What is the best biomarker to track your oxidative stress burden? Joshua Fessel explains why F2-isoprostanes provide the best assessment of our ongoing oxidative state.

Today’s topic is understanding your oxidative stress levels via lipid peroxidation. We previously took a broad look at measuring and lowering oxidative stress in episode 4 with Dr. Cheryl Burdette.

Now, we are going to take a look specifically at one of the more accurate and reliable markers: F2 isoprostanes, a measure of lipid peroxidation. This is an important marker for the fact that every cell membrane in the body is comprised mainly of lipids and damage to these delicate structures can lead to a host of degenerative health conditions, including cancer.

“…I have a personal sort of one-man crusade to actually get rid of the term oxidative stress because I think it’s too nonspecific. It sort of carries with it the idea that every free radical that’s produced in a living system is bad and we know that’s not right.”
– Joshua Fessel

Our guest is Joshua Fessel, Assistant Professor of Medicine and Pharmacology at Vanderbilt University. His research interest focuses on pathways that control molecular metabolism looking at the Krebs cycle. For example, mitochondrial function and interactions between oxidative stress and cellular metabolism is what we’re looking at today.

Dr. Fessel has done 49 studies on these subjects and he’s worked on research in isoprostanes directly with L. Jackson Roberts, one of the researchers responsible for the discovery of isoprostanes in 1990.

He’s also the founder of Vanderbilt’s Mitochondria Interest Group, which is the multidisciplinary group of nearly a hundred investigators who study all aspects of mitochondria, biology, and metabolism. Obviously mitochondria is another thing that comes up in his show quite often.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • Dr. Fessel distinguishes between “good” oxidative stress (oxidant signaling) and “bad” oxidative stress (oxidant injury) (7:15).
  • The site of free radical production within a cell or within the body may determine lifespan (12:35).
  • Current relevance of tracking levels of F2 isoprostanes and other biomarkers of lipid peroxidation products (17:15).
  • Lack of reliable intervention for slowing the aging process at this time (17:15).
  • Study that found caloric restriction decreases F2 isoprostane levels (20:15).
  • Types of markers that exist today and relative usefulness of F2 isoprostane (22:35).
  • Measuring the byproducts of free radical reactions vs. measuring actual free radical levels helps distinguish between signal and injury (23:30).
  • Chemistry of F2 isoprostane formation is well-known and the molecule tends to be stable and measurable compared to other biomarkers (24:49).
  • Biomarkers of Oxidative Stress (BOSS) studies established isoprostanes as among the most robust biomarkers for oxidative stress (26:55).
  • Distinctions between in vivo (within a living organism) and in vitro (in a test tube or petri dish) (27:55).
  • Lipid oxidation products are useful to study because lipids are present in every cell of the body (29:57)
  • Effects of dietary antioxidants and exercise on isoprostane levels (33:27).
  • Single high-fat meal doesn’t significantly raise isoprostane levels (36:06).
  • Most advantageous times of day to collect blood and urine samples (37:50).
  • Seasonal variation with regard to sample collection (38:56).
  • Effects of acute illness or injury on biomarker levels (39:38).
  • Ability of supplements to lower TBAR and MDA levels (41:10).
  • Dr. Fessel’s tips on how to weed out poor-quality studies when reviewing research on a supplement (43:42).
  • Dr. Fessel describes the Feeding Danny Project: a year-long case study on an organic, whole-foods dietary intervention for a morbidly obese man that is being made into a documentary (47:03).
  • Baseline metabolic functions and biomarkers Dr. Fessel will be testing on Danny: cholesterol, HbA1c, blood sugar, triglycerides, kidney and liver function (52:56).
  • Dr. Fessel’s wish list of comprehensive testing he would do in the absence of budgetary constraints: thyroid function, isoprostane levels, malondialdehyde levels, TBARS, hsCRP, plasma ascorbate, vitmain E and other antioxidants (53:42).
  • Discussion of health parameters that can improve in response to dietary or lifestyle interventions before weight begins to change: blood sugar management, cholesterol levels, LDL particle ratios, inflammatory markers, correlating fitness tracking data with lab biomarkers (55:15).
  • Dr. Fessel’s personal weight loss journey (61:25).
  • Biomarkers Dr. Fessel tracks on a daily basis and his recommendation for the one best way to use data to improve health, longevity and performance.

Joshua Fessell

The Tracking

Biomarkers

    Lipid Oxidization Levels

  • F2 isoprostanes: Inflammation-promoting byproduct of lipid peroxidation. A byproduct of cellular aging and a more direct marker of lipid peroxidation levels in your body than TBARS and MDA. F2 isoprostane levels in urine should be below 8.4 pg per ug creatinine. Pubmed lists 1330 studies that include F2 isoprostanes.
  • Isofurans: Byproducts of oxidation of arachidonic acid. Exert similar effects to isoprostanes. Used as a measure of mitochondrial membrane damage.
  • Lipid Peroxidation

  • Malondialdehyde (MDA): A naturally-occurring byproduct of fatty acid oxidation and arachidonic acid metabolism. A highly reactive free radical used as a biomarker for oxidation. Can be monitored but doesn’t provide actionable information.
  • Thiobarbituric acid reacting substance (TBARS) Assay: A method for measuring free radical activity, that is commonly used but problematic. It is difficult to obtain accurate values because the test itself causes free radical formation. As with MDA, this marker has been used extensively in the research.
  • DNA Damage

  • Guanosine: Nucleic acid base that forms part of the structure of DNA. A biomarker that can be monitored but doesn’t provide actionable information.
  • ADO DG guanosine: Analog of guanosine and a byproduct of cellular aging.
  • 8-OHdG: 8-hydroxy-2′ -deoxyguanosine: Byproduct of free radical interaction with DNA. A potential biomarker for oxidative injury vs. oxidative signaling. Tested via a first void urine test to show levels of oxidative stress in the body. This marker is supported by over 2000 research studies. See the Pubmed entry here.
  • Cardiovascular Risk

  • High Sensitivity C-Reactive Protein (hsCRP): A gold standard measurement for inflammation that other inflammatory biomarkers, such as F2 isoprostane, can be measured against. This is an inflammation marker that is used to also track cardiovascular risk. Values of below 1 are shown to represent low cardiovascular disease risk, however the most desirable level is close to 0 (e.g. 0.1 or 0.2 mg/dL). Pubmed currently contains over 2,900 research studies on hsCRP.
  • LDL-P: Measures the density of your LDL particles. Research shows that small LDL particles are the ones that play a role in cardiovascular disease. This test is not yet routine, but provides the most accurate evaluation of cardiovascular risk today.
  • Biomarkers Used on Feeding Danny Project

  • Cholesterol: The cholesterol panel covers a number of markers related to lipoproteins in the blood. There are standard markers that all doctors and labs will run, and some newer specialist labs that are more specific and accurate.
  • Triglycerides: Should be below 100, optimally under 70.
  • Fasting Blood sugar: Typically taken first thing in the morning after an 8 hour fasting period. Ideal healthy levels are around 73 mg/dL. A cut off point to keep below is 92 mg/dL as an indication of blood sugar disregulation.
  • Hemoglobin A1c (HbA1c): Measure of glycated hemoglobin, or hemoglobin to which glucose has become attached – a process that occurs when blood sugar levels become excessively elevated. A proxy measure used to assess your average blood sugar over a period of time. Since haemoglobin is part of the red blood cells it is exposed to blood sugar over the lifetime of the red blood cell, thus giving a measure. As such this measure is used to identify blood sugar control issues. Levels of 5% or higher can be indications of blood sugar disregulation. HbA1c has been well researched and has been included in more than 34,000 studies published on Pubmed.
  • Basic Kidney Function Test: Blood screen for basic kidney function that Dr. Fessel plans to monitor in the Feeding Danny project. May include uric acid, blood urea nitrogen, creatinine and albumin.
  • Basic Liver Function Test: Blood screen for basic liver functions that Dr. Fessel plans to monitor in the Feeding Danny project. May include bilirubin and liver enzymes such as alkaline phosphatase, LDH, SGOT/ALT and GGT.
  • Basic Thyroid Function Test: Can include thyroid stimulating hormone (TSH), T-4, T-3 uptake, Free Thyroxine Index. Dr. Fessel noted these as nice to have, but too expensive for the project’s funds.
  • Other Biomarkers of Oxidative Stress Mentioned

  • Glutathione: Major antioxidant enzyme used by the body. Dr. Fessel has seen that this is depleted in smokers. The optimum range Christine Burdette’s Dunwoody Labs (from episode 2) uses is 658.3 – 988.5 µM, sample report here.

