Mark Newman transcript

Written by Christopher Kelly

Feb. 11, 2016

[0:00:00]

Christopher:    Hello and welcome to the Nourish Balance Thrive Podcast. My name is Christopher Kelly and today I am joined by Mark Newman. Hi, Mark.

Mark:    Hi. Glad to be here.

Christopher:    Cool. I'm so excited about you and the DUTCH hormone test. I've been looking forward to this interview for an awfully long time. You are one of, if not, are you the founder of Precision Analytical? Is that right?

Mark:    Yeah. Yeah. I started the company about four years ago.

Christopher:    For people who don't know what the DUTCH test is, it's a hormone test. Maybe I should start by asking you to tell us a little bit about yourself, how you became interested in hormone testing in the first place.

Mark:    Sure. The answer to that kind of dovetails right into the test itself. For me, I'm a chemist so I got a degree in chemistry and a master's in forensic science so I was into building lab tests and that sort of a thing. Then I started my career at a lab doing 24-hour urine testing and got to kind of rebuild that from the ground up and see the pros and cons of urine testing with that model, and then a couple of other stops along the way but ended up running one of the more prominent saliva testing labs for about six years and so really got the ins and outs of saliva testing.

    About ten years ago, I started putting together a model that for me was a better fit for people in terms of just how to do this thing well in terms of hormone testing when we're talking about reproductive and adrenal hormones. That's where we put together the DUTCH model which is just an acronym. It stands for Dried Urine Test for Comprehensive Hormones. It's uniquely comprehensive and it's uniquely easy for patients and that's kind of…

    My approach was really about the information. The fact that it's easy, it's sort of a natural byproduct because all the patients' have to do was saturate these urine collection devices, which are just filter paper essentially, with urine several times throughout the day, and then from that we can get a unique combination of information because we can get the pattern of cortisol throughout the day as well as all the stuff you usually get out of a urine hormone test which is really rich with metabolites and different information so we can see a lot of information from that.

    We started the company about four years ago and just been working on perfecting it and then educating people on how to implement it into their practice and in what situations it's a good fit.

Christopher:    Right. That's what so excited me about – well, a lot of things excited me about the test but it was in particular you. I think it was a webinar I heard you speak on. I didn't actually see your face. More recently, I came to the DUTCH testing website, which I will link to in the show notes, and watched some of your educational videos. They are quite fantastic and your enthusiasm is obvious.

    It's kind of caught between the webinar style, the presentation style and then actually seeing you sit on the chair, but it's the way that you sat on that chair and just leaning forward ever so slightly as if you can just see your enthusiasm and knowledge of this test is obviously absolutely incredible so thank you so much for making those videos. That's awesome.

Mark:    Yeah. The education is really what -- our main driver behind what we do is trying to educate on that stuff. What we do is kind of the culmination of my entire career so for better or worse, I'm fairly passionate about hormone testing. At a cocktail party, maybe not that much fun but in this context it's a good place.

Christopher:    No, no. I think you're fantastic. That's kind of my goal with this podcast, with the work that I do. I offer these lab tests and I try and explain to people in probably too much detail what the results mean. My goal is to engage them. The reason is nobody cares more about the test results than you do. Quite often, I'll gift someone something and they come back and it seems like a couple of months later that they know more about the topic than I do which I think is just fantastic. I absolutely love that.

    But, yeah, to kind of to rewind to why I was interested in the hormone testing in the first place was of course through my own personal experience with it. A few years ago, I had a pretty rough time with my own health. Some of my symptoms I'm sure you'll recognize as kind of fatigue but still unable to sleep at night which is just the worst combination.

    There was a saliva test that I know that you know very well that I did, a four-point cortisol test. At the time I did that test, I didn't even really know what cortisol was. I'd heard of it but I didn't really know what it did or much about it. The test also measured DHEA and testosterone and a couple of forms of estrogen.

    The result came back and it showed I had a disrupted circadian rhythm. My cortisol was high at night. It was pretty low during the day. That kind of coincided with my symptoms pretty well and it really didn't feel good.

[0:05:13]

    I was super excited by this finding because it seemed like I could manipulate the results and do something about that which I did. I've since done many of those saliva tests and my cortisol now looks like what the doctors who trained me would consider to be normal. Since then, I counted last night, we've run 546 of these saliva tests –

Mark:    Oh, wow.

Christopher:    -- on mostly athletes. More recently, I stopped ordering the saliva test. The reason is I just couldn't justify it. Obviously, there's a huge selection bias in the people that I'm working with, right? They're mostly endurance athletes, mostly slightly overtrained, and they all looked just like I did. They all have kind of moderately low cortisol, in some cases very low; low testosterone. Low everything, basically.

It's really hard to take $300 of someone's money for this test if it's not going to show anything useful. But I still had questions which was like, okay, so if this person has low cortisol, why do they have low cortisol?

Mark:        Right.

Christopher:    Can they not reduce it? Is it being metabolized really quickly? Maybe we could talk or I could have you talk a little bit about how the dried urine compares to saliva for testing cortisol.

Mark:    Sure. Yeah. Those are the main driver behind me developing the test. I was in the world of saliva testing and had developed quite a few tests there, managed probably over a million saliva tests.

