A Different Type of Gene Testing Which Might Outperform Current Testing with Dr. Joe Veltmann

I have not been impressed with the data supporting gene testing, so I was curious to speak with a specialist in this area to air my concerns. I must admit that Dr. Joe Veltmann piqued my curiosity with his approach. He makes an interesting critique that much of today’s gene testing is more entertainment than it is informational. Fortunately, he does offer a testing option for those who want to pursue gene testing he feels to be truly informational and able to impact one’s health.

Episode Intro

Dr. Michael Ruscio, DC: Hey, everyone. Welcome to Dr. Ruscio Radio. This is Dr. Ruscio. Today I’m here with Dr. Joe Veltmann. And we’re going to be talking about gene testing. And it’s definitely a topic I’ve been wanting to have someone who specializes on this topic on the podcast for a while. So I’m happy to have him here. Joe, welcome to the show.

[Continue reading below]

Dr. R’s Fast Facts Summary

Research examples of when gene testing doesn’t appear to offer any benefit

  • Diet FITS trial to guide decision on whether or not to eat lower carb or lower fat
  • APO-E testing to predict best diet for improving cardiovascular markers Food4Me trial
    • Healthcare practitioners wanting Dr. Ruscio’s full summary. Not a subscriber to Future of Functional Medicine Review? Click here.
  • MTHFR in Asian’s preventing stroke risk, regular folic acid reduced risk.  Although there is some suggestion that those with MTHFR may do better with methylated folate. [1] [2]
    • Healthcare practitioners wanting Dr. Ruscio’s full summary click here and here. Not a subscriber to Future of Functional Medicine Review? Click here.

Research examples of when gene testing does appear to provide benefit

  • MTHFR testing predicted those who responded better to methylated folate (specifically TT genotype responded better than CT or CC)
    • Terminology
      • MTHFR 677CC = a common MTHFR genotype with no risk alleles
      • MTHFR 677CT = a heterozygous genotype with one risk allele
      • MTHFR 677TT = a homozygous genotype with two risk alleles

Dr. Veltmann’s gene testing is different, it’s not monogenic testing

  • Often times researchers are looking at monogenic design models
  • Genes are encoding for multiple proteins within multiple biological systems, it’s imperative to be looking at a interrelationship and a connectedness to various other genes that are part of multiple other pathways in the body.
    • When testing for weight loss for example they look at more than 25 genes
    • Just testing one gene like MTHFR for example is a sub-optimal approach
  • Dr. Veltmann’s lab tests within a specific ethnic group as well
    • Most research is done on caucasians which doesn’t inform other ethnicities

Conditions and symptoms that genomic testing may help

  • Vegetarians – Fat intake
  • Vitamin D
    • From sun or supplement, or if higher levels are needed, or if higher calcium intake is required
  • Fatigue; CoQ10

Direct to consumer gene testing may be more ‘entertainment’ testing than ‘clinical-based genomics’ testing

  • Many of the direct to consumer internet gene testing companies are using Pubmed abstracts to draw inferences from

Where to learn more about Dr. Veltmann:

Dr. Ruscio Podcast
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In this episode…
Episode Intro … 00:00:40
When Gene Testing Doesn’t Seem To Work … 00:09:20
Polygenic approach … 00:13:30
Testing and Treatment … 00:18:25
Conditions Genetic Testing May Help … 00:30:10
Neurological … 00:40:24
Influence of Genomix … 00:50:00
Direct to Consumer Genetic Tests … 00:51:30
Episode Wrap Up …01:02:15

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Dr. Joe Veltmann: Thank you very much. I appreciate you offering the invitation. And I’m excited about being here today.

DrMR: I’m excited also. And before we get into the topic more deeply, can you tell people a little bit about your background and how you got into gene testing specifically?

DrJV: Yes, I’ll be happy to. I’ve been doing functional medicine, integrative medicine for almost 25+ years. I’ve had lots of experience working with individuals with serious chronic illnesses from my time in New York, as well as here in Santa Fe, New Mexico.

And one of the things that I tried to do early on in my clinical work is come up with a model that was going to be very useful, both for the patient, as well as myself, to be able to hit all of the high notes on a particular person’s chronic illness. And I was working with a chronic fatigue patient in New York. And I jotted down some things that I wanted to share with her and flesh out. And I wanted to explore genes, how environment was impacting her health and her diagnosis of chronic fatigue syndrome. I wanted to look at nutrition, her emotional body, stress, inflammation, and spirituality. And spirituality here, for my orientation, is her belief systems. And she reflected very quickly that if I took the first letter of those 7 variables, it spells Genesis. And I said, “Well, thank you very much. I think this is the model that I’m going to be using for the next 25, 30 years or however long I’m on this earth” because it really encapsulates how all of the biological systems are interrelated.

And it contained the element of genes. DNA StrandBut I was limited—this was almost 25 years ago when this happened—I was limited just by looking at her inherited family disease conditions. I didn’t have genomics as a tool to help me explore some of the conditions that were related to gene SNPs—single nucleotide polymorphisms, that’s the acronym for SNPs—that play a role in whether a particular biological system is functional. And so when I learned in 2001 that there was a company that was actually looking at genomic SNPs, I jumped at it because it really helped flesh out this Genesis Matrix Model even more than just being able to look at inherited disease. So for the last 17 years, I’ve been actually unzipping people’s DNA using many, many, many different platforms that have come available.

