Bruce Ames on Triage Theory, Longevity Vitamins & Micronutrients
Posted on February 12th 2015 (over 4 years)
In this video Dr. Rhonda Patrick interviews Dr. Bruce Ames about his triage theory, which he proposes that the body has developed a rationing response to shortages of micronutrients (vitamins and minerals) throughout evolution. When cells run out of a vitamin or mineral, that scarce micronutrient is allotted to proteins (in the body) essential for short-term survival. Proteins needed for long-term health, including those that protect DNA, lose out and become disabled and lead to diseases of aging. In addition they discuss how RDAs are chosen and what Bruce calls “longevity vitamins” which he calls a class of nutrients that exist mostly to prevent degenerative diseases of aging in addition to essential vitamins and minerals."The obese are eating the worst diet in the country if you define worse as ratio of calories to essential micronutrients. They're just eating empty calories." - Dr. Bruce Ames Click To Tweet
Rhonda: Dr. Rhonda Patrick here. Today I'm sitting here with my friend and my mentor, Dr. Bruce Ames. Bruce has had an enormous influence over my research, and as you hear him speak today, that will become quite evident. Bruce has had an amazingly prolific scientific career. He's published over 550 papers, naming him the title as the 23rd most top-cited scientist across all different fields from 1973 to 1984. Most recently, Bruce and I have co-authored two papers together, one that was published last February on the role vitamin D plays in serotonin production and how this relates to autism. And the second paper which was just recently accepted for publication is on vitamin D and the marine omega-3 fatty acids, EPA and DHA, and what role they play in ADHD, bipolar disorder, schizophrenia, and impulsive behavior.
Bruce is a Professor Emeritus at University of California in Berkeley, and he is now the Director of the Nutrition and Metabolism Center at Children's Hospital Oakland Research Institute, where I have the pleasure of working with him every day. Bruce is the inventor of the Ames Mutagenicity test, which for those of you that don't know what that is, it's a very simple and cheap test that uses bacteria to test whether or not chemical compounds can be immunogen, which means that they contain things that can damage DNA and cause a mutation, and thus can be a carcinogen, which can cause cancer.
It's Bruce's Ames test that identified that one of the main components in permanent hair dyes back in the 1970s contained a chemical in it that was mutagenic, and thus a potential carcinogen. And he published a paper on that, sent it to all the hair dye companies, and told them they had to do something about this, and eventually, they pulled the compound out of their permanent hair dyes. In addition, the Ames test also identified that the main chemical in flame retardants that was used in children's pajamas also were mutagenic and thus, could be a carcinogen. So we have the Ames test and Bruce to thank for our children's pajamas not having carcinogens in them.
More recently, Bruce has gotten into nutrition, and he is come up with something that he calls "the triage theory," which I would like to talk about today. And I'll let Bruce elaborate on what the triage theory is, but the underlying principle is that just because we are walking around today without acute deficiencies, like acute symptoms of deficiencies like scurvy or beriberi, doesn't mean that there aren't some long-term consequences to not getting enough vitamins and minerals. So, Bruce, why don't we start there? Why don't you tell us about the epiphany that led you into nutrition and, ultimately, to come up with the triage theory.
Bruce: I seem to change my field every 10 years or so, and I love getting into new fields because I read very widely, and usually can make some contribution. Anyway, nutrition just seemed horribly complicated, and I never paid too much attention, but I got a little bit interested because of oxidation and antioxidants. And then a fellow named Jim MacGregor came to my lab on sabbatical. He's a cytogeneticist, and he was studying what happens when mice get irradiated. You break chromosomes. And that's the most dangerous aspect of radiation. And right before MacGregor came to my lab, he had done this gorgeous experiment with a person. He had found that when he was feeding mice...he was treating mice with radiation and looking at the various things that affected that. And one day, all of his control mice were full of chromosome breaks. He said, "What's going on?"
And he tracked it down. So the company that sold him the vitamin mix had by mistake left folic acid out of the vitamin mix. And so he did a dose response in folic acid, and the less folic acid the mice got, the more chromosome breaks. At some point, with no folic acid, they'll all just die, but there was always a trace around. And so folic acid deficiency does the same thing as radiation. Everybody's worried about Fukushima and radiation coming from Japan, which was incredibly tiny amounts, and meanwhile they're eating these bad diets that do the same thing. So after McGregor showed that folic acid deficiency broke human chromosomes and broke mouse chromosomes, I got a bit of an epiphany. I said, "Gee, half the poor are at that level of folic acid. How would I get into nutrition? Maybe other vitamin and mineral deficiencies do that." And this is huge compared to little bits of pesticide or something in your water. Those all seemed trivial to me. And so...
