Specialty Lab Testing Guide — When and What to Order

Standard blood work gives you the broad strokes. Specialty labs give you the mechanistic detail — the why behind the symptoms. These tests look at metabolic pathways, gut ecology, hormone metabolism, and immune reactivity at a resolution that serum chemistry cannot reach. They are not screening tools. They are investigative instruments, ordered when clinical suspicion warrants a deeper look.

This guide covers the four most clinically useful specialty panels in functional medicine: the Organic Acids Test, the GI-MAP, the DUTCH test, and food sensitivity testing.

Organic Acids Test (OAT)

Laboratory: Mosaic Diagnostics (formerly Great Plains Laboratory) Sample type: First-morning urine What it measures: 76 organic acid metabolites — intermediate compounds from metabolic pathways that spill into urine when pathways are blocked, overloaded, or nutrient-depleted.

The OAT is the single most comprehensive functional test available. It simultaneously evaluates mitochondrial function, neurotransmitter metabolism, detoxification capacity, B vitamin status, oxidative stress, and microbial overgrowth — all from one urine sample.

Key Sections of the OAT

Fatty Acid Oxidation Markers

• Suberic acid, sebacic acid, adipic acid, ethylmalonic acid
• Elevated levels indicate impaired beta-oxidation — the mitochondrial process of burning fat for fuel
• Clinical significance: carnitine deficiency, CoQ10 deficiency, riboflavin (B2) deficiency, or genetic fatty acid oxidation disorders
• Cross-reference with serum carnitine levels and acylcarnitine profile if markedly elevated

Carbohydrate Metabolism

• Pyruvic acid, lactic acid
• Elevated pyruvate and lactate suggest impaired conversion of pyruvate to acetyl-CoA — the gateway into the Krebs cycle
• This step requires thiamine (B1), lipoic acid, CoQ10, magnesium, and manganese
• Clinical picture: fatigue after eating carbohydrates, exercise intolerance, brain fog

Energy Production — Krebs Cycle Intermediates

• Citric acid, isocitric acid, alpha-ketoglutaric acid, succinic acid, fumaric acid, malic acid
• Elevated intermediates indicate bottlenecks in the Krebs cycle — specific elevations point to specific nutrient deficiencies:
  • Citric/isocitric elevation: impaired aconitase (needs iron, cysteine)
  • Succinic acid elevation: CoQ10, riboflavin (B2) deficiency, or succinate dehydrogenase issue (Complex II)
  • Malic acid elevation: impaired malate dehydrogenase (needs NAD+ from niacin/B3)
• This section is the mitochondrial function report card

B Vitamin Markers

• Methylmalonic acid (MMA): the gold standard for B12 sufficiency. Elevated MMA = functional B12 deficiency, even if serum B12 is “normal.” Serum B12 above 500 pg/mL with elevated MMA means B12 is present but not being utilized — check for transport issues or genetic variants
• Formiminoglutamic acid (FIGLU): folate marker. Elevated = folate deficiency or impaired folate metabolism
• Xanthurenic acid: B6 marker. Elevated = pyridoxine insufficiency. Also related to kynurenine pathway dysregulation (tryptophan shunted away from serotonin toward quinolinate)
• Beta-hydroxyisovaleric acid: biotin (B7) marker
• Glutaric acid: riboflavin (B2) marker

Neurotransmitter Metabolites

• HVA (Homovanillic acid): Primary dopamine metabolite. Low HVA = low dopamine turnover (fatigue, low motivation, depression, ADHD-like symptoms). High HVA = excess dopamine breakdown
• VMA (Vanillylmandelic acid): Norepinephrine/epinephrine metabolite. High VMA = excess catecholamine production (chronic stress, anxiety, sympathetic overdrive). Low VMA = catecholamine depletion
• HVA/VMA ratio: Assesses dopamine-to-norepinephrine balance. A high ratio suggests dopamine is being produced but not efficiently converted to norepinephrine (needs vitamin C, copper)
• 5-HIAA (5-Hydroxyindoleacetic acid): Serotonin metabolite. Low 5-HIAA = low serotonin (depression, insomnia, carbohydrate cravings, IBS). High 5-HIAA = rapid serotonin turnover or carcinoid (rare)
• Quinolinic acid: A neurotoxin produced from tryptophan via the kynurenine pathway. Elevated quinolinate = neuroinflammation, chronic infection, or immune activation. The kynurenine pathway steals tryptophan from serotonin synthesis when inflammation is present — this is a key mechanism linking chronic inflammation to depression
• Quinolinate/5-HIAA ratio: If quinolinate is high and 5-HIAA is low, inflammation is shunting tryptophan away from serotonin toward neurotoxic quinolinate

