FoundMyFitness - #004 Bruce Ames on Triage Theory, Longevity Vitamins & Micronutrients

Episode Date: February 12, 2015

Dr. Bruce Ames In this podcast, Dr. Rhonda Patrick interviews her mentor, Dr. Bruce Ames, about his triage theory and other nutrition topics. Dr. Ames was the 23rd most-cited scientist between 1973 and 1984, which is evidence of his long and productive career investigating human health and disease. Dr. Ames continues his research expanding our knowledge of nutrients such as vitamin D and its role in Autism spectrum disorder. In this episode, we discuss... (00:00) Introduction (04:18) Dr. Ames discovers vitamin deficiency-induced DNA damage (10:35) Triage theory explains nutrient rationing  (14:37) Nutrient deficiencies cause insidious damage and accelerate aging (25:25) Expanding the list of essential vitamins (e.g., lutein & zeaxanthin)  (31:05) A Western diet pattern is mostly empty calories (36:46) Challenges running randomized double-blind clinical trials in nutrition (38:12) Nutrition is not the focus of our current healthcare system (42:15) Dr. Ames' philosophy about healthy and delicious foods If you're interested in learning more, you can read the full show notes here. Join over 300,000 people and get the latest distilled information on triage theory, longevity & micronutrients 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

Dr. Ronda 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'll 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 scientist's, 23rd most top cited scientists across all different fields from 1973 to 1984. Bruce, 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 at Meritus 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 Mutagenity test, which, for those of you who do not know what that is, it's a very simple and cheap test that uses bacteria to test whether or not chemical compounds can be a mutagen, 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, that was used in children's pajamas also were butogenic and thus could be a carcinogen. So we have the Ames test in Bruce to think for our children's pajamas not having carcinogens in them.

More recently, Bruce has gotten into nutrition and he has 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 berry berry 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? 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. I never paid too much attention, but I got a little bit interested because of oxidation and antioxidants. And then a fellow named Jim McGregor 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 McGregor came to my lamb, he had done this gorgeous experiment with a person. And he had found that when he was feeding mice, he was treating mice with radiation and looking at various things that affected that. And one day all his control mice were full of chromosome breaks.

He said, what's going on? And he tracked it down to the company that sold them 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. I would have to 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 were all seen trivia to me. And so... Can you explain? I know, you know why I, folic acid deficiency can cause double strand of breaks, which is like being irradiated.

But can you explain to... Well, 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 the work, some work. And one pathway that folic acid is involved with is putting one carbon. 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 uricil is an RNA, and the cell has tagged the base pairing is the same, but the cell is 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 uricil, that can come from a deamination of the cygocene, so it gets taken out of the DNA.

It shouldn't be in DNA. 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 folds apart. And people think radiation works in the same way.

Because 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 understood how it was working, and one of my students and one of Phenic 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 of 15 years, I seem to change my field. And so the last 10 of 15 years, I've been in nutrition, and it's a wonderfully muddy field. It's just, I love being in a field like that, and there's not a lot of competition of people who have my kind of background in nutrition. Anyway, I think I've made a few contributions. So one of the things we found is I looked in 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 of a vitamin is that the mice die or people die or get scurvy or berry or some horrible disease. But

When I asked about DNA damage, lots of deficiencies caused 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 were the literature, some studies we did. And one day, it hit me. And I got, this theory came into my head. It's just what nature wants. Because through all of the 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 2,000 enzymes that have zinc fingers or otherwise need zinc. zinc and magnesiums and 500 enzymes or so. Every DNA repair enzyme has magnesium in it,

and calcium is in your, 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 the soils with very little iron, The selenium, too much selenium is a poison and too little seed linoin 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 they're poisoned by too much selenium. but there are also areas where they don't get enough so many. 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, don't have enough selenium or vitamin K or magnesium or whatever. What's nature going to do? Well, it's going to put it into those proteins that say

the 25 selenium proteins or 16 vitamin K dependent proteins. It's going to put it into those proteins that are essential for survival is what nature wants to do is survive and reproduce. That's strong selection. And living to 90, nature really doesn't care about your 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 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 is doing is trading long-term health for short-term health. And it wants short-term survival. And it made perfect sense, and evolutionary biologists discussed 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 McKen 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 want to do? Go to it. She's a really smart cookie. And she said, well, I'll research.