And 4 years ago, my partner and I decided that what we needed was our own chip as opposed to using someone else’s platform. So we have 144 different genes that we look at today across many different biological systems. And as a consequence, when we work with someone using the Genesis Matrix and this tool called Genomic Medicine, it really, really flushes out the underlying mechanisms that are participating in that individual’s chronic disease process.

DrMR: And now I’m assuming that how you remedy some of those mechanisms would be a combination of lifestyle, diet, nutritional supplements, and then also perhaps some herbal medicines and then maybe in select cases medications. Is that kind of the therapeutic repertoire you’re using to modulate your findings?

DrJV: Yes, exactly. Those are the springboards that we use based on someone’s genomic data because once you have that information, you now understand how genes are encoding for specific proteins. That may be enzymes. They may be skeletal proteins. They may be receptor cites. And by using the things that you just identified, we can either turn up the volume on gene expression, or turn it down. Or we can circumvent it. And as a consequence of that, we then use biomarkers to evaluate an N of 1, which is a statistical term, rather than using a cohort of thousands and thousands of people. We’re using the individual patient before and after biomarkers as our measure of success.

DrMR: Gotcha. So you’re looking at the genes to tell you essentially what biomarkers may be skewing underneath a given condition or set of symptoms. And then of course you can change the genes with treatment and then retest and see a gene change. So you’re using biomarkers to essentially track the efficacy of the treatment.

I’m wondering are you using or have you used some kind of symptomatic questionnaire? As an example, for IBS, there aren’t really great biomarkers. There’s not a great biomarker, at least as I understand it, for something like bloating. But there are validated symptomatic questionnaires that can be used. So how are you assessing when there’s not a great biomarker available to track something?

DrJV: Good question. We first start out with an individual filling out a comprehensive health questionnaire. This is about 32 pages long. And what we are trying to do is help fill in those 7 variables associated with the Genesis Matrix. And as part of that health questionnaire, we’re getting values, if you will, both quantitative as well as qualitative values. For example, stress. Or for example, IBD. Or for someone’s emotional health. So we are using that as our baseline. And then after we do our nutrigenomic interventions or pharmacogenomic interventions, then we will come back and ask that individual to fill out that questionnaire again and give us both the quantitative and qualitative answers that we’re looking for.

DrMR: Okay. That’s practical. I like that. So I’m sure the audience is wondering the same thing that I’m wondering, which is there have been some studies published making me a bit tenuous about how quickly I engage into the world of gene testing. And what I’d like to do is air some of my concerns. And I’m hoping that you can help me, I guess, reconcile how we account for those concerns and what you’re finding solution to be. So if you’re ready, I’ll just launch into a short diatribe here and then I’d be very curious to get your response.

DrJV: Go for it!

When Gene Testing Doesn’t Seem to Work

DrMR: Okay. And, again, I think the audience knows that I have never posed myself to be a gene expert. But I do maintain a cursory glance at the literature. And, again, there’s a few things that I’ve caught that have made me a bit circumspect.

DIETFITS StudyNow, there was the DIETFITS Trial by Christopher Gardner over at Stanford. And for people listening, I’ll include all the links to these studies. And essentially they were trying to look at various, I guess you could say loosely, gene markers that could predict whether or not someone should be on a low carb or a low fat diet. And I thought this was a very well executed study. And they didn’t find that genes had any predictive value on who would respond best to each diet.

Food4Me StudyThere was also the Food4Me trial that tried to use ApO-E genotype testing to predict, again, said loosely, if someone should be on a lower fat diet or not and how that could predict beneficial changes in cardiovascular biomarker profiles.

And then the final is really one data set. Two studies were published out of this one data set. It was a large Asian population study looking at giving folic acid. And to be clear, not giving methylated folate, but actually giving folic acid to those with the MTHFR gene polymorphism. And they found a notable reduction in homocysteine and in stroke risk when people with MTHFR folic acid. And, now, to be fair, there may have been a trend showing that those with more MTHFR polymorphisms—so the Tt genotype, which is kind of your double risk genotype—there may have been a trend there, to be fair, that suggested that those with MTHFR, the double MTHFR mutation, may have had the least benefit.

MTHFR StudyAnd then there was one other study showing that those with MTHFR did see a better reduction. Those with the Tt genotype, again, did see a better reduction in homocysteine when on methylated folate. So I think there’s a little bit of a case there, but also some contradictory points.

So curious how you’d reconcile that?

DrJV: You’ve brought forth a lot of interesting questions based on these three examples that you’re referring to. One of the things that makes us unique because when we do our genomic testing platform, one, we are specific for an ethnic group. So if that individual is Asian, there is very, very limited data with respect to gene polymorphisms for the Asian population. That’s changing. That’s getting better. Where most of the research has been done is in Caucasians. So when we interpret these gene polymorphisms for a particular racial group, we need to be mindful that oftentimes, particularly if you’re talking about African Americans, if you’re talking about Asians, or if you’re talking about Mideastern ethnic groups, there hasn’t been a lot of research done.

