Antioxidants are healthy, right? So, to really understand why an antioxidant is healthy, you got to understand first oxidants, then oxidative stress. So let's chat about oxidative stress.
Body Biology with Ryan Goodwin, LifeVantage Chief Marketing Officer, and Brian Dixon, PhD, SVP of Research and Development.
Flip the “Antioxidant” Switch: Turn the Antioxidant Factory on in Your Body Audio Transcript:
Ryan Goodwin:
Hi and welcome to flip the switch. I’m your house to Ryan Goodwin with Dr. Brian Dixon.
Brian Dixon:
Hey everybody.
Ryan Goodwin:
Hello Brian.
Brian Dixon:
Hey, thanks for having me again.
Ryan Goodwin:
Yeah, absolutely. We’re stoked to be chatting about one of my favorite topics here. We’re going to be talking about how to flip the antioxidant switch. So oxidative stress, antioxidants. I think the best place to start is just telling our listeners what oxidative stress is. Because I would imagine that the layman has no idea what that is.
Brian Dixon:
Well, why don’t even take a step back further than that and just even just talk about what even an oxidant is.
Ryan Goodwin:
Totally.
Brian Dixon:
So forgive me if I get too scientific here. And Ryan, you can always reign the scientists back in, and we’ll play a little good cop, bad cop again here. But –
Ryan Goodwin:
Can I be the bad cop?
Brian Dixon:
I’m usually the bad cop. So it’d be a nice role reversal, sure. But when we’re talking about an oxidant for example, what we’re really talking about is the molecular structure of any molecule. And specifically what we’re talking about is what those electrons are doing. So not to get into too much of our bad science chemistry classes, but when you’re thinking about chemical bonds and how even the individual atoms inside of a molecule are held together. If you remember, they’re actually held together by electrons. So electrons like to form almost this cloud or kind of soft attachments that are happening with each other and because they’re sharing these almost magnetic charges through the nucleus of these atoms, and then this interaction of these electrons being spun around outside of each of these atoms. That’s really what’s forming these chemical bonds of the atoms, to make up molecules.
Brian Dixon:
Now the important thing when we’re talking about atoms and how they want to live, you can almost think of them like lovebirds. They want to always be in pairs, so these electrons in a perfect world will pair and mate for life. When we run into problems is when these electrons become unpaired or when we get into some sort of molecular structure where an electron can either be easily accepted, or easily given off. So really the whole name of the game when we’re talking about oxidants, antioxidants, oxidative stress, is really what are these electrons doing inside of these various molecules?
Ryan Goodwin:
Yeah. And when they get unpaired, that’s what a free radical is, right?
Brian Dixon:
Yeah. And there’s –
Ryan Goodwin:
Or it can be.
Brian Dixon:
Yeah. And if there’s a little bit, it’s scientific semantics to some extent. In the general world, non-scientific world, we tend to use oxidants and free radicals interchangeably. But maybe just to clear up some definitions for the one or two people that might care: all oxidants… How do I want to say this? All free radicals are oxidants, but not all oxidants are free radicals. So because the definition, scientifically speaking in redox chemistry, the technical definition of a free radical is having an unpaired electron. So that’s a free radical. So an oxidant can also have an unpaired electron, but an oxidant can also do some other things in biological structures, but they don’t necessarily have to have unpaired electrons. There would just be some interesting things that are happening with the molecular structures and what’s going on with those electrons.
Ryan Goodwin:
Yeah. So now that we understand a little bit more about oxidants and how a free radical can be an oxidant. Let’s get into oxidative stress. Because when it comes into this topic, I feel like the average American or let’s make it even more global; the average person may have heard of antioxidants and their level of understanding usually is: antioxidants are healthy, right? So, to really understand why an antioxidant is healthy, you got to understand first oxidants, then oxidative stress. So let’s chat about oxidative stress.
Brian Dixon:
All right, so oxidative stress. Well, let me take another step back. Again, I apologize, but a lot of people don’t appreciate the fact that in a normal, healthy living organism, we actually need some low level of these oxidants floating around. They’re actually essential for cellular function. In fact, inherent in our DNA, we have the ability to make enzymes that actually produce oxidants. So if you can imagine, but these oxidants are important for a number of biological functions. The thing that’s probably the best characterized is that oxidants are needed for cell division.