Lab Tests and Devices

  • NMR Lipoprofile Test: LDL particle number testing was mentioned. This lab test is currently the gold standard of cardiovascular risk assessment which it does by looking at the LDL particle number and size.
  • Precision Xtra Blood Glucose and Ketone Monitoring System: Pinprick blood sugar and blood ketone measuring device that you can use at home.
  • Fit Bit Charge: Fitness tracking device. Suggested by Damien as a way to monitor progress in the Feeding Danny project.

The Tools & Tactics

Supplements

  • 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.

Other People & Resources

People

  • L.Jackson Roberts II: Medical researcher who discovered isoprostanes and founder of Vanderbilt University’s Mitochondria Research Group.
  • Aubrey de Grey: Mentioned by Damien regarding his research on longevity. Listen to Aubrey deGrey discuss his longevity research here.
  • Bob Troia: Tech entrepreneur mentioned by Damien regarding his long term experiment in which he tracked his own blood sugar levels for an extended period of time. Damien’s interview with Bob Troia on his n=1 experiments.

Resources

  • Biomarkers of Oxidative Stress Study (BOSS): Series of studies sponsored by the National Institute of Environmental Health Sciences and NIHS to determine the best markers of oxidative stress or oxidant injury in a living system. Mentioned by Dr. Fessel in regards to establishing isprostanes as the gold standard.
  • Feeding Danny: Documentary of a year-long dietary intervention that Dr. Fessel is involved with.