Christopher:    Oh, wow.

Mark:    In digging through the data, one of the things I noticed is a lot of people running around saying, "Hey, cortisol makes you fat." Okay. Well, there's a connection in the literature between central adiposity and cortisol and all of that, but when I look in the data the salivary results actually correlated negatively with like BMI, fat, whatever you want to call it and it didn't really jive with me and so I started digging through the literature and going: okay, hold on.

There's this very basic correlation that we think exists and as you look in the literature what you find is that the free cortisol, it's just one piece of the puzzle. It's the place where most people start and I think rightly so because if you want to get simpler, yeah, you can use serum. In serum testing, you're just looking at a total cortisol. As you migrate from serum to saliva, now I have not only free cortisol, which is better, but you have free cortisol over time.

It's a significant improvement but in the urine testing what you find is that you also get to look at the metabolites. It's a huge advantage to be measuring those concurrently because when you say, "Well, why is my cortisol low?" we don't even know that your cortisol production is low when we're looking at salivary cortisol because – and here's why – the free cortisol's only about 1% of the total. The metabolites of cortisol represent about 75% of the total.

When I started doing this test, I was expecting to find in 1%, 2% of the patients where you'd find this discordant, this story that didn't really agree in terms of the free cortisol and the metabolites and what you find is it's a lot more than that – 30%, 40% of patients. As an example, 40% of patients who have low, flat free cortisol in urine, which tells the same story you get in saliva, right? You can look at free cortisol on saliva; you can look at free cortisol in urine. The patterns parallel each other well.

But 40% of the people, to have that low free cortisol where you start to say things like, "Oh, you don't make any cortisol. You don't have enough cortisol," their metabolites are actually relatively elevated in almost half. The interpretation of what that person is with respect to cortisol starts to shift dramatically.

Obesity is like the easiest place to see this. What happens in obesity? Cortisol production goes up. So you say, "Oh, okay. So salivary cortisol goes up?" No, it doesn't. It goes down. Urinary free cortisol also goes down. Why? Because what's driving the cortisol production also drives cortisol clearance or cortisol metabolism so the rate at which you process that cortisol for excretion goes up in obese people. What we see in obesity all the time is elevated cortisol metabolites which tells you, okay, they're making lots of cortisol; and lower levels of free cortisol, whether you're in saliva or in urine.

[0:10:08]

People run around treating those people as if their adrenal glands aren't making any cortisol and they get worse because that's not their story. Their story is more complex than that. There are a number of cases: if you have thyroid issues, again obesity, a number of situations where the rate at which you clear cortisol is messed up. It's slow like in hypothyroidism where your cortisol can back up so you get this high picture of free cortisol and lower levels of metabolites. You're not actually producing that much cortisol but your brain, for example, is seeing a lot of cortisol because you're not getting rid of it appropriately.

You see those types of situations that they're just more complex. It's a three-dimensional picture. Serum gives you one dimension and a saliva test gives you two dimensions and a urine test, a traditional urine test like 24-hour urine, gives you two different dimensions. This is the only way to get all three: free cortisol over time and a better marker for the total production of cortisol.

That's at the heart of what we do is getting a better picture of cortisol so that we can make better decisions with people and not run in the wrong direction half the time not knowing what's really going on with them. The cortisol is pretty central to the distinction of what we do.

Christopher:    Wow. Part of me feels bad for having people spend money on a test that didn't really give us much information but I have a feeling that all of the tests that we do right now are fairly primitive and maybe in ten years' time everything is going to look dated. I'm sure it's like a really rapidly evolving area.

    But the first thing I think of when you tell me that you've seen a million of these saliva results, so is what I've seen consistent with what you've seen on a much larger scale? What I've seen is basically everybody has low free cortisol as seen on the saliva test but then maybe five times out of a hundred, I'll see somebody who has type 1 diabetes or post-traumatic stress disorder or something really crazy who has very, very high cortisol.

Mark:    Yeah. I mean, it's such a multilayered complex issue. When you say everybody's low, to be honest with you, I get my skepticism up pretty high when I hear that because there can be issues in which a lab test is inaccurate and there's going to be an issue in which a lab test, maybe the reference ranges aren't quite set the way that they should be.

    I've seen, to be honest, in at least three different labs where they had to go in and really reevaluate their reference ranges because – I'll just give you an example. I'm not going to name the lab but one particular group had developed a cortisol I'll say but they essentially borrowed the reference ranges from another lab. The problem is there were multiple ways such as cortisol so there are testing systems that they buy. The testing system that I use at my lab, for example, ran right about 30% higher than what some of the other testing systems ran.

    Now, I don't have a problem with this at all. We were doing cortisol. Our reference ranges are 30% higher. So what? I can tell if you're low, I can tell if you're high, you're fine, right? But this particular lab was using an assay that ran right around 35% lower but using reference ranges from somebody whose assay runs higher and then guess what? Instead of 20% or whatever of people coming out low, it gets to be like 40%, 50%, right? Soon you have all these people running around with, "I have adrenal fatigue," whatever, and it's really just a matter of like a fundamental problem with the lab testing.

