A New Understanding of Genetics - with Dr. Ben Lynch | The Empowering Neurologist EP. 63

Hello everybody, Dr. David Perlmutter here. Welcome again to our show, The Empowering Neurologist. You have heard me say this before, I am very excited about today's program. I, I do get excited about these programs. We get the opportunity to I spend time with some really influential thought leaders, and today is no different. We'll be talking with Dr. Ben Lynch, who is the author of this exceptional new book called Dirty Genes, really become a very, very popular book. We're going to talk all about it. Dealing with a very interesting topic, and that is not just our genetics, but really the nuances of our gene expression that may have a bearing on our health, on our longevity, Our ability to resist disease, and more importantly, when we learn this information about our genes, we can make very important lifestyle changes. Dr. Lynch is going to talk us through this, what we can do when we know what our genes look like. And it has to do, of course, with getting a genetic profile through one of the various companies that offers that and really looking at the data, what does it mean, but beyond that, we have some other things in his book that we'll talk about that can give you some insight as to what may be going on with respect to your gene expression. Let me tell you a little bit about Dr. Lynch. He received his Bachelor of Science in Cell and Molecular Biology from the University of Washington and then went on to get his ND degree from Bastyr University. Currently, he is vigorously researching and writing and lecturing around the world on the topic of what is called MTHFR. Many of you know what that means, what methylation is all about, and many of you may not know what MTHFR is all about and will certainly know a lot about it by the time we're finished today. Again, he's the author of this really wonderful book called Dirty Genes. He's also the president and founder of the website seekinghealth.com. A company that's oriented towards disease prevention and health promotion. So without any further discussion, let's just jump into our interview. Dr. Lynch, how are you doing today?

I'm doing awesome. Thanks, Dave. Dr. Perlmutter?

I am totally excited, as I said in the intro, to jump into this discussion. Your book is great, Dirty Genes. I commented on the back. Just talking about how the notion that we are determined by our gene profile is really very out of date. And I want to again commend you for the book because it really brings— it really is very empowering because, you know, you bring to light this idea that there are variations in gene expression over which we have control. So why don't you lay this out for us? What's the big premise behind Dirty Genes?

The big premise behind Dirty Genes is empowerment. It's letting you know the why behind your symptoms and giving you a deeper understanding that you are actually in charge of your genes rather than they are in charge of you. Yes, they absolutely do play a role in how you're thinking or behaving or, or experiencing chemicals in your environment or foods. But ultimately, you are in charge of how they're functioning. And when you understand that these particular genes do certain roles for you, have certain jobs, and you know what those jobs are, then if you don't provide them the right tools, they don't get their jobs done. And when they don't get their jobs done, you get symptoms. And so I teach you how to get the right job done.

And for our viewers, I want you all to know that I have sent my genome profile To Dr. Lynch through his company StrateGene. The website is stratagene.org. Any luck at all, it's going to appear on the bottom of your screen right now. Hey. It's not just that you know what your genes look like through the sequencing, but more importantly, what do these SNPs— and we'll talk about that in just a minute— what do these nuances of your genes mean in terms of your risk for problems, and more importantly, as Dr. Lynch just said, what you can do about it? I'm a lot older than you. I grew up in a time when our genes were thought to be locked in a glass case and determined everything about our future, but it looks as if the ball has been hit back across the court to us to play. So it's a very, as you say, very empowering situation. So this is kind of where you are right now in the world. You positioned yourself as an expert, rightfully so, in understanding these nuances of genes that we call SNPs. Can you tell our viewers what that actually means?

A SNP? Yeah, so a SNP is basically a slight alteration in a particular gene, and all it does is it changes how the gene functions, but not always. I mean, there are actually about a million SNPs in every single one of us, but the majority of them have no impact at all. None. And so this little change in how your gene is produced This little DNA switch, like one DNA, will cause a single nucleotide polymorphism. That's what it's called, right? SNP stands for single nucleotide polymorphism. And if you insert a different nucleotide, i.e., kind of a protein, if you will, it's not totally accurate, but just to keep it simple, if you insert a different letter in your gene, it could change the shape. And if you change the shape of a gene, you change its function. So it— well, you change the enzyme because genes, majority of the time, will make enzymes. And if the enzymes are the ones that do the work, so the, the gene is like the conductor that makes the map. It has the map to make the work get done. And so once the gene is produced, if there's an alteration in how that is made, it will change the shape. So if my hand is shaped like this and you throw me a ball, I can catch it. But if my hand is shaped like this and you throw me a ball, I can't catch it. So that's all you need to know is that SNPs can alter how the gene functions, but not always. And it can either slow it down or speed it up. So it can speed up your genes or it can speed them up or it can slow them down. And it's not bad. It's not bad. It's different. It could be bad, but it also could be good.

