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.
Webinar Transcript
This is an automated AI transcript of the Webinar video seen above. For the most accurate account of Dr. Woeller’s presentation, please watch the webinar video on this page.
Good afternoon everyone. Thank you for joining us in the Mosaic Diagnostics webinar. This afternoon, we have with us Dr. Kurt Woeller. He is a doctor of osteopathic medicine, integrative and functional medicine physician and biomedical autism treatment specialist and clinical practice for over 25 years. Dr. Waller is the education director and main course developer for his Integrative Medicine Academy and online Academy for health professionals. He is also the organic acid tester, oat seminar creator and a presenter for Mosaic Diagnostics, edge seminars and webinars. He’s been involved in monthly educational webinars for Mosaic Diagnostics and other organizations for over a decade. His private practice, sunrise Functional Medicine, focuses on specialized diagnostic testing and treatments for individuals with complex medical conditions like autism, autoimmune disease, gastrointestinal, and certain neurological disorders, and other chronic health conditions. Dr. Woeller is a fellow of the Medical Academy of Pediatric Special Needs or Maps.
We are quite happy to have Dr. Woeller with us today. We will be doing a live q and a at the end of Dr. Woeller’s presentation. I will be monitoring that, so please do put any questions you have into the q and a section throughout the webinar. We’ll get to as many as we can in the time allotted.
Dr. Woeller the floor is yours.
Okay, excellent. Hello everybody. So I’ve gotta wear my computer glasses here, so I know I show up as a little image in one of the corners of the screen. So, happy to launch 2025 here with another talk on the organic acid test. And so I thought in this particular talk would get into some clinical strategies that you can think about when you’re confronted with not only an, an individual who has some complicated issues, but a complicated organic acid test. And so I know that might mean different things to different people depending on your skill level on, on using the test or sort of your, what you participated in, whether it’s through Mosaic Edge and the OAT seminars or things on your own. So I think you’re gonna find this information very interesting, very compelling.
So here’s our disclaimer, understanding that this information is for educational purposes only. So, as Michelle was introducing me, I’ve been around for quite a while now. I’ve been an integrative and functional medicine physician since the late nineties, actually, have been working with the autism community since about that time. And, prior to Mosaic worked with Great Plains for many years. In fact, the first functional medicine test that I ever ran in my practice, going way back to the late nineties, was an organic acid test. And it was a lot of information then. It’s still a lot of information. Now, I love talking about this topic. It’s a very important test to understand.
So I’m involved in a lot of things, ed from an educational standpoint, my integrated Medicine academy, I do monthly webinars through MosaicDX Autism Recovery System. I have my own podcast and then my own practice. I work with a wide variety of patients from autism to, you know, chronic and environmental induced health conditions, et cetera.
So here’s the OAT, right? This is a document that is worth having access to the clinical significance of the organic acid test. And so what I want you to think about is, are some questions to ask yourself when you’re actually reviewing an oat, any oat. Just kind of, these are things that I ask myself. And then I would encourage you if you’re a practitioner, some questions to ask for yourself when you’re reviewing a patient’s o.
So the big thing is, is which oat markers are of primary concern for the patient that’s sitting in front of you. Now, in many cases, that can be related to bacterial problems, fungal markers, high oxalate, for example. Maybe there’s mold markers present. And so you’re always trying to think about what’s kind of the primary issue that I want to try and focus on first for a given patient.
And then the next question is, is which oat markers may be influenced by actually those primary markers? And in the OAT seminar, we talk about how the presence of fungus, so candida, the mold markers, the presence of bacteria like clostridia, the high level of oxalate, often those markers can create other imbalances on the organic acid test. So sometimes you’ll see elevated mitochondrial markers, you know, likely because we’ve got bacterial problems or we’ve got fungal issues. And then there could be a myriad of, you know, other imbalances too, nutritional imbalances, et cetera.
And then always, like in anything in medicine is you’re trying to correlate the, the information from the lab to the clinical presentation of your patient. So how does the overall oat align with the clinical history of the patient? Do things tend to line up?
The other thing you want to ask yourself is, do certain oat markers indicate a potential significant conditions such as a genetic disorder, or are they most likely just being influenced by other imbalances, for example? So you can have nutritional imbalances that might affect mitochondrial markers. You could have a, you know, fatty acid metabolism markers that might just be influenced by a lack of certain nutrients. So again, you’re taking that information and applying it again to the clinical presentation of the patient.
What’s the age of the patient? That’s important to know just from the standpoint of reference ranges. So one thing on the organic acid test is that the reference ranges change based on sex, male, female, and less than 13 years of age and greater than 13 years of age. And then what do you know about the clinical history, the individual symptoms, their lifestyle, medications, environmental exposures, because that also plays into this as well when you’re interpreting a given organic acid test.
