Nathan Morris: It maybe because I am not that sophisticated. So maybe it works to my advantage.

Kara Ware: Well that is a skill of yours. So are there insights we can gain about this cytokine storm and who may be more predisposed, I mean you’ve said those inflammatory diseases of course, of hypertension and diabetes and obesity, but even beyond, just people who don’t have those diagnoses as well. What insight can practitioners glean from the pure genomics report to apply in practice when we’re looking at how to advantage the immune system?

Nathan Morris: Well, when we were talking about cytokine storm, it is really where we lose the brakes… Here is another analogy. We lose the brakes for runaway inflammation. And the brakes for runaway inflammation, you’ll hear the term Th1 and that’s the side of the immune system that Dr. Yanuck we’ll go into further, that really helps us kill viruses, kills bacteria, kills or removes cancer from our system, but it also acts as a balance to this inflammation that it becomes chronic and leads to autoimmune problems and can lead to the immune system actually attacking our own body.

Nathan Morris: And so that’s where Th2 of which interleukin-6 which is a polymorphism in our gene report on pure genomics and tumor necrosis factor-alpha, these are upregulated and they are an advantage in some scenarios, but they’re really at a disadvantage in chronic inflammation because it’s a feed-forward cycle where we have ongoing inflammation that gets more and more and it attracts [00:05:00] the wrong players into the tissues that then lead to more inflammation, the more interleukin-6, more tumor necrosis factor and all of a sudden you’ve got this thing called a cytokine storm, which is kind of an oversimplification. But as you say, that’s what I do best. And so-

Kara Ware: Exactly.

Nathan Morris: .. and what’s really important about this is that we can look at these genetics that tells us who’s going to be probably predisposed to things like cytokine storm. And I think the literature supports that. We know that if you have more interleukin-6 and tumor necrosis factor, it really does predispose cytokine storm. And you take those genetics and you add that to our living matrix report, which really is a great tool that just came out that identifies patients that are at higher risk due to their history of chronic inflammation type diseases. And it allows us to be proactive in this time, which is, as you mentioned earlier, going to be a long journey. Let’s just not sit back and wait on people to get sick. Let us go ahead and be proactive and power them and get rid of this, “Oh, we’re just going to get it eventually anyway.”

Nathan Morris: No, let us be ready. Let’s get these patients ready and that’s really going to be awesome for us because now we’re able to reactivate old patients and do a real service for them and attract new patients and do a real service for them because this is not going to be over next month or in two months. It is going to be 12 months or 18 months. And I think that’s where I really… Our next guest, Dr. Yanuck, who is a great friend of mine and he’s immune system extraordinaire, gets into more depth of what I’m talking about and I can’t wait to hear more of his explanation right after this.

Nathan Morris: So, we’ve identified hypertension, diabetes, obesity. What is the genetic role here? I want to say that before we get into genetics of inflammation, which plays a big role in these diseases as well as I’ve already mentioned, we really need to… I want to make sure we emphasize that lifestyle changes, which is what we are after as functional medicine practitioners are the most important thing before we even start going after genetics.

Nathan Morris: And so, if we can use genetics to guide lifestyle changes, that is fantastic. But after we address these lifestyle changes, we need to now look and say, “Is there some genetic underpinnings to these people that are going to have more problems if they get Covid-19?” And so, I think also there is been, “Oh this is a new virus. This is something new. We don’t know much about it.” But I think somethings stay the same and I think that’s where Dr. Yanuck, I would love to hear from you about what this means, especially in what we know right now.

Dr. Yanuck: Thank you, Nathan. I really appreciate being here and always nice to do something professional with somebody that I have a friendship with, so I really appreciate that a lot. So I would agree. The thing that I’ve been seeing in all the discussions I’ve been having with friends and colleagues about Covid-19 and in [00:09:30] all the work that I’ve been doing on the paper that’s coming out soon that we can talk about at the end, all of that suggests to me that we know a lot about immunology, about biology, about respiratory function, about all of these different things that have very important application in Covid-19. I think what’s happening, and I think it makes sense that it’s happening from a human nature point of view, there is this tendency to think, “Oh my God, this is a brand new thing. We don’t know anything about it.”

