Dr. Carrie Jones and I went to medical school (National College of Natural Medicine) together. She was a brilliant, awesome friend then, and still is. What a privilege it’s been to watch her grow into the expert she is today. As you’ll see in her bio, Dr. Jones has been focused on women’s health and hormones her entire career which has spanned academia, clinical practice and now as the chief medical officer at Precision Analytical, home of the DUTCH dried urine hormone panel.
Given Carrie’s background, she’s uniquely suited to train us on using the DUTCH panel, as she’s literally interpreted thousands of these tests over the years. Her podcast is chock full of Monday morning pearls of the best kind- actionable content I think you’ll appreciate and use immediately.
In this podcast we discuss:
- The difference between a dried urine, saliva and serum hormone testing.
- Evaluating hormone metabolites
- COMT and estrogen clearance
- Understanding and favorably augmenting testosterone metabolism (men and women)
- Assessing thyroid status through looking at adrenal hormones and metabolized cortisol
- Identifying and treating hormonal imbalance root causes
- How exogenous steroids and opioids suppress the HPA axis.
- The difference between DHEA-S and DHEA.
- Is the “pregnenolone steal” a real thing?
- A new marker added to the DUTCH hormone test: 8OH2DG an oxidative stress marker.
- Why melatonin is tested using first morning specimen.
- The melatonin and cortisol relationship
Precision Analytical exists to make it easier for patients and their health care providers to find answers to complex clinical questions that affect their lives every day. Our unique hormone testing and reporting methods create better tools for health care providers to explore hormone issues with their patients.
Download Sample Report – Female
Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine. I’m your host, Dr. Kara Fitzgerald. I am so excited to be talking to a going on decades-long friend, who happens to also be a brilliant clinician and now is medical director at a great laboratory. Anyway, let me back up and tell you about her before I brag on her. Dr. Carrie Jones graduated from the National University of Natural Medicine School of Naturopathic Medicine located in Portland, Oregon, where she was adjunct faculty for many years teaching gynecology, advanced endocrinology. She completed a two-year residency in advanced women’s health, gynecology, and hormones and later went on to complete her master’s of public health at Grand Canyon University in Arizona. She’s been the medical director for two large integrative clinics in Portland, Oregon and she is currently the medical director at Precision Analytical. She often writes for women’s health websites and takes part in podcasts and interviews and lectures and does all sorts of stuff all over the planet these days. Carrie, welcome to New Frontiers.
Carrie Jones: Thank you. I’m so excited to be here. It’s great talking to you after knowing you for decades.
Kara Fitzgerald: I know. I know. I know. I know. It gets a little frightening. Yeah, so we graduated together, as I mentioned. Now Carrie’s the medical director at Precision Analytical. You’ve met already, if you listen to my podcasts, Mark Newman, who founded Precision Analytical. He’s their chief analytical chemist. He develops all of their tests. They’re on the map for these amazing urinary hormone assays. I think Mark has really revolutionized the field. Carrie, in her role as medical director, is just doing a fabulous job training clinicians on how to use these tests and how to interpret them.
Today, we’re going to be talking. We’re going to back up. My conversation with Mark was a little bit geeked out, a little bit more analytical. Today, we’re going to keep it very clinically relevant and kind of fill in some of the gaps. Dr. Jones, let’s just talk. Talk to me about the DUTCH. What does the name stand for? What is this amazing test that you guys are doing over there?
Carrie Jones: It’s funny. Everybody always asks me, “Oh, doctor, are you testing Dutch ancestry? Is this a DNA test?” I’m like, “No, no. No, no.”
Kara Fitzgerald: That’s so funny.
Carrie Jones: It’s an acronym. It actually stands for dried urine test for comprehensive hormones, so we aren’t a saliva test. We aren’t a 24-hour test like where you collect in a bucket for 24 hours. We’re not a serum test. We are dried urine test and hormones and adrenals and a few other markers is what we do and what we look at, so it’s really, really pretty easy and, just as you said, it’s pretty revolutionary.
Kara Fitzgerald: Yes, it is. I just want to underscore that. If you’re new to this, if you’re new to the DUTCH, there’s four sample collection time points, so your patient is not carrying around their bucket for 24 hours to capture all of their urine, nor do they have to go for a blood draw, so it’s really an easy test to do and I think the data are relevant. Talk to me about its relationship to saliva and serum. I know there’s some differences and then there are some and 24. Let’s throw it all. Is it as reliable as serum, which is the gold standard, and etc.?
Carrie Jones: Yeah. Actually, we have a study that’s coming out. It’s going to be published comparing dried urine to serum, so that should hopefully be out or be selected, I should say, here soon. Then we can have that for maybe your next podcast.
Kara Fitzgerald: Okay.
Carrie Jones: Yes, and so with serum, of course, obviously, like you said, it’s our gold standard. We can get all your basic hormones, your estrogen, your progesterone, your free and total testosterone. You can do a single blood cortisol, but of course, you miss out on is it the bound up cortisol? Is it the free cortisol? Then with saliva, the great thing about saliva, which is what made it so neat was that you could spit in a tube four times in the day and you would get your free cortisol, so you get your circadian rhythm through the day, but you miss out on your metabolites, which is the way your hormones are being processed in your body.
