, then let's talk about does cholesterol,
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02:06:17.960
can you get cholesterol in your diet?
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02:06:20.220
Yes, you can eat foods that are rich in cholesterol.
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02:06:24.820
What was known in 1960,
link |
02:06:28.480
but somehow escaped everybody's imagination
link |
02:06:31.840
until finally the American Heart Association acknowledged
link |
02:06:34.320
this a few years ago, is that the cholesterol you eat
link |
02:06:37.960
does not really make it into your body.
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02:06:40.240
And the reason for that is it's hysterified.
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02:06:42.680
So we have, and not to get too nerdy,
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02:06:45.040
but I think people, I really think it's important
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02:06:47.440
people understand how this thing works.
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02:06:48.680
So we have cells in our gut, enterocytes,
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02:06:51.800
they're the endothelial cells of our gut.
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02:06:54.400
They have, each one of them has basically
link |
02:06:57.520
two transporters on them.
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02:06:58.700
So the first is called the Niemann-Pick C1-Like1 transporter.
link |
02:07:03.040
The second is called the ATP-Binding cassette G5-G8.
link |
02:07:08.320
Okay, the Niemann-Pick C1-Like1 transporter
link |
02:07:11.440
will bring in any sterile, cholesterol,
link |
02:07:14.820
zosterol, phytosterol, any sterile
link |
02:07:17.520
that fits through the door will come in.
link |
02:07:20.840
Virtually all of that is the cholesterol we produce
link |
02:07:25.240
that gets taken back to the liver,
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02:07:27.480
that the liver packages in bile and secretes.
link |
02:07:30.960
So that's what aids in our digestion,
link |
02:07:32.800
which is another thing I should have mentioned earlier.
link |
02:07:34.400
In addition to using cholesterol
link |
02:07:36.800
for cell membranes and hormones,
link |
02:07:38.760
we wouldn't be able to digest our food without cholesterol
link |
02:07:41.200
because it's what makes up the bile salts.
link |
02:07:44.080
So our own cholesterol is basically recirculated
link |
02:07:47.200
in a pool throughout our body,
link |
02:07:48.880
and this is the way it gets back into the body.
link |
02:07:51.580
It's through this Niemann-Pick C1-Like1 transporter.
link |
02:07:54.720
When it gets in there, the body,
link |
02:07:56.640
this is the checkpoint of regulation.
link |
02:07:58.560
This is where the body says,
link |
02:07:59.540
do you have enough cholesterol in the body, yes or no?
link |
02:08:02.340
If yes, I will let that cholesterol
link |
02:08:05.160
make its way into the circulation.
link |
02:08:07.360
So it'll go off the basolateral side of the cell,
link |
02:08:10.060
not the luminal side, into the body.
link |
02:08:12.080
Alternatively, the body says,
link |
02:08:13.680
you know what, we have enough cholesterol.
link |
02:08:16.080
I'm gonna let you poop this out.
link |
02:08:17.440
And now the ATP binding cassette will shoot it out.
link |
02:08:20.040
It'll go back into the luminal side, and away it goes.
link |
02:08:22.740
So all of the cholesterol in our body is not esterified,
link |
02:08:27.900
and it doesn't have that big,
link |
02:08:29.140
bulky side chain attached to it.
link |
02:08:31.840
The cholesterol you eat is esterified,
link |
02:08:34.460
and an esterified cholesterol molecule
link |
02:08:37.180
simply can't physically pass
link |
02:08:38.940
through that Niemann-Pick C1-Like1 transporter.
link |
02:08:41.220
Now, we probably manage to de-esterify
link |
02:08:46.740
10 to 15% of our dietary cholesterol.
link |
02:08:50.260
So in other words, there are small amounts
link |
02:08:52.340
of dietary cholesterol
link |
02:08:53.500
that do make their way into our circulation,
link |
02:08:57.140
but it represents a small fraction
link |
02:08:59.780
of our total body's pool of cholesterol.
link |
02:09:02.160
Again, this was known even by Ancel Keys,
link |
02:09:05.420
the guy who turned fat into the biggest bogeyman of all time.
link |
02:09:09.580
Ancel Keys acknowledged this in the 1960s.
link |
02:09:12.760
Dietary cholesterol plays no role in serum cholesterol.
link |
02:09:17.340
Again, it took the American Heart Association
link |
02:09:19.100
another 60 years to figure that out,
link |
02:09:21.380
but even now, they acknowledge that.
link |
02:09:23.540
Dietary cholesterol has no bearing.
link |
02:09:25.500
So why is it that it's pretty easy to find studies,
link |
02:09:29.980
or at least people who are highly credentialed
link |
02:09:32.940
from good institutions,
link |
02:09:34.020
claiming that eating saturated fat, cheese-
link |
02:09:37.260
Saturated fat's different.
link |
02:09:38.380
Saturated fat and red meat,
link |
02:09:39.620
things that are rich in cholesterol,
link |
02:09:43.240
to be more specific, is bad for us
link |
02:09:45.940
in terms of our eventual LDL.
link |
02:09:47.940
So this is two different things.
link |
02:09:49.140
So saturated fat consumption in many people
link |
02:09:52.660
will raise LDL cholesterol.
link |
02:09:55.760
So it's important to differentiate
link |
02:09:56.940
between what is saturated fat.
link |
02:09:58.900
So saturated fat, of course, is a fatty acid,
link |
02:10:00.860
just so people understand.
link |
02:10:01.940
Totally different molecule from cholesterol.
link |
02:10:03.580
Cholesterol is this very complicated ring structure,
link |
02:10:05.980
multiple rings stuck together.
link |
02:10:08.100
SFA, saturated fat, is just a long-chain fatty acid
link |
02:10:11.320
that is fully saturated, meaning it has no double bonds,
link |
02:10:14.160
and it can exist in isolation.
link |
02:10:16.100
It can exist in a triglyceride, triacylglyceride,
link |
02:10:19.540
or a phospholipid, or all sorts of things like that.
link |
02:10:23.180
So when we eat foods that contain fat,
link |
02:10:27.780
basically there are three distinctions for that fat.
link |
02:10:30.380
Is it saturated?
link |
02:10:31.460
Is it monounsaturated, one double bond?
link |
02:10:33.260
Or is it polyunsaturated, two or more double bonds?
link |
02:10:37.280
The observation that eating saturated fat
link |
02:10:40.680
raises cholesterol is generally correct.
link |
02:10:43.980
But again, because if we're gonna start talking about LDL,
link |
02:10:47.660
we have to explain what LDL is.
link |
02:10:49.120
This is another one of those things
link |
02:10:50.140
that's just so grossly misunderstood
link |
02:10:52.400
that it makes having discussions about this very complicated.
link |
02:10:58.620
Let's go back to the cholesterol problem.
link |
02:11:00.340
So every cell in our body makes cholesterol.
link |
02:11:04.420
And almost without exception, they make enough.
link |
02:11:08.460
There are a handful of times, however,
link |
02:11:11.300
when a cell needs to borrow cholesterol from another cell.
link |
02:11:16.400
Okay, so how would you do this, right?
link |
02:11:17.960
So if you're playing God for a minute
link |
02:11:20.840
and you wanna design a system,
link |
02:11:22.700
you have to be able to transport cholesterol
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