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Welcome to the Huberman Lab Podcast,
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where we discuss science
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and science-based tools for everyday life.
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I'm Andrew Huberman, and I'm a professor of neurobiology
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and ophthalmology at Stanford School of Medicine.
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Today, my guest is Dr. Sachin Panda.
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Dr. Sachin Panda is a professor and director
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of the Regulatory Biology Laboratory
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at the Salk Institute of Biological Studies.
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His laboratory has made numerous important contributions
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that impact mental health, physical health,
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and human performance.
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For instance, his laboratory discovered the neurons
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in the eye and neurons within the brain
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that regulate our so-called circadian rhythm.
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Circadian rhythms are 24-hour rhythms
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and everything from gene expression
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to the overall functioning of tissues,
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our levels of mood and alertness,
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our ability to sleep, appetite, and much, much more.
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In addition, over the last decade,
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Dr. Panda's laboratory has made critical discoveries
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in terms of how our patterns of eating over time
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impact our biology and our health.
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In particular, his laboratory pioneered discoveries
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related to so-called intermittent fasting,
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also sometimes referred to as time-restricted feeding.
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Today, Dr. Panda and I discuss how our circadian behaviors,
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everything from when we wake up to when we view light
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to when we avoid viewing light
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to when we eat and what we eat
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and when we socialize and how we socialize,
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impacts our biology and our psychology
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and how all of that has a strong impact on our health.
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During today's discussion,
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you will learn how restricting your feeding
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to specific periods within each 24-hour cycle
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or perhaps even exploring longer patterns
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of fasting and eating cycles
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can impact everything from the health of your liver
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to your gut, to your brain,
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and how all of that impacts things like mood
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and your ability to perform cognitive work.
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Indeed, today's discussion goes deep
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into all aspects of intermittent fasting,
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aka time-restricted feeding.
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We talk about the basic science,
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as well as the recent clinical trials
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that have explored time-restricted feeding
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in a diverse range of people,
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including men, women, children, people with diabetes,
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people who are otherwise healthy, and much, much more.
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I'm quite aware that intermittent fasting
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is a topic of much debate these days.
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We go deep into that debate,
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and by the end of today's discussion,
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you can be certain that you will have learned
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all the latest and all the details,
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all made very clear to you
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thanks to the incredible expertise, discovery,
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and clear communication of Dr. Panda.
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As some of you may already know,
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Dr. Panda has authored several important books
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on the topic of intermittent fasting
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and how it can benefit various aspects of health.
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Those books include The Circadian Code
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and a more recent book, The Circadian Diabetes Code,
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both of which we've provided links to
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in the show note captions.
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In addition, if any of you are interested
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in learning more about Dr. Panda's work,
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including seeing his publications
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and reading those publications,
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or supporting his laboratory,
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you can do that by going to his laboratory website,
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which we have also linked in the show note captions.
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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 HVMN Ketone IQ.
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HVMN Ketone IQ is a supplement
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that increases blood ketones.
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I want to be clear that I am not following a ketogenic diet.
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Most people fall into this category.
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They are not following a ketogenic diet.
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They are omnivores and they do eat carbohydrates.
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So their standard fuel source for the brain and body
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is not ketones.
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However, I found that by taking ketone IQ,
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which we know increases blood ketones,
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I can achieve much better focus for longer periods of time
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for any kind of cognitive work
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and much greater energy levels for exercise,
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especially if I'm going into that exercise,
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fasted and find myself a little bit hungry
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when I start that exercise.
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And this is no surprise.
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We know that ketones are the brain and body's
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preferred fuel source,
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even if you're not following a ketogenic diet.
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So in other words, I and many other people
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are now starting to leverage endogenous ketones
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as a fuel source for the brain and body,
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and yet we are not following a ketogenic diet.
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And of course, if you are following a ketogenic diet,
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ketone IQ will further allow you
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to increase your blood ketones as a source of brain
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and body fuel.
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If you'd like to try ketone IQ,
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Again, that's hvmn.com slash Huberman.
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with cooling, heating, and sleep tracking capacity.
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As I've talked about before on the Huberman Lab podcast,
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there is a critical relationship
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between sleep and body temperature.
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That is, in order to fall asleep and stay deeply asleep,
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your body temperature needs to drop
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by about one to three degrees.
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And in order to wake up in the morning and feel alert,
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your body temperature needs to increase
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by about one to three degrees.
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The problem with most people's sleeping environment
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is that even if you make the room cool,
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the actual environment that you sleep on,
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that is your mattress and underneath your covers,
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is hard to regulate in terms of temperature.
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With 8 Sleep, regulating the temperature
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of that sleeping environment becomes incredibly easy.
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In fact, you can change the temperature
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of that environment across the night,
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making it a little bit cooler at the beginning of the night,
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even cooler still a few hours into your sleep,
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which really helps getting into very deep sleep,
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and then warming it as you approach morning
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so that you wake up feeling most alert.
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I've been sleeping on an 8 Sleep mattress cover
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and it has completely transformed my sleep.
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If you'd like to try 8 Sleep,
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Again, that's 8sleep.com slash Huberman.
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Today's episode is also brought to us by Thesis.
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Thesis makes custom nootropics.
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Now, I am not a fan of the word nootropics
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because it translates to smart drugs.
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And as a neuroscientist, what I can tell you
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is that you have circuits in your brain
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that allow you to focus.
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You have circuits in your brain
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that allow you to be creative.
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You have circuits in your brain
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that allow you to task switch and on and on.
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In other words, there is no specific brain circuit
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or even circuits for being quote unquote smart.
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Thesis understands this and has developed nootropics
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What do I mean by that?
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Well, they have formulas that can put your brain
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into a state of increased clarity or focus or creativity,
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or that can give you more overall energy
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for things like physical exercise.
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I often take the Thesis Clarity Formula
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prior to long bouts of cognitive work
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and I'll use their energy formula
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prior to doing any kind of really intense physical exercise.
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Again, that's takethesis.com slash Huberman.
