Written by Christopher Kelly
June 11, 2015
[0:00:00]
Christopher: Hello and welcome to the Nourish Balance Thrive podcast. My name is Christopher Kelly and today, I'm joined again by Dr. Tommy Wood. Hi, Tommy!
Tommy: Hi, Chris!
Christopher: Today, we're going to talk about -- oh, before I go any further, I should mention if you want to know more about Tommy, who is a wise and interesting guy to have on the podcast, go back and listen to my episode on hydration. We had a fantastic conversation -- it looks like I'm starting again.
Today, I want to talk about something completely different and it's something that's been troubling me for some time and it's the topic of oxidative stress. Maybe I should start by defining what oxidative stress is or at least what I've seen and that's some markers on an organic acid's urine test.
The way this test works is you just collect a sample of urine at home and then you send the sample to the lab using a FedEx mailer, and then the result comes back to you electronically. There are 46 different markers on this test, but there are two in particular that I'm interested to talk about today, and those are p-Hydroxyphenylacetate and 8-hydroxy-2'-deoxyguanosine.
These metabolites, when they build up high in the urine sample show that you're under a great deal of oxidative stress. It makes sense in theory, I guess, to just take antioxidants to try and reduce this like oxidative stress causes inflammation and inflammation causes oxidative stress. It doesn't sound like a good thing and certainly there are lots of people out there selling supplements especially to athletes to reduce oxidative stress.
The reason athletes are so likely to be affected is because you're just running metabolism more often. You're generating more energy, more free radicals, more oxidative stress.
When I originally saw these markers years and years ago, I approached my uncle who is an Emeritus Professor of Pharmacology at Edinboro University and said, "Hey, what do you think about this? Is it quackery?" He said, "No, it's real. Oxidative stress is a real problem and I would suggest that you take or experiment with using tomato paste, which has a very high lycopene content to reduce your oxidative stress. I think this is going to improve your health and longevity and it's something you should really look at."
And so, that's what got me started. Since then, I've seen opinions all over the map. So maybe I should ask someone that really knows what they're talking about and that's where you fit in, Tommy. Why don't we start by defining what exactly is oxidative stress?
Tommy: Okay. Oxidative stress, the reason that we call it oxidation, which sounds a lot like it's to do with oxygen but it's not necessarily, when something becomes oxidized, what happens is you've given it an electron or taken away an electron.
Electrons like to come in pairs. If anybody remembers all the way back to basic science at school, they might remember those pieces of the elements and you have those electrons that circled around the nucleus of your atom.
Christopher: Right, of course, so we've got an atom -- I say "of course". I've been doing -- and this is like my top tip ever if you want to understand biochemistry. Go to the Khan Academy Chemistry module. I will link to this in the show notes, but you can Google it, just Google "Khan Academy Chemistry".
Now, you've got this organic acids test. You have a reason to care about this stuff. And so, when you go redo the chemistry that you did in high school or maybe even college or something, it's all going to stick like glue. It's going to be so adhesive and so compelling to you. I know it sounds boring doing chemistry lessons, but this time around, you're going to love it and this is why. You're talking about the actual structure of an atom, right?
Tommy: Yeah. In an atom, and if you think about it in a traditional sense, there are layers of electrons that circle around the outside.
Christopher: Right, so [0:04:27] [Indiscernible] with protons and neutrons --
Tommy: In the middle, yeah.
Christopher: In the middle, and then on the outer shell, spinning around this nucleus, we have electrons.
Tommy: Exactly. And then if you create a molecule -- that could be anything. Say it's just a molecule of oxygen, so you have two oxygen molecules --
Christopher: Stuck together?
Tommy: Stuck together.
Christopher: So it's nothing really complex. We've used these words like atom and molecule, but there's not really a thing -- well, obviously years and years of science and research, and it's still developing.
[0:05:06]
That was the one thing that surprised me. You've seen the sign, the symbol in The Simpsons on the cooling tower at the power station that's got this neat model of an electron circulating around the nucleus. We know that that's not really correct and that the electron could appear in any place around the nucleus. There's a high probability of it appearing in one place rather than the other, so it's not quite correct.