Rhonda: Can you explain...you know, I know why folic acid deficiency can cause double-stranded breaks, which is like being irradiated. But can you explain to...
Bruce: We showed, in fact, the mechanism. Folic acid delivers one-carbon groups. Vitamins, most of them, are co-enzymes for some enzyme in metabolism that's doing some work. And one pathway that folic acid is involved with is putting one-carbon units into DNA and into RNA. So it's involved with nucleic acid synthesis. And therefore, if you don't have enough, you cause problems in nucleic acid synthesis. And so some students in my lab showed that the reason that folic acid deficiency causes problems is you don't put a methyl group on thymine.
Now thymine is in DNA, and uracil is in RNA, and the cell has tagged the base pairings the same, but the cell has tagged what's DNA and what's RNA. And if you don't do that, the repair enzymes cruising along the DNA all the time looking for trouble, if they see a uracil that can come from a deamination of the cytosine, so it gets taken out of the DNA. It shouldn't be in DNA. And you make a transient nick in the DNA. So you break one of the two strands, but the other strand is holding it together. But if you have two nearby lesions, one on one strand and one on the other, the chromosome falls apart. And people think radiation works in the same way because if you get a cluster of electrons in radiation, and you damage both strands near each other. And that's a rare event, but when it happens and you then repair both of them out at the same time, the oxidative damage, you get a chromosome break. And so that's the most dangerous part of radiation.
So, anyway, it all made mechanistic sense. We've understood how it was working, and one of my students and one of Fenech's students compared radiation to folate deficiency. So it was a pretty solid case that it worked in both mice and in people. So when I realized that half the poor were at a level of folic acid where they were breaking their chromosomes, and the poor tend to eat the worst diet. In fact, so I said, "I ought to get into nutrition." And I love getting into new fields because I read broadly in science and often can make a contribution to a new field. So I've been doing that. Every 10 or 15 years, I seem to change my field. And so the last 10 or 15 years, I've been in nutrition, and it's a wonderfully muddy field. I love being in a field like that, and there's not a lot of competition, people who have my kind of background in nutrition. Anyway, I think I'd made a few contributions.
So one of the things we found is, I looked into literature, put in the...Google is wonderful. Now you put in the 30 vitamins and minerals. You need 30 different substances to run your metabolism. They're co-factors for enzymes mostly, and if you don't get any one, you die. But the criteria for calling something a vitamin is that the mice die or people die or get scurvy or beriberi or some horrible disease. But when I asked about DNA damage, lots of deficiencies cause that. And I kept on wondering, "Why is nature doing that? Why is it breaking your chromosomes or damaging your DNA when you don't get enough?"
And some of the literature, some of the studies we did. And one day, it hit me, and this theory came into my head. It's just what nature wants because through all of evolution, animals have been running out of vitamins and minerals. You need 30 different ones, and there are about 15 minerals, and you're getting them from the soil. The plants take them up out of the soil. You need magnesium. You need calcium. You need iron. You need zinc. Anyway, there are all these that are involved in metabolism. Zinc is in 2000 enzymes that have zinc fingers or otherwise need zinc. And magnesium's in 500 enzymes or so. Every DNA repair enzyme has magnesium in it. And it's also in the bones, and calcium. So we need these substances.
Anyway, what I postulated is, since the minerals aren't spread evenly through the world, the red soils with a lot of iron, and in the soils with very little iron. The selenium, too much selenium is a poison, and too little selenium is a poison. This selenium is necessary for 25 enzymes or so, as a co-factor. And so in Europe, the patches of too much selenium and too little selenium. In China, there's a disease called Keshan syndrome, where people get heart disease and other bad things. This is the poison by too much selenium, but there are also areas where they don't get enough selenium.
So each one of these vitamins has been studied very extensively. And so what I postulated, just as an idea that came to my head, is that when you get a little low on any vitamin or mineral, it's in nature's benefit to ration it. And so the way it rations it, where would you expect if you don't have an enough selenium or vitamin K or magnesium or whatever? What's nature gonna do? Well, it's gonna put it into those proteins that say they have 25 selenium proteins or 16 vitamin K-dependent proteins. It's gonna put it into those proteins that are essential for survival because what nature wants you to do is survive and reproduce. That's strong selection.
