The Organic Acids Test: Focus on Energy, Nutrients and Detoxification

Adapted from episode 77 of The Perfect Stool podcast with your host and gut health coach, Lindsey Parsons, EdD.

This is my second blog post on interpreting Organic Acids tests, a test that I use with a lot of my clients that can tell you about your gut health, in particular with regard to candida and mold, bacterial overgrowths, and overgrowths of clostridia, oxalate levels, your production of energy from carbs, fatty acids and protein, your neurotransmitter levels, nutrient levels of B vitamins, vitamin C, CoQ10 and NAC and detoxification markers. In the last post, I focused on the gut stuff, oxalates and neurotransmitters. In this post, I’ll be focusing on energy production, nutrient levels and detoxification markers.

So I’m going to jump right back into the test, noting briefly that this is the Great Plains Organic Acids Test and there is another from Genova called the Organix that some practitioners use. One some of these sections, the Organix does have one or two advantages over the Great Plains OAT, one of which is that it lists the nutrients at the top of each section that are involved, such that if there’s an issue, you know what to supplement with, although dosages, timing, etc. aren’t given. So I’ll mention those nutrients as we go along.

And I do want to forewarn you that I’m going to be using a lot of big, science-y words and not to get intimidated. Just have the sample test open and glean what you can from what I’m sharing. If at some point you take the OAT or already have one of your own, you can key in on the markers you have elevated or low and dig in further.

Glycolytic Cycle Metabolites

So we’re jumping first to p. 3 and markers 22 and 23 lactic and pyruvic, under Glycolytic Cycle Metabolites. The glycolytic cycle, also known as glycolysis, is the metabolic process that converts glucose (which you get primarily from eating carbohydrates) into pyruvic acid, which is turned into acetyl-coA, which then enters into the Krebs cycle to produce energy. This process is a sequence of ten reactions that are catalyzed by enzymes, and those enzymes require co-factors, which are nutrients, like B vitamins for example, that are necessary for those reactions to take place.

Now when pyruvic is high, as it is in this test, it means that the pyruvic acid isn’t converting into acetyl-coA, which when it gets bad enough, indicates insulin resistance. So this is an early sign of a diet that’s likely too high in sugar and refined carbohydrates. Interventions at this point are usually dietary, like eliminating all added sugars and white carbs. And then in terms of supplement support, you’re looking at alpha lipoic acid, which helps stabilize blood sugar and the B vitamins, in particular B1 or thiamin, B2 or riboflavin, B3 or niacin and B5 or pantothenic acid. But it’s best to take a B complex whenever you’re taking B vitamins, because they work together synergistically. Chromium can also be useful if you’re dealing with blood sugar dysregulation, both on the hypoglycemic side, meaning low blood sugar, a sign of which is dizzy spells and shaking when your blood sugar drops, and the hyperglycemic side, which means high blood sugar and is typical of type 2 diabetes, and also characterized by blood sugar highs and then crashes in which you feel exhausted.

High lactic, number 22, can be from vigorous exercise, because when oxygen is in short supply, pyruvic acid is converted to lactic acid through an anaerobic process, leading to sore muscles, like after you’ve lifted too many weights or done something new to your muscles. Lactic can also be elevated from bacterial overgrowths in the GI tract, B-vitamin deficiencies like I described before, which can lead to blood sugar dysregulation, mitochondrial dysfunction or damage and anemia, among others. There can also be genetic reasons, but the numbers are generally much higher (above 300 mmol/mol creatinine) when you start suspecting that. Pyruvic can be elevated for the same reasons as well, with possible genetic causes over 100 mmol/mol creatinine. If you have enzyme issues that are genetic, you can see neurological problems and seizures.

If lactic is high but pyruvic isn’t, it is more likely to point to anemia, zinc deficiency, but also excess alcohol or toxic metal exposure. If either is high, because there is a lack of energy production, CoQ10 is also a helpful supplement to help with energy.

Mitochondrial Markers – Krebs Cycle Metabolites

The next section, Mitochondrial Markers – Krebs Cycle Metabolites, markers 24-29, are markers of the metabolites of the Krebs cycle, also known as the citric acid cycle, or TCA (tricarboxylic acid cycle), which is the intermediate step in the creation of energy from food, which takes place inside our mitochondria (which are in all of our cells).

