Adapted from episode 110 of The Perfect Stool podcast and edited for readability, with Lindsey Parsons, EdD, Gut Health Coach and Bryce Wylde, DHMHS, of VennMed in Toronto and co-founder of The DNA Company, who did a DNA sequencing report for Lindsey. To best follow along, download the PDF report.
Lindsey:
Before we launch into my DNA results and what they say about my gut health, can you first tell me about how you arrived at the conclusions that you make in the DNA reports from The DNA Company?
Bryce Wylde:
Well, I had the privilege of under studying with Dr. Mansoor Mohammed, who’s revered probably by most genetic experts, and genomists around the world as within the top 10. So I’ve been in clinical practice over 20 years, and we shared a significant degree of patients between us in this very eclectic multicenter practice called P3 at the time. We no longer practice under the same brick and mortar, but with his IP, and his insights was born a lot of what he would see in this particular DNA report.
Lindsey:
Okay. And this was based on patients that he saw and in their DNA reports?
Bryce Wylde:
Yeah, so Dr. Mohammed had a long standing company and had seen at the time, I believe it was about 2000 individuals, patients of his that he’d done genetic reports on. He has a double PhD from UC Baylor, and was a UC Davis graduate focused in genomic pathways. At that time, along with a team at the DNA company, we amassed another 6000 or so patient samples. Of course, some of this was from his actual clinical experiences, and his former education. From thousands of individuals, we were able to extrapolate a lot of what you now see within the DNA report.
Lindsey:
I think I heard you on another podcast, and you were talking about the fact that there were interviews with patients that was then cross referenced with their genetics.
Bryce Wylde:
You’d have to remind me of exactly what that podcast was, but we certainly would have had a lot of endpoints within any given patient that we consulted with as it pertains to them having gone through genomics. This wouldn’t be exclusively genetics, it would be on all types of functional genomic endpoints and laboratory studies and their full clinical medical histories that would have been taken in combination. Absolutely.
Lindsey:
Okay. I think maybe it was Chris Kresser. Have you been on his podcast? No, I haven’t yet. Okay. It wasn’t Chris Kresser. I can’t remember whose it was then. I’ll have to look it up. So can you explain for people who may order their own reports what the letters mean for each gene. So for example, I show a list of relevant genes under the hormone section. Here’s an example: CYP17A1 and then after that, there’s an AA, and then there’s another one, SRD5A2, and after that, there’s a CG. And then after another one, there’s a CC, and after another one, a CT, and another one, there’s a 2.
Bryce Wylde:
It’s an alphabetical soup. So that’s going back to biology 101, grade 11. Most people that are concerned and are interested in this world of genomics, they’ll often come across the term SNP first or single nucleotide polymorphism. We all have them, they’re not the more revered mutations, but we’ve all started to come to learn to understand and appreciate them. They’re a natural occurrence, a variation of a particular gene, or your SNPs, Single Nucleotide Polymorphism variation. So how your particular gene expresses itself, given some genes are nonsense, or non code, and then others are actually making proteins and hormones and doing other things for us. So out of these important genes that we care to learn about, you have different variations. Some are more common to the population, some are considered to be the preferred variant, while others are considered the poor, or not-so-preferred variant, depending on the context. So when you’re thinking or seeing an A variant, given a particular gene, or an AG, or a GG variant, these variations may be, given that particular gene and whether what it does is optimal, sub-optimal, average, or poor. So it’s kind of like getting a report card, but I should say that there is no perfect combination. No one has the best genes. There’s simply variants that you have and knowing what those variants are can help you get through this game of life. I mean, genes are the cards that mom and dad have dealt you. I like to say that how you play them in this game of life is really what matters. So understanding what those cards are, is akin to understanding what variations or the numbers or letters that add up and how they pertain to your SNPs. So at the DNA company we go further than just looking at SNPs and the conglomerate of variations of those SNPs, we look at pathways. Inclusive within those pathways, often we’re looking at copy number variation. So to your question around numbers, these are like instruction manuals. We’ll talk about this a little bit later on as it pertains to detoxification, for example, the glutathionization pathway. So how our bodies manufacture glutathione and its detox process, you’re getting a whole manual of instruction on how to do that from mom, and from dad. Unfortunately, in some cases, we end up with only one or in many instances, zero copy number variations, or no variant. And then there’s the case of inserts and deletions, whole lines of code. So maybe not the entire instruction manual is missing, but sentences are missing within paragraphs. They’re just not there. Or in some cases, double sentences, so that’s two sentences being redundant. These are known as indels, or inserts and deletions. So we’re looking at SNPs with the AA, AG, GG variation, which one do you have. We’re looking at inserts and deletions, and we’re looking at copy number variations, and putting them all together. You can never take one gene out of context, I like to always add that. You have to consider numerous genes, in many cases, dozens of genes together before drawing even remotest of conclusions.
Lindsey:
Interesting. So when I look at this gene and the letters after it, I don’t know what the default preferred variant is for CYP17A1. I have AA, but I don’t really know if AA is good or bad.
Bryce Wylde:
Well, it’s good, let me tell you, but again that’s taking one gene out of context and looking at it on its own, because it depends on what we’re trying to accomplish in that instance. When we get to hormones, and we certainly will, we’ll cover that that. When we’re talking about the hormone pathway, most folks don’t understand that whether you’re male or female, which is decided by the XX or XY chromosomes, we all produce hormones with the exact same cascade. So look forward to talking about that. With the gene you described, it’s really more specific to how fast you might actually produce estrogen from progesterone. I mean, we’ll get into it. And it’s a really interesting pathway.
Lindsey:
I didn’t want to get to the details of that yet. My comment was more about understanding that as I look at the report, and I see those letters, there’s nothing to tell me right off the bat whether what I have is the preferred or not preferred variant, correct?
