Ruth Patterson, Ph.D. on Time-Restricted Eating in Humans & Breast Cancer Prevention

Ruth Patterson, Ph.D. on Time-Restricted Eating in Humans & Breast Cancer Prevention

November 3, 2019 83 By William Morgan


[Rhonda]: Hello, my friends.
Today my guest is Dr. Ruth Patterson, who’s
a professor at the UCSD Department of Family
Medicine and Public Health and leader of the
Cancer Prevention program at Moores Cancer
Center, UCSD.
Thank you, Ruth, for being here.
I am very interested in some of the research
that you are have been doing for the past
few years and ongoing, in terms of looking
at this interface between metabolism and specifically
breast cancer risk and breast cancer…increased
breast cancer recurrence.
So when I think, you know, of lifestyle factors
that are modifiable and that are actually
known to increase breast cancer risk, obesity
comes to mind.
[Ruth]: Sure.
Obesity is definitely one of the big ones,
and also physical activity.
More recently we’ve become aware of the importance
of physical activity.
What’s been harder for us to identify is exact
types of foods that could reduce risk.
In fact, we’ve not really had a lot of success
in identifying individual foods or individual
nutrients that seem to make a difference.
Although, I think there’s more acceptance
now, the idea that an entire dietary pattern,
let’s say the Mediterranean dietary pattern
may, you know, influence risk over decades.
So I would say those are the probably top
concerns, is diet quality, obesity, physical
activity, those are the…and even tobacco
can increase…some increases breast cancer
risk.
So there’s many things individual women can
do to reduce their risk.
[Rhonda]: I was reading, I think it may be
the American Cancer Association had published
some statistics on how obesity can increase
the risk of breast cancer by twofold.
And also, specifically looking at some of
the mechanisms by which obesity can increase
breast cancer risk.
There were a variety of them including increased
inflammation, increased hormone to estrogen,
and also increased fasting insulin levels.
[Ruth]: Mm-hmm.
Yes.
I think we’ve known for a long time about
sex hormones in particular, estrogen is a
risk factor.
Because some of our first really successful
drugs were based on blocking the action of
estrogen.
Estrogen is a growth factor so it appears
if we can block that, it can reduce your risk
or reduce your risk of recurrence.
And we have some pretty effective drugs that
have made a big difference.
It’s more recently that we’ve realized that
other growth factors have the same type of
impact, and it makes…it’s almost common
sense.
If estrogen is a growth factor and that increases
growth rates of tumors, well, what about insulin?
It’s also a growth factor, it encourages metabolism.
So we do believe that perhaps high levels
of circulating insulin may be really central
to the whole process of developing breast
cancer and promoting its growth.
And high levels of insulin are definitely
found in women who are overweight, if you’re
less physically active, and then of course
among diabetics often have high circulating
levels of insulin.
So we do…are becoming more aware that sort
of that may be kind of a common road where
many different syndromes lead to the risk…increased
risk of breast cancer.
[Rhonda]: And so you mentioned that people
that are overweight and people that are obese
have higher circulating insulin levels.
They also have higher circulating estrogen
levels, right?
So does fat can secrete?
Is it…am I right, fat can secrete estrogen,
or is that something that…
[Ruth]: Fat can…yes.
So that’s pretty central.
And then, what we also know is that people
who have high levels of insulin have lower
levels of serum-hormone binding globulin,
something called SHBG which binds estrogen.
So it can prevent it from being active.
So they seem to be related, they’re not just
two independent pathways, they actually play
off each other.
[Rhonda]: Interesting.
And you say…you brought up something that
was very I think important, and that is you
said that these growth factors, they promote
the growth of tumor cells, of cancer cells.
[Ruth]: Right.
That’s in a very general way.
[Rhonda]: Right.
[Ruth]: Right.
[Rhonda]: Yeah, so you’re…
Something, you know, something’s causing the
initial damage, the cells become damaged and,
you know, we have a lot of mechanisms inherent
in our cells that can sense damage and say
well, okay, I’m going to die, I’m going to
kill myself because if I don’t, may potentially
lead to, you know, a cancer cell.
[Ruth]: Right.
[Rhonda]: But if you have all these growth
signaling factors happening in the presence
of that damage, it’s sort of saying, “Hey,
no, no keep going, keep growing, don’t die.
Grow, grow, grow.
[Ruth]: Yes.
[Rhonda]: And, you know, so that’s sort of
like I think the combination between things
that are causing the damage which possibly
high inflammation, so obesity also is associated
with high inflammation and then, you know,
the combination of the inflammation and the
high insulin, the high insulin like growth
factor, the high estrogen it’s sort of like
this detrimental combination of damage and
growth signals to allow them to survive.
You also mentioned that the serum binding
hormone that…
[Ruth]: Serum-hormone binding globulin, SHBG.
[Rhonda]: Thank you.
And you mentioned that binds estrogen and
sort of makes it inactive from going to, you
know, activate I guess in breast tissue or
whatever tissues.
