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

Sample Collection

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

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

Labs Performing Test

Name of LabLab CodeEstimated CostProcessing TimeComments
Great Plains  $2402-3 weeksCash 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

Elevated yeast/fungal metabolites suggest a yeast or fungal overgrowth in the gastrointestial tract [GP].

Citramalic (Methylmalic) Acid

5-hydroxymethyl-2-furoic Acid

3-oxoglutaric Acid

Furan-2,5-dicarboxylic Acid

Furancarbonylglycine

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

Arabinose

Carboxycitric Acid

Bacterial Metabolites

4-hydroxybenzoic Acid and 4-hydroxyhippuric Acid

2-hydroxyphenylacetic Acid

4-hydroxyphenylacetic Acid

3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA)

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

Oxalate Related

Glyceric Acid

Glycolic Acid

Oxalic Acid (Oxalate)

Glycolysis Intermediates

Lactic Acid (Lactate)

Pyruvic Acid (Pyruvate)

2-hydroxybutyric Acid

Krebs Cycle Intermediates

Succinic Acid (Succinate)

Fumaric Acid (Fumarate)

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

Aconitic Acid

Citric Acid (Citrate)

Amino Acid Metabolites

2-hydroxyisovaleric Acid

2-oxoisovaleric Acid

3-methyl-2-oxovaleric Acid

2-hydroxyisocaproic Acid

2-oxoisocaproic Acid

2-oxo-4-methiobutyric Acid

Phenyllactic Acid

Phenylpyruvic Acid

Mandelic Acid

Homogentisic Acid

4-hydroxyphenyllactic Acid

3-indoleacetic Acid

Neurotransmitter Metabolites

Homovanillic Acid (HVA) and Vanillylmandelic Acid (VMA)

5-hydroxyindoleacetic Acid

Pyrimidines

Uracil

Thymine

Fatty Acid Metabolites

3-hydroxybutyric Acid

Acetoacetic Acid

Ethylmalonic Acid

Methylsuccinic Acid

Adipic Acid (Adipate)

Suberic Acid (Suberate)

Ethylmalonic Acid (Ethylmalonate)

Sebacic Acid

Toxic Indicators

Pyroglutamic Acid (Oxoproline)

Orotic Acid

Hydroxyhippuric Acid (hydroxy-benzoylglycine)

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 (Ethylmalonate)

  • Elevated values may be due to the genetic disease methylmalonic aciduria [GP].
  • 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 [GP].

Ascorbic Acid (Vitamin C)

  • An important antioxidant.
  • Low values may indicate dietary deficiency (scurvy).
  • Frequently low in chronic fatigue syndrome.
  • High values are usually due to dietary intake and are 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. Treatment includes Lactobacillus rhamnosus [GP2010].
  • Other sources that increase benzoic acid are the environmental toxin toluene and the food preservative sodium benzoate, as well as foods such as apples, pears, tea, coffee, sunflower seeds, carrots, blueberries, cherries, potatos, tomatoes, eggplant, sweet potatos, peaches [GP2010].
  • 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.

[GP2010]Great Plains Lab Report, 2010.

[Metametrix] Metametrix Handbook: Clinical Reference Manual, 2nd Edition. (2010).

[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.

[Routledge1998] Routledge et al. Toxicol. Appl. Pharmacol. 153, 12-19 (1998). Cited by [GP2010].


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