Unlocking the Secrets of Nutrigenomics - Episode 350

that you eat and things that you do can help turn genes on or off. So that is the nutrigenomic, or that is the thing that you will never be able to measure in other tests. So if you eat broccoli sprouts, it's going to turn the, the sulforaphane that you get from broccoli sprouts when it digests will be helping to activate your oxidative stress systems, your antioxidant systems, and your detox systems. So little things like that that you can really be quite specific about.

Today I have the honor of talking with Annaliese Smith. She works with an organization called 3X 4 Genetics or 3x4 Genetics. She's a nutritionist by trade, but, uh, has really kind of progressed into the genetic space. And we talk a lot about systems biology in this conversation, which I think is quite honestly the hottest topic in medicine at this point in time. And you're gonna see how this weaves itself into concepts around nutrition, hormone replacement. I think you're gonna find this a really interesting conversation.

He went from saving hearts as a cardiologist to rewriting the entire aging playbook. Dr. Jeffrey Gladden believes 100 is the new 30. And he's got the science to back it up. This is the Gladden Longevity Podcast.

Welcome to the show, Emily.

Thank you very much.

Yeah, it's good to have you here. So let's talk a little bit about how you got so involved with genetics. Um, you've gone on a path with nutrition, some other things, as I saw. And, um, what led you into this, uh, area?

So I, yes, I'm trained as a dietitian and I worked for many years with my patients in my private practice and found nutrigenomics quite early on, maybe already 20 years ago. I, I went to a talk and was quite interested and I found myself just being able to go to more talks because I'm in South Africa. So there was a company who started out here and I just managed to learn a lot about it at the time and working with the company. And in my practice, I found that that was a really interesting thing to follow because I, as a nutritionist or as a dietitian, it was often really hard to tell if you're on the right path because you are trying to put the whole recipe together and there's not too many tests that you can do to figure out, you know, you can obviously do blood levels and things, but in nutrition, you want to often be more preventative. So, when I started working in genetics, it was really a place that I found it gave me more confidence to know what I want to look at, where vulnerabilities are, and to take it forward. So, I started in those days just looking at nutrigenomics. And then as time went on, learned more about it. And then about 10 years ago, started really digging into it. And I think there was quite a big wave in nutrigenomics then and found myself where I am today.

Okay. Yeah, our courses kind of parallel each other a little bit in that I think I got really involved with it in about 2014 in terms of looking at it. I was impressed because, you know, one of the problems I think with diets in general is that they all start with the food instead of with the individual. And so, understanding, yeah, maybe it's a good food, but maybe not as good food for this person, right? So, being able to sort that out, I think, lets us some higher degrees around precision. And I think if you're listening to this, there are a million diets out there. And the real question is, what's the one that fits you? And it's not the easiest thing to figure out. You've got to really kind of understand your genetics and your gut biome, your gut, your digestive system, how you're digesting foods, whether you're digesting them appropriately. Then, you got to understand the immune system and inflammation and things going on there, interactions with foods. And then, back to the genetics again in terms of what nutrients you need and what quantities to make everything work well. So, it's actually a complex field even though people tend to gloss over it and say, "Well, it's about macros or it's about this and that or whatever. It's really quite interesting. So you're now working with a nutrigenomic company, it looks like. And they're doing some interesting things, right? 3x4, if I'm not mistaken.

Yeah, that's correct. 3x4, like your ex-girlfriend.

Yes.

Yeah.

So tell us a little bit about that journey. How did you get associated with 3x4, 3x4, whatever.

Yes, it's quite interesting. So I, when at the time that I was really interested in nutrigenomics, there was nowhere to go. I just didn't know where to study because you can study genetics. But nutrigenomics was quite a new field. And getting that translation down exactly what you were saying now to finding out, it's not just one SNP, right? It's not that there's a diagnosis, you want to be looking at groups of SNPs or gene variants, how do they influence metabolic pathways, how do these metabolic pathways influence each other. And so, like you said, it actually can become quite complicated. And at that time, I was so interested in that, I just knew I just didn't know what I was doing. So I thought I needed more help. And I found Dr. Yael Joffe, who at the time was testing it. She was building genetic tests, and we decided to start a clinic together in Cape Town. To have people come to us who wanted to know more about their genetics. And we started there. And as time went on, we, we realized that we, the test we were using was just a list of SNPs for us, and we were doing a lot of other things with it. And so 3x4 was born out of really frustration as clinicians to see what, you know, sort of we were building spreadsheets and putting SNPs into pathways. So we really used a systems biology approach. And so that's where the test started. And I've, so I'm just a founding member.