What about also the insulin, so I mentioned
the insulin like growth factor pathway which
is separate but from insulin they’re two separate
growth factors but they’re also very interconnected.
[Ruth]: Yeah.
I think the data on…into like growth factors
a little less consistent and a little harder
for us to understand.
So there’s…we think it’s also playing a
role but studies have been…some studies
have found it to be a risk factors and other
study haven’t.
You’re talking about circulating levels, I’m
sure.
Because it’s also very complex because there’s
receptors for these things on the cells that
may also play in.
[Rhonda]: Right.
[Ruth]: So it’s a very complex system which
is why we’ve had such a hard time coming up
with cures.
It is because all…there’s lots of redundancies
and one system affects another system, and
so just finding like that magic pill that
can turn of all these different related pathways
is virtually impossible, there’s so many workarounds
for our body.
[Rhonda]: Right, yeah.
[Ruth]: Our body is incredibly resourceful.
[Rhonda]: Right.
So these three factors that are known, the
fasting, high-fasting insulin, the high free
estrogen…
[Ruth]: Right.
[Rhonda]: …and the high inflammatory markers.
[Ruth]: Right.
[Rhonda]: So as measured by certain biomarkers
like C-reactive protein.
[Ruth]: Right.
[Rhonda]: So these are all associated with,
in some, cases even two to threefold increased
risk.
[Ruth]: Yeah, I say definitely twofold and
maybe a little bit more.
I think that’s generally what we…what the
metric we use, each one of them increases
the risk individually by twofold.
Combination wise we don’t know, it’s probably
not quite additive, but they still would have
a combined effect too that’s, you know, reason
to look at all these different pathways.
But those are definitely the three major metabolic
pathways that we think feed into.
Having kind of fertile soil so that when these
DNA changes happen, they’re in a place where
they’re kind of like fertile soil and more
likely to go to an invasive tumor type.
[Rhonda]: Okay.
And what’s so interesting about this is that,
your work, so your work and the work of others
is showing that these three different biomarkers,
let’s say, they can be modified by changing
your lifestyle pattern.
[Ruth]: Right.
Much of my research lately has focused on
timing of meals, which I think is a little
bit of a newer hypothesis.
We all, you know, evolved to eat during the
day when we’re out getting our food and then
fast at night when we’re in a rest state.
But now with, you know, modern lighting and
with modern lifestyles and short…longer
and longer work weeks, you know, our meal
patterns less and less resemble the way we
evolved to eat.
And we believe that it’s very metabolically
detrimental to eat a lot of energy and then
right away lay down.
You know, what are you doing?
You’re laying down, you don’t need to have
all the energy on board and all that metabolism
going on, when actually you should be in a
fasting catabolic state.
[Rhonda]: And most people probably actually
eat one of their largest meals in the evening.
[Ruth]: Right.
Which is just so counter…and just even in
a common sense way, why do you need all that
energy right before you’re about to become
completely comatose?
It makes no sense, right?
You really need the energy during the day,
you know, when you’re busy up walking.
[Rhonda]: That’s a very good point.
And I think you also mentioned another important
point and that is eating during the day when
we’re supposed to eat, and timing it with
our circadian rhythm.
[Ruth]: Right.
[Rhonda]: Which is the biological clock inside
of our…every cell we’ve got a master regulator
and different, you know, tissues which we
can talk about in a minute.
But that master clock, what’s interesting
is that it does…it…you know, between 10%
to 15% of the human genome is regulated by
these clocks.
And about 50% of those genes are involved
in metabolism.
[Ruth]: Right.
[Rhonda]: And humans are the most insulin
sensitive upon waking, you know, first thing
in the morning.
And then as the day goes, insulin sensitivity
goes down.
And so, you know, eating your biggest meal
in the evening when you’re the most insulin
insensitive would increase one of those biomarkers
you’re talking about.
[Ruth]: Absolutely, right.
Or just metabolically dysregulate you which
is what we’re trying to have regulated metabolism,
and that definitely dysregulates it.
And the whole circadian rhythm concept is
the idea that, as you mentioned, the master
clock is entrained to light, you know, it
responds to light.
So the master clock’s getting the signal,
let’s say, in the evening, you’re done.
But if you’re eating, the peripheral clocks
like in your liver are going, “No, we’re waking
up, we’re getting energy.”
And we believe that when those two clocks
are out of sync that that itself leads to
some type of metabolic dysregulation.
And we don’t have fully metabolic, you know,
or molecular understanding of exactly how
this works.
But it’s a pretty solid theory, at least what
we’ve seen in animal research.
[Rhonda]: Yeah, and so I mentioned to you
earlier that I talked about this meal timing
with a collaborator of yours, Dr. Satchin
Panda who is at the Salk Institute.
And, you know, a lot of his research had focused
on elucidating this important regulator of
the peripheral clocks, meaning the clocks
in the non-brain, so the liver, the heart…
[Ruth]: Pancreas, right.