The second is that when we look at a particular health issue, in this case that you’re talking about whether genes will influence a particular person’s selection of whether it’s a high fat or a low fat diet, or using ApO-E to determine whether that’s going to impact someone’s cardiovascular risk, or whether somebody’s supplementation of folic acid is actually going to decrease homocysteine levels, what we understand—and this has been the evolution of genomic testing over the last 5, maybe 8 years—is that oftentimes when you look in the literature, researchers are looking at monogenic design models, meaning that researchers are looking at a single gene—just like if they were looking at a single drug—to see if that was going to have an impact on that individual.

Polygenic Approach

We look at a polygenic approach. So when we’re talking about whether somebody ought to be on a low fat, low carbohydrate, or a high fat, high carbohydrate diet, within the profiles that we’re looking at as it relates to weight loss, we’re looking at more than 25 genes rather than just one gene that may be somebody selecting for as to whether that’s going to be an indicator of whether somebody ought to be on a low fat or a high fat diet. Same thing for ApO-E. Because these genes are encoding for multiple proteins within multiple biological systems, it is imperative to be looking at an interrelationship and a connectiveness to various other genes that are part of multiple pathways in the body.

AdobeStock69978466 WEBFor example, if you’re looking at MTHFR…And remember that when you have a gene SNP, it’s not a mutation. Mutation is either an on or off switch, whereas a polymorphism means that there’s, particularly if you have the Tt alleles, that indicates that individual is compromised between 60% to 80% of their ability to use folic acid. So what we look at is…And this is going to get a little gnarly for those that are not biochemistry aficionados. But when you’re talking about the folic acid pathway or folate pathway or transmethylation pathway, you also need to include the transsulfuration pathway because that’s where homocysteine is playing a role. And there are multiple genes encoding for multiple enzymes, both in the transmethylation and transsulfuration pathway that are going to influence someone’s homecysteine level.

So, again, it’s really important that if you’re thinking about doing some genomic testing that you work with a clinician who understands or who has evolved beyond the monogenic model and can actually look at multiple genes in multiple different pathways to identify how those are going to impact a particular biomarker as in the case of homocysteine.

DrMR: I think that’s fair. As you’re describing this, I’m thinking of, firstly, why people should be cautious with describing themselves as MTHFR homozygous or heterozygous, almost like people are describing their ethnicity. It’s such a definitive piece of evidence now that people are, I think, really overextrapolating from. I would caution people not to do that. And also looking at gut testing, I’m not an advocate of looking at just one gut marker—as an example, candida—and then making all of one’s digestive healthcare strategies centered around the candida. So I can totally relate to this approach.

The thing that I’m wondering, I guess here, is one of the things I’ve been doing in the clinic is much less testing because there’s such a confection of different markers, it can be hard to use the markers to steer the treatment. And so I end up using less testing and much more of an empiric approach. As an example, using IBS again because I referenced that earlier. So irritable bowel syndrome, gas, bloating, abdominal pain, altered bowel function. There’s a certain set of tools in our toolkit that we can apply. And we can apply a certain treatment and see how someone responds and proceed empirically to personalize the treatment plan to the individual based upon how they change or improve or in some cases regress symptomatically.

And so I wonder, compared to that type of approach, are some clinicians able to steer this process empirically? Or is there some data that you get from this testing that is really important and changes the way that you would treat someone and is not able to be obtained empirically?

Testing and Treatment

DrJV: Great question. And I have three examples for you if you’re ready because I think it’s important to understand, as you’ve identified, we have a toolbox. And genomic testing is another tool in our toolbox. If someone comes in that’s experiencing fatigue and your inclination is, “Okay, maybe this individual might have a coenzyme Q deficiency” because coenzyme Q is a rich antioxidant that works in the electron transport system, which is responsible for generating ATPs. And ATPs are energy sources for our cells. And I use this example because most clinicians understand that we can actually synthesize coenzyme Q-10 if you have all of the right cofactors and substrates available for that synthesis to occur.

coq10However, coenzyme Q-10 is a provitamin. That means it does not have any biological activity unless it undergoes an enzyme biotransformation to ubiquinone. So from ubiquinone, an enzyme has to work on that molecule. Ubiquinone is the same thing as coenzyme Q-10. But in order for coenzyme Q-10 to function in the electron transport system, it needs to get reduced to ubiquinol. And there’s a specific gene that encodes for a particular enzyme. That gene name is NQ01. If that individual has an impairment in that gene’s ability to manufacture that enzyme, then that individual’s coenzyme Q content, the active coenzyme Q-10—ubiquinol—is diminished. If you use a functional medicine test that is readily available to clinicians to measure coenzyme Q-10, you’re measuring the inactive form, ubiquinone. So with genomic testing, you can overlay a functional medicine test biomarker with that person’s genomics to identify whether they’re actually converting ubiquinone to ubiquinol and whether they need to supplement with ubiquinol as opposed to ubiquinone or coenzyme Q-10.

