Breast Cancer Insights: Important Markers To Watch Using the DUTCH Test®

Full Transcript and Time Stamps

(0:06) Dr. Carrie’s Intro

(1:16) Webinar Begins

(5:11) Estrogen Excess

(10:42) Androgen Excess and Estrogen

(16:52) What about progesterone?

(20:15) Phase 1 metabolites: 4-OH-E1 and 16-OH-E1

(26:39) Phase 2 metabolite: methylation

(32:53) Circadian Rhythm

(39:18) Improving the circadian rhythm

(42:47) Melatonin

(49:25) Pyroglutamate and Glutathione

(54:13) 8-OHdG

(1:00:13) Q&A

 

0:06 Dr. Carrie Jones Introduction
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So, we have about 86 slides, and I'm going to try to get through them in about 45ish minutes, so that we have plenty of time for questions. But as Tim said, if you have questions at the end, or questions we don't get to, please feel free to e-mail us, and we will do our best to answer them.

0:22

So, Breast Cancer Insights: What Markers to Watch When Using the DUTCH Test, I would say we get this question on the clinical team over and over and over again because, of course, this webinar is being done in October, which is Breast Cancer Awareness Month,

0:36

and breast cancer is a really big deal to a lot of our population, and while both males and females can develop breast cancer, it is largely, largely, largely the female population that will go on to develop breast cancer. So, as we go through the cited literature, and as I'm going through and talking about this, I will be primarily referring to females and women.

1:01

Although, some of it, of course, men have breast tissue too, and could go on to develop breast cancer.

1:07

So according to breastcancer.org, I'm going to give just a few statistics and we will literally take the large majority to go through the DUTCH /test because that's the most important.

1:16 Webinar Begins
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But just so we're on, like, a level playing field of what we know what's going on with breast cancer,

1:21

one in eight women will develop invasive breast cancer in her lifetime. Which is, again, it is over a lifetime, but one in eight women, and as of January 2021, there are more than 3.8 million women with a history of breast cancer, including women currently being treated and women who have finished treatment

1:39

around breast cancer.

1:41

It is the most commonly diagnosed cancer among American women, and in women under 45, under 45 years old,

1:49

breast cancer is more common in black women than white women, and overall, black women are more likely to die of breast cancer because of the aggressive form, they are more likely to develop

1:59

the triple negative form, as opposed to like an ERPR positive, which is generally more reactive to any kind of hormonal-related therapies against cancer.

2:11

When it comes to genetics, five to 10% are associated with known genetic mutations, like BRCA. These are known genetic mutations.

2:19

Of course, there are a number of, I've seen lists of, you know, 10, 15, 20 other mutations that sort of circulate around breast cancer and, and maybe print breast cancer development, or BRCA is probably the most famous, it's the one that's talked about the most, but it's really a small percentage of those who develop breast cancer.

2:39

And 85% of women with breast cancer have no family history.

2:43

It is definitely…

2:46

Women tend to think they have no family history, that they will never go on to develop breast cancer. And women tend to think if they have a family history that they're absolutely going to develop breast cancer.

2:58

And of course, we know this is not the case, 85% of women with breast cancer have no family history.

3:05

So, when it comes to breast cancer, estrogen gets all of the press, right? It gets a bad rap, it is generally blamed.

3:12

The finger was pointed right at estrogen, all the time.

3:15

And breast cancer is actually an unfortunate combination of genetics, hormones, lifestyle, and environmental factors.

3:25

So, genetics, hormones, lifestyle, and environmental factors, and they come together at a deep cellular level, that's when things go awry and in the breast tissue, cancer forms.

3:38

So, the objective of this webinar, I have one, one objective: it’s to understand the key markers in the DUTCH Test and how they relate to breast cancer, in order to possibly mitigate risk.

3:50

Again, it's not just estrogen. It's a number of things that can swoop in and effect at a cellular level, what's going on.

4:00

So, we have seven areas of the DUTCH Test that we look at.

4:03

We look at estrogen excess, as it relates to estrogen itself for estrogen, progesterone, estrogen and androgens, we look at your phase one metabolites, your phase two metabolites, your cortisol pattern,

4:14

your melatonin, your pyroglutamate, which is a marker for glutathione,

4:19

and your DNA damage marker, known as 8OHdG, eight-hydroxy-two-deoxyguanosine.

4:26

So, right before we jump in, I just want to, you know, make this point. Please remember, if one or some of these markers are concerning, it does not always immediately indicate cancer. There is no absolute.

4:40

So, if you see somebody with excess estrogen in their luteal phase compared to progesterone, please do not automatically think, oh, Carrie talked about this in the breast cancer webinar, this patient's going to develop breast cancer.

4:50

Or if somebody has low melatonin, it's not absolute, we take it into consideration with the individual in front of you.

4:59

These are just the seven areas of the DUTCH Test that when taken together, could increase the risk for cancer, and we are trying to reduce the risk of cancer in any way that we can.

5:11 Estrogen Excess
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So, let's start off with estrogen excess, we're going to start right off with the first one and just work our way through all seven areas. I will also say that because, we only have about 45 minutes to an hour to go through this.

5:23

You could imagine that each key area I could probably talk about for a good, solid hour or more, so I will be touching on all of these. So, you have a good, solid baseline foundation, if you will, about the DUTCH Test and breast cancer.

5:39

But I'm going to point you into other resources that you may need to explore further to really hone in on each of these sections, because I unfortunately just don't have the time to make it worthwhile for all of these.

5:52

So, let's think estrogen excess. On the DUTCH Test,

5:55

of course, we look at estrogen as estrone E1.

5:59

Estradiol E2, which I have circled, because it is the more the most potent estrogen, especially at the estrogen receptor level.

6:06

And then we have E3, which is known as estriol, but estradiol, is what most all of the literature focuses on.

6:14

So, when it comes to estrogen and cancer, I'm just going to get this right out of the way.

6:19

Does estrogen cause cancer?

6:21

Should someone take estrogen, especially as women age, because aging, and being female are the two biggest risk factors for breast cancer? Should somebody go on estrogen replacement therapy, should somebody go on estrogen as part of their menopausal hormone replacement therapy?

6:37

The answer is, we have entire webinars about this, where Doctor Doreen Saltiel literally goes through a deep dive into the evidence. She lays it all out very methodically, and you can find that webinar.

6:48

Well, there's two webinars actually, for free on the DUTCH Test website.

6:53

If you go under education, which I have circled as a tab, go down to webinars, you can find this exact picture and there's another one.

7:02

And you can watch and learn and go through all of the evidence and the literature with her as she works through estrogen to show you that estrogen is not, is not nearly as bad as everyone, especially back from the WHI trial, made it out to seem.

7:19

Now, you throw in a progestin in there, and then, absolutely, we've got some problems, but estrogen itself by itself,

7:25

when it comes to cancer and getting a bad rap, is not nearly as bad, as everyone typically thinks. Obviously, you have to do a lot of due diligence. Obviously, you have to do a full workup. Obviously, you have to make sure the person sitting in front of you is a good candidate from some sort of hormonal therapy.

7:43

And of course, if she has her uterus, you want to make sure you counter it with a counter, her estrogen with oral or vaginal progesterone, but this is the very first place I want to point you.

7:54

If you're working with women, looking to go on estrogen replacement, and you really want to understand the literature that has come out since the WHI trial, go here, and you will really become well-versed in all the literature that's out there.

8:08

Now, the other thing I get asked a lot is dense breasts.

8:12

We know that radiographic reporting has changed and if somebody has dense breasts, they now get the paragraph that says, you have dense breasts. You're at a higher risk of breast cancer, and when it first came out, it freaked out everyone because that paragraph didn't used to be on the mammogram report. So, what is a dense breast? A dense breast is considered high amounts of glandular,

8:35

fibrous tissue, and lower amounts of fat tissue. So, dense does not necessarily mean fat

8:41

or adipose, it does mean glandular and fibrous tissue.

8:44

So, dense breast tissue on mammogram do have an increased risk of breast cancer, hence the paragraph that has been added to those who get a mammogram and have dense breasts, because if you are greater than 75% of density, you have a 4 to 6 times the risk of cancer.

9:00

So, there was a study in 2018, they used estrogen replacement therapy, ERT.

9:05

Use was not associated with dense breasts and breast cancer, but when you added in a progestin, it was then associated with it.

9:24

And so having dense breast is a lack of adipose tissue, more glandular and fibrous tissue, therefore more at risk for mutations to go on and develop.

9:26

Breast cancer, and as we work through each of the rest of the six markers on the DUTCH Test, you will see why.

9:32

But if you put somebody on estrogen replacement therapy, and also add in a progestin, then your risk goes up, and put them on a progesterone, a bio-identical progesterone, it does not seem to.

9:44

But please remember, breast pain and breast density are different. They are not the same thing.

9:50

You can have mastalgia, which is breast pain, which is estrogen-related or can be estrogen-related.

9:56

But this does not mean that it is directly going to increase your glandular and fibrous tissue.

