Organic Acids Test (The Great Plains Laboratory)

Organic acids are chemical compounds excreted in the urine of mammals that are products of metabolism. Metabolism is the sum of chemical reactions in living beings by which the body builds new molecules and breaks down molecules to eliminate waste products and produce energy. Organic acids are organic compounds that are acidic. Organic acids are substances in which carbon and hydrogen are always present but may also contain the elements of oxygen, nitrogen, sulfur, and phosphorus.

The Organic Acids Test offers a comprehensive metabolic snapshot of a patient’s overall health with 75 markers. It provides an accurate evaluation of intestinal yeast and bacteria. Abnormally high levels of these microorganisms can cause or worsen behavior disorders, hyperactivity, movement disorders, fatigue, and immune function. Many people with chronic illnesses and neurological disorders often excrete several abnormal organic acids in their urine. The cause of these high levels could include oral antibiotic use, high sugar diets, immune deficiencies, acquired infections, and genetic factors.

2-Hydroxybutyric

Optimal range: 0.03 - 1.8 mmol/mol creatinine

What is 2-Hydroxybutyric acid?

2-Hydroxybutyric acid (aka α-Hydroxybutyrate) is a by-product of glutathione production. Levels of 2-Hydroxybutyric acid in the urine may reflect levels of glutathione production.

What is Glutathione?

Glutathione is an important antioxidant that can prevent damage to cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals.

Glutathione is constantly being used up in the removal of toxic molecules and prevention of oxidative damage.

2-Hydroxybutyric acid is a by-product from the process in which the body forms more glutathione. When that process is running at high rates, α-hydroxybutyrate excretion is increased.

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2-Hydroxyhippuric

Optimal range: 0 - 1.3 mmol/mol creatinine

2-Hydroxyhippuric acid is a conjugate of hydroxybenzoic acid (salicylic acid) and glycine.

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2-Hydroxyisocaproic

Optimal range: 0 - 2 mmol/mol creatinine

2-Hydroxyisocaproic acid (aka Leucic acid / α-hydroxyisocaproic acid / HICA) is a metabolite of the branched-chain amino acid leucine.

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2-Hydroxyisovaleric

Optimal range: 0 - 0.42 mmol/mol creatinine

2-Hydroxyisovaleric acid (aka 2-Hydroxy-3-methylbutyric acid) is a branched-chain amino acid metabolite.

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2-Hydroxyphenylacetic

Optimal range: 0.06 - 0.66 mmol/mol creatinine

The metabolite of phenylalanine via phenyl pyruvate.

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2-Oxo-4-methiolbutyric

Optimal range: 0 - 2 mmol/mol creatinine

2-Oxo-4-methylthiobutanoic acid, also known as 4-(methylsulfanyl)-2-oxobutanoate or 2-keto-4-methylthiobutyrate, belongs to the class of organic compounds known as thia fatty acids. Thia substituted fatty acids are saturated fatty acids which are modified by insertion of a sulfur atom at specific positions in the carbon backbone.

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2-Oxoglutaric

Optimal range: 0 - 35 mmol/mol creatinine

2-Oxoglutaric acid is an organic acid that is important for the proper metabolism of all essential amino acids. It is formed in the Krebs cycle, the energy-producing process that occurs in most body cells.

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2-Oxoisocaproic

Optimal range: 0 - 2 mmol/mol creatinine

2-Oxoisocaproic acid (also known as Ketoleucine) is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids.

2-Oxoisocaproic acid is both a neurotoxin and a metabotoxin.

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2-Oxoisovaleric

Optimal range: 0 - 2.1 mmol/mol creatinine

2-Oxoisovaleric acid is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids (=BCAA). 2-Oxoisovaleric acid is a neurotoxin, an acidogen, and a metabotoxin. 

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3-Hydroxy-3-methylglutaric (HMG)

Optimal range: 0.17 - 39 mmol/mol creatinine

- A precursor in the production of cholesterol in both humans and yeast.

- Elevated levels may also indicate decreased CoQ10 synthesis.

- Moderate increases are probably due to yeast overgrowth of the GI tract and might also implicate yeast overgrowth with elevated serum cholesterol.