So I wanna do a, a review of the mitochondrial markers on page three of the oat, specifically the amino acid metabolites. And so this kind of sits about midway through page three of the mosaic oat. And we’re looking at markers 30, 31 and 32. So there’s three methyl glutaric, three hydroxy glutaric, and then three methyl glut. And you’ll notice in this particular individual, all three are elevated, but the marker 31 is very significantly elevated in this case.
I’m gonna get into this a little bit more when we think about metabolism, okay? It’s not just about metabolizing carbohydrates. We’re also metabolizing fats, and we’re metabolizing proteins and amino acids that get funneled down essentially through their different biochemical pathways to enter the mitochondria to produce a TP. So that’s sort of the end result of metabolism is the production of a TP. We get most bang for our buck metabolically when we engage the mitochondria, particularly the electron transport chain, to produce a TP. We do get some a TP production by just simple glucose metabolism. So all of these things are kind of funneling down to sequence themselves or enter the kreb cycle, uh, within the mitochondria at various levels.
So the first marker in this section is three methyl glutaric. So any of you out there who kind like looking at, you know, the chemical structure of molecules, for example, from an organic acid, uh, standpoint, we can see that glutaric is our base chemical here. It’s got two carboxylic acids and it has a methyl group at carbon three. So that’s where it gets its name 3-methylglutaconic.
So what is it? Well, it turns out that this marker is a metabolite of the amino acid leucine. So leucine is very much involved in metabolism pathways to produce compounds that get, that activate the kreb cycle. And when we see elevations of 3-methylglutaconic, it can come about from various things. So very high levels of 3-methylglutaconic can be seen in certain rare genetic disorders. So this 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. A lyase deficiency would be genetic inborn errors of metabolism defects that could cause elevated 3-methylglutaconic. But keep that in mind is that, you know, those are generally rare genetic conditions. It’s much more common to see this particular marker elevated at a slight level here in this particular case of 1.5 in somebody who doesn’t have these genetic conditions.
So it comes about often because there’s some sort of maybe glitch or something interfering with downstream metabolism that causes some of these markers to elevate even to a slight degree. The second one on this list is the 3-methylglutaconic marker 32. So this is also linked to leucine metabolism, and it turns out that there are five metabolic disorders that can impair the body’s ability to make energy in the mitochondria that are linked to this particular pathway. And so if there is a block in leucine metabolism downstream multiple steps, it could be multiple steps downstream, we can see an increase of 3-methylglutaconic and 3-methylglutaconic. Okay? But again, a level at 2.2 of a reference range of two is not really that high. It’s a fairly common thing that you’ll actually see on the organic acid test.
And so you have to think of and keep this in mind, given the type of patient you’re, you’re consulting with, understanding that very severe genetic disorders are, you know, very rare, okay? And so it’s much more common to see these markers just slightly elevated in a wide variety of people probably coming about because there’s just some kind of underlying imbalance happening in some of these biochemical pathways.
And so, for example, this very rare 3-hydroxy, 3-methylglutaconic deficiency, okay? When it is expressing itself on an organic acid test, you will see elevated levels of 3-methylglutaric and 3-methylglutaric. And we know that these organic acids can be stressful. So they can come about when there’s a lot of oxidative stress in the body. And the organic acids themselves, if there’s a lot of them, can add to that acidic nature in the body so they can sort of stress the body in other ways, even if there’s not a genetic disorder, just from the fact that we’re just have an increased circulating pool of these various organic acids, that in itself can create sort of internalized stress within the body.
So technically, elevations of 3-methylglutaric can occur because of this particular enzyme deficiency. But again, if you think about the incident, the new cases of three hydroxy, 3-methylglutaryl-coenzym, it occurs in fewer than one in a hundred thousand live births in many of these individuals. The mortality rate is fairly high. So if you’re working with somebody who’s 30 or 40 years old and their level is slightly high, you’re not looking at somebody who has this genetic disorder, okay? Because more than 95% of patients who have this particular enzyme defect will have rapid metabolic decompensation usually happening in the first year of life, okay? So very few individuals who have a very severe genetic condition linked to an enzyme deficiency, like I’m discussing, remain asymptomatic throughout their life, okay?
And so here’s the, the basic chemical pathway leucine funnels down through these different chemicals. And one thing I want you to pay attention to with these is that leucine ends primarily at as at acetyl coenzyme A and that is a major entry point into the kreb cycle. So acetyl coins ma essentially enters the kreb cycle and activates step one of the kreb cycle within the mitochondria. So this is one of the ways that certain amino acids can funnel their way into the kreb cycle. It turns out that glucose metabolism also creates acetyl-coenzyme. And so whether we have an enzyme deficit or we’ve just got some maybe glitch, or maybe there’s a nutritional imbalance, or it’s possible that some of these pathways might be adversely affected by various toxins, we can start to see mild increases of the 3-Methylglutaconic and the 3-Methylglutaric.
