Ketogenesis and Fasting: Fuel for the Brain

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.
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