Lab Guide
Diagnostic tests beyond standard bloodwork, compiled from ME/CFS, PVMS research, clinical guidelines and patient experience.
⚠️ Important Notice
This guide does not replace medical advice. It is designed to help you have an informed conversation with your doctor. No test should be performed or interpreted without medical supervision.
NASA Lean Test / 10-Minute Standing Test
Measures heart rate lying down vs standing. An increase of more than 30 bpm suggests POTS. Recommended by the US ME/CFS Clinician Coalition as a mandatory test.
Details ↓
Why relevant:
Free, simple, ME/CFS-specific. Can be done at home or by any GP. First screening tool for autonomic dysfunction.
Availability:
Home / GP
Autoantibodies against adrenergic receptors – CellTrend Panel
Tests for beta-2, M3 and M4 autoantibodies. Developed by Scheibenbogen/Charité. Affects approximately 20-30% of patients. Only available through CellTrend laboratory in Luckenwalde, Germany.
Details ↓
Why relevant:
Mechanistically explains autonomic dysfunction in a subset of patients. Positive result may open treatment options. Not covered by most insurance.
Availability:
CellTrend Luckenwalde (Germany)
Blood Volume Measurement
Measures actual blood volume. ME/CFS patients often have significantly reduced blood volume despite normal haematocrit – a finding standard blood tests miss entirely.
Details ↓
Why relevant:
Reduced blood volume is a central mechanism in ME/CFS autonomic dysfunction (Wirth/Scheibenbogen). Explains why patients feel worse upright.
Availability:
Specialised centres
Tilt Table Test
Gold standard for diagnosing POTS and orthostatic hypotension. Patient is tilted from lying to standing position while heart rate and blood pressure are continuously monitored.
Details ↓
Why relevant:
Definitive diagnosis of POTS and other forms of orthostatic intolerance when NASA Lean Test is positive.
Availability:
Cardiology / Neurology
Capnography during standing test
Measures exhaled CO2 lying down vs standing. Reveals hyperventilation and orthostatic hypocapnia – a common but overlooked finding in ME/CFS.
Details ↓
Why relevant:
Recommended in Tier 2 of US ME/CFS Clinician Coalition guidelines. Can explain cognitive symptoms worsening on standing.
Availability:
Specialist / Pulmonology
Folate Receptor Autoantibodies (FRAA)
Autoantibodies that block folate transport into the brain. Blood folate levels appear normal. Particularly elevated in EBV-triggered ME/CFS cases. Causes neuroinflammation and mitochondrial damage in the CNS.
Details ↓
Why relevant:
Almost never tested despite high relevance for brain fog and neurological symptoms. Folinic acid – not folic acid – can cross the blood-brain barrier and may help if FRAA positive.
Availability:
University of Aarhus / specialist laboratory
Holo-Transcobalamin (Holo-TC)
Measures only the active B12 fraction actually available to cells. Total B12 can appear normal while Holo-TC is low – the classic diagnostic trap that misleads both patients and doctors.
Details ↓
Why relevant:
Highest added value of any B12 test. Standard B12 systematically misleads. Always order Holo-TC instead of or alongside total B12.
Availability:
Specialist laboratory
Methylmalonic Acid (MMA)
Elevated MMA confirms functional B12 deficiency at cellular level even when blood levels appear normal. Key decision point: low Holo-TC + high MMA = functional deficiency very likely.
Details ↓
Why relevant:
Confirms what Holo-TC suggests. Together they form the most reliable functional B12 assessment available.
Availability:
Specialist laboratory
Homocysteine
Elevated homocysteine indicates problems in both B12 and folate metabolism. Helps narrow down which deficiency is driving the problem.
Details ↓
Why relevant:
Available in many standard laboratories. First step before ordering more expensive specialist tests.
Availability:
Standard laboratory / specialist
RBC Folate (Red Blood Cell Folate)
Measures folate stored in red blood cells – a long-term marker more accurate than serum folate for assessing cellular folate availability.
Details ↓
Why relevant:
Serum folate reflects recent intake, not cellular availability. RBC folate shows what is actually available to cells over weeks.
Availability:
Specialist laboratory
MTHFR Gene Mutation
Genetic test. Impairs conversion of B12 and folate into their active forms. Relevant when homocysteine is elevated or family history exists. One-time test, result permanently valid.
Details ↓
Why relevant:
Common mutation (~10-15% of population). If positive, explains why standard B12/folate supplementation may be insufficient – active forms (methylcobalamin, methylfolate) needed instead.
