The Organic Acids Test (OAT): Your Metabolic Blueprint

Why the OAT Matters

Most lab tests measure what is floating in your blood. The Organic Acids Test does something fundamentally different: it measures what your cells are actually doing. These are metabolic byproducts — the exhaust fumes of cellular chemistry — excreted through urine. Over 70 markers in a single specimen. One morning void, and you have a metabolic map that would take dozens of blood tests to approximate.

Think of it this way. Blood work is like checking the oil level in your car. The OAT is like hooking up a diagnostic computer to the engine. You see which cylinders are misfiring, which fuel injectors are clogged, which sensors are sending bad data. Blood tells you what is circulating. Urine organic acids tell you what is happening inside the machinery.

The IFM Matrix places cellular energy production, nutrient cofactors, oxidative stress, neurotransmitter processing, and detoxification capacity at the core of chronic disease. The OAT touches every single one of these nodes in a single test.

When to Order

Fatigue that defies explanation. Brain fog that does not clear with sleep. Mood disorders — anxiety, depression, OCD-like behaviors — that resist conventional treatment. Suspected gut dysbiosis, especially when stool testing shows an incomplete picture. Mitochondrial dysfunction. Nutrient deficiencies that persist despite supplementation. Autism spectrum and neurodevelopmental concerns. Chronic illness of any kind where the mechanism remains unclear.

The OAT is particularly powerful as a first-pass screening tool. When a patient walks in with vague, multisystem complaints and you do not know where to start, this test gives you traction.

Major Labs and Ordering

Three primary companies dominate the space. Mosaic Diagnostics (formerly Great Plains Laboratory) runs the most widely used OAT panel, covering 76 markers. Genova Diagnostics offers the Organix Comprehensive Profile with a similar scope, and adds amino acid metabolites. US BioTek provides a streamlined organic acids panel that integrates well with their food sensitivity and environmental testing.

Collection is simple: first morning urine, fasting preferred. The patient collects at home, freezes the specimen, and ships it. Results arrive in 10-14 business days.

Yeast and Fungal Markers

This is where many clinicians first learned to love the OAT. Arabinose (D-arabinitol) is the primary candida metabolite. Levels above 35 mmol/mol creatinine are clinically significant. Tartaric acid is another fungal byproduct — William Shaw’s original research at Great Plains identified this as a yeast metabolite that inhibits the Krebs cycle by blocking malic acid enzyme. Citramalic acid rounds out the fungal triad.

When all three are elevated, you are looking at systemic fungal overgrowth, not just a superficial candida issue. The yeast is colonizing the gut, producing metabolites that enter systemic circulation and disrupt mitochondrial energy production. This is why patients with candida overgrowth are chronically fatigued — it is not just the yeast itself, it is the metabolic sabotage.

Cross-reference these markers with GI-MAP fungal findings. OAT tells you the yeast is metabolically active and producing toxins. GI-MAP tells you where it is living and in what quantity.

Bacterial Markers

HPHPA (3-(3-hydroxyphenyl)-3-hydroxypropionic acid) is arguably the most clinically actionable bacterial marker on the OAT. It is a metabolite of Clostridia species — specifically, these organisms produce an enzyme that converts dopamine into HPHPA instead of its normal metabolite. The result: dopamine depletion at the synapse. Clinically, this manifests as OCD-like behaviors, anxiety, rage episodes, and in children, behavioral dysregulation that looks like ADHD or autism flares.

William Shaw documented cases where treating Clostridia overgrowth with high-dose probiotics and targeted antimicrobials (often Saccharomyces boulardii and herbal protocols) normalized HPHPA and resolved behavioral symptoms that had persisted for years.

4-Cresol is the Clostridioides difficile marker. DHPPA reflects beneficial bacterial metabolites — low DHPPA suggests inadequate commensal populations. Hippuric acid reflects benzoate metabolism, often elevated with toluene exposure or certain bacterial overgrowths.

Oxalate Markers

Glyceric acid, glycolic acid, and oxalic acid form the oxalate triad. High oxalates produce a constellation that many clinicians miss: kidney stone formation, vulvodynia, joint and muscle pain that migrates, burning urination, and crystal deposits in tissues.

Three primary sources feed the oxalate pool. Dietary intake — spinach, almonds, sweet potatoes, beets, and chocolate are major contributors. Candida overgrowth — Aspergillus and Candida produce oxalic acid directly. And genetic factors — primary hyperoxaluria from mutations in AGXT or GRHPR genes.

When oxalates are elevated, the clinical approach involves reducing dietary oxalates, treating underlying fungal overgrowth, supporting oxalate degradation with Oxalobacter formigenes probiotics (VSL#3 contains related species), calcium citrate with meals (binds dietary oxalates in the gut), and B6 as P5P (cofactor for AGXT, the enzyme that metabolizes oxalates). Reduce oxalates gradually — rapid reduction can cause an “oxalate dump” that flares symptoms.

Mitochondrial Markers: The Krebs Cycle

The Krebs cycle intermediates on the OAT read like a diagnostic flow chart for mitochondrial function. Citric acid, succinic acid, fumaric acid, malic acid, and 2-oxoglutaric acid each represent a specific step in the energy production cycle. Elevations at specific points indicate blockages — usually from nutrient cofactor deficiencies.

High citric acid with low downstream metabolites suggests an aconitase block — often from mercury or fluoride toxicity, or iron deficiency (aconitase is an iron-sulfur enzyme). Elevated succinic acid points to Complex II dysfunction — CoQ10 and riboflavin deficiencies. High fumaric acid may indicate fumarase deficiency or heavy metal interference.

