Sleep, Daylight Anchoring, and Effects on Memory & Obesity with Dan Pardi

Sleep, Daylight Anchoring, and Effects on Memory & Obesity with Dan Pardi

Rhonda here. Today I’m excited to be sitting with my friend,
Dan Pardi. Dan is a soon-to-be PHD. He researches sleep neurobiology at Stanford
University and also at the Leiden University. I know you guys are all a bunch of sleepyheads,
so I think that Dan, why don’t you tell us a little bit about sleep? It is a topic near and dear to my heart. Yeah, so I got into sleep probably 12 years
ago, and it was very serendipitous. There was a job opportunity for a place called
Orphan Medical, and it’s a pharmaceutical company that was working with the FDA to develop
drugs for orphan disorders, which are usually considered disorders with 200,000 people or
less. So they’re not populations that are large
enough to get large pharmaceutical companies to develop medications for them. So Orphan was looking at how to develop drugs
for these populations. Narcolepsy, which is a sleep disorder, was
on the radar. So they had a medication, sodium oxybate,
or GHB, and they were hiring. I applied for the job, and I knew nothing
about sleep, narcolepsy, or sodium oxybate before I started. And it was a very fortunate experience for
me, because as soon as I started to understand more about sleep, it’s just a window into
our world that’s so important, it’s so interesting, and it’s truly one of these topics where the
more you learn, the more you want to know. Absolutely. I am convinced that sleep is one of the key
determinants of health, both performance and the way we age, and it’s regulating a lot
of things. If you could talk a little bit about the circadian
rhythm, and how that’s connected to sleep and why that’s so important. Yeah. So that’s a great point. So, sleep is a circadian rhythm, and what
a circadian rhythm is is a repeatable, 24-hour process that usually we have cyclic activity
for things like behavior, for cell cycle growth and repair processes for all different activities
in the body. The timing of these rhythms are dependent
on basically this system in the brain called the suprachiasmatic nucleus, which is synchronizing
with the light-dark cycle of the environment. And so, then, we have what are called clock
cells within every tissue and cell in our body. And so there’s basically two levels of synchronization
that are taking place; the master clock in the brain, with the light-dark cycle of the
environment, and then all the cells in our tissues with the master clock. And that keeps our body in-time, so it’s doing
a right behavior at the right time of day. Yeah. I think, if I’ll just add on here, the thing
that’s, to me, so striking is that these circadian rhythms, you say they run on the day-night
cycle or the light-dark cycle, over 15% of the human encoding genome is regulated by
the circadian rhythm, and what that means is that genes are being turned on, so they’re
active and doing what they’re supposed to do during a function, or they’re being turned
off so that they’re not active, according to this rhythm. So you’re talking about a huge amount of metabolic
processes, behavioral processes, all these different processes that are controlled. That’s right, and that’s why there’s really
no part of the body that goes untouched when we’re not getting good sleep, or when we have
mistimed circadian rhythms from what are called aberrant light environments, or we’re getting
weird, funky light environments that our bodies are not used to, in terms of our physiology. And so that is actually pretty descriptive
of the modern world. We spend 90% of our time indoors. Two-hundred years ago, 90% of the population
was working in agrarian capacity, outdoors, all day long. In the evening, we can turn on artificial
light, and we can watch high-definition screens, and we can use our e-readers, and all of these
are emitting light, and our brains are trying to figure out, “What time of day is it?” And because of that strange lighting environment,
instead of having this waxing and waning of activity controlled by circadian clocks, then
we have what’s called asynchronization, where there’s not really a robust message that,
“Hey, it’s daytime. Do daytime activities,” and, “It’s nighttime. Do nighttime activities.” And I think we’re running a huge experiment
with our biology right now, and the outcomes are probably not going to be very favorable. And we know that already, through looking
at people that have chronic sleep disorders where they have disrupted sleep, or shift
workers, where they’re working during the day sometimes a week, and during the night
other times a week. We see that when you don’t have good sleep,
and when you have highly fluctuating or highly variable periods where you’re sleeping, and
therefore mistimed circadian rhythms, that you have really four-fold increases in cancer
risk, you have multi-fold increases in risk for diabetes and for metabolic syndrome, cardiovascular
disease. It’s not a nice-to-have, it’s a must-have. Right. Let’s dive into that a little bit. So I know, with the cancer, for example. The cancer incidents I’ve become particularly
interested in with sleep, the connection between lack of sleep and cancer, and one thing in
particular, you’re talking about the suprachiasmatic nucleus and the sensing of light, I know that
one hormone involving that is melatonin, right? That’s right. And you mentioned something about exposure
to light at night and things like that, so that’s messing up our melatonin. Correct? Yeah, that’s right. I’ll tell you about how it’s produced, and
I bet you can tell me a lot more about how that works then in the body. There are these cells in the back of the eye
that are called retinal ganglion cells, and they were discovered in the mid-90s, and they
act almost like rods and cones do, which detect light…excuse me. They’re looking at light to detect color and
light intensity, and then they can transduce a light signal into a nerve signal. Now, when rods and cones are triggered in
that way, that message goes back to the primary visual cortex, where we turn light into image. In the mid-90s though, a different type of
cell that previously had not been discovered was identified by a researcher, Ignacio Provencio,
and he found that okay, there’s another retinal ganglion cell that can also do this, it can
also turn light into a nerve signal, but that nerve signal’s not going back to what’s called
the suprachiasmatic nucleus, or the master clock. And that was a very important discovery. So anyway, when melatonin is produced under
something called “dim light melatonin onset,” when the light dims in intensity, and also
the tone of the light changes, or the color of the light changes, then melatonin is produced
in the pineal gland, this multisynaptic loop. So it is the perception of light by the eye
which is eventually the trigger to say, “Okay. It’s becoming dark. Produce melatonin.” And then melatonin, we think of that as a
sleepiness hormone, but it has fairly weak soporific activity, which means it’s not a
very strong stimulator for sleep, but it’s more of a reinforcer that it is in fact dark
out. And so it’s telling all the clocks within
the suprachiasmatic nucleus, “Yeah, it’s now nighttime. Do nighttime activities.” So it will affect the transcription and the
translation activity that’s happening. One thing that you might find really interesting
is that, you’re talking about this discovery back in the 90s; recently, they discovered,
in some sort of aquatic organism, I think it was like flagella, or some dinoflagellate,
or something. I don’t recall what specifically the organism
was. But they produce melatonin, and the melatonin
that they produce regulates them swimming up and down. And I thought that was so fascinating, because
it’s just so evolutionary conserved that it’s like being produced in these little, tiny
sea creatures. But back to the melatonin, the functions,
it’s a hormone, and it controls over 500 genes in the body, and as you mentioned, it’s shutting
down certain metabolic processes, and the shutdown of those processes are important
for other ones to be turned on at certain times, so it’s very important for regulating
metabolism. But what’s also really interesting, to bring
it back to the cancer that you mentioned, you mentioned there was like a four-fold increase
in cancer incidents with lack of sleep. And that’s so interesting, because there’s
been a couple of studies recently that have shown, for example in mice, when you engineer
them to get breast cancer. You probably have seen this study. And these mice, when they’re exposed to light
during their nighttime cycle, they are resistant to traditional chemotherapeutic treatment,
so the breast cancer cells won’t die. But, if you expose them to this pure darkness,
the cancer cells become sensitive to death. And what’s interesting is that, this is something
in people, there’s been for example, blind people, who are blind, they actually make
more melatonin, and they have twice less cancer incidents than people that are not blind. There has been studies that have been done
with supplemental melatonin in breast cancer patients, two small clinical trials I’ve seen. There’s been other cancer studies as well,
but they’re given them really high doses of melatonin, and in conjunction with other traditional
therapies like radiation, it increases, like, the one-year survival rate from 36% to, like,
65%, or something like that. Fantastic. So it’s really interesting, this link between
melatonin and cancer. And if you look closely at some of the genes
melatonin regulates, angiogenesis, which is the growth of new blood vessels, which is
how cancer cells metastatize and spread, it regulates natural killer cells, which are
important for killing cancer cells. So very important in cancer. But some of the other things you had mentioned
in a conversation that we’ve had before is the role of sleep in, since we’re talking
about diseases, clearing out toxic substances in the brain. This is a very interesting and hot subject
right now. There’s been two pretty major studies that
have come out, one in 2013, which was looking at something called beta-amyloid, which is
this potentially toxic protein, that we believe is involved in Alzheimer’s disease. There’s one study that came out that showed
