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Unlocking the secrets of nutrigenetics

March 16, 2023
Dr. Yael Joffe

As an expert in the field nutrigenomics, Dr. Yael Joffe is also at the forefront of nutrigenomic education and has helped develop and supervise nutrigenomics courses around the world, including her own Manuka and 3X4 education courses, which have trained hundreds of healthcare practitioners.

In this episode of the Ag Future podcast, we're joined by Dr. Yael Joffe, founder and chief science officer at 3X4 Genetics, to discuss the emerging field of nutrigenetics. Dr. Joffe explains how understanding the relationship between food, genetics and health can be used to personalize diets and lifestyles for optimal health. They also discuss the importance of personalized nutrition and the challenges of building trust in the field of genetics.

The following is an edited transcript of the Ag Future podcast episode with Dr. Yael Joffe hosted by Tom Martin. Click below to hear the full audio or listen to the episode on Apple Podcasts, Spotify or Google Podcasts.

Tom:            Welcome to Ag Future, presented by Alltech. Join us from the 2022 Alltech ONE Conference as we explore our opportunities within agri-food, business and beyond.


                     We think we know ourselves pretty well, but do we really? So much more information about who we are and how we respond to the world around us has been locked up in our genetic codes. But now, it's possible to understand that code and use that information to actually switch genes on and switch them off.


                     I'm Tom Martin for the Alltech Ag Future podcast series, and I'm joined by Dr. Yael Joffe, founder and chief science officer at 3X4 Genetics in Seattle, where she has mastered the emerging field of nutrigenetics to build products that are shaping the future of healthcare. Thank you for joining us, Dr. Joffe.


Yael:             Thanks, Tom. I'm very happy to be here today.


Tom:            First is this term, this science: nutrigenetics. How do you define that?


Yael:             It's pretty much exactly as it sounds — the idea of nutrition and genetics. It's a little bit bigger than that. Sometimes I use the word “lifestyle genetics”. But in essence, we can think of it as: What is the relationship between the food we eat, the food we expose ourselves to, the world we expose ourselves to and our genes? And what is — the relationship between those two elements really defines our health.


Tom:            Your company name, 3X4 Genetics — why 3X4?


Yael:             It's a little bit of a story, and it goes back about four or five years. One of the challenges that I've had in my career is: How do you get genetics to become something that every one of us can use in our daily life? I'm sure everyone listening has been to a practitioner, be it a dietitian or a doctor, and you've come away going, “That was all very well, but that really wasn't about me.” We know that one of the greatest trends in the field of medicine, nutrition, health and wellness is personalized nutrition, personalized medicine. So, I was trying to figure out: How do we really make genetics so consumable that, in one page, I can understand how my genes are going to personalize every single thing that I do every single day?


                     The reason we came up with (the name) 3X4 is — I actually started an education company called Manuka Science to teach practitioners how to bring genetics into their practice. We built this kind of methodology called 3X4, and the idea is (that), by using genetics, you should be able to understand, for an individual, the three most important places to focus on when you're starting to work with that client — the three most important dietary changes that you need to make. Not 300, not 10, not 20, because we know that overwhelms (people) completely. The three most important lifestyle changes, and the three most important supplements. So, when you put three, three, three (and) three together, it comes up to 3X4 — essentially, one page of a real summary that shows why you're different and how your genes would really personalize your intervention.


Tom:            Your approach is based on a set of principles. Can you tell us about those?


Yael:             My approach is based on, I'd say, two major principles. Let's go with that. The most important thing in genetics is to have science you can really trust and understand and that is proven, because we know that the genetic-testing industry has actually, largely, failed the consumer and actually failed the practitioner as well. We've been around now for 20 years. The human genome was mapped in 2003, but genetics hasn't really delivered the promise and the dream that, 20 years ago, we thought it was going to change our lives (and) prevent disease.


