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Dr. Warren Brown of Genova Diagnostics speaks about Nutritional Testing with Dr. Ben Weitz at the Functional Medicine Discussion Group meeting on March 25, 2021.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 

 

Podcast Highlights

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This podcast episode is essentially a Tutorial on the NutraEval test from Genova Diagnostics, which is a very detailed test to assess the functional need for various nutrients in patients.  For reference, here is a link to a sample report for the NutraEval.

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4:55  Some of the common reasons for ordering the NutraEval test include conditions like Fatigue, Chronic stress, Chronic inflammation, Mitochondrial dysfunction, Digestive disorders, Hormone imbalances, and Mood disorders.  The NutrEval is a great way to assess nutrient status in someone with a poor diet, for athletes looking for peak performance, for those looking to optimize their health as part of their anti-aging protocols, when patients are on a restricted diet, have had GI surgery or are on medications that can lead to nutritional deficiencies.

6:15  The NutraEval includes organic acids, oxidative stress markers and antioxidants, amino acids, essential fatty acids, nutrient and toxic elements and you have the opportunity to add on vitamin D and genomic SNPs.  There’s about 125 biomarkers in the test and it really casts a wide net looking at what’s going on in the patient’s biochemistry.

10:27  The NutraEval measures organic acids and amino acids, which gives us a perspective on the metabolome, which are the various metabolites that provide a functional readout of the activity within the cells and this is based on medical biochemistry.  The NutraEval measures both nutrients directly, like DHA, which is one of the omega 3 fats, and it measures the functional need for various nutrients. This is based on the concept that if we’re looking at a given metabolic pathway and A converts to B, which converts to C, and we know that that pathway is driven by enzyme one and two and if enzyme two has a nutrient co-factor that is not being met due to a nutrient deficiency, we can see an accumulation of metabolite B that is measurable in the urine or the blood. Methylmalonic acid is a good example, which is a nutrient that accumulates if we lack B12. The NutraEval is measuring things both intracellular, like red blood cell magnesium, and extracellular, like plasma amino acids, plasma copper and zinc, and serum CoQ10.

16:24  The first page of the NutraEval now has Functional Imbalance categories with scores from 0 to 10, so you can zoom in on which are the most significant areas to focus on to help the patients feel better. These categories include oxidative stress, mitochondrial dysfunction, omega imbalance, toxic exposure and methylation imbalance.  A score of 0 to 4 is a minimal need, 5 to 7 is a moderate need for support and 8 to 10 would be a high need for support.  This helps clinicians take a systems approach with patients.

19:08  The second page of the report lists the nutrient needs with a score from 0 to 10 and there is room on the right for the practitioner to list specific recommendations or write in a product name for that particular patient.  Page 3 through 6 are the interpretations at a glance pages and these list the nutrients, the causes of the deficiency, and some food sources of each nutrient. Each nutrient recommendation is supported by between 5 and 14 biomarkers.

23:20  If conventional MDs are skeptical of the NutraEval, you can point out that it includes many markers that are very well represented in the published literature, including methylmalonic acid, the omega-3 index, RBC magnesium, CoQ10, and glutathione.   

25:08  Organic acids are on pages 7-9 and these are byproducts in a number of different body systems. There are end products in these pathways that help us to biopsy the metabolome. And they are indications of vitamin and mineral co-factor needs because of the enzymes involved in those pathways. The enzymes that drive these pathways are nutrient dependent. And there are heavy metals and toxins that can inhibit these metabolic pathways, like the Kreb’s Citric Acid Cycle, and some of these toxins are measured on the NutrEval.  This includes the fatty acid pathway, the beta oxidation pathway, which is how we move long chain fatty acids into the micochondria and if that pathway is inhibited, then we might see high levels of adipic and suberic acid and this often indicates an unmet need for magnesium or B2 or L-carnitine.  Dysfunction here contributes to a higher score on mitochondrial dysfunction on page 1. Page 8 shows markers for malabsorption, dysbiosis (bacterial and fungal), cellular energy and mitochondrial metabolites, B vitamin markers, toxin and detoxification markers, and oxalate markers, which those will be listed on the following page.

26:57  If we look at the section for malabsorption and dysbiosis markers, the first 2 markers are indoleacetic and phenylacetic, which can be elevated if there’s bacterial fermentation of tryptophan or phenylalamine, which could be an indication of poor protein digestion.  This would help us make a recommendation for digestive enzymes. A more direct measure of the need for digestive enzymes would be the pancreatic elastace that is measured on the GI Effects stool profile.  The dysbiosis markers are metabolites of gut bacteria, and there are 5 markers including Dihydroxyphenylpropionic acid (DHPPA) and benzoic acid.  If these dysbiosis markers, you should consider ordering stool testing or you might want to recommend probiotics. The next section are markers of fungal overgrowth, including D-arabinitol, which is a marker that was recently added, replacing arabinose, and D-arabinitol is a direct metabolite of candida albicans.  If D-arabinitol is elevated, you might think about supplementing with Saccharomyces boulardii or limiting simple carbohydrates in the diet to reduce candida overgrowth.

39:33  There are a number of markers for the need for B vitamins and for alpha lipoic acid, including Fomiminoglutamic acid (FIGLU), which indicates the need for folic acid, and Methylmalonic acid, which indicates the need for vitamin B12.  There are also markers for B1, B2, B3, and Biotin.

41:07  Neurotransmitter metabolites.  These are metabolites of things likes tryptophan (Kynurenic acid and Quinolinic acid), dopamine (Homovanillic acid), tyrosine (Vanilmandelic acid), norepinephrine (3-Methyl-4-OH-Phenylglycol), and serotonin (5-Hydroxyindolacetic acid). 

 

 

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Dr. Warren Brown is a Naturopathic Doctor who graduated from Bastyr University and he practices in Scottsdale, Arizona.  Dr. Brown has spoken at functional and integrative medicine conferences across the United States on the topic of laboratory testing.  In his work with Genova’s Medical Affairs department, Dr. Brown enjoys consulting with practitioners from all medical disciplines and providing the support needed to help improve clinical outcomes. In his private practice, Dr. Brown helps athletes and active individuals to reach their highest levels of health and performance through his advanced clinical approach.  Here is a link to the NutraEval Test from Genova Diagnostics: NutraEval.  Here is a link to Dr. Brown’s website: Clinical Advances for Sport.

 

Dr. Ben Weitz is available for nutrition consultations, including remote consults via video or phone, specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or go to www.drweitz.com. Phone or video consulting with Dr. Weitz is available.

 

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Podcast Transcript

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 everybody, I’m Dr. Ben Weitz, in case you don’t know, and welcome to our Functional Medicine Discussion meeting this evening. And tonight, we’re going to take a deep dive into learning about how to interpret and apply clinically, the newly designed NutrEval test from Genova Diagnostics with Dr. Warren Brown. I want to thank Genova for sponsoring this evening. I encourage all of you to participate and ask questions by typing in your question in the chat box, and then I will either call on you, or simply ask Dr. Brown your question when it’s appropriate.

Please consider joining some of our upcoming functional medicine discussion group meetings. April 22nd will be on integrative dermatology with Dr. Julie Greenberg. May 27th is with Dr. Dale Bredesen on prevention of Alzheimer’s disease. June 24th, we have Dr. Felice Gersh and she’ll be speaking about hormone replacement in post-menopausal women, and she’s actually just published a paper on post-menopausal hormone therapy for cardiovascular health in a journal called Heart, which is in the British medical journal family. And then, July 22nd, Dr. Mark Pimentel will be joining us again to give us another update on IBS and SIBO.

And if you’re not aware, we have a closed Facebook page, The Functional Medicine Discussion Group of Santa Monica that you should join, so we can continue the conversation when this evening is over. I’m recording this event and I’ll include it in my weekly Rational Wellness podcast, which you can subscribe to on Apple Podcast, Spotify and there’s also a video version on YouTube, so please check out the Rational Wellness podcast and if you enjoy it, please give me a five star rating and review on Apple Podcast.

So now, I’d like to introduce our speaker for tonight, Dr. Warren Brown from Genova Diagnostics. Dr. Brown earned his doctorate degree from the School of Naturopathic Medicine at Bastyr University. He’s spoken at functional medicine and integrative conferences across the United States on the topic of laboratory testing. In his work with Genova’s Medical Affairs department, Dr. Brown enjoys consulting with practitioners from all medical disciplines in providing the support needed to help improve clinical outcomes. In his private practice, Dr. Brown helps athletes and active individuals to reach their highest levels of performance through his advanced clinical approach. Dr. Brown, you have the floor.