And so that’s the point of what are some of the causes, right? So, you know, you know, genetic defects, for example, very rare we could have downstream problems in the mitochondria. So if you actually dive a little bit deeper into the mitochondria, and particularly the electron transport chain and the way things are moving through those particular pathways, if there are imbalances happening there that can cause a backup, it’s sort of like the, the, the biochemical pathway sort of backs up and it doesn’t run efficiently. A lot of times these issues can occur because of just significant underlying nutritional imbalances, but there can also be chemical influences. There may be other toxic influences that are affecting the mitochondria. So there could be a host of things to just consider pregnancy, kidney disease, other non-genetic conditions. Nutrient deficiencies could also be a cause of slight elevations of these organic acids.
And then it, it’s, we’re looking at some type of severe disorder, speech delay, psychomotor delay, metabolic acidosis, poor muscle tone, for example, that can occur because of the presence of these. But these, the presence of these can also be elevated in just people who are manifesting with, you know, severe underlying metabolic imbalances.
The next marker in this particular section is 3-Hydroxyglutaric, marker 31. So it’s that same glutaric acid base, but now we have a hydroxy group at carbon three. So that’s where it gets its name. 3-Hydroxyglutaric. Now, this one you want to pay attention to, especially if it’s really high. And so one of the things that’s important to know is that this particular marker can be associated with glutaric acid urea type one. That’s a very severe inborn error of metabolism.
Now, this individual’s level is very elevated. This is not a marker we commonly see this high, but again, you have to always go back and say, “What’s going on clinically?” This is a three-year-old. This was a test that was sent to me by a colleague. I actually don’t have a full clinical history. I was asked to kind of evaluate the test from an organic acid perspective. So if I was the consulting doctor, I’d want to know more. Is this child showing psychomotor delay? Are there any seizure problems? Are there any problems with gait? Do they walk funny? You know, do they have a big head? Things like that can be signs of a very significant inborn error of metabolism.
So this particular marker, when it’s very elevated, in the absence of those clinical issues, it’s still likely worth having that child screened with a genetic test or talk to a genetics doctor to rule out glutaric acid urea type one. But if this is the only thing on the OAT that’s a problem, and let’s say it was 1.2 or 1.3, I wouldn’t be worried about this at all. This is a metabolite of lysine and tryptophan. So if you’re metabolizing lysine and tryptophan, you can see this. And if you go back and think about the pathway, it’s a downstream effect.
So again, glutaric acid urea type one is associated with elevated 3-Hydroxyglutaric and glutaric acid. Now, glutaric acid is not on the organic acid test. It’s on the amino acid urine test. So that’s another test you could run. If you want to know, is glutaric acid itself elevated in this person’s urine? That’s a different test, different technology. But again, for the most part, we’re going to see that if there’s a genetic disorder and you’re going to see this, usually within the first year of life, very few people that have these problems go on to live, you know, 30, 40, 50 years. And so it’s a very serious issue if it’s a big problem. And it’s something we just need to be mindful of. But again, it’s really going to depend on how high is it and what else is going on with the individual.
So here’s the pathway of how lysine gets metabolized into glutaric acid. There are multiple different intermediary compounds. So we see lysine, alpha-ketoadipate, glutaric acid. Then glutaric acid can convert into three hydroxy glutaric acid.
Now, where this becomes a problem is when you have enzyme deficiencies—typically this glutaric acidemia type 1. This is an inborn error of metabolism that happens usually at birth. This is a deficiency of the enzyme glutaryl-CoA dehydrogenase. This enzyme is encoded by the GCDH gene. It results in elevated concentrations of glutaric acid, 3-hydroxyglutaric acid, and glutarylcarnitine.
The typical clinical features are macrocephaly, subdural hemorrhage, dystonia, seizures, and developmental delay. It usually presents between 6 and 18 months of age. The prognosis depends on the timing of diagnosis and initiation of treatment. So, treatment consists of dietary lysine restriction, carnitine supplementation, and riboflavin.
So I mentioned earlier that carnitine is one of the things that’s often used when you see elevated levels of these organic acids. Carnitine helps bind up these toxic organic acids, escorts them out of the body, and you’re less likely to have problems. That’s why carnitine is considered a standard treatment for many organic acid disorders.
Now again, this patient did not have the full clinical history submitted. I was asked to review the test. So if I was the clinician reviewing this and I saw this value, I would definitely want to go deeper into what the clinical history is. How is the child presenting? Are there any movement disorders? Are there seizures? What’s going on developmentally? If there’s anything suspicious, a genetics referral is warranted.
If the child is doing okay and this is the only marker on the test that’s elevated, then this might be due to some minor disruption in metabolism and is not indicative of a serious disorder. But because of the clinical implications of this compound being so high, this is a marker that deserves attention.
Related Tests
So I wanna touch briefly on mitochondrial markers and some patterns that you might see. We covered the three amino acid metabolites, but there are other sections of the OAT that deal with mitochondrial function, including the Kreb cycle intermediates and the markers related to fatty acid oxidation.
