00:00:00:07 - 00:00:23:14 

Noah Reed 

Welcome back to the DUTCH podcast, where integrative medicine providers can expand their understanding of functional endocrinology. And everyone, no matter who you are, can learn more about their body’s most complex communication system. I'm Noah Reed, vice president of sales and marketing for the DUTCH Test. And coming up on this week's episode, it's another weekly dose of endocrine essentials, organic acid style. 

 

00:00:24:05 - 00:00:57:18 

Noah Reed 

The DUTCH test measures 12 key organic acids that help providers see possible nutrient deficiency or cellular oxidation. Today, Dr. Alison Smith will be focusing on the oxidative stress marker eight hydroxy two dioxin guanosine or more lovingly called ADHD. Before I introduce Dr. Smith, I want to say thank you to all of our listeners and subscribers. We are so thankful for you joining us in this journey and I want to take a second to acknowledge that we had some technical difficulties while filming Season one that made some of the audio a little difficult to listen to at times. 

 

00:00:58:05 - 00:01:31:17 

Noah Reed 

So, as we're preparing to record season two, I want to assure you that we've taken the steps to make sure that we deliver the best audio experience available. We look forward to wrapping up Season one with some amazing episodes and bringing you an even better content and a very exciting Season two. But for now, onto this week's episode After completing her doctorate at the National University of Natural Medicine in Portland, Oregon, Dr. Allison Smith worked at a private practice focusing on primary care, women's health and dermatologic laser therapy over the last eight years. 

 

00:01:31:22 - 00:01:55:14 

Noah Reed 

She has consulted with providers on thousands of cases in the context of hormone testing. She is also supported providers in clinical practice through consulting webinars, case presentations in articles. In her spare time, you can find her out playing with her dogs, composing music at the piano, sitting out in her backyard, or going on local adventures with the family in the gorgeous Pacific Northwest. 

 

00:01:56:06 - 00:01:59:16 

Mark Newman 

Thanks, Noah. And thanks to Dr. Alison Smith for joining us today. 

 

00:01:59:23 - 00:02:01:20 

Allison Smith 

Thank you for having me. I'm honored to be here. 

 

00:02:02:06 - 00:02:25:07 

Mark Newman 

So today, we're not talking as much about hormones as typical way back when. We built this test with the attempt to be as comprehensive as we could be on reproductive and adrenal hormones. And then we started adding to it. So, our goal was to add pieces to the puzzle that helped fill in the same story about a patient so that it's more comprehensive, gives you more value as a provider. 

 

00:02:25:07 - 00:02:45:11 

Mark Newman 

So, one of the things that we've added, as you know, is ADHD, so oxidative stress markers. So, let's talk about that a little bit today. So first, before we get too far, we probably need to know how to pronounce this thing because the real name is long, and people hate it. And to just the whole concept of oxidative stress of what is it? 

 

00:02:45:11 - 00:02:51:12 

Mark Newman 

So, what is the marker that we measure for oxidative stress and what in the world is oxidative stress? 

 

00:02:52:14 - 00:03:19:17 

Allison Smith 

Well, I think that's a really excellent question and it's a little bit of a nebulous concept because we're talking about something that's happening very deep inside each of one of our cells essentially. And oxidative stress is really talking about the delicate balance between oxidative products of regular old normal metabolism of carbohydrates that you're eating fats that you're eating and absorbing. 

 

00:03:19:17 - 00:03:57:04 

Allison Smith 

Everything has to be oxidized and utilized in order to create energy. So, in a way oxidation is a normal process in the body and we want to foster that and create energy. But we also have all of these wonderful mechanisms to protect ourselves from all of those reactive oxygen species that are generate it during those oxidative processes. And you know, ADHD is just one example of one way we can look at oxidative stress damage once it's crossed through that barrier through our antioxidant system and damage the DNA, we can look at ATO fatigue and see, gosh, we've got some oxidative damage here. 

 

00:03:57:08 - 00:04:09:19 

Allison Smith 

And so, when we're assessing oxidative stress, we want to see are our antioxidants able to guard the DNA against oxidative damage? Yes, no, we need ATO Fdg to make that assessment. 