That’s when 24 hour became really cool, like okay, now we can get hormones and we can get the metabolites to see which way does estrogen go? How much cortisol are you making in total? Where are your androgens going? As we know, it’s a giant pain and it’s not very convenient for people to collect their urine over 24 hours in one bucket. With the dried urine, it fit this really neat niche of you get the four points during the day so you get the free cortisol, you get your circadian rhythm, and because it’s urine, you get all your metabolites. You get your phase one and phase two detox pathways of estrogen. You get your alpha and beta of androgens. You get your metabolized cortisol. You get the best of all the worlds in one nifty little test.
Kara Fitzgerald: Yeah. Right. Right. Indeed, it is. Why do we want to know about estrogen metabolites?
Carrie Jones: I think that the big one everyone always thinks about is oh, the 2/16 ratio. It’s got to be all about the 2/16 ratio. Now, of course, as we know, the 2/16 ratio is not nearly as important. 16-
Kara Fitzgerald: Give me a little background on 2/16.
Carrie Jones: Oh, yeah. Let me go back even further in case your listeners, so with estrogens, obviously, we know the body makes estrone and estradiol and estriol, but estrone and estradiol have to get broken down. They go through phase one detox and those create the phase one metabolites collected later. You have your 2-OH, your 2-hydroxy estrone, your 4-hydroxy estrone, and your 16-hydroxy estrone. Then those get recirculated and then to get out of the body, they generally go through what we’re looking at in our test is through methylation, through what the COMT or COMT gene. Once the 2, the 4, the 16 goes through methylation, the act of methylation, then it becomes methoxy, so 2-methoxy, 4-methoxy. Then it gets excreted out of the body and we can test for that.
When a man or a woman has a really healthy phase one and phase two detox, it means their estrogen is being taken from estradiol or estrone through phase one, through phase two, and then leaves the body nice and safely. It reduces the risk of breast cancer, maybe prostate cancer, estrogen-dominant symptoms, heavy periods, long periods, tender breasts, PMS, things like that because things aren’t recirculating. They’re getting moved out.
Then to answer your question, what was tested originally was everyone thought oh, the 16-OH, the 16-hydroxy was the one that actually causes DNA damage and cancer. Then the 2-OH or the 2-hydroxy is considered the safer of the phase one metabolites, so everyone wanted to know what’s the 2/16 ratio was what is was called. People didn’t really know about or kind of forgot about the 4 or the 4-hydroxy and it comes to find out the 16-hydroxy, the 16-OH, for sure, I call it the estrogen-dominant metabolite because if you have a higher 16, for sure you’re going to probably have heavy periods or PMS or estrogen proliferation is what we refer to it as.
Really, it’s the 4. It’s the 4 that goes down this other naughty pathway, the quinone pathway, and if it doesn’t get stopped as it goes down the quinone pathway, which is, again, it’s not going through methylation like it’s supposed to. It turns tail and and goes the other way. Then that’s when you get risk for DNA damage and your cancer risk goes up, so it’s important to look at all the pathways and see where your patient’s headed.
Kara Fitzgerald: Right. Right. Right. There was quite a little controversy abuzz some years back when 2/16 was being challenged. I think it was a nice starting point, but it did push us to expand and I appreciate having 4-hydroxy, 2-hydroxy, and being able to look at 2-methoxy and seeing what’s going on with methylation. It’s for sure a very helpful addition and gives clear treatment direction for us. We can see the 2-methoxy, which has actually been shown in the literature to be protective, so we want that as robust as we can.
Carrie Jones: Right. Right. Absolutely. Absolutely. Everyone assumes, as you know, they see the word methylation and they’re like, “Okay, folate. It must be MTHFR.” I’m like, “Well, it’s helpful, but no. Actually, no, it’s COMT.”
Kara Fitzgerald: That’s right. Yeah, yeah, it’s a whole different gene, but it does rely on S-adenosyl, methionine for-
Carrie Jones: Yes. Yes.
Kara Fitzgerald: Okay. Talk about looking at progesterone and the progesterone metabolites, what was like that.
Carrie Jones: Yeah. Urine is a little different, so progesterone itself you might get a serum test or saliva test. Doesn’t show up in urine, but what shows up are the progesterone metabolites. There’s really great clinical data, I should say literature data, to show that the progesterone metabolites often match what’s going on in the serum or the saliva. What’s really neat about the two metabolites, so in the human body, we have an alpha metabolite and a beta metabolite. It’s the alpha metabolite of progesterone that crosses the blood-brain barrier and basically helps with the GABA A receptor in the brain.
The classic example is your perimenopausal woman who used to sleep really well and maybe didn’t have that much anxiety and now she’s not making much progesterone anymore. She comes to you and she says, “I don’t understand. I’m having anxiety all the time and I can’t sleep.” It’s because that alpha metabolite is not there anymore to stimulate GABA and maybe she has some GABA issues and then it’s worsening her sleep and her anxiety. It’s really neat to see on the DUTCH test. I can go, “Oh, look. You’re an alpha-dominant person and your levels are low. This is what used to protect you in the past and it’s not anymore. No wonder you can’t sleep,” or, “No wonder your anxiety is through the roof.”
Kara Fitzgerald: Wow. Isn’t that fascinating? The research on progesterone is being useful for hot flashes. Is it this mechanism, you think?