- Very elevated levels may be due to HMG aciduria (=3-hydroxy-3-metylglutaric aciduria)

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3-Hydroxybutyric

Optimal range: 0 - 3.1 mmol/mol creatinine

3-Hydroxybutyric acid is a typical partial-degradation product of branched-chain amino acids (primarily valine) released from muscle for hepatic and renal gluconeogenesis. This acid is metabolized by 3-hydroxybutyrate dehydrogenase. The enzyme functions in nervous tissues and muscles, enabling the use of circulating hydroxybutyrate as a fuel.

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3-Hydroxyglutaric

Optimal range: 0 - 6.2 mmol/mol creatinine

3-Hydroxyglutaric is a marker for glutaryl CoA dehydrogenase deficiency.

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3-Indoleacetic

Optimal range: 0 - 11 mmol/mol creatinine

3-Indoleacetic is a Tryptophan byproduct of Clostria: C. stricklandii, C. litusburense, C. subterminale, and C. putrefaciens.

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3-Methyl-2-oxovaleric

Optimal range: 0 - 2 mmol/mol creatinine

3-Methyl-2-oxovaleric acid is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids. 

Moderate increase may result from lactic acidosis, episodic ketosis, or thiamine/lipoic acid deficiency. Significant elevations are associated with genetic issues, MSUD, and pyruvate dehydrogenase deficiency.

- 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.

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3-Methylglutaconic

Optimal range: 0 - 4.5 mmol/mol creatinine

The marker, 3-methylglutaconic acid in high values indicates a reduced ability to metabolize the amino acid, leucine. This abnormality is found in the genetic disease, methylglutaconic aciduria and in mitochondrial disorders.

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3-Methylglutaric

Optimal range: 0 - 0.76 mmol/mol creatinine

3-methylglutaric acid is an organic acid classically associated with two distinct leucine pathway enzyme deficiencies.

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3-Oxoglutaric

Optimal range: 0 - 0.33 mmol/mol creatinine

3-Oxoglutaric indicates yeast overgrowth in the gastrointestinal tract. 

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4-Cresol

Optimal range: 0 - 75 mmol/mol creatinine

4-Cresol has been used as a specific marker for Clostridium difficile.

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4-Hydroxybenzoic

Optimal range: 0 - 1.3 mmol/mol creatinine

4-Hydroxybenzoic Acid is a marker for intestinal dysbiosis.

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4-Hydroxybutyric

Optimal range: 0 - 4.8 mmol/mol creatinine

A moderate urinary increase in 4-hydroxybutyric acid may be due to intake of dietary supplements containing 4-hydroxybutyric acid, also known as gamma-hydroxybutyric acid. Very high levels may indicate the genetic disorder 3-methylglutaconic aciduria involving succinic semialdehyde dehydrogenase deficiency.

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4-Hydroxyhippuric

Optimal range: 0.79 - 17 mmol/mol creatinine

4-Hydroxyhippuric is a glycine conjugate of 4-hydroxybenzoic acid, the paraben metabolite.

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4-Hydroxyphenylacetic

Optimal range: 0 - 19 mmol/mol creatinine

A tyrosine metabolic product of GI bacteria.

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4-Hydroxyphenyllactic

Optimal range: 0 - 2 mmol/mol creatinine

4-hydroxyphenyllactate is present in relatively higher concentrations in the cerebrospinal fluid and urine of patients with phenylketonuria (PKU) and tyrosinemia.

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5-Hydroxyindoleacetic (5-HIAA)

Optimal range: 0 - 4.3 mmol/mol creatinine

5-Hydroxyindoleacetic acid (5HIAA) is a breakdown product of serotonin that is excreted in the urine. Serotonin is a hormone found at high levels in many body tissues. Serotonin and 5HIAA are produced in excess amounts by carcinoid tumors, and levels of these substances may be measured in the urine to test for carcinoid tumors.

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5-Hydroxymethyl-2-furoic

Optimal range: 0 - 14 mmol/mol creatinine

A metabolite produced by Aspergillus and possibly other fungal species in the GI tract.

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Acetoacetic

Optimal range: 0 - 10 mmol/mol creatinine

Acetoacetic acid (=acetoacetate) is a ketone body and a weak Beta-keto acid produced from acetyl-CoA in the mitochondrial matrix of hepatocytes.