When you’re reviewing a test, one of the things that I always look at is: are the mitochondrial markers elevated in a pattern? Are they clustered? Are there multiple in the same pathway? Do they correlate with symptoms that are energy-related—fatigue, low tone, exercise intolerance, etc.?
Because if we’re seeing elevations of things like succinic acid, fumaric acid, malic acid—those are all intermediates in the Kreb cycle—it can be an indication that the cycle is not running efficiently. That inefficiency could be due to nutrient deficiencies, could be due to toxic exposures, could be due to mitochondrial dysfunction, oxidative stress, or other factors like a lack of CoQ10.
We also want to keep in mind that the reference ranges for these markers are based on age. So a mildly elevated succinic acid in a three-year-old may not mean the same thing as a mildly elevated succinic acid in a 40-year-old.
I also like to look at whether or not lactic acid and pyruvic acid are elevated, because those can give us insight into whether glycolysis is being pushed too hard, possibly because mitochondrial function is impaired.
When mitochondrial function is compromised, more energy has to be generated through glycolysis, and that can result in lactic acid buildup. Pyruvic acid can also build up if it’s not being converted efficiently into acetyl-CoA because of problems in the pyruvate dehydrogenase complex, which, as we discussed, requires many B vitamins.
So the next thing I wanna touch on briefly is oxidative stress and glutathione status. These are markers that are seen on the last page of the Organic Acids Test.
When we look at things like pyroglutamic acid, which is marker 58 on the Mosaic OAT, that’s commonly elevated in the setting of glutathione deficiency. And then marker 59, 2-hydroxybutyric acid, often shows up when there’s an increased demand for glutathione production.
So the first one, pyroglutamic, means you’ve burned through your glutathione or you don’t have enough of it. The second one, 2-hydroxybutyric, means your body’s trying to make more. So these two can show up together or separately. And when both are elevated, it’s often a clear sign that your patient is under a great deal of oxidative stress, and they’re burning through or needing more glutathione.
Glutathione is your body’s master antioxidant. It’s one of the most important defenses we have against internal and external toxins. It’s made in the liver, and it’s required for detoxification. It also protects the mitochondria from oxidative damage.
So when I see those two markers elevated, I’m thinking, okay, this person probably needs glutathione support—either through N-acetylcysteine, liposomal glutathione, or other means, depending on what’s tolerated.
You might also consider the context. If you’ve already identified markers of mold, Clostridia, Candida, environmental exposure, etc., those could all be things that are depleting the glutathione pool and driving up those detoxification indicators.
So, you know, I tend to look at that section and say, okay, I’ve already seen page one with the fungal markers, the bacterial markers. I’ve seen the Clostridia markers. I’ve seen mitochondrial dysfunction. Now I see signs of oxidative stress and detoxification strain. That’s a pretty complete story.
I also look at how all of these things connect back to what the patient is experiencing.
Now, when we consider the nutritional markers on the OAT, sometimes people expect to see a ton of things out of range. And occasionally we do, but more often they’re subtly trending—low normal or high normal—and that still gives you useful insight.
So in this individual, B6 looks kind of low. It’s in range, but it’s trending toward the lower end. B12 looks okay, but the methylmalonic acid is slightly high-normal, which can indicate a functional need for B12. Ascorbic acid is low, so there’s likely an antioxidant issue.
And then there’s marker 55, the 5-hydroxy-3-methylglutaric acid. This is a very important one, because when it’s elevated, it’s associated with CoQ10 deficiency.
Why does that matter? Because CoQ10 is an integral part of the electron transport chain. It’s needed to shuttle electrons across the mitochondrial membrane complexes to ultimately produce ATP—our cellular energy currency.
Without adequate CoQ10, you start to see sluggishness in mitochondrial performance. And that can cascade into fatigue, brain fog, cardiovascular issues, immune dysfunction, and so forth.
So again, when we think of the mitochondria, these energy factories within our cells, they’re most abundant in cells coming from highly metabolic organ systems: the brain, nervous system, the musculoskeletal system, the cardiovascular system. Even the immune system is dependent on mitochondria.
The citric acid cycle, called the Krebs cycle, is sort of the first place of metabolic transformation happening. And then we’ve got the electron transport chain, which is embedded within the inner mitochondrial membrane.
If you can remember that the electron transport chain is doing exactly what its name describes—it is transporting electrons through these protein complexes with the end goal to generate ATP, that cellular energy currency. And we need CoQ10, which is found in the first three complexes, and we need a bunch of other nutrition linked to these complexes.
This particular child has a CoQ10 deficiency. So it’s a no-brainer to say, yeah, we actually need to give some CoQ10 from a supplement standpoint.
Where it gets even more complex in this particular case is we have every single marker in the indicators of detoxification section elevated.
I’m not gonna say much about the 60 and 61. It can be elevated because of the inability or some difficulty in processing ammonia. It might be coming because we have a lot of digestive system bacterial problems. So we’ll have to see upon repeat testing.
