Functional Genomics with Kashif Khan: Rational Wellness Podcast 309

Kashif Khan discusses Functional Genomics with Dr. Ben Weitz.

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Podcast Highlights

4:12  Genetics vs Functional Genomics.  The difference between genetics and functional genomics is that genetics might tell us here’s what this gene does and we’ll speak about it independently.  For example, when it comes to methylation, you might say that you have the MTHFR gene and you need to take folate is genetics. Functional genomics looks at how the body actually works and recognizes that methylation is one part of phase two of detoxification. There is also glutathionization, glucuronidation, and antioxidation.  There’s all these detox functions happening in the body.  And if I don’t pair them, I haven’t understood the full cascade.  What does my body do from the point that a toxin enters to the point that it gets out?  So first understand that, and there’s not one gene that does every single step along the way.  There’s multiple processes.  When you connect them and you have your full functional answer, you can then solve the problem fully also. 

5:39  Kashif made an appearance on Ari Whitten’s Energy Blueprint and Ari asked if a woman has the BRCA gene should she have her breasts cut off?  The genetic answer is yes, but that is because pure genetics is pharma and disease backwards.  If you have the genetics and you ask why are you waiting to treat the disease, then you would remove the breasts.  If you ask the wrong question, you get the wrong answer.  But instead, if you ask why does the disease happen in the first place?  You understand that BRCA doesn’t cause cancer. BRCA is actually a tumor suppressor and when you have breast cancer, BRCA is supposed to come along and fix it.  And if you have the wrong version, you just have a bad repair tool. So you’re more likely to die from breast cancer because you can’t come back from it. So we’re solving the wrong problem once again. Why did the cancer happen to begin with?  That question is better answered by looking at if the woman is estrogen dominant and does she make a lot of estrogen?   Also, how does she metabolize her estrogen, which can be analyzed with DUTCH testing that measures which pathway the body uses to metabolize estrogen–the 2, the 4, or the 16 hydroxyestrogen pathway, with the 2 being healthiest and 4 and 16 being more toxic.  Bad genes do not equal disease. You also have to look at diet, lifestyle, and environmental exposures.  This woman’s bad choices may be that she goes on the birth control pill for 10 years that elevates her estrogen level.  Then she goes on Bioidentical Hormone Therapy (BHRT).  Not that you shouldn’t go on BHRT, but if you take the wrong form of estrogen and if you cook with a teflon pan and use conventional cleaning chemicals and get exposed to pesticides on her lawn that fuel the 4-hydroxy pathway.  Why do we see breast cancer more commonly around the menopause age?  It is because at that age, you no longer have a menstrual cycle and you no longer have the ability to get rid of this toxic load that you’re making every month. And your body stores it in fat, such as in your breasts, to protect you because it doesn’t want your organs and your vasculature getting damaged.  This reduces potential inflammation in the arteries, but it leads to inflammation in the breasts and you may get cellular degradation, mutation, and eventually cancer. And if you have the wrong version of BRCA, you’re not going to fight the cancer so well.




Kashif Khan is the Chief Executive Officer and Founder of The DNA Company, where personalized medicine is being pioneered through unique insights into the human genome. The website is TheDNAcompany.com. With a background in business, Kashif dove into healthcare and functional genomics and he has a successful podcast, The Unpilled podcast, and an upcoming book being released on May 16, The DNA Way.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.



Podcast Transcript

Dr. Weitz:            Hey. This is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting-edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast.

                                Hello, Rational Wellness podcasters. Today, we will be speaking about personalized medicine based on your genetics. We’ll be speaking with Kashif Khan, who’s the chief executive officer and founder of The DNA Company, where personalized medicine is being pioneered through unique insights into the human genome. With a background in business, Kashif dove into healthcare and functional genomics. He also has a successful podcast, the Unpilled Podcast, and an upcoming book to be released on May 16th, The DNA Way.  Kashif, I recently heard you on Ari Whitten’s The Energy Blueprint, and I was blown away with the way you were able to couple explanations of various SNPs, DNA variants, and how they affected various metabolic pathways and how certain diet, lifestyle and supplement approaches might help to steer a patient towards greater health. Prior to this, I’ve spoken to other experts on genetics. And often, we get simplistic explanations like you have the C677T or the A1298C variant of the MTHFR gene, and therefore you need to take methylated folate and B12. And that’s pretty much the end of the story.

Kashif:                  Yeah. Something as complex and powerful as a human genome has been brought down to “Here’s a supplement you need because of one gene, and that’s all we’re going to talk about.” And I’m not saying that that’s not useful information, but the clinicians that are using these tools haven’t… So the tools are too difficult to use. Let’s start there. So when it’s too difficult to use, there’s one or two tricks up your sleeve that you stick to and that’s it because how much time do we have to reeducate ourselves? And so there is so much more, and that was part of our mission, is making it easy to use so it’s easy for people like yourself to implement. And there’s so much more we can do than just “Here’s your folate.” Right?

Dr. Weitz:            Right. And I just want to let you know that we have a fair number of healthcare practitioners and also educated consumers. So in our discussion, feel free to dive deep into the science if it’s appropriate.