Yeah, we've introduced these fancy words, but that's what we're really talking about. So when you're talking about molecular oxygen, you're just talking about two atoms of oxygen stuck together.
Tommy: Exactly. And then what happens is when you create a molecule like that, so that's more than one atom stuck together and it could be a protein or an amino acid or a fat or whatever, they start to share electrons and that's what creates the bonds between them. They will tend to come in pairs.
And then what happens when you oxidize something is either you take away one of those electrons or an electron is donated to it. The name for oxidation is usually to take away one of those electrons, but in general when we say that something is oxidized, it could've been taken away or given.
So if you have a single electron that doesn't really have a partner, then you've created something called a free radical. What happens is that can go on and react to other things and that can damage proteins, damage DNA, damage the fats and the membranes of the cells, and so that's what we tend to talk about when we're talking about oxidative stress.
If you're thinking about it particularly in terms of exercise, then the major reactive oxygen species -- and that's what we tend to be talking about -- are these free radicals or oxidizing molecules or oxidized molecules that are based around oxygen. And so, the oxidation is almost a coincidence.
Something that's oxidized doesn't have to have oxygen in it, but the ones that we generate when we're following metabolism or we're doing exercise, the commonest one is superoxide, that we make superoxide. Superoxide is basically just a normal oxygen molecule with an extra electron attached to it.
Christopher: Okay. So you can think of it almost like a jealous friend, so it's this thing that doesn't have enough electrons. It's looking for somewhere to steal another electron. So it could be you're happy and stable and it'll just grab that electron from whatever. It's a bit like taking candy from a baby.
And so, if it takes that electron from the phospholipid bilayer that surrounds the cell, then it seems feasible that if that were to happen often enough, then it might break the bilayer that surrounds the cell and then something bad would happen to that cell, right?
Tommy: Yeah, if the oxidative stress or damage is high enough, absolutely. One of the first things when we were first discovering that exercise could induce oxidative damage was that in athletes, they measured pentane, which they breathe out and pentane basically just becomes a byproduct of the oxidative damage to fats in cell walls, so that was one of the first things that we saw 40 to 50 years ago when we were looking at what exercise can do in terms of generating reactive oxygen species.
Christopher: Right, and there's so much research out there. A lot of people listening to this will have done the organics profile and you won't really find anything if you search for organics profile or anything like that. The magic keyword you're looking for are the names of the organic acids.
So if you search for 8-hydroxy-2'-deoxyguanosine, PubMed, you will find tons of papers that describe this organic acid is a way to quantify oxidative stress. This metabolite is actually a breakdown product of the guanine of DNA. So what this is telling you is the DNA, the bit that actually instructs the cell on how to make proteins is actually being destroyed in some way. And so, the metabolite is building up in your urine.
This sounds like a really bad situation. My next question is then if this is bad, is less better?
Tommy: It really depends on the situation and that's I think where we're heading and it's definitely one of those things where originally in the '70s and '80s, we thought that reactive oxygen species were bad and that anything we could do to reduce them would be good because obviously, by their nature, they are damaging.
[0:10:09]
We do have some processes by which we break down reactive oxygen species. If you're generating superoxide, again, let's say this is during exercise, then it's generally converted into hydrogen peroxide by an enzyme called superoxide dismutase, and there's a version that sits inside the cell, inside the cytosol at the main void of the cell, and there's also a version that sits inside the mitochondria.
And then that hydrogen peroxide is converted to water by catalase or glutathione peroxidase. People would have heard of glutathione, which are three amino acids. It's glutamate, cysteine, and glycine, and they're bound together. And then two glutathione molecules will take the hydrogen peroxide and then it will remove -- it will donate in hydrogen to create water.
And then you'll stick those two glutathiones together and then you recycle them through -- you have to use ATP and you also get some help from Vitamin E and Vitamin C and potentially things like alpha lipoic acid. You just recycle your glutathione. That then just turns your superoxide into water and then you obviously don't have any problem with it.
But what we are saying is -- so you talk about 8-hydroxy-2'-deoxyguanosine and that is a potent marker of oxidative stress. You can measure it in the urine and that's going to give you an idea that your chronic oxidative stress burn is quite high and it's causing direct damage to your DNA because that's what you're measuring. You're measuring DNA breakdown products and that is obviously a problem.