But notice that 58 and 59 are both elevated. 58, pyroglutamic, when it’s elevated, is linked to a glutathione deficiency. Well, glutathione is a very important antioxidant. If we don’t have enough glutathione, we’re gonna have a difficult time detoxifying toxins like mycotoxins. Plus, it leaves our mitochondria more vulnerable to oxidative damage.
Then we’ve got the 5-hydroxybutyric, which—its elevation—is most commonly linked to an increased demand for glutathione production. So the elevated pyroglutamic indicates a glutathione deficiency. The question to ask is: Why is glutathione deficient in the first place?
Are we not getting enough nutrition to support it? Or are there many environmental toxins or maybe even endogenous toxins that are just putting an increased demand on the glutathione system?
Elevated 2-hydroxybutyric is most commonly indicating an increased demand for glutathione production. Again, why? Why would those markers be elevated?
We get an idea by looking at some other things on the OAT, particularly those markers on page one. But I know that I’d wanna do additional testing, like the MycoTOX, perhaps. That’s what’s draining the glutathione.
Okay, so I wanna just show the relationship of 2-hydroxybutyric and pyroglutamic.
Here’s a typical image of the methylation/transsulfation pathway. So if I draw a line right here — here is methylation. So it’s converting homocysteine to methionine. Here’s our folate cycle. Notice MTHFR is dependent on riboflavin.
And right here is methionine synthase, dependent on B12. Coming down is what’s called our transsulfuration pathway. And it’s linked to bile salts, it’s linked to sulfation, it’s also linked to glutathione.
So when the body is being challenged with toxins—and it could be endogenous toxins, exogenous toxins, or both—there generally is an increased demand to maintain glutathione.
So preferentially, what happens is when the chemistry starts pulling towards that direction, we often get an increase in the 2-hydroxybutyric. So that’s why elevations of 2-hydroxybutyric are most commonly thought of as being linked to an increased demand for glutathione production.
There’s a couple of other things on this individual’s OAT that are worth knowing about, even though you may not see these things that often.
So this is the last page of the organic acid test, looking at the amino acid metabolites. Notice we have an elevation of marker 64: 3-methyl-2-oxovaleric. There’s also an elevation of marker 75, the 4-hydroxybutyrate. I’ll come back to that in a second.
Markers 62 through 66 — when those are elevated, you wanna pay attention, okay? Because they may be related to certain genetic conditions. But more commonly they’re reflective of a specific enzyme complex that is often compromised because of nutrient deficiencies, the most common nutrient being thiamine.
Now from an organic acid terminology standpoint, these chemicals have different names. So 3-methyl-2-valeric is the same thing as 2-oxo-3-methylvaleric.
This marker is considered a neurotoxin — basically an abnormal metabolite. And basically that’s kinda what happens with many of these abnormal organic acids that are elevated over a long period of time, and it can cause damage within the nervous system.
Now, chronically high levels of this particular compound are associated with a condition called maple syrup urine disease. Maple syrup urine disease is a metabolic disorder caused by a deficiency of what’s called branched-chain alpha-keto acid dehydrogenase complex. This leads to a buildup of metabolites of leucine, isoleucine, and valine. In this particular one, it’s isoleucine that’s most preferential.
Now, the symptoms of maple syrup urine disease often show up in infancy and can lead to severe brain damage. So again, it’s a rare genetic disorder. If you’re dealing with somebody, again, who’s in their forties and they’ve never had this, you’re not looking at somebody who has maple syrup urine disease in a full genetic expression.
In older individuals, during times of metabolic stress, symptoms of maple syrup urine disease can include a wide variety of things: inappropriate and erratic behavior, rapid neurological deterioration, hallucinations, weight loss, seizures, nausea, and vomiting.
I think we have to start looking at the organic acid test and the manifestation of some of these conditions. There is the full genetic expression that’s pretty consistent, but there’s a lot of people who may have just sort of imbalances that don’t necessarily have this rapid deterioration or outward expression of a genetic disease like this, but they might have characteristics that are somewhat similar and still cause stress and imbalance in the body.
In fact, if I ever had anybody who had new-onset seizures, first, yeah, their brain needs to be scanned. But an organic acid test is an absolutely appropriate thing to do because you might find an individual who has some elevated organic acids that might be linked to some of these metabolic imbalances that could be treated appropriately—even just with some nutritional supplementation.
So again, maple syrup urine disease is a metabolic disorder linked to a deficiency of this particular dehydrogenase complex.
Well, remember when I introduced you to the pyruvate dehydrogenase complex, it required all of those B vitamin nutrients—B1, which is thiamine, B2, B3, B5—throwing a little bit of lipoic acid into the mix.