Kashif:                 MTHFR.  Well, let’s use that as an example. You’re talking about a methylation gene. And just this morning, I was speaking to this influencer from the UK that calls herself the MTHFR guru or something. I said, “That in itself tells me you’re not a guru because you don’t understand methylation, that that’s one gene in a cascade that builds up a system.”  You have to first understand human biology, and this is where genetics is broken. A gene is not independent of the process happening in the body. It’s like looking at one link in a chain and then making a judgment on the whole chain, and they’re all different sizes and different qualities.  And so methylation is a cascade of a multitude of genes, six or seven of them. So if I tell you, “Your MTHFR is off. You’re not doing so well there,” you still don’t know where to intervene because it starts at B12 metabolic pathway B9. Is it folate or is it folinic acid? And what do you actually need? And if you know what part of the chain isn’t working, MTHFR means the cascade in itself is inefficient, but how and where do you intervene? So we can be a lot more precise and we can give someone exactly what they want. And then it’s no longer “This has a 80% chance of working.” It’s now “100% of the time, we’re going to get it right.”

Dr. Weitz:            And that’s an example of the difference between functional genomics and genetics.

Kashif:                 Exactly. Genetics is “Here’s what this gene does, and we’re going to speak about it independently.” Functional genomics is “Here’s how the body actually works, and let’s look at that first. And not only let’s look at the system, but let’s look at how several systems interlink.”  And I’ll use methylation as another example. Methylation is phase two of detox. If I only focus on that and don’t understand phase one first, methylation is like, “Here’s the door open to take the garbage out.” If I don’t understand who’s picking up the garbage and bringing it to the door, I’ve only solved half the problem, right?

Dr. Weitz:            Right.

Kashif:                 There’s glutathionization. There’s glucuronidation. There’s antioxidation.  There’s all these detox functions happening in the body.  And if I don’t pair them, I haven’t understood the full cascade.  What does my body do from the point that a toxin enters to the point that it gets out?  So first understand that, and there’s not one gene that does every single step along the way.  There’s multiple processes.  When you connect them and you have your full functional answer, you can then solve the problem fully also.

Dr. Weitz:            Yeah. Well, we don’t really need to do that because as soon as the person brings the garbage to the door, you just shoot them in the head. No, I’m just kidding.

Kashif:                 That works.

Dr. Weitz:            So when you were talking to Ari Whitten, Ari Whitten asked you a question about the BRCA gene. And I loved your answer, so I want to ask you the same question again. And he basically said, “If I’m a woman and I have the BRCA gene, should I have my breast cut off?”

Kashif:                  Yeah, so that’s exactly the… That paints a picture of genetics. So genetics is pharma and disease backwards. Here’s the disease, and how do we treat this disease? They’re asking the wrong question to begin with. If you have somebody’s DNA in hand, their human instruction manual that tells every cell in the body what to do, why are we waiting to treat a disease? Why don’t we ask, “Why does the disease happen in the first place?” and not have it? So when you ask the wrong question, you get the wrong answer.  And so the answer we now have is a certain version of BRCA means cancer risk. That in itself, by the way, is a false statement. BRCA doesn’t cause cancer. BRCA is a tumor suppressor. So when you have breast cancer, god forbid, BRCA’s supposed to come along and fix it. And if you have the wrong version, you just have a bad repair tool. So you’re more likely to die from breast cancer because you can’t come back from it. So we’re solving the wrong problem once again. Why did the cancer happen to begin with?   So I can give you one example, the same example I gave Ari, because I would say it’s the most prolific and easiest to deal with. Some women in their hormone pathway make a lot more estrogen. They’re estrogen dominant, and this is very easy to predict genetically the hormone cascade and how you go from progesterone to testosterone to estrogen. The genes that do each one of those steps, to what degree are they working efficiently or not efficiently? So some women just make a lot more estrogen. There’s a big pool of it every month. Step one of three.  Step two is when you have your monthly cycle, you’re not clearing estrogen. You’re clearing a metabolite. And there’s three options: 2, 4 or 16-hydroxy estrogen.

Dr. Weitz:            Right.

Kashif:                 Some clinicians listening here have done DUTCH testing and looked at these things, right?

Dr. Weitz:            Right.

Kashif:                 So 2 is the good, clean stuff you want. 4 and 16 are toxic. 4 has a lot of publications and education around its connection to breast cancer, but we still haven’t answered the full question as to why.  Then we look at functionally okay, I’m estrogen dominant. I make too much. The version that I make is a toxic version. I go down the four pathway. Well, let’s look at how well I detoxify it because again, how does the human body work? So you do look at glutathionization, antioxidation, COMT, which is the tail end of methylation, and you start to look at the jobs that your body does well or not so well. And you may understand that not only am I estrogen dominant, estrogen toxic, but I also don’t have the right detox genes kicking in to help me get rid of it.

                                So now you have the avatar, the profile of the woman who truly is at risk, but she still may not get sick. So what’s the difference between the woman at risk and the woman that gets sick is the epigenetics. You have to pair these two, and that’s another layer to functional genomics. It’s not just “Here’s your genes.” It’s also what are your habits? Because bad genes doesn’t equal disease. Bad genes equals elevated risk, right?

