Are You Nutrient Deficient? The Hidden Factors Accelerated Aging | Rhonda Patrick

Coming up on this episode of the Dr. Hyman Show.

What the study found, these are randomized controlled trials, placebo controlled, right? The multivitamin actually did improve brain aging. So they were less, people taking the multivitamin mineral supplement were less likely to experience cognitive dysfunction, memory loss. And in fact, they experienced an improvement in their brain aging that was equivalent to reversing two years of brain aging. Wow. Okay.

Yeah.

Randomized controlled trial. Here we are 10 years later.

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Yeah.

Before we jump into today's episode, I'd like to note that while I wish I could help everyone via my personal practice, there is simply not enough time for me to do this at scale. That's why I've been busy building several passion projects to help you. If you're looking for data about your biology, check out Function Health for real time lab insights. And if you are in need of deepening your knowledge around your health journey, check out my membership community, the Hyman Hive. And if you're looking for curated and trusted supplements and health products for your health journey, visit my website@DRHyman.com. .com for a summary of my favorite and thoroughly tested products. So Rana, it's so great to have you on the Dr. Hyman Show. Welcome. And I've been looking forward to this for a long time. I think, you know, you're one of the few scientists out there in the public sphere who's actually communicating science and data in ways that have a lot of integrity and that adhere to kind of some common sense principles that, you know, a lot of things out in the vlogosphere or the podcast world are often, you know, a little bit, you know, extreme and you kind of really take a very science-based approach. So I'm really thrilled to have you on the podcast. And, and the topic I want to really dive into is micronutrients, vitamins, minerals, maybe some phytochemicals. But, you know, there's so much confusion and controversy. And, and, you know, the medical profession has historically said, you know, you don't really need multivitamin mineral. if you're eating a healthy diet? Well, first of all, most of us don't eat a healthy diet. And second of all, you know, the idea that that vitamins and minerals just cause expensive urine doesn't quite make sense. I always say, if you know you say, why should you drink water? You're just going to pee it out. It's like your body uses what it needs. And I think there's, there's a lack of understanding of the widespread insufficiency and often deficiencies of nutrients in, in America. You know, we're overfed and undernourished. And so there's a A problem that I think we're facing, which is people don't understand the need to actually obtain the right nutrients in the right amounts for not just preventing a deficiency disease, but for optimizing health, preventing the disease of aging. And I want to sort of dive into that with you where I want to go through sort of the overall framework of like, you know, where we're at in terms of the nutritional status, American population, what things we should be worried about. and, and, you know, can dive into the science of each of the key nutrients and what they do and how they affect us. And, you know, one of the things that kind of really got me excited when I was sort of, you know, gonna have you on was that you studied with a scientist named Bruce Ames, who is someone I've, you know, really admired, has been someone who inspired me. And a lot of my work and thinking has come out of a lot of his work, which was really looking at how do we, how do we really understand the nature of Aging and micronutrients and and how do we get a metabolic tune up? You know, he wrote these incredible papers that were, I think, landmark papers. And, you know, you, you had the privilege of actually working with him, studying with him. So maybe kind of you can share with us how you sort of got into this with Bruce and what, you know, what you learned from him and what the sort of whole idea of the role of micronutrients is in health and, and wellness.

Well, first of all, Mark, I want to thank you for having me on the show. I appreciate what you do as well, and I also appreciate the, the kind words. So, sorry.

Did I make you cry?

Bruce Ames passed away a couple months ago, and he was my mentor and a very good friend of mine. Unbelievable guy. And it kind of a funny story about how I ended up in his lab. You know, I was, when I was wrapping up my graduate research, my PhD at St. Jude Children's Research Hospital, While I was there, I really got into health and for just wanting to be healthy. And also, I had done some previous research before graduate school in an aging lab at the Salk Institute in La Jolla. And so, I was already very interested in aging, even though I was in my 20s when I was working in that lab. There was always- the thing people think.

About when they're 20s is living to 100. But yeah.

I was definitely thinking about it. And specifically, I was thinking about things that I can do in my diet and lifestyle. because I had done some research on how insulin affects aging and glucose metabolism. And so it was very real to me that there's a very strong connection between our diet and lifestyle and the way we age. And so that led me to reading a lot of Bruce's studies on mitochondrial health, on micronutrients. And I continued reading him throughout grad school. And I started a blog at that time. I was blogging about vitamin D and omega-3 and I kind of decided I I didn't want to be a professor necessarily. I didn't necessarily want to go and write grants and do this sort of classical pathway that a lot of scientists do when they're doing their training. And I had told that to my mentor and my mentors at the time, and they were very distraught about that because they were saying that I was a very good scientist and I was completely destroying my scientific career. They begged me to please at least go interview for some post-doctoral you know, positions. And so I did, I said, okay, well, I'll go ahead and interview. And I went on a few interviews and some very prominent labs I interviewed for very even aging labs. In fact, one of the guys that I interviewed with at Stanford looked me up and saw that I was blogging and said to me, you can't do this if you're gonna come to my lab. You need to work for me. So then I go to Bruce and I meet Bruce and he is absolutely just, he blew me away with not only his excitement for science, but his excitement for science communication and what I was doing. And he was so enthusiastic about it. And he was basically like, oh, you need to continue doing this. This is a very important thing you do. Now, remember Bruce, you know, he kind of switches fields every few years or so. He started out looking at enzymes, and then he developed this test known as the Ames test that is a very, very simple test for testing for mutagens, things that can damage your DNA, which is the precursor for cancer. It's still widely used today. And he had done a lot of research back in the late 70s and early 80s, and he found that chemicals that were in things like women's hair dye, children's pajamas, were mutagens and carcinogens. And he published this paper on it, and nobody was doing anything about it. And so he was on the phone calling up these companies. Have you seen my paper? And he was responsible for getting these chemicals out of women's hair dye, out of children's pajamas. I mean, he has had an amazing impact on public health, continues to have an impact on public health.

Isn't he one of the most cited scientists of all time?

He is. He is. And then he got into, you wonder, okay, he's doing this cancer research, and then he gets into micronutrients. So, you know, these are about 30, or 40 essential vitamins, minerals, amino acids, fatty acids that we need to get from our diet. We need them to survive. But as Bruce would argue, we also need them to age optimally. And he got into this field quite, I would say, it was an accident. He had a guy in his lab doing a sabbatical, Dr. McGregor. And this guy was a cytopathologist. He was He was looking at red blood cells and doing a lot of experiments with red blood cells. And it turns out he used a media that didn't have folate. And all of a sudden he started noticing all these double-stranded breaks in DNA. DNA.

So the DNA was being damaged.

Being damaged. And so he was like, oh, what's going on? And he finally traced it down to, oh, we have this media that we've used that doesn't have folate. So then he decided to do some animal work. Well, let's see what happens if we deprive rodents of folate and sure enough, widespread DNA damage, just completely, and double-stranded breaks in DNA are the precursor to basically oncogenic mutations.

Cancer.

Exactly, cancer. So Bruce, of course, was like, wow, this is amazing. Not having a important micronutrient can potentially cause cancer. And that's kind of what it was doing in the rodent studies. And then he had found some humans that were low in folate and did some experiments as well, found a similar thing, gave them back the folate, DNA double-stranded breaks went away. He worked out the mechanism, which was folate is a precursor for making DNA. And so if you don't have that there, your body will put something there from RNA, a uracil, instead of a thymine.

Those are like nucleotides, DNA, they build DNA.

And so it basically causes these double-stranded breaks. So long story short, that's how Bruce got into micronutrients. And he started to really dive into understanding how these vitamins and minerals are affecting the way we age, because cancer is a disease of age for the most part. There are some childhood leukemias and childhood cancers, but those are mostly linked to genetics. Aging in general is a major driver of cancer. Bruce came up with this theory called the Triage Theory.

Yeah.

And this- Tell us about that. Yeah, this is a, it's a theory that he came up with that posits that vitamins and minerals that we get from our diet, they get triaged to essential functions in our body that are important for preventing basically acute death, right? So if you think about blood coagulation, vitamin K1, very important, like you need to have your blood clot. Otherwise you could have, you know, a pretty severe injury and you could have a hemorrhage and that would be detrimental, right? So vitamin K is one example and there's some other examples like selenium, that Bruce has published and showed there are proteins that have a stronger binding to vitamin K1 that are important for coagulation. So these are proteins in the liver versus, for example, other proteins that stay in circulation and are activating proteins that are important for calcium signaling and trafficking, moving calcium out of the bloodstream, moving it to muscle, moving it to bones.

Right.

So So he's published a couple papers showing that, so the idea is that your body will triage them to essential functions to prevent short-term death at the expense of these long-term sort of health functions, right?

So your body hijacks whatever nutrients we have to deal with the immediate needs you have, but then it kind of misses the boat on what they're doing to protect us long-term from the ravages of aging.