10:05

In fact, a lot of dense breasts, when I have like seen lots of mammograms over the years, talked with my patients done, hundreds and hundreds and hundreds of consults. A lot of people have known that they had dense breast from a younger age, it tends to be genetic, tends to run in families.

10:22

It's not always, again, it's like one of those things we don't always rush in

10:26

and blame estrogen. Breast development is much more complicated, much more comprehensive than that.

10:34

Mastalgia, different. Density, not necessarily estrogen related.

10:42 Androgen Excess and Estrogen
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So, what about androgens? We're going to pick away at all the things, menopausal estrogen, I pointed you to resource, dense breasts

10:47

we just talked about, what about androgen excess and estrogen? Which not many people think about not many think about androgen excess and breast cancer ,so what they have found, this is a 2020 article,

10:58

elevated circulating androgen levels are consistently associated with increased breast cancer risk, but the underlying mechanism of action is unclear. They do know that breast tumors, they do have androgen receptors, AR, androgen receptor expression has been detected in up to 85% of cases.

11:17

Although this varies by breast cancer subtype, while almost all ER positive cancers express the androgen receptor, only 10 to 35% of the triple negative breast cancers express the androgen receptor.

11:30

So, if you have excessive androgens, maybe even in like a PCOS

11:36

case, polycystic ovary syndrome, where they have the hyperandrogenism, than at an increased risk because of these androgen receptors on the tumor itself. Now, this is an extremely long quote,

11:52

but it's really important, because I want to show that when it comes to looking at androgens, it's not as simple is just saying, oh, they're testosterone or oh, they're DHT.

12:03

So, at the top of the quote, I see the highlighted part or what I want to really hit home, is as it relates to the DUTCH Test.

12:10

So, they say absolutely, elevated levels of circulating post-menopausal androgens have an increased breast cancer risk with women in the top quartile of these hormones have a 2 to 3 fold, increased risk versus women.

12:22

Now, remember, this is elevated levels, as opposed to physiologic levels.

12:27

So, if you have somebody on testosterone or on DHEA supplementation, don't necessarily freak out. This is where appropriate, follow up testing is important.

12:36

You can push them into a supra physiologic level.

12:41

But, if you're just getting them back into a typical healthy post-menopausal level, then that's different. So, make sure, don't associate, put on testosterone means breast cancer increased risk.

12:53

Where are they when you do their testing?

12:55

Elevated levels have a 2-to-3-fold increased risk, but it is not known whether their observed effect is independent of the estrogen association, so for one, we talked about the androgen receptor on tumors, and for two, we know that androgens have to come first, and then they aromatase into estrogens.

13:14

So, all the estrogen you make in your ovaries, all the estrogen you make in your peripheral tissue, comes from androgens first and then they aromatase.

13:23

So, is that part of the equation as well?

13:26

But the quote goes on to say that when we're looking at androgens, what happens is that a lot of us, right, a lot of practitioners really focus on DHT, dihydrotestosterone.

13:38

Now, dihydrotestosterone gets a bad rap, because of it's effect on female pattern baldness, cystic acne, hirsutism, and men with prostate cancer.

13:49

But in this quote, they say, if you're using assay, we are, which is immunoassay, that the DHT is often below assay detection, and does not reflect peripheral five alpha reductase activity. Now, thankfully, DUTCH does not use assay, we use mass spec, we're a lot more sensitive in our testing.

14:11

But what it goes on to say, and what we've known with men in prostate cells, is that DHT tends to be an intracrine or paracrime hormone. Meaning it tends to stay in its cell that it's in. The circulating levels don't necessarily line up with what's happening inside the cell itself.

14:31

And so, this study was saying that you have to actually step out and back and look at other androgen markers, because these other androgen markers have been shown to reflect total tissue level androgenic activity better.

14:46

Everyone focuses on DHT, absolutely, I understand why. But this is why at DUTCH, this is why at DUTCH, we look at all the other androgen markers, because what they say in this study actually shows total tissue level better,

15:02

we look at. So, not only do we look at DHEA-S, we look at testosterone, we do look at DHT.

15:07

We do look at the five alpha and five beta androstanediol in both males and females. We look at it both. Now in the male test, we do show it as a dial. So those of you who see male patients and have seen a male test,

15:21

you know that on page three, these extra dials are added. These dials are not currently added to the female report only, mostly because of spacing. That will probably change in the future. But do know it's just on the page before, this information is on page two. So, when we're trying to get an idea of their androgenic tissue exposure, we want to make sure we look at everything and DUTCH does that.

15:43

So, if they are androgen excess, and then estrogen excess, research is showing that they have maybe because of the two of them, the androgen receptor on tumor cells have an increased risk for cancer.

15:58

You're going to work with her to get her androgens back under control. If you have or on androgenic replacement therapy, maybe you have around too high of a dose, if she is coming into this with PCOS, she’s hyper insulinemic, that's pushing on the LH, and LH is pushing on androgen production, you're going to back yourself up and work on that insulin, right? That's what you're going to work on, they’re highly inflamed and that's also pushing on the LH.

16:22

You're going to back yourself up, work on that inflammation, and take the gas pedal off the androgen production. Again, we're trying to get her back in a physiologic range for her age,

16:34

as opposed to a supra, or too high physiologic range.

16:39

But the good thing is, we look at that we have these markers when you're doing the DUTCH Test.

16:45

So, you are actually using this information, as the study said, to look at total tissue level androgenic activity.

16:52 What about progesterone?
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Don't just look at DHT, look at the whole picture. Now, what about progesterone, right? Our savior, our savior progesterone on the DUTCH Test, we look at the beta, the beta pregnanediol, and the alpha pregnanediol, and then we do a weighted average of them to give you an idea of the progesterone that's been exposed in the tissues.

17:12

So, the thing about progesterone, though, is it sure is complicated because we know that to a certain degree progesterone can be quite protective. But if you've got ERPR positive breast cancer, a lot of oncologists are like, no, absolutely not. You cannot give them progesterone.

17:28

It's adding fuel to the fire. This is problem. This is an extremely well written article. It's from 2020, so last year, and I recommend if you are trying to get a better grasp of progesterone as it relates to estrogen, and as it relates to breast tissue, that you give it a read. It's easy to read. It has great pictures.

17:46

So, I do recommend it, but right at the top they say synthetic progestogens, which of course is progestin.

17:54

Fake has been linked to increased breast cancer risk, which I said at the beginning and if any of you have watched Dr. Saltiel’s webinars on menopausal hormone therapy, she talks about it, as well.

18:05

However, the role of endogenous progesterone in breast physiology and carcinogenesis is less clearly defined.

18:12

Mechanistic studies using cell culture, tissue culture, pre-clinical models, implicate progesterone, breast carcinogenesis. In contrast, though, limited epidemiological data generally do not suggest or do not show an association of circulating progesterone levels with risk, and it is unclear whether this reflects methodological limitations are truly a null relationship, and then it goes on to explain in just the abstract, how it's hard to separate estrogen from progesterone at the tissue level.

18:42

Because progesterone in the cell, and progesterone in circulation can be different. You can have high levels in the cell and low levels in circulation. You can have low levels in circulation, or high levels in circulation and low in the cell.

18:56

And then it depends on the receptor and because we know estrogen helps push out

19:03

the action of estrogen, helps push out progesterone receptors, I mean, they have a very good relationship, right?

19:10

Between the two, between estrogen and progesterone. So, when you read the abstract, it goes on to explain why it's hard to peel them apart when it comes to breast cancer, so this is another resource, and this article also explains like what progesterone does in the body and breast tissue development. So, it's kind of like the 101 to progesterone moving all the way through breast cancer, so I do recommend reading this,

19:33

especially if you feel like you need to brush up on your progesterone physiology and anatomy, especially a breast tissue, because this one can be can be really helpful.

19:42

So please don't automatically assume that

19:46

if you take progesterone, it's, again our savior, and going to completely protect you against breast cancer.

19:53

Because really, ultimately, it's more complicated than that.

19:56

And it involves, as I said, in the beginning, you know, chemicals and lifestyle and genetics. Nothing is in a silo.

20:04

You can't just think that progesterone is going to, you know, be like a big shield and protect you.

20:11

It's great for a lot of things, but it is not perfect.

20:14

So, let's move on.

20:15 Phase 1 metabolites: 4-OH-E1 and 16-OH-E1
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Let's focus on estrogen metabolism, because we've talked a lot about estrogen excess and androgens and dense breasts and estrogen replacement therapy and estrogen against progesterone, but how do you process estrogen and how does that have to relate to breast cancer? So, we're going to start with phase one, and then we'll move into phase two.

20:34

So, phase one: estrogens can initiate cancer by reacting with DNA, which we don't like, leave our DNA alone. Specific metabolites of endogenous estrogens, the catechol estrogens-3, 4-quinones.

20:48

React with DNA to form these depurinating estrogen-DNA adducts.

20:52

Loss of these adducts, basically holes, holes in your DNA, leave apurinic sites in the DNA,

20:57

generating mutations that can lead to the initiation of cancer.

21:01

We don't want holes in our DNA. The more holes you have, then the more your DNA repair system has to come in and fix the hole, so to speak. And, of course, it has more chance to get it wrong, which can lead to cancer, according to this article.