Dr. Brown:

All right, thank you, Dr. Weitz. Let’s see if I can share my screen here. Okay, are you seeing that first slide?

Dr. Weitz:

Yeah.

Dr. Brown:

Okay, great. All right, so Biopsy the Metabolome with the new NutrEval profile. And here I am, I’m the clinical science liaison for Genova Diagnostics. Been with the company about six years. Been in practice since 2012 and so, I’ve relied pretty heavily on specialty diagnostic testing to help make decisions about my patients and the NutrEval is one of my favorite tests to talk about and to utilize as well.

Here are the objectives for this presentation. I just want to have on the agenda this evening, please feel free to use the chat box for any questions, I’ll try to address those as they come in. I’m planning on 45 minutes here and some time at the end for questions as well, if needed. So we’ll take an overview of the NutrEval, we’ll talk about some of the most common clinically applicable questions that I get from clinicians in talking to them about the test as well, and we’ll try to handle the questions along the way as well.  

So, here are some common reasons why clinicians might order a NutrEval profile. It’s not a complete list of reasons, but as Functional Medicine clinicians, I’m sure you’re all aware that nutrient deficiencies are commonly found in these conditions here. Things like fatigue, chronic stress, chronic inflammation, mitochondrial dysfunction. We also see them with digestive problems, hormone imbalances and mood disorders. And you might also consider a NutrEval if you’re looking to evaluate the patients and the quality of the nutrients that’s coming in through diet.  It’s often used for sports fitness and for people interested in optimal health and it’s also a good tool if you have a patient on a gluten-free diet or a special diet. Those diets do have a place and they’re really important, but anytime there’s a narrowing of the diet, there’s a narrowing of the opportunity to get all the nutrients that we need and the NutrEval can help to cover some of those nutrient deficiencies. GI surgeries, medications, those can also lead to or contribute to nutrient deficiencies as well.  

These are the tests and the biomarkers included within the NutrEval profile. So the organic acids, the oxidative stress markers and the antioxidants, amino acids, essential fatty acids, nutrient and toxic elements and you have the opportunity to add on vitamin D and for genomic SNPs as well. So this is the big picture, and we’ll cover all of these in more detail as we work our way through the test, but just wanted to lay it all out here. There’s about 125 biomarkers in the test and really cast a wide net looking at what’s going on in the patient’s biochemistry.  If you were to lay out all of the pages on the test, there would be 13 pages. The first few pages would consist of the overview and the interpretation at a glance. That’s followed by three pages of organic acids, one page of amino acids, fatty acids that would cover the biomarkers and their layout and their metabolic pathway, as well as nutrient toxic elements. And, of course, the genomics which are optional, they’re issued as a separate report, but it is an optional add on for the NutrEval.

I included this slide here, just in case some of you were more familiar with the ION or with the Metabolomix. This is a quick comparison between the NutrEval and those tests. They all do answer many of the same clinical questions, but we can come back to this a little bit later if needed, but I just wanted to illustrate here that these tests are looking at a lot of the same things, so organic acids, amino acids, oxidative stress markers.

And the other interesting thing that I was talking with Dr. Weitz about a moment ago, was telemedicine. And of course, the NutrEval requires both a blood draw and a urine collection and the Metabolomix would be an alternative to that, because that is a test that patients can collect entirely at home, so it’s a first morning urine and a finger stick for the blood spot. So the tests are very similar, but if you’re looking for a test, if you do a lot of telemedicine, you’re looking for a test that patients can collect entirely at home, the Metabolomix would be a really attractive option for that.

Dr. Weitz:

By the way, since you just mentioned the urine part, how crucial is it if the patient, let’s say, we’ve had a number of occasions where the patient came in for a blood draw in the morning. We usually have a mobile phlebotomist come in and do the blood draws in the office and they didn’t collect their urine ahead of time, right?  You’re supposed to collect the urine ahead of time, freeze it for a period of time and then bring it in before it’s sent in. And let’s say they didn’t do that and we just collected then, how much would that change your results?

Dr. Brown:

It could be a problem if the creatinine is low. That’s probably the most common thing that we see in patients who don’t collect their first morning void. Maybe they run it from a second morning void. If the creatinine is too low, because their organic acids are reported as a ratio to creatinine, you could potentially see very high organic acid markers. Wouldn’t affect the blood markers in the test, but it could potentially affect the organic acids. And the creatinine is reported in the test, so you’ll be able to see if it’s too low. That would be something to look out for, if you know it’s not a first morning void.

Dr. Weitz:

Right, okay.

Dr. Brown:

All right, moving into this. So, the title of this presentation, Biopsy of the Metabolome. The metabolome is basically metabolites that provide a functional readout of the activity within the cells and this is based on medical biochemistry and this is a picture of a poster I used to have on my wall that looked at an amino acid metabolism and organic acid metabolism and the Krebs cycle and all of that and how those related to each other.  And so, by looking at organic acids and amino acids, we really get a glimpse of the metabolites and the precursors. This is the virtual biopsy that I’m referring to, and the NutrEval report, and even the Metabolomix report as well, do a really nice job of taking into account those organic acids and the amino acids and fatty acids and trying to acknowledge the nutrient co-factors that drive those pathways and that is the functional readout, in my opinion, so this is sort of the groundwork that I’m trying to lay for our discussion here in a moment about the new report.

Two more little issues I think will be helpful and will answer a lot of questions, is the conceptual framework behind the NutrEval. So, we have a combination of direct indicators of nutrient deficiency, like DHA, for instance. This is one of the omega-3’s. We measure this, if we see it low, it’s something we can intervene directly, to address, so very important, omega-3.  A functional indicator of nutrient deficiency would be looking at metabolites, looking at organic acids and amino acids and, for instance, if we’re looking at a given metabolic pathway here, A converting to B converting to C, we know that pathway is driven by enzymes, enzyme one and enzyme two. And if enzyme two has a nutrient co-factor that is not being met due to a nutrient deficiency, we can see an accumulation of metabolite B, and that will be measurable in the urine or in the blood. Methylmalonic acid is a really good example of that, it’s something that accumulates if we lack B12, which helps to convert it into its next step.

So, the NutrEval, you’re getting both, you’re getting some things measured directly, some things from more of a functional assessment. And speaking of methylmalonic acid, which is, we make a case that’s a functional metabolite, we also have direct, or let’s say, intracellular and extracellular measures of nutrient deficiency. So, I’ve included some examples here of what we might consider intracellular, things like red blood cell magnesium, the essential fatty acids which are reported in the red blood cell, the citric acid cycle which happens inside the mitochondria, and methylmalonic acid is one of those reactions that happens in the cell as well.   However, because there is a strong body of literature behind plasma amino acids, plasma copper and zinc, serum CoQ10 for instance, those kinds of things are also included in the report and they also help us to make recommendations for those things. So, in the NutrEval, you’re really getting the best of both of those intracellular and extracellular.

Dr. Weitz:

It’s interesting, there’s another popular nutrient evaluation test that looks at white blood cells kind of through a complicated process and they’re always describing theirs as intracellular evaluation.

Dr. Brown:

Right. Right. Yeah, and citric acid cycle intermediates, this is something that happens inside the mitochondria, so it’s a direct readout of that.  So, now we get into our page by page analysis, and I know that you all like literature citations, I do as well. I’ve linked the NutrEval support link in the chat box. Should be the first comment in the chat box. But it has over a thousand literature citations in it and more than I could include in the slide, so I highly recommend you check that out. It’s a great resource to have. It lists all the literature citations here.  So, this is the first page of the new report and you can see, it has two main components here of results overview, which has these colorful icons here. Patients seem to like that. It’s been a very nice addition to our GI Effects profile, so we’ve carried over some of that.

Dr. Weitz:

Hang on a second, Doc. One of the participants ask, “Can you link it again, please? I think I joined after you posted it.”

Dr. Brown:

Sure, certainly.

Dr. Weitz:

I didn’t know it worked that way.

Dr. Brown:

Give me just one second. This should be it here. You’re seeing it now? All right.

Dr. Weitz:

Yes, she said thank you.

Dr. Brown:

Okay, excellent. All right, so this is just the overview of the first page. So we have a scoring system now. That’s also similar to the GI Effects, that was a change that really helped a lot of clinicians and patients in making sense of the GI Effects, so we’ve added some of that here. And if we zoom in on those functional imbalance scores here, we can see they’re ranked zero to 10 in terms of the significance of the score. So, zero to four is a minimal need, five to seven is a moderate need for support and eight to 10 would be a high need for support. And these areas include oxidative stress, mitochondrial dysfunction, omega imbalance, toxic exposure and methylation imbalance.