Exactly. And so magnesium would be another one. Magnesium is essential mineral. It's involved in over 300 different enzymatic, you know, processes and ATP production and utilization is one of those. And ATP is the energetic currency of our cells. We need to make energy to survive. Right.

So cells runs our cells is energy, everything. Exactly.

But it's also essential for DNA repair enzymes. They use it to repair damage to our DNA. Every time we make a new cell, whether that's a skin cell or a liver cell or a blood cell, There's damage that occurs even with just the process of cell division, right? Let alone the external processes that were exposed to UV radiation, unhealthy diet, things like that. So we need to repair that damage. But magnesium is essential for those DNA repair enzymes. And so if you don't get enough magnesium, it's only going to those essential roles of ATP production and not the DNA repair enzymes. And this is important because about 50% of the US population does not have adequate levels of magnesium. 50%. Close to 50%. Yeah. And, you know, magnesium, as Bruce would say, is at the center of a chlorophyll molecule. Chlorophyll give plants their green color. So magnesium is very high in dark leafy greens. You're supposed to eat your greens, you get your magnesium. And so people aren't eating enough of their greens and they're not getting enough magnesium. Greens and beans. Greens and beans and nuts, almonds, exactly.

Things that aren't typically staples of American.

Diet, which is 60% ultra processed food, right? Right, exactly. So, you know, the magnesium RDA is about 350 to 400 milligrams a day, depending on if you're male or female. Males require a little bit more. And so you really supposed to be getting the majority of that from your diet. People aren't getting that from their diet. And, you know, just in terms of We talked about triage theory in cancer. There are a variety of studies that have looked at these are observational studies, so it's always difficult to establish causation, of course, from observational data. But nonetheless, there are studies that have found a dose-dependent effect of low magnesium. So for every 100 milligram dose, 100 milligrams less intake per day was associated with a 24% increase in pancreatic cancer incidence.

Wow.

So instead- Magnesium. Of magnesium. So eventually, and that's dose dependent, right?

So let's back up a little bit. Years ago, more than 20 years ago, I wrote an article called Paradigm Shift, really about the sort of end of normal science, which is this sort of our current view of how things are in medicine and how the body works and shifting more toward a systems view and understanding the body as a network, as a sort of an integrated organism that requires basic raw materials to function optimally. And what I wrote about in that in that article was that, you know, micronutrients are really kind of miraculous because back in the turn of the century, we didn't really know about them of the 1900s, not 2000s, but we still, I kind of don't know that much about them from the consumer and, and medical point of view, for sure. The, the amount of serious deficiency diseases like pellagra and berry berry and rickets and, you know, zerop Fama, which is like a vitamin A deficiency and causes blindness, just widespread zinc deficiencies. And these cause really significant, serious diseases that could literally be cured almost in minutes with infinitesimally small amounts, milligram amounts of nutrients. There's no drug that can do that. And you were talking about magnesium having 300 different enzymatic reactions. When you take a drug, it usually has one target, like one receptor and one action. But nutrients have are pleomorphic, which means they can do many, many, many things, and they do many things. And each nutrient literally can have hundreds of different reactions in different systems of the body that regulate almost everything we can think of. And, and what's really frightening to me as a physician, and, and we do testing of this. I co-founded a company called function health, and we do a lot of micronutrient testing as part of that, which is not typically done, whether it's, you know, methylation testing for homocysteine, methanolic acid, you know, the B vitamins we're talking about, like folic acid or the, you know, vitamin D or the Omega-3s and, you know, zinc, I mean, the selenium list goes on and we see iodine, the tremendous amount of deficiencies that exist in red blood cell magnesium, you know, that exist within the population that are being undiagnosed. I mean, and we're seeing, I don't, I'm just, we have 110,000 people in our cohort, 67% last time we looked at the data of the cohort, which is, I think, more health forward cohort who would be proactive about their health, going to function health, getting rid of jobs done, 67% have a nutrient deficiency. Iron, omega-3s, vitamin D, homocysteine, whatever, at the level that the lab reference range says, not at what you or I would think would be optimal. So we probably would think vitamin D should be over 45 or 50, but their level's 30 or ferritin, I think their level 16, which is your iron stores, probably, I think it should be a 45 or more, you know, for optimal health. So we're talking about 67% being deficient at like a level that I think is already pretty low. So what about the general population? And maybe you could talk about the degree of nutrient deficiencies and then talk about like how these things actually do their magic and why they're not just causing expensive urine. And then I want to sort of get into, you know, what should people be taking? Because that's, I think we're going to get into that at the end because I think it's important to know what are the foundational things that are going to protect you long term, you know, for pennies a day that could actually save your life.

Well, I want to start out with the multivitamins and vitamins don't do anything in their expensive urine, which you also mentioned earlier because this is a pet peeve of mine, I guess.

Me too.

And I'll tell you, I'll tell you-.

Well, it was funny that I just get interrupted. Sorry. I go to these medical conferences and I'm like, I ask, okay, doctors, how many of you recommend supplements to your patients? And like a few hands will go up. How many of you personally take supplements? And like almost everybody's hand goes up.

Oh, really?

Yeah, it's very funny.

That's a great question. Yeah.

So there's no evidence, but I take it.

But I take it. Here's a big flaw with a lot of those studies that are cited by journals, great journals like JAMA, for example.

They're poorly designed.

They're poorly designed.

So, you know- like drugs.

Exactly. Exactly. Right. Exactly. So the problem is when you, when you have a drug trial, randomized controlled trials are the gold standard, right? You have a drug and then you have a placebo. But the thing is, is that with a drug, everybody has zero levels of that drug in the start of the trial. That's right. So you don't have to measure anything, right?

Because there's nothing to measure until you take the drug. There's no, like, pre ozempic level, although.

They actually the way those ozempic is really you have a GLP-1. Yeah, bad example, but like statins, so, you know, but when you, when you're.

Doing a, you don't have a normal.

Blood level of lipitor, right? Right, exactly. When you're doing a, a study on vitamin D or Omega-3 or fill in the blank vitamin mineral, everybody has varying levels of these micronutrients in their body. And so you have to measure things. You have to measure things at the start of the trial. You might have someone that's already got sufficient levels of vitamin D. They may have 50. nanograms per milliliter level vitamin D. And so you give them a vitamin D supplement and it's not gonna do anything because they're already sufficient, right? Or the converse is they're so deficient and you give them a supplement that's 400 IUs or 800 IUs, which doesn't raise their blood levels hardly at all, that it doesn't really do anything.

And so you won't dose is wrong. You don't measure who's sufficient. Like, yeah, I mean, like if you don't have a headache and aspirin doesn't do anything, right? So it's like if you, if your.

Levels are great of omega-3s and you add omega-3s, you won't see a change in your health.

Right?

Exactly. So that's the fundamental flaw of clinical trials in nutrition. That right there is that the MDs that are running these trials are running them like they're drug trials and they're not. You have to measure things. With that said, there have been some well done trials and in fact, everybody-.

But it's just been a trap. The other thing, the other flaw is that they will use a single dose of a nutrient that usually works as a team and that can actually make things worse. The beta carotene trials and smokers show that it can cause cancer, but oxidative stress is managed by a whole team of nutrients. So, like I would say, you could be Michael Jordan, but if you're playing one against five on a basketball team, you're going to lose every time, right? Even if he's the best player in the world. So, you need a team of of these nutrients, particularly in terms of oxidative stress cascade, to actually modulate free radicals. And if you give a high dose of one nutrient, you're going to kind.

Of screw up the whole chain. Yeah, that is possible. Not to mention the fact that smokers, I mean, if you give beta-carotene to non-smokers, it doesn't cause cancer. But smokers are doing so much oxidative damage and they're getting DNA damage that a high dose of something like beta-carotene, which can be an antioxidant, may then allow, you know, some of that. It's basically, it's allowing some of the cells that would otherwise die from the oxidative stress, you know, not to die. Right. And so it's, yeah, it's a very complicated thing when you're doing things like that. But, you know, I think, like, it was about 10 years ago, there was a huge study in the annals of internal medicine, and it was called the enough is enough vitamins and mineral supplements not only don't do anything that may be harmful. Yeah. I think that was. Do you remember that study? Yeah. It was about 10 years ago.

Yeah.

And, you know, I was, I just dug in and it was a meta-analysis and I went and looked at all those studies and I found that all these flaws again come into play.

You looked at the actual studies that they made their conclusions from. So they do a review and they go, we're gonna look at all these day studies and we're gonna make a, it's a summary and it's called a meta-analysis.