Oxidative Stress and Detoxification

• 8-OHdG (8-hydroxy-2-deoxyguanosine): DNA oxidative damage marker. Elevated = significant oxidative stress and mitochondrial DNA damage. This is one of the most actionable markers on the OAT
• Pyroglutamic acid: Elevated = glutathione depletion. The body is recycling glutathione precursors and losing them in the urine. Indicates need for glutathione support (NAC 600–1800mg/day, liposomal glutathione, glycine, whey protein)
• Orotic acid: Elevated = ammonia detoxification issues or arginine deficiency. Can also indicate urea cycle dysfunction

Microbial Metabolites — Yeast and Bacterial Overgrowth This section alone justifies the test for many patients.

Yeast/Fungal markers:

• Arabinose (arabinitol): The primary Candida marker. Elevated arabinose = yeast overgrowth in the gut. Arabinitol is neurotoxic — it depletes NAD+ and impairs brain energy metabolism
• Tartaric acid: Another yeast metabolite. Named because it is also found in wine (produced by yeast fermentation). Elevated tartaric acid blocks the Krebs cycle at the fumarase step
• Citramalic acid, 3-oxoglutaric acid: Additional fungal metabolites

Bacterial markers:

• HPHPA (3-(3-hydroxyphenyl)-3-hydroxypropionic acid): Produced by Clostridia species. HPHPA inhibits dopamine-beta-hydroxylase, the enzyme that converts dopamine to norepinephrine. This creates a functional dopamine excess with norepinephrine deficiency — manifesting as anxiety, aggression, or behavioral issues. This is one of the most clinically significant findings on the OAT
• DHPPA (3-(3,4-dihydroxyphenyl)propionic acid): Beneficial bacterial metabolite from polyphenol metabolism. High levels suggest healthy Clostridia species or high polyphenol intake
• 4-Cresol: Produced by C. difficile and other pathogenic Clostridia. Elevated = dysbiotic gut flora
• Hippuric acid: Benzoate metabolism. Very high levels suggest toluene/chemical exposure or bacterial production of benzoate

Oxalate Markers

• Glyceric acid, glycolic acid, oxalic acid
• Elevated oxalates = dietary excess (spinach, almonds, chocolate, sweet potatoes), Candida-produced oxalates, B6 deficiency (B6 is needed to convert glyoxylate away from oxalate), or genetic hyperoxaluria
• Clinical: kidney stones, vulvodynia, joint pain, fibromyalgia-like pain

How to Read the OAT Report

Mosaic provides a color-coded report. Values above the 75th percentile are flagged; above the 95th percentile require attention. Read sections as clusters, not individual values. A single elevated marker may be a lab artifact. Three elevated markers in the same pathway tell a story.

GI-MAP (GI Microbial Assay Plus)

Laboratory: Diagnostic Solutions Laboratory Sample type: Stool (single collection) Technology: Quantitative PCR (polymerase chain reaction) — measures DNA of organisms, providing precise quantification

The GI-MAP is the most clinically useful stool test in functional medicine. Unlike culture-based stool tests (which miss 50–80% of organisms), PCR detects organisms by their DNA regardless of whether they can be cultured.

Pathogen Section

Helicobacter pylori: The GI-MAP quantifies H. pylori AND its virulence factors:

• CagA (cytotoxin-associated gene A): Associated with gastric cancer, peptic ulcers, and more aggressive disease
• VacA (vacuolating cytotoxin A): Damages gastric epithelium
• H. pylori positive without virulence factors = lower risk, may not require treatment in asymptomatic individuals. H. pylori with CagA positive = treat.

Clostridioides difficile: Toxin A and Toxin B genes. Even low-level C. diff detection warrants clinical attention.

Parasites: Giardia, Cryptosporidium, Entamoeba histolytica, Blastocystis hominis, Dientamoeba fragilis, Cyclospora, Endolimax nana. PCR catches parasites that microscopy misses — sensitivity is dramatically higher.