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The Huberman Lab Podcast
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is now partnered with Momentus Supplements.
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To find the supplements we discuss
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on the Huberman Lab Podcast,
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you can go to Live Momentus, spelled O-U-S,
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livemomentus.com slash Huberman.
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And I should just mention
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that the library of those supplements is constantly expanding.
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Again, that's livemomentus.com slash Huberman.
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And now for my discussion with Dr. Sachin Panda.
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Sachin, Dr. Panda, so good to see you again.
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Yeah, good to see you.
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We are colleagues still,
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but we used to be right across the street from one another.
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Yeah, I remember those days, yeah.
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Yeah, so I'm delighted that you're here.
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I think we're going to talk about a number of things,
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mainly intermittent fasting, time-restricted feeding,
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and health, but also the many other things
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that you're doing.
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Just before we started recording,
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we were discussing your recent paper in Nature
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that involved recordings from postmortem human retina.
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So maybe if there's time at the end, we can get back to.
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Your lab has shown that it can essentially maintain
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or resurrect neurons from dead people
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in order to potentially and eventually provide transplants
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to rescue vision in the blind.
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So that's extremely exciting.
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But of course, not the main focus of today's discussion,
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so we'll have to split it up.
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The first question I have is how am I supposed to define
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fasting and time-restricted feeding?
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Meaning when I go to sleep every night, I'm not eating.
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So in some sense, everybody is doing time-restricted feeding
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to some degree or another.
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At what point can we start thinking about
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a pattern of eating as time-restricted feeding,
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so-called intermittent fasting?
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Does it have to do with how regular one is
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about the start and stop times?
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How do you think about defining intermittent fasting,
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time-restricted feeding, and maybe,
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just to simplify the conversation,
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is one term more correct than the other
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in terms of describing this incredible pattern of feeding?
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Well, you know that intermittent fasting
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covers many types of fasting.
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Actually, it started a long time ago,
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and it's embedded into the history of caloric restriction.
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Almost 100 years ago, people showed that
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if you reduce calorie intake in a rat,
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then that rat can live for a long time.
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And in those experiments,
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the calories were reduced every single day.
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And that led to the idea that if we cut down our calories
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by 20%, say, then we can potentially live longer
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by doing two things.
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One is preventing AIDS-related disease,
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or even if we fall sick, maybe we can accelerate cure
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and keep the repair mechanism going
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so that we can live longer.
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But it was very difficult to count calories every day
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and reduce, maintain that.
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I must say that it's not that
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caloric restriction is impossible,
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or we are not doing it.
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In fact, a lot of us, we do count calories
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in our subconscious mind.
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And so every time we take out a soda bottle or something,
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I'm looking at it, okay, 160 kilocalorie,
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30 kilocalorie, zero kilocalorie, we are doing that.
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So the point is we are doing subconsciously
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some kind of calorie counting,
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but reducing calorie by 20%, 30% every single day
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is not possible for many people.
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So then the idea came in mouse and rat experiment
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whether they can eat every other day.
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And in fact, this every other day feeding
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also led to very similar, almost equivalent
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00:10:50,240 --> 00:10:54,600
health improvement as continuous calorie restriction.
266
00:10:56,720 --> 00:10:59,760
So then the idea was, well, every other day
267
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is a little bit hard for humans,
268
00:11:01,480 --> 00:11:04,560
but just imagine I'll just get to eat
269
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only one day and then another day.
270
00:11:07,520 --> 00:11:09,800
Then the idea came, well, for humans,
271
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can they eat less for one or two days in a week?
272
00:11:14,680 --> 00:11:16,440
So that led to this five, two diet
273
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where people can eat for five days,
274
00:11:18,360 --> 00:11:20,320
and then two days they have to reduce calories.
275
00:11:20,320 --> 00:11:23,560
So that's also, intermaternally people are fasting.
276
00:11:24,740 --> 00:11:27,960
Then as you know, Walter Longo also came with this idea
277
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that periodic fasting, maybe four or five days
278
00:11:30,320 --> 00:11:32,620
in every month or two months, three months,
279
00:11:32,620 --> 00:11:35,280
you can fast or reduce calorie.
280
00:11:35,280 --> 00:11:37,840
And he also found many benefits
281
00:11:37,840 --> 00:11:40,440
of calorie restriction was there.
282
00:11:40,440 --> 00:11:42,600
Were those studies on humans?
283
00:11:42,600 --> 00:11:45,080
Many of the studies started in mice,
284
00:11:45,080 --> 00:11:48,480
but alternate day fasting, five, two,
285
00:11:48,480 --> 00:11:51,520
and Walter's periodic fasting,
286
00:11:51,520 --> 00:11:54,040
all of them have now been done in humans,
287
00:11:54,040 --> 00:11:55,440
not for longevity, of course,
288
00:11:55,440 --> 00:11:58,460
because you cannot do those for a long time,
289
00:11:58,460 --> 00:12:00,820
but for weight maintenance,
290
00:12:00,820 --> 00:12:03,820
for reducing some signs of aging or reversing,
291
00:12:03,820 --> 00:12:04,780
those things have been done.
292
00:12:04,780 --> 00:12:07,580
So all of them have been done in humans,
293
00:12:07,580 --> 00:12:10,860
mostly healthy humans, and in some cases,
294
00:12:10,860 --> 00:12:14,340
people with pre-diabetes or some aspects
295
00:12:14,340 --> 00:12:15,180
of metabolic disease.
296
00:12:15,180 --> 00:12:20,180
So that led to the idea that all these forms of fasting,
297
00:12:20,260 --> 00:12:25,260
in which the total calorie intake on any given day
298
00:12:25,260 --> 00:12:30,260
is reduced for one or more days in a week, a month,
299
00:12:30,700 --> 00:12:35,580
that umbrella term became intermittent fasting.