    I have a little bit of an issue when people test. I mean, not everybody has low cortisol, right? So if I test 20 people that I don't know have a severe condition that's related to low cortisol, I'm not expecting to find half of them out of the reference range. I'd slow a little bit in terms of my conclusions on that. But if you have legitimately low cortisol then, yeah, that's –

One of the main points that we make is slow down. If your free cortisol's low, you don't yet know that you're in a hypo or a low cortisol state, that's where the metabolites can be so important. That's not to be super critical of saliva, right? I mean, how many people in this country are getting a morning serum cortisol? It's better than nothing but it's substantially better to get a free cortisol measurement in saliva. But I would argue that what we are doing is yet again substantially better than that in terms of getting to the right conclusion about a particular patient. So, no, I don't think everyone is low cortisol.

[0:15:14]

There's also this really significantly moving conversation within this field that we're in that, you know what, this term "adrenal fatigue" really needs to be reworked a lot because most people, when their adrenal gland gets hit with ACTH from the brain, which is the signaling hormone that tells the adrenals to make cortisol, most of them respond.

The adrenal glands are not like your ovaries. If you're 70 and you're a woman, your ovaries are done. They wear out. But the adrenal gland's not made to do that. It's a fairly rare occurrence that the adrenal gland doesn't work right. Typically, when you have a cortisol issue, what people are really starting to say, and rightly so based on the literature – PTSD as a good example – is it's in your brain. It's a signaling brain chemistry issue there in terms of the cortisol response. So, yes, it's a cortisol issue but it's such an oversimplified model to say, look, if your cortisol's low, that means your adrenal glands don't work right.

Most of the thinkers in this field -- which I wouldn't really consider myself one of them. I'm in the lab industry; not in the clinical side of cortisol as an example. But the people who are that are really digging into the literature are saying: you know what? We need to rethink what we've been talking about in terms of what it means to have a dysfunctional cortisol.

Christopher:    Right, right. Of course, I think part of it has been that story is so easy to tell, like the adrenal fatigue story. When you try to explain it to someone, it's far easier to talk about clapped-out adrenal glands than it is to start talking about the HPA axis and how your brain might be involved and perhaps the sensitivity to a bunch of hormones.

Mark:    Yeah. There's also this easy story that says, look, everyone in the world falls into three buckets, right? Phase one, phase two, phase three adrenal fatigue. You know what? I can show you a person who has low, flat cortisol because they're taking too much thyroid medication and it's driving their cortisol to be metabolized. I can show you someone with the same exact picture that is because they're obese. Then I can show you someone with the same free cortisol picture – they look the same in saliva, they look the same as free cortisol – and their metabolites are also low and, yes, they truly don't make that much cortisol.

Those are three vastly different stories and their salivary results – or urine if you're just looking at free cortisol – would look roughly the same, right? But they're so different from one another and we need more information if we're going to make smart decisions about how to treat or if to treat a particular case for a particular thing.

Christopher:    Right. Before I forget, let me ask you this. How do you define the reference ranges on the DUTCH report?

Mark:    The basics of it is test a whole bunch of otherwise healthy folks and then you get into these philosophical arguments about, okay, if I'm a traditional lab, I test a bunch of "healthy people," which of course, as it relates to cortisol, that's kind of hard to define. You do some math, right? They would take the average, plus or minus two standard deviations, and you have a reference range. But what you're doing when you do that is you're defining 95% of the population as normal and the real extremes as abnormal. That's really smart if you want to go looking at tumor markers or if I'm looking for Cushing's disease or Addison's disease or these things that are really rare, right? But it doesn't work with vitamin D.

Just as an example, I'm in Portland. I haven't seen the sun in two weeks. If you take the average person around here who says, "Yeah, I'm healthy" and you take a plus or minus standard deviation, the bottom of your reference range would be probably like zero. Maybe it's ten. If your vitamin D is 10, that's not good enough. So you get to think your way through the reference ranges a little bit more than that.

For us, we have a more sophisticated way of doing that but at the end of the day at least it's a more aggressive reference range. But I would never use for cortisol a reference range that would define 95% of the people as normal. Now, having said that, we just talked about situations in which sometimes there are scenarios where you can find a particular lab test where everybody's low. I have seen, just reflecting back, in a particular saliva lab that had a progesterone-estrogen ratio and like, oh, that's interesting. Then when you look at the reference ranges, they're like the way the ratio range is set up, you'd actually have to be highly abnormal in your progesterone production to ever be normal on the ratio. So everyone is low. Everyone's estrogen-dominant.

[0:20:04]

The reference ranges are really important but there's no set of rules that says: does your lab do X, Y, Z? It's a case by case thing. I determine my progesterone ranges differently than my estrogens and differently than testosterone because they're all unique in terms of the significance of elevation and to what degree and those sorts of things but you also have to be testing people that don't have obvious issues, right? If I'm looking for an estrogen reference range and I use people on birth control pills, obviously that's not going to work.


Christopher:    Right.

Mark:    So, yeah. It's quite the process really to get reference ranges that are as useful as they can be.

Christopher:    So that's part of the expertise that you're offering then is the reference range.