Dr. Weitz:            Right.

Kashif:                 You have to do something to create chronic disease. You’re not born with breast cancer or Alzheimer’s or diabetes. These things develop because of your choices that you make. One other thing…

Dr. Weitz:            Because of your diet, your lifestyle, et cetera.

Kashif:                 Exactly. And some of these things are obvious. Some of them are completely counterintuitive, that you would never think are related to the problem. So for this profile, now we say this woman’s bad choices may be that she goes on the birth control pill for 10 years and elevates that estrogen level. She goes on BHRT. Not that you shouldn’t take BHRT, but where do you intervene? What hormone are you taking? Is it estradiol? Is it estriol? Where do you actually plug in that hormone, and are you fueling that 4-hydroxy pathway or not? She may not understand the hormone disruption in her environment and what her Teflon-coated frying pan and her cleaning chemicals and her pesticides that make her lawn so beautiful are doing to her body.  So now, you have… The woman has a profile. She also has the wrong choices that are misaligned to that profile and what it’s capable of. And now, you get to the level where the genes can’t handle it anymore. There’s too much of that net 4-hydroxy causing too much inflammation.  So then last step, going back to biology, why is it that you typically see breast cancer around the menopause age?  It’s not because that’s when BRCA magically creates a problem. It’s because at that age, you no longer have a menstrual cycle and you no longer have the ability to get rid of this toxic load that you’re making every month.  And your body, to protect you because it doesn’t want your organs and your vasculature, your veins, getting damaged, will store it in fat.  It says, “Hey, I’m smart. I’m going to get rid of this stuff and not cause inflammation. Let’s put it in fat.” And women have fat in their breasts, and in the breasts you have all these glands and ducts for which the cellular structure was not designed to deal with that level of inflammatory insult. Then you get cellular degradation, mutation, eventually cancer. And then if you have the wrong version of BRCA, you’re not going to fight the cancer so well.

Dr. Weitz:            Right.

Kashif:                 Right? After all of that. So now you name a chronic condition. It can be laid out in this manner so that we can understand how to prevent it. Why would it happen to me? And my why might be different than somebody else’s why. That’s functional versus genetics.

Dr. Weitz:            What are some of the important genetics related to cardiovascular disease? We know about familial hypercholesterolemia.

Kashif:                 Yeah, so that’s a perfect example.  Cholesterolemia, to me, is a myth. It’s not a disease. It is the response to the true disease, which is endothelial inflammation.   So when we look at the genetics of heart disease, which is the number one killer, still number one drug prescribed is statins.  Why is that so?  Because most of us are not genetically designed for today’s reality.  What does that mean?  Our hardware, our endothelium, the actual inner lining of the blood vessel, most of us don’t have the best quality endothelium. We can actually predict that genetically. Is it stainless steel resilient or is it more paper thin, this papyrus that’s prone to inflammation, right?

Dr. Weitz:            Right.

Kashif:                 Most of us are walking around with that, the not so good stuff. So if that’s the case, and just like this breast cancer woman you happen to be breathing in the wrong stuff, eating the wrong stuff, having the wrong stress load, the wrong sleep load, et cetera, et cetera, et cetera, and you may also pair that with the wrong detox pathway or inefficient detox pathways that can’t support the inflammation being caused here, you’re going to get endothelial inflammation, which is the actual disease. Your body then responds with cholesterol as a hormone to reduce the inflammation. It acts like a Vaseline dealing with all these microabrasions and tears and inflammation and resolves them. The same oxidation and toxicity that caused the inflammation also oxidizes the cholesterol and causes it to harden and deposit because our body didn’t understand that our 200,000 years of caveman habits were going to be deposited in this industrial reality at some point. And so it hasn’t changed yet, and we still are not prepared for this.  So that’s the true why behind cholesterolemia. And if you understand this, not only can you predict it and prevent it, but if you have it, you can deal with the root cause and then prevent it. Or sorry, reverse it.

Dr. Weitz:            Right. Okay. How can our DNA blueprint help us to determine what type of diet might be best for each person?

Kashif:                 Yeah, there’s a lot that can be said there. Starting with the brain, and this is… What I’ll speak to is the unique things. There’s obvious things like there’s genes that tell you how you metabolize fats and starches. There’s genes that tell you how you break down chickpeas, lentils and “Should I actually be a vegan?” My primary protein sources, do I actually make the enzymes efficiently to digest them, or do I get bloated and not eat enough? Right?

Dr. Weitz:            Right.

Kashif:                  So those are the basics. Then there’s things that are a little more functional in nature. So how do we look at the human mind and determine why some people just perceive things differently? So do they not produce or bind enough dopamine, so it’s hard for them to experience pleasure? In which case, they may lean on food as a source of pleasure and overeat without even knowing it. Is their serotonin pathway dysregulated and they’re slightly more irritable?  It’s easy to dysregulate their mood because their serotonin receptors are a little too short and they can’t bind it efficiently. These people end up leaning on food as coping mechanisms because they’re constantly stressed.