Full Interview Transcript

Click Here to Read Transcript
[Damien Blenkinsopp]: I just want to thank you so much for joining us today.
[Josh Fessel]: Sure. Thanks for having me. This is really fun for me. This is a new thing for me, but I’m really looking forward to it.
[Damien Blenkinsopp]: Excellent, Dr. Fessel. I really enjoy these too, so we’re both coming at it with enthusiasm.
[Josh Fessel]: Absolutely.
[Damien Blenkinsopp]: First of all, I always like to hear people’s stories a little bit about how they started working with what they’re working with. How did you get interested in the subject of oxidative stress and start working on that?
[Josh Fessel]: Oh, that’s a great question. I’ve been thinking about oxidative stress for the last almost 16 years and it really started when I was in graduate school or looking to start graduate school. I started a training program to train both as an MD – so it was clinical – a clinically trained physician – but also to get a PhD to do a research degree in some area. I was casting about, looking for what I thought would be an interesting area of study for my PhD research and I ended up talking to a guy named Jack Roberts, goes by Jack. His full name is L. Jackson Roberts, II. If you looked for him in the literature, that’s how you’d find him.
I sat down to talk to Jack and found out that he and I – the important part of the conversation was that he and I were very much of a like mind when it came to thinking about science. That the idea was that you could take the fundamental principles of chemistry and physiology and apply those to living systems in a way that you could learn meaningful stuff. It turned out that what Jack studied and still studies actually – he still has a very active lab – is oxidative stress and free radical injury in biological systems. I was really drawn to the approach that the lab took, basing things in organic chemistry and biochemistry and then going all the way to studies in living people. So that’s how I first got interested in it and what was going on in the lab. It was one of those things that I thought it would be fun when I started and it turned out to be even more fun than I thought it would be.
[Damien Blenkinsopp]: That’s great to hear.
[Josh Fessel]: Yeah. So that’s really how I got started and things really took off. We did some work to discover a new class of biomarker for oxidative injury and that led to an interest in mitochondrial function and how oxygen is regulated dynamically in a living system. That kind of led to what I do now, which is more focused on a broader perspective, looking at mitochondrial function and molecular metabolism, carbon source utilization in living systems. What are the fuels, how do they get used, and how do those decisions get made.
[Damien Blenkinsopp]: Great. So does that still involve oxidative stress that you’re looking at?
[Josh Fessel]: Absolutely, yeah. The two are very closely linked. I think about it like a car engine and if a car engine runs perfectly with perfect efficiency, every drop of fuel is converted to motion to useful energy. But we all know that that doesn’t really happen and that you get leaks in the system. Some of that from a car engine leaks out as heat – sometimes it leaks out as an actual sort of fuel or other things and the human body is really no different. And so if the cellular engine runs perfectly, every molecule of fuel is converted to carbon dioxide and water and useful energy, but that doesn’t happen perfectly and the byproduct – the leak – is free radicals and that gets you right into oxidative stress.
[Damien Blenkinsopp]: Right. Why do you feel this is an important subject? Oxidative stress. Are these leaks? And maybe we could talk about the broad strokes of where the leaks are bigger and smaller. But, in terms of oxidative stress, why do you think that’s something worth looking at? And would it be worth tracking, for instance, in people as they age or as they through different health conditions or even, perhaps, when they’re looking at performance.[Josh Fessel]: So, I definitely think it’s something worth looking at. I’ll tell you, I have a personal sort of one-man crusade to actually get rid of the term oxidative stress because I think it’s too nonspecific. It sort of carries with it the idea that every free radical that’s produced in a living system is bad and we know that’s not right. Some of them are quite useful and serve signaling roles, bacterial killing roles. Some of them, under particular circumstances, are harmful and I think that’s what we really worry about. So, I talk a lot of times and I’m trying to be more rigorous in my scientific writing talking about oxidant injury versus oxidant signaling and teasing those two apart. But I definitely think it’s something worth studying, quantifying, tracking in detail because fundamentally, I think, we still don’t really understand all of the concepts that tease apart useful oxidant production from harmful. And so one of the ways I think that we can start to get at that is collect data and be careful about how we define the conditions that we’re studying and then from there you can begin to kind of back calculate and figure out okay in this situation a little bit of stress to the system maybe was actually useful; whereas in this other situation, it was clearly harmful. So I think in spite of the fact that people have been studying free radical biology and oxidative stress for decades now, there’s still a lot we need to learn before we really can translate those findings into something actionable.
[Damien Blenkinsopp]: Alright. Yeah, there’s still many different theories. I guess you’re juggling and trying to prove and disprove different ones. Let’s take a step back. It’s always interesting to see how someone, especially someone working in this area and doing the studies and everything, it’s interesting what they do themselves. Have you tracked your own oxidative stress or you follow that? Do you ever look at that in yourself and have you compared it over maybe a few years or anything like that?
[Josh Fessel]: That’s a great question. So, I have measured my own levels of – I probably shouldn’t admit this. We aren’t really supposed to do this, but we all do in science where you need a so called normal sample and so a lot of times that ends up being you. So in some small studies, yeah, I have actually done that. On a routine basis, there’s nothing that I track as far as oxidative stress or products of redox reactions. This question always comes up as to what would a person track. I think in a research setting there are a lot of things that are useful to look at and I’ve certainly participated as I say in research studies of, for example, looking at products of lipid peroxidation and looking at oxidized lipids that float around in the plasma. And I think that’s really useful, but when it comes to what I would recommend to a person or what I do myself, I tend to be a little more conservative because I really – hang up isn’t exactly right – but I focus on that word actionable because I might be able to tell you that on any given day [unclear 10:47: oh [ axles of] isoprostanes] are this, and my levels of guanosine are this and my levels of malondialdehyde or whatever the product is. But I don’t really know what to do with that and so when it comes to a person in the real world – whether it’s you or me or a patient of mine or whoever – I tend to focus on pretty low level stuff and this is true in my own life. I tend to focus on pretty low level stuff that we know has a pretty clear impact on health and wellbeing.
[Damien Blenkinsopp]: By that you mean that you like to focus on biomarkers which are being used consistently for a longtime of 20 years of research behind them, a link to specific disease conditions or aging?
[Josh Fessel]: That’s exactly right. You got it.
[Damien Blenkinsopp]: My understanding is that – I’ll maybe start calling it oxidant injury. Maybe that would be the correct term. But as I understand it, like F2 isoprostanes and Ado DG guanosine – I always have a problem with pronouncing that one – but these are linked to aging as one byproduct, just as we get olderthese tend to correlate where they’re kind of sloping and steadily get higher. Is that true?
[Josh Fessel]: In general, that is true. In a broad sense, most products of oxidant injury will tend to increase with age and this gets at the whole free radical theory of aging. The idea that at the molecular level, one of the things that drives the aging process is that slow leak of free radicals that’s just part of the normal process of being alive and having an active metabolism in an environment that is or an atmosphere that’s 21% oxygen. And I think there’s some core validity to that idea. In general, I think its right. In the specifics, I think there’s still a lot more learning. I was just reading a paper this morning, for example – it was just published – that where in a given cell or organism free radicals are produced can have a pretty profound impact on lifespan. Now this was in a very simple model organism and how this actually maybe applies to you or me – that’s anyone’s guess. But I think that’s what makes it fun that in general I think the theory has validity and that’s evidenced by the fact that somebody that’s 80 years old, by and large, is going to have a higher circulating level of F2 isoprostanes than somebody who’s 20. But there are a lot of variables that come into play and we’re just teasing all those out and I think it’s really fun to do that.
[Damien Blenkinsopp]: Yeah, I guess there’s like two things we’re often trying to do. Sometimes we’re trying to diagnose or basically zero in on something we can act on. [Inaudible] is actionable. Here at The Quantified Body we’re all about action. Exactly the same like idea. If we’re measuring it and it’s not actionable, we’ll there’s not much point especially as a lot of these tests of devices or things out there are relatively expensive and we talked about that on shows before. So you have to really be careful about which measures you’re wanting to invest your time in because it also takes times, conveniences, all sorts of pay offs in our equation in terms of your lifestyle and the benefits you’re getting out of it. So, in terms of the payoff for these, would it be interesting, for instance, to relate that to age? If you’re interested in longevity, would it be interesting to track? You’ve focused a lot of your work on F2 isoprostane and the benefits of that marker. So, based on your knowledge, would it be something useful? If I started tracking it right now and continued for the next 10 years, would it be possible to compare myself to benchmark people of the same age? And then also maybe get concerned if it tended to go into an upward trend that I felt was sharper than I’d want at this stage of life?