[Rhonda]: Right.
And how, when you eat your first meal or even
taking your first non-water beverage starts
that clock.
And so, if you start that clock, let’s say
you wake up at 7:30 in the morning and you
have a sip of coffee, 7:30 in the morning
the clock starts.
And he’s shown that eating all your meals
within at least a 12 hour time from that when
that clock starts seems to be very important
for, you know, having a good metabolic health.
[Ruth]: Right.
[Rhonda]: You know, good glucose regulation,
good insulin sensitivity, being able to maintain,
you know, lean muscle mass and keep fat loss
off.
But what’s really in my mind, I was trying
to understand, and like you mentioned, we
don’t know all the molecular mechanisms between
the timing of the two, both the master clock
and the peripheral clock, but how they do
seem to be working together.
So, you know, let’s say someone fasts in the
morning, they don’t eat breakfast, they don’t
eat lunch.
And then, so they’re fasting, let’s say, they’re
fasting for 12 hours and then they eat a meal
right before bed.
[Ruth]: Right.
[Rhonda]: We don’t know if that’s necessarily
going to be as good as fasting during the
evening in sync.
[Ruth]: We totally don’t think it’s as good.
You know, so our research seems to show that
two things, one we see great…our biggest
reductions in breast cancer, for instance,
recurrence, with at least 13 hours of fast.
And we really believe that fast needs to start
around 7 maybe to 8 p.m. at night.
When people talk about breakfast, what I often
say is, when you’re talking to people who
skip breakfast, I think skipping breakfast
is actually a marker of eating at night.
Because if you stop eating early in the evening
and don’t eat for 13 hours, when you wake
up you’re starving.
You don’t skip breakfast.
So a lot of times, I think the research showing
that not eating breakfast or skipping breakfast
is bad, is actually not studying breakfast,
it’s the people who skip breakfast we’re eating
late into the night.
So we think it’s both, it’s that we need a
long stretch of time and there might be some
improvements in gut rest or the microbiome.
Like, we don’t think that your GI tract also
was meant to have food constantly in there,
you know?
So we think it’s important to have a long
stretch of gut rest but that that gut rest
happens at night, starting fairly early, 7
or 8 p.m. and then 13 hours after that.
So it’s both of those things, either one is
not sufficient.
[Rhonda]: And the microbes in your gut are
also on that circadian rhythm.
[Ruth]: Absolutely.
Oh, yes, the GI tract is very, very tied to
circadian controls.
[Rhonda]: Right.
You also mentioned another study that you…one
of your research kind of said in passing that
13 hours of…at least 13 hours of fast was
associated with a lower breast cancer recurrence?
[Ruth]: Right.
[Rhonda]: So, do you mind talking about that
study for a little bit?
[Ruth]: Yeah.
I’d be glad to.
So this was a study in about 2,500 breast
cancer survivors and they completed over about
seven and a half years of follow-up, they
completed many food records, right?
So we collected all this information about
what they ate.
But then, more recently when this hypothesis
came out, we went and dug up all their food
records and said, well, how about if we don’t
care what you ate, but we just care about
when you ate it?
So, we reentered all the data as far as when
they started to eat, you know, when they stopped,
how long their fasting interval was, how much
they ate at night, and then reanalyzed that
data.
And that’s where we found that it seemed at
least in this sample of women that the cutpoint
of 13 hours reduced their risk of breast cancer
recurrence by about 40%.
It also reduced the risk of mortality by about
20% or a little more than that but that was
not statistically significant.
But it was just trending in the same direction,
you know, it’s possible.
Because we do believe it’s…although my area
of research is breast cancer, we actually
believe this dietary pattern could have really
positive effects on other diseases and conditions,
including Type II diabetes, or liver…fatty
liver, NAFLD, also with acid reflux.
You know, the first thing they tell you is
try to sit up when you go to bed, don’t eat
a big meal so that which often leads to esophageal
cancer.
So we actually feel it can have a positive
impact on many aspects of metabolism, not
just cancer, it’s just that we’re very interested
in teasing out its impact on cancer.
[Rhonda]: That’s phenomenal, Ruth, those statistics
that you just kind of just threw out there,
like 40% reduction in breast cancer recurrence
in women that were just simply fasting in
the evening for 13 hours.
[Ruth]: Right.
[Rhonda]: And that is…
[Ruth]: Regardless of what you eat.
[Rhonda]: Regardless of what you eat.
[Ruth]: It controls for whether you’re overweight
or not.
[Rhonda]: Wow.
[Ruth]: Right.
[Rhonda]: Because it’s really not that difficult
to…I think it’s much easier to…for people
to make a modifiable change of just stopping
what they’re…you know, stop eating after
7 p.m., versus eat all your vegetables, stop
eating your…
[Ruth]: Right.
[Rhonda]: …cake.
I mean, people should do that, but just saying.
[Ruth]: Yes, I still think diet quality matters,
but we’ve done some pilot studies with women
adapting a longer nightly fasting interval.