300
00:12:35,580 --> 00:12:39,580
So if you look up the scientific literature,
301
00:12:39,580 --> 00:12:42,020
most intermittent fasting involves
302
00:12:42,020 --> 00:12:44,220
intentionally reducing calories
303
00:12:45,260 --> 00:12:48,020
for at least one or two days in a week
304
00:12:48,020 --> 00:12:51,000
or few days in a month.
305
00:12:51,000 --> 00:12:55,440
So when we published time-restricted feeding,
306
00:12:56,800 --> 00:12:58,240
the initial mouse experiments,
307
00:12:58,240 --> 00:13:01,040
and even now, most of the mouse experiments,
308
00:13:01,040 --> 00:13:04,440
we want to test what is the impact of time restriction
309
00:13:04,440 --> 00:13:06,660
versus calorie restriction.
310
00:13:06,660 --> 00:13:07,680
So in these experiments,
311
00:13:07,680 --> 00:13:12,080
we don't reduce calorie on any day of mouse life.
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00:13:12,080 --> 00:13:14,960
So the mice eat the same number of calories
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00:13:14,960 --> 00:13:16,760
as the ad libitum-fed mice,
314
00:13:17,780 --> 00:13:20,040
but still they see health benefit.
315
00:13:20,040 --> 00:13:22,839
So that's why we call it time-restricted feeding.
316
00:13:22,839 --> 00:13:27,839
But since it involves living without food for several hours,
317
00:13:28,760 --> 00:13:32,439
for some people, it can be very difficult.
318
00:13:32,439 --> 00:13:36,160
The initial experiments were done for eight hours
319
00:13:36,160 --> 00:13:38,719
of feeding and 16 hours of fasting.
320
00:13:38,719 --> 00:13:40,620
That kind of became popular.
321
00:13:40,620 --> 00:13:44,120
And so that's why people use the same term
322
00:13:44,120 --> 00:13:45,459
as intermittent fasting.
323
00:13:45,459 --> 00:13:48,800
And now if you say intermittent fasting
324
00:13:48,800 --> 00:13:51,280
in popular literature or popular media,
325
00:13:51,280 --> 00:13:54,640
then people usually refer to time-restricted eating.
326
00:13:54,640 --> 00:13:57,920
So now coming back to how do you define
327
00:13:57,920 --> 00:13:59,180
time-restricted feeding.
328
00:14:00,319 --> 00:14:04,680
So the way we have been trying to define experimentally
329
00:14:04,680 --> 00:14:08,680
and also in literature is trying to confine
330
00:14:10,479 --> 00:14:15,479
all your energy intake from solid and liquid food combined
331
00:14:15,480 --> 00:14:19,920
within a consistent window of eight to 12 hours.
332
00:14:19,920 --> 00:14:21,440
Because that's something that's doable.
333
00:14:21,440 --> 00:14:24,560
Of course, people have done time-restricted feeding
334
00:14:24,560 --> 00:14:26,160
with four hours, six hours,
335
00:14:26,160 --> 00:14:28,000
and some people even try to eat everything
336
00:14:28,000 --> 00:14:29,920
within two hours, one meal a day.
337
00:14:31,600 --> 00:14:34,760
But the point is those are not feasible
338
00:14:34,760 --> 00:14:37,800
to maintain for a very long time for a lot of people.
339
00:14:38,920 --> 00:14:42,080
One question about the six hour versus eight hour
340
00:14:42,080 --> 00:14:43,760
versus 12 hour feeding window.
341
00:14:43,760 --> 00:14:48,760
Is it important that the feeding window
342
00:14:48,800 --> 00:14:51,960
begin and end at the same time, more or less?
343
00:14:51,960 --> 00:14:52,800
Yeah, more or less.
344
00:14:52,800 --> 00:14:54,439
And if so, how much flexibility is there?
345
00:14:54,439 --> 00:14:56,920
So for instance, I'm somebody that
346
00:14:56,920 --> 00:14:59,280
I am not terribly hungry in the morning.
347
00:14:59,280 --> 00:15:03,360
I like to drink water, usually some caffeine
348
00:15:03,360 --> 00:15:06,800
and electrolytes in the period before my first meal.
349
00:15:06,800 --> 00:15:08,480
And my first meal always lands sometime
350
00:15:08,480 --> 00:15:12,640
between 11 a.m. and 12 noon.
351
00:15:12,640 --> 00:15:14,920
There are exceptions occasionally.
352
00:15:14,920 --> 00:15:18,360
I'll have a proper breakfast as it's called.
353
00:15:18,360 --> 00:15:19,360
I guess it would be improper
354
00:15:19,360 --> 00:15:21,520
if you're intermittent fasting for me.
355
00:15:21,520 --> 00:15:25,439
But typically 11 a.m. or noon is when I first eat
356
00:15:25,439 --> 00:15:27,600
and my last bite of food is typically around,
357
00:15:27,600 --> 00:15:29,720
I don't know, 8.39 p.m.
358
00:15:29,720 --> 00:15:30,960
That's what works for me.
359
00:15:32,439 --> 00:15:35,360
Is that consistency affording me any benefit?
360
00:15:35,360 --> 00:15:37,720
And let's just leave aside total caloric number,
361
00:15:37,720 --> 00:15:40,040
macronutrients, plant-based meat, et cetera.
362
00:15:40,040 --> 00:15:44,520
But is there any benefit to shortening that feeding window
363
00:15:44,520 --> 00:15:48,120
that we are aware of or extending that feeding window
364
00:15:48,120 --> 00:15:51,560
or being even more rigid about the start
365
00:15:51,560 --> 00:15:53,120
and end of that feeding window?
366
00:15:54,000 --> 00:15:56,040
Yeah, so the start of the feeding window,
367
00:15:57,319 --> 00:16:01,560
that's interesting because the concept of time-restricted
368
00:16:01,560 --> 00:16:04,319
feeding, when I describe animal studies,
369
00:16:04,319 --> 00:16:07,319
it's feeding for humans, it's eating.
370
00:16:07,320 --> 00:16:10,600
So the concept actually came from the science
371
00:16:10,600 --> 00:16:11,800
of circadian rhythm.
