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Dave: Hey, I'm Dave Asprey with Bulletproof Radio. Today's cool fact of the day is that
goldfish which are reported to only have a 3-second memory actually can remember things
up to five months which is why you might want to take care of your own memory. Today's guest
is Alan Cash. Alan's never been on Bulletproof Radio. He's the CEO of Terra Biological and
the clinical trial supervisor and medical researcher for Upgraded Aging, which is why
I was talking about goldfish memory before because if you can do upgraded aging on your
memory, you're going to like what happens as you get older, protecting those neurons
is something that I do every single day. You, if you were at least the Bulletproof
conference, would have already heard Alan Cash talking about Oxaloacetic, the active
ingredient in Upgrade Aging. At the Bulletproof conference, I asked the Bulletproof team to
interview Alan Cash while I was on stage presenting so I could get this content out to you. Alan
is an amazing, amazing researcher and I'm really excited with how podcast turned out.
Enjoy the interview. I came up with the questions myself. Alan and I have met and talked many,
many times. I just couldn't be there in person to get this info out to you on video. This
is an amazing podcast. Speaker: Alan, thank you so much for being
here with us today. Can you tell us what you're speaking about at the 2014 Bulletproof Bio
Hacking conference? Alan Cash: Absolutely. Thanks for inviting
me. I'm going over some recent research on Oxaloacetic which is part of the Krebs cycle.
It's up here in the upper left hand corner. This way goes to citrate, this way goes to
malate. When we give Oxaloacetic to animals, we wanted to see what happened to their brain.
We saw some really exciting things. One, we saw an increase in mitochondrial density.
Those are the little power plants that make your cells work. It gives you energy. By increasing
the amount of that mitochondrial mass, we're seeing an improvement in brain functioning.
Second thing we saw is that glucose uptake is improved. Here's a way, as we age, we lose
the ability to bring glucose into our cells. It just starts circulating in our bloodstream
and the levels go up and up and up. This way, it's being brought into the cells where it
can be used by those little mitochondrial power plants. That's exciting too. Then we
saw a decrease in brain inflammation which is always a good thing because that's another
thing the aging brain tends to do, is be saddled with inflammation problems.
The last thing we saw which is just incredibly exciting is an increase in the number of neurons
that are produced by the hippocampus. Now, it used to be thought as we age, the brain
was static. If you lost those brain cells in college, you'll never get them back again.
I know you know what I'm talking about. What really is happening is there's a place in
the brain called the hippocampus which is constantly producing new cells to replace
the cells in our brain. But as we age, that ability declines and declines and declines
and declines. here is a method that we found that's able
to turn the body's natural process of producing those cells back on and produce them in a
much, much higher rate. We're replacing those cells that were damaged in the brain. Very
exciting stuff. Speaker: I knew we're going to dive more into
that in a minute. Can we start with you just telling us what Terra Biological is?
Alan Cash: Terra Biological started off as a research company. I was doing post graduate
work at University of California down in San Diego. My partner was working at UCLA. We
looked at aging, specifically why does calorie restriction increase lifespan? I mean, it
does this throughout the animal kingdom from the single celled animal all the way up to
primates. We have 30-year tests in monkeys now, and possibly in humans. We see a lot
of good things in humans with people who calorie restrict. Why does this work though?
It was discovered in the 1930's, in 80 years, you think we'd be able to figure out what's
going on. Some of that work in the molecular basis of calorie restriction started mid-1990's
and continued on, well, through today. One of the things we found is an increase in the
NAD to NADH ratio seems to be the start of the whole process. That then activates this
chain of molecules that turn on genes and turn off genes that improve our overall health
and condition. Very exciting stuff. We started off as a research into this back
in 2004. It started getting more and more exciting as we gave this one compound, Oxaloacetate,
which again, part of the Krebs cycle. It's a human metabolite. It's in every cell of
your body. When we gave these to animals in excess to what they normally have in their
diet, they started to live longer, by a lot, 25 to 50% longer. We started in very simple
animals like worms and then we went to more complex animals, flies and then mice. We kept
seeing this increase in lifespan just as we did in calorie restriction.
We thought, "Well, I wonder if anyone's ever given this to human beings." We started looking
through the literature, scientific literature. What we found is a clinical trial that was
done back in the 1960's in Japan. They were looking at Oxaloacetic for diabetics because
a mountain plant traditional Japanese and Chinese herb, [Unomius Salatis Sieb 06:37]
was the Latin name, was found to help with diabetics. They looked at all the components
of this plant and that Oxaloacetate was the thing of interest. They did a clinical trial
with it. They took 25 people. They all had reductions in their fasting glucose levels
without side effects. I thought, "This is pretty exciting stuff."