And living to 90, nature really doesn't care about you. You're past your reproductive age anyway. So there's not much selection for that. So the enzymes that are keeping you having a long lifespan, and those are the enzymes like DNA repair enzymes, that DNA damage is insidious and it accumulates through your lifespan and increases your risk of getting cancer all the time. Or one of the vitamin K enzymes is blood clotting. And if you cut yourself and you didn't have blood clotting, you'd just bleed to death. And that happens often enough that it's an essential protein where one of the vitamin K proteins prevents calcification of the arteries. They're all calcium-binding proteins, vitamin K proteins.
And if you don't have that protein, you slowly accumulate atherosclerotic plaques, calcification of the arteries. And that will eventually lead to heart disease, but it takes 10 years or so. So basically what nature's doing is trading long-term health for short-term health. And it wants short-term survival. And it made perfect sense, and evolutionary biologists discuss that concept in other ways, not in the biochemistry. So, anyway, I wrote a theoretical paper saying, "Hey, this is an interesting theory and has a lot of implication for human nutrition."
And then later, Joyce McCann in my lab, she came into my office one day and said, "I'm a little skeptical of your triage theory. I think there's a better way to attack it." I said, "Joyce, what do you wanna do? Go to it." She's a really smart cookie. And she said, "Well, I'll research one vitamin and one mineral that has been well-studied, and see is this triage idea that there's a rationing really built in?" I called it triage. And I said, "Terrific, Joyce. Go to it." So she turned out two beautiful reviews, one on vitamin K and one on selenium. And they both have the system for rationing so that, for example, in vitamin K, the clotting proteins get it first, and only after they're satisfied do you prevent calcification of the arteries or prevent cancer or prevent bone fractures. All these things are proteins that help in these things, but it's all insidious damage that you get that's a long-term consequence. In fact, we call those "the disease of aging." Your brain slowly goes out, and your heart slowly goes out, or your DNA gets damaged, and you get cancer. And so she showed it's true for both of these systems, and I think it's gonna be true for all the vitamins and minerals.
Rhonda: I mean, I agree with you. It makes perfect sense, you know, that the vitamins and minerals that you're getting, of course, your body's gonna find a way to make sure that you can maintain short-term survival so you can reproduce and pass on your genes, but, you know, the consequence of these vitamins and minerals that are required for proteins that are needed to maintain long-term function. So, you know, with vitamin K, I think that's a beautiful example of how the blood clotting works.
Bruce: Yeah, you can understand why blood clotting. Some Dane named Dam got the Nobel Prize for figuring out that there's something in greens that is essential for blood clotting. And what it is is a compound used in photosynthesis in plants, so anything green has it. And it's a co-factor for an enzyme that adds an extra acid group to glutamic acid, which already has one acid group. So you have two acid groups sticking out, and you can bind calcium. So all the 16 vitamin K-dependent proteins are calcium-binding proteins. And blood clotting is some network of calcium in the protein, and it makes a clot in your blood, and you don't bleed to death.
Rhonda: Yeah, I think the vitamin K is a good one to talk about because I think, you know, there's two biologically active forms of vitamin K, vitamin K1 and vitamin K2. And, you know, like you mentioned, vitamin K1 is, you know, found in plants. So phylloquinone, and, you know, this type of vitamin K, K1, is lipophilic. And so it goes directly to the liver, and that's where it activates all these proteins that are involved in blood clotting, that they're in the liver. But, you know, and if you get enough of that, you know, K1 to activate those proteins in the liver, then more of it can stay around in the circulation, where it can then activate these other proteins that are important for pulling calcium out of the bloodstream to prevent calcification of the arteries, take it to the bones where it's supposed to go, right?
Rhonda: Like vitamin K2, which is found in, you know, fermented, you know, foods like natto...
Bruce: Yeah, the Japanese have a health food called natto, and most Westerners think it looks a little yucky, and it tastes a little yucky, and it smells a little yucky. But the Japanese love it because they consider it a health food. And the epidemiology shows that people who eat natto...it's a bacterial-fermented soybean, B. subtilis-fermented soybean, and the people who eat that get less heart disease, and they get less bone fractures. Well, one of the proteins that's vitamin K-dependent is something called matrix Gla-protein, and the function of that is to bind calcium phosphate crystals, which form very easily in the blood and is the beginning of an atherosclerotic plaque, and prevent it causing an atherosclerotic plaque.
