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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,