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Dr. Ames is a Senior Scientist at Children’s Hospital Oakland Research Institute, director of their Nutrition & Metabolism Center, and a Professor Emeritus of Biochemistry and Molecular Biology, at the University of California, Berkeley. Rhonda Patrick has a Ph.D. in biomedical science. Dr. Patrick is currently a postdoctoral fellow at Children’s Hospital Oakland Research Institute with Dr. Ames. Bruce Ames Sr Scientist at CHORI, and Prof Emeritus of Biochem and Molecular Bio, at UC Berkeley. Rhonda Patrick Ph.D. biomedical science, postdoc at CHORI in Dr. Ames lab. The effects of micronutrients on metabolism, inflammation, DNA damage, and aging.TranscriptSpeaker 1: Spectrum's next. Speaker 2: Mm mm mm Speaker 3: [inaudible].Speaker 1: Welcome to spectrum the science and technology show on k a l x [00:00:30] Berkeley, a biweekly 30 minute program bringing you interviews featuring bay area scientists and technologists as well as a calendar of local events and news [inaudible]. Speaker 4: Good afternoon. My name is Rick Karnofsky. I'm the host of today's show. This week on spectrum we present part one of a two part interview with our guests, Bruce Ames and Rhonda Patrick. Dr Ames is a senior scientist at Children's Hospital, [00:01:00] Oakland Research Institute, director of their nutrition and metabolism center and a professor Ameritas of biochemistry and molecular biology at UC Berkeley. Rhonda Patrick has a phd in biomedical science. Dr. Patrick is currently a postdoctoral fellow at Children's Hospital, Oakland Research Institute in Dr Ames. His lab, she currently conducts clinical trials looking at the effects of [00:01:30] micronutrients on metabolism, inflammation, DNA damage and aging. Here's Brad swift and interviewing doctors, aims and Patrick Bruce Speaker 5: Ames and Rhonda Patrick, welcome to spectrum. Thank you very much. Sue, can you help us understand the term micronutrient and briefly explain what they do? Sure. Speaker 6: About 40 substances you need in your diet and [00:02:00] you get it from eating a really well balanced style, get them more about eight or 10 of them are essential amino acids. So they're required for making your all your protein. And then there are about 30 vitamins and minerals, roughly 15 minerals in 15 five minutes. So you need the minerals, you need iron and zinc and calcium and magnesium and all these things, you know, and the vitamins [00:02:30] and minerals are coenzymes. So you have 20,000 genes in your body that make proteins, which are enzymes that do bio or Kimiko transformations. And some of them require coenzymes, maybe a quarter of them. So some require magnesium and they don't work unless there's a magnesium attached to the particular pace in the enzyme. And some of them require vitamin B six which is something called [00:03:00] paradoxal, goes through a coenzyme paradox of phosphate. Speaker 6: And that's an a few hundred and enzymes and they make your neurotransmitters and other things. And if you don't get any one of these 40 substances, you'd die. But how much we need is, I think there's a lot of guesswork in there and we have a new idea I can talk about later that shakes a lot up puppet. And so when your research, you're trying to measure these [00:03:30] micronutrients obviously, well people can measure them in various ways. Somebody can just measure in blood and say, ah, you have enough vitamin D or you don't have enough vitamin D. But some, for example, calcium and magnesium marine, your bones, but they're also used for all kinds of enzymes and if you get low, the tissue might get low, but you keep your plasma up because you're taking it out of the bone. So just measuring [00:04:00] plasma isn't useful in that case. Speaker 6: But anyway, there, uh, each one is a little different. Do you want to talk about the triage theory? Okay, I could talk to about that. Now. Some years ago we kept on finding when we had human cells in culture or mice, that when we left out various vitamins and minerals or didn't have enough, we got DNA damage. I'm an expert in DNA damage and we're interested in how [00:04:30] to prevent DNA damage. We sat leads to cancer and so I kept on wondering why is nature doing this when you're not getting enough of magnesium or iron or zinc, you getting DNA damage and then one day it hit me. I, that's just what nature wants to do. Through all of evolution, we'd been running out of vitamins and minerals. The minerals aren't spread evenly through the soil. The red soils with a lot of iron and the souls that have very little iron. Speaker 6: [00:05:00] Selenium is a required mineral, but there's soils with too much saline and we get poisoned. And then the areas where it, you don't have enough selenium so you get poisoned. So it's a little tricky. Back in 2006 I had this idea that nature must do a rationing when you start getting low on any vitamin or mineral, and how would you ration it? The proteins that are essential for survival get it first and the ones that are preventing [00:05:30] some insidious damage that shows up as cancer in 10 years or calcification in the arteries. That's the [inaudible] papers, those proteins lucid. And I call this triage ship. It's a French word for dividing up those wounded soldiers that the doctors can make a difference on. So anyway, I publish this with what data? That wasn't the literature, but it wasn't completely satisfactory. We didn't, hadn't