Not a day goes past that we don’t hear about oxidative stress in the news and interwebs, and how it is shortening our lifespan or causing diseases like heart disease, diabetes and cancer.
Unless you’ve been living under a HUGE rock, you also know that antioxidants protect us from oxidative stress. And you most probably spend some of your dollars on antioxidants through healthy food choices and supplements.
But how do you know if those dollars spent.. or the time you spend thinking or reading about antioxidants, rewards you with any real benefit?
Today we look at measuring oxidative stress and how you can use biomarkers to assess your health status and whether your efforts, such as making buying choices based on antioxidant content, are paying off.
– Cheryl Burdette
Dr. Cheryl Burdette is president of Dunwoody Labs, a lab that specializes in cutting edge labs for integrative medicine, and a practicing physician at Progressive Medical Center, the largest center for integrative medicine in Atlanta, U.S.
She is currently lecturing on nutrition and cancer at the University of Bridgeport and has a number of published studies in the journals Alternative Medicine Review and Clinical Chemistry.
As education director at Dunwoody Labs she is involved in clinical trials of different nutritional products as well as development of functional testing profiles – and an area she has looked at in particular is oxidative stress.
The show notes, biomarkers, lab test and links to everything else mentioned are below. Enjoy the show and let me know what you think in the comments (click here – in the comments)!
What You’ll Learn
- The usefulness of oxidative stress markers for managing and improving health.
- The implications of high oxidative stress found in the body with connection with damage and cancer, heart disease and neurological conditions.
- The two perspectives to understand your oxidative stress status: the direct measure of oxidative damage and reduced intracellular anti-oxidant status.
- Glutathione’s role in protecting your body from oxidative stress and its relation with health and disease and what you can understand from its status.
- The relationship to goals of longevity and physical performance of antioxidant enzymes like Glutathione.
- Lipid Peroxides and the specific damage they relate to in the body, and the differences in biomarkers available: TBARS, MDA (MalonDialdehyde), F2-Isoprostane.
- How oxidative stress levels negatively impact methylation processes and its negative feedback dynamic with mitochondria.
- Some of the criteria Cheryl has used to select the oxidative stress markers for her assays and panels from amongst the over 30 currently used in research.
- How taking supplements like bioavailable forms of curcumin, sulforaphane from Broccoli, and alpha-lipoic acid or resolving chronic infections can resolve raised oxidative stress levels.
- Trends in use of the oxidative stress markers that Cheryl has noted such as use by integrative medicine practitioners and across the U.S. geography.
- Appropriate testing strategies for healthy individuals for routine assessment of oxidative stress and how it can highlight future potential health risks vs. individuals that have some chronic or pathological condition.
- Do we need oxidative stress? Can you overload on antioxidants so that they have a negative impact on your biology rather than positive?
- Looking at oxidative stress markers in athletes or people who exercise heavily to understand issues they may have with their performance and their recovery.
- Some of the trends, new research and tests Cheryl Burdette is looking forward to coming out in the next 5 years.
Dr. Cheryl Burdette & Dunwoody Labs
- Dr. Cheryl Burdette: Her profile on Progressive Medical Center, where she works as a physician.
- Dunwoody Labs: Cheryl’s lab, where she is president and education director.
Used and Recommended by Dr. Cheryl Burdette
- F2-isoprostane: A more direct marker of lipid peroxidation levels in your body than TBARS and MDA.
- Oxidized LDL: A measure of the amount of your LDL (Low Density Lipoproteins) that are oxidized. This is considered to be a much more predictive marker of cardiovascular disease than straight LDL measures.
- Glutathione Peroxidase (GPx): The body’s main enzyme for detoxification and for neutralization of free radicals (oxidative stress). This biomarker measures your current blood levels.
- Superoxide Dismutase (SOD) I: Levels of an intracellular antioxidant that resides in the cytosol (inside your cells). More association with conditions like ALS.
- Superoxide Dismutase (SOD) II: Levels of an intracellular antioxidant that resides inside the mitochondria. More association with fatigue and cancer, and general health status of mitochondria.
- 8-OHdG: 8-hydroxy-2′ -deoxyguanosine is tested via a first void urine test to show levels of oxidative stress in the body. This marker is supported by over 1000 research studies. See the Pubmed entry here.
Lipid Oxidization Levels
Intracellular Antioxidants and Enzymes
Mentioned But Not Recommended by Dr. Cheryl Burdette
- MDA (MalonDialDehyde): MDA is one of the most widely used markers for lipid peroxidation found in the research.
- TBARS Assay (ThioBarbituric Acid Reactive Substances assay): As with MDA, this marker has been used extensively in the research.
- Advanced Oxidative Stress Profile: The advanced oxidative stress profile containing the biomarkers discussed in today’s episode. An example report can be seen here
The Tools & Tactics
- Curcumin: Bioactive compound in the spice turmeric. Works as an antioxidant in part through the process of hormesis – a low-dose form of stress that stimulates the stress adaptation response in a healthy way. The most effective forms of curcumin are Curcumin BCM95 and Liposomal Curcumin. Learn more about hormesis in episode 8 with Todd Becker.