Well, before we get too deep and everybody gets really overwhelmed, let me just start by saying that I had my genome sequence at 23andMe, and then I beamed my data, I emailed my data to stratagene.org, and within a number of minutes I got back a beautiful report that demonstrated that I have some SNPs in certain of my genes that I'm glad I know about. Okay. One of the things that I learned is that I am what we call homozygous, meaning I had both things positive for a specific— and I'm going to be technical here as well— MTHFR gene pathway. I've learned about that over the years. It has to do with a process called methylation. But I think that, you know, most people who know you know you in relationship to your expertise as it relates to MTHFR. So tell us, if you will, what MTHFR is all about, and also let's start off by how common are these polymorphisms for MTHFR? In other words, what percent of the population really needs to pay attention to this?

Yeah, well, I would say if your ancestry, your ethnicity is Chinese, Hispanic, Caucasian, or Italian, then you should be really thinking that you might want to be looking at your genes. And if you're scared to look at your genes, then just be aware that the likelihood of you having a SNP like we talked about in your MTHFR gene is pretty up there, like 40 to 50% likelihood. It's pretty staggering in this population. Now, if you have a SNP in your MTHFR gene, as we just discussed, it can slow your MTHFR Gene down. Okay, and I keep saying gene just trying to keep it simple, and I don't want to bring in other words like enzyme. So I'm not 100% correct when I say these terms, but I'm just oversimplifying to keep it simple. So Dr. Perlmutter's MTHFR gene is reduced in function by about 70%. So that means he has about 30% capacity of his gene to still do work. Now I have the same Very similar to Dr. Perlmutter's. I have compound heterozygous, so it's slightly different SNPs, but it still slows the gene from working as well as someone who does not have these SNPs. But it means that he and I both have a 30% capacity for our MTHFR genes to do work. Okay, so what's the work? What does it do? Well, its job is to produce the body's number one form of folate. The main form of folate in your blood. Now you're thinking, well, that's fine. I supplement with folic acid. That's no big deal, and I take supplements with folic acid. Well, not so fast because folic acid is way up here in your biochemistry, and it has to go through actually 1, 2, 3, 4, 5, 6— I'm looking at a map— 6 different genes to get even to your MTHFR. So folic acid is synthetic, it is recognized by the body, but in order to be useful, it has to be transformed. So if, like, think of like Christmas wrapping paper, right? So you've got Christmas wrapping paper, it comes to your house, and you need to use it for wrapping presents. Well, the Christmas wrapping paper is not a wrapped present. It's in your house, but you still have to do the work to put the paper around the box. Well, folic acid is like Christmas paper. You have to— your body has to transform it into methylfolate, and if you do not have adequate methylfolate, as Dr. Perlmutter mentioned earlier, your methylation cycle is not working very well, and that can lead to a whole slew of problems.

Well, again, this is a very, very common situation, and the only way that you will ultimately know is if you have Your gene testing, and I want to I want to get back to MTHFR in just a moment and the whole notion of folic acid versus folate versus taking a methylated folate. But that said, in your book, I thought it was really interesting. You quiz people who maybe don't have their 23andMe or don't have their genetic profile. You offer a series of questionnaires that people can answer and determine might they have MTHFR or COMT or MAOA or B or any. issue with relationship to a specific enzyme pathway. So tell us what some of the things people might check off the box that would then possibly relate to being MTHFR.

Yeah, so this is a— this goes back into the title of the book, Dirty Genes. And so if you can be— let me define that really quickly before I answer your question, which is a great one. A dirty gene is a gene that's not Functioning optimally. That's it. Okay, so a dirty gene is just not getting the work done. Think of it like a, you know, a lazy employee, or you wake up in the morning, you're not feeling as good as you, as you can be as other mornings. So it's just not functioning as optimally. That's all. So there's a few ways your genes can not function optimally. You can be born with an MTHFR SNP, what you received for one copy from your mom and maybe received a good copy from your dad, or vice versa, or maybe you received a SNP from each of them. Like Dr. Perlmutter did, and so did I. I got one bad copy from my mom and my dad, but they're not really bad, they're just different. Or you can be born with perfectly fine MTHFR. Your mom and your dad passed you a perfectly fine MTHFR gene. There's no SNPs at all. It can get dirty. So when I ask the questions in the book, I'm seeing if your MTHFR is dirty. And I don't really care how it's dirty, if it got born dirty or got dirty. I don't care. So questions are like, you know, if you look at your family history, do you have a lot of bipolar disease or schizophrenia or mental disorders? Or is there depression? Is there mood fluctuations? Is there high homocysteine? Is there cardiovascular risk? Is there infertility? You know, preeclampsia? Do you take folic acid supplementation? And Do you eat your leafy green vegetables or not? So, you know, do you consume liver? So these types of questions give me an inkling right away to see if your MTHFR gene is dirty, and if it's dirty, then you need to clean it up.