                     The first principle that I built 3X4 in is: How do we build a company that the consumer and practitioners can really trust? That meant going back to (the) basic principles of science and going, like, “How do we build something with a science we can trust, that is transparent, that is robust and resilient?” That was the first thing, and there's quite a long story to that.


                     The second thing is, if you just have great science but you have no way of translating it into a person's life, then all you're selling is data. One of the things that I've spent most of my career on is trying to figure out: What is that clinical translation? What is that translational value? Tom, you wake up in the morning and you have a whole lot of decisions to make. You can grab your phone and check your emails. You can immediately put on the coffee machine and have a double espresso. You can meditate for 20 minutes. You can go for a walk. You can have a look at the weather. You can have a cold shower. We make all these decisions, and every single decision is going to impact the way our genes express themselves, the way our genes behave.


                     If we can understand our genetics, we can make these decisions so much better. For me, one of the foundational principles of 3X4, really, is this idea of translation. How does it actually change my decision-making? How does it actually change my life? So, I really wanted to build a company that gave all of us — whether you're a practitioner or a consumer or a client — better decision-making. We needed to, really, not just build another genetic-testing company or build another genetic test; there are 300 to 400 (of those) in the U.S. alone. How do you fix the whole industry so that we can really raise (its) value? I'm not sure that was the question, but I hope I gave you a good enough answer.


Tom:            No, it certainly did. I'm wondering, (and) tell me if I'm right about this — am I understanding that we can actually have more control over our bodies or our health than we may have realized? How's it possible to manipulate our own genetic codes and overcome issues that might have been hereditary or unavoidable?


Yael:             That's an excellent question. In fact, I think one of my talks (at the Alltech ONE Conference) is going to be exactly on that, is that, for the last couple of decades, we've had this sense that our genes are our destiny. I think that this is very much part of the media conversation, is that our genes are set in stone and there's not much we can do (about them), so we might as well just get on with it and hope for the best — hope we don't get cancer or hope we don't get Alzheimer's. This was genuinely believed to be the truth, but actually, it couldn't be further from the truth.


                     We need to understand, in genetics, that there are two different parts to the conversation. I call it insight and action. The first part is we all have this genetic code, which you refer to. It's a language like English or Spanish. It's got an alphabet. It's got words. It's got sentences. It's got chapters, and it tells a story. Our DNA sequence code is exactly that. We have a code that tells a story of who we are and how we live in this world and how we respond to the world around us. But at 0.1% in our code, we differ from each other.


                     You and I have 0.1% of our code, which means — at three to four million places in our code, in our spelling, we differ from each other. We look different. We sound different. I don’t have and wish I had such a beautiful voice like you do. You're taller than I. We're different from each other, and that's at 0.1%. But it's also: How do I respond to the coffee that I had this morning. How do I respond when I eat gluten? How do I respond when I go and do a five-kilometer run?


                     A lot of the work in genetics has been in understanding why we're different from each other, and I call that insight. But one of the most exciting transitions in the world of genetics deals with the question you asked, which is: If I know who I am and I know how I'm different or how I respond to the world around us, what can I do about it? What we've discovered, really, (is that) genes are just a series of switches. Imagine you walk into your house and you switch on a light switch and something happens. It's exactly the same as genetics. As I described, I had some lovely lunch before I came here. I chose to have, for lunch, some salmon and some salad. Excellent choice. I probably wouldn't have told you if I'd had the pulled-pork sandwich, so I had the salmon.


                     When I had the salmon, there were nutrients in that salmon that had an impact on my genes. What they do is they actually send a signal to the gene to switch on, to make an enzyme or a hormone or a brain message. It's these switches, this signaling, that switch on hormones and enzymes in our body, which is actually what runs our body, which actually allows our body to heal (and) to optimize our health.


                     So, in one sense, we use genetics to understand what we are. On the other hand, we use the choices we make — whether it's nutrition, supplements, exercise, meditation, stress management — to switch on these genes, which is ultimately what's going to determine whether we choose health and heal ourselves or whether we choose behaviors that actually lead us to ill health. This idea that genetics is set in stone or is our destiny is simply untrue. We actually, every minute of every day, have the choice to change the way genes behave.