                                There’s a gene called MC4R that determines the satiety of the palate. So as an ancestral trait, typically there wasn’t enough food. So we developed this desire to seek variety in our palate, a lot of us. And so it’s like, “Give me the crunchy. Give me the soupy. Give me the salty. Give me the sweet to make sure that I got enough nutrition.” And we’re still walking around with this trait and then going to the grocery store and filling our carts where it’s so convenient to overeat. And then when you get home and you have your meal, it’s not enough. You still need to graze to the pantry, the Doritos and the cookies, because you’re not satisfying the palate.  Same thing for the gut. There’s genes that determine how efficiently you feel full, that signal from the gut to the brain, and maybe your plate being appropriate just isn’t enough. You need to wait. Maybe you need a glass of water. So there’s a lot we can speak of these hidden areas when it comes to diet planning that go far beyond calories in and calories out.

Dr. Weitz:            Let’s talk about one particular gene, the APOE gene. And if a patient has one or two copies of the APOE4 variant, we know that they have an increased risk of Alzheimer’s. What does that tell us about what we can do about that?

Kashif:                  So another great example of how functional genomics can support that genetic question, so genetic… We do test for APOE and we do report on it, but there’s a lot more you need to know than just APOE. So APOE is how well do I, to keep it simple, transport lipids and more likely to develop amyloid plaque in the brain?

Dr. Weitz:            Okay.

Kashif:                  Which is highly connected to Alzheimer’s and dementia. So even then, people walk around with APOE34 and 44 don’t get sick. What’s the difference? Something has to trigger the inflammation.  Everything that we talk about that’s chronic in nature is typically rooted in inflammation. So if you do everything right, you could have the APOE 44 and have a better brain than somebody that has the APOE 33 that did everything wrong. All we’re saying is that this is a priority for you. This is a red flag. If you’re APOE34 or 44, you need to focus on this. What’s your health plan to make sure it doesn’t happen? What are the potential things you look at? Same thing as the breast cancer.   If you produce toxic estrogens, which is why, by the way, 80% of Alzheimer’s and dementia cases are in women. The vast majority are in women, and it’s much harder for women to reverse and deal with because they’re also dealing with the estrogen toxicity which leads to more inflammation.   A vast majority of today’s dementia is rooted in inhalation. What are we breathing? I spoke to a brilliant guy, Dr. Tom O’Bryan, that deals with a lot of [inaudible 00:17:39]-

Dr. Weitz:            Oh, yeah. I know Tom well.

Kashif:                 Yeah. So what he told me is that 66% today of what he sees is inhalation based, what we’re breathing.

Dr. Weitz:            Huh.

Kashif:                 One hour of LA traffic is equivalent to a pack of cigarettes.

Dr. Weitz:            Wow.

Kashif:                 So if that’s what you’re doing on your drive home every day and you’re creating that level of inflammation, if you have the APOE34, that may be the trigger that causes the inflammation for which you don’t transport the lipids that well. So again, go to the why. This is your… Genetics is red flag. You need to focus here. Functional genomics says, “Well, what do we do about it?”

Dr. Weitz:            Right.

Kashif:                 Right. “80% chance of Alzheimer’s. Good luck,” is not enough of an answer.

Dr. Weitz:            Do we know what kind of diet is going to be best for somebody who is APOE44?

Kashif:                 Well, it depends on what the actual trigger is. So if it’s-

Dr. Weitz:            Okay.

Kashif:                  So for example, if it is the inhalation-based, diet may not be their problem. Right?

Dr. Weitz:            Ah, okay.

Kashif:                  For a lot of people, it’s insulin based. So low insulin, low glycemic index. There’s some people that don’t metabolize fat so efficiently and [inaudible 00:18:50].

Dr. Weitz:            That’s exactly the question I was going to ask, because I know some people employing a keto diet to help reduce risk and other people are employing vegetarian, low-saturated fat diet to reduce risk. And you’re saying it depends on what other genes-

Kashif:                  Yes.

Dr. Weitz:            … are involved.

Kashif:                  There’s a lot of people we work with that got on to Keto and they felt amazing in the first three or four weeks. It’s impossible to not feel amazing because you start burning your fat as fuel and you get ketones firing in your brain. Everything feels good. But then you get five, six week in into it and you start feeling sluggish and like, “Well, what else do I need to change? There’s something…” Because you felt so good, you don’t blame it on the keto. But if your APOA2 gene, a different gene, is off, you don’t metabolize saturated fat so well. And five, six weeks into it, you’re going to feel horrible.  And that can actually drive an insulin response, by the way. We don’t think of fat driving an insulin response, but ultimately if you eat too much fat, it turns into glucose anyway and it can drive an insulin response. So yeah, we can be hyper precise on the exact plan.

Dr. Weitz:            Interesting. So fats can drive an insulin response. I’ve not heard that before.

Kashif:                  And the reason you haven’t heard that, and I’m going to poke fun at you for some time right now.

Dr. Weitz:            That’s fine.

Kashif:                  Medical research is all done on Western European white males. It’s designed for you. It’s not designed for my pigmented skin. It’s also not designed for women. This is why dark people and women suffer more in our healthcare system than Western European white men. So the truth is that the genetics of South Asian people, brown people, we get an insulin response from fat.