People and Other Resources Featured
Other Organizations Mentioned
- JAMA: The Journal of the American Medical Association, also the most widely peer-reviewed journal circulated in the world. JAMA covers general medical topics with no specific focus.
Full Interview Transcript
[Dr. Cheryl Burdette]: Absolutely. I think that the reason that these are important biomarkers are because they help us to answer some of the critical questions that we are looking at when we seek out preventative medicine and when we are trying to slow an aging process in the body or to turn down the inflammation of a pathology. And so oxidative stress markers, simply put, are ways that you can measure antioxidant status in the body.
And you are hard-pressed to find somebody out there who hasn’t heard that antioxidants are good for us or the fruits and vegetables that are the things that protect our DNA and lower our risk of cancer and heart disease and really the major players out there in terms of pathology; however, for some reason they are not routinely done. And so, for example, a marker called 8-OHdG, a hydroxy-2 deoxyguanosine – long name.
But basically it is a simply first morning urine that tells you you have too many free radicals in your body and it tells you if the DNA is being damaged. And when we go to the research and see how predictive is this marker, how strong is this marker, if we look at the peer-reviewed research in the past five years, you find about 1,000 clinical trials that show that it is predictive for things like cancer and heart disease.
Yet for some reason it is not routinely done yet. So that was another part of my drive for starting the lab, to be able to take these well-researched biomarkers and make them more available to people so that we could use them to help predict health, and to have better outcomes.
[Damien Blenkinsopp]: So you mentioned cancer in particular there, but where are the main areas where most of the research is being done? I also saw you talk about things like neurology, neurological conditions. Now what would you say the brunt of the research that is already existing has been done relating these two issues and things we can track?
[Dr. Cheryl Burdette]: So when we talk about oxidative stress it would depend on which marker we are speaking to and if we are talking about 8-OHdG, then that one probably is most often seen in terms of a risk factor for cancer. The higher it is the more damage there is to your DNA, and the more damage there is to the DNA, the increased chance there is for cancer occurring.
So, for example, we can think of cancer as a seed and not every seed will always sprout, not every seed will always produce a plant; however, if the environment is right around that seed this is what allows it to grow. So if 8-OHdG is high, that is an environment that is more favorable to a cancer growth. If we can see it is high then we can do something about it. We can increase antioxidants in our diet, we can use certain nutraceuticals to help with that.
But this is not the only oxidative stress marker out there, there are also markers for how damaged our fats are in addition to DNA or how damaged the mitochondria is or how damaged proteins are and so when we are looking at the body of neurological evidence now you look at a marker called F2-isoprostane. WHen this is high it tells us about our fats being damaged. Well, the brain is 85% fat, the outside of the nerve is all made up of fat, and the membrane of every cell is made up of fat. So if your fats are damaged then you are more likely to have conditions where there is fat in the body – i.e., your central nervous system, your peripheral nervous system, as well as cellularly.
So in general we see a lot of oxidative stress research around things like cancer, heart disease, and neurologic conditions. And from there you would pick and choose markers. Certain ones will have certain strengths base don the tissue type and based on the condition.
[Damien Blenkinsopp]: So as I understand, you have talked about lipid peroxidation and DNA damage markers there. As I understand it there are kind of two ways to look at this. There is the direct measure of oxidative stress and damage, which is already being done and the two markers you brought up, look at that. And then there is also reduced antioxidant status in the cells. Is that the correct way to look at it coming from those two perspectives?
[Dr. Cheryl Burdette]: Yes, absolutely. I would say that is spot on.
[Damien Blenkinsopp]: Okay, so some of the other areas that I saw that you are looking at, you have the antioxidant intracellular status and the enzyme assays – could you talk about those a little bit in the context of those?
[Dr. Cheryl Burdette]: Absolutely. So glutathione is our major intracellular antioxidant. What that means is the antioxidant that is most preferred in the tissue – so when we take in things, for example people may have heard of resveratrol from grapes, that is in wine and is associated with longevity and what is called the French paradox – even though they eat more fat they don’t get fat, and why is that?
Well, because of the resveratrol and so these plant-based antioxidants will often have the effect in the body of increasing our own production of glutathione and that is one of the more powerful ways that they work, to turn on our own antioxidant systems. So we can measure something like glutathione to see if people have the right level of this in their cells and then when we think about okay, what is that associated with?
Higher levels of glutathione are associated with a low risk of cancer, low risk of neurologic conditions, and glutathione is the major intracellular antioxidant for the liver. So it helps us to detoxify and keep up with toxic body burden from the environment and from chemicals on food, etc. It is also a highly-useful antioxidant in lung tissue. So if it is low you are more at risk for different respiratory conditions and we can use it as a treatment.
By increasing glutathione status in the lung tissue you will see improved respiratory outcomes and you will see decreased shortness of breath and a wide range of improvement. If you think about it, if every cell needs glutathione then increasing the levels can help many, many things.
[Damien Blenkinsopp]: Great, one of the things I was thinking about as you were talking about that, on this side we have the resources or the capacity to fight oxidative damage. So with glutathione, for instance, you are looking at that. Does that necessarily mean that our DNA damage markers and our lipid peroxidation markers – there is actually going to be damage?