And this is one of my favorite changes about the report, because the previous version of the test, we just listed the nutrient needs on the first page and I think this is a better way to do it, because we want to talk about a systems approach and a functional approach to health and wellness and these are areas where a lot of patients need support. So this is really framing it more in terms of function and in terms of a systems approach, rather than just looking at nutrient needs. Those scores are based on the biomarkers listed below each score and we’ll talk about a lot of those as we go through the test, but this gives you a little bit of insight into how we calculate the scores as well, which is based on the severity of the abnormal biomarker and the strength of evidence behind that biomarker, so it is a weighted algorithm in terms of how we generate the score.

Dr. Weitz:

I noticed you have FIGLU under mitochondrial support, and I think FIGLU is an indicator of the need for B vitamins, right? Folic acid?

Dr. Brown:

Yes.

Dr. Weitz:

But you don’t think about that for mitochondrial support so much?

Dr. Brown:

Yeah, it is, because of its strong association with the need for folate that it’s also listed under the methylation imbalance heading, so some of these biomarkers are connected in more than one of these functional pillars here. FIGLU is a good example of that. Carries a little bit more weight in terms of methylation imbalance, but because folate is important to so many of aspects of cellular health, it also carries a little bit of importance in terms of mitochondrial function.

Dr. Brown:

This is now the second page of the report, so we used to have in the first page and the second page, there was a lot of overlap between that. We’ve sort of condensed that into one page and tightened that up a little bit. And we have recommendations here for antioxidants, B vitamins, minerals, essential fatty acids, digestive support, so you’ll see a probiotic and an enzyme recommendation in some tests. And of course, amino acid recommendations are at the bottom of this page, just like last time as well. There’s also space provided on the right side of the page for you to make any adjustments, since you know more about your patients than just looking at the biomarkers alone. You can make some adjustments, write in a product name, however you would like to use that column on the right. We always encourage you to customize further if you deem that necessary with your patients.

This is the interpretation at a glance page. So page three through six of the report are laid out like this, pretty similar to last time. We list the nutrients need there. This is also ranked one to 10 scale. We’re looking at a high need for alpha lipoic acid here. The nice thing about these pages is that this can help to explain the test results to the patient and you also have the function of the nutrient provided, the causes of deficiency, the complications of deficiency and some food sources, which is a really nice tool if you don’t want to prescribe a supplement for everything for your patients, you can circle a few of the foods listed like spinach and broccoli and Brussels sprouts. Those could be good sources of alpha-lipoic acid and it might be good enough to meet a moderate need.

Dr. Weitz:

So, can you explain where, say, this eight for lipoic acid comes from? What exactly are you looking at that you’ve come up with this recommendation?

Dr. Brown:

Things that trigger alpha-lipoic recommendations are things like pyroglutamic acid and oxidative stress markers, because it’s an antioxidant, so if we see evidence of an up regulated glutathione recycling pathway, like pyroglutamic, or if we see oxidative stress markers, those kinds of things are used to help make the decision about how important alpha-lipoic acid would be, but it’s not-

Dr. Weitz:

So, how many markers are you looking at that go into this recommendation on average?

Dr. Brown:

For alpha-lipoic acid?

Dr. Weitz:

Yeah.

Dr. Brown:

These vary, depending on the analyte, but anywhere from five to 14 markers, depending on the nutrient need.

Dr. Weitz:

And that explains why sometimes you’ll get one of these tests and it’ll say, for example, over here that they need magnesium and then you go in the back and you’ll see that their red blood cell magnesium is fine.

Dr. Brown:

Yes, that’s a good point and I’ve got a good example of that on the Krebs cycle page for this test, where we see magnesium as a co-factor in one pathway that. Does have an influence on our recommendation for magnesium, but red blood cell magnesium also helps us make the decision. So we ultimately have to look across different body systems to try and make that recommendation and it’s based on the balance of the information and whether or not we see it as a pattern. That’s a good point.

Dr. Weitz:

I think that’s one of the really unique things about the NutrEval as compared to just measuring serum levels of some nutrient.

Dr. Brown:

That’s right. That’s right. If we see needs for a nutrient across different pathways, it tends to make a more reliable recommendation and so, that’s why there are so many biomarkers in this test.

Dr. Weitz:

Now, how well has this test been standardized and proven for people who are, let’s say, we talk to a primary care doctor, conventional doctor, who’s very skeptical of this test.

Dr. Brown:

Yeah, I’ve talked to quite a few of those about this test and I always try to focus on the markers that they might have seen before, or might have heard at some point in their training, like methylmalonic acid. There are even some pretty mainstream organizations that acknowledge that methylmalonic acid is a stronger marker for tissue level of B12 status, than serum B12. And a lot of those same clinicians that are very conventionally focused are still measuring serum B12, unfortunately.  So, I always try to point to those markers where they might have heard of, or come across in their training at some point just to sort of remind them that yes, there’s a lot of this that is very well validated and very well represented in the published literature, so I think you could point to the omega-3 index as one of the markers that has a wealth of data behind it. You could point to red blood cell magnesium, you could point to CoQ10, glutathione. There’s quite a bit in the test that should be at least familiar to some degree for conventional providers, but it kind of depends on how open-minded they are and there’s a lot of nuances that goes into-There’s a lot of nuances that goes into that from what I’ve seen.

Well, the organic acids would be page seven through nine in the report, and these are byproducts in a number of different body systems. There are end products or byproducts in these pathways that help us to biopsy the metabolome. And they are indications of vitamin and mineral co-factor needs because of the enzymes involved in those pathways. The enzymes that drive these pathways are nutrient dependent.  And these are grouped into sections. So what you will see on the Krebs Cycle page is fats, carbohydrates, and proteins metabolizing into acetylcholine and that entering the citric acid cycle. Ultimately the end goal of that is to support the electron transport chain and make ATP. And this, we lay things out here in pathway format to help visualize some of the backups or blockages in these pathways. So there are nutrient co-factors that drive the pathways, of course, but there are, in some cases, metals, heavy metals or toxins that can inhibit the pathway.

So we do measure some toxic elements in the report. And if I see a report here where we’re sending a lot of activity, citric acid cycle, a lot of things that are color-coded red indicating highs or lows, and I usually flip to the back of the report look and see if there’s elevated mercury or elevated lead. That can help me know if it’s a toxic reason for an elevation or a nutrient reason for an elevation, or maybe even both. So that kind of information is laid out here in pathway format and a useful tool for trying to understand these energy metabolism pathways.

Here’s the example I was mentioning just a moment ago. So I’m going to zoom in on the fatty acid metabolism pathway, the beta oxidation pathway, which would be how we move long chain fatty acids into the mitochondria ultimately. And if that pathway is having trouble, if there’s inhibition in that pathway, we could see high levels of adipic and suberic acid.  And it’s often that inhibition is related to an unmet need for magnesium and or B2. So this is the carnitine shuttle here. And if that’s not working very well secondary to some nutrient co-factor deficiencies, you might see high levels of adipic acid, high levels of suberic acid.

A patient who is having difficulty losing that last five to 10 pounds of weight, they’re doing everything right, hormone-wise, lifestyle-wise, diet-wise, but they just can’t quite get that last little bit of weight off. Sometimes it’s because their beta oxidation pathway is struggling and it could be related to an unmet need for magnesium or B2. And this does factor into our recommendations for magnesium and B2. But, of course, it’s not the only thing that we look at to make those recommendations.  Moving on. So this is kind of how I look at this pathway page. I sort of chunk that top part of the page together and just sort of remind myself that this is an indication of some mitochondrial dysfunction. It contributes to that mitochondrial dysfunction score.

And the bottom of that page, we can see some antioxidants like coenzyme Q10 and glutathione. And we can also see if there’s oxidative damage with lipid peroxides or 8-OHdG, which we’ll talk about those in a little bit more detail in a moment. But that’s kind of the overview here of this Krebs Cycle page.

The page right behind that would be page eight, which is the organic acids. And this would include malabsorption and dysbiosis markers, some cellular energy and mitochondrial metabolites, which are shown in pathway format on the previous page, vitamin markers, which help us to make recommendations for B vitamins, and toxin and detoxification markers, as well as oxalate markers, which those will be listed on the following page.  We’re going to zoom in on that section by section here, starting with the malabsorption and dysbiosis markers. And the first two markers in that section would be indoleacetic and phenylacetic. These can happen if there’s bacterial fermentation of tryptophan or phenylalamine, which could be an indication of poor protein digestion. And that helps us to make the recommendation for enzymes that we saw on the second page of the test. We also have some dysbiosis markers here for bacteria and yeast, and these are metabolites of bacteria and yeast in nature.

