Organic Acid Test Panel (OAT)

Dr. Weyrich's Naturopathic Functional Medicine Notebook

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Test Overview

The Organic Acid Test Panel examines metabolites found in a patient's urine that are products of body metabolism and of gut microbes. It can reveal imbalances in metabolic pathways, nutritional imbalances, as well as abnormal microbial overgrowth in the small and large intestines. The OAT Panel complements the Comprehensive Digestive Stool Analysis Panel, which can reveal abnormal microbial overgrowth in the large intestine.

Test Indications

First-line test for evaluating Autism Spectrum Disorder (ASD), Pervasive Developmental Delay (PDD), Asperger's Syndrome, Attention-Deficit Hyperactivity Disorder (ADD, ADHD), and learning disability.
First-line test for evaluating depression, anxiety, and other mood disorders.
First-line test for evaluating environmental toxicity.
Seizure disorders.
Chronic Fatigue Syndrome.

Sample Collection

Your doctor will provide you with the sample collection kit that includes sample container, gel-pack, and shipping materials.
Avoid eating apples, grapes, pears, and cranberries or foods/juices containing them for 24 hours before collecting urine.
Place gel-pack in the freezer the night before sample collection.
Collect 10 mL of FIRST MORNING URINE, before eating or drinking (or use special pediatric collection bag overnight if patient is not potty trained).
Refrigerate sample (do not freeze) until ready to send to lab.
The sample must be sent via overnight FedEx directly to the lab on a Monday through Thursday using the prepaid mailer provided.
Detailed instructions are in the sample collection kit.

Your doctor or lab may have different instructions that supersede the above.

CPT CODES

CPT-Code	Description	Comments
82507	Citrate
82570	Creatinine
83150	Homovanillic Acid (HVA)
83497	5-Hydroxyindolacetic Acid (5-HIAA)
83605	Lactate
83921*56	Organic Acid, Quantitative, Each	56 different OA
84210	Pyruvate
84585	Vanillylmandelic Acid (VMA), Urine

Labs Performing Test

Name of Lab	Lab Code	Estimated Cost	Processing Time	Comments
Great Plains		$240	2-3 weeks	Cash discount and some insurance

Costs cited are subject to change and may be reduced by insurance or cash discounts and increased by sample collection fees.

Theory

Yeast/Fungal Metabolites

Citramalic (Methylmalic) Acid

A byproduct of Saccharomyces yeast species, as well as Propionibacterium acnes.
Suggests dysbiosis.
An analog of the Krebs cycle compound malic acid; may interfere with the production of malic acid in the Krebs cycle.

5-hydroxymethyl-2-furoic Acid

A byproduct of the fungus Aspergillus and probably other species of fungi and yeast as well.
Suggests dysbiosis.

3-oxoglutaric Acid

Slightly elevated values are found in autism and other disorders.
An analog of the Krebs cycle compound 2-oxoglutaric (alpha-ketoglutaric) acid.
Elevated 3-oxoglutaric acid may correlate with low 2-oxoglutaric acid, possibly indicating an interference with 3-oxoglutaric acid in the Krebs cycle.
Presumably formed from the amino acids lysine and tryptophan.

Furan-2,5-dicarboxylic Acid

A byproduct of the fungus Aspergillus and probably other species of fungi and yeast as well.
Suggests dysbiosis.

Furancarbonylglycine

A conjugate of furancarboxylic acid and the amino acid glycine.

Tartaric Acid (3-Hydroxymalic Acid or 2,3-Hydroxy-succinic acid)

An analog of the Krebs cycle intermediate malic acid that inhibits the Krebs cycle enzyme fumarase that converts fumaric acid to malic acid [Shaw2008].
A toxic fermentation product of Saccharomyces yeast species.
High levels are associated with autism and fibromyalgia [Shaw2008].
Damages muscles and kidney [Robertson1968].
Suggests dysbiosis.
Treatment with antifungal drugs can significantly lower level in urine (also consider naturopathic treatments).
Also found in grapes, cream of tartar, and as a food additive. In low doses is Generally Recognized As Safe (GRAS) by the FDA, but a 12 g dose may be fatal [Shaw2008].

