The Internal Antioxidant System (The Most Underrated Factor In Health) with Dr. Chris Masterjohn Ph.D.

Content By: Ari Whitten

The internal antioxidant systemIn this episode, I am speaking with Dr. Chris Masterjohn—who has a Ph.D. in Nutritional Science and is widely regarded as one of the top nutritional biochemistry experts in the world—about the science on the body’s internal antioxidant system.

In this podcast, Dr. Masterjohn will cover:

  • Why our body’s antioxidant defense system is maybe the most underrated factor in health and energy levels
  • Why the theory of free radicals is outdated (and it’s a HUGE mistake to think you need to constantly neutralize free radicals)
  • What is oxidative stress? And why it’s critical to understand how it differs from “oxidative damage.”
  • The secret key to building your body’s resistance to oxidative stress
  • How vitamin C can preserve your health (How much vitamin C should you actually consume? And how should you get it — food or supplements?)
  • How oxidative stress and free radicals affect your health and energy levels
  • Should you get your iron and selenium levels tested?
  • The vitamins and minerals that build and strengthen your internal antioxidant system
  • How to increase your iron levels (And the shocking truth about iron absorption)
  • The two keys to building up your internal antioxidant defense system to prevent cellular damage (the damage that drives many diseases and aging itself)
  • The must-have tool for eliminating any potential nutrient deficiency

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The Internal Antioxidant System (The Most Underrated Factor In Health) with Dr. Chris Masterjohn Ph.D. – Transcript

Ari Whitten:  Everyone, welcome back to the Energy Blueprint Podcast. I am your host Ari Whitten and today I have with me again for the third time Dr. Chris Masterjohn. I’ll give you the brief intro for Chris. He has a Ph.D. in nutritional sciences and, well, I’ll just tell you from my perspective I consider him one of the world’s top experts on nutritional biochemistry and especially as it pertains to anything related to vitamins and minerals. So, he is really a brilliant guy when it comes to this stuff and I’m excited to have him on again and that is why he is here for the third time.

Also, I want to mention very quickly he’s got a wonderful, amazing new e-book called “Testing Nutritional Status: The Ultimate Cheat Sheet .” And you can get that at And then you can get a 20% discount if you go to that “/Ari”. And basically, this is a resource for people to learn about, to basically figure out, it’s sort of like a roadmap or a blueprint to figure out what potential nutritional deficiencies might be causing certain symptoms. And then, you know, kind of zero in on those specific things and then test it in various ways. And he gives you a guide to the best lab test to get and how to correct those deficiencies. So, this is for anybody who is health conscious which is pretty much everybody who is listening to this Podcast. This is a must-have tool, highly, highly recommended. So, with that said, welcome again Chris.

Dr. Chris Masterjohn:  Thanks, Ari, it’s good to be here.


What is the body’s antioxidant system? And why it is important

Ari Whitten:  Yeah. So, I have a long list of disconnected topics for us to talk about, but fascinating stuff that you are an expert in. On the last Podcast we talked about cholesterol and heart disease, and you know, kind of all aspects of that which was a great topic. On this Podcast, I want to talk to you about the body’s antioxidant system and some kind of corollaries of that.

In particular, I think this is one of the most underrated topics and least talked about topics, but it is one of the most important topics in health. And so, there’s also some myths to be debunked here, but kind of give people an overview of what the body’s antioxidant system is all about and why it matters.

Dr. Chris Masterjohn:  Yeah, I think from a big picture level the best way to think about oxidative stress is as the wear and tear that happens on your system and the wear and tear that happens naturally as you age, but then it accelerates under certain conditions. So, if you are aging, and of course age really is just the accumulation of insults over time. I mean underneath what we call aging there has got to be a natural process of evolution. But layered on to that is just the accumulation of so many insults from our environment, from diseases that are happening within us and so on.

And so normal metabolism generates oxidants that cause oxidative stress which is that wear and tear on our tissues. And that is why, no matter how healthy you are, as you get older you will have accumulated more and more exposure to those natural oxidants just generated as a natural byproduct of metabolism. But if you have a metabolic disorder, like if you have diabetes for example, then because there are inefficiencies in your metabolism and things going wrong in your metabolism you are generating far more of these oxidants. So metabolic problems is one thing. Exposure to toxins, whether that is environmental toxins from gasoline or plastic or, you know, whatever industrial activity, or it is exposure to ethanol from all the drinks you are having or it is exposure to cigarette smoke from what you are smoking or what someone else is smoking in the enclosed room with you. Exposure to any of those things can accelerate oxidative stress.

Now, if you want to get a little bit more technical, one thing that we have appreciated mostly over the last 10ish years, I mean really it goes back a little further than that but we are really, more and more it is really accelerating the degree to which we are starting to appreciate this in the scientific community is that these oxidants are not just causing damage. They are actually normal products of metabolism which have regulatory roles. And so, if you go back to, “Why does normal metabolism generate these oxidants?” Well one of the things that happens is because a certain percentage of the fuel you have burned in your mitochondria are generating these oxidants, they will have feedback loops where if you start generating too many oxidants then they will regulate pathways that stop energy from coming into the mitochondria because, as a feedback loop to prevent damage because they’re exposing an inefficiency in your ability to burn that energy and they are shutting down the energy burning to prevent further damage.

So, there are things like that. But that means that if you have something wrong with your metabolism that is generating too many oxidants, then maybe it is just that adaptation that causes problems, right? Because you may not be causing a lot of damage to your body. You may not see the wrinkles developing in your skin from damaged collagen, but you might feel like crap because your mitochondria are always in self-protection mode by using these oxidants to turn themselves off essentially. And so, people who are more sophisticated in talking about oxidative stress and damage will separate the discussion into oxidative stress, which is either dysregulation of the pathways or regulation of pathways that it is proper but bad. So, like let’s take that example that I just gave. The mitochondria shut down their burning of energy when it is not safe for them to burn energy.

Well, on the one hand maybe the oxidants are generated by the mitochondria and they are part of that feedback loop. On the other hand, maybe you have next to that some inflammation going on and you have this immune cell that is trying to kill pathogens by making lots of oxidants and the purpose of those oxidants is to kill the pathogens. But because they are right next door then the oxidants start leaking over. And if there’s a lot of them, maybe they leak into the cell and maybe they shut down the mitochondria because of the signaling pathway that the mitochondria are supposed to use. So, it’s sort of like, it is not even a hijacking because there is no deliberate process here. It’s just an accidental thing where the right normal regulatory role is misfiring.

Ari Whitten:  Yeah. Do you mind if I interject a couple things here?

Dr. Chris Masterjohn:  Oh yeah, go ahead.


The old paradigm on free radicals – and why it is outdated

Ari Whitten:  Okay. So first of all, I just want to point out to everybody listening mitochondria obviously are our body’s cellular energy generators. So, the links here to energy levels should be very clear. That if you have this kind of oxidative stress going on that is leading to mitochondrial shutdown, you know, one of the key symptoms on a subjective level as far as what a person would feel of this happening is of course fatigue. Now I want to sort of present a frame to you that I think will be helpful for a lot of people to understand some of these things because probably some of what you just said is over a lot of people’s heads.

