FoundMyFitness - #011 CHORIBar: Micronutrients, Fiber & Polyphenols in a Bar

Episode Date: August 20, 2015

CHORI Bar Team Meet some of the CHORI bar team: Dr. Bruce Ames, Dr. Joyce McCann, and Dr. Mark Shigenaga. On this podcast we talk about the different types of HDL and LDL cholesterol and what they do in the body. We discuss a low-calorie, micronutrient- and fiber-dense nutrition bar (referred to as the CHORI bar) that Bruce and I briefly touched on in a previous conversation, how each of the components of the bar from the vitamins and minerals to the fiber and polyphenols are all really important but have separate functions in the body that can work together in much the same way an orchestra play their individual parts to create a symphony that is larger than their individual roles, how the chori bar raised a certain type of HDL in lead adults in just two weeks, how eating the CHORI bar raised HDL, lowered triglycerides and small LDL particles, and improved insulin sensitivity after eight weeks in overweight/obese individuals all without them changing their diet.   The CHORI bar is not available for consumers yet but you can keep up with choribar updates on bruceames.org/choribar. Join over 300,000 people and get the latest distilled information straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

Hello, fine ladies and gentlemen. I'm super excited about today's podcast because I speak with Dr. Bruce Ames, Dr. Joyce McCann, and Dr. Mark Shigganaga about so many interesting topics. This is the first time that I interviewed three people at once and I was a little nervous about how it would turn out, but I must say this is a fantastic discussion about general health. There are so many nuggets of gold in this conversation because Bruce, Mark, and Joyce are all fabulous. scientists that contribute a unique perspective. We talk about so many different things, including the different types of HDL and LDL cholesterol and what they do in the body. We discuss a low calorie micronutrient and fiber-dense nutrition bar referred to as the Corey Bar that Bruce and I

briefly touched on in a previous conversation. We discuss how each of the components of the bar from the vitamins and the minerals to the fiber and polyphenols are all really important but have separate functions in the body that can work together in much the same way that an orchestra play their individual parts to create a symphony that is larger than the individual roles themselves. We discuss how the cori bar raised HDL in lean adults in just two weeks, how eating the cori bar raised HDL, lowered triglycerides and small LDL particles, and improved insulin. sensitivity after eight weeks in overweight obese individuals, all without them changing their diet. We discuss so much more that if I tried to summarize it all, it would take another hour.

Please keep in mind that the Corey Bar is not available for consumers yet, but you can keep up with the Corey Bar updates on Bruce Ames.org. That's Bruce Ames.org, forward slash Corey Bar. But before we get started, I want to take a moment to remind you guys of just two quick items. If you're not on my email newsletter, you're missing out on a golden opportunity to have sweet, sweet health, nutrition, fitness, science, and other lifestyle information transported straight to your brain via your eyeballs. I send out awesomely comprehensive articles approximately once a week. These emails are usually the perfect companions to these podcasts. I'm not ashamed to say that I really outdo myself on these emails. So go to my website at foundmyfitness.com right now and

sign up for my newsletter. The second thing I want to bring up is that this episode of the Found My Fitness podcast is brought to you by super awesome people, probably much like yourself. Over 500 people have now pledged to support my podcasting related efforts via patreon.com. Do you like this podcast? You can show it by pledging anywhere from $1 to $20 or more. Whatever you like. Learn more about that on my website or skip the nonsense and head right over to the support page at Patreon, p-a-t-r-e-o-n.com slash found-my-fitness. And now on to the podcast. Dr. Montepatrick here. Today I have the extreme pleasure of sitting with my mentors, my colleagues, and my friends. Dr. Bruce Ames is a senior scientist at Children's Hospital, Oakland Research Center,

and he's the director of the Nutrition and Metabolism Group. Dr. Joyce McCann is a staff scientist and the co-director of the Ames and Nutrition Metabolism Group, and Dr. Mark Shiginaga, is a scientist at Corey and is also an expert on gut health. Today we're going to be talking about an ongoing project that Bruce, Mark, and Joyce have been working on over the past several years involving a low-calorie micronutrient and fiber-dense nutrient bar, also referred to as the Corey Bar. So I was thinking maybe we could start by talking a little bit about how the idea of the Corey Bar came to be what precipitated this idea to make a low-calorie micronutrient fiber-dense bar.

Well, why don't I... I was interested in vitamins and minerals. There are about 15 minerals that you need in your diet, and about 15, they're the essential minerals, and about 15 vitamins. So there are about 30 substances, you have to get the right amount of in your diet to work your metabolism because what these compounds mostly do is they're co-factors for enzymes enzymes of proteins that do all the work in the body to do your metabolism and if you don't have zinc you inactivate 2,000 enzymes or enzymes with same fingers and they're P53 which is mutating half of human tumors anyway each

one of these vitamins and minerals is a component of many proteins, and so maybe a quarter of your metabolism, not exact numbers, a little fuzzy, but will be inactivated if you don't have them. And in a way, our definition of a vitamin is if you don't, you need it in your diet to help your metabolism. And if you don't give it to a rat, it dies, then it's a vitamin. It's somewhat different people who give you different definitions. And my field was DNA damage, what's causing it, and how do you prevent it?