Dr. Weitz:

Can you just explain those malabsorption markers a little more? And how much does that really tell us if we’re dealing with a patient with functional gut disorders?

Dr. Brown:

Yeah. These are metabolites. When bacteria come into contact with amino acids, we’re assuming that protein hasn’t been fully digested and absorbed in the small intestine, and it’s made its way to the large intestine. That’s where huge amounts of bacteria can come into contact with it and metabolize it.  Ultimately, those metabolites are absorbed by the body and excreted in the urine. So it is an indirect way of looking at how well somebody might be digesting or absorbing protein. I would put more confidence in pancreatic elastase in something like the GI effects profile. That’s a more direct way to look at the exocrine function of the pancreas.  But if I see those elevated and my patient’s telling me that they’re bloated, they have fullness after meals, they notice undigested food in their stool, then I’m more inclined to say, let’s try some enzymes with your larger meals and see if that gets better. If it doesn’t, we’ll look at a stool test, but it’s a good way to-

Dr. Weitz:

So is this something that would occur at the same time or as a result of SIBO, or this is a possible alternate explanation for bloating to SIBO?

Dr. Brown:

That’s a great question, because if there is overgrowth of bacteria in the small intestine, there are more bacteria coming into contact with those amino acids as they’re trying to be digested and absorbed in the small intestine. So that is a possible scenario where you could see high levels of indoleacetic or phenylacetic.  So that’s another thing where if your patient says, well, I’m worse when I have a lot of fiber or fermented foods, those make me bloated. My bloating is progressively worse through the day. Those things that clinically make you think about SIBO, that could be a possibility.

Dr. Weitz:

That’s interesting because a lot of times with SIBO patients, we’re taking them off of a lot of the carbohydrates on a low FODMAP or similar diet, and they may be eating more protein. And this could possibly explain why some of those patients are not getting better or getting flares.

Dr. Brown:

That’s a good point, a really good point. The dysbiosis markers, similar in the sense that these are metabolites of gut bacteria, things like DH, PPA, and benzoic acid. That if you see those elevated, you might think about stool testing as a potential follow up. Or maybe probiotics, because those will, if there is some mild dysbiosis, probiotics might be enough to help correct that. Maybe increasing fiber intake, things like that.  But if I have a patient who has a lot of gut symptoms, usually I’m ordering a GI effects comprehensive at the same time or shortly after, or maybe sometimes before this test. I think it’s just a more direct way to look at gut function.  The use of metabolites. We did make a change there, which this is another thing I’m excited about in the report. So zooming in a little bit on the use of metabolites here, we’ve added D-arabinitol. We’ve replaced the arabinose marker that was in that section. And the reason why is because D-arabinitol is a direct metabolite of candida albicans, and it has a stronger association with intestinal yeast. So this is a marker that we feel provides a greater degree of detail around intestinal yeast.  So if you’re seeing a high level of that we could be looking at a patient with some intestinal yeast, if that’s elevated. And you might think about Saccharomyces boulardii or limiting simple carbohydrates in the diet, or however you prefer to deal with these for your patients. This marker could help you make that decision.

Dr. Weitz:

Now, let’s say we see some of these yeast markers high, but it doesn’t show up on the stool tests. They still could have fungal overgrowth, and this could be an indication of that, right?

Dr. Brown:

That’s true. Probably from a published literature perspective, I think mycology culture in stool is the best tool we have. But I wouldn’t say it’s a perfect tool. So anytime I’m interpreting the yeast markers, I’m always trying to make the clinical history part of that interpretation, because I think that’s really important. And I think if I’ve ruled out other things like bacterial dysbiosis, SIBO, other GI issues, inflammation in the gut, if I’ve ruled out all of that, and I’m looking at high D-arabinitol or maybe I see yeast in the mycology culture and the GI effects, then that’s usually my next step.  Brings us to these markers. I didn’t mention this, but this was a new addition to this section of the NutrEval. We added alpha-hydroxybutyrate acid. We list it here, on this page, as a carbohydrate metabolism marker. Really this marker is one that you might see elevated if the patient has some early insulin resistance.  Or you might see it elevated if they just have very poor lifestyle habits, too much alcohol, smoking, maybe too sedentary, those kinds of things. You might see alpha-hydroxybutyrate acid elevated in those scenarios. So that was a new addition to the report as well. And there’s a lot more detail about that in our support work guide.

These are the vitamin markers and these help us make decisions about B vitamins and also has a little bit of impact in our alpha lipoic recommendation-

Dr. Weitz:

Doc, could you just go back to cellular energy mitochondrial for a second?  What do we really get out of some of these markers?  What is carbohydrate metabolism?  What is that really telling us?

Dr. Brown:

It gives you some insight into how efficient the glycolytic pathway is, how effectively they can take carbohydrates and move it into acetylcholine. And so, if you’re seeing accumulations of pyruvic or lactic acid, if those are building up, it could be an indication that maybe there are some nutrient co-factor requirements that aren’t being met for B1, B2, B3, even lipoic acid, alpha lipoic acid, to some degree.

Dr. Weitz:

Or could this indicate somebody who just has an intolerance to a lot of carbohydrates?.

Dr. Brown:

This would be after carbohydrates are already absorbed. And after that you really wouldn’t necessarily be able to tell us much about their digestion or absorption of carbs, but after that step.  And one thing that I’m seeing more and more of these days is, patients who are doing more low carb diets or paleo diets, is the pyruvic or lactic acid low, on the low side of the range. And that could be an indication that the patient’s not consuming many carbohydrates. So you can also use the pyruvic and the lactic in that way to help you gauge carbohydrate intake. Did I answer your question, Dr. Weitz?

Dr. Weitz:

Yeah, sure. Yeah. Thank you.

Dr. Brown:

Sure. That would bring us to these vitamin markers here. And these are helping us make decisions about the need for B vitamins and alpha lipoic acid. And these are things like branch chain amino acid metabolites and formiminoglutamic acid and methylmalonic acid. And these are all informing those nutrient recommendations that we saw earlier on in the report.  And they’re listed, there are some headings here that will sort of provide clues about those nutrient needs. So, for instance, this first part of the section mentions that B1, B2, B3, and lipoic acid are something to think about when these are elevated.  The next subsection there is formiminoglutamic and methylmalonic acid into heading, also to folate and B12, or something to think about if those elevated. FIGLU is the one that’s more specific for folate.  And, of course, we have a couple of biotin markers as well. They help us make the recommendation for biotin. So those are just classic. They participate in a pathway that’s B-vitamin dependent, and that’s how they’re interpreted. Functional indicators, in other words.

That brings us to the neurotransmitter metabolites. And these are metabolites of things like tryptophan and tyrosine. We look at them in the context of nutrient co-factor needs. So if we’re seeing elevations in these, they also help us make decisions about nutrient needs.  And there are some things like chronic inflammation, chronic infections, high stress levels that could influence those results. And I think that’s helpful to keep in mind when you’re interpreting. You might see a patient who’s carrying a lot of stress. They may have higher levels of kynurenic acid. There’s some data to support that.  If it’s acute stress and it’s earlier on, maybe in the earlier stages of adrenal dysfunction, then it’s more of an acute stress. You might see some of the catecholamine metabolites elevated. Regardless, if those are elevated, or if a patient has genomic snips that could impact those pathways, the answer is often B vitamin support. So that is also factored into our algorithm. And there’s a lot more detail and a lot more pathways to look at in our support guide for those.

Dr. Weitz:

And these give us an indication of brain health, neurotransmitter, psychological health?

Dr. Brown:

It’s a good question. And these are measured in the urine. So we’re not measuring these in the central nervous system between the neurons where it really counts. There’s some debate on if you can interpret them that way, or if they are a reflection of what’s going on between the neurons. Some clinicians feel pretty strongly that is the case. Others are not completely convinced.  So there is some, I would say, I have some hesitancy in determining them as a direct reflection of what’s going on between the neurons. But clinically, and just speaking from my own clinical experience, that does seem to make sense, typically, if I often see high kynurenic acid in patients who are carrying a lot of stress. And if they’ve been doing it for a long time and if they’ve been chronically stressed for a long time, you might start to see lower catecholamine metabolites over time.  So there’s a lot of factors that factor into this. But I would say it gives us some insight, but I don’t know if we can say there’s a one-to-one relationship between what we see in an epi- and norepimetabolite, and what’s going on in the brain.

Dr. Weitz:

Could the serotonin marker help us with the management of patients with depression and/or is serotonin an important factor in the gut in terms of motility?