Yeah, got it. So you've touched on a couple of really important things here. I think, you know, a lot of people have had their genetics tested and the reports they get back are basically with SNPs, S-N-P, little s for plural. It's a single nucleotide polymorphism, essentially. And so it's basically the way we think about it is it's the configuration of the gene. It was kind of, you inherited half of it from mom and half of it from dad. Don't necessarily know which half came from where, but it can predispose you to, you know, either tolerate a food or be intolerant of food or need a food or need a nutrient.

Yes.

Need less of that nutrient or need a very specific kind of nutrient depending on the configuration of each of those SNPs. So to your point, when we started all this, it was looking at each individual SNP and trying to make sense of those and then kind of in our minds weave those together into an integrated plan. You introduced a second idea which we're incredibly enamored with here, which is a systems biology approach to longevity is how we're looking at it through really the 5 different circles that we look at: life energy, psychospiritual space, longevity itself, the hallmarks of aging, health. Of course, all the organ systems and subsystems, and then performance, which is being fast, agile, strong, et cetera. And then, the environments where we reside in and integrating all of those into sort of the ecosystem for the individual. And, of course, a piece of that is genetics filters across all those circles, how you handle toxins in the environment, what kind of athleticism you're best at, things like that, certain health predispositions, dispositions, predispositions around managing some of the hallmarks of aging like mitochondrial function or oxidative stress or inflammation or things like this. And then Life Energy has SNPs that are incorporated there too with anxiety, depression, things like that, how you handle those things. So, it becomes rapidly very complex when you're looking at, you know, hundreds of SNPs and you're integrating them across, in at least our world, 5 different circles. And then looking for what I call the elegant solution where you basically are looking for what's the minimum impact or what's the minimal input that we can have to get the optimal output, right? Because it's easy if you just line up all the SNPs to end up with 100 pills, and that's not necessarily— or 100 recommendations— that's not necessarily what a person can actually implement. So, the systems biology approach, I really think, is the future of medicine. And instead of slicing everybody up into their, you know, composite organs, if you will, we can look at them as an entire system. So, I really applaud the fact that you're doing this. The way we're doing it is with AI. I'm curious how you're doing it on your side. It may be a lot of clinical expertise and, you know, limiting the field of view to where you can actually manage that and do things, or I'm not sure what you're up to, but maybe you can explain that to us.

Yes, so that has changed quite rapidly, hasn't it? So I guess what we have done up to now is built those gene variants into, like I said, pathways. So we start upstream, so we're looking at cellular functions, which you've mentioned, which would be sort of things like oxidative stress, inflammation, methylation. So how these genes influence those cellular processes. And it's really important to be able to look at genetics to, to see where your vulnerabilities are in those processes. So like you said, if you want to start figuring out where you want to start, which would be your, like you say, your minimal for your maximum output, that is often always a good place to start. And then moving into how the systems speak to each other. So if we think about what my favorite topic at the moment is, the neuroendocrine axis, is where you think about— it's not just that hormones are declining, for instance, as you're aging, is also what's happening on a neurological basis. So how do these— the manufacture, the transmission, and even the breakdown of those neurochemicals are influenced by genetics. And so when you know how that's happening, you know how it's going to influence all your HPA and HPG and HP— T accesses. So that's a really great idea to, to know where your vulnerabilities are and to start there. And then, like you say, instead of having— otherwise everything looks important, doesn't it? Because there's so many ideas out there. So you want to know for that individual where would be the best place for you to start. If it's, let's say, I want to influence the synthesis of this neurochemical because I can see that the dopamine is low and that's influencing the ability to have, or you might have too much cortisol because I'm just using as one example. So it really helps you build that puzzle and not waiting for things to show up in labs or even in symptoms that you can work in that manner to, to support the individual early on.

Yeah, I think that's right. And then in our world, there's another layer of complexity, probably in yours as well, where we're actually measuring hormone metabolites and breakdown products and things like that. And what we found is that just because you have a genetic pathway for a hormone doesn't always mean that the levels reflect that. In other words, there are other things in play, right? So it can become a very complicated sort of rainforest of things that are all interfacing and interacting with each other that ultimately produce the final output. So it's a really, really cool space. I'm so excited that with the advent of AI, we finally have enough sort of compute power to actually start to bring this forward in a meaningful way for people.