And DNA damage leads to cancer, as you all know. And I saw, I had a scientist Jim McGregor come to my lab, and he had just published a paper showing that when a mouse doesn't get enough folic acid, which is one of the vitamins, all the chromosomes get broken, just like radiation. I thought that was pretty interesting. And then he showed the same thing as true in people. And when he looked at the level of folic acid, if you're below that, you're breaking chromosomes, it was 10% of the U.S. population and half of the poor.

So that sort of, I said, wow, that's really important. I'm going to work on vitamins and minerals. And so I became all enthusiastic about vitamins and minerals, and I thought the poor tend to eat terrible diets. They're just mostly empty calories, and we should figure out how to get vitamins into the poor. And Mark here is an expert on the gut, And he was telling me how important all the different kinds of fiber were.

And we were chatting and sort of got interested in how do you get these into the port? He'll tell you about fiber in a minute. And clearly, he can't put all this fiber in the pill. And a drink didn't work very well either. So we decided we'd have to put it in a bar. and the local USDA had made a fruit bar, and so we knocked on the door and said, could you add some vitamins to the bar? Could you add some fiber to the bar? And food has all these polyphenols, which Mark will tell you about. And anyway, we stumbled into this, stumbled into this project,

and we were stumbling along, and then Joyce came along, and she's, terrifically organized and pretty soon she was running the project so she'll give you the history of it all. And the people at the USDA, we collaborated with Tara McHugh and Donald's and were very good and we've had fun collaborating with him for 12 years now. So Bruce, how did you decide on what vitamins and minerals to add to the bar and what amounts to Well, that depends on how much you need. We weren't trying to, people get some of them in their diet. We weren't trying to put big doses in. We were just trying to get people up to the normal level. So we started off, you need two bars a day because of all that fiber. And so we started off just trying to get to the RDA of the official amount. Yeah, let me just add.

So basically the default in the bar is that each bar has roughly a quarter of the RDA. So if you eat two bars a day, you're only getting half the RDA. And we actually had a lot of internal debates about this while we were developing the bar. And the idea is nothing in the bar is there at levels that are over what's normally present in a diet. diet. So that includes vitamins and minerals who are actually there at lower amounts, many of them that are in a vitamin pill, but there are deviations from that default. So depending on like vitamin D we have more, vitamin C we have more. So it's not exact, but that was the default that we finally agreed to after multiple meetings and intense discussions and disagreements.

The point of such a great balance and not to... overwhelm the body and we know that excess of various nutrients can actually lead to adverse outcomes and so that was one of the very important variables that we're trying to control. Yeah and I think the underlying thing that Bruce maybe was going to say in a minute by maybe not is that what we ended up realizing is what we were doing was filling gaps in bad diets. We were just filling gaps. We weren't putting anything in addition to what would be in a good diet. And so that's really what the bar is all about, is filling gaps and underneath that is this idea that if you do that, you're going to improve metabolism.

Even if you do that on top of a diet that isn't well balanced, it has too many carbs or too much fat. And so that the fact that the bar actually worked when we did that was actually a big surprise to us, I must say, when we did our first experiments. The conventional wisdom is obesity is just too many calories in and too little exercise out. But there are a whole series of papers showing the obese are eating the worst diet in the country if you define worse as ratio of essential minerals and vitamins to calories. They're just eating empty calories. And so we thought it's important. So they're fouling up all their metabolism,

and how much damage that's doing. We all suspect it's a lot of the damage. Obesity is linked to every possible disease in age. Cancer, brain decay, immune system being shot, heart disease, you name it. If it's been tested, it's accelerated than the obese. And it seems reasonable that a lot of this is due to their fouling up the metabolism by not getting the vitamins and minerals and not getting the fiber, which again, Mark will talk about.

So the fiber is interesting. How did you choose what types of fiber to add to the bar, and why is that important for gut health? Well, we chose two basic types of fibers. In soluble fiber, which has been known to promote laxation or movement of the gut. So essentially what you want to do in healthy gut metabolism is to ensure that nutrients flow through the gut get absorbed and the waste get passed through in a timely manner. So that's what insoluble fiber helps in. The other part of the fiber equation is to include soluble fiber.

And what soluble fiber does is it provides a viscous barrier between the food that you're ingesting and its absorption through the gut wall. The other thing that soluble fiber does is it gets metabolized by gut bacteria and the metabolites of which are actually feeding the gut wall. The feeding of the gut wall is very important because not only doesn't make it stronger,

but it also provides it. provides the nutrients to power the immune system that sits right behind or within the gut barrier. So by providing those types of nutrients, you're actually boosting the metabolic and the immunologic fitness of the GI tract, all of which is really important for overall health. Mark keeps on telling us that the more bacteria in the gut than cells in your body, And the gut barrier function that keeps the bacteria from getting into the body is really important. And it needs constant energy. Exactly.