[Josh Fessel]: That’s a really interesting question and I’m trying to think if I know of a study where anybody’s done that where they’ve actually looked over time of a cohort of people to see what happens. I can’t call one to mind, which is not the same thing as saying it hasn’t been done. It might be very interesting. You’re exactly right when you say that the way that you’d want to think about that, the first thing you’d want to know is fairly large group of essentially normal people or more or less normal people of varying levels of fitness and varied diets and all that kind of thing. What does the population look like with respect to any biomarker be it F2 isoprostanes or whatever? And then that gives you a basis for comparison. And then it might be very interesting to see what one’s individual trend over time was with regard to that some markers would be easier to do that with than others. There are lots of ways to measure these things and some of those – some of the methods are more robust than others and that kind of thing. And so, for example, we’ve talked a little bit about F2 isoprostanes and related lipid peroxidation products that I’ve studied over time. Those are really, really robust markers. They’re chemically stable. They’re detectable in every biological sample type you can think of. They’re detectable at pretty small levels, so you don’t need a huge signal to confidentially say okay the level of F2 isoprostanes in the blood or the urine or whatever was this. The problem is that they are expensive to quantify and for a really robust measurement it requires a pretty sophisticated setup. It’s mass spectrometry and blah, blah, blah. So, it sort of fails that aspect or it fails on that criteria and for an ideal test which should be easy, cheap, reliable, robust, [and] applicable to a wide range of situations. So I think we’re still – in terms of what a person would do on a day to day basis, I think we still don’t have the perfect thing to look at and I’ve had people ask me, “Well should I send in a sample for this array of tests for oxidative stress or whatever?” And my general answer is if you want to know and you’ve got the disposable income to do it, yeah that’s probably okay. But it shouldn’t be the top thing on your budget because there are lots of simple things to do that we know are going to have a positive impact on oxidative stress and on every other aspect of health. You know dietary things to think about, regular exercise, [and] all that kind of stuff. So in that regard – the other thing is that as far as the normal aging process goes, I don’t yet have an intervention that I can tell you to try that will reliably slow down or modify the aging process. There are few things that look promising, but I couldn’t say oh you seem to be aging rapidly. Why don’t you try this?
[Damien Blenkinsopp]: That’s an interesting discussion and longevity is one of the things we look at and we recently had Aubrey de Grey on the show. If you’ve heard of him or you follow some of his work, he’s very focused on longevity and promoting ending the aging equation and investing in research. He actually wrote a book about the mitochondrial theory of radicals and so on. So I’m sure you’ve connected there. So, he’s looking at a whole bunch of markers every year – 160. But I think he feels like you do, he’s really looking for something that goes perhaps an extreme, I think. I think maybe this is like an angle that could be interesting. It’s like if something goes extreme in terms of its nearly off the normal curve. It’s in the top 10% or the top 5%. Then he gives you reason to kind of look at it. But while it’s remaining within a range, which has been detectable, then I think what you’re saying is like it’s not like it’s very actionable or you already can think of something. And I guess oxidative stress – there’s still a lot of controversy around it – oxidative injury. So, when it comes to vitamins – vitamin C, vitamin E, succinate, and other interventions that people use to try to increase their antioxidant levels and lower oxidative stress, I guess in terms of the actual research supporting that and evidence that’s not really there yet. But we were just talking about it before this chat and we’ll talk about it more is the diet. And there’s obviously a lot of people doing different diets today and it’s a subject we’ve discussed before and we’ll keep coming back because there’s so much confusion over which diets work and which don’t and what they’re useful for. But I think it does come to mind that your diet could have an impact on your oxidative stress levels. So, potentially tracking F2 isoprostane once per year and changing your diet for a year and seeing what happens or perhaps a shorter amount of time, might be something relevant just to see if that has an impact in terms of how would you compare it to say inflammation such as high sensitivity CRP, which is a bit very common standard measure of inflammation. So you can often see an impact in CRP when it comes to diet – pretty substantial. It varies. I’ve been following mine, for instance, for a very, very long time and as I’ve changed my diet and optimized it, like it’s virtually zero at this point where it started at closer to 1, like around .8 – it was somewhere around. Which isn’t high, but it’s just you can see the difference over time. So, I’m wondering if you could see that kind of change over time if you feel that you might be able to see that. I know maybe in the research it might not exist, but sometimes if we’re looking to kind of go ahead of the research and just see – it’s like then it equals one experiment and maybe we can inspire someone to do some research if we go ahead.
[Josh Fessel]: Absolutely. I think that kind of thing could be very valuable and in small studies those sorts of interventions have been done where people have been transitioned to – for example, Jack Roberts – the guy I mentioned – the guy that discovered isoprostanes did a small study where he took young, relatively healthy – in other words, no chronic diseases – nonsmoking adults, but who were overweight and measured F2 isoprostane levels and they were increased and had them participate in a program of caloric restriction. So they did and it was pretty robust. It was about a 40% caloric restriction. So 60% of their typical core needs average over like a 3 day period or something like that.
[Damien Blenkinsopp]: So, could you just specify? Is that caloric restriction based on normal human needs or was it based on their original intake?
[Josh Fessel]: If I remember – I got to think about that. It may have been based on normal dietary recommendations. I’m trying to remember the specifics of that.
[Damien Blenkinsopp]: We can check that. We can link to the study or whatever.
[Josh Fessel]: Yeah.
[Damien Blenkinsopp]: It’s not essential, but I thought it was interesting. I imagine they probably did it at normal human intake.
[Josh Fessel]: I think that’s probably what they did actually. Although, as I recall, they did sort of do a food diary and the caloric intake that these people had, while they were overweight, it wasn’t wildly off what the normal recommendations were. Maybe 10% different or something like that. But the only intervention of this short period of time was a caloric restriction and there was a rapid fall in plasma F2 isoprostane levels well before there had been any substantial weight loss. I think the average weight loss at the time of the nadir of F2 isoprostanes was something like a pound or two. So it was not a significant percentage of bodyweight, but there was this really pretty impressive effect on this marker of oxidant injury and so I think what you’re describing – tracking over time within and individual and modifying diet in some way, be it increased antioxidant intake or even somebody had weight to lose and they wanted to try a more calorically conservative diet and then track markers like that, I think that could be very informative if the means exist to do it and all that kind of thing.
[Damien Blenkinsopp]: Well so let’s talk a bit more about the isoprostane because you’re work has kind of shown, as I understand, that it’s one of the better markers compared to the ones that are used more popularly, we’ll say today, still because they’re kind of the ones – I don’t know how you say it – the ones that have been in place a long time. So, what kind of markers exist today and why do you feel the F2 isoprostane has been a more useful marker?
[Josh Fessel]: That’s a great question. So there are tons of markers that you can look at and most of them are some byproduct of free radicals reacting with some large class of biological molecules. So you can look at the products of free radical reactions with sugars or lipids or proteins or DNA or – and depending on where you start from, that determines what kind of product you end up with.
[Damien Blenkinsopp]: So it’s kind of like you’re just trying to measure the volume of free radicals by what happens when they hit other thing and –
[Josh Fessel]: That’s right. That’s exactly right. Yeah because, by their nature, free radicals are fairly evanescent things. They’re reactive and they don’t last long. There are techniques to actually measure the radicals themselves and those rely on techniques like electron paramagnetic resonance measurements and that sort thing. So they’re specialized techniques and they’re really kind of research only sorts of deals. So if you really want to know about the radicals themselves that’s what you end up doing. But for most of us and again if you’re thinking about oxidant injury in particular, I actually find it more useful to look at the byproducts of reactions that we know to be fairly uncontrolled reactions because, in my mind, that conceptually gets you back to a process that’s injury as opposed to a deliberate signal. So you can look at anything from – we mentioned 8-oxo guanosine. That’s a product of free radical interaction with DNA. You can look at malondialdehyde, which comes from lipids and can come from some protein oxidation. There are protein carbonyl assays you can look at and they all tell you some information. The reason that we’ve settled on F2 isoprostanes and related compounds is that we know a lot about the chemistry of formation. We know from the moment the inciting radical is generated, we can walk through the reactions that lead to F2 isoprostane formation. And this is through work that Jack did. When these things were first discovered in the 1990’s, we know that once they’re formed, they hang around in a more or less unchanged structure – a more or less unchanged form. And further when they do get metabolized, we know what the metabolites are. So there’s no source of spurious generation. When you look at things like malondialdehyde or like the TBARS assay, the thiobarbituric reacting substance – the problem with assays like that is that they tend to generate some signal in the process of the measurement of itself and so it’s hard to know, except in a relative sense, how much of what you’re measuring was there to start with and how much of it came about as a result of the measurement itself. By contrast, I’ve heard Jack tell this story a few times of when they discovered the isoprostanes back in the early 90’s, they did an experiment where they took a beaker of urine and sat and measured the level of isoprostanes in the urine and then sat the beaker of urine on a hotplate for about 72 hours which ought to – any spurious generation’s going to happen, that’ll do it and the levels were exactly the same as they had been 3 days before.
