[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 have 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 blood stream to prevent calcification of the arteries, take
it to the bones where it's supposed to go, right? [Bruce]: Yeah. [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. [Rhonda]: Rickets. [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. 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 burned 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 not they're 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 latitude, 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. And... [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 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.