Now, MTHFR, which I have, is the pathway that is responsible for what we call methylation. The biggest concern for me and for you and other people who are MTHFR at risk because of these SNPs is that we might not methylate our genes as we should. Can you walk us through what methylation means and why it's important that we're all good methylators?

Yeah, it's really important. It has very significant importance in certain— well, all through our life it's super important, but when you're pregnant, It's very, very important. So when you— you know, you know the RDA, the recommended daily allowance of folate. Unfortunately, it's folic acid, but folate is 400 micrograms a day for the general person. But in pregnancy and breastfeeding, it's doubled. Well, why is it doubled? Well, it's because the woman is methylating a ton. And so she's methylating not only for her body, but she's producing an entirely new organ, the placenta, and she's developing a whole new baby in her uterus. So the amount of nutrients that she needs— In order to methylate is staggering. So that's why you see the requirements go up. So what is going on? What does that mean? So methylating is simply an action, and it's taking the body's simplest compound, a methyl group, a carbon and three hydrogens. Who really cares? But that's what it's taking, and it's performing an action. So when you see -ation at the end of a word, it's performing an action. So it it's it's taking a methyl group and it's putting it onto something. So the majority of methylation. in terms of genetic function is used to actually quiet your genes. It's telling them to turn off. Okay, and that's really, really important because, you know, we have nucleus in most of our cells, not all of them, but we have nucleus in most of our cells, and that houses our DNA all coiled up safely and secure inside the nucleus, which is inside the cell membrane. But we don't want to have our genes working constantly because they have different functions. I mean, I have genes in my arm for eye stuff and heart stuff, but they're turned off, right? So methylation turns that off. So methylation's primary job is to keep your genes quiet, and then they will— methylation will also turn some genes on. Now, outside of genes turning on and off, methylation also does 200 other things in your body. which is staggering. And so just, just to tie this into MTHFR a little bit, if MTHFR's job is to make methylfolate, and that's its job, and then methylfolate is your number one form of folate in your blood, and then methylfolate goes to support your methylation, well, if your MTHFR isn't working, then your methylfolate levels could be low. They're not necessarily low, could be low, and as a result, your methylation is low. Now your genes could be firing, but on and they shouldn't be, or you could have 200 other reactions not performing. And 200 of these other reactions, I'll talk about some really, really big ones for you right now. One is your cell membranes. Your cell membranes are produced by methylation. Every single one of your cells has a jacket around it called a cell membrane, and these jackets house receptors and signals, and they take impulses from the environment. They bind vitamins and minerals and sugars and hormones, and they pull them into your cell to create actions. If your cell membranes are dirty, are not functioning well, then you've got significant problems. A lot of methylation is going towards producing phosphatidylcholine, which is what your cell membranes are made of. About 80% of your methylation goes towards that alone.

There is a— I don't know if it's a tendency, but the way that people seem to talk about MTHFR at times would almost make it look like it's some kind of disease. Right. I really want to get the notion out that it is not a disease. It's simply a variation, and because of this variation, there are things that a person needs to do to methylate because methylation, as we've just learned, is so darn important in terms of forming our cell membranes, in terms of keeping our homocysteine levels low, detoxification, you name it, a lot of functions. So, I don't surely want to stigmatize people, and that'd be half the population or so, who may have some mild deficiency or significant deficiency in this whole process of methylation. And it takes me to a place of, okay, you have these SNPs, either you're homozygous or heterozygous. In my case, and I think in your case, we're homozygous, meaning— Uh-huh. It's not necessarily favorable. But how might you know if then you're taking the right supplements because you know you have this predisposition for not methylating appropriately? What are some of the things you can look at on your blood work to determine that you've done a good job in overriding this potential problem?