And then from that, you didn't just take their conclusions. You actually went and looked at the data itself from the original studies. Exactly. Yeah. And, I put out a video about it like years and years ago. and again, all these flaws that we just talked about were there. And here we are 10 years later, and the Cosmos Trials was just published, right? So this is another meta-analysis of a couple randomized controlled trials where older adults were given a multivitamin. They had about 20 or so essential vitamins, essential minerals, omega-3 fatty acids, vitamin D, right? Magnesium. This was all present in this multivitamin, and they were given it for two years. What the study found, these are randomized controlled trials, placebo controlled, right? The multivitamin actually did improve brain aging. So they were less, people taking the multivitamin mineral supplement were less likely to experience cognitive dysfunction, memory loss. And in fact, they experienced an improvement in their brain aging that was equivalent to reversing two years of brain aging. Wow. yeah. Brand mice control trial. Here we are 10 years later.

Yeah. And there's many, many other studies that show the value of nutrients in many, many different conditions. Right.

Exactly. Yeah. I, you know, I think that it, it comes down to, yes, you should try to get your micronutrients from diet. However, taking, you know, a multivitamin supplement, taking vitamin D, taking Omega-3s like these are insurance. Right. This is insurance to make sure you're getting your Optimum levels. So you asked about deficiencies and what are some of the common ones. Well, omega-3, okay, so about 80% of the world's population and 90% of the US population does not meet the requirements for omega-3 fatty acids.

Yeah.

That's a lot.

Which is basically what your body's made of, you know, the cell membranes, your brain, you know, nervous tissue. It runs regulatory inflammation.

I mean, it's critical to everything. Exactly.

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Try it risk-free with their 90-day money-back guarantee and feel the difference. And there's been a lot of work by Dr. Bill Harris. So I'm an associate professor at the Fatty Acid Research Institute with Bill Harris, and so I'm involved in a lot of research on Omega-3. And he's published just an array of studies that are quite convincing. So looking at the Omega-3 index, so this is the Omega-3 levels in red blood cells, which is sort of like a long-term marker for Omega-3 because they take about whatever.

What does the index actually measure?

It measures the EPA and DHA levels, along with a bunch of other fatty acids, if you're interested in that. But it's really the EPA and DHA level in the red blood cell membrane.

It gives you the index and you.

Want a certain number. Exactly. So he's published studies using like the Framingham cohort, so these are large cohort studies with a lot of people. And he's looked at the Omega-3 index and correlated with all cause mortality, so dying from a variety of different causes. And what he's found is that people that have what is defined as a high Omega-3 index, so this would be 8% or more, have a five-year increased life expectancy compared to people that have a 4% Omega-3 index, which is low. and actually the average omega-3 index of the US population is about 5%, pretty close to that 4%. Yeah, yeah.

Well, that's why we actually measure that in the function health labs. Yeah. It's great to see when we see.

That five year increased life expectancy. If you think about Japan, Japan, who eat, they eat a lot of seafood in Japan. Yeah. Their omega-3 index on average is like 10%. So they're above the high, the 8%.

Yeah, yeah.

But their mercury levels are probably also very high. What's funny, what's funny that you say that, Mark, there's been studies like in pregnant women. Yeah. you probably remember this, that decades ago women were advised to stop eating fish because of the high mercury. And that actually had a detrimental sort of effect because omega-3 fatty acids, as you mentioned, they're so important for the brain, very important for neurodevelopment. And there have now been a whole host of studies that have come out showing that omega-3 fatty acids actually protect from any potential mercury toxicity in the developing fetus. And in fact, there's been studies looking at children that were born to mothers that had a high level of Omega-3 and high mercury. Those children had scored higher on intelligence tests. So IQ scores, even like, even if so, so high mercury was actually biomarking intelligence. It wasn't actually the mercury. It was high Omega-3 crazy. But, yes, you get, you get the.

Although in Japan, they eat a lot of seaweed, which. And seaweed is a chelator for heavy metals.

Oh, is it? So is green tea, by the way, I think garlic Garlic, that beta mercaptans in garlic as well. But back to the Omega-3 and this study I was talking about from Bill Harris is so interesting because he also, this is a huge cohort of people, the Framingham, there's people that have all sorts of lifestyles, including smoking. And so he did a sub-analysis looking at smokers and non-smokers and their Omega-3 index. And what Bill and his associates and colleagues found was that smokers with a high level of Omega-3 so they had a high Omega-3 index of eight percent. They had the same mortality as non-smokers with a low Omega-3 index.

Okay, everybody, this does not mean you can smoke and take your own fish oil pills. I don't get any ideas.

Or if you're not getting enough Omega-3 it's like smoking, right? I mean, if you look at the graph of this, I mean, Incredible. The overlay is perfect.

Yeah.

Perfect.

Fascinating.

So having a low Omega-3 index had the same mortality risk as smoking.

Okay, so we're talking about 90% of the American population is in that category.

Yes, yes. And, you know, there's also been a whole host of randomized controlled trials looking at Omega-3s being cardio protective, right? So they're very important for cardiovascular health. triglycerides.

Yeah, there's actually prescription Omega-3s which you can pay much, much more than you would if you go get a basic Omega-3 for lowering triglycerides as a therapies. Right.

Yeah. And you mentioned inflammation, you know, so this is another thing they do. They play a major role in lowering inflammation. And so that's a driver of Aging in, in many ways, brain aging, you know, cardiovascular aging. So Omega-3s are, I would say, one of the most profound lifestyle factors that can play a role in negating inflammation aside from exercise.

Yeah, they're so, like the word I use is pleomorphic, but it's a big medical word, but essentially it means it does a million things, right? It's not just one thing, it's great for your skin, for your hair, for your nails, for your brain health, for preventing dementia, cardiovascular disease, cancer. I mean, it regulates inflammation. So these are nutrients that do so many things in the body. then they're worked differently than drugs and they're essential, they're called essential because they are essential. And one of the challenges is that we're looking for that quick fix and we're trying to diagnose a real disease that's directly connected to that particular problem. So I'm sure familiar with Robert Heaney who was a vitamin D researcher and he wrote this beautiful paper years ago called Long Latency Deficiency Diseases. And the basic thesis was that in the short term, if you're a nutrient deficient at severe level, like we used to see, you know, in the 1900s, if your vitamin D is super low, you'll get rickets. Or if you don't have enough vitamin C and you're a sailor, you get scurvy, right? Or if you don't have enough, be too much white rice and white flour, which they started doing at the third century, you get berry berry and plegora and all these horrible B vitamin deficiencies. The, the thesis you had essentially is that you can correct those vitamin deficiencies in the short term to fix those deficiency diseases. Like if you're low in folate in the short term, it'll cause anemia, a form of anemia we call, which is big cells called megaloblastic anemia. But in the long run, it can cause cancer and heart disease and dementia. And same thing with vitamin D. You know, in the short run, you'll get rickets. In the long run, you'll get osteoporosis and cancer and die sooner. And so medicine hasn't really gotten that concept. It's yeah, if you're deficient, take a vitamin, but otherwise you don't need them, right?

And that's also very much in line with Bruce's triage theory, right? These micronutrients are running our metabolism, which runs everything from our heart pumping blood to neurotransmitter function to repairing DNA. So there's a lot of, you know, you can look in the mirror and if you're vitamin C deficient and your gums start falling apart, you can see, oh, I've got scurvy. I've got scurvy, right? But like when you're magnesium deficient, like you're not gonna see DNA damage happening.

But you might feel muscle cramps and you might have anxiety, you might have constipation, you might have muscle twitching or headaches or a million other things that are symptoms of magnesium deficiency. Right. Stimulate the loud noises. And so like as a functional medicine doctor, I take a deep history to look at micro nutrient deficiency symptoms that are not necessarily pure true deficiency, but more like insufficiency. and I think people sort of don't make that distinction. And I think when you treat people, it's often a miracle when you get them a pleat and the nutrients are deficient, so many things get better.

I like it is insufficiency because most people are not deficient. We do have a lot of fortification even in our ultra processed foods because of, you know, preventing neurotube defects, preventing pellagra, like all these diseases that were sort of cropping up, like you mentioned.

In the early Fortified, but it's like junk fortified.

It is, it is. But it seems to stop some of those deficiencies, right? But it's the insufficiency and with vitamin D, it's a really big one because it is converted into a steroid hormone. So this is something that is going into the nucleus of our cell and binding and interacting with DNA. It has a little sequence of DNA called a vitamin D response element. It's so important there. it's encoded in our DNA, right? So to not have enough vitamin D, so 70% of the US population doesn't meet the sufficient levels of vitamin D, which is about 30 nanograms per ml. 70%.

30. Which would be- and if you add it up to 45 or 50, it's probably like 80 plus 90%.

Right, yeah. So that would be- there have been studies looking at all cause mortality and vitamin D levels. Of course, this is, again, observational. Lots of meta-analyses out there even dating back for like 30 years. And it seems as though having at least 40 nanograms per ml seems to be a sweet spot. You know, 40 to 60 is a really good place to be where you're having a good level of vitamin D. But again, it's a steroid hormone. It's regulating over 5% of the protein encoding human genome. that's like thousands of genes. You know, everything from immune function, it plays an important role in preventing autoimmunity, brain function, it regulates genes that are important for converting tryptophan into serotonin. Serotonin is an important neurotransmitter that regulates mood, cognitive function, impulse control.