Bryce Wylde:
That’s because you’ve got to take them all together. You really look at this as a big book on you. This is your instruction manual. And there’s no such thing as good or bad, really. In instances where we reflect back to or refer back to the literature, and we look at these individual genes as optimal variants, or sub optimal variants, based on population dynamics, it’s very interesting. In some instances where someone has what might be considered the perfect gene, two of them might actually not only cancel each other out, but maybe create a suboptimal combination. So you have to take them all in context, considering where you live, your ethnicity, and your environment, all these things.
Lindsey:
One other question related to that. So if I see two, that means I have two copies of that gene, correct?
Bryce Wylde:
That would be correct. In this instance, we’re looking at copy number variations, or CNV, specific to glutathione, and glucuronidation. The specific ones we’ll be focusing on today are the pathways that are responsible for both detoxification and hormones.
Lindsey:
Let’s start with the detox pathways. How do they relate to gut health? And what does my DNA report say about mine?
Bryce Wylde:
Well, let’s just look. When we put all of these together, and we look at one full and complete list, it’s many pages long, so we’re going to take a minute just to get down to the very bottom of this. Just to summarize, one of our primary focuses being how do you intracellularly produce glutathione. Glutathionization is one of the most important antioxidants, if not the most important. Remember, I was telling you at the top, off-camera, that we don’t actually list a specific detoxification sub report. Detoxification is on page 10 of your hormonal report (p. 144 of PDF), since we’re going to come back to this momentarily. And so what we’re looking at in this instance is, as I mentioned, glutathionisation, GSTT1, or glutathionized theta. Before I get into the depth of your particular findings, you would probably agree with me that elimination of toxins, the liver-gut axis, the microbiome interaction, and the barrier function all play a role, and of course the gut plays a vital role in eliminating toxins and waste products. And efficient detoxification ensures that harmful substances are promptly removed from the system, safeguarding gut lining integrity. GST plays a huge role when it comes to the liver-gut axis. That’s the primary detoxification organ, and its function is very closely linked to gut health. Bile, produced by the liver, aids in digestion and carries waste products and toxins for elimination through the gut. This is also very much involved in microbiome interactions, so it can influence detoxification. Conversely, if you’re not able to rid yourself of toxins and metabolites, this influences the composition and function of the gut microbiome. This is good news for you: we see the number two here next to yours, GSTT1. I shouldn’t forget to mention barrier, so efficient detoxification eliminates the interaction or inflammation between the barrier and maintaining that gut barrier essentially prevents leaky gut, and even leakage of toxins into the system and substrates into the bloodstream. So GSTT1 is supposed to have a copy from mom, and a copy from dad, you got two, so you’re lucky, this is excellent. This is associated, as our report says here, with an increased enzyme function clearance of substrates. So that’s good. We’re also looking at how many GSTM1 or mu 1 copies you have now. This is the master gene that GSTT1, let’s call the GSTM1 a very close, but important, second. You’re supposed to also have a copy from mom and dad, which you also have, which is amazing. Therefore, relating to clearance and processing of xenobiotics and pharmaceuticals and reactive oxygen species, you’re doing very well. So in fact, you are gene blessed, as it relates to glutathionization. GSTP1 is a good example of some variation in a SNP or the Single Nucleotide Polymorphism that sits on this gene RS1695. This is where things may get backed up slightly with you. G variations in individuals we know relate to the ultimate clearance of some things like Tylenol. So that might get a little bit held up. Certain aspects of environmental xenobiotics, those that impact us as it pertains to hormone mimickers, and so forth. This gene, it’s a member, obviously, of the glutathione S-transferase gene family. But looking at this as a single phase two detoxification SNP you are a little more susceptible to certain things, certain health concerns that are associated with toxins, chemicals and certain heavy metal exposure and gut permeability. While there’s no direct evidence linking GSTP1 to gut hyperpermeability, we know that oxidative stress is known to influence the integrity of the gut barrier, obviously. And so it’s very likely that GSTP1 through that role in mitigating oxidative stress might very much influence gut permeability. Superoxide dismutase is very important, as we know, a manganese-driven enzyme and gene. Again, here we’re looking at a SNP, and yours being a CT variation. There’s this association of a 30 to 40% reduction of superoxide dismutase. When we’re seeing the essentially reduced clearance through the GSTP1 and superoxide dismutase, there’s that increased risk of reactive oxygen species accumulating. So you’re going to be interested in managing antioxidants. One of my favorites is the tocotrienols. I’ve done a lot of deep dive into this. Forgive me Lindsey, I’ve seen your whole report, so it’s hard for me to hold back. There’s some instances where we’re talking about gut health, we just mentioned the linkage to liver and that interconnectivity, but because I know about an aspect of your cardiovascular health related to the 9P21 gene. We look at three different SNP variants of that gene and anywhere there’s a G, it’s considered an elevated risk. What we’re talking about with this gene is the potential of inflammation to the endothelial lining. As we’ve known for a long time, the recommendation in this case is to suggest even something like tocotrienols is manyfold. This endothelial lining inflammation predisposition that you have signals to me appropriate consideration for tocotrienols, so not just because of SOD, you’ve got the CT, and GSTT1, you’ve got also the hybrid AG variant, which tocotrienols do a great job of eliminating or sweeping up the mess. This was the work by the way, Dr. Chandan K. Sen of Ohio State University who’s projects get funded $25 million year over year by the NIH, so we know there’s something to them. There’s really great work done there. They looked at post-MI, post-stroke, revascularization and recovery, and white matter lesion reversal. So it’s really amazing stuff. I’ve been to Malaysia, by the way, and I’m not speaking on behalf of the tocotrienols that might come out of Africa or Indonesia, because I’ve never been there. But I hear very terrible things about deforestation. Anyways, tocotrienols from Malaysian Sustainable Palm Oil might be the indication here for you, because of the 9P21 variation and the predisposition to your endothelial lining, and also how it might actually do a great job managing the very slight Achilles heel within your own detox pathways. By the way, the research shows tocotrienols have an amazing capability to reverse NAFLD or non alcoholic fatty liver disease. So there are a lot of little nuggets there to take away.