that during sleep, the space between neurons expands, and that gives room for this goopy
substance to actually get out of cells and get cleared by the cerebral spinal fluid. So the brain goes through this power cleanse
in the evening, and it might be one of the major functions of sleep. The more recent paper out of Berkeley, by
Matt Walker’s lab, or he was on the paper. I’m not sure if his lab did it. They showed that this beta-amyloid protein,
particularly when it clusters in a part of the brain called the medial prefrontal cortex,
then that will suppress the generation of something called a type of[SP] slow wave sleep. So maybe I’ll pause and I’ll just mention
the different stages of sleep real quick to give a little context. So when we go to sleep, generating sleep is
an active process by the brain, and you go through different sleep stages. So you’ll have non-REM, and out of non-REM
you’ll have stage one, stage two, and then what’s called slow wave sleep. And then you will switch over into what’s
called paradoxical sleep or REM sleep, and you will go through five of those cycles over
the course of the night. It’s funny, because I get questioned a lot
because of the work that I do, evangelizing the importance of sleep. People are always wanting to know, “What’s
the important stage of sleep?,” and really, they’re all important. They’re all doing something that’s really
critical for the brain and body to restore itself. So this study in particular showed that this
area of the brain that I mentioned previously, the medical prefrontal cortex, it’s very important
for generating a type of slow wave sleep that then is important for clearing out beta-amyloid. And so if you’re not generating a lot of that
type of sleep, then you’re going to have an accumulation of beta-amyloid. And conversely, if you have a lot of beta-amyloid,
it’s going to suppress that type of sleep. It’s a feedback loop. It is. Wow, that’s really cool. I didn’t read that study, but I remember seeing
the headline, the second. The glymphatic system, which is what Dan was
referring to when he was talking about how cerebral spinal fluid squirts up through the
brain, washes out all the toxic substances, including amyloid-beta, which aggregates outside
of neurons and is thought to play a role in disrupting synapses, the connection between
neurons and things like that, is really important. Your brain swells. It literally swells, at least in rats or mice,
they swell. It’s extremely important, because that’s one
of the major ways that we can clear amyloid-beta plaques from our brains, and so that sleep
becomes just so critical. Not to mention you’re repairing damage when
you sleep. DNA repair, enzymes, antioxidant enzymes. These are all being turned on, some of them
by melatonin, some of them by possibly other circadian rhythm genes, but those are being
turned on during sleep. So it’s just so important to take the garbage
out, to repair the damage we’ve done throughout the day, you know, things like that. I know, personally, like when I don’t sleep,
while I’m more susceptible to like…anything inflammatory that’s going on is exacerbated. And that’s very interesting. There’s some other studies, I don’t know if
you’ve seen, pointing to, for example, the guy. There’s bacteria in our gut are also on a
circadian rhythm. Yeah. Crazy. So when our sleep is disrupted, these bacterias,
their circadian rhythm is also disrupted, and that affects metabolism, it affects the
way they’re metabolizing foods and things like that. You also mentioned type 2 diabetes and obesity. Can you talk a little bit about mechanisms
for how sleep… Sure. This is an area that I do my work in, and
I’d say that this subject became pretty hot probably 10-15 years ago. And it started when people were doing sleep
deprivation studies, and they were looking at blood glucose levels, and they found that,
by either getting inadequate sleep, so not a complete night, or total sleep deprivation,
that people were looking pre-diabetic, where before, they were not. And so you’d have this profile of regulating
blood glucose. If this was tested, that seemed that you were
just in a different place in your life, because they would start with young, healthy adults,
and then all of a sudden, after one night of sleep loss, they would look like they were
pre-diabetic. So that finding, which was fairly serendipitous,
stimulated a whole line of research. After that, the next area of exploration was
looking at all sorts of metabolic hormones, hormones that are involved in the regulation
of energy expenditure or hunger. And these are things like leptin, which is
released from fat tissue, and is a signal to the brain of how much fat we’re storing
on our body. Also, another hormone called ghrelin, which
is released by oxyntic cells in the stomach. And that’s a fascinating hormone, because
it does quite a lot of things, but it’s the only gut-derived hormone that will actually
stimulate hunger. Must gut-derived peptides are actually in
response to a meal and they stimulate satiety[SP]. So this hormone, ghrelin, actually will episodically,
which means over the course of the day, its own activity will wax and wane. It’s low after a meal, but it will gradually
rise, and that is going to stimulate hunger. And what they found, after sleep loss, is
that leptin levels were lower and that ghrelin levels were higher. And without getting into too much detail,
that profile would mean that you’re going to be hungrier and you’re going to have less
energy expenditure the next day. Wow. Yeah. So that was really exciting. That’s a pretty big consequence. It also tells you that you probably, if you’re
going to get your blood tested by your doctor, whoever, probably do it more than once. Because if you go and do it after a terrible
night’s sleep, you might look like you’re insulin-positioned[SP] or pre-diabetic, right? Absolutely. That would be kind of terrifying. What about the effects of loss of sleep. We’re talking about obesity, type two diabetes,
and these hormones related to satiety and hunger; what about those hormones or neurotransmitters
related to reward or food reward? Yeah. It’s a great question because, as that line
of research evolved, basically there were several things that became of interest to
understand this association between sleep loss and obesity that seemed to be present. So at one point, it was a couple years ago,
but I had a slide on a presentation that was 81 out of 89 studies, epidemiological or longitudinal
studies, that looked for an association between sleep loss and weight gain had a positive
finding. So you had a 55% risk increase for obesity
if you were getting less than six hours of sleep per night. So there was like, “Okay, something’s there,
but what’s going on?” And actually, when you looked further into
this hormone regulation by the body, and I’ve actually published one study in narcoleptics
and ghrelin, and we didn’t find that there was any difference. And so I know that literature pretty well,
because some early findings showed, “Wow, there’s really something going on here,” but
then subsequent findings didn’t show that there was a change. And so, it was equivocal. Sometimes it said there seemed[SP] that there
was something going on, other times there wasn’t. Whether not one side of that is wrong, or
there was something else happening, like a lot of things in science, always good to repeat
the study, right? But the next kind of hot thing became, because
fMRI became more broad in terms of its usage, we started to look at the brains of sleep-deprived
people and how they would function after sleep loss, and particularly after sleep loss in
response to palatable foods, foods that we know that we really like a lot, but may not
be so good for us. Like junk food? Like junk food. Yeah, exactly. This is usually energy-dense foods. A doughnut could be another example, or ice
cream, stuff that we really do think is very tasty, and the response that our brains have
to those foods that we like is elevated, so that if you were to look at things like, for
example, the activity of certain areas that process hedonic stimuli, what that means is
areas that light up to pleasurable stimuli, they would light up like a Christmas tree
after sleep loss. Wow. So your brain basically, your…okay, so there’s
two things I’m thinking. One, that your reward center is hyperactive,
so you’re of course eating some terrible food, and then you’re getting this major reward
from it. But the second thing is, what about addictive
behavior, and if you think about most people that have insomnia, for example, they go to
the doctor and they say, “Doc, I can’t sleep. I have insomnia. What can I do?” and the first sort of thing
the doctor says is, “Here’s this drug, this prescription pill,” whether it’s like Ambien
or some other sleeping pill, “This may help you sleep.” That may actually be a terrible thing for
someone who’s already, their brain chemistry is a little off because they’re not getting
sleep and so their reward circuitry is all screwed up. Now they take this sleeping pill; they may
become more addicted to that sleeping pill, theoretically. That’s interesting. Yeah. I hadn’t actually ever thought about that. It’s interesting to think, whenever you’re
doing science, it’s easier to study the short-term effects of things, but then it’s harder to
study the effects of persistent, chronic exposure to whatever that situation is. There’s something called the allostasis, which
is a type of stress response that can happen over longer term exposure. Is there a favorable kind of adaptation or
acclimation that the body makes through repeated exposure to certain things, where maybe you
would have a blunted response to these sorts of foods if you’re always sleep-deprived? I don’t know. This is kind of speculation [inaudible 00:23:27]. I’m so glad you brought this up, because we’ve
been talking a lot about some of the consequences of sleep loss, so you mentioned obesity and
type two diabetes, Alzheimer’s disease, because the glymphatic system, if you’re not sleeping,
you’re not clearing out the amyloid-beta plaques. Cancer, you mentioned. Brain atrophy is another one, right? Learning and memory problems, I guess. There’s a couple of studies I’ve seen. In fact, I’ve seen you share one study that