Arabinose

A metabolite produced in the liver from arabitol (also called arabinitol), which is produced by various yeast species such as Candida albicans, Candida tropicalis, Candida parapsilosis, etc.
Arabinose is a 5-carbon aldose sugar that is not made in significant quantity by human metabolism, but can be found in apples, grapes, and pears and can serve as a marker for yeast overgrowth [Kiehn1979] [Wong1990] [Larsson1994] [Roboz1992].
Arabinose may be a particular problem for patients with a defect in their pentose metabolism; this defect can be tested for [Shaw2008].

Carboxycitric Acid

An analog of the Krebs cycle compound citric acid; may interfere with the metabolism of citric acid in the Krebs cycle.

Bacterial Metabolites

2-hydroxyphenylacetic Acid

Produced by overgrowth of several species of bacteria in the GI tract by metabolizing the amino acid tyrosine.
Very elevated values are present in celiac disease and enteritis.

4-hydroxyphenylacetic Acid

Produced by overgrowth of bacteria in the GI tract by metabolizing the amino acid tyrosine.
Treatment with the antibiotic neomycin can significantly lower level in urine (also consider naturopathic treatments).
Very elevated values are present in celiac disease, enteritis, and intestinal resection.

3-hydroxyphenyl-3-hydroxypropionic acid (HPHPA)

Produced by Clostridia species, including but not limited to Clostridium difficile [GP].
Elevated values are common in autism, depression, schizophrenia, seizures, and chronic fatigue syndrome colitis tic disorders muscle weakness or paralysis [Shaw2008] [GP].
Treatment with the antibiotics vancomycin or metronidazole (Flagyl) can significantly lower the HPHPA level in urine [GP]. Addition of probiotics such as Lactobacillus acidophilus GG is also recommended [Shaw2008] (also consider naturopathic treatments).

According to [Shaw2008, page 14], Clostridia spp. deaminate the amino acid phenylalanine (which is the precursor of the important neurotransmitters dopamine, norepinephrine, and epinephrine) to form 3-phenyl-propionic acid, which is then hydroxylated in the meta position by Clostridia spp. to form 3-(3-hydroxyphenyl)-propionic acid [Elsden1976] [Bhala1993]. This intermediate is then subjected to human beta oxidation to form 3-(3-hydroxyphenyl)-3-hydroxy-propionic acid (HPHPA), which is detectable in the urine.

An alternative pathway for formation of HPHPA from phenylalanine is via microbial meta-hydroxylation of phenylalanine to form 3-hydroxyphenylalanine (an analog of tyrosine, which is 4-hydroxyphenylalanine), which is then deaminated to form 3-(3-hydroxyphenyl)-propionic acid, which then proceeds to HPHPA as above [Shaw2008].

Vanillylmandelic Acid (VMA) Analog

Metabolite of the amino acid tyrosine produced by Clostridia species.
Clostridial overgrowth may interfere with the body's production and metabolism of the important neurotransmitters dopamine and norepinephrine, which are made from tyrosine. Elevated values are common in autism, depression, schizophrenia, seizures, and chronic fatigue syndrome.
Treatment with the antibiotics vancomycin or metronidazole (Flagyl) can significantly lower level in urine (also consider naturopathic treatments).

Oxalate Related

Glyceric Acid

Elevated values may be due to microbial sources such as yeast or due to dietary sources containing glycerol (glycerine).
Elevated values may also indicate an inborn error of metaboilism (see oxalaic acid).

Glycolic Acid

Elevated glycolic acid without elevated oxalic acid is most likely a result of GI yeast overgrowth.
Elevated values may also indicate an inborn error of metaboilism (see oxalaic acid).