 

00:04:10:12 - 00:04:20:00 

Mark Newman 

So, eight-hydroxy dioxin guanosine, how so? How exactly is that make like what's the process? Where's it coming from, what's the substrate or like what turns into that? 

 

00:04:20:02 - 00:04:23:13 

Noah Reed 

Can you say that a little bit slower for me, eight hydroxy? 

 

00:04:23:13 - 00:04:29:12 

Mark Newman 

Eight-hydroxy dioxin. OK, there's a two in the middle of there, so it will that's an extra syllables around doing that. 

 

00:04:29:14 - 00:04:30:05 

Noah Reed 

OK, thank you. 

00:04:30:12 - 00:04:59:11 

Allison Smith 

But the actually Guanosine actually is coming straight from the DNA. So, you're really looking at an oxidized ized product of a two-dioxide guanosine. It's one of the base pairs that make up our DNA. So, in essence, when we're looking at a fdg in the bladder, we're looking at it in the urine. In this case, we're looking at little pieces of DNA in the urine that are essentially building up there because there is a increased cell turnover or increased DNA damage. 

 

00:04:59:21 - 00:05:04:00 

Mark Newman 

So, a functional marker for DNA damage caused by oxidative stress. 

 

00:05:04:01 - 00:05:06:23 

Allison Smith 

That's right. And that is a reasonable yes. 

 

00:05:07:01 - 00:05:21:05 

Mark Newman 

OK, and we find it on a page. And at the top of the page, you find the words organic acids. Yes. Which is a bit of a misnomer in this case. So is eight hydroxy dioxin. Guanosine eight always. DG Thank you. Is that an organic acid? 

 

00:05:22:06 - 00:05:25:12 

Allison Smith 

No, not technically interesting. 

 

00:05:26:04 - 00:05:30:10 

Mark Newman 

See, now she's critiquing the building of this panel, which she can critique me for because. 

 

00:05:30:10 - 00:05:39:07 

Allison Smith 

I think all of these are nucleic acid like we're talking about D Actually Guanosine is arguably a nucleic acid and B maybe it's an organic acid. Sure. I think we could say that. Yes. 

 

00:05:39:07 - 00:06:01:00 

Mark Newman 

You know, you find melatonin and ADHD G on this page of six organic acids which actually have a carboxylic group on them. Yeah, sure. And then these two markers sort of fold in with the story that's being told there. But technically they're not actually in that category of organic acids, but they belong in that category because of the story they tell. 

 

00:06:01:00 - 00:06:07:19 

Mark Newman 

So, what is the story that eight H tells you? Like, how do you utilize that? What's the story that's been told to you? 

 

00:06:07:19 - 00:06:36:10 

Allison Smith 

Well, I think, you know, whenever you're thinking about hormone metabolism and some of the phase one, you know, mid-level metabolites of estrogen, we worry about the four hydroxy metabolites because they have the ability by structure, they are very unstable and they have the ability to form these reactive quinones with neighboring Quinones, they become how to call Quinones complexes. 

 

00:06:36:12 - 00:07:16:10 

Allison Smith 

It's all these long names or just mean that they can glom onto the DNA and bind to guanosine residues that they are highly susceptible to these estrogen quinones compounds. And once you have that DNA addict formed, then you kind of open the the door to changes in the DNA that if they're not repaired, can initiate cancer. So, when we're looking at a two fdg, we're really looking at it in the context of cancer sometimes, you know, breast cancer, prostate cancer, endometrial cancer in particular, those estrogen driven cancers that are being driven by those four hydroxy phase one metabolites. 

 

00:07:16:10 - 00:07:38:00 

Allison Smith 

I think you guys are probably already covered estrogen metabolism pretty well previously in the podcast, but it really fits here as well because, you know, phase one metabolism of estrogen is the is the first step in making a lipid into a water soluble, ready to enter the urine in the stool and leave the body kind of a state. 

 

00:07:38:19 - 00:08:32:11 

Allison Smith 

But step one creates this pretty reactive intermediate in some cases. And so, you know, for people who maybe have inflammation or toxic exposures or they're hypothyroid, they're going to maybe favor this for hydroxy pathway of estrogen metabolism more than the average bear. And if you're hydroxyl that fourth carbon you're creating those more structurally unsound estrogens. And if you're accumulating them because your phase two detox isn't functioning well, maybe you have problems with your C OMT activity because of genetics or because of cofactor deficiencies or or maybe your good if iron system is down and you're not able to, you know, backtrack that for hydroxy metabolism, then you're you're in trouble. 

