One of the things that people have done
to even take this idea
of time restricted feeding and fasting one step further,
is to look at one of the most Hallmark metabolic shifts
that takes place when we fast.
And that is the production of something called ketone bodies
by the liver as a source of fuel for the brain.
So when individuals for example, run marathons,
and the reason that they load up with carbohydrates
is so that they can go as long as possible,
by allowing the liver to generate glucose
from the glycogen that it deposits,
as a function of all that carbohydrate consumption
the day before.
And the intent is to have glucose be produced by the liver,
for long enough to allow for the fat tissue in our bodies
to mobilize fat and send that fat to the liver,
for the live to then turn that fat into glucose.
And so you have a continuous supply of glucose,
and the liver also makes something called ketone bodies
from that fat that go to the brain specifically
and allow us to remain alert, aware,
and on top of things,
even though we haven't eaten since the night before,
and we're in the middle of running a marathon.
But if people don't manage
the carbohydrate consumption correctly,
and if they're devoid of sufficient glycogen to bridge
until the fat reserves from the fat go to the liver,
and the liver can make ketone bodies with them,
you will have a fuel gap.
And if you are unable to make ketone bodies
for your brain before the glucose supply runs out,
then you hit the wall,
and I think you many of you may have seen images
of people who do that around mile 20 or 21.
And that shows how vulnerable we are in the brain
to the need for a constant supply of fuel.
And ketone body production by the liver
is that evolutionarily conserved source of fuel,
that keeps us alert and aware
when it's been a long time since our last meal.
So what we've learned is that carbohydrates,
and their consumption is what shuts off
the generation of ketone bodies,
because it's associated with the production of insulin,
it means that we've now eaten a meal,
and all of our physiology goes to the Fed state again,
it resets like a typewriter back to the beginning.
And so, by learning this,
we've been able to harness specific diets,
which we now call ketogenic diets,
by limiting the amount of carbohydrates in favor
of protein and fat,
allow us to enter a state of mild ketosis,
even though we're not fasting specifically to do so.
And what we found is that if we can limit the ketosis
and keep it in a very mild state,
there are a lot of health benefits
that come from that as well,
because we are evolutionarily very,
very conserved to rely on ketones,
because it is our hormonally driven indicator
of a prolonged fast,
and we can mimic that by putting ourselves
on a specific diet Asian.
All right, so this is just a quick overview
of the ketogenic diet.
I think I already went over this.
But normally, when we fast fats are liberated
from our fat tissue.
That's one of the reasons why we have fat
is to actually provide a fuel source when we're fasting.
Those fats go to the liver,
the liver turns the fat into a number of different things,
including glucose for itself,
fat to send to the heart and other muscles for fuel,
and ketone bodies which primarily as I said,
go to the brain.
We can recapitulate that by just eliminating
or lowering the amount of carbohydrates
that we consume sufficiently,
to reduce insulin levels.
And by doing that,
fool the body into thinking we're fasting
in a manner of speaking,
and liberate this ketogenic cycle purposefully.
And we can also, by the way,
engage in the same kind of thing by consuming ketones.
And that's another area of precision medicine
and nutrition that you are gonna see
coming out over the next few years.
And that is supplemental nutraceuticals
that are designed to provide ketones,
so that we can get that increased ketogenic bump
without having to substantially alter our diets at all.
Now, the science in that area is really new,
but that's one direction where many researchers
are trying to take it.
And so the ketogenic diet is again,
like time restricted feeding associated with a number
of different health benefits,
and the ones that are shown in dark
are the ones that have a lot of evidence
to back them up both in animal models as well as in people.
And the other areas that are more gray
are a little bit less well recognized
as being bona fide benefits of the ketogenic diet,
but are emerging areas that we think are also relevant
to what you might be able to expect
in response to this diet.
And we're trying to find out mechanistically,
how all of these health benefits work,
and that's a very vibrant area of research right now
in nutritional physiology.
Okay, so even more recently,
this again is just a couple of weeks old
and this is from another colleague of ours who we work with,
named Peter Turnbow.
And his lab has done a study showing that,
not only does ketogenic diet produce physiological effects
that have contributions to metabolic health,
but they also produce immunologic effects.
And immunological aging is another aspect of healthspan
that we would like to intervene in.
And so they looked at people on a ketogenic diet
and what they found was,
that the levels in the gut lining, as well as in the blood
of a cell type a T cell type called Th17 cell,
which is elevated in individuals with cardiometabolic risk
and in comparisons of people with diabetes
versus no diabetes,
goes down in response to consumption of a diet
that is ketogenic in nature.
And in their study they showed that,
one of the mediators of that relationship
between ketogenic diet and immunological improvement,
was a change in the nature of the microbiome.
And so this is another area I think, now, really,
the frontier area of precision nutrition,
that is really coming to the fore,
and that is the microbiome.