Oxalic Acid

Elevated values may be due to many causes, including:
- primary hyperoxaluria,
- diabetes mellitus,
- cirrhosis,
- vitamin B-6 deficiency,
- sarcoidosis,
- steatorrhea due to pancreatic insufficiency,
- celiac disease,
- bacteria overgrowth,
- ileal resection,
- biliary tract disease,
- small bowel disease,
- ethylene glycol poisoning,
- increased intake of foods high in oxalate including rhubarb, spinach, raspberries, and peanuts,
- increased vitamin C intake.
If glycolic acid is also elevated, it may indicate the genetic disease hyperoxaluria type I.
If glyceric acid is also elevated, it may indicate the genetic disease hyperoxaluria type II.

Glycolysis Intermediates

Lactic Acid

Elevated values may indicate infection, recent vigorous exercise, B vitamin deficiency, poor perfusion, or intestinal bacterial overgrowth.
Extremely elevated values indicate genetic diseases such as pyruvate dehydrogenase deficiency, glycogen storage diseases, and disorders of fructose metabolism, severe trauma, or life-threatening infections.

Pyruvic Acid

Elevated values may indicate infection, recent vigorous exercise, B vitamin deficiency, poor perfusion, or intestinal bacterial overgrowth.
Extremely elevated values indicate genetic diseases such as pyruvate dehydrogenase deficiency, glycogen storage diseases, and disorders of fructose metabolism, severe trauma, or life-threatening infections.

2-hydroxbutyric Acid

Slightly elevated values may indicate infection, recent vigorous exercise, B vitamin deficiency, or poor perfusion.
Significantly elevated values may indicate genetic diseases such as pyruvate dehydrogenase deficiency, glycogen storage disease, or disorders of fructose metabolism, or be the result of severe trauma or life-threatening infections.

Krebs Cycle Intermediates

Succinic Acid

A Krebs cycle compound that may be elevated due to a deficiency in riboflavin or coenzyme Q10, bacterial conversion of glutamine to succinic acid in the gastrointestinal tract, or inborn error of metabolism.

Fumaric Acid

A Krebs cycle compound produced by the dehydrogenation of succinic acid by the enzyme succinic acid dehydrogenase.

2-oxoglutaric Acid (Alpha-ketoglutaric Acid, AKG)

A Krebs cycle compound.
2-oxoglutaric acid may be derived from the conversion of glutamic acid to 2-oxoglutaric by deamination or transamination.
Very low values may sometimes be encountered in chronic fatigue syndrome.
Anecdotal reports indicate that autistic symptoms sometimes improve with AKG supplementation in response to low values of this metabolite.

Aconitic Acid

A Krebs cycle compound.
May be elevated as a result of a deficiency in glutathione since the enzyme aconitase requires reduced glutathione to metabolize aconitic to citric acid.

Citric Acid

A Krebs cycle compound.
Do not confuse citric acid with ascorbic acid (vitamin C). They are both found in citrus fruit, but are not the same compound.

Amino Acid Metabolites

2-hydroxyisovaleric Acid

Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

2-oxoisovaleric Acid

Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

3-methyloxovaleric Acid

Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

2-hydroxyisocaproic Acid

Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

2-oxoisocaproic Acid

Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

2-oxo-4-methiobutyric Acid

Elevated in the genetic disease methioninemia.

Phenyllactic Acid

Elevated in the genetic diseases PKU and tyrosinemia.
Slight elevations may result from increased dietary intake of phenylalanine.

Phenylpyruvic Acid

Elevated in the genetic diseases PKU and tyrosinemia.
Slight elevations may result from increased dietary intake of phenylalanine.

Mandelic Acid

Elevated in the genetic diseases PKU and tyrosinemia.
Slight elevations may result from increased dietary intake of phenylalanine.

Homogentisic Acid

Elevated in the genetic disease homogentisic aciduria (alkaptonuria).

4-hydroxyphenyllactic Acid

Significantly elevated in the genetic diseases tyrosinemia and in phenylketonuria.
Slight increase may be due to increased tyrosine intake.

3-indoleacetic Acid

A metabolite of the amino acid tryptophan.
Elevated values may be found in Hartnup's disease, a genetic neurological disease due to defective renal and intestinal transport of certain neutral amino acids.
Elevations of lesser magnitude appear to be of bacterial origin.