[Damien Blenkinsopp]: Wow.
[Josh Fessel]: Yeah, so really robust and –
[Damien Blenkinsopp]: Yeah. So that means you could ship it around the world. So you’re talking about urine samples here?
[Josh Fessel]: Yes, yes.
[Damien Blenkinsopp]: Right. So that’s also very accessible –
[Josh Fessel]: Correct.
[Damien Blenkinsopp]: Compared to blood. Yeah.
[Josh Fessel]: That’s correct, yeah. So exactly what you say has been done. We’ve analyzed urine samples from the deep jungles of Southeast Asia looking at measurements in patients with malaria and all that kind of stuff. So it really is robust in that regard. There’s also a series of studies actually that are sort of interesting reading called the Biomarkers of Oxidative Stress Study or the BOSS study. And this was published in four or five installments. It was a study sponsored by the National Institute of Environmental Health Sciences and the NIHS wanted to know exactly the question that you’re asking. What are the best markers of oxidative stress or oxidant injury in a living system and so they did head to head comparisons of a variety of different biomarkers in a bunch of different contexts starting with different oxidants, looking at different biologic samples and the isoprostanes emerged as of one of the most robust. I don’t want to overstate – it’s certainly not the only thing that’s useful to look at. But in the BOSS studies, the isoprostanes emerged as one of the most robust across a variety of context, samples, that kind of thing. But the BOSS studies are NIH sponsored. They’re publicly available. They’re kind of interesting reading actually.
[Damien Blenkinsopp]: Great. Yeah, we’ll definitely link to all of this stuff in the show notes. One of the big things I understood was there was a difference between in vivo and in vitro. Could you talk a little bit about that because sometimes people go and read studies or they go to a link for a study and it’ll be in vitro. They just assume that it’s going to be exactly the same in the body. So, first of all in vivo means inside the body and in vitro basically means in a test tube.
[Josh Fessel]: In a living system.
[Damien Blenkinsopp]: Right.
[Josh Fessel]: That’s right. So most of the time when people talk about in vitro they’re talking about something up to cells growing in a dish. So, it might pure chemicals in a test tube, it might be cells growing in a dish, something like that. In vivo is referring to in some intact living system. Sometimes as simple as a worm or a fly, but it’s an intact organism. Worm, fly, mouse, human, something like that. So the distinction is really important. You can make lots of things happen in a test tube or in cells in a dish that may never happen in a living system for a thousand different reasons. Just as one sort of easy example to grasp, if you’ve got cells growing in a dish, they have a very limited capacity to respond to any insult you throw at them and you know that’s not true of an intact human being for example. You’ve got all sorts of immune responders and chemical antioxidants and the liver and the kidneys eliminate toxins and this and that. So there’s interplay of a hundred different systems in an intact organism that may run counter to or may enhance the effect that you’re looking at and so to extrapolate from a test tube or cells in a dish to a person or even a mouse in a cage, that’s a long stretch. Now what we constantly do in our research is exactly that. We find something interesting in a very simplified system in vitro and then we say can we find any echo for this in the living system, can we see the same thing, or how was it modified between the cells and the dish and the person in the lab.
[Damien Blenkinsopp]: Great, great. And in terms of these oxidant injury markers, I’m trying to adopt your expression there, what did you find in terms of the markers? Were there some of them which were working better with in vivo? Because I mean at the end of the day we want to know what’s going on in the body of course.
[Josh Fessel]: That’s exactly right. One of other reasons we really like lipid peroxidation products in general or that I really like lipid peroxidation products in general and isoprostanes in particular and related compounds is that every cell with a membrane is fair game for study. So, for example if you wanted to measure DNA oxidation products, well there are are cells in your body that lack DNA. Red blood cells, for example, have no DNA in them. Platelets have little shreds of DNA. But every cell has a membrane, so every cell is fair game for study and it lets you really refine your question. It also means that if I can get ahold of the membrane, I can study it in vivo even down to the subcellular level. So I can take a sample of liver tissue, skeletal muscle, whatever and get the mitochondria out of it and measure the levels of isoprostanes or isofurans or whatever in the mitochondrial membrane and I can tell you something about what happened to that level of detail in a living system and so that’s how we try to bridge that gap between things that are very simplified in vitro and move into in vivo. But there are lots of things you can do in that regard. There’s a lot of literature for example on looking at oxidized DNA floating around in the plasma as a marker, not only of oxidant injury, but of cellular injury. So people are looking at the DNA contained within mitochondria, for example, and looking not only at how much is there floating around in the plasma because it’s not really supposed to be there in it’s free form, but of that how much of it is oxidized and how extensively. And you can get a really pretty granular view of what must be going on at the cellular level. Now, it doesn’t tell you things like is it in one specific spot in the body or is this a whole body thing, but you can get pretty detailed information in a living human. From a research standpoint, a living human is a really complex and sort of filthy place to do your research, right. It’s very uncontrolled. There are a million variables that you can’t do anything about and yet that’s what you have to do and the techniques are such that we, in a research setting, we can get pretty detailed.
[Damien Blenkinsopp]: Yeah because I mean the body has so many variables. If you’re just thinking about it. It has a long dynamic equation – some crazy calculous. There’s so many variable that to do science is actually really difficult because you can’t control so many different variables that are going on. So, you have to appreciate the efforts people are making to study how we work just in the incredible in-complexity. We’ve looked at hormesis quite a bit, which I think illustrates quite well the concept you’re explaining here about in vivo being different where we have things like our hormetic curcumin for example. You put it into the body and it ends up creating some kind of anti-stress kind of like an antioxidant effect. Although the mechanism as we understand it today is actually a small oxidant kind of injury as I understand it. So there you see it’s causing the opposite of what you thought. I’m sorry – It’s very illustrative of the importance of focusing on the in vivo. So, okay we understand why you like isoprostane. What kind of things have you seen our reduced high levels of isoprostane if anything? You mentioned caloric restriction as being seen. Are there any other things that have been seen that have some kind of impact on it?
[Josh Fessel]: Yep. You can supplement dietary antioxidant intake and see a measurable effect on isoprostanes and there are a number of studies that have done that using various dietary sources. Regular exercise is a pretty clear – it’s interesting and this may get to that idea of hormesis. There was a study where they took people – and this maybe isn’t surprising when you say it out loud. They took ultra-marathoners and measured their levels of isoprostanes right before and right after an ultramarathon and then maybe up to a week later. And not surprisingly, right after the run and obviously these are extremely fit people, right after the run their levels of isoprostanes were incredibly high.
[Damien Blenkinsopp]: Sky high, yeah.
[Josh Fessel]: Yeah.
[Damien Blenkinsopp]: Cancer patient levels.
[Josh Fessel]: Right, right or more. I mean if you just looked at the numbers and didn’t know what had happened, you’d say oh my God, what’s going on with these people. But as you say, it’s the biological of that which doesn’t kill you makes you stronger and so clearly these are fit and when you look at their baseline levels, their baseline levels were quite low. So regular exercise we know improves the efficiency of the machinery that tends to leak free radicals or improves the ability to respond and maybe both. So it’s a lot of the things that you might guess at anyway. The healthy diet that’s low in fat and high in fresh fruits and vegetables, that kind of thing. Oh, the other really big thing is we know from a number of studies that smokers are under a huge constant oxidant stress. It not only enhances the formation of free radicals and masking goes hand in hand with this, depletes levels of multiple different endogenous antioxidants. So, the other thing that we know is beneficial is if you smoke, please stop.
[Damien Blenkinsopp]: Alright. So, you’re talking about glutathione and –
[Josh Fessel]: Yep. Glutathione, ascorbate. I can’t remember if there was a measurable effect on vitamin E or not. Lipoic acids – many of the usual suspects and they were all depleted in the smokers.
[Damien Blenkinsopp]: Great, great. So, I guess increasing your glutathione or having low glutathione is going to have an impact on your isoprostane levels just because you’re indigenous antioxidant system is different. You brought a very important aspect of it there. They weren’t for a run for a few hours and they completely changed their isoprostane levels. So then we have to think about, okay we really have to control. If this can change that rapidly – give that that was quite an extreme circumstance. But what kind of things do we have to control for it to make sure that we’re not getting some kind of useful reading with isoprostanes.
[Josh Fessel]: Yeah, that’s a really good question. So, we know that people who are heavier – who are overweight or obese – have higher levels. So you got to control for that. As I say, we know that smokers have higher levels, so you have to control for variables like that. It ends up being a lot of the variables that you would control for in a fitness type of study anyway. It turns out that the specifics of – at least in a short time window – the specifics of dietary composition aren’t as important as you would think. So, year’s back we actually did an experiment in the lab where a bunch of us – because we wanted to know is it possible that what you’re measuring when you measure a plasma level of isoprostanes for example is coming in with the food you’re eating. A bunch of us in the lab went and got a very high fat meal from a popular fast food chain and measured our levels.