Carrie Jones: That’s a really great question because I find with hot flashes, and you may agree or disagree, with hot flashes, depending on the person, you can use oral or sublingual or vaginal or topical. Topical might work for one person, oral works for the other. However, to get that alpha metabolite up and to cross the blood-brain barrier and stimulate GABA, it’s oral. It’s oral or sublingual that does it and so it’s different delivery system.
Kara Fitzgerald: Yup. Without question I’ve observed that, that we have to go oral. Okay. That’s an extremely useful pearl. You’ll see it on the test. I’m actually looking at a patient’s DUTCH test now. In fact, this is the complete panel that I’m looking at. If you go to the transcription page, folks, there’s a PDF of a sample test so you can take a glance at what we’re talking about here. Extremely useful pearl. Ideas for interventions when you see the alpha really low, do you just go for oral progesterone to bump it up?
Carrie Jones: Yes.
Kara Fitzgerald: Are you using GABA, as well? Are you doing anything else?
Carrie Jones: I do. Yeah, I’ll use GABA derivatives, especially if … It obviously depends on their complaints, but when I see that they’re not an alpha-dominant person, so it’s going to take more on my end to get their alpha up, that may be the woman who needs more oral progesterone. For example, her friend may only need 100 milligrams of oral progesterone, but she may be alpha-dominant. Then somebody who’s beta-dominant may find they need 200 milligrams of oral progesterone to get the same effect. That’s how I gauge it when I’m looking at the diols.
Kara Fitzgerald: Okay. Then what are your GABA derivatives that you’re referring to?
Carrie Jones: I guess I’ll use GABA, but my concern with GABA is that it’s not supposed to cross the blood-brain barrier, correct?
Kara Fitzgerald: Totally. Yup. That’s right.
Carrie Jones: Then if it does, you’re like oh, dang.
Kara Fitzgerald: GABA no question works for some folks, so maybe it’s some kind of a metabolite product or something. Something is doing something with straight GABA, even as we know it doesn’t directly cross. Are you using a phenylated GABA?
Carrie Jones: Yes. Yeah, I was going to say I use like phenibut stuff, yeah.
Kara Fitzgerald: Perfect. Okay. Let’s talk about testosterone then and the testosterone.
Carrie Jones: Yeah, so speaking of alpha and beta pathways, they go down the same way, which people maybe don’t quite realize, so DHEA and testosterone keep going down the steroid pathway and there’s an alpha pathway for testosterone, which, of course, is your alpha DHT, and there’s a beta pathway. What can happen is if you go down the alpha pathway, that’s when you get your typical PCOS-like symptoms. You get facial hair or acne, anger and irritation, maybe hair loss on the head. Men may experience male pattern baldness, prostate enlargement, BPH. You may have a man or a woman with completely normal levels of testosterone and yet, they have really bad acne or they’re really angry or their hair is falling out of their head. I look and I go, “Oh, okay. You actually greatly favor the alpha pathway.” That’s why you can have normal levels of testosterone, but when it gets broken down, you’re going down this aggressive pathway and it’s being aggressive on your skin or on your hair and we need to do things to mitigate that.
Now, from a lifestyle standpoint, big things that push the alpha pathway, sometimes it’s genetic, for sure, but inflammation, blood sugar and insulin dysregulation, which, of course, we see all the time. The more inflamed somebody is and the more that blood sugar and insulin is out of whack, then usually the higher their alpha. If I can just get those things cleared up from a lifestyle standpoint, then great. The hair stops falling out. Their anger starts to get better. Their acne gets better, what have you.
Now obviously, there are a lot of herbals and supplements, like zinc is a good one. We tend to think prostate herbs, saw palmetto, stinging nettle, pygeum, reishi mushroom is a great one for blocking that alpha pathway, so to speak. It’s funny. I’ll give women prostate support and they’re just horrified. They’re like, “Wait. Dr. Jones, I don’t have a prostate.” I’m like, “No, no. I know. I need the herbs inside. Just try to explain it to your husband or your partner.”
Kara Fitzgerald: Just go with it.
Carrie Jones: “I promise. I know. Yeah, I’m not crazy. I promise it’ll help.”
Kara Fitzgerald: I know. I know. That’s so funny, Carrie. I know. Since PCOS is pretty rampant at this point, companies would do well to relabel.
Carrie Jones: Yeah. That’s what I always tell people, too. I’m like, “It says prostate. I wish we could come up with another term or another sort of gender neutral.”
Kara Fitzgerald: That’s right. That’s right. Another extremely useful piece of this test that separates it from serum or saliva, having those derivative compounds from testosterone and so you’re able to measure testosterone directly plus the derivatives, so different than progesterone.
Carrie Jones: Right. Different than progesterone, right. Exactly.
Kara Fitzgerald: DHEA is there, as well, so you can see-
Carrie Jones: Yeah, so we do DHEAS, actually, so yeah, the sulfated form.
Kara Fitzgerald: Good. Great.
Carrie Jones: One of the things I forgot that’s a great clinical pearl is that inflammation lowers sulfation and so sometimes, when you don’t have those extra metabolites to look at, you may think oh, this person makes really low DHEAS levels. I’m going to put them on DHEA as a supplement. It turns out really, their metabolites, their downstream metabolites, are perfectly normal and their testosterone is perfectly normal. It means their DHEA is making DHEA. It’s just not sulfating it because of the inflammation. Then people say, “Well, what do I do now?” I’m like, “Well, you address the inflammation.” If you address the inflammation, of course, as we should, the sulfation improves and then their DHEAS will go up naturally because it’s not a DHEA production problem. It’s just a conversion into the S form.