And if you disrupt that, then you get bacteria or bacteria outsides getting into the body, and you're really in trouble. You're invaded, and the body goes crazy, deepening. So one of the ideas that prompted us, the thing, about what should go into the Gloria bar is based on this very simple premise that you want to keep the gut barrier as strong as possible and you want to resist the ability for the food to cause what's called gut leakiness or leaky gut or small intestinal formability because if that happens then you have either flex of food antigens that can promote allergy or pieces

a bacteria that could provoke an immunologic response or inflammation. And we know, we've known for the last few decades, that chronic inflammation is what's causing or provoking a lot of the metabolic problems that associate with things like weight gain, insulin resistance, diabetes. And so if you can avoid that by strengthening the gut, then you can prevent all the these secondary consequences of this invasion. So the parts of the quarry bar are essentially informed by what's known by biochemists, things that power the mitochondria.

And if you can power the mitochondria, then you can make sufficient ATP to maintain the integrity of the GI tract. The mitochondria are the power plants in the cell that are making ATP, which is the chemical energy. that powers your muscle, your brain, and all your uphill, the towels. So the bar is actually quite complex. It has vitamins and minerals in it. It has several kinds of fiber. It has omega-3 fatty acid. It has fruit with fruit polyphenolics, et cetera.

And it also has small molecules that Mark has added to benefit gut health. So it's very complex, yet it doesn't weigh much. It's only 30 grams. There's no added sugar. And it's very low calorie. It's about 125, 130 calories. And a major hurdle for us with this bar was in making it edible. So the early bars, the first trial we did had four people in it.

I was one of them. I think you were one of them. Teresa, maybe. Anyway, four people. And we were the only people that were willing to eat the bar twice a day for two weeks. because it tasted so awful. And at the end of that trial, we saw this big rise in HDL that was statistically significant with only four people.

And we were so surprised, but we were buoyed for the future. So we really dug in them and started this collaboration with the USDA to try to make the bar edible. And they did a fabulous job over it, but it took a number of years to do that. So now the bar, here it is, actually tastes pretty good. And there's different flavors as well? There are different flavors we've used, depending on the trials. We've done, this is a cinnamon sugar.

We have a sweet and sour flavor for a trial that we did in obese adolescent asthmatics kids. We made up a number of other flavors. We had white chocolate, blueberry, we had cinnamon, we had a series so that they didn't have to eat the same flavored bar all the time. Because a major hurdle is, of course, getting people to eat the bar for long enough to do a meaningful trial, particularly if they're adolescents. And some of these people that we did work with are maybe not used to being compliant, following rules, etc. So compliance is a major issue in carrying off these trials. I think there's obviously a lot of science we're going to dive into in a minute here

because this nutrient bar, this Corey bar, has two peer-reviewed studies that have been done involving it, which is quite exceptional. If you think about it, there are so many different bars on the market. There are bars that are protein, high in protein, those that claim to add vitamins and minerals, claims to add fiber. But I don't know if I've ever seen a bar with omega-3 fatty acids on the market, and you guys definitely overcame some challenges

getting DHA into the bar. No, there are now. Yeah, there are now. Okay. So they're very easily oxidized, and you have to be really careful, and there are traces of minerals in the bar, and you put iron together with an omega-3 fatty acid,

you get oxidation. And so we had to solve all those problems along the way. Yeah. And, you know, so having one bar with all of these components together with the fiber and the micronutrients, the vitamins and minerals, polyphenols, the omega-3 is so, it's just, it's something that you, I haven't seen anywhere. And the fact that you now have science showing that this bar is improving a variety of different metabolic factors, which I think we can get into. And most of the bars on the market, not all of them, but most of them are basically candy bars disguised as health bars. You know, if you actually look at what's in them and what the calories are, and they might focus on one thing, you know, omega-3 or high-protein or energy.

But this bar is unique because it really is trying to fill holes in, in, you know, the typical Western diet, which has a lot of holes. And so I think it's far more complex than anything on the market. Do you think people that would benefit the most from eating a bar like this would be people that are obese, people that eat a bad diet, or perhaps even people in developing countries that have severe micronutrient deficiencies? Well, that's a complicated question because we actually see improvements in lean people who think they're eating great diets. So let's talk about that. So that's the first publication, peer-reviewed publication.

But on the other end, let me just add to that, on the other end of people, say, in third-world countries who are, you know, really starving, this may not be the bar for them. Because this isn't a high-protein bar. It's not aimed at malnutrition. But it's perfect for our Western societies and increasingly in Asia and Europe where there's too much people are eating far. too many carbs, you know, they have diets that are low in vitamins and minerals, low in fiber, et cetera, et cetera, and where there's a lot of obesity, the bar is perfect for that. That makes sense. So it's really for people that are eating terrible diets, not for people that are malnourished. Yeah, or even people, it's very hard to eat a perfect diet.