[Damien Blenkinsopp]: I wish you would say the name, but we can guess.
[Josh Fessel]: I won’t necessarily say the name.
[Damien Blenkinsopp]: Have they been in the news lately?
[Josh Fessel]: Almost certainly. So we measure our levels beforehand – blood and urine. And then ate a very fatty meal and then I think it was something like 6 to 8 hours later, measured plasma and urine levels and they really didn’t change. Which was kind of a surprise, but it was very reassuring. It suggested that what you’re measuring is more reflective – or at least, if it’s not more reflective of a steady state, it’s at least not so sensitive that you can tip with –
[Damien Blenkinsopp]: With just one meal.
[Josh Fessel]: That’s right.
[Damien Blenkinsopp]: Right, right. Okay.
[Josh Fessel]: But, overall dietary composition is something you would want to know something about if you were doing a controlled measurement.
[Damien Blenkinsopp]: Is there anything about time of day or with a lot of blood tests we do fasting. Will it make any difference if we fast say 6 or 8 hours or 12 hours and then do it in the morning? Or is it okay to do in the evening – to take your sample then if urine for example? Are those kind of influences important? How about like summer or winter? Are these good questions because if I imagine if I’m interested in tracking this just say for aging or for some other aspect, then I want to know that I’m not just going to get hectic data basically. Like one day up, one day down. One season up, one season down and basically can I be completely fooling myself that I’m tracking anything useful?
[Josh Fessel]: That’s exactly the right question to ask. So, as far as we know – at least in plasma levels – there’s no diurnal variation and that’s true actually of a lot of the different measures, not just isoprostanes. If you’re measuring anything in urine, in general, the best time to measure is the first morning urine. Not necessarily because you get diurnal variation, but what happens is you’re awake throughout the day. You tend to take in fluid and that’s going to tend to dilute your sample. But that’s true of almost literally anything you would measure in the urine.
[Damien Blenkinsopp]: Well that’s a great rule that you just gave use there.
[Josh Fessel]: Yeah. And then as far as seasonable variation – that’s a really interesting question. To the best of our ability to determine, no there isn’t any seasonal variation. I actually did a study when I was in graduate school to see if sun exposure had any impact because you’re delivering radiation to a large area of the body if you’re out in the sun and radiation is ionizing and creates free radicals and so I wanted to know was there any acute effective of sun exposure and the short answer is no there isn’t. So, for all those reasons, these tend to be pretty robust measurements and like I say, some measures are going to be a little more noisy than others, but in general these are things that – the one thing that would have an impact on the acute measurement of any index of oxidant injury would be if you had some sort of acute illness. So, if you had that flu for example. We know that people who are acutely ill have – and we’ve probably best studied oxidant injury in the setting of acute illness. We know that people who are acutely ill will have higher levels and the sicker you are the higher they’ll tend to be. So, if you were doing any kind tracking of any biomarker really over time, you’d want any individual measurement to be fairly representative of how you are on a day to day basis.
[Damien Blenkinsopp]: Absolutely. So I actually ran into this problem very early in my tracking. I was tracking high sensitivity of the C reactive protein. And the second time I ever tracked it – this is going back like 8 years or so – very early – and I actually had an injury to my coccyx by falling – I can’t remember – falling over something. Very painful, it was really horrible.
[Josh Fessel]: That sounds awful.
[Damien Blenkinsopp]: Yeah, yeah. It was because you can’t sit down. It’s very difficult. But anyway, I took my CRP and it was like much, much higher of course. I can’t remember the levels. I think it was 8 or something, which it was completely off the chart compared to what it was. I honestly had to look and it really wasn’t worth me spending my money on that CRP this time just to find that yes, you have a coccyx injury or any other injury, you kind of expect these kind of things. So very, very important point there.
So just wind of the isoprostane discussion. So we didn’t’ really talk about TBARS. The thing about TBARS and the MDA is when you look at, for instance, supplements and things like this, you often see that they talk about the TBARS as supporting evidence that it’s lowering lipid peroxidation. Do you feel like it’s reasonable to trust statements from backing supplements and stuff? Should we really be looking at the isoprostane levels? And can we trust – if we’re reading stuff on supplements and it seems that lowering lipid peroxidation, would you trust that or what issues would you see with trusting that TBARS method?
[Josh Fessel]: Yeah, that’s a great question. So, what I often tell my patients when they ask about supplements is remember the job of the person who printed that label is to sell you the supplement. So know that whether they’re making a claim about TBARS and MDA or isoprostanes or protein carbon meals – so know that. The question, I guess, is to dig in and find out what are the quality of the data that they’re sighting? And it seems like you’re speaking to a really engaged and educated audience here and so my advice would be dig into it and see do they site a study? And if so, go find the study and look at it. And if it doesn’t make sense, go talk to your physician or whoever – somebody that you know has some background to help you pick through it and say – because some of the studies that are out there that have looked at TBARS and malondialdehyde and all that – they’re fine studies. They’re well designed and you’re going to get relative quantifications that probably do tell you something. There are plenty of studies of isoprostanes out there that are not as well designed and probably not as informative as better design study of TBARS. So whether you trust the claim or not – I always go in with skepticism and my first question is okay well let me see if I can find the study they’re actually talking about. If I can, I’ll look at it and say okay this is actually pretty good or this has some problems. And then the other thing is independent of that, I’ll look for other investigations of the same thing. So maybe the study they site isn’t that good, but there are 10 other studies that have been better done and they actually seem to suggest yeah there’s something here or the conclusion is no, there’s really nothing here. So I say take each on a case by case basis, but get as much data as you can before you spend your hard earned money and educate yourself on the front end.
[Damien Blenkinsopp]: Great. Is there anything in particular which would, if you were reading a study and it had TBARS in it, is there anything in particular you would look at for that marker which you’d be like, “Ah that could be an issue.
[Josh Fessel]: Yeah. Sometimes it’s hard to pick out what can be the issues. If I’m reading a study – this happened once. I was reading a study that were analyzing samples that were 10 years old and that gave me pause because anything that sits around long enough, unless it’s stored under really rigorous conditions will show generation of malondialdehyde and isoprostanes and all the other products of oxidant injury or oxidative stress just by virtue of sitting around. So, when I saw that it was red flag to me that oh, I need to interpret this data cautiously. Are they making comparisons between groups and how comparable are those groups, really? Exactly as you eluded to? You’re controlling for the things that could influence that. Did they study? Was there intervention in a group who, on average, was 10 or 20 years younger than their control group? Well that’s a problem for reasons that we’ve already discussed. So, I look for things and these may sound goofy. Like of course they would control for that, but sometimes they don’t or can’t or won’t or didn’t or whatever and so you just look for things like that. That’s true not just for TBAR’s measurements, but for anything.
[Damien Blenkinsopp]: So there’s nothing specific that you highlight that you know is a weakness of the TBARS?
[Josh Fessel]: Not really. I’ll say that the one caveat I guess with TBARS, Is that the more complex the sample that they’re measuring, the more cautiously I’d interpret the data. So, for example, if it’s a study of TBARS in urine, urine is a biological sample. It’s pretty simple. It’s got salt and a little bit of protein and few other things and that’s about it. Plasma on the other hand, is really complex. It’s got proteins and lipids and a few cells. So if you were making measurements using the TBARS protocol in urine, I would tend to hang a little more validity on that than if you were in the plasma. I think it’s a dirtier biological matrix.
[Damien Blenkinsopp]: That’s interesting because I think most people assume that blood’s the ultimate measure. So, just of now, does an isoprostane – does urine correlate well with the blood sample levels? So, are they pretty much exactly the same?
[Josh Fessel]: They’ll tell you the same information. And the nice thing with isoprostanes is that – because we’ve had it come up before where people say, “Well how do you know they aren’t being made in the kidney and that’s really what you’re measuring?” That’s a fair question. So the one nice thing about isoprostanes is that we also have defined metabolites that are excreted in the urine. So the only way you can get that is if you formed the compound, released it in the blood, and then the enzymes that metabolize isoprostanes have a chance to work on it. So, you can measure urinary metabolites and they’re very stable compounds and say there’s no way this was generated in the kidney, this had to come from the total body pool. But in general, yes, they do correlate.
[Damien Blenkinsopp]: Great, great. Thank you very much. Okay, so I know that you’ve been starting to get involved in a project that’s going on. We have someone who wanted to change something in their life and so I brought that up and it’s very interesting case study to bring up on the program. So, it’s called Feeding Danny. Could you give us a quick background about it?