Well, downstream in the Krebs cycle is another dehydrogenase enzyme complex called alpha-ketoglutarate dehydrogenase. It too requires the same nutrients. It turns out that branched-chain alpha-keto acid dehydrogenase complex requires the same nutrients. So this is involved. It’s higher upstream in the amino acid pathways of these branched-chain amino acids. And notice that leucine, isoleucine, and valine funnel downstream through all of these different conversion states to create either acetyl-CoA or propionyl-CoA, which becomes succinyl-CoA that enters the Krebs cycle at different stages.
But if that enzyme is compromised because of nutrient imbalances—and I’ll give you a hint: thiamine is the rate-limiting nutrient for all of these dehydrogenase complexes—pyruvate, alpha-ketoglutarate, and the branched-chain dehydrogenases, because it’s involved in the first step of a series of protein reactions or chemical reactions within that complex.
So thiamine is a very important nutrient in these enzyme complexes. We’re going to start to see some abnormal elevations of some of these organic acids.
This is just another view. So the BCKDC is the branched-chain keto acid dehydrogenase complex. It’s dependent on all of those nutrients we mentioned.
By the way, that’s another name for the marker that was elevated on this child’s OAT—this last marker, 2-hydroxybutyric. I see this from time to time, and it’s actually linked to— I mean the compound itself is called gamma-hydroxybutyric acid or 4-hydroxybutyric acid. It turns out it’s actually linked to glutamic acid.
Glutamic acid gets converted to GABA. GABA, interestingly enough, gets converted to succinic acid, which is another entry point within the Krebs cycle. So the Krebs cycle’s interesting—it has multiple doorways for things to move into it and then move out of it, actually.
And so 4-hydroxybutyric acid could be elevated in somebody who’s taking GABA supplementation, but I don’t think it’s a—I don’t see that as a real strong association. I’ve seen a lot of people take GABA supplementation and not have abnormal 4-hydroxybutyric. So I’m not quite sure where this is coming from.
We’re probably looking at some type of defect, for example, in this particular enzyme—the succinic semialdehyde dehydrogenase. As far as I know, even though this is a dehydrogenase enzyme, I don’t believe the same nutrients that I just mentioned are working in this particular enzyme.
So again, sometimes what you find with the organic acid test is that when you start dealing with the primary issues—in this particular case, the primary issues are a lot of the stuff on page one—and you give some additional added nutrients and you repeat the organic acid test, you know, 60 to 90 days later, some of these other downstream markers within the organic acid test will often self-correct.
Because if we were to think about succinic semialdehyde dehydrogenase deficiency, it has a prevalence of 1 in 500,000 people. So again, a true genetic disease expression is pretty rare. And this child really doesn’t manifest from a standpoint with regards to severe things linked to that particular genetic disorder.
So the clinical approach—there’s a lot of ways you could go with this. Where we have started in this process is additional testing, looking at the MycoTOX profile. So that would clearly be indicated in this particular case.
Other considerations—stool test, TOXDetect, glyphosate—I have no problem in doing that. Blood chemistry, for example, that could also be something considered. Perhaps genomics, looking at other genetic factors. MitoSwab, which is another test I do in my practice— all of those could be appropriate.
But from a Mosaic standpoint, mycotoxin profile would be absolutely high on the list.
From a supplement standpoint, you always have that clinical decision of antibiotics, antifungals, maybe—in a young child where we’re still trying to do some detective work to figure out what else may be going on in a complicated OAT like this—plus many special needs kids have a lot of sensitivity to supplements. They can have an increased tendency for die-off.
So a lot of times you have to go low and slow with your approach. So an approach of just introducing some probiotics, for example lactobacillus, bifidobacterium species, some soil-based organisms like the CoreBiotic—try to bring some of the fungal and clostridia and bacterial markers down with some botanicals slowly over time—often has its advantages instead of rushing in with 15 different products loaded in on day one.
This is a scenario where other supplements for mitochondrial support—clearly there’s a need for carnitine, ubiquinol (which is reduced CoQ10), activated thiamine—all of that is appropriate and implemented as well in various stages.
Now there are some resources if you are interested in learning more about this particular case and looking at the organic acid test, my commentary on the organic acid test and then follow-up posts—you could actually go to my Substack: https://drwoeller.substack.com/. It’s free to join. You can access that there. There’s a series of articles and I have a lot of other posts on my Substack as well.
Through our Integrative Medicine Academy—if you are a healthcare practitioner—we have many courses available. We’re in the process of developing a new website, a relaunch of our website, that’s gonna have everything housed in one website—all of our courses from autism to toxicity, to mitochondria, to candida, to clostridia—all of those courses are available for purchase at any time.
If you are a parent or caregiver of an individual with autism, you’re always welcome to join my Autism Recovery System website. There is a private forum where you can post questions to me on an ongoing basis. There’s a lot of other information in this website as well.
And then I also have a podcast—past interviews, more planned in the future. You can access those podcasts at https://functionalmedicinedoctalk.com/.
And then if you’re interested in consulting with me directly, there’s our website: https://mysunrisecenter.com, our email and phone number.