So, the typical way of thinking about free radicals and antioxidants is free radicals are bad, free radicals damage our cells and we need more antioxidants to neutralize the free radicals. And most people think about this, like, you know, free radicals are just sort of bad period. So, the more antioxidants we can dump into our system to neutralize them and keep them as low as possible the better off we’ll be. So why is that thinking wrong?

Dr. Chris Masterjohn:  So that thinking is outdated. Around 1985 there was a landmark paper where scientists came out and said simple definition of oxidative stress is an imbalance between too many oxidants and not enough antioxidants. In that framework, you say, “Oh, I want less oxidants, fewer oxidants and I want more antioxidants.” That has become very outdated because we have realized that these oxidants are playing a normal role in cell metabolism to regulate the pathways. So back then you would think of oxidative stress… You wouldn’t separate oxidative stress and oxidative damage because it’s all just one thing. Having too many oxidants doing things they are not supposed to and causing damage. What we are realizing now is that your mitochondria are the powerhouse of the cell is supposed to generate a little tiny bit of these oxidants during metabolism because it helps gauge how much energy should be coming in.

But like we were just talking about, that normal regulatory role can cause problems, right? In the ideal situation, you have those oxidants and they are just, you know if you have a trillion cells in your body and one cell is overburdened and generates more oxidants and says, “I’m not taking up any glucose from the bloodstream,” for example, no problem. Your blood glucose isn’t even going to go up even though the glucose didn’t go into that cell. Why? Because there are a trillion other cells that are perfectly happy to take up that glucose and you just share the burden. And so it’s just the, you know, in a healthy person, this regulation is happening and it’s doing something positive by helping mitochondria only take on the burdens that they can handle, to be efficient burners of energy, to produce the cellular energy that makes you feel good.

And this, you know, the cells that can take on a better, more of a burden, do. The cells that can’t, don’t. So that’s a good thing, a positive thing. Another positive role would be to help you adapt to changes. So one of the things that helps that happens when you exercise is you generate more of these oxidants and then your body adapts by saying, “Okay, that means I need to make more mitochondria to burn more energy and I need to make more of my own antioxidant protection to burn that energy cleanly.” And then you go home from the exercise, you rest, you re-feed, all those processes happen. The result is you get more fit. So, one of the things that people are interested in is this question of can you actually do too much? Can you actually prevent getting fit in response to exercise by trying to suppress the generation of oxidants when we know that generating oxidants is part of what produces the fitness response to exercise?

Ari Whitten:  Right. And just to be clear, like it used to be thought maybe 10 plus years ago or maybe even for a lot of people more recently than that, it was recommended for a long time or it was thought for a long time that like exercise is good. We know that exercise is associated with disease prevention benefits of various kinds. We know it is very clearly healthy for us. But the problem with exercise is that it creates this burst of free radicals. And so, what if we can do the exercise and get the benefits but take antioxidant supplements before, after, or before and after the exercise, get the benefits without the harms of exercise. Now, why, you know, obviously there are several studies that tested this, why did that turn out to be misguided?

Dr. Chris Masterjohn:  It turned out to be misguided because those oxidants are what cause the fitness response. I mean that is the simple answer. And it is not, I mean, there’s a whole other topic that is very analogous which is inflammation. You know, we are very down on inflammation and people think the same thing. Like, “Oh, I will exercise and then I’ll load up on NSAIDs,” the common anti-inflammatory drugs that you can buy at the drug store to prevent the soreness and the other issues that happen. And that also prevents the adaptations to exercise. So, these oxidants are a part of a normal signaling process that help your body communicate what is going on and what to do. And so, if exercise generates more of them it is because exercise wants, I mean, you know, wants you to be more fit and those oxidants are the signal that communicates that that helps you go from exercise to fitness.

Ari Whitten:  Can you go a little bit more in-depth on that to what specifically are the reactive oxygen species or the free radicals, what are they triggering? What adaptations are they triggering like let’s say in response to exercise? Or maybe you can either potentially also include some other hormetic stressors, things like sauna exposure or other types of hormesis as well.

Dr. Chris Masterjohn:  Sure. So, there is a few, there is quite a jumble of overlap in terminology here. So, I like the word oxidants because it’s sort of very generic. But within that framework, you have reactive oxygen species which is anything that falls into this category of oxidants that contains oxygen which is basically all of them. Then you have reactive nitrogen species. That is ROS and RNS. And reactive nitrogen species usually contain oxygen, but they also contain nitrogen.

And then free radicals. A free radical technically is something that has an unpaired electron and that goes back to chemistry. All electrons want to exist in pairs. If one of them is missing, then that atom has a voracious appetite to pair up that electron. And so, it’ll take anything in its path to get that electron so free radicals are extremely reactive. But most of the oxidants… I don’t use free radicals in the general terminology usually because most of your oxidant exposure is not to free radicals. So, for example, in the electron transport chain, which is where you generate your ATP which is the main energy currency of the cell, you have oxygen and normally you are adding electrons and hydrogens to it to make water. But if you add fewer electrons to it and just add one electron to it you’re going to get superoxide which is a free radical. It is a reactive oxygen species.

It’s an oxidant. It’s not a reactive nitrogen species because it doesn’t contain nitrogen. Because it’s a free radical, incredibly reactive. It’s so reactive that it will almost instantaneously be converted into hydrogen peroxide. Hydrogen peroxide is quite toxic. You probably have a bottle of it in your cabinet because you pour it on, you get a wound and you pour hydrogen peroxide on it. You have really good defenses to it to convert it to water. But the pathogens that are going to infect your wound don’t. And so, it just kills them, right? So, this is highly reactive stuff. Hydrogen peroxide is not a free radical. And so, if you look at the cell’s exposure to these things, the exposure to hydrogen peroxide is probably, you know, especially in a healthy person but even in a lot of disease states, hydrogen peroxide can be the main signaling molecule. And superoxide is just going to be like a very minor portion of that. So, most of what… In fact, there was a guy named Dean Jones who is a specialist here.

He wrote a paper called, “The Radical-Free Biology of Oxidative Stress.” And he made it, “Radical-Free” instead of “Free Radical” because he is saying that most of this doesn’t have anything to do with free radicals. So, in that, imagine, I mean I’m simplifying this but imagine that hydrogen peroxide is the main thing that is being generated here. So, in normal cell metabolism, you are always generating a little bit of hydrogen peroxide instead of water in the electron transport chain. That hydrogen peroxide is going to do a handful of things. One of those is that it is going to shut down the incoming energy. So, it’s going to shut off glucose transport at the cell membrane. That glucose is not going to make it into the cell. It’s going to be left in the blood. Not cause high blood glucose because the cell next door just takes that glucose up. But if the preponderance of the cells in your body is not taking up glucose your blood glucose will rise. And so, on the one hand, this plays a positive role in the proper allocation of resources. Because if you’re a healthy person in energy balance with no metabolic disorder, you just have some cells that can’t handle the glucose load. They give it to the next cell over and nothing bad happens. But, if you have someone who the whole preponderance of the cells in their body are not taking up glucose, they are going to wind up with diabetes. So, this is playing a role in the development of diabetes even though it’s playing a role in normal healthy metabolism. Another thing that it is going to do, is prevent you from burning fatty acids. And that is going to primarily happen not at the level of taking fatty acids up into the cell.