So yeah, so I was thinking while I was answering you, what was your question? You wanted to know about AI. So yes, so we obviously started off building those things and now with AI, we can generate recommendations for people that, you know, because obviously if you work like I work in this field all day, every day, so I can look at somebody's gene variants and I can come up with a plan. But for most, we want people to be able to have access to it through many practitioners who's going to be using it. And we are obviously supporting them in that. But what we're doing with AI now is we helping to support practitioners to when they see the result that they will have you know, use a lot of these resources that we've built together with AI to then come up with a type of a plan, but not— it's obviously not computer generated. They say this is because they still have the patient in front of them. So we can input what, what are the type of things that you want to do? What is the patient's environment? Where do they come from? What are their genes? And come up with the type of plan and then obviously assess it to see if it will work for them. So yes, AI. Is, um, so we're not just throwing it out there, but we are building great systems to, to be able to do that.

Yeah. Yeah, exactly. I think it's critical. I think what's interesting is I think finally people are going to get the healthcare that they always intuitively wanted. But, um, because we've, um, deconstructed medicine so deeply into all these different subcomponents, organ systems, basically, it's been very hard to put it back together. And certainly, we've learned a ton by breaking it all apart, right? And but now I think we're at a point in history where we can actually start to take all the parts and put them back together into a unified field kind of theory or approach that again enables the person to thrive and to have ultimately to have confidence that they know they're getting what they need. And not doing stuff that they don't need, right? So I think it's the most exciting time in medicine ever, quite honestly.

Exactly. And I think that what you also describing is the patient having the buy-in, because if they— if you can pinpoint what your lowest hanging fruit are initially and you're starting to get good results early on, they will also be more confident in, in carrying on with that trajectory. And we have found so much that people, when you engage with them, obviously through many ways of personalization, adding genetics as well, that the buy-in from the patient is also so much better.

That's right. Yeah, that's right. I think it's— and once, you know, in one sense, and this isn't completely true, but in one sense, we've moved beyond or in addition to kind of the population-based studies of what works or doesn't work, right? Because, you know, it may or may not work for you just because it worked in the population at 76%. I mean, well, is it going to work for me? That's the real question everybody's asking, right? So now, with the amount of data that's available, and, and there's data also being developed inside practices where you can sort of make interventions and see what's working and not working. So in working with practices that are using the AI, you continue to iterate and refine for that individual. Um, it becomes an incredibly powerful tool.

So yeah, yes, exactly. So, um, you obviously just documenting things that you may maybe bad at documenting before because you were so busy and there was so much going on. So that's exactly— so you able to put those things together, and AI can then start picking up things that you might have not been able to do just because you don't have the, the power, the brain power, the bandwidth.

Yeah, yeah, the brain power or the bandwidth, um, to be able to, to look at it all simultaneously, right? I think That's kind of the beauty of it. I think we can— we're pretty good at posing the questions, but AI can even be helpful there in terms of refining questions. And we're pretty good at actually putting the pieces together. But what I'm impressed with is AI's ability to continue to enhance those conclusions or in some cases challenge portions of the of the conclusions, but in many cases enhance the conclusions, right? And that to me is very exciting.

So, yes, but you still have to be there to see if that conclusion makes sense. So you still need people like you and me to know, okay, that was— that's what they said about that system is not going to be.

Yeah, no, that's right. The AI is not perfect, right, at this point in time, for sure. And so, you know, clinical judgment superimposed, and then obviously client feedback in terms of what's working, not working, is super important. And I think that will continue to be important. So what are you most excited about now? What are you working on now? What's the latest for you?

So, I mean, we obviously know that we are just at the tip of the iceberg where it comes to genetics, and there's so much more that we can— I mean, part of it is maybe affordability. So we are, like, for us, we're using an array. So the ability to do a test for many people has become cheaper, but you do want to eventually maybe map the whole genome, and go and look at things that we haven't done before. So, I mean, that's obviously in the future. We're not there yet, because it's like, really diving too much data, not really know what we're going to do with it. So, that's the future. But for now, we want to build out, obviously, more from a company point of view, we definitely want to build out pathways, make it a bigger test and look at more information. But the main thing is maybe what you were talking about now is bringing in a way for people to not look at it and, oh, that's very interesting, and put it down and carry on with their lives, or not being able to carry on with the information beyond what their practitioner is telling them, but actually being able to use it in their everyday life where they'd be able to sort of, you know, if they want to— something happens, I'm tired, to be able to look at my genes, say what are the best things I can do if I have an injury, or if I'm having a pregnancy or something, that there's a way to always interact with your genes. So that's really what we are working on, is to have for people to have everyday steps they can take that's unique to them, and then when they need more help, that they be able to go to, to somebody who can support them in a more advanced way.