a couple of one vitamin and one mineral that have been well studied and see this triage idea that this erasioning 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 a system for rationing so that, for example, in vitamin K, the clotting proteins get it first, And only after they're satisfied do you do 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 or your heart slowly goes out or your DNA gets sick. damage and you get cancer. And so she showed it's true for both of these systems. And I think it's going to be true for all the vitamins and minerals. I mean, I agree with you. It makes perfect sense that, you know, that the vitamins and minerals that you're getting, of course your body is going to 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, there is, at the consequence of these vitamins and minerals that are required for proteins that are needed to maintain long-term functions. And so, you know, with vitamin K, I think that's a beautiful example, how the blood clotting works. Yeah, you can understand why blood clotting. Right. 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 and the protein, and it stops, it makes a clot, and you don't bleed to that. Yeah, I think 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, vitamin K2. And, you know, like you mentioned, vitamin K1 is, you know, found in plant, so phyloquinone, and, you know, this type of vitamin 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 clottings, 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, than more 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? But vitamin K2, which is found in, you know, fermented, you know, foods like natto. 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 people, the epidemiology shows that people who eat natto, it's a bacterial fermented soybean, a besuddlest 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 arthroscopic plaque. And so we sort of understand how it's working. People who take kumidin 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 of the arteries at a much higher rate, and they get bone fractures at a much higher rate. So all this fits together. Anyway, Joyce McKeon. You know, I saw a paper on the fact that people that were taking warfarin, if they also took manichinone, 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 blood clotting process and that it negated some of the negative effect. Oh, okay. That might make sense. So the really good, we, Dr. McCann in my group did a beautiful review. We didn't do any experimental work on this. It was all theoretical. But it was it, I thought it was a beautiful review. And she showed that bone fractures is 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 the 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. If you don't have, and if you don't have your vitamin K, K, you don't make that protein. And similarly, matrix glob 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, cummidin, tend to get both bone fractures and calcification of the artery. So this explains all sorts of medical things we didn't understand before. So anyway, I call this idea triage, because on the battlefield, it's a French word. The docks used to divide the people up into three groups. Those who were wounded so badly that he couldn't do anything about it, and they go to one side. And those who are going to 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 have called it BIGE, not triage, but anyway, I use that word. And 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? Yeah. And how we define them what they are and are they, are we getting enough of these vitamins and minerals to prevent the long-term consequences, right? 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 the teeth would fall out. It was a horrible disease. 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 lymies or Brits were called lymies. Anyway, people, over the years, people figured out there were these vitamins that were necessary for our metabolism. And Barry Berry 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 analysis turned out to be involved with long-term things, not short-term. And calcification of 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 your brain decay or heart disease.

And as humans, we're interested in that. We want to live a long lifespan. I'm 86 and I'm still running a big lab and I work Saturday afternoons. I don't want to kick off if I can help it, but I have an Italian wife who feeds me a wonderful diet. She kept on nagging me. I should get more exercise. And one day I said, when I feed like exercise, I run my experiments,

I skip controls and I jump to conclusion. So I like that joke so much. I must have told it 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. So the RDA, you're saying, is set on preventing acute deficiencies.

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. 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. Yeah. 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. Right. But it's all based on short-term. For vitamin D, they based it on a short-term effect, which is calcium. So. So the question is, then, how do we know if we're going to? getting enough vitamin K, if we're getting enough of the vitamin A, vitamin D, vitamin B vitamins, how do we know we're getting enough of these to prevent the long-term diseases of aging?

Well, we don't really, but the committees usually put in a safety factor. And so, but it could be too much or too. So I want to make things, what you want to 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.

There are 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 macular of the eye, there's a yellow spot that has two carotenoids in them, lutein and ziazanthi, which nobody called vitamins, but there are natures putting them in the macular 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 oranges have all these conjugated double bonds. and if you have light and the dye, you can, the energy of that light gets transmitted to oxygen and you can make something called 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 a cell, because it starts destroying all your structure. And what plants use in their own, out in the light all the time in strong light. What they do is they have these carotenoids which dissipate that extra energy of cinglet oxygen as heat in this double bond chain and detoxify it. And people have worked all that out. So, and in the macular of the eye, that yellow color absorbs blue light, which is the most toxic form of light. So it keeps your

eye from oxidizing in the key part of your eye. Well, so 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. Do these committees determine RDAs only based on things that can kill you, or do they determine, like, for example, luting in ziazantin, if they're, they're most certainly preventing, you know, age-related macular degeneration. Yeah. So,

you know, is it just because it's a long-term, it's something that happens later in life? Well, practically no attention has been paid to that kind of thing. And we don't, the definition of a vitamin is you don't give it to a mouse and it dies. Sort of. So it is basically