So as I mentioned above, glucose from carbs converts to pyruvic acid then to Acetyl-coA. Acetyl-coA enters into the Krebs cycle and then there are all these chemical reactions that happen, so Acetyl-coA is converted into citrate (which is the oxidized form of citric acid, when it loses its hydrogen). By the way, these markers on the Genova Organix form of the test are all listed in the –ate form like citrate whereas on the Great Plains OAT they’re all listed in the –ic form or acid form like citric. So then citrate is converted into cis-aconitate (and the corresponding marker on the Great Plains OAT is aconitic), which is converted to isocitrate (which is on the Organix but not on the Great Plains OAT), then alpha ketoglutarate (which is the same as 2-oxoglutaric acid on the Great Plains OAT), which is converted to succinate, then fumarate, then malate (and there are a few steps in between that I didn’t mention). One of the byproducts of the citric acid cycle is NADH, which then is fed into the electron transport chain through a process called oxidative phosphorylation, which is the final step in the creation of energy or ATP – adenosine triphosphate. Now forgive me if I have anything not quite right in this description, I was a French literature major in college, so I’ve had to do a lot of catch up in my chemistry and biology to understand this stuff, but the long and short of it is, each of these markers on the OAT can indicate if there’s a break in the process of the creation of energy or a problem with it entirely, like there’s not much of it going on, because your mitochondria have collapsed and been destroyed by oxidative stress, like toxins and not enough antioxidants, like vitamins C and E.

And if you see one of these markers elevated, it can be because of a missing co-factor or nutrient in the process. So for example, to convert isocitrate to alpha ketoglutarate, you need B3 or niacin, Magnesium and Manganese, so if one of those is missing, you’ll have excess isocitrate because the conversion isn’t taking place. Or to convert succinate to fumarate you need B2, also known as riboflavin, so if you’re short on that you’ll see succinate elevated because the conversion isn’t taking place. That’s the general background. And a deficiency of CoQ10 or its active form ubiquinol, is also a common problem when there are breaks in the citric acid cycle.

So specifically, high succinic can be from a deficiency of B2, CoQ10, bacterial degradation of unabsorbed glutamine supplementation, or from heavy metal or other toxic exposures and mitochondrial dysfunction.  It’s also possible to have a genetic issue with an enzyme. Low levels indicate a need for supplementation of the amino acids leucine or isoleucine.

Elevated fumaric can be from a defect in the enzyme fumarase that catalyzes the conversion to malate, a defect in mitochondrial function or impaired Krebs cycle function. Symptoms will be fatigue and weakness. You can support it with the addition of CoQ10, NAD+ (which is a derivative of niacin or vitamin B3 called nicotinamide adenine dinucleotide), nicotinamide, another form of B3, the amino acid l-carnitine, riboflavin or B2, biotin or B7 and vitamin E.

Elevated malic can point to a need for more niacin or CoQ10 or hyperinsulinism, which impedes weight loss, and again this represents a break in the citric acid cycle, so you’ll again see fatigue and weakness.

When 2-oxoglutaric (also known as alpha ketoglutarate) is elevated, if it’s not from supplementation, it can be due to vitamin deficiencies, such as B5 (also known as pantothenic acid or FAD (flavin adenine dinucleotide) derived from riboflavin and thiamine, or from undereating. Symptoms of this would be fatigue or reduced stamina.

Now if you see citric, fumaric, and 2-oxoglutaric acids simultaneously elevated, it strongly suggests mitochondrial dysfunction.

Then when aconitic is elevated, it could be a mitochondrial disorder or the need for additional reduced glutathione, which is your master antioxidant. Low levels aren’t significant or problematic unless you see multiple Krebs cycle metabolites low. Now if you see all or most of these markers very low, this indicates mitochondrial collapse, which means that there are not that many mitochondria. In this case, you’ll want to give free form amino acids or protein powder to stimulate the growth of new mitochondria, which is done at a particularly high dosage at one time to stimulate something called mTOR, but this is a complex topic that would probably require an entire blog post on it alone.

Then citric can be elevated from intake of citric acid containing foods, intestinal yeast that produces citric acid, amino acid deficiencies of taurine and methionine, problems with the citric acid cycle, ammonia toxicity (which can be from H pylori or other bacterial overgrowth as well as poor protein absorption), or a lack of glutathione, our master antioxidant. You may also see pyroglutamic values low along with this, which is in the detoxification section, marker 58, in which case you know you should supplement with either NAC (N-acetyl cysteine), an antioxidant that increases the glutathione reserves in the body, or glutathione itself, preferably in some format like liposomal or trisomal (available in my Fullscript Dispensary*), which is more absorbable, but at minimum in the reduced glutathione* format.

But in general, when there multiple high markers in the Krebs cycle, you’re looking at supplementing with CoQ10, Magnesium, amino acids and the B vitamins. And then you should be figuring out if there is an underlying cause for the dysfunction, like gut health issues or toxins like heavy metals, environmental chemicals or mold.