The fatty acid oxidation markers — suberic acid, adipic acid, and ethylmalonic acid — reveal a different layer. When these are elevated, the mitochondria cannot properly burn fatty acids for fuel. The patient is essentially running on glucose alone, which explains exercise intolerance, fasting difficulty, and hypoglycemia patterns. The primary interventions are L-carnitine (1-3g/day, transfers fatty acids into mitochondria), riboflavin/B2 (supports electron transfer flavoproteins), and CoQ10 (200-400mg ubiquinol form).

Neurotransmitter Metabolites

The OAT does not measure neurotransmitters directly — it measures their metabolic end products, which is arguably more useful. You see production and turnover, not just a snapshot.

HVA (homovanillic acid) reflects dopamine metabolism. VMA (vanillylmandelic acid) reflects norepinephrine and epinephrine turnover. Low HVA suggests low dopamine production — consider tyrosine, iron (cofactor for tyrosine hydroxylase), B6, and folate support. High HVA with behavioral symptoms — check HPHPA, because Clostridia may be shunting dopamine metabolism into abnormal pathways.

5-HIAA (5-hydroxyindoleacetic acid) reflects serotonin metabolism. Low 5-HIAA = low serotonin production. Consider tryptophan availability, B6/P5P status, and whether the kynurenine pathway is stealing tryptophan.

This brings us to the neuroinflammation markers. Quinolinic acid is an NMDA receptor agonist — excitotoxic at high levels. Kynurenic acid is neuroprotective, an NMDA antagonist. The quinolinic-to-kynurenic ratio is a functional neuroinflammation index. When quinolinic acid is elevated, the immune system is shunting tryptophan down the kynurenine pathway (via IDO enzyme activation), producing a neurotoxin instead of serotonin. This is the metabolic signature of neuroinflammation — driven by chronic infections, mold exposure, heavy metals, or systemic immune activation.

High quinolinic acid demands investigation: check for mold exposure (mycotoxin panel), chronic viral infections (EBV, HHV-6), Lyme and co-infections, and heavy metals. The intervention includes addressing the upstream trigger, BH4 support (SAMe, methylfolate), NAC (precursor to glutathione, which detoxifies quinolinic acid), and curcumin (inhibits IDO).

Nutrient Markers: Functional Testing at Its Finest

This is where the OAT outshines standard blood work for nutrient assessment.

Methylmalonic acid (MMA) is the most sensitive marker of functional B12 deficiency. Serum B12 can be normal at 400 pg/mL while MMA is elevated — meaning the cells do not have enough active B12 to run the methylmalonyl-CoA to succinyl-CoA conversion. If MMA is high, supplement B12 regardless of serum levels. Methylcobalamin for methylation support, hydroxocobalamin for detoxification and slow-release delivery, adenosylcobalamin for direct mitochondrial support.

FIGLU (formiminoglutamic acid) is the functional folate marker. When folate is insufficient, the histidine degradation pathway stalls, and FIGLU accumulates. More reliable than serum folate, which reflects recent dietary intake rather than tissue status.

Xanthurenic acid and kynurenic acid double as B6 status indicators. High xanthurenic acid = insufficient pyridoxal-5-phosphate (P5P), the active form of B6. This is common in oral contraceptive users, alcoholism, and genetic B6 dependency states.

Glutaric acid reflects riboflavin (B2) status. 3-Hydroxy-3-methylglutaric acid (HMG) serves as a CoQ10 marker — elevated HMG suggests increased CoQ10 demand or impaired mevalonate pathway.

Pyroglutamic acid is the glutathione depletion marker. When glutathione recycling is overwhelmed, pyroglutamic acid accumulates. This is a direct measure of oxidative stress burden. High pyroglutamic acid tells you the patient’s detoxification capacity is compromised — support with NAC (600-1800mg/day), glycine (3-5g/day), glutathione precursors, and reduce toxic exposures.

Detox Markers

Beyond pyroglutamic acid, orotic acid reflects ammonia detoxification capacity. Elevated orotic acid means the urea cycle is struggling — often from arginine deficiency, liver dysfunction, or genetic urea cycle defects. Arginine supplementation (2-4g/day) and liver support are first-line interventions.

2-Hydroxyhippuric acid reflects salicylate metabolism — elevated in patients using aspirin or with salicylate sensitivity. This is a clue for patients who react to foods high in natural salicylates (berries, tomatoes, spices).

Clinical Pearls

Run the OAT alongside a GI-MAP for the most complete functional picture. The OAT catches what the stool test misses (systemic effects of gut organisms), and the GI-MAP catches what the OAT misses (specific organism identification, immune markers, digestive function).

HPHPA is the single most underdiagnosed bacterial marker in clinical practice. Any patient with OCD, tics, rage, or treatment-resistant anxiety should have an OAT to check this marker. The dopamine disruption from Clostridia metabolites is a reversible cause of neuropsychiatric symptoms.

High quinolinic acid in a fatigued, brain-fogged patient should trigger an immediate investigation for mold, chronic infections, or heavy metal burden. Neuroinflammation is never idiopathic — there is always a driver.

The OAT is a first-morning void. No special preparation required, though avoiding high-dose supplements 48 hours before can reduce interference. Hydration should be moderate — overly dilute urine reduces marker concentration.

Retest in 3-4 months after implementing interventions. The OAT responds to treatment — watching markers normalize provides both clinical confirmation and patient motivation. This is functional medicine at its most elegant: measure, intervene, remeasure, refine.