Brian Dixon:
So there’s actually an oxidative burst. So for example, one of these enzymes might get up-regulated to actually generate free radicals, and that will be one of the triggers for a cell to grow and then especially divide. So really when we’re talking about this oxidative stress, what we’re really talking about is having a nice healthy balance of oxidants and antioxidants inside of the cell to keep a nice balanced level inside of the cell so the cell can easily determine or go back and forth between a more pro oxidant state or a more antioxidant state depending on what it needs. The problem becomes when the balance falls too far one way or the other. And not to get too derailed off the original question, but there’s also something that can happen inside of the cell called a reductive stress. And that’s when you basically have too much, or too many antioxidants floating around the cell.
Brian Dixon:
Because we’re, we’re trying to achieve this balance. But the term, again coming back to the technical definition of an oxidative stress, is when you’ve really overloaded that balance, the balance tips too far in one direction, and when that balance gets tipped too far in one direction, those oxidants can escape the normal kind of regulatory mechanisms, if you will
Ryan Goodwin:
Yeah. So when you say that oxidative stress is, when that balance is getting out of whack, does that mean that oxidative stress could also mean that you actually don’t have enough oxidants, or does oxidative stress typically mean that it’s swaying in that direction where you’re getting too much oxidants?
Brian Dixon:
Yeah, it would be where the level or that balance has tipped too far towards having too many oxidants around. So again, scientifically, they’ll say you’re more pro oxidant or pro oxidative than antioxidative. And just to maybe even go back and talk about our biology a little bit more, when we’re young… Well, there’s a number of ways you can measure whether or not you’re pro or anti oxidative. But one way they’ll do it is look at, especially like glutathione levels, for example. So if you’re not familiar with what glutathione is, don’t worry. It’s the most important molecule that nobody’s ever heard of. Molecule for molecule in our body other than water, it’s the molecule that is found in our bodies at the highest concentration. It’s found in really astronomically high concentrations, especially in our liver. So glutathione exists in one of three states, well four actually, but one of three for the sake of this conversation.
Brian Dixon:
So it’ll exist as reduced glutathione. So it’s going to be that antioxidant like we want. Then it can exist, ironically, as a free radical itself. So maybe as it’s giving away an electron during its antioxidant roles, it actually becomes a free radical in itself.
Ryan Goodwin:
That’s crazy. I didn’t realize that.
Brian Dixon:
And then realize that, and then it actually becomes fully oxidized in this called GSSG or, or glutathione disulfide. So what researchers will do, and because glutathione is present in such high concentrations in our bodies, a lot of researchers like to measure what they call the glutathione redox couple. So how much of that reduced glutathione is around? How much of that fully oxidized glutathione is around? And they’ll look at the ratio. So to put that into context; when we’re young, that ratio is about a 100:1. So we’ll have about a hundred reduced glutathione molecules for every one oxidized molecule. What’s so interesting is as we age, you can see how this balance starts to shift and we become much more oxidative.
Brian Dixon:
Balance starts to shift and we become much more oxidative relative to when we’re young and that ratio can shift all the way down to 30 to 1.
Ryan Goodwin:
Wow.
Brian Dixon:
So pretty crazy.
Ryan Goodwin:
Is that one of the main mechanisms that people look to when they’re defining biological age?
Brian Dixon:
Absolutely. There’s a few, a few different redox couples they can look at. Glutathione tends to be one of the easier ones to measure. It’s still technically pretty difficult to measure in a laboratory setting, but you can measure literally any redox couple inside of the cell. For example, you can measure the redox couple of NAD, which is the oxidized form. And then you have NADH, which is the reduced form. And again, those couples will be in very similar ratios, definitely much more reducing and then seeing that decline as we get as we get older. So it can be vitamin antioxidants I think that are maybe more common for individuals like vitamin C. But the most stable and probably best surrogate to measure your total oxidative load or antioxidant load is the reduced glutathione to oxidized glutathione ratio.
