The Top 5 Organic Acids Test Marker Patterns

Webinar Transcript

The material contained within this presentation is not intended to replace the services and/or medical advice of a licensed healthcare practitioner, nor is it meant to encourage diagnosis and treatment of disease. It is for educational purposes only. Any application of suggestions set forth in the following portions of this article is at the reader’s discretion and sole risk. Implementation or experimentation with any supplements, herbs, dietary changes, medications, and/or lifestyle changes, etc., is done so at your sole risk and responsibility. Views expressed are those of the presenter and not necessarily those of Mosaic Diagnostics.

This is an automated AI transcript of the Webinar video seen above. For the most accurate account of Dr. Woeller’s presentation on The Top 5 Organic Acids Test Marker Patterns, please watch the webinar video on this page.

Hi everybody. This is Dr. Woeller for Mosaic Edge. 

I thought what we would do in this webinar is go through the top five organic acid test marker patterns, not just markers, but patterns of markers that you’ll commonly see on this profile. And this is timely having just come off of a, organic acid test summit seminar that we just did through Mosaic Edge. And towards the end of this lecture, I’ll show you a slide where you can go get more information about upcoming seminars. And so there’s a lot to think about and, and there are more than five patterns, but these are kind of the common ones that you’ll see. And I, I tried to pick those as I was going through this list to think, okay, you know, what can we talk about here that maybe gives, people an understanding of what are sort of the more common things? And there’s obviously a lot to talk about, and there’ll be more webinars in the future where we delve into this topic more in depth. So here’s the disclaimer, understanding that the information in this video and lecturers for educational purposes only.

If this is the first time that you have heard me speak, I have been doing webinars now for Mosaic since they took over. And then for many, many years prior to that, through Great Plains Laboratory. I’ve been an integrative and functional medicine physician since the late nineties. I do a tremendous amount of speaking, written a number of books. I love education. I’m a practicing clinician. I’m also co-founder and education director of a number of other website educational websites, Autism Recovery System, as well as my Integrated Medicine Academy, which is an online academy with different courses in, fun in integrative medicine. And then in my own practice, I work a lot with individuals with autism, chronic and environmental induced health conditions, mold, et cetera.

So, oat patterns, right? What does this mean? Well, this is where we’re looking at a primary marker that is linked to one or two, or a series of other markers that might show up in other parts of the test. So we’re gonna first start with candida overgrowth and or aspergillus colonization markers plus oxalic acid. And I thought about ranking these, trying to rank these, like the number one oat pattern, the number two oat pattern. And it was kind of challenging to do. I would probably say the number one pattern you will see is the candida/aspergillus colonization with oxalic acid. Maybe the number two would be the elevated clostridia and homovanillic acid. The other one’s listed here kind of run in different, you know, third, fourth, fifth positions, whatever.

So this is the way that we’re gonna go through it. So there’s a bit of a sequence to how I’m gonna present this. So we’ll talk about mold marker elevations and lactic acid, elevated succinic acid. And then what we’ll also just mention sometimes, pyroglutamic or 2-hydroxybutyric. And those are commonly linked to environmental, chemical and heavy metal exposures. And then the last one is elevated lactic acid, elevated alpha keto glutaric acid. And then sometimes, and I’m, I’m, I’ll mention this towards the end, sometimes we might see also elevated amino acid metabolites, specifically those 62 through 66. So I’ll get to that last.

So first off, before we get into this though, maybe for those of you this might be new information. And I just took these slides actually from this previous seminar we did, what are organic acids? Well, organic acids are chemical compounds that are excreted in all of us as products of metabolism. So they’ll often concentrate in urine about a hundred fold of what we would find in the blood. And so then a urine test becomes obviously a convenient way of analyzing these organic acids. Now, organic acids are organic compounds and they’re acidic. So lactic acid, for example, is something that all of us produce naturally in our body. Some labs will list lactic acid as lactate, which is the conjugate base of the acid, meaning the acid lost its hydrogen, and in the process, you know, acted as an acid, then became a base. And then organic acids are substances in which carbon and hydrogen are always present. But some organic acids might have oxygen, some might have sulfur, some might have nitrogen, et cetera. And so the organic acid test itself, this profile that we’re talking about is a compilation of these chemical metabolites that are representative of various endogenous biochemical pathways that are linked to cellular metabolic imbalances when there is an imbalance. And then these can be associated with sometimes different types of diseases or disorders. So for example, succinic acid, which we’ll get to here shortly, is linked to mitochondrial dysfunction, often caused by environmental chemical exposure, but not always. Okay? So there’s always sometimes four or five things that might cause a marker to be elevated. Certain oat markers, particularly those on page one, are representative of intestinal colonization or overgrowth of opportunistic organisms. So for example, there’s a marker tartric acid that’s linked to aspergillus mold exposure and colonization within the digestive system.