We think that chronic high level of oxidative stress increases the risk of Type 2 Diabetes or increases insulin resistance, increases the risk of cancer, and there are a lot of potential chronic diseases that are associated with a high oxidative stress burden. But what we're learning more about is that definitely we need some reactive oxygen species. A chronic high level is bad, but peaks in reactive oxygen species are actually good. They have a lot of benefits that hopefully we'll talk about.
It's definitely not a case that we just need to get rid of them completely because without reactive oxygen species, cell signaling, life essentially wouldn't happen. It's an incredibly important part of signaling and reacting to the environment. It's one of the ways that we react to the environment and then come back better and stronger if we need to.
Christopher: So this seems like a really common theme in biochemistry and physiology that you have maybe a U-shaped curve like a dose response type thing, and that was the quandary I got myself into quite quickly. I could take the antioxidants and whether or not they reduce the oxidative stress, I'm not sure, but it seems certain that this is part of the mechanism by which we get stronger.
So by taking the supplements, I might be squashing the benefits or the potential adaptations that come from training and almost negate me training at all. Do you think that's true or again it just depends how much oxidative stress you're under?
Tommy: I think it could absolutely depend and maybe it will also depend on the antioxidant that you're talking about and the situation that you're potentially taking it in.
Originally, we saw that the harder you make somebody work on a treadmill, the more oxidized glutathione they have, so the more they're using up their glutathione stores and that pretty much increases linearly with something like blood lactate, so the harder you're working somebody, the more glutathione they need to deal with all the reactive oxygen species they're making. And then if you give people some Vitamin C or some extra glutathione, then you can dampen down those reactive oxygen species.
Christopher: So they do work then. The water-soluble vitamins do work as antioxidants.
Tommy: They do work as antioxidants and they absolutely increase your antioxidant capacity, but if you or somebody who's trying to get a performance benefit from training, then that's not necessarily a good thing. They do work. They will reduce oxidative stress, but what we're seeing more and more is that actually, what you want from exercise is a certain amount of oxidative stress. If you dampen that down with various antioxidants, then you're actually removing that training benefit.
[0:15:04]
Christopher: Okay. I've been accused in the past of providing a lot of information and not much prescriptive, so maybe I should take heed of that advice and start thinking about it. I take personally the Thorne EXOS multivitamin and it has antioxidants in it. Do you think the timing of those supplements is important?
I've tended towards these days taking -- I work out in the afternoons and then I'll leave a gap of several hours before I take that supplement. I'm not saying that this is the only reason I do that. It's more of a habit than anything else, but do you think that's a good idea? Would you try and space it out? If there are other nutrients in that multivitamin that I'm after, do you think it makes sense to space that out?
Tommy: I think it would make sense such that your peak antioxidant levels won't peak with your peak oxidative burden from your exercise. You could potentially be reducing a native effect there, but all of the studies -- the antioxidants that are the most well studied probably and which people talk about a lot are Vitamin C and Vitamin E, and they tend to come together.
Vitamin E, what it does is it will take the extra electron from something, from some kind of reactive oxygen species and then it's recycled by Vitamin C and glutathione, so they work together and there's a cycle there. So you just having more of one on its own don't tend to have much of an effect.
Actually, they did one study about ten years ago where they had Ironman triathletes and they gave them just Vitamin E and told them not to take Vitamin C or not taking extra Vitamin C. What they actually saw was an increase in lipid peroxidation, so they measured F2-isoprostanes in the blood and urine and they saw increased inflammatory sites gone, so the proteins that increase in response to inflammation and activate the immune system.
Interestingly, and I think maybe it was just because it was measured in just a short time after the race, they didn't see an increase in 8-hydroxy-2'-deoxyguanosine. They actually measured that and didn't really see a difference there and that's after the Ironman Triathlon. That's a huge oxidative burden.
So even though it's a long period of time, maybe it's just because it's a one-off and then the rest of the time they don't have that much or they're recovering well because this was at the Kona World Championships, so these are Ironman triathletes at the top of their game, so they'll have their recovery sorted. So maybe overall, their levels of that kind of DNA damage are fairly low.