I mean here, a human metabolite, a natural compound, we're seeing reductions in fasting
glucose levels in diabetics on average of 25% which is huge, where's the follow on work?
I'm searching through the literature and searching through the literature, I couldn't find any
follow on work. I flew to Japan and I interviewed the department where this all took place.
The conversation went something like this. I said, "Are you familiar with this paper?",
"Yes. We wrote that paper." I said, "Oh great," I said, "Were there any issues with the Oxaloacetate
or the test?" , "No, it worked quite well." I said, "Where's the follow on work?" They
said, "No follow on work." I said, "Wait, you've got a natural compound, a human compound
that reduces fasting glucose levels in diabetics and you're not following up with it? Why not?"
They said, "Well, it's a natural compound." I said, "Yes, yes, yes." They said, "No patents."
That was the end of the conversation. Although it's not perhaps being able to patent it for
diabetic use, for anti-aging, it's certainly very exciting.
Speaker: Well, that brings us to the Bulletproof Upgraded Aging formula. Can you tell us what
that is? Alan Cash: Well, Bulletproof Upgraded Aging
is a combination of 100 milligrams of Oxaloacetate and 150 milligrams of vitamin C. We combine
the two together because they work a little bit synergistically and they also help to
preserve the Oxaloacetate. When we first started working with the Oxaloacetate, it degraded
almost daily. We had so much trouble. We had to learn how to synthesize it and stabilize
it, thermally stabilize it so that we can have a two-year shelf life so that we could
use it as a nutritional supplement which is probably why you don't see it anywhere else
in the marketplace. After we learned how to stabilize it, we found
that adding vitamin C to it helped with that stability. That's what it is. It's very simple
compound. There aren't any excipients. There aren't any preservatives. It's in a veggie
shell of a capsule. We had to actually pay more to take out all that stuff and just have
a pure product. I think that's what Bulletproof is all about.
Speaker: What does it taste like? Alan Cash: It's a cross between an orange
and a lemon, excuse me, an orange and a lime. Because it's in the citric acid cycle, it
has that characteristic citric taste but it's a little different. I actually liked the taste.
I open up some of the capsules and I'll put two or three in a glass of ice water and stir
it up and with a little bit of honey and I drink straight.
Speaker: Bio hackers strive to achieve better cognitive function daily. Can you share with
us some new research in cognitive functioning and how it can be achieved?
Alan Cash: There was just a paper published in the journal human molecular genetics in
July of 2014. I mean, this is hot off the press. Where they took Oxaloacetate and they
fed it to mice. They wanted to see what was happening with their brains. The reason they
wanted to do this is this was some pre-clinical work. They were looking at perhaps using this
compound for Alzheimer's disease. I'm not suggesting that you use this for any disease.
It's a nutritional supplement. They looked at giving Oxaloacetate to mice and what they
found is an increase in mitochondrial density in the brain, the little power plants that
power your brain, that power your thoughts. They also found the brain was able to uptake
glucose at a much higher level. Not only are we building more power plants, we're providing
more fuel into the cells to power the brain. Then we saw a decrease in the inflammation
in the brain which is always a good thing. The last thing they saw in the paper was an
increase in the number of neurons that were produced in the hippocampus. Not just the
number but the length of the connecting dendrites, I think that's the word, that connect the
neurons. These little fibers are longer to allow them to interact a little bit better.
Pretty exciting stuff. Speaker: You brought up mitochondria. What
are mitochondria and how do they feed the brain?
Alan Cash: Mitochondria are, there's debate on what they are. A lot of people feel that
they're a foreign organism that were brought into a cell and they got along so good together
that they stayed that way. They have their own DNA which is interesting. Not very many
genes, I think 13, but they work together with the nucleus. One of the things that the
mitochondria do is they provide ATP which is our energy currency, our bitcoin of how
to run the cell. It does that through a chemical reaction taking glucose in and breaking it
down and producing much more ATP than other other processes.
One of the things about mitochondria is they've been tied to many disease states lately. It
just seems like every chronic disease that's out there is tied to misfunctioning mitochondria.