And then the OAT itself is separated into various sections, each representative of some individual metabolic pathway or nutrient status. And so when you’re using the OAT, it’s important to understand that certain sections on the OAT and their markers may influence other sections on the, on the OAT. So for example, tartaric acid, which we know is linked to aspergillus mold, can cause high oxalic acid. And it’s not that the tartaric acid is causing high oxalic acid. I probably need to actually rephrase that sentence, but the aspergillus is causing high oxalic acid, just the tartaric is a reflection of the presence of aspergillus.

So the concept of pattern recognition within the organic acid test is a very powerful way of using this profile. And it’s an ongoing area of study. There’s new things and new patterns that I come across even after all of these years of using this test. And so in many situations, it’s not just one marker being elevated, the clinical significance in all cases, although there can be that, but it’s what these elevated markers mean in the clinical context of your patient or you as an individual. So again, succinic acid can be associated with environmental chemical exposure that would be causing mitochondrial problems, which is would then causing the elevated succinic acid. And this could be linked or associated with elevated citric acid. Elevated citric acid sometimes is linked to oxidative stress. Oxidative stress can occur when we’re depleted in glutathione. And there’s a marker for glutathione called pyroglutamic. And when it’s elevated, it indicates a glutathione deficiency. And so that in itself is a pattern: high succinic acid, high citric acid, high pyroglutamic.

Let’s start with the first pattern. This is a very common pattern to see, and this is candida overgrowth and/or aspergillus colonization and high oxalic acid. Does it happen in every single case? No, there are many organic acid tests you’ll see that will only have candida elevated, the AOS marker, for example. So, but there is a relationship between candida, the aspergillus markers, or a combination of those that can be linked to oxalic acid. And I would say in probably 80% of the time, when you have elevated oxalic acid, you’re gonna see candida and/or one of the four aspergillus markers high. So in this particular case, we can see an individual has high arabinose. So the AOS is the candida marker. On the Mosaic OAT, we also see an elevation of tartaric acid. So there’s just one marker linked to aspergillus exposure. This person also has high lic acid. Is the oxalic acid 100% caused by the aspergillus and candida? We can’t make that claim. It, it, it certainly could be part of the equation, but we could also have somebody who’s eating high oxalate foods too. So we always have to take into consideration some other factors that might be going on. But the test itself gives us some insight into a pattern. So we know that diet, so for example, we’ve got food that may be consumed that could be high oxalate could lead to oxalate elevation. And we know that yeast and fungal can also contribute to it. And there are some genetic factors and different enzyme defects that might be contributing factors too. B vitamin deficiencies, B6 for example, could be contributing factors, but by and large, the yeast and fungal component and the diet component play a very big role in oxalate elevations.

So candida has an enzyme called isocitrate lyase that takes isocitrate from the Krebs cycle, converts it to glyoxal, converts it to oxalic acid. So that, that is the link here for candida. Many fungi, particularly mold, I should say, have an enzyme called oxaloacetate hydrolase. And so this is specific for aspergillus, nigar or Nigel, however it’s pronounced. But what this mold does is it produces oxalate. So it has this enzyme, oxaloacetate hydrolase, that converts citrate, which comes from the Krebs cycle, and it converts it, um, over into oxaloacetic acid, which gets converted into oxalic acid or oxalate, and then that is pumped outta the cell. That happens naturally in the environment. If this is happening in our digestive tract, well, it’s gonna pump the oxalate into our gut.

So that is how we can make an association between high oxalate and aspergillus. And before that, oxalate and candida, what are some other things to consider? Well, there could be some genetic influences. So you’ll notice in this particular person, they have high oxalic acid, and there’s a couple other markers that are high—glycolic and glycine. Now, many times these are high just because of some type of deficiency state in certain nutrients like B1 or B6 or magnesium. But these markers can also be elevated because of genetic reasons. Does the test tell us what it is? It does not. Okay? But those are things that cause us to then go look at things further, look at other aspects clinically, um, and just start to understand some of the, the pathogenicity or the biochemistry, if you will, of what may be linked to elevated oxalate, increased oxalate absorption associated with poor fat digestion. There’s nothing on the organic acid test that tells us about this, but this is a phenomenon that can happen. So people have poor fat digestion that can increase oxalate absorption. And the reason is, is fat carries a negative charge, and oxalates also carry a negative charge. But the calcium that’s in our digestive system carries a positive charge. And what happens is when we have a lot of undigested fat, it binds to the calcium and leaves this oxalate unopposed to be absorbed. And so this is called enteric hyperoxaluria, and it’s a, it’s a real thing. And so it’s, it’s, you know, again, in order to figure that out, you’d have to do further testing on stool analysis and look at fat digestion, et cetera.

