Organic Acid Test Part 6.1: Neurotransmitters

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“Neurotransmitter metabolites on the OAT help identify imbalances in dopamine, serotonin, and stress chemistry, offering clues to mood, behavior, and cognitive function.”

In an Organic Acid Test (OAT), the Neurotransmitter Metabolites section evaluates how well your body is producing, metabolizing, and clearing key brain chemicals like dopamine, serotonin, and norepinephrine. While the test doesn’t directly measure neurotransmitter levels in the brain, it provides insights through their breakdown products (metabolites) found in urine.

Key Neurotransmitter Metabolites Measured:

1. Homovanillic Acid (HVA)

  • End-product of dopamine metabolism

  • High HVA: Stress, stimulant use, high dopamine turnover (ADHD, mania, certain gut bacteria)

  • Low HVA: Dopamine deficiency, poor tyrosine intake, iron/B6 deficiency

  • Dopamine Metabolism Overview: Phenylalanine → Tyrosine → L-DOPA → Dopamine → HVA (Cofactors: B6, iron, vitamin C, SAMe, magnesium)

2. Vanillylmandelic Acid (VMA)

  • End-product of norepinephrine and epinephrine metabolism

  • High VMA: Stress, adrenal overactivation, anxiety, stimulant use

  • Low VMA: Fatigue, poor adrenal output, B6/iron deficiency, low tyrosine

  • VMA is produced when norepinephrine (noradrenaline) and epinephrine (adrenaline) are broken down by the enzymes:

    • MAO (monoamine oxidase)

    • COMT (catechol-O-methyltransferase)

  • It reflects sympathetic nervous system activity and adrenaline turnover.

3. 5-Hydroxyindoleacetic Acid (5-HIAA)

  • Breakdown product of serotonin

  • High 5-HIAA: High serotonin turnover, SSRIs, gut serotonin overproduction

  • Low 5-HIAA: Low serotonin, tryptophan deficiency, B6 deficiency, gut dysbiosis

  • Serotonin Metabolism Overview: Tryptophan → 5-HTP → Serotonin → 5-HIAA (Cofactors needed: B6, iron, magnesium, vitamin C)

4. Quinolinic Acid (QUIN) & Kynurenic Acid (KYNA)

  • Metabolites of tryptophan (alternative to serotonin pathway)

  • Reflect neuroinflammation, oxidative stress, B6/B3 status

  • High quinolinic = neurotoxic, inflammation

  • High kynurenic = neuroprotective (in balance)

  • Imbalance suggests need for tryptophan support, B3, B6, or antioxidant support

  • Tryptophan Metabolism Overview:

    Tryptophan can follow two major pathways:

    1. ➡️ Serotonin Pathway (→ 5-HTP → Serotonin → Melatonin)

    2. ➡️ Kynurenine Pathway (→ Kynurenine → Kynurenic acid or Quinolinic acid)

  • KYNA:QUIN Ratio – Why It Matters

    • A healthy balance leans toward kynurenic acid (protective).

    • A low KYNA:QUIN ratio suggests a pro-inflammatory or neurotoxic environment in the brain and body.

5. Picolinic Acid

Picolinic acid helps regulate metal absorption and immune responses, with levels reflecting immune activity and metal metabolism balance.

  • Another product of tryptophan metabolism

  • Supports mineral absorption and immune regulation

  • Very high or low levels may indicate B6 deficiency or tryptophan metabolism imbalance

6. 4-Hydroxybutyric acid (GABA metabolism)

4-Hydroxybutyric acid reflects how well your body is breaking down GABA, with imbalances pointing to stress, neurological strain, or GABA pathway dysfunction.

  • A byproduct of GABA metabolism, closely tied to the calming, inhibitory neurotransmitter system.

  • It is structurally related to GABA and has sedative, anxiolytic, and neuroprotective effects.

  • Elevated 4-Hydroxybutyric Acid May Indicate:

    1. Impaired GABA breakdown

      • Could reflect a backup in GABA metabolism or impaired enzyme activity

    2. Increased GABA turnover

      • Possibly due to:

        • Chronic stress (overuse of inhibitory calming mechanisms)

        • Seizure activity or neurological inflammation

        • Use of GABAergic drugs (e.g., benzodiazepines, barbiturates)

    3. Detoxification overload

      • GHB also interacts with mitochondrial and redox pathways, so elevated levels may indicate oxidative stress or impaired detox (especially in liver or CNS)

    4. Mitochondrial dysfunction

      • GABA and GHB metabolism require mitochondrial enzymes, particularly succinate semialdehyde dehydrogenase (SSADH)

  • Low 4-Hydroxybutyric Acid May Suggest:

    • Low GABA activity or reduced GABA production

    • Could relate to:

      • Anxiety, restlessness, insomnia, ADHD-like symptoms

      • Low glutamine or glutamate availability (GABA precursors)

      • Vitamin B6 deficiency, which is essential for converting glutamate to GABA

7. Quinolinic acid

  • Quinolinic acid is a red flag for brain inflammation—when high, it signals that the body is converting tryptophan into a neurotoxin instead of serotonin.