It’s going to happen at the level of the outer mitochondrial membrane. So those fatty acids are there, but they can’t get into the mitochondria where they would be burned for energy. And so even though you are testing someone’s blood glucose when you are concerned about diabetes, and you are probably in most cases not testing their fatty acid levels. In a research study, you would test their fatty acid levels and you would see diabetics have very high levels of free fatty acids in their blood. And there is a couple of reasons for that, but one of them is that oxidants such as hydrogen peroxide are preventing the fatty acids from getting into the mitochondria and they are all being left over. And so even though they can get into the cell, if they are not being burned for energy, they build up and the building up of them, like the cell, is just too overstuffed with the fatty acids and it’s not going to take as many up from the blood.

Another thing that they do is they help you… So that’s on the one hand. Like if you are in an energetic crisis and you’re like, “Geez, I can’t handle this energy load. I’m generating all these oxidants.” You are going to have two responses. One is, “Right now I’m not ready to take up any more energy.” And that’s the stuff we just talked about. No glucose, no fatty acids. The other is, “Geez, I got to build up a better capacity to burn energy.” So, you want to do two things. You want to make more mitochondria and that is called mitochondrial biogenesis. And the other thing you want to do is you want to burn that energy cleanly, so you are going to make greater antioxidant protection. And so, there are genes, some of your genetic information is in the nucleus. Some of the information is in the mitochondria. You have hydrogen peroxide as a key signaling molecule acting on all those genes to regulate this very broad umbrella set of genes related to burning energy and burning it cleanly.

So, the genes that regulate mitochondrial biogenesis are regulated there. And then also antioxidant protection is the whole antioxidant network. And that’s sort of like a whole, I mean we can open that box if you want to, but, that is a bunch of enzymes, a bunch of, you know, a couple of small molecules that are important that are all going to act in concert to help you minimize, to help you burn energy without generating all that hydrogen peroxide. So, in effect, your hydrogen peroxide might go up temporarily, but it sets into motion all these things that help it go back down to normal.


The roles of vitamins in oxidant balance

Ari Whitten:  Got you. I think I do want to delve into that topic a bit now. I want to sort of present my perspective on some of this. I want to see whether you agree with me or to what extent you kind of, where you want to take this. But, from what I’ve seen with when it comes to antioxidants supplementation, so taking vitamin C, vitamin E, vitamin A or beta carotene supplements, the research is overwhelmingly clear that these things do not extend lifespan, do not extend longevity. So, going back to kind of the old free radical theory of aging theory that basically the more free radicals that you have in your body or the more oxidants you have in your body the more that they are going to cause damage to different cell parts. And the more that you can take antioxidants, you know, kind of naturally it leads people to think, “Well, if oxidants are causing aging of myself, I want to extend lifespan and prevent these diseases of this oxidant-induced damage by just taking tons of antioxidants pills every day.” And from what I have seen the research is extremely clear that it does not work to either prevent the diseases that were theorized to be prevented by this or to extend longevity and slow the aging process down more broadly.

But what does seem to be relevant and granted there’s some kind of holes in the literature, but what does, in my opinion, seem to be extremely relevant to extending longevity and preventing disease is hormesis and doing the things that strengthen and build the internal antioxidant system. So, from my perspective on this is basically like you can’t override the way that our bodies regulate the balance of oxidants to antioxidants internally through taking antioxidant supplements. But what you can do is through transient metabolic stressors, hormetic stressors, you can build, you can grow more mitochondria, but you can also build that internal antioxidant system. And we know that those hormetic stressors do seem to be linked with disease prevention and extensions of longevity. So, I’m curious kind of what your take is on that whole thing that I just presented there.

Dr. Chris Masterjohn:  When you’re talking about longevity research, are you talking about supplementing animals with these things and then watching how long they live or…?

Ari Whitten:  Are you talking about antioxidant supplements?

Dr. Chris Masterjohn:  Yeah. Well, what you were just saying about not seeing vitamin C or E play out in longevity.

Ari Whitten:  No, I’m talking about human trials.

Dr. Chris Masterjohn:  On disease prevention.

Ari Whitten:  Yeah. So, there are various studies looking at…

Dr. Chris Masterjohn:There are no human trials on longevity directly, right?

Ari Whitten:  Well, looking at all-cause mortality.

Dr. Chris Masterjohn:  Okay.

Ari Whitten:  So, diabetes and vascular disease, various types of cancers have been studied…

Dr. Chris Masterjohn:  Oh, okay. Yeah. All right. I think I see what you are saying. I kind of agree with that in the context of trying, I mean in the context of the free radical theory of aging and the idea of just trying to increase that bucket of antioxidants in a very generic way, I think that is true. However, even the RDA for vitamin C, which is old of course, but the RDA for vitamin C is based partly on the fact that there are consistent observational studies showing that there are, there is a certain plasma level of vitamin C that is associated with the lowest risk of cardiovascular disease and a handful of certain diseases that seem to correlate with vitamin C levels. And there is a level above which you don’t go after that. So, a male is 90 milligrams, a female adult is 75 milligrams. And they, the main markers that they were looking at to derive that were human trials showing the effect on immune function. These were in vitro assays where which means like in a test tube. So, they would feed people the vitamin C and then they would take out their white blood cells and look at markers of how well they were functioning in terms of their ability to defend against pathogens or their ability to support their own antioxidant system. But the numbers that supported immune function and antioxidant protection in these in vitro assays, and I should clarify this, this really isn’t in vitro. It’s really in vivo because they are feeding the people the vitamin C, it’s just that they’re not looking at a disease endpoint. It’s not a clinical trial. It is a human experimental trial looking at in vitro markers of functions, right? Those correlates very well. The numbers with the plasma levels that are associated with minimal disease risk in the bucket of vitamin C responsive diseases. And, I think they were being too conservative in where they set the RDA based on their own data. And I think if you took a somewhat more liberal perspective you would have concluded that 100 to 150 milligrams of vitamin C a day is really where you want to be for maximal protection.

And those include a lot of diseases that are part of the human, the realistic human longevity story. And, the reason I asked you about that is that I’m not that interested in longevity research itself because, like longevity research in animals looks at like how long does the animal live in this highly confined, controlled thing. Whereas like in humans, the reason that we don’t live that long is that we don’t reach the point where we are just dying like that. We are getting heart disease first or we are getting a hip fracture and dying a year later, etc., etc. So, I think at the level of specific diseases, I don’t think anyone is getting 100 to 150 milligrams of vitamin C from foods. The people that are getting that are supplementing it.

Now most people that are supplementing with vitamin C who are like, “Oh, I’m going to live forever,” are probably taking grams of vitamin C. And so, there is probably no benefit to that. Because the level of, I mean they basically like, the level of vitamin C that is likely to maximize your protection against vitamin C responsive diseases is way above what someone, what the average person is getting from whole foods, but well within what you would get from whole foods if you are eating a very vitamin C rich diet, and way below what anyone who is taking vitamin C supplements is getting.