[Josh Fessel]: Sure. I’d be happy to. Thanks for asking about it. Yeah, so this is a project that started with my friend and my wife’s friend, Danny. Danny, like a lot of people has struggled with his weight over time and Danny is very overweight. In medical terms, you would say he’s morbidly obese. He carries a lot of extra weight. I’m guessing and I don’t know for sure – I’m guessing he weighs he weighs somewhere around 350-400 pounds. He’s a big dude and has health problems associated with his weight. He’s got joint problems, sleep apnea, asthma, all sorts of things. And so he has tried many different ways to get a handle on this and has had a lot of trouble and like I said, he’s clearly not alone in that. And so what came about is two friends of his approached him with the idea that they wanted to stage what you might describe as a dietary intervention. They said, “If you’ll allow us to do it, we will take over your diet for a year’s time and change everything about what you’re eating. We will make sure that the only thing going into this system are all natural, organic, pesticide-free, hormone-free foods and that by doing that we feel certain that you will, not only lose weight, but you’ll see improvements on any number of health related measures and act scenes.” And so when I heard about this I said I would love to help out if I can because I love my friend Danny and I want to help him, but beyond that I thought this was a really interesting concept on a single person as you say case study and that’s really what it is. Can you do this dramatic intervention and see a positive change. What I thought I could offer was to bring the medical perspective to things just in terms of overall fitness, but also bring the science perspective because I come from a slightly different place than the women that are doing this. Their names are Leilani and Vanessa. I tend to think about things in a very sort of pragmatic, low level kind of way. I think this will work because if you’re eating a diet like they’re describing – and it does include meat and that sort of thing as we discussed. This is not a strict vegan diet or anything like that. But I think if you’re eating a diet that’s high in fruits and vegetables and whole grains and lower in saturated fats and all that kind of stuff, you’re going to lose weight because your caloric intake is going to go down. I suspect what we’re going to learn is that as we go along they are thinking more along the lines of eliminating toxins from the diet and that sort of thing and I always halt a little at that because as I say, just as I don’t like the term oxidative stress because it’s nonspecific, I don’t like the idea of toxins because that’s nonspecific. What do you mean -What toxin, can I measure it, what are the levels, that kind of thing. And so, it doesn’t really matter who’s right as long as it works and so I’m excited to participate in this. What they’re proposing to do is to do this intervention for a year. They’ve uprooted their lives in Chicago and have moved to Nashville. They just got here about a week ago. What they want to do is do this for a year and document it on film and hopefully at the end of it have a true representation of what happens over the course of that year.
[Damien Blenkinsopp]: Alright. Those things are great – documentaries – because they can be inspiring for people, often more inspiring than this show when we’re talking about scientific data like this one for a lot of people. So, they’re really, really great, but it would also be like really cool if there were some controls in place to kind of understand a little bit like what really did happen. So, my understanding is that the intervention is basically a diet of organic foods, right. So they’re going to be buying specifically organic, certified organic produce and probably they’re going to basically eliminate all of the stuff in the middle of the supermarket. So you’ll walk around the edges and you’ll grab all the vegetables, fruits, meats and so on, but most of the stuff in packages isn’t going to be included in the diet.
[Josh Fessel]: That’s correct and ideally they’ll actually, in as many instances as possible, eliminate the supermarket and go to the farm where it’s being raised. And Nashville’s actually a good place to do that. There are a lot of certified organic farms and you can locally source just about everything. So this is kind of an ideal place to try what they’re proposing.
[Damien Blenkinsopp]: I guess somebody other kind of confounders in terms of diet because the diet world is so complex in terms of all the people have different opinions. Whether it’s grass-fed meat or its grain-fed meat, there’s a whole question of grains. In this case it seems like grains isn’t the issue. But like we were just talking before like it’s just important to define exactly what the diet intervention are in it – what limitations are and what the limitations aren’t to kind of get started. What kind of other things would you feel would be worthwhile controlling for? I understand the budget probably isn’t going to be really high, right, in terms of testing and things like that? But there’s probably some things they could track and it would probably maybe help the documentary or just be useful to kind of look at afterwards and be like yeah. So maybe we can say that toxins did play a role or – although I haven’t come across so far a kind of generic marker of toxins like you’re kind of alluding to. I’m not sure it is a generic toxin marker unless you want to say oxidant injury potentially. So what would be your thoughts on kind of if you wanted to get a baseline today before everything started and to see where things are at and then I know what kind of time scale would control certain things and at the end, in one year’s time, what would you like to control for if you could?
[Josh Fessel]: Yeah, that’s a great question and this is something that we’re in discussions about right now because, you’re exactly right, budget is going to be limiting and so there are some things that I think we’ll need to do just from a general sort of health monitoring standpoint. There are some things I’d like to do that we may or may not be able to do, but all of it is in service to trying to figure out did anything actually work. Where my thinking is, is that we’re going to need to look at some really standard, basic measures of health, particularly metabolic health, and this is real simple stuff like cholesterol, like hemoglobin A1C, blood sugar, triglyceride levels in the blood, if I had basic kidney and liver function, that kind of thing. If I had a complete wish list, I’d probably want to know about thyroid function and that kind of thing. And then to branch out from the traditional, clinical indices as far as biomarkers and thinking about what else I would want to know. I would actually be really interested to know what the circulating levels of isoprostanes were and compare that with circulating malondialdehyde or TBARS. I would love to know high sensitivity CRP. I would love to know what plasma levels of ascorbate and vitamin E and all the other small molecule antioxidants. I think that would all be fascinating and to see how those change with this fairly profound diet modification that’s going to happen. How much of that we’ll be able to do I don’t really know. Since some of those things make sense clinically, some of those things are more on the research side and this is an interesting case study, but in the strictest terms this is not a research study. So, we’re going to have to be a little judicious in how we go about these things. But nonetheless, I think what we’ll end up doing is certainly hitting all the things that we need to look at just from a basic health and safety standpoint and then I hope that there’s additional funds available to dig into some of these other things, not only to get a baseline, but hopefully to measure them periodically over time and see what did we really do.
[Damien Blenkinsopp]: Yeah. That’s great. And I think you’ve mentioned a lot of different things and I think especially for people to get the value out of the markers they’re tracking and given how most things are still pretty expensive today. Some of the things you mentioned I thought particularly kind of practical are blood sugar regulation. You mean just taking like the blood sugar reading.
Recently, had a conversation with Bob Troia on The Quantified Body. He was on the one of the recent podcasts and he tracked his blood sugar every day for a long time. It was interesting to see it went up and down all time based on what he’d been doing the night before and everything. so the problem that I realize is like sometimes when I’m having my blood panels, I’ll get my fasting blood sugar taken and I realized I’m kind of wasting my time because, unless I’ve been very careful about what I’m doing the night before, in terms of exercise and intake and everything. But on the other hand, there’s a pretty cheap method. It’s the Precision Extra pinprick blood sugar devices where you can take a couple of reading. It’s pretty cheap. Unfortunately you have to prick your finger and you have to think about okay is Danny going to want to prick his finger like once every day or maybe once a week or like whatever you’re trying to control for. Obviously, blood sugar regulation’s one thing that’s going to fit with the research that there’s definitely going to be some changes there. One of the things I was thinking of is cardiovascular risk. Is that something he’s worried about? Given the weight and everything, we worry about that a lot. There’s one other test out there that I’ve been meaning to get someone on the show for, for a while is the LDL particle number, which the research has been looking at more sharply because it correlates better. They are looking at some other things they are using CRP which is one you mentioned too. So, just kind of figuring some of the other things I thought would be interesting and of course like a weighing scale because in terms – like I think one of the great things about this project is that you could take pictures every day and obviously there’s going to be video footage, which is going to motivating for other people, but sometimes you can’t see it yourself as well when you’re measuring. But if you got a scale and you’re just jumping on it every day, that’s a very easy thing to keep you motivated to see that something is happening. We have to be aware of something that you said earlier in our conversation today. Which is that there were benefits being seen with caloric restriction before any of the pounds were coming off in your example, right. So we have to also be aware that although sometimes maybe the weight isn’t’ coming off, there are other improvements that are going on inside our bodies.