Mark:    Yeah. I mean, it's a package. That's the thing that people need to understand too about lab testing. In this field, oftentimes, people are somewhat critical of serum testing because there are some limitations here and there. But you know what? It's standardized pretty well. I'll take my testosterone and a reference range for a serum lab and I feel pretty comfortable and pretty confident that it's reasonable.

When you get into saliva testing, when you get into urine testing – so we include myself in that – you're much, much more dependent on the competence of the lab. I mean, you can find some pretty awful stuff in terms of just accuracy and reference ranges and reproducibility and some of those things and nobody's giving full disclosure to you to come look behind the curtain.

I think it's important to work with labs you trust. A good sign of that is when labs are involved in research and they've got their own research to kind of support what they're doing. Like for us, I just – just last week – did a study where we had people take ACTH, which is a signaling hormone for cortisol, and we shot some up our noses so it's like intranasal ACTH, like a physiological dose, and we're tracking. What's our cortisol doing? What's the salivary cortisol doing? When that's done, we can write that up and it'll make a nice little study. Whether we publish it or not, we'll see but it's like clinical validation to say, look, the pattern you see in free cortisol, we're clinically validating that. If labs aren't involved in that type of stuff and they're not curious enough to be digging through that stuff all the time, I think there's a real advantage to that. I worked for ZRT as a saliva lab and I think they're about as good as it gets with saliva because they're always doing that stuff – digging through their data, looking for correlations, those types of things. I mean, I think that's really important.

Christopher:    I do too. Yeah, I know. It's fantastic. I love the transparency. I can't stand it when just everything – oh, here's the test – and you can't really find out much about what it means or how they decided on the reference ranges or any research that's kind of led to the decisions that they're making. Yeah, I love that transparency that you have. But maybe we should talk about why someone would want to measure cortisol in the first place. What situation do you think is a good idea to measure cortisol?

Mark:    Obviously, the lab answer is everybody should get tested.

Christopher:    Right. It's my answer too, actually.

Mark:     The thing that's tricky is if you look at hormonal symptoms, if you're just in the world of reproductive and adrenal hormones, I mean, the symptoms really overlap a lot. You can take a guy and stress him out and have all these sorts of issues related to cortisol and guess what? He starts to get some symptoms that, when you listen to the radio about low testosterone, gee, that sounds like me as far as sexual function. Some of those things can be compromised so, gee, I must have low testosterone. Well, maybe, but the cortisol can really affect that. It can affect hot flashes.

    So that's kind of the tricky thing because if you have a situation where you're generally unhealthy, then it's kind of a good idea to make sure your cortisol's in check, right? Because if you have infection, it can drive cortisol. If you have inflammation, it can drive cortisol. If you have stress of some sort or perceived stress that does drive cortisol, that can drive like you talking about a lack of sleep. I mean, there're just so many situations that I think if there's general unhealth, cortisol tends to be a good thing to check off your list of like, okay, this is either in check or it needs addressing.

    But, certainly, fatigue on the low end, things like depression, anxiety on the high end in terms of high cortisol, and then as you get into the reproductive hormones which is what we're doing a lot of as well, then obviously there's the whole menopause conversation and things just related to aging, a lot of those things are going to be shifting around and they're worth exploring.

    But any sort of really lack of well-being emotionally and physically, you can make a justification. At least once is probably good to kind of get a good rundown of what's going on with your reproductive and adrenal hormones. Again, those symptoms really do overlap a bit between those hormonal groups.

[0:25:20]

Christopher:    Yeah. It's good to hear you say that because I think the same way. It's like everybody I talk to is tired. It really could be anything when you say that you're tired.

Mark:    Well, and that's why I always say 120% of the population has adrenal fatigue. When you go on the Internet and say, "Do you have adrenal fatigue?" well, are you tired? Like, yeah, everybody's tired. But then you'd find people who say, "I have adrenal fatigue" and they test and their cortisols are high. You're like, okay, I believe you that you're tired and I believe you have potentially a profound fatigue that you have to deal with but it's not from a lack of cortisol in a case like that. But then sometimes it is, right? So I think it's a good test to kind of look at.

    I'll just give you an example. I've got a sister-in-law that she's low. She is healthy and she is not a hormone producer. She does not have a lot of testosterone. She does not have a lot of estrogen. I think that's valuable to know too because when she has health issues and she goes to test and her testosterone's a little bit low, you know what? That's how it's always been.

    There is some value too in just knowing kind of where you're at generally speaking. I mean, in her case, her bone health, she probably should know that and at some point kind of address that because maybe some DHEA or something to kind of just build the general hormonal milieu up a little bit or whatever. I'm not saying it's necessarily okay that she's low but when she has some profound change in the way she feels and then she tests and realizes, "Oh, my goodness. I'm low for testosterone," well, guess what? It was when you felt healthy too. So that can be valuable too just to kind of know what's normal for you.

Christopher:    Yes. Absolutely. Establishing that baseline and then you can do the same obviously with any test, right? With the blood chemistry and –

Mark:    Yeah. Absolutely. Absolutely.

Christopher:    Yeah. That's a really great point. So let's talk about DHEA then. How does DHEA differ on the DUTCH test versus what I've seen? Normally, I just get one number on the saliva report. How does it differ with DUTCH?