And those studies have been amazing in terms
of how simple it was for women to do it.
We actually had a little app they used and
they would text us, “Starting my fast.”
And then we’d text back saying, “Great.
Don’t forget, don’t eat again before 8 a.m.
or 9 a.m.”
You know, and so many participants said, you
know, “I never understood percent energy from
fat.
It was always so confusing to me, it made
me just feel stupid, I didn’t even know how
to do it but I just got this.
In five minutes I got this, I could do it.”
And self-report ways, they reported often
sleeping better.
And we did it with a group of Latino women,
Latinas in South Bay.
And they were particularly positive about
it, they said, you know, “In my family, if
I tried to change up our entire way we eat,
sometimes my family members weren’t that positive
about that.
Where’s our favorite foods?”
And she goes, “But this, I could do it right
away, it was really simple and it didn’t affect
the family or food ways.
So it’s very easy for me to do within our
family without disrupting all of our family
behaviors.”
They were very positive and often even reported,
“I felt so proud of myself, okay, finally
I’m doing something, I feel better, well I’m
going to start walking too.”
You know, that kind of self-efficacy kind
of spread to other health behaviors, which
is our hope.
[Rhonda]: Yeah, great.
So these women were being more compliant which
is…
[Ruth]: Well, they feel successful…
[Rhonda]: Right.
[Ruth]: …instead of feeling like a failure,
right?
[Rhonda]: Right.
[Ruth]: You know, writing down everything
you eat, running up the calories, you know,
you only can do that for a couple days before
you just burn out in the entire exercise.
So you feel like, “Oh, I can’t do it,” you
know, where this they’re like, “I can do this,”
you know?
[Rhonda]: Yeah.
[Ruth]: So we think it’s incredibly…that
some of the value is the simple feasibility
of it.
People can understand it and they can generally
implement it.
Now, we don’t think it necessarily is going
to have huge impacts on weight.
Like you’re not…probably not going to lose
50 pounds by just making this one change.
But we believe it could be an incredible public
health intervention where if everybody did
it, we could move like the whole disease risk
curve down a little bit.
And that would have huge impacts on disease
risk.
You know, which is the alternative is of course
we spend millions of dollars trying to help
a small number of very obese people lose weight
which is very unsuccessful.
But if we could move the entire population
this way, to this more healthful pattern,
we think that could actually affect disease
rates in the United States.
[Rhonda]: That’s awesome.
You also, just to kind of dive a little bit
deeper into some of your more recent research,
you mentioned the 13 hour fast overnight and
how that was very robustly associated with
the 40% reduction in breast cancer recurrence
and non-statistically significant reduction
in breast cancer mortality.
But you also have looked at some of the biomarkers
that are known to increase breast cancer risk.
And also there was an effect on some of those
biomarkers like inflammation as well, correct?
[Ruth]: Mm-hmm.
We’ve actually seen probably our most consistent
effect on something called Hemoglobin A1C,
which is a marker of your average glucose,
over about three months.
So interestingly enough, we saw the association
both in a general sample of women from what’s
called the NHANES survey, it’s a nationally
representative survey of women.
We saw that women who fasted longer had lower
hemoglobin A1C, and then in our own sample
of breast cancer survivors we found the exact
same association which means, you know, which
to us means this is probably strong.
So that’s one of the reasons we think it might
influence…have a huge effect on reducing
the risk of diabetes.
As far as inflammation, interestingly enough,
we only found that it reduced inflammation
among women who didn’t eat a lot of food late
at night.
In other words, you know, if you’re fasting
interval was 9 p.m. to 9 a.m., it didn’t seem
to matter.
But if you’re fasting interval was early in
the day, like 6 to 6, then it seemed like
the fasting interval reduced CRP, C-reactive
protein, this measure of generalized inflammation.
So that’s what made us think.
It’s not just the 12 hours, it’s the 12 hours
only if they start fairly early in the evening.
That’s when the positive effects happen.
[Rhonda]: Very interesting, very interesting.
So you…a couple of points that you mentioned,
I just want to circle back to the glycated
hemoglobin you mentioned, that basically fasting
in the evening had a pretty robust effect
in reducing that.
[Ruth]: Yeah.
[Rhonda]: And that’s a marker obviously, it’s
a marker of your long-term, you know, blood
glucose levels.
[Ruth]: Absolutely, they use that to approve
diabetes drugs.
You know, if a diabetes drug reduces hemoglobin
A1C, that’s how it gets approved.
So it’s a pretty powerful marker of risk.
[Rhonda]: So we’re talking about, for example,
metformin…
[Ruth]: Yes.
[Rhonda]: which is a very…
[Ruth]: Any diabetes drugs has to move hemoglobin
A1C down a certain amount before it can be
approved.
So if we can do this with a non-pharmacologic
approach, just rechanging when you stop eating
and the fasting interval, I mean, that’s pretty
exciting.
[Rhonda]: It’s in the brain.