Dr. Weitz:            Interesting.

Kashif:                  It’s not spoken of anywhere. And it’s not just South Asians. There’s other ethnicities as well. So we have a global medical model that was designed on one cohort of people, which great. You’re going to do well. But the uniqueness, the bioindividuality is there. We’re not all the same, and we’re starting to understand that. That’s part of what we’re pioneering, is how do we make this thing unique to the individual? It’s not about one set of research for everybody.

Dr. Weitz:            Right. And it’s not even about one set of research for a race either. We don’t want to just make a simplistic conclusion and say all Asians should follow this program or something like that.

Kashif:                  Yeah. So China is not Asian and it’s not Chinese. There’s two races that make up China, and they’re very different. So if you look and… Picture this. People from China either look like Bruce Lee or they’re big like [inaudible 00:21:41] the panda bear. And that’s what you get. There’s nothing in the middle. And there’s actually two major races that make up China, these highly androgenized, testosterone-dominant, rippled muscle 90-year-old grandma walking around doing her own groceries or these big, thick people that have a lot of fat on them and big heads. Those are the two races.  So even between those two races, it’s not the same answer. And we’ve learned this genetically that the uniqueness of how people… And why. These people are highly estrogen dominant. These people are highly androgen dominant. Eventually at some point, they came together and formed China. So you can’t give the same answer to those two people even though they both think they’re Chinese.

Dr. Weitz:            Huh. It’s all based on their genetic differences.

Kashif:                  Yep. Exactly.

Dr. Weitz:            What about the relationship between genes and mood?

Kashif:                  Oh, huge. So that’s the first place we always start. It’s very hard to support someone in their health journey if they don’t understand how they think.   So first of all, the way they think things are happening and their perception versus what’s really happening, and there’s no good or bad to that. There’s just always a gap. Everybody has some unique perspective.

                                Also, as a coach or a healthcare practitioner, how do you actually guide this person? So how do they seek reward? What motivates them? Do they burn out? Do they procrastinate? Do they have highly reward-seeking tendencies, the opposite, where they may overdo it? Are they highly skeptical, and then do they only learn experientially? They need to go through it. You can’t just tell them, “Go do this,” and they’ll do it.

                                So everything about if… Let’s just say this. If I had your DNA in hand, I don’t ever need to speak to you to understand your personality and habits to a T. I can describe you and who you are, whether you should be an accountant or whether you should be an entrepreneur to a T, and it’ll blow your mind. Why? Because we spent three years clinically studying 7,000 people.

                                So one by one by one, we interviewed 7,000 people, sometimes a single interview to many months of work depending what they were dealing with, and we understand how the neurochemicals drive behavior. And it’s indisputable, because this chemical causes you to feel like this. And this is how you make it. This is how you bind it. This is how you clear it, so this is how long it lasts. I can now predict how you deal with that. And there’s multiple things we look at. And now all of a sudden, here’s your personality map. I know it. It’s very, very clear.

Dr. Weitz:            That’s amazing. I saw somewhere where you said the COMT gene plays a role in altruism.

Kashif:                 Yeah, so the COMT gene clears-

Dr. Weitz:            Does altruism actually even exist? I have my undergraduate degree in philosophy.

Kashif:                 Well, here’s what I believe about all mood and behavior and behavior traits. They are based on your context. So we are all wired to do something. We’ve inherited our ancestral genetic legacy. Take me, for example. I have what we call warrior genetics. I need to be on the frontline fighting. Whatever I did yesterday is not good enough anymore. And if you look at my ancestral lineage, it comes from Afghanistan from some level of royalty, let’s call it, that were constantly fighting for the throne. Right?

Dr. Weitz:            Okay.

Kashif:                  So stress was just part of life. Fighting was part of life. The status quo is not good enough. That causes depression for me because I can’t experience pleasure like the average person. I need to fight.  So when it comes to COMT, COMT clears your neurochemicals. Not all of them, but a couple of key ones: dopamine and noradrenaline. And so your ability to experience emotional recall is based on noradrenaline. And if you clear it quickly, you may be a little bit confused about what things actually mean and then what they feel. Your recall may be a little off. But the opposite is also true. If you clear it very slowly, you’re really deeply connected to the impact or the emotion that you had in any given scenario, and you use that as a tool moving forward. And that’s your filter.

                                So now when you’re dealing with people, you may have more empathy. You may have more EQ. You may be able to read them and understand exactly what they need and want, and then they perceive you as that person. And it becomes a superpower. But put it in a different context where, god forbid, there’s a car accident, every time you go down that street it’s trauma because you’re remembering the feeling, not just the information.

                                So this innate understanding of how you’re wired, whether we use words like anxiety, depression, addiction, is based on what context you’re using that tool in. The same thing that can cause depression for me can also cause addiction because my baseline ability to feel pleasure and reward is very, very low. So if I just go do the average thing, I’m going to be depressed. If I find the thing that gives me pleasure, I’m going to be addicted. If I find the thing that gives me reward, because dopamine powers both pleasure and reward, I’m going to achieve. And guess what? I’ve experienced all three of these things. So context is key. Understanding who you are first and what the ideal context is and knowing what the more deleterious context is and what may cause you a problem, then you can choose how you feel.