I found particularly interesting, was sleep, during sleep, I don’t know what part of sleep
it was, but oligodendrocytes…no, it was dendritic spines reproduce, and they help
form synapses or something, and this happens after you learn something, or like an episodic
memory occurs, or you’re doing something where you’re learning through an event, and then
you go to sleep, you make these dendritic spines, and they’re somehow finalizing the
synapses or something like that. Anyway. So I found that was very interesting, and
I remembered you shared that study. I can share a little more about it. Awesome. So this is, basically, to kind of summarize
my research a little bit, after wanting to understand more about how the body responds
to sleep loss, particularly related to food decisions and obesity, I was also very interested
then to understand, “Well, what are the cognitive effects of sleep loss, including learning
and memory?” And so during the day, like for example right
now, you’re listening to this message and your synapses are getting challenged and stimulated,
and that is going to cause kind of a modification of them. At night, you’re going to have two things
that are going to then facilitate a consolidation of that memory, which means it’s going to
then make it stronger. Your brain is going to replay that activity
pattern in a very selective use pattern. Wow. Yeah. So if you use that part of the brain, that
part of the brain at night is going to be replayed. Isn’t there a chemical, like 4BP-something,
that you produce that’s like involved in that? I remember reading a paper… There’s several. Yeah. So the key aspects are NMDA receptors, and
then protein kinase A. So if you block protein kinase A, then you will not have any long-term
transformation of hippocampal memories, which are what you kind of…it’s where memories
go during the day when you’re learning, over to more cortical areas at night, where then
those memories, they move. They move from the hippocampus to the cortex. And you don’t have that transformation if
you basically get sleep deprivation, or if you block NMDA receptors. And what ends up happening is, usually you
see a real enhancement of declarative memory, which is the learning of certain types of
facts. It’s two types of long-term memory. You basically see a suppression of that. So usually, you might see an increase in 20%,
in terms of memory retention after, say, you were to study a list of words. You’d have 20% improvement in performance
the next day after sleep. Without good sleep, or blocking these NMDA
receptors, you’re not going to see any of that benefit. Wow. What about GABA? What about the GABA system in the process
you were talking about, where you’re reliving the memory or the experience you just had? Does GABA play a role in that? So GABA plays, it’s a critical role, as it’s
the major inhibitory neurotransmitter in the brain. The way that the cortex…there’s a good way
to think about sleep, is there is a system, it’s not one monolithic kind of system that’s
waxing and waning, but you actually have a wake network, which is a clustering of different
nerve cells. So you’ve got, for example… A wake network? A wake network, yeah. So you’ve got a group of cells in the basal
forebrain that use glutamine to activate the cortex. You’ve got a group of neurons in the dorsal
raphe, which is a part of the brain that produces all sertogonergic cells or serotonin producing
cells that is activating the cortex. You’ve got an area in the locus coeruleus…you
could name a bunch of these that are all involved in activating the cortex, and those are orchestrated,
or basically they’re coordinated by one group in the area called the hypothalamus, that
produces hypocretin cells. And the reason I know about this pretty well
is because people that have narcolepsy are missing these neurons. So what are they doing? So hypocretin, a good way to think about hypocretin
is that it’s a symphony conductor, and it is telling the wake network, “Hey, it’s daytime. Be on. Play. And not only play, but play at a certain volume.” And the reason not only it’s giving like two
levels of messaging, “Play and play at this level,” is because the wake network is always
acting proportional to how much sleep pressure you’ve built up. Sleep pressure is something that builds from
the moment you wake up, and it keeps building, building, building, until you go to sleep,
and the wake network is counteracting that all day long. And at the end of the day, the wake network
goes to sleep, or turns off, and then you’ve got all this unopposed sleep pressure, and
that will initiate sleep and keep you asleep for the rest of the night, so consolidated
as well. So that’s kind of that dance that’s going
on during the day, behind the scenes. And at night, the activity of GABA will activate
in one area that is…it’s funny. Parts of the brain become more active at night
than at any other part during a 24 hour period, and one of those areas is called the ventrolateral
preoptic area. It turns on to turn off the wake network,
and that’s what is enabling you then to kind of get overcome by the feeling of sleepiness,
and then that’s why you feel sleepy and fall asleep and stay asleep. So what happens when you are not getting sleep? Let’s say you have insomnia, and we can talk
about some of the causes of these sleep problems later, but what happens to that sleep network
then? Or, sorry, the wake network. Yeah. The wake network, the timing of the wake network
is off, all right? It has shifted. And so, what ends up happening is that you
have an under-alerted brain for most of the day, because of artificial light, because
of the lighting environment, which is the first thing we talked about. Because we are getting too much light at night,
it is telling our brain that it is daytime, and that causes our circadian rhythms to shift. A good way to think about how these circadian
rhythms shift is, let’s say you were to go from, we’re in San Francisco right now, and
if you were to take a plane and you were to go to Italy, when we arrived, our biological
time would be still set to San Francisco. But over the course of five, seven days, because
of light entering into our eye at a time that’s appropriate for Italy, our own biology would
shift to match that environmental pattern. Okay. So that’s kind of a good way to think of it,
because we all usually can understand, yeah, it takes a while to adjust to a new time zone. Well, we’re basically putting ourselves in
mini-jetlag when we do this and by living in this manner, where we’re getting not enough
light during the day, and we’re getting too much at night. And what that does, our brain thinks that
it’s daytime later than it should, and that shifts our alertness rhythm, and there’s two
consequences to that. It means that, because it’s shifted, our wake
rhythm is starting too late in the day the next day, and that means it’s going to be
kind of under-stimulated during the day, our brain is not going to have enough of that
wake drive. And so therefore we need coffee, right? I was going to say, that’s why you wake up
and you feel like you need coffee. Totally. And then at night, it’s over-active, because
it’s this kind of cyclic activity. And so now you want to go to bed, I mean,
I’m sure people are going to have experienced this; “I was sleepy all day, and then right
before bed, I woke up and I felt more alert than I did all day, and I couldn’t sleep.” And that is, again, characteristic of a normally
functioning body in an abnormal environment. So we’re getting signals that our body is
responding to appropriately, but it leads to inappropriate physiology, as well. Why don’t people that live in like Alaska
or Norway, where it’s like the daylight is all crazy at certain points, has there been
any research on their circadian rhythm or are there polymorphisms they have that adapt
them to that? Do you know? You know, I don’t know about that, but I know
that a colleague of mine did some work at the Concordia Bay[SP] Station in Antarctica,
and the reason you would do that is if you’re looking at the importance of light on health,
it’s great to go to a place like that where there’s zero light for certain times of year,
so you can study the effects of artificial light only on human physiology. And what they found is they had people in
the space[SP] station that were living under normal room light, and what they found is
that their mood was altered, they wanted to go to bed a little bit later every night,
they didn’t have a good anchored rhythm, and their reaction time on something called a
“psychomotor vigilance test,” which is a measurement of alertness, which the way that you can think
about that is it’s how energized the brain feels. Basically, they were performing very poorly. And then when they put in blue-enriched white
light, when they replaced normal light with blue-enriched white light, everything improved. Their reaction time was better, their mood
was better. And they went two weeks with normal light,
two weeks with blue light, two weeks with normal light. They kept switching, and every time they would
switch back and forth, they would notice that there was either really good effects or really
bad effects, and it just speaks to the importance of having the right type of light. So bright light shuts off melatonin, the blue
light, right? Yeah. You want a lot of it during the day, and then
you don’t want too much of it at night. Yeah. Talking about some of the causes of sleep
problems, you were mentioning that being a major one, what about…I know for me, if
I drink coffee late in the day…I actually drink mostly tea, so I drink coffee maybe
one to two days a week, because there are some benefits I like from the coffee. If I’m having an interview, I’ll drink coffee,
so I’m all pumped up. I’m a little more sensitive to it. But one of the things that really affects
me personally in terms of sleep is negative thoughts, things that are causing anxiety. If I have a problem I haven’t solved or addressed,
that can keep me up all night. And that’s something that I’m sure a lot of
people relate to. Everyone’s probably experienced that. Totally. Everybody. But things that can help overcome that, obviously
