Organic Acid Test (OAT): Neurotransmitter Metabolism

The Organic Acid Test (OAT) has gained popularity among many functional and alternative health experts in recent years. However, is this popularity justified when it comes to testing neurotransmitter metabolites? Read on to find out. What is the Organic Acid Test (OAT)?

The 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 neurotransmitter metabolites, which are found in the OAT, weighing in on whether they’re worth testing. Neurotransmitter Metabolism Markers

Phenylalanine and Tyrosine Metabolites

The catecholamines – norepinephrine ( noradrenaline ), epinephrine (adrenaline), and dopamine – are released when the body is under physical or emotional stress . Their metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA), also increase as a result.

Certain drugs ( L-dopa , dopamine, epinephrine, and norepinephrine ) that can be metabolized to HVA and VMA, may falsely elevate their levels in urine.

Proponents of OAT state that HVA and VMA can be elevated due to stress, from lead toxicity, due to the intake of L-DOPA, dopamine, phenylalanine, or tyrosine, or due to Clostridia metabolites. Elevated HVA/VMA is supposedly commonly caused by the by-products of the Clostridia bacteria. 1) Vanillylmandelic Acid (VMA)

VMA is the end product of the breakdown of ‘fight-or-flight’ hormones norepinephrine and epinephrine , also known as noradrenaline and adrenaline.

Adrenalin and noradrenalin are produced in the adrenal gland and released into the bloodstream. Their main role is to prepare the body for physical stress – they make the heart beat faster, increase blood pressure, expand the lungs, and increase energy supply by mobilizing energy stores in liver and fat cells [ 1 ].

Studies have found that VMA levels increase in response to severe stress and anxiety [ 2 , 3 ]. However, they increase only slightly.

Significant elevations in VMA levels are found in tumors , such as pheochromocytoma, a tumor of the adrenal gland or neuroblastoma, a nerve tissue cancer that occurs mainly in children [ 4 , 5 ]. This particular test is, in fact, often used by doctors to detect those kinds of tumors.

Vanillylmandelic acid (VMA) is a breakdown product of adrenaline and noradrenaline. It’s measured to detect tumors of the adrenal gland. 2) Homovanillic Acid

Homovanillic acid (HVA) is the breakdown product of the ‘feel-good’ brain chemical dopamine.

Dopamine is most famous for controlling reward-motivated behavior. But it also has many other important roles in humans – it’s involved in movement, memory, attention, learning, sleep , and mood [ 6 , 7 , 8 ].

Abnormal dopamine levels in the brain have been associated with Parkinson’s disease, schizophrenia, and ADHD [ 9 ].

Dopamine is produced in the brain, but large amounts are also made in the adrenal glands, especially in response to stress. That is why the urine levels of HVA don’t reflect the brain (cerebrospinal) dopamine levels [ 10 ].

Studies have found that the following may increase blood and urine HVA : Eating dopamine-rich foods such as bananas, and flavonoid-rich foods such as cocoa , tomatoes, onions ( quercetin ), and tea [ 11 , 12 , 13 , 14 , 15 ]

A rare genetic disorder resulting in beta-hydroxylase deficiency – that’s the enzyme needed to convert dopamine into adrenalin [ 22 ]

Note that most of the studies above are small and of limited value/quality.

Studies have also found an association between low HVA values and:

Using this test to diagnose genetic disorders in infants and to screen for specific tumors , are the only scientifically supported, approved uses to date.

Homovanillic acid (HVA) is a breakdown product of dopamine. Dopamine is produced in the brain, but large amounts are also made in the adrenal glands. Urine levels don’t reflect brain levels. HVA is measured to detect rare genetic disorders or tumors of the adrenal gland. 3) HVA/VMA Ratio

An elevated ratio indicates a decreased conversion of dopamine to norepinephrine by the enzyme dopamine beta-hydroxylase (DBH), which is a copper -dependent enzyme. This can happen in:

Some studies also suggest that issues with this enzyme may happen in:

However, these associations require further confirmation. Tryptophan Metabolism Tryptophan is an essential amino acid that can be metabolized through different pathways.A major route is the kynurenine pathway, resulting in the production of the NAD (nicotinamide adenosine dinucleotide). About 95% of tryptophan is metabolized this way [ 34 , 35 , 36 ]. Some of the metabolites of the kynurenine pathway can be toxic [ 34 ].Another important pathway is the one through which tryptophan (<5%) is converted into serotonin , which is further metabolized to melatonin and 5-hydroxyindoleacetic acid (5-HIAA) [ 37 , 38 ]. 4) Quinolinic Acid Quinolinic acid is a product of the breakdown of the amino acid tryptophan via the kynurenine pathway.Quinolinic acid can be toxic for the brain. Evidence suggests that quinolinic acid is involved in [ 39 , 40 ]: Neurodegenerative diseases, such as Huntington’s and Alzheimer’s Studies have found that quinolinic acid impairs learning and memory in animals [ 41 , 42 , 43 ].However, urine levels of quinolinic acid are not a reflection of the levels in the brain [ 44 ]. Proponents of OAT state that quinolinic acid may increase due to inflammation from microbial infections, central nervous system degeneration, excessive tryptophan supplementation, and exposure to phthalates. However, clinical evidence for this is lacking. They suggest reducing excess quinolinic acid by avoiding tryptophan supplementation and avoiding brain damage induced by quinolinic acid by using supplements containing acetyl […]

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