 

00:08:32:15 - 00:08:56:14 

Allison Smith 

And usually, patients will present with either a family history of cancers or they'll present to your office and say, gosh, I want to do everything I can to prevent cancer. Because my friend just got done going through this. You know, we can look at these things and and assess based on the phase one metabolism of estrogen, how how predisposed you are to accumulating these four hydroxy estrogens. 

 

00:08:56:21 - 00:09:19:15 

Allison Smith 

Then turn around and assess the ATO fatigue and see, well, you know, your ATO looks really normal. We're still in preventive territory. Let's apply some some good antioxidant support, try to move more metabolism down to the two hydroxy estrogen which by structure are very much more stable. They're much less likely to go on down those negative pathways to damage the DNA. 

 

00:09:19:15 - 00:09:27:02 

Allison Smith 

So, a lot of things that you can do ahead of time to kind of prevent these processes from happening ten years from now. Right. 

00:09:27:11 - 00:09:49:19 

Mark Newman 

So, you you mentioned the big C word, cancer. So, if we look at people who have high eight hydroxy eight H GS does that mean they have cancer? And on the flip side, you look at a lot of reports, right? You see lots of patients like when someone has cancer. How often do you tend to see that marker high? 

 

00:09:49:19 - 00:09:51:16 

Mark Newman 

So, can you kind of go from both angles there? 

 

00:09:51:23 - 00:10:16:04 

Allison Smith 

Yeah. So so, when when we know a patient has cancer, often a G is elevated while they're going through treatment. And early in in the process, once it's been caught and, you know, early on in the process, we'll see it elevated that's a given. But there are plenty of times where you have patients who are just coming in for regular preventive lab work. 

 

00:10:16:04 - 00:10:40:04 

Allison Smith 

You're looking at hormones, you're looking you're kind of thinking you're in preventive territory and they come back with a high rate of fatigue and maybe it's just a little bit high. You know, if the range goes up to six, it's an eight or so. It's definitely raising an alarm bell. But I like to ask questions like, you know, what was your diet like around the time of testing are you are you intermittent fasting? 

 

00:10:40:04 - 00:11:08:12 

Allison Smith 

Are you you know, there may be situations where ADHD could be transiently elevated and not consistently elevated like you would expect to see with cancer is process, you know, or I would expect we're in Ramadan time. You know, if somebody is fasting for Ramadan and they're going to do their their DUTCH test, they might have an elevated A2 during that time because they have more rapid cell turnover. 

 

00:11:08:12 - 00:11:43:02 

Allison Smith 

There's more more activity, more oxidation in those cells. So, the body's having to work a lot harder to create energy right you're not getting it from your food. You're having to create it de novo. So, there can be times where it's kind of benign, actually. And so, you had to figure that out. You know, it doesn't necessarily mean we got to send you for a mammogram immediately, but, you know, it can, you know, create a space for a conversation and you can put it together together with other markers like pyro glutamate tells you about glutathione status or GTI levels in the serum. 

 

00:11:43:22 - 00:12:04:21 

Allison Smith 

And you can put all of that together to figure out how how well somebody, including my own system, maybe is working or not to protect the DNA and put that together with the information you get for ADHD. And so there can be other other ways to put this info together that helps patients not freak out about it. And also, it helps us not freak out about it. 

 

00:12:05:00 - 00:12:28:07 

Mark Newman 

Not diagnostic of cancer. No, but it tends to be elevated in patients who have cancer and in those who don't. And they have an elevation. You've mentioned a couple of causal factors, and that's, of course, a huge obsession of functional medicine providers is to ask the why question. Right? Why is this elevated? Well, it indicates oxidative stress. OK, well, why do you have high levels of oxidative stress? 

 

00:12:28:07 - 00:12:34:14 

Mark Newman 

So, when that question comes for you, what's what's your thought process in terms of what you're looking for in that in that patient story? 