One of the things we should aim for in any kind of nutritional supplement is keeping
your mitochondria healthy. Speaker: What are the steps to take today
to build more mitochondrial mass? Alan Cash: We've learned a couple of interesting
things about how to build more mitochondrial mass. One is calorie restriction, eat less,
a lot less, like 25% all your life. Put down that spoon of ice cream and a lot of other
things. It's kind of funny, I tried calorie restriction for 30 days because I study it.
I know you'll find this amazing but my wife suggested that I was irritable. I know, it's
a rumor. But it's hard to calorie restrict that well. I mean, there are people who do
it and my hat's off to them. I think they're incredible but food is such part of our life
and you want to be able to enjoy that part but you also want to be able to increase your
mitochondrial mass. How do we do that? Well, one of the ways is through Oxaloacetate
supplementation. Another way you can do it is through chronic exercise, run several marathons
every week. But that also takes a toll on your body too. we're thinking that the Oxaloacetate
might be your have your cake and eat it too supplement.
Speaker: How is aging a major threat to cognitive functioning?
Alan Cash: How is aging a major threat to cognitive functioning? Well, there's several
issues there. One, we see a decrease in mitochondrial density. That's a little, the power plants
that power your brain and your thoughts. As those decrease, the brain fails in its ability
to get the job done. Another thing we see is glucose which is circulating through our
bodies, from the food we eat, the brain has difficulty in taking that up. If you can't
get that glucose into the cells, it doesn't do you much good.
As a matter of fact, it does you a lot of harm because that glucose can then react with
other proteins that are floating around and cause these advanced glycation end points
or age points which are the acronym says it all. They're age related molecules. Then lastly,
we see that the hippocampus which generates new cells in the brain to replace the cells
that die off lose its ability to do that as we age. Your ability of your brain to repair
itself, for a while, we thought that the brain couldn't repair itself. Now we know that it
can. That's very exciting. How do we stimulate it to not only repair
itself but to keep it very top shelf. That's some of the things that we worry about with
the aging brain. Speaker 1: The idea of brain inflammation
might scare people but in reality, it actually happens to all of us, right?
Alan Cash: Well, as we age, yes. There's a lot of other causes of inflammation in the
brain other than just again. One is like a bacterial infection or a fungal infection,
mold, chlorinated pesticides has been shown to increase inflammation in the brain, head
injury. There are a lot of different causes for brain inflammation but certainly aging
is one of them and hopefully that happens to all of us.
Speaker: What can we do to lessen brain damaging inflammation?
Alan Cash: Well, it's kind of interesting. Oxaloacetate is being used in Europe now in
clinical trial. They're looking at closed head injury for instance in football or car
accidents or whatnot. What they've seen in animal models anyway, is that when you get
hit in the head, the actual damage to the brain is only about 20%. 80% of the damage
to the brain is caused by something called a glutamate. It's when your neurons excrete
all this glutamate and that excites the neurons so much that it kills them. We call it excito-toxicity.
It's too much of a good thing. If they can reduce that glutamate level, they,
at least in animal models, they've been able to show 80% less brain damage from closed
head injury. That's exciting. That's one of the things that they're looking at very closely
in Europe with Oxaloacetate because what happens with the Oxaloacetate is once it goes into
the bloodstream, it reacts with the enzyme glutamate oxaloacetate transaminase which
is a huge word but you can call it GOT. Through GOT, it combines with the glutamate.
The Oxaloacetate and glutamate combine and together they make something called alpha-Ketoglutarate
which is brain protective as opposed to brain excitatory. Because of this, it gives us some
chance that we may in the future be able to help with some of these brain inflammation
and brain excito-toxicity, that's for sure. Speaker: With Oxaloacetate, can it help us
rebuild brain power as we age or rebuild the brain power that's lost as a result of injury
or exposure to some of these toxins that you've talked about?
Alan Cash: Well, we can't really say for any kind of injury that Oxaloacetate will help.
This is just a dietary supplement but can it help with the ravages of aging. I've seen
it time and time again. My mom's 90 years old. When I give her the Oxaloacetate, when
she takes her capsules, she remembers where the keys are. That's not necessarily a good
thing because she's 90 but we see this time and time again with, especially with elderly
people that they seem to have more cognitive functioning, they seem to have clear thoughts
and when I talk to other people about Oxaloacetate, I say, "Why do you take it?" They go, "I take
it because I have brain fog." "What does it do?" , "Well, it helps me when
I'm tired. I can write better. I can recall better." This is the comments that I'm getting
back as a researcher from people who are actually taking Oxaloacetate products.