Kara Fitzgerald: That’s a great pearl. I want to restate it, make sure I’ve got it. Normal testosterone, normal testosterone metabolites, low DHEAS, think inflammation, think sulfation imbalance.
Carrie Jones: Yes. Yup.
Kara Fitzgerald: Perfect. Okay. Okay. Then, of course, the test is pretty nicely laid out. It’s laid out in that steroidogenic pathway kind of style so you can see where the hormones flow to each other. Testosterone, of course, is aromatized to the estrogens and you can see when that might be upregulated, as well, which, incidentally, I tend to see estrogen dominance in PCOS. You see the aromatase seems to be up and galloping. Any comments on that, just when you see or in men, of course, you can see the estrogen dominance picture in men, so what do you do when you find that on your patients?
Carrie Jones: The reasons, of course, are very, very similar to maybe an alpha pathway person or a low DHEAS, things that stimulate aromatase, inflammation, blood sugar and insulin dysregulation, having extra fat tissue, having extra adipose tissue because aromatase happens in the fat tissue. That’s where it starts. Sometimes you can look at a DUTCH test and see this big picture pattern. Oh, my gosh. You’re an alpha person. You over aromatize. Your DHEAS is low. Everyone wants to know what supplement do I give them. No, no. Figure out why are they so inflamed. What is going on with their blood sugar and their insulin? Are they having a difficult time losing weight? Are they overweight? Start with the basics and work backwards. Obviously, there’s stuff you can do to prevent aromatization, but if you don’t start with the cause, if you don’t get the inflammation down or get the blood sugar under control, it’ll just keep happening. A poor man will continue to gain weight and have man boobs and women will continue to be estrogen-dominant and with low sex drives.
Kara Fitzgerald: Right, right, or concurrent elevated androsterone with [crosstalk 00:19:06] hirsutism, etc., etc. Absolutely. It’s nicely laid out. We can see what’s going on. I want to just back up and talk a little bit, I’m saying back up because I’m scrolling up to the very first page of the test, and just talk about cortisol and what we’re looking at with cortisol and thinking about you look at cortisone as well as cortisol, so just talk about what we’re seeing here. Then I also want to ping you about how we might think about, how we might get an indirect snapshot into thyroid function when we’re looking at adrenal hormones, so cover all things adrenal hormones.
Carrie Jones: And go. Definitely what sets the dried urine test or urine testing apart, for sure, we look at cortisol. We look at free cortisol. We look at cortisone, which is inactive. The one thing I want to point out, people will say, “Oh, I take hydrocortisone cream. That’s the same thing.” I’m like, “No, no, no. Hydrocortisone is cortisol,” which a lot of people don’t realize, so cortisone that’s gone through hydrogenation is cortisol. That’s why it’s a terrible naming thing on the end of the pharmaceutical companies. Hydrocortisone cream is really cortisol.
We look at cortisone, which is inactive, cortisol, which is active, and then we look at something called metabolized cortisol. That gives you a snapshot or a window into how much cortisol is your patient making in total, so basically, we answer the questions can they make cortisol, how much is free and active, and how much is getting deactivated into cortisone? Then just like on saliva tests, we graph it out through the day. We do a morning, mid-morning, and then around dinner and before bed. With those patterns, I can see okay, you’re either making enough cortisol or you’re not. How much is free and active? Okay. You have enough that’s free or you don’t or I can look at then cortisone to say, “Oh, my gosh. You are deactivating all of your cortisol to cortisone. That’s where the problem is.”
The treatments are different. Usually when somebody has low cortisol, as an example, they’re really tired. Maybe they have a lot of stress. We hear a “chronic fatigue-type symptom” or even “adrenal fatigue”, which I would definitely argue is much more an HPA axising in its entirety. They’ll say, “Okay. I’m going to put them on all these … I’m going to Cortef. I’m going to put them on adaptogens. I’m going to put them on all these things to stimulate cortisol.” Actually, look at their cortisone. If they’re just deactivating their cortisone, you want to reactivate, so the treatments are different and it can be really life changing for a lot of people who say, “I’ve been on these protocols for a long time and they’re not working,” or, “I had an adverse reaction. What’s the deal?” I can look at these three diols and say, “Oh, it’s actually just a bigger picture. Here’s really what’s going on.”
Then you brought up thyroid, which is a great example, so when the … Oh.
Kara Fitzgerald: Wait. Oh, actually, yes. No, no, no, no. Go. Finish. I’m so sorry. Then I’ll talk about it.
Carrie Jones: No, that’s fine. With the thyroid, you can’t do thyroid testing in urine at all. That’s a serum test, but when the thyroid slows down, so when you have somebody that’s hypothyroid or maybe cellular hypothyroid, everything slows down, as we know. Digestion slows down. Metabolism slows down. Hair growth slows down. The production of cortisol slows down. The clearance of cortisol at the liver slows down. When you look at a DUTCH test, when you’re looking at those diols, what you’ll notice is metabolized cortisol, which kind of indicates production is really low. Then because it’s not getting cleared out the liver because the liver is slowed down, you have all this excess free cortisol that can’t get metabolized and so it’s really high. It’s this really neat window to go, “Huh, you know what? I think you actually have a thyroid problem, either overtly or subclinically, and it’s showing up in the adrenals.” If you address the thyroid or if you address both at the same time, then you’ll actually have a much happier patient and better outcomes.