Mark:    DHEA is reasonable I think in saliva. I'm such a cynic and a skeptic when it comes to lab stuff, right? Any time something seems a little bit off, my first thought is: is there a problem with the lab? One of the things that you can do to make yourself more comfortable with that is multi-variant testing. When you look at DHEA, you look at DHEA but we also look at the downstream metabolites. I'll give you an example as to why I think this is important.

    DHEA can be measured as DHEA or DHEAS – DHEA-sulfate. In saliva, there were some nerdy explanations as to why one's better than the other and it's not that interesting but they both have their benefits and whatever. You can use either one.

    But let's say you're using DHEAS, okay? So I'm measuring DHEAS and I'm saying this represents me for DHEA, okay? We measure DHEAS also but then downstream from DHEA you get two metabolites called "etiocholanolone" and "androsterone."Not very easy to say but they're nice to have.

Christopher:    I'm glad you said those.

Mark:    They are huge, meaning they represent a big chunk of the DHEA you've made. Let's just take an example and say you or your patient has raging inflammation, okay? May you know it; maybe you don't. One of the things inflammation does is it blocks sulfation. So now I make DHEA and I try to make DHEA-sulfate and I can't. Now my DHEAS is low. But where is it going? What's going to go to those downstream metabolites?

    So now I have a situation where etiocholanolone and androsterone, which I still can't pronounce well but I look at them and I know, okay, these represent a lot of my DHEA and they're elevated. I look at my DHEAS and it's in the low side. Aha! I can learn something about inflammation maybe but that's secondary. The main point is the DHEAS misrepresents my DHEA story if it's given by itself.

    In that type of a situation, let's say you have another person who's just flat out low for DHEA. So guess what? Their DHEAS is low, so are those two downstream metabolites. If I juxtaposed those two patients, I can't tell them apart potentially with a salivary test. Serum's going to need to be somewhat more comprehensive in order to tell it apart. I don't want just one marker.

So if I've got all those markers, that for me is the biggest benefit. A secondary benefit would just be simply that our test represents most of the day. You collect in the early morning, you collect in the afternoon, you collect at bedtime, you collect right when you wake up. All told, it's about 14 hours worth of time that it represents.

[0:30:02]

    The salivary test, the serum test, they're going to be more of just a moment in time, and that stuff changes throughout the day. That to me is somewhat interesting but having the multiple markers, that to me is what I really like about the urine. You can test estradiol? I'm going to test eight estrogens. I'm going to get so much more thorough.

    It's the same with the cortisol. I'm measuring free cortisol four times. Guess what? I'm also measuring cortisone, the inactive form, and the metabolites. So it's just this big picture of each family of hormones instead of a single marker.

Christopher:    Yeah. This big picture is what I love, having this extra information. For example, we've been testing a bunch of Masters Athletes and it seems like the men are worse affected. They all seemed to have like a mild case of ion overload. One of the markers we look on the blood chemistry is ferritin which just happens to also be an acute phase reactant so you kind of have to rule out just like acute inflammation when you're trying to decide whether or not this really is ion overload.

You've just given me an extra piece of information there in the sulfation thing. Does this person – are they inflamed? I'm not saying this is going to be then a concrete diagnosis but, as a detective, you've just given me another piece of information that I can add to the totality of the test results to help me form this overall picture.

Mark:    Right. And it keeps going. If you talked about inflammation, what does inflammation do? It makes you make prostaglandins. What do prostaglandins do? They promote aromatase like nothing else so your androgens then turn into estrogens. What else do they do? They push cortisol away from its inactive form, cortisone, and towards cortisol.

    When I see people that have this sort of inflammation picture if you will – not that it's diagnostic of course -- but in DHEA and elevated estrogens and cortisol that tends to look that way as well, sometimes it's a process of elimination trying to figure out what's going on with somebody and it starts to paint this picture that's much richer than just having those four or five basic markers. That to me is one of the biggest values of the test.

Christopher:    Yes. You've kind of narrowed this down from like a list of possibilities to a list of probabilities and then that gets really exciting. When you start drilling down and you kind of see that picture, it's really great.

    So let's talk about DHEA as it relates to women. I know there're two different pathways, the 5 alpha and the 5 beta. I mean, they're relevant to both men and women but in particular I just wanted to talk about DHEA in women and how those two metabolites might differ.

Mark:    Yeah. The 5 alpha and the 5 beta pathway are relevant because if I have testosterone and it shoves down the alpha pathway, it becomes DHT. DHT is three times as potent as testosterone. This is usually the conversation you start having about people with PCOS – polycystic ovarian syndrome – because the central piece of that is usually insulin and high insulin tends to, but not always, push 5 alpha metabolism.

    Essentially, every androgen, when it goes down the alpha pathway – think alpha androgen – it gets more androgenic. Let's say you have two women and they both have fairly normal levels of androgens, if one of them – like me, I do this – push it down the beta pathway, they're going to get slightly less androgenic. If the other woman pushes it down the alpha pathway – they may have the same testosterone levels, same DHEA levels and one of them may be struggling with facial hair, acne, thinning scalp hair and the culprit in those cases can be DHT.