Mitochondrial Markers of Amino Acid Metabolites

The next section, markers 30-32, are Mitochondrial Markers of Amino Acid Metabolites. Markers 30 and 32 will be increased if there’s a reduced ability to metabolize the amino acid leucine, which can be genetic, or a mitochondrial disorder. In any case, supplementing with CoQ10, niacin, l-carnitine, the B vitamins and vitamin E may be helpful. So in these cases I usually look at a multivitamin with high B vitamins like my favorite multi, Perque Life Guard (which you can find in my Fullscript Dispensary*), plus a CoQ10 or ubiquinol supplement. Slight elevations in marker 31, 3-Hydroxyglutaric may indicate mitochondrial dysfunction, while high elevations are usually from genetic issues.

Pyrimidine Metabolites – Folate Metabolism

The next section, 33-40, the neurotransmitters, I covered in my previous post, so I’m jumping to 41 and 42, the Pyrimidine Metabolites – Folate Metabolism. The Pyrimidines are one of two chemical compounds that cells use to make the building blocks of DNA and RNA. Elevated uracil, or marker 41, may indicate a defect in folic acid metabolism, which is present in about 10% of children with autism, or a folate deficiency. If it’s elevated for a client, I just make sure they’re getting a good quality multivitamin or B complex with the active form of folate, not folic acid or folinic acid, which many people have genetic issues metabolizing. So I look for the active forms of folate, which might be listed as methylfolate, l-methylfolate,5-methyl-THF, L-5-MTHF or 5-MTHF.

Slightly elevated thymine isn’t significant, but very high values on thymine have been associated with inflammatory diseases and cancer. And elevated thymine along with elevated pyrimidines has been associated with a genetic disease that’s associated with seizures and autism.

Ketone and Fatty Acid Oxidation

Then the next section, Ketone and Fatty Acid Oxidation, markers 43-49, is one of my favorites. I like this section because if there are issues here with elevated markers, it’s one of the quickest and easiest fixes that usually has a dramatic effect on how people are feeling. So fatty acids, like carbs, must be converted into Acetyl-coA to be brought into the Krebs cycle to create energy. This process is called beta oxidation. Now to do this you need two things, the amino acid l-carnitine, and vitamin B2 or riboflavin. This is where I often see issues in vegetarians, vegans or people who only eat chicken and fish or just seafood. Carnitine is most plentiful in red meats like beef and lamb. For example, 4 ounces of ground beef has 87–99 mg of carnitine, four ounces of steak, 56–162, but four ounces of chicken breast, only 3-5. Four ounces of codfish, 4-7, a glass of milk 8. Pork is sort of moderate with 31 mg per 4 ounces. And lamb is the highest with 180 grams in 4 ounces of lamb filet. So over time on a restricted diet, carnitine will become depleted, then you aren’t bringing fats into the Krebs cycle to be burned for energy; instead they’re getting stored as fat. So this leads to weight gain and low energy, muscle aches, weakness, recurrent infections, migraines, age-related cognitive decline and in extreme cases, dementia. And because you don’t have fats to supply energy when carbs are quickly digested (which usually happens in about 2 hours) you’ll have blood sugar highs and lows. So you’ll usually see blood sugar high followed by a crash and symptoms like nausea, confusion or hypoglycemia.

Of course all this can happen to a meat eater with a deficiency of B vitamins as well, which can be dietary if not enough is consumed, there’s malabsorption, like with certain gut issues like Crohn’s disease, ulcerative colitis or celiac, low stomach acid so proteins aren’t getting broken down properly into amino acids, or it can be from excessive exercise, like when training for endurance sports, or alcohol abuse.

But since B2 is most plentiful in dairy foods, fortified foods like oats and breakfast cereals, meats and nuts, if you’re on a gluten-free, vegan diet and eating no processed foods, you could end up deficient in both carnitine and B2.

So issues in this area are relatively easy to fix with the addition of l-carnitine* or its active form acetyl-l-carnitine*. I usually use the former when there are physical issues like fatigue or weight loss resistance, and add the latter if there are brain issues like memory issues, age-related cognitive decline or brain fog.

All that I was just talking about applies specifically to markers 45, 46, 48 and 49. They can also be elevated because of fasting or high intake of coconut or MCT oil.