It's, in fact, there's some publications on this. There are vitamin and mineral deficiencies in diets that people are eating that they think are really good. You think wealthy Americans would be eating a wonderful diet, but they're not because it's a lot of work. Carbohydrates are very tasty. You eat a cake and you're getting all that carbohydrate or you're drinking coke or whatever, but you need a very balanced diet to get all your 30 different vitamins and minerals. And when you're low in one, it turns out you're affecting your meal.

metabolism. So, and the body rations, if you start getting a little low on a vitamin or mineral, Joyce showed in two beautiful reviews looking at vitamin K and selenium. It's built into metabolism that you do a rationing, the minute you get a little low. And how do you want to ration it? Well, those proteins that are essential, that need that vitamin, that are essential for survival and reproduction, they get it first. And the ones that are protecting you against some long-term damage, DNA damage or calcification of the arteries, those get starved because you're trading long-term health for short-term health.

So the body has figured out humans have been migrating over the whole earth and every time you move the diet changes. and the soil, some soils are red, they have a lot of iron, some soils don't have much iron. Selenium is a required nutrient, and if you get too little selenium, it poisons you. But if you get too much selenium, it poisons you, and the patches of too much and too little all over Europe and in China. So one has to get the right amount of each of these to keep your metabolism going. So the body responds by doing this rationing, training, trading long-term health for short-term health. I call it triage.

And you and I talked about that previously in another podcast people can listen to. Ronda has a podcast on that. So I want to kind of get back to this idea of people that are, I think they're eating a healthy diet, it still can benefit from having more of these micronutrients and fiber and polyphenols and that's found in the bar because that's very interesting. Most people wouldn't think that. And there was a study that you guys all published together a few years ago in 2012 that was done in lean people.

And so maybe we can talk a little bit about what those results were. Well, the primary effect, these weren't all lean people. were, it was a range, but they were mostly at the lower end. So they were also tended to be adults, middle-aged people, so they weren't kids. And the primary result that we found in that was a strong rise in HDL. And particularly, Mark might want to talk about the particles. Do you want to talk about the HDL 2B and why it's so significant that the rise that we saw was almost exclusively with a particle called HDL 2B.

So HDL is usually described by the physician as a level of cholesterol that the HDL particle is carrying at any given time. But then you can take the HDL particle and you can break it down into a range of sizes with a larger size of HDL particle being a healthier type and what that the larger particle of HDL reflects a very important function of HDL, and that is this thing called reverse cholesterol transport. So when reverse cholesterol transport

is occurring, that is, when the HDL particles taking cholesterol back from the periphery to the liver, which is a healthy function. In fact, if I can just interrupt for one second, And just so people really understand what that means, you know, these, these big HDL particles are taking cholesterol from the periphery, meaning even cholesterol plaques that have been on the artery and removing them and bringing them to the liver. So there's two basic types of lipoprotein particles. There are those that contain this thing called APOB that's on LDL, VLDL and chylmicrons. And the function of that type of bee-containing apilipotene is to deliver lipids to sites that need it,

whether it's for growth or whether it's for repair. And when the vasgature is being, I guess, affected by chronic injury due to either high blood pressure or chronic inflammation, it needs these building materials to be delivered from the liver. or from the circulation. But when all the repair is done, then you can take that cholesterol that's been deposited in the vasaturn, you can remove it. And if the net effect is removal is better than deposit, then your arteries never have atherosclerotic plaques.

But if you're depositing it faster than you're removing it, then you accumulate lipids in your blood vessel, and that leads to anthosclerosis. So the point being, there are these range of H.D.L. particle sizes. If they're large, it means that reverse cholesterol transport is occurring. When there's inflammation that is driving cardiovascular disease, that reverse cholesterol cholesterol transport is not occurring, and the HDL particle remains small in general. And so what the Corey Bar does is it takes.

takes the profile and it shifts it towards the larger particle. And that informs us that what the quarry bar is doing, it's helping to improve the activity of that HDL particles. It's making it function better. And I think the other corollary to this is these are in lean people who are what I call adults. Right. middle-aged, to me that's an adult.

Can you define lean for people? Well, there's a measure called body mass index, BMI, and lean is typically is supposed to be anything less than the BMI of 25. And you guys measure waste circumference as well, right? And we also measure waist circumference. But the point I want to make is that we've just completed another study where we don't observe an increase in HDL in what I call teeny boppers, people who are under 30. And we did a whole trial in young people that we've never looked at. We've never looked at that age group before.

And we don't see the same increase that we see in people who are a little older. And so it's as though what's happening, and maybe Mark can comment on this, but is that when you're really young, you don't need any reverse cholesterol transport, but as you get older, even if you take care of yourself and eat a great diet and exercise and so on, inevitably there's some accumulation that requires this, and the bar works very robustly in lean people who are middle-aged in that over 30 and up group but doesn't appear to work so well in the really young, which is we've just observed actually in the last couple of months. That's very interesting.