    So what does that mean? Well, I can't give her a DHEA. Well, not necessarily because there are things you can do to block that – saw palmetto, nettles, progesterone. They were things that are active 5 alpha blockers. I'm just speaking more theoretically. If you have someone you think needs DHEA and every time they take it they get facial hair, and then you look on the test and you go, "Ah, look at you. You're an alpha metabolizer," then maybe you preemptively can give them something to block that. Start your dose low and maybe you can get a little bit further up in terms of what you give them, helping their sense of well-being without causing unsightliness or whatever the negative effects of that would be.

    That's just another benefit of urine testing is I've got – one, two, three – four different 5 alpha, 5 beta pairs on the test so when someone really pushes down that alpha pathway, you can see it pretty clearly and then you can adjust and whatever. So sometimes it's relevant; sometimes it's not. When it is, it's a nice bit of information to have.

Christopher:    Yeah, I know. I think this is really exciting. For the women, of course, PCOS is one of the leading causes of infertility.

Mark:    Right.

Christopher:    The doctor that I work with, Jamie [0:35:01] [Indiscernible] – she's just recently married. Her surname was recently Busch. But, yeah, she's been sending me lots of interesting study showing that DHEA can improve egg quality. I wonder whether some women would like kind of shy away from DHEA as a supplement because of this, the danger of pushing down this into kind of the 5 alpha pathway.

[0:35:22]

    Do you think it's just good practice then just to take one of these 5 alpha blockers to like some supplement just as a kind of standard of care rather than having to do the test or is everybody different?

Mark:    Ah. Well, if you take me as an example, I'm a guy with let's say low normal-ish testosterone and my androgens tend to head towards the less androgenic pathway. I don't think it would be appropriate, to be honest, at all for me to preemptively take something that's going to take a preference I have and make it even more extreme.

    I think for a female, I mean, yeah, I don't know that I would be into blocking pathways if there isn't a call for it, to be honest with you. I'm not trying to push more testing on people but it's not like 5 alpha, 5 beta only work on your androgens. They metabolize progesterone. They metabolize cortisol. So if I don't have an alpha preference, I probably wouldn't take anything to block it unless you just want to be pragmatic and say, "Look, I took DHEA and I got a beard." Okay. Well, scale back your dose a little bit. I don't mean me. Obviously, from a female perspective. I already have a beard.

    Then, yeah, okay. If you don't want to test, I mean, people do this all the time. Take your saw palmetto and nettles or whatever and you can be a pragmatist and you can – smart doctors that are very pragmatic do great but how much better I think to have something where you can look at that and say, "Aha. That is it" or that isn't it. Maybe like a symptom that would make a lot of sense for that isn't as much the facial hair as the thinning scalp hair. I can have thinning scalp hair because of a thyroid issue. So, okay, I've got low thyroid, my hair's falling out. Gee, I better take saw palmetto, stinging nettles, and then you do the test and you realize, "Ah, crap. I'm not even high for those things. What am I doing?" The answer is going to evade you but it doesn't –

    Your level of pragmatism can be higher or lower and sometimes there are budget reasons that people can't test or whatever but if you can get the information, I think you can make better decisions generally speaking.

Christopher:    Right. Some of the supplements, they're so expensive that by the time you've been taking them for a few months, you could have paid for the test to find out whether you needed it or not.

Mark:    Right. Well, like DIM is a good example, right? DIM is something people take to help with their estrogen metabolism. Some people just put everyone on it like, yeah, everyone needs DIM like it's magic. Well, it has a specific action. I guess multiple actions but primarily it pushes your estrogen down the 2-hydroxy pathway.

    I've had friends who I've tested and their estrogen, like estradiol, estrone, it's high. So, okay, your estrogen's high and the 2-hydroxy estrogens are low. You are not good at this thing that DIM helps. And then they get on DIM and guess what? They think I'm really smart because their estradiol comes down as well it should because you're increasing its clearance. Your 2-hydroxy estrogens go up and their estrogen dominance goes away and they feel better. It makes sense, right? And then you find somebody else who feels the same way but maybe for a different reason. You just shove DIM down their throats. Well, it's expensive. Maybe they have low estrogens and guess what you just did? You just lowered their estrogens further and now when they break their hip when they're 75, they're going to blame you.

    I think that some of the supplements people take is a little bit too much of a kneejerk reaction with symptoms although I think in some cases you can make really sound decisions without lab testing. But in some of these situations, it really does help give you more clarity.

Christopher:    Uh-hmm. I also wonder about – have you heard about this? DIM is the concentrated extract of cruciferous vegetables which can act as goitrogens which basically means that they block the uptake of iodine, iodine being one of the nutrients that's required to make thyroid hormone. Have you ever seen this, people taking DIM, mess up their thyroid?

Mark:    I have not dug into that enough to pretend to be intelligent on that front. I'm not sure. I3C is an extract from cruciferous vegetables. It metabolizes to DIM. So DIM is the metabolite.

Christopher:    Right.