But when they've looked at the studies giving Vitamin C and Vitamin E to people, what they've seen is that actually overall, maybe half of them don't really have any effects, so you're giving maybe 500 mg to 1000 mg of Vitamin C a day and 400 units of Vitamin E a day, and both in resistance training and in endurance training, they don't really see any difference and there's a reason.
The thing is that there's a really good review paper by Peternelj and Coombes in 2011, Sports Medicine Journal, if anybody wants to look it up. They found over 150 studies of various antioxidants in exercise and looking at the potential negative and positive effects.
What they talk about is the fact that most of these studies are in a very small number of people. You're talking about sometimes five people in the intervention group. When you're talking about statistics and actually trying to find something meaningful, it's almost impossible to do that. Then if you're seeing a negative effect, it could be completely by chance. If you're seeing no effect, it could be that you don't have enough people to actually see that there's actually a negative effect there because you need enough people and enough of a change to actually get some kind of difference.
Overall, what's useful is people are actually looking at performance. If you're trying to take antioxidants to boost performance, then what you want is a measure of performance. It's not necessarily blood levels of this or that because that doesn't necessarily correlate with the actual performance on the bike or when you're running, but there was a study and it's probably one of the best ones that's been done that came out in PNAS in 2009 and they had 19 untrained men and 20 previously trained men.
[0:20:11]
The first half, they did it so that the participants knew what they were getting, and then the second half, it was like a placebo-controlled trial. They've got a gram of Vitamin C a day and 400 units of Vitamin E a day and those are fairly standard doses. Those are fairly low doses.
They were trained for five days a week, and so they were on a bike for 20 minutes and then they did some circuit training. What they saw was that in the antioxidant group, the antioxidants prevented an increase in insulin sensitivity, which you saw in the placebo group, so obviously one real benefit of exercise is you improve your insulin sensitivity, so they didn't see that in the intervention group.
It also prevented an increase in adiponectin, which is a very important signaling molecule in terms of glucose metabolism and fatty acid metabolism. It also prevented increases in some co-activators of transcription, which basically means that they activate making of proteins that control various things in metabolism, and that's PGC-1 alpha and PGC-1 beta.
All of these things, what they do is they coordinate insulin sensitivity and they coordinate the improvement in reactive oxygen species handling like increasing glutathione, increasing superoxide dismutase, increasing catalase. And actually, if you're taking antioxidants and you're not getting that peak of oxidative damage or oxidative stress to do with exercise, then you don't get those benefits.
And so, you don't get that improvement in insulin sensitivity and you don't get that improvement in your ability to handle oxidative stress, and that's in one of the better studies, I think. That's probably why it was published in PNS, which is a very good journal, is because actually compared to all of the other studies that have been done, they use some reasonably robust techniques and a reasonable number of people.
Christopher: Right. I've got two studies to link to here. I'll have to get the full reference from you so that I can link to that in the show notes. It seems like what you just described to me, those cyclists, 20 minutes -- it takes me 20 minutes to warm up. It's like a totally different ballpark.
A couple of weekends ago, I did a hundred-mile bike race off-road and I'm sure I look the same. Obviously, I couldn't see how I looked, but when I looked at people at the finish line, their eyes are bloodshot because they're so full of dust and we're at 8000 feet and we've all been breathing God knows how much dirt.
Understanding what causes oxidative stress -- and it seems like it's generating energy for an athlete and then inflammation are like the two things, so obviously that's going to be very different in a pro athlete who just finished a hundred-mile bike race than it is some college kid that you just recruited into your study to ride an exercise bike for 20 minutes. These are completely different scenarios.
Tommy: I think that's absolutely part of it. Interestingly, actually the generation of reactive oxygen species doesn't seem to come from the generating of energy. Traditionally, we think about the fact that the complexes in the mitochondria, complex one and three of the electron transport chain, that's where a lot of reactive oxygen species are made and that's completely normal, but actually during exercise, they seem to produce less superoxide and more of it is produced by something called NADPH oxidase, which is an enzyme which sits on the cell surface, but there's also some associated with something called the cytoplasmic reticulum.