Yeah. Do you have, do you have examples, any case examples you'd like to share with the audience? So we've been speaking a little bit abstractly, but maybe making it more concrete.

Of course, I am. Maybe, maybe if I— because I used the neuroendocrine axis earlier as an example. So I've had an example of a case where a patient, well, that's a patient that we were trying to look after. So, it was a male in his sort of maybe early 50s, starting to lose a bit of resilience, you know, nothing was wrong, you know, he was just feeling a bit more tired, not sleeping so well, the weight getting up, libido went down. He went to get some blood tests done and his testosterone was low, had a bit of cholesterol going on, but that was it. So, then he went and had um, he was given testosterone. So, no, wait, he was first given, um, what's the other one, uh, Clomid, the Clomid. Yes, yes, thank you. Um, that didn't really help. And then he was treated later with testosterone, and of course his testosterone levels went up in the blood because he was given it, but he still didn't feel that it was making a difference to, you know, sort of what he was— he was still not— his energy wasn't great, he was tired, so was still tired. So we went and looked at his genetics and the 3 top things that we found with him was number 1, he had a lot of oxidative stress going on. So that was— so the way the test works is it will give you— it reads the genes, it's grouped in pathways, and then we can see where the most genetic vulnerability is for lack of a —better word. So we sort of score it. So he had a lot of genes that influenced oxidative stress. So that was high. He also had genes that influenced how his estrogen regulated. So his hormone regulation was specifically in terms of estrogen clearance. And I also must mention, besides the testosterone, he was also given DIM, which helps, you know, which is often given to help to regulate estrogen in men. And then he was— yeah. And then he was The other pathway was his neurochemical pathway. So what we— those were really high. So what we think what happened is he— the testosterone, because the clearance wasn't great in terms of his hormone pathway, so the ability to clear those big, you know, sort of breaking down the hormones, and also then when he got to his estrogen pathway to clear it was quite poor. So those waste products from the hormone balance pathway was heaping up. So that was maybe causing more oxidative stress, which could have by itself reduced his testosterone. The other thing was— let me just interject for a quick sec.

So as you're listening to this, um, you know, testosterone replacement, um, is incredibly common, maybe one of the, you know, along with estrogen, progesterone, for women, testosterone for men now has become incredibly common. The interesting thing though is that men need estrogen just like women need testosterone to be fully balanced. They just need it in different relative amounts. And genetically, some men will take their testosterone and turn it into estrogen. All estrogen comes from testosterone, quite honestly, through the biochemical pathways. But some men will aromatize the testosterone or make significantly more estrogen than other men will. Yes. Right. And so if you're taking a fairly high dose of testosterone, looking at boosting your testosterone level, and yet you're converting a fair amount of it into estrogen, and you can see this in your genetics, you can also see it in tests that look at the metabolites of the testosterone, the estrogen, and then the estrogen metabolites. You can get an idea that just shooting for testosterone levels of a certain, you know, level, let's call it, either total testosterone or free testosterone, if you're not looking at estrogen and its metabolites, you can actually be really overloading the estrogen pathways because you can end up with too much estrogen, which can have sort of feminizing effects for for a man. You can also overload the detox pathways, which are responsible for breaking down the estrogen through the 2, 4, and 16-hydroxy pathways. And then you have to be able to methylate it out of the 2-hydroxy and the other ones to get rid of it. So it's complicated. And I think one of the great disservices that is done to men in general and to women also, we see this, is that they're put on hormones and they're testing the blood levels or the saliva levels, but nobody's really looking at the metabolites. Or the relative ratio of how much of this they're converting to that, which again is found in the genetics. So, it becomes a little bit more of a complex issue. And, if you've been, you know, using hormone replacement and not getting the results that you're after, I think the solution for you is to deconstruct the whole pathway both genetically and then also to test for those metabolites and actually see what's going on. Because you can, you know, she was talking about diindolymethane, DIM, as a way to kind of maneuver estrogen metabolites out of unsafe pathways that can predispose to breast cancer or prostate cancer and down safer pathways. And of course, if you don't methylate well, then you've got to boost methylation to get rid of even the good metabolites. So I want you to understand, and just as you may not be able to hold all that in your minds as you're hearing this, but It is a complex thing to replace testosterone. It is a complex thing to replace estrogen and progesterone, right? And DHEA and other things that are commonly used. It is a complex equation. It's not just looking at the blood levels. And you can expose yourself to significant risk of cancer, either prostate, breast cancer, endometrial cancer, et cetera, if you're not looking at this from a systems approach where you're looking at all the different pieces and doing it from the genetics up through the biochemical levels of these different hormones and their metabolites. So I think I just want to make that point because I think hormone replacement is probably one of the earliest forms of "functional/longevity medicine" when people realize that they could feel better if they had hormones put back in. And what we've discovered also is that growth hormone is very important. Not too much and not too little, but being able to boost growth hormone. We don't really give growth hormone, but it's really the balance of all those hormones— growth hormone, IGF-1, testosterone, estrogen, progesterone, DHEA, the metabolites. When you get that all dialed in, people can feel remarkable. I mean, you can feel amazing. You can have, you know, bone density and muscle strength and a clear brain and you know, lots of energy and things like that. But if you're doing hormone replacement therapy and you're not getting where you want to go, chances are it hasn't been looked at thoroughly enough to actually understand how to make it work for you. So I'll just point that out. Yeah, exactly.