Dr. Yanuck: There’s no research about it at baseline because of course it’s something new and any new research that comes out is thought of as the only thing that exists in terms of the knowledge base about Covid-19. But we do know that Covid-19 is a coronavirus. We have had research on other coronaviruses. We also know how the immune system works overall. We shouldn’t just let go of all that. And we know about very particular immunological functions that are crucial broadly and that are known to be central in Covid-19.

Kara Ware: So, Dr. Yanuck speaking to that point of particular immunological functions, there are two inflammatory cytokines. Nathan mentioned earlier in the show that plays a large role in inflammation, interleukin-6, and TNF alpha. So, Dr. Yanuck, what are your thoughts on the role of the genetics and the insight that they give you for the intervention?

Dr. Yanuck: There are gene defects that we can test for, which relate to inadequate zinc status and there are gene defects that we can test for, which relate to excessive interleukin-6 production. So, whenever you talk about a gene defect, you have to ask, does this gene defect make something happen more or does it make it happen less? In the case of zinc, the gene defect gives you poorer zinc status, less ability for zinc to do a thing, lower zinc levels, and so on.

Dr. Yanuck: And interleukin-6 it’s the opposite. When you have a gene defect related to interleukin-6, you’re talking now about the body making too much interleukin-6. And the research shows that older folks who have this function defect for interleukin-6 have a greater need for zinc and it’s also been shown that older folks who have an interleukin-6 gene defect, that means they make more interleukin-6, they do better when they’re given zinc. So there’s plenty that can actually be done to try to understand for a given person, where are they with this, what do you need to do? Do you have to give them some zinc? Are they at risk of having higher interleukin-6 levels? If they are at risk, that means that they are more likely to have problems or maybe more likely to have problems. If they get the coronavirus disease because they might spin up into this excess of inflammatory manifestation.

Kara Ware: That’s great. That is a great point on excessive inflammation and the inability to fight infections like the coronavirus. So, can you make it a little bit simpler in regard to the immune system to help me understand how the immune system is much more dynamic than just a one response mechanism?

Dr. Yanuck: Yeah. And I think one thing that I think is especially important is we don’t want to think of the immune system as one thing [00:14:00] that just goes up and down, right? There are a lot of different parts of the immune system and I tend to think of it like a football team. So, at the beginning of the game, the whole team runs onto the field together and because they got the same helmet and the same jerseys, it looks like a big pack of one thing. But the reality is that the punter of the football team is not the same as a defensive back, right? They play very, very different roles.

Dr. Yanuck: And in the immune system, there are cells responsible for killing pathogens through one kind of mechanism or another kind of mechanism. There are cells that quiet things down. There are cells that instruct other cells about what to do and so on. Now the inflammatory part of the immune response is necessary to kill pathogens.

Nathan Morris: Sam, you mentioned earlier zinc playing a role in our immune system. Can you go into more detail and how genetics, things like interleukin-6 and tumor necrosis factor being up-regulated or more active, can let us know what we can supplement to address this?

Dr. Yanuck: There’s a lot of interest in the role of zinc, right? And there are medications like Hydroxychloroquine that are drawing attention. It’s not clear that Hydroxychloroquine is at the center of things, but it is clear that zinc, which is a big target of the effect of Hydroxychloroquine. We know that zinc is central to immune function broadly and we also know that interleukin-6 is a big driver of the cytokine storm in Covid-19. So, we know we want to pay attention to zinc. We know we want to pay attention to interleukin 6, and there is a lot that we know about these things. So zinc is necessary for the function of all immune cells. We know that zinc deficiency makes you more vulnerable to infection. That’s true for all humans.

Dr. Yanuck: Now, we also know that zinc inhibits the expression of interleukin 6 and TNF Alpha, two very, very inflammatory cytokines. With coronavirus, early in the game, what you’re trying to do is support activation of the immune system to get ahead of the virus. But as a person who is sick with coronavirus goes on across time, what can happen that can be dangerous is that their immune system can crank up and make them too inflamed. When that happens, it’s less about so-called immune support and more about quieting down the dangerously activated inflammatory process, and quieting down interleukin 6 is at the center of that, and zinc is known to play a very important role in that process.