The cytoplasmic reticulum is basically an organelle. It's a membrane-bound body that sits inside the muscle cell and it contains all the calcium, so you need calcium for muscle contraction. Obviously, so that you don't get one sustained contraction, you need to be able to regulate calcium in and out of the cell body where you have the contracting muscle.
So as you start to contract, NADPH oxidase actually increases superoxide, and what superoxide does is it increases the amount of calcium that comes out of the cytoplasmic reticulum via something called ryanodine receptors and it also reduces the amount of calcium that goes back into the cytoplasmic reticulum.
Actually, in one way, the generating of superoxide is really important in making sure that you get maximal and efficient muscle contraction. The problem is then if you overdo it, that's associated with fatigue, so there's absolutely a balance there.
[0:24:59]
So you need some for good performance, but if you overdo it, then you can start to get problems with the way the calcium signaling happens in a cell, or another thing is that you get the effects, the potassium sodium ATPase, which affects where sodium potassium are inside the cell and the reactive oxygen species can affect that particular transporter and you end up with lots of potassium outside the cell, which is where you don't want it. That's another aspect of fatigue, so then the reactive oxygen species can affect that.
It does seem to come back to the level of training of the athletes. The study I just talked about, in the average person, either the recreationally trained athlete or somebody who's trying to get fitter, I think that study is geared at them. Those are the weekend warrior or somebody who's looking after their health, training two to three times a week, or somebody who's trying to train more. And then I think the extra Vitamin C and Vitamin E supplementation, it's not going to necessarily be beneficial and it may blunt some of those effects that you're getting.
Christopher: Okay. Let me just be clear about that. It sounds to me like you were saying that doing more cellular respiration doesn't necessarily increase oxidative stress. Is that right? So if I generate more energy in my mitochondria, that doesn't necessarily increase oxidative stress?
Tommy: No. If you look at the state of the mitochondria, when they're in that standard taking over metabolic state, that's probably the state when they're producing the most reactive oxygen species, and it seems that when you're actually in full blown muscle contraction, actually you're producing -- you actually have -- as long as you have properly functional mitochondria and they haven't been damaged by something, then actually you have much more efficient electron transfer through the mitochondria and actually less of it gets passed on to oxygen to make superoxide.
Christopher: Now, I'm starting to think that this whole thing like selling antioxidants to athletes is completely bogus and we really shouldn't do it at all.
Tommy: One of the reasons I got interested in this actually is because there's a drink that's marketed particularly in the Crossfit world there's a reasonable dose of Vitamin C and a reasonable dose of Vitamin E, and there's also some caffeine in there and it's sort of a recovery drink. That's exactly the time you don't want that, but with the right level of marketing, you've said it, so absolutely. I don't think, especially in that setting, that those are the kinds of things you want to be taking.
Christopher: Yeah, super interesting how all those stuff works. I should probably point out actually, you're using a lot of fancy words there, but I've already mentioned the Khan Academy chemistry, also Bryan Walsh's Metabolic Fitness Pro, which I've mentioned more than once. He describes all of the stuff that you've just been talking about, at least the biochemistry and some of the physiology. The physiology class is not out yet, but the biochemistry is really what's most appropriate here. And so, I think that's really useful for understanding this.
Something else I wanted to say was I know it's just a stupid n=1, but those elevated markers of oxidative stress that I saw on my original organics profile, they came right back down into -- so the organics test is divided into quintile, so it's not -- I mean, they do give you the raw data, but I'm not sure how meaningful those numbers are as standalone data points. It's kind of like you look at the bullets and see where you are in the quintile ranking amongst healthy people.
I was up into the red for both of those two organic acids. Once I sorted out my gap, so I got rid of small intestinal bacterial overgrowth and a pinworm and whatever else, I just got healthier, less inflammation. My C-reactive protein came down. The oxidative stress came down with it and I didn't change my training. I still train as much as I've ever done. Maybe that's not quite true. Perhaps my plan is a little bit more minimalist, but certainly I'm racing as much as I ever have. My oxidative stress still looks in the normal range when compared to these healthy individuals.
Tommy: I think that's definitely a part of it and I think that there's a real difference between the oxidative stress that you're getting from something like -- and you're doing long races every weekend. You're doing long training sessions multiple times per week.