Some of the other markers like 3-hydroxybutyric and acetoacetic acids can also be elevated because of a ketogenic or very high fat diet, so it’s important to ask about diet before jumping to the conclusion that someone has a defect in their fatty acid oxidation. Those two can also be elevated because of prolonged fasting, protein malnutrition, a B12 deficiency, pulmonary infections and a severe candida overgrowth in the GI tract.

But overall, generally the more markers high in this section, the higher I think of raising carnitine dosing. I try to find the 1000 mg pills* to reduce the quantity people have to take. 3000 mg a day in 3 doses is ideal, best on an empty stomach like all amino acids. It smells and tastes gross, so it’s best to do in pill format rather than in a powder. And you can go up to 5000 mg/day if you’re not getting results at lower doses. Or add in up to 2000 mg a day of acetyl-l-carnitine* if you have the brain symptoms too, as it easily crosses the blood brain barrier and helps increase acetylcholine, which is an important neurotransmitter for learning, memory and general cognition, which can help with Alzheimer’s, as a severe depletion of acetylcholine is associated with Alzheimer’s.

Of course as with any markers, very high levels can indicate a genetic issue, and for adipic in particular, gelatin and other junk foods may have adipic acid as an additive, causing an elevation.

Nutritional Markers

The next section, Nutritional Markers, 50-57, indicate deficiencies in different B vitamins, which are listed by each one, vitamin C, CoQ10 and NAC. This is pretty intuitive, with low markers for most of them indicating deficiencies, generally flagged if below the mean, except that some of them are inverse markers and have an asterisk, which means that a high value indicates a deficiency. This is the case for B12, methylmalonic, which is much more sensitive and will show up earlier than a blood test for B12, B2(glutaric), CoQ10 (3-hydroxy-3-methylglutaric), and Biotin (methylcitric).

Deficiencies of different vitamins can have a variety of causes, but for B12 for example, a vegan diet, pernicious anemia, and gut issues are common causes. For B6, low values are associated with high oxalates and low neurotransmitters but those are not causes per se and are more likely the result of having low B6.

I often see marker 52, pantothenic, elevated, which is a marker of B5. It can be from recent supplementation but isn’t of concern if high or indicate a need to reduce, but if values are more than 20 times the upper limit of normal, there could be a genetic issue with conversion of B5 in a disease called pantothenate kinase-associated neurodegeneration. In mild variants of this disease, psychiatric illnesses such as schizoaffective disorder, hallucinations, obsessive compulsive disorder, speech defects, and depression are common. Generally, I assume that more severe manifestations of these types of genetic disorders are uncovered with regular doctors because of the early onset of severe symptoms.

Also, high glutaric acid for B2 (which is one of the inverse markers, so high means low) besides meaning low B2 can also be because of a lack of carnitine, so the B2 isn’t getting used as it should, or because of celiac disease. Supplementing both with riboflavin and CoQ10 is helpful when this is elevated. 

Next is ascorbic acid or vitamin C, which when elevated usually isn’t a concern, as that usually means you’re supplementing with it. Low levels are pretty typical if supplementation is stopped prior to testing and dietary intakes are inadequate, which is the case for most people, given the nutrient levels in our foods have decreased so markedly with the advent of modern agriculture and transport practices. So if you get a low level, it’s good to supplement with vitamin C. The only concern would be with someone with high oxalates or a history of kidney stones, as ascorbic acid or vitamin C could convert to oxalic acid, increasing the risk of kidney stones and other symptoms of high oxalates, which I discussed in my previous post. With normal levels of oxalic acid, vitamin C supplementation shouldn’t be an issue.

I’ve virtually never seen the marker for CoQ10, 3-Hydroxy-3-methylglutaric Acid (or HMG), to be high, and again this in an inverse marker, so high means low levels of CoQ10. But one reason that it may be high is use of statins, which decrease HMG and CoQ10. If you’re on a statin, you should be taking CoQ10 preventatively. Very high levels would point to a genetic disorder.

Biotin deficiency marked by high methylcitric acid I’ve also never seen. But causes could be dietary deficiencies, dysbiosis, or excessive intakes of raw egg whites. And again very high levels could be from genetic causes.

I’ll also note that I think I’ve only seen one OAT in which someone didn’t show up as deficient in B6. So not sure if there’s test error there or all people with gut issues have low B6 (which is not unlikely because gut issues can inhibit absorption) or there’s a population level deficiency issue, but just to let you know I’ve observed that, as have other mentors of mine in the functional medicine community. But I tend to recommend B vitamins to almost everyone I work with in any case, so I typically suggest one with high B6 for a time. Now it is possible to overdo B6 and symptoms of that are a lack of muscle control or coordination, skin lesions, heartburn, nausea, photosensitivity, numbness and reduced ability to sense pain or extreme temperatures. So I don’t recommend super high B6 supplements indefinitely (and when I say super high I’m talking 100-200 mg/day). But usually 6 months then retesting is ideal or move to a more reasonable dose like 25-50 mg/day.