 

00:12:34:14 - 00:13:01:22 

Allison Smith 

Yeah, I think you know, oxidative stress can arise when when we're not taking care of our other endogenous stressors, you know, our endogenous stressors or stressors that are happening just inside of our bodies. We are we're managing our blood sugar all the time. So maybe we're having hypoglycemia or hypoglycemia at different times. Maybe we're inactive, maybe we have times where we're hypoxic because we have sleep apnea or disordered breathing at night. 

00:13:02:08 - 00:13:36:01 

Allison Smith 

Maybe, gosh, it could be all kinds of reasons. You could be pushed towards oxidative stress in kind of a silent way really. If you're not getting checked up regularly and looking in on these things and also getting enough micronutrients, I mean, are you are you eating the rainbow of fruits and veggies and really making sure that you're getting all your vitamin A, C, E, selenium, zinc, magnesium, all of those cofactors that support phase two detox. 

 

00:13:37:08 - 00:13:55:07 

Allison Smith 

And and really, you know, phase two detox is that, you know, putting the methylation cap on those hydroxyl related phase one metabolites that can go on to initiate cancers processes and then, you know, supporting sulfur rich foods that can help feed some of our, you know, salvation processes in the body. 

 

00:13:56:02 - 00:14:10:10 

Mark Newman 

And so, I have high levels of oxidative stress. I die at 102 and never get cancer. Yeah. What are you concerned about in a patient that has oxidative stress outside of the big C word in terms of how that would negatively impact their health outcomes? 

 

00:14:10:10 - 00:14:42:05 

Allison Smith 

Sure. I think it can play into even just chronic inflammatory issues, chronic immune and even just accelerated aging. And so, I think a lot of people are really interested in slowing the aging clock down or stopping the aging clock. I mean, aren't our kids supposed to never die? Right. But you know, the oxidative stress and oxidative processes overrunning our anti oxidative system is probably the number one reason we, we age the way we do. 

 

00:14:42:05 - 00:15:15:16 

Allison Smith 

And so, I think if we can find ways to incorporate, yes, good habits, proper supplementation where we maybe have holes and making sure that our detoxification is supported in a way that's consistent with maybe our extra needs. If we have some maybe a genetic deficit here or there, you know, to try to overcome that. And, and that can help to sustain health and keep us out of, you know, chronic chronic conditions chronic high blood pressure or chronic cardiovascular disease. 

 

00:15:15:16 - 00:15:15:23 

Allison Smith 

You know. 

 

00:15:16:06 - 00:15:39:21 

Noah Reed 

Right now, you've said a lot of things chronic that are like alarm bells and the C word and and stress like big words here. I'm sure there are people like me who are try to be the dabbling in the biohacking world and going to put things into practice that you're saying is there a way that we can take this too far with trying to go with oxidative stress and and detox properly and in our bodies? 

 

00:15:40:17 - 00:16:20:06 

Allison Smith 

That's a good question. I think that it's hard to overdo the antioxidants, honestly. So, I think I think doing an antioxidant supplementation protocol is fine. But if you can eat in a way that pushes the pathways we want to push and there are really well-studied ways of doing that and we have families of, of vegetables like Braska family vegetables that's been really well studied for increasing, you know, positive phase one metabolism and up regulating even phase two metabolism and methylation. 

 

00:16:20:06 - 00:16:44:21 

Allison Smith 

And so, and frasca family veggies are not just broccoli. You know, if you hate broccoli, you can still get it. And if you like arugula and you like, you know, cauliflower and kale and you know, you can get it in and other ways and still, you know, get a lot of those positive benefits. And there are other polyphenols like resveratrol and spices, I would say, you know, dabble around in spices. 

00:16:45:01 - 00:17:12:08 

Allison Smith 

Americans have a hard time. Some Americans have a hard time spicing their food. We're from Texas we don't have any trouble spicing our food. But, you know, like curcumin and and there's so many wonderful, pigmented, beautiful spices that are essentially medicine that do push and pull pathways and help us to detoxify not only our hormones, but also, you know, fats and all of those byproducts from oxidation. 