Or can that also be if someone has had a very solid diet and they have lived a very healthy lifestyle with plenty of antioxidants, could those markers be higher than usual? And would the opposite be true – would they have used up, if they have some kind of chronic condition, would they have used up a lot of those resources, these antioxidant and glutathione peroxidase, so they would actually be lower and that is how you use it? You can use it as an indicator that there could be some chronic issue there because it is used up, even if perhaps it is not lipid peroxidation or DNA damage?
[Dr. Cheryl Burdette]: It’s an excellent question. So typically if you have high levels and you have strong levels of glutathione you should see less levels of damage in the system, less damage to the DNA, less damage to the lipids, and less damage to the protein; however, there will be times when let’s say, for example, maybe somebody has a chronic viral load and the infection is brewing but it hasn’t created symptoms yet and you can begin to see a depletion of glutathione before harm is done.
And so it allows us to capture things early and then also to intervene so that we don’t continue to slide into a state of disrepair. So on one hand you would think maybe if I am low on this antioxidant I would feel it but for example we measure things like cholesterol once a year for heart disease and we don’t necessarily feel it when that is increasing. The same could be true here. Your glutathione could be decreasing and you might not have outwardly signs yet but if we take time to look at it we can capture this trend and we can treat accordingly.
[Damien Blenkinsopp]: Right, right. And i think people are interested in longevity and human performance, whether it be in terms of brain performance or physical performance in terms of athletics or fitness and so on – would these markers, do you think it would be a useful thing to keep an eye on them in those contexts also?
[Dr. Cheryl Burdette]: Absolutely. That is a great point that you bring up. First of all, preventing pathology, but also optimizing. Because glutathione is the major intracellular antioxidant it is critical to the part of the cell called the mitochondria and the mitochondria is the part of the cell that makes energy, or ATP. So that ATP is what gives us energy, what gives us good performance, what gives us good muscle building, etc. So inherently necessary for optimizing performance as well.
[Damien Blenkinsopp]: So there you are talking about – correct me if I’m wrong – are those the enzyme assays, so superoxide dismutase I and II that look specifically at the mitochondria?
[Dr. Cheryl Burdette]: Yeah, so superoxide dismutase I is in the cytosol, and II is the one specific to the mitochondria. So the one specific to the mitochondria helps to improve function there, lets us know that the mitochondria is recovering like it should, and if we see that low then we can choose the right things to increase that, and know that we need to do more mitochondrial work.
[Damien Blenkinsopp]: Okay, great. So with these it looks like you can actually identify where different problems are; however, why is it that when we have oxidative stress in our bodies it doesn’t necessarily affect the whole body? You are talking as if it is different parts of the antioxidant and oxidative stress systems that will potentially give different patterns.
You take all of the biomarkers and it will give a different pattern depending on the chronic disease you have or the potential issues you have or potentially you are dire in antioxidants. Is that what you have seen in the labs? That people can have different patterns which can show you interesting facts and sort of paint different pictures? Or do you find it can be more or less across the board that there are problems?
[Dr. Cheryl Burdette]: It depends on the markers. So the glutathione might have more ubiquitous issues because again that is the antioxidant everywhere, but yes, you are absolutely right – certain markers are more associated with certain conditions. For example, that is why i choose to not do a total superoxide dismutase and tease them out because one is in the cytosol of the cell and it will have more association with particular conditions like ALS, whereas the one in the mitochondria has more association with fatigue and cancer. So if you are just lumping them all together you won’t get that picture.
[Damien Blenkinsopp]: Right, perfect. When I was looking at this I saw there were at least 30 biomarkers currently available in labs related to oxidative stress in some areas. Why is it that you chose these particular ones? I noticed that some of the areas you haven’t looked at include protein oxidation. You mention this a little bit – protein oxidation and nitration, the reactive oxygen species, assays, and RNA damage and repair. Could you talk a little bit about what you see the merits are and why you made the choices you did about the markers you chose?
[Dr. Cheryl Burdette]: Yes, I think the first thing is I wanted markers that were extremely well-researched. So like the 8-OHdG, if we just look at the past five years, over 1,000 clinical trials with that marker in terms of predicting oxidative stress and free radical loads. So that was my first consideration – do they have a strong body of research? Are they clinically relevant?
So I chose the ones that had the highest clinical relevance and then of course as a lab, the second part is how reproducible are they? How stable are they? How much changes once it goes into the test tube from coming out of the body? So, for example, F2-isoprostane, that is a lipid peroxide. That is a marker of how damaged fats are. And there are other lipid peroxides out there and people – some of the more common ones are things like T-BARS or MDA; however, those are not produced in the body so the T-BARS – the RS on the end of that stands for ‘reactive substance.’
And so it is an extrapolation that is done in a lab and it is a pinnacle reaction that is used to then say, okay, but we don’t make T-BARS inside of our system. They are not endogenously produced. It is extrapolation that is happening in the body; however, F2-isoprostane we make – it comes when you measure the blood. There is F2-isoprostane in it and so it is a better marker because it is more directly related to pathology and symptoms.
So two things for me, how evidence-based is the marker and then how reproducible is the marker as well. So those are the things that I look to. A third thing is then is it unique, does it bring us new information that we are not able to get? So as clinicians, one thing that you will often notice is you will go to the research, you will read about something, and you will think, ‘Wow, that is fascinating. I didn’t know that could be looked at. I didn’t know that could be measured.’