But just understand that there’s multiple reasons that oxalate could be high, but the pattern on the OAT shows us that it partly could be linked to candida, partly could be linked to aspergillus as well.

Okay, so let’s go through the second pattern. This is very common. Elevated clostridia marker or markers and high homovanillic. So there are three primary Clostridium markers on the organic acid test that can cause high homovanillic acid. One is the elevated HPHP A, which would be the most common reason for clostridia, and then elevated 4-cresol and 4-hydroxyacetic. So if we look at this particular individual, we can see two of the three are elevated. The third, 2-oxoacetic, is not known to cause an elevation of homovanillic acid. But marker 15, 16, and 17 are, so we have an elevation of HPHP A and an elevation of 4-cresol. And we also have an elevated homovanillic under the neurotransmitter section. And by the way, these are on separate pages of the organic acid test.

Now, when you look at the prevalence within the organic acid test that could show elevations of clostridia, about 25% of OATs, regardless of a person’s age or diagnosis, will have at least one clostridia bacteria present about 80% of the time. That’s the Clostridium marker of HPHP A. That’s most common. About 15% of the time it’s the 4-cresol. Another 5% is the 4-hydroxyacetic. Less than 5% of positive Clostridium markers will have a combination of two or more. So it’s not very common, but you’ll see it. Okay, so a lot of them will be either the HPHP A or 4-cresol. And what’s happening, why is the homovanillic marker high? Well, it turns out that 4-cresol and HPHP A are known inhibitors of the dopamine beta hydroxylase enzyme, and dopamine beta hydroxylase converts dopamine to norepinephrine. And if that reaction goes on long enough and is strong enough, well we can start to get an increase of dopamine. And what gets registered on the OAT is the organic acid test. So we see elevations of homovanillic as a reflection of dopamine beta hydroxylase interference from these clostridium bacteria.

And so this is a classic scenario where we’ve got very high levels of clostridia. And you’ll also notice this other marker 4-hydroxyphenylacetic is also very high. It turns out that 4-hydroxyphenylacetic and 4-cresol are linked together when they’re being produced by Clostridium difficile. So Clostridium difficile is one of the bacteria that can produce both of these particular compounds.

Now it’s thought that 4-hydroxyacetic could also be an interfering factor on dopamine beta hydroxylase because of its similar structure to 4-cresol as well as HPHP A. Now, in this particular individual, they had very high levels of homovanillic—homovanillic acid, excuse me, which is the main dopamine metabolite. In fact, the level is just absolutely massive. And they were taking a number of different supplements that boosted or were attempting to boost dopamine. So they’re taking L-dopa from Mucuna herb, they’re taking tyrosine powder. They’re also taking another combination product that had tyrosine in it. So why is that a problem? I’ll show you in a second.

So what we have is we have the clostridia interfering with the dopamine beta hydroxylase causing the homovanillic level to be extremely high. And that’s why the numbers are so inflated. Well, it turns out that when we inhibit the enzyme—and by this way, this enzyme is not just in the brain, this is the nervous system reaction, both central nervous and peripheral nervous system involved in this reaction—when we have clostridia, so Clostridium difficile, for example, or perhaps even other species of clostridia, the clostridia will grab that tyrosine to make more 4-cresol, these other clostridia will grab the tyrosine to make more HPHP A. So we’re driving up clostridia markers that’s gonna be causing further inhibition of the enzyme, or over here, HPHP A, for example. And so this person was taking large amounts of tyrosine at the same time. They had C. diff that was causing massive elevations of 4-cresol. They were also taking L-DOPA as a supplement. I don’t know why this cursor thing does that. I think I’m gonna try and get rid of this, see, like, see if I can get, I’m just gonna use a laser pointer. Let’s do that instead. So they were taking a product that had DOPA that was causing pushing dopamine as well. But because the enzyme was being inhibited, it was causing massive elevations of homovanillic acid.