You know, so vitamin D- maybe I.

Need more of that then. Well, and the problem is, is that, you know, vitamin D typically you make it from UVB radiation exposure from the sun.

But we're all told to shield ourselves from the Sun and Sun's locked. And so we live indoors, work indoors, and, yeah, it's a problem. And when you're all running your half naked, hunting and Gathering, we got a lot of vitamin D. And we ate and we're Coastal areas and we ate, you know, fish, small fish like herring and so on. They're higher in vitamin D. Or if you're forging mushrooms, you're high in vitamin.

D. So there's ways in which our historical population got it, the, you know, paleo-anthropic ancestors, but we don't get that. Right. Exactly. We don't. And so You know, I do think, so people, the simple solution is a vitamin D supplement, right? And so about 4,000 IUs a day will generally get someone from a deficient range, which is 20 nanograms per ml up to a sufficient range.

Okay, but you're just talking about 10 times what's normally in a multivitamin or what doctors will recommend. 10 times.

I am. Because you really do, it's about 1,000 IUs of vitamin D will We'll raise blood levels between 5 to 10 nanograms per ml. But we have genes, we have different variations of our genes that are able to do this. And this again comes down to these clinical studies showing that nothing happens when... We're all different. We're all different. And so some people actually have to take a much higher dose, right? Because they have genes that aren't doing, converting vitamin D3 into 25-hydroxy vitamin D, which is this circulating form of vitamin D or the steroid hormone, 1,25-hydroxy vitamin D. you know, so let's go down.

This rabbit hole because I, I think, you know, there's a paper you just reminded me of the Bruce Ames row. It was published, I think, the American Journal of Clinical Nutrition years ago about how one third of all of our DNA codes for enzymes. And, and an enzyme is a catalyst that converts one molecule to another molecule. The catalysts or the co enzymes or the helpers are micronutrients. And so what he said in that paper was that there's a huge variation in the population's need for different nutrients. So some people might need 400 micrograms. some people might need 4,000 micrograms of folate. And so it's really about personalized nutrition. It's about testing, not guessing. It's about figuring out what your body needs, what your genetics are. And it gets really fascinating that you can actually start to customize your own diet and your own supplementation based on what your own particular genetics and your levels are. And so I think there's this, it was sort of a wake up call for me like, holy cow, when you think of our DNA and everything it does, if one third of it is coding for enzymes. And all those enzymes require vitamins and minerals. If we don't have enough of those nutrients, it's like an assembly line in a factory. If you don't have one station, the thing can't get made, right? So you gum up the whole works of your metabolic machinery if you don't have the right levels of nutrients to optimize the function of your body. And that's why we call it functional medicine, because it's about how do we optimize function. Right?

It's true. You know, these minerals and vitamins, so you're talking about magnesium, zinc, calcium, B vitamins, like these are co-factors for these enzymes to make these enzymes run properly. And if you don't have sufficient levels of those vitamins and minerals, what happens is those enzymes do not work optimally, right? So in the case that we talked about DNA repair enzymes, they're not gonna be repairing damage as well. Zinc is also involved in DNA repair as well. So B vitamins are involved in serotonin production, magnesium is involved in vitamin D production, right? You were talking about nutrients working together, and it's very true. So I think a really great way to think about eating and diet is what do I need to run my metabolism, right?

And when you say metabolism, what do you mean by that? Because it's not like my weight, you're talking about metabolism as sort of a bigger concept in medicine.

Yeah, I guess when people hear the word metabolism, they think about weight loss.

I got a slow metabolism. Right.

What I'm talking about is much more a biochemist definition of metabolism, which is all these enzymes. You're talking about, you know, one-third of the protein encoding genome. that are doing enzymatic reactions that are making proteins function. So they are producing energy. They are running neurotransmitter synthesis. They are causing your liver to function properly, your heart to function, lungs, everything.

So every chemical reaction all the time.

Exactly.

I don't know if I heard, I read this somewhere and I can't find the original citation, but that there's 37 billion trillion chemical reactions in the body every second. It's just like an insane amount of activity is going on chemically and biochemically and converting one molecule to another. And if you don't have enough of these nutrients, that whole 37 billion trillion.

Chemical reactions may not work optimally. Exactly. So, you know, getting the micronutrients you need from food and nature sort of color-coded them in a way, right? I mentioned, you know, chlorophyll, that's magnesium, you have vitamin K, Also, the, the.

What color is that? What color is vitamin K?

I guess it's green, too. I would say green, green, green, green. Vitamin K one. And then the orange ones. The orange, right. And then you've got like the phytochemicals, right? So that would be the purples. But you know, you really do need to get a lot of vegetables and fruits and then you need your protein, right? And fiber. When you're getting your micronutrients, you're also getting the fiber because a lot of the micronutrients are coming from plants. which are a great source of both fermentable and non-fermentable fiber. Right? So I think it's a really simple way. There's so many fad diets out there, right? Carnivore, keto, vegetarian, paleo. And although I do think paleo is the closest thing to what I'm talking about, but what I'm talking about is even simpler because what it really means is that you understand why you need food. What's the purpose of food, right? The purpose of food is to provide you with these essential vitamins and minerals and fatty acids like omega-3 and protein and fiber to improve gut health. That's the purpose of eating.

And fuel. Right.

And so that means you don't need ultra-processed foods. That means, you know, if you're eating something like just carnivore diet, you're gonna be missing out on a lot of micronutrients.

It's gonna be very hard. I have a theory, which is, is like I have many theories. One theory I have is that, you know, we're so depleted in these nutrients and it dysregulates our appetite. And so when you're eating ultra processed food, there's no nutrients in there. And, and so when a kid is iron deficient, it'll eat dirt. It's called pica and try to get some iron from the dirt. And I think so many people in this country are so nutrient deficient that they're just. eating more and more of the ultra-processed food. It's like they're looking for love in.

All the wrong places. Have you heard of the protein leverage hypothesis? Yes. Yeah, so it's kind of the same thing where, you know, your body needs a certain amount of protein to run optimally. And if you're eating, there's been a couple of randomized controlled trials on this. I think it's like Stephen Simpson is one of the proponents of it. It was like 2000s or something. And, that essentially if you're eating ultra-processed foods, which are high in, you know, a lot of refined carbohydrates, low in protein, that you overeat to sort of try to get enough protein. Exactly. So it does make sense if your body's looking for more of micronutrients, more vitamins, more minerals, more protein that you start to overeat.

And are you familiar with Kevin Hall's.

Study that he published a couple of years ago? You mean the ultra-processed food? Where they had 500 calories more. They had 500, yeah. So for people listening, I mean- For processed food. Exactly. They had, you know, two diets. They had a whole foods diet, which was essentially mostly they were getting salads and they were getting poultry and lean meats and some fish, oatmeal, and then there was the Ultra Processed Foods diet.

And they were trying to match them for macronutrients.

So they were, yeah, so they were matched for calories, they were matched for total sugar, although the added sugar in the Ultra Processed Foods group was, it was like a huge difference. I mean, it was like, something like 70 or 80% versus 1%. So the sugars in the Whole Foods diet were coming from fruit, which has a fiber matrix, right? So they were matched for that. Exactly. So the added sugar was not matched, although total sugar was, right? And then protein was somewhat matched. The Whole Foods had a little bit more protein. It was something like 15.6% in Whole Foods diet versus 14% in the Ultra Processed Foods diet. And they were given, so a lot of things were matched and they were given these foods, you know, in a sort of metabolic ward where they came in and eat, they had 60 minutes to eat the meal ad libitum, right? So they could eat as much or.

As little as they wanted. Yeah, so you got a big, as much like giant buffet, eat as much as you want, like you got 60 minutes. Right. And then they did it. And then the group that eat the ultra-processed food ate 500 calories more a day. And I just to do the math on that, 500 calories times seven is 3,500 calories. That's one pound. of weight gain. So you add that up as 52 pounds of weight gain in a year.

The Order America is overweight. Yeah. I didn't do that math. I know that I just read the results, which was two pounds. They gained two pounds in two weeks.

Whereas the whole foods diet lost two pounds. Well, let's say two pounds, right? Two weeks, 20. It's like, you do the math. It's like, but you add that up over a year and then you add up year over year. It's like, that's why we're seeing this sort of just incredible level of severe obesity and diabetes and I mean, it's just, you know, the latest date I saw was sort of shocking, was that 38% of teenagers have pre-diabetes. Wow. I was like, what? I mean, it didn't exist when I graduated. I'm old, but it didn't exist when.

I graduated from medical school. Like, we didn't have it. We never saw a kid. There's been studies that have looked at, like, healthy individuals, and they've given them, they were actually young men. They gave them a 20-ounce sugar-sweetened beverage, sort of akin to, like, a soda Coke or something. And they did this for three weeks. And after that three week mark, their C-reactive protein biomarker for inflammation went up 100%. They are small, dense LDL. So these are lipoproteins that are transporting- the bad ones.