Availability:
Standard genetics laboratory
Intrinsic Factor Antibodies
Detects pernicious anaemia – an autoimmune condition preventing B12 absorption in the gut regardless of dietary intake.
Details ↓
Why relevant:
If positive, explains functional B12 deficiency definitively. Standard laboratory test.
Availability:
Standard laboratory
EpiSwitch CFS Blood Test – Oxford Biodynamics
Not yet available96% accuracy using 3D genomics from a blood sample. Identifies a unique epigenetic signature specific to ME/CFS. Close to clinical approval as of 2025. Will transform ME/CFS diagnosis.
Details ↓
Why relevant:
Watch for availability. Once approved, this becomes the first objective diagnostic test for ME/CFS. Published in Journal of Translational Medicine, 2025.
Availability:
Not yet available – Oxford Biodynamics
Red Blood Cell Deformability – Microfluidics
Not yet availableME/CFS patients have significantly stiffer and larger red blood cells that cannot pass through capillaries normally. This directly impairs tissue oxygenation and may explain fatigue and brain fog mechanistically.
Details ↓
Why relevant:
Research only. No clinical lab yet. But the finding is consistent and well-replicated – explains why standard blood oxygen levels appear normal while tissue oxygenation is impaired.
Availability:
Research only – not yet available
Autoantibodies against neuronal structures (anti-brain antibodies)
Tests for autoantibodies targeting brain and nervous system structures including locus coeruleus, thalamus and adrenal gland. A 2026 landmark study showed these autoantibodies from Long COVID patients cause fatigue, balance problems, hyperalgesia and small fiber neuropathy when transferred into mice – the first causal evidence.
Details ↓
Why relevant:
This is the first study establishing a causal mechanism linking autoantibodies to core ME/CFS and Long COVID symptoms. Positive results directly support therapeutic approaches such as plasmapheresis or immunoadsorption. Distinct from the CellTrend adrenergic receptor panel – these target broader neuronal structures.
Availability:
Research laboratories – clinical availability emerging
NK Cell Function / Cytotoxicity
NOT NK cell count (often normal) but killing activity. The most consistent finding in ME/CFS research over 30 years. Must be analysed within 24 hours of blood draw at room temperature – specialist laboratory essential.
Details ↓
Why relevant:
Reduced NK cytotoxicity is one of the most replicated findings in ME/CFS. Distinguishes from simple fatigue. Rarely offered by standard labs.
Availability:
Specialist laboratory (time-critical)
Full EBV Panel – VCA IgG/IgM + Early Antigen IgG + EBNA
Full panel mandatory. Early Antigen IgG (EA-IgG) specifically indicates active reactivation. Ordering only VCA IgG misses active reactivation entirely.
Details ↓
Why relevant:
EBV reactivation is one of the most common triggers and maintaining factors in ME/CFS. Most doctors order incomplete panels – insist on full panel including EA-IgG.
Availability:
Standard / specialist laboratory
Immunoadsorption / Plasmapheresis eligibility testing
Before apheresis-based therapies (immunoadsorption, plasmapheresis) a panel of autoantibodies should be measured to confirm immune-mediated disease and establish a baseline. Key markers: autoantibodies against GPCRs (CellTrend), neuronal structures, and immunoglobulin levels (IgG subclasses).
Details ↓
Why relevant:
Multiple studies now show autoantibody-mediated mechanisms in ME/CFS and Long COVID. Apheresis can remove these antibodies – but patient selection based on confirmed autoantibody presence is critical for treatment success and justification.
Availability:
Specialist immunology / haematology
Mast Cell Activation Panel – Histamine, Tryptase, Chromogranin A
Tests for mast cell activation syndrome (MCAS) – a common comorbidity in ME/CFS. At least two body systems must be affected to meet diagnostic criteria.
Details ↓
Why relevant:
MCAS can explain food sensitivities, allergic-like reactions, and symptom flares in ME/CFS. Recommended in Tier 2 of US ME/CFS Clinician Coalition.
Availability:
Specialist laboratory
HHV-6 IgG + Avidity Test
Low avidity indicates recent reactivation rather than old infection. Standard HHV-6 IgG alone cannot distinguish these. Avidity test is the critical addition.
Details ↓
Why relevant:
HHV-6 reactivation found in significant subset of ME/CFS patients. Without avidity test, a positive IgG is uninterpretable.