So what are some other things that we could consider in this? And, and this is honestly for another discussion, and I’ve talked about this in many of my webinars. I also teach on this within the organic acid test seminars. We could have variance in the dopamine hydroxylase genetically, so that is something that could occur. And that tends to occur about 4% of the US population, about one in 25 people. Copper and vitamin C deficiencies can also be a contributing factor because dopamine beta hydroxylase is dependent on those nutrients, dopamine precursors, okay? That could be amino acids like tyrosine or phenylalanine or L-DOPA from herbal products for taking large amounts of ’em. They may push very heavily into that dopamine pathway. Some people are on Parkinson’s medications. You’ll see elevated dopamine metabolite markers as well, or certain, medications like risperidone in some cases. Not all, but, but again, understand that those can happen. And then aspects of heavy metals and aspartame—what’s the link there? Well, there are some other potential causes of elevated homovanillic acid. It’s not all caused by Clostridium. So heavy metals are thought to be an interfering factor on the dopamine beta hydroxylase I mentioned before, vitamin C and copper deficiency can also be a contributing problem, aspartame maybe. And the reason with aspartame is that its metabolite has a similar chemical structure to those bacterial metabolites from clostridia. My experience is, I don’t find that it’s, if it is an inhibitor of the dopamine beta hydroxylase, it doesn’t appear to be a strong inhibitor of it. It’s certainly not to the level of the Clostridium markers. And that really just comes from the fact that I’ve seen plenty of people come back very high in the aspartame metabolite called 2-hydroxyhippuric acid, even at very high levels, even in these two individuals who are drinking a ton of NutraSweet and their dopamine metabolism was normal. So I’m not saying it can’t happen, I just don’t think it’s as, as occurring as often or as significant as you will see with the Clostridium markers.

So really the Clostridium markers are a major interfering factor. So just take all that into consideration.

So let’s look at the next pattern here. Let’s see, this thing’s not gonna—let me get rid of this little laser pointer. So the next OAT pattern is the mold marker elevations and high lactic acid. Okay, so we’ve got lactic acid and then we can have things that feed into it, either the aspergillus or the F marker. So by the way, in most situations that I have seen on the organic acid test, when lactic acid seems to be linked to mold, that’s primarily the aspergillus markers or the markers are representative of mold exposure. We’ll get more into that here.

So where’s lactic acid coming from? Well, lactic acid is a byproduct of glucose metabolism as it’s converted to pyruvic acid. The primary pathway is to move pyruvic acid towards the citric acid cycle, also called the Krebs cycle. But we can also form lactic acid through the actions of lactate dehydrogenase. Now, there are many causes of lactic acidosis. They’re generally broken down into two categories, type A and type B. And so if you just look at this list and think about yourself or a patient, right? I mean, it’s pretty obvious. We’re not gonna have somebody in septic shock who’s in our typical integrative, functional medicine practice, unless they’re extremely ill and they need to go to the hospital. So, you know, but type A lactic acidosis is generally much more serious and immediately life-threatening than, let’s say, type B. Although type B lactic acidosis could be seen in malignancy, for example.

But what do we most commonly come in contact with? Okay, that would be things like trauma, excessive exercise, somebody who has diabetic, unstable diabetes or ethanol intoxication, mitochondrial problems, maybe certain medications like metformin or even a thiamine deficiency. But probably even more common than those would be a mycotoxin exposure. And this is where the Mosaic Diagnostic MyTax profile comes into play. And this particular profile in its current state looks at 11 different mycotoxins linked to different molds. Aflatoxin, ritoxin and gliotoxin are linked to aspergillus mold. What do these mycotoxins do? Well, they can damage the immune system in all categories, the innate, adaptive, and they can even take out natural killer cell activity. They can lead to suppression of secretory IgA and the digestive system along the mucosal lining of our body. They can generate free radicals, which then can deplete glutathione. They can also target and go directly after mitochondria.

And this was a classic case. It took this from the seminar. This was a young child who actually was living in a moldy home of aspergillus contamination. Very high gliotoxin marker that we see here, which is a common mycotoxin of aspergillus. We have high lactic acid and we have a number of other elevated mitochondrial markers too. Can I with absolute certainty say that the lactic acid marker that’s elevated in this particular case is 100% from mold? I can’t say that, but I can think of the clinical situation, the, the—what else, the other information we have from other testing. He’s not on medication, he’s not diabetic, he’s not in shock, he doesn’t have malignancy. So you start going through the list of differential diagnosis and you start to, you know, cross a number of things off your list and you start to land on things that would be more commonly associated with high lactic acid. Anything that is causing this level of mitochondrial disruption could lead to lactic acidosis. And one of the things that Great Plains, prior to Mosaic, had recognized when they developed this test and analyzed, you know, people within the lab and correlating the information, was that elevated lactic acid had a high association with the presence of mycotoxins.