Ari Whitten:  Right. So just to be clear, the studies I was referring to are vitamin C supplementation using, like you said, grams of vitamin C.

Dr. Chris Masterjohn:  Right. And so, and that, like the whole idea of that goes back to Linus Pauling’s idea, you know, decades ago. His theory was that humans, somewhere in the evolutionary pathway we lost the ability to make our own vitamin C. And so, we should get the amount of vitamin C that all the species that make their own vitamin C get, which would equate to us getting several grams a day of vitamin C. But yeah, I don’t, there is not very much evidence at all for grams of vitamin C doing anything to prevent diseases that are relevant to human longevity. With that said, I’m not going to take that to conclude that you only need the hormetic stressor and you don’t need the response, right? Because I think you do need 100 to 150 milligrams of vitamin C., I think you’re probably not getting that. Maybe some of the people listening to this are. But, you know, if I were designing, actually I designed a custom multivitamin for my girlfriend.

I’m pretty sure I put in 150 milligrams of vitamin C. And I, you know, I put a little note in the product insert that said, “The RDA is only this, but the studies that they looked at said 150 milligrams is maximally protective.” Anyway, yeah. So, I would put 100 to 150 milligrams into a multivitamin if I were making a multivitamin. And if I weren’t taking any supplements, I would try to get 100 to 150 milligrams of vitamin C per day from whole foods, which is very doable, but you kind of got to think about it.

Ari Whitten:  Yeah. And by the way, the research that I’ve seen has shown that whole food consumption rich in vitamin C is linked… And, by the way, and other dietary, what they call dietary antioxidants from whole food sources, there are clear links with disease prevention and extension of life.

Dr. Chris Masterjohn:  Yeah. So, it is hard with studies like that., it is very hard to tease apart what you’re saying from what I’m saying because all the foods that are rich in vitamin C are also rich in polyphenols that act as hormetic stressors. So…

Ari Whitten:  Yeah, and to be clear I should also clarify my position is not anti-vitamin C, we should avoid vitamin C. As I said, the research is solid that vitamin C containing whole foods is supportive of good health. But from what I’ve seen, it’s extremely unimpressive when we start talking about grams of supplementation with, you know, concentrated vitamin C or vitamin E.

Dr. Chris Masterjohn:  Yeah. Well, okay. But I mean this is sort of like maybe not practical to really tease apart. But I believe that if you were to make a chemically defined diet that like astronauts are going to live on or something like that, and you take out an extract of plant polyphenols to put in it and you leave out the vitamin C, I think you’re going to do some damage.

Ari Whitten:  Yeah, I’m with you. I agree.

Dr. Chris Masterjohn:  So, that is not whole foods, right? It’s totally divorced from the whole food context. But the amount of vitamin C that is in those whole foods is an operative factor as well as the other thing. Like, so if you just took the 150 milligrams of vitamin C and you left out the hormetic stressors, you are going to have a problem as well. So, but the, you know, the end result is like if we zoom back up to the big picture, right? We have oxidative stress which is either proper regulation of the pathway in a bad context that makes you feel like crap, right? So like way too much energy demands that are placed on your body, natural signaling shutting it down, you feel terrible because you shut down your energy metabolism. Or, dysregulation pathways from inflammation or other sources like that.

And then there is the oxidative damage, which is just damage to the tissues and that, you know, if it’s on the surface you see that. And then to protect ourselves against that we have an antioxidant system and there are two ways of supporting that system. One is to provide the raw materials to that system so it can function properly. And the other is that components of the system, not all the components but actually the vast majority of the components are synthesized by our bodies. Some of the components are essential nutrients. Some of the components are synthesized by our bodies. The ones that are synthesized, we make more of those components making more of the full system in response to hormetic stress. So, if you want to nourish that system you need the hormetic stressors like you were emphasizing.

And you also need the raw materials which are the essential nutrients. So, vitamin C, vitamin E, zinc, copper, manganese, selenium, and protein are, oh, and iron. I left out iron. People think of iron as a pro-oxidant, but iron is also an essential part of the antioxidant thing. So, the raw materials and the hormetic stressors are the two key parts of the picture.


The link between hormesis and the antioxidant system

Ari Whitten:  Okay. So, this is perfect. So, first of all, let’s, I want to dig into the raw materials part more. But let’s talk, just kind of connecting the dots back to what you were talking about before as far as oxidative stress and oxidative damage. How does the internal antioxidant system relate to that? So, like in other words if we build up this internal antioxidant system well enough through these two avenues of the building blocks plus the hormetic stress, what are the benefits of doing that as far as how it relates to oxidative damage?

Dr. Chris Masterjohn:  The goals of the antioxidant system are twofold. One is to prevent oxidative damage entirely. And so, like that whole category is just, there’s no known benefit to it, it’s just damage. And then in the other category, we have the regulatory roles of the oxidants. And when those regulatory roles go wrong, that’s oxidative stress. When those regulatory roles go right, that is normal metabolism. So, antioxidant system is trying to shut oxidative damage down to zero and is trying to shift the oxidants away from bad roles, which I call pathological roles, and into good roles, which I call physiological roles.


The connection between healthy mitochondria and the internal antioxidant system

Ari Whitten: Yeah. With that in mind, going back to kind of how the mitochondria fit into this, would you expect the mitochondria to be more likely to stay online and to be less easily shut down and less susceptible to being overwhelmed by oxidative stress and kind of go into that shutdown state if you have more mitochondria and the internal antioxidant system is built up? You follow what I’m saying?

Dr. Chris Masterjohn:  I think so. Let me try to repeat the question back to you. You’re asking are you more likely to have a proper mitochondrial function and feel good if you have more mitochondria and a robust antioxidant system?

Ari Whitten:  Correct.

Dr. Chris Masterjohn:  Yeah. I think that more mitochondria are, well actually, yeah, both of them. Right? So, if you have more mitochondria then you… So, one of the things that happens is if the number of oxidants that you generate is not just sort of a linear function of your total metabolism. It’s also like when you cross a certain threshold of being overloaded then all of a sudden, it’s really going to spike up. And so, if you have more mitochondria you can distribute the demands of energy metabolism more evenly so that none of the mitochondria are really crossing any key threshold where that is really spiking. And then the other thing, of course, is just that when you do generate the oxidants if you can neutralize them right then and there before they slip away and start slipping into the nucleus where they are going to change gene expression or slipping way out into the edges of the cell where they are going to shut glucose metabolism down, then, you know, then you’re not going to have those adaptive responses of shutting down the incoming energy and turning off energy metabolism.


The building blocks of a healthy antioxidant system

Ari Whitten:  Exactly, exactly what I was getting at. So, okay, so let’s dig more into the building blocks now. So, like what are the key moving pieces of the internal antioxidant defense system and what are some of the key building block materials? I know that you mentioned, you kind of listed them off, but what, and you don’t have to go crazy deep into the nuances of all these different enzymes and systems. I know that you have the ability to do that, but kind of like big picture overview of how the system kind of works and how these building blocks fit into that. What is sort of the key components people need to get from their diet?