So that one size fits all, isn't it? Because you're putting it in one side and then it has to go through all these pathways and then coming out the other side. So for this guy specifically, what you described there, he had in his estrogen pathway the ability to conjugate or to bind those estrogen metabolites to make them a water-soluble excrete. That was— those enzymes were— he actually had some deletions there. So, those enzymes, some of those enzymes were obviously making a big difference there. So, those metabolites were heaping up and obviously putting more and more in was overloading the system and then because those toxins hang around and they cause more oxidative stress which causes damage. So that in itself was causing inflammation so it was just not clearing. It's like not clearing the bathtub that we often say easily. So that was happening. So, when we went and then said, let's look at supporting that oxidative stress because we can easily do that through diet and lifestyle. What he was also trying to do, he was exercising more and more because he was trying to lose weight. Also contributing to his oxidative stress. So, we looked at that, we looked at what he was doing around there. And the other thing was his neurochemical balance where the— that was also, I mean, I'm not going to go into all the details, but because of imbalances in those levels, it was also driving his HPA axis, which is his stress axis. So, the cortisol was building up. He was also quite a in a stressful job like a lot of people at that, you know, and so that stress. So, so then going back to say, how can we, um, regulate your neurochemical balance? We need to look at dopamine regulation, serotonin regulation, again, not through medication, drugs, but really through how— when are you exercising, what are you eating? So then we could balance that. And because we balance that, it also helped to balance the testosterone in a way, because we know that HPG axis is going to be influencing that. So just bringing things a little bit into balance and not just hammering the, the hormones, like you say, and seeing what we can do to support it.