It wasn’t making the claim that mycotoxins was the only cause, but it was a strong association. What are some other things that we could consider with elevated lactic acid? Well, one of them could be a thiamine deficiency. And a thiamine deficiency could also be a contributing factor to mitochondrial dysfunction. I’m gonna come back to that topic here shortly.

So I want, I wanna go to the next pattern that’s fairly common, but we will come back to the thiamine discussion here in a few minutes.

So the next pattern is elevated succinic acid and environmental, chemical and heavy metal exposures. And so succinic acid is a very interesting marker. It plays a critical role in bridging the Krebs cycle and the electron transport chain. And it can be interfered with by a number of things, heavy metals, glyphosate, environmental chemicals like organophosphates, and even mycotoxins.

One of the things that Great Plains found when they originally were looking at this was that succinic acid was often highly associated with the presence of environmental chemicals and heavy metals. And so a very common pattern to see on the OAT is high succinic acid and sometimes high pyroglutamic. Now there’s two markers under the indicators of detoxification section. We have pyroglutamic and 2-hydroxybutyric. Notice they have an asterisk next to both of them. What that means is that they’re indirect markers. So with pyroglutamic, when it’s elevated, which it is in this case, it indicates a glutathione deficiency. 2-hydroxybutyric has a number of reasons. It could be high, but a very common reason it’s high is it’s an increased demand to maintain glutathione production. So when you have both elevated, it’s a strong reflection of glutathione deficiency being caused by something. If we have an elevation of succinic acid, we know that it is often linked to some type of chemical exposure. Heavy metal exposure could be, mycotoxins, but mycotoxins are chemicals too. Those would be kind of things that we have to think about at the top of our list. So 2-hydroxybutyric—the most common reason it’s high is trying to maintain glutathione status.

And I’m not gonna go into this in great detail, but let me just see if I can get this pen. All right, so here is our methylation cycle. Here is our folate cycle. And if we draw a line underneath these two cycles, coming down in this particular direction is what’s called transsulfuration. And so ultimately when our body needs glutathione, we’re gonna have a, a pulling in the downward direction with a preferential movement towards glutathione. But because of that movement biochemically, we can get a chemical expression of 2-hydroxybutyric as a reflection of that. And pyroglutamic is a little bit more straightforward with regards to a glutathione deficiency. Here’s glutathione. And here is pyroglutamic, also called 5-oxoproline. Now I’m not gonna go through all of the sequences, but if you just remember that decreased glutathione will cause an increase in our pyroglutamic. So elevated pyroglutamic is an indicator of decreased glutathione.

So succinic acid, right? Why do we want to pay a lot of attention to succinic acid? Well, one, it’s a fairly common marker to see elevated on the organic acid test, and it plays a critical role in Krebs cycle activity. There’s an enzyme called succinic acid dehydrogenase that is very important as a connecting point between the Krebs cycle and the electron transport chain. So here is our electron—excuse me, our Krebs cycle, and here is our succinic dehydrogenase. And so this enzyme connects the Krebs cycle to the electron transport chain. Okay, so here it is again. We actually connect directly from, or we, we connect chemically from our Krebs cycle to the electron transport chain through Complex I and Complex II. But Complex II is almost a direct connection because the enzyme itself is part of both systems. Complex I is a chemical connection through NADH. So when we go back and we look at the Krebs cycle, we make NADH in three different areas and then that connects over to Complex I. But Complex II is actually this enzyme that now, that enzyme is connecting through something called FAD to FADH2. But when you interfere with this enzyme, you’re gonna not only interfere with the Krebs side, but you’re gonna interfere with Complex II. And ultimately the electron transport chain changes moving electrons down this chain reaction. It then reduces oxygen to water. At the same time, it causes an accumulation of these hydrogen ions that accumulate in the mitochondrial inner membrane space. And that’s what produces ATP. So whenever you see elevated succinic acid, try to hold the imagery of where this system is being affected, because it does play a significant role. Because when we can’t engage things in these early complexes within the electron transport chain, it ultimately affects the production of ATP. And we get maximal production of ATP when we engage the electron transport chain at Complex I and Complex II.

