Working document · updated as we go

Our ME/CFS Research Log

A running, evidence-graded review of what's actually been studied on ME/CFS causes and treatments — built because "have you tried googling it" is not a referral pathway. Every entry below is graded by source quality, not vibes.

5 of 24 categories reviewed 60 sources logged 2 promising leads so far Last updated 30 Jul 2026

What we know so far

The categories reviewed as "Promising"

Two things have cleared the bar for genuinely decent evidence. Everything else reviewed so far is real but inconclusive — see the full board below.

Infection can genuinely trigger this

Promising

A large NIH-funded study (RECOVER-Adult, 2025) tracked 11,785 people infected with SARS-CoV-2 against 1,439 uninfected people. The infected group was roughly five times more likely to go on to develop ME/CFS. Earlier studies going back to 2006 show the same pattern with other infections (glandular fever, Ross River virus) — the people who got sickest during the initial infection were the ones most likely to develop lasting illness afterward.

This doesn't explain every case — plenty of people develop ME/CFS with no clear preceding infection — but it's the single best-evidenced trigger found in this research so far.

Why it matters: this is a measurable, replicated, physiological response to infection, tracked in large controlled studies. Not a mystery, not "in your head."

12 sources reviewed · see sources.csv, category "Post-viral/post-infectious onset"

Pacing is the one thing every guideline agrees on

Promising

NICE (UK) and the CDC (US) both recommend staying inside a personal "energy envelope" — tracking what you can actually do without triggering a crash, and not exceeding it — over any fixed, incrementally-increasing exercise program. In 2021, NICE formally reversed its older guidance and now explicitly warns against Graded Exercise Therapy (GET), the "push through it, build up slowly" approach.

A 2019 patient survey of 2,310 people found roughly 45% reported improvement from pacing, versus roughly 10% from GET or CBT-based approaches — that survey was part of the evidence that led to NICE's reversal.

Why it matters: if a GP, an old leaflet, or a well-meaning