Kara Fitzgerald: This is so helpful. I want to run through these patterns and have you add or correct.
Carrie Jones: Yeah.
Kara Fitzgerald: You wouldn’t have this if you were just looking at serum cortisol or if you were only looking at saliva. We wouldn’t get this scan back and check it out.
Carrie Jones: Correct.
Kara Fitzgerald: It’s extremely useful to me. I love it. I have got this functional thyroid assay built in. It’s not really thyroid. I always measure thyroid in blood, but if I see somebody with a cranked up free cortisol, which if that’s all I had, I’d be like wow, you’re really revved up. We need to tone you down. That’s how I would’ve interpreted that if I did not have the metabolites. I see this cranked up free cortisol, but then I look and see whether they’re metabolizing it or not and they’re absolutely not, then I’m thinking thyroid.
Carrie Jones: Yeah.
Kara Fitzgerald: That is interesting. You’ve got somebody with they might have half thyroid picture. They’ve got really dry skin. They’re losing hair. They’re constipated, etc. They’ve got some degree of fatigue, but they also have this buzzy cortisol thing going on, as well. Would you say that you’re seeing that collection of symptomatology in these people?
Carrie Jones: All the time. All the time. I talk to practitioners and I’ll say, “Oh, they have the classic thyroid picture.” Then the practitioner will go, “That’s so interesting. They have all the thyroid symptoms,” or, “That’s so interesting. I just ran their thyroid panel and they either have overt hypothyroidism,” or, “Wow, their T4 and T3 are subclinically low and they have all these symptoms.” I’m like, “Yeah, it’s showing up in the adrenals.”
Kara Fitzgerald: You can throw all of the cortisol interventions. You could throw all sorts of botanicals at them for adrenal function and not turn anything really appreciably around because really, it’s pointing strongly to the thyroid.
Carrie Jones: They may feel, as we know, we had this experience before, they may feel better for a little while and then they get worse again because the thyroid is never addressed.
Kara Fitzgerald: Yes.
Carrie Jones: Yeah.
Kara Fitzgerald: Right. It’s such a pearl. Okay. Now, what if they’ve got really cranked up metabolized cortisol, so they-
Carrie Jones: It’s the opposite picture. Yeah. When metabolized cortisol is super, super high, then I start to think fight or flight reasons, so really high stress, pain, inflammation, infection, insulin dysregulation because, of course, as we know, cortisol, it’s primary job is to handle blood sugar management, obesity because the stupid fat tissue can make cortisol on its own, and the opposite, hyperthyroid. We see patients, I’m sure you do, too, that are maybe on too much thyroid medication or they’re on heaps of thyroid supplements and they’re actually in a hyperthyroid state or Graves’ sometimes or they’re in the hyperthyroid state of Hashimoto’s. They have Hashimoto’s, but they can go back and forth between hyper and hypo and so sometimes that will occur.
Usually it’s the fight or flight reasons. Usually it’s that infection, inflammation, pain. When I ask the practitioner or when I’m digging with the patient, sure enough, there’s something they have. They’re overweight or they have Epstein-Barr. They have Lyme or they have a lot of gut dysregulation, of course. They have SIBO, food intolerances, food allergies, celiac. It’s amazing what you can pick up on just on that diol when you go back and ask the patient. They’re like, “Oh, yeah. I’m a mess. I have all these things and I feel very inflamed all the time.” I’m like, “Yeah, it’s showing up in your cortisol.”
Kara Fitzgerald: Gosh. It’s another great window. Again folks, really high metabolized cortisol and low or even normal free cortisol, but just an aggressive breakdown of cortisol.
Carrie Jones: Yeah.
Kara Fitzgerald: You’ve just outlined pretty much everything that walks into a functional medicine office. If you’re working with chronic disease folks, you can see that it really weighs down. If you think of the person as a web, an interconnected being, it weighs heavily on adrenal function.
Carrie Jones: Then what people will say to me, which this is my biggest soapbox thing, is they’ll say, “Oh, okay. The metabolized cortisol is really high,” as an example. “Oh, yeah. I did a stool test.” They have SIBO and candida and they need to go off gluten. They’re very inflamed. I’m like, “Okay.” Then they’ll say well, what supplement do I put them on? How do I get the metabolized cortisol lower? I’m like remember, the cortisol is responding to what’s happened in the body. Cortisol does blood sugar management. Cortisol is anti-inflammatory to a point. Cortisol responds to inflammatory cytokines, of course. Cortisol does the circadian rhythm and manages stress. It’s not like a supplement is going to magically drop the metabolized cortisol. You still have to go for the cause. You still have to, in that example, clean up the gut, get rid of the infections, eliminate the gluten, and then naturally, cortisol, the HPA axis will say, “Oh, the inflammation’s dropped. I’m not needed anymore. I’ll stop pumping out so much cortisol.” Then it will start to drop.
Kara Fitzgerald: Extremely useful. I get it and that’s what I see. I think in our world, we do tend to jump on pushing adrenal interventions and pushing thyroid interventions when, in fact, what you’re arguing for and I agree is just backing up and working with underlying causes.