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Aconitic

Optimal range: 6.8 - 28 mmol/mol creatinine

Elevated in mitochrondrial disorders. Aconitase metabolizes citric and aconitic acids, and is dependent on glutathione.

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Adipic

Optimal range: 0.04 - 3.8 mmol/mol creatinine

Adipic Acid, together with Suberate and Ethylmalonate are all functional markers for deficiency of carnitine.

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Arabinose

Optimal range: 0 - 29 mmol/mol creatinine

Breakdown product of hyaluronic acid; also found in certain foods.

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Ascorbic

Optimal range: 10 - 200 mmol/mol creatinine

Ascorbic Acid is a natural water-soluble vitamin (Vitamin C). Ascorbic acid is a potent reducing and antioxidant agent that functions in fighting bacterial infections, in detoxifying reactions, and in the formation of collagen in fibrous tissue, teeth, bones, connective tissue, skin, and capillaries.

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Carboxycitric

Optimal range: 0 - 29 mmol/mol creatinine

Carboxycitric is a metabolite of yeast/fungi and general indicator of gastrointestinal dysbiosis. Elevated yeast/fungal metabolites indicate overgrowth in the GI tract.

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Citramalic

Optimal range: 0 - 3.6 mmol/mol creatinine

Metabolite of yeast or anaerobic bacteria, including Clostridia.

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Citric

Optimal range: 0 - 507 mmol/mol creatinine

Citric acid, cis-aconitic acid, and isocitric acid are the first three metabolites in the Krebs Citric Acid energy production cycle, which operates in the mitochondria of your cells. 

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DHPPA (Beneficial Bacteria)

Optimal range: 0 - 0.38 mmol/mol creatinine

Produced when Clostridia acts upon unabsorbed tryptophan, tyrosine or phenylalanine.

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Dihydroxyphenylacetic (DOPAC)

Optimal range: 0 - 3.5 mmol/mol creatinine

HVA and DOPAC are the major metabolites of dopamine.

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Ethylmalonic

Optimal range: 0.44 - 2.8 mmol/mol creatinine

Ethylmalonate, together with Adipate and Suberate, gives information about your ability to process fatty acids.

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Fumaric

Optimal range: 0 - 0.94 mmol/mol creatinine

Fumarate (together with Succinate and Malate) is used in the body’s metabolic pathway that generates cellular energy – the Citric Acid Cycle.

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Furan-2,5-dicarboxylic

Optimal range: 0 - 16 mmol/mol creatinine

Furan 2,5-dicarboxylic is a byproduct of Aspergillus and other fungal species.

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Furancarbonylglycine

Optimal range: 0 - 1.9 mmol/mol creatinine

Furancarbonylglycine is a metabolite produced by Aspergillus and possibly other fungal species in the GI tract.

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Glutaric

Optimal range: 0.04 - 0.36 mmol/mol creatinine

Glutaric acid is made from lysine & tryptophan via alphaketo-adipic 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.

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Glyceric

Optimal range: 0.77 - 7 mmol/mol creatinine

Normal values rule out genetic causes of significantly elevated urinary oxalic acid.

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Glycolic

Optimal range: 16 - 117 mmol/mol creatinine

Indicator of genetic disease of oxalate metabolism called Hyperoxaluria type I due to a deficiency in the enzyme activity of alanine glyoxylate amino transferase (AGT).

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Hippuric

Optimal range: 0 - 613 mmol/mol creatinine

Hippuric acid is a conjugate (=a compound formed by the joining of two or more compounds) of glycine and benzoic acid formed in the liver.

Most hippuric acid in urine is derived from microbial breakdown of chlorogenic acid to benzoic acid.

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Homogentisic

Optimal range: 0 - 2 mmol/mol creatinine

Homogentisic acid is a breakdown product of 4-Hydroxyphenylpyruvic Acid (4-HPPA). 

Elevated in the genetic disease homogentisic aciduria (alkaptonuria).

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Homovanillic (HVA)

Optimal range: 0.8 - 3.6 mmol/mol creatinine

Homovanillate (aka Homovanillic Acid) is a dopamine metabolite.

Homovanillate and Vanilmandelate are breakdown products from neurotransmitters involved in hormone and nerve impulse transmission, called catecholamines.