 

00:17:12:14 - 00:17:48:23 

Mark Newman 

So so, on the hormone side of that, you know, we end up talking about dim a lot, right? You're talking about cruciferous vegetables and one of the things that that can promote is two hydroxylase, which we think of as protective. And, you know, in my sort of like nerd quest to understand some of those at a deeper level, you know, when you look at the genetic the genetic snips that impact that pathway, the ones that up regulate the pathway actually can lead to more cancers because two hydroxylase and this is my understanding of estrogens is protective. 

 

00:17:49:05 - 00:18:08:03 

Mark Newman 

But two-hydroxylase of some other like poly aromatic hydrocarbons and things like that can make them carcinogenic. So, when I think to myself just being like simple minded, I think there's no way I'm eating enough broccoli that you could overdo anything like that or curcumin or whatever. But I can take a little dim capsule and I can take 400 milligrams. 

 

00:18:08:03 - 00:18:30:05 

Mark Newman 

And now you have like this pretty unnatural situation where you're two hydroxyl eating things like crazy. So, if you take that, that makes sense to me. But the oxidative stress I'm less competent on. So, if you take some of those potent things that dampen that down, is there a way with nutraceuticals in the top five or six things that would do that? 

 

00:18:30:05 - 00:18:46:17 

Mark Newman 

And if you just went crazy with those, like what would be a potential downside to that, or would there be a downside to that in terms of, you know, overdoing the oxidative stress or overdoing lessen your oxidative stress? Can you put it out completely and then have issues? 

 

00:18:46:18 - 00:19:04:18 

Allison Smith 

I think I think it would be difficult too, to be honest with you, even if you just took tons and tons and tons of them. But I think you could probably find that isolated case in the medical literature where, you know, somebody ended up with hepatitis and you know some other issues. And I think that people do end up in trouble. 

 

00:19:04:18 - 00:19:26:20 

Allison Smith 

Yeah, I read a case report the other day about somebody who OD'd on Kirkman. It's like, wow, that can happen. And they ended up with hepatitis from taking Kirkman. And so absolutely, I think any time you do any bio hacking, you're taking supplements that you're still going in for your yearly visits, you're getting liver function tests, maybe even every six months just to make double. 

 

00:19:26:21 - 00:19:51:16 

Allison Smith 

Sure. That there's like you're saying that there's not, you know, something that's kind of ramrodded you in one direction and kind of changing the way you metabolize everything else, everything you didn't think of. But I think in general, directing traffic down the two hydroxy pathway with dim, we think of topping out at 200 milligrams a day is is prudent. 

 

00:19:51:16 - 00:20:21:08 

Allison Smith 

That's what most studies are really looking at. 180 milligrams of them and there and there are other constituents too that have been looked at not so much dim but I see you know and all three carbon all which funnels into them sometimes people are using them together and they don't realize that they're kind of the same thing in a way and that people can run into problems that way where maybe they don't have much at all going down the four hydroxy or the 16 hydroxy pathways. 

00:20:21:15 - 00:20:55:22 

Allison Smith 

This can be problematic. And post-menopausal women certainly who maybe need 16 hydroxy estrogen and some of the other phase one metabolites of estrogens that are more estrogenic at the tissue level, you know we want 16 hydroxy. There's there's a way that 16 hydroxy estrogen can protect the bones from bone loss from osteopenia and osteoporosis. So, and it's well documented I feel like in the medical literature that if your 16 hydroxy is low compared to two hydroxy and you're postmenopausal that that can lead to more bone loss. 

 

00:20:56:02 - 00:21:21:00 

Allison Smith 

So, and it's the total opposite of what we want for our pre-menopausal women. We want to have more metabolism, you know, going down the two hydroxy we're less worried about those sixteens in pre-menopausal but you have to kind of flip your mindset when once somebody is postmenopausal, especially if we're thinking about their bones, we got to we got to have the 16 showing up and, and maybe maybe higher levels are OK. 

 

00:21:21:01 - 00:21:22:17 

Allison Smith 

It's not really been established actually. 

 

00:21:23:00 - 00:21:50:21 

Mark Newman 

Right. Yeah, I think oversimplifying the story and then going to extremes in terms of the patterns that you're trying to see generally doesn't seem like a good way to approach that. So, I appreciate that one of the things that I've seen in the, in the literature in terms of correlation for eight hydroxy is that it tends to be elevated when cortisol is elevated, and it tends to be elevated when melatonin is low. 