Neurotransmitter Metabolites

Homovanillic Acid (HVA)

A metabolite of the neurotransmitter dopamine.
Elevated values are encountered in the tumors neuroblastoma, ganglioblastoma, and pheochromacytoma.
Values may also be elevated due to L-DOPA administration or after IV dopamine drips.
Elevated levels may occur with tyrosine or phenylalanine supplements.

Vanillylmandelic Acid (VMA)

Elevated values are found in the tumors pheochromacytoma, neuroblastoma, ganglioneuroma, and carcinoid tumors.
May be elevated after administration of the catecholamine L-DOPA.
Elevated levels may occur with tyrosine or phenylalanine supplements.

5-hydroxyindoleacetic Acid

A metabolite of tryptophan that is commonly elevated in carcinoid syndrome, celiac sprue, tropical sprue, Whipple's disease, oat cell carcinoma of the bronchus, and in bronchial adenoma of carcinoid type.
May be elevated due to intake of foods high in hydroxyindoles such as walnuts, bananas, avocados, eggplants, pineapples, plums and tomatoes.
Low values may be found in depressive illnesses, small intestine resection, mastocytosis, PKU, and Hartnup's disease.

Pyrimidines

Uracil

A pyrimidine (DNA building block) that is elevated in the genetic disease dihydropyrimidine dehydrogenase deficiency. In this genetic disease, the pyrimidine thymine is also elevated.
Elevations of uracil and orotic acid are found in the genetic diseases OTC deficiency and citrullinemia.

Thymine

A pyrimidine (DNA building block) that is elevated in the genetic disease dihydropyrimidine dehydrogenase deficiency. In this genetic disease, the pyrimidine uracil is also elevated.

Fatty Acid Metabolites

3-hydroxybutyric Acid

Ketone derived from excessive fatty acid oxidation.
May be elevated due to fasting or starvation, diabetes mellitus, use of high fat (ketogenic) diets, and in several genetic diseases.

Acetoacetic Acid

Ketone derived from excessive fatty acid oxidation.
may be elevated due to fasting or starvation, diabetes mellitus, use of high fat (ketogenic) diets, and in several genetic diseases.

Ethylmalonic Acid

Fatty acid metabolites.
Value may be elevated in ketosis, fasting, deficiency of the fat-transporting molecule carnitine, genetic deficiencies of fatty acid metabolism and the genetic disease multiple acyl dehydrogenase deficiency, excessive intake of adipic acid-containing foods such as Jell-O, and by increased intake of foods containing medium chain triglycerides such as coconut oil.

Methylsuccinic Acid

Fatty acid metabolites.
Value may be elevated in ketosis, fasting, deficiency of the fat-transporting molecule carnitine, genetic deficiencies of fatty acid metabolism and the genetic disease multiple acyl dehydrogenase deficiency, excessive intake of adipic acid-containing foods such as Jell-O, and by increased intake of foods containing medium chain triglycerides such as coconut oil.

Adipic Acid

Fatty acid metabolites.
Value may be elevated in ketosis, fasting, deficiency of the fat-transporting molecule carnitine, genetic deficiencies of fatty acid metabolism and the genetic disease multiple acyl dehydrogenase deficiency, excessive intake of adipic acid-containing foods such as Jell-O, and by increased intake of foods containing medium chain triglycerides such as coconut oil.
Isolated high values of adipic acid only may be found in patients with ADD, lethargy and seizures.

Suberic Acid

Fatty acid metabolites.
Value may be elevated in ketosis, fasting, deficiency of the fat-transporting molecule carnitine, genetic deficiencies of fatty acid metabolism and the genetic disease multiple acyl dehydrogenase deficiency, excessive intake of adipic acid-containing foods such as Jell-O, and by increased intake of foods containing medium chain triglycerides such as coconut oil.

Sebacic Acid

Fatty acid metabolites.
Value may be elevated in ketosis, fasting, deficiency of the fat-transporting molecule carnitine, genetic deficiencies of fatty acid metabolism and the genetic disease multiple acyl dehydrogenase deficiency, excessive intake of adipic acid-containing foods such as Jell-O, and by increased intake of foods containing medium chain triglycerides such as coconut oil.