So I hope that you found that interesting, everybody. I know it’s a lot of information, but it’s important to be able to look at these organic acid tests that generally have more than just a few markers and try and understand some of the complexities of how to move forward. So thanks so much.
Thank you, Dr. Woeller. We’re gonna plow through some of the questions that we got, and don’t worry everybody, if you have not had a chance to pop your questions in, please go ahead and do so now. And we’ll just kinda work our way down the line.
I do wanna point out—somebody pointed out to me that people may not realize that thiamin is B1. A lot of us aren’t used to hearing the names of B vitamins—we’re just used to the alphabets and the numbers. So thiamin is B1. I’m just gonna put that as a little PSA. I’ll remember that in the future too.
Michelle just said it actually took me a long time to remember.
Yep. Yep. I had a cheat sheet. I had a very lively debate with my husband just the other night over what B6 was. He was like, “It’s folate.” I’m like, “No, it’s not.” Like, “No, no, it’s not. You’re wrong.”
So let’s see. When you’re looking at those ketone and fatty acid oxidation markers, is there a particular pattern that weighs a little bit more heavily on you? Or like if one is high but one is low, or something along those lines, do you have any kind of ketone patterns or flow between them that red flags for you?
So I learned about—I have a patient who actually traveled back east to basically see a mitochondrial specialist. They actually did some blood testing on those ketones. There was a panel that I didn’t know about, and it turned out—and I’m trying to remember now, I could probably go look it up—but they looked at the 3-Hydroxybutyric and the acetoacetic, and determined that the elevations of those and the ratios between those was an indication of what’s called a redox problem, because those two things will cycle back upon themselves and it’s required on B3—so essentially NADH—to do that.
In that particular situation, they actually recommended high levels of niacinamide or high levels of niacin first, and then they could transition to niacinamide if the individual is getting the flushing from the niacin. And that wasn’t something I had really thought much about or knew about.
Right now it’s trying to be determined—can the organic acid test give us that same kind of accurate information? And right now, I don’t know if that’s the case. I’m suspicious that it can, but it may not be completely correlatable—if that’s a real word—to blood testing. So I look at it as a suspicion that there may be a redox problem.
Typically though, what I look at in that pattern is, for example, if you had all of those markers elevated and they’re all relatively about the same level—okay, and I actually have a slide of this in the OAT seminar I do—one of the things I always look for is like, “Okay, what kind of cooking oil are they using?” Because MCT or coconut oil can cause those markers to elevate, but usually they all elevate about the same level.
If you find that the 3-Hydroxybutyric and acetoacetic are way much higher than the others, now you’re looking at something that’s usually dietary driven or metabolic driven that needs some investigation. As I mentioned, it could be that they’re doing a ketogenic diet, or they’re trying to do it. But maybe it’s somebody who—with diabetes or they’re developing diabetes—and you need to do an insulin and a fasting glucose and those types of things.
So that’s kind of how I view it. We’ll see where it goes. If the information can be correlated to a redox problem, I’m not sure, but that’s always in the back of my mind that that might be something to consider. I hope that helps.
Yeah, for sure. Let’s see—are there areas of the OAT that give insight into the biopterin pathway and influences on the neurotransmitters?
Oh, boy. There’s nothing on the OAT as of now that would directly link—well, let me take that back. Folate can have some influence. So the pterin and the uracil—you know, it’d be kind of indirect. There’s not a biopterin marker.
However, if you look at where biopterin works—so it is the cofactor for phenylalanine hydroxylase, tryptophan hydroxylase, and tyrosine hydroxylase. So if you find that the homovanillic, the vanillylmandelic, as well as the 5-hydroxyindoleacetic acid are all low, you’re probably looking at somebody who has a BH4 deficiency. And that would be found under the neurotransmitter section.
And how do you give BH4 supplementation?
You can get it as a supplement. It’s not cheap.
I was like, I’m trying to cycle through my pictures of pill bottles in my brain.
Yeah. What’s the company? Is it Ecological Formulas? I think they have something called Tetrahydrobiopterin (Tetramin 4). New Beginnings Nutritionals, I think, still carries it. There’s a medication called Kuvan, which is a BH4—I don’t know if it’s a derivative or whatever—but it’s actually indicated for phenylketonuria, so you could use that, but that requires a prescription.
But the Tetramin 4 from Ecological Formulas—I think it’s 2.5 milligrams per tablet. But it’s expensive, but it is available as a supplement.
And what about quinolinic? When you see that quite elevated, do you have anything specific that you do?
When you see quinolinic high, that should—you know that thing about, “Ask the question, why is it high?” So say, “Okay, what are some things that can cause quinolinic acid levels to go elevated?”
Related Tests
And again, we cover this in the OAT seminar. Stress—cortisol—can drive it up. Chronic infections can drive it up. So does a person have some kind of chronic infection? Are there chronic stressors, for example, that might be inducing it?