21:17

So, on the DUTCH Test, we look at phase one here, in these three dials. So, first, we have what's known as two hydroxy, or 2-OH-E1.

21:27

Then, we have four hydroxy E1 and 16 hydroxy E1. Each of these dials collectively are under the umbrella, known as phase one metabolism, these your three options. Your estrogen, your E1, and your E2 can go down.

21:43

So, as a little introduction to each metabolite if you're unfamiliar. So, you've got your 2 hydroxy E1.

The sip, or the CYP enzyme, it that works on it, is the 1A, family: 1A1 and 1A2, it's primarily done in the liver, but it can be done extra-hepatically, not as much, but that means like it can be in the breast tissue.

22:04

But it's primarily in the liver.

22:06

It is considered, quote, less carcinogenic.

22:09

It's a less carcinogenic, toxic metabolite: it's not free and clear of carcinogenic activity, it's just less carcinogenic.

22:18

It does bind to the estrogen receptor. So, all of these phase one metabolites do have the ability to activate an estrogen receptor.

22:25

But it's like not thrilled with it. It binds with less affinity, not as tightly. It can easily get knocked off by somebody else.

22:32

And it forms, what are known as stable adducts in the DNA. And anything with the word stable, as it relates to cancer, is a good thing.

22:39

Therefore, it's less likely to result in mutations.

22:42

It's not going to form the holes. It's going to stay in the DNA and wait for the DNA repair system to come through and fix it.

22:50

Now, can the repair system still mess up and accidentally create a mutation?

22:54

Of course, this is why this is not zero

22:57

carcinogenic. It's still a toxic metabolite. It is still forms adducts,

23:01

they are just considered stable. As opposed to its buddy four hydroxy E1.

23:08

This one sure can be naughty.

23:09

This one is under the influence of your CYP 1B1, CYP1B1 enzyme, was what pushes this pathway.

23:18

This is primarily in your breast, in your ovary, in your uterus, lung, and kidney, and a little bit in the liver. So, it's in all the places you don't really want a whole lot of your 4 hydroxy E1 to be as a female.

23:30

So, it does bind to estrogen receptors with higher and tighter affinity than the two.

23:35

So, it is estrogenic, but not as estrogenic as 16, 16 of the metabolites, as your more, seems to be your more estrogenic one.

23:44

It's considered free radicals. And there's what's called a semi-quinone or quinones state.

23:48

So, again, as you, as you move along the pathway, if we go back, if you move along the pathway, this pathway, which is the red pathway, you can see, it says below the big thick red circle, it says, quinone reactive, and then it points to your DNA.

24:06

So, as you move progress along this path, if you are not neutralized somehow, this is where, you become worse and worse of a metabolite and can really affect the DNA.

24:18

So, it is considered much more carcinogenic because they form unstable, so anything unstable is not good, or what are also known as deep urinating adducts, resulting in increased risk of mutation.

24:30

However, I will say that there's some there's mix in some literature around this, and around the adducts, the depurinating adducts that they form, and the risk of breast cancer.

24:42

How absolute is this information?

24:46

But I knowing what I know, just about breast cancer and how we do want to make sure that we are metabolizing, your detoxifying estrogen.

24:55

And I know these are toxic intermediaries.

24:59

I want to make sure that I have them neutralized or redirected as quickly as possible overall to mitigate risk.

25:06

So then, that leads us to our 16 pathway, the 16 hydroxy.

25:10

This uses CYP3A4, CYP 3A4.

25:14

It can also become estriol, so you form 16, and then it can it can form estriol. This loves the estrogen receptor, it binds tightly and has a very high affinity for it. In fact, some literature says that as women enter into menopause, if they have higher levels of 16, as their estradiol is dropping,

25:32

but they have higher levels of 16, they're less likely to develop osteoporosis.

25:37

Why is that? It's because it binds to the estrogen receptor and can be supportive of the bone.

25:43

Obviously, estradiol is where it's at, that's really the big guns, but it's interesting that research says that 16 can be helpful for bone,

25:51

preservation of bone. Fortunately, though, it can be proliferative and can stimulate cell proliferation in someone with breast cancer.

25:59

So, if you have active breast cancer and your 16 is elevated on the DUTCH Test, then it could act like fertilizer or fuel to the fire and make it proliferate even more.

26:10

So, like, everything in about the body, it is a delicate balance.

26:14

So, then, that leads us to phase two. So, we have phase one. So, we're, we're trying to get towards the two pathway.

26:22

Minimize the four pathway, be concerned about the 16 pathway, but really, ultimately, we just want everyone to move through your two and your four. We want them to move through methylation.

26:34

We want them to be essentially neutralized, so to speak.

26:39 Phase 2 metabolite: methylation
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So, on the DUTCH Test, on page three, it looks like this.

26:43

And so, we move from an OH state, which is a hydroxy, go through methylation via the enzyme, COMT or COMT, and we form a methoxy.

26:54

Now, on the DUTCH Test, we are not a genetic test. We are not evaluating your snip of COMT.

27:01

What we are evaluating is your activity of the hydroxy and the ability of it to become a methoxy. What is that ratio?

27:09

And then on the far left-hand side, we let you know if the ratio is low, which is not a good thing, in range or high, how well, based on the end result, do you appear to be methylating?

27:21

If you actually want to know your COMT results, your COMT, you will have to get additional genetic testing for that to see where you are at, but looking at the DUTCH Test, we kind of give you an idea of the active activity of what's going on, the outcomes I could say.

27:39

So, with that, you get the two methoxy.

27:41

We like two methoxy, so you get your two hydroxy or, or four hydroxy, both of them. But on the DUTCH Test, we specifically show you the two hydroxy is methylated.

27:52

Using COMT, COMT stands for catechol-o-methyltransferase. It is basically an assistant that takes methyls and transfers them onto estrogens.

28:05

Where do you get your methyl? You get it from SAM, will also known as a supplement CME with a little E, but you make SAM in your body naturally. So, you take the M off of SAM.

28:16

Using magnesium is a co-factor, and you transfer it to your or two hydroxy estrogen.

28:21

And now, it becomes two methoxy, as seen on the DUTCH Test. You can use zinc as a backup for magnesium.

28:28

So since so many people are magnesium and zinc deficient,  just know that it could be really affecting the way that they methylate using COMT.

28:37

If you have low methylation, if your COMT is slow, if you're missing magnesium or zinc or SAM or any of the other co factors, then what you, what happens is you can head down that naughty Quinones adduct pathway, increasing your risk for DNA mutation, which we're trying to avoid.

28:53

The metabolite two methoxy itself is thought to be anti-proliferative, which is amazing.

28:59

And it's anti proliferative through these microtubule disruption, apoptosis induction, and angiogenesis inhibition.

29:06

So, all the things that cancer cells start to do, the two methoxy can nip that in the bud, and, again, thought to be very helpful. It's considered to have anti aromatase activity. So, you cannot convert your androgens to your estrogens as well.

29:21

Thus, helping to reduce the burden of estrogen going through detox, and it's not thought to bind to the estrogen receptor, much. In fact, most literature that I read about two methoxy says that it doesn't bind to the estrogen receptor, but other a few papers are like, well, maybe. Maybe it does, and we just haven't figured it out yet.

29:38

So, not thought to bind, not like your phase one metabolites, which absolutely bind to the estrogen receptor.

29:46

So, when you're working on estrogen metabolism, again, I'm going to point you the resources, because this is an entire hour-long webinar unto itself.

29:54

If you go back to our education drop-down, you will see what looks like this. This is Doctor Tara Scott, who was doing estrogen metabolism from start to finish.

30:01

So, she will walk you through the different phases on the DUTCH Test. We do look at phase one and phase two.

30:06

Please remember, phase three: detoxification occurs in the, well, in, through the kidney and out the intestines.

30:12

But those of you who are doing stool testing, you want to make sure that you're looking there as well. Make sure they're not constipated. Make sure they don't have any kind of bugs, parasites, critters, inflammation. Make sure they're there, that enzyme, known as beta glucuronidase in normal levels and so that is not seen on the DUTCH Test, that does require some additional stool testing.

30:33

But Doctor Scott goes through that sheet in and a full hour to explain way more in depth phase 1, 2, and 3.

30:40

Highly recommend you watch it. So, you can understand that portion of the DUTCH Test better.

30:45

But some highlights, some highlights of what you will see on there is when, when we all explain it, we all explain it is, in order.

30:51

You go through Phase one, then to Phase two, and then out through Phase three. But, if you think about it, you have to address it in reverse order. If you're constipated, why are you busy working upward in the liver?

31:03

Get her having regular bowel movements. Get her GI tract under control, right?

31:07

Unplug the drain, and then work backwards and into COMT and then work backwards into her Phase one which, which dial she chooses for that, the 2, 4, and the 16.

31:19

So, don't just jump in and give everybody DIM, that's naughty and you know it. You want to start with the intestines and work backwards.

31:26

So, when we're working backwards, you will see in her Webinar where she talks about different co nutrients, I already have just mentioned SAM, Magnesium, I already said zinc can be used as a backup. Feel free to look up the methionine cycle online.