Yeah, the ones that are causing more heart disease.

Exactly, causing more atherosclerosis. They went up as well. This was just after three weeks, you know, and- Beating a healthy process. Of a sugar-sweetened beverage, which is the ultimate. Right, that's the ultimate. Yeah, ultra processed. But the reality is that it's gluten free. It's gluten free, yes, but it's definitely, it's causing inflammation, massive inflammation at the level of the gut. And so you can take healthy people and dramatically change their profile within a matter of weeks of having, you know, this ultra processed foods, these sugar-sweetened beverages, you know, which again, like- and they.

Deplete nutrients because I think people don't realize that one, you're not getting them, but two, you actually need nutrients to actually run your biochemistry. And so you're trying to burn these calories and burn the food, but you're actually depleted in the very nutrients required to run them metabolic Pathways to actually metabolize the food. So you're kind of, you know, getting it from both sides.

Yeah, yeah. Yeah. So again, it's. It comes down to, I think, you know, thinking about why you need to eat is so important because then it's like, I need to get micronutrients, I need to get my. My fiber, I need to get protein. When I say fiber, carbohydrates, right, but it needs to be carbohydrates in the form of fruits and vegetables, which have the micronutrients and the fiber.

Right.

And nuts and seeds, yeah, and oats. And then avoiding ultra processed foods. I think if people were to do that and think about eating that way, and then you have to move, right, you have to be physically active. Being sedentary is a disease. Yeah. Like that's, like there's data out there that show people with a low cardiorespiratory fitness, so this is a marker of, you know, I mean, it's a marker of how physically active you are, essentially. That's an oversimplification, but people with a low cardiorespiratory fitness have the same disease risk as people with diabetes, cardiovascular disease smokers. So how do you measure your cardiovascular fitness? Well, cardiorespiratory fitness is something typically you can measure if you go into like a lab that measures them and they put that like mask, it's a VO2 max. So it's measuring your maximal oxygen uptake under maximal exercise. They put a mask on you and that's really how you empirically quantify it. However, if you have like a smartwatch, Apple Watches do sort of measure it. It's not really entirely accurate.

I like mine Garmin because it says I'm 45, but I don't believe it.

Well, you can actually do it. You can do what's called the Cooper Test. And so that's basically you do a 12-minute run on a flat surface like I track. If you have hills, it's harder to run hills. And so you can't, you're trying to run as fast as you can maintain for that 12 minutes. So it's like a, it's a maintainable 12 minute pace, right? And, and that is, and there's a calculation, you can look it up, the Cooper test, and you can sort of get a good estimate of your VO two max.

Yeah, yeah, yeah. But essentially, you know, having that's assuming.

You could run for 12 minutes, which most Americans can't. You know, there is, there's an argument to be made for exercise snacks, you know, so these are short bursts of, you know, physical activity where you're getting your heart rate above, you know, 70% max heart rate. So you're getting to more into the vigorous exercise, you know, range. And there've been some studies, they're called the Vilpa studies. Are you familiar with these? These are vigorous intermittent lifestyle activity studies. And Martin Gibala, who he's a, you know, expert on high intensity interval training.

I've had him on my podcast he's.

Involved in a lot of this.

Jump down and do 10 burpees and.

Then go back to work? Sort of, yeah. People are wearing these wearable devices that they can measure their heart rate and so scientists can see when they're getting these bursts of high intensity exercise. So, this type of exercise is actually not structured. What you're talking about would be structured, right? Where you get up and do burpees or air squats or high knees or jumping jacks. This is where people sort of take advantage of everyday situations. So, they sprint up the stairs, right? run, you know, they're running to some some place rather than walking. So they're really using their everyday lifestyle to kind of get their heart rate up.

Yeah.

Well, people that do that do anywhere between three to nine minutes a day have a 40% reduction in cancer mortality, a 50% reduction in cardiovascular related mortality, all cause mortality. So this is beneficial for people and this is even in people that identify as non-exerciser. so just getting some sort of exercise does have benefits for people in general.

Yeah. I mean, you look at the data on mortality and longevity. One of the biomarkers that's the most correlated with longevity is VO2 max, is your level of cardiovascular and respiratory fitness, which is basically how fast your metabolism can run. Because it's basically an indirect measure of how much calories you can burn per minute. and how much oxygen you can burn per minute because they're very correlated. And your metabolism being having a slow or fast metabolism is really about your VO2 max. Because if you have a high VO2 max, you can burn a lot of oxygen and then you can burn a lot of calories because you need both to actually combust in your mitochondria. The energy factories actually produce ATP, which is the source of energy for the runs everything in your body. So it's like you, you actually, you actually have this incredible system. but we don't really take advantage of it and we don't maximize our fitness, which is so cool. And I think the other number that's sort of a little easier to get is your waist-to-hip ratio, which you need a tape measure. And that, again, is the bigger your waist, the shorter your life, basically. Is that also for visceral fat, measuring visceral fat? Yeah, I mean, your waist-to-hip ratio is a crude measure of visceral fat. I mean, but yeah, if you did a DEXA scan or an MRI you could look at body composition for sure. It's like that, it's that belly fat. But again, that's all relates to insulin resistance and prediabetes and inflammation, which again, I want to getting back to the micronutrients, all those things actually accelerate your risk of, of how many of these. Like, magnesium is very involved in blood sugar regulation, right? So if you're talking about 45% of Americans being deficient in or 50% being deficient magnesium, that affects blood sugar. We have a epidemic of diabetes and pre-diabetes in this country.

Are you familiar with some of the, there's some gene variations in the transporter that transports magnesium into cells and people with a gene variation that obscures the transport. So basically they're not getting as much magnesium into their cells are much more likely to have type 2 diabetes. So there's really some, I would say more causal evidence there, right? Because one would argue well, people that are low in magnesium are also eating refined sugar diet and they're not exercising and all these other potential unhealthy lifestyle factors that could be contributing. But when you look at the genetics, right, I mean, it doesn't lie. So you're looking at someone that's not getting enough magnesium. There are, you know, insufficient and deficient in some cases, and their risk for.

Type 2 diabetes just skyrockets. Yeah, I mean, I think this is so important that, you know, we are walking around with a population that is got such treatable, cheap solutions for so many issues. And that, and we're looking for sort of drugs to treat this and drugs to treat. I'm not against drugs at all, but there, it's like we're missing the boat because, yeah, somebody doesn't have scurvy or rickets, but they're still insufficient and they're gonna, they need these nutrients and actually to optimize their health. And you kind of started to unpack the, the degrees of different nutrient deficiencies. And, you know, as, as you're going through the list, you're going through the things that are the most common deficient in our country. Omega-3s, vitamin D, magnesium, and there's others. So, you need every essential vitamin and mineral. You need all those for sure. But, the ones that are really causing havoc are deficiencies in the methylation nutrients like the B vitamins, folate, B6, B12, deficiencies in iron, deficiencies in zinc, potassium. These are like, yeah, because we need to die this very plant poor. And that's where you get your, you know, potassium, which is from, you know, plants. And, and, and you need to actually not get as much sodium, which is what we're eating on lots of processed foods. So not like salt is bad. We need salt. It's just, it's all the salt added by corporations to your food to make you palatable, because otherwise it tastes like cardboard. They had sugar and salt and fat, and it makes you addicted to it. So we, and we leave out all the key nutrients that are needed to regulate everything. and our body. And so, so maybe you can kind of take us down that, that list a little deeper. So we've got, we've got to get Omega-3s, we've got to get vitamin D, we've got to get magnesium, and, and literally we could spend a podcast on each nutrient and probably 10 podcasts on each nutrient. But, but we're just gonna go through. So people understand, like these are the things that are non-negotiables that you've got to have and that you've got to test, you've got to measure and figure out whether your levels are okay because the average physician or a practitioner isn't gonna and they don't know how to do it and they don't get taught this in medical school. And I'm working on trying to change that in Washington. But it's kind of a travesty because it's like a staring us in the face that we have this epidemic of micronutrient deficiencies or insufficiencies and they're not being addressed and often worse, we're being told not to fix them.

Yeah, so the vitamin D, magnesium, omega-3 we talked about, right? you know, believe it or not, a lot of people, I don't remember the exact percentage, but quite a bit of people are not getting enough vitamin C. Something like 30 or 40, 40% or something like that. I'm not getting enough vitamin C. Yeah.

I heard that 10% are deficient at the level that would cause scurvy in America.

That's unbelievable. Just not eating any vegetables or fruits, because vitamin C is also in vegetables, not just in fruits. Calcium is another one. so, I mean, these are things that can be tested for and measured. Another one is vitamin E. People are not getting enough vitamin E. Again, that's also found in things like avocados, nuts, whole grains. And then potassium is a big one because it's so important for the sodium-potassium pump, which plays a role in blood pressure. And so when you're talking about too much sodium and not enough potassium, it's really exacerbating. that not getting enough potassium aspect, right? Because that ratio is so important. And so not only are, I think it's something like 96% of the US population doesn't meet the adequate intake for potassium. It's essentially everyone.

