Episode 90 - More SNPs and CYP450

Speaker 1: 00:00 This is Dr Chad Edwards and you’re listening to podcast number 90 of against the grain.

Speaker 2: 00:05 This is Diana Edwards and I’m here with Dr Chad Edwards and our last episode number 89. We discussed genetic snips, however, Dr Chad was not quite done. He had a little bit more to say. So what say you sir.

Speaker 1: 00:23 So yeah, last time we talked about these genetic snips, snips or single nucleotide polymorphisms and this is a huge topic and the more I got to thinking about it, there’s, there’s some other stuff that I want you guys to understand to the best of your ability because I think it impacts your overall health and how we can, you know, especially within functional medicine, how we can affect change in your overall health. And a lot of it has to do with some of these genetic variations. So I wanted to spend a little bit more time talking about that and I’m pretty excited about this. There’s some cool stuff.

Speaker 2: 01:00 Oh yeah, I can see you geeking out.

Speaker 1: 01:04 So. But you, you’re going to be excited about this too. So, you know, you don’t know me very well. So we’re going to make you excited. Trust me, everybody listening, you’re going to be like, wow, that’s the most coolest stuff I’ve ever heard my story and I’m sticking to it. So, you know, we talked about these genetic snips or single nucleotide polymorphisms. What else? I got to thinking about that and thinking about how, what we do, you know, the nutrition that we eat, the medications that we use, the supplements that we recommend, uh, how, why these things play a role. And so, you know, when I got to thinking about, you know, we do a lot of bioidentical hormone replacement. We’ll use hormone pellets, which obviously we do in the clinic and I highly recommend for men and women who need hormone replacement or optimization will often recommend that those patients take a supplement with a combination of dye and old methane or dim and Luca Raffin.

Speaker 1: 02:03 Now, both of those things are broccoli seed extracts. And why do we recommend to them? Well, we recommend to them because it helps with estrogen metabolism. So one of the most common questions that I get in regards to biodentical hormone replacement therapy is, well, what about estrogen and breast cancer now that will be at the topic of a, another podcast in the near future, but I will argue over and over and over again that it is not so much the estrogen as it is the estrogen metabolism. So I will sit here and explain this hormone optimization pathway, which I know I have discussed at least on some level in previous podcasts. Go through there and take a look at the hormone replacement estrogen, about a nickel hormone podcasts that I’ve done in the past and I will intro those topics, but I think of those things play a role or the or the genetic snips and the manipulation of them.

Speaker 1: 03:06 Meaning a, how do we turn the enzyme up or down, or how do we induce the DNA to express more of that enzyme row? How do we shut that down? And the nutritional supplements that we recommend in this case, specifically, that combination product. Uh, and we call it hormone foundation. It has diacetyl methane and Gluco Raffin. And I think it’s a great supplement, works very, very well for trying to enhance how you metabolize your estrogens. So I, you know, a picture’s worth a thousand words and I should, we should probably put this in the show notes of this diagram. And most people, when they look at this diagram, they’re like, are you kidding me? I mean, it’s, it looks very complex, but you can break it down and maybe I need to redraw it and put it in just three different things that maybe the best way, you know, if we do a Dutch test, which is a dried urine test for complete hormones, if we do one of those, if we’ve done a saliva, well, mainly urine for the complete hormones, then you will see the three different types of estrogen metabolites.

Speaker 1: 04:14 And there’s three different pathways. There’s the preferred pathway, which is two hydroxy estrogen, whether it’s estrodiol or estrodiol. Uh, there’s the 16 hydroxy and there’s the four hydroxy. And when we’re talking about estrogen metabolism, we want those estrogens to go through the two hydroxy pathway. That’s the preferred pathway. So how do we, um, how do we prevent it from going through the 16 or the two hydroxy pathway, what we do that by some of these nutritional supplements and the reason for that is because nutritional supplements can induce or turn up some of these enzymes that are controlled by these genetic snips. So I wanted to take an example. Last time I used Mthfr this time because we’re expanding this topic a little bit. I want to talk about, uh, the, uh, the Cyp one, a one and a two as well as the Cyp one b one.