Nathan Morris: You know, Sam, I try not to see genetics as good or bad. I personally up-regulated interleukin-6 and tumor necrosis factor, which is great because the common cold is not as much of a challenge for me. I tend to go long periods without getting as ill or getting these little viruses that everybody else gets. But when I get sick, I really get sick. I have a very robust response and then I tend to ease over to that. So, there are some advantages and disadvantages. Could you speak to that and how we should be looking at the immune system?

Dr. Yanuck: Sure. I think that each of us has a kind of a mosaic of what we have and as you say, it confers advantages and disadvantages. It’s probably going to be hard for pathogens to live in your system because you have a very exuberant capacity to knock them out, up to a certain point. When those kinds of processes go awry, you can actually undo some of the effectiveness of the immune response. So your goal is going to be more quieting things down. I think it is similar to the people who love to go to the gym because they have huge muscles, they need to do more yoga. But the people who love to go to the yoga studio because they’re so stretchy, they need to lift more weights. [00:20:00] You know what I mean? So each of us has a sense of certain kinds of advantages and disadvantages, and figuring out what parts of the function are overemphasized for you, will help you figure out how to quiet those parts down and how to maybe bring up some other area that’s under-functioning.

Dr. Yanuck: And that’s what’s so interesting about genetic testing is that if you can figure out what your mosaic is, then you know, okay, instead of just thinking generically about things like, “Oh look, I’m not very good at converting beta carotene to vitamin A. I actually need to take some vitamin A.” Maybe I have read about vitamin A and I think it’s pretty cool stuff. So, I’ve been eating carrots, but it turns out that I’m not a guy who can get a lot of vitamin A from carrots. So maybe I just have to take some vitamin A.

Kara Ware: It’s clear that Genomics plays an important role in determining how someone’s immune system is going to respond to their circumstances. So how do you integrate genetics into your practice, and will you please give us an example of how this is useful to you?

Dr. Yanuck: Yeah, well I do a pure genomics test on every new patient. I have them go get a 23andMe test. I have them get the less expensive of the two 23andMe tests because it has all the information we need. They get the response… They got the result back, they unzip the file, they upload it to pure genomics and their report appears on our [00:21:30] computers. We share it with the patient. And I combine that with the lab testing results-

Dr. Yanuck: … so there is what the test result… What the genomics results show and then there’s what their manifestation is in terms of lab work. And that has a few different layers to it, right? One layer is if a person has a, for example, BCMO1 gene defect and they’re very inefficient at converting beta carotene to vitamin A, I want to know does that show up as a low vitamin A level. So, one kind of correlation between the genetic tests and the lab results is when the expectation is that the gene defect would show up as a low level of the substance in the blood, that’s the easy thing to interpret.

Dr. Yanuck: And if their A level is low then it’s low. But what I then want to know is let’s say a few months down the road, the person’s stress [00:17:30] level changes or they get into an accident or something changes about their biology that puts them under more duress. I want to retest their A  level because they may get a manifestation of low vitamin A. They may get a greater representation phenotypically of that genotypic defect then they had at baseline. So, and I’ve seen cases like that where the A or the D or the whatever is fine, [00:18:00] but then when their biology gets stressed out, the thing they have a vulnerability to genetically shows up in their phenotype, in their manifestation.

Dr. Yanuck: Because they may get a manifestation of low vitamin A. They may get a greater representation phenotypically of that genotypic defect then they had at baseline. And I’ve seen cases like that where the A or the D or the whatever is fine, but then when their biology gets stressed out, the thing they have a vulnerability to genetically shows up in their phenotype, in their manifestation.

Nathan Morris: That’s fantastic. I think you brought up a great point that was brought up by Dr. Greenblatt in our previous podcast is that, in times of stress, [00:23:30] which now definitely qualifies for most everybody, so I think that’s just a real pearl to take away from this is that in times of stress and these sort of things, we need to retest. We need to see if this is becoming a problem because we do see that and that was just a great point.

Kara Ware: Since it is spring and early summer, may we talk about some seasonal relevance to the immune system in addition to our COVID conversation? In an earlier conversation you and I had, you mentioned the DAO SNP and I’m curious, where do you see DAO and histamine fitting in?