Ryan Goodwin:
Yeah, that’s absolutely fascinating. And I think that even with how people are now starting, what you just described around both glutathione and just what oxidative stress really is doing in the body there. I’m hoping that by now they’re understanding how they can control that a little bit, right? That there’s decisions that we can make in order to help support that healthy balance of oxidation or even glutathione within the body. And that’s really what our entire message here at LifeVantage is all about, right?
Brian Dixon:
Yeah, absolutely. So we want to do all we can to protect or preserve that reducing environment inside of our cells, but then especially as we start to get older. And just like most of the things we see changing as we get older, these things are starting to happen in our twenties and definitely by our early thirties. So doing all we can to try to preserve that redox ratio is is incredibly important and making sure that we’re keeping those reducing equivalents, if you will, around inside of the cell. And maybe just another little side commentary, but you might be asking yourself, well, why is this even so important? Well, we talked about, one, the need for the balance and some of the just normal cellular function that has to happen in this balance, but our bodies just may be very similar to pH.
Brian Dixon:
Our bodies regulate pH in an incredibly tight manner and that’s nothing more than our bodies are used to doing all of that biochemistry within this very limited pH range. Maybe another example would be body temperature, right? If we get too cold, you become hypothermic. The reason that’s a problem is your biochemistry slows down and you can’t make all of the molecules that you need to make in such a timely manner. If we get too hot, that’s also incredibly life-threatening. So if we get just as warm as 104 degrees Fahrenheit, forgive me, I don’t remember that conversion to Celsius right off the top of my head, but if we get to about 104 degrees, again life threatening, because our bodies are used to doing biochemistry within this really tight window of a normal body temperature. And the same thing is exactly true with the redox range or the redox balance within the cell. We want to conduct all of our biochemistry in this very reducing environment.
Brian Dixon:
And as we start to become more pro oxidative, that has tremendous consequences, to your cells’ ability to be able to do all of that biochemistry that needs to be done.
Ryan Goodwin:
Yeah. And so antioxidants are basically the main way that we’re looking to affect ox oxidative stress?
Brian Dixon:
Yeah, because we’ve got a number of issues that are working against us. I think a lot of us know what can contribute to our overall oxidant load inside of the cell. It can be toxins that we’re exposed to, whether it’s through air pollution, whether it’s through maybe things we’re putting on our skin, the air we breathe, if it’s not clean that’s going to add to the oxidant burden. But again, I think an issue that most people overlook is just the act of breathing oxygen is incredibly oxidative. More than that, just a little comment on oxygen. Oxygen is the most toxic gas on the face of this earth. We’re just lucky that we live in an environment where it’s only 21% oxygen. It becomes incredibly dangerous to breathe pure oxygen for a long period of time. And the reason it’s so dangerous is it actually turns out to be a very harsh oxidant.
Brian Dixon:
I mean, that’s where the word comes from, oxygen. Its molecular structure is such that it leaves a couple of electrons just hanging off of the end where they can react with things. That’s the act of oxidation. That’s kind of that rusting of a car sitting in a field, if you will. But just also metabolizing our food. So generating our body heat or doing all of those things that our bodies need to do every day, our hearts beating, our brains thinking, that’s creating oxidative stress. And the reason it’s doing that is, as we’re eating our food, digesting our food, that food’s getting into the mitochondria ultimately and effectively. The mitochondria are taking that food and further breaking the bonds of that food. And as they’re doing that, electrons are also released. So we need these electrons for our metabolism and our mitochondria especially have this amazing ability to harness this potential energy that’s found in these electrons.
Ryan Goodwin:
Yeah, they’re critical to the Krebs Cycle, the energy making cycle.
Brian Dixon:
Exactly. So the bonds are broken during the Krebs Cycle, but then we’ve got a few molecules that actually harness those electrons as they’re being broken down and they get shunted or shuttled into the electron transport chain, which is another kind of enzymatic system that’s leveraging the stored energy or potential energy that these electrons have. And it’s an amazing process. It’s so intricate. And the best analogy I can come up with to explain what’s going on in the electron transport chain, maybe if you can in your mind’s eye envision just some massive river system. And I grew up on the border of Oregon and Washington in the Western United States, and there’s a massive river that flows between those two States called the Columbia River. Or maybe you want to think about the Mississippi River kind of flowing down the heart of the United States.