Yeah, if you're listening to this, it may sound a little confusing, but essentially what she's saying is that your brain also has a big impact on your hormones and how much stress you're under has a big impact. This hypothalamic-pituitary axis, hypothalamic-pituitary-gonad axis, The stress that we carry in our nervous system will have a big impact on the adrenal glands and also on gonadal function and thyroid function and things like that. So in many respects, a lot of it always comes back to helping people understand how to mitigate stress. And there's a lot that goes into that. We do a lot of that here in terms of walking people through the Life Energy Circle and looking for at the psychospiritual space, we call it, to figure out where's the stress coming from. You know, we've all experienced traumas. And so that's a piece of it. And then, you know, there's really this kind of triad of we do what we do in order to feel safe, in order to feel acceptable, and in order to be lovable, right? And so if you look at it that way, it's like, okay, well, what am I doing here in order— if this didn't happen, I wouldn't be lovable, or I won't be safe or these kinds of things. So you can start to actually get to some of the underlying constructs that we carry mentally that predispose us to stress. And managing stress is not about managing stress. For me, it's about rebuilding the constructs that are generating the stress and replacing those with, what shall I say, more durable and maybe more healthy and more substantial constructs that allow us to feel safe, allow us to feel loved, allow us to feel connected. And when you have that, then you can go through life unencumbered by past traumas. You can go through life knowing that you're lovable, knowing that you're loved, knowing that you're safe. And at that point, it's like, oh, okay, well, now we're just, we're here to have fun. 'Let's have fun,' as opposed to, 'Oh my gosh, if this doesn't happen, my world is going to crater,' which is really kind of a terrible way to live, but it happens for a lot of people. We get attached to an outcome, and if the outcome's not forthcoming in the way that we anticipated it, then that leads to stress. And why does it lead to stress? Because we don't feel safe. Why don't we feel safe? Because that outcome was required by us in order to feel safe. So if it's not coming, then we don't feel safe. Well, that's a losing proposition because there's always going to be an outcome that doesn't show up and there's always going to be another outcome after that one does show up. So then it's like, well, that's, you know, that's a treadmill I want to get off. So how do we get off that treadmill? Well, now you're coming back to, okay, well, where do you ultimately have safety? Where do you ultimately feel loved? Once you can give yourself that and figure that out, then the point of my little monologue here is that has a massive impact not only on your hormonal system or your gut health, but it actually has a massive impact on the aging process itself. Every hallmark of aging is positively impacted by decreasing stress in the system. Yeah. And even if you go in for stem cells or exosomes or whatever else, you will get a much better response if you feel safe and you're in a very parasympathetic sort of zen state than if you go in stressed. The body can't heal when it's stressed. So, and even if you get hormone replacement, if you're stressed, it's not going to work as well because the stress is overriding things, right? So again, a lot of this comes down to what's going on in our nervous system. So, yeah. Yeah.

And I mean, that's how we put together, isn't it? Because if we're stressed, we're not supposed to be having babies. So there's that thing about suppressing those hormone systems when you're stress and then that chronic stress. So, um, and, and what's also interesting is just also knowing things about yourself. So I'm thinking where you were talking about getting stuck in a loop. So when we think about brain plasticity and how we could also influence that, that pathway where, um, if we know that we can, like if there's a, a bit more information about how your Well, I'm obviously going to talk about genetics, but how your genetics would influence your neuronal pathways, your brain-derived neurotrophic factor, which is a protein that helps with the plasticity of the brain. I'm just using one example. So that also something that you can do from your side to support. You can, as we know, exercise, some fasting, and having enough of certain nutrients like omega-3s can support that neurochemical or those neurotrophic factors. So little things like that to say what is going to be a little bit more important for me than the next person.

Yeah, I think that's right. I think, you know, what she's really talking about here is if, if optimizing our nervous systems and kind of reprogramming the nervous system to go into a less stressed state and a more calm, relaxed, sort of zen state, let's call, call it, the genetics play into that. So if you're actually doing things, taking things, and eating things that predispose you to allow those genetics to work in a favorable way, you'll have a much easier time of getting to that Zen state. You know, one of the things that we see frequently is that people will come in and they're drinking alcohol, and I don't have anything against alcohol, but we find that in certain people, because of their genetics, it actually makes them much more anxious, not while they're drinking, but the next day., right? They have kind of a rebound in terms of anxiety, and then they drink again in the evening to soothe themselves, right? But then they wake up anxious again the next day. So, you know, when you, when you start to put together some of those patterns, and that can happen with THC, that can happen with alcohol, it can happen with other things. Um, you know, if you're really interested to optimize your nervous system, and by, you know, virtue of that, everything else in your body then you have to look at, am I taking things in that's actually sabotaging the genetics that I have? So it's making it even harder for me to really bring my nervous system into a regulated state. Right. So that's a good question for anybody that's listening to this to ask themselves.

Yeah, exactly. Because it's like one of the genes we look at is called GABA. It's the GABA receptors. So that's GABA. Amino acid that helps calm your brain. And it's— we've seen that, or in research they show that when you have less GABA receptors, you can actually— when you drink alcohol, you need to drink more alcohol to calm you. So those people tend to drink more because— to get that effect. Um, but then, like you say, so then there's that vicious cycle of having to drink more and more to get that effect, and that anxiety that just perpetuates. The other thing is that you could maybe get high histamine levels from drinking alcohol. So the histamine is high, that causes anxiety because we know it makes you more anxious. Champagne's the highest. Yes.

Yeah. Champagne's the highest histamine drink. Right. So, um, yes. Yes. Yeah. And it's, it's really interesting. You know, there's things like histamine, sulfur, different people's, uh, genetics. They're built in different ways. And, uh, when it comes to food, This is why I say that the diet is never about the food, it's really about the individual. Because, you know, garlic may be great. I mean, it may be great for your endothelium and your coronary arteries, but it may be exactly wrong for you because, you know, it's activating anxiety or other things that you're unable to manage. So this is why this systems approach is really, I think, the whole— is going to become the holy grail of medicine, quite honestly. So Yeah. Yeah.