[Ruth]: Yeah.
[Rhonda]: Yeah.
[Ruth]: It’s really exciting because the truth
is all these drugs have side effects, they’re
not that pleasant to take.
A lot of people simply discontinue them on
their own.
You know, so pills aren’t necessarily always
the answer, and this offers people a lifestyle
choice.
[Rhonda]: And you mentioned that you’re…there
were women that were involved that you had
basically…they made changes, they started
fasting in the evening and they also reduced
their H1.
[Ruth]: In our pilot studies, we were really
focused on the feasibility and acceptability
of it.
So we didn’t have any biomarkers, we were
testing, could they do it and how hard was
it for people to do.
[Rhonda]: Okay.
[Ruth]: So that was really a test of…because
there’s no point in recommending something
if people can’t do it.
[Rhonda]: Right.
[Ruth]: And that…so that’s what we really
focused on there, in our personal pilot work,
is just could they do it.
And truthfully, the vast…they almost all
did it and they also all said they would recommend
it as an eating pattern to their friends,
so they would recommend the study, you know,
which told us, okay, this is feasible and
this is acceptable.
And, you know, that’s what we’re interested
in, is not, you know, if it works but it’s
like impossible to do, then it’s not a valuable
public health intervention.
[Rhonda]: Yeah.
I was wondering, what I was trying to get
at is how quick or how soon do you think it
could change…
[Ruth]: Yeah.
[Rhonda]: …those…
[Ruth]: We don’t have data on that.
[Rhonda]: …levels that would…
[Ruth]: Right.
[Rhonda]: …be very interesting to see…
[Ruth]: Yeah.
[Rhonda]: …if some of that can be moved
pretty quickly or, you know, if it takes longer.
I don’t know how quick these other…like
metformin works.
[Ruth]: Oh, yeah, most of them…the thing
about hemoglobin A1C is since it reflects
average blood sugar over the past three months,
it takes about three months to move it.
[Rhonda]: Okay.
[Ruth]: Even with a really effective intervention,
it just…since it reflects the whole vast
three months of cycling through, you have
to go whole three months to see it.
[Rhonda]: Red blood cells to turn over.
Yeah.
[Ruth]:Yeah.
[Rhonda]: Right, that makes sense.
[Ruth]: Other markers may be faster, but the…you
know, because we already know that if you
want to measure these markers, you want people
to be fasting.
So we know just even one fast, one night’s
fast makes a difference, right?
[Rhonda]: Right.
[Ruth]: If you do one night’s fast, a lot
of these markers will be flatter in the morning
than if somebody eats breakfast, right, before
they come in.
You know, so you’re really…what you’re doing
is you’re extending the period of time where
you have very low basal levels of a lot of
these markers.
[Rhonda]: Right.
I just kind of wanted…
All of a sudden something came to my mind
because, you know, we’ve been talking a lot
about inflammation and these fasting blood
glucose levels, fasting insulin.
And it just hit, I remember having a conversation
with Dr. Panda, and he mentioned something
to me that I wasn’t aware of about repair
mechanisms and fasting.
I knew that repair mechanisms were regulated
by the circadian rhythm, and I always knew
that when you sleep is when you’re repairing
a lot of damage.
[Ruth]: Right.
[Rhonda]: But it didn’t occur to me that also
when you sleep is when you’re fasting.
[Ruth]: Right.
[Rhonda]: And he had mentioned that there’s
something inherently important about fasting
and repair mechanisms.
And so, you know, which of course that kind
of made me think, wow, that that’s really
interesting, I never thought about it like
that.
But if you think about, you know, that the
timing of these repair mechanisms and fasting
and how, you’re repairing damaged, DNA repair
mechanisms and also these autophagy, clearing
away damaged cells, damaged cells secrete
inflammatory mediators.
So if you’re clearing away the cells that
are damaged and secreting more, you know,
inflammatory molecules, then possibly that
would, you know, the lower the inflammation.
But it’s really interesting how your data
suggested that it really had to occur earlier
in the evening.
[Ruth]: Right.
[Rhonda]: Do you have any speculation as to
why that is?
[Ruth]: Oh, I suppose we really do think that
your body works best when its aligned with
the circadian rhythm.
But I think that is a really good observation.
Certainly, the parallel I tend to think of
is, you know, we work out, we actually hurt
our muscles.
And the muscles don’t repair and get stronger
unless we stop.
We have to stop, we have to give them a rest
period.
And the same thing, eating is metabolism,
there’s a lot of oxidative damage that happens
just as we eat.
And then the theory is that you need a time
off from that damage for the repair mechanisms
to come in.
So it’s an interesting observation in parallel.
Personally, I don’t…I think that’s a little
molecular for my research, but, yeah, I think
it’s a good parallel to compare it with like
working out.
[Rhonda]: Yeah, that is, actually.
You know, like you mentioned you need a repair
time.
Stress can activate stress response pathways
that can be beneficial, like in the case of
exercise.