Speaker: Do supplements like this help daily or over time?
Alan Cash: People have asked me when is the best time to take Upgraded Aging. Right now,
right now. I mean, why wait? Should you take it in the morning, should you take it in the
evening, how long should you take it? The most important thing is to take it daily because
what you're trying to do is turn on the genes that simulate this calorie restricted metabolic
state. The best way to do that is everyday, everyday, everyday, everyday. In our animal
models, we gave it to them their entire lifespan because we wanted to see what would happen
over their entire lifespan. What we saw is a decrease in inflammation.
We saw a decrease in chronic conditions such as curvature of the spine. We saw improved
energy. We just saw healthier animals and they live longer. It should be taken daily,
really timing doesn't matter as long as you take it during the day. Some people if they
take it late at night, it causes them a little bit of sleeplessness because they're just
so alive. Maybe a morning supplement. Other people need it in the mid-afternoon to just
kind of get through the day. Speaker: The effects of this supplement felt
immediately? Alan Cash: This is a very subtle supplement
because you're turning on genes as opposed to a pharmacological effect. In pharmacological
effect, you feel the results immediately. It's kind of like you have a hammer, you hit
your hand, your hand hurts. With genomic type things, you turn on the genes and then you
have to wait because the genes then produce proteins and in order to produce enough proteins
to have a measurable effect, it takes time. In the case of Oxaloacetate, most of the effects
can be felt within 30 to 45 days. Some effects can be felt immediately but they're very short
lived. For instance, an increase in endurance can be measured with Oxaloacetate for two
hours after you take it. For that reason, a lot triathletes and bicycle type people
take the product before they race. It's kind of funny. I asked one of them to
do a testimonial for me. They said, "What are you, crazy? I don't want to tell people
about this. No way." Anyway, the pharmacological effects increase in endurance, that can be
felt immediately. A reduction in glutamate, the can be sometimes felt as a feeling of
peace and better focus but the real huge effects are after you take it for 30 to 45 days where
you get those gene expression changes, where you get the increases in mitochondrial density,
where you get increase in glucose uptake to the cells, these are critical fun, fun things
for your body. Speaker: What are your top 3 recommendations
for kicking more ass at life and being more Bulletproof?
Alan Cash: That's a great question. Obviously, take Upgraded Aging, that's number one because
it puts you in that calorie restricted metabolic state that is so hard to achieve any other
way. Another way, another thing I would take is vitamin D. Then the last thing I would
do is short term interval exercises. Diet and exercise, it's kind of what you've been
told all your life, right? Speaker: Alan, thank you so much for being
here with us today. Alan Cash: You bet you. My pleasure.
Dave: If you haven't had a chance to check out our Upgraded Aging formula, it's worth
a look. It's an amazing molecule you can take that helps you to mimic the effects of caloric
restriction. You're probably already practicing Bulletproof intermittent fasting, adding something
like Upgraded Aging formula helps your body to get the benefits of reducing calories without
actually reducing calories. On top of that, Upgraded Aging formula helps your brain deal
with large levels of glutamate which is something that causes toxicity in the brain. It helps
a healthy brain stay healthy. It also has other very positive effects on
maintaining healthy blood sugar levels and on other aging risk factors. This was the
only supplement I've ever come across that very clearly impacts four different facets
of aging, that's why I call it Upgraded Aging formula and it's available on upgradedself.com.
Featured Terra Biological LLC
Resources Oxaloacetate
Kreb�s Cycle, or Citric Acid Cycle Citrate
Malate Mitochondria
Calorie restriction and aging: review of the literature and implications for studies in
humans (American Journal of Clinical Nutrition) Nicotinamide adenine dinucleotide (NAD)
Oxaloacetate Activates Brain Mitochondrial Biogenesis, Enhances the Insulin Pathway,
Reduces Inflammation, and Stimulates Neurogenesis (Human molecular genetics)
Adenosine triphosphate (ATP) Advanced Glacation End Products in Foods and
a Practical Guide to Their Reduction in the Diet (Journal of American Dieteics Association)
The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated
by its blood glutamate scavenging activity (Journal of Neurosurgery and Anesthesiology)
Pictorial Review of Glutamate Excitotoxicity (American Journal of Neuroradiology)
Gluctamate oxaloacetate transaminase (GOT) Alpha-ketoglutarate
Bulletproof Upgraded Aging Formula
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Bulletproof Toolbox Podcast #183, Alan Cash
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� The Bulletproof Executive 2013