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Organic Acid Test (OAT): Amino Acid Metabolites

Written by Biljana Novkovic, PhD | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Biljana Novkovic, PhD | Last updated:

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Organic acid test (OAT) has gained popularity among many functional and alternative health experts in recent years. However, does testing amino acid metabolites, found in OAT, actually make sense? Or is it a hoax? Read on to find out.

What is the Organic Acid Test?

Organic Acid Test, popularly known as OAT, measures the levels of organic compounds in urine that are produced in the body as a part of many vital biochemical pathways. It’s used to check for RARE inborn genetic defects of metabolism, most often in newborns.

A defect in a particular pathway can result in either accumulation or lowered levels of its byproducts. Thus, measuring the levels of these markers can help to identify which metabolic process is blocked or compromised.

However, OAT has been increasingly available as a pricy, direct-to-consumer test recommended by many alternative practitioners. In this article, we will break down the science behind testing amino acid metabolites, which are tested as a part of OAT, to find out if testing them has merit.

Amino Acid Metabolites

Low levels of amino acid metabolites are good. Higher levels mean there is impaired enzyme activity, most often due to genetic causes.

1) Keto and Hydroxy Derivatives of Amino Acids

Various markers can be included in this category, such as:

  • 2-hydroxyisovaleric acid (2-HIV)
  • 2-hydroxyisocaproic acid (2-HICA)
  • 2-oxoisovaleric acid (alpha-ketoisovalerate)
  • 2-oxoisocaproic acid (alpha-ketoisocaproate)
  • 3-methyl-2-oxovaleric acid (2-Keto-3-methylvaleric acid or alpha-keto-beta-methylvalerate)

All of them are metabolites of branched-chain amino acids (BCAA) leucine, isoleucine, and valine [1].

These can increase keto and hydroxy metabolites of amino acids:

  • Protein meals; habitual intake of lots of red and processed meat and eggs, and BCAA supplements [2, 3]
  • Exercise (short-term) (2-HIV) [4]
  • Prolonged fasting [3]
  • Alcoholism (2-HIV) [5]
  • Disturbances in blood pH (lactic acidosis, ketoacidosis) [6, 6, 7]
  • Primary biliary cirrhosis, an autoimmune liver disease [8]
  • Bacterial dysbiosis in short bowel syndrome (2-HICA) [9, 10]
  • Peroxisomal diseases, such as Zellweger syndrome (due to bacterial dysbiosis) (2-HICA) [11]
  • Rare inborn metabolic disorders such as maple syrup urine disease and dihydrolipoyl dehydrogenase deficiency [12, 13, 14, 15, 16, 17, 18]

People who can’t process branched-chain amino acids (BCAAs) are usually put on a low protein diet supplemented with a mixture of micronutrients and all essential amino acids except BCAAs [16].

Studies suggest that some supplements may help in these metabolic disorders, including:

  • Thiamine (vitamin B1) supplementation (in some forms of maple syrup disease) [19]
  • L-carnitine supplementation to remove toxins by conjugation [16, 1]

Remember, always speak to your doctor before taking any supplements, because they may interfere with your health condition or your treatment/medications!

Proponents of OAT testing state that these metabolites can be used to access deficiencies in vitamin B1 (thiamin) and lipoic acid. We couldn’t find any proof that this holds true in people who don’t have inborn metabolic disorders. If your doctor thinks you may have vitamin B1 deficiency, they will test for it directly.

Keto and hydroxy metabolites of amino acids are mainly used to help diagnose inborn metabolic disorders such as maple syrup disease. Some of them can also be elevated in other conditions.

2) 2-Oxo-4-Methylthiobutyric Acid

2-oxo-4-methylthiobutyric acid (also 2-keto-4-methylthiobutanoate or 4-methylthio-2-oxobutyrate) is elevated in several inborn metabolic disorders involving methionine metabolism [20].

If levels are elevated, doctors will run further tests to find out what’s going on.

2-oxo-4-methylthiobutyric acid increases in inborn disorders in the metabolism of the amino acid methionine.

3) Phenyllactic acid / Phenylpyruvic Acid

These are metabolites of the amino acid phenylalanine.