Dr. Weitz:            Interesting. We screen for vitamin D quite often with our functional medicine clients. I find most people, we have a tough time actually getting the vitamin D up to a really target level. So depending upon the person, 50 to 70, 60 to 80. And then yet a few people, we give them a modest amount of vitamin D. What I consider a modest amount, 5,000. All of a sudden, it goes over 100. And I saw an article where you were talking about how genes control vitamin D metabolism and why most people are vitamin D wasters.

Kashif:                  Yeah. So what’s going on there, of all the micronutrients, vitamin D has the most complex metabolic pathway, the genes that drive it. Because again, ancestral traits, our ancestors weren’t indoors on Zoom calls. They were outdoors most of the day. Agricultural. They were outdoors doing stuff, which means that they were overexposed to vitamin D so their bodies had to learn how to mitigate that exposure.

                                And so what do we do? The first gene takes D2 from the sun and converts it into D3 and gets it into the blood. Step one, I need to metabolize it and turn it into the active form that I can use. Then once it’s in the blood… And this is why the measure of what’s in the blood is not enough of a measure. That’s only step one. That’s only telling you how much the person metabolized.

                                There’s a second gene that then takes that D3 and transports it to the cell. So picture these little taxi cabs that are moving it along and getting it to where it needs to be. Once it gets there, there’s a third gene that binds it and gets it into the cell. And any one of these can be off.

                                So you might have somebody that metabolizes vitamin D really well, but they don’t transport and bind it really well. So that person needs multiple doses because if you give them 5,000 IU, they will only use 1000 of it. They just can’t efficiently get it there and fast enough and bind it fast enough.

                                The opposite could be true. They may be really efficient at binding and transporting, but they don’t metabolize. So they might need 10,000 IU. They might need a lot more, especially in the winter, depending where they live.

                                So you can be really precise. And of all the micronutrients, the number one priority is vitamin D. That’s where you need to focus. Of the 22,000 genes that make up your genome, all of these little instructions in your cells, 2000, so almost 10% of your biochemistry, is dependent on vitamin D. So these genes don’t express if you don’t have the right vitamin D, which is why it affects-

Dr. Weitz:            Wow, wow.

Kashif:                  … anything from mood to skin, everything. So it’s really more so… And you know this. It acts more as a hormone than it does a vitamin.

Dr. Weitz:            Yeah.

Kashif:                  And so it’s key to be precise there, and this is why we built that specific pathway because it really… My niece is a perfect example. She was almost being prescribed a anxiety pill. She was getting anxiety attacks and couldn’t breathe, and I figured out all it was is because she was being homeschooled during COVID when schools were locked down and she got zero vitamin D. She hadn’t been outside in five months.

Dr. Weitz:            Oh, wow.

Kashif:                 And her vitamin D pathway is horrible. And she just needed more vitamin D and a little bit of L-theanine to boost her dopamine levels. That was it. And she was being prescribed an anxiety pill, which she would’ve probably still been on today.

Dr. Weitz:            Right. That’s awesome. Couple more questions. How do our genes tell us about our ability to fall asleep?

Kashif:                 Sleep is… That’s one question, how do I fall asleep, then there’s also how do I stay asleep? And there’s also how do I sleep through the night and actually feel rested? [inaudible 00:31:23]-

Dr. Weitz:            How do I get quality sleep? How do I get good deep sleep? How do I get good REM sleep?

Kashif:                 And those are all different things genetically. So the first one is based on circadian rhythm. So how efficiently does my clock work? So if my clock… There’s two genes. There’s literally a gene called CLOCK, which makes a CLOCK protein which allows your body to understand what time it is. And then there’s BDNF, brain-derived neurotropic factor, which also heavily regulates circadian rhythm. And so if you’re not doing well there, then your body is going to need a very strict routine to be able to fall asleep on time, which means waking up at the right time, getting sunlight and vitamin D at the right time, pausing to breathe a few times during the day, some kind of light sauna or stretching type activity in the evening, no blue light, turning off the TV a couple hours before. We can be very precise about your sleep problem and why you can’t fall asleep, but that same problem doesn’t affect why you can’t stay asleep. That’s a different problem which is more based on serotonin and cortisol.

                                Those are very different problems where if your serotonin is dysregulated, which means your brain is more sensitive to stimulus, it notices everything. And you make your serotonin in the second half of the night in your gut, and your body uses serotonin to wake you up. And it’s literally waiting for sunlight to say, “Okay, time to get up. Let’s bind that serotonin.” But if your brain can’t prioritize stimulus because your serotonin pathway is off, then it’s responding to everything in that second half of night. When the temperature changes, when there’s a smell, when the hubby pulls on the blanket and it touches your skin, every little stimulus in that second half of the night your brain confuses for the sunlight coming through the window and you get up, go to sleep. Get up, go to sleep. Get up, go… So it’s a different problem to solve.

Dr. Weitz:            Right. Interesting. What are some of the strategies to combat some of those?