And so we sort of understand how it's working. People who take Coumadin or it's also called warfarin, it's an anti-clotting protein so you don't get thrombosis, 30 million people take that. Well, they get calcification in the arteries at a much higher rate, and they get bone fractures at a much higher rate. So all this fits together. Anyway, Joyce McCann...
Rhonda: Yeah, I saw a paper on the fact that people that were taking warfarin, if they also took menaquinone, which is vitamin K2 from natto, a natural source, that because vitamin K2 does not go to the liver to activate blood-clotting proteins, it's not the lipophilic, it stays around in the circulation, they could take it. It doesn't interfere with the blood clotting process, and that it negated some of the negative...or, you know, so it negated some negative effects.
Bruce: Okay, that might make sense. Dr. McCann and my group did a beautiful review. We didn't do any experimental work on this. It was all theoretical. But I always said, I thought it was a beautiful review. And she showed that bone fractures, there's a protein called osteocalcin, and if you knock out that protein in mice so they can't make it, then you test the mice and their bones break much more easily. So you need that protein to make a strong bone. It's located in the bone. It's moving calcium around in the bone, and it helps make a strong bone. And if you don't have your vitamin K, you don't have make that protein. And so, and similarly matrix Gla-protein. If you don't have enough vitamin K, you don't make that protein. You get calcification of the arteries. And people taking warfarin, Coumadin tend to get both bone fractures and calcification of the arteries.
So this explains all sorts of medical things we didn't understand before. So, anyway, I called this idea "triage" because on the battlefield, it's a French word. The docs used to divide the people up into three groups, those who are wounded so badly that they couldn't do anything about it, and they go to one side, and those are gonna get better anyway, whether they treat them or not, and then those where it pays to treat them because you can make a difference. Well, somebody said I should call that biage, not triage. But anyway, I used that word, and...
Rhonda: So, Bruce, the question is, you know, the RDAs, can you explain, like, how an RDA is set? What an RDA is, a DRI, and an EAR?
Bruce: Yeah. Okay.
Rhonda: And how we define them, what they are, and are we getting enough of these vitamins and minerals to prevent the long-term consequences, right?
Bruce: Well, all of nutrition is basically short-term. That is, you're looking for some disease, scurvy. A third of British sailors on these long trips would die, and their teeth would fall out. It was a horrible disease.
Bruce: It was something called scurvy. And then they found that if they picked up a load of limes in the Caribbean, and the sailors munched the limes, they didn't get any scurvy. And so that's why British sailors were called Limies, or Brits were called Limies. Anyway, people over the years, people figured out there were these vitamins that were necessary for our metabolism. And beriberi was another one. And over the years, we've discovered these 15 vitamins and 15 essential minerals, but it's all based on some disease that shows up, or people die.
And in fact, I'm writing a review now saying, "Hey, we should rethink vitamins because half the proteins in Dr. McCann's analyses turned out to be involved with long-term things, not short-term. And calcification of the arteries or DNA damage or other things that were more long-term. And those are what we call the disease of aging, this insidious damage that eventually gives you brain decay or heart disease. And, as humans, we are interested in that. We wanna live a long lifespan. I'm 86, and I'm still running a big lab, and I work Saturday afternoons. I don't wanna kick off if I can help it. But I have an Italian wife who feeds me a wonderful diet, and she kept on nagging that I should get more exercise. And one day I said, "When I feel like I exercise, I run my experiments, I skip controls, and I jump to conclusions." So I like that joke so much, I must have told that 50 times. And she said, "I've heard enough of that joke. I'm getting you a personal trainer." So now I go and work out twice a week. Anyway...
Rhonda: So the RDA, you're saying, is set on preventing acute deficiencies.
Bruce: Yeah. So the two numbers that the committees come up with, one is the EAR, estimated average requirement, and that's some distribution in the population of the vitamin or the mineral. And the other is the RDA, which is set at two standard deviations above that. That's for the population. So if you're below the EAR, that's the definition of you're not getting enough. And it's not a pretty picture because Americans are eating all these empty calories.
Rhonda: Right. Wait. So let me interrupt. So the EAR is actually set two standard deviations lower than the RDA, and people still aren't even meeting that? So, and that's what, you know, National Health Statistics, they use the EAR to determine whether or not populations are getting enough of certain vitamins and minerals.
Bruce: Right. But it's all based on short-term. For vitamin D, they based it on a short-term effect, which is calcium. So...