  • Derived from the amino acid tryptophan, when it’s metabolized via the kynurenine pathway rather than the serotonin pathway.

  • Acts as a powerful agonist at NMDA (glutamate) receptors, meaning it can overstimulate the brain.

  • Plays a role in:

    • Neurodegeneration

    • Mood disorders

    • Mitochondrial dysfunction

    • Oxidative stress

8. Vanillactic acid

  • Vanillactic acid is a microbial and dopamine-related metabolite that can reflect gut dysbiosis or neurochemical imbalance when elevated.
  • High Vanillactic Acid May Indicate:

  1. Gut dysbiosis or yeast overgrowth

    • Certain species of Candida and Clostridia can produce vanillactic acid.

    • Suggests fermentation or abnormal microbial activity in the GI tract.

  2. Altered dopamine metabolism

    • May reflect excess catecholamine turnover or detoxification pathway congestion.

    • Associated with neurobehavioral issues, particularly in ASD or ADHD contexts.

  3. Mitochondrial stress or oxidative stress

    • Elevated levels may appear when cellular energy pathways are impaired or overwhelmed.

  • Low Vanillactic Acid:

    • Typically not clinically significant unless part of a broader pattern of neurotransmitter or gut metabolism suppression.

Important:

These metabolites reflect peripheral (whole-body) metabolism, not direct brain levels—but patterns can indirectly indicate neurotransmitter imbalances, especially when viewed in context of symptoms.

HVA/VMA ratio: This ratio gives insight into the balance between dopamine and norepinephrine in the nervous system and can reflect neurotransmitter dominance, stress adaptation, or enzyme function (like COMT or MAO activity).

Enzyme Considerations:

  • COMT and MAO genes play key roles in metabolizing both dopamine and norepinephrine
  • COMT variants (especially Val158Met) can affect the breakdown speed of catecholamines
  • B-vitamin status, methylation, and mineral cofactors (e.g., magnesium, copper, iron) also influence this balance

Quinolinic acid / 5-HIAA ratio: The Quinolinic acid / 5-HIAA ratio reveals whether tryptophan is being used for healthy serotonin production or diverted toward inflammatory, neurotoxic pathways impacting mood and brain health.

Clinical Importance:

  • A high Quinolinic acid / 5-HIAA ratio is often seen in:

    • Autoimmune conditions

    • Chronic infections

    • Chronic stress

    • Mood and anxiety disorders

  • This ratio can help target anti-inflammatory, antioxidant, and nutrient therapies (e.g., B6, B3, magnesium) to rebalance tryptophan metabolism.

 

Alex’s Results: The results under Neurotransmitters were unremarkable.

Neurotransmitters: 

There are over 100 identified neurotransmitters, but between 10-15 core ones which are mostly discussed in health and mental function.

Major Classes of Neurotransmitters:

1. Amino Acid Neurotransmitters (Fast-acting, most abundant)

  • Glutamate – primary excitatory neurotransmitter

  • GABA (gamma-aminobutyric acid) – primary inhibitory neurotransmitter

  • Glycine – inhibitory (especially in the spinal cord)

  • Aspartate – excitatory (less common than glutamate)

2. Monoamines (Involved in mood, attention, motivation)

  • Dopamine – reward, motivation, motor control

  • Serotonin (5-HT) – mood, appetite, sleep

  • Norepinephrine (noradrenaline) – focus, alertness, stress

  • Epinephrine (adrenaline) – fight-or-flight response

  • Histamine – sleep-wake cycle, immune response, digestion

3. Peptide Neurotransmitters

  • Substance P – pain perception

  • Endorphins / Enkephalins – natural painkillers, mood elevation

  • Oxytocin – bonding, trust

  • Vasopressin – water retention, social behavior

4. Purinergic Neurotransmitters

  • ATP (adenosine triphosphate) – also acts as a neurotransmitter

  • Adenosine – sleep regulation, calming effect

5. Acetylcholine (ACh)

  • Unique category

  • Important for learning, memory, muscle activation

  • Depleted in Alzheimer’s disease

6. Gaseous Neurotransmitters

  • Nitric oxide (NO) – involved in blood flow, memory, and relaxation of smooth muscle

  • Carbon monoxide (CO) – also acts as a signaling molecule

 

PLEASE NOTE: ANY VIEWS REGARDING THE RESULTS ARE MY UNDERSTANDING AND DO NOT SERVE AS PROFESSIONAL ADVICE. THE TREATMENT RECOMMENDATION IS STRICTLY RELATING TO ALEX’S RESULTS AND NOT MEANT FOR SELF-TREATMENT. ALWAYS SPEAK TO YOUR HEALTHCARE PROVIDER BEFORE STARTING ANY TREATMENTS.

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