31:39

You will see all the co factors that go into the methionine cycle, moving round and round from the methionine cycles where you have homocysteine, converting into methionine binding into SAM and then back around again.

31:52

And so, by looking at that, by studying that cycle, you will become much better versed on how the body methylates at large, not just with estrogen, which is very important.

32:02

And then of course, like I said, phase one uses your cytochrome P450 enzymes, such as your 1A family your 1B family, your 3A4 family, and then different supplements.

32:12

She will talk about different supplements that help shift those pathways.

32:16

Just be sure, you start with Phase III, and then workgroup self backwards to phase one.

32:22

When I showed you on the DUTCH Test, the red arrow, that pointed to the DNA, and I showed you where it says Quinones on the DUTCH Test. Your body is very intelligent. And on that same red pathway, it puts two stopgaps, one is known as Quinone Reductase (NQ01)

32:38

the other is Glutathione-S-Transferase

32:40

and by supporting those with either glutathione, an acetyl cysteine, which we will talk about, Quinton Reductase can be supported with things like Sulforaphane.

32:49

You also help to move that estrogen along.

32:53 Circadian Rhythm
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So, let's go into cortisol pattern. Circadian rhythm, who knew the circadian rhythm had such a play when it came to breast cancer.

33:00

The typical circadian rhythm, of course, starts with the cortisol awakening response. It goes up like a mountain and then falls gradually throughout the day so that nighttime cortisol should be nice and low. It turns out this does play a big part in immune and cancer.

33:17

So, their Circadian System temporally, not temporarily, but temporally, regulates physiology to maintain homeostasis.

33:26

If you mess it up, disrupting circadian signals appear to be distinct attributes that are functionally important for the development of a tumor, and can enable or give rise to the hallmarks that tumors use to facilitate their initiation, growth, and progression.

33:40

Because circadian signals are also strong regulators of immune cell proliferation, trafficking and exhaustion states, they play a role in how tumor's respond, to immune based cancer therapeutics. So, your cortisol rhythm plays a big role.

33:56

The biggest question we get, our round our shift workers. Everyone talks about shift workers because they are the opposite schedule, as the 9 to 5, they're working the 7  PM to seven AM, they're working through the night.

34:08

So, we love our shift workers.

34:10

They are crucial for making the world go round, but how about shift workers in breast cancer?

34:15

So, the research leans towards having them have a higher risk for breast cancer development. It's not absolute.

34:22

There's some research says no. Some research says yes, but more research says yes. So that's why he said it leans towards

34:28

having higher risk for breast cancer development due to circadian rhythm dysfunction.

34:33

The International Agency for Research on Cancer has listed shiftwork as a possible carcinogen.

34:39

Now, unfortunately, when it comes to shift work, what I don't know is if you are an all the time shift worker, for example, you are shift worker Monday through Friday or Monday through Saturday. And so, most of your life is spent in a shift work, as opposed to lot of shift workers are like 3 or 4 days on, and then maybe have 10 days off. So, they are 3 or 4 days in a nighttime schedule, and then they get a lot asleep and they flip back to a daytime schedule until they have to go back to work again.

35:07

I don't know the difference in risk between some shift work or all the time shift work, or if it matters, does it?

35:16

Does even a little bit of shift work mess you up?

35:19

I don't, I don't have the answer for that, unfortunately, still to be studied.

35:25

So, what about the slope of the cortisol curve? What if you're like, well, I'm not shift work. Carrie, I work 9 to 5, 8 to 6. You know, that's not me.

35:32

Well, it turns out your daytime slope of cortisol plays a big role as well.

35:38

So, way back, I learned about this a while ago, so way back in 2004, this article said we have allostatic load, which we know about stress.

35:45

The static load, the physiological accumulation of the effects of chronic stressors has been associated with multiple adverse health outcomes.

35:53

A flattened diurnal cortisol rhythmicity is one of these, one of the prototypes of allostatic load, and has been shown to predict shorter survival among women with metastatic breast cancer.

36:05

So, while a flat curve may not increase your risk for breast cancer, if you are actively being treated for metastatic cancer, knowing what your cortisol curve is, could be helpful for survival, which is amazing, because we want you to survive as long as possible.

36:25

Fast forward to 2020, this article came out, elevated salivary cortisol as a single stress marker - or elevated – evening, but elevated, evening salivary cortisol as a single stress marker in women with metastatic breast cancer.

36:39

So, what they say in the conclusion is evening cortisol levels are a sensitive indicator

36:44

flatten diurnal cortisol slopes suggesting evening cortisol, may also be a useful predictor of breast cancer survival.

36:50

So, it's not only your slope in general, can you, can you rise or not?

36:55

But what if your nighttime cortisol is inching up,

37:00

then that's by default going to flatten your curve. And it's going to unfortunately shorten your survival.

37:07

So, this is a female. In her fifties, she doesn't have elevated cortisol, she doesn't have the rise in the morning, she is the red line, she is supposed to be in-between the black, solid line, She's not.

37:19

So, she's, her waking point is low or on the border,

37:22

her morning point is low, and then she's kind of has this flat line through the day, but she's rising as the nighttime hit.

37:28

She's starting to rise, which is of course, making her slope look even flatter.

37:33

So, this is concerning, if she had metastatic breast cancer, I would want to be working with her on her circadian rhythm, to get her morning up and her nighttime down to, hopefully cross fingers, improve her survival.

37:47

But what about high cortisol? Like, what if it's not a shift worker and what if it's not a flat curve?

37:51

What if they're just high cortisol, the time we know cortisol, chronically elevated cortisol can be damaging to tissue, right.

37:59

High cortisol is helpful, acutely, in stress response, in glucose, in inflammation.

38:06

But what if it's kind of all the time? You're on this chronic high cortisol picture as shown on these pictures, where the red or the blue line is now above the reference range, which, above the black lines, what does that mean?

38:19

So, it turns out, some tumor mets have an increased number of glucocorticoid receptors, and the glucocorticoid receptor of course, is the home for the goal for cortisol. That's where it binds.

38:29

So, when you have a lot of cortisol, it stimulates these glucocorticoid receptors.

38:33

So, now you have these the increases colonization heterogenous heterogeneity of the cancer leading to short and survival of someone with cancer.

38:43

So again, it's about survival.

38:44

So, if you have a flattened curve, an elevated cortisol point, if you're chronically elevated cortisol, it's survival, so we, if you're working with oncology patients, take their cortisol into consideration. Much like Goldilocks, it has to be just right.

39:01

Do you want them to go up normally in the morning with the cortisol awakening response, gradually fall through the rest of the day, and by improving the circadian rhythm, again, back on the DUTCHTest.com website, we have a number of webinars about the cortisol awakening response, about cortisol in general.

39:18 Improving the circadian rhythm
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And what I have here is just the real basics around re-establishing the circadian rhythm. So, you want to work with them on the stress response,

39:26

however that looks. They have cancer, they're working through cancer. So hopefully, they have a number of outlets that you are working with them, or pointing them in the right direction on how they work with that.

39:36

And then you're going to use light to your advantage, light and dark are clock

39:40

genes, our clock genes that are the genes in our brain that set our circadian rhythm and reset a dysfunctional rhythm, rely on light and dark at appropriate timing.

39:52

So, full spectrum light on waking. Make sure you go outside, open a window, you know, opened the door and get that full spectrum light. If you wake up and it's still dark, feel free to buy yourself an inexpensive, full spectrum light box, put it on your counter and you know, get some exposure in the morning.

40:10

Some people have them on their desk and they'll turn them on while they're working to help get them a little more energy and oomph in the morning for that cortisol to go up.

40:20

The CAR does rise.

40:21

The cortisol awakening response does rise in about the first 30 to 45 minutes of waking.

40:26

So, if you're working with them on morning supplementation, consider timing, consider the timing of their supplements to be within about 30 minutes of waking.

40:35

Don't have them eat breakfast, take a shower, do this, do that. And suddenly it's 2 or 3 hours later and you're like, Oh I forgot to take my morning supplements.

40:43

Try to take them within 30 minutes of waking so you can follow the pattern of the CAR.

40:48

Having said that, I fully understand those of you who are on thyroid medication or your patients who are taking thyroid medication in the morning. We all know thyroid is a diva. She's extremely high maintenance. She likes to be the only thing in your stomach by a good solid while, otherwise she won't absorb properly.

41:03

So, just do the best that you can.

41:05

If you have somebody your patient or client is taking thyroid in the morning and you cannot give them these supplements for an hour or two hours, that's fine. Use the light and just do the best that you can.

41:16

If they're not on thyroid, or maybe they take their thyroid at night, or they take it in the middle of the night for some reason, then you can do the supplements on waking. Minimizing blue and white light exposure in the evening.

41:28

We know that blue and white light was what helps trigger the melanopsin in our retina, so that we suppress melatonin and keep us awake. So, we want, that's great in the morning, not great before we go to bed.

41:39

Consider wearing blue light blocking glasses in the evening as you wind down. Sleeping in complete darkness.