dealing with the problem…what about like meditation, being mindful? Yeah. So give a little context to this. We talked about that a little bit ago, is
there’s basically two different systems that are controlling how alert or how sleepy you
feel at any point during the day. And one of them is this pressure for sleep
and the other one is this wake drive, which is counteracting it. But then there are other modulators, too,
which is social interaction, which is urgency of situation. And so those things can activate other resources
that can then further activate the brain. So people that are experiencing, for example,
post-traumatic stress, they have an overactive fear center, which is in the amygdala. And you have, I don’t want this to be too
much of a neuroanatomy lesson, but earlier, we talked about the medial prefrontal cortex,
and that actually talks to the amygdala. That part of the brain, remember, is the part
that’s generating that really important slow wave activity which is then clearing out beta-amyloid. The amygdala is a fear center, and what happens
if we are ruminating on something that was perhaps really horrible that we saw or that
happened to us, that can then suppress the activity of this medial prefrontal cortex. Additionally… Interesting. …what that amygdala can do is it can directly
activate parts of the wake network, like the locus coeruleus. Wow. So what ends up happening is people that have
post-traumatic stress – or it could be any sort of a stress, or it could be a love lost,
it could be stress at work, it’s a lot of things – it can interfere with sleep in a
very significant way. And the really crappy thing about that is
that when you don’t sleep well, you worry about your sleep. It’s a vicious cycle. When you’re not sleeping well, you’re more
emotional, you’re more stressed. Worried. And so it’s like this horrible feedback loop. Yeah. It’s rough. There was an interesting study that was done…where
was it? I don’t remember where it was done. I think it was published 2014 or 2013. You may have seen this, but it was interesting
because most people associate exercise with being able to sleep better. It seems like if you’re thinking about basic
mechanisms, it seems logical. You’re stressing your body, you’re stressing
your mind, you’re going to sleep better to recover from that, I guess. But what was interesting is that there was
a study, and there’s been a lot of associative studies saying exercise is associated with
improved sleep, but this particular study that I remember was interesting to me because
it was done on women that had insomnia, and they were sedentary. So they didn’t exercise, they had insomnia,
they went for treatment, so were part of this controlled trial where they were then prescribed
exercise. It was like 30 minutes a day for, I don’t
remember how long, I think it was like a few months. But the interesting thing from the study was
that, so they did like an acute dose, like once or twice or a few times, and that did
not make them sleep better. It actually exacerbated their sleep problems. But it wasn’t until, and you mentioned this
earlier, the repeated response and how you have feedback loops happening, so it wasn’t
until they had exercised for like a few months that they were able to really have significant
improvements in sleep. And so, if you think about it, if you’re a
stressed person, if you’re emotional, if these things things are causing sleep disturbances,
and you exercise, continually exercise, then you start to sort of dial back some of that
arousal of emotional centers[SP]. It’s kind of funny, because my mom has sleep
problems, and I’ve been telling her about exercise, and she’ll do it like once, and
then it has no effect, and she gives up. So really, the bottom line here is, don’t
give up. You need a routine. You need a training program. I don’t know if you know anything about the
types of exercise, or if there’s been any studies showing different types affect sleep
differently. Yeah. Early on, in the ’70s and ’80s, when we were
just trying to understand some of the fundamentals, it was presumed that exercise had a favorable
effect on sleep, and the investigation into that, the early investigations, didn’t actually
show that there was really much of a connection at all. Later though, and I wish I knew this well
enough to describe what the differences were between the studies, a friend of mine, Matt
Beuman[SP], who is on a paper that we’re about to submit for some of my research, which we
kind of talked around a little bit earlier, but he’s actually done quite a bit of work
looking at, “Does good sleep help you maintain a physical activity program, and does a regular
physical activity program help you get good sleep?” And basically he’s published several different
papers that have looked at that kind of idea different ways, and you see that kind of directionality,
there. So good sleep helps you be a physically active
person, and being physically active helps you sleep well. Both sleep and exercise are a fundamental
part…again, they’re not nice-to-haves, they’re need-to-haves, to have our body work well. And now we’re, in a lot of ways, trying to
just play catch-up, or we’re trying to figure out, “What is the minimal dose that I need
to perform well? Because my job really requires that I sit
at my desk all day.” It’s such a frustrating thing, but I think
life is going to be a lot different 15-20 years from now, because there’s already real
significant awareness. Environments are changing at work, people
are using standing desks, even treadmill desks. I think that in the future, when we go to
work, we’re going to be doing physical work and our mental work. There’s an understanding that daytime physical
work is going to stimulate a good, positive mental state that will help get work done,
and it’s also going to help you sleep well. I think that environments and cultures, environments
will be designed and cultures will be designed for keeping the person healthy, and that will
help keep the person productive. That would be awesome. I would love that, and I’m on that mission. Totally. I’m really trying to help promote that. So what do you think is the optimal amount
of sleep? I’ve seen several studies showing different
factors. What are your thoughts on optimal sleep and
how… So I like to promote…so the determinants
of good sleep are timing, intensity and duration. So duration is easy, and that’s like, “Well,
how much sleep do I need?” and that’s the one that most people go to readily, “How much
time should I spend in bed?” That’s one important component. That one is really dependent on you, and it
changes across the lifespan, and it can also change on whether you’re fighting an infection,
or doing really intense physical activity; you might need more than your average. So you’re going to have some night-by-night
variation. What I like to do in order to get enough time
in bed, I let my body determine how much sleep I want, so I try to give myself a little more
time in bed, for the amount of sleep I expect to get. So let’s say I usually get eight hours, I
try to be in bed for eight and a half. And yeah, maybe I’ll wake up not by an alarm
clock, by external means, but by my body waking up. I always want that to be the case. So the alarm clock is kind of like the stopgap,
like I really can’t sleep in beyond that, but I’m trying to plan enough time in bed
so that I don’t actually need it. That’s awesome. That’s kind of what I do. I most of the don’t use an alarm, but it’s
there programmed as a fail-safe, like, “Okay, if I don’t get up, if I have to be somewhere
and I have to get up.” But I think that’s a really great bit of information,
is to give yourself more time, and that probably means getting into bed earlier, right? It does, and that’s kind of the hard part,
because we, as work times extend and the work permeates into our life, because we’ve got
the ubiquity of devices that make, you know, there’s no boundaries anymore to work. It follows us everywhere we go. So if you’re in a culture where you’re getting
emails really late at night, it can make it really difficult. And if you’re in position where, let’s say,
a boss is sending you emails, it might be hard to say, “All right, I’m just gonna turn
it off and pay attention to it in the morning,” but it’s also good to be able to do that. So anyway, I try to do exactly what you do,
so I focus on getting into bed at a certain time every night, and that keeps it really
simple, and I know I want to be in bed by 11, and that’s easy, you know? And I know, unless my time that I need to
wake up changes, then I basically work backwards from the time I think I need, and that’s my
time to be in bed. Yeah. The other thing is, something that I do is
I, because as you talked about, we talked in the beginning how important light exposure
is at the right times, and not having a lot of exposure at night. I’ve got these Philip Hues lights that are
orange light, and I have them in the house, and so those go on at night. And then I also have an app on my computer
screen, because we don’t have a TV, Dan and I watch movies from a computer screen. So then we’ve got this app that filters out
the blue light, so try to kind of minimize the amount of blue light. I have a hard time with the emails because
I’m answering them. But that’s my biggest thing I need to work
on, because you will, you’ll get emotional. And being emotional about something, even
like good emotion, like I’m excited, whatever, it doesn’t matter, just emotional, I have
a hard time getting to sleep. Yeah. Under sleep deprivation, and also during stress,
emotions are heightened. So if it’s negative, it’s more negative, if
it’s positive, it’s more positive. Pain, you have a greater sensitivity to pain. There’s just kind of a heightening…I know
that pain is not an emotion, but there’s just a heightening of sensitivity. So everyone should sleep. Yeah, exactly. Interestingly, and this is going to sound
contradictory to what I’ve been saying so far, but a lot of creative thinkers and artists,
like if you think about when are a lot of albums made, they’re made late into the night. And there’s an untethering of…so there’s
something called the neuro-competitive model for decision-making, and if you think about
how the brain works is that you have this impulsive brain that is just like saying yes