And our potassium intake as hunter-gatherers would be 10 to 1 potassium to sodium.

Now it's the other way around. It's the other way around, exactly. And so there's all sorts of problems with blood pressure and, you know, Gosh, it's like even like 30% of like individuals age 20 to 39 have hypertension.

Yeah.

You know, these are young adults with hypertension. And we now know that hypertension isn't just a risk for cardiovascular disease, it's a risk for dementia and Alzheimer's disease, particularly if you start earlier, right? If you're like a younger person, so like it's cumulative exposure to hypertension.

Yeah.

You know, it's important because you have to get blood flow to your brain. and, you know, you've got all these tiny, like 90% of the, of the brain vascular, vasculature surrounding the brain is made of these tiny, tiny blood vessels that are like the smaller than the size of a hair in terms of diameter. And they have to get blood flow to them. So exercise helps that. But hypertension exacerbates the lack of blood flow going to those blood vessels. And what happens is they're so tiny.

They start to sort of constrict and, and sort of fall fall off. And you can get mini strokes.

Mini strokes, but also neurons don't get the nutrients and the oxygen they need. And so then you start to lose neurons, right? And you get brain atrophy. And so there's this connection between hypertension and dementia. And, you know, I'm talking about potassium here because potassium does play an important role in- Very lean and blood pressure. Yeah, right.

So there's magnesium though, too.

So there's magnesium.

So does magnesium. It's the relaxation mineral. And then exercise, of course, is one the best things that you can do.

I mean, as a doctor, when a.

Patient comes in with preeclampsia, which is a problem of high blood pressure in pregnancy, or as preclamptic seizures, where they can get seizures, the treatment is intravenous magnesium. Right. Think about it. And so, like, this is something with uncontrollable high blood pressure, what do we do? We give them intravenous magnesium because all the drugs don't work.

I think there's some evidence also I've seen that vitamin D plays a role in preventing that as well. And it was, it's funny, like when I was pregnant, I asked my OBGYN for a vitamin D test. Do you want to know what his answer was? You don't need it. Why it's going to be low?

Why is it going to be low? Why?

It's going to be, you're going to.

It'S going to be low anyway.

Like, just take it anyway. Are you kidding me? Are you kidding me? Like you're, you're telling me why do I need a test? It's just going to be low. And, you know, and I'm like, well, I want to test and I, yes, I'm going to be supplementing, but I want to know with how, how much I'm going to be, you know, should we be supplementing with?

Right.

But it was just really astonishing to me, that mentality, you know, and actually just recently I went in for, I didn't go to my normal doc, I went into, it was like a, you know, a sort of ER kind of or urgent care doc, and I wanted to get my vitamin D levels measured. And he goes, you know, that's falling out of vogue now. And I just gave him this long lecture. I mean, I was like, I went in deep. I looked at him and he goes, Is this your area of expertise? And I was like, Yes, it is. I've done research on it. I've published studies on it. and he kind of was like, okay, all right.

I mean, it's not their fault. I mean, I'm a physician and, you know, I don't fault them. And, you know, my daughter's graduated from medical school this year and, like, zero nutrition.

It is.

It is. Like, it's even micronutrients. Like, I don't even think they covered any of that. And. And it, to me, it's like, this is the center of our biology. And if we don't. We don't understand how our bodies work and how to work with them and how to facilitate normal function. and it's not like the micronutrients are the only thing, but they're a very key foundational part of being healthy. And when you go through the litany of things that we're deficient in, you know, it's a lot of things and we're insufficient in and it's different degrees of insufficiency in the population for different nutrients, but you know, widespread deficient, you know, iron, zinc, selenium, a lot of things that iodine, I mean, I see this all the time in our testing that function health, and I'm like kind of shocked. And I've done testing for, you know, a lot of patients who've come to see me over the decades, but this is like 110,000 people. It's not like I can see 10,000 people or 20,000 in my lifetime, but like this is a huge amount of people and it's sort of shocking to me. And yet it's not really being talked about as a sort of critical step in helping address her chronic disease epidemic. And what you're saying is that yes, you can get deficiency diseases like scurvy, but what's really the issue is how these contribute to our long latency deficiency diseases like Alzheimer's and cancer and heart disease and diabetes and osteoporosis and all muscle aging and all the things that we don't want, right?

Yeah, so one of the last papers that Bruce published is his second to last paper was called Longevity Vitamins. And it was about these vitamins like vitamin D and magnesium and omega-3 taurine or some other essential amino acids. that play a role in the way we age and slowing age-related decline. And, you know, there was just a recent study that came out on vitamin D, sufficient levels of vitamin D, people that supplemented with vitamin D were 40% less likely to have dementia. You know, so the reality is, is.

That- I mean, vitamins don't just create expensive urine. They don't.

They don't. You know, these micronutrients are running everything in our body. And when you have insufficient levels of them, You're not going to necessarily see it, although you probably feel it. You might have symptoms, but you don't.

Attach it to that. Right.

You don't attach it to that. But it's causing this insidious damage, right? This insidious DNA damage, a little bit.

Of oxidative stress, a little bit of inflammation. I get sick all the time because my vitamin D is low.

Right.

Or you're getting sick. My muscles ache, you know, because I'm vitamin D is low. Or, you know, I'm muscle cramp because my magnesium is low, right? or I have depression because my, you know, methylation vitamins are low. Like people have symptoms, they just don't correlate it with nutrient deficiencies.

Depression is interesting. There's a pretty classic study that no one ever talks about where healthy individuals were injected with lipopolysaccharide. So for those listening, this is a component of your bacterial outer cell membranes. that's present in our colon because we have about, I don't know how many trillions of bacteria, like so many bacteria in there, right? 40 or 50 trillion. Okay, 40 or 50 trillion. There's about a gram of lipopolysaccharide in our gut because those bacteria do die off.

And these are bacterial toxins. This is what increases off your immune.

System to know it. It does, and when we have gut permeability, lots of things that cause that, it releases it. Right. Also known as leaky gut, it leeches the LPS into our bloodstream. Well, this study took healthy individuals and injected them with an amount of LPS that would be equivalent to something that you could get from intestinal permeability. And it caused depressive symptoms in these individuals. Okay, one, that links inflammation to depression. Hundred percent. Two, if those individuals were given EPA, so this is one of the omega-3 fatty acids, it does play a major role in dampening inflammation through a variety of mechanisms like resolvins and marines and the SPMs. they're all molecules that are resolving inflammation very quickly, they did not experience those depressive symptoms if they were injected with the LPS. If they got Omega-3s. If they have the Omega-3s. So it comes down to, again, you.

Know- and Omega-3s have been shown to actually help with depression. They have. And ADD. They have. Yeah.

But depression, specifically EPA seems to be very important for depression. And I think that's because there's a really big inflammatory component to depression, where there's now studies showing that people that don't respond to classical SSRIs, so serotonin reuptake inhibitors.

So like Prozac.

Exactly. People that don't respond to that, they typically have very, very high levels of C-reactive protein, inflammation. So there's like a subset of people, some people respond and it helps them. But there's a subset, a quite large subset of people that have very high inflammatory biomarkers and do not respond to SSRIs. And so logically the next question would be, should we lower their inflammation? How can we lower their inflammation?

I read some paper that was like hypothesizing that we should use TNF alpha blockers, the biologics for depression. In other words, these are drugs that massively suppress inflammation in the body used for serious autoimmune diseases. And they're talking about using a red depression. I'm like, wait a minute. how about we find out why there's inflammation in the first place and get to the root cause of it, which is really what we do in functional medicine. I think what you're kind of hitting on, just sort of proofly, and I want to sort of tie the, tie the dots together, is that when you don't have enough of the right nutrients and you don't have a proper functioning metabolism, there's a lot of downstream consequences. You get inflammation, you get oxidative stress, and you get damaged mitochondria, and you get DNA damage. And you, you look at these processes, these are the fundamental things that have to be working for you to be healthy across every organ, across every disease state. And it's what we're now calling hallmarks of aging or including many of these things. And what you're talking about is, and Bruce Ames figured this out even before there was a word hallmarks of aging. He figured out that these nutrients are critical in these pathways that degrade and become problematic as we age, but that we can offset that and actually take longevity nutrients and get a metabolic tune up. And he's even talking about things that I think are we don't think of typically as essential nutrients that are we call conditionally essential nutrients. And whether it's carnitine or taurine or things that may not be kind of a typical deficiency disease vitamin or mineral, but that are still really important for our biological function and we're still low on them. So I have this theory I want to, I want to come back to in a minute about that I, that I kind of made up called symbiotic phytoadaptation, which is a big mouthful, but essentially it means that we've co-evolved with plants to borrow their phytochemicals to regulate key pathways in our body so we can stay healthy. and that without them we don't get a deficiency disease. Like you don't get like, you know, like broccoli deficiency, but actually we kind of do because the phytochemicals like sulforaphane or the glucosinolates or isothionates, these are molecules that regulate key pathways in our body. For example, liver detoxification or removing heavy metals or whatever, controlling oxidative stress, they work to actually facilitate these pathways. And so I kind of this theory that it's more than just like essential vitamins and minerals. There's a whole bunch of stuff that's essential if you want to be really healthy.