41:44

Consider a sleep mask, check to see nightlights, blinking lights, lights through the window,

41:51

consider getting blackout curtains to help because darkness is what resets a dysfunctional circadian rhythm with those clock genes. So, light sets it.

42:00

Darkness resets it. And light and dark are free, cheap and easy, so use them to your advantage.

42:06

Getting exposure to sunset light, if you can, that reddish orange, sunset light, helps with triggering,

42:13

you know, sleep will be within a few hours. Melatonin should start to come out. Obviously, it's not possible all the time.

42:19

But there is some research on it so I wanted to include that in here for those who can. Avoiding caffeine and alcohol before bed, evaluating melatonin, which we're about to talk about.

42:28

And considering calming herbs and nutrients and amino acids before bed, Again, talking about the circadian rhythm is a whole multi hour long lecture, but I want to just give you some key takeaways.

42:41

And then you can search on the DUTCH Test website, under education, and see those webinars to learn more.

42:47 Melatonin
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So, let's talk about melatonin. Melatonin by far is my most favorite antioxidant. This is how melatonin is made.

42:54

It is predominantly made in the gut in the enterochromaffin cells. But of course, it's the pineal gland.

43:00

That is what really helps us with our sleep, our sleep-wake cycle. So, in our gut we have the Shikimate pathway from our bacteria, they make us some tryptophan, thank you very much.

43:10

We take tryptophan and run with it. We take tryptophan and convert it into 5-HTP,

43:15

then into serotonin, then into N-acetylserotonin, then into Melatonin.

43:19

On the left-hand side, by tryptophan, you can see I have E2 in a little box, I added that, estradiol has to be like Goldilocks too little, like a menopausal state,

43:31

or too much, like an estrogen excess state, will deflect change shift this pathway and then you won't get as much serotonin, and you won't get as much melatonin.

43:41

So, you have to pay attention and go back to number one, pay attention to that estradiol, because if it's high or low, it's going to affect the way you make

43:49

Serotonin, the very first step, the way you get from tryptophan to 5-HTP.

43:53

But you can also see, I think it's on my next slide, in a couple of slides.

43:59

I'll show you the SNPs that make melatonin Although they are there on here, serotonin to N-acetylserotonin, and then, acetylmelatonin is ASMT, so if those of you who are doing testing, you can see what their SNPs are there as well. So, this melatonin becomes 6 Hydroxy Melatonin Sulfate, which is then urinated out and we pick it up on the DUTCH Test.

44:19

And so, melatonin facts is it's old, billions, several billion years ago, billions old, it's had a lot of happy birthdays.

44:26

We have speculated that melatonin is phylogenetically the oldest antioxidant in existence, and it is major part of the circadian rhythm. Circulating levels are primarily made out of the gut, but also the pineal gland. Which is what we all we pick up on the DUTCH Test, and adults tend to make about zero point five milligrams a day, physiologically.

44:47

Yes, there are supplements out there that are one milligram, three milligrams, 10 milligrams, 20 milligrams, humans tend to make less than a milligram a day.

44:57

So, be aware.

44:58

If you are supplementing them physiologically or supra, over physiologically, you can make a big difference. When it comes to oncology,

45:08

a lot of integrative oncologists will use the really high doses because of the cancer, the antioxidant, anti-cancer effect,

45:15

but please make sure you don't just randomly put yourself on 10 or 20 milligrams of melatonin without working with somebody who knows what they're doing.

45:22

Melatonin is heavily concentrated in the mitochondria. It is now accepted that the mitochondria make their own melatonin, all of them.

45:29

But it's primarily in the cell, it's intercurrent, it doesn't seem to contribute much to the circulating levels. But how cool that are mitochondria are like you?

45:38

I need you to help me put out reactive oxygen species to quench them, to quelch them.

45:44

So, let's go ahead and make melatonin right here and set up our little melatonin factories to help me write within the cell. And it acts as a direct free, radical scavenger.

45:53

As shown on this picture here, if you have high levels, or normal, good levels of melatonin, it acts as a scavenger to help improve, or reduce, the reactive free radicals, the reactive oxygen species.

46:08

It also increases one of your SRT2 and SRT3, which then increases superoxide dismutase, which is a very important antioxidant in your mitochondria as well. So, it all in all melatonin does a lot. And in fact, it has this thing that I, they call it the antioxidant crew.

46:25

So, if you remember, or if you picture those Russian dolls, where it's a big doll, and you take off the part, and there's a little doll, and you take off, and there's a little doll. Melatonin does the same thing, but it's attacking free radicals, it will grab free radical and neutralize it, and then it will presto change into something else,

46:42

and that's something else, that metabolite of melatonin can grab another free radical. It can become a different melatonin metabolite that can grab another free radical.

46:50

So, one molecule, one hormone of melatonin can actually neutralize several free radicals. Versus, like, it does its job, and then has to get, you know, go through redox again.

47:03

It doesn't. It can do multiple times before it's done.

47:07

And I think that's really intelligent of melatonin, but it's had several billion years to figure this out, so go melatonin.

47:14

Research in animal and human models have shown that that light, the light at night, induce disruption of the circadian nocturnal melatonin signal, promotes growth metabolism, and signaling of human breast cancer, and drives breast tumors to endocrine and chemotherapeutic resistance.

47:31

So, when you're working with your clients, make sure that you are evaluating the melatonin on the DUTCH Test and working with them on their sleep hygiene habits.

47:39

Different mechanisms of melatonin's anti-cancer effects were identified successfully, such as inducing apoptosis.

47:45

It's anti-estrogenic through the estrogen receptor signaling pathway and inhibiting aromatase activity modulation of melatonin receptors, because you have a few, and inhibition on invasion and angiogenesis.

47:56

So, it's really quite multi-talented what melatonin does.

48:00

This is why I like melatonin more than glutathione because I mean, I like glutathione, which we'll talk about in one second.

48:07

But melatonin's billions of years old, so I just think it's the queen.

48:11

And lastly about melatonin, they're now doing a lot more research on melatonin and the gut microbiota as it relates to a regulatory agent.

48:18

And so, and this was in cancers, and I, I'm so glad to hear that, because it's primarily made in the gut, we talk about the pineal gland.

48:27

But in as part of all of the research about the microbiome they are now studying melatonin, the gut, in breast cancer, which I love.

48:36

What suppresses melatonin, the typical things you expect: caffeine, tobacco, alcohol, white and blue light exposure at night, variants in SNPs, which I mentioned, and certain medications, beta blockers and NSAIDS, especially at night, will suppress melatonin. So, be aware of those.

48:52

How do you increase melatonin?

48:54

Obviously, see the prior slide, what we just said, improve the circadian rhythm, improving gut health.

49:00

You might want to check them for their SNP's, if they have the problem with melatonin, and they may need to supplement with melatonin.

49:06

And, as I said, physiologic is less than a milligram at zero point five milligrams, and oncology, they tend to use a lot higher doses for specific reasons.

49:14

There are foods with melatonin in them, such as pistachios and tart cherries that can actually have a couple milligrams of melatonin in them when you eat them.

49:25 Pyroglutamate and Glutathione
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So, let's go onto pyroglutamate, glutathione, pyroglutamate is pyroglutamic acid. It's also known as 5-Oxoproline.

49:33

Same, same, it is the metabolite in the glutathione cycle, it shows up like this on the DUTCH Test as pyroglutamate.

49:40

It may be deficient just of glutathione if this marker is high or low. Why is that?

49:46

Here's the cycle you can see on the bottom sort of leftish, it says 5-Oxoproline which is pyroglutamate.

49:53

So, if you cannot get around the cycle of glutathione

49:55

is low, then 5-Oxoproline will build up and be elevated on the DUTCH Test.

50:00

On the flip side, if you can't, if you can't keep going around the other side, it could be low than 5-Oxoproline might be low on the DUTCH Test.

50:07

So, either way, high or low suspect a glutathione issue.

50:12

So, how does glutathione work? What does it do, why is it so cool? So, you take glutathione.

50:16

You make it with B6, glutamate, cysteine, and glycine.

50:20

That gives you your reduced glutathione, your GSH.

50:24

There are eight types of glutathione. Five of them rely on selenium, is a co-factor.

50:30

So, you take Selenium and reduce glutathione.

50:33

You convert hydrogen peroxide, which is a naughty free radical, into water, which is neutral and great. And now you were known as oxidized glutathione, but you have to go back around the circle again so you take FAD from vitamin B2.

50:48

And now you're reduced glutathione again. So, majority of the glutathione types you selenium and then everyone uses FAD from Vitamin B2.

50:56

Along, with NADPH, E3, to get back around again. So, you can see where these nutrients, these co nutrients are so important for glutathione so may actually have nothing to do with glutathione.

51:06

It may be a nutrient deficiency, which is to why your marker on the DUTCH Test is low or high. So, reactive oxygen species I mentioned hydrogen peroxide, I've mentioned before as it relates to melatonin. Are they all bad? It's a balance. They form from normal bodily functions too like eating, digesting, exercising, creating ATP.

51:28

Reactive oxygen species do act as a signaling molecule to the immune system, but they can be toxic to tumors, which is, you know, controversial.