And there’s an economic reason there because ubiquinol is more expensive, usually anywhere between 3 to 4 times more expensive than the coenzyme Q-10 that you can get for anywhere between $10 to $15 at a health food store. So with that information, what we can do is say to that individual, “You don’t have the right machinery to be able to convert this ubiquinone molecule, whether you synthesize it yourself or whether you take it, or whether some clinician has actually recommended coenzyme Q-10 because you’re on a statin. If you are not converting that ubiquinone to a ubiquinol molecule, you are not going to benefit from that particular molecule, both acting in the cell membrane as an antioxidant, as well as an electron transport system.”

“part of genomic testing is really to help the clinician personalize and individualize that person’s nutrient requirements”tweet e1540485375388

So part of this new tool that we’re calling genomic testing is really to help the clinician personalize and individualize that person’s nutrient requirements because for most of us, we are familiar with the inactive forms of nutrients, but not the active form. And so with genomic testing, we can help that transition from the inactive coenzyme Q-10 to the one that is biologically important as part of the lipid bilayer, as well as someone’s electron transport system.

DrMR: Okay. That’s a great example. And it’s a nice transition into the next question that I’d like to ask. And this may be an area where we’re kind of between that chasm of having the clinical data and the scientific literature hasn’t quite caught up with it. So I’m certainly open to that. But I want to play devil’s advocate here for a moment. And I’ll use an example that’s a bit more familiar to the language I speak, which is mostly gut geek. And one of the things that I try to be cautious with is looking at mechanistic data and not counterbalancing that with outcome data. Again, I’m open. But this is the concern that runs through my head when I’m hoping to better understand this issue from both sides.

There was quite a bit of razzmatazz regarding prebiotics because they exhibit and facilitate an anti-inflammatory mechanism. However, for many people with gastrointestinal symptoms, the net effect in that biological system tends to be detrimental more often than it is beneficial. And one of the things that I find to be a very helpful navigating light is taking that mechanism and then trying to juxtapose that with, okay, has the hypothesis that certain genotypes or alleles may require one from of CoQ-10 over another, has that been verified in some sort of outcome study? So we can say, “Okay, this was the hypothesis. Now we’ve tested the hypothesis in a group of humans looking for a certain outcome, in this a form of CoQ-10, looking to achieve a significant impact on fatigue.” So do we have data of that sort to help us ensure that we’re going to be seeing a therapeutic effect from what’s happening on more of a cellular or mechanistic level?

DrJV: Yes, well, I think you’ve given me two points. One is probiotics, and the other one is CoQ-10. I think, again, when we look at an individual…Because fatigue is something that we have our case histories in our clinic showing that when you work on multiple levels, when you can work on the physical body, the emotional body, and the spiritual body, as well as looking at someone’s nutrient requirements and personalizing those, then you are making a significant impact on the individual. When we isolate certain mechanistic approaches like just looking at CoQ-10 for a particular fatigue syndrome, what we also want to explore is, one, inflammation. And we have now genes that are associated with the GI tract, specifically IL17A and IL21A. That tells us a little bit about how that individual’s gut is responding to certain foods that they’re consuming. We also looked at IL6 and IL1B. Those are two pro-inflammatory cytokines that are in the on position relative to where they ought to be if that individual has a gene SNP on it. So that’s upregulation of that particular gene that’s encoding for these cytokines.

Secondly, if you have a gene SNP on IL10, which is acting as a brake on these pro-inflammatory cytokines, now this individual is in a state of inflammation, both at the GI tract level, as well as total body. And one thing that is really, really fascinating—and I’m trying to bring this back into this concept of a comprehensive, holistic model—IL6 is very much tied to someone’s stress. So if somebody is experiencing a lot of emotional stress, physical stress, mental stress, or even spiritual stress, that is jacking up IL6 value levels and creating a pro-inflammatory response in that individual that really needs to be downregulated before you start doing anything else. And you may need to work on that individual at the emotional level rather than just trying to Band-Aid IL6 by giving them a particular supplement that will help downregulate that particular gene.

DrMR: Okay. I’m seeing some of the outline of the approach you’re advocating come into focus.

Sponsored Resources

diagnostic solutionsDrMR: Let’s talk about one of my favorite tests for digestive health, the GI map from  Diagnostic Solutions, who has helped to make this podcast possible. Now, if you’ve been reading any of the case studies I’ve published in the Future of Functional Medicine Review clinical newsletter, you’ve likely seen that this test, the GI map, is a test I frequently use in my practice. Why? Well, one of my favorite things about this test is it has excellent insurance coverage. This is a few hundred dollars I save patients. This lab is also CLIA certified, which is essentially the quality assurance bureau for labs. So it’s important that these labs are being monitored, not cutting any corners. That’s where you get your CLIA certification.

Now, this test uses quantitative PCR technology, so it’s a DNA test. And you’ll get a good read on dysbiosis with this test, because they will assess and report out various types of bacteria, yeast, and parasites, including protozoa, worms, and amoeba. They also have some valuable and helpful clinical markers, like calprotectin, which can help rule in or out inflammatory bowel disease, and zonulin, a marker of leaky gut. So head over to DiagnosticSolutionsLab.com to learn more, and to order your test.