Speaker 1: 05:14 And we’re going to spend most of our time talking about the one, one, one, a two a because those, those see cyp 4:50 enzymes. It’s part of what we call the cytochrome p four or 50 enzymes. They are responsible for breaking down a whole lot of chemicals, a whole lot of, uh, drugs, chemicals, things like that. Uh, and, and things like antidepressants like amitriptyline and imipramine and some atypical antipsychotics like Haldol, a caffeine can go through this enzyme at least a little bit Melatonin. The awful in some of your antidepressants, estrodial is definitely one of them. We’re going to talk about, I’m on dance Tron, which is Zofran propranolol or Verapamil, warfarin. All of these things can go through, uh, through this, um, this enzyme pathway. So when you take the, so you have this enzyme and it’s job is to basically hydroxyl late this chemical, which it, it alters this chemical, uh, whatever it is that we’re talking about.

Speaker 1: 06:23 So in this case, we’re talking about estrogen and in some of the others, uh, you know, that were there like caffeine, you know, we’re breaking these things down or we’re trying to metabolize these things. So you have one enzyme that’s trying to break down all these chemicals. Well, if you flood your system with a whole lot of chemicals, like a whole lot of caffeine or a whole lot of Haldol or whole lot of estrodiol or Flexeril, which is a muscle relaxer or a number of these other chemicals, then it inhibits that ability, that enzyme in some of the other pathways. So you’re flooding your system with a bunch of things and hoping that it will break it down. Now that’s just what we then that’s cool. You call impeditive competitive inhibition where you just, you’re flooding the system and just trying to do the best they can, but you also have a case where you can induce this enzyme.

Speaker 1: 07:18 So that’s where you’re kind of revving that inside. I’m up expressing more genetically increasing the activity of that enzyme. And there are a few chemicals that can do this. Things like Cipro, it’s an antibiotic. Some of the other fluoroquinolones can do this on an Ssri antidepressant. Fluvoxamine, the Verapamil, St John’s wort can do this. The old school Tagamet, one of the H, two receptor blockers for the stomach, uh, or I’m sorry, receptor antagonist for the stomach. Caffeine can do this. [inaudible] Neisha can do it. Uh, and then, uh, there’s some other things like grapefruit juice can actually alter or, or in inhibit that I say induce. I’m sorry, take all those chemicals. They inhibit this enzyme. So what that means is that you can’t break down. We’re talking about estrogen in this case. So you can’t break down the estrodial effectively through that two hydroxy pathway. And remember, that’s the pathway that we want to go through.

Speaker 1: 08:18 So if you’re trying to break down these estrogens, one or two things is going to happen. You’re either going to build up or have an excess of amount of these estrogens, or you’re going to go through one of the other pathways you’re going to go through with the 16 or the forehead Roxy Pathway, which you don’t want those, you want to go through the two hydroxy pathway. So you want to do things that help inhibit that enzyme, meaning it backs things up. Uh, so, but there are some other things that you can do that induced this enzyme, meaning that it revs it up. Uh, so those are what we want to focus on. Um, so things like tobacco, ironically, don’t use tobacco, not bad, don’t do that. But some of your, um, some of your Broccoli, cruciferous vegetable, things like cauliflower, Brussels sprouts, Broccoli, interestingly char, grilled meats can induce this enzyme, insulin, a Modafinil, which is a, um, I think that’s a pro vigil, if I remember right.

Speaker 1: 09:22 Um, and, and [inaudible] all the Proton pump inhibitor also do, don’t do that. You’ll have to stay tuned to a future podcast and we’ll talk about why Proton pump inhibitors can increase your risk of cardiovascular disease, which is a very interesting topic to me. Um, and one of the many reasons that I do what I can to get people off of those medications. Um, so you’ve got these inhibitors, the drugs like Cipro, floxacin and St John’s wart and submitted in or, or, um, uh, Tagamet antibiotics and some of the antibiotics, you know, in those kinds of things that will inhibit it making where you cannot break down the extra dial or the estrogens to the one that you want to make. You can’t go through the two hydroxy pathway or it slows that process down. And then the flip side of that is you’ve got some things that you can do to help increase that enzyme, that Cyp one, a, one, one, a two, a, so that you break these down through the optimal pathway through that two hydroxy estrogen pathway to make sure that you are optimizing your overall estrogen metabolism.

Speaker 1: 10:29 And I, I, uh, and then there is some literature in, in regards to this that a women that had breast cancer, when they looked at the tissues, they actually had very high levels of the four hydroxy estrogen dial. And that’s the one, one of the ones that you don’t want. And that’s the four hydroxy, that’s the really bad one. And if you can’t methalate, so go back and listen to the, uh, our podcast on Mthfr. If you don’t methylate well, then going through phase one detoxification, which is what we’re talking about in the four hydroxy two hydroxy, that hydroxylation, that’s phase one, detoxification. And if you cannot methalate, which is part of phase two detoxification, then you have a buildup in these four hydroxy estrogens which are potentially carcinogenic because they will convert over into three, four quinones. And that’s bad Juju. And there are things that we can do.