Dr. Brown:

Yeah, that’s a great question. I think it’s just, in my own experience, I think it does seem to line up really well. I think it also depends on what the upstream amino acid metabolite is.  So if tyrosine levels are low, which we’ll see on the amino acids page, if somebody is across the board low in their amino acids, it does become harder to see elevations. And you might see more low levels in the neurotransmitter metabolites because of that.  However, when I see a low 5-hydroxyindoleacetic acid, knowing that is a direct metabolite of serotonin and ultimately of tryptophan further upstream, I do think about supplementation with tryptophan or 5-HTP, especially if the patient’s telling me that they’re having trouble sleeping or their mood is not very good. I do think it’s definitely worth considering. I’ve often seen that be helpful.

The toxin and detoxification markers, in the bottom right of this page here. The first one is pyroglutamic acid, which is part of that glutathione recycling pathway. It’s one of the ways that we can recycle glutathione more specifically through the gamma-glutamyl cycle.  But pyroglutamic acid, if we’re seeing that elevated, it could be because the glucose levels are low, there’s not enough glutaphan around in the body. It’s working harder to try to recycle it. You might also see that elevated if a patient has a current toxic exposure and their glutathione is being oxidized and reduced more quickly. You might see pyroglutamic acid borderline high or high.  And then, of course, you’ll also be able to see the glutathione level towards the end of the report. And you can put those pieces of information together to help make some useful recommendations.  

There is a styrene metabolite here, and a metabolite of MTBE, which those are pretty common environmental toxins. Styrene could be from food packaging or paints or carpeting, things like that can off gas styrene. And the MTBE metabolite is a pretty common water contaminant.  So if you see the MTBE metabolite elevated, you could think about encouraging water filtration, that’s often helpful. However, I have often seen the MTBE marker elevated in patients who do have a good quality water filter, or what they tell me is a good quality water filter. And my next thought, when that happens, is do they have enough B vitamins to help support detoxification of it?  And I often see the MTBE metabolite elevated in patients who are deficient in B2, and folate, and B12. And to me, that makes sense that if they’re lacking those nutrient co-factors that are really important in liver detoxification, you might be more likely to see an elevation of a toxin.

Dr. Weitz:

I have to say, when I see this section, there’s so many toxins that we’re always talking about and thinking about and worried about that, the toxins that you have included here seem somewhat random, like why would you pick MTBE?

Dr. Brown:

These are common toxins. Of course, there are thousands, you’re absolutely right. And we have to draw the line somewhere. We do have some toxic metals later on in the report. But this gives us a little glimpse into what they might be exposed to in terms of some common toxins. And that does give us a little bit of insight. Of course, you could run a more specific toxic panel, but this is just sort of scratching the surface here. Not meant to be an exhaustive work.

Dr. Weitz:

I know. I guess, just from my perspective, if you have like BPA… And, I mean, I can think of some really common ones that everybody’s concerned about that-

Dr. Brown:

I can appreciate that perspective. Yeah, I certainly can. I believe that you raise a good point. It’s something that we’re always looking to evolve the test and just because it’s not there now, you might see that make it into the next version of the test. But it’s a good point. Well, any other questions on that page?  So more of the organic acids show up on page nine, including the new oxalate markers. And these are things like glyceric, glycolic, and oxalic acid. And oxalic acid is the one that, in my opinion-and oxalic acid is the one that, in my opinion, carries maybe the most significance out of the three. That is the one that has the association with kidney stones. And when we think about why we might see high levels of oxalic acid, it could be from oxidative damage. So if there’s not enough antioxidants around or there’s too many pro-oxidants in the body, you might see more oxalic acid or some of these other oxalates show up.  You could also see that say if somebody is breaking down their collagen, so if they’re more catabolic, if there are your high cortisol levels and they’re breaking down lean mass and body tissues, that they’re more catabolic, you could potentially see more of these metabolites as well. So a useful tool to have, if you’re seeing patients with family history of kidney disease, or a nice tool to help protect them against that.

Dr. Weitz:

And then can this be helpful if we’re treating patients with gut problems and we’re suspecting that maybe they have problems with oxalates and needs to be on a low oxalate diet?

Dr. Brown:

That’s a great question. If I see high oxalates or oxalic acid high, I do think about that as an option. I also think about, do they have enough beneficial bacteria in their gut to help metabolize those oxalates.  Lactobacillus, Bifidobacteria and Oxalobacter can degrade oxalates.  And that can be really helpful if you’re putting together a treatment plan to help try to lower the oxalates.  Oxalate-rich foods or avoidance of oxalate-rich foods, that I think is a valuable tool for some patients. I try to think of that as a last resort, because a lot of those are [inaudible 00:52:14] for other reasons, but it something to consider if you’re seeing high oxalic acid in particular.  Let’s see here. There’s a lot more about this glycosylate pathway in our support guide, it goes into these in a lot more detail. But if I had to pick one of those oxalate markers that I put the most confidence in, it’d probably be oxalic acid.

So speaking of oxidative damage, that could be a reason for elevated oxalate, but you also have this assessment for oxidative damage with things like lipid peroxides and 8-OHdG. And they’re on the right side of this slide, but lipid peroxides is telling us about oxidative damage to cell membranes and 8-OHdG is telling us about oxidative damage to DNA, and really useful to be able to measure those. And there’s quite a bit of published literature on those, looking at signs of oxidative damage.  Of course, on the other side of it [inaudible 00:53:36] here is a measurement glutathione and the [inaudible 00:53:40] and measurement of enzyme Q10 and the serum. And so you can see some pretty potent antioxidants for through a direct measure of those. So we’re always trying to balance the pro-oxidants that the patient has in their body with amount of antioxidants need to protect themselves. And this is one place in the report where you can really get into those side by side. Of course, you also have that assessment on the first page, which even broadens the approach even further. But some things measured directly here.

The amino acids… We were talking about that earlier Dr. Weitz, this sec at the bottom of this slide talks about the difference between the NutrEval Plasma and the NutrEval FMV. So no matter what kind of NutrEval is ordered, it will require blood and urine. The difference is in what part of the specimen we look to report the amino acids. And the plasma amino acids, as you would get in the NutrEval Plasma, will tell you more of a steady state of amino acids and protein intake. And this would be about anywhere from several days to three weeks of status. So if you have a patient who’s got an inconsistent diet in terms of the amount of protein they get from day to day, it might be more valuable to look at a NutrEval Plasma.  However, if your patient’s pretty consistent in terms of their protein intake from day to day, you could do just fine with the NutrEval FMV, which would give you about 48 hours status for their amino acids. So that is the difference.

Now, as far as what we’re measuring, we’re measuring all of the essential amino acids and the non essential amino acids. And they’re listed here on the left side of the page. And the importance of these is that they are building blocks for tissues, hormones, enzymes, and even precursors to neurotransmitters as well. But they’re essential, they have to come from the diet or from supplementation, and you can see the levels measured here directly. So a useful tool to have. If I’m seeing signs that the patient has detoxification needs and things like taurine are low, or maybe they’ve got some hypertension and their arginine is low, these are things that by correcting these amino acid levels, we might be able to make some headway in those areas.

Dr. Weitz:

Should there really be an upper range for these? Is it really bad if they’re higher?

Dr. Brown:

It’s a great question. I think it can only be a bad sign if they’re high. And the reason why is, we do need B vitamins and minerals like magnesium and zinc in order to utilize the amino acids. And there may be situations where you have a patient who is not utilizing their amino acids and they’re building up and they’re circulating, but they’re not making their way into tissues or neurotransmitters or enzymes, or what have you. And it can be due to a nutrient co-factor need. So that is a scenario where I think high levels could be a bad sign, but it could be easily corrected with some nutrient co-factor support.

Dr. Weitz:

Now, what if some of these on a high protein diet, like a keto diet?

Dr. Brown:

High protein diet, I would expect to see them at the upper end of the normal range. If they’re really high, I do have some concerns about kidney health, but I rarely see them really high. I think most patients, if they’re… Unless they’re just at the extreme in terms of protein intake, I think are going to be okay on a keto diet a higher protein diet. But it’s a good question. I think one thing that would also concern me potentially is if you see the essential amino acids very high or robust, and you see the non-essential amino acids kind of at the lower end of the range, that could be an indication that they’re not converting some of the essentials into some of the non-essentials, which could also be an indication of a need for B6 and a few other B vitamins. So there are some circumstances, but you’re right. I mean, therapeutically, those diets can be really helpful for some patients. So I don’t think they’re all bad.