What people are talking about now is talking about exercise as an antioxidant in itself, and the reason that is, is because in response to all the reactive oxidant species that you make, your body up-regulates all those things that then handle or deal with the reactive oxidant species, so you get an increase in superoxide dismutase and you get an increase in glutathione production.
[0:30:14]
So actually, you get a natural increase in those things because your body has responded to the stress you've put on it and then you get that beneficial boost.
Christopher: Right. This makes sense.
Tommy: And so, I think a real problem we've had in a lot of medicine and biochemistry and in the world of supplementation and things is that we've assumed that just because something is bad that we should always try and reduce it. There are actually a lot of examples particularly when it comes to something like health, but also sports performance, so things that we originally thought were bad.
Inflammation, everybody talks about how inflammation is associated with chronic disease and it absolutely is if it's chronic. You have a low grade inflammation the whole time that's associated with atherosclerosis and cardiovascular disease and cancer, but if you get peaks in inflammation caused by something like exercise, that reduces your overall inflammation burden the rest of the time.
One of the things we call now are myokine, they're basically signaling molecules created by muscles that go out and do stuff in the rest of the body. One that's studied the most is IL-6, so interleukin-6, which people may have heard of because it stimulates production of CRP. CRP is one of those things that you measure as one of your potential risk factors for cardiovascular disease because it's associated having a high CRP. It's associated with a high inflammatory burden.
But if you ever peak in IL-6 because of exercise, what that does is it actually modulates the receptors for IL-6 and then overall, your inflammatory burden reduces, so the rest of the time, you have a low inflammatory burden. A very similar thing and one of the downstream effects of that, people might have heard of a transcription factor called NF-kappaB. Have you heard of that?
Christopher: I have vaguely. I have no idea what it does though.
Tommy: People talk about it a lot and it's because it does -- it's literally associated with half of the processes in the body where you're activating a gene or activating the creation of a protein or an enzyme or something.
I've seen some people say that you should do this and this to reduce your NF-kappaB expression, but NF-kappaB is increased after exercise and it's part of the inflammatory response, so chronically elevated NF-kappaB expression or activation in your cells is absolutely associated with that chronic inflammation, but if you again increase the NF-kappaB directly after exercise, then that is associated with all those kinds of adaptations.
So you get things like more glutathione and you get more mitochondrial biogenesis, so you start to activate and make more of the proteins that then go into your mitochondria, and then what they do is they get bigger and then they split, so you're mitochondria efficient, so then you have more mitochondria and you can produce more energy and you're more energy efficient.
If you're blocking that inflammatory response -- and this is a whole another podcast -- so if you take something like ibuprofen or a naproxen after exercise, then again you dampen down that inflammatory response and you don't get those beneficial downstream effects of that peak of inflammation.
A very similar thing is recently found out. Cortisol, we always think that high cortisol can be a bad thing, but if you're looking at sports performance or guys in the gym trying to put on muscle, those who have a big cortisol peak after exercise, they tend to put on the most muscles, so you get that cortisol peak, you get that stress increase, and then you get a lower level the rest of the time.
You see the same thing in something like obesity and diabetes, so they're both associated with an increase in chronic cortisol levels, but if you get people exercising, then you get a peak in cortisol because of the stress of exercise, and then your basal, your resting level of cortisol decreases the rest of the time.
So these kinds of peaks of stress are something that can be really beneficial to the body because of the way you're going to adapt to it. If you stop that happening, then you stop getting those beneficial effects.
Christopher: The best example I can think of for this that everybody will understand is going out into the sun. I used to live in the East Bay here in Northern California and there are no trees. I'd ride around my road bike in the sun and by this time of year, I would look like somebody of Greek descent or something. I'd have a really good suntan and I wouldn't even think about it.
Now, we've moved into the redwood trees here in Santa Cruz. I don't really get as much. It's very sunny and hot here, but there's not as much sun exposure, and so I don't have that base tan like I normally would at this time of year.
[0:35:07]
Of course, I go out into the sun and if I'm not careful, I get fried. That's the normal hormetic response to the sun. This is what your body does and it's kind of a similar situation, I think, with suntan cream. If you slather your body in factor 50 or factor 99 or whatever the hell it is they sell here in the US and never get any sun explore, then guess what? You're blocking that response. You're blocking the process of getting stronger.