[Ruth]: Right.
[Rhonda]: But if you keep on stressing yourself…
[Ruth]: You actually get weaker.
[Rhonda]: Right.
There will…
You know, repair.
[inaudible 00:27:12] stress.
[Ruth]: You do need to time off.
[Rhonda]: Right.
[Ruth]: Right.
Exactly.
[Rhonda]: What about meal frequency?
So is that…did that play a role?
So if you’re…I don’t know how long between
the fasting and fed state.
Let’s say, we’re within the 12 hours in day
we’re within that 12 hour…
[Ruth]: Right.
[Rhonda]: …you know, feeding time, allotted
time.
Does the amount of meals that we eat within
that time matter?
[Ruth]: I think it’s a little bit of a separate
question.
We tried to control for it, in case it did
make a difference.
Because it makes sense if you’re eating, let’s
say 18 hours a day, you’re probably going
to have more eating episodes per day than
if you’re only eating for let’s say 10 hours
a day.
So just reducing the number of hours that
you eat may actually have some impact on how
many eating occasions, which may also relate
to disease risk.
But we didn’t see that to be a really important
determinant of disease risk.
So we’re not really…that’s sort of a little
bit of a different question, we’re not really
quite sure.
I think that the evidence is really out on
meal frequency and disease risk.
[Rhonda]: Okay.
[Ruth]: And I, you know, if you want my…my
gut feeling is that if you keep your eating
interval fairly short, it may not matter very
much.
But when your interval is very long, so you’re
getting, you know, a meal impact and then
a long time with no meal.
And then, you know, throughout the day all
those spikes might be more detrimental.
But the data on that are really unclear at
this time.
[Rhonda]: Yeah.
I think you made some really good points and
that is, you know, if you reduce the amount
of time that you’re eating, that naturally
you would probably then reduce the frequency…
[Ruth]: You may reduce the frequency, yeah.
[Rhonda]: …that you’re eating.
I just remember, I don’t know if this is like
one of those wives’ tales where, you know,
the smaller number of meals you eat was supposed
to lower your blood…you wouldn’t have as
big of a blood glucose.
[Ruth]: Right.
[Rhonda]: You know, but then again, you’re
constantly doing it.
So I don’t know, you know?
[Ruth]: I think, you know, I know of at least
one study in the field that’s actually testing
that.
You know, testing five meals a day versus
three.
So I think they’re starting to realize we
don’t really have a good answer to that and
trials are underway to clarify that.
[Rhonda]: Okay.
One other thing that I was kind of thinking
about in the parallels between how this meal
timing is having a pretty profound effect
on, you know, for example your…what’s considered
your long-term blood glucose levels and also
to some degree on inflammation, and these
are markers of…these markers are known to
be associated with increased breast cancer
risk.
But you said that weight loss may not necessarily
occur, but what’s interesting, so you may
not…let’s say you don’t change the types
of foods you eat but just you’re basically
only eating, you know, during a 12 hour window
during the day.
So that in itself may not cause you to lose
weight, or it could.
[Ruth]: Or a significant amount.
[Rhonda]: Or a significant amount.
But what’s interesting is that, on the flip
side, weight loss, weight loss itself has
also been shown to have a positive effect
on these same biomarkers.
[Ruth]: Yes.
Right.
[Rhonda]: And so…
[Ruth]: So we actually think that some of
the positive effect might be independent of
weight loss.
You get the positive effect whether or not
you lose weight.
In our pilot study, women over a month lost
about a kilogram, or about a little over two
pounds.
So we did see a modest weight loss, that’s
very modest.
But even the mice study that…studies that
Dr. Panda does also tend to suggest that the
impacts may be independent, like, it just
helps you regardless of whether you lose weight
or not.
[Rhonda]: Yeah.
That’s kind of what I was getting at.
[Ruth]: Right.
[Rhonda]: It seems as though it may just really
be affecting your metabolism and making sure
that your timing your food intake with when
you are…when your metabolism’s at its best,
when you can process…
[Ruth]: Right.
[Rhonda]: …these, you know, the sugar and
the fats and…
[Ruth]: Right.
[Rhonda]: …just everything that you’re throwing
at it.
And that seems to be in of itself extremely
important, so.
[Ruth]: Right.
And, you know, we have seen, in our breast
cancer survivor study, we definitely saw an
improvement in hours of sleep per night when
people had a longer fasting duration.
And, you know, sleep…bad sleep can also
affect biomarkers, and it’s its own risk.
So that might be partially…you know, it’s
partially working through direct metabolic
effect but it might be working through other
behaviors too by improving sleep and getting
more sleep could also help regulate your metabolism
and kind of feed into the positive impacts.
Similarly, it’s very interesting but in several
mice of studies, they’ve shown big improvements
in spontaneous activity when they’re put on
this…when they’re not on this fasting regimen.