Carrie Jones: Right.
Kara Fitzgerald: Okay. Then the third pattern would be tanked free cortisol, tanked metabolites.
Carrie Jones: Yeah. It could be a couple reasons, but that’s your classic what people say “adrenal fatigue” or HPA axis dysfunction, so if the brain is not telling the adrenals to make cortisol, it won’t. Therefore, you maybe don’t even have the free cortisol floating around. Now, the big thing I always ask and man, it is surprising to me how many practitioners come back and say, “Oh, gosh. My patient’s taking this,” but remember steroids suppress the HPA axis. It’s Spring or it’s Winter wherever you are and I’m like, “Remember steroid inhalers. Remember steroid nasal sprays for allergies. Your patients are out in their garden and they’re using cortisone creams, hydrocortisone creams because they’ve got a rash or they got poison ivy.” You have to ask your patient, “Hey, are you taking anything?” Even as the practitioner, if you didn’t prescribe it, maybe they just forgot to tell you that in allergy season they take Nasonex nasal spray every single day or in the Fall and Winter they use their steroid inhaler every day. You didn’t prescribe it, but they just forgot to tell you because it was the wrong season when you saw them.
Now, the other big thing, which is a huge epidemic in the United States, are opioids. Opioids will completely shut down the HPA axis. I’ve actually had, when I see these suppressed cortisol values, I’ll say, “Any chance they’re on steroids? Any chance they’re on opioids?” Funny enough, I’ve had some practitioners come back and say, “Well, I didn’t prescribe the opioid, but turns out,” and then they’d have this wild and crazy story of how the patient either hurt themselves or recently had some sort of minor surgery or decided they got into opioids for some reason and did the DUTCH test and it showed up.
Then lastly is Accutane. Accutane has been shown in the literature in some people to affect the hypothalamus. It will destroy cells of the hypothalamus and so you can get this I had an endocrinologist describe it as a pseudo Addison’s disease and it was Accutane-induced and so for those teenagers and college students who are on Accutane for acne and then finding out their cortisol is tanked later in life, be aware. It potentially could be Accutane-induced.
Kara Fitzgerald: When you see a very low free cortisol and a very low metabolized cortisol, do you need to move towards an Addison workup? Any comments on what to-
Carrie Jones: I do. I run through all those things first. I’ll run through history of TBI, anything that affects the hypothalamus and pituitary that will then not have cortisol become released from the adrenals. I’ll run through medication history, like steroids, Accutane, opioids. I’ll run through all the typical stuff and if it’s like, “No, no, no. I swear, not even a possibility,” I’m like, “Okay. Now we need to work them up for Addison’s.” Yes.
Kara Fitzgerald: Okay. Just keep that in mind folks. I think we’re evolving our understanding from adrenal fatigue, which is what we were taught in school this was to HPA dysfunction, axis dysfunction, but we are absolutely responsible. You could pick up Addison’s with this test and you just need to be mindful around that and either refer or initiate a good workup yourself.
Carrie Jones: Especially if they have other autoimmune. They’re like oh, they have Hashimoto’s and celiac. I’m like, “Well, there’s your triad. You should test for Addison’s.”
Kara Fitzgerald: Yup. Absolutely. Any comments on DHEA, just DHEA’s relationship? You want to just give a little snapshot of that?
Carrie Jones: Yeah. On the DUTCH test, what happens is if you do the complete, which is the test that you’ll have linked in the comments, we have DHEAS and then we have an adrenal page to our test and it says total DHEA. People go, “Well, what’s the difference?” Total DHEA is where we add DHEAS plus the metabolites up and that lets you know if your patient can make DHEA. Then which direction it’s headed is why we give you each individual metabolite.
For example, if you’re looking at page three, we have DHEAS and then we have two metabolites. One starts with an E. I don’t know why they have to be the most difficult words in the world, but one starts with an E. It’s etiocholanolone and the other one is androsterone. We add the three of them together and that gives you the picture of can your patient make DHEA? Do they need DHEA supplementation? Those diols tell you which way they’re headed, alpha pathway, beta pathway, sulfation pathway.
Now, but as we know, DHEA can definitely go up for totally protective reasons. It protects against cortisol’s damage in the brain, so sometimes, somebody will have a really DHEA, but they’re also super stressed out and they have elevated cortisol. I get asked, “Oh, what do I do to bring their DHEA down?” Like, “Nothing.” “But they’re stressed out.” “Don’t worry about the DHEA right now. It’s probably protecting the body from the damage of cortisol. Focus on the cortisol and the stress and then DHEA will gradually drop over time.”
Of course, we know DHEA, if you suspect PCOS, that’s different. DHEA androgens can go up with PCOS. Androgens can actually go up with certain medications. There’s research to show Wellbutrin, Xanax, and certain ADD medications, I think it’s Ritalin is the biggest one, I’d have to look that back up again. I definitely see that. I’ll see patients on Wellbutrin and on Ritalin and their DHEA were really high. I’m like, “Well, I’m pretty sure that’s medication-induced,” so not much we can do about that other than work to maybe address the cause and get them off the medications, but nothing right in the moment I can say, “Here, take this supplement. It’ll drop your DHEA.”