51:35

Do you want the reactive oxygen species helping the tumor, being toxic to the tumor, or is the excessive reactive oxygen species creating gas for the tumor.

51:46

So, it's controversial, depending on where you are in the literature, but with breast cancer, since that's what we're talking about today, oxidative stress change the redox potential of the breast tissue.

51:58

This leads to a drastic change in DNA base lesion's, which we don't want, which are conducive to oxidative conditions and breast cancer formation.

52:06

So, when it comes to breast cancer, this goes a lot, especially with the chemicals, these reactive oxygen species.

52:13

So, glutathione is low.

52:15

This can cause your reactive oxygen species to become out of balance, and with unbalance, now you can lead to cancer development.

52:23

And so that's what we're trying to avoid, is the progression in the breast tissue to cancer development.

52:32

There's also these advanced glycation end products. We hear about these all the time with diabetes, these glycation end products and what they do with diabetes, but turns out they play a role in breast cancer too. And glutathione can affect them.

52:44

So, proteins and lipids or fats, they go through glycation when exposed to sugars. As they advance, they are associated with more inflammation,

52:54

oxidative stress, and disease development.

52:56

Again, like I said, diabetes is a big one, uncontrolled diabetes, and the outcomes of that, but research shows it's their increased, ages are increased and associated with breast cancer.

53:08

One of the things that can be helpful is glutathione. It reduces the ages effect on the body. Now, can this also be helpful for damaging diabetes effect?

53:17

Yes, but we're talking about breast cancer, so it can be, glutathione could be really helpful here, especially if you have that diabetic person,

53:26

and you're concerned about their risk for breast cancer, or they're actively getting worked out for breast cancer.

53:32

So how do you improve glutathione?

53:34

Obviously, you address the cause, what's causing all the glutathione to get used, increase the precursors like N-Acetyle-Cysteine, known as NAC,

53:43

and vitamin B6, increase the co factors like selenium and B2, and then increase other antioxidants that help recycle glutathione like ascorbic acid and Vitamin C.

53:54

They help glutathione, they act like cogs and a clock.

53:58

They all turn when they get reduced and go back around again.

54:02

So that they work in unison, they all help each other recycle so they can continue to affect other reactive oxygen species.

54:13 8-OHdG
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Finally, in the last couple of minutes, that leaves us with 8-OHdG, eight-hydroxy-2-deoxyguanosine.

54:21

When it's elevated, we have a problem.

54:25

So, it's a sensitive, but not reason specific, marker used for estimating DNA damage due to oxidative stress, reactive oxygen species creation.

54:35

So, the higher this is, you have DNA damage. I just don't know why, but it's not good. It's considered pro-mutagenic, as it's a biomarker for various cancers and degenerative disease initiation and promotion.

54:47

And it's used to estimate, DNA damage after exposure to cancer causing agents, tobacco smoke, asbestos, heavy metals, benzine, radon, et cetera, et cetera.

54:57

So, the more you have this chemical, environmental type exposure, then the more DNA damage you can have, and this marker could go up.

55:05

So, what is it?

55:06

Well, it turns out, when your local antioxidant system fails, the oxidative damage permanently occurs to lipids of cellular membranes, proteins, and DNA.

55:17

So, the reactive oxygen species attacks the guanine bases easily forming this 9-OHdG. So, 8-OHdG binds to thymidine, so you get this G to T transversion, which is not good, we don't want this.

55:28

It's the most frequent somatic mutation. We don't want somatic mutations. We don't want mutations in general.

55:34

So, they get removed by the DNA repair mechanism, it gets released, and it shows up in the urine.

55:40

So, know that this whole tricky cascade of events is happening in your DNA to form 8-OHdG in the first place.

55:48

And if you're a picture person like me, I found this to be really helpful. You want a balance between oxidative stress and antioxidants, hence smiley face. This is not my picture, but I love authors

55:58

who put super simple pictures in like this.

56:01

If you get a burden of things like smoke, UV radiation, heavy metals, pollution, et cetera, they win over the antioxidants, frowny face.

56:11

This leads to the conversion of 8-OHdG due to DNA damage.

56:15

And the one thing I want to point out here is the author's emphasis on environmental and lifestyle factors, not estrogen, not estrogen.

56:24

So, while estrogen gets a bad rap for everything related to breast cancer, you have to, have to, have to remember, environmental and lifestyle play a massive, major role when it comes to cancer development, DNA damage.

56:38

The last thing in this study that I wanted to show, this was a 2018 study.

56:42

We concluded that a significant, significant increase in serum levels of 8-OHdG in patients with breast cancer can be used as a potential noninvasive biomarker for the early detection of breast cancer.

56:55

But I do want to say not everybody with high 8-OHdG has cancer. So please don't think if yours is elevated,

57:02

OMG I have cancer, do your due diligence, workup. You know, make sure that you've had imaging if you need imaging.

57:09

I did a consult yesterday on a woman, who was in her early fifties. She'd been on unopposed estrogen for a long time,

57:15

unfortunately, and her 8-OHdG was elevated. And so, I was like, she's been on an unopposed estrogen.

57:23

When was the last time she had any kind of breast imaging, when’s she had a mammogram, like, let's get some, when she had a colonoscopy, like, let's get some bases done here.

57:30

She is early fifties and I want to make sure that the 8-OHdG is not cancer related, but it could be, it could be. So, hopefully she is going to get worked up.

57:42

So, improving 8-OHdG, addressing the cause as best you can, try to figure out: is it chemical exposure, right? What is, could it be cancer? What's happening?

57:50

Is it a diet that's lacking in antioxidants?

57:52

Is it, you know, medications that are affecting, is that severe insomnia? Do they have low melatonin on this,

58:00

on the DUTCH Test, low glutathione on the DUTCH Test, use breast imaging if warranted or needed, evaluate for antioxidants because that's what's going to quench or quelch, improve, the status of those free radicals, reactive oxygen species, and then look at their diet, look at their supplementation, consider testing and see what's going on.

58:23

So, in summary, breast cancer is complicated. Please don't just blame estrogen.

58:28

The two biggest risk factors are being female and aging, however, as I said in the very beginning, is an unfortunate combination of genetics, hormones, lifestyle, and environmental factors, don't just blame estrogen. When they have a lot of environmental or lifestyle issues that are causing free radicals, reactive oxygen species, inflammation, DNA damage, it's completing their antioxidants and it's completely just throwing off the system, and the breast tissue responds with mutations.

58:56

So, prevention and risk reduction are the goals. And as part of your prevention toolbox, use the DUTCH Test and look at these seven markers. And just remember, just because one marker might be off, doesn't automatically mean breast cancer.

59:10

But, if you've got several of these markers that are off, then you really want to act fast, because, again, prevention and risk reduction are our goals.

59:19

And, that concludes our talk, I really appreciate you guys listening, and I am happy to answer questions. But hopefully, by having pointed you in the different resources. Like Dr. Saltiel’s talk on menopausal hormone therapy, Dr. Scott's on estrogen metabolism, all of our lectures on cortisol, then you will have a much broader, better foundation around the DUTCH Test in cancer.

59:44

This was just the intro into the seven markers and what you're looking for and why, and as Tim said in the beginning, if you are a new provider listening to this, we do have a special where you can get 50% off up to

59:59

five DUTCH kits, when you order for the first time. And if you are a current provider, we do have exclusive access to a provider networking Facebook group.

1:04:08

You can click the link in the chat that marketing has supplied.

1:00:13 Q&A
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So, I am happy to, I'm happy to answer questions in the time allotted.

1:00:19

Thank you so much, Dr. Jones. This has been fantastic.

1:00:23

I really enjoy how dedicated you are to equipping other providers to protect their patients through education and so much more, and how your team does a fantastic job of

1:00:35

walking every new provider and experienced provider through learning how to use the DUTCH Test for, you know, patients that may have potential risks of breast cancer and other types of issues they may face.

1:00:50

So, from what I understand, you know, providers can call in, let's say that they're concerned about a patient, and you and your team will walk them through how to use DUTCH because there's a lot that you talked about today, right?

1:01:07

You can walk them through where to start, how to get going, kind of how to get out the gates, correct? How to understand, yes.

1:01:16

When you, when you have a DUTCH account, and you've run a DUTCH Test on someone, and you have questions around how to read the test, how to understand the test,

1:01:27

that's when it's great to call my clinical consulting team for DUTCH, who can help you walk through all of the markers, not just the seven that I talked about today, but on all of the markers on the DUTCH Test to better understand what's going on with your patient.

1:01:40

That's fantastic. OK, I have a lot of questions. But let's see how many we can get through here. Yes.

1:01:47

First question: How accurate is the DUTCH Test in menopausal women not on MRT with low estrogen levels? So, we are really very accurate. So, well, honestly, that depends on how much estrogen or progesterone or testosterone she has. So, on estrogen progesterone.

1:02:06

We have specific post-menopausal reference ranges that are low. They're meant to be low.

1:02:12

Because, in post-menopause, you have low compared to somebody who is in the luteal phase.