Levels of phenyllactic acid and phenylpyruvic acid are normally very low in blood or urine. They get elevated in phenylketonuria, a genetic disorder. Untreated, this disorder can impair brain function, leading to cognitive impairment, seizures, behavioral and mental disorders [21].

People who are carriers of the disease, but don’t have it themselves, will also have somewhat elevated levels [21].

Finally, people who consume higher amounts of phenylalanine in the diet may have slightly elevated levels. Phenylalanine is found in many protein-rich foods, such as milk, eggs, and meat. It can also be used as a supplement. In addition, the artificial sweetener aspartame contains phenylalanine.

Phenyllactic and phenylpyruvic acid are used to screen for phenylketonuria, an inborn metabolic disorder.

4) Mandelic Acid

High levels can be observed due to:

  • Increased dietary intake of phenylalanine (found in aspartame) or supplementing with phenylethylamine (PEA) [22]
  • Occupational styrene exposure [23, 24]. This acid is an intermediate chemical that is widely used in the synthetic rubber and plastic industries. Its urine levels reflect exposure to styrene and related toxic chemicals.
  • An inborn genetic disorder called phenylketonuria [25]

In a study of over 5,000 men, higher urinary mandelic acid levels were associated with lower testosterone [26].

Mandelic acid is used to screen for phenylketonuria, an inborn metabolic disorder. However, it can also be used to check exposure to styrene, a chemical used in rubber and plastic industries.

5) Homogentisic Acid

Homogentisic acid increases in a genetic disorder called alkaptonuria, in which the body can’t process amino acids phenylalanine and tyrosine. Urine that has significant levels of homogentisic acid darkens after air exposure [27, 28].

Homogentisic acid is used to test for a genetic disorder called alkaptonuria.

6) 4-Hydroxyphenyllactic Acid

4-hydroxyphenyllactic acid is a breakdown product of the amino acid tyrosine.

Levels can be elevated due to:

  • Bacterial overgrowth [29, 10, 9]
  • Liver disease or damage [30, 31]
  • Severe malaria [32, 33]
  • Rare metabolic disorders phenylketonuria, tyrosinemia, and Zellweger syndrome [10, 34, 35, 36, 37, 38]

Slightly elevated levels may be caused by increased consumption of tyrosine-rich foods.

This test is mainly used to help diagnose rare inherited metabolic disorders.

4-hydroxyphenyllactic acid is mainly used to help diagnose rare genetic metabolic disorders, but can also be slightly elevated in some other conditions or due to intake of tyrosine-rich foods.

7) N-Acetylaspartic Acid

N-acetylaspartic acid, also known as N-acetylaspartate, is the second most abundant amino acid in the human brain. It is essential for brain function and decreases in Alzheimer’s, Huntington’s, multiple sclerosis, and substance abuse disorder [39, 40].

Urine levels of N-acetylaspartic acid are generally very low, and increase in:

  • Human papillomavirus infection [41]
  • Gestational diabetes [42]
  • Amyotrophic lateral sclerosis, a disease that causes nerve damage [43]
  • Some types of cancer [44]
  • Canavan disease, a rare metabolic disorder that causes a buildup of N-acetylaspartic acid in the brain [45, 46, 47, 48]

There is probably little benefit for testing this metabolite except to screen for Canavan disease.

N-acetylaspartic acid is mainly used to help diagnose a genetic disorder called Canavan disease, but can also be slightly elevated in some other conditions.

8) Malonic Acid

Malonic acid is an intermediate compound in the breakdown of fatty acids. It accumulates in the case of rare inborn metabolic disorders [49, 50, 51, 52, 53].

Other than checking for inborn (genetic) metabolic disorders, this test has no other known use.

Malonic acid is used to help diagnose genetic disorders.

Takeaway

Amino acid metabolites are used to help diagnose rare genetic disorders, and don’t really seem to have a purpose beyond that.

Unless you and your doctor suspect a rare metabolic disorder based on your signs, symptoms, medical history, and other test results, testing amino acid metabolites provides no clear benefit.

Further Reading

To find out which parts of the OAT test can be useful, and which are nonsense, we delve into the science and look into each of the marker types in isolation:

About the Author

Biljana Novkovic

Biljana Novkovic

PhD
Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science and health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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