372
00:16:11,800 --> 00:16:16,800
So that means our body has an internal timetable
373
00:16:17,640 --> 00:16:20,760
that's present in every cell, in every organ
374
00:16:21,960 --> 00:16:26,960
that pre-programs many molecular aspects of the cells
375
00:16:28,200 --> 00:16:30,280
that leads to physiology and all that stuff.
376
00:16:30,280 --> 00:16:34,800
So that essentially there is a predetermined timetable
377
00:16:34,800 --> 00:16:37,640
for every cell, every organ to do certain things
378
00:16:37,640 --> 00:16:39,199
at certain time.
379
00:16:39,199 --> 00:16:44,199
And the circadian clocks, as you and I know,
380
00:16:44,880 --> 00:16:47,079
are more sensitive to light.
381
00:16:47,079 --> 00:16:51,640
Light is the most dominant time giver.
382
00:16:51,640 --> 00:16:55,079
So for example, when daylight saving time changes
383
00:16:55,079 --> 00:16:58,680
or when we travel from one time zone to another time zone,
384
00:16:58,680 --> 00:17:03,439
we feel kind of crappy because our daily activities
385
00:17:03,440 --> 00:17:06,880
are out of sync from our internal clock.
386
00:17:08,160 --> 00:17:10,480
So that was known for a very long time,
387
00:17:10,480 --> 00:17:13,360
but then around the year 2000, 2002,
388
00:17:14,320 --> 00:17:17,600
there was a famous experiment by Uli Sibler
389
00:17:17,600 --> 00:17:20,160
from Switzerland.
390
00:17:20,160 --> 00:17:23,920
What he did, he just fed the mice at the wrong time.
391
00:17:23,920 --> 00:17:27,120
Mice are nocturnal there, night feeders.
392
00:17:27,120 --> 00:17:30,280
And when he fed the mice during daytime,
393
00:17:30,280 --> 00:17:34,480
the liver clock, instead of following its own routine,
394
00:17:34,480 --> 00:17:37,120
liver clock actually started following food.
395
00:17:37,120 --> 00:17:41,080
So that means by changing our feeding time,
396
00:17:41,080 --> 00:17:45,240
we can change, we can tune our liver clock.
397
00:17:46,160 --> 00:17:47,760
And subsequently the same experiment
398
00:17:47,760 --> 00:17:49,600
has been repeated many times
399
00:17:49,600 --> 00:17:52,360
and we repeated that in 2009.
400
00:17:52,360 --> 00:17:57,360
And we figured out, yes, actually outside this brain center
401
00:17:57,360 --> 00:18:00,439
called suprachiasmatic nucleus or SCN,
402
00:18:00,439 --> 00:18:05,439
which is considered the master circadian clock,
403
00:18:06,080 --> 00:18:11,080
almost the rest of the brain even follows when we eat.
404
00:18:11,360 --> 00:18:15,800
And that came out from Pierre Chambon's lab in Europe,
405
00:18:15,800 --> 00:18:19,840
where they systematically looked at even places
406
00:18:19,840 --> 00:18:21,360
that are very close to the SCN.
407
00:18:22,600 --> 00:18:24,520
For those who are, who know
408
00:18:24,520 --> 00:18:28,240
those medial hypothalamus, paraventricular nucleus,
409
00:18:28,240 --> 00:18:32,240
all of this within a couple of four or five millimeters
410
00:18:32,240 --> 00:18:35,000
of the SCN, but they were following food cue.
411
00:18:35,960 --> 00:18:36,800
Amazing.
412
00:18:36,800 --> 00:18:40,320
So then, now if we think about it,
413
00:18:40,320 --> 00:18:43,680
so for example, when the daylight seven time changes,
414
00:18:43,680 --> 00:18:48,680
just one hour change, or one hour change in alignment
415
00:18:48,800 --> 00:18:51,920
between our internal time and external time
416
00:18:51,920 --> 00:18:55,200
leads to kind of feeling groggy and feeling
417
00:18:55,200 --> 00:18:58,480
not at a peak performance for one or two days.
418
00:18:58,480 --> 00:19:01,520
So the rule of thumb is when the time giver
419
00:19:02,800 --> 00:19:06,480
changes by one hour, then our internal clock
420
00:19:06,480 --> 00:19:08,680
takes at least a day to catch up.
421
00:19:08,680 --> 00:19:13,680
So that means if you're flying from LA to New York,
422
00:19:14,280 --> 00:19:17,040
you're moving through three time zones,
423
00:19:17,040 --> 00:19:20,880
then on an average it will take three days
424
00:19:20,880 --> 00:19:22,360
to catch up with the New York time.
425
00:19:22,360 --> 00:19:24,920
For some people it can be even slower,
426
00:19:24,920 --> 00:19:27,040
and for some people it can be two days,
427
00:19:27,040 --> 00:19:30,480
but the bottom line is, yes, there is a desynchrony.
428
00:19:30,480 --> 00:19:33,880
So then what does it mean for the body?
429
00:19:33,880 --> 00:19:38,120
So one of the function of the clock is to anticipate
430
00:19:38,120 --> 00:19:40,040
when you're going to wake up, for example,
431
00:19:40,040 --> 00:19:43,240
so the blood pressure slightly goes up,
432
00:19:43,240 --> 00:19:46,040
our heart rate goes up, our breathing goes up.
433
00:19:46,040 --> 00:19:50,680
Similarly for food, almost every organ
434
00:19:50,680 --> 00:19:54,920
that is involved in feeding or eating digestion,
435
00:19:54,920 --> 00:19:57,200
all of them have clocks.
436
00:19:57,200 --> 00:19:59,400
So even from saliva production,
437
00:20:00,320 --> 00:20:03,080
there is the first phase of digestion
438
00:20:03,080 --> 00:20:06,880
to secretion of all the digestive juice in the stomach
439
00:20:06,880 --> 00:20:10,400
and then absorption of nutrient and liver metabolism,
440
00:20:10,400 --> 00:20:13,520
everything, the whole village expects
441
00:20:13,520 --> 00:20:16,400
when you're supposed to eat, and they're getting ready
442
00:20:16,400 --> 00:20:18,680
for you to eat their first meal
443
00:20:18,680 --> 00:20:20,960
after fasting for a long time.