Lindsey:
Yeah, let me interrupt you for a second because I actually had Dr. Barrie Tan on the podcast, who discovered a source of annatto-tocotrienols. And we talked all about that, and I have subsequently suggested that for a lot of my clients, and I think I have my parents on them and my fiancé on them.
Bryce Wylde:
Well, we’re on the same page then. He has an incredible product that he talks about. The annatto derivative is perfectly good. It doesn’t have to be the Malaysian Sustainable Palm Oil. But the tocotrienols themselves are an incredible antioxidant. So it sounds like we both agree.
Lindsey:
Just so people understand what we’re talking about, we should clarify this is a form of vitamin E.
Bryce Wylde:
Correct. Thank you. And then GPX, glutathione peroxidase. . . . . . of that report. You’re going to scroll down until you hit the hormone report, and then it’s page 12 of the hormone report. We see GPX, and your variation here is a CC. First of all, this gene provides instructions for making the glutathione peroxidase enzyme, so that plays a very crucial role in protecting the body as well from oxidative stress. You’re doing well here. It basically takes hydrogen peroxide and other harmful peroxides in the body, turns them into a very benign and neutral water molecule. Here’s where I just took a quick peek as I scroll down to the end of page 12 and reminded myself of this 9P21 and the fact that you’ve got this between 4 and 6G association. Again, this is the endothelial lining, so this is all relevant within the context of hormones. We stop the detox conglomerate when we go through the GSTT1, GSTM1. You’re doing amazing there with both copies from both parents. On the other hand, GSTP1 and SOD2 are where we want to tweak things a little bit for you, and manage your clearance from phase 2 and just get this sweated out, pee it out, poop it out, get it out. If I’m talking to a client that has this variation combination, if they can afford it, obviously, I often recommend infrared saunas. It’s amazing. Your gut is like inverted skin, and so getting that skin active and sweating out certain things is really good for it. Especially studies show with heavy metals we might do a better job getting rid of them through our sweat pores than we do through our kidney clearance. So that would be the detoxification report in a nutshell.
Lindsey:
We’re on page 12 now (p. 148 of the PDF) Well, let’s move on to methylation. So I’m sure many people have heard about MTHFR. I know there’s a lot of confusion about what that means and how important it is, and maybe some exaggeration of its importance, as well as ignorance about other genes that play into methylation. Let’s dig into that.
Bryce Wylde:
I’m going to go back up a bit here to immunity. And I apologize for flipping all over the place here, but soon I’ll give you the page number within the immunity report.
Lindsey:
All right, and just note that the page numbers restart with each report. So the first one was within the hormones section, pages 10 through 12. And now we’re going to be inside the immunity section.
Bryce Wylde:
Going back to our earlier conversation, a lot of these genes and genetic genomic pathways, you will see some repetition. It won’t be exclusively in the hormone report that you’ll see detoxification, rather it’ll be scattered throughout all the reports. It’s also very relevant to cardiovascular health and disease. It’s very relevant to the hormone clearance that we just looked at. Let’s focus for now on the cardiovascular support. So rather than scrolling all the way up to immunity, because both immunity and cardiovascular involve methylation. Methylation is almost sort of synonymous with inflammation, but not quite. Without oversimplifying, because it is quite a delicate biochemical dance, I look at it like it’s a relay race, where in this race, you’ve got five racers and the baton stands for the methyl group, and the methyl group is CH3. If any of your racers obviously dropped the baton, that’s a problem. It’s not a problem that’s very easily solved by throwing more batons at the race. You’re disqualified if you drop the baton, but it’s of no use to just lay three or four batons on somebody, because more is not always better. So it’s a careful dance, these methylation, biochemical pathway circles. The endgame here for us is to understand what type of support you might need. Through the use of very specific types isomers of B12 and folic acid, we may support and fuel this particular pathway, given the various SNP associations that you might have. As they pertain to gut health, particularly, cellular health is huge, and our guts turn over at a very rapid pace. The immune function plays a role here. As does the microbiome that we already alluded to, in respect to detoxification. As it relates to cellular health, just for example, the methylation pathway and optimal methylation needs an availability of B12 and folic acid. They are imperative for maintaining the health and for repairing the gut lining with that speed of turnover. Obviously, for nutrient absorption, macro and micronutrient, and barrier function are important. When it comes to immune function, methylation plays a very important role in regulating the immune system at large, but it’s also crucial for managing gut health and preventing conditions like IBD, inflammatory bowel disease and leaky gut. The microbiome is a two-way street, but B12 status influences the composition of the microbiome and it plays a role in producing some of it. It also significantly impacts overall gut health in this dance with B12.
Lindsey:
We’re on page nine of cardiovascular report.