So an example is an enzyme called diamine oxidase, and that is something that we measure – it is the enzyme that degrades histamine. Well, you can see if you have a lower level of that you are going to be more at risk from anything that is histaminergic, meaning yes, of course hives, itchy eyes, runny nose, but also headaches and guy issues and a whole host of symptoms that can be made worse in a high histamine environment.
So you read about this and you say, well, how interesting that would be to know my body’s ability to break down histamine. But then you go to laboratories and you can’t find it. So a lot of these things are very heavily researched in academia but for some reason don’t make the crossover to be available to the general public. So that’s another focus for me as well, taking things that are highly researched and making them more available.
[Damien Blenkinsopp]: Right. I noticed one thing that you have done and correct me if I am wrong you have two different panels. So you have grouped a lot of the markers that you have been talking about today – you have grouped them into one panel so you take those all at the same time. Is that correct? I think you have a blood and a urine panel.
[Dr. Cheryl Burdette]: Yeah, we have probably 20 different panels that we offer – some are blood, some are urine, some are saliva, and some are even hair and some are stool – it just depends on what the best specimen is for what you are looking at. But yes.
[Damien Blenkinsopp]: Is this all on oxidative stress?
[Dr. Cheryl Burdette]: No, we have an oxidative stress profile, a leaky gut profile that looks at zonulin and diamine oxidase and lipopolysaccharide with a neurotransmitter profile that measures things like serotonin, epinephrine, and norepinephrine, adrenal stress testing, thyroid testing, heavy metals.
[Damien Blenkinsopp]: What I was trying to get at is have you tried to simplify – because you are saying each marker should kind of contribute something which is unique to decision-making and tracking and understanding status. So have you combined all into one oxidative stress profile the markers we have been talking about today? Or do you have two or more?
[Dr. Cheryl Burdette]: It’s a little bit of a tricky question because so many things can result in oxidative stress. But in general, the ones that are more intimately considered oxidative stress markers are on that profile but from a clinical standpoint you never have to order the entire profile. You can order single analyze – that is something that is more appropriate for that patient. Let’s say you do the entire profile first and only one thing is abnormal.
For followup purposes you can just run that one thing so that it is less expensive and more targeted to that patient; however, there are a couple of other markers that might get to the question of oxidative stress that are on different profiles – like on my cardiovascular profile, oxidized LDL. And so that is definitely a marker of oxidative stress and it is the truly bad cholesterol.
So people are taught that LDL is the bad cholesterol but it is once it is oxidized, the fat, that the whole story changes. LDL is taken up by the liver and it is utilized in cell membranes and in the brain. But once it is oxidized the liver can no longer recognize it and that is when it starts to be moved instead into these plaques in our arteries.
That does not occur until it is oxidized. That is definitely a marker of oxidative stress but it is not on that profile, it is on the cardiovascular profile.
[Damien Blenkinsopp]: And just to be clear, that is not typically available? Because we have all had cholesterol lab tests and it is pretty general to get your LDL and so on. But that is not a typical test to get?
[Dr. Cheryl Burdette]: No, and it is a great example of what I am talking about. Even journals like JAMA say that it is 17 times more predictive for heart disease than cholesterol itself but yet it is not being routinely offered. The research is much stronger than oxidized LDL and it would give you different treatment options too because if we’re trying to produce the LDL, which is the opposite of oxidizing – oxidizing is when it is charged by a free radical, reduced is when you have antioxidants to accept that free radical. And so if we are trying to reduce it so that it doesn’t become sticky and doesn’t become a plague former.
Then now you are going to use different treatments than just lowering the overall level. You are going to add more CoQ-10. You are going to add things like sulforaphane from broccoli sprouts. It improves our ability to treat these things too.
[Damien Blenkinsopp]: That’s great. So who today is actually using these? When it comes to Dunwoody Labs, what sort of people are using these markers and how are they using them? You mentioned some people use just one marker or some people use a whole panel. So what kind of trends do you see in the moment? Who is using what?
[Dr. Cheryl Burdette]: Because we’re a laboratory, you have to have a physician’s orders in order to get to the testing. So obviously, doctors are the people using them but more specifically the type of doctors that tends to be ordering these are what I would call an integrated physician practicing integrative medicine.
And these are people that are combining things like pharmaceuticals or standard of care, but adding to that – adding lifestyle interventions, adding vitamins, adding supplements, adding these other pieces and so these are typically people that have seen limitations in standard of care and so they are looking for more cutting-edge biomarkers to match their more cutting-edge therapies.
[Damien Blenkinsopp]: Great, thanks for that. Are there any particular trends that you have seen at all in the types of those? You said integrative medicine, but I don’t know, are there different areas of the US which seem to be working more on this? Do you work internationally? Are there specific cases, like you have seen a lot of people using cancer or for other chronic conditions?
[Dr. Cheryl Burdette]: In terms of areas of the country, interestingly I would have had a different answer ten years ago. There were more pockets where you were seeing it, and you likely might expect more West Coast, maybe a little stronger up in the New England area, but really now it has permeated much more than just kind of the periphery of the country.