And finally, I just want to say that I’ve never seen N-acetylcysteine Acid or NAC not in range, so it’s not a terribly useful marker. The next section on detoxification usually alerts us to the need for NAC supplementation. So let’s jump there.

Indicators of Detoxification

So this section, Indicators of Detoxification, markers 58-61, helps you understand how well your liver is clearing toxins from your body. The first marker, 58, pyroglutamic, is a metabolite of glutathione, which is our body’s master antioxidant, and one of its roles is to bind to toxic compounds in the liver. High levels, meaning a lack of glutathione as it’s an inverse marker, are usually due to toxic exposures like acetaminophen toxicity, or other toxins, genetic disorders, the metabolic effects of certain antibiotics, or the path to mitochondrial failure from oxidative stress. You can supplement with NAC or N-acetyl-cysteine* to support phase 2 detoxification, increase glutathione and bring this into the normal range. Sometimes other components of glutathione are missing, like glycine or glutamine, or you need other sulfur amino acids to support phase 2 detoxification, like taurine, methionine and cystine, so you may need to add those as well, or just take free form amino acids that contain them all, or just supplement with liposomal glutathione, which is the preferred form.

If glutathione is low, you should usually also supplement with magnesium (I prefer Magnesium glycinate form if you’re not constipated and citrate if you are). If you’re just going off the OAT results, check the Krebs cycle markers, and if they’re all low, meaning mitochondria have collapsed and given up and you’re feeling tired, depressed or have chronic fatigue, you’ll need both magnesium and glutathione or its precursors.

This is also an issue if this maker is very low, which means your body is working really hard to get rid of toxins, so you should also supplement with NAC or glutathione in this case.

The next marker, 2-hydroxybutyric, is also an inverse marker and high values indicate either methylation defects or toxic exposures. Again this points to the need for glutathione or NAC supplementation. It can also be elevated due to genetic SNPs in the methylation pathway or deficiencies of methyl tetrhydrofolate, the active form of folate, Methyl B12, the active form of vitamin B12 or betaine, or could be elevated due to the onset of diabetes, or from excessive alcohol use. Again sometimes genetic issues show up here but this is less common.

The next marker, orotic, is another one I really like because it’s usually an easy fix. It gets elevated when ammonia levels are high from either drug toxicity to the liver, bacterial overgrowth, particularly H pylori, GI bleeding, or inborn errors of the urea cycle, which is our process for ammonia metabolism, like a CBS mutation. So when you eat protein, you need to get rid of the nitrogen, but if you have a problem with your urea cycle and you can’t do that efficiently, you end up with buildup of ammonia, which can be because of faulty enzymes due to very common genetic issues. Symptoms of hyperammonenia are headache, fatigue, confusion, poor concentration, loss of muscle control and food intolerances. To help the urea cycle function, you take high doses of l-arginine, which pushes the cycle and helps clear out the ammonia.

The next to last marker I’ll mention is 2-hydroxyhippuric, which is elevated from aspartame consumption, high salicylates, like in aspirin and also an additive to personal care products and naturally occurring in many fruits and vegetables. Some people have a sensitivity to salicylates, so if you’ve tried everything else diet wise and this is high, it could be a salicylate sensitivity. It can also be elevated from overgrowths of certain bacteria in the gut that convert the amino acids tyrosine or phenylalanine into salicylic acid.

Amino Acid Metabolites and Mineral Metabolites

The remaining markers under Amino Acid Metabolites are rarely elevated and mostly point to genetic issues so I’m not going to discuss them much here. And finally, under Mineral Metabolites, phosphoric acid is also rarely off because phosphates are in processed foods, but if it is low, it could point to a vitamin D deficiency.

If you have an OAT test you need help interpreting or would like to order one and work with me on it, or if you’re dealing with either gut issues or mental health issues or chronic all over body problems, the good news is that this stuff is quite fixable, and the Organic Acids Test is often a great way to start to uncover what’s going on underneath. I work with clients using this test to reveal these issues and their root causes and educate you on how to fix them. So if you want to talk to me about what you’ve been dealing with and see if I think I can help, you can set up a free, 30-minute breakthrough session with me. I can let you know if I think I can help you and tell you about my 5-appointment gut or autoimmune healing program and you can decide it that seems like a good fit for you. Or you can just sign up for a single appointment.

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