Yeah, that's a great question. And, you know, I love your comment that MTHFR is not a disease, and that's what happens. You know, people get their genetic results back and they see that they have MTHFR. Maybe that's the only gene they tested, and oftentimes it is. You know, maybe they had recurrent miscarriages or infertility and their OB said, okay, let's run MTHFR, and they did. And you get it back and you're like, oh gosh, that explains why I'm not fertile or why I'm having pregnancy complications. Well, not so fast. It could be, but not necessarily. So it's not a disease. It's not something that we run out and fix. You know, anytime we see a potential problem, the first thing we want to do is force a solution to it. But first, you have to see if there's a problem, and that's where the quizzes in Dirty Genes comes in, and that's why you're bringing up labs, and that's important. You know, the appendix of Dirty Genes, there's a whole series of labs that you can order and why. And so, in the MTHFR chapter, a couple of the labs I recommend are homocysteine. Homocysteine is readily available by doctors. It's understood, but I will have to say that the range of homocysteine is not entirely They— if your homocysteine is 15 or, you know, above 15, standard medicine will say, oh, that's too high, you got to lower it. Well, if you look at research, they show that anything right around 6 is ideal, you know, depending on what paper you want. So you kind of want to have your homocysteine levels around 6, 7, 8, and that's looking pretty good. Now, the problem with just looking at homocysteine in isolation is what if you're not eating enough protein? What if you are not consuming enough cruciferous vegetables or consuming enough glutathione, or maybe there's high amounts of oxidative stress? Your homocysteine— nobody really understands this— homocysteine isn't bad. You have to have homocysteine. So if your homocysteine is like 3 or 2 in an adult, that's a problem too, because homocysteine helps support your methylation, and homocysteine is one of your building blocks for your body's number one antioxidant called glutathione. So you want to check your blood levels for homocysteine. for homocysteine. That's one. Another one you can get a lab that's very inexpensive, it's called Organic Acids, and you want to look at your riboflavin. And your riboflavin, there's a, there's a marker there, and I'm forgetting what that specific marker for riboflavin is, but it's in the appendix. And if it's high, the marker, I believe that's a riboflavin deficiency. And why riboflavin? Well, vitamin B2 is riboflavin, and that's what your MTHFR enzyme needs in in order to work. If you don't have enough riboflavin, MTHFR isn't going to work. Whether you have a SNP there or not, it's not going to work.

Interesting. You brought up a very, I think, very fundamental point, actually 2 points. First, that what the lab says is so-called in the normal range, and our viewers are well aware of this, it's not necessarily what you want to go for. For example, If vitamin D normal is between 30 and 100 and you're at 31, you're supposed to feel like, well, I'm in the normal range, everything's great. Similarly, blood sugar of 90 to 105, our viewers know that that is not good enough. We want optimal. Right. We want optimization of all these parameters, and lower blood sugars than that are better. The same thing, I think, with homocysteine. The normal range is really average. It's what, you know, is developed by looking at thousands and thousands of lab results and then doing 2 standard deviations saying, well, that's pretty much what everybody has, so we're going to call that normal. And it's certainly not good enough for our viewers. We want you to have the best. So, we talked about homocysteine in Grain Brain 5 years ago about being a risk factor potentially for things like cardiovascular disease. and Alzheimer's disease, and unlike carrying, for example, the APOE4 allele, our viewers know all about that, that's a genetic determinant to a significant degree in terms of risk. You can lower your homocysteine, you can do it today, but you're not going to know where your starting point is unless you get the blood test. So that's why—

Uh-huh.

Having a homocysteine. Hemoglobin A1c directly relates to brain shrinkage over time. These are valuable blood tests. I also want to get back to the notion of, you know, the whole sweet spot in terms of how we look at things. I mean, there's a real notion in America that cholesterol is bad, the lower the better. Right. And we see efforts to lower homocysteine— I mean, cholesterol into the toilet. I mean, it's just breathtaking. I recently did a video blog. Our viewers will remember about sleep. We know that less than six hours of sleep is not good for your brain. So you think, well, I'll get ten, eleven hours. Well, it turns out that anything over nine hours is actually out of the Goldilocks zone as well. So I want to get to this point then about you know an individual like you, like me, gets these results back. So now what? What is my next step? I know that I have the MTHFR. I'm homozygous for the C77 polymorphism. What should I— what's the next step you'd recommend to somebody?