Tom:            This is fascinating. To me, a layperson, it borders on profound. It sounds as though, if we can determine our genetic code and it's time for lunch, we can determine what we should have to manipulate something that's going wrong with us, perhaps, or that we want to enhance.


Yael:             Spot on. That's actually my work, and that's what I've been doing for 20 years. I can do a test on you. Remember, I spoke about these differences, these spelling changes in your DNA. I can understand — let's call it metabolic dysfunction, things in your body that are not working as optimally, whether it’s enzymes or hormones. It’s around areas like: How do you detox toxins that you respond to? How do you manage your glucose and insulin, especially around hormones? It could be around cholesterol. It could be around how you consume calories, how hungry you feel, how you store energy. I could go on for hours.


                     If I understand that about you, I can now help you make a much better choice at your lunch, for two reasons. One is (that) I want to make sure that, knowing those spelling changes, those differences, I'm optimizing your choices. But to take it a step further, I'm going to help you choose foods that actually go further than that and switch on genes or switch off genes — because my salmon that I had for lunch was doing a couple of things. One is it was switching on genes that decreased inflammation in my body. We all know about these amazing omega-3 fatty acids that we get in oily fish that actually switch off inflammatory genes, but it also can switch on what we call anti-inflammatory genes, and there's a whole lot of other stuff it does.


                     So, knowing this knowledge — and I talk about “know thyself,” the self-knowledge, and working with someone who really understands how nutrition can change gene expression and not just nutrition. Let's talk about profound. You go and you hug someone. (You make a) connection. We know that, (because of) COVID, the last couple of years have been really hard, because we've all been at home. We haven't had connection. Suddenly, we come to an amazing conference, and we see someone that we've only seen onscreen, and we give them a big, solid hug. That connection, in itself, can switch on genes.


                     So, when I say (that) every single thing that we do in our life changes the way our genes switch on and off, I literally mean every single thing. One of my favorite topics is cold-water immersion — to have a cold shower versus a hot shower. We go and dip in a cold tub or in an ocean or in a lake when we go hike a mountain (or), obviously, when we exercise. Every single thing we do is now in our control. To be able to change the way our genes are behaving — that is how we step forward to health and wellness.


Tom:            Can a consumer obtain a customized set of data that helps guide them in their diet and lifestyle?


Yael:             Yeah, absolutely. There are many, many companies in the marketplace that are doing this. I've tried, at 3X4, really, to try build the best company, and one of the fundamental things that we do differently, perhaps, is we insist that you have a professional work with you. Genetics is only data if you don't have someone to translate it for you, (someone who) knows who you are, what's important to you, what your goals are, what you want to achieve, what your concerns are, what your medical history is.


                     You're able to get a test. We look at everything that I've described — how you consume energy, your exercise activity, your nutrition, stress, mood, anxiety, depression, detox, you name it. And then we have these amazing (people), whether they're dieticians or medical doctors or chiropractors, who have been trained, mentored and educated to sit with you and say, “Well, this is what I'm understanding about you. Let's plan ahead and see what we can do better.” So, that's exactly what we do.


Tom:            Can you give me an example of a case study, let's say, of someone who has done this, who has realized that they had something to overcome, and they've managed to do that through genetic manipulation?


Yael:             Yeah, I have many cases. Let me think. One of the interesting areas — I'll give you just one off the top of my head. I'm actually presenting a whole lot of case studies (at the Alltech ONE Conference). I won't use one of those, but we actually had a staff member at 3X4 who suffered from recurrent migraines. Migraines are so debilitating. They really are extraordinary, and we are seeing them more and more often. Even in our company, which is a health and wellness company, we probably have 20% of our staff members who are suffering from migraines. One of them in particular was suffering it recurrently, (which has a huge impact) — never mind the loss of productivity and days of work, but in terms of family and quality of life.