Brian Dixon:
But whatever river, one way that we’ve come up with to generate energy for our population is to put dams up. So if you can think about maybe going to the Mississippi River and going way up north towards the Canadian border, and we put a dam there. So what we’re doing is backing up all of this water behind a dam, which is doing nothing more than creating potential energy that this weight of the water has as it’s being pulled by gravity down to sea level. So we’ll put a dam in the middle of this river and we will slowly release that water through these turbines that get spun and generate electricity. But then a little further down the river, we can put another dam and harness some more of that energy. A little bit further we can put another dam and so on and so forth, but eventually that water’s going to run out to the ocean and it’s going to have no more stored energy anymore. This is exactly how this electron transport chain in our mitochondria is working. It’s using this potential energy of these electrons to slowly release energy so that we can ultimately make the energy currency for the cell that’s known as ATP. But in doing that, as you heard me say the word electron a bunch of times, that process is imperfect and so some of those electrons can actually escape the electron transport chain and shoot off in whatever direction and start to oxidize various molecules, damage various molecules, inside of the cell. Our very metabolism is actually working against us. And then a couple of factors are working even more against us, and that’s the aging process. It’s been very well documented that as we get older, probably a result of some of these electrons escaping as we’re young, they become less efficient and so more and more of those electrons escape, thus further …
Brian Dixon:
And so more and more of those electrons escape. And so you get this vicious downward cycle. And maybe just to put that into context, it’s been estimated that as we get old, especially up into our probably 70s and 80s, somewhere between one to 2% of all the oxygen we breathe ultimately gets converted into some of these oxidants and free radicals.
Ryan Goodwin:
Wow. That’s crazy. So what are the main ways that we get antioxidants in there to help support these systems and help bring that balance back into homeostasis, if you will?
Brian Dixon:
Yeah, so what’s so interesting, I think most people when they think of antioxidants, they think about these dietary factors that we’re getting. So there’s no doubt that we can get antioxidants from our diet, most people tend to think of maybe vitamin C or vitamin E is being antioxidants and they definitely are, but it’s not their necessarily primary role inside of the cell. I mean, let’s take vitamin C for example. Vitamin C is an essential nutrient first that also happens to have antioxidant activity. But what’s been shown is that vitamin C is absolutely required for at least 15 different mammalian enzymes. So if you don’t have vitamin C around, these enzymes don’t work. And maybe the best example I can give is collagen formation. So if we don’t have vitamin C around, we can’t make collagen, and literally the cells and tissues in our body start to slowly disintegrate because collagen is literally the glue that’s holding all of our cells together. And again, just a little aside, but if you think about pirates back in the day.
Brian Dixon:
Their teeth would fall out of their face. If you could look at it more closely, they would bruise really easily. And then they ultimately ended up dying from some sort of cardiovascular event because literally the gums, the tissue around our gums turns over incredibly quickly. And because you don’t have fresh collagen there to put back and hold the those cells together, your teeth just start to fall out of your face. You bruise easily because your blood vessels also require collagen to stay together. So just even touching your skin will break some of those blood vessels and you’ll see that bruising occur. And then ultimately your blood vessels literally just disintegrate because there’s no collagen around. So these vitamin antioxidants, they have these essential roles in our body. And what’s so ironic is they tend to be working as oxidants for these enzymes.
Brian Dixon:
So for example, there’s an oxidative process that has to happen in the formation of collagen. You have to oxidize one of the amino acids so that collagen can take on this interesting three shape that it has. But it’ll cycle back and forth between reduced and oxidized and you can make collagen. There’s also antioxidant activity that can come from non essential nutrients. So a lot we like to refer to those as phytonutrients or phytochemicals. They have antioxidant activity in a test tube, but it turns out they tend not to raise to very high levels inside of our body. But it turns out the mechanism that’s the most important for protecting and supporting our body’s balance of this pro-oxidant, antioxidant balance are enzymes that are ingrained into our DNA. In fact, almost every single organism on the face of this earth has some antioxidant mechanism built into its DNA. When you talk to evolutionary biologists, they’ll say that if something is so important for overall cellular function and cellular health, it will encapsulate that ability into its DNA. So this whole aspect of antioxidant protection, probably just to guard us mostly against ourselves in these different pro-oxidant roles that the mitochondria or maybe some of these other enzymes can have inside of the cell is so important that our cells inside of our DNA and genes have the ability to make these antioxidant enzymes.