Dr. Chris Masterjohn:  Yeah. So, I think the, I think a good way of kind of breaking it down is to think of the antioxidant defense system in terms of preventing dysregulation and the pathway shutting down is primarily happening at the environment immediately around the mitochondria. And, then there is a sort of extension of that system that is protecting, like fully defending against oxidative damage that is not limited to cell membranes but much more focused on protecting the membrane. So if you imagine that an oxygen atom in, or an oxygen molecule rather, in the mitochondria got turned into superoxide, the first thing that you are going to want to do is convert that to hydrogen peroxide as quickly as you can because superoxide is the super reactive free radical. Hydrogen peroxide is very reactive but like many times less.

And then ideally what you want to do is convert that fully to water. And, so it’s sort of a shunt because the normal metabolism oxygen just goes to water. Here you have got to slip out and you’re like, “Shoot that oxygen didn’t go to water.” So, you take a couple extra steps to bring it back to water. Right? Water is a safe thing. And so, in the mitochondria, you have an enzyme called superoxide dismutase that uses manganese as a cofactor. And manganese, you know, this is probably one of the reasons that plant-rich diets are associated with good health because pretty much most of the manganese you get is from plants. And if, there is more that could be said, but like basically the more plants you eat the more manganese you get. Vegetarians have much higher manganese intakes than omnivores.

Vegans have the highest manganese intakes. Then the next thing that you are going to do is you are going to convert the hydrogen peroxide to water. And there are two enzymes that could be involved in doing that. One is called catalase which uses heme iron as a cofactor. And so even though iron can cause oxidative stress when you have too much of it, iron is an essential mineral involved in minimizing oxidative stress. And then there is another enzyme, glutathione peroxidase, which uses selenium as a mineral cofactor. And then also uses glutathione as a cofactor. Glutathione appears all over the place in this system. And it’s not limited to just this system, it does many other things. But inside this system, it does lots of things. And so right there what you are seeing is manganese, selenium, and iron as your nutritional things. And glutathione is a small molecule that you make yourself, but you make it from protein.

And so, you need to eat enough protein, and no one thinks of protein as an antioxidant. But protein is like one of the key things you need to think about when you are thinking about defending yourself against oxidative stress. And that, I guess that is the more practical reason why that 1985 idea of the balance of antioxidants and oxidants is so misleading is because when it comes down to the nutritional implications, you know, no one is talking about iron as an antioxidant. No one is talking about protein as an antioxidant. And yet these are the most important things. Now, if that superoxide has been generated outside the mitochondria, which is very possible because you do have enzymes that produce superoxide outside the mitochondria for various purposes. And your immune system can generate a ton of superoxide. And in fact, in the thyroid gland, you actually deliberately produce superoxide so that you can make hydrogen peroxide because you use the hydrogen peroxide to make thyroid hormone.

Or you can’t make that thyroid hormone without hydrogen peroxide. So, anyway, there is a version of superoxide dismutase in the cytosol that is also the same as the version that gets sent out into your blood. And that uses zinc and copper, both. Can’t have one or the other. It’s zinc and copper. It doesn’t work if you’re missing one of them to do that. So, we add to the list. We had selenium, manganese, and iron. Now we’re adding zinc and copper as essential minerals. Then everything else that I was saying before follows as well. Glutathione is going to be important there. Then that is the main system defending against oxidative stress. If you think about the system as defending against oxidative damage to the lipids in the membranes, vitamin E is going to be inside the cell membrane. It is going to be the first thing that is going to stop oxidative damage. But that vitamin E gets oxidized and needs to be recycled.

Vitamin C comes in and recycles it. Vitamin E is inside the membrane. Vitamin C is at the edge of the membrane, recycles vitamin E. That vitamin C gets recycled by glutathione we now see for the third time. And then glutathione then takes that burden of neutralizing the oxidants. That burden went from the membrane itself to vitamin E to vitamin C to glutathione. Glutathione is going to take it and put it on the system of energy metabolism through an enzyme called glutathione reductase that uses niacin, vitamin B3 and riboflavin, vitamin B2, as cofactors. And then that is now, it is sort of out of the antioxidant system and in the system of energy metabolism. Ultimately you trace that support to protect the cell membrane from damage, you trace it all the way down to glucose. And so, you can draw out on a map where the electron that saved the membrane from damage went from glucose to niacin to riboflavin to glutathione to vitamin C to vitamin E into the fatty acids in the membrane.


The best way to use the “Nutritional cheat sheet” to optimize the internal antioxidant system

Ari Whitten:  Excellent job. It’s not often that I am amazed at someone’s ability to explain very complex concepts. But I am amazed at what you just said. So well done. I want to connect this back to your Testing Nutritional Status Cheat Sheet and kind of what we talked about at the beginning of the Podcast or what I talked about briefly as far as this being sort of a road map for people to help them identify certain deficiencies of compounds and as it relates to their symptoms. What, I’m going to ask this in kind of a big picture, but you can take it specifically with some of these compounds. What kinds of symptoms might someone notice if they have deficiencies in this internal antioxidant system or, and you can address it like that or you can sort of address it as like what kinds of symptoms might someone notice with zinc, copper, manganese, selenium deficiencies or anyone of them?

Dr. Chris Masterjohn:  Right. The way that I organize this in the Cheat Sheet is to put all these in a section on the antioxidant, vitamins and minerals and then to break them down individually. Because, you know, one of the obvious implications here is that if oxidative stresses the wear and tear on your system, you’re going to get worn and torn town if you have a deficiency in any of these things. And that might be fatigue because your mitochondria are shutting down your energy. It could be diabetes because mitochondria shut down their energy burning, and all the energy is being left in the blood, so blood glucose rises. It could be, you know, your skin wrinkles more easily. Like why do I look like a 57-year-old when I’m a 37-year-old? That can be, I mean, that’s an exaggeration, but that, you know, that kind of thing as well.

If you don’t have antioxidant protection, your thyroid gland is going to get all messed up because, so like if you imagine what is happening in the thyroid, in order to make thyroid hormone you need to make a ridiculous amount of hydrogen peroxide. And that is why in the thyroid gland, the thyroid gland contains the highest amount of selenium of any tissue in the body because it needs to protect against that. Well, on the one hand, if you know, in this situation what you do is in the thyroid gland, you sort of like, there’s all these cells, right? And then in the middle, they carve out this territory where they say all the thyroid hormone is going get made in here. And so, they try to shoot the oxidants all into that middle space so that the cells themselves aren’t swimming in hydrogen peroxide.

But you send all this hydrogen peroxide there, you are still going to get some leakage back into the cells because its ability to cross membranes is zero. And so, if the cells don’t have their selenium and selenium is most studied. So, there are a number of trials supplementing selenium for Hashimoto’s thyroiditis and they are promising, they are not perfect. My suspicion is that they would get a lot better results if they bifurcated the people into the people who have good selenium status and bad selenium status. And, you know, that’s the limitation, a lot of trials. But the other thing is, you know, if selenium is important to preventing Hashimoto’s thyroiditis, obviously glutathione is important because what is selenium doing there? It’s acting as the cofactor for glutathione peroxidase. And if you don’t have glutathione there you can put all the selenium there you want and you’re not going to do jack.