444
00:20:20,960 --> 00:20:23,520
So that's why it's breaking the fast of breakfast.
445
00:20:24,680 --> 00:20:27,040
And when that time changes,
446
00:20:27,040 --> 00:20:28,880
when you change it by two or three hours
447
00:20:28,880 --> 00:20:32,240
from one day to another, then sometimes they're like,
448
00:20:32,240 --> 00:20:37,000
oh, food didn't come, maybe we'll come at the wrong time.
449
00:20:37,000 --> 00:20:38,560
We were at the wrong time.
450
00:20:38,560 --> 00:20:42,360
And then they'll track the new eating times.
451
00:20:42,360 --> 00:20:44,920
So suppose say one day you have been eating every day
452
00:20:44,920 --> 00:20:48,080
at eight a.m., I eat at eight a.m.
453
00:20:48,080 --> 00:20:50,480
Is that when you start your feeding window?
454
00:20:50,480 --> 00:20:53,240
When does your feeding window shut?
455
00:20:53,240 --> 00:20:56,159
Six p.m., so I eat for around 10 hours.
456
00:20:56,159 --> 00:20:57,000
Okay.
457
00:20:58,080 --> 00:21:00,919
And then one day if I switch to 10 a.m.,
458
00:21:00,919 --> 00:21:04,080
then what happens is a clock is thinking,
459
00:21:04,080 --> 00:21:05,919
well, the food didn't arrive at eight,
460
00:21:05,919 --> 00:21:07,159
but it arrived at 10.
461
00:21:07,159 --> 00:21:08,800
Maybe tomorrow the food will arrive
462
00:21:08,800 --> 00:21:10,320
somewhere between eight and 10,
463
00:21:10,320 --> 00:21:11,800
so we'll be ready around nine.
464
00:21:12,879 --> 00:21:13,720
I see.
465
00:21:13,720 --> 00:21:17,439
So then the next day if I come back and eat at eight o'clock,
466
00:21:17,440 --> 00:21:21,400
then I may eat, but my clock is not ready
467
00:21:21,400 --> 00:21:22,760
to digest that food.
468
00:21:22,760 --> 00:21:27,480
So that's why this idea is you have to be consistent
469
00:21:27,480 --> 00:21:30,560
to take advantage of this anticipatory activity
470
00:21:30,560 --> 00:21:32,840
of our clock in different systems
471
00:21:32,840 --> 00:21:34,360
to get the best out of it.
472
00:21:34,360 --> 00:21:37,760
Is there evidence that those anticipatory systems,
473
00:21:37,760 --> 00:21:39,480
as they relate to digestion,
474
00:21:39,480 --> 00:21:41,360
help us better assimilate our food?
475
00:21:41,360 --> 00:21:42,200
I would imagine so.
476
00:21:42,200 --> 00:21:43,680
I mean, if you have the gastric juices
477
00:21:43,680 --> 00:21:45,400
that are gonna help digest the proteins,
478
00:21:45,400 --> 00:21:49,440
fats, and carbohydrates and already deployed
479
00:21:49,440 --> 00:21:50,600
at the time when you eat,
480
00:21:50,600 --> 00:21:52,960
I could imagine that food will be better utilized
481
00:21:52,960 --> 00:21:54,840
than if you don't.
482
00:21:54,840 --> 00:21:57,080
So in other words, what is the advantage
483
00:21:57,080 --> 00:21:59,720
of having these anticipatory signals
484
00:21:59,720 --> 00:22:01,920
in terms of potential health benefits?
485
00:22:01,920 --> 00:22:04,440
The anticipatory signal is really important
486
00:22:04,440 --> 00:22:06,760
even from waking up.
487
00:22:08,480 --> 00:22:12,880
The reason why many people feel not ready completely
488
00:22:12,880 --> 00:22:15,560
when they wake up to an alarm clock,
489
00:22:15,560 --> 00:22:18,040
because the alarm clock wakes you up,
490
00:22:18,040 --> 00:22:19,680
but your body is not prepared.
491
00:22:19,680 --> 00:22:23,320
So that sleepiness after waking up to an alarm clock
492
00:22:23,320 --> 00:22:26,680
is due to our body is not prepared for that.
493
00:22:26,680 --> 00:22:28,160
And then the best example is when
494
00:22:28,160 --> 00:22:32,800
the daylight saving time changes,
495
00:22:32,800 --> 00:22:36,440
particularly when we have to wake up one hour early,
496
00:22:37,360 --> 00:22:40,840
what happens, people who have underlying heart condition,
497
00:22:40,840 --> 00:22:44,919
when they're waking up, when the body is not ready
498
00:22:44,919 --> 00:22:46,679
or heart is not ready and all of a sudden
499
00:22:46,679 --> 00:22:49,320
the heart has to start pumping a little bit harder,
500
00:22:49,320 --> 00:22:53,360
then there is chance of heart attack.
501
00:22:53,360 --> 00:22:57,439
And in fact, people have looked at hospital records
502
00:22:57,439 --> 00:23:00,159
and they find that on those days,
503
00:23:00,159 --> 00:23:03,120
there is a sharp rise in heart attacks.
504
00:23:03,120 --> 00:23:04,120
And car accidents.
505
00:23:04,120 --> 00:23:05,199
And car accidents too,
506
00:23:05,199 --> 00:23:06,959
because your brain is not coordinated,
507
00:23:06,960 --> 00:23:11,720
so you cannot make those fine decisions.
508
00:23:11,720 --> 00:23:14,720
So that's a great example of anticipatory activity.
509
00:23:14,720 --> 00:23:17,880
But coming back to digestion, one thing is,
510
00:23:19,720 --> 00:23:21,280
and this is something that many people
511
00:23:21,280 --> 00:23:23,320
might have experienced.