On the right side of the page, we have some intermediary metabolites, these are amino acid metabolites, and they sit in various pathways that are nutrient co-factor dependent. And B vitamin markers, these, of course, aren’t the only B-vitamin markers in the tests we look for multiple other ones as well. But one of those I always look at in the reports and it’s cystathionine, which is the fourth marker from the right. And here in this example, it’s kind of hard to see, but the cystathionine level is really high in this patient and cystathionine sits right in between homocysteine and cysteine in the conversion of methylation to transsulfuration. And you might see that elevated in somebody who has a CBS snip. And it might prompt you to think about a methylation panel to look at the methylation and transsulfuration cycle in a little more detail, but that’s something that I found helpful to look at in patients where I’m suspecting CBS network problems with methylation or transsulfuration.

Dr. Weitz:

And you guys offer a methylation panel?

Dr. Brown:

We do, we have a methylation panel and it’s in addition to some amino acids and metabolites of amino acids that make up the methylation cycle and transsulfuration cycle, there is also the opportunity to add on some genomic snips to that profile as well.

Dr. Weitz:

I guess the only issue I have with every time we get into a discussion about methylation and looking at the snips, it gets very complicated, but then the answer to everything is just, “Take more B vitamins.” So I wonder sometimes how helpful it is.

Dr. Brown:

Yeah, I find that methylation panel helpful for ruling out methylation issues, if I’m highly suspicious of it. With the help of the genomics snips and the biomarkers included in our profile, I can see if the patient’s hitting the target in terms of how well they’re methylating and if that looks good, then I tend to move on towards other things. Cause that methylation cycle touches on so many different areas of our biochemistry. I think the panel has a lot of use in ruling out methylation issues as well, but it does focus the lens a little bit more on methylation.  And one of the things that I’ve found helpful about that profile too, is that B3 and B2 are often forgotten about in the methylation discussion. And there’s been a pretty heavy focus on folate and B12 and B6, but B2 and B3 are also supportive. And if you see backups at steps that are B2 and B3 dependent in that test or this test, that can be helpful for supporting methylation without giving higher doses of folate or B12. So it could potentially help you make a clinical decision about some of the lesser known B vitamin co-factors in that cycle.

Dr. Weitz:

Somebody asked if the CBS snip is one of the snips that you can add on?

Dr. Brown:

Unfortunately not for this test, but it is included in the methylation panel if you add on the genomics to that test.

Dr. Weitz:

We have a question about how do we choose first morning void or plasma tests for a particular patient?

Dr. Brown:

I favor the NutrEval Plasma, and the reason why is because my patients don’t always get the same amount of protein from day to day. So for me, I always go with NutrEval Plasma. Usually after I have that conversation with clinicians about what you’re getting with the NutrEval FMV versus what you’re getting with the NutrEval Plasma, they’ve often sort of lean that way towards plasma as well. There’s nothing wrong with the NutrEval FMV test, but it is just a shorter snapshot of the amino acids, which for some patients, I think if they’re just not consistent with their protein intake, I think it becomes more important to look at a NutrEval Plasma.  So I would say make that your default and you’ll probably be okay, but that’s sort of just my own perspective on it. We still have a lot of clinicians that order the NutrEval FMV

Dr. Weitz:

Somebody asked, “Is the FMV a shorter window for all the markers or just the proteins?” And the answer is, it’s only for the amino acids, everything else-

Dr. Brown:

Correct. And that’s about 20% tests. So it doesn’t make a huge difference in the grand scheme of things, but it could make a difference in how you interpret the amino acids.

Dr. Weitz:

Okay.

Dr. Brown:

Good questions. Peptide markers. This is also worth looking at on this page because if you see these peptide-related markers elevated, and you’re seeing low amino acids at the same time, it could be somebody who’s not digesting or absorbing their protein very well. And it’s because the peptide-related markers here at the bottom right of this page, they sit right in between the crude protein that comes in through the diet and the amino acids that we ultimately need to break it down to. So if you’re seeing a lot of these dietary peptide related markers or seeing those elevated rather, then that might prompt you to think about the pancreatic enzyme recommendation on page two a little more seriously, especially if you’re seeing amino acids low cause that could be a patient who’s just not digesting or absorbing their protein very well. So that is the amino acids page.

Dr. Weitz:

What do you think about recommendations for specific amino acid supplements based on this panel?

Dr. Brown:

I sometimes do that, if I see taurine low, that’s one that I like to replete, especially if the patient’s feeling fatigued or they’re having detoxification issues. If I see arginine low and somebody who has vasoconstrictive headaches, or maybe some hypertension, I might think of that as part of the strategy. Methionine, you know those kinds of things-

Dr. Weitz:

I know there are labs that will put together like a multiple amino acid profile based on this test that is higher levels of the ones that are lower.

Dr. Brown:

Right, right. And some compounding pharmacies will do that as well. I think those are great options. Those can make a big difference for people. So I do think those are valuable tools. You could take another approach though. You could say, “Well, if the peptide related markers are elevated, if the patient’s telling me they’re feeling fullness after meals,” or something that makes you think that they might not be making enough enzymes, you could go that route and they may be able to get more amino acids out of the protein that they’re already consuming.

Dr. Weitz:

So you’ve seen giving digestive enzymes and/or hydrochloric acid?

Dr. Brown:

Yeah. I mean, that could be an option. Mm-hmm (affirmative). Absolutely. And I think also too, if you’re saying low amino acids and low peptide markers, then you might have to think about telling that patient to increase their protein intake a little bit or add in a protein snack or a protein powder.

Dr. Weitz:

Right.

Dr. Brown:

Yeah. You have a lot of options in terms of how you want to support amino acids, but I think digestion should also factor into it, I think how much protein is coming into the diet should also factor into it.

Dr. Weitz:

Somebody asked, “Is this issue common with diabetics?”

Dr. Brown:

Well, it’s a good question. It kind of depends on their diet, cause I haven’t always seen low results for amino acids or high results for amino acids with diabetic patients. So it may depend on the diet. Also, there is at least a couple of studies that mentioned that the branch chain amino acids might be a little higher in diabetic patients or patients with metabolic syndrome and it might be due to utilization of those amino acids. It’s a good question, but it they’re probably a lot of other factors that weigh into that.

Dr. Brown:

I see another question here, “I have a patient who seems to have fullness after meals, even when meal is not large. He is diabetic.” Okay. Yeah. Fullness after meals, if it’s because of bloating, then you might consider a SIBO test or you might do a therapeutic trial of some digestive support. Those could be some things to look at.

Dr. Weitz:

By the way, when is Genova going to be getting the additional marker on the SIBO test?

Dr. Brown:

Yeah, it’s something we’re looking into. I haven’t heard a timeline for that, but it’s an interesting point. We measure hydrogen and methane.

Dr. Weitz:

Okay. And now the new test also measures hydrogen sulfide that Dr. Pimentel developed.

Dr. Brown:

Yeah. Any other questions on this page? (silence) All right. So a central and metabolic fatty acids here, we’re looking at omega-3s, 6s and 9s, really important for neurological function, cardiovascular function, skin health, brain health, so many different things depend on omega-3s and managing chronic inflammation, which we’re often trying to fight in our patients with chronic illness. Just sort of a quick way to get a sense of these 3, 6s and 9s is to look at the bottom of each category. The omega-3 percentage is listed right there, the omega-6 percentage is listed right here. And we can see the 3s are kind of at the bottom of the range and the 6s are borderline high here, the omega-9s look fine. So this is a patient who’s not getting enough omega-3s here and has more of a pro-inflammatory pattern based on that. Of course, you can-

Dr. Weitz:

Why is there a top range for omega-9? Is it the more olive oil, the better?

Dr. Brown:

Some say that, but what I’ve seen with omega-9s is that if patients are getting a lot of omega-9s are often not getting enough omega-3s, and that would be something to consider if you’re seeing omega-9 is high.

Dr. Weitz:

And olive oil is the main source of omega-9s, right?

Dr. Brown:

Right. Exactly. And it has health benefits, no doubt about that, but if they’re overemphasizing olive oil or olives themselves, then they might be forgetting about the omega-3s. So, that could be important.  Saturated fats are listed at the lower left. You can really kind of get an overall sense of saturated fat intake by looking at that percentage at the bottom of the saturated fat category. In this particular example, it was fine. But if you’re seeing saturated fats high and you know the patient has an APOE issue, or if you’re seeing the saturated fats high and the omega-3 is low, then that could help you make some valuable recommendations in terms of healthy fats for the patient. So that’s a nice tool to have.

There’s also a trans fat marker in this test. On the right side, there’s a trans fat marker called elaidic. If you’re seeing now in borderline high or high, that could tell you something about a patient’s diet in terms of trans fat exposures, so that’s a nice one to have. And the cardiovascular risk markers are at the bottom right of the page. The omega-3 index has a lot of published literature behind it. And if we’re below four for the omega-3 index, that puts us that increased cardiovascular risk. If we’re between four and eight, it’s intermediate risk and if we’re above eight, it’s lower risk.