Mark:    This whole argument from people that I don't really get all that interested in of which one is better to take, all I know is they both increase your 2-hydroxylation. In some cases, that can really help people with respect to their estrogens. If there are other considerations people need to take, I don't speak that intelligently to that but on the hormone front, the sex hormones, there really is a pretty good effect and sometimes that can be really useful.

[0:40:11]

Christopher:    Okay. One of the problems I think with the saliva testing is say you're taking a supplement orally, well, that kind of rules out the possibility of testing orally, right? If you're taking progesterone and you do the saliva test, you're just going to measure some of the progesterone that you just put in your mouth, right? Can you talk a little bit –

Mark:    Uh.

Christopher:    Oh. Well, sorry. Did I say something wrong?

Mark:    No. Yeah. I mean, you're just like that's a really big conversation. I mean, of the things that I end up lecturing on to doctors, that's probably the top one. It's an hour conversation of like what's your hormone, what's your route of administration and which test –

Christopher:    Okay.

Mark:    On our website, I have a testing matrix that has a chart, this whole like decision-making thing and it's all hyperlinked to videos so if you went in there and you clicked on "oral progesterone," what I would end up telling you is that you are better off not testing than using serum or saliva. Serum and saliva are reasonable ways to test progesterone and they're not reasonable ways to test progesterone when you take it orally. It's not because it contaminates your saliva. The problem is when do you take oral progesterone? When do people take it?

Christopher:    Yeah. I guess at night would be –

Mark:    Exactly. Because it helps you sleep, right?

Christopher:    Right.

Mark:    Okay. But the kinetics are such that it's gone in a couple of hours. So you take progesterone, it gets metabolized. Literally, four hours later, it's pretty much gone. So then what do you do? Well, you wake up eight hours later. You go do…

    I'll just give you a quick example. I had a patient with a doctor that's very well-known, put her on like 100 milligrams of oral progesterone. She tests the next morning. Her saliva progesterone is low to which I would have said that's irrelevant. Then she took 200 milligrams. Still low. Then she took 300 milligrams actually against the doctor's wishes and guess what? Still low, right? It has nothing to do with saliva being a bad test. It has nothing to do with oral progesterone not working. It's a terrible match to take oral progesterone and test in serum or in saliva because the kinetics don't work out.

    A urine test is actually – and this is probably a longer conversation than you want to get into but the urine test is actually a pretty good way to monitor oral progesterone. It's the only way I would really trust it if you do it well because you got to measure multiple metabolites and it's a little bit complicated. But, on the other hand, oral estrogens; urine is not a great way to test. Blood probably works better.

So it really depends on how you take the hormones as to which test is best but, overall, the DUTCH model is I think probably the best catchall. We've kind of thought our way through a couple of scenarios that are tricky with other tests and it works a little bit better. But hormone monitoring with hormones is tricky.

Christopher:    Okay. Okay. Yeah. Maybe I should not go down that route. That's kind of --

Mark:    Well, that might be a good follow-up conversation or something because, like I said, there's no five-minute way to get good answers all up but just as a reference. I've spent literally over ten years piecing that exact question together. What if I take it sublingually? What if I take it transdermally? What if I take it vaginally?

    At dutchtest.com, if you get the testing matrix, it's always said it has the information and then it's hyperlinked to educational videos to kind of walk you through why I conclude what I do.

Christopher:    Right, right. No, and of course I will link that in the show notes for this episode. Okay. So maybe just one more stupid question. Can you talk about how some of the estrogen metabolites might relate to your methylation status?

Mark:    Yeah. If you're testing estrogen, you can test estradiol as your main estrogen, right?

Christopher:    Right.

Mark:    You can test it in blood. You can test it in saliva. You can test it in urine. This is one of the areas where I think people really do themselves a disservice by using saliva testing, with all due respect, is that when you test –

    I just did a study, right? I had premenopausal women at different phases of their cycle test. I had post-menopausal women test. When I test them in blood, guess what? There's a ten-fold gap between premenopausal women and post-menopausal women. When I test them in urine, ten-fold gap, okay? When I test them in saliva, the labs that have good tests, it's about a two-fold difference so much less. If the tests aren't so good, more like the same, meaning with some labs there's entire overlap between pre- and post-menopausal women. That's the main thing with the estrogens. It's just one of the main reasons why I switched from saliva to urine is because the testing method.

People get all caught up in, "Oh, but it's free hormone." Well, that's nice conceptually but the analytical methods really aren't sensitive enough to do as good of a job of differentiating the haves from the have nots for estrogen. They can for progesterone. They can for cortisol, et cetera, et cetera. But with the estrogens, there's just not enough of it there. That's been my experience.

[0:45:05]

    Then you go on to metabolism, right? We talked about DIM and that's called "phase one metabolism." Which of the phase one metabolites am I making or am I doing it at all very well. That's an issue and that relates to some things. Lastly, there's phase two and part of that is methylation. Methylation has been real hot of late and it makes sense because there are all these genetic defects. I'm a perfectly good example. There's one called MTHFR and there's one called COMT – and you're probably real familiar with these – but they both relate in different ways to your ability to methylate. You methylate estrogens but you also methylate all over the place – catecholamines. It's a really important thing to do well.