Well, the next step is awareness. First, I always like to inform people what the gene's job is. If you understand the work that each one of these genes performs, then you will understand what it also requires in order to perform the work. And so, just purely education. So, MTHFR's job is to make your body's number one form of folate, which is methylfolate. In order to do that, it needs riboflavin. And you can get riboflavin from nuts and seeds, and you can also get— and other foods— and you can also get good, healthy forms of folate from salads, leafy greens, and liver. Make sure it's from, you know, Calf livers and organic free-range preferably. And so that's, that's in a nutshell. And then you need to understand that, okay, well, its job is to make methylfolate. Well, what is methylfolate used for? Well, it's used for methylation. All right, so what hurts methylation? And so I talk about methylation before I even get to MTHFR in the book because you have to know what that means first. Yeah. So, and you learn that certain things will tax your methylation like yeast overgrowth, heavy metals, reactive oxygen species or free radicals, low glutathione, which I'm sure you talk about a lot. Then you can also have alcohol, which also forms acetaldehyde. So these things will tax your methylation and require higher levels of methylfolate. So my, my thinking is I'm all about efficiency. So we have 30% capacity of our MTHFR gene to work. We don't have to be supplementing with methylfolate. We just need to make it not work as hard. So let's not make it not work as hard. So I decided to say, well, I don't drink. I cut that out. If I cut down on my carbohydrates, then I cut down on my reactive oxygen species, my free radicals, and I conserve that. I also conserve my glutathione. And I also am less susceptible to yeast overgrowth, which also slows the methylation cycle down. I also avoid heavy metals. I don't eat farm-raised fish, period. I don't eat it. I limit my intake of tuna significantly. I filter my air. So I— and I check my supplements. I look at certificates of analysis to make sure that there's no, you know, very low levels of heavy metals, because heavy metals are pervasive now in everything. So I'm all about understanding it from that level. And I believe that supplementation is very useful, but it's, it's like the end. You know, I, I discussed yesterday on an interview, and I used an example for the first time. Dr. Perlmutter, everybody knows not to sit in the garage with the engine running. They all know that. It's because you're sucking down carbon monoxide and all these chemicals, and you can suffocate and die because it blocks the oxygen. So what's, what's happening is most people with MTHFR are literally— not literally, but they're, they're like sitting in a car with the engine running, and then they're taking supplements like an oxygen mask and putting it on for a second while still smelling the exhaust. You know, it's shut off the car. So that's how I like to use it first. And then once you've done that, if you feel that you need additional support, then you can supplement, but only after the basics are done.

Well, I think you talked about The carbon monoxide analogy is actually very good, and I think when you were interviewed by Mike Mutzel, you were talking about how aggressive that— this artificial folic acid can be in terms of binding to the receptor more so and keeping folate from binding to its receptor. You used the analogy, I think, of oxygen and carbon monoxide, how much more aggressive carbon monoxide is at binding. Yes. to the 4 points of binding in the hemoglobin molecule. That said, we support methylation in our food choices. We want to have cruciferous vegetables. You've talked in another interview about hard-boiled eggs and how they smell when you open them up because of the sulfur, but helping with detoxification, supporting that sulfuration pathway. But that said, in terms of methylation per se, we know that there are other supplements that people are taking— dimethylglycine, methylated B12, for example. What other things can people who want to enhance their methylation and want to revert to at least take a safeguard supplement— what should they also be looking at, or could they be looking at?

Well, you brought up some big ones there. I mean, you brought up methylcobalamin, which is a major one. There's betaine, which is also trimethylglycine. DMG is also useful, but DMG can actually slow down the gene called BHMT, and if that's slowed down, you're actually— homocysteine can go up. So, and that's according to research as well. So if you're taking higher levels of DMG, just, just know it's not necessarily going to happen, but your homocysteine levels can go up because of, you know, feedback inhibition. But vitamin B6 is another one. The, the only way your homocysteine is eliminated by your body is through an enzyme called CBS, a gene called CBS, and that requires vitamin B6. It also requires iron. It's an iron-containing gene or enzyme. So you need vitamin B6 as well, and you need to have sufficient glutathione because if your glutathione is, is not working right, your methylation cycle stops in order to produce glutathione. It's, it's a pretty cool system. So if you have adequate glutathione, your methylation cycle will zip, zip, zip around. And as soon as there's a— there's like a little sensor in the really key gene called methionine synthase, MTR, and it's— as the hydrogen peroxide levels go up, this gene will actually turn off, and hydrogen salt— hydrogen peroxide will stimulate the CBS, take the homocysteine and turn into glutathione. So that's pretty neat. Another one for supporting methylation is choline. And choline does go to betaine, which goes which is TMG, which goes to DMG. But 90% of pregnant women, according to some research papers, are deficient in choline. 90%. And this one researcher, I forget his name unfortunately, he does a lot of choline research, but he did an amazing study where he took pregnant mice and he gave them some choline, and then he gave them, you know, another set more choline, another even more choline, and then he checked their babies and how they performed in a quiz because the rats remember where the cheese— you know, which ways they need to go to get the cheese. And as they age, he'll keep quizzing them to see if they've gotten more forgetful. Well, the pregnant mothers who had more choline during pregnancy had babies which grew up all through their life, they had no dementia. None. They had no decline in memory, and the mothers had higher levels of choline. And what you need to know about choline, what's really cool, is if your folate levels drop, your choline requirement goes up. And as your choline requirements go up, your folate levels drop, because choline and folate kind of have this tag-team relationship. And so folate you get from your leafy greens, choline you get from your meats mainly. You can also get them from beet and quinoa. But mainly from meat. So vegetables providing methylation, but also meat, which is really interesting if you look back at our ancestors, what they ate. I mean, if, you know, if our ancestors were in an environment where they had a lot of veggies, maybe they had an MTHFR variation because they got their methylfolate from the veggies.