Bryce Wylde:
So MTHFR, or methyl tetrahydrofolate reductase. We’re looking at the SNP variant you have here being a CT. I don’t want to get overly complicated here, but this is the one people focus on most often. Sometime the single gene is presented to them, and they think this is the end all and be all even though it absolutely isn’t. I want to remind folks of that analogy I said before. It’s a race. It’s a circular race around the track. They’re really racers. MTHFR is just one of the racers, and it’s a really important racer. It’s part of the pathway catalyzing specifically the conversion of the 5,10-Methylenetetrahydrofolate to the active folates. This 5MTHF is then utilized as a methyl donor to B12 for the conversion of homocysteine to methionine. Homocysteine to methionine, this is the job that this is doing. In you, it’s associated with CT variant to a 30 to 35% reduction of enzyme activity with the intermediate 5MTHF production. We’re not just reporting on this saying that there might be a little bit of an issue here. I’m going to tell you at the end of this, what kinds of B12 and folate are the right ones for you. Because as I was alluding to, just throwing more batons at your racers is not the solution here. That’s called hypermethylating, that can be a problem as well. A lot of folks when they came to learn that they might have a CT or a TT as you do, just throwing extra folic acid at it may not be not only the right solution, you can also throw the wrong kind of folic acid at some some folks, depending on genes within the methylation pathway that are nonspecific to the variations of the MTHFR gene. You wouldn’t know what kind of folic acid to consume unless you went on in this report. Low blood folate is associated with elevated homocysteine levels and increased risk of cardiovascular disease. It’s relevant to you because of the 9P21 gene, and some others. We’ll talk about the maybe the APOE factor. We know all about early pregnancy and normal fetal development. The speed and turnover of the endothelial lining is important to manage. Folate serves as an ingredient to manage DNA turnover. You have this association of 30 to 35% of this enzyme activity and as folate’s crucial for synthesis and repair. And you know it’s vital in maintaining the health of these rapidly dividing cells in the gut lining. It doesn’t stop there. SHMT1 is a co-conversion of the L-serine and tetrahydrofolate, to glycine and the 5MTHF actual end results. So this is an intermediate, kind of little clinical pearl. The GG genotype that you’ve got here, when considered with the context of the MTHFR, is associated with optimal folate metabolism. This is looking at concomitant disease risks reduction associated with dysfunctional folate metabolism. Many who have a poor variant also have issues with the cellular processes, including this gut cell turnover and repair. But in your case, it’s associated with optimal bioavailability and efficient homocysteine to methionine conversion. So here’s the bottom line for you. It’s not the case with everybody, but you’re fine with methylfolate. If somebody didn’t have this genetic sequence, then they may want to be taking folinic acid where you’re getting down to the end of the conversion. In your case you’re fine with folate, methylfolate, more 5MTHF or quadrafolate. Really you’re fine with any of those types that are out there with the MTHF assignment. And then we’ve got MTR: you’re an AA. MTR catalyzes homocysteine to methionine and uses B12 to do it, as the methyl donor in this particular reaction. So this is associated with optimal enzyme activity and conversion of homocysteine to methionine. That’s the AA assignment. It turns out because of this, and I’ll explain some other variants in a second, that you’re fine with methylcobalamin, or the methylated form of B12. If you had any of these other variants down here, we might be wanting to give you a adenosylcobalamin so we’re not hyper methylating you. In studies done on autistic children who found that they had the 5MTHFR. They call it the SNP. Everyone’s got that SNP. It matters what variation of that SNP you have. Right when they found out they had this poor variation of this particular SNP, which is the TT variation, they were giving them in many cases methyltetrahydrofolate, in the methylated form. And in about 15 to 20% of them they were doing worse. And the question was why? And this was one of the answers that Dr. Mohammed was able to answer because they weren’t assigned these other variants that actually helped them to pass that baton in this race and effectively do so in a way that they were able to methylate properly. And then lastly, your MTRR, this reactivates methionine. You have the version AG associated with a slightly reduced enzyme activity, which won’t affect its precursor here, the MTR. So by the way, MTR and MTRR together influence B12 availability, which of course is crucial for DNA synthesis and maintaining the health of the gut lining. But just having this AG here does not all of a sudden screw you up and cause you to require the adenosylcobalamin. So again, we’re still giving you that form of methyl B12. It’s important because this can contribute to things like B12 anemia.
Lindsey:
Which I had following SIBO and and what turned out to be post infectious IBS and for a time positive for pernicious anemia. My hematologist recommended that I get on methylcobalamin. And I’ve essentially been on it continuously for the last 10 years.
Bryce Wylde:
And it would have worked, but guess what in some other combinations and in other folks with the same looking red blood cell count and differentiation, given that, they may not do as well. They may need adenosylcobalamin.
Lindsey:
Lucky guess for him!
Bryce Wylde:
Right. Then lastly, fucosyltransferase, FUT2 the AG is associated with slightly suboptimal enzyme function and plasma levels. This encodes for an enzyme basically, and this is releveant to you, by the way, found in epithelial tissues in the gastrointestinal mucosa and salivary glands. So this SNP shows a significant association with plasma B12 concentrations. And in your case, as you mentioned, this would be the gene that I would associate with poor enzyme function, and poor plasma and B12 levels. All G-allele carriers, whether you’re AG or GG, are associated with significantly lower plasma B12 levels, so what you said doesn’t surprise me at all.
Lindsey:
We’re on page 11 (p. 56 of the PDF). So those two markers that are in the suboptimal variant of AG basically mean that it’s not unusual that I should have to continue to supplement with B12 and folate, methylfolate.
Bryce Wylde:
Yep. And also by the way, combined with a vegetarian diet, these variants are associated with extremely clinically low, and vegan obviously, B12 level. So really important to get on the . . .
Lindsey:
Yeah, I’m not a vegan . . .
Bryce Wylde:
intramuscular in some instances or sublingual various forms of supplementation. Perfect. Yeah, so by the way, most folks that run this test the DNA, we should remind anyone who doesn’t know this, and I’m sure most of your listeners would definitely know this, DNA is one and done. You run this test once your DNA is going to change. The most incredible thing is that where you can’t alter your DNA, you can manage genetic expression, that’s epigenetic. And that’s what we’re talking about, through in this case, a perfect example, methylation. Manage this, by quelling the fire, I don’t care what you call it, subduing and mitigating inflammation, but you’re managing it in a way, your variations of methylation and how you’re able to carry the baton in this relay race with the right types and formats of B12 and folic acid. It really boils down to that for me anyways. There’s other implications here. But that’s really what it boils down to for me, for gut health.