Dr. Weitz:

Now some people argue that human beings at one time consumed a diet that was close to the 1:1 omega-3 to 6, and that getting below 4:1 is optimal.

Dr. Brown:

Yeah. Yeah, it’s a good point. I think for some patients that might be where they need to be. And we are currently in the standard American diet, we’re getting far more 6s than 3s.

Dr. Weitz:

Right.

Dr. Brown:

Yeah. It’s a good point. So this provides you a sense of what their omega-3 intake like, their omega-6 intake, their omega-9s and saturated fats as well. Any questions about saturated fats, the low fat, non-fat diet? It’s a good question. Sometimes you do… Every now and then I get these patients that are avoiding fat. They’re like, “Oh, I’m just doing protein and avoiding saturated fat. I don’t want to have any saturated fat.” But saturated fat comes along in the diet with cholesterol and cholesterol is the backbone for the sex hormones. So I’ve seen a few times where patients have had what looks like hypogonadism because they’re so depleted in saturated fats. I think that’s a good reason why you would have a low end or a high end for the saturated fat percentage there. But it’s a good question.

Dr. Weitz:

Unfortunately, when it comes to diet there’s still huge disagreement. I’ve interviewed vegans, vegetarians on my podcast who are promoting dairy, low fat, high carbohydrate diet. And I interviewed a couple of guys who are type 1 diabetics and find that the super low fat, high carb-

PART 3 OF 4 ENDS [01:15:04]

Dr. Weitz:

And that the super low fat high carb diet is the best diet for diabetics. And they claim that getting the fats low improves insulin resistance.

Dr. Brown:

That’s a good point. I think there’s some individuality to that and my own set point, my own belief on that is that, the more extreme the diet is the more concern I have for the patient in terms of other nutrient needs and there may be patients, based on their genetics, where they do much better on a low fat diet. There may be other patients who would perform terribly on that. So I think there’s a lot of individuality that we’re still trying to sort out. And I think it might have a lot to do with genomics, but it’s a good point.  But this at least gives you something that you could compare your patients to and track the effectiveness or their compliance to those particular types of diets.

Dr. Weitz:

So would you say the go-to thing to look at on this page, if there was one thing you’re really going to honing in on, would it be the Omega-3 index? Would it be the 3:6 ratio? What would be you think the best measure? [inaudible 01:16:27]

Dr. Brown:

I would say the Omega-3 index in my personal opinion. I think that one has the most literature support behind it.

Dr. Weitz:

And optimal levels should be above 10, right?

Dr. Brown:

Above eight, according to the published literature on it.

Dr. Weitz:

Do you think it should be above 10 for optimal?

Dr. Brown:

It’s not a bad idea if the patient has a chronic inflammatory condition or a significant cardiovascular family history.

Dr. Weitz:

Or it doesn’t want to have one?

Dr. Brown:

Well that’s true too. I’m okay with seeing it above eight but you could make an argument to see it higher than that. Yeah.

Dr. Weitz:

Okay.

Dr. Brown:

The fatty acids are also reported in pathway format here and the color coding would apply here as well. So green indicating a normal level, yellow indicating a high or a low level and red indicating, or I’m sorry, yellow indicating a borderline finding and red indicating a high or low level.  I do find this page helpful to look at because if we see that linoleic acid is normal, which is one of the Omega six, with the very first Omega six at the top right. That has to convert into gamma-linolenic acid and then ultimately into dihomo-gamma-linolenic acid. This is driven by enzymes with nutrient co-factor needs. Sorry, let me go back to that slide. And if we’re low in dihomo-gamma-linolenic acid, as we’re saying in this example, the patient loses out a little bit on the anti-inflammatory benefit of dihomo. And it’s not because they didn’t have enough linoleic acid it’s because they’re not converting it very well into gamma and then ultimately into Dihomo. So just to the left of those arrows, which is showing up here in the middle of the page, you can send nutrient co-factor requirements and the enzymes make those conversions for us.

I see a question in the comments, which ratio? I think that from the previous page omega-6:3 ratio. The omega-3 index is probably the one I’d put the most emphasis on. No, they’re all good markers.

That brings us to the final page here of the elemental markers. And we’re looking at nutrient elements and toxic elements on this page. And the magnesium that you’re saying here is measured in red blood cell. But as Dr. Weitz said, sometimes you can see a normal level in red blood cell, but still see a nutrient mutation for magnesium on page two of the report. And that would tell you that there were some other pathways involved that were acquire magnesium, where the patient might need to be a little higher up on the reference range. So based on a functional analysis. So it’s ultimately, would really try to bring all of the patient’s biochemistry into this to make that nutrient recommendation for my magnesium. Serum plasma, I’m sorry, serum copper and plasma, copper and zinc, sorry, are reported here directly to, so you can calculate a copper to zinc ratio here by dividing the copper by the Zen care if you so choose.

Dr. Weitz:

You might want to add that to the report. That would be something that would probably be helpful.

Dr. Brown:

Yeah. It’s something I’ve been pushing for a while, but hopefully the next version of the test, but that’s a nice tool to have. That’s what most of the published literature is looked at for copper and zinc ratios.

Dr. Weitz:

But by the way, that’s an important marker for helping patients to reduce cancer risk. And it would be really neat to put a bunch of those markers, that functional medicine practitioners who are trying to improve the milieu for reducing risks for cancer and have a panel that had a bunch of those markers in it like CRP and there’s all bunch of them that… It would be neat to have a panel like that.

Dr. Brown:

That would be.

Dr. Weitz:

Answer the lube panelists.

Dr. Brown:

Good points.

Dr. Weitz:

So I am going to asks what do you use the zinc-copper ratio for?

Dr. Brown:

Well. I believe it’s been looked at in terms of neurological function, immune function, various different health issues. But if you were to plug the copper into the calculator, hit the divide sign, plug the zinc into the calculator, you’d be looking for a ratio between 0.7 and 1.7 typically.

Dr. Weitz:

I think one of the issues is, if you’re taking a lot of zinc, you could end up being low on copper, and that could be an issue. And copper is important for a number of functions. On the other hand, a lot of people get exposed to copper. Maybe they have copper pipes, maybe they have other reasons for getting copper and having higher copper levels is generally considered to be a potential negative for health. And I had mentioned the cancer issue and higher copper levels are generally thought to increase the likelihood for new blood vessel formation, which could make it easier for cancer metastasis or for cancer tumors to grow. So that’s another thing to think about when it comes to copper.

Dr. Brown:

A great point, Dr. Weitz, and I know copper, if it’s too high, can be pro-inflammatory.

Dr. Weitz:

Yes. Like all the metals really?

Dr. Brown:

Yeah. That’s a good point on the right side of the page, you can see the toxic elements they’re measured in whole blood, and that would give us estimated exposure of maybe a few months leading up to the blood draw. So it’s a nice tool to have, because most of the enhanced data looked at whole blood measures of those toxic elements. So there’s a lot of good, useful data we could compare that to, and that helped us to establish our reference ranges there for those. So it’s a good snapshot of exposure, not the full story there, but it does list lead, mercury, arsenic and cadmium.

Dr. Weitz:

Is there really an acceptable level of mercury?

Dr. Brown:

Yeah, that’s a good question. 4.35 is our tolerance. And I think that was somewhere between the maybe 80th or 95th percentile of the [inaudible 01:24:06] NHANES data for that. But I generally like to see it as low as possible.  There is a link to the support guide embedded in the report now. That’s new, so when you get to page 13 of the report, if you order this on your patients, you can just click on the link there in the commentary and it will take you right to that support guide that I shared earlier in the comments there.  Then of course, if you added on vitamin D for this test, the result will be right here on page 13, it’s 25 hydroxy vitamin D, which we like to see somewhere between 50 and 80. That is the profile. And I know we’re running up on time here. I wasn’t going to go into some of the genomic add-ons, but Dr. Weitz, it’s up to you. Do we need to wrap up now?

Dr. Weitz:

No, no. As long as people want to stay, I’m okay with saying a little bit.

Dr. Brown:

Okay. Well, we can go through these fairly quickly and I’m sure some of you are probably familiar with these already, but I will give you the brief overview and feel free to chime in with questions. You have the option to add on four different genomic snips to the NutrEval, the first one you’ll see is APO E and here the patient’s genotype is a two for genome type. APO E is an Apo lipoprotein. It helps to remove cholesterol from the bloodstream. So you’ll see the patient’s results here. Generally. I think if patients have an APO E2 genotype, they tend to have a higher triglyceride response from carbohydrates in the diet and folks who are [inaudible 01:26:11] forging no type. They tend to have a harder time removing cholesterol from the bloodstream and have a harder time with saturated fats, metabolizing, saturated fats. So this could potentially help you make some decisions there about coaching them on their macronutrients.