Toxic Indicators

Pyroglutamic Acid (Oxoproline)

A metabolite of the antioxidant gluthathione and is extremely elevated in the genetic disease pyroglutamic acidurea and following the use of the antibiotics flucloxacillin and netelmicin.
Low values may be found due to glutathione depletion following oxidative stress or after exposure to toxic solvents or pesticides such as chloroform, DDT, or polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs).

Orotic Acid

Elevated level suggests urea cycle defect.
Elevated levels are most commonly associated with ammonia toxicity. When ammonia is elevated, it is biochemically converted to carbamyl phosphate and then orotic acid. Elevated ammonia may occur due to liver toxicity, viral liver infection, GI bleeding, portal systemic shunting of blood, drug toxicity, Reye's syndrome, as well as inborn errors of ammonia metabolism.
Elevated orotic acid may also be found in leukemias and lymphomas, possibly due to the increased production of pyrimidines.

Hydroxyhippuric Acid (hydroxy-benzoylglycine)

A conjugate of the amino acid glycine and hydroxybenzoic acid (salicylic acid).
Elevated values may be due to the use of aspirin (salicylates) or due to the growth of GI bacteria producing salicylates [GP].
Also increased after the ingestion of the artificial sweetener aspartame (Nutrasweet) [GP].

According to [Shaw2008, page 14], HPHPA, which is a metabolite derived from Clostridium spp. metabolism, can undergo further human beta-oxidation to form 3-hydroxy-benzoic acid, which is then conjugated with glycine in the liver's phase-2 detoxification step to produce 3-hydroxy-benzoylglycine, also known as 3-hydroxyhippuric acid.

Vitamin Indicators and Metabolites

Methylmalonic Acid

Elevated values may be due to the genetic disease methylmalonic aciduria.
Moderate increases may be due to vitamin B-12 deficiency, defective B-12 absorption, or bacterial overgrowth of the GI tract that uses up vitamin B-12.

Ascorbic Acid (Vitamin C)

An important antioxidant.
Low values may indicate dietary deficiency (scurvy).
Frequently low in chronic fatigue syndrome.
High values are usually of no concern except that in individuals with bacteria overgrowth of the GI tract, ascorbic acid may be converted to oxalic acid, which can lead to kidney stones. There is a low probability that elevated vitamin C will cause kidney stones if oxalic acid is in the normal range.

Kynurenic Acid

A tryptophan metabolite that may be elevated with vitamin B-6 deficiency or due to excessive tryptophan uptake.
The reaction by which kynurenine is converted to hydroxyanthranilate is catalyzed by an enzyme requiring vitamin B-6. Thus, elevations of kynurenic acid may indicate a vitamin B-6 deficiency.
High values in individuals with the yeast overgrowth syndrome may be due to yeast interference.

Methylcitric Acid

High levels indicate biotin deficiency and/or an inborn error of metabolism affecting biotin pathways.
Low values of methylcitric acid have no known significance.

Pyridoxic Acid

The main urinary metabolite of pyridoxine (Vitamin B6) and is a measure of recent dietary intake.
Low values of pyridoxic acid in the urine indicate low recent intake while high values indicate high recent dietary intake.

Pantothenic Acid (Vitamin B5)

Urinary excretion reflects dietary intake.
High values are not necessarily undesirable.
Individuals may have a much higher than usual requirement for this cofactor.

Miscellaneous Organic Acids

Glutaric Acid

Elevated in the genetic diseases glutaric academia types I and II.
Moderate increases may be due to deficiencies in riboflavin and coenzyme Q10,
or celiac disease.
Moderate increases are common in autism possibly due to defective vitamin absorption or microbial production in the GI tract.

N-acetyl Aspartic Acid

High values are due to the genetic disease Carnavan's disease, a potentially fatal disease causing spongy degeneration of the brain.