really nailed it, but it was an idea. Speaker 6: And then Joyce McCain [00:06:00] in my lab wrote two beautiful reviews, one on selenium and one on vitaminK , and they both fit beautifully. And people who work in these fields had shown that the clotting factors get it first because you don't get your blood clotting and you cut yourself every week or two, you'd just bleed to death. But the price you pay is you don't make the protein that prevents calcification of the arteries so [00:06:30] people can die of calcification the arteries. But that takes 10 years. So when nature has to face keeping alive now so you can reproduce or you're getting calcification arteries in 10 years, it does this tradeoff. And also you don't have enough vitamin K. My ptosis doesn't work quite as accurately. So you'll lose the chromosome here or there and you get cancer in 10 years. But again, it's the trade off between short term survival and longterm health. Speaker 6: It all [00:07:00] makes perfect sense. It was a very plausible theory. That's why I came out with it. But it's true for vitaminK and the mechanism used in vitaminK is different than the mechanism and sleeping. So each system has developed a different mechanism for doing this racially. And so that changes our view of vitamins and minerals base. You're paying a price every time. You're a little low on one with them. So it's the disease of aging. So basically when you should have any vitamin or mineral, [00:07:30] it accelerates your aging in some way. You can accelerate some kind of insidious damage. And we're talking about huge numbers of people. 70% of the population is low in vitamin D and we're talking about magnesium, what we said the third 45% 45% these are big numbers and they're cheap boldly saying Speaker 7: [inaudible]Speaker 8: [00:08:00] you are listening to spectrum on a l x, Berkeley. Today's guests are Dr. Bruce Ames and Dr Rhonda Patrick Speaker 9: with the micronutrients and the activity of DNA, RNA. Talk about the effect there, the impact, is there more to talk about that? Absolutely. So there are many different micronutrients [00:08:30] that are required for functions in your body that involve DNA replication involved DNA repair, preventing DNA damage. Things are all very important because we're making 100 billion new cells every day to make a new cell, we have to replicate the entire genome of that cell to make the daughter cell. And that requires a whole holster of enzymes. So if you don't have enough magnesium for those DNA polymerase to work properly, when ends up happening is that their fidelity is [00:09:00] lessen, meaning they don't work as well and they're gonna likely make more errors in that DNA replication that they're performing. And if they can't repair that error, then when ends up happening is that you can get every rotation and depending on whether that mutation has any functional consequences, sort of random, but the more times as occurs, then the more chances you're having of getting a mutation that can, you know, something that's not good and can either cause cell death or it can also [00:09:30] be something that causes dysregulation of the way your genes are expressed. Speaker 9: So it's very important to make sure you have the right co factors such as magnesium for DNA replication, also in your mitochondria and your mitochondrial DNA. When you make new Mitochondria, this is called mitochondrial biogenesis. It's an important mechanism to boost the number of mitochondria per cell. And this can occur during things like exercise when your mitochondria also have their own genome and they have to replicate this genome. Well guess what? Those mitochondrial [00:10:00] DNA were preliminaries. This also require magnesium. And so if there's not enough magnesium around, you're not making your mitochondria as optimal as you could be in Mitochondria. Play an important role in every single process in your body, including, you know, neuronal function. So that's really important to make sure that your Mitochondria Hobby. Also, this is very relevant for things like aging. These micronutrients like vitamin D gets converted into a steroid hormone that regulates the expression of over a thousand genes in [00:10:30] your body and some of those genes are involved in DNA repair and also in preventing DNA damage. So these micronutrients are extremely important for a variety of different physiological properties that are going on in your body every single day. Things that you can't see when you look in the mirror, we're talking about something that's not an acute deficiency that's going to lead to a clinical symptom like scurvy. Speaker 6: We think bad nutrition is the main thing, accelerating all these degenerative diseases of aging and contributing to these huge medical costs and [00:11:00] all of that. And it's something you can do something about because they're all very cheap minerals that are cheap. So the sourcing of the minerals and vitamins, it's not crucial at this point you think? I don't think so. Yeah. Getting them is the the really the key factor think and I think to really reform people's diet, we're going to need the numbers and we're working to try and show that there's some vulnerable protein that goes first when you're short of McNeese. I [00:11:30] mean you should measure that and then you'll know you're not getting enough and all the consequences or you're disabling all your DNA repair fronts. I'm so whatever. Speaker 9: It