Right? So, it’s really the whole antioxidant system that is very important in the thyroid gland. It’s not just selenium. And so, a deficiency in…

Ari Whitten:  A real quick tangent on glutathione. Some people obviously supplement directly with glutathione. Is there any negative feedback loop that is present there where if the body is getting it exogenously, would it not produce as much internally?

Dr. Chris Masterjohn:  There is a negative feedback loop that is definitely there, but no one yet has shown it to be relevant to glutathione supplementation even at levels that are way above what you synthesize every day. And I don’t know why that is. It could be that they are looking at… So, there was a trial, it was six months of supplementing, I forget the dose off the top of my head, but it was big, and I think it was like 2000 milligrams.

But six months of supplementing some glutathione dose way above the total body synthesis did not lower glutathione synthesis in blood cells. I think it might, I can’t remember, probably white blood cells, but I can’t remember for sure. Anyway, the point is no one has been able to show the glutathione synthesis is lower. But I don’t know if that is because the way that it, you know, maybe taking out those blood cells and looking there wasn’t the main place that you should look. Maybe what you would want to look at is a liver biopsy because the liver is the main place where you are making glutathione in terms of a whole-body level. And so, I don’t know. What I do know is that I don’t think it matters. I think if you take out the glutathione it is just going to go right back up.

And so negative feedback loops are usually acute regulations, not long-term regulations. I think it is very different if you are dealing with an endocrine organ because one of the things that, and an endocrinologist would be a better person to talk about this than I would, but, or an endocrine researcher rather. But, one of the things, you know, one of the things with endocrine organs is that the tissue mass is regulated by the need to produce the hormones. And that is why you get goiter when you are hypothyroid or you can get goiter when you are hyperthyroid is because all this pressure is exerted on the thyroid gland to grow, to try to produce more thyroid hormone. And because there is a problem of not being able to, it just keeps growing and growing. Conversely, if you take thyroid hormone your thyroid gland is going to shrink.

And so, you know, you can take testosterone and wind up with testicular atrophy if you don’t do it properly and you do it long-term and you don’t have the dosing right and stuff like that. So, there’s no such thing with glutathione. Like your liver does so many things besides make glutathione that your liver is not going to shrink if you’re taking glutathione. You are just going to inactivate the enzymes involved in glutathione synthesis because that, basically glutathione attaches to the enzyme and decreases its activity. That’s the main thing. So, if all the sudden the glutathione goes away, all of a sudden that enzyme becomes active. So, I don’t think it going to matter that much. And maybe that is what, I would have to go back and look at those studies to be sure I’m not, I don’t remember the exact model, but it might be that they were giving enough time for it to recover.

And so, like you came in fasting that day and they took it out and like the last time you took glutathione was yesterday and it went back up. But it is almost certainly the case that if you’re taking more than… You make like 180 milligrams of glutathione a day. Every supplement is more than that. So, it has to be the case that when you are taking glutathione your production of it goes down. But I just don’t think it matters long-term.

Ari Whitten:  Got you. [crosstalk]

Dr. Chris Masterjohn:  What was the original one?

Ari Whitten: The original thing was like talking about some of the cofactors of the internal antioxidant system. So, you were talking about selenium, glutathione…

Dr. Chris Masterjohn:  Oh, right, right, right. Oh yeah, you were asking me about signs and symptoms. Right. Okay. Sorry, that was a long tangent. Okay.

Ari Whitten:  That was my fault. I distracted you.

Dr. Chris Masterjohn:  It is my fault. I rambled off. Okay, anyway, we don’t have to play the blame game. All right. So, okay. So, in the thyroid gland if you are deficient in any of those things there is a couple things that could happen. One interesting theoretical possibility is if you are not neutralizing hydrogen peroxide enough you might actually make more thyroid hormone than you should because regulating the amount of hydrogen peroxide is actually one of the ways you regulate the thyroid hormone production. People don’t appreciate this, but there is… Glutathione peroxidase is actually in that central depo of thyroid hormone production and it is actually there regulating how much hydrogen peroxide there is to regulate the amount of thyroid hormone that you produce. So, you could wind up producing too much thyroid hormone at least acutely if you don’t have things here. But I think more likely what you’re likely to, what you’re going to see is oxidative damage.

Because if you don’t have the ability to stop hydrogen peroxide from leaking back and damaging the cell, you are going to have damaged tissue there. That is going to elicit inflammation there. So, I really think Hashimoto’s, especially when you view it in light of the promising studies with selenium supplementation, I think Hashimoto’s thyroiditis is basically oxidative damage combined with inflammation in the thyroid gland. So, I think that is going to be one of the central things that you might see.

And then, of course, most chronic diseases, pretty much every chronic disease has a component of oxidative stress. So just generalize the vulnerability to chronic diseases might be what you see. And then there are other things inside you, genetic and otherwise that is going to determine which disease course that takes. And so that might not be the overwhelming thing determining why one person gets cancer and another doesn’t, why one person gets diabetes, and another doesn’t, why one person gets heart disease and why another doesn’t. But if you’re predisposed to heart disease, your heart disease is going to be worse if your antioxidant protection is lagging behind.

If you’re predisposed to get diabetes for other reasons, your diabetes is going to be worse if your antioxidant production is lagging behind and so on. But then the thing is like, you can then take most of these nutrients down to talk about other things that they do. The one that you can’t is vitamin E. Its only well-established role is to protect cell membranes from oxidative damage. And there are lots of studies on other things that vitamin E does. It pretty much all falls into one of two buckets. Either it’s a thing that is a byproduct of its protection against oxidative damage or it’s, you know, some other thing that some form of vitamin E that you don’t normally have high circulating levels of is giving you mega doses.

So like tocotrienols are a sub-fraction of vitamin E that in really high doses that in capsules that are designed to help you absorb more than you would from food to lower your cholesterol. But that’s not really, that’s not like a role of vitamin E. So, I wouldn’t list high cholesterol as a symptom of vitamin E deficiency. Vitamin E deficiency has been associated with neurologic, very bad neurological damage in cases where there is malabsorption or there is a genetic defect in its circulation. But that’s kind of, but that even still, that is a byproduct of cell membrane damage and it is associated with hemolysis, which is the breaking apart of your red blood cells. That’s because of its need to protect cell membranes. So, there are things… The thing with vitamin E is those. And most people are not deficient enough to have those things happen unless they have a malabsorption disorder or rare genetic disorder in circulation.

But, to the extent those things are unique to vitamin E it is because they are focused on the cell membranes falling apart versus, you know, minimizing hydrogen peroxide and its consequences on thyroid hormone, energy metabolism, all those other things that we were talking about. Vitamin C, then the next down component is very well characterized in its deficiency of scurvy. Scurvy has almost nothing to do with oxidative stress and antioxidant production. Basically, it has everything to do with vitamin C as an enzymatic cofactor that is involved in stabilizing collagen. And, it’s not needed to make collagen. It is needed to make that collagen strong and stable. And so, what happens is you produce a lot of dysfunctional collagen in scurvy that leads to bleeding in the inside of your mouth. That could be, probably the most, you know, probably the most sensitive thing that is going to happen is you floss your teeth and your gums bleed.