Conditions Genetic Testing May Help

DrMR: Let me ask you this because this may help have more of a concrete understanding. Are there certain conditions or symptoms or biomarkers that you found this genetic testing type approach tends to work better for than others?

DrJV: Yeah. If you’re working with a population of strict vegans, vegetarians, and they are relying upon plant-based omega-3 fatty acids, that is ALA (alpha linolenic acid), to then get biotransformed into the eicosapentaenoic or anti-inflammatory fatty acid…And they have a gene SNP on FADS1, which is basically encoding for a desaturase enzyme that is part of this cascade of taking ALA to eicosapentaenoic acid. What happens is that when this individual—and I evaluate this essentially by looking at their fatty acid composition using a functional medicine laboratory—we can then help them understand that while ALA is supportive of other biological systems, it’s not generating the anti-inflammatory fatty acid EPA. And we can then recommend for those that are strict vegetarians an algae-based EPA that will suffice in order to meet that nutritional need for EPA. And by the doing so, what we help that individual see is that this one-size-fits-all or one-size approach towards nutrition is not appropriate if you understand someone’s genotype and see how they are, that certain biochemical and biological pathways are compromised.

DrMR: Okay, and that certainly makes sense for vegetarians. And that could be a big miss from a dietary standpoint for them. Are there other dietary modifications that you’re finding the testing is very helpful for people being able to realize?

Tablet mit der chemischen Strukturformel von Vitamin D

DrJV: Vitamin D… we have a vitamin D epidemic in this country where many people are actually subclinical as it relates to vitamin D levels. And while this may take 5 or 10 minutes to talk about, I think it helps to, again, use someone’s genotype to superimpose on the biochemical process by which we can either use sunlight and UV radiation to activate certain precursors to the active form of vitamin D, which is 1,25-dihydroxy vitamin D. When an individual is evaluated by a clinician, they are measuring 25-hydroxy vitamin D. When you can use someone’s genotype and superimpose how that individual is getting a very low level of 25-hydroxy vitamin D, you can recommend a supplement as opposed to relying on the sun because they don’t have a gene that’s encoding for a particular enzyme that is necessary to convert cholesterol to 7-dehydrocholesterol, which is the first step in the synthesis of vitamin D.

And by looking at whether that vitamin D molecule, whether it’s the 25-hydroxy or the 1,25-dihydroxy vitamin D molecule, is being transported. We now understand that vitamins, particularly the fat-soluble vitamins, need transporters to take them from the kidney to the liver or to the various organs and cells in the body. If that particular gene, which is called the vitamin D binding protein, is compromised, then you may be generating lots of 25-hydroxy vitamin D, but it’s not actually getting transported into the kidney to convert to 1,25-dihydroxy vitamin D.

We also understand now that vitamin D needs a receptor in the cell nucleus in order to function. That’s called a vitamin D receptor. And we evaluate 3 of them. And these are related not only to how well 1,25-dihydroxy vitamin D is actually communicating to the nucleus of the cell and the cell’s DNA to then generate certain proteins that are necessary for someone’s optimal health over and above bone health. But we also are finding that these vitamin D receptors are influential in whether that individual has a deficiency in calcium. So part of our understanding of vitamin D is looking at its relationship to, one, its synthesis, two, its transport, and three, how it’s actually being utilized by the cell nucleus, and third, how is that vitamin D receptor in the intestine influencing someone’s calcium requirement.

DrMR: Okay, so in terms of how this translates into clinical actionables, one would be, I’m assuming, calcium intake. Would the other be if they have a vitamin D receptor polymorphism, would you then advise people to shoot for the highest end of the range of vitamin D compared to being the meat of the middle of the curve?

DrJV: Perfect, yes. You’ve got it.

DrMR: And then regarding the binding protein, that would steer whether someone should supplement predominantly or obtain sun exposure predominantly?

DrJV: Absolutely. If they are able to synthesize that cholesterol molecule to the 7-dehydrocholesterol molecule, which is what UV radiation is actually doing, facilitating.

DrMR: And now I’m assuming that we don’t have any outcome data yet to show clinical endpoint outcome, which is fine. It sounds like we’re ahead of where some of the published randomized control trials probably are. But I just want to make sure I don’t miss that if there is any of that data available.

DrJV: Yeah, I’ve got a ten-year longitudinal study associated with women who are either predisposed toward ER positive—estrogen receptor positive—breast cancer, or those that have already been diagnosed with ER positive breast cancer and what to prevent its recurrence. And I have about 200 women who, based on their genotype, are at risk. They’re susceptible. They’re predisposed towards creating an ER positive breast cancer if they don’t do any nutrigenomic intervention.

breast cancerAnd I have 75 women who were diagnosed with ER positive breast cancer. And to date, those women have stayed on the nutrigenomic recommendations based on their DNA. And no one has, one, either come down with ER positive breast cancer in the group that didn’t have the disease. And for those 75 women who are doing the nutrigenomic interventions, no one has had a recurrence in more than ten years of doing this work.