So what are some causes of high succinic acid? Well, we’ve already kind of gone through a few of them. Chemical exposure like organophosphates, glyphosate, other chemicals, heavy metals, this is not a common occurrence. This malic acid, for example. Um, I’ve seen a few cases where that marker is elevated on the OAT under the inborn error of metabolism section, which is on the last page, those amino acid metabolites. But that’s not common. Now I’ll leave that topic for another day. And then there can be genetic factors. Complex II is a complex center within the electron transport chain. It actually consists of four protein subunits. It’s the only complex that does not pump protons from the matrix into the inner membrane space. And it is a, again, a major connecting point between the Krebs cycle and the electron transport chain. What’s interesting is that all of the subunits of this particular complex are coded by DNA within the nucleus of the cell. The mitochondria have some DNA as well. And about 13 proteins within the electron transport chain are coded by mitochondrial DNA. This is the only one where all of them are coded by nuclear DNA, which means that if something’s happening at the nucleus of the cell, it could be affecting the way this enzyme is working, or excuse me, this complex is working.

Now I talk about these concepts, particularly with regards to some of the aspects of mitochondria or other mechanisms. For example, if you’re interested in learning more, I do have a website or a webpage through YouTube, for our Integrated Medicine Academy. So you can actually go to youtube.com and type in Integrated Medicine Academy. And I create these videos called Mechanisms. One of them I created was actually the role of succinic acid dehydrogenase and mitochondrial function, where I go into these topics in more detail. And each video I try to keep anywhere between, you know, seven to 10 minutes or so, not make them too long. But again, I, I create these all the time and put them up through our Integrated Medicine Academy. So you’re welcome to go there and check ’em out.

So what then are the most common OAT markers? I actually thought that I might make this the last category, but I thought, well, this is kind of straightforward and a little bit too easy because I can show it in one slide. The most common OAT markers are arabinose number one, oxalate number two, and something called suberic, which you find under the fatty acid metabolite section at number three. And for the vast majority of people, suberic is elevated probably just because of some kind of fasting effect, an overnight fasting effect, maybe a little bit of need for carnitine, for example. But, but those are the three most common markers you see elevated on the OAT, but not really as a true pattern, for example, that we could maybe link up clinically.

But this last one is important, and that is elevated lactic acid, elevated alpha keto glutaric acid, and/or elevated amino acid metabolites. Now I really should—this last thing here: these elevated amino acid metabolites are not very common. So the more common part of this pattern is gonna be lactic acid and elevated alpha keto glutaric acid. But I wanna go through this and just show you when you start thinking about things clinically and also from a biochemical standpoint.

So lactic acid we know can be caused from a lot of things. A lot of those mitochondrial markers can also be elevated because of many things as well. Some of those things that could cause problems in the mitochondria could be due to a thiamine deficiency, or they could also be linked to other B vitamin deficiencies. And then very, very rarely there might be some kind of genetic or inborn error of metabolism. Those would be linked more to those amino acid markers, 62 through 66. You’ll also notice that I put elevated lactic and/or 2-oxo glutaric. Another name for alpha keto glutaric acid is 2-oxo glutaric. So a lot of times these compounds have four or five different names depending on the nomenclature being used in which, you know, organic chemistry system is being used to name them.

So to talk about this, we need to go back into the mitochondria. So the mitochondria, these organelles that exist in our cells, there’s thousands of ’em that exist in an average cell, okay, are those components that produce the ATP. It has an outer membrane, an inner membrane, this inner membrane space. Inside the matrix of the mitochondria is where our Krebs cycle functions. It’s also the place where we have mitochondrial DNA. Now, from a very simplistic standpoint, we produce ATP in various ways. So we can take glucose, convert it to pyruvate to make ATP. So that’s one of the ways, or the way that let’s say a red blood cell would produce ATP, for example, or that’s just basically average glycolysis. And we get about 5% of our ATP from that route.

But where we really get our biggest bang for a buck metabolically is when we convert pyruvate, for example, to acetyl CoA. We can also make acetyl CoA through fat as well as protein metabolism. And we spin it through our Krebs cycle and we get about another 5% in what’s called ATP equivalents through the Krebs cycle. But when we transition those compounds over into the electron transport chain is where we get 90% or so of our ATP.

So again, we’ve gotta be able to engage the mitochondria through the electron transport chain to get this massive amount of ATP that we need to run the machinery of our body. And so what’s happening at the electron transport chain level is critical to overall function. And we know that as we’ve mentioned, Complex II and Complex I play a major initiating role in electron transport chain activity.

So when we take back and think of the, what’s called the citric acid cycle or the Krebs cycle, there’s an initiating point even before the Krebs cycle gets engaged. And that is the actions of an enzyme called pyruvate dehydrogenase. So if we look at pyruvate, glucose gets converted to pyruvate, pyruvate gets converted to acetyl CoA through the actions of pyruvate dehydrogenase.