Kashif:                  Well, for the second one, so this is actually… All of these things that we see as problems are actually our ancestral superpower. So think about the caveman who had to not be eaten by a wolf while he was sleeping.

Dr. Weitz:            Right.

Kashif:                  Right? So the person who was able to have that hypersensitivity to stimulus would survive because they would hear that branch breaking far before the wolf arrived, right?

Dr. Weitz:            Right.

Kashif:                  So that trait is designed to wake you up, but our context is not aligned to the sleep cocoon we actually need, which means heavy weighted blankets so that your body feels safe. Head to toe, the skin is signaled. There’s this weight on me. It is sleep time right now.        Cooling of the mattress. So there’s mattress coolers you can actually get that mimic what it meant to sleep on a cave floor, right?

Dr. Weitz:            Yeah. We use one.

Kashif:                  You use one? Yeah. So it’s an amazing hack that completely changes your sleep because if you have the heavy blanket, a couple hours in you’re going to overheat. How do you mitigate that? You get the cooler, right?

Dr. Weitz:            Yeah.

Kashif:                  Zero light leakage. If there’s light, that’s signaling serotonin to bind. And depending where you live, the light may start at 4:30 AM, which is not the right time. So zero, zero light leakage, potentially an eye mask.  You potentially may have a separate blanket from your spouse. You cannot have that stimulus. So those are the things to consider. How do you make that sleep cocoon?   And now if we know that serotonin is the gene pathway is off, you can also modulate serotonin with the right supplements. So 5-HTTLPR is the gene. There’s a supplement called 5-HTP which helps regulate your serotonin level so you can take one before going to sleep. You know?

Dr. Weitz:            Right.

Kashif:                  There’s things you can do, these adaptogen type things that help you get into a deeper sleep state. So there’s a lot of things available. You just need to know, again, what your body needs. Where do I start?

Dr. Weitz:            Right. Let’s see. One more question. What about our genetics and weight control?

Kashif:                  There’s so much. We need an hour just for that.

Dr. Weitz:            And obviously, obesity is such a big, big risk factor for chronic diseases, or maybe is a chronic disease itself.

Kashif:                  Yeah. So let me give you the fast bullets.

Dr. Weitz:            Okay.

Kashif:                  Hormones is one of the areas that is where people get stuck. So I’m going to the gym. I eat properly. Why can I not lose these last 20 pounds? Hormones. Are you estrogen dominant? Are you androgen dominant? Maybe you don’t have enough fat or enough muscle. You can’t get bigger. You can’t put on the muscle. Maybe not enough of the estrogens. So hormones is a first area, and it’s very easy to use basic supplements to change these gene pathways and change your body.

                                Second one is your brain perception and what you think you’re eating versus what you’re actually eating. Your addictive tendencies, your binging tendencies, your emotional eating tendencies, and these things that never get counted in your calorie count. So that’s another big one.

                                Then there’s actual gut and mouth brain connection, which we talked about a little bit earlier, and understanding your ability to actually feel satisfied and how to hack that. So if you are the person that has the palate need of variety, you have to create it. Give yourself a little bit of cheese, dark chocolate, nut, grape, all the textures and varieties right when you’re with done your meal so that you hack your brain to get the variety it’s desiring. Another big one that nobody looks at is-

Dr. Weitz:            Or you just take Ozempic.

Kashif:                  Or you take Ozempic. Yeah, that’s another way around. And then you get off Ozempic and you balloon up like never before. Yeah. And-

Dr. Weitz:            We’ll call that the Ozempic balloon.

Kashif:                  Yeah. It’s sad, but the federal government went on 60 Minutes and said like a week before Ozempic was released, coincidentally, that 80% of obesity is genetic.

Dr. Weitz:            Wow.

Kashif:                  That’s what they said. They said it’s not lifestyle. This was on 60 Minutes. I don’t remember the name of the person, but it was some health advisor for the Biden Administration went on and said that “We believe that obesity is 80% genetic. It’s not lifestyle or nutrition based.”

Dr. Weitz:            Pharmaceuticals will solve all our problems.

Kashif:                  Yes. A week later, Ozempic gets released. Pure coincidence.

Dr. Weitz:            Yeah.

Kashif:                  Right? So now, yes it’s true that 80% of it is genetically driven if you’re making all the wrong choices, but it’s absolutely false that you don’t have control and that it’s going to happen, that it’s innate. There are genetic conditions like sickle cell syndrome. There’s a gene that’s broken, and you have it-

Dr. Weitz:            Right.

Kashif:                  … [inaudible 00:38:25]. Obesity is not something that you have. It’s something that’s caused. There are some people that have genetic obesity. That’s a tiny fraction of the people that are actually obese.  So the other big one, sorry, I was going to say is environmental toxins. So we’re so overburdened by environmental toxins, what we breathe constantly, that our body is storing fat as a place to deposit the toxins. So if somebody that goes for a run every day in Manhattan that can’t understand why they can’t lose that little bit, because you’re running and breathing in pollution every day and you might not have the right detox pathways to deal with that. And so your body’s trying to protect you by storing fat to deposit that toxin to keep it away from your organs.

Dr. Weitz:            Interesting.