People everywhere want good medicine. And good medicine demands that we think about lifestyle, that we think about diet, and that we look for better answers because nobody out there would say that we have the best answer to cancer, heart disease, or even the common cold yet.
So there is a lot of area where we still need to dig deeper. We need better answers, and we need better treatment. And so i am finding that really it is not just pockets of the country, but it is everywhere. And it is international as well. So we have associations with labs in South Africa and England, so really people are demanding better answers to help solve problems.
[Damien Blenkinsopp]: So you talked about a few areas where there is a lot of research. Which areas do you think these kind of markers would be very promising or potentially you are kind of experimentally, or others are experimentally, using them for treatment. But the research isn’t strong enough and we kind of need more research to strengthen up our opinions there and the clinical evidence?
[Dr. Cheryl Burdette]: These are applicable to many areas of research and the reason for that is because so often the way we have defined conditions is to say what is the condition? And that is important, absolutely, and they need to know a diagnosis. So for example, why do I not feel like myself? Well, I have a condition, I have a diagnosis of depression.
And then the way that is approached is to say well, in depression, we know that serotonin is low, so we will give a medication that increases serotonin; however, it misses a whole piece of the puzzle and that pieces of the puzzle is that even though there is depression and serotonin is low, why i shte serotonin low?
And so it turns out that an environment that is very high in oxidative that has too many free radicals would be an environment that makes it harder for serotonin in the brain to be made. And so in research they have often been focused on here is a medication, now does it make serotonin go up rather than saying what are these other pathways, what are the other things that are influencing this level of serotonin?
So we are seeing more and more studies wanting to look at underlying cause, measuring things like oxidative stress markers, measuring things like gut health, perceive patterns for the process that is causing the diagnosis. Is there a process of toxic body burden, nutritional deficiencies, inflammation, oxidative stress, and mental and emotional stress that is contributing to this.
[Damien Blenkinsopp]: Right, right. So it sounds like you really see that there is a lot of potential across the board with all sorts of applications which haven’t been explored fully in the research.
[Dr. Cheryl Burdette]: Correct, yes.
[Damien Blenkinsopp]: So in the conference where I saw you, you talked a lot about the link between mitochondria function and methylation function and oxidative stress. Could you talk a little bit about how they are related and how one can influence the other?
[Dr. Cheryl Burdette]: Absolutely. So methylation is a very complicated topic because it is not like there is one site in the body that is methylated. We have methylation of DNA, we have methylation of enzymes, and some things that will increase methylation in one place will decrease methylation in another. You might find something that up regulates methylation in the liver but can down regulation methylation in the brain.
So it is complicated and it gets very tricky to identify that singular pathway and then modulate that accordingly; however, we know that there are broad strokes and then we know that again there is this process that can influence changes in methylation. So for example, high oxidative stress will impact the body’s ability to methylate appropriately – whether or not that is hypo- or hyper-methylation. You will see improvements with that when we lower this burden of oxidative stress.
So for example, one of the things that is really starting to be understood mroe about oxism is they have a lot of problems with methylation and this will make it difficult to turn on neurotransmitters; however, that same problem with methylation makes it difficult to eliminate toxicity from the body. And so what you see is that there is often an insult of oxidative stress that skews the methylation and it is this one process that then causes worse outcomes. And so if we can look and see how much oxidation is going on then this gives us another way to improve methylation in the body too.
[Damien Blenkinsopp]: Great, because that sounds a little bit like a vicious cycle – once you have oxidative stress it is negatively affecting methylation which, as you said, affects your ability to resolve so many issues in the body.
[Dr. Cheryl Burdette]: Yes.
[Damien Blenkinsopp]: I haven’t heard of this before. Is that something that is quite new or unique to you? Or is it something that people are starting to talk more about? What kind of stage of development is methylation versus linked to oxidative stress, as being discussed in research?
[Dr. Cheryl Burdette]: I think that you would see hints of this back even a decade ago, but really this deeper level of understanding and how intimately intertwined they are. I would say that is probably a little newer. And again it gives us – when you speak methylation you are talking about genetically.
What people are measuring is probably polymorphism and you see these little snips, these little mistakes in the DNA pattern. And there is not a lot to do about it at that time; however, if we can improve the environment of oxidative stress we can improve the ability for those damaged genetics to function better so it gives us something very treatable to go after.
[Damien Blenkinsopp]: That’s great. So as i understand it, mitochondria has a similar kind of vicious circle dynamic going on with oxidative stress as well.
[Dr. Cheryl Burdette]: Yes.
[Damien Blenkinsopp]: It is similar, right? Correct me if I am wrong, but the oxidative stress will damage the mitochondria and the mitochondria will start to create more oxidative stress, which creates a negative dynamic.
[Dr. Cheryl Burdette]: Absolutely, and so while I characterized that marker 8-OHdG as a marker for DNA damage, what they are seeing in the research is that the damage in the DNA will also influence expression of the mitochondria too, so you can think about it as a marker for causing damage there as well.
[Damien Blenkinsopp]: Okay, so looking at some kind of typical scenarios where you have been using these biomarkers and found them of the most use, where would you say they are very useful for assessment of status, for help with diagnosis at the moment? Where would you mostly use them or mostly see the types of tests that people are most using it for at the moment? In which kind of cases?