Ryan Goodwin:
Yeah, I’ve always found that to be absolutely a fascinating that are body… The way I like to think about it is that our body has the equivalent of an exhaust system that’s built in there in order to deal with this very, I don’t know if the issue is the right word but, I’ve always found that absolutely fascinating.
Brian Dixon:
Yeah. I just like to think of it as it’s just a side effect, this oxidant production is a side effect of living and breathing. It’s a necessary evil for us to even be alive, but our bodies have these defense mechanisms built into it.
Ryan Goodwin:
Yeah, totally. So there are ways that you can affect antioxidant activity through nutrition, but they might be different than what the average person might think.
Brian Dixon:
Yeah, absolutely. Our cells, our bodies, they are amazing at adapting to its environment. I mean, think about when you exercise and if you exercise regularly, whether you go run, the more you run, the further and faster you can run. When you go to the gym and lift weights, if you’re consistent, you can slowly over time gain that strength to lift even more weight. You start to put on muscles, so our ourselves and our bodies are adapting to whatever situation we throw at it. And very interestingly, our cells have adapted to this ability to be able to combat this constant barrage of oxidants that it’s facing literally every second of every day. But it’s built in an even more beautifully complex system into it. There’s this whole cell signaling pathway that’s referred to as the Nrf2 pathway that is integral into being able to sense when maybe there’s an oxidative burst, whether it’s coming from an enzyme, whether it’s coming from the mitochondria, whether it’s coming from exposure.
Brian Dixon:
So this protein called Nrf2 is normally anchored to the cell membrane to a protein that’s called Keap 1, and it’s anchored with a very interesting chemical bond. And it’s a chemical bond, well, actually it’s the same chemical bond that glutathione forms when it becomes oxidized. It’s called a disulfide bond. But that bond is incredibly susceptible to being reduced of all things. So as soon as something comes along that wants to basically interact with that chemical bond releasing it, it goes into the nucleus and it literally flips the switches of these antioxidant genes so that your body can turn on these defenses to combat against itself. But what was so interesting is back in, oh right around the year 2005 not long after the Human Genome Project had been done, this whole notion of nutrigenomics came along. So they found that a lot of the food that we were eating was really acting like signaling molecules to ultimately turn on various genes.
Brian Dixon:
The scientists went on to research that’s just a little bit more, and they found that a lot of these nutrients are also activating this protein called Nrf2. Fast forward a few more years that’s been extensively studied and what nutrients can actually interact with Nrf2 to activate it, to basically bring ourselves to a heightened state of defense. Because Nrf2, the system works incredibly intricately, incredibly well, but the one rub in the whole system is that there’s a time lag that can occur. So by the time Nrf2 is first release, it can take hours, if not days for these antioxidant enzymes to ultimately be turned on and activated so that they can go on and do their normal function. So the fact that these discoveries have been made that a small handful of nutrients can effectively activate Nrf2 has been just really revolutionary. So we can give compounds in the right doses, now we’ve been able to show in the right ratios as well, where you can preemptively activate Nrf2, bring yourself to this heightened state of defense and provide protection from that falling out of that normal balance of that pro-oxidative and antioxidant state.
Ryan Goodwin:
Totally. So when you activate the Nrf2 pathway, is that the primary way that you increase gluta-
Ryan Goodwin:
it’s way. Is that the primary way that you increase glutathione levels in the body?
Brian Dixon:
Yeah, absolutely. So glutathione is an interesting molecule. It turns out that it’s actually a protein, and it’s one of the few proteins in our cells that’s not made by a ribosome. So again, if you can remember your bad high school biology and chemistry courses, most proteins in our bodies are made on these little structures called ribosomes. But glutathione is an exception to that rule, and it’s made by two different enzymes. Glutathione is a combination of three amino acids, glutamate, cystine and glycine. And so, the first enzyme is catalyzing the first two amino acids coming together, and then the second enzyme is facilitating that third amino acid being put onto the final glutathione molecule. It turns out that there are two ways you can control glutathione concentrations in your body. One is just making sure you have enough of the amino acid that’s present in our bodies at the lowest concentration, and that turns out to be cystine.