Kashif:                  And that may be your number one thing. That could just be the one thing you have to work on.

Dr. Weitz:            Right. Great. So how can patients get your DNA test done? Is there an option for practitioners to become providers or is this a direct to consumer, or are both options available?

Kashif:                  Yeah, for sure both. So we do work with functional medicine, chiropractors, naturopaths, everybody in that sort of wellness space that thinks the way we think, and a few MDs that have learned about life and what they need to change. So we do work with practitioners. It’s very easy. You open an account. We send you some kits. There’s training if you want. There’s free training. There’s paid training, depending how deep you want to dive.   And then for consumers, it’s thednacompany.com. You simply go there. The test is called the 360. The way it works is you get shipped a kit. You spit in a tube. You ship it back to the lab. We extract your DNA. A few weeks later, you’re going to get an email to access your reports, and the reports are very, very easy to use rather than “Hey, you have this gene, the MTHFR CC.” Nobody knows what that means. It’s more like, “Here’s how your body deals with cholesterol and inflammation. Here’s how you deal with anxiety. Let’s speak in the context you actually can apply this stuff.” And there’s recommendations built right in. So where do you actually supplement? What do you actually change in your diet, et cetera?  Beyond that, there’s some people that have the need for clinical support. I have breast cancer and how do I deal with this? So we do have functional genomic-certified coaches that can take on patients and help them through programs, and we can also train practitioners to do the same. So all of the above.  So it’s thednacompany.com, the 360 test. And to work with us as a practitioner, you can also send us an email through there. You can find us on Instagram if you’d like. It’s my… K-A-S-H-K-H-A-N official. A lot of news and stuff that we put out there. Think about things like Ozempic. So you can keep learning. Yeah, but all of the above. We’re here to support.

Dr. Weitz:            What if the patient already has their DNA run by 23andMe or Ancestry? Can they send that in, or are your tests more extensive or different?

Kashif:                  We would love to be able to do that because there’s 80 million people out there that have done those tests, and business wise it would make a lot of sense. The challenge is that they don’t test for what we test for.

Dr. Weitz:            Oh, okay.

Kashif:                  So remember, these are data collection companies. Their business is sell something on the front end that’s infotainment and then sell the data on the back end to a pharma company. That’s where they make their real money. So they have to build the product in a way that serves that customer, the real customer which is a mass data dump, a bunch of SNPs for the practitioners that are on here. It’s the spelling mistakes in genes.  When it comes to the major pathways that we need to understand, there’s things called copy number variations, where it’s far more complex than a SNP. It’s like, “Do I even have the gene? Am I completely missing it?” You have to test for that separately.

                                When it comes to things like APOE, I can’t tell you how many customers have called us and complain and said, “I have my 23andMe done, and your APOE result is different. And you guys are a scam.” And then we have to explain to them that APOE, we sequence the entire gene. We treat it as an independent test because it’s so complex. So there’s one thing to look for a SNP, and there’s one thing to look for all 20,000 letters in that gene. We test for a lot less, but we are going a lot deeper in those genes that actually are meaningful, the functional genes that drive the main pathways.

Dr. Weitz:            I don’t quite get that one on the APOE. So aren’t you just either an APOE34 or 33 or 44? What else is there?

Kashif:                 The way you determine that is not as simple as it seems.

Dr. Weitz:            Oh, okay.

Kashif:                 And have you heard of Dale Bredeson?

Dr. Weitz:            Yeah, of course.

Kashif:                 [inaudible 00:43:30].

Dr. Weitz:            I’ve had him on the podcast.

Kashif:                 Yeah. So in his book on reversing Alzheimer’s, he says something like, “23andme is something like 65 or 70% accurate,” and that’s why he refuses to use genetics, because genetics isn’t as simple as run a test and get a result. There’s a lot of science behind what that result actually means, and that’s why you see variability between different testing companies.  So what we do, again, we test for less. We’re not looking for thousands and thousands of genes. We’re looking for the 100 that actually matter that are functional, but we go a lot deeper on each gene to make sure it’s accurate and that we inform more. It’s not just a SNP. It’s a copy number variation. It’s also the indel. An indel means that a whole paragraph might be missing or there’s a extra paragraph, not just a letter or a variant. We’re deeper on what matters, and APOE’s a perfect example. You can assume by looking at certain markers or you can sequence the entire gene from beginning to end and be certain, and that’s what we do.

Dr. Weitz:            Fascinating.

Kashif:                 Yeah.

Dr. Weitz:            Awesome. Okay, thank you very much.

Kashif:                 Oh, It’s a pleasure. Good talking to you, man.



Dr. Weitz:      Nice talking to you. Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify and give us a five-star ratings and review. That way, more people will discover the Rational Wellness Podcast.   And I wanted to let everybody know that I do have some openings for new patients, so I can see you for a functional medicine consultation for specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions or for an executive health screen and to help you promote longevity and take a deeper dive into some of those factors that can lead to chronic diseases along the way. And that usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing, and we’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective. So if you’re interested, please call my Santa Monica Weitz Sports Chiropractic and Nutrition office at 310-395-3111 and we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.



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