That's not to say that you should go out and get burned. In the same way, it's not to say you should go out and chronically elevate cortisol as much as you possibly can. There's a balance to strike here.
Tommy: Absolutely.
Christopher: I think I'll end it there. Obviously, this has been quite dense. Thank you so much for all this really technical information. I'm probably going to go back and listen to this one myself and then maybe re-watch some of the videos from Bryan because I think he does a really good job of describing this biochemistry in front of his whiteboard. And like I said, the Khan Academy Chemistry is really handy as well.
It seems like if we were to create a prescriptive at the end of this interview, it would be to do not take antioxidant supplements just because you read about it in a magazine or a friend told you about it. Really, the only way to know whether your oxidative stress is chronically elevated is to test, and even then, it still might not be a good idea to take antioxidants. Do you think that's fair to say?
Tommy: Well, I think for some people, they can absolutely be beneficial. A lot of people, if they have gut inflammation or -- for some people, if you're talking about problems of the gut and then something like histamine intolerance, something like that, some kind of autoimmune disease potentially with some gut involvement, then I think antioxidants can potentially be beneficial, and that's if you're seeing those chronically elevated markers of oxidative stress.
Christopher: Right. So for the prescription -- I've talked to Jamie Busch, who's my medical director, and we've talked about this quite a lot. We've gone back and forth on which is the best supplement. At the moment, we're settled on N-acetylcysteine actually is a glutathione precursor.
So rather than trying to load you up full of things which are able to donate electrons directly, we're giving you this amino acid, which I think most of the studies agree is the main, right limiting step in the production of glutathione. And so, you can just give your body more of what it needs in order to produce the molecule that's helping out with the chronic inflammation.
We never really know whether there's a true cause and effect when we do tests, but it does seem to be helping or something we're doing is helping, and the biochemistry makes sense.
Tommy: Absolutely. N-acetylcysteine, that is actually one of the other best studied supplements in terms of sports performance for that exact reason because you're giving a glutathione donor, which can then balance some of that reactive oxygen species.
Christopher: The only thing I would say about it, it's such a tricky supplement, the N-acetylcysteine. It tends to oxidize very easily and you have to watch for it. I'll mention it to someone and then they'll go buy a bag of bulk powder from -- I don't know. I don't want to name any names, but some company on the internet and they're like, "Oh God, I have to keep taking that. It stinks like eggs" and it's because it's like --
Tommy: Yes, and people would often -- you could get quite bad farts for other people actually. That's what I hear a lot of complaints about actually.
Christopher: I think that's the case. Originally, I was selling a supplement called PharmaNac, which is N-acetylcysteine that comes in a blister pack, and so it can't oxidize. And then you drop it into a glass of water and it turns into an effervescent drink, and so it doesn't really get a chance to oxidize like a powder certainly would. I think the capsules are somewhat air-type. I've heard reports of even the capsules stinking like sulfur if they've been left around for long enough.
Tommy: Yeah. It's because the cysteine in the NAC is a sulfur-based compound and that's what you're smelling. You're smelling the sulfur.
Christopher: That's the breakdown. Hopefully, this has been useful to people. My advice, I'm going to keep doing the organic acids test. And then what other markers -- is there anything cheaper that you know of that you can test for -- what about uric acid on the blood chemistry? Do you know if that's useful?
Tommy: I think that's really difficult. It's not something that people traditionally look at. What they traditionally look at is various breakdown products of fats and proteins in DNA, so that's stuff like your 8-hydroxy-2'-deoxyguanosine. In terms of a direct measure that's cheap and easy, I'm not sure actually.
[0:40:18]
Christopher: Okay. I'm always looking for things. These tests are so goddamn expensive. It's $370 for this urine test. The blood chemistry is $26. I can't see any obvious reason why one should be cheaper than the other. Maybe I don't know enough about the way that the tests are done, but I'm sure it's just a question of quantity. They do a lot more basic blood chemistries and they do these organic acid tests.
Tommy: And it's also how expensive the machine was to buy and then they have to adjust what you're paying for and how difficult they are to work and things like that.
Christopher: Yeah. Okay. Thanks very much, Tommy. I really appreciate this.
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