DrMR: Fantastic. So you’re still collecting on this cohort?

DrJV: Oh, yes. As a matter of fact, I just spoke with a woman in New Orleans who was diagnosed with PR—progesterone receptor—as well as ER—estrogen receptor—positive breast cancer. She’s filling out the comprehensive health questionnaire because she’s very much interested in doing more than what the oncologist is recommending. And she’s premenopausal. And so she is being recommended Tamoxifen. And one of the things that I shared with her is that Tamoxifen is like a pro nutrient. Tamoxifen doesn’t have any biological activity until it undergoes a cytochrome P450 enzyme biotransformation in the liver to convert Tamoxifen to Endoxifen, which is acting as a SER, a selective estrogen receptor modulator.

What we’re going to be doing for her is actually doing a pharmacagenomic test to see how her genes match up with drugs that her oncologist is recommending. Because someone can be prescribed Tamoxifen, but if the cytochrome P4503d6 enzyme is impaired, they’re not going to benefit from the selective estrogen receptor modulator Endoxifen.


DrMR: Now, there’s one area I’d like to touch, which is neurological. And whether it be brain fog or fatigue or anxiety, there is talk in certain functional medical circles about sulfur processing, COMT polymorphisms, I believe CVS polymorphisms. And it’s again, interesting. But I’m a bit cautious. But I’m curious to hear your thoughts in terms of people who are struggling with brain fog, fatigue, anxiety. What does the gene testing you’re advocating offer them?

DrJV: We have an emotional health panel where we are looking at 16 different genes that are associated with someone’s—

DrMR: I’m sorry, quick question there. Is there one panel? When you said you had, I believe was it 144 markers, is that one test? Or is it broken down into a couple different subsets?

DrJV: Yeah, we partition it out based on specific disease types. For example, if someone has an estrogen exposure issue and they’ve been diagnosed with ER positive breast cancer, you can just get that particular panel. Nine times out of ten, a clinician is going to recommend getting the ultimate, which is the 144 genes.

DrMR: And just really quick here, what’s the cost difference? Just to help give people a sense, if you don’t mind me asking.

DrJV: Yeah, the cost on the ultimate is about $1,000. And if you actually look at some of the subpanels, let’s say you’re just interested in, say, the estrogenic exposure, you’re looking between $400 and $500. That’s why most people get the ultimate because you get so much more information. And as a clinician, what I like to do is if somebody’s coming in with an acute situation, we certainly want to address that ASAP. But we also, by looking at someone’s genomic information, can look at something that’s working in the background. And we can start looking at this from a preventative medicine standpoint, true prevention, true preventative medicine as opposed to just winging it and not understanding how these biological systems are going to be impacted over someone’s lifetime.

anxious anxiety stressSo the emotional health has about 16 different genes that we look at. Again, we use a polygenic model. So part of the issues that I have with some of the people that are recommending or focusing on the transmethylation pathway or COMT, COMT is catechol-O-methyltransferase. And that’s the gene that encodes for a specific enzyme that helps you degrade norepinephrine and epinephrine. Now, this is just part of the issue associated with anxiety. So when we look at someone’s emotional health, we’re looking at how the brain’s plasticity is connected to whether someone has a gene SNP on COMT because if they have a gene SNP on COMT, typically they are actually anxious or hypervigilant or in a state of anxiety because they’re not degrading these neurotransmitters—epinephrine and norepinephrine—rapidly. So they stay in a fight or flight response much of the time.

What we also want to look at is BDNF, which is a gene that encodes for a particular protein in your brain that has actually been documented to show whether you have plasticity. In other words, if you are confronted with a particular problem, does your brain lock in on one particular solution? Or can it see multiple solutions to a problem?

DrMR: And this BDNF, is that the brain-derived neurotrophic factor?

DrJV: Yes, it is. And as well as looking at dopamine receptors, that’s one of the other genes that we look at within this emotional health panel over and above COMT because if you have a gene SNP on the dopamine receptor, that means that that receptor is ultra, ultra sensitive to dopamine. So now there are lifestyle recommendations that we encourage people to do based on that genotype.

DrMR: And the way this translates, I’m assuming kind of this landscape of different genes that may switch on or off or perhaps would suggest one thing compared to the other. And I’m assuming you kind of look at these in aggregates to be able to say, “Okay, here’s a few takeaways that you could experiment with that, based upon your genetics, may be beneficial.” Is that kind of how this is translating into actionables?

DrJV: Yeah. Because I’ve been doing this for more than 17 years, I have a high level of confidence that if I’m going to be recommending something rather than experimenting with something, it is going to be an aggregate. And we have a gene function matrix that we use to help us identify those genes that have high impact, moderate impact, or low or no impact so that we’re actually quantifying and qualifying how we look at a particular panel or subpanel, in this case emotional health, so that we’re not making a determination based on just one gene, but an aggregate of many, many genes that are associated with someone’s emotional health.