Not going to say that means you have scurvy because there could be a lot of other causes of that. Pretty much anything that causes your gums to be inflamed is going to do that. But, you know, with someone with very well-developed scurvy, you look inside their mouth and all around the oral cavity just has spontaneous bleeding. They’re not gushing blood out of their mouth. But when you shine a light, a flashlight into their mouth and you’re like, “Oh, there’s all these little spots of blood developing under the skin and in some cases breaking through.” Their hair has become like corkscrew shaped. And I would like really hate to be the person who’s diagnosing someone with kinky hair as having the corkscrew-shaped hairs. Like it is very obvious in someone with straight hair. The curlier your hair you get is sort of like… You know, you look at these case reports and they have a little arrow pointing at the corkscrew hair in the picture and you’re like, “Yeah, you know, I can see that.”

But like if that arrow wasn’t there it would have been kind of hard to pick out. And then you have all kinds of things going wrong inside your own internal organs because collagen isn’t just supporting your skin. At the mucous membrane it’s, I’m sorry, it’s not just supporting your mucous membranes, it is also supporting all of your skin. It’s 95% of the protein in your bones and the membranes that support all your internal organs have a collagen component that is needed to like keep everything in place. So, there’s a lot of other things that would go wrong in vitamin C besides just antioxidant protection. When we were talking before about cardiovascular disease and cancer, that’s more related to its antioxidant role. There are some theoretical things that you could say might happen in vitamin C deficiency and these are not well demonstrated in scurvy cases.

But if you did a look at what vitamin C does, there are some interesting things you point out. So, vitamin C, and actually copper is another antioxidant mineral that we talked about. Copper and vitamins C cooperate together. And actually, zinc is here too. So, zinc, copper and vitamin C, all part of the antioxidant network, all cooperate to do something that has nothing to do with the antioxidant network and that is to activate half of all neuropeptides. And neuropeptides are, you could think of them as neurotransmitters. In some cases, you think of them as hormones, depending on which ones they are. But they really are neurotransmitters that are big ones, right? So, most neurotransmitters are very small molecules or a single amino acid or maybe two or three amino acids linked together with a dipeptide or tripeptide. These neuropeptides can often be long chains of amino acids.

But these do things like oxytocin is one of them that is called the love hormone by some people. It is basically facilitating the pair bonding response to physical intimacy. So, it helps you bond with your dog when you pet your dog. It helps a nursing mother bond with the child when she is nursing the baby. And it, you know, it really spikes in orgasmic sex with someone that you are in love with. And so, you know, when you want to cuddle after, that is oxytocin. And…

Ari Whitten:  Now I know why you formulated your girlfriend’s multivitamin with extra vitamin C.

Dr. Chris Masterjohn:  Yeah, she doesn’t need it. But anyway, if you notice that if you ever noticed that your girlfriend or wife is more important to her to cuddle after sex than it is to you as a dude because they have higher oxytocin levels. You still get the oxytocin spike; it is just calibrated to the male level of oxytocin and the male brain’s response to oxytocin.

So, it is a little bit different than it plays out in a woman, but it is the same principle. Another one is vasopressin which stops you from peeing. And you always have to make some of that to regulate how much water you use relative to minerals. But it’s regulated by your circadian rhythm and so your circadian rhythm makes it spike at night so that you can sleep enough to not wake up and pee. And so, a lot of these people who are waking up in the middle of the night to pee I think have depressed levels of vasopressin and it could be that their circadian rhythm is just messed up, right? Because if you’re not sleeping regularly and you don’t have a regular light hygiene program, then you might not have any circadian rhythm and you might not have a spike in vasopressin. And so there might not be any reason as far as your body is concerned to go longer than you usually would without peeing.

Ari Whitten:  Yeah. And there is research, I don’t know, you’ve probably seen it based on what you are, that you are talking about it. But there is research linking circadian rhythm disruption or circadian rhythm, you know, function with nocturia, with nighttime urination.

Dr. Chris Masterjohn:  Right. And so, this kind of is very analogous to what we were talking about, the hormetic stressor versus the raw material. You need both. And so, you need, in this case, it is the circadian rhythm that is the regulator rather than the hormetic stress. You still need the raw materials, right? So circadian disruption is probably almost universal in modern society. And so that probably more often than not is a limiting factor.

But, you know, vitamin C levels, copper levels and zinc levels in the brain are also going to determine your ability to obey your circadian rhythm by making vasopressin. And, there are a number of other neuropeptides that require this that are involved in appetite regulation, pain regulation, libido, and interestingly, all of the releasing hormones made by the hypothalamus that control the pituitaries’ control of endocrine organs, right? So, a lot of people are probably familiar with the term HPA-axis, hypothalamus, pituitary, adrenal axis. And then there is the hypothalamus, pituitary, thyroid axis and the hypothalamus, pituitary, gonadal axis that are responsible respectively for thyroid hormone and sex hormone production.

All of those hypothalamic hormones are neuropeptides that are biologically activated in this manner using vitamin C, copper and zinc. And so, you know, you can imagine if one of these things is really depleted in the brain that you could have a person walking around with pretty serious fatigue and brain fog. Because if you are not making thyroid hormones, you are not making sex hormones and you are not making adrenal hormones then you are just flattened out all over the place like that would be sort of the, I think the gold standard of diagnosing this hypothetical loss of these nutrients in the brain. And you are going to feel like crap, right? Because if you are hyperthyroid and you just pump, you know, adrenal hormones to compensate for it, you can feel okay. But if you can’t do that, that is when brain fog really sets in. And if you are not making sex hormones either, yeah, you’re going to be out.


The best sources of selenium, zinc, and copper

Ari Whitten:  Yeah. I’m sure that you could go deeper in a lot of these other layers and probably spend five hours on this. But this has been just awesome stuff. I love this conversation on this whole topic. It’s excellent. So, the last thing I want to do is maybe wrap, like kind of connect the dots of what you were just talking about with the building blocks of some of these compounds back to like big picture nutrient intake, food intake. Like what, and this kind of goes back to your book, too, of like… So let’s say you are identifying some of these deficiencies and the symptoms sort of line up with what you are experiencing and maybe you even go the next, the extra mile and get it tested and your show that you have a deficiency in some of these things. So, what is the best way to get these compounds from foods and understanding that this is also a very complex deep topic you could spend a lot of time on? But could you list off like maybe some, what are the best sources of selenium, zinc, copper, things like that?

Dr. Chris Masterjohn:  I think first I would start at a high level and say that if you just wanted a couple of dietary principles like to kind of try to get all of them without thinking too much about it, then I think you want to get enough protein and that is like a half a gram to a gram of protein per pound of body weight. That is also going to help you make enough glutathione so that was very specific. But also, if you get enough protein and you diversify it across meat, fish, shellfish, eggs, and dairy, then that is going to go a long way to provide a lot of these nutrients. Shellfish, in particular, are great sources of at least half of those nutrients. And then if you eat a few cups of vegetables a day and you diversify those across red, orange, yellow and green vegetables, you can put white in there though you don’t really need to. You just diversify the color spectrum but especially red, orange, yellow and green, especially again, at least like a cup of dark green vegetables a day.