 

00:21:50:21 - 00:22:08:00 

Mark Newman 

So, which is one of the reasons why we added it into that panel. So, can you just sort of walk us through the story of what is the connection between someone who's likely to have a high cortisol or low melatonin? Maybe both, and why those cases would tend to see eight hydroxy elevated? 

 

00:22:08:06 - 00:22:40:16 

Allison Smith 

Yeah, well, cortisol can be high when we're stressed, and it can be any kind of stress. It can be an endogenous stressor inside your body. Your blood sugar is dysregulated because you're insulin resistant or you're inactive or, you know, or you have a family history, or it can be elevated because you're stressed at work. You know, something is stressing you from the outside in and the body really doesn't care why cortisol comes up and goes higher in the bloodstream. 

 

00:22:40:16 - 00:23:00:20 

Allison Smith 

That cortisol gets taken up into the tissues and it gets utilized to do whatever it's there to do. It's managing your blood sugar, it's managing inflammation, it's down regulating the immune system. Whatever it's doing is needed for it's there to do that in the tissues. And and on the DUTCH test, you look at it as a tetrahydrate cortisol and tetra hydrocortisone. 

 

00:23:00:20 - 00:23:31:15 

Allison Smith 

We can get a sense of how much is actually getting in there. And doing the nitty gritty work compared to what's circulating free in the in the in the bloodstream and then kind of entering the urine or the saliva at each time point, you can build a diagonal rhythm and that's great. You can kind of see how the axis is functioning, but I really like using the metabolites because sometimes those cortisol metabolites can be really high and give you an indicator of, you know, adrenal stress over a longer period of time. 

 

00:23:31:15 - 00:24:02:14 

Allison Smith 

And also, the sense that the liver and the adipose tissue are sort of gobbling up all that it can of cortisol, that there's a high need for cortisol in those tissues. And I think, you know, when especially the metabolites of cortisol are high, you will often see a lower melatonin level because the sustained high cortisol levels, especially when it's in the evening and at night, you know, cortisol can decrease the acetylation of serotonin you get less formation of melatonin over time. 

 

00:24:02:23 - 00:24:31:16 

Allison Smith 

And so that's kind of I feel like the link there. And then you can get some independent changes of melatonin, too. You know, melatonin breaks down to more than just the sulfate and metabolite of melatonin that that you're looking at on the DUTCH test that also can metabolize down into all these different electronic acceptors, basically. So, whenever I see a low sulfate in melatonin, I always think about salvation. 

 

00:24:31:19 - 00:24:59:23 

Allison Smith 

You you not so fading very well. And salivation can be hindered by inflammation and stress. Certainly, but if you have a lot of oxidative stress, arguably a lot of your melatonin is going to go down some of these other pathways and, you know, maybe won't be sulfate in your melatonin as well. So, I feel like in a in a big way, low melatonin sulfate and melatonin on the test we're looking at, it is related to oxidative stress by a couple of possible mechanisms. 

 

00:24:59:23 - 00:25:00:04 

Allison Smith 

Right. 

00:25:00:07 - 00:25:20:06 

Mark Newman 

You know, it sounds like an answer from a former biochemistry. It's a good job. So given that you've seen so many of these tests, you use it in your own practice, can you give us an example of maybe just a case study that comes to mind where this was sort of somewhat of a central player and what was going on and it was addressed and you see the follow up testing. 

 

00:25:20:06 - 00:25:23:15 

Mark Newman 

That's sort of the start to finish of where this is a central player. 

 

00:25:24:01 - 00:26:01:06 

Allison Smith 

Yeah, absolutely. I had a case of a 42-year-old female, approximately 42-year-old female who presented with a breast mass who we ended up using them with. But on initial testing, she had a very low to hydroxy metabolism. She favored the four hydroxy, I want to say she was about 30% like significantly high. And when you think about, you know, where we want the four hydroxy estrogen metabolism ratio to be, you want it to be under 11%. 

 

00:26:01:11 - 00:26:25:05 

Allison Smith 

I mean eight to 11 she was closer to 30 and and she had a fairly high 16 hydroxy metabolism too so very almost kind of look genetic right where the the two hydroxy pathway is like less than 30%. You start getting a little worried we want to be at least 60% if not 75% of all your metabolism of estrogen going down that two hydroxy pathway. 