[Dr. Cheryl Burdette]: Well on one hand, in my ideal world, I would love to see most people looking at their markers of oxidative stress once a year. And the reason for that is because I find them to be highly more preventative in their nature than cholesterol ever thought of being, for example. So if once a year we could get an idea of antioxidant status in our system and know if our antioxidant level is keeping up with damage in our body, it just gives us a much better window into prevention.
But otherwise if we are thinking about them in terms of where is oxidative stress, what pathology is oxidative stress most linked to, then I would say that the area where that shows up the most is probably cancer, heart issues, and neurologic.
[Damien Blenkinsopp]: Is that to assess status, like how bad it is? Is that kind of what you are trying to do with that?
[Dr. Cheryl Burdette]: You are trying to assess the environment and that pathology that it is in. Is this an environment that is going to cause the pathology to flare more? Or is this an environment that is a possibility of remission?
[Damien Blenkinsopp]: Right, great, so it gives an indicator. So you mentioned that it would be appropriate to get these taken once a year. Does that vary per biomarker? Basically, how quickly did these change in values over time? Are there some markers that it is relevant to take more often?
I mean, depending on the context as well. So for instance, someone who is just healthy and they and they just want to understand the level of oxidative stress for aging or performance preferences like optimum health, would it be most appropriate for a year because they don’t really change that often?
[Dr. Cheryl Burdette]: So if you were in a state of pathology, many pathologists deplete your antioxidants, so that is going to cause them to change more frequently. If we are generally well then once a year is probably enough because we are not seeing huge shifts in the system.
But any time there is a pathology or it gets advancing then I would say you want to look at it more often, maybe every three months, to make sure that you are changing the environment so that the pathology doesn’t continue to flare.
[Damien Blenkinsopp]: To go kind of out on this, if you do the intervention, say you did a month intervention would it be worthwhile redoing these biomarkers of oxidative stress tests again, or would you have to wait for three months because it isn’t really enough time to assess any change?
[Dr. Cheryl Burdette]: Some will change more quickly than that but in general to really get to see saturated and to really change terrain, you want to get the body – it is more of the body probably. You want to give the body – it is more the body, probably. You want to give it a good three months to really have that opportunity as it is more like building a muscle. That doesn’t happen overnight.
[Damien Blenkinsopp]: Right. So are there any inaccuracies or confounders to this data? For example, do they vary, a bit like cortisol can throughout the day? Does it vary throughout the day so that it would depend on what time of day? Are there any other confounders involved in how you collect the data that you have to be careful of?
[Dr. Cheryl Burdette]: Yes, some can change throughout the day; however, if the marker that is susceptible to that, then we do things to control for that. We say this one has to be withdrawn fasting in the AM before a certain time. So depending on the test it will do some things to adapt to that; however, if there aren’t specific instructions in terms of collection then know that those are the ones we have found to be stable when we look at multiple samples throughout the day and throughout the week, that they are consistent.
[Damien Blenkinsopp]: You mentioned also earlier that you try to choose the best, most accurate labs, which don’t have issues that say they move out of the body. I know you have seen labs in the past where you can get them taken and sometimes if they are not frozen immediately with the correct protocol that can skew the lab values and then you have got inaccurate data.
Are there any of these markers which require kind of a very careful protocol which has to be followed? Or are these kind of like standard blood tests where you can basically just give the blood sample and as long as you get the blood sample in reasonable standard condition it is fine?
[Dr. Cheryl Burdette]: So we have checks for that too, so when we receive a sample if it looks off for any reason, if it is hemolyzed or something of that nature, then we notify the clinic that we reject the sample. We we don’t run anything that we are suspicious of how it how it looks, but otherwise we have tried to choose things that are pretty stable because just for that reason, it will improve the validity.
Now, some things have a timeline so many of them will have them shipped overnight or shipped with ice to help preserve the quality of that specimen. And then we are very picky about, from our end, on receiving how quickly those things get processed and even moved to a -80 freezer in order to store these things in a way that they don’t degrade.
[Damien Blenkinsopp]: Right, that sounds like standard procedure, rather than any of these markers having specific instabilities, which would mean it would be more difficult – I think I am thinking of TGF-beta I and markers like that. I may be wrong here, but I have had had a history of the values being different based on the way the blood was taken.
[Dr. Cheryl Burdette]: Absolutely. So we try to do a lot around education. Every kit comes with very specific instructions that whoever is drawing it should follow and so we try to do a lot around quality control.
[Damien Blenkinsopp]: Right, so you have leaflets and brochures explaining how it should be taken. Because these are getting drawn now in different places, right, your samples?
[Dr. Cheryl Burdette]: Right every tube for every draw comes with a set of instructions that says exactly how it should be handled.
[Damien Blenkinsopp]: Okay, so at the conference you talked about some specific interventions which may have an impact on some of these markers. I would love for you to talk about those a bit. Now, you talked about things like [inaudible 00:34:32]. Which interventions have you found to be effective against these markers and to effectively lower them or increase them in terms of the antioxidant status?