Lindsey:
Yeah, I have always taken it sublingually since that time, because of the pernicious anemia and the SIBO. Right? Okay, so the third area you suggested we focus on is hormone pathways as it relates to gut health. So how are they related? And what does my DNA say about that?
Bryce Wylde:
Let’s just scroll right back down to the hormonal report to keep it simple. Toward the end, we call it hormones fitness and body type (p. 143 of the PDF). We use the traffic lights just to give a visual description of speed. What I want to emphasize here is that again, I alluded to this earlier, but everyone, whether you’re an XX or an XY individual born into this world with those chromosomal differences, we all have the same pathway, hormonally. It’s the speed at which we produce certain hormones that’s going to make the difference here. Again, this is not going to define whether you’re male or female. Within each of those categories, male XY and female XX, you’re going to have this spectrum of androgenized females through to estrogenized females and those in between. Same with men. There’s androgenized guys and estrogenized guys. The team at the DNA company have gotten pretty close now to looking at somebody and phenotypically being able to give a rough estimate of what their hormones probably exude from a genomic perspective. For example, we’re all wearing our heart on our proverbial sleeve here, I’m an estrogenized guy. I’m probably going to have a full head of hair until my late 80s, as my father and both grandfathers did. So that’s just one phenotype. Obviously, the challenge, in my instance, is retaining muscle mass as one additional phenotype. It’s hard for me, so I have to work extra hard. Then you’ll have the guys in the gym and they take one or two days out of the week, and they do half an hour and they’re ripped, and they’re bald. And guess what, they might have that advantage, but then certain hormones an androgenized guy has might predispose them further to prostate cancer, or a BPH (benign prostatic hyperplasia) for that matter. This relates to the gut because it could affect the speed at which you produce progesterone into testosterone, testosterone into estrogen. We know too much excessive estrogen is very proinflammatory, particularly in the gut, and then how you take estrogen and the genes that help clear or metabolize estrogen into their end metabolites. So these are known well for their predisposition unto estrogen-related cancers, breast, ovarian, and colon. And then step three, how you detoxify those, and we’ve been through some of that, but we can reiterate them. So obviously, there’s the hormonal influence on gut permeability, we’re coming to know that. So variants, and we’ll come back to CYP19A1, which is how quickly you take androgens and make estrogen, which affects estrogen synthesis. And that might directly actually influence gut barrier function. There’s the stress response. That’s not just an executive function thing. That’s a hormone thing, and integral to the body’s stress response, causing us to, depending on our variations and genetics, be susceptible to irritable bowel syndrome. Genes like CYP17A1, that you mentioned at the top, that starts this whole cascade here, involved in synthesizing stress hormones. You know that plays probably plays a role. And there’s gut motility, like hormones and neurotransmitters of course influence the speed at which our guts move, right? And how transit time works. Inflammation, particularly sex hormones implicated with an inflammatory response in the gut. So variants here, the androgen receptors, the AR gene, and the variations there affects androgen receptor function, of course, but influences inflammation, inflammatory pathways in the gut. There’s the microbiome composition, there’s immune function, nutrient metabolism, of course, detoxification, all of these things are going to have a major influence on gut health. So your CYP17A1, how you take progesterone in the steroidal sex hormone pathway and produce testosterone, you see this red light, that’s you, you’re slow. That’s actually great. I mean, we call it great, because it depends on everything else I see here. But it’s great because it’s slower, or red light, by the way, does not mean somehow you’re stopped, whether you’re not making enough, it’s not a bad thing, it’s the speed at which you’re taking this. So given that you have a yellow or a green light on the CYP19A1 or in this case, taking testosterone making estrogen. This would be your saving grace if you were green, the speed at which estrogen over spills in the body. But if you were an amber light here, or even a green light here on the CYP17A1 is what I’m pointing at. But then you are an amber or red light on the CYP19A1. That’s a different picture. But I’m painting the scenario of one compensating for the other in terms of overspill, in particular as it relates to gut health of estrogen metabolism. So your variation, and we can flip down to those variations, but I know what they are. So I’ll just refer to them in context of this picture here for you, your CYP17A1, you’re an AA. So this is again, responsible for biotransformation of pregnenolone, progesterone to testosterone, and the Cytochrome P450 cascade. So first step in hormone production critical in determining degree with all your hormones, the rest of their influence on your overall health. So you are a slow converter of progesterone to testosterone, the SRD5A2 is your testosterone into the very virulent dihydrotestosterone or DHT. And the speed at which you do that is average, we’re in the middle in between. Now, one of the things, were talking phenotype, might as well bring it up, it’s not so relevant to gut health, but I can tell you, compared to your peers, your counter, your friends, whoever, that they’re complaining, I mentioned the gym that they’re complaining the degree of what it takes them to work out in the gym and have some level of definition or be lean, and somewhat muscular. And then other friends are always complaining about cellulite and fat retention, all these different things. Obviously, I know, you pay close attention to your diet, I don’t know, maybe there was a time that you didn’t. But even in those times, so long as you did exercise somewhat. And if we consider this, the androgen receptor gene here, and the speed at which you clear testosterone, you don’t have to work as hard as the average person to actually retain muscle mass, and you’re not going to be one of those that really notices cellulite. It’s just the phenotype that you have. I mean, feel free to correct me if I’m wrong, but at least your genes.
Lindsey:
No, not wrong.