based on survival. It's a very short-term stuff. Wow. I want to say there should be these longevity vitamins that are, maybe in antioxidant like some of these carotenoids or other things that are giving you a long lifespan. Right. So the other question, I guess, would be then, can we as scientists devise certain biomarkers then that we can measure as right now as a biomarker of something that is a disease of aging? 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 are going to be another couple of dozen that are helping us live a long lifespan. Those compounds, we want to know how much we should be getting from our diet. Most of it's nutritional. And in the future, all this is going to come within 10 years, I think. You put your finger in a machine, and already there's a company in Boulder that can measure 1,500 proteins in a finger prick of blood. And so we're going to 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 we said, Ronda's trying to prove experimentally right now, but nobody's proven it yet, that what you do in the assured of magnesium, because of triage, you eliminate one of the DNA repair enzymes and put the magnesium in some more essential protein. Yeah, well, you need magnesium to make and utilize ATP. That would be an essential function. 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. It's the vulnerable protein when you start getting low. But you don't want to get low to the point of disease. You want to 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 worse as ratio of calories to essential micronutrients. They're just eating empty calories. You need to eat your greens to get vitamin K and magnesiums 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 six bases, three-based spacer, and then another six 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 have vitamin D deficient, you're in deep trouble.

And that has a lot to do with skin color because a dark skin prevents you getting UVB radiation. That's the burning rays of the sun. And, you know, you can get burnt if you get too much sunshine all at once. And in the tropics, you need a lot of melanin in your skin to keep UVB radiation out. And you have racially completely different people. The Africans and the Southern Indians and people in New Guinea all have very dark skin, but they're not racially related. And the reason is they're living in the tropics where you need a dark skin to prevent getting fried by the sun.

If you put an Irishman in Australia, they're in deep trouble, and the solution is a hat and sunscreen. And if you put an African American in Chicago, they're in deep trouble because in a northern Latin. if you have a dark skin, you're in trouble. You're not making your vitamin D, and you need to do something about it. And so every dark, I tell all my Indian friends and my Hispanic friends and my African-American friends, hey, you better get your vitamin D tested because 90% of them are too low. Yeah, 70% of the U.S. population, you know, is...

Yeah, we're playing video games and watching TV, and we're not out in the side. time. Right. And we're in our car rather than walking. And then there's the 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, like, 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 mill. And It takes 1,000 IUs a day to raise blood levels by five points, right, five nanograms per milliliter. So if you're very deficient, you're still not going to 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 it. We don't have rickets anymore.

But we do have rickets. 80 patients at Children's Hospital, where I work, came in with, the kids came in with rickets. They don't get straight bones. Well, rickets have 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, had a little vitamin D in it. So it's one we haven't eliminated rickets, though for a long time, doctors never saw a case of rickets. But you don't want to just look at rickets. You want to 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. 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're not doing anything, but they're doing harm. That was an awful. Brandon, I agree that was a horrible paper, an appalling paper. Because, see, the docs are all used to randomize 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 want to test it on that 10%? Otherwise, you'll never see anything, because you're diluting it with a 90% who has enough. So you have to measure it. And then, as Rhonda pointed out, 600, if you use the RDA for vitamin D,

you're not going to 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. Well, so you mentioned that nutrition is a muddy field. And I think this is part of it where we have, we really have to rethink the way scientists are designing clinical trials. You know, it's not the same thing as a pharmacological drug. And how do we do that?

how do we get other scientists and MDs and epidemiologists to understand the importance of doing this trial correctly? You know, that's because it's important. Well, one is medicine is sort of abdicated. Docs, most docs, physicians know nothing about nutrition. They don't get any training in medical school, maybe an hour or two lecture. And nutrition is going to be the thing that's doing, bad nutrition is what's doing us in. You can just see that people aren't getting the 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 Ronda figured 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 going to involve different people. It's going to involve people who know some nutrition and can figure out mechanism. And the analytical methods are coming fast, so you'll be able to put your finger in a machine. It will send the results to your iPhone and say, hey, you're short of vitamin K. nature's 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 so it cuts out the docks.

It will make it more individual medicine. Plus, if you have a genetic, 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 want to 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 going to come over the next 10 years if we can get people to rethink things, which we're trying to do.

Right. I know I was recently looking at my multivitamin, and I saw that it 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, sequestered cinglet oxygen well, but, you know, you've got these people now that can't convert beta-carotene and 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 and blood, measuring proteins that are biomarkers for, you know, cancer or neurodigener of diseases that also respond to vitamins and minerals are also very important. And, you know, definitely is 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 good insurance? Well, I have an Italian wife, and she feeds me a wonderful Mediterranean diet. We eat lots of fish and veggies, and I love Italians cook veggies in wonderful ways, the little olive oil and garlic. 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 a wonderful, 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 don't think there's any, I'm not out in the sun both for a genetic reason and other, 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 Polyin Institute has a terrific website that discusses micronutrients, and you can get advice on the web. but I think of multivitamin minerals, good insurance.