 

00:26:26:03 - 00:26:48:15 

Allison Smith 

So, she had this very odd-looking pie. So, you know in a way you kind of say well obviously we need to do some work here she was an OK methylater, so we weren't too too worried about, you know hypo methylation being the issue. We want to feed the phase two pathways for sure. But that seemed like really, we wanted to rearrange the phase one metabolism. 

 

00:26:49:04 - 00:26:56:11 

Allison Smith 

And then looking at the fatigue, she was not elevated ironically in the fdg at all, but her PIRA glutamate was high. 

 

00:26:57:22 - 00:26:59:03 

Mark Newman 

Glutathione deficiency that. 

 

00:26:59:03 - 00:27:30:20 

Allison Smith 

Potentially exactly included an iron deficiency along with high four hydroxy estrogens. And her four hydroxy estradiol included. So not just for hydroxyl Citroen but also for hydroxide yesterday. OK, so I would say you know that all together with the breast mass, that's enough to kind of move forward with rearranging that phase one metabolism, getting the glutathione support on board we were a little freaked out about it, so we retest it again at three months. 

 

00:27:31:18 - 00:27:53:13 

Allison Smith 

And so, she went on to therapy, she was on her good a thousand supports and her Dem 200 milligrams and there was an i3 C component to that. Two and three months later we did the retest, the 16 hydroxy estrogens had come down to below 30%. So, she's, you know, right where we want her to be for the sixteens. 

 

00:27:53:20 - 00:28:34:07 

Allison Smith 

But her four hydroxy has had not changed at all. They were still 30% of the metabolism. But what had changed was that her two hydroxy pathway, I mean it was normal, it was in the normal 60%, right? So, pyro glutamate had normalized popped right back down. And so we were, we were feeling pretty good melatonin. We also did a high dose melatonin, and I often don't care what melatonin is, whether it's coming out normal or low or high, when somebody has a a breast mass, I always think about using melatonin regardless. 

 

00:28:34:07 - 00:28:53:16 

Allison Smith 

That is just me. And it's not a recommendation necessarily to anyone else. But we know that melatonin in the higher doses, like ten milligrams and up. If you're listening to Doctor Shellenberger, and I would tell you to use 180 milligrams, so some people are really, you know, shooting it to the moon. And I think you can do that probably pretty safely. 

 

00:28:53:16 - 00:29:17:15 

Allison Smith 

But until we know I feel more comfortable with 20 milligrams is kind of what people are using in oncology these days. And anyway, so we were doing some some higher dose melatonin. So, we tested again six months after the initial treatment plan. So, she stayed the course right at the six-month mark. We finally started chipping away at that four hydroxy estrogen. 

 

00:29:17:15 - 00:29:45:19 

Allison Smith 

So, when people ask me, how long does it take? When should I retest my breast mass patient on the demand, I usually will say six months because you might be disappointed if you test at three months because it's kind of like might be a work in progress depending on how far you have to go. Right, you know, and she did have what always sticks out this patient in particular is that her breast mass did completely disappear and resolve. 

 

00:29:46:12 - 00:30:05:10 

Allison Smith 

So not in that six-month period of time, but it's now resolved. Right. So, I think you absolutely can do these things just with supplements and careful monitoring and having everybody on board and proper testing to make sure you're moving in the right direction. So. 

 

00:30:05:18 - 00:30:28:04 

Mark Newman 

Yeah, no thanks. Um, that's a great example. Um, so we've talked a lot about what do I go hunting for and thinking about when the eight hydroxy is high. Uh, a lot of times people don't quite understand how we set reference ranges. There's some arbitrariness to them, so our reference range is set at the 90th percentile. So, for eight hydroxide you actually guanosine. 

00:30:28:09 - 00:30:50:18 

Mark Newman 

If you're higher than nine out of ten of your peers, then you're going to be outside of that range. And to what degree is interesting now on the low end we've set, you could say arbitrarily the reference range starts at zero, which means it's impossible to be low because you can't get a negative number. But that doesn't mean conceptually that there isn't something interesting going on when you're on the low end for that marker. 