Cool. Yeah. Yeah. So I think that to bring that home with nutrition is we want to— when we— if obviously lifestyle also works like that, where certain lifestyle habits or factors can activate certain systems, what we think about with nutrients, if we know what nutrients, specific nutrients we need to maybe help activate certain enzymes, because we know maybe there's there's some genes that are coding for enzymes that are too slow, but you can add some nutrients to help them work better. That's the one thing. But we also know that things that you eat and things that you do can help turn genes on or off. So that is the nutrigenomic, or that is the thing that you will never be able to measure in other tests. So if you eat broccoli sprouts, it's going to turn the sulforaphane that you get from broccoli sprouts when it digests will be helping to activate your oxidative stress systems, your antioxidant systems, and your detox systems. So little things like that that you can really be quite specific about.

Yeah, I would say that of every nutrient that I've looked at from a nutrigenomic standpoint, um, it's hard to beat sulforaphane. Um, I mean, vitamin D is massive, right? Magnesium's massive. There's so many things that are massive, But I think sulforaphane may be one of those things that most people are not aware of. And you do find it in broccoli, and broccoli sprouts have 10 times more than broccoli, and broccoli seeds have 10 times more than broccoli sprouts. And then you can get supplements that have sulforaphane accompanied with the enzyme that activates it, myronase, called Avocall and Avocall Extra, which is an interesting supplement. But the point is that when you're taking high doses of sulforaphane, it's anti-cancer, it's anti-dementia, it decreases detox, it decreases, you know, lots of different gene expressions that you don't want to have. So it's one of the go-to things that we put almost everybody on is sulforaphane, some fashion. Yeah.

Yeah, I think we do too. I think we've got this Everybody walks out with at least some sulforaphane and something else. Right. Because it's got so many properties.

Yes. That's right. Yeah, it's pretty magical. Well, cool. So how do people find out more about what you're doing? You've got a website and some other things. You're still talking with patients or how? So tell us how people expand on understanding what you're doing.

Yes. So The website is 3x4genetics.com.

So 3x4genetics.com.

And people can go on there to see what we are about. It's very informative, the website. We do have a discount code, I can say that, for your listeners, if we can share it afterwards. So if they would like to go onto our landing page, Yes. What is the discount code? I'll share the— it is, let me quickly give it to you.

I'll put it in the show notes as well, but people can hear it.

It's GLADDEN, G-L-A-D-D-E-N, 20. Okay. Great. And they will get a $20 discount off our test. Okay, great. Perfect. And we do actually have a landing page for that as well, just to make it easier. Dr. Jeffrey Gladden. Great.

Yeah, if you haven't done genetics, I would really encourage you to do genetics. And I think you want to do it in a way that's looking at it through a systems biology lens. It's— and, you know, we continue to learn more and more about genetics and how the genes and the SNPs, if you will, are interplaying with each other. Because they're typically— there are some, you know, some mutations that are strong enough to be definitive, right? Like for sickle cell or for Tay-Sachs or cystic fibrosis or things like that, right? It's a single polymorphism that sets an entire health course. But for most other things, it's a combination of 20, 30, 50 genes that are all interplaying with each other. That in aggregate are moving you towards either greater or lesser susceptibility for a particular thing like either dementia, heart disease, cancer, some of these kinds of things. So, the only way to get at that is with a systems biology approach where you can start to see what is the interplay between all these different SNPs and genes and what is my actual real risk. And, not to say that there aren't some isolated SNPs like BRCA and PALO2 and things like that that that, you know, are associated with cancer, those are important to understand as well. But really, a lot of this is polymorphic information, meaning it's multiple SNPs that are colluding together or working together to create a risk. So yeah, very important to look at it through that lens.

Thank you. Yes. And I think that what also listeners must remember is that you only do it once. It's a very good investment. You do it once. Your genes don't change. You can always go back to it depending on what's happening. And so your environment's always changing, you are changing. So those things change, but your genes stay the same. So if you've done it once, that is something you can always use in the future.

Yeah. Yeah, exactly. Well, thank you so much, Nelly. It's been really a pleasure chatting with you.

You too. Thank you very much.

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