DrMR: And how have you gotten here? Has this been a process of working with people and looking at their tests, looking at your recommendations, contrasting those with their filling out the form a second time and looking at how certain patterns and genes related to certain predictive recommendations that you were making and then relating that back to—

DrJV: Yeah, I’m a researcher. So I’m looking for patterns. And part of the work that I’ve done… And I’ve not only worked with individuals, but I was affiliated with a company in South Florida for 4 years who had a brilliant idea to actually use genomic testing as part of a wellness program. So there were 16,000 people as part of this organization. I didn’t do genomic testing on all 16,000. But we did enough genomic testing on 1,000. And we used essentially a crisis management because in any kind of corporate wellness program, about 10 to 15 percent—and this has been documented in the literature—of your patients both of the population of that corporation are going to be using the most healthcare dollars.

So we were addressing during those 4 years the crisis management, the people that were using the most healthcare dollars. And we were able to save this company 20% of their healthcare expenditure for 4 years in a row. So by having lots of experience, by looking at patterns, by looking at multiple systems and multiple genes within a particular panel, what you gain is an intuitive sense about what needs to be done.

DrMR: And this intuition, is this something that you’re not using a computer program to calculate so you almost have this algorithmic assistance? Or does this all live in your brain?

DrJV: It’s living in my brain currently. We are in discussions with a company to actually use artificial intelligence, to use the comprehensive health questionnaire, to use laboratory testing—traditional and functional medicine testing—as well as genomic testing to help clinicians prioritize directives for that individual, whether it’s oxidative stress, inflammation, whether it’s looking at someone’s emotional health or whether it’s looking at environmental triggers that are causing lots and lots of difficulties with that particular individual.

Influence of Genomix

DrMR: And, Joe, for the clinicians, let’s say they use the test that you’ve put together. You also mentioned certain genes highly influential, others moderately, and others minimally. Does that data flag within each category to help the practitioner adjudicate what kind of decision to make?

DrJV: Absolutely, yes. Rather than us talking about a particular genotype because in some instances—and I’m going to use the genetic terms here—where you talk about homozygous, you talk about heterozygous, and wild type, we have gotten away from that particular model because that’s genetics. We’re genomics. And so what we try to do, in some instances, a wild type actually will have a more serious impact on someone’s health than the homozygous. And so what we try to do is through our interpretation of literature is to give the clinician basically high impact, moderate impact, and low impact for a particular gene within a particular category within a particular panel.

DrMR: Yeah, I could see that being very helpful. And that begs another question, which I’m sure clinicians are wanting me to ask, which is how would this compare to 23andMe, which is a pretty popular test that you hear about? And you can then take that raw data and spin it through something like Genetic Genie to get an interpretation? How is the approach? Because it sounds like the approach you’re advocating, I’m inferring here, is different than that. If so, how so?

Direct to Consumer Genetic Tests

DrJV: Yeah, on our website, we actually have a table that actually helps the clinician understand the differences between what I call entertainment genomics versus clinically based genomics because oftentimes when you get raw data from a direct-to-consumer testing company—and I’m not specifically identifying 23andMe because there are lots of direct-to-consumer testing companies out there. They don’t have the quality controls that actually a laboratory that is serving a particular clinician.

And secondly, we’ve researched this. And many of the internet companies that are trying to interpret this data are using essentially PubMed abstracts to determine whether that particular genotype has a significance to someone’s health. You know and I know that you have to read the whole damned paper in order to understand, one, statistics, two, what the hypothesis is, and whether they are hyping the conclusion because they want additional funding.

DrMR: I see. So they’re just taking a quick bullet from the abstract and not understanding the greater point of the paper?

DrJV: That’s correct. To be able to look at gender, to look at ethnicity, to look at the experimental design in our training course for clinicians who want to get certified in genomic medicine, we actually show how oftentimes clinicians use the genetic model in order to talk about genomics. And unfortunately, when that paper is published, the take-home message is that genomics is not contributing to someone’s overall health. So you have to look at the design. You have to look at the population that they’re selecting from, ethnicity. You have to be a researcher in order to understand all of the nuances that go into an experimental design to be able to interpret the results.

DrMR: And I can absolutely appreciate that. And that’s one of the underlying reasons why I’m a bit cautious about drawing too much in the way of conclusions from some of the gene testing that I outlined earlier. But what you’re advocating is approached differently than that. And it’s definitely got my curiosity piqued. I’ll admit that.

View Dr. Ruscio’s Additional Resources

I’m also wondering what are you doing in terms of publishing? I know you have some of the cancer research that you mentioned a moment ago. But what else are you working on or have you published already that people may want to be aware of?

DrJV: Well, there is actually a chapter in a textbook for orthopedics that is actually being published this month. It’s by CRC Press. And Dr. Roberta Klein and I were asked to co-author a chapter bringing this concept of genomic medicine into the arena of orthopedics. And we have through that particular chapter published case histories because in our model, we are using the N of 1, which I referenced earlier. We are using that individual as their own control rather than using a cohort of people to try to bring in significance as it relates to a certain output or outcome based on genomic testing because we are all uniquely different at the genomic level.