3-hydroxy-3-methylglutaric (HMG) Acid

A precursor in the production of cholesterol in both humans and yeast.
Moderate increases are probably due to yeast overgrowth of the GI tract and might also implicate yeast overgrowth with elevated serum cholesterol.
Both yeast and humans produce these same compounds as a precursor of steroid hormones.
Elevated values are found in the genetic disease 3-hydroxy-3-metylglutaric aciduria.

Malonic Acid

Elevated values may be associated with the genetic disease malonyl CoA decarboxylase deficiency.

Methylglutaric Acid

Elevated values may be associated with the genetic diseases 3-hydroxy-3-methylglutaric aciduria and in 3-methylglutaconic aciduria.

Hippuric Acid

A conjugate of benzoic acid and glycine formed in the liver as part of the normal phase-II detoxification pathway.
May be elevated due to bacteria overgrowth of the GI tract producing benzoic acid which is absorbed into the portal circulation.
Other sources that increase benzoic acid are the environmental toxin toluene and the food preservative sodium benzoate.
Low values of hippuric acid may be due to depletion of glycine due to competing detoxification reactions or due to low amounts of bacteria after antibiotic use.

4-hydroxybutyric Acid

Elevated values may indicate the rare genetic disease 3-methylglutaconic aciduria.
Elevated values may also indicate excessive intake of the muscle builder 4-hydroxybutyric acid (also called gamma-hydroxybutyric acid), which can cause severe myalgia or death.

Phenylcarboxylic Acid

Elevated values indicate overgrowth of GI bacteria.

Indole-like Compound Acids

Most likely derived from tryptophan.
Elevated values indicate overgrowth of GI bacteria and are commonly elevated along with 3-indoleacetic acid.

References
Unless specifically noted above, references used in the construction of this web page include the following:
[FDM] Lecture notes from Functional Medicine University.
[SCNM] Lecture notes from Southwest College of Naturopathic Medicine.
[UT] Lecture notes from the University of Tennessee graduate programs in Chemistry and Biochemistry.
[Shaw2008] Shaw W. Biological Treatments for Autism & PDD, Third Edition. (2008).
[GP] Great Plains Laboratory Physician Training lecture notes and documentation.
[Shaw2005] Shaw W, Kassen E, Chaves E. Increased urinary excretion of analogs of Krebs cycle metabolites and arabinose in two brothers with autistic features. Clin Chem. 2005 Mar;51(3):672-3.
[Elsden1976] Elsden SR, Hilton MG, Waller JM. The end products of the metabolism of aromatic amino acids by Clostridia. Arch Microbiol. 1976 Apr 1;107(3):283-8.
[Bhala1993] Bhala A, Bennett MJ, McGowan KL, Hale DE. Limitations of 3-phenylpropionylglycine in early screening for medium-chain acyl-coenzyme A dehydrogenase deficiency. J Pediatr. 1993 Jan;122(1):100-3.
[Robertson1968] Robertson B, Lonnell L. Human tartrate nephropathy. Report of a fatal case. Acta Pathol Microbiol Scand. 1968;74(3):305-10.
[Kiehn1979] Kiehn TE, Bernard EM, Gold JW, Armstrong D. Candidiasis: detection by gas-liquid chromatography of D-arabinitol, a fungal metabolite, in human serum. Science. 1979 Nov 2;206(4418):577-80.
[Wong1990] Wong B, Brauer KL, Clemens JR, Beggs S. Effects of gastrointestinal candidiasis, antibiotics, dietary arabinitol, and cortisone acetate on levels of the Candida metabolite D-arabinitol in rat serum and urine. Infect Immun. 1990 Feb;58(2):283-8.
[Larsson1994] Larsson L. Determination of microbial chemical markers by gas chromatography-mass spectrometry--potential for diagnosis and studies on metabolism in situ. Review article. APMIS. 1994 Mar;102(3):161-9. Review.
[Roboz1992] Roboz J, Katz RN. Diagnosis of disseminated candidiasis based on serum D/L-arabinitol ratios using negative chemical ionization mass spectrometry. J Chromatogr. 1992 Mar 27;575(2):281-6.

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