 

00:30:50:18 - 00:31:04:10 

Mark Newman 

So, what are you thinking? And this is, I think, a question we get a lot because it's hard to like yeah. I would have no idea to guess actually. So, what is the implication potentially if it's on the low side compared to what most people are coming in at? 

 

00:31:04:10 - 00:31:28:16 

Allison Smith 

Yeah, well, I think of hypo metabolism, and you know, we look at a few patterns of hypo metabolism. When we look at a DUTCH test, for instance, when we look at metabolized cortisol and that's really low, we would think about, gosh, why aren't you metabolizing cortisol? That's weird. If you're making free cortisol, why isn't it being metabolized I think of it in the same way with ADHD. 

 

00:31:28:17 - 00:32:02:18 

Allison Smith 

If your ADHD is really low, where are your oxidative processes that are fueling your cell energy and if if it's not there, then, you know, are we looking at a hypothyroid case or a or even a mitochondrial dysfunction in case where you're just in a really low ATP state? Now, if I have somebody in front of me who's like a marathon runner and they're, you know, really healthy and they're getting good nutrition and they're having regular cycles and and I'm not worried about them if they're ADHD is low, of course not. 

 

00:32:02:18 - 00:32:36:12 

Allison Smith 

But if I have my chronic Lyme patient in front of me who, you know, can barely complete their, you know, adls, and I will be very worried about an ADHD g of zero, and we would be trying to think about ways to support mitochondrial health so that we can get some of those oxidative processes up and running right but I think, you know, ADHD being low, we don't really see very often, but sometimes we'll see low kind urinate and lows and urinate zero sometimes. 

 

00:32:36:14 - 00:32:56:02 

Allison Smith 

And I think of the same thing because those pathways are running towards an aide. And now, you know, in ADHD, niacin production de novo niacin production and that's also energy currency of the body too. So, if that's going hand in hand with the DG being low and kind of everything looks low got a little worried about those guys. 

 

00:32:56:16 - 00:33:02:04 

Mark Newman 

Well, that's interesting. So those are markers. If elevated, they imply a vitamin B six deficiency. 

 

00:33:02:05 - 00:33:02:16 

Allison Smith 

That's right. 

 

00:33:02:16 - 00:33:11:20 

Mark Newman 

But like you said, they're on their way to NAD. Yeah. And if you're just not seeing any of them, then you've got to worry about maybe some more foundational issue that's maybe potentially going on there. 

 

00:33:11:21 - 00:33:41:21 

Allison Smith 

That's right. Yeah. Yeah, that's interesting. And and there are other things to consider too. You know, you got to you got to have tryptophan in order to get down those pathways too. So, you know, if you have somebody with protein malabsorption or maybe they're going through a gut treatment or they maybe they're going through cancer treatment or you know, we think about people who maybe have protein malabsorption or Hypochlorite Adria where they just don't don't have the stomach acid to start the the protein digestion. 

 

00:33:41:21 - 00:34:10:19 

Allison Smith 

You know, people can be low, and all their amino acids and it can kind of lead to, you know, all of their all of their oats on their oats page looking really low. So sometimes you can tie it back to just nutritional stuff. But but, but in particular ADHD G together with lower Kinnear and Aiden's anti urinate and even even a low higher a glutamate, you know that could be low low oxidation status in general in the body so. 

 

00:34:11:00 - 00:34:26:15 

Mark Newman 

Well, lots of different angles on this that are interesting and fun to get in the weeds a little bit on that marker. It's been nice to have it on the panel to bring that piece of the story to light. But thank you for illuminating that for us. Dr. Smith. Yeah, well, thank you for being with us. We appreciate your time. 

 

00:34:26:20 - 00:34:27:15 

Allison Smith 

Thanks for having me. 

00:34:28:15 - 00:34:52:21 

Noah Reed 

Thanks for joining us on this week's podcast. We loved getting to understand oxidative stress better and its role in our day to day lives. Next week on the podcast, we get to kick off a series of conversations where we talk about the DUTCH test and things like Hashimoto's, Grave’s Disease, and Addison's disease. You won't want to miss Dr. Debbie Rice talking about what these symptoms might present like on the DUTCH test. 

 

00:34:53:08 - 00:34:54:03 

Noah Reed 

Until next time.