Rhonda: So the question is, then, how do we know if we're getting enough vitamin K, if we're getting enough, you know, of the vitamin A, vitamin D, B vitamins? You know, how do we know we're getting enough of these to prevent the long-term diseases of aging, right?
Bruce: Well, we don't really. But the committees usually put in a safety factor. But it could be too much or too little. So what you wanna know is does it shorten your life? And you could do that in mice, and do those kinds of questions. But those are expensive to do, and nobody's been really doing them. Anyway, I'm writing a theoretical paper why there are lots of things out there that we probably should be calling vitamins that are more long-term things. I'll give you just one example.
The two carotenoids are these orange pigments in every plant. The reason they turn orange in the fall in New England is because the chlorophyll goes away and you're left with this orange carotenoid. Beta-carotene is a good example. Now that also goes to vitamin A, but that's a different thing. So there's 600 carotenoids in nature, but humans have about 15 or 20 of them in the brain. And in the macula of the eye, there's a yellow spot that has two carotenoids in them, lutein and zeaxanthin, which nobody called vitamins, but nature's putting them in the macula of your eye, and if you don't get them, you get macular degeneration. The eye people have shown that.
So what do carotenoids do? Well, the reason they're orange is they have all these conjugated double bonds. And if you have light in the dye, the energy of that light gets transmitted to oxygen, and you can make something called the singlet oxygen, which is a very energetic form of oxygen that can oxidize things much better than just plain oxygen. So that's nasty in the cell because it starts destroying all your structure. And what plants use, and they're out in the light all the time, in strong light, what they do is they have these carotenoids which dissipate that extra energy of singlet oxygen as heat in this double bond chain, and detoxify it. And people have worked all that out. And in the macula of the eye, that yellow color absorbs blue light, which is the most toxic form of light. So it keeps your eyes from oxidizing in the key part of your eye. Well, some people sort of understand that. But shouldn't that be a vitamin? It's just a longevity vitamin. It's something that's helping your long-term health. And I think it should be.
Anyway, I'm writing a paper arguing all of that.
Rhonda: Do these committees determine RDAs only based on things that can kill you? Or do they determine...like for example, lutein and zeaxanthin, they're most certainly preventing, you know, age-related macular degeneration. So, you know, is it just because it's something that happens later in life that...
Bruce: Well, practically no attention has been paid to that kind of thing. And the definition of a vitamin is you don't give it to a mouse and it dies. Sort of...
Rhonda: So it is basically based on survival.
Bruce: ...it's a very short-term supplement. I wanna say there should be these longevity vitamins, maybe an antioxidant like some of these carotenoids or other things, that are giving you a long lifespan.
Rhonda: Right. So the other question I guess would be then, can we, as scientists, devise certain biomarkers then that we can measure, right now, you know, as a biomarker of something that is a disease of aging?
Bruce: Yeah. That's something we're thinking about all the time. I think the future is preventive medicine will have a lot to do with nutrition. Because these 30 micronutrients they're also called, the vitamins and the minerals, and I think there can be another couple or dozen that are helping us live a long lifespan, those compounds, we wanna know how much we should be getting from our diet. Most of it is nutritional. And in the future, all of this is gonna come within 10 years I think. You put your finger in a machine, and already there's a company in Boulder that can measure 1500 proteins in a finger prick of blood.
And so we're gonna find which is the vulnerable protein that indicates that you're magnesium-deficient, and that's half the country, and tell you, "Hey, you're magnesium-deficient." That's what Rhonda is trying to prove experimentally right now, but nobody's proven it yet, that what you do when you're short of magnesium, because of triage, you eliminate one of the DNA repair enzymes and put the magnesium in some more essential protein.
Rhonda: Yeah. Well, you need magnesium to make and utilize ATP. That would be the essential function.
Bruce: Yeah. So every DNA repair enzyme requires magnesium, and some of them may be the things that go first. Anyway, we're trying to determine what's the vulnerable protein when you start getting low. But you don't wanna get low to the point of disease. You wanna get low to prevent some insidious damage that leads to aging. So I think when you eat a bad diet, you're accelerating your aging in some way or another. And the obese are eating the worst diet in the country, if you define worst as ratio of calories to essential micronutrients. They're just eating empty calories. You need to eat your greens to get vitamin K and magnesium in the center of the chlorophyll molecule, and folic acid. All those you get from your greens. So you need to eat greens. And then you need to eat some nuts. You get some good things from nuts. And then you need to eat fish because you get the omega-3 fatty acids, which are critical for brain function. And Rhonda showed critical for disease, like autism and ADHD and impulsive behavior.