I completely, a thousand percent agree.

I think they just made this up.

So, I think that humans evolve, we evolve to eat of plants and meat and things, but plants because of the phytochemicals. You know, there are, so you mentioned sulforaphane, right? So sulforaphane is present in a variety of cruciferous vegetables like broccoli. It's much more, it's not present, I'm sorry, the precursor to it, glucoraphanin is present in it and it gets converted into sulforaphane when the plant matter is broken, chewed because it activates an enzyme.

Called myrosinase which converts glucoraphanin into sulforaphane. Big mouthful of words, but essentially when.

You chew your broccoli you get cool chemicals that help your body. Exactly, and if you go even further and eat and chew the young plant.

The broccoli sprouts, there's about a hundred times more glucoraphanin in it. Damn, I'm trying to grow broccoli sprouts and I keep trying to forget. And then I'm like, I gotta get back on that.

Yes, broccoli sprouts are really, really high in glucoraphanin. I also take a supplement that's been used in a lot of clinical studies called AvmaCol. I don't have any affiliation with them, but they've got a really great method of stabilizing the myrosinase enzyme, which is very unstable. It's also very heat sensitive. But before I get sidetracked, sulforaphane is the most potent dietary activator of a what's called transcription factor in our body. It's NRF2. And this is- Yeah, it's a master regulator of, as you mentioned, detoxification enzymes. So they're called phase two detoxification enzymes. Also phase one biotransformation enzymes. So those are enzymes that will convert procarcinogens into carcinogens. So Nrf2 activation will blunt that, it'll stop that from happening. So think things like nitrites being converted into nitrosamines. Nitrites are present in a lot of processed meats. And so Nrf2 activation, typically it's like it gets activated every 80 minutes or so inside of our cells. But if you take sulforaphane, it gets, sorry, it gets activated every 130 minutes. but if you take sulforaphane, it gets activated like every 80 minutes, something like that, where it's like you're getting like a 60% increase in the activation of this important transcription factor, which is regulating just hundreds of different genes that are antioxidant involved in antioxidant function, anti-inflammation. Clinical studies showing that if you give someone broccoli sprout extract or sulforaphane or glucoraphanin plus the enzyme myrosinase, It increases glutathione in plasma and in the brain by FMRi. I mean, this is unbelievable. Glutathione, as you know, it's one of the major, major antioxidants that our body has and it's very important for the brain. Other studies in China where there's a lot of air pollution show that people that take about 40 micromoles of sulforaphane, they start to excrete some of the chemicals that are in air pollution like benzene, which is a carcinogen. They excrete it by 60% after 24 hours. again, because the activation of the phase two detoxification.

I'm thinking of all the people in LA right now.

Exactly. It's very, so I've been telling all my friends in LA.

Toxins get released into the air, dioxin and all the organic compounds and heavy metals and plastics. I mean, it's pretty frightening. So I think people can protect themselves to some degree by upregulating these pathways and taking the right foods and the right supplements.

I think the phytochemicals, again, I'm 100% with you. I think we were supposed to eat these. These are pathways in our body that are activated by a little bit of stress. They're stress response pathways. And the phytochemicals provide that tiny bit of stress that activates them in a way that's powerful enough to not only deal with a little bit of stress, but to like deal with the stress of aging. And anthocyanins from blueberries, I mean, this is another one. We've got so many randomized controlled trials now on giving people blueberry extract powder with actual anthocyanins versus like the, you know, just taste of it. So it's placebo. It improves cognitive function across the lifespan, kids, adolescents, older adults. It lowers damage to DNA. It improves blood flow to the brain. You know, these, this is equivalent to like a cup of blueberries a day. So it's so important to get these phytochemicals. It's not only important to the fruits and the vegetables because of the micronutrients, but the phytochemicals as well. And Bruce would argue that some of these phytochemicals, they're longevity vitamins.

We need them. And he argues that. I mean, that's sort of striking to me as I started digging into this 25, 30 years ago, I was like, wait a minute, how do these molecules know what to do and how do they know to bind to this receptor? It's from a plant. So why is it working in my body? and how is it regulating all these different enzymes or pathways that regulate, you know, immune function and your microbiome? I mean, just, it's, the list goes on and on. And I, and I, and so it occurred to me that, you know, we, we grew through Evolution, consuming over 800 different plant species. And now I think we have three are the main Staples, you know, corn, wheat and soy and, and. rice, depending where you live, and then another 12 make up the total amount of vegetables and plants. We typically like onions and cabbage and whatever carrots and tomatoes. But, like, when you look at the full array of, of, of plants out there, we, we ate all these plants, and those molecules are not there for us. Like, those plants didn't say, oh, gee, I'm gonna, I'm gonna make this, like, sulforaphane so I can help my little human friend over there. They're the plants defense mechanisms, so they're, they're actually there to help. the plants protect themselves against damage, predators, UV radiation from the sun. Pretty much they're their immune system. And so they are a little, can be a little toxic, right? But that's what you're saying. It's a little kind of tiny stress, the xenohormesis kind of concept where you're taking some foreign thing and stressing your body with like a sauna or a cold plunge or being up at altitude or being under the sea level. hyperbaric chamber. These are all stresses on the body that activate our body's own innate healing response.

And so that's kind of how I see these phytochemicals. Exactly, exactly. The antioxidant response element, you were talking about DNA having, there's a sequence in our DNA and genes in our DNA called antioxidant response elements that respond to this NRF2 activation, right? So it is, it's evolved into our DNA and there's ways to do it, xenohormesis, you're talking about plants and phytochemicals exercise, all these different ways that were meant to basically stress ourselves a little bit, right? And not just sit and be sedentary and have all the calories we want and consume all the ultra processed foods.

I mean, Instacart, holy cow, terrible. I mean, it's crazy. You don't actually have to leave your house with Amazon, Instacart, like, Uber Eats or whatever. you don't need to go anywhere.

Yeah, and we really do need to move. I mean, it's not an add-on. It has to be something that's part of your hygiene that you do every day, like brushing your teeth. You have to do it. It's not, like even if it's just 10 minutes of exercise, you have to do it. It makes a difference. And our bodies need it. You're depriving your body of it if you don't.

Okay, so let's kind of back up a little bit. We were talking about all these incredible things, and yes, exercise 100%. but that's another podcast. This one is about micronutrients, the widespread deficiency we have in the population that's undiagnosed, that's not tested for, that people walk around with, that's fixable for pennies a day at levels that are relatively infinitesimally small. Like when you, for example, eat a piece of chicken breast, it's four ounces, that's 30 grams. we're talking about milligrams or sometimes microgram doses, like tiny little bits of stuff in micronutrients can have profound effects on our well-being and our health, on our mental health, our risk for chronic diseases. And, and yet most of us are walking around in this invisible cloud of insufficiency or deficiency and, and have no clue. And then you know a doctor and a practitioner, but you're like a PhD doctor. not like an MD doctor. What do you recommend? And does it have to be difficult and onerous and expensive? How do you sort of stack the deck so you're getting the basic things you need and not running into this trouble?

Yeah, I do have some of the basic things that I think, well, that I take, but also I think that would help a majority of people that are insufficient in a lot of these micronutrients. and first and foremost, vitamin D supplement. And again, I think generally speaking, vitamin D, 4,000 IU's a day, pretty, for the most part, gets people to a sufficient-ish level. You have to do a blood test to really know for certain. You may have to take a little more, but starting at 4,000 IU's a day, which is the upper tolerable intake, is safe.

And this is actually by the National Academy of Sciences saying this is a safe level.

Exactly. Number two, omega-3 fatty acids. And, you know, this is something where Bill Harris has published studies, published studies looking at how do you get someone who is low omega-3 index, so 4% omega-3 index, up to an 8%. Turns out it takes close to about two grams a day. Two grams of EPA and DHA.

So when you get this for clarification purposes, if you get a pill and it says a gram of fish oil, It might not have a gram of EPA and DHA. It might be like 300 or 200 milligrams. So you have to look at the concentration of EPA and DHA in the milligram amounts on the label. Otherwise, you know, it might take one pill or it could take five pills.

Exactly. So that, I think, is a pretty simple solution. So one to two grams? 1.5 to two grams. You get most people that are in a 4% low range to an 8% low range.

And the balance of EPA and DHA, does it matter?

Not really.