And so you think possibly that could be due to the fact that as you do get older, you do accumulate more of these. It's a guess. Yeah, it's a guess. One of the things that we know about youth is that you're very resilient. and part of that resiliency has to do with the fact that you're still in the growing phase. So, for example, kids can tolerate high-sugar content foods without really showing the impact until they take in a little bit too much.

But they tend to tolerate it much better than adults and much better than middle-aged adults, for example. And that probably has a lot to do with the fact that growth hormone is very protective. So you can either use growth hormone for growth or you can use it for repairing injury. And so kids happen to be able to deal with. I didn't think about that before. That's true. Yeah, that's true. It's very interesting. Right.

Yeah. And so what about the effects of the Cori Bar in people that are not considered lean or people that are overweight or even obese? Well, this is the topic of our paper we just published. In fact, it just appeared in print yesterday, I think August 1st. Congratulations. And, well, there we see a different pattern, and it has a lot to do with inflammation. We see robust changes not only in HDL, but also improvements in LDL, improvements in insulin resistance, improvement.

in waist circumference, weight loss, improvements in blood pressure, heart rate, provided people don't have a higher level of this internal chronic inflammation. So we could see in the obese these two groups, the one group that was very sensitive to the bar, and they had low inflammation, the other group that was quite resistant to almost all of the effects

of the bar, and they had a higher level of this internal chronic inflammation that Mark is so. So the bar, inflammation means to your signaling system that you're invaded. And inflammation is your immune system combating this. And your diabetic cells pour out hypochlorite, which is chloroxide, which is chloroxin, hydrogen peroxide, and nitrogen oxides, all these nasty things to kill the invader. And it's a really serious business because that could kill you.

So when the body is inflamed, it means the alarm bells are ringing in your body, and it's paying attention to that and not paying attention to a lot of other things. So it makes it when Joyce and her colleagues found that we could really get the obese to lose weight if they're not inflamed. But if they're inflamed, it blunts everything. And, but it makes sort of physiological sense why that's true. And the bar will affect inflammation, but we have to maybe tune it up to be good at as an anti-inflammatory bar, too. Well, it did begin to decrease inflammation, but the trial is only two months long.

So it's possible that if we kept going, it would eventually have, have reduced inflammation enough so we could see the other changes. But we don't know because we haven't done that yet. But if we could get it to move earlier, then that would be enormously helpful because those are the people that most need the bar, the people with these higher levels of chronic inflammation. Right. Oh, and one thing, so the obese are eating these awful diets, but Joyce and these clinical

trials, nobody's telling the obese to change the diet. We're just saying, take two bars a day on top. So if all the fiber in there is a little satiating and makes you feel less hungry, maybe they're eating a little less where Joyce is trying to determine a lot now. But it's people have tried to change the diet of the poor and the obese for years with very very, very, little success. And this is another approach to see if we fill in all the important substances that are lacking, will that help? And it does seem to really help a lot. Yeah, I think the other aspect of that is that if it can help move people sort of off the dime, then it may give them the incentive to actually make real changes in their diet.

And we did see some of this when we did do an eight-week trial in sort of inner city obese parents and children a couple of years ago where they ate the bar for two months, twice a day. And they were eating very poor diets. They were all very obese. And they actually, many of them, it's anecdotal, but they started to actually feel better. And it seemed that as a result of that, they started to get cured. curious about diet, you know, that it can really make a difference. So I sometimes call it like a Nicorette bar, you know, if it can help people transition, that would be a really a wonderful thing.

Absolutely. What's, I'd like to go back a little bit to some of the specifics of how the bar affected these obese and people that weren't as inflamed and how it changed. Because you mentioned the lean people in the first study that was published, that it changed the HDL, so you see higher amounts of these bigger HDL particles, which is great. But in this second trial that was published, which were done in people that were overweight or obese and either really inflamed or not inflamed as much, it changed also the LDL lipid profile. So can you talk a little bit about that?

About how the bar changed the LDL lipid profile in people that were obese and overweight, but not too inflamed? Yes, so the quarry bar led to reductions in a certain quest of LDL particles without affecting. Okay, so LDL is like HDL, and there's a range of particle sizes. There are the large LDL particle sizes which reflect our neutral risks. They may be a certain benefit to them. And these particles become smaller. We think as they sit in the bloodstream a little bit longer. And then finally you have another class of very small dense

LDL particles that associate with increase cardiovascular roots. So it runs the gamut of small dense to large buoyant LDL. And what the quarry bar did was it did not affect the large buoyant particle. In fact, what it did, it led to a slight increase in those particle sizes, whereas it led to a drop in the small dense particle. So it improved the general profile and made the LDL cholesterol look healthier. And this is in contrast to statins, which tend to reduce all classes of LDL, whether it's productive in trying to train. transfer lipids from the liver to the periphery. Which, as you mentioned earlier, is very important.