Normal/Commensal Flora

• Lactobacillus spp.: Should be present in reasonable quantity. Low levels suggest probiotic depletion, antibiotic history, or hostile gut environment
• Bifidobacterium spp.: Low levels correlate with inflammation, poor fiber intake, antibiotic use, and C-section birth
• Escherichia coli: Normal commensal when present at appropriate levels. Absent E. coli suggests severe dysbiosis
• Enterococcus spp.: Normal resident. Very high levels may indicate overgrowth displacing other flora
• Akkermansia muciniphila: Mucin-degrading bacterium associated with metabolic health. Low levels correlate with obesity, diabetes, and inflammatory conditions
• Faecalibacterium prausnitzii: Major butyrate producer. Low levels correlate with Crohn’s disease and inflammatory conditions

Opportunistic Bacteria

These organisms are normal residents that become pathogenic when they overgrow:

• Citrobacter spp.: Overgrowth associated with leaky gut, UTIs
• Klebsiella pneumoniae: Linked to ankylosing spondylitis (molecular mimicry with HLA-B27), UTIs
• Pseudomonas spp.: Biofilm former, difficult to eradicate
• Proteus spp.: Associated with rheumatoid arthritis (molecular mimicry), UTIs, kidney stones
• Staphylococcus spp.: Overgrowth can cause GI symptoms and toxin production
• Candida spp.: Yeast overgrowth — cross-reference with OAT yeast markers
• Morganella, Enterobacter: Opportunistic overgrowth indicators

Gut Health Markers — The Clinical Gold

Pancreatic Elastase-1

• Normal: >200 mcg/g
• Moderate insufficiency: 100–200 mcg/g
• Severe insufficiency (EPI): <100 mcg/g Low elastase = exocrine pancreatic insufficiency. The patient is not digesting proteins and fats adequately. Treatment: pancreatic enzyme replacement with meals. This is missed constantly in conventional medicine.

Steatocrit (fecal fat): Elevated = fat malabsorption. Cross-reference with elastase and bile acid markers.

Beta-Glucuronidase

• Normal: <2000 units Elevated beta-glucuronidase is produced by certain gut bacteria and reverses Phase II liver detoxification (glucuronidation). Estrogens, toxins, and medications that were conjugated for excretion get deconjugated and reabsorbed. This is a major driver of estrogen dominance. Treatment: calcium-d-glucarate (inhibits beta-glucuronidase), probiotics (Lactobacillus), fiber.

Secretory IgA (sIgA)

• Normal: 510–2010 mcg/g
• Low (<510): Mucosal immune deficiency — the gut’s first line of defense is down. Increased vulnerability to infection, food reactivity, and dysbiosis. Common in chronic stress, IgA deficiency, and burnout
• High (>2010): Acute immune response — active infection, acute food reaction, or parasitic infection
• Very low (<200): Severe mucosal immune suppression — often seen in chronic fatigue, post-viral states

Anti-Gliadin IgA: Secretory antibody to gliadin (wheat protein). Elevated = active immune response to gluten in the gut, even without celiac diagnosis. This is a mucosal-level marker more sensitive to non-celiac gluten sensitivity than serum testing.

Calprotectin

• Normal: <120 mcg/g (some labs use <50 for true normal)
• Elevated: Active intestinal inflammation. Values >200 raise concern for inflammatory bowel disease (Crohn’s, UC) and warrant colonoscopy. Values 50–200 suggest significant mucosal inflammation from any cause (infection, food reactivity, NSAID use, dysbiosis)

Zonulin

• Elevated: Increased intestinal permeability (“leaky gut”). Zonulin is the protein that modulates tight junctions between enterocytes. Elevated zonulin = tight junctions are opening. Triggers: gluten (gliadin directly stimulates zonulin release), dysbiosis, infections, NSAID use, alcohol, stress. Cross-reference with anti-gliadin IgA.

DUTCH Test (Dried Urine Test for Comprehensive Hormones)

Laboratory: Precision Analytical Sample type: Dried urine (4–5 collections over 24 hours) What it measures: Complete hormone metabolite map — not just hormone levels, but how the body is metabolizing and clearing hormones

The DUTCH test is superior to serum or saliva for hormone assessment because it captures metabolites. Serum tells you the level of a hormone at one moment. DUTCH tells you the level, the diurnal pattern (for cortisol), and every downstream metabolic pathway.