All your social hormones are controlled by vitamin D. You don't get enough...and vitamin D is a special one because that goes to a hormone. It's really more a hormone than a vitamin. But it's a steroid hormone, just like estrogen. And the nice thing about these steroid hormones is they bind to a receptor, which goes to the DNA and recognizes 12 bases in the DNA, the 6 bases, 3 base spacer, and then another 6 bases. And what that does is that's the telltale signature of estrogen or vitamin D hormone. So it's a steroid hormone, and it's controlling a thousand genes, lots of them in your brain. So if you're vitamin D deficient, you're in deep trouble.
Rhonda: Yeah. 70% of the U.S. population, you know, is not getting enough.
Bruce: Yeah. We're playing video games and watching TV, and we're not out in the sun, and we're in our car rather than walking.
Rhonda: And then there's a problem with physicians not knowing what...you know, the RDA right now for vitamin D is 600 IUs, of international units of vitamin D. That's what people are required to take, you know, orally as a supplement. But the question is, if you're very deficient, so deficiency is defined as 25-hydroxy vitamin D levels precursor to the hormone, less than 20 nanograms per mil. And it takes 1000 IUs a day to raise blood levels by 5 points, right? 5 nanograms per milliliter. So if you're very deficient, you're still not gonna raise yourself up to a sufficient level, which is considered 30 nanograms per mil or above. And I think that there's a lot of difficulty in terms of, like, what's in the scientific literature for people to figure out what is the optimal amount of vitamin D? How much do we actually need? And, you know, I think part of that problem is due to the fact that some of the things that you've been mentioning, and that is people are looking at these short-term consequences. Well, rickets, you know, bone homeostasis. And that's really what most people and most doctors are looking at when they're thinking about how to...
Bruce: We don't have rickets anymore. But we do have rickets. 80 patients at Children's Hospital where I work came, the kids came in with rickets. They don't get straight bones. Well, rickets had been eliminated. But they were all African-American women, who were nursing their babies, and they didn't have any vitamin D. If you used formula, it'd have a little vitamin D in it. So it's when we haven't eliminated rickets...though for a long time, doctors never saw a case of rickets. But you don't wanna just look at rickets. You wanna look at these long-term proteins that are helping you live longer. So, and that means changing people's thinking. And so you look at all of vitamins and minerals, just one after another, some appreciable percentage of the population is really deficient. And nobody seems to care.
Rhonda: Right. And then you get studies coming out, like the "Annals of Internal Medicine" publishing papers saying, "Enough is enough. You shouldn't even take your vitamin and mineral supplements because not only are they not doing anything, but they're doing harm." So...
Bruce: Rhonda and I agree that was a horrible paper, an appalling paper. Because, see, the docs are all used to randomized, double-blind clinical trials, which makes a lot of sense because if you test a drug in people nobody has it to start with, and you're treating the whole population. But applying it mindlessly, nutrition is stupid because if 90% of the population has enough of vitamin X and 10% are really deficient, you wanna test it on that 10%. Otherwise, you'll never see anything because you're diluting it with the 90% who has enough. So you have to measure it. And then as Rhonda pointed out, if you use the RDA for vitamin D, you're not gonna get somebody into the sufficient range. So what you need to do is measure it before and measure it afterwards. And that's not a big deal, but people who publish papers, who don't do that, just pollute the literature.
Rhonda: Well, so you mentioned that nutrition is a muddy field. And I think this is part of it where we really have to rethink the way scientists are designing clinical trials. You know, it's not, you know, the same thing as a pharmacological drug. And how do we do that? How do we get other, you know, scientists and MDs and epidemiologists to understand the importance of doing this trial correctly? You know, because it's important.
Bruce: Well, one is medicine has sort of abdicated. Most docs, physicians, know nothing about nutrition. They don't get any training in medical school. Maybe an hour or two lecture. And bad nutrition is what's doing us in. You can just see that people aren't getting their vitamins and minerals, and they're disabling all sorts of genetic pathways in the body, pathways of metabolism. So geneticists are busily isolating, working out genes that are involved with this, and genes that are involved with that. There are 400 genes involved with autism. But Rhonda figured it out which micronutrients are key in autism.