                     So, we ran our genetic test on them, and this is interesting. One set of genes that we look at in our test is around something called histamine. I'm sure anyone who's at this conference knows about histamine, especially in agriculture. It's a molecule that is found in a lot of foods, but for some people, they're not able to break down histamine, so it stays in the body, and it does kind of weird things. It's very pro-inflammatory. A lot of people who suffer from a lot of allergies, seasonal allergies, have a lot of histamine in their system.


                     Histamine can manifest in different ways, one of which — of the ways it does — is migraines. Often, when you get a migraine, you'll often go to a doctor and they'll give you a whole lot of drugs, a whole lot of medicine that you'll take, and you'll end up getting into bed and be wiped out for the whole day to manage your migraines. We discovered that this person had an inability. Genetically, it was missing the kind of amino acids that help break down histamine.


                     So, what we did — it's amazingly simple, actually — is we removed all the foods in their diet that are high in histamine. Now, the interesting thing about histamine is that some of the foods that we think are the healthiest — like avocado is actually a high-histamine food. So, we put them on what we call a low-histamine diet, and it's just extraordinary. Just from that, we were able to resolve all the migraines. We talk about genetics as this idea of “You don't know what you don't know.” We think we know ourselves, but we don't necessarily.


Tom:            Well, if we are able to take this level of control over our personal health, doesn't that have enormous implications for healthcare in general?


Yael:             Absolutely. This is the journey we've been on for 20 years, is trying to move away from what I call those “USA dietary guidelines” concept, that every single person gets the same diet, or it's the ketogenic diet, or it's the intermittent-fasting diet, or it's the Paleo diet. This idea that every single person will respond to the same diet is completely flawed.


                     I've been working with health professionals for 20 years now, and we have had incredible traction in certain groups of practitioners. We call it integrative medicine, lifestyle medicine, functional medicine. But in terms of mainstream Western healthcare, the big healthcare systems, we haven't (been completely accepted). It's starting. It's taking our time. But if you think about it, why wouldn't you want to understand?


We call it trying to get rid of trial and error because, at the moment, what happens with the practitioner is you'll have migraines and they'll say, “Well, let's try this drug. Oh, that didn't work. Let's try this. Oh, that didn't work. Oh, let's try this.” We’re trying to get away from that, because if we can know what we don't know, we can save not only financially, for a patient, but we can actually save (them from) psychological and emotional (damage), because every time we fail — don't even get me started on weight management. Every time we fail, we set someone back emotionally, psychologically and financially.


So, we're starting to see some traction. There's an inevitability to it that, ultimately, we'll all know our genetics, and every single piece of advice we get will be through the lens of genetics, and that's where we're headed. We've certainly grown exponentially in the last 10 to 20 years, but we've got a long way to go.


Tom:            Your company maintains a global network of accredited practitioners. Is this service widely available? Is it expensive? Is it covered by health insurance?


Yael:             It is not covered by health insurance. Everything is cash pay. Unfortunately, some of the best medical care outside, at the moment, is cash pay. At the moment, it's only available in the USA and in South Africa. We're starting to look at other countries as well and how to expand globally. But right now, we're still quite a young company. It's only launched four years ago in South Africa — I'm from South Africa — and launched in the USA two and a half years ago.


                     The way it works is the test is $349, but you only do it once in your lifetime. Your genes don't change. Your code does not change. You do it once and you're done. But then you need to have a consult with a practitioner who's been trained by us, educated and mentored, to make sure that you get the value out of it that you really need. I always say, “If you don't know what to eat for breakfast the next morning, you've bought data, and then it doesn't matter whether it's $349 or $1,999. It's just not valuable.”


                     We've got 2,000 practitioners in the USA at the moment that are trained and up and running. We do also a lot of telehealth, of course, but at the moment, we haven't quite got to global domination. We're working on it.