Sex Hormone Metabolites

Estrogens: E1 (estrone), E2 (estradiol), E3 (estriol) plus their Phase I metabolites:

• 2-OH estrogen (2-hydroxyestrone/estradiol): The “protective” pathway. 2-OH metabolites have weak estrogenic activity and are generally considered anti-proliferative
• 4-OH estrogen (4-hydroxyestrone/estradiol): The “genotoxic” pathway. 4-OH metabolites can form reactive quinones that damage DNA — associated with increased breast and uterine cancer risk
• 16-OH estrogen (16-alpha-hydroxyestrone): The “proliferative” pathway. 16-OH metabolites have strong estrogenic activity and promote tissue growth

The 2-OH:16-OH ratio is a cancer risk assessment tool. A ratio >2.0 is considered protective. A ratio <1.0 raises concern.

4-OH methylation: The critical safety valve. 4-OH metabolites must be methylated by COMT to 4-OH-methyl-estrogen (4-MeOE1/E2) to be rendered safe. This methylation requires COMT enzyme activity, magnesium, SAMe (methyl donor), and adequate B vitamins. If 4-OH is elevated AND 4-OH-methyl is low, the patient has impaired methylation of genotoxic estrogen metabolites — this is clinically urgent. Support with DIM (shifts metabolism toward 2-OH), magnesium, methylfolate, methylcobalamin, and consider direct COMT support.

Progesterone metabolites: Alpha-pregnanediol measures total progesterone production. Beta-pregnanediol reflects 5-beta-reductase activity.

Testosterone metabolites: 5-alpha-DHT pathway (androgenic — hair loss, prostate growth) vs 5-beta-androstanediol pathway (less androgenic). Elevated 5-alpha-reductase activity = excess DHT. Interventions: saw palmetto, zinc, nettle root.

DHEA-S: Adrenal androgen precursor. Low DHEA-S = adrenal depletion, aging, chronic stress.

Cortisol — The Complete Picture

Free cortisol (diurnal pattern): Four samples across the day. Normal pattern: highest upon waking, declining through afternoon, lowest at bedtime.

• Flat pattern (low morning, low evening): HPA axis suppression — “adrenal fatigue,” burnout
• Inverted pattern (low morning, high evening): Circadian disruption — insomnia, chronic stress
• Elevated all day: Cushing’s-like, chronic high stress, pain, inflammation

Metabolized cortisol: The total cortisol production over 24 hours. This is what serum and saliva miss. A patient can have low free cortisol (suggesting adrenal insufficiency) but high metabolized cortisol — meaning adrenals are producing plenty but clearance is too fast. Or high free cortisol with low metabolized cortisol — meaning clearance is impaired (liver/thyroid issue).

Cortisone/Cortisol ratio: Reflects 11-beta-HSD (11-beta-hydroxysteroid dehydrogenase) enzyme activity. 11β-HSD1 converts cortisone to cortisol (activating). 11β-HSD2 converts cortisol to cortisone (deactivating). An abnormal ratio changes the clinical picture entirely.

Organic Acid Markers on DUTCH

The DUTCH includes several OAT markers:

• Methylmalonic acid (MMA): B12 status
• Xanthurenate: B6 status
• Pyroglutamic acid: Glutathione status
• 8-OHdG: Oxidative DNA damage
• Melatonin (6-OH-melatonin-sulfate): Total melatonin production — critical for sleep assessment. Low melatonin production = inadequate serotonin-to-melatonin conversion, light exposure disruption, or aging
• HVA, VMA, 5-HIAA: Neurotransmitter metabolites (same as OAT)

DUTCH vs Serum vs Saliva

Serum measures total hormone levels at one timepoint — affected by binding proteins (SHBG, CBG). Saliva measures free hormone levels — useful for cortisol diurnal pattern but misses metabolites and total production. DUTCH measures free hormones, metabolites, diurnal cortisol, total cortisol production, and organic acids. For comprehensive hormone assessment, DUTCH provides the most complete clinical picture.

Food Sensitivity Testing

Food sensitivities are among the most controversial areas in functional medicine. Understanding the immunology is essential for clinical decision-making.