Alcohol, that’s another big one and I will see that. I’ll talk to practitioners or to patients who are like, “Well, yeah. I have a couple glasses of wine every night.” I’m like, “Okay. Well, you’re affecting your blood sugar and you’re also affecting your DHEA, so let’s work on that.”
Kara Fitzgerald: You see the DHEA increase?
Carrie Jones: I do, up. It goes up, yeah.
Kara Fitzgerald: Wow. Do you see changes to testosterone or to the metabolites, as well?
Carrie Jones: I haven’t noticed that as much. I notice it just more with the DHEA when I’m running through my why might it be elevated questions.
Kara Fitzgerald: Right. Isn’t that fascinating? When I first moved back to Connecticut, I was in a tertiary care pain center and everybody, of course, was on opioids and I did, indeed. I had saliva back then, but I would absolutely see HPA suppression and, of course, hypogonadism. Testosterone was always very low in people on opiates, so another thing to think about if you’ve got anybody. Now, what about the classic cortisol steal and DHEA? Any comments on that?
Carrie Jones: With that one, you mean with progesterone? Is that what you mean?
Kara Fitzgerald: DHEA being used as being commandeered for cortisol production.
Carrie Jones: Oh. I think that’s a hot topic.
Kara Fitzgerald: Yeah, tell me, so what’s the deal?
Carrie Jones: It’s made an entirely different layer of the adrenals and it’s made … When the body wants to make a hormone, it pulls cholesterol in. My example is pregnenolone. When the body wants to make a hormone, it pulls cholesterol into the mitochondria. Pregnenolone happens to be a hormone along the way and then it keeps going. It keeps going to make whatever hormone it needs to make, estrogen, progesterone, whatever, testosterone. You and I got taught the pregnenolone steal all through school and it turns out the mitochondria don’t steal from each other’s mitochondria as far as we know and because the pregnenolone is being made in the mitochondria, the pregnenolone steal is probably not true like we were taught.
However, pregnenolone still works. What happened is pregnenolone, when you take it orally, when you take it as a supplement, it turns into those same alpha metabolites as progesterone that cross the blood-brain barrier and work from the brain down. People will say, “Well, I give my patient pregnenolone and they feel better.” I’m like, “I know.” It’s just a different mechanism of action than we were all taught in school.
Kara Fitzgerald: Okay. All right. Fabulous, fabulous. This whole idea of DHEA’s involvement in cortisol is a fallacy?
Carrie Jones: I don’t know that. I don’t know. I don’t know that I fully believe that just because again, they’re made in different layers of the adrenal gland and the mitochondria don’t steal from each other, so it’d be tough to convince me otherwise. I get why people say it. I see it on the steroid pathway, absolutely. I was taught the same thing in school, but the more I read the literature, I’m like, “That’s not how mitochondria work.”
Kara Fitzgerald: Right. Right. Right. I think it goes all the way back to Selye, right, doesn’t it?
Carrie Jones: Yeah. Yeah. Yeah, actually.
Kara Fitzgerald: Girl, you set that record straight.
Carrie Jones: Thanks.
Kara Fitzgerald: You heard it here first.
Carrie Jones: Exactly.
Kara Fitzgerald: Anyway, yeah, no, I think it’s really great that we’re pushing the paradigm along and cleaning our language up and moving towards HPA dysregulation versus “adrenal fatigue” although when I wrote the case studies in integrative and functional medicine, in it, we had an adrenal fatigue case in there and I made an argument why I thought we should adopt the term. I have to say that we’ve moved along and it’s true. HPA function does make sense. It’s just-
Carrie Jones: I tell people who argue, who obviously, people really identify with their symptoms, as they should, and their diagnoses. I’m like, “I’m not telling you you don’t have it. I think you’re tired, absolutely. I believe you’re tired.” It’s just the mechanism of action may be a little bit different than what used to think or how it works. It’s just different. Then just like you were saying with DHEA and cortisol and pushing this paradigm that we all do in functional medicine, it’s ever evolving and we’re trying to just be as accurate as possible. I fully believe the symptoms are real, absolutely. The treatments work. It’s just the how and the why are evolving.
Kara Fitzgerald: Yes. Yup. I agree. Then we’re able to actually refine and expand on our treatment when we have a fuller understanding. All right. A couple other things you’ve got going on this test, which is pretty handy dandy, is you are measuring 8-hydroxy-2′-deoxyguanosine. Let’s talk about that.
Carrie Jones: Yes, so OHdG, so that is an oxidative stress marker and a marker of DNA damage. It’s a really neat marker when you’re following somebody who maybe has cancer risk or active cancer, inflammation, things that involve a lot of oxidative damage to the body. Then you can be proactive about it and try to help heal your DNA and get your own antioxidant system back up to snuff.
Kara Fitzgerald: That’s lovely, so you could flip back over on back to page three and you could look at all of these amazing functional insights into inflammation that Dr. Jones just went through, so we could see increased aromatase activity in testosterone moving towards the estrogens. You could see increased 16, the estrogen derivatives. You could see increased 4-hydroxy, which then is potentially going to initiate cancer by forming quinone adducts on the DNA. We can see an increase in some of these more androgenic testosterone metabolites, etc., etc. You pointed out a whole bunch of ways that we can see inflammation. Then you can scroll down to 8-OH-2dG and see whether or not that’s elevated, as well, which is really corroborating that full picture.