1:02:18

So, if she is post-menopausal then likely, it will show up, you know, around somewhere in the post-menopausal range, which is really important on the DUTCH Test. We use, like I said earlier, we use mass spec when we're testing because the post-menopausal range, and the luteal range should be very distinct. There should not be any overlap. Like the high-end of menopause should not be the low end of the luteal range.

1:02:40

That's not how it works in females in their production of hormones.

1:02:44

Once they cross into menopause, there is a distinct gap of where estrogen and progesterone are and so it's great on the DUTCH dials.

1:02:53

When I showed at the beginning, you will see the results are, so in-between the star on the DUTCH dial, or the luteal range, and then the purple, there's a little purple box, and it says post-menopausal range.

1:03:05

That is clear and distinct.

1:03:07

So, if she's menopausal, and if she's not on HRT, absolutely feel free to do the DUTCH Test, we do them all the time. All the time on menopausal women not on HRT.

1:03:19

When should a providers start looking at a patient, say they have a younger patient, do you have an age range that you like to start

1:03:31

looking for potential risk factors using the DUTCH Test, or yeah, just in general? So, I would so when I was in practice, I had a lot of women that were like,

1:03:39

I just want to know my hormones, I just want to know a baseline, and so I find, and several of my colleagues that I've talked to find that, you know, starting maybe starting at 20 years old, like just having a baseline. Where are you? And if they're like, I'm not really symptomatic. I'm feeling pretty good.

1:03:55

I just want to know, like, just do a baseline at some point 20, 25, somewhere in there,

1:04:00

if they come to you that young, then they may not need it every year, but every couple of years or as things are going on, but to have that baseline, that can be really, really helpful as you watch them progress through their twenties, into their thirties, into their forties, what have you?

1:04:15

They have that information about themselves versus somebody who comes in, maybe in their forties or fifties or sixties and they get testing done, they get a DUTCH Test done. They've never had any kind of hormonal work done. They don't know what their baseline is, they don't know if that marker is going up, going down. If that's their normal, because this is their first exposure or experience with any kind of hormone testing. So, I do wish,

1:04:37

and the same for cortisol, it's not just the sex hormones.

1:04:40

So, I do wish that we are taught to try to find, to do baseline testing, and at a younger age, so that we can track it.

1:04:49

So, we can track and see what's going on.

1:04:51

Yeah, that totally makes sense.

1:04:52

How often should a provider check patients with the DUTCH Tests when they, when they move into that higher risk age bracket?

1:05:00

What do you recommend? Then it's going to 100% depend on the person in front of you. So, if they, and their symptoms. So, let's say they feel terrible. They're going through menopause; they have a lot of the symptoms.

1:05:11

You test them. You may find that, initially, you have to test them a little more often.

1:05:16

Maybe you put them on a whole protocol plan. Maybe you do menopausal hormone therapy, maybe, you don't.

1:05:22

So, you may find you test them, four months later, to see where they're at, because you're actually putting them on a protocol, and you want to see what's happening. Eventually, you may find, is that you're dialing it in, they're feeling really good.

1:05:35

You've got the risks dialed in as best that you can. You may find they move to a yearly plan, that you, you've got them on, some sort of therapy.

1:05:43

You're just going to check in with them yearly to make sure, you know, like, they're good, you're good. Everyone's happy with the results of where they're at. So, nothing is set in stone. And I just, it depends on the person in front of you.

1:05:54

But if you do have them on any kind of hormonal therapy, then you will have to do, don’t just put them on therapy.

1:05:59

Let them fly to the wind, and you know, best of luck. Don't do that. Keep an eye on them at least yearly at that point. Okay, at least annually. Thank you so much, how about all the markers on the DUTCH Test, or all the markers to watch for breast cancer. Are those included in the DUTCH Tests? Are there other types of testing that you do, along with the DUTCH Test, to

1:06:22

have kind of the whole, like, the whole gamut of things that could possibly appear?

1:06:31

So, all the markers obviously, everything we talked about is on the DUTCH Test, if you do a DUTCH Complete or a DUTCH Plus, then you will get all of those markers. So, other markers I run it, again, it depends on the person in front of me, and so if I'm running thyroid, know that I'm looking at blood markers, serum, if I'm running glucose and insulin, then I'm doing a serum. If I'm doing additional GI testing, then I'm looking at stool testing,

1:06:56

stool collection.

1:06:57

If I'm sending them for breast imaging, then head off to an imaging center.

1:07:03

And so, it kind of depends on their history, their symptoms, and, of course, what's going on, what they're going through, the person in front of me.

1:07:14

So, I don't actually have a, every woman who hits 50 should run, you know, all of these markers, because maybe not everybody needs a GI test,

1:07:22

like maybe somebody in front of me like just had a mammogram last year so they don't need it,

1:07:27

you know, or six months ago, where, you know, they don't need it right at that moment because they're within their range.

1:07:32

Maybe they just had glucose and insulin tested couple of months ago, and all was good, and I'm not concerned about that, and this is around breast cancer.

1:07:40

This is, there are other obviously, as women, like, head into menopause, and you will hear this on Dr. Saltiel’s

1:07:47

webinars, where she talks about all the cardiovascular risk, cardiovascular disease, and she has a whole list of cardiovascular workup that she encourages and prefers.

1:07:58

And so, I suggest watching her webinars.

1:08:01

You can see those markers as it relates to aging because that's important to the woman in front of you.

1:08:09

Absolutely.

1:08:10

You talked about the shift workers right? And it's a big population out there that they work when we sleep.

1:08:18

So, how long after a shift worker, you know, stops, maybe they move from night shift to day shift.

1:08:27

Can you rebalance the circadian rhythm or is it is the damage already done?

1:08:31

How do you get someone back to a good place? No, I think the circadian rhythm is very malleable.

1:08:38

Thankfully, our bodies are resilient and so, there are shift workers that are able to make the switch very easily, and there are other shift workers that it just takes time because of neuroplasticity and their brain.

1:08:49

They've now become accustomed to being up at night and not in the day, so you're going to have to work with them about flipping their circadian rhythm and doing the things in the morning that they would normally do at night. And, you know, using light exposure in the morning that they would normally try to turn on and work through at night. So, if somebody was a shift worker and they're switching off, it's thankfully, it's all in that slide of how to get the Circadian Rhythm back.

1:09:13

Then it's using those and watching some of our webinars, but I find the Circadian Rhythm is,

1:09:20

what's a good word, bounce-back-able? I don't find that it's permanent. I don't find I can take time, it can take time, but I don't, I don't think it's always and forever. Once a shift worker, always a shift worker.

1:09:33

I don't think that.

1:09:36

Well, I loved all the information that you and the guidelines that you provided wit, how people can stay healthy and the value of sleep and melatonin. We have a question here on melatonin. It says, what dosage of melatonin

1:09:48

from a supplement is the best to start with the patient?

1:09:53

I would, it depends on the person in front of you, but I would suggest starting with physiologic, start, I start personally, I start with zero point five.

1:10:01

So, I start with less than a milligram and work up from there if I need to, I don't jump into the 1-3-5 milligram

1:10:09

right away.

1:10:10

I do know practitioners who do that and for some people, that works great and it's super successful, or they're taking 1, 3 or 5 milligrams and they sleep like a baby, and they feel amazing. Fantastic.

1:10:20

But the question is where do I start? I generally start low because I know physiologically what the humans make.

1:10:25

And then go up from there if I need to.

1:10:27

Yeah. I really like how Dr. Saltiel says, start low, go slow, and that probably applies not only to hormones, but also to supplementation.

1:10:36

Yes, and with melatonin, you know, some of the biggest side effects in melatonin people will get a paradoxical reaction. So, they'll start with three milligrams and they'll get crazy, vivid dreams, so that they can't sleep at all. And then they’ll be exhausted in the morning and they're like, melatonin's crap, it doesn't work for me.

1:10:50

I'm like, well, you took three milligrams. And the physiologic dose is zero point five. Well, maybe we dial it back.

1:10:57

So, can you help our listeners?

1:11:01

How did you think about giving your patients melatonin to treat breast cancer, because melatonin really helps with, it's an antioxidant, right? It’s helping. So, can you tie those two together?

1:11:20

Yeah, well, so I'll be honest, so, I'm not an oncologist. I'm not even a naturopathic oncologist. I'm not, I'm board certified in naturopathic endocrinology, not oncology.

1:11:28

And so, anything around melatonin, melatonin use, and breast cancer, I deflect and defer to my oncology colleagues.

1:11:36

But, when you, there are a number of integrative cancer centers, like the Cancer Treatment Centers of America and other wonderful Integrative Oncologists that I know that use melatonin when it's appropriate with their breast cancer patients.

1:11:52

But I personally don't have, I don't do it, because I send my breast cancer patients to them to get expert workup.

1:12:00

Yeah, that makes total sense, but there's great research on our webinar on melatonin and breast cancer.

1:12:07

Absolutely.

1:12:08

How about, can the DUTCH Test be beneficial if a woman is taking hormone replacement therapy following breast cancer treatment or a mastectomy?