    I do not do it well and I know why because I have two really messed up COMT genes. My MTHFR is fine. My COMT is all kinds of messed up and it's something I probably should deal with. But you know what? When I look on my test and I look at 2-hydroxy, 2-methoxy, that is methylation converting one to the other and I stink at it and that's why.

    So when you look at anyone with a pretty significant genetic issue with that, they stink at methylation too. There are things you can do about that. There are people who have genes that are just fine but they're deficient. They're not getting enough B12. They're not getting enough all these methyl cofactors and so they stink at methylation too.

    So this is a functional test to just simply ask the question: do you methylate? You want to methylate your estrogens well but it's also kind of the canary in the coalmine to say, look, if you're not methylating this well, you're also not methylating your catecholamines. You're also not methylating elsewhere where it's important. It's a pretty big deal to be a "good methylator."

Christopher:    Right. This is kind of another situation where you're giving me this extra piece of information that I can then compare to… In the organic acids test that we do, we measure methylmalonic acids and [0:47:03] [Indiscernible] glutamate which show the need for B12 and folate. It's kind of related topic and so you stop to form this big picture of how well a person is methylating.

    Well, this has been fantastic. I'm super duper excited about this. Apparently, my test result is going to be ready tomorrow. I think we've ordered about maybe ten of these I would say. Certainly, my wife is going to do one. The registered nurse I work with has done one. One of the doctors I work with is Dr. Tommy Wood. He's a research scientist that works at the University of Oslo. I've sent him one.

    That's another cool thing about this test is it costs me $4 to send that test kit to him in Norway which I think is going to be huge. If you're listening to this and you're in France or you're in Canada or you're in the UK, it's really not going to be expensive for you to do this dried urine test.

Mark:    Yeah. The shipping is really easy and is a lot because it's just a flat envelope, right? The kit is so simple.

Christopher:    Right.

Mark:    The test itself is obviously not $4. I wish. But for what you get, it's very, very cost-effective. We have been very intentional about – I mean, there are people actually copying our model of testing, which is fine, and they're about $150 more. We've really tried to make this cost-effective but it's also top-of-the-line instrumentation. We're using more so than what other people are typically doing. We're using GC-tandem MS and LC-tandem MS which isn't interesting enough to talk in detail on but it really does help. The results are done by methods that are the most sensitive, accurate methods you can use.

Christopher:    That's awesome. Yeah, I know. I'm really excited about it. I might have to get you back on to talk about some of the test results. I'm sure I'll have a billion questions. But, in general, what do you have for say there's a practitioner or a doctor or someone listening to this that's interested in ordering some of these DUTCH test with their patients or clients?

Mark:    For providers, I mean, we really want to work through providers as much as possible. If providers go to our website, dutchtest.com, and just click on "BECOME A PROVIDER," we have an introductory deal that we always offer people that you can get up to five tests; it's a half price, as a provider if you're willing to prepay. That's a really good way to just kick the tires and see how this thing fits and looks. We really help a lot with the interpretation.

    There are actually four different videos embedded right on the front page of the report that can help both patients and providers to understand the different subcomponents of the report. If you understand it all but the cortisol's a little fuzzy, you can just get click on that video and it'll be more of this voice just rambling through like, hey, let's digest this a little bit together. So we really try to help people, educate them before and afterwards.

But, yeah, if new providers are interested, we love educating people on testing and this in particular. They can just go to our website and sign up and we'll get them started.

[0:50:05]

Christopher:    Cool. When I've got some test results, I can get Tommy on the line and you can explain to his what the results mean.

Mark:    Yeah, for sure, when yours are done. It's unfortunate the timing that they weren't quite done but we usually run around eight to ten days. That is one thing with the test like this too is there are some saliva labs that do an awesome job of like two-, three-day turnaround time. When you start moving into the world of urine and mass specs, it's a four-day process just to do what we do. So it's a little bit slower but within the field we're rather efficient but it's a lot more sophisticated process. But I think it's worth it because you just get so much more information.

Christopher:    Yeah, I know. For sure. The urine organic acids take quite a long time as well. They typically take a couple of weeks, sometimes three weeks. I wonder whether they sometimes – do you know if they do that? They run them in batches so they wait until they have a big batch and then do them all at once or something?

Mark:    Oh, for sure. For sure. Organic acid procedure is actually pretty quick but the urine, you've got this big hydrolysis process so it's usually like at least a two-day process no matter how you do it. I actually developed organic acid testing for US BioTek in a former life so I've wrestled with that a little bit. But, yeah, always run with it because your cost will just be higher if they didn't. If they ran a single one –

Christopher:    Right. It's expensive enough as it is.

Mark:    There's a whole thing that goes into running a batch of those things so, yeah, for sure.

Christopher:    Awesome. Well, if you'd like to order a DUTCH test, I can certainly act as a provider and order one for you. I'd love to get you on Skype and figure out what the results mean. That would be really fun.

    Mark, thank you so much for your time. I would love it if we could connect again in the future and maybe dive into some of the details that there's not time to and some of the things I brought up.

Mark:    Sure. I'd be happy to. Thanks for having me.

Christopher:    Yeah. Thank you.

[0:51:52]    End of Audio

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