is ideal to try and get as many of these micronutrients essential vitamins and minerals that you can from your diet. For example, I personally make a smoothie for breakfast every morning, which consists of Kale, spinach, Swiss carrots, tomato, avocado, berries, and I'm getting a broad spectrum of vegetables and fruits [00:12:00] just from that one smoothie. And I think in addition to these essential vitamins and minerals that we know are in these various plants and fruits, I think there's also a lot of micronutrients in there that we have yet to discover that also may be doing important things. However, it's extremely difficult for people to get all of these micronutrients from their diet. And I think in that instance, supplementation can help fill those nutritional gaps. And we've actually shown that Speaker 6: in general, people in nutrition don't like the idea of pills, but people [00:12:30] are learning about all this. But you shouldn't overdo it. Mae West said too much of a good thing is wonderful, but she was saying about sex, not micronutrients, and particularly for minerals in minerals, there's a sweet spot. Too much can hurt you into little canary, Speaker 5: and that's what you're hoping these next generation devices would help people understand where they are situated within, right? The class of vitamins and minerals. What are they up in? What are they down? Speaker 6: So this may be a decades [00:13:00] worth of science to do this, but we're trying to frame the ideas and say, look, this is where we're going. And it isn't drugs that are gonna help you. It's getting your diet tuned up, your metabolism [inaudible] Speaker 9: your doctor can look at a few different nutrients and vitamin D is one test that they do. But there's a couple of companies that are out there right now such as something called wellness effects. They're measuring a variety of different micronutrients in people's blood, including omega [00:13:30] three fatty acids, vitamin D, magnesium, potassium, calcium. So looking at all these different vitamins and minerals and people are quantifying. It's called the quantified self movement where people are getting their vitamins and minerals and essential fatty acids measured. They're making dietary changes. If they find out they're low in vitamin D or they're low in mega three or they have low magnesium, they're making dietary changes and then about three months later they go back and they'd quantify the levels again so they can physically measure and quantify this, this change that they're making in their diet. And I think really that's the direction [00:14:00] to go. Speaker 6: Yeah, and analytical methods of Guinea. So wonderful that you can do it on a finger prick of blood. I have two entrepreneurs, scientist friends. One of them has put a machine in every hospital in China and he measures couple of dozen proteins of medical importance and the Chinese are subsidizing this. They think it's going to save money. And another friend of mine from Boulder, first one is built routed. The second one is Larry Gold. And he developed [00:14:30] an alternative to monoclonal antibodies and he can measure 1500 different proteins in one fingerprint compliant. I mean, it's fantastic and he's working to get them all right now it's a discovery system, but we're going to discover what protein tells you. You're low in magnesium and what protein tells you you're low in vitaminK or protein tells you low in paradox and then it's all going to go to your iPhone and you'll get the diagnosis. Speaker 6: We'll cut out the doctors [00:15:00] because they don't know much about Olis anyway, and they're too expensive. So it's not drugs you need for all of this. It's tuning up limit tap of the drugs that youthful. I'm not saying that not and for some things that are absolutely essential, but this area of getting your metabolism tuned up, see, people are worried about a pot Papillion a pesticide and it's all irrelevant. We, we published a hundred papers on that in that era, just saying, look, it's all a distraction from the important thing and important thing [00:15:30] is all these bad diets where eating and obesity isn't just calories in, exercise out a beach. People are starving and what this starving for vitamins and minerals because they're eating sugar and carbohydrate and every possible disease of aging is accelerated and hippies and plus huge costs, years of expensive diabetes and heart disease and cancer, you name it, it's been linked to obesity. So I think it's a big [00:16:00] opportunity to tune people up. Speaker 8: Spectrum is a public affairs show on k a l x Berkeley [00:16:30] is this part one of a two part interview with Bruce Ames and Rhonda Patrick. Speaker 9: So Rhonda, the recent paper you published on vitamin D explain that. So vitamin D gets converted into a steroid hormone in your body and the steroid hormone can regulate this expression [00:17:00] of between 900 and a thousand different genes. And the way it does that is that there's a little telltale sequence in your gene and it's basically a six nucleotide sequence repeat that's separated by three nucleotides. And this nucleotide sequence itself can determine whether or not vitamin D will turn on a gene or turn off aging. And so vitamin D can do both of these where it turns on genes and turns off genes. Well, what we found is that there's two different genes that encode for Tryptophan hydroxylase, [00:17:30] which is the rate limiting