Now it turns out that pyruvate dehydrogenase is a complex of different proteins that convert pyruvate to acetyl CoA, and we need a number of nutrients to make that work. Coenzyme A is linked to B5, NAD is linked to B3. Thiamine pyrophosphate is linked to B1, FAD is linked to B2. We could throw a little lipoic acid into the mix and we’re pretty much good to go in order to activate this pyruvate dehydrogenase complex, which is made up of E1, E2, and E3 protein components.

And so this is the structure or the flow of how this complex works. So here we have E1, which is linked to thiamine; E2, which is, basically it’s this cross bridge between lysine, for example; and then we’ve got E3, which is linked to both B3 and vitamin B2 or riboflavin. And then B5 basically comes in at sort of this angle here, along with lipoic acid to sort of make run the show.

What’s interesting is that thiamine is actually the rate limiting nutrient. So for thiamine deficiency, we can’t really even gauge the enzyme fully. And so the enzyme shuts down or doesn’t function appropriately, which means we can’t convert pyruvate to acetyl CoA well. What happens to all that pyruvate? Well, it ends up getting converted over into lactic acid. And this is why you can get an elevation of lactic acid because of a pyruvate dehydrogenase deficiency.

Okay? And so that answers the question for pyruvate dehydrogenase. So it requires those nutrients and function of the enzyme as a complex. Well, it turns out that the pyruvate dehydrogenase complex is similar to the alpha ketoglutarate dehydrogenase complex and it requires the same nutrition.

And so this is our alpha ketoglutarate dehydrogenase. Here’s our thiamine component. Here’s lipoic acid. Here is NAD, which is B3. Here’s FAD, which is B2, and here’s coenzyme A up here, which is B5. But again, thiamine is the rate limiting nutrient.

Okay, if we break it here, we’re not gonna get good activity downstream. There’s another enzyme complex called branched chain alpha keto acid dehydrogenase complex. Now, forget, don’t get overwhelmed by the name, but let’s just follow this down through these pathways. Notice we’ve got leucine, isoleucine, and valine. Where are they all heading? Well, they’re all heading towards the TCA cycle, what’s called the Krebs cycle. We know that that’s occurring within the matrix of the mitochondria.

Notice prior to it we make acetyl CoA or propionyl CoA. Acetyl CoA gets converted, okay? Moves to a couple steps and enters the Krebs cycle.

Okay, on this side we convert, we make propionyl CoA, which becomes succinyl CoA. Both of these enter the Krebs cycle. When you study the biochemistry of the Krebs cycle, you’ll notice that there are various entry points into it. So there’s not just one; there’s multiple entry points. So it has a number of doors that allow different biochemical pathways to access energy production within the mitochondria.

So leucine, isoleucine, valine—as branched chain amino acids—are fed down through these pathways to help move substrate into the Krebs cycle. Well, it turns out that there’s this enzyme called branched chain keto acid dehydrogenase. And you’ll notice that thiamine, okay, plays a primary role, but B3, B5, and B2 are also part of the picture. So a thiamine deficiency can be a causative factor of defects within these enzyme complexes that could lead to elevations of lactic acid. We can see how other B vitamins could also play a role and there are genetic factors that would of course affect the function of these enzymes too.

And so just purely from a nutritional standpoint, thiamine is pretty important as far as overall mitochondrial activity and body metabolism.

There’s other things that’s actually involved in, and one of those, very interestingly, is called 2-hydroxy fatty acid metabolism via an enzyme called HACL1. So again, there’s not, for this particular enzyme, there’s not anything on the OAT specifically that allows us with absolute certainty to view that. But I wanted to just kind of bring this into full view. This particular pathway is how we metabolize certain fatty acids, okay? Certain amino acids and even cholesterol. And you’ll notice that where this thing ends essentially is at a chemical called succinyl CoA. Succinyl CoA may now, remember, is one of the doorways into the Krebs cycle.

So odd chain fatty acid, cholesterol, plus other amino acids—leucine, isoleucine, threonine, methionine—and even propionic acid get metabolized into propionyl CoA, get converted to succinyl CoA to enter the Krebs cycle. Now, very rarely—and it’s not very common—but another pattern that you can see on the organic acid tests, in some cases, as you can see, elevated lactic acid, you can see elevations of alpha keto glutaric acid, and you might even see elevations of the marker linked to biotin. And biotin is one of those markers that’s represented by methylcitric on the organic acid test under the indicators of nutrition or the vitamin indicator section of the test. And methylcitric, when elevated, indicates a biotin deficiency because biotin is necessary to convert propionyl CoA down into methylmalonyl CoA, down into succinyl CoA. Not very common, but it is another thing just to pick up on. And, and when I do additional webinars in the future, I am going to come back and do some webinars where we do a deeper dive into the OAT, particularly looking at more advanced patterns off the organic acid test.