[Dr. Cheryl Burdette]: In general some of the things I have found to most profoundly shift these markers of oxidative stress are nice, bioavailable preparations with things like percumins and cuminoids and those are compounds that come from turmeric and when those are put with certain black pepper extracts that really increases the plasma bioavailability and to see various shifts of the markers.
Also things like sulforaphane, which comes from broccoli, that I have seen be quite helpful in terms of improving glutathione and lowering F2-isoprostane; however, the interesting things about it is what is going to be the most effective for shifting the marker is going to be to treat the pathology – to treat the cause of what is going on.
And so sometimes it is not an antioxidant at all, but figuring out there is an underlying infection and getting that under control, or figuring out that there is some heavy metal toxicity and lowering the toxic body garbage. Or figuring out that there is a particular nutritional deficiency and increasing that or figuring out that somebody’s main reason for the oxidative stress is coming from a gut issue and treating that accordingly.
So that can be one thing that is really nice about these markers. There is no profile out there that is going to measure every chemical and every bug and every exposure that we have that you can see that it is doing damage to the body and now you can track that to make sure you are getting improvement.
[Damien Blenkinsopp]: RIght. So have you seen scenarios where you talk specifically about pathogens and infections and metals where you have targeted those or moving those and you have seen these markers improve without adding [inaudible 00:36:25] or any other thing to help with the markers?
[Dr. Cheryl Burdette]: Yeah, Lyme disease is a good example of that for two reasons. First of all, the infection itself is hard on the mitochondria and then second of all many treatments that are used for Lyme involve antibiotics and in fairly high doses and long term. So in terms of getting those up, treating the Lyme infection will help to improve some of the glutathione status and the mitochondrial status. So yeah, definitely, we see it all the time.
[Damien Blenkinsopp]: So does alpha lipoic acid have an impact on the oxidative stress or is it more working around moving heavy metals, so it is kind of working around the origin of the problem rather than the oxidative stress itself?
[Dr. Cheryl Burdette]: Things like alpha lipoic acid have so many different ways they work in the body that I think that is the nice thing about it. One the one hand it is a gentle chelator but it is a big chelator of metal, so it is a lower toxic body burden. on the other hand it is going to even just decrease the lipation of the foods you eat, which is going to decrease oxidative stress on the body that way.
It will facilitate and acetylcysteine part of the peptide that makes up glutathione and helps to pull that into the cell. So it helps to make glutathione that way. It recycles glutathione so that is the other way it is going to reduce oxidative stress. So think that is the beauty of the natural therapies, that they are not limited to just one mechanism by which they work and that is why we see such changes in things like that.
[Damien Blenkinsopp]: Great, thank you. We are coming towards the end of the interview now. There is one particular dynamic that I have seen discussed quite a bit lately, and that is there can be too much antioxidants. So I was wondering if these biomarkers, some of them have a U-curve or an N-curve, I guess you could call it also.
There is an optimum value and if it is too high often people will look at it in the media and the news and it will be like the more antioxidants you can get the better, no matter how much you take. So potentially you can take a ton of [inaudible 00:38:24], for example. But do you see scenarios where you could be overloading the body with antioxidants and it would push it the other way and cause problems to people who are potentially thinking about being aggressive with these kind of antioxidative stress strategies? Do you see that kind of dynamic in the labs?
[Dr. Cheryl Burdette]: You can, like for example there is a condition where if someone is missing the enzyme to recycle glutathione that can build up and that can even cause certain pathology; however, it is hard to do on planet earth. We are so assaulted by pollution and junk in the air and junk in our food that it is more difficult to overload in terms of the antioxidant piece of it now.
On the other hand, for example one of those markers we are talking about, 8-OHdG, there is more oxidative stress and to my knowledge there aren’t studies that talk about that if it is too low being a problem. But you could have an overload of an antioxidant causing issues elsewhere, it is just that 8-OHdG is not predictive on the low side for the condition.
[Damien Blenkinsopp]: Right, I see. So it is kind of missing the DNA breakdown because you are keeping it low. Because I understand that your 8-OHdG is a blood marker for damage that has taken place. Is there any way that you can have DNA damage taking place but somehow you have suppressed that marker? Is that what you are saying?
[Dr. Cheryl Burdette]: Well I don’t know that there are conditions that are associated – I don’t know that it is bad to have low DNA damage is I guess what I am saying. I don’t know that.
[Damien Blenkinsopp]: It sounds like in general in the labs you haven’t seen any – it is better to have high antioxidant status on one side of the markers and low damage and you haven’t really seen any cases where that isn’t the case?
[Dr. Cheryl Burdette]: Absolutely. I mean I am with you though. We have to have some oxidative stress. That is what causes us to have improved performance with athletics and some oxidative stress that comes up opens up our blood vessels. So yes, it is absolutely possible.
[Damien Blenkinsopp]: You just mentioned athletic performance oxidation. Do you have benchmarks? Would you be able to tell the difference to someone who has been training too heavily, for example, or when someone is not training? Can you tell the difference between someone who exercises a lot every week and someone who doesn’t based on oxidatives tress?
[Dr. Cheryl Burdette]: Yes, because in general even though exercise creates some oxidative stress when someone is performing well they will have better recovery. And so you won’t see DNA damage. You won’t see damage to the fats because those are more long term and they are more tissue markers and more of that long-term status.