You need LDL cholesterol to either repair damaged cells or for new growing cells. So being able to have the healthy type of LDL, in fact, seems beneficial. It's the small deaths. It probably is beneficial. What we don't want to do is we don't want to have the LDL particle sit in the bloodstream belong and there's this thing called the LDL receptor that gets down regulated when you're inflamed when you're inflamed so what that means is that the LDL particle stays in the bloodstream longer yeah and it stays in the bloodstream longer the lip the

enzymes that can break down the LDL and remove the lipids are still operating so that LDL particles which starts out big gets gets progressively smaller as these lipases that are used to extract lipids and move it to the peripheral tissues are operating. So you end up with something that's small and dense. And the small dense particles essentially are biomarking inflammation. So the LDL particle being small and dense means that there's inflammation going on. So the quarry bar is able to change this whole lipid profile. It's able to increase the good type of HDL.

It's able to decrease the bad type of LDL. It makes you a healthier metabolism. See, people kind of naively thought cholesterol is bad. You have to get rid of all our cholesterol. But cholesterol is an important player in your metabolism. If you didn't have any cholesterol, you'd die. So it's getting the right particles and getting everything tuned up for a healthy metabolism. Right.

Which leads me to the next question is any thoughts or insights on the mechanism by how this 4A bar is able to change the lipid profile in such a positive way? Sure. Or can you talk about that? Well, we can talk about it from a couple of angles. I mean, one is what in the bar is doing this? So there's a lot of different components in the bar, a lot of different vitamins and minerals, omega-3s, et cetera, et cetera, et cetera. So we've been doing a series of what we call deconstruction trials to try to figure out what's critical.

So we suspected it wasn't going to be a single ingredient. There's no magic bullet. The beauty of this bar is that there are multiple ingredients working together. That's what we suspected. but we didn't know. So we've done now a series of four, five deconstruction trials and what we now know, and we've targeted HDL in lean people for the reason that HDL and lean people goes up in only two weeks

and that means we could afford to do these trials. And lean people that are adults. That are adults, yes, that are not teeny bobperous, yes. And so what we've found now, and I don't think I want to say exactly what they are, but that we know that at least three and probably four different ingredients in the Corey Bar all have to be there in order to raise HDL. And this makes an incredibly important point about how important the diet is as opposed to these sort of magic bullet supplements that people take.

These are simply normal dietary amounts of critical ingredients that are missing from poor diets. And all we've done is put them back in and we get this dramatic change in metabolism. So it says a lot about how ingredients have to work together and complement each other in order to change metabolism. Do you think that has something to do with the way they're absorbed in the gut, for example? So if you think about taking a vitamin pill, how the gut sees that versus something in the bar with the fiber and the food matrix. Absolutely. So maybe can you explain that a little bit?

So whole food works in concert. Each component of whole food has a function that's like operating a factory where you need all the different pieces for manufacture of the product. You can't manufacture a product with one ingredient. same thing with human nutrition. You need bits and pieces of the whole food being placed in proper temporal sequence. So in relationship to the diet, coming in at the same time is actually a useful thing for a lot of these nutrients. Some of the nutrients are helping to power the engine and to facilitate the absorption of another ingredient. And if you know, that basic mechanic, then you can understand how whole food works.

And then you have other components that are impeding the absorption so that it doesn't come in too fast, the purpose of things like fiber. And Mark had this great analogy that I loved, and then Bruce came up with another one. Mark's was that if you have a complicated machine with a lot of joints and it's stuck, They're all rusted out. The machine can't move. If you come in and oil one joint, the machine's still not going to be able to move.

You have to oil all the joints. And then Bruce has another one. All these different analogies. I said if you're tuning up the orchestra, you don't want to not tune up the horns. You have to tune them all up. And your metabolism needs all these substances. mostly the vitamins and minerals are antioxidants or the co-enzymes that are making an enzyme work.

But some of them are hormones. Vitamin D is a steroid hormone, just like estrogen. And over a thousand genes have a signal on the gene that says that's where vitamin D and vitamin D receptor land and either turn on the gene or turn off the gene. It's all this complicated regulation and metabolism. And if you don't get your vitamin D, which is 70% of the country is officially deficient, you're fouling up thousands of genes. So it's important to get all this tuned up.

And nutrition is a pretty muddy field. And it's because it's so difficult. It's, you can't, you do epidemiology, and half the time they get the wrong answer. They say, did they establish some association? My epidemiologist joke is that study shows Miami a weird place. Everybody's born Hispanic and dies Jewish. So people can jump to the wrong conclusions if you don't understand the metabolism. We're mechanism, people.

We want to really understand what's going on. And what Joyce has shown with these deconstruction experiments is this is a fantastic tool in nutrition. You can say the Mediterranean diet is wonderful, but why it's raising H.O. It's so complicated to figure it out, looking in people. But you can try doing experiments in rats and then extrapolating the people. But it's just muddy. And the nice thing about the bar is you can leave out the vitamin group. Does the bar still work to raise HDL in two weeks?