So organic acid test markers that could be linked to thiamine influences—lactic acid, high alpha keto glutaric acid, for example—and then we’re left over with these amino acid metabolites and I, I won’t read ’em off, you can see ’em there. These include 2-hydroxyisovaleric, 2-oxoisovaleric, et cetera. Well, where do these come from? Well, if you actually read the organic acid test interpretive document that Mosaic has, these particular markers are linked under the amino acid metabolite section of the OAT. And this comes on the last page of data of, basically all of these particular markers in this section of the test. These amino acid metabolites are confusing for some people because they look at this section of the test and, and most often, for most people, all of the markers are normal and sometimes the markers end in zeros—like there’s nothing that shows up—and that’s normal because these are not a reflection of amino acid status. These are a reflection of a biochemical disturbance in the pathway of these markers. And so when you have a zero on this test, it’s actually normal. It means that there is no inborn error of metabolism in these biochemical pathways.

But sometimes these markers can be slightly elevated because of nutritional deficiencies. And so for example, markers 62 through 66 can be slightly high if there is a thiamine deficiency. And so just keep in mind that usually in genetic diseases these markers would be very, very elevated. But you know, most of the time we see in most people markers that might be just a few points above normal. But this particular grouping has a strong association with a thiamine need. So more commonly lactic acid is elevated, you know, plus alpha keto glutaric acid; uncommonly would also be these markers being high, but keep a clinical suspicion when you start to think of this particular pattern.

So it’s much more common to see high lactic acid that could be linked to a thiamine deficiency. It’s also much more common to see high alpha keto glutaric acid. Now, I’m, again, I’m not claiming that in every single case, high lactic acid or high alpha keto glutaric acid is only caused by thiamine deficiency. Remember we went through some other scenarios where mycotoxins could be associated with things as well. And there are other factors, medications that people are on. It’s not very common to see these amino acid markers elevated.

Okay? So keep this particular image in mind if you need to go online and do a search for “causes of lactic acid” chart. And there’s all kinds of diagrams online that you could print out just as a reminder. But thiamine deficiency is one of those things that is associated with lactic acidosis.

So in this particular case, we can see a number of different mitochondrial markers, high in fact succinic acid high, and we see 2-oxo glutaric acid, which is another name for alpha keto glutaric acid, is high. This person also has high lactic acid, 2-hydroxybutyric acid as well. So this is a common pattern, okay? And you just have to start to know, well, what are some of the reasons that can cause these things to be elevated? And hopefully some of what I presented here will help in that interpretation.

So I mentioned upfront that we do a lot of seminars on organic acid test interpretation through Mosaic Edge. And so if you want to take part in a webinar—I would recommend going to mosaicdxedge.com. So here’s the website down below. There is another seminar coming up in December of this year, 2023. And then there’ll be more scheduled in the following year as well.

So to go get a complete list of upcoming educational events, make sure to go to mosaicdiagnosticedge.com.

Now, if you’re interested in many of my mastery courses I have through my own academy, you can go to integratedmedicineacademy.com. You can also email us at IntegratedMedicineAcademy@gmail.com. So I have a lot of courses that we’ve created over the years. One of them is the Mitochondria Mastery course, which was probably one of the most in-depth courses that I have through the academy. We go into a lot of detail with regards to mitochondria, its function, genetics, it’s linked to different disorders and diseases, lab testing, different interventions, clinical applications. This is a ton of stuff.

So for more information, you can go to mitochondriamasterycourse.com. I’m also on Substack, if you would like to follow me there. I try to post, new content twice a week. That could be articles, that could be videos or both. So you can go to drwoeller@substack.com.

And then there is my private practice information. If you care to consult with me directly, the website is mysunrisecenter.com and there’s our email and phone number.

So just remember when it comes to the organic acid test, it’s, it’s always an evolving process of learning. It’s an incredibly important test. I think it’s a, a fundamental test. That’s why I do so much teaching about it, and it’s why I’ve used it now for so many years. And it opens up a lot of doorways as a clinician to, to see patterns within the OAT and also correlate that information to different types of clinical situations.

So I would encourage you to just keep asking questions, keep learning how to use it, keep connecting with Mosaic and their lab consultants on interpretation. And then, just keep looking for additional learning opportunities about what the test provides and the information that it presents.

So I hope you found that interesting. Again, I’m Dr. Kurt Woeller, Thank you so much.

End webinar transcript.