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HPHPA

Optimal range: 0 - 208 mmol/g creatinine

HPHPA is a clostridia metabolite and dysbiosis marker and stands for 3-(3-hydroxyphenyl)-3-hydroxypropionic acid.

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HVA / VMA Ratio

Optimal range: 0.16 - 1.8 Ratio

The Organic Acids Test measures levels of HVA (homovanillic acid) and VMA (vanillylmandelic acid), the metabolites of the neurotransmitters, dopamine and epinephrine/norepinephrine. It also measures the ratio of the two metabolites.

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HVA/ DOPAC Ratio

Optimal range: 0.17 - 1.6 mmol/mol creatinine

HVA and DOPAC are the major metabolites of dopamine. HVA stands for Homovanillic acid and DOPAC stands for Dihydroxyphenylacetic.

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Kynurenic

Optimal range: 0 - 2.2 mmol/mol creatinine

Kynurenic Acid is product of the metabolism of L-Tryptophan and appears in urine in Vitamin B6 deficiencies. Your body needs vitamin B6 (pyridoxine) to utilize amino acids derived from dietary protein.

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Lactic

Optimal range: 0 - 48 mmol/mol creatinine

Formed from pyruvate in anaerobic or oxygen-starved (hypoxic) conditions to allow for ongoing production of ATP.

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Malic

Optimal range: 0.06 - 1.8 mmol/mol creatinine

Malic Acid is involved in the citric acid cycle (aka. Krebs cycle). The citric acid cycle is a series of reactions that occur in the mitochondrion to generate chemical energy that fuels the metabolism.

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Malonic

Optimal range: 0 - 9.7 mmol/mol creatinine

Malonic acid is found to be associated with malonyl-CoA decarboxylase deficiency, which is an inborn error of metabolism. The name “Malonic” originates from Latin malum, meaning apple. Malonic acid is the archetypal example of a competitive inhibitor: it acts against succinate dehydrogenase (complex II) in the respiratory electron transport chain. 

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Mandelic

Optimal range: 0 - 2 mmol/mol creatinine

Mandelic acid is the major metabolite of styrene. Styrene (vinylbenzene) is used as an intermediate in plastic synthesis. Values less than 5 mg/L are due to normal metabolism of phenylalanine or tyrosine.

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Methylcitric

Optimal range: 0.19 - 2.7 mmol/mol creatinine

Methylcitric is an organic acids that reflects decreased activity of the biotin-dependent enzyme propionyl-CoA carboxylase.

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Methylmalonic

Optimal range: 0 - 2.3 mmol/mol creatinine

Methylmalonic acid (MMA) is a substance produced in very small amounts and is necessary for human metabolism and energy production.

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Methylsuccinic

Optimal range: 0.1 - 2.2 mmol/mol creatinine

Methylsuccinic acid is a normal metabolite found in human fluids and is an intermediate metabolite in the breakdown of fatty acids.

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N-Acetylaspartic

Optimal range: 0 - 38 mmol/mol creatinine

Elevated N-acetylaspartic acid is due to the genetic disorder Carnavan’s disease, a potentially fatal disease causing spongy degeneration of the brain. 

What is Carnavan’s disease?

Canavan disease is a rare inherited disorder that damages the ability of nerve cells (neurons) in the brain to send and receive messages. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies disrupt the growth or maintenance of the myelin sheath, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses.

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N-Acetylcysteine (NAC)

Optimal range: 0 - 0.28 mmol/mol creatinine

N-Acetylcysteine (NAC) is a powerful antioxidant that increases the glutathione reserves in the body. 

Together with glutathione, N-Acetylcysteine (NAC) directly binds to toxic metabolites. Although N-Acetylcysteine (NAC) may be beneficial under certain conditions, excessive use of the supplement could be harmful.

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Orotic

Optimal range: 0.06 - 0.54 mmol/mol creatinine

Orotic Acid is a sensitive marker of your liver’s capacity to convert toxic ammonia to non-toxic urea that you can excrete. That capacity can be increased by additional arginine. Ammonia toxicity can also be reduced by supplementation with α-ketoglutarate, magnesium, aspartic acid, and glutamic acid. Ammonia impairs brain function, causing difficulty with thinking, fatigue, headaches, and increased food sensitivities.