to things that it finds pleasurable, and then there’s an editorial component, which is in
the frontal cortex, and it’s saying, “You know, maybe that’s not such a good idea. Maybe you shouldn’t have a doughnut, more
or less than 12.” And so, depending on which part of the brain
wins out, it’s going to determine the behavior that follows. What I didn’t mention previously, during sleep
deprivation, not only do you have heightened emotional reactivity, but you also have suppressed
cognitive control. So those areas of the brain are basically
like offline. Yeah. So you have what’s called a shift in your
economic preferences, which means that you’re going to be more likely to, if you’re gambling,
you’ll be like, “All right! Put it all on black!” You’re going to take larger risk and you’re
going to take more frequent risk. And you’re going to get rewarded, I mean,
you’re going to have that rewarding going on more for those, right? Yeah. Like the doughnuts, you’re going to eat more
doughnuts. Anyways, it sounds like sleep, there’s so
many different lifestyle factors that it’s affecting. It’s been associated with shorter telomeres,
aging, neurodegenerative disease, cancer, obesity, emotional arousal, what else did
we say? Addiction. Yeah. It’s… Endless. It is. It’s that fundamental part of our physiology,
and it’s a need-to-have, not a nice-to-have. So when I speak about sleep, I’m always interested
to show the connections, so that people will kind of escalate its value, because it comes
down to the decision, the actual practical decision is, “Oh, one more episode of Game
of Thrones,” right? It’s something that you really want to do,
and you’re already in this state where you’re more likely to just say yes to that. The point that I didn’t make clearly earlier
is that, as work kind of gets into our life, we’re always going to try to fight for a little
bit of personal time, and that oftentimes means that sleep is suffering. So knowing some of these connections, whether
you could repeat these back or not, that’s not important. You know that it’s important. Now it’s kind of on you to say “Okay, I need
to then create what I call a “sleep practice”,” which just means, “All right, what are the
things that I need to do in order so that I’m getting good sleep regularly?”, because
not only will you benefit in the short term, you’ll benefit in the long run, and it can
change so much about how you’re living your life. So what do we need to do? Okay. All right. We were talking earlier, so the things that
matter are timing, intensity and duration. We talked about duration. Timing is really critical… We’re talking about light, right? Exposure? Or no, sleep. Sleep duration. With my company, Dan’s Plan, we try to help
people live as a restorative sleeper. So the aspiration there is, you wake refreshed
and you feel alert all day, every day. Cool. I want that. What do I do, right? So then the determinants of good sleep, the
things that matter for sleep are timing, intensity and duration. Duration is just getting adequate time for
sleep within a 24 hour period. Timing is everything to do with our circadian
rhythms, right? So if you usually go to bed at midnight and
wake up at eight, but then on one night you go to bed at four and wake up at noon, even
though it’s eight hours, it’s not going to be the same, right? And that’s because so much of sleep is based
off of a circadian rhythm. So when you’re doing memory formation, when
memory formation is happening in your brain at night, there is a component of that that
is absolutely determined by what time of day your body thinks that it is. So to get very efficient REM sleep, then if
you’re usually getting great amount of REM sleep at 4 a.m., but if that’s now all of
a sudden shifted to 8 a.m. because that’s just happened to have been when you’re getting
your REM sleep, it’s just not going to be the same. You’re not going to be storing memories as
well, you’re not going to be clearing beta-amyloid as well, you’re not going to be doing all
the things you want sleep to do. How long do those effects last? Can you recuperate from them? You can, but think about, a great way to kind
of answer that question is, think about how long it takes when you go from San Francisco
to Italy, right? That the body can only adjust its circadian
timing by about three hours a day. Excuse me. What do you mean by that? Like you have a three hour wiggle room kind
of thing? It’s not necessarily a wiggle room, but if
I think, if my body knows that it’s midnight tonight at midnight, but then if I want to
adjust my schedule so that I’m on New York’s clock, it can take me one day if I do everything
right to fully adjust my physiology so that I am adjusted to New York time. But if it’s more than that, right, so basically
you can adjust your own physiological clock by three hours per day. I see. Okay. And no more than that, and that’s only under
like perfect conditions. So when you are shifting the timing of your
sleep back and forth, then yeah, there’s going to be a little bit of consequence to that. You’re not going to be getting as much benefit
as you would otherwise if you were sleeping within the same circadian phase. So the lesson there is, not only worry about
getting the right amount of time in bed, but also that you’ve got very consistent timing
of your sleep. Consistency. Yeah. For intensity, it’s not a directly actionable
thing, but physical activity and light exposure are going to affect the intensity of your
sleep, which is really important, because we want to get, again, a lot of that slow
wave activity, between .6 and 1 Hertz, which is the one that’s going to clear the beta-amyloid. We want a lot of slow wave sleep, delta sleep,
which is from 1-4 Hertz, that’s going to clear away a lot of the adenosine which makes you
sleepy. All this stuff is happening during different
processes. Then REM sleep, you’re doing a lot of what’s
called synaptic rescaling. That’s where memories are getting played over
and over again, and it’s another component of memory formation and brain health. The idea is, what’s that one phase of sleep
that’s important? No, they’re all important. And one way to facilitate is, again, adequate
time, good, regular timing, so you’re sleeping always in the same phase, and then having
enough physical activity during the day and enough appropriate light exposure. So that kind of segues into the last part
of “The Enduring Mover,” which is to not only kind of know what time you should go to bed…knowing
what time you should go to bed solves a lot of problems, because it’s both timing and
duration, really. But then you also want to maintain smart light
rhythms day, evening and night. And so what that means is you want to get
about a half an hour of bright sunlight during the day, because that strong light signal
is going to help anchor your rhythm, and then you’re going to want to get, in the evening,
dim environmental lights. Do exactly like Rhonda does, if you can: adjust
the light bulbs in your house. I actually wear glasses in the evening that
kind of solve a lot. We have those. And I’ve got a nice pair made, so they’re
not really awful-looking. Oh, really? You have to show me. I will, I will. I wish I had them here. And I’ve been wearing those very consistently. What I tell myself is that, all right, if
I start to wear these two hours before bed, that is going to help me perform better tomorrow,
because, again, it’s helping my circadian rhythm know that it is nighttime when it’s
nighttime. And you can create something called circadian
or virtual darkness, where you can see, so you can be in the room with artificial light
and you can look at a television screen, you can look at an e-reader, but because it’s
filtering a lot of that blue light, that blue light is the really potent signal to those
cells in the retina that it’s day, and you want to block that. Philips Hues makes a good light package where
you can have the white, the blue and the orange, and have them turn on the white in the day
and the orange at night. It’s the future. It sounds like getting the bright light earlier
in the day is probably the most important, right? Yes, because if you don’t get enough adequate
light during the day, then your susceptibility to artificial light at night, shifting your
rhythms is much greater. So I always call daylight “anchoring.” It helps really anchor your circadian rhythm. So if you get outside, take every opportunity
that you can. If you work in an office, have lunch outside. If you want to take a break, go for a walk. Get outside. If you can exercise indoor versus outdoor,
do it outside. It’s funny, because some researchers looked
at the difference between exercising indoors and outdoors, and some have shown that the
same type of exercise, it’s healthier for some reason outside, and it’s probably circadian
rhythm effects. Wow. Probably it’s healthier outside if it’s during
the day. Yeah. Right. That’s really interesting. Some things people can do if they have trouble
sleeping are exactly what you mentioned; the timing, making sure they go to bed at the
same time, filtering out the blue light at night and getting enough blue light during
the day and filtering it out at night, exercise. Some other things that I’ve personally been
interested in but I think they’re a little less likely to be have a very robust effect
on sleep, is some stuff coming out of a sleep lab in Oxford, and they’ve been doing some
studies, some clinical trials, on nutrition. So I’ll tell you, one of the interesting studies
that I’ve read not too long ago, I do a lot of research on omega-3 and serotonin, and
serotonin gets converted into melatonin in the pineal gland, so I know a bit about that. But DHA, DHA is important for one of the enzymes
that converts serotonin into melatonin, one of the N-acetyltransferases, I think. But it’s been interesting, because there have
been associative studies that have looked at omega-3 fatty acids and sleep, and they’ve
shown that there is deficiencies correlated with poor sleep and vice versa, but the courses[SP]
are associative, there are millions of other things that could be going on. But there’s been a couple of controlled trials
out of this sleep lab in Oxford that have shown, in children at least, they’re given