So what you are seeing is that someone is not recovering from that oxidative stress that the exercise is creating and that is markers that start to go up. And I think of a particular patient who was a triathlete and she was not seeing improvement in her performance anymore and she was having troubles with recovery. When we got her oxidative stress markers down into more of a normal range then her performance picked up again.
[Damien Blenkinsopp]: Which markers specifically in that case were out of range?
[Dr. Cheryl Burdette]: Her 8-OHdG was elevated and her total glutathione was low.
[Damien Blenkinsopp]: So you basically helped her to rebuild the glutathione. Was she training too much? What did you link for the 8-OHdG to be too high?
[Dr. Cheryl Burdette]: Actually, interestingly it was part of the training but she ended up being one of those who had an underlying infection as well. So when we got her infectious load down her 8-OHdG came down and her marker of oxidative stress. Her performance went up and we also saw an increase in her white blood cell count.
[Damien Blenkinsopp]: I think you make a great, important point there. I think a lot of people are seeking – when you try to push yourself to performance, maybe it is working extremely hard or it is like doing fitness and athleticism. If you see problems in your performance it could well be there is a tiny infection or other issue that is holding you back.
So it is probably worth looking at these oxidative stress markers and that might help you. And seeing a physician to see if that can be resolved, then you can get back to performance. So it is interesting that people should really be thinking about this if they are suffering in their performance and what they are doing.
[Dr. Cheryl Burdette]: Absolutely, and you see a lot that just the wear and tear of training is a big deal. For example, athletes are uniquely susceptible to leaky gut all the time and [inaudible 00:42:41] less time than it takes to digest, so they will have markers of leaky gut that are off. And then when we treat those the oxidative stress improves as well.
[Damien Blenkinsopp]: So we talked a little bit about how these markers aren’t so widely available at the moment. What do you think are the main challenges to get them? What can be done to spread the use of these oxidative stress markers more?
[Dr. Cheryl Burdette]: Education – I think that people understand that having good antioxidant status is protective and preventative. Just the more we understand about them, I think the more motivated people will be to look at them. But the education needs to happen for physicians as well.
Now, in the States part of it is the way that our healthcare system is structured in that our health care says if things are for prevention they are given certain codes and these are less likely to be reimbursed by insurance companies. Now, as backwards as that seems you would think that insurance companies would be interested in prevention but it is not quite logistically the way it is set up at the moment. So education of patients, of physicians, and of our infrastructure too.
[Damien Blenkinsopp]: Okay, so what kind of things do you think will help or that you are carrying out in terms of projects at the moment, to improve the education? I know that you do a lot of conference talks.
[Dr. Cheryl Burdette]: Yes, absolutely out there they are talking about these things. But that is another reason that Dunwoody Labs is so intimately involved with research, because the way we are going to make our big breakthroughs is to publish more, to get the data out there, and then when that happens and we are able to validate these things more and more they will end up in clinical practice.
And so unless we support this research, we are never going to see that happen. So I am a big advocate of that and more training as well, increasing things like nutritional training in medical schools. All that will be important to really seeing a shift.
[Damien Blenkinsopp]: Great, thank you for that. Now, looking towards the future – I know in the next ten years, are there any areas you are looking forward to with excitement? In terms of the evolution of these markers. Are there new markers that are going to be available? New tests or anything interesting that is going to happen over the next ten years that you can foresee that is going to be pretty cool and going to help us to see a lot more?
[Dr. Cheryl Burdette]: Yeah, I think that what a lot of these markers are coming out and helping us to realize is that I think before there was a focus to find a biomarker that was shifted by a drug, and if you had those two things together – a drug and a biomarker – then that was really the package that healthcare was looking for to sell, so to speak. However, I think a lot of these markers that are coming out now, what the natural consequence of them is is that the real way you would treat them would be to change the diet, to increase exercise, to make some lifestyle changes.
So I think we are seeing more and more emphasis on markers that let us know about how lifestyle is affecting us and therefore more and more people will be motivated to change that. But beyond that the second thing I am really excited about is we are bringing on a suite of genetic testing and this is just fascinating because now I can look at somebody’s genes and I can say, ‘Based on your genetics, here are some of the functional markers that we need to look at once a year in you.’
So you could even individualize someone’s testing workup based on areas of weakness and you could say based on your genetics you should not take this medication because you are more likely to have these side effects or it just won’t work for you or here is a botanical that makes the most sense for you based on your genetics. Here are some food interventions that make the most sense.
[Damien Blenkinsopp]: That sounds great for preventative health, in particular. So what kind of time table are you looking at for that? Is it five years? A lot of people get 23 and Me today. Is that something you can use or does it need to be a lot more specific than that?
[Dr. Cheryl Burdette]: I think that is a great start and it gives you some information. But we are bringing on this genetic testing and it will be in the next month or two.
[Damien Blenkinsopp]: Well that’s great to hear. Cheryl, thank you very much for your time today. It has been a great chat and we have learned a lot about these markers. I look forward to seeing them in the [inaudible 00:46:40].
[Dr. Cheryl Burdette]: Yeah, thank you for having me on. I really appreciate it.