Immunoglobulin Classes

IgE (Immediate Hypersensitivity): Classical allergy. Mast cell degranulation within minutes. Hives, anaphylaxis, throat swelling. IgE testing (skin prick, serum specific IgE) is well-validated and clinically reliable.

IgG (Delayed Sensitivity): Reactions occur 4–72 hours after exposure. Mechanisms include immune complex formation, complement activation, and inflammatory cytokine release. Symptoms: fatigue, joint pain, headaches, brain fog, eczema, GI disturbance.

IgA (Mucosal Immunity): Secretory IgA responses reflect gut mucosal immune reactivity. IgA food panels may be more clinically relevant than IgG for GI-predominant symptoms.

Testing Options

IgG Food Panels (various labs): Test IgG antibodies to 96–200+ foods. The controversy: conventional immunologists argue that IgG to foods represents normal immune exposure, not pathology. The functional perspective: markedly elevated IgG (3–4x above reference) to specific foods, especially when combined with symptoms, often correlates with clinical improvement on elimination. The truth is nuanced — IgG testing is a guide, not a diagnosis.

MRT (Mediator Release Test) / LEAP Protocol

• Laboratory: Oxford Biomedical Technologies
• Measures mediator release (histamine, cytokines, prostaglandins) from white blood cells when exposed to 170 foods and chemicals
• Unlike IgG testing, MRT measures the end result (inflammation) regardless of the immune mechanism (IgG, IgA, complement, T-cell, or non-immune)
• LEAP (Lifestyle Eating and Performance) is the structured elimination/reintroduction protocol based on MRT results
• Clinical utility: higher than IgG panels for complex food sensitivity cases, especially when multiple mechanisms are involved

Cyrex Laboratories — Specialized Arrays

• Array 3 (Wheat/Gluten Proteome Reactivity): Tests antibodies to multiple wheat proteins and peptides — not just gliadin. Includes transglutaminase-2 (celiac), transglutaminase-3 (dermatitis herpetiformis), transglutaminase-6 (neurological gluten sensitivity), wheat germ agglutinin, gluteomorphin, prodynorphin, and deamidated gliadin. This is the most comprehensive gluten sensitivity panel available.
• Array 4 (Gluten-Associated Cross-Reactive Foods): Tests for foods that cross-react with gluten peptides — the immune system mistakes them for gluten. Includes dairy (casein, whey, milk butyrophilin), oats, yeast, corn, millet, rice, and coffee. Essential when a patient is strictly gluten-free but not improving.
• Array 10 (Multiple Food Immune Reactivity Screen): Tests IgG and IgA to 180 foods (raw and cooked forms). Unique because it tests both raw and cooked versions — some patients react to raw but not cooked (or vice versa).

Elimination Diet vs Testing

The gold standard for identifying food sensitivities remains the elimination diet: remove the most common triggers (gluten, dairy, eggs, soy, corn, sugar, alcohol) for 21–30 days, then reintroduce one food every 3 days, monitoring symptoms.

Pros of elimination diet: Free, no false positives, directly measures clinical response. Cons: Requires high compliance, takes 2–3 months to complete, may miss less obvious triggers, difficult for patients with complex diets or eating disorders.

Pros of testing: Identifies specific foods quickly, guides a more targeted elimination, useful when elimination diet is impractical or incomplete, can reveal unexpected triggers. Cons: Cost ($200–$600+), false positives (IgG testing especially), does not replace elimination/reintroduction, results must be interpreted in clinical context.

Clinical approach: Use testing as a starting point, but always confirm with elimination and reintroduction. A positive test result that does not correlate with clinical improvement on elimination is not clinically significant. A food that produces symptoms on reintroduction — regardless of test results — should be avoided.

Are IgG Panels Reliable?

They are reproducible (same sample tested twice gives similar results) but their clinical validity is debated. They are most useful when: the patient has multiple systemic symptoms (not just GI), there are multiple elevated foods (suggesting gut permeability — fix the gut, not just avoid the foods), and results are used to guide a structured elimination protocol rather than permanent food avoidance. Elevated IgG to many foods simultaneously is itself diagnostic — it indicates intestinal permeability allowing food proteins into the bloodstream, triggering immune responses. Treat the gut, and many of those “sensitivities” resolve.