supplemental DHA from an algal source, like 600 milligrams or something like that a day,
which dramatically improved their sleep quality. So I found that was interesting, just because
there possibly is a mechanism with the conversion of serotonin into melatonin. I don’t think that, like I said, I think the
other things that you discussed are paramount, much more important. But there’s also this interesting literature
with B vitamins, B6 specifically, and magnesium, both affect, again, B6 affects the conversion
of tryptophan into serotonin, which then gets converted into melatonin, and magnesium affects
the conversion of serotonin into melatonin, and it’s a GABA agonist. So I know there’s been some associative studies
with magnesium, and personally there’s been people that have reached out to me and told
me that, after drinking a smoothie, my smoothie recipe, which has a lot of magnesium, because
it’s a lot of dark greens, that they sleep better. So it’s totally anecdotal, but I find that
interesting. Probably good nutrition, cutting out the crap
and eating the good stuff, I think that’s also probably playing a role, and we may not
know all the mechanisms yet, but I think people will start to tease those out soon. So I am not at all incredulous to the idea
that good nutrition helps with sleep, because like sleep and exercise are fundamental parts
of a healthy physiology, so is nutrition, obviously. And so, part of the ability of the body to
generate good sleep is going to be dependent on the health of its cell that are doing that,
that are involved in it, which are going to have these nutritional factors that are part
of. So there’s not great research, there’s not
really robust research in nutrition on sleep, and I get asked that question a good amount. It’s more like if you have a carbohydrate-rich
meal before bed or a fat-rich meal, all those sort of things, does it have an effect. And really, it’s very equivocal. You might see a little bit of an effect one
time, but then it’s gone the next time. Yeah, that’s a short-term. Yeah, short-term. Right. It’s like, what about the effects of chronic
inflammation? Yes. If you’re eating processed carbohydrates and
sugars all the time and you have chronic inflammation, how does that affect your sleep? It probably does. It probably does. So that’s the area that is harder to really
evaluate super well, but it’s also one that’s, of course, just as important as anything else. I think generally having a very sound, nutrient-adequate
diet, and adequacy is a term that sounds like, I don’t know, maybe not that impressive, but
it means you’re getting enough of whatever you need. All the parts that are kind of involved, all
the constituents that are involved in healthy physiological processing. We need a good diet to help us feel kind of
robust enough to exercise, for our body to be able to execute on all the components that
are necessary to generate good sleep. All these things are connected. To repair the damage that we do when we sleep. Repair the damage. Or create more. You’re CEO and co-founder of Dan’s Plan Health,
and that’s a health and wellness and technology company where you kind of talk about some
of these important factors and help people measure things, which I think is super cool,
because you have to be able to measure something to know what’s really going on, or if you’re
improving it. Yeah. As Peter Drucker says, “What gets measured,
gets managed.” It’s funny, because this is the field of quantified
self, which is trackers like Apple Watch or Fitbit are just some examples of that, and
it’s this growing movement where there’s a lot of excitement. And I speak on this quite a bit, because we
can’t put too much faith…these devices help when they help us do the activities that get
us results. They’re not going to be healthy for us, right? So sometimes people think, “Well, if I could
just track everything, then everything would be fine.” I’m also not really in that camp, either. I created a behavior model called “The Loop
Model to Sustain Health Behaviors,” and a part of that model is looking at how trackers
can help us be more mindful of how we’re living, and can also generate adequate insights to
kind of maybe find things in our behavioral patterns that we might not be able to see
readily or easily otherwise that can help us kind of shift how we live, right? It’s all about creating an effective, in my
opinion, an effective daily pattern of living, that is going to then affect your trajectory
of what your life looks like, in terms of health, and also what you choose to do. I mean, if you have poor health, it’s going
to significantly affect your own energy, and it’s going to affect the version of you that
shows up on a day-by-day basis. So all this really has been motivating to
me since I lost my father to cancer, and I was in a position where I thought I could
help him, and I couldn’t really bridge the gap between what I knew and what he needed
to hear in order for him to kind of take some behavioral action. And so that kind of sent me off into this
mission to say, “Okay, how do you really bridge that gap?” And Dan’s Plan, I’ll even announce it here,
Dan’s Plan will cease to exist, and we’re launching Human OS later this fall, which
I’m really excited about. And so we’re going to have health courses,
so that you learn what do you need to know on a subject that’s important to your health,
and so that you can learn it in a way where you can repeat it eight months later after
the course. And then programs that should make it really
easy for you to kind of follow through on a day-by-day basis, some tracking that helps
keep you mindful of how you’re living. I’m very, very excited about what I’m doing
and why, and It’s totally a passion. I heard somebody say the other day, “From
misery to mission,” and that was kind of my experience. The sadness of experiencing the loss of a
loved one to like okay, this is kind of who I am and what I do. Right, and you’re going to help a lot of other
people out there. It’s really awesome, Dan. So where can people learn more about this
Human OS and about what you’re doing, your research and etc.? Sure. You can go to right now. If you sign up…everybody that is a member…it’s
free, you get rolled into Human OS when that launches. My research, you can go to PubMed, and I’m
going to be submitting a paper to one Nutrition Journal soon, looking at…so I’ll just give
you a little quick synopsis. The research study that I just finished was
looking at cognitive performance after sleep loss, but it was what we called “ecologically
relevant.” So instead of one day with no sleep at all,
it was just, “How did people perform on their cognitive performance tests if they just got
one or two less hours for one night?” And what we found is that there was a significant
impairment in attention, or alertness, excuse me. Somebody felt either subjectively sleepy,
or they have an objective sleepiness or objective reaction time deficit. And both of those, the feeling of sleepiness
or a slower reaction time, changed the way that people ate, and so they were much more
likely to choose foods that they rated as low-health. And if you think about that, it could be a
marker of a defection from personal standards. If you kind of extrapolate or speculate on
what else that might lead to, if you’re not getting enough sleep, even if you have a standard
or a goal to eat a certain way and make it to the gym and do all these things that are
related to your health, sleep loss can give you a serious case of the “F-its,” and you’re
like, “You know what? Eh.” It’s called effort discounting, where you’re
much less likely to make an effort toward something you value. That’s super interesting. Congratulations on that. So it also affected attention, though. That could affect the way you’re learning
and the way you do a task. Absolutely. Wow. That was just one to two hours you said? Yeah. In one night? For one night. Yeah. So all other previous researchers looked at
either one night of total sleep deprivation, or five nights of four hours of sleep. So those types of studies are testing the
capacity of the system, so, “Is there anything there at all?” What we were looking at is more like the sensitivity
of the system. What’s really exciting about this is, yeah,
it’s great to know that something is there, but it might not be relevant if that’s just
not realistic or what it’s like in the modern world. But missing an hour or two of sleep loss on
any given night is very common, very relevant. That’s common. Yes. What this study shows is that our eating behaviors
change in a significant way with just a little bit of sleep loss. Wow. Yeah. I’m excited about it. So what about like social media? Oh, yeah. So I tweet on DansPlanHealth, and I have to
admit, it’s mostly just when I read research papers. It’s the most like consumer-friendly Twitter,
but… But they’re interesting. Your Twitter is interesting. I really like those things[SP] you tweet. Thanks. Yeah, there’s definitely an audience for it,
for now. I comb through articles, and the ones that
I take and read, I’ll usually tweet out some segments of them or the title, just so that
people get some exposure. I tweet a lot about microbiota. I’m fascinated by that subject. Right. Totally. A lot about sleep and weight, some about cognition,
the occasional Golden State Warriors post, just when they win the championship. Oakland last night, it was crazy. I bet. It was like honking and hollering and fireworks
going off just like all night. You’ve done really well on very little sleep,
then. I’ve actually gotten sleep. He didn’t. Oh, you didn’t? Okay. But thanks again, Dan. This was such a like interesting conversation,
and I think that people will really enjoy hearing what you have to say, and how important
sleep is, and the simple solutions and lifestyle practices they can do to improve their sleep. Thank you so much. Yeah, I call it the “mundane but meaningful.” So it’s easy to overlook, but once you’re
armed with knowledge, you can benefit if you act on it. And before we go, I also want to say that
I really admire your work and learn a lot from you, so it’s an honor to be on your show. Thanks for having me on. Oh, thanks, Dan. Glad we’re friends. Yeah. Me, too. We’ll have conversations in the future, for
sure. I hope so.