Bryce Wylde:
Yeah. So SRD5A2, this is the 5-alpha reductase that converts testosterone into dihydrotestosterone. For you there’s moderate enzyme activity. And you know, we call this potential for elevated dihydrotestosterone. It’s worthy of mentioning at this point. These are genes and depending on your environment, your lifestyle, so many other factors. The only thing it’s going to tell you any conclusive evidence of what’s happening at this moment in time right now are laboratory biomarkers, right? So endpoints, you can test for DHT, right, you can test for these things. Depending on where you are in your life. These are just the signals or the genes that dictate the average amount over your life and where you sit there. But at any given time, you can test for all these different things to know where you are. By the way, in menopause, and I’m sorry to take another tangent, but it’s so relevant in so many things. How you come into menopause, is entirely predicted by where you started this cascade. If somebody is very quick to make an abundant amount of testosterone, and by the way, guess where all estrogen comes from? Testosterone. In guys and and females, it comes from testosterone. It’s the CPY19A1 gene that makes it, in what speed, but if you’re greenlit here from progesterone into testosterone, and you’re greenlit from testosterone into estrogen, what do we call that? We call that estrogen dominant, particularly if how you convert into DHT is relatively slow. It’s like a cascade or waterfall. Everything is going into estrogen. And then if you have over here your estrogen metabolites, I’m giving a hypothetical situation, this is not you. If you’re producing very little 2-hydroxy but a ton of 4-hydroxy and 16-hydroxy, well, then we know what the risks are from that in these estrogen scenarios. Now your estrogen dominant plus estrotoxic, right? So these are these sort of scenarios. That’s not you, thankfully, in again with with you the if there’s potential for producing high amounts of DHT. And I just described some of the various phenotypes. We’ve got to be concerned or thinking about things like PCOS when there’s an elevation or retention of DHT. But your CPY19A1 gene is not at all sluggish or too slow. It’s right right there in the middle, which is exactly what you want. So again, just to remind everyone listening, this catalyzes aromatase and this is the very rate limiting step in the conversion of androgens into estrogens both men and women. And of course, you’re this moderate expression with enzyme activity with modestly reduced estrogen and estrogen to androgen ratios. And again, in postmenopausal, here’s my prediction for you ready? I don’t have a crystal ball, but you’re going to have a quite an easy menopause. You know, I can tell you the reality is that the hot flashes are insufferable, and I’ve had to go on hormones. Oh, you have? Okay, that’s interesting. So the hot flashes may be related to some of those other genes as they pertain to the 9P21 and detox, but, but I would have predicted a relatively easy menopause.
Lindsey:
No other symptoms besides the hot flashes.
Bryce Wylde:
Okay, good. Well, that’s another predictor. By the way, these are all symptoms that the body uses to prepare, inevitably, this shift. So the speed at which you actually go through menopause is another thing, and nothing I can predict through what I’m seeing here. But how quickly obviously, your estrogen supplies dwindle, controlled by other genes, would be would be related in this as well.
Lindsey:
So first question. Is there anything in here that predicts that I’m going to be low on progesterone?
Bryce Wylde:
So we don’t look at the genes that ultimately cascade down from cholesterol, because they’re not as important. Obviously, if you’re on a statin, and certain things suppress cholesterol, or some of the other precursory . . . pregnenolone, and so forth. But what this suggests is the amount of progesterone that is otherwise circulating at any given time, is otherwise average to higher than the average individual. So and that doesn’t mean menopause because those are all going to blink a little bit. But here’s really what I want to drive home depending on what kinds of hormones people are otherwise supplementing, bioidentical hormone replacement therapy, there are certain qualifications we like to look at. And this is relevant to gut health, very relevant to gut health. If you are estrogen dominant, and estrogen toxic by taking progesterone even on its own, what’s it going to do? It’s turning into testosterone into estrogen. It’s not exclusive, you are producing more of that stuff. So if I’m looking at you, and I’m looking to determine a candidacy, if you will, for BioIdentical Hormone Replacement Therapy, or even regular HRT, you’re a great candidate. Anyone looking at this would say, or any of our team anyways, would say yes, she’s actually qualified with the exception. And it’s a mild exception down here. This is what we’re going get into step two here is looking at the degree of metabolite production again, the speed at which you produce these metabolites. In an ideal world, you’d have a green light over here, in an ideal world, and what this is a 2-hydroxy estrogen I’m looking at controlled by the CYP1A1 variant. And the reason I say that in an ideal world is because being slow on the protective 2-hydroxy is to suggest you’re a little more at risk studies show. And then over here, the 4-hydroxy, in an ideal world, it’s fine that it’s this yellow variant that, you know, it would be red and 16 would also be red. So how we work this through though is, and you’re very familiar I’m sure with the research around indole-3-carbinol or diindolylmethane (DIM) and some of these cruciferous family of vegetable extracts, that this helps flip the switch on this helps to slow down the 4OHe and over to the 2-hydroxy estrogen so helps to increase or helps to speed up the metabolism of the estrogen and clear it.
Lindsey:
So eat my broccoli?
Bryce Wylde:
Eat your broccoli. Bowls and bowls of it. So in the gut health circles, depending on your FODMAP assignment or how well you do on some of the insoluble fiber levels and so forth. And obviously that’s a whole different story. But yes, at the very least take an extract and I tend to prefer a diindolylmethane over indole-3-carbinol. I think in these instances, anyways, I don’t think you can eat yourself to a therapeutic range of broccoli.
Lindsey:
I have at various points taken that for various and sundry reasons. So definitely something I can go back on.