enzyme that converts trip to fan into Serotonin. There's one that's in the brain called Tryptophan hydroxylase too, and there's one that's outside of the blood brain barrier in tissues like Mosley got also in your t cells and your Peniel gland and placenta tissue if you're woman, and this is called Tryptophan hydroxylase one and what we found is that both of these genes have what's called a vitamin D response element that tell a sequence I was telling you about. Speaker 9: However, they had [00:18:00] completely opposite vitamin D response elements. One, the one in your brain had an activation sequence turn on and the one in the gut had a repression sequence. The turnoff sequence, which suggested that vitamin D hormone was controlling the expression of these two different genes in opposite directions. Vitamin D's important to turn on Tryptophan hydroxylase and two and your brain so you can make serotonin and it's important to turn it off and your gut to blunt the production of Serotonin in your gut. Serotonin in your gut. Too Much of it causes GI inflammation. [00:18:30] This was a really cool finding because there was a recent paper where they found that autistic individuals, 90% of them had some abnormal tryptophan metabolism and they didn't really identify what it was, but sort of like an Aha moment where it was like trick to fan metabolism. Well, chuck did fan, you need to make Serotonin, and so I started doing some reading and sure enough, there's a whole literature connecting Serotonin to autism. Speaker 9: Serotonin is made in your brain. It's an important neurotransmitter, but during early, early brain development, [00:19:00] it is a brain morphogenic meaning it actually is a growth factor that guides the neuronal proliferation, the development, the migration of neurons to different regions in the brain. It plays an essential role in shaping the structure and the wiring of the early developing brain. And so not having enough serotonin in early, early brain development in Utero can lead to very aberrant brain morphological and functional consequences. You know, this was kind of like, wow, well what if you're not getting enough vitamin D during that critical [00:19:30] period, which is important to activate that gene that converts Tryptophan into Serotonin? Is it possible then that you wouldn't be making enough serotonin in that early brain and therefore you wouldn't have a normal brain development? Also, the Serotonin in the gut can cause a lot of GI inflammation and also quite a few autistics have high GI inflammation. Speaker 9: Also, they have high levels of Serotonin in their blood. There's something that we call the Serotonin anomaly where they've measured brain levels of Serotonin autistics from SMRI and have also measured blood levels [00:20:00] of Serotonin. And there was sort of this weird dichotomy where autistics had high levels of Serotonin in their blood, but they had low levels in their brain and so it was like, well, why is that? Why would they have high levels in their blood, the low levels in the brain and we think we found a mechanism why if you're low in vitamin D, your vitamin D won't be turning on the one in your brain and you won't be making enough Serotonin in your brain and it won't be repressing the one you've got and you'll be making too much and you've got this sort of a a really cool finding. We also in our paper discuss how estrogen can [00:20:30] activate Tryptofan hydroxylase to in the brain pretty much the same way vitamin D does also a steroid hormone and the sequences, the receptors bind to a somewhat similar under dug out of the literature that people showed. Estrogen can turn Speaker 6: on the Messenger RNA for the brain enzyme making serotonin in girls, but it's not doing it in boys, which explains why five times as many boys get autism as girls. [00:21:00] Anyway, she worked out all this mechanism. We kept on explaining one thing after another render would come in every week, hopping up and down. Look what I found and look what I found and I think she walks on water, but she did this wonderful scholarship, which is a good metaphor, but she used to be a surfing instructor when she was incentive. Speaker 9: It's pretty exciting. It was largely theoretical work where we did find a underlying mechanism to connect these dots. So we're hoping now that people in the field are going to continue on and look even deeper. Speaker 6: So [00:21:30] what we think we know is how to prevent autism. But what we are not sure of is whether you can give vitamin D to people who have autism and help some of the symptoms. Uh, biggest people need to do clinical trials on all of this and they haven't done them right. But now that we have the mechanism, you can do them right. The trouble is drug companies aren't going to make money with vitamin D and they know that. And so [00:22:00] they're trying to develop a new drug. But we're hoping that these biochemicals trip to fain and vitamin D and nowhere to tone and and may get threes, which are all seem to be involved, which you can find out by reading Ramdas paper that that is going to at least give him mechanisms so we can do more focused clinical trials. Speaker 8: [inaudible] [00:22:30] to learn more about the work and Patrick are doing visit their websites, Bruce ames.org and found my fitness.com Speaker 7: oh Speaker 6: papers take a lot of polishing. Basically we're going into all these fields [00:23:00] that we don't know an