Brian Dixon:
But an easy way to overcome that is just eating a healthy, well balanced diet that’s providing protein, that’s rich in cystine. It’s very easy to get enough cystine from the diet. And it’s limiting in our bodies because cystine turns out is actually toxic in high concentration. So our body goes out of its way to limit how much free cystine is floating around. The other way you can really turn on and activate your glutathione production is by turning on these enzymes that are responsible for making glutathione, and they are especially tightly under the control of this protein, NRF2.
Ryan Goodwin:
Boom. NRF2, baby. And that’s why I absolutely love working for LifeVantage, the company at the forefront of Nutrigenomics. The products that we get to promote are really the founding fathers, if you will, of how to take this fledgling science of nutrients affecting gene expression and turning that into products that can maximize this homeostasis that we’re all looking for, right? The extended health span.
Brian Dixon:
Yeah. There’s such an arrogance in my opinion of medicine and science. And very generously speaking, how long has science and medicine been around? You can argue there was some pretty primitive medicine happening back in the medieval days, but what would that be? 500, 600 years? Science really hasn’t made a lot of advances, especially in biology, biochemistry, chemistry, definitely in the last a hundred but you’d be hard pressed to even get 200 years out. So there’s just this arrogance out there that scientists have figured everything out, that they know everything. But for me, it’s just always great to just come back to nature, to come back to biology. Doesn’t nature tend to know best? I have a background in agriculture, so I don’t mean to maybe talk bad about agriculture. I don’t mean it to come out that way. Farmers are the heart and soul of this country and the world. They’re providing all the food that we need to make, to eat and live every day, and all they want to do is provide for their family.
Brian Dixon:
The quickest, easiest way they can do that is by spraying harsh chemicals on their crops to keep pest damage down so that it can maximize yields, so they can maximize profits, so they can feed their families. Well, maybe that wasn’t the best approach. It was the easiest approach, but it wasn’t the best. And now a lot of agriculture is really turning back into nature, and instead of managing their crops like a sterile canvas and trying to keep every other organism out of there except for their crops, now a lot of farmers are looking at managing their farms like an ecosystem. So they’re using good bugs to combat the bad bugs, right? In my backyard garden, when I see aphids floating around, I want to make sure I do everything I can to encourage the good, healthy ladybugs that’ll come in and eat those aphids. So, that’s exactly similar to what’s happening inside of our bodies. We’re trying to use biology to fight biology. It’s just amazing, and we’re turning back to nature to find those answers.
Ryan Goodwin:
Yeah. I’ve always found it fascinating that the more we do find out about what’s going on inside our bodies, that it always comes down to the proper balances. That too little is often not good and too much is often not good, and so trying to figure out how to get those balanced, as many of those things that got those dualities in play balanced is really what great health comes down to. And so, that’s why I really love this conversation around antioxidants, and I think you’ve done a really good job of taking a pretty complicated topic and make it a little bit more approachable for the average person so that they can better understand the benefits of NRF2 and what that means to oxidative stress, how our product competes with other products that might call themselves antioxidants, and ultimately what we’re trying to achieve as bio-hackers.
Brian Dixon:
Yeah. Well I appreciate that. And it just comes back to turning back to nature to find the answers and just support those inherent mechanisms that we’re literally born with to try to maximize their effectiveness.
Ryan Goodwin:
Yeah. I love how you wrapped that up because I believe that’s ultimately our core philosophy here at LifeVantage, that we can maximize that. Now that we know that there’s those cell signals, that our food is more than just nutrients, it’s information. We can fine tune that message so that we can maximize it. In this example, for oxidative stress and antioxidants, we can maximize those glutathione levels so that we can get closer to how our bodies were operating in their prime right?
Brian Dixon:
Absolutely.
Ryan Goodwin:
Killer. Well, thanks for your time today talking about antioxidants Brian.
Brian Dixon:
Hey, always my pleasure. Thanks Ryan.
The views expressed in this podcast are those of the authors and do not necessarily reflect the official policy or position of LifeVantage or any other agency, organization, employer or company.
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