[Josh Fessel]: That’s absolutely true and that’s why I hope we’ll be able to quantify as many different parameters as possible as you say. In terms of a quantified body, a quantified life a bathroom scale is probably one of the most useful things you can have. But you’re exactly right in that let’s say that weight loss – let’s be pessimistic and say there isn’t as much weight loss as we there’s going to be, we might still have one real victory, but you’ve got to know what to look for. You got to be able to look for it. And so for exactly that reason I think the more carefully selected data we can have in this case – and this is true, not just in the case of Feeding Danny, but in a broader sense I think that’s useful. My clinical life is in part spent in the intensive care unit taking care of critically ill patients and that’s about as quantified as you can get on an acute basis and all of that information can be really helpful, not only as individual data points and not only as trends, but also as a gestalt of what’s going on with the person. And i think this maybe a similar conceptual exercise over a much longer time scale. So I’m hopeful that we’ll be financially able to look at all these things. But if nothing else, like you say, daily weights and looking at blood sugar over time and things like -one of the things that I hope we’ll be able to do – one of the sort of quantified self-measures that I haven’t personally gotten into, but that I think has a lot of potential utility for not much investment is looking at actigraphy things like the fitness trackers and whatever. But just getting a sense of over days/weeks, what is your activity level? What are you really doing? And patterns emerge that you would never observe as you say on a day to day basis.
[Damien Blenkinsopp]: That will be interesting for this project as well because like I’m sure as your weight goes down your activity naturally tends to rise.
[Josh Fessel]: That would be my hypothesis.
[Damien Blenkinsopp]: And then as a benefit that most people aren’t going to think of like straight away, but it would be great – just have a Fitbit – be wearing a Fitbit. We discussed on one of our last episodes about the whole market and basically the Fitbit tends to be one of the better trackers at the moment. Or another one as long as it’s giving you directional info, it would be really interesting just to see that. So I think these projects are great, like I said, for inspiring other people for change. So good luck with that. In terms of your own personal life, just always interested to find out what people are doing with themselves. Are there any biomarkers or personal data you track on any kind of routine basis or monitor just related to health, longevity or performance, anything about your body really?
[Josh Fessel]: Yeah. So, the bathroom scale is there. So I track my weight every day and I track that pretty closely. At times I’ve even charted it out, made graphs, that sort of thing. That’s been really informative. I’m a pretty careful calorie counter. I keep a really close count on a daily basis of the calories going in and –
[Damien Blenkinsopp]: Is that just by kind of eyeballing? Like that’s roughly 200 I’m consuming right there.
[Josh Fessel]: It’s about that. I mean I spend a lot of time reading labels and that kind of thing. I’ve had periods where I had the flexibility in my schedule to actually weigh foods and that sort of stuff and carefully measure out serving sizes and I love being able to do that. In terms of satisfying the practical demands of every day, it’s a lot of times by eye, but I’ve been doing it for a while and so actually have a pretty good database built up of “Oh okay I know that this is going to be this many calories and so on”. And I do that essentially on a daily basis.
[Damien Blenkinsopp]: Okay, great. So you kind of track roughly how much you consumed in a day of calories and you track your weight. Has anything interesting come out of that for you whether it be accountability? What kind of value have you got out of that?
[Josh Fessel]: Yeah, absolutely. Like so many people, I’ve struggled with my weight for a long time too and so at my heaviest I was probably about 230, 240 pounds.
[Damien Blenkinsopp]: Just out of interest, how are you now?
[Josh Fessel]: So now I weight between 145 – 150.
[Damien Blenkinsopp]: Okay. So like a big deal, a lot of difference.
[Josh Fessel]: Yeah. So I lost a lot of weight. Some of it was diet modification, some of it was activity, most of it was diet actually. But by being very careful about tracking calories and tracking daily weights and that sort of thing, I’ve been able to take that weight off and keep it off and that’s worked really well for me. It’s also made me very conscious about the dietary choices that I make. So, in general, I’m – lazy isn’t the right word – but I like to spend mental energy on particular things. And one of the things that I don’t love to spend a lot of time thinking about is what am I going to eat for any given meal? Or, if I’m hungry and I want a snack, I want to sort of check that box and get on with whatever it is I’m actually interested in doing. And so that coupled with being careful about calorie accounts has really had a great positive impact on my diet because the things that you can mindlessly eat without destroying your daily calorie count, tend to be pretty healthy things. So that’s worked really well for me and I’ve had some patients that that’s worked really well for. Others are much more exercise oriented and that’s the area that I’ve started more recently tracking my exercise over time with following either how many calories burned in any given workout session or I’m mostly doing treadmill and cardio aerobic kind of stuff.
[Damien Blenkinsopp]: So you’re using the machines or using your own device?
[Josh Fessel]: I use the machines typically. I haven’t yet invested in, like I say, an actigraph or a Fitbit or anything like that, which I think would be really interesting. But I’ve started tracking what kind of distance do I do and to motivate myself a little bit because I know that the piece that I am personally missing is regular physical activity. I think the data are really solid that that has health benefits beyond weight control and that sort of thing. So I’m trying to live by example as when I tell my patients to do this – and these are people – so I’m a pulmonary doctor by specialization. So the patients that I see all have lung disease. So here I am telling these people that have difficulty drawing breath to go exercise and it’s pretty hypocritical of me if I don’t make the effort myself.
[Damien Blenkinsopp]: Great, thank you for that. Okay, so last question. We’re talking about data on this show. So, do you have one recommendation? Like what’s the most important insight you have about using data in a way that’s going to be valuable to improve health, longevity, or performance? What would recommendation would it be?
[Josh Fessel]: If I were going to say anything about using data to guide performance, health status, anything, it would be to pay close attention to know what it is that the data are telling you or going to tell you before you get it and know what you’re going to do about it before you get it. This gets to the whole actionable thing. So, not all data are useful. If you don’t know what the data are really telling you, not useful. And if you know what they’re telling you, but you can’t do anything about it, not useful. And this is true in really any context I think. So before I would get a test results or order any kind of assay or whatever, I would want to know. And I do this in my research lab, I do this in my clinical practice. Before you order a test, before you run an experiment, have an idea of what it’s going to tell you and what you’re going to do with the likely or the potential outcomes. If it’s this, then I’ll do this. If it’s that then I’ll do this other thing. And if you can’t set that up on the front end, that’s not going to be a useful piece of data to you, so don’t waste your time or spend your money.
[Damien Blenkinsopp]: Great and we talk often about things being actionable, which is kind of like a jargon. It’s a bit of a jargon word, so I really liked the explanation you just gave, which was very clear and it was kind of like an exercise. It’s like before, plan what action you’re going to take once you find out the data is this, once you find out the data is that. And that’s a way of learning if it’s actionable – that it’s actually going to be valuable. But I think a lot of people don’t think about it. So I think that’s really a great piece of advice. It’s a great exercise before anything you’re going to think through that way. It will kind of force you to understand if it’s going to be of value to you in terms of taking action on it.
[Josh Fessel]: Well thank you. Yeah, that’s exactly right. That’s why I force myself to do it because if you don’t know – if you can’t make a plan, then it’s probably not actionable. And so maybe wait until you have other information or maybe discard it entirely and change the line of inquiry.
[Damien Blenkinsopp]: Well Josh, like final thing. Where can we reach you, get in contact? Are you on Twitter? Are you on a website? Where can people find you?
[Josh Fessel]: That’s a great question. No, I’m kind of a lead eye. I don’t even have a Facebook page, but I’m pretty findable. So, google search for Josh Fessel will find me. I’m on the faculty at Vanderbilt University. So, I’m that Josh Fessel. And I think there are a couple other people out there with the same name, but a google search and if you include Vanderbilt you’ll find me. That will link to my faculty page that talks about my particular background and my research interests and that sort of thing. And I think email addresses are there too. So, I can be reached any number of ways. I’ve spared the world my thoughts a 140 characters at a time. So, like I said, I’m a little behind the times there. But, yeah, I’m pretty findable online and that’s probably the best way to do it.
[Damien Blenkinsopp]: Great. Well Josh, thank you so much for your time today. I really appreciate it. It’s been a great discussion.
[Josh Fessel]: Oh, no. Damien, thank you. It’s a pleasure.

Leave a Reply

The paradox: We spend a lot of money and time on increasing our antioxidant intake through foods and supplements. Yet most of us never know if this effort is making any impact on our health. Should we be checking our oxidative stress levels as often as we check our cholesterol?

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.

“In my ideal world, I would love to see most people looking at their markers of oxidative stress once a year…. 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.”
– 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)!

itunes quantified body

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.

The Tracking

Biomarkers

Used and Recommended by Dr. Cheryl Burdette

    Lipid Oxidization Levels
  • 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.
  • Intracellular Antioxidants and Enzymes
  • 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.
  • DNA Damage
  • 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.

Mentioned But Not Recommended by Dr. Cheryl Burdette

    Lipid Peroxidation
  • 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.

Lab Tests

The Tools & Tactics

Supplements

  • 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

Transcript - Click Here to Read
[Damien Blenkinsopp]: Cheryl Burdette, thank you very much for coming on today. It is a real pleasure to have you on. I was recently at a conference where I saw you highlight the importance of oxidative stress biomarkers for working on both disease conditions and aging. Could you give us a quick overview of why you think it is an important area of biomarkers and where it is most useful?

[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.

Leave a Reply