And then you can leave out the fiber group. Does the bar still? And Joyce has been doing these experiments, and it's complicated. There are more than one thing. And you can pin it down, and you couldn't do that in epidemiology in a Mediterranean diet. Yeah, I think the other thing, and Mark is very interested in mechanism, is by it with this technique where we have, can control what's going in and what's not going in, we can actually look at what's happening in the body mechanistically. I mean, what's the stream of events that leads to HDL going up? And how is that affected by not having an essential component in the bar?

And so we have some good leads about that, and so we're working on that. So what's on the horizon for the Corey Bar research is looking more at the mechanism as to how it raises HDL, or how it lowers the lower, smaller dense LDL particles, and also what nutrient components are important together. And moving the obese to a more instant-resistant state faster. So we're identifying new components that are not in the current version of the bar that in cell culture models. systems that were identifying those types of compounds that work really well together to improve the resiliency of those cells to environmental stresses like diet, dietary fat, for example.

So this is just the beginning. We're hoping to have a Corribar 2 and a Corribar 3 to tune up so the bar is good for old people. The bar is good for tamping down your inflammation. down your inflammation of the bar is good for this or that. And basically it's tuning up your metabolism. That's what it's all about. I think the other sort of angle that we've already done a little bit on is that the bar,

in theory, should be helpful in all the obesity-related conditions. And we've already done two trials in obese, adolescent asthmatics, with some very encouraging results that were just down. writing up. But you can just go down the list. I mean, this should be helpful in prediabetics preventing their transition to diabetes. It should be helpful possibly as an adjunct or instead of statins. You know, we'd love to do a trial, have this, have a Cori Bar arm in a statin trial. And so it's the power of food. And I don't think that's really fully appreciated by people. It's incredibly powerful. You don't necessarily need a drug. I mean, I'm sure sometimes you do.

Now, drugs have been useful, but now we're learning about nutrition. Preventive medicine is a different field. It's not finding a drug that'll cure that make you live longer. I mean, there may be some of that in the future, but I think the low-hanging fruit in getting us all to live long lives is in nutrition. It's just sorting out this horribly complicated field. I mean, I think one thing with drugs, people have to remember, the reason they work is they perturb something. Right. They interfere with a metabolic process where a balanced diet is simply making everything work better in a healthy way. So you wouldn't expect side effects, for example. Or long-term effects. Or long-term effects. But,

every drug. I mean, look at statins. I think 30% of people who take statins have some kind of side effect. Yeah, their muscle wasting is a big one. They target, you know, mitochondria and lead to muscle wasting. Also, because there's two different main ones on the market, one of them is able to get across the blood brain barrier and stops cholesterol synthesis in the brain, which can be a problem because you need cholesterol on your brain. And so, you know, there are definitely side effects, you know, to taking some of these drugs. And, of course, in some cases, you may save a person's life, so I'm not saying. Oh, course.

No, drugs have the use. We're not packing drugs. And pharmaceutical companies have been wonderful in coming up with all these. But prevention is a different field. I'm convinced in a decade we're beginning to be sticking our finger in a machine and on the finger prick of blood, you can measure 1,500 different human plasma proteins. I mean, the analytical methods are getting fantastic, and it's going to be cheap, as we see from Theranos and other companies that are trying to disrupt the regular. So it's, and what we need to know is you'll see when your, the machine tells your eye, you're low in magnesium, it'll go to your iPhone, and you'll be controlling your diet.

to make, get more magnesium. Now, magnesium's in the center of the chlorophyll molecule, so nature's conveniently color-coded green for you. Magnesium isn't green, but chlorophyll is. And so you eat a big plate of kale or spinach, you're getting your magnesium. You can also get some from nuts. But your mom told you to eat your veggies.

To get a balanced diet with these 30 different vitamins and minerals, You really need to eat a very balanced diet, not just bagels and donuts. I mean, that's going to kill you. Well, I think the Corey Bar's results are so extremely exciting for multiple reasons. The fact that it can lower these small, dense LDL particles and raise HDL and in a comparable way to even statins without actually lowering total LDL cholesterol, which, as we mentioned, you actually need some LD cholesterol. I think that's fantastic. And also the fact that it's able to raise these large HDL particles in people, adults that

are already, you think they're eating a healthy diet and are not overweight or not obese, that's also very exciting because HDL is very, very important for preventing heart disease. And, you know, there was a study that was published not too long ago where scientists have made a synthetic version of HDL, where they've infused it. intravenously into people that had previously had a myocardial infarction. So they'd had a heart attack. And these people had terrible lipid profiles. They had small dense LDL particles. They had atherodes, scrotic plaques built up in their arteries. And so they infused this synthetic form of HDL and it literally stripped the plaques off the arteries and lowered, you know, this small

dense LDL by something crazy like 200%. You know, so that's quite striking. And quite telling about how important raising HDL is and this Corey Bar is so far seems to be very good at doing that at least in people that are adults or people that are not too terribly inflamed and you know I thought I remembered that after some of the inflammation was resolved in your most recent published study that there was some increase in HDL is that well in the obese unless I'm forgetting it already having moved on to other things but I don't think so because Because we saw, we did start to see a decline in inflammation in eight weeks, but not a lot. Enough to be significant, but not a lot.