We don’t necessarily think that if women or
humans adopt a prolonged nightly fast they’re
going to start working out at the gym, but
there might be some more subtle effects on
spontaneous activity which frankly is the
majority of the physical activity most people
have, is just spontaneous everyday normal
activity.
So now, the animal studies lead us to believe
it can have several behavioral impacts in
addition to the direct metabolic impacts.
[Rhonda]: Yeah, that’s very interesting.
I wonder if there’s just changing the brain,
you know, lots of…
[Ruth]: You know, the data is showing that
eating a bunch of food and going to sleep
disrupts your sleep, has been around a long
time.
[Rhonda]: Yeah.
[Ruth]: You know, it’s just you don’t sleep
well on a full stomach, [inaudible 00:33:01].
You know, so it’s kind of…that’s literature’s
been out there while.
[Rhonda]: I’ve been practicing this time restricted
feeding…
[Ruth]: Mm-hmm.
Yeah.
[Rhonda]: …now for…once I, you know, Dr.
Satchin Panda’s work was really eye-opening
and I, you know, thought well I’m gonna…
I usually try to stop, you know, stop eating
earlier, like earlier in the day.
And it’s a lot easier for me in the winter,
fall and winter months when it gets darker
earlier and I’m not working so late.
The thing for me is when I’m working late,
you know, once you start working later, it’s
light out, I’m like, “Oh, I got to keep working,
I got to keep working,” then you start to
like extend your workday.
[Ruth]: Right.
[Rhonda]: And that becomes the issue.
[Ruth]: Surprise, Western lifestyle is carcinogenic.
In case you didn’t know that, now you do.
[Rhonda]: So now we have the bright light
exposure in the evening.
[Ruth]: Many things about our lifestyle are
carcinogenic.
[Rhonda]: Right.
But I do.
It’s really not that difficult to do and I’m…just
now I’m…I start the clock once I have my
first cup of coffee and it’s at, okay, well
I got to start cooking dinner, you know, at
least two hours before that or something so
that way I’m done.
And you don’t…you’re not hungry, you know,
you’re not like starving when you go to bed.
[Ruth]: Right.
[Rhonda]: Some people I think their fear is,
well, you mentioned it’s hard to sleep when
you’re super full, but on the flip side a
lot of people have this mentality that if
they’re really hungry, you can’t sleep.
[Ruth]: Right.
[Rhonda]: You know?
But I think there’s a nice balance between
those two, and that is if you just eat something,
you know, in a reasonable time, you know,
7, 8 p.m., stop.
[Ruth]: I mean, along with that, I have to
say I probably think it’s probably best for
you to go to bed at a reasonable hour.
[Rhonda]: Right.
[Ruth]: You know, not be staying up till 2
in the morning playing video games or whatever,
you know, so you know, it can all be synergistic
or in a positive way or in a negative way.
[Rhonda]: Yeah.
I want to kind of shift gears one more time.
I think a lot of people have in their minds,
at least in the context of breast cancer,
many women think about risk factors being
genetic, you know, there are certain gene
polymorphisms which are variations in the
sequence of DNA that alter the function somewhat
that can put a woman at risk.
Particularly genes that are involved in repairing
DNA damage, specifically in the breast tissue.
[Ruth]: Right.
[Rhonda]: BRCA1, BRCA2, I think many people
are familiar with these genes.
But really what your research and what a lot
of research out there has shown is that there
are lifestyle factors that play a if not equally
important role, and certainly in combination
with these genetic risk factors would probably
be very, very important in modifying breast
cancer risk.
And not only risk but recurrence.
So there are a few types of lifestyle factors
that we talked about today that may, you know,
dramatically lower a female’s breast cancer
risk, and also people out…women out there
that have had breast cancer, certain lifestyles
they should adopt in order to lower their
recurrence.
[Ruth]: Right.
[Rhonda]: So what do you…if you want to
talk about maybe top one.
[Ruth]: Yeah, you know, sure.
You know, BRCA1 and BRCA2, if you have that
gene, you know, polymorphism, that’s a pretty
special case.
And those women are at very high risk of breast
cancer and recurrence.
And it’s hard to know for that small percentage
of women, how much lifestyle matters.
But again, they’re a special case, majority
of cancers are just sporadic.
We think that less than 5% overall of breast
cancers are the result of genetic factors.
And more like 65% to 75% are the result of
lifestyle factors, including obesity, diet,
physical activity, and smoking.
And alcohol we think maybe for breast cancer.
So those are all things you can modify.
So the idea that you’re doomed biogenetics
couldn’t be more wrong.
For the majority…the vast majority of women,
it is your lifestyle choices that will make
the biggest difference in your risk, which
is not the same thing as saying you’re to
blame because a lot of cancers are sporadic,
but that there are things you can do to reduce
your personal risk, a lot.
[Rhonda]: Well, that’s good news.
[Ruth]: Yeah.
[Rhonda]: So don’t smoke, moderate drink,
you know, don’t drink a lot.
Lose weight.
[Ruth]: Lose weight if…and even a small
amount of weight.