awful lot about us and that requires a lot of double checking and sending it to experts and getting criticism. Speaker 9: First you have to learn everything and then you'd have to put, make the connections together and then you have to write it and then there's a whole process. It's very, it's a lot of work. Personally, my favorite part of it is the creative part where you just make all the connections and you find things and you start fitting things together and it's like, oh yeah, you know, it's just, it's almost like awesome rush, but then once you've make all those connections and you do that creative work, then you really have to [00:23:30] do all the tedious, hard digging and working diligence. Yes and that it's not as much fun. Then once you have a good theory Speaker 6: you assume no. Is it explaining new things that you didn't expect and right away this idea explains so many things and it was all really lying on the ground and round it just picked it up and put it together. Speaker 9: People like Bruce and I who liked to make those connections. I think that we play an important role in science as well. Like this paper that we published recently, [00:24:00] while we didn't physically do any experiments, we didn't test our theoretical work. We made a very interesting connection with a mechanism for other people to test. And I think that every once in awhile science needs that because there's so much data out there and now with Google we have access to all this data. So I think that taking people that are familiar with the fields and can put things together like pieces of a puzzle, I think that also advanced the science in a very creative way. Speaker 6: Biology's so complicated that there hasn't been much room for people [00:24:30] who just sit in their office and do theoretical work. And we do a lot of experimental work in lab and Rhonda is carrying on an experimental problem while she's doing all this. But I like to get it in between fields. I was always half a geneticist and half a biochemist and it was wonderful because I saw all these problems. The geneticists turned up and the biochemists didn't know existed and the geneticists didn't know how to tackle this was before Watson and crick and all of that. Uh, I'm pretty [00:25:00] old anyway. I think science is so competitive, but if you know two fields in this an interface, you have a big advantage on everybody else and we like to have people in the lab with many different expertise and put things together. Speaker 10: [inaudible]Speaker 4: you can tune into the rest of Brad's interview with Bruce Ames and Rhonda Patrick [00:25:30] two weeks from now. Speaker 7: [inaudible]Speaker 4: irregular feature of spectrum is a calendar of the science and technology related events happening in the bay area over the next two weeks. On Thursday, July 10th the bay area skeptics will host a free lecture by Glenn Branch. The deputy director of the National Center for Science Education Branch will present untold stories from the scopes trial. [00:26:00] If you thought that you knew everything about the scopes monkey trial. Thank you again to commemorate the 89th anniversary of this seminal episode in the long contentious history of evolution. Education in the United States branch will tell the story of the scopes trial as it has never been told before. Focusing on obscure under appreciated and amusing details. The event will be at the La Pena Cultural Center, three one zero five Shattuck avenue in Berkeley [00:26:30] and it will start@seventhirtypleasevisitwwwdotbaskeptics.org for more info and here's the new story we think you'll find interesting in a paper published in nature neuroscience on June eight University of Minnesota researchers at B Steiner and a David Reddish report that they have made behavioral and neuro physiological observations of regret [00:27:00] in rats to regret is to recognize that taking an alternative action would have produced a more valued outcome than the action one took. Speaker 4: The research team created a circular runway with four spokes and feeding machines at the end of each spoke that contained different flavors of food pellets. The feeding was preceded by a tone that indicated how long the rat would wait at a particular machine for food if the rat left one of these restaurants with waiting time below [00:27:30] its threshold only. Do you find an even longer waiting time at the next spoke? The team hypothesized that the rat may regret the choice. Indeed, the rats that fit this description were more likely than control rats to look toward the spoke. They just left and electrodes indicated that neurons in the orbital frontal cortex fired at the same time. Science news talk to cold Spring Harbor Neuro scientist Alex Vaughan about the paper. He [00:28:00] said, the researchers did a great job of designing a task that can discriminate between the regret of making a poor decision and the disappointment that results when one is punished despite making all the right choices. Speaker 8: [inaudible] spectrum shows are archived on iTunes university. [00:28:30] We have created a symbolic for you. The link is tiny, url.com/calix spectrum. Speaker 7: Oh Speaker 3: [inaudible]. The music [00:29:00] heard during the show was written and produced by Alex diamond. Thank you for listening to spectrum. If you have comments about the show, please send them to us via email. Email address is Doug KLX. Hey, young com. Speaker 8: [inaudible].