Bryce Wylde:
Yeah, I think so. I think it’s indicated for you. So far, I think there’s two things that I would really consider in your daily regime. And that would be the tocotrienols and some indole-3-carbinol, or probably even better, some diindolylmethane (DIM). And then this step here that we’ve already somewhat discussed today at length, glutathionization. We haven’t talked about the detoxification ramifications of catechol-o-methyltransferase, which is also involved in executive function, very important in methylation and converting all the neurotransmitters into active metabolites, etc. But it’s very important here in excreting estrogens. Now, the reason, and I’m just going to highlight this real quick, you’re seeing a red light on GSTs, and our algorithm works in very mysterious ways. Sometimes this is one of them. If your GSTP1, which is true, you have the AG variant, it’s going to show up automatically, even though you have a great GSTT1, two copies and a great GSTM1, two copies, your SOD, you know, hybrid variant AG, and your GSTP1. So that’s why it says considered suboptimal. So the other thing is maybe, again, when we’re talking gut health, I still think one of the best things to consider for folks is upregulating glutathione. And I think, if you do a quick PubMed search, there’s like 32, or four, something like in the realm of low 30 studies have been done on supplemental glutathione. And 30 or more of them have basically resulted in either no effect or very little effect. And I think what the studies show in summary is that yes, the glutathione that you might consume in glutathione format, whether it’s liposomalized or otherwise, reduced, acetyl- or whatever, is probably entering to the system, but it’s not getting into the cell, intracellular, whether it’s the cells of your intestine or into your red blood cells beyond homeostasis. So it’s probably doing some antioxidant good outside of that, but it’s not getting beyond homeostasis into the cell. So we like to recommend precursors.
Lindsey:
Like NAC or glycine?
Bryce Wylde:
You got it. NAC, glycine, exactly. Alpha Lipoic Acid, selenium, a little bit of selenium, or three Brazil nuts a day, non irradiated, organic, if possible, Brazil nuts. But there’s also some interesting ingredients, I think out there worthy of further due diligence by anyone listening to this, and that’s gamma-glutamylcysteine. So some interesting studies out of Australia, taking this gamma-glutamylcysteine, seems to actually upregulate glutathione intracellularly. Beyond homeostasis. So it’s like the direct precursor. Anyways, all of that to say, we’re huge fans of precursors to glutathione. We don’t think glutathione itself is really going to work, it’s probably just going to dissolve in the stomach and in the gut, and not really do. . .
Lindsey:
What about S-acetyl-glutathione?
Bryce Wylde:
Any of those variants, you look at any of those things, and it just doesn’t survive, it just gets taken down.
Lindsey:
Well, it’s a lot more expensive, so certainly easier to get the precursors.
Bryce Wylde:
And there you go, exactly. So in a generalized summary of detoxification and gut health, and methylation and gut health, we’re talking about elimination of toxins, liver-gut axis, microbiome interaction, cellular repair, that’s so huge, immune regulation, all these things factor in neurotransmitter synthesis. We didn’t get into that. But obviously, we look at the whole brain-gut axis and executive function, energy metabolism and methylation. All that plays a role and the interaction between detoxification and methylation oxy toxin elimination, microbiome, I think I mentioned that, hormone balance, we just finished some of that. Both detoxification and methylation influence hormone metabolism and elimination, which can impact various aspects of gut health as well, including motility that we very briefly alluded to, and even immune function. So you’re getting to see how all of these things, you can’t look at any single gene on its own. All of them play a significant interaction, and they need to be looked at in context of pathways. And we’re very proud of that at the DNA company, not just what we look at and how we report on them. But the science that supports these various pathways and pathway interactions, I guess, would be the quick and dirty summary.
Lindsey:
Do you have time for one more question?
Bryce Wylde:
Love it.
Lindsey:
Okay, so this is a little off topic. But one of the reasons I was really excited to have this report done by the DNA company was because in my 23andme results, when I ran them through Genetic Genie, it indicated that I had APOE 4 and 4, which is the worst genotype for the risk of Alzheimer’s. And I recall reading that that meant I had something like an 85% risk of having Alzheimer’s by age 80, but correct me if I’m wrong. So I was waiting for independent confirmation of this. And so I was really relieved when you ran this report, and I saw that I only have APOE 4 and one APOE 3. So can you tell me a bit about this and the degree of difference in risk profiles for 3 versus 4 and what people can do who have the APOE 4 genes and other genes that are relevant to Alzheimer’s?
Bryce Wylde:
Absolutely, yeah. So starting at the top with when we’re thinking about where we’re getting our information from, or that is to say the results of a genetic report, we have to consider where it’s coming from. And ultimately, unfortunately, some of these genetic reporting companies that are involved in looking at a tremendous amount of genes all at once, this is really more of a cost savings iInitiative, or let’s call it a business model. They can’t run small runs of gene sequences. And this gets a little bit complicated, but just save it to say they’re running tens of thousands, so your entire genome essentially, at one time. That’s going to lead to a varying degree of inaccurate reporting. And it’s quite widely available, the literature boils this down, it’s basically 15 to 20% of false positive on the APOE4, so either receiving a 4 or a 3/4 or 4/4 a variation wrong 15-20% of the time. I probably shouldn’t say this, I’ll just use a very famous TV doctor had this done. And we did these genetic tests for that person, very unique, actually, presentation. But I’m saying this because he reported his variations on the air. So but I’m just holding back a little on the story. But at the end of the day, same kinds of situation went down as I’m assuming went down with you is he was falsely reported on. We correctly reported on, and here’s why we’re able to correctly report on these. It’s because we run very small runs, really small batches of genetics at a time, so the chances of making a mistake is very low. When you look at the literature, what you have to understand about these studies, by the way, see, I’m showing you this on p. 4 of the cardiovascular report (p. 45 of the PDF). That’s because we don’t report APOE in context of some kind of dementia report. So we’re not making anything that we can talk about it in context of cognitive decline. Dementia is very relevant to that. But we report first and foremost on this cholesterol carrying capable capability of the apolipoprotein. And that plays a role. But so you look at these populations, and you see, those that have essentially had diagnoses of Alzheimer’s, that