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Oxalic

Optimal range: 6.8 - 101 mmol/mol creatinine

Oxalic acid may be associated with dysbiosis from Aspergillus, Penicillium, Candida, or high dose vitamin C. If yeast or fungal markers are elevated, antifungal therapy may reduces oxalates. Also associated with anti-freeze (ethylene glycol) poisoning.

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Pantothenic (B5)

Optimal range: 0 - 10 mmol/mol creatinine

Pantothenic acid is an essential B vitamin (=Vitamin B5) that is converted to coenzyme A (unrelated to vitamin A). Coenzyme A is needed for the synthesis of fatty acids, cholesterol, and acetyl choline and is also needed for the Krebs cycle and fatty acid catabolism.

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Phenyllactic

Optimal range: 0 - 2 mmol/mol creatinine

Phenyllactic acid is a metabolite of phenylalanine.

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Phenylpyruvic

Optimal range: 0 - 2 mmol/mol creatinine

Phenylpyruvic acid is a keto-acid that is an intermediate or catabolic byproduct of phenylalanine metabolism. It has a slight honey-like odor. 

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Phosphoric

Optimal range: 1000 - 5000 mmol/mol creatinine

Phosphoric acid is a marker of vitamin D and calcium. This marker indicates whether vitamin D receptors are activated. If phosphoric acid is low, then the person is likely vitamin D and/or calcium deficient. Low levels can be due to low phosphate consumption, low digestive juice production, or deficiencies in vitamin D, vitamin K2, or magnesium.

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Pyridoxic (B6)

Optimal range: 0 - 34 mmol/mol creatinine

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.

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Pyroglutamic

Optimal range: 10 - 33 mmol/mol creatinine

Pyroglutamate (or Pyroglutamic acid) is an intermediate in the glutathione metabolism and a marker of glutathione deficiency.

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Pyruvic

Optimal range: 0 - 9.1 mmol/mol creatinine

Pyruvic Acid feeds into the citric acid cycle & converts into acetyl CoA. Pyruvate is formed from carbohydrate via glucose or glycogen & secondarily from fats (glycerol) & glycogenic amino acids.

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Quinolinic

Optimal range: 0.85 - 3.9 mmol/mol creatinine

Quinolinic acid is a neurotoxic substance produced by our own bodies and a metabolite of tryptophan.

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Quinolinic / 5-HIAA Ratio

Optimal range: 0.42 - 2 Ratio

A high ratio of quinolinic acid to the tryptophan metabolite, 5-hydroxyindoleacetic acid, indicates excessive inflammation due to recurrent infections, excessive tryptophan intake, immune overstimulation, excessive adrenal production of cortisol, or excessive exposure to phthalates.

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Sebacic

Optimal range: 0 - 0.24 mmol/mol creatinine

Increased urinary products of the omega fatty acid metabolism pathway may be due to carnitine deficiency, fasting, or increased intake of triglycerides from coconut oil, or some infant formulas.

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Suberic

Optimal range: 0.18 - 2.2 mmol/mol creatinine

Suberic Acid, Adipate, and Ethylmalonate elevations can indicate that you may need additional carnitine and/or vitamin B2 to assist your cells in converting fats into energy efficiently.

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Succinic

Optimal range: 0 - 9.3 mmol/mol creatinine

Succinate (or succinic acid) is an important metabolite that is involved in several chemical processes in the body.

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Tartaric

Optimal range: 0 - 4.5 mmol/mol creatinine

Breakdown product of hyaluronic acid; also found in some foods.

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Thymine

Optimal range: 0 - 0.56 mmol/mol creatinine

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.

- Thymine is one of the five bases used to build nucleic acids.
- It is also known as 5-methyluracil or by the abbreviations T or Thy.
- Thymine is found in DNA, where it pairs with adenine via two hydrogen bonds. In RNA, thymine is replaced by uracil.

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Tricarballylic

Optimal range: 0 - 0.44 mmol/mol creatinine

Marker for exposure to certain fungal contamination in foods.

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Uracil

Optimal range: 0 - 9.7 mmol/mol creatinine

Vanillylmandelic (VMA)

Optimal range: 0.46 - 3.7 mmol/mol creatinine

Metabolite of epinephrine and norepinephrine. Often elevated due to stress induced catecholamine output or lead toxicity.

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