Yeah, I was going to ask you that. I mean, if it is such a bad thing, then why would it have persisted as, you know, in our society today? Why would we have so many people that carry these polymorphisms. You touched upon something just now that I think is really intriguing, and that is our ancestors who— we're all told these days that women to become pregnant or when they're becoming pregnant should make sure they're taking a folic acid supplement. As you pointed out, that might not be their best choice as opposed to taking folate, but nonetheless, having low levels is associated with spina bifida, a neurodevelopmental issue. which can be minor and of no consequence, or it can be a cause of paralysis. So, that said, one wonders then in our more paleo times, if— what was it then that was the resource that women had? And as you mentioned, certainly vegetables, but I think it's important to note that virtually every species of Bifidobacterium in the gut Hmm. So that we're making this in the gut, and having a healthy microbiome is a wonderful adjunct in terms of amping up folate availability, vitamin B12 as well, although there are some individuals like yourself, I think, who have called into question the ability for us to utilize the type of B12 that our gut bacteria manufacture. Correct. To a significant degree anyway. Now, we've been talking about MTHFR, which downregulates or turns down the activity of enzyme systems. There are some SNPs that are part of your report that actually, when you carry these SNPs, are associated with turning up the activity of certain enzymes. And let me, if I may, focus first on monoamine oxidase A. MAOA is one of the parts of your report. So in that result, it indicates— and I noted it in my results as well— that I have upregulation or turning on of the activity of MAOA. So what might that do biochemically, and what might that do clinically? And third, we'll get to what then should I do in terms of my choices.

Right. So as you mentioned, there's And we talked about even the beginning of this is, you know, a SNP can speed up or slow down or make no difference at all in how your genes work. Now, in this particular gene, MAOA, its job is to process monoamines. And one of the monoamines is serotonin. That's a big one. And it also does epinephrine and norepinephrine. So, but monoamine A, if it's quicker, It can do its job quicker, so it can burn through your serotonin faster. So you're thinking, well, that's— that could be good. Well, it can be good. It'll help you fall asleep quicker. It will help you calm down in more stressful situations. It will help make you more calm in general than someone who has a slower monoamine oxidase, or MAO-A. So it tends to have you be able to be a more calm person. More collected and fall asleep faster, and it will probably also help you. You know, I think MAO-B works with tyramines and other things, you know, histamines, so I won't bring up those for MAO-A. Mm-hmm. But so the flip side is, well, if it's faster, then you can have lower serotonin. And, you know, there's the— you know, you look at drug companies, they're talking about SSRIs, selective serotonin reuptake inhibitors, or MAO-A inhibitors. So MAO inhibitors, they will slow this gene down in order to keep serotonin levels higher, but they don't really always work for various reasons. But so these people are taking MAO inhibitors in order to reduce their depression. Well, that is one of the susceptibilities to having a faster MAO-A is symptoms of depression, you know, a little bit of gloom. And another one is That you are susceptible to waking up earlier in the evenings. You can fall asleep, but you don't stay asleep. And the reason is your serotonin moves to produce melatonin. So a component of melatonin production in your body, it requires your serotonin. So if you have lower serotonin levels, by default you're gonna have lower melatonin. So you're like, wow, you just described me that, you know, I tend to be calm and collected. I do somewhat get depressed at times, and, you know, sometimes I wake up in the evening and You know, earlier than I want to. And you also, in order to build serotonin, it requires tryptophan. And tryptophan comes— it's found in meats, yes, like turkey and so on, but it's— you don't really get the tryptophan from the turkey because of absorption competition. So you get tryptophan mainly when you eat carbohydrates in isolation. And so if you find yourself carb binging, then you, you feel a lift in your mood and that could be also a faster MAOA. And so that, that is a potential issue because you, you gravitate towards carbs to improve your mood, and but you're also increasing inflammation. And you've been watching Dr. Perlmutter's work for a long time with Grain Brain and say, okay, I'm gonna cut out these carbs because I don't want the inflammation. Well, that's great, but for folks like Dr. Perlmutter and myself, I have a faster MAOA as well, and We can tend to get— I tend to get depressed at times, and I even tried the ketogenic diet. I did it for about 6, 7 days. I didn't check my ketones, but I was high fat, moderate protein, and very low carb. Then I felt like a loser because I was gravitating towards carbs, carbs, carbs after about the 6th, 7th day because I was starting to get gloomy, and my sleep was struggling. I wasn't sleeping through the night. There's a lot of nuances. I'm oversimplifying it, but those are some key things to It's really important to know about, and the cool thing is you can support this too.