were extrapolated, and then looked at, depending on literature, you read, 30 to 40% of those with Alzheimer’s had an assignment of genomic APOE 3/4 and upwards of 70% had 4/4 variants. But you can’t just jump the gun and so quickly reverse engineer that to mean, if I have an APOE 3/4, I have a 30 to 40% increased chance of getting Alzheimer’s. And really, there’s so many different factors involved, as we all know, right? Diet, lifestyle, sleep, can get into so much here. But so there’s a definite association. We don’t report on this as the Alzheimer’s gene. We could talk Alzheimer’s, because having your variation here of a 3/4, there’s implications of again, cardiovascular disease, coronary artery disease, ischemic stroke, and we haven’t talked about the combination. But putting this in combination with the 9P21. It’s definitely a highlight risk for me for you. And it’s something that you want to take away from this report outside of gut health and its implications, is cardiovascular disease. So this is very much an old story of cholesterol being part of it, obviously size, particle size, oxidative cholesterol, how angry it might be and how quickly it might want to deposit within the lumen of the artery lining. But when we combine APOE, as a 3/4 with a 9P21 multiple G, we’re much more concerned about the predisposition of inflammation that warrants the deposition of that cholesterol, right? Does that make sense? So yes, you know that the studies are there. By the way, third ingredient for you, for me, anyway, would be a very bioavailable form of curcumin. And there’s multiple ones out there. I like the liposomal curcumin in this case. It’s all about bioavailability because it doesn’t easily, speaking about the gut, doesn’t easily get through the gut, into the general circulation. So piperine or pepper can help that. But liposomal or micellized. Micellizing is getting it to even smaller, tiny little lipid particle size that can get absorbed easier. So yeah, I’d say with this gene, we like to make these recommendations in combination with other factors, consider that curcumin is advisable for you. But that’s a long way of saying there’s some inaccuracies in certain other companies reporting on this gene. We can’t take it out of context and say it’s a direct upregulation or assignment to getting Alzheimer’s. But at the same time, can you mitigate or do certain things given the rest of the genome pathways that you’re expressing risk. And I think yeah, you can, that’s our whole MO is what can we do through diet, lifestyle and supplementation to tweak or mitigate genetic pathway expression?
Lindsey:
Awesome. Well, this was all super interesting. And I love hearing this about my genes. I wish I could go through the entire report with you, but I will certainly read it more in detail myself. I really appreciate you giving your time to this. And we will include links on how to order your own DNA report from The DNA Company in the show notes.
Bryce Wylde:
I appreciate you having me on.
Lindsey:
Yeah, thank you so much for being here. Any final thoughts?
Bryce Wylde:
I just think understanding our genetics and our gene pathways is an incredibly useful starting point to knowing what more we need to focus on. A lot of people are confused about, if they’re biohacking, or what might be the underlying – we hear this term all the time underlying cause – so you know, obviously genes and environment play a role and how we grew up and all these different things. But I think it’s a great starting point for most people. And if you think about it, it’s a one and done test, which I also love, so you’re spending in, but you never have to do the test again. And it informs on so much more of what you want to put your efforts toward and I think that’s what people are so confused as to where do I start. Well you know, what’s a great place to start the journey, start the process of wellness biohacking. Understanding potentially what other physicians, clinicians, consultants, like yourself, you might want to consider talking to to help you navigate and wade through. There’s so much to know and learn, right, but it’s a great starting point. This is your instruction manual. And if you don’t know it, you’re at a disadvantage.
Lindsey:
Yeah. And I think for people in particular who have very complex health problems that are deep like chronic fatigue or fibromyalgia or some combo of gut issues and mental health issues and something else, that’s the kind of situation where I think that something like this would be useful.
Bryce Wylde:
Can we have time for just a quick anecdote?
Lindsey:
Sure,
Bryce Wylde:
Okay, thank you. So on that note, this is where we see incredible stuff come out of the weeds. So in our clinic and I mentioned this is going back top to the top talking with Dr. Mohammed, I give him such kudos for figuring this out. The light bulb that went off. We had all these young female patients at P3 Health coming in, and you know, what you call out for, what you see more of and do well for, you get more patients, right? So we had all these women come in with chronic fatigue and fibromyalgia and misdiagnosed Lyme and we did well at diagnosing Lyme, still do and couldn’t figure out. It was a huge pool. There was like dozens of these women and again, in their mid to late 20s. Otherwise should be healthy, eating healthy tried everything. Okay. What did they all have in common genomically? I’ll just cut to the chase. They were null variant detoxifiers; they did not have the instructions to properly detoxify. In combination. The two most striking things, there was a third, but it came third, distant third. The second thing, estrogen dominance with estrogen toxicity. So alluded to that a little bit. Third thing, distant third, methylation, poor methylators, but nonetheless poor like terrible detoxification, methyl estrogen dominant, estrogen toxic. This is a story more about what we got them off versus what we gave them. What did we take them off? Birth control pills. They were probably just adding fuel to the fire so they had these predispositions, but they were taking birth control pills, hyper dominant estrogen, not able to clear it. Because that COMT and GSTs are reliant on that information, they’re genetically there to get estrogen out of the body. So just dumping more estrogen, like fuel right onto the fire. So yeah, nine times out of 10, maybe more, taking them off their birth control pill, has solved their chronic fatigue and fibromyalgia.
Lindsey:
Wow. Very interesting. Well thank you so much for your time. This was awesome.
Bryce Wylde:
Thanks, Lindsey. I appreciate it. Thanks for all you do.
If you’re struggling with bloating, constipation, diarrhea, soft stool, acid reflux, IBS, IBD or any type of chronic disease, etc. and want to get to the bottom of it, that’s what I help my clients with. You’re welcome to set up a free, 30-minute breakthrough session with me (Lindsey). We’ll talk about what you’ve been going through and I’ll tell you about my 3- and 5- appointment health coaching programs in which I recommend lab tests, educate you on what the results mean and the protocols used by doctors to fix the problems revealed. Or if you’re ready to jump in right away or can just afford one appointment at a time, you can set up an 1-hour consultation with me.