That is going to be another key part of it. And then, you know, some people are on low carb diets. But if you are tolerating carbohydrates, if you diversify your carbohydrate load across fruit and then the different types of starches. So whole grains if you tolerate grains. If you don’t you can cut them out. Legumes, starchy tubers and fruits like across that spectrum. Then just those principles are going to help you get enough of everything. If you take individual ones, I think the two that are most important to test are selenium and iron and there are different reasons for each one. So, selenium is largely a function of soil selenium and unfortunately, there are no nice and neat rules to what soils are high and low in selenium. So, if you are looking at iodine, there is a certain pattern of climate that’s dictating where iodine is low and where it is high.

If you are looking at a lot of other minerals, it’s like where have they been tilling the soil the longest and where has the most loss occurred? Selenium results from really ancient geological processes that have absolutely nothing to do with the last hundreds of thousands of years and is totally random. And even worse than that, all of these other minerals play a central role in plants and plants have homeostasis controlling how much they take up from the soil. Plants have no use for selenium and they actually take up selenium as a completely random linear function of soil selenium. And so, you can have plants grown in… If plants are grown in toxic selenium soils, they are going to have toxic levels of selenium in them. Whereas plants could be grown in like toxic levels of copper and they will have more copper, but they are not going to have, you are not going to get copper toxicity from it.

So, I think it’s like totally random, 50/50 regardless of your diet, whether your selenium is high or low. And I think everyone should get their plasma selenium tested at least a couple times, you know, in a given situation where you lived here, you ate the local food. Like, test your selenium while you are eating it because you don’t really know what is in your food. There are other things you could say about it, but I think that is the most important thing to say about it. I mean other people are going to say like, “Eat Brazil nuts.” But, you know, Brazil nuts range 20-fold in selenium because of what I was just saying. And so sure, eat some Brazil nuts but go test your plasma selenium, especially if you are eating like 20 Brazil nuts a day because you don’t have a damn clue how much selenium is in those Brazil nuts.

I’m sorry. But, so iron. It’s because, on the one hand, women who menstruate lose iron in the blood that leaves as menstrual fluid and the need of a woman for iron can range across almost four-fold, a three-and-a-half-fold range based on variation in menstrual flow. And so, I mean, you can guess based on your menstrual flow how much iron you might need. But that is a very good reason to get it tested. And then on the flip side, you can have genes that cause you to not… Most people will stop absorbing iron from their food when they get too much. You can have genes that don’t allow that to function properly and you absorb too much. Men are at very high risk if they have those genes of getting too much iron.

Women who have those genes and a heavy menstrual flow don’t have a damn clue what their iron levels are. Right? And most people don’t know what their genetics are on that, which goes back to the fact that if you are a woman and you can guess based on your menstrual flow you still don’t have a damn clue. Right? So, I think iron and selenium are the two big ones where it is like, even if you don’t have a lot of money and no insurance, you should probably get those tested every once and awhile. But iron in foods is not random. So red meat, shellfish, and organ meats are the best sources of iron.

I’ll tell you, I get most of my iron from plants and I have the genes for hemochromatosis, which means I absorb too much iron from my food and I can eat ridiculous amounts of iron from plants and my iron levels, if I donate blood like once every two years, don’t get out of hand. And meanwhile, there are tons of people out there who are anemic eating tons of iron from plant foods. Plant foods that are rich in iron are also rich in things that inhibit the absorption of iron. And so, if your iron levels aren’t going up even though you are eating ridiculous amounts of iron from plant foods, you need to eat red meats, shellfish, and organ meats, period.

Okay. And then zinc, very aligned with iron. So, oh, and by the way, animal protein causes you to absorb more iron. Plant protein causes you to not absorb iron. Is that ridiculous or what? Right? So, it’s just like no matter what your iron is, right? Anyway, so zinc. A diet that is rich in animal foods and low in whole grains, nuts, seeds, and legumes is going to lead to the highest zinc status. And oysters, beef and cheese are the best sources.

Copper is a little more complicated. Liver is an excellent source of copper. You eat liver once a week, your copper is set. Certain, like basically organ meats in general, shellfish in general, mushrooms, in general, are very good sources of copper and that is the simplest thing to say about it. I already said plant foods are the best source of manganese. And does that cover everything, or did I leave anything out?

Ari Whitten:  Yeah, that is pretty much everything. So…

Dr. Chris Masterjohn:  Oh, fresh fruits and vegetables for vitamin C. If you are a carnivore, eat adrenal glands and pituitary.

Dr. Chris Masterjohn:  Okay, perfect. Okay, so just list off those strategies again, like the big picture. So the protein, veggies…

Oh yeah. Big picture. So, eat a half a gram to a gram of protein per pound of body weight per day. Diversify it across meat, fish, shellfish, dairy, and eggs. Veggies, eat at least a few cups a day, at least a cup of those as dark greens. But try to diversify across the color spectrum. And then the carbohydrates to the extent that you eat them, to the extent you tolerate grains include whole grains. You can cut those out if you want to but diversify your carbohydrates around legumes, starchy tubers, and fruits. And those principles right there will give you, will mostly make sure that you are getting all those nutrients without having to micromanage too much.

Ari Whitten:  Beautiful. This has been for everybody listening, this has been a masterclass on the internal antioxidant system, which is again, in my opinion, one of the most important and underrated topics that almost nobody is talking about or knows much about. I’m pretty convinced that this hour Podcast is now going to be pretty much the best thing on the Internet on this topic maybe other than the other, you know, series of lectures that you’ve done on this topic. So, thank you so much, Chris. This has been awesome. For everybody listening, make sure you go to and grab a copy of Chris’ “Testing Nutritional Status: The Ultimate Cheat Sheet.” Again, must have for everybody who wants to eat optimally and figure out some of the nutritional factors that may be responsible for their symptoms. And hopefully, now that you have just listened to the last hour of this Podcast you now understand why I am so highly recommending that you go get this from Chris.

He is obviously brilliant at what he does. I think there’s nobody better at this particular domain of knowledge. So, get the Cheat Sheet. Do yourself a favor. I think it’s what, 30 bucks or something like that, Chris?

Dr. Chris Masterjohn:  Yeah, I reduced it to $29.99 just for looks. And the 20% discount, too, brings it down to like $23.99.

Ari Whitten:  Okay, cool. So, 24 bucks, guys. This is, I mean, ridiculously cheap for the brilliance, for the amount of wisdom that you are getting packed into this must have. Just go do yourself a favor and get it.

The Internal Antioxidant System (The Most Underrated Factor In Health) with Dr. Chris Masterjohn Ph.D. – Show Notes

What is the body’s antioxidant system? And why it is important (01:40)
The roles of vitamins in oxidant balance (20:16)
The link between hormesis and the antioxidant system (32:27)
The connection between healthy mitochondria and the internal antioxidant system (33:55)
The building blocks of a healthy antioxidant system (35:49)
The best way to use the “Nutritional cheat sheet” to optimize the internal antioxidant system (42:36)
The best sources of selenium, zinc, and copper (1:02:26)



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