Dr. Yanuck: Yeah, that’s a great question. Thank you, Kara. DAO, diamine oxidase is necessary to get rid of histamine. And histamine is problematic in a whole variety of ways and of course, people who are Th2 dominance tend to generate a lot more histamine. One of the things that are I think underappreciated is that the level of gastric acid covariates with histamine level. And you will see a lot of people with reflux have an underlying difficulty with histamine. And if you’ve got a gene defect related to less DAO production, meaning if you have a gene defect that yields underproduction of DAO for you, then realizing that and managing that process clinically becomes pretty central to your ability to get over your reflux. But then also there are several kinds of receptors for histamine and on brain cells. There are three histamine receptors, H3 receptors. And when histamine stimulates H3 receptors on brain cells, the production of certain neurotransmitters, serotonin, norepinephrine, and acetylcholine, the production of those neurotransmitters goes down. Well, serotonin, if you lose serotonin, you are going to have the potential to get depressed.

Dr. Yanuck: If you lose norepinephrine, you can’t really turn the lights in your prefrontal cortex on so well. So, you may have some cognitive problems. And acetylcholine is associated with memory. So a lot of people are walking around in kind of a haze and have cognitive deficits that are related to high histamine and they don’t know it. Now is it skyrocketing histamine? No, but it’s high enough to make a difference in their own brain biology. And so taking measures to lower histamine levels and take measures to support DAO turns out to be very important. And then I would say the other factor here is that in addition to DAO, there’s a second step of histamine clearance and that second step involves an enzyme called aldehyde dehydrogenase. And aldehyde dehydrogenase depends on vitamin B2, vitamin B3, iron, and molybdenum, which is a trace mineral. And what’s often missing those folks is the molybdenum. So taking a little bit of molybdenum every day can make a huge difference in how well you do in getting rid of it.

Kara Ware: That is wonderful Dr. Yanuck, you are a wealth of information. This compliments Dr. Greenblatt’s episode number two regarding the support of our neurotransmitters beautifully. So, of course, we want to hear about the resources that you have to help in a practitioner’s education learning curve.

Dr. Yanuck: Sure. Well as you mentioned, Cogence Immunology is an online functional immunology course for clinicians. There are about 4,000 clinicians in that online community. And people can go to cogenceimmunology.com to access that. There are plenty of webinars that I have recorded for Pure Encapsulations and folks can go to the website and find that. There is a paper that by the time this airs we’ll have come out on functional medicine treatments to support people who are involved with Covid-19.  And if folks are interested in brain-related things in terms of functional medicine, there’s a paper that I put out in Frontiers in Psychiatry in October of this past year that I can send you a link to. And it’s about the neuroimmunological mechanisms involved in things like and PANDAS and persistent post-concussion syndrome. Really, it’s all about the immunology of how these central nervous system based disorders can either go well or not well and what the details are there and what kinds of influence can be exerted there.

Nathan Morris: Sam, that was fantastic.

Dr. Yanuck: Good. Thank you. I appreciate that. Well, this was fun.

Kara Ware: So Nathan, this is a big topic. Will you help us summarize how genetics gives us insight into chronic inflammation on how to better understand managing our susceptibility to COVID and other threats of all kinds really and what to do in practice.

Nathan Morris: Well, I think there are three or four things that we should take away in summary. Genetics gives us insight into the upregulation of cytokines, interleukin-6, and tumor necrosis factor. These upregulations if left unchecked can lead to chronic inflammation which can lead to cytokine storm. And so we really want to make sure we have support for that and that that can be explored in more detail in our Thought Leaders Guide to Immune System, which will have a link to. Th1 and Th2 responses are neither good or bad, but the long term imbalance is. And so that is really what we’re talking about is creating balance. And that’s where lifestyle choices come in. We’re creating balance when we’re sleeping when we’re eating correctly when we’re doing the things, we need to do from a lifestyle perspective. We can also look at… After that, we can look at things that taking that we supplement wise like zinc, vitamin C, vitamin D, vitamin A.

Nathan Morris: We really have a lot of choices here and we should not feel powerless in any way balancing the immune system.

Nathan Morris: The thing that I’m so excited about is we can use this information especially now and combine it with somethings where we can reactivate these patients that may be sitting at home with hypertension or diabetes or obesity and say, “Hey, you need to get back in the office and we need to talk about your risk factors and we’ll look at your genetics and we’ll create a plan for you that allows you to be more-”

Kara Ware: On the offense.