Availability:
Specialist laboratory
4-Point Salivary Cortisol (Day Profile)
Cortisol measured at waking, noon, 4pm and bedtime. A flat cortisol curve is characteristic of ME/CFS. Critically: single morning blood cortisol does NOT show this pattern.
Details ↓
Why relevant:
Only test listed by US ME/CFS Clinician Coalition as directly supportive of ME/CFS diagnosis. Saliva test can be done at home. Flat curve indicates HPA axis dysfunction.
Availability:
Saliva test (home) / specialist laboratory
Small Fiber Neuropathy – Skin Punch Biopsy
Small punch biopsy of the skin measuring density of small nerve fibres. Frequently reduced in ME/CFS. Provides objective evidence of neurological damage.
Details ↓
Why relevant:
Rarely performed despite high relevance. Explains pain, autonomic symptoms and sensory amplification in ME/CFS. Recommended in Tier 2 and 3 of US ME/CFS Clinician Coalition.
Availability:
Dermatology / Neurology
Transcranial Doppler Sonography during standing test
Measures blood flow velocity in cerebral arteries lying down vs standing. Can objectively demonstrate cerebral hypoperfusion as a cause of brain fog.
Details ↓
Why relevant:
Non-invasive. Provides mechanistic explanation for cognitive symptoms worsening on standing. Rarely used in ME/CFS context but evidence base is growing.
Availability:
Neurology
2-Day CPET (Cardiopulmonary Exercise Test)
Gold standard for objectifying PEM. Two maximal exercise tests 24 hours apart. ME/CFS patients show significant decline on day 2 – a pattern not seen in any other chronic illness. Documents disability objectively.
Details ↓
Why relevant:
Only objective test that directly demonstrates PEM as biological phenomenon. Used in disability and insurance cases. Warning: can trigger severe PEM – only when absolutely necessary.
Availability:
Specialist exercise lab
Mitochondrial Function Test + Fatty Acid Oxidation Panel (incl. VLCADD)
Measures mitochondrial function and ATP recycling capacity at cellular level. The M1 and M2 tests from AONM (via Magdeburg Molecular Detections laboratory) are specifically used for ME/CFS patients. Includes acylcarnitine profile to screen for fatty acid oxidation disorders such as VLCADD – a condition preventing conversion of long-chain fatty acids into energy.
Details ↓
Why relevant:
A Reddit user with 23 years of severe ME/CFS achieved full remission within 48 hours of starting MCT oil after VLCADD was identified via mitochondrial function testing. Results were confirmed by the NHS Rare Mitochondrial Disorders Service in London. Important: standard metabolic screening almost never includes fatty acid oxidation disorders in adults. The acylcarnitine profile is a standard blood test that can be ordered independently. Key tests to request: M1 + M2 mitochondrial function test (AONM, available self-order, ~£350, results in ~3 weeks) and acylcarnitine profile (blood test, can be requested from GP or ordered via iollo.com in the US). For genetic confirmation, full genome sequencing or specific VLCADD gene testing at a specialist centre.
Availability:
AONM (aonm.org, self-order, ships to Europe) / NHS Rare Mitochondrial Disorders Service London (referral needed) / GP (acylcarnitine profile)
Acylcarnitine Profile (Fatty Acid Oxidation Screening)
Blood test measuring acylcarnitines – metabolic markers that reveal whether fatty acids are being correctly converted into energy. Abnormal results indicate a fatty acid oxidation disorder (FAO) such as VLCADD, MCAD or other variants. This is the standard first-line test before specialist referral for full mitochondrial workup.
Details ↓
Why relevant:
In the US all newborns are screened for FAO disorders – but late-onset forms can be missed. Adults with ME/CFS are almost never screened. The test can be requested from a GP or ordered via direct-to-consumer services (e.g. iollo.com in the US). If abnormal, refer to metabolic specialist or NHS Rare Mitochondrial Disorders Service. Note: a normal result does not fully exclude mitochondrial dysfunction – the M1/M2 test from AONM measures function directly and is a complementary next step.
Availability:
GP (blood test) / iollo.com (US, direct-to-consumer) / specialist laboratory
Lactate step test at submaximal exertion
Measures lactate build-up at low exercise levels. ME/CFS patients switch to anaerobic metabolism much earlier than healthy controls.
Details ↓
Why relevant:
Less invasive than 2-day CPET. Available in sports medicine. Shows mitochondrial stress at low exertion levels.
Availability:
Sports medicine