512
00:23:23,320 --> 00:23:25,560
There are many rhythms in our digestive system.
513
00:23:25,560 --> 00:23:29,040
And one of the rhythms is our intestine
514
00:23:29,040 --> 00:23:31,160
has this peristaltic function.
515
00:23:31,160 --> 00:23:33,720
So it kind of contracts and expands,
516
00:23:33,720 --> 00:23:38,720
and that moves food, food doesn't move due to gravity.
517
00:23:38,800 --> 00:23:40,840
So it goes back and forth.
518
00:23:40,840 --> 00:23:44,960
And that peristaltic action actually slows down at night,
519
00:23:44,960 --> 00:23:47,480
few hours after our last meal.
520
00:23:47,480 --> 00:23:52,480
And so that's why when people eat late at night,
521
00:23:52,760 --> 00:23:56,360
for example, then that food doesn't get digested
522
00:23:56,360 --> 00:23:59,720
because there is not enough digestive juice, first thing.
523
00:23:59,720 --> 00:24:02,280
And second, even if it gets digested in the stomach,
524
00:24:02,280 --> 00:24:04,040
it doesn't move properly.
525
00:24:04,040 --> 00:24:07,040
So then the next morning people get up and think,
526
00:24:08,120 --> 00:24:11,200
of course, people consume some alcohol very often,
527
00:24:11,200 --> 00:24:13,160
and then they think that this is hangover.
528
00:24:13,160 --> 00:24:15,440
But those who don't consume alcohol,
529
00:24:15,440 --> 00:24:19,399
then they have the food hangover because it doesn't digest.
530
00:24:19,399 --> 00:24:23,720
So that's one extreme example where food at the wrong time
531
00:24:25,160 --> 00:24:29,399
can, so healthy food at the wrong time can be crap or junk.
532
00:24:29,400 --> 00:24:32,600
Yeah, I've experienced that where if I've worked late
533
00:24:32,600 --> 00:24:34,760
or I couldn't eat dinner or something, and then I get home,
534
00:24:34,760 --> 00:24:37,920
I always debate whether or not to try and sleep.
535
00:24:37,920 --> 00:24:40,360
But if I'm too hungry, oftentimes it's challenging.
536
00:24:40,360 --> 00:24:42,880
And so for me, sometimes consuming something
537
00:24:42,880 --> 00:24:45,120
that at least seems easily digestible,
538
00:24:45,120 --> 00:24:47,400
like yogurt or something in a liquid form,
539
00:24:48,640 --> 00:24:51,960
is better for me than if I eat a meal.
540
00:24:51,960 --> 00:24:53,720
I've made the mistake of going to the refrigerator,
541
00:24:53,720 --> 00:24:55,640
being super hungry and eating a bunch of food
542
00:24:55,640 --> 00:24:58,200
at 10 or 11 p.m. and then falling asleep.
543
00:24:58,200 --> 00:25:01,000
And indeed, the sleep, if I'm tired enough,
544
00:25:01,000 --> 00:25:03,000
can be quite deep, but the next morning,
545
00:25:03,000 --> 00:25:05,560
I feel just completely physically
546
00:25:05,560 --> 00:25:07,280
and cognitively weighed down.
547
00:25:07,280 --> 00:25:09,880
So I think what you just described makes a lot of sense.
548
00:25:09,880 --> 00:25:13,920
So if someone were to select a feeding window,
549
00:25:13,920 --> 00:25:16,120
regardless of whether or not it falls
550
00:25:16,120 --> 00:25:17,560
into classic intermittent fasting,
551
00:25:17,560 --> 00:25:20,120
time-restricted feeding, sounds like eating
552
00:25:20,120 --> 00:25:23,560
your first bite of food and eating your last bite of food
553
00:25:23,560 --> 00:25:28,360
at more or less the same time each day has benefits.
554
00:25:28,360 --> 00:25:31,520
I have this question, you mentioned feeding versus eating.
555
00:25:31,520 --> 00:25:33,120
And I think it's actually not just
556
00:25:33,120 --> 00:25:37,040
a grammatical semantic issue.
557
00:25:37,879 --> 00:25:38,800
And here's why.
558
00:25:40,399 --> 00:25:43,200
We tend to think about when you take your first bite of food
559
00:25:43,200 --> 00:25:45,159
and then when you take your last bite of food.
560
00:25:45,159 --> 00:25:47,919
But of course, food's digested at different rates.
561
00:25:47,919 --> 00:25:50,399
More fat in there is gonna make carbohydrates
562
00:25:50,399 --> 00:25:51,760
digest slower, et cetera.
563
00:25:51,760 --> 00:25:54,160
I mean, there's all these adjustments to the glycemic index
564
00:25:54,160 --> 00:25:56,280
and so forth with foods in combination.
565
00:25:57,480 --> 00:25:59,879
Is it better to think about not eating
566
00:25:59,879 --> 00:26:03,040
but your fed state and blood sugar?
567
00:26:03,040 --> 00:26:07,800
So for instance, I often get asked on social media,
568
00:26:07,800 --> 00:26:09,960
does blank break a fast?
569
00:26:11,360 --> 00:26:13,240
And so I like to think about it scientifically,
570
00:26:13,240 --> 00:26:15,920
like, okay, does plain water break a fast?
571
00:26:15,920 --> 00:26:17,520
No. Does air break a fast?
572
00:26:17,520 --> 00:26:18,400
No.
573
00:26:18,400 --> 00:26:22,120
Does one grain of sugar, of sucrose break a fast?
574
00:26:22,120 --> 00:26:23,240
Well, probably not.
575
00:26:23,240 --> 00:26:25,920
But does one teaspoon of sugar break a fast?
576
00:26:25,920 --> 00:26:28,800
Well, you could say yes, but transiently.
577
00:26:28,800 --> 00:26:30,800
Like, so I mean, when we're talking about breaking a fast,
578
00:26:30,800 --> 00:26:33,440
are we talking about a rise in blood glucose?