And that's the thing that we need to do because you can intervene there. You can give them to people and prevent it. So I think prevention is gonna involve different people. It's gonna involve people who know some nutrition and can figure out mechanism. And the analytical methods are coming fast, so you'd be able to put your finger in a machine, and it will send the results to your iPhone and say, "Hey, you're short of vitamin K. Nature has conveniently colored it green for you because it's in plants. And so eat something. Eat a plate of spinach or kale or whatever, a couple often, because you need to get your magnesium." And that cuts out the docs. It will make it more individual medicine. Plus, genetics is really important, too. So if you have a polymorphism, an alternate form of some gene, that means that you need more magnesium than the next fellow or more vitamin D than the next fellow, then you'll wanna know that. There are lots of genetic variability, and I think a lot of it's been selected for because of nutrition.
So we'll need to know both the genetics and what you're deficient in by analyzing vulnerable proteins that are long-term, not short-term. And that's all gonna come over the next 10 years, if we can get people to rethink things, which we're trying to do.
Rhonda: Right. I know I was recently looking at my multivitamin, and I saw that for vitamin A, which, as you mentioned, beta-carotene is a carotenoid that can be converted into vitamin A, that, you know, the vitamin A source was beta-carotene. And I thought, you know, well, a good percentage of the population has a gene polymorphism that doesn't allow them to convert beta carotene into retinol, into the vitamin A. And so now you have people possibly taking a multivitamin that, you know, they're getting beta carotene, which does good things, in addition, to...you know, it's an antioxidant and does, like you mentioned, sequester singlet oxygen well, but, you know, you've got these people now that can't convert beta carotene to vitamin A but they don't know it. So I think, you know, these analytical methods where we're looking at both our genes and also, you know, measuring vitamin and minerals in blood, measuring proteins that are biomarkers for, you know, cancer or neurodegenerative diseases that also respond to vitamins and minerals, are also very important and, you know, definitely something that, over the next few decades, will help us to prevent and live longer.
And one question I have, do you think that most people can get all their micronutrients from just their diet? Or do you think that supplementing is also a good choice?
Bruce: Well, I have an Italian wife, and she feeds me a wonderful Mediterranean diet. We eat lots of fish and veggies, and Italians cook veggies in wonderful ways, with a olive oil and garlic. And so I don't eat veggies with a meal, I feel deprived. But I think we all should try and eat a good diet, and it's actually wonderful to eat a good diet because you're eating all these different kinds of food, and they all taste good, and when you get used to it, you feel better. But I'm not out in the sun, both for a genetic reason and because I'm in the lab all the time, so I make sure to take a vitamin D pill. And I think supplements really serve a purpose. And not everybody you expect to be a biochemist knowing exactly how much of each vitamin and all of that to take. The Linus Pauling Institute has a terrific website that discusses micronutrients, and you can get advice on the web. But I think a multivitamin, mineral is a good insurance. And I take some fish oil just to be sure, and I take some vitamin D to be sure. And am I getting enough calcium and magnesium? I take a calcium-magnesium pill.
Metals. Mae West said too much of a good thing is wonderful, but she was thinking about sex not micronutrients, particularly for metals because calcium and magnesium are one above the other on the periodic table. Magnesium's here and calcium's here. And they're similar kind of molecules. And it's hard. So there are a lot of calcium-dependent proteins, and a lot of magnesium-dependent. Well, nature cares about the ratio. You can put in too much calcium and cause magnesium shortages, and vice versa. But we tend to be short of both of them. So I think we shouldn't sell calcium pills. We should sell calcium-magnesium pills.
And same thing, everybody says they're getting too much salt. That's sodium chloride. But partly, we're not getting enough potassium. Potassium comes from veggies and bananas and fruit and all these things, and you really wanna get enough potassium because the body cares about the sodium-potassium ratio. Anyway, that's...so you can get too much of a lot of things. So...
Rhonda: Do you take a B complex as well?
Bruce: Yeah, I do.
Rhonda: Because you published a paper about, some time ago in talking about how, with aging, you know, cellular membranes get stiffer, and how that may change the B vitamin.
Bruce: Yeah. No. As you get old...I'm 86, and still working full-time, and Saturday afternoons when Rhonda's interviewing me. But I hope I'll live to 90. But who knows? But I have some big ideas I'm trying to get out there before I kick off.
Rhonda: Well, your triage theory is certainly one that's made a huge impact in my life and my thinking, and I'm doing my best to try to get that out in the public. I think most people need to realize that, you know, just because they're not walking around with acute deficiencies doesn't mean they're getting enough of their micronutrients. So...