Well, that was the next question, but let me just say that there are a lot of things that can help compromise the availability even of tryptophan to make serotonin. The kynurenic acid pathway, for example, which is induced by inflammation, by disruption of the microbiome, by eating foods to which you're sensitive, having lots of gluten in the diet. Various medications, having a high hemoglobin A1c, glycating our proteins, leading to inflammation. So there's a lot of convergence of lifestyle choices that can ultimately lead to increased mood issues that then tend to be feed-forward, meaning now you feel crappy and you're not paying attention to what you should be doing to pull yourself out of the ditch and continuing to eat those foods that increase inflammation. And further lower your ability to convert tryptophan into serotonin. Sometimes you got to jump off the merry-go-round a little bit and reestablish some balance in biochemistry. Then what is our next step? We have this issue where we have MAOA overactive based on our results from the StrateGene test. What do we do?

Well, you brought up a huge point, Dr. Perlmutter, of how your tryptophan can get Stolen. And there's actually— if you look up tryptophan steal in the research, that is actually what they call it, which is pretty cool. So tryptophan can go to make your serotonin, and if you have a fast MAO-A, you're burning through your serotonin. But if you have a tryptophan steal, you know, from infections, inflammation, and stress, then your tryptophan can't even get to your serotonin. Your tryptophan is being stolen. And so now your serotonin levels are dropping because of infections and stress. So I tell people, well, calm down. That's easy to say, and people hate hearing it, right? They just like— everybody keeps hearing that, but I give you great ways.

Reduce stress in your life. Yeah, right. You don't know what my life is like.

Right. And so it's, it's, it's so patronizing, but I hear you, you know. And, and so there, there are ways to reduce stress. So I And I share a lot of those in the book as well that I personally do because, you know, I'm a fast-paced guy, I'm driven, and I get stressed out. So you, you really have to harness that though. And then you have to reduce the inflammation. Well, you hear that all the time too, and— but there's ways to approach that. So, and then you have to— if you have infections, there's chronic persistent underlying infections that a lot of people struggle with that get missed. And so what they do is they go through life with their headaches and their fatigue and their, you know, you know, psoriasis or eczema, and they focus on their gut and other things, but they don't really look for hidden viral infections or Lyme or molds. And then they continue to have tryptophan steals, they continue to have depression, and then they look for supplements and they look for meds to support that. And while they work, they still feel fatigued and their skin is a mess and they're still not working right. Let me, let me share something about the tryptophan steal a little bit. Where in terms of how, you know, why the body is doing this. And it's pretty interesting because if you're happy, what do you tend to do? You tend to be more outgoing. You tend to go out and do things and be more active. Well, if you have an infection, then your body doesn't want you running out and being more active. It wants you to lie flat. Don't be around other people. And recover. And, and by being depressed, you tend to be away from other people, you tend to be less active, and you have more energy to fight the infection. The problem is we have chronic persistent infections because of our diet, our lifestyle, and we're not getting adequate sleep, and we're surrounded by Wi-Fi and other things. So we have these constant assaults. So I think that is why there's a tryptophan fan steal. Again, the body is not doing this to harm you. It's doing this for— because it's been selected for for thousands and thousands of years.

Well, it doesn't take much to influence the pathway. I mean, 95% of tryptophan is diverted away from making serotonin. If we're only on a good day with a tailwind going downhill, using 5% of our tryptophan to make serotonin, it doesn't take very much to have an impact. Right. And, you know, we've all seen that people can get sick, whether— I mean, right now there's a big flu thing going on, whatever, any sort of illness, infectious illness, anything that's going to raise the level of inflammation in the body really has an effect upon mood. We all go through that. You feel crappy when you're ill. So you're right, that might be a very good protective mechanism. Let's talk about, if we can, what StrateGene is all about. And as an entrée, I would indicate to our viewers, I had my 23andMe data looked at by StrateGene, and I'm hugely happy that I did so. It's not 100% the results I would have wanted, but it's 100% satisfaction on my part because I know this stuff now and I know what I can do about it. But tell us what went into StrateGene, why you did it, and what people can

expect Yeah, well, there's, there's a lot to StrateGene, and first, I made StrateGene because I was sick and tired of the current genetic reports out there. I did not actually want to take my time to make StrateGene, but I, I felt compelled to do it. And it's because what's happening is people are getting their 23andMe reports and they want more information, which I totally get and appreciate, but there's a lot of reporting companies out there that are Just taking the 23andMe raw data and they're making these massive reports and they're just showing reds and yellows and SNPs all over the place and like 70 pages and then people immediately look for the reds. They're lost, they're confused.

And worried.