100 thoughts on “Sleep, Daylight Anchoring, and Effects on Memory & Obesity with Dan Pardi

  1. Does anyone know how old Dr Rhonda Patrick is? She looks late 20's at most, yet given her qualifications I'd be led to assume she's late 30's early 40's. Cannot compute.

  2. you should use me as a test project. I haven't slept much for years. I eat in the middle of the night sometimes. I even got breast cancer since I live in L.A. And for 4 years they built the Metrorail behind my apartment and I haven't slept through the jackhammers for four years

  3. Is there a range of time that I can fall asleep every night and have good circadian rhythm practices? For example, I try to be in bed by 11 every night, two nights a week I work late and this gets pushed back to 12/1230.

    Also, Dr. Rhonda Patrick I am a huge fan! Thank you for sharing your knowledge and passion as a cancer biologist and health/wellness scientist.

  4. at 29:31 there is a bizarre screen blackout with a counter that rapidly counts up to 299…. any explanation? great info in the video… but wondered what the purpose could be.

  5. I have listened to several talks by both separately and have always enjoyed them and found them to be educational so it was really a treat to to see this!

  6. Interesting about the issue of less sleep,and over eating.I watched a British TV show that ran an experimental demonstration of that problem.The show is Secret Eaters,season1 episode 3.You can see the segments at 20min,and 33min.

  7. This was such a profound podcast!! I knew sleep was important… but was not aware of all of the metabolic functions that sleep dictates!! Thank you sooo much for this information!!

  8. Very informational, thank you.  I would have liked to also hear about 1-having sex before sleeping 2-noise as in you're in a hotel room and there is a humming sound 3-does warm milk before bed really helps with sleep 4-is it better to sleep alone or with someone else

  9. Is there such a thing as too much melatonin? I take 10mg before bed, and sometimes still have insomnia. Is it ok to take another dose at 2am? I wish I could turn my brain off as I'm thinking negative thoughts constantly (doesn't help to have 2 family members with autism – thanks vaccines – yeah I'm off on a tangent but just had to mention it). Anyway I get so frustrated when I can't sleep and end up getting 4-5 hours – every emotion is heightened. I eat so so well, exercise and do absolutely everything else right, incl. intermittent fasting, all the stuff Rhonda Patrick suggests. By the way, her low carb lemon tart recipe is the best – I have made it 3 times.

  10. check out a sunrise alarm clock for a simple thing to improve your sleep rhythm its helped me loads

    its an alarm clock that lights up your room before it goes off and wakes you up with the light

  11. One can create melatonin when sun gazing. I already slept pretty good before, but since I have been sun gazing I sleep very hard. So hard that I wake up in the same position. This I don't like very much because I like to flip at least once, so since I learned that I don't need to wake up, I make myself. ; )The other thing that has occurred from sun gazing is my memory has improved, I feel even more amazing then I did after I went to a plant based diet 4 years ago. I never thought I could feel even that much better! …That's not all!! My eye sight has improved so much already. Everything is sharper, brighter and its getting clearer everyday!!  Oh by the way Cancer is easy to fix if you know how, and it's preventable! I got rid of my tumor in my left breast in 4 months.. It's been a wild ride on self healing!! ….and that's not all… for me to know and you to try!

  12. Is there a way out of the negative feedback loop between the beta amyloid accumulation and the medial pre-frontal cortex, or once you're far enough down the rabbit hole are you basically screwed and are likely to develop Alzheimers?

  13. What would be classed as a reasonable time to be awake for before requiring sleep? Or, what is the effective limit of time we can be awake for and still function well? Ironically, I'm currently watching this after not going sleep, and have been up for 18 hours, but I still feel very alert (pretty sure this feeling isn't going to last long now though =P!).

  14. First off, thank you. secondly, have you considered having some kind of conference where you have 2 or 3 experts come on and talk about the similarities of their recommendations?

  15. I believe enough of vids on importance of sleep…. now there should be something on how to manage health of Night shift workers… as world has millions of people working in military, police, hospitals etc. and they can't enjoy night sleep much frequently

  16. I get that Ronda, is a doctor and highly intelligent, but how does she have do much recall? She seems to recall more than this guy about the subject he actually works on.

  17. Nice to see scientists getting better looking. 🙂 But seriously, great info and data being shared here. No politics, just science at its best, moving forward in discovery. Love these guys.

  18. I feel like WHEN you eat is a crucial part of metabolism, but I have no idea how the zirconia rhythm and metabolic system work together. Does anyone know?

  19. oh gosh i know imnotgna like this bc im naughty with my sleep its1:25am already im good with my nutrition but my sleep is No good im not disceplined in this area! 😴😴😫👎👎👎

  20. I produce electronic music and have found that this translates to sound also – certain frequencies or sounds right before sleep keep me awake for longer – is there any research into this? Maybe it's simply the excitement parameter.

  21. Also, sending this to a few MDs I know who are sadly not very well informed on the subject.

  22. funny I just started watching this today and he said last night's golden State game was wild….i had to look at the date….lmao

  23. funny I just started watching this today and he said last night's golden State game was wild….i had to look at the date….lmao

  24. Great video! Decades of information condensed in just 1-hour. AMAZING 👊 Amazing information Dr. Rhonda Patrick from 52:00–54:00! That was some very useful, practical and effective information! The mechanistic cascade of reactions you described was so incredibly insightful. Listening now. Love the study on the algal source and sleep! I know this is about science and I'm enjoying this precious amazing info. But wow, you look sexy Rhonda 😊

  25. food is a much more significant driver of circadian rhythm then light that's why in some countries people have Siesta after lunch and it's not like it's very dark at 14:00

  26. Bottom Line, a lot of theories that sound good, but in the end it's better to be lucky.
    It's better to ride your bike outdoors, unless you are tiding in traffic or get killed by a wild animal or hit a pothole and break your neck…

  27. At 40 seconds in they illustrate the disconnect endemic in this– perverted –capitalist society.  An 'orphan disorder' hmmm.. one that doesn't generate enough revenue for a revenue oriented business to address it.  Pathetic.  Any society that puts profit before the health of its constituents is anathema to the very idea of a society, capitalist or otherwise, because without a healthy constituency the society cannot prosper.  The same can be said for a monetized government, or education system, or prison system, or legal system.Capitalism, or more properly, a free market economy, is essential, but regulation of that economy to avoid manipulation and extortion is at least as essential.The apparently universal acceptance of this status quo is the most pressing general problem facing the sustainability of the system that most of us in the first world have grown to know and accept as our due.  While I don't think that that is necessarily an accurate, objective way of at looking at the macrocosm of the Earth, the general outcome of this specialist navel-gazing is only a product of lazy, spoiled minds, and will be corrected for, either by conscious effort or by abrupt changes brought on by the realities of a finite ecosystem…

  28. Have you tried the Philips Wake Light (dawn simulator)? It's an alarm clock that wakes you up by slowly increasing light intensity coming from the lamp/clock, until it is at it's brightest.