Tom:            It sounds like you're on your way. Well, I was perusing your website, the company website, and it says on your website that you are obsessed with your customers. What does that mean?


Yael:             Yes. Well, we are obsessed with our customers — be it the practitioner or the consumer — because, ultimately, we have this dream. When people (ask me), why did I start 3X4? Well, I wanted to build a genetic testing company that did everything right, and so many companies (are) just not. To do everything right, I needed to create an experience and engagement for the consumer that had great value to them, that really changed their life.


                     We have this idea of ten million lives. We believe we will impact ten million lives, and that means something different to everyone. It might be having enough energy to get out of bed in the morning. It might be managing that migraine. It might be managing anxiety. It might be preventing Alzheimer's or cancer. We wanted to take genetics, which has traditionally been quite a dead science — almost like computer science has zeros and ones; genetics is just kind of data letters — and bring it alive and make it meaningful.


                     We've done this in multiple ways, (including) engagements, using color, infographics, pictures and storytelling, because we want to make sure to bring value to your life. I think this is something that has been missing from the genetic testing industry. So, we're quite obsessed with (learning): What is your experience of genetics? How does it feel to you? Is it meaningful? Because remember, these are your genes, not mine. I might be able to drink coffee all day, but you may not be able to drink coffee all day. What does it really mean to you, and how does it really change your life?


We spend a lot of work working on (understanding), how do we have, (as) we call them, visual conversations with you — not just the way medicine is normally done, which is, “Here's a lab report, and good luck, and off you go.”


Tom:            If you are able to wave a magic wand and you have a vision of a world that understands and makes use of nutrigenetics, what would it look like? What would life be like in that world?


Yael:             Interestingly, in 2005, I wrote a book called "It's Not Just Your Genes!" and that was quite optimistic of me in 2005. There was this chapter at the end of the book. It was kind of (asking): What does the future look like? As I said, this was almost 20 years ago. I had this idea that every single person had, like, a DNA passport. Imagine a credit card with a little chip, and everywhere you went, you had your DNA passport. Now it’ll probably be like a smartphone or a chip under your skin or something. Anyway, you would go to Whole Foods or the shops and everything, and you would scan your DNA passport. It would make recommendations on the best foods for you to buy. “You better buy organic. Here's some broccoli for you.”


Ultimately, I guess what I'm trying to say is that, in the future — and I think it's a magic wand in terms of timing, but I do think there's an inevitability to it. Every single decision we make will have a lens, whether it's shopping on Amazon, whether it's sports training. It's how we prevent injuries. (It will help determine) the foods we eat, the supplements we take — we'll never take a supplement ever again without knowing our DNA — the drugs you take, the pharmaceutical drugs you take. We already know the field of pharmacogenomics is huge. Only 50% of drugs work, and that's (due to) genetics, because genes determine how a drug is metabolized. So, imagine that this big lens that covers every single decision that we make and that we do — that is the future of health, of wellness, of medicine, of sport, of fitness.


I think the ultimate part of that wand is integration. One of the amazing areas we're working on now is (asking): How do we take genetic information and integrate it with other data about us? I've got a Garmin watch on my hand. I've got an Oura ring. These two devices give me information about my heart rate, my heart rate variability, and whether I slept well. The way we see the future, the next five to ten years, is that there will be genetic integration into all our data. So, we're not just measuring my heart rate and my heart rate variability and my sleep, but we’re layering it with some amazing lens of genetics and finding out, “How does this look at a personal level?” I think that's the future we're looking at.


Tom:            That magic wand has already been waved, actually. It's hard at work.


Yael:             We're waving. We're waving.


Tom:            Dr. Yael Joffe, founder and chief science officer at 3X4 Genetics, based in Seattle. Thank you so much.


Yael:             Thanks, Tom. Thank you so much for having me.


Tom:            For the Alltech Ag Future podcast, I'm Tom Martin. Thank you for joining us. Be sure to subscribe to Ag Future wherever you listen to podcasts.