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If exertion makes you crash for days afterward (post-exertional malaise), pushing through exercise can cause lasting harm. How pacing protects you ›

Symptom cluster

Fatigue and post-exertional malaise

Exhaustion that rest doesn't fix, and crashes that follow activity by hours or days. This page covers: Post-exertional malaise (PEM/PESE), Chronic fatigue, Myalgia, Exercise intolerance / reduced VO2.

What causes it

The leading explanations, each with its evidence grade and audit status. Several are shared with other clusters.

Mitochondrial / metabolic dysfunction produces Post-exertional malaise (PEM/PESE).

grademoderate-strongauditwell-founded-for-association
sources: S64, S65, S72

EBV / herpesvirus reactivation produces Chronic fatigue.

grademoderateauditwell-founded-association
sources: S134, S135, S139

Mitochondrial / metabolic dysfunction produces Exercise intolerance / reduced VO2.

grademoderateauditwell-founded-for-associationnotenormal tests can miss this
sources: S101, S103, S104, S64, S69, S97

Deconditioning (as cause) contested-cause Exercise intolerance / reduced VO2.

graderefuted-leaningauditcitation-inertiasafetydrives harmful GET prescription
sources: S26, S64, S70

Dysautonomia / autonomic dysfunction produces Exercise intolerance / reduced VO2.

grademoderateauditwell-foundedendpointphysiologic-surrogatenotenormal tests can miss this
sources: S95, S96, S98, S99

What has been tried

No treatment is approved. Each row shows how strong the evidence is, what outcome it was measured on, and any safety or conflict flag. Note that a drug can help a lab number without helping how you feel.

Pacing / energy-envelope management manages Post-exertional malaise (PEM/PESE).

grademoderate-consensusauditwell-foundedendpointpatient-reported-outcomesafetyprotective
sources: S21, S23, S26, S27, S32

Graded exercise therapy (GET) harms Post-exertional malaise (PEM/PESE).

gradeharm-well-documentedauditwell-foundedendpointpatient-reported-outcomesafetyCONTRAINDICATED when PEM present
sources: S21, S22, S23, S24, S26, S27, S71

Oxaloacetate (anhydrous enol) treats Chronic fatigue.

gradevery-lowauditthinendpointpatient-reported-outcomeconflictmanufacturer-run
sources: S73, S75, S78

Low-dose naltrexone treats Chronic fatigue.

gradelow-emergingauditthinendpointpatient-reported-outcome
sources: S32, S79

Metformin treats Chronic fatigue.

gradenegativeauditwell-founded-negativeendpointpatient-reported-outcome
sources: S59, S62

Fluvoxamine / SSRI treats Chronic fatigue.

grademixed-weakauditcontestedendpointpatient-reported-outcome
sources: S62

H1/H2 antihistamines (fexofenadine, famotidine) relieves Chronic fatigue.

gradelow-moderateauditemergingendpointpatient-reported-outcome
sources: S74

Pyridostigmine improves Exercise intolerance / reduced VO2.

gradelow-moderateauditemergingendpointphysiologic-surrogate
sources: S76, S77, S79

Recumbent / supine-biased rehabilitation (PEM-bounded) manages Exercise intolerance / reduced VO2.

gradelowauditthinendpointpatient-reported-outcomesafetymust respect PEM threshold
sources: S102, S99

How it is measured

2-day cardiopulmonary exercise test (CPET) indicates Post-exertional malaise (PEM/PESE).

grademoderateauditwell-founded
sources: S26

Invasive CPET (iCPET) diagnoses Exercise intolerance / reduced VO2.

gradereference-standardauditwell-founded
sources: S104, S95
Under review this week

A new 399-person trial suggests fluvoxamine reduces fatigue. The tracker has proposed strengthening that claim; until a reviewer accepts it, the page above shows the current audited state, not the proposal.