  29. A friend of mine heard/read that melatonin supplements could CAUSE cancer. Has anyone else heard this? What is the best time to go to sleep?

  30. These are the best rated blue blockers according to some article I read and they are only 9 dollars. They make me feel relaxed within minutes. They look goofy but that is half of the fun!

  31. Great video
    I would love to hear what they think of magnetico sleep pad and incline bed therapy? Both have helped my sleep along with the tips they suggest.

  32. .
    I have a PhD Friend who has received a Patent which rather than exposing the Body to Light Spectrum via Eyes, actually exposes the Body to Visible & Invisible Light Spectrum via the Behind the Knee section of Skin.

    It has been determined that the Light Absorptive capability of this Area of Body exceeds anywhere else.

    We wold welcome working with Dr Pardi in this regard

  33. I wake up at 3 am and have a hard time going back to sleep. Happened this morning. I stayed in bed until 4am, switched off the alarm, and found this vid.

  34. Re: sleep and exercise (exercise physiologist here). Acute exercise in a sedentary individual increases sympathetic drive. Chronic exercise training effect creates down regulated sympathetic drive. Another great interview. Thanks.

  35. I sleep for 7/8 hours but 2 hours later each day ie. every 26 hours or sometimes 28. I call it "round the clock".
    I get more life that way. My brain doesn't care what time of day it is. My circadian clock doesn't exist. Never has.

  36. Super interesting how important sleep really is! I listened to a podcast with Mathew Walker (I assume they are colleagues) and it has totally changed my evening sleep practice

  37. FoundMyFitness — Excellent interview! And thank you for mentioning melatonin in relationship to regulation of gene(s) that regulate angiogenesis. I'm not fat, nor do I have rosacea, but worse, I have the gene(s) for Osler-Weber-Rendu syndrome [Hereditary hemorrhagic telangiectasia] + some of the more mild symptoms.

  38. Dr. Rhonda. I first saw you on Joe Rogan. I went through pharmacy school before going into cyber sec. I’m so thrilled to have a brilliant person like you talk science to me and not talk down to me. I love the actionable intelligence and steps I can take to improve my health. I appreciate all you do and hope you come to Oregon one day soon.

  39. great so my body is basicly so hard destroyed that im pretty sure ill die in the next 1-2 years… why does no one teach you this kind of information in school or why does no doctor tell you this stuff… since years i changed my sleeping pattern from ah fuck it… life has no meaning and value anyways… im 23 and daily i feel like dieing , i go to bed when its getting light outside since 5 or 6 years… im constantly under heavy stress i dont work out i have psychologoical problems etc… this basicly means i shoveled my own grave hm .. on top of feeling like pure *** oh and i smoke since im 11 and i also wondered all those years why i dont get the feeling of getting tired anymore… cause my brain is probably not creating melatonin at all anymore and i rly dont wanna know what kind of bullshit this will trigger in this robotic body…. i feel like this headpain in my cortex is probably some sort of tumor or maybe ftd or even real dementia cause idk i dont live like a normal human should be.. means i can basicly jump from a cliff and it wouldnt make any difference ? … oh and i smoked weed for years pretty heavily…what could i possibly do at this point ? i feel exhaustet i tried to ride my bioke for 3 weeks daily but after a while i couldnt anymore i feel exhausted and near death… depression is also a thing went trough a terrible heartbreak which im not recovered from to this day..seems like im screwed hm

  40. why dont we change the word human to biological robot , jesus , what is not driven by certain chemicals harmones and genes man ? … can you call "you" even you anymore ? i mean…

  41. Lol you can see the camera dude, I’m guessing that’s what he’s there for, just sitting there in the fire place reflection.

  42. Very touching at the end, talk about not being able to convey to your father what you know which might have helped him. Many of us can relate.

  43. you say sleep allows for removal of beta amyloid plaques. Then, 2 years after this video, Dr. Wenk presented on a 2017 video, presenting data where 'a puff of cannabis a day" was shown to reduce brain inflammation and prevent neurodegenerative diseases in rat models. Questions to ponder: Would you agree that the 'puff a day' is best taken at night (assuming you use an indica), to insure good sleep. That would not only fulfill the 'puff a day' advantage of less brain inflammation, but also help one sleep and thus improve removal of beta amyloid plaque. Seems the benefit is 2-fold, or maybe they are 2 ways of looking at the same phenomenon. thoughts? Another consideration, is this: does taking a puff of indica before bed (or late in day) an in any way effect sleep quality and efficacy, either beneficially or detrimentally? thanks!

  44. This just popped up on my feed. It's so refreshing to find scientists who take sleep deprivation/insomnia seriously. I've been to too many doctors who think a) it is not serious or b) that it is a result of a personal failing or lack of character. I've just ordered a happy light. Many thanks!

  45. Rhonda! I cant thank you enough for feeding the world all this amazing information. I found you through Joe Rogan and immediately I was hooked. You speak with so many interesting people, I find myself listening to your podcast 2x/3x just because they're so informative. I hate youtubers that say "Sleep is good" but cannot explain how.. You leave nothing out! I send you videos to my little cousins and family everywhere~

    As for Dan, you're amazing! Among all of Rhonda's guest you are my favorite. Thanks for spreading your knowledge.

  46. Just wanted to mention a small correction to Dan's comment on retinal ganglion cells. He is actually referring to a subclass of retinal ganglion cells called Melanopsin retinal ganglion cells which are intrinsically photosensitive themselves (like rods and cones) and make up roughly 5-8% of the total ganglion cell population (these are the main cells in controlling the release of melatonin and are interestingly most sensitive to blue light – this makes sense). Not all (actually most) ganglion cells are not photosensitive themselves. I am a retinal neuroscience Phd student. Just thought Id mention this small error. I love your videos. Keep providing all of this awesome info to the public, you are appreciated.

  47. 19:00 : Despite the fact that these foods might have a high load of macronutrients, aren't these foods actually quite nutrient deficient?? I mean, they're lacking all of the important micronutrients in the equation. That might add additional stress to the immune system as this doesn't naturally occur in such a way.

  48. 19:00 : Despite the fact that these foods might have a high load of macronutrients, aren't these foods actually quite nutrient deficient?? I mean, they're lacking all of the important micronutrients in the equation. That might add additional stress to the immune system as this doesn't naturally occur in such a way.

  49. This woman is basically living off other peoples research. But its a good thing that she is spreading the message and information regardless of the source. Only problem is if she makes money from other peoples hard work but idc

  50. Love this! Love all you do here. Thank you. Very informative. PS, the mirror reflecting the cameraman moving around and the tripod is very distracting.

  51. ypou make it so difficult with all this medical jargon you only understand..go to the point.. u end up boring

  52. I worked night shift 7p-7a for 11 1/2 years and you certainly don’t have to tell me how important sleep is. My whole body was screwed when I finally quit that job. I gained 30-40 extra pounds, probably didn’t get REM sleep for many years before I quit. When I was “sleeping” my mind was running, dreaming constantly. I used to say that I was in a dream from the time my eyes closed till the time they opened for years. I also never slept for more that 4 hours at a time. But these symptoms are pretty common for night shifters. I’ve been off of nights for a little over a year now, and I’ve lost 20lbs, get much more restful sleep, and am able to function more on my days off. Before I could barely get out of bed to do my laundry. All I can say is, no more night shifts for me, if I can help it.

  53. It would useful if questions arising from these presentations could be answered here. I have found that chances of getting a reply from FoundMyFitness are slim and none. FYI – You might want to try a setting without a reflective object in front of the camera. The camera man and technical setup is present throughout in the fireplace glass. Oops!

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