Carrie Jones: Yeah. Yeah.
Kara Fitzgerald: Then the patient in front of you, of course, has got truncal adiposity and they’re eating at McDonald’s etc. and yes, it’s lovely. I think it’s great that you added it on and I knew that you were thinking about it. It was just a neat thing for me to pop open one of my more recent reports and say, “Oh, cool. Wow, there’s 8-OH-dG.” Next to that, Carrie, is melatonin.
Carrie Jones: Yeah. What’s interesting, because of the urine test, people always get concerned and confused. We test melatonin off the very first urine sample. The waking sample is what it’s called. People go, “Well, melatonin’s low in the morning. Why do you do that?” The reason is because you have been sleeping all night and all your urine has been collecting in your bladder and then we collect it first thing in the morning, so all the melatonin is used up, pushed into the bladder, and we catch it. That’s why we do it on the morning and not the evening sample. You get this really great picture into your baseline melatonin. Can you make it? Is it too high? Is it way too low and that’s the problem? Then it helps with go with sleep and antioxidants. Obviously, melatonin’s a really powerful antioxidant, so it’s really neat information.
Kara Fitzgerald: That’s great information. You’re looking at as long as the patient doesn’t have nocturia, you’re basically looking at an overnight specimen, is that what you’re saying?
Carrie Jones: Yeah. In all the kits, we do include five strips and that way, if they do get up in the middle of the night, for example, if you get up at 3:00 in the morning to urinate, you collect a fifth strip and we can pull the melatonin off of the fifth strip and the waking sample, so we don’t miss it, I should say.
Kara Fitzgerald: That’s fabulous. All right. Let me see if I’ve got any other questions. You’ve been a font of really useful information. I think people will really love it. Any comments on melatonin’s somewhat antagonistic relationship with cortisol?
Carrie Jones: Yeah. Actually, I always say that cortisol’s the bully and so if you have really high cortisol at night, you will often have lower melatonin just because cortisol seems to, not in every patient, of course, but I see it often enough on the DUTCH test and I know I’ve talked to other practitioner doctors who work at other competitor companies and they’re like, “Yeah, we see the same thing,” that they’ll have lower melatonin.
Now, melatonin, as we know, is made from serotonin and it’s primarily for circadian rhythm made in the pineal gland, but obviously, it can be made in the gut, as well, and can change with gut inflammation, but is regards to the pineal gland. I tell people you have to get off your phones. You have to get off your computers at night or you have to buy those sexy blue light blocking glasses. You have to buy your orange-lensed glasses to cut that out in order to get the melatonin up. Then you also have to do all your sleep hygiene things to get your cortisol down at night, as well. Like I said earlier, if your melatonin’s really low, it’s a big antioxidant in your system and if you don’t make enough melatonin, it’s not just sleep. It can affect a lot of things like DNA damage and cell turnover, so it’s pretty important.
Kara Fitzgerald: You might see a low melatonin and a high 8-OH-dG although-
Carrie Jones: You might, actually.
Kara Fitzgerald: Yeah, although 8-OH-dG is impacted by many other variables, a lot of which you’ve outlined. Great job today. You’ve interconnected the dots lovely.
Carrie Jones: Thank you.
Kara Fitzgerald: You have a lot of good educational resources over at the website.
Carrie Jones: We do and we’re actually expanding it quite a bit. We have a list of about 30 videos that we are in the process of making, diving more into some of these clinical pearls and herbs and nutrients, the hormones, supplements, how it affects the tests, things you might consider if you see a high or a low value, just to give people more guidance because we know our test is really thorough and just like you had said earlier, when people first see the test, sometimes it can be very overwhelming. I say it’s just like a steroid pathway. Just follow the arrows and that’s the way a steroid pathway moves, so you can see above and below. We’re hoping to really expand all of our videos. However, right now on the website, on dutchtest.com, they are completely free. You don’t have to be a provider signed up to get access to them. You can just go. They’re about five to 10 minutes long and you can just dive right in yourself.
Kara Fitzgerald: Go for it, folks. It’s quite, quite useful. Incidentally, as a clinician, so when you order the DUTCH test, you do have access to Dr. Jones if you need to pick her brain. I think initially, Carrie, you do give some interpretive.
Carrie Jones: We do, yeah. We actually have five doctors that work for the lab now.
Kara Fitzgerald: Wow.
Carrie Jones: Yeah. We’ve expanded a little bit and so there’s five of us that do all … Three of us are full time and so you can pick a lot of people’s brains, but yes. The very first test you ever do, we do send you an email and it does put it into layman’s terms. We can say, “Hey, this is what your patient said. This is what we see on the report. This is what we suggest. Let us know if you have any questions.” It’s pretty thorough. It’s several paragraphs long that we go into.
Kara Fitzgerald: Then they can request, so clinicians, you can talk to the medical tech team ad nauseum until you understand and you understand all of these nuances that we’ve pointed out today. You can also grab the transcript of this. I’m going to try to harvest as many pearls as I possibly can and put them into bullets for you, so you can glean the material that you’ll be applying immediately from this podcast. Anyway, again, Dr. Jones, it was great to reconnect with you and thank you so much.
Carrie Jones: I know. It was so fun. Thank you. I really appreciate it.
Kara Fitzgerald: Absolutely.