Speaker 1: 11:21 There’s also nutritional supplements that are very beneficial for trying to prevent that. But the, uh, uh, these broccoli seed extracts that Broccoli, the Diane Methane, the Gluco Glucoraphanin, and there’s some really good evidence, in fact, the Glucoraphanin, uh, the intellectual property of Johns Hopkins University, they’re the ones that kind of developed it. And, and um, and formulated that and there are, I think 400 plus studies showing anticancer benefit, really, really cool stuff. So that both of those combined together, I’ve seen some amazing things for optimizing estrogen, even in men, of course, to your testosterone converts to estrogen specifically to Estrodiol and that, you know, we want to limit some of that. We want the estrogens to be in the appropriate level for men. And the, the, uh, hormone foundation does an excellent job of that because of its effect on many of these enzymes that upregulate, that Cyp one, a one, one a two enzymes.

Speaker 1: 12:31 And so, you know, when you’re talking about these genetics and these genetic snips, single nucleotide polymorphisms, you have some people that come to the plate and their enzyme is functioning at a hundred percent and they take something like Cipro, floxacin and that may cut it’s. And I’m making these numbers up, but it may cut the enzyme activity in half where they’re only 50 percent functioning at 50 percent. Well, if you have somebody that has a genetic snip, were there one, a one, one a two is altered, they may come to the table only making 50 percent to begin with. So then you take cipro on top of that. I don’t mean to pick on Cipro, it’s just, you know, one of the top of my list and now their only function, they’re only, you know, breaking down like 20 percent their enzymes only functioning at 20 percent.

Speaker 1: 13:18 So that’s going to put that person at that much increased risk. And we want to do everything we can to optimize the way someone metabolizes and um, and breaks down these estrogens. And so when we’re talking about bioidentical hormone replacement and optimizing overall health and reducing risk of breast cancer, we want to make sure that those enzymes are functioning to the highest level possible. And it’s really not a bad idea to get something like the Dutch test. Again, that’s dried urine test for complete hormones, which will measure your four hydroxies. You’re to Hydroxys, you’re 16 hydroxys, testosterone, all kinds of things. Excellent, excellent test. Uh, I highly recommend that test and it will tell us exactly how we are doing so when people recommend supplements, then we can actually measure how we’re doing and what impact we’re having. So a really, really cool way to evaluate specifically what we’re doing with our supplements in the clinic.

Speaker 1: 14:20 So the genetic snips alter what you bring to the table to begin with the nutrition that you would like grapefruit, as we discussed, reduces the effectiveness of that enzyme or the amount of that enzyme. Uh, and so what you eat alters these enzymes in the expression of these enzymes, both in a good way or a bad way, depending on what your, what it is that we’re eating in which ends, I’m, we’re talking about. So these snips are very important and it really can alter your overall health. And I think it’s important for everyone to understand those things. And I’m not saying run out and get all of your cyp four, five, excuse me. Cyp Four, five, zero enzymes checked because it’s very difficult and you can run yourself crazy by saying, oh, I can’t eat that because it’s going to regulate, this is what she’s going to mess up that, which I mean, you can, you lose a lot of sleep over that stuff.

Speaker 1: 15:10 So it’s just when you’re having an issue, measuring these things may help us understand why you’re having a problem. So that’s kind of what I wanted to focus on, um, as far as the, the snips and another example of how it applies in this case specifically to bioidentical hormones and risk for breast cancer and optimizing the elimination of these hormones, but also how your nutrition can play a role, uh, in these, uh, in these cyp enzymes which are many of them are, are snips or single nucleotide polymorphisms. So that’s Kinda where I wanted to go with that.

Speaker 2: 15:54 I think it’s great. And guys, make sure you check out the show notes. We’ll have this beautiful chart with the good, bad and ugly breakdown between the 16 four and two hydroxy of your estrogen. So you can check that out.

Speaker 1: 16:08 There you go. If you have any questions, need anything, don’t hesitate to let us know. Be sure to go on itunes and leave us a review. We want to get our information out as much as we can and as always, just let us know what you think.