And I have an identical twin brother where I have actually looked at his genome and my genome. And we may have been identical at birth. But we’re not there anymore because genes, in their infinite wisdom, make mistakes as we age, as we develop, as we grow, as we mature. And as a consequence, depending on someone’s environment, those gene variants can contribute to a metabolic, biochemical, or biological system impairment that will manifest very gradually as you age. And that’s why we see a preponderance of chronic diseases in 50, 60, 70, and 80 year old individuals.

DrMR: I’d love to see you set up a study where your control is essentially the—for lack of a more accurate term—the genomic type. And what I’m envisioning in my head is taking a hundred people, testing them. And I’m sure they would aggregate into a couple different genomic types. And then you could vector or render your treatment and then track the outcome. I think would be incredibly powerful for people who are skeptical in being able to endorse this. Because as I know you know, the N of 1 is nice. But it also makes it harder for clinicians who are a bit more conservative or skeptical in being able to say, “Well, how does this translate into my practice and help me with what I’m doing?”

DrJV: Yes. And to be honest with you, we’re not appealing to those individuals who are really conservative and conventional and want to see double-blinded placebo, yada, yada, yada studies because they’re missing the point that everyone is unique. And everyone who comes into a clinician’s office needs to be revered as being—

DrMR: But quick question there. If everyone is unique, then how are you learning to treat the patterns that you see? Because this is the paradox. If everyone is unique, you’re treating a certain genotype for the first time every time. And then how do you learn and carry that forward? So there has to be some kind of commonalities that you can boil this down to.

DrJV: Yes. And that’s where, if you have enough genes…For example, there are some genomic testing companies that are using 20 genes or 40 genes. What you need to be looking at is a good sampling of genes that, one, that are evidence-based, that we know in the literature are, one, have a high frequency in the population. Two, that actually impact a biological system. Three, that has a biomarker associated with it. And if you have the ethnicity associated with those individuals, now you start seeing patterns. And when you have 144 genes that you’re actually looking at, we’re looking at gene variants that total into the thousands across many, many different biological systems.

DrMR: But as you’re saying that, I envision in my head all these papers I’ve read on the microbiota. And they can be consolidated down to these trend lines where there seem to be different, they term the phylotypes. And whether or not we’ve gotten the clinical relevance there, I think is a different conversation. And pardon my prod here. But I’d love to see you continue to try to translate this into how can we take all this data and see if it condenses into certain genomic types because that would be really powerful data if we could say, “This trend of genomic skewing,” if you will, “is very favorably affected by x, y, z.” That would really help make this more applicable, more broadly.

DrJV: That is our goal. And as I suggested, we are working with a company to help us do that through artificial intelligence because we have this unique model, the Genesis Matrix Model because if you are only looking at genomic data without any kind of appreciation for the hologram that each individual is, you are missing the whole point of this new tool.

DrMR: And when you use the hologram, you mean like the context of their lifestyle?

DrJV: That’s right. And their belief systems, their lifestyle choices. And where they are in their own evolution as a human being.

DrMR: Sure. Well, Joe, this has been a fantastic call. I want to be respectful of your time here. We didn’t even work our way around to biomarkers. But that’s for a future call.

DrJV: Well, I put a few in there for people to appreciate.

Episode Wrap Up

DrMR: Yeah, this was a very interesting discussion. I’m very appreciative of the time. Will you please tell people your website or anywhere you’d like to point them to if they want to learn more?

DrJV: Yeah, our website is www.GenomaInternational.com because we work with people all over the world. If you are interested in communicating with me specifically, you can reach me at [email protected]

DrMR: And a question I’m sure people will be asking, is this clinicians only? Do you have any kind of direct-to-consumer? How does that work?

DrJV: Because we feel that genomic testing is rather complicated and complex, we only work with clinicians. But we do, on our website, have general information for the general public who are interested in exploring this concept further. If you are a clinician, you can register. We will then evaluate you to see if, in fact, you have the goods to be able to use this information in a clinical practice. And once you’re approved, then you get to actually see what’s behind the green door.

DrMR: And is there a directory of providers on your website, also?

DrJV: What we’re doing is actually training healthcare professionals. We have an 11-month certification course. We actually have 2 courses, a Wednesday night and a Thursday night course of clinicians from around the world who are very much interested in getting certified in genomic medicine. And this is explained on the website.

And we will have another course being offered in January of 2019 for those individuals that might want to take this course. The feedback that we have received from clinicians who are taking this course is that it’s very dense. And it is applied biochemistry, as I’ve tried to share with you today, that when you’re working in this area of genomic testing, it’s really, really important to understand the biochemistry that’s associated with how these genes are influencing metabolic pathways.

DrMR: Sure. Well, Joe, thank you again for taking the time. This has been a pleasure chatting with you.

DrJV: Thank you. And I hope everyone has a great afternoon. And be well.

What do you think? I would like to hear your thoughts or experience with this.

Dr. Ruscio is your leading functional and integrative doctor specializing in gut related disorders such as SIBO, leaky gut, Celiac, IBS and in thyroid disorders such as hypothyroid and hyperthyroid. For more information on how to become a patient, please contact our office. Serving the San Francisco bay area and distance patients via phone and Skype.


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