But we did not see a lot of rise in HDL. I think we did see some in HDL2B. I have to go back and look. But by and large, I think you're right, actually, now that I think about. I think we did start to see it at eight weeks. That's right. It was very delayed. Yes.

And at eight weeks we did see some decline and inflammation. It was a particle size. It was the particle size. It was a particle size. You're right. You read that paper very closely. Good for you. Yeah, it did start to go up, but it was a big lag compared to the group that was not highly inflamed.

It's also very promising. The mitochondrial machinery is not working on a lot of the insulin. There's just an obese, and that's pretty well known. So you're calling the inflame. the insulin resistant obese or were they insulin resistant? These are insulin resistant ovies. So there's a there's so... Well the lower inflamed obese were also insulin resistant. Okay, yeah. So it didn't crack just within...

Right, well, insulin resistance. Right. So insulin resistance is associated with a shift of metabolism that shifts away from what they call fatty acid oxidation by the mitochondria. And what that does, the net effect of having lower ability to burn fat is that it's hard to lose weight. That's one thing. But the other thing that's associated with poor burning of fat is that things tend, your blood lipids tend to go up or associate with increased blood lipids like triglycerides and cholesterol. Is part of the reason why the insulin-resistant obese people don't oxidize fat, does that have to do with the inflammation inhibiting the transport of fatty acids into the mitochondria? Yes. Via the connoissement transfer is.

No, Mark is also an expert on mitochondria, and mitochondria are making all your energy. And so right now, his research is mainly to tune up mitochondria. How do you get mitochondria optimized? In the gut. In the gut. Because the gut is very long and it's very important. The idea is actually relatively simple. If the thing that is triggering the inflammation is in the gut lumen, what you want to do is

you want to prevent it from getting inside the body. If you prevent it from getting inside the body, then you prevent the inflammation that associates with that. penetration. But you also, I think most importantly to a lot of people, is you prevent the triggering of an endocrine program that leads to fat deposition around the belly. And I think that's really important to a lot of people. Because we know that this fat that sits around the belly is the biomarker of risk. It itself is not the problem, but it's a response. So what in the endocrine system is aberrant.

Well, part of the protection of the body to this type of invasion is that the insulin goes up. That's one of them. And insulin is part of the program that enables the fat cell to start pulling in more glucose so that it can store glucose in the form of fat. So you can build fat much easier around that area that's exposed. to the stuff that should be kept in the gut loom, and these are like gut bacteria in their cell wall components.

So. So I think that in all, this is very exciting, the Corey Bar research, everything that you've done up into this point and what's on the horizon in terms of all the new stuff you want to figure out. And I think if people want to learn more, first of all, I know that most listeners, one thing they're going to ask is where can I buy a Corey Bar? We'd like to commercialize it. Right. So if the people want to learn more about the updates on the Corey Bar, I'd like to tell them they can visit Bruce Ames.org or it slash Cori Bar.

That has information on the Cori Bar and hopefully will be updated with any new leads and what's going on with the Corey Bar in terms of... We feel as scientists, not only do we want to understand things, but we're going to. We want to help getting it out to the public, and this is something that's going to do that. And so we like some big company to start selling Corey bars. Yeah, we're talking to a number of companies. But the bar is kind of its own niche, so it's not going to fit on the grocery shelves, along with all those other bars. It's more complex.

It'll probably be a little more expensive. You know, it's different than what's out there now. But we're working on it. And 10 years and 15 clinical trial, we haven't quite agreed on how many clinical trials we've done. It's a few or only on a few people, and some of us count them and some of us don't. So we need Joyce to tell us, do we use 15 or do we need 18 anyway? But we've had a lot of clinical trials. Yeah.

Yeah, I think let me just say one thing. too, that the reason this has worked over a dozen years is that Bruce created this environment where we have a group of scientists who are each doing their independent work, but who are working together as a group. I mean, this is truly a group effort, and there should be other people here too. I mean, we've had Michelle Mehta Snyder, she's a pediatric cardiologist led this program in the beginning. She's now co-directing the briefings. program at Children's National Hospital in Washington. Ash Lal, who's here and MD, is directing all of our trials. He's been here from the beginning. Jungsa is an expert in

metabolism. So all of us have literally worked together for like a dozen years on this. And that's the reason it's worked because we have complementary skills. And so no one's in competition and we were able to bring all of these together productive. And I think it's been a great journey. Nutrition is a horribly complicated subject. And physicians have sort of abdicated. They're not taught any nutrition. They know much nutrition.

And the public is vitally interested in it. And I think it's wildly important. But you need multidisciplinary groups to tackle it. So we come up from the mechanism point of view. So we look at things in a little different way. And you've done a few. fantastic job. So the Corey Bar publications are really, really excellent. And so thank you all for joining us today. I really think that this was a fabulous conversation. And I hope to learn

more about the Corey Bar. I know people will be interested in learning more about the Corey Bar on bruceaims.org or slash Corey Bar.