Is it 50/50?

Usually it's like a two to one ratio. BHA. Yeah, for the most part, something close to that.

Okay.

But I wouldn't sweat the small stuff. Like number three and number four kind of tie, but I think I think a multivitamin is a really good insurance because, you know, there's selenium, boron, you know, boron. Yeah, there's, you know, the B vitamins, you know, you're getting, there's vitamin A, there's so many different micronutrients and that really covers a lot of the bases. so I think a pretty high quality multivitamin is good along with magnesium. So magnesium, because such a large percentage of people are not getting enough magnesium, it is so important for a variety of, you know, processes, DNA damage, brain function, muscle function, you know, people that are physically active, they sweat out magnesium, so you might need anywhere between 10 to 20% more than the RDA.

And stress and coffee also.

Stress and alcohol. Exactly.

So you're like, what is the American life? stressed, coffee and alcohol. That's exactly right. That's why we're all deficient.

We're literally peed out. Yes. And so you want to make sure you're getting an organic salt. So that would be something like magnesium citrate, magnesium malate, magnesium glycinate and- Citrate if you're constipated.

Right. So those are the organic salts which are more bioavailable. Tell a funny story. I just aside, I was in the hospital recently for a back surgery and I wanted to get magnesium and I talked to the hospitalist and he gave me magnesium oxide and I'm like, that's not bioavailable. And I sort of went through this with him and like you did. Yeah, it wasn't as confrontational as that, but, but, you know, he's like, oh, you're right. I look it up and actually, no, true. I'm like, yep. So, but that's the main nutrient form of magnesium that you get in, in a lot of the supplements that you buy over the counter because it's the cheapest form. So magnesium oxide, if you see that on the label, just skip over.

Right. So that would be another one. And then I add to my essentials the sulforaphane. I used to sprout and I no longer do that because life is busy. My excuses. Yeah, I'm, I'm, who knows.

So, you're busy telling the world how to eat better and be healthy.

It's like the worst thing you can do for your health. But I trust the science that I've read looking at the supplement that I which again, it's a really good supplement, Abmecall, and they have about the advanced formula is what I take, I take.

About two to four a day depending.

On the-: and we'll put the link in the show notes for that. They're great, and they like publish studies on them, improving autism, so it's affecting the brain, so it's approved autism spectrum disorder in kids with autism, adolescents with autism, but it's a very strong activator.

Of glutathione, right, so NRF2 pathway. So that's my phytochemical. I actually wrote a blog about glutathione years ago. If anybody wants to sort of find out more about glutathione, go to Hymen and Glutathione and you'll find it. I mean, it's kind of the master detoxifier, the master antioxidant, the master immune regulator. It's like it's so critical and you get it through some of these plant foods. You get it by sulfur containing amino acids, you know, which are found often.

In animal foods or in whey protein. It's a great source. It is, yeah. So it's a major, major antioxidant in the body. So I think those are really some.

Of the- Vitamin D, fish oil. Vitamin D4000, fish oil, one or two grams of the actual EPDHA, a multivitamin and high quality, high quality, meaning it shouldn't be blue or purple or green or yellow and comes in tetracyanium and dyes and should be just, you know, the right and, and the, the bioavailability, the formula nutrient matters. I mean, I, I think you and I both done a lot of work on this and people can dig around, but it's, it's not just like go to get your, you know, Walgreens or CVS multivitamin. A little more judicious. And then magnesium. And how much magnesium?

You know, it depends. So some people get a laxative effect and they want that.

That's what's great.

Even with higher doses of other forms they can. But yeah, so I mean, I think it depends on your diet. Like if you're not eating a lot of plants, shame on you, you need to increase that. But you know, about 250 300 milligrams, you know, is a good range. Now, if you're trying to treat like migraines and stuff, you might have to go higher, like some studies show like 600 milligrams. And then there's the form of magnesium, magnesium threonate, that's thought to cross the blood-brain barrier more effectively for brain health, 'cause magnesium doesn't cross the blood-brain barrier very well. But magnesium threonate isn't essentially, it's not necessarily gonna do the DNA damage, repair aspect of magnesium. So make sure you're getting both if you're doing that. Yeah, so for me, I take about 250 milligrams, maybe 300 milligrams.

Yeah, it depends on you. I remember I had a big magnesium aha when I had a patient decades ago who was a radiology resident, a radiation oncology resident at Mayo Clinic, and she had debilitating migraines. I mean, she saw the best doctors at Mayo Clinic. She says everybody, she tried every drug, she'd done everything, and she came to see me and we took a history. Amazing thing to do in medicine these days is to take an in-depth medical history, but it's like critical. I'm being facetious, but like, they don't.

Doctors only know the root cause.

Yeah, I mean, I have a 32 page questionnaire, so I was like, oh, you're constipated. Oh, you have muscle twitches and muscle cramps. and you have headaches and you have anxiety and you have insomnia and you have palpitations. Hmm, this sounds like pretty severe magnesium deficiency. So why don't we load you up? And so we gave her like 1200 milligrams of magnesium. Like migraines just went away and she was fine and everything else kind of corrected. And so she had all these, quote, different problems, right? Everything constipation to insomnia to palpitations, which you don't think are related, but they're all connected. as the body's one system. And that's what I'm talking about. These nutrients have so many different functions and they're so critical. So anybody listening to you, you can't really get away from the fact that we live in a nutritionally depleted world, no matter how hard you try, even the foods, if you're eating organic, may not have the nutrients that they did 50 years ago. And most of us should test. And that's why I created Functional Health with my co-founders to allow people access to this data because they weren't getting it. Like you said, doctors like, oh, you don't need vitamin D. Why bother testing? that's what people are facing. And then, you know, just take a multivitamin, fish oil, vitamin D, magnesium, and.

Then, you know, maybe a broccoli pill.

Yeah.

Then there's a bunch of other things.

You could add to that list as you're going through this. That's a dollar or two a day, you know, and, and that's not an insignificant amount of money. But, you know, given the, the benefits, you know, the, the risk benefit, cost benefit ratio is pretty good on this.

It is. It's amazing. I mean, I, I I think it's, as Bruce would say, it's affordable, it's easily correctable for pretty cheap, and it will have a huge difference in the way you age.

Yeah, this is amazing. So we're going to link to a lot of these studies from Bruce Ames, from your work. I want people to follow you, to learn about what you're doing, to listen to your great podcast, Family Fitness. You've got a great website. Tell us all the places that we can find you and learn more about your work and keep up with science.

Okay, great. Thank you. So I have a podcast. It's called found my fitness. I'm on, you know, YouTube, which I.

Hope to be on someday.

Yeah. Let me know when you're in San Diego.

Okay. All right.

So found my fitness. It's on YouTube. It's on Apple podcast, Spotify. I have a website, foundmyfitness.com. and I also, I'm on, you know, social media, Instagram X as found my fitness. Or you can look up Rhonda Patrick. I have some free guys out there. I've won on Omega-3 we talked a lot about it. So how choose a good Omega-3 supplement. So I kind of have a guide on that in terms of like, and I talked about some of the science of Omega-3. So you can find that at omega3guide.com.

And then I have free guides on how to do this and go into.

More detail and have the scientific papers and yeah. And then I have another free guide on improving brain health through brain-derived neurotrophic factor and a variety of exercise protocols and polyphenol protocols that have been published to improve brain health. and that's bdnfprotocols.com, you can find that there. I have a new guide out, How to Train from all the exports that I've had on the podcast.

Oh, I want to see that one.

It's a good one. It's How to Train, so it's like to improve VO2 max, we talked about that. How to Train to improve muscle mass, strength, function, and it's according to all the incredible experts that I've had on my podcast, and that is the howtotrainguide.com, so those are all just free information that people can get by going and downloading the guide. So, thank you so much, Mark, for having me on the podcast. Very interesting discussion. We share a lot of common passions with nutrition and micronutrients. Totally.

Totally. And, you know, we didn't cover a thousand topics from protein to exercise to hermesis. So I think I can see three or four more podcasts. I'd love to have you back to talk about these things because there's so many people out there who are, quote, health influencers. who don't have a degree who may be educated some better than others. I'm not saying you need a degree to be smart or to have an opinion, but there's a lot of noise out there and if people want signal and they want the kind of juicy truth, go to Rhonda.

Appreciate it. Thank you, Mark.

If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. reach out. I'd love to hear your comments and questions. Don't forget to rate, review and subscribe to the Dr. Hyman Show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on the Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic and Function Health where I am Chief Medical Officer. This podcast represents my opinions and my guests' opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my the Ultra Wellness Center at ultrawellnesscenter.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public. So I'd like to express gratitude to sponsors that made today's podcast possible. Thanks so much again for listening. Don't forget, there's a way to listen completely ad-free. With Hyman Plus on Apple Podcasts, you can enjoy every episode without any breaks. Just open Apple Podcasts and tap Try Free to start your seven-day free trial.