Nathan Morris: “… on the offense.” Yeah. On offense Kara. That’s exactly what we’re looking for. We want to be on the offense and feel empowered. I use that word a lot, but it’s so true. It’s so many changes our perspective on life when we’re empowered instead of in a victim state. And right now-

Kara Ware: Absolutely.

Nathan Morris: … yeah, we’ve just kind of been told we should be in a victim state and I hate that.

Kara Ware: So again, that goes back to our first episode when we were saying fear won’t sell. We want to talk to them about being proactive and being on the offense and making a plan that’s reasonable for them to be able to put into action and build on success.

Nathan Morris: Proactive instead of reactive. This is the functional medicine way of approaching the pandemic. I think that sums it up.

Kara Ware: Right. And Dr. Greenblatt gives us an insight on how to have more purposeful action rather than being in a reactive state. Because of course if we don’t have, our dopamine and serotonin, we are going to feel more reactive and victim like so it all ties in beautifully together.

Kara Ware: All right, so now it’s time for our Good Medicine On The Go Practice update.  We’ve been working on our Gantt. I love Gantt charts to make a three-month plan. It helps me wrap my head around everything that we need to do and break it down into incremental steps, just like we were talking about with the patient’s plan. So our-

Kara Ware: … yeah, our business development is remarkably similar to how we cocreate patients’ plans with them and we’ve divided up the tasks and who’s responsible for the tasks. So, we’re working diligently on that. We, of course, are making our decision on our internet phone system this week. RingCentral is the leading option for us. We are also looking at our 1099 contracts and how to personalize them for all of your collaborative care team members and then you’ve been looking into malpractice for telemedicine. Will you tell us about the resource that you found?

Nathan Morris: Yeah, I go back to 1099, I’m going to actually because I think it’s important that I’d rather not have employees and pay a lot of the overhead that comes with the taxes and all of these things. So 1099… Yeah, payroll, it’s a lot and you have to pay a payroll service. So, 1099 works really well whether it’s going to be you, my health coach, it’s going to be Morgan, who’s going to be helping with my genetics. It is going to be the other doctors that are joining me. So, I just wanted to mention that’s why we’re looking at 1099.

Nathan Morris: … NORCAL Mutual is basically a kind of malpractice oriented to concierge services, but if you have less than 750 patients, and I’m not really going to be a concierge service, but less than 750 patients, I get almost a 75% discount on my malpractice. And most functional medicine practice is never more than five or 600 active patients, usually at one time. So I think it’s something worth looking at.

Kara Ware: And we will have that link in the show notes. And then, of course, we are revising your new patient paperwork and you set up a meeting for us today with Cerbo, the EMR. Why did you choose that EMR? Tell us because we’re making a move from what we were using originally.

Nathan Morris: Yeah, we are making a move. I think what I’m hearing, and fortunately, in my position, I’m able to talk to a lot of the industry leaders and it seems like a lot of functional medicine practices are moving over to Cerbo because they’re really kind of built around that model. They have telemedicine, they have the scheduling the way I want it, I’ll have the ability to… Hopefully, when they set up the schedule, we’ll find out today, we’ll be able to get credit card information at that time because I really make sure I get that.

Kara Ware: And they will be integrating with LivingMatrix. So that’s a tool that’s going to be kind of an all in one solution. And that is what our next episodes about actually. Is that we’re still working on your patient process, really diagramming out each point of contact of your patient and who is that point of contact that they meet within your practice and what is that online tool [00:37:00] that we use to create organization and efficiency so that it’s easy for them to stay in the process with us and therefore that enhances their patient activation. And we’ll use features like that LivingMatrix COVID risk assessment that you were mentioning earlier to reengage former patients. And we’re going to be talking about how we’re using pure genomics to attract a new audience and we’re going to kind of go through the next episode of these nuts and bolts of building your back-office systems that then lead your website messaging and that patient experience in episode number four.

Nathan Morris: Looking forward to it Kara.

Kara Ware: And just one last thing we want to hear from you. So, go to karawarecoaching.com\podcast. There is a form to submit and we want to hear topics that you would like us to discuss in future episodes. Thanks so much for being here.