Recently there was a study that seemed to
show like they saw a huge improvements in
metabolic health in the first 5% of weight
loss.
And then they said, if you looked at 5% to
10% of weight loss, it’s like it flattened
out.
There wasn’t, you know, it isn’t like a linear
thing.
So it looks like even modest weight loss can
really improve your metabolic health.
So I think there’s this perception that, well,
if I don’t get to model skinny, there’s no
point in even trying.
And I think that’s a really wrong way of looking
at weight loss.
Five percent weight loss could really make
a difference.
[Rhonda]: Five percent of your…
[Ruth]: Five percent and keep it, you know,
keep it off.
You know, and maybe in a year or two you might
go, “Well, maybe I’ll lose another 5%,” you
know?
But, the idea that there’s like some very
linear thing going on, I’m not sure the data
really support that.
So even modest weight loss, you know, work
on the quality of your diet, work on the timing
your diet, get some physical activity, please.
You know, avoid long periods of sedentary
behavior, all those things combined, good
sleep, you know, and good food choices I think
are…that’s the total combination of things
is the best thing you can work toward.
And just make it a lifestyle to always be
working on improving those things as your
whole life.
[Rhonda]: I think that’s fantastic advice.
And I just want to mention that number again
because it really is, you know, the best obviously…no
one wants cancer, you know?
That…if you can do whatever you can within
your, you know, control to give yourself the
best possible chance of not getting cancer…
[Ruth]: Right.
[Rhonda]: …then really, really, really,
really, really you should do it.
That’s, you know…
[Ruth]: And there’s a super benefit here,
is that it likely will reduce your risk of
cardiovascular disease which after all is
still the number one killer of women.
So, you know, you’re really getting a 360
effect on your risk of all the major killers
in America, some unpleasant conditions like
diabetes and also, hopefully, just feeling
better every day.
[Rhonda]: Absolutely.
And that’s…
[Ruth]: Quality of life.
Basic quality of life.
[Rhonda]: I think there’s been studies showing
like weight loss…
[Ruth]: Right.
[Rhonda]: …improve your mood.
You know, inflammations associate with depression…
[Ruth]: Yeah.
[Rhonda]: …you know, and inflammation associated
with obesity.
So yeah, you’re right.
[Ruth]: Right.
[Rhonda]: All these things, quality of life.
[Ruth]: Physical activity is associated with
reduced risk of depression or ameliorating
some of the effects.
So there’s, you know, it’s not like there’s
a separate list of things you should do for
one disease versus another, it’s like the
total benefit package.
[Rhonda]: Right.
Yeah, they’re all overlapping.
[Ruth]: Much more overlapping.
We used to not think that as much.
We used to think they were completely…here’s
the disease pathway for cardiovascular disease,
it’s very metabolic, it’s blood pressure,
it’s cholesterol.
And here’s cancer, and it’s a genetic disease
and there are two separate pathways.
Now, we see that they’re actually way more
overlapping than we ever knew and it’s really
good news because it means you don’t have
to do separate things for each disease.
It means the same suite of healthful behaviors
can give you 360 protection.
[Rhonda]: Well said.
And just one last time, that meal timing,
women that had breast cancer and had fasted
for at least 13 hours overnight had a 40%
reduction in breast cancer recurrence.
[Ruth]: Right.
[Rhonda]: I think that’s a pretty good incentive
for women to set that clock when they put
the first bite of food in their mouth, or
the first non water beverage, that clock set,
and making sure that you don’t eat food past
7 p.m.
[Ruth]: 7, right, or 8.
[Rhonda]: 7 or 8.
[Ruth]: Satchin Panda’s work was…he did…the
most recent article he published which I thought
was very good, looked at mice where he just
had them do restricted feeding five days a
week, and then all around the clock, you know,
kind of break it, the fast, on the weekend.
And he saw much of the same effects which
means, you know, you don’t also have to be
perfect.
As long as you most of the time you do it,
you don’t need to feel like a failure like,
“Oh, I went out, I ate so late,” it’s fine.
You know, just pick up the next day and get
started again.
[Rhonda]: Thank you for bringing that up,
because, you know, weekends are when we have
that social pressure.
[Ruth]: Right.
[Rhonda]: You know, we’re having later dinners,
we’re having drinks, you know, so it’s nice
to know that at least if the animal studies
do translate to the human studies, that we
can at least break the rules or cheat a little
bit on weekend.
[Ruth]: I think that’s a plus side, is that
it’s not about being perfect, it’s about mostly
doing it and you’ll get most of the benefit,
right?
[Rhonda]: Agreed, agreed.
Well, Dr. Ruth, thank you so much for your
time and for the phenomenal research that
you’re doing and…
[Ruth]: Thank you.
[Rhonda]: …I really look forward to reading
more and keeping an open line of discussion
with you to learn more about some of what
your research is showing in terms of the meal
timing and breast cancer incidence.
[Ruth]: Great.
Thank you, Rhonda.