579
00:26:33,440 --> 00:26:36,280
Or are there molecular signals downstream
580
00:26:36,280 --> 00:26:41,280
of a rise in blood glucose that cannot be reversed?
581
00:26:41,360 --> 00:26:43,160
In other words, if I'm gonna eat my first meal
582
00:26:43,160 --> 00:26:46,120
every day at noon and I'm gonna eat my last bite of food
583
00:26:46,120 --> 00:26:50,600
at 8 p.m. and at 9 a.m., for whatever reason,
584
00:26:50,600 --> 00:26:53,239
I have coffee with one teaspoon of sugar in it,
585
00:26:54,800 --> 00:26:58,040
I suppose in the strictest sense, I've broken my fast.
586
00:26:58,040 --> 00:27:00,600
But maybe if I went for a hard run that morning,
587
00:27:00,600 --> 00:27:03,959
maybe by 9.30 a.m., I'm back in a quote unquote fasted state.
588
00:27:03,959 --> 00:27:06,040
So what is the fasted state really?
589
00:27:06,040 --> 00:27:07,959
Because when I'm eating at 8 p.m.,
590
00:27:07,959 --> 00:27:09,840
just to give another example,
591
00:27:09,840 --> 00:27:13,959
I start fasting at 8.01, perhaps,
592
00:27:13,960 --> 00:27:16,000
but I have my blood glucose is elevated,
593
00:27:16,000 --> 00:27:18,760
so I'm not really fasted, I'm fed.
594
00:27:18,760 --> 00:27:21,040
It's just that I'm not eating the verb, right?
595
00:27:21,040 --> 00:27:25,480
Okay, so again, I don't wanna get overly detailed
596
00:27:25,480 --> 00:27:26,720
just for sake of getting detail,
597
00:27:26,720 --> 00:27:28,520
but I think a lot of the confusion out there
598
00:27:28,520 --> 00:27:31,920
about what breaks a fast is related specifically
599
00:27:31,920 --> 00:27:34,480
to this issue, which is if I eat a whole pizza
600
00:27:34,480 --> 00:27:36,120
after sitting around all day, it's very different
601
00:27:36,120 --> 00:27:38,160
than if I eat a whole pizza after having run
602
00:27:38,160 --> 00:27:40,760
a 26-mile marathon that day.
603
00:27:40,760 --> 00:27:43,880
Very different metabolically speaking.
604
00:27:43,880 --> 00:27:48,640
So how should people think about fasted versus fed?
605
00:27:48,640 --> 00:27:51,560
Can we be mildly fasted versus severe fasted?
606
00:27:51,560 --> 00:27:55,400
Can we be fed-ish versus very fed?
607
00:27:55,400 --> 00:27:58,760
Anyway, I'll stop asking questions now,
608
00:27:58,760 --> 00:28:00,720
but because they all relate to the same theme.
609
00:28:00,720 --> 00:28:04,240
Yeah, now these are very interesting question,
610
00:28:04,240 --> 00:28:08,560
and then unfortunately, as you might have seen in life,
611
00:28:09,600 --> 00:28:12,800
the most obvious questions are often unanswered
612
00:28:12,800 --> 00:28:16,080
because it's so hard to do these damn experiments
613
00:28:16,080 --> 00:28:18,960
because if you really want to address this in humans,
614
00:28:18,960 --> 00:28:21,760
you have to bring humans, put them in isolation.
615
00:28:22,760 --> 00:28:26,159
Just like you said, I can now imagine planning
616
00:28:26,159 --> 00:28:27,639
five or six different experiments.
617
00:28:27,639 --> 00:28:30,800
Each experiment should involve eight or 10 volunteers,
618
00:28:30,800 --> 00:28:33,720
each gender, sex, and then do it.
619
00:28:33,720 --> 00:28:34,560
So it's difficult.
620
00:28:34,560 --> 00:28:38,520
So now let's go back to see how do we,
621
00:28:38,520 --> 00:28:43,080
let's dissect it in terms of indirect calorimetry.
622
00:28:43,080 --> 00:28:46,879
So for example, indirect calorimetry is based
623
00:28:46,879 --> 00:28:50,280
on this principle that whatever oxygen we breathe in
624
00:28:50,280 --> 00:28:53,000
and carbon dioxide we breathe out,
625
00:28:53,000 --> 00:28:54,360
if we can measure these two,
626
00:28:54,360 --> 00:28:57,720
then we can figure out whether our body in total,
627
00:28:57,720 --> 00:29:00,560
we are not saying whether it's the liver,
628
00:29:00,560 --> 00:29:03,160
gut, or fat, or muscle, in total,
629
00:29:03,160 --> 00:29:08,160
whether it's consuming glucose or fat as energy source.
630
00:29:09,560 --> 00:29:14,560
The idea is when we are without food for several hours,
631
00:29:16,120 --> 00:29:20,200
then ideally our body will tap onto glycogen first
632
00:29:20,200 --> 00:29:22,640
and then do a little bit of fat,
633
00:29:22,640 --> 00:29:25,480
and then when the body is mostly running on fat,
634
00:29:25,480 --> 00:29:29,840
then that ratio of CO2 to oxygen will come to 0.7.
635
00:29:29,840 --> 00:29:34,840
But what is interesting is we can do these experiments
636
00:29:34,840 --> 00:29:37,080
in mice, so we can go to mice and ask,
637
00:29:37,080 --> 00:29:38,879
okay, so what happens in mice?
638
00:29:38,879 --> 00:29:42,280
So in mice, mice are a little bit very different
639
00:29:42,280 --> 00:29:44,520
because mice are not simply little people.
640
00:29:44,520 --> 00:29:47,520
Their metabolism is different.
641
00:29:47,520 --> 00:29:52,520
They store relatively less glycogen than humans do
642
00:29:52,879 --> 00:29:55,240
in terms of total metabolism.