It turns out that a niacin deficiency—a B3 deficiency—can cause quinolinic acid levels to go elevated. So one of the questions I always ask myself is, “Okay, if you look at the pathway of quinolinic acid to nicotinamide adenine dinucleotide (NAD), why do we want NAD to be produced?” Because it plays such an important role in metabolism with regards to energy production, particularly within the mitochondria.
It’s a brilliant system if you think about it. We have all these things that flow in and out of these different pathways. But NAD is a very important thing for Kreb cycle activity, and it’s the thing that also helps to engage Complex I of the electron transport chain.
So if quinolinic is high, perhaps we have this increased demand for NAD production to just try to maintain normal mitochondrial activity throughout the body.
And the question is, “Why is that happening?” Somebody who’s chronically stressed—physically, mentally, emotionally—they have chronic infections, they have chronic exposures—all of these things put increased demand on our body and our body’s trying to deal with it. So it’s cranking up these chemicals to just try to maintain some sort of normal energy output.
So the basic thing is always ask the question, “Why is it elevated?” Or can we even figure that out?
But a simple thing to do is—this person could probably benefit from some niacin or niacinamide. So that’s kind of an easy thing to plug in there while you’re trying to figure things out.
Would you take any different approach if it was in a pediatric patient versus an adult?
I wouldn’t give them niacin. Yeah. You know, so niacinamide would be a better option.
But, you know, I will use individual, Michelle—use individual nutrients. Like this particular case—we used some benfotiamine as activated B1.
But on top of that was also—hey, we’ve gotta talk about trying to optimize nutrition, diet, foundational supplements to try to just sort of fill in those gaps nutritionally.
And I’m always selective at what I’m using, and I’m also very selective at what I use based on the individual. A 3- or 4-year-old child—sometimes you have to be more selective than somebody who’s 35 years old. All of that comes into play.
Awesome. All right, let’s see. In the nutrient markers, specifically vitamin B2, what are some signs or symptoms that you might see in a patient that might reflect an insufficiency or deficiency?
So B2 is used to convert B6 into its active form. It’s used to convert folate into its active form. So if you see elevations of things like methylmalonic, and then also elevated xanthurenic acid, and then elevated folate markers—uracil and FIGLU—that person could be low in B2. If you’re seeing elevations of adipate, suberate, ethylmalonate, glutarate, B2 deficiency has been associated with that as well.
Signs and symptoms of B2 deficiency—cracks on the sides of the mouth, red, inflamed tongue, sore throat, sensitivity to light, watery eyes—so there’s a variety of things that can be indicative of that.
But again, I always try to correlate those markers to those clinical signs and symptoms.
Great. All right. Let’s see. This one says, “Does the OAT detect mold exposure or mycotoxin exposure?”
Not directly. So if you look at what the OAT is reporting—right now it has two fungal markers: arabinose and tartaric acid. Arabinose is not a specific mold marker; it’s a sugar. So we see it with mold. We also see it with candida. We can see it with kids that have autism that have no candida and no mold, and they’ve got sky-high arabinose. I’m not sure why that happens. So there could be some genetic variation that’s happening. It’s probably more of a marker of dysbiosis. But it’s not a mold marker.
Tartaric acid, again, it’s a fermentation product. So it’s not a mold toxin, but it is associated with fungal or yeast overgrowth. So those are the two markers that are on there. That’s why we don’t call the OAT a mycotoxin test. It’s an organic acid test.
So if somebody is looking for, “Hey, is my patient dealing with mold exposure?” Then you’d want to run a urine mycotoxin test from Mosaic, and then you could run an organic acid test to see how it’s affecting the body.
Awesome. I’m going to throw a couple of quick ones in here because I know we’re short on time. Somebody asked, “Do you need to stop probiotics before taking the test?”
We usually say stop for 24 to 48 hours. But we’re not talking about stopping a week ahead of time or anything.
Perfect. Somebody said, “If someone’s gallbladder was removed, how does that affect some of these pathways?”
Fat digestion. So some of the fatty acid oxidation markers, perhaps some of the ketone markers. You know, bile is made in the liver and stored in the gallbladder. And when we eat fat, the gallbladder contracts and delivers it. So if you don’t have a gallbladder, you don’t really have the ability to deliver bile in the way it was supposed to be delivered.
So you’re going to see a reduction in fat digestion and perhaps a change in fatty acid oxidation. So you might see elevations in sebacic and adipic and suberic. I think I showed one that had sebacic elevation.
Some of the other ones would be—maybe you’d see some changes in the ketones as well. But you have to look at the big picture.
Perfect. And somebody said, “How long after starting a supplement should you wait to retest the OAT?”
If you’re doing methylation work—six weeks. If you’re doing some of the B vitamin stuff—maybe 30 days. If you’re doing detox, mitochondrial, neurotransmitter stuff—30 days to 45 days.
Great. Thank you, everybody, for all your questions. There’s a few we didn’t get to—we’ll try and get to them in a follow-up or email or something along those lines.