Dr. Weitz:

So what you’re saying is from your reading of literature, patients who have one or two of the APO E four variants, will tend not to do as well on a higher fat diets, such as the ketogenic diet.

Dr. Brown:

Yeah. I have some concerns about folks doing an acute agenetic diet who are APO E44.

Dr. Weitz:

Or a 3-4.

Dr. Brown:

Yeah. Exactly. That’s a good point too. In a 3-4 or a 4-4, I am a little more hesitant in terms of recommending a higher fat diet. Of course not all keto diets are the same, so I don’t want to vilify all of that, I also don’t want to say across the board, it’s not a good idea, but I am a little more cautious about saturated fat intake if somebody has an APO 4, for either or both copies. I don’t know. How do you feel about that? Dr. Weitz?

Dr. Weitz:

Yeah, in general, I had a patient a couple of weeks ago, a 40 year old guy and he had a 4-4 and he was, doing a kind of a paleo diet, bulletproof coffee, and he had a heart attack. The guy was in great shape. Everything seemed healthy. And that was a significant factor for him.

Dr. Brown:

Yeah. Wow.

Dr. Weitz:

Somebody just asked about blood draws, unfortunately on the West side of LA, there’s no labs in the Santa Monica West side area that will draw for a NutraEval for Genova labs or actually functional medicine labs in general. So I think the nearest lab is in Beverly Hills, which, once traffic gets back can be a pretty long drive. Do you of any labs or we’ll draw for Genova on the West side of LA?

Dr. Brown:

I don’t, let’s see here…

Dr. Weitz:

There is a Beverley lab. I forgot what they’re called. What, by the way, what I do, [inaudible 01:28:50] Jessica, is we use a mobile phlebotomist. I use Rosemary Mata. So what I usually do is, when I have patients for blood draws, we group them together and then she’ll come in the office maybe every two weeks or so. And then she charges each patient, a $50 for the draw, or she can go to their homes, if they rather do that. So that’s another option and of course, there’s other mobile phlebotomists around.

Dr. Brown:

A good recommendation, and I can reach out to the Genova lab in the area and see if she has some other suggestions, but she would be a good resource.

Dr. Weitz:

It’s been an issue with not having… There was one lab that was withdrawn for all the functional medicine labs. And they got bought out about four years ago. And since then we don’t have a single lab in the whole Santa Monica West side area that will draw for any of the functional medicine testing.

Dr. Brown:

Okay.

Dr. Weitz:

Yeah. Unfortunately conventional labs like Quest and Lab Core only want to draw up their labs.

Dr. Brown:

Yeah. The metabolum X plus would be worth considering as an alternative [inaudible 01:30:22] test can be collected entirely at home and you’ll get a lot of the same markers.

Dr. Weitz:

One more time. The name of that test, cause you broke up. I think when you were saying it.

Dr. Brown:

The metabolum plus and I’ll see if I can just flip back to that slide so you can see the name here, but it’s this one here, this one in the middle metabolomics plus, this one does not require phlebotomy. And you can see that it does have quite a bit of overlap between this and the nutri[inaudible 00:15:58].

Dr. Weitz:

Can you add on a blood spot, vitamin D with that test?

Dr. Brown:

You can’t get vitamin D unfortunately, but you can get the fatty acids in blood spot. That’s what’s run from the blood in that test.

Dr. Weitz:

You guys should consider adding on a blood spot, vitamin D.

Dr. Brown:

Yeah, It’s a great suggestion. I’ll definitely move that up the ladder at Genova. See if we can make that happen, but is the…

Dr. Weitz:

Maybe as a follow-up to this, somebody’s asking about a phlebotomist service in Orange County. Maybe if Genova has a list of phlebotomists that work with the genomic testing and or labs that will draw for Genova in Southern California, maybe if you could compile a list and then we could email it out to everybody.

Dr. Brown:

Yeah. It looks like Jamie mentions [inaudible 01:32:00].

Dr. Weitz:

Yeah. [inaudible 01:32:02] Kimberly Jones we’ve used her as well.

Dr. Brown:

Okay, great. I’ll reach out to Jamie. Jamie’s listening it looks like, so I’m sure she’ll have some other suggestions.  All right. The next SNP that you can add on to the NutrEval or the metabolomics would be the MTHFR SNP. And I won’t go into a whole lot of detail about this one, but this is one where if a patient has a snip peer, it could potentially mean higher homocysteine levels. This is the enzyme that helps us convert full late into the active form, which helps to convert homocysteine into methionine ultimately as a really important part of the methylation cycle. We looked at two different locations on the gene, the 677 and the 1298 location. And of course at each location, looking at both copies of the gene, one from the mother, one from the father, and it’s a nice tool to help add more context to the evaluation for methergine.

COMT, another methylator, another SNP that tells us about methylation or the propensity towards methylation. And I think of this more of a detoxification type of methylation helps us to remove catacholamines like benefrine or epinephrine dopamine helps us to eliminate estrogens and environmental toxins as well. So in a lot of ways, it’s helping us to detoxify those substances. And as part of the second phase of liver detoxification and has associations with a lot of different clinical conditions in the published literature, which we tried to summarize in the right side of the slide there, but this is one where if you see a snip here, you might see higher recommendations for a full aid B12 and the rest of the B-vitamins when patients have this snip.

But an important thing to remember though, that the genomic snips don’t factor into our nutrient recommendations in the NutrEval, they’re typically consistent with what we would expect to [inaudible 01:34:41] see in terms of need, but they are not interpreted as part of the NutrEval recommendations. They’re completely independent, but I don’t often see you when patients have COMT snips that we’ve recommended some B vitamins.

TNF alpha is a pro-inflammatory cytokine. And this is one that’s used by macrophages. Snips for TNF alpha would mean an up regulation of production of pro-inflammatory cytokines, and would mean that the patient might be making or more, I should say more susceptible to chronic inflammation. And you might see higher needs for antioxidants in the neutra realm, because if there’s chronic inflammation that can deplete antioxidant status more quickly potentially, and you could see, you’d think about antioxidant support to help protect the body against some of the damage that might be produced from the up regulation of these cytokines. It also has associations with auto-immunity. That’s also something you would see mentioned in the commentary there.

Dr. Weitz:

So what would this SNP tell us?

Dr. Brown:

And that snip might help you determine how important antioxidants are going to be in terms of a long-term strategy for the patient. So if you’re seeing some of the oxidative damage markers elevated, and you’re seeing a TNF alpha snip, where they’re homozygous, they’ve got mutation on both copies, then you might think about antioxidant support with another supplement or, or through the diet as part of a long-term strategy for that patient, not just something, do this for the next six months and you’ll be good, but not that we’re doing that anyway, but it might mean that the patient is fighting this battle against chronic inflammation. There’s going to be more of a long-term strategy in terms of supporting them in that battle. And antioxidants can be helpful for that.

Dr. Weitz:

Probably not a good idea to be prone to a cytokine storm at this time.

Dr. Brown:

Yeah. That’s a good point. Good point. Well, the educational resources that Genova offers are numerous, and that includes the NutrEval and metabolomic support guide that just got updated and earlier this month. We’re really happy about that. That is hot off the press. So to speak, let’s see here, we’ve of course have video modules on our websites and webinars. We call them live GDX webinars, and we have the lab report podcasts as well.  Patty and Michael are just really entertaining and lots of great information about Genova testing and a really nice resource to have. And of course we have medical education consults as well. And that’s if you have a Genova account and you want to talk about a patient test result with us, you can let 800 number and set up a phone consult. You can request to speak to me if you’d like on that consult, but there are a great team of doctors here at Genova that can offer assistance with picking the right test or answering questions about the test. Those kinds of things.

Dr. Weitz:

Okay, great. Thank you so much, Dr. Brown. It doesn’t look like we have any additional questions. So I thank everybody and we’ll see you next month. The discussion of dermatology is going to be really good. Julie Greenberg has some great clinically useful information to help us with our patients.

Dr. Brown:

Yeah, she’s great. I’ll be tuning in for that one as well.

Dr. Weitz:

Oh, okay.

Dr. Brown:

Thank you for having me, Dr. Weitz.

Dr. Weitz:

Thanks much everyone in attendance. I appreciate that. Thanks for your time. Take care.