1:12:22

So, hormone replacement therapy and breast cancer treatment are usually very different. So yes, absolutely on hormone replacement therapy.

1:12:31

There are a few caveats with that, that on our website we have some great resources to help guide you through that, but yeah, absolutely if you're on

1:12:39

MHT, Menopausal Hormone Therapy,

1:12:43

you can use the DUTCH Test. If you were on breast cancer therapy, though, this is where it gets tricky. And this is where, as an oncologist, we go like, well, what are you looking for? Are you looking to see? Like maybe they're in-between chemo sessions, and they want to see what their phase one and phase two estrogen is doing. Maybe we're beyond, they just finished chemo,

1:13:03

and now they're on an aromatase inhibitor, right? They’re on the estrogen suppressive, anti-aromatase type of medication and they want to see, is it working? And what is phase one and phase two doing?

1:13:17

So, we do have breast cancer patients, usually they are newly finished with treatment.

1:13:25

Or they have a history of breast cancer, and they're trying to do what they can to prevent re-occurrence, who do the test? But actively in the middle of chemo or radiation we…

1:13:39

Most, they have other stuff going on there and they don't tend to do the test at that time. They tend to do it

1:13:46

later. I'm not saying you can't, we just historically don't have that.

1:13:50

So usually, it's after the fact, that makes sense.

1:13:55

There's a definitely a big group of our listeners that come to us from the UK and I don't believe they can prescribe melatonin there.

1:14:04

So, what do you, what do you recommend for other ways?

1:14:09

So obviously, it's doing things like all the lifestyle stuff to try to help their body make their own melatonin. The problem gets into as we age, we make less melatonin,

1:14:20

and if you happen to have a variant in either of the SNPs that move you into the production of melatonin, then it's going to be a real struggle no matter what you do.

1:14:35

I’m trying to think what my UK friends do when they're trying to get melatonin back when they could travel, they were like, I love coming to the US because I can get melatonin. But, if you're a patient, unfortunately, you either have to find somebody who can prescribe. If your GP will prescribe it for you, has prescribing rights, and obviously working on sleep hygiene is one of the best bets.

1:14:56

And then there's you know, there's the foods, tart cherry and pistachio, there's a whole list of foods that do have some melatonin in them to help sort of circumvent this the situation.

1:15:09

And when you look at the, you know, things like 5-HTP.

1:15:15

When you're looking at the cascade of how melatonin is made, sometimes doing 5- HTP might be helpful. Just be very careful though. I mean 5- HTP, when you when you make 5- HTP, and then when you're making dopamine, which is different pathway, but they use the same enzyme, is part of their conversion.

1:15:33

So, if you're if you're 5- HTP heavy, you could actually end up depleting the enzyme that makes dopamine and now you’re dopamine light.

1:15:40

So, everything's a balance. Nothing works in a silo.

1:15:44

But I have seen some people temporarily use some 5- HTP to hope it will help go downstream to melatonin.

1:15:52

Interesting. Very interesting.

1:15:54

This is a little bit more technical question about melatonin.

1:15:57

But physiological melatonin is zero point five milligrams, but the gut destroys a lot of it. So, what do you know?

1:16:09

What dose approximates zero point five milligrams given?

1:16:16

Not been studied. I have no idea.

1:16:19

I have no idea.

1:16:21

Unfortunately, yeah, there's no, nobody's putting money towards how much gets to… And remember, everybody's first pass is different. Everybody's gut is different. So, some people may destroy it a whole lot more.

1:16:31

Some people's first pass may be more effective than others, and so it's not that simple to say oh, three milligrams is the equivalent of zero point five in the body.

1:16:42

It doesn't work that way unfortunately, so that hasn't been studied.

1:16:46

Yeah, yeah, it's a good question. It's a good question.

1:16:49

But, if you think about your really gut inflamed folks, right? They’re going to be different than somebody who has gone through an entire process, cleaned up their gut,

1:17:01

And are much healthier, or liver, right?

1:17:06

Their first pass is very effective versus somebody else who has maybe fatty liver disease in their liver is just not that effective at first pass, OK? It'll be different. Yup.

1:17:16

You talked a little bit about different pathways.

1:17:21

Does the 16-OH-E1 and E3 conversions,

1:17:26

are those bidirectional or how do you?

1:17:29

So gosh, that's such a great question. It is predominantly towards estriol, it's the much better, bigger, edgy arrow in research shows that the 16 Hydroxy heads towards estriol. The reason we have it is like a small bidirectional, is, I believe, the owner and founder Mark Newman has

1:17:45

a paper, has a few papers where it's seems to go back.

1:17:50

Estriol can make the 16, but the large majority of it goes towards estriol, so it's not equal back and forth, like a fun tollgate. It doesn't work that way.

1:18:02

Then, how do you, how do you think about lowering 16-OH?

1:18:08

I think it's important to lower 16-OH, except remember nothing works in a silo.

1:18:15

So, if you are taking, if you're trying to slow down CYP3A4, CYP3A4 is your biggest mover and detoxifying pathway in your body, it's not just exclusive to estrogen. It's literally handling chemicals and other hormones, and medications and everything.

1:18:35

So, if you take something to slow it down, you're going to slow down the detoxification of everything.

1:18:42

Please, always keep that in mind.  This is why with, like, medications, like blood pressure medication and other heart medications, they say don't drink it with grapefruit juice.

1:18:53

It affects that 3A4 pathway, which affects the concentration of the medication in your body, and the same applies to estrogen.

1:19:01

So instead of trying to halt that pathway, I generally am trying to, I'm looking at, like, the two and the four pathway, and I'm looking at things like the next phase. I'm looking at phase two on the DUTCH Test, we're looking at methylation.

1:19:18

But remember, there's sulfation and glucuronidation, that there's a whole, we just talked about breast cancer and a lot about estrogen today. But phase two is much broader, much broader.

1:19:28

Like that's a whole liver lecture on into how phase two works. Yeah, so be careful

1:19:34

when you slam on the brakes to 3A4, you could end up making them sick, or toxic.

1:19:41

OK, that's good to know.

1:19:43

You've been with us for almost an hour and 25 minutes.

1:19:49

Giving your time to not only prepare and provide this lecture, but also to answer a bunch of great questions, and just leaving the listeners with a final thought.

1:20:02

How would you guide them, and, you know, how do you know how to get started, if you have a new provider,

1:20:09

how would you guide them to get started with us, and then, how they could be thinking about their patients that may be at risk? If you're a brand-new provider and, you know, definitely first and foremost, if you've not signed up, please do sign up, talk with our sales team.

1:20:25

They're extremely knowledgeable around the DUTCH Tests and everything, and then take advantage of our clinical team.

1:20:33

Who, when you run your first test are here to help you go through all the dials, go page by page and explain it to you? And so, we've a lot of ways and we take advantage of all the educational webinars that we have as it relates to estrogen as it relates to cortisol, as it relates to men's health.

1:20:51

Because we're really trying to help you better understand hormones as much as possible, so that you can turn around, and then, help the patient in front of you.

1:21:00

But talk to our sales team, and then, you know, reach out to our, our clinical team once you have your first test ready.

1:21:07

How long are those clinical consults usually?

1:21:11

So, for a new provider, we strongly recommend going for the 30-minute route. We do have 15-minute options.

1:21:18

We find that new providers have so many questions because they're brand new to the DUTCH Test, that they just cannot get through it in 15 minutes, but most of our clinical consults run about 30 minutes.

1:21:29

Absolutely, and you know, it can be a lot for a new provider to take in, right, a lot of information, trying to understand it all the best help their patient.

1:21:41

So, what should a new provider expect, how long, would you say on average, because you've been doing this for quite some time, do you see that people start to get the hang of this?

1:21:55

So, it depends on your hormonal experience.

1:21:57

If you have a pretty broad knowledge of hormones, then it's just understanding the test. Because it can be a little overwhelming and complicated, over six pages, but then you already understand hormones.

1:22:09

And so, once you understand the layout of the test, you're like, OK, I got this. If you're new to hormones, maybe you come from a different field. You have a different background. Maybe you specialized in cardiology or gastroenterology or you're just new to medicine in general. Then it might take you a little longer.

1:22:24

You might find that your, it's going to take you 4 or 5 tests to really feel like you've gotten your feet wet. And then maybe 4 or 5 more to really have a sort of grasp around hormones in general and how the test works.

1:22:39

But, because of all the visuals on the test and following the arrows and color coded, we try to make it as, sort of, user friendly as possible by, like, follow the arrows, and look at the colors.

1:22:54

Yeah, you bet.

1:22:55

And we're just thankful for, for all of our listeners today, everybody who could attend the Wednesday webinar. We do these every month.

1:23:04

And I encourage you wholeheartedly to follow Dr. Jones on Instagram because she posts a lot of valuable information on her own Instagram page. And then you can also follow us at DUTCH Test on our social media. But thanks for listening today, and viewing, and spending time with us. We will be sending out the slides and the webinar, a link to the webinar, so you can watch it, and if you're a new provider, you're interested, make sure that you call in, and one of our customer service reps would love to help you, and the onboarding process. Thanks again for your time, and we hope you have a wonderful day.