Bruce: Well, one problem is randomized double-blind clinical trials are hugely expensive. To get something through FDA, you have to spend a billion dollars. And nobody can afford that for nutrition. Nobody makes money out of nutrition. So it means that you might have a small clinical trial in some micronutrient, but you can't patent magnesium. You can't patent vitamin D. So that's the roadblock right now. And Rhonda and I and Rhonda's husband, Dan, have come up with a way to get around that block, but we need to get funding. But that's another matter.
Rhonda: Yeah. Well, thank you for joining us today, Bruce, and talking about the triage theory and some of the other important theories that you've come up with longevity vitamins, and I really appreciate all your work you've done.
Bruce: It's a pleasure.
Rhonda: I'm Dr. Rhonda Patrick, and I'll catch you next time.
Adenosine Triphosphate (ATP)
An energy-carrying molecule present in all cells. ATP fuels cellular processes, including biosynthetic reactions, motility, and cell division by transferring one or more of its phosphate groups to another molecule (a process called phosphorylation).
A molecule that inhibits oxidative damage to DNA, proteins, and lipids in cells. Oxidative damage plays a role in the aging process, cancer, and neurodegeneration. Many vitamins and plant-based compounds are antioxidants.
A disease characterized by the deposition of fatty plaques on the inner walls of arteries. Something is said to be atherogenic when it promotes the formation of fatty plaques in the arteries. Atherosclerosis causes coronary artery disease.
Organic pigments that are found mainly in the chloroplasts of plants and are responsible for absorbing light. Plants use carotenoids to create energy and protection from harmful UV rays and animals commonly use carotenoids as a precursor for vitamin A.
The process by which the body responds to stressors in order to regain homeostasis. This can be carried out by means of alteration in hypothalamic–pituitary–adrenal axis, the autonomic nervous system, cytokines, or a number of other systems.
A substance whose presence is essential for the activity of an enzyme. Many minerals and vitamins are cofactors for enzymes.
A major contributing factor to aging, cellular senescence, and the development of cancer. Byproducts of both mitochondrial energy production and immune activity are major sources of DNA damage. Additionally, environmental stressors can increase this base level of damage. DNA damage can be mitigated by cellular repair processes; however, the effectiveness of these processes may be influenced by the availability of dietary minerals, such as magnesium, and other dietary components, which are needed for proper function of repair enzymes.
A type of water-soluble B-vitamin, also called vitamin B9. Folate is critical in the metabolism of nucleic acid precursors and several amino acids, as well as in methylation reactions. Severe deficiency in folate can cause megaloblastic anemia, which causes fatigue, weakness, and shortness of breath. Certain genetic variations in folate metabolism, particularly those found in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene influences folate status. Inadequate folate status during early pregnancy increases the risk of certain birth defects called neural tube defects, or NTDs, such as spina bifida, anencephaly, and other similar conditions. Folate deficiency and elevated concentrations of homocysteine in the blood are associated with increased risk of cardiovascular disease. Low folate status and/or high homocysteine concentrations are associated with cognitive dysfunction in aging (from mild impairments to dementia). The synthetic form of folate is called folic acid. Sources of folate include most fruits and vegetables, especially green leafy vegetables.
A medical condition that may result in blurred or no vision in the center of the visual field. A combination of genetics and environmental factors that cause oxidative stress, such as smoking and obesity, play a role. Often referred to as “age-related macular degeneration.”
A diet pattern thought to confer health benefits found traditionally in Mediterranean countries, characterized especially by a high consumption of vegetables, olive oil, and a moderate consumption of protein.
A result of oxidative metabolism, which causes damage to DNA, lipids, proteins, mitochondria, and the cell. Oxidative stress occurs through the process of oxidative phosphorylation (the generation of energy) in mitochondria. It can also result from the generation of hypochlorite during immune activation.
A disease caused by a deficiency of vitamin C. Humans and certain other animals require vitamin C from the diet in order to synthesize collagen. Scruvy can cause spongy gums, bleeding from the mucous membranes, and eventually, loss of teeth and open suppurating wounds form impaired wound healing.
Theory proposed by Dr. Bruce Ames which proposes that when the body is deficient in a micronutrient it will allocate its scarce supply to enzymes necessary for short-term survival and reproduction at the cost of long-term survival enzymes. This may result in the acceleration of the aging process.
A finger like loop of peptides enclosing a bound zinc ion at one end, typically part of a larger protein molecule (in particular one regulating transcription).
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