And worried and scared and then they're told, you know, how bad each one of these are and then there's— the thing is, is remember I said that each of us have a million SNPs. But very few are actually clinically relevant. So StrateGene, it's not like we're holding back on people in terms of the amount of SNPs that we report. We report the SNPs that only have research and data on them. So there's no point in running an 80-page report if you have no idea what the SNP does, if it has no impact, faster or slower. You're guessing. And that's what's happened. There's a lot of theory that is being thrown out, conjecture and misinformation. So... So, StrateGene's job is to help neutralize that and get people on the right track, and using clinical experience and also the National Library of Medicine, PubMed. So, we have a full bibliography. So, everything that is written on StrateGene, unless it says otherwise, and it will, is from research, which is a huge difference.

One of my reports— entries indicated that I was— I had— I was heterozygous for one, I think, or two of the vitamin D receptor polymorphisms, meaning that I, I take it to mean, correct me if I'm wrong, that my ability of my vitamin D in my body to bind to the receptor and then to do what that receptor is supposed to trigger might not be as effective as it could be. That's fair? Right. So, that said, for all of you guys who I have been talking to you about vitamin D all these years for other reasons. You know, the fact that it stimulates in the brain an antimicrobial peptide, the vitamin D receptors in the brain, all the great things that it does in addition to the association of low vitamin D with things like Alzheimer's, Parkinson's, multiple sclerosis. So, I was gratified that I've been hitting the vitamin D over the years, but you know, you might, with that result, think maybe a little more might be better, following of course your blood levels with your healthcare provider. So I also found that to be very helpful. Is there any company that you're aware of that looks at the 23andMe data and gives out the BRCA gene information?

Um, you know, I don't know. I don't know. I've— I mean, I could have pulled it into StrateGene, but I didn't because I feel that it requires genetic counseling. I— we exclude genes that are really fearful like that. It's not my job to report that without, you know, someone sitting next to that person. So

I'm very glad to hear that. And yeah, because you can look at, you know, one of the things that you do report and is also reported on the 23andMe are the APOE genes.

Yes.

And we've talked about, you know, the fact that carrying the APOE4 allele, which is in 20 to 25% of Americans, is associated with increased risk for developing Alzheimer's disease and also coronary artery disease for that matter, but it doesn't mean that you will, and it also doesn't mean that not carrying that allele means that you won't get Alzheimer's. So you can get it even if you don't have the so-called Alzheimer's gene. Well, what I think we are learning, as many of you recall the interview we did with Dr. Dale Bredesen, that even if you carry a specific gene, in this case the APOE4 allele, there's a lot to do to offset what that gene profile might increase your risk for. So this is a great example of knowledge is power, and again, I want to walk our viewers through the process. You get your 23andMe, which is wonderful. You submit a salivary sample and you get back your 23andMe. Then what you do— and they'll give you some great information there, but— You need more. You take that information, when you go on the 23andMe site, you ask to download your raw data, and you can. They'll email it to you. It takes— I think it took an hour. And then that is the file that you forward to stratagene.org. And I got my results back in, I think, in 10 minutes. It was great. Wow. It's all good to know. That's, I think, what Dr. Lynch is telling us today is you can't really act until you know what— who the players are. Right. This is terrific information that gives you what should you be doing, what you should favor in your diet, in your other aspects of lifestyle, and supplements as well. This is a great example of empowerment through knowledge. The system is you take your 23andMe data, and then StrateGene takes that data and gives you a report so you know much more what to do. You did a great job. You really did a great job.

Thank you.

I was delighted to read your book and endorse the book. I think this is hugely empowering information. I grew up at a time, as I mentioned in the intro, that we all thought we were at the mercy of our genes. That they were holding the strings of the marionette. We now know quite the opposite, that more than 70% of the gene pathways that code for health and longevity are under our control to varying degrees. I think you made that very, very clear. You did a heck of a job.

Thank you, Doctor. Appreciate that.

Folks will be seeing all these links, websites, etc. I'll show you this in the closure, but there's the book. Dr. Lynch, I hope I get to see you soon. I'll make my way out west, and I'm going to track you down.

All right, appreciate that. Thank you.

Okay, bye for now. Well, that was really exciting. Dr. Lynch is such a wealth of information, and how empowering it is to know that we can change our destiny with respect to expression of certain gene pathways, these nuances of gene pathways that we call single nucleotide polymorphisms or SNPs, and very important one being the MTHFR SNPs that are involved in the processing or actually methylation of things like folate. We know that's very important based upon our discussion today. Again, the book is Dirty Genes and it's an excellent book. I very, very strongly recommend it. As you know, I did recommend it on the back. So thank you all for joining us today. Hope you enjoyed the program. I'm Dr. David Perlmutter. Bye for now.