[Rhonda]: 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