643
00:29:55,240 --> 00:29:59,679
So they, overnight, within 12 to 14 hours,
644
00:29:59,680 --> 00:30:02,600
the RER, respiratory exchange ratio,
645
00:30:02,600 --> 00:30:04,480
or this ratio will go from one,
646
00:30:04,480 --> 00:30:07,600
when they're consuming mostly glucose or carbohydrate
647
00:30:07,600 --> 00:30:09,880
as energy source, it will slow down,
648
00:30:09,880 --> 00:30:13,280
slowly go to 0.7, 0.75.
649
00:30:13,280 --> 00:30:14,720
So after 12 to 14 hours,
650
00:30:14,720 --> 00:30:18,120
they're kind of mostly running on fat.
651
00:30:19,480 --> 00:30:21,600
So now, as we give them food,
652
00:30:23,160 --> 00:30:24,520
within 10 or 15 minutes,
653
00:30:24,520 --> 00:30:27,680
they're not actually consuming couple of grams of food.
654
00:30:27,680 --> 00:30:30,600
They might have consumed, say, 100 or 200 milligram
655
00:30:30,600 --> 00:30:33,360
of that chow, so which is less than, say,
656
00:30:33,360 --> 00:30:35,240
5% of their food.
657
00:30:35,240 --> 00:30:38,560
And then the RER will immediately begin to rise
658
00:30:38,560 --> 00:30:42,480
as if that small amount of food
659
00:30:42,480 --> 00:30:44,680
stopped that fat burning process
660
00:30:44,680 --> 00:30:48,880
and cranked up the carbohydrate burning process.
661
00:30:48,880 --> 00:30:50,360
When you say fat burning process,
662
00:30:50,360 --> 00:30:53,080
you mean body fat stores being burned, right?
663
00:30:53,080 --> 00:30:54,600
Not dietary fat, correct?
664
00:30:54,600 --> 00:30:56,360
Yeah, so it's all body fat.
665
00:30:56,360 --> 00:30:58,760
That's why I said we don't know
666
00:30:58,760 --> 00:31:00,159
where that fat is being burned
667
00:31:00,159 --> 00:31:01,560
because we're just measuring
668
00:31:01,560 --> 00:31:04,600
how much mice is breathing in and out.
669
00:31:04,600 --> 00:31:07,240
So for example, it can be from the skin,
670
00:31:07,240 --> 00:31:10,520
so subcutaneous fat or belly fat.
671
00:31:10,520 --> 00:31:12,399
But not dietary fat.
672
00:31:12,399 --> 00:31:14,760
No, by that time, the dietary fat is already absorbed
673
00:31:14,760 --> 00:31:17,639
and digested and hopefully it's sitting in the liver
674
00:31:17,639 --> 00:31:19,000
or adipose tissue somewhere,
675
00:31:19,000 --> 00:31:21,240
but it's the fat that's body fat.
676
00:31:21,240 --> 00:31:22,080
Yes, thank you, Paul.
677
00:31:22,080 --> 00:31:23,919
Yeah, the reason I ask is that nowadays,
678
00:31:23,919 --> 00:31:25,879
I think more than half of the battles
679
00:31:25,880 --> 00:31:27,720
about nutrition that I see online
680
00:31:27,720 --> 00:31:30,120
relate to this issue where, I won't name names,
681
00:31:30,120 --> 00:31:32,080
but someone will come along and say,
682
00:31:32,080 --> 00:31:35,560
low carbohydrate diet allows you to burn more fat.
683
00:31:35,560 --> 00:31:40,320
And the more nuanced people out there will say,
684
00:31:40,320 --> 00:31:43,440
well, that's true, but you're also talking about dietary fat.
685
00:31:43,440 --> 00:31:45,440
The word fat can confuse people.
686
00:31:45,440 --> 00:31:46,920
I realize you're not doing that.
687
00:31:46,920 --> 00:31:48,680
You are certainly not one of the people guilty of doing this,
688
00:31:48,680 --> 00:31:51,040
but indeed, you eat more fat, you'll burn more fat,
689
00:31:51,040 --> 00:31:52,960
but that doesn't mean you'll burn more body fat.
690
00:31:52,960 --> 00:31:56,560
In fact, I think the data say that under conditions
691
00:31:56,560 --> 00:31:58,640
of caloric restriction, you'll actually burn less.
692
00:31:58,640 --> 00:32:01,880
I hope I don't, I'll probably get pitchforks
693
00:32:01,880 --> 00:32:04,480
sent through the mail toward me on that one.
694
00:32:04,480 --> 00:32:07,480
But I think that's true, whereas people who consume
695
00:32:07,480 --> 00:32:09,280
carbohydrate can still burn body fat,
696
00:32:09,280 --> 00:32:11,440
even though the majority of the fuel they're burning
697
00:32:11,440 --> 00:32:13,240
is from carbohydrates.
698
00:32:13,240 --> 00:32:15,680
So here in this case, for example, for mice,
699
00:32:15,680 --> 00:32:17,680
we know that as soon as they start eating,
700
00:32:18,680 --> 00:32:20,600
the RER goes up.
701
00:32:20,600 --> 00:32:21,800
Coming back to your question,
702
00:32:21,800 --> 00:32:23,399
what would be ideal for us to do?
703
00:32:23,399 --> 00:32:26,120
The experiment would be, okay, so we'll go back to that
704
00:32:26,120 --> 00:32:29,080
and then give the mouse maybe 100 milligram of food,
705
00:32:30,000 --> 00:32:32,600
and mouse runs around in the case,
706
00:32:32,600 --> 00:32:35,480
and then we'll continue to measure to see how long it takes
707
00:32:35,480 --> 00:32:37,480
for the mouse to come back.
708
00:32:37,480 --> 00:32:39,440
So that's one aspect.
709
00:32:39,440 --> 00:32:43,720
So now let's see, let's stay on this,
710
00:32:43,720 --> 00:32:46,560
and then I'll come back and talk about non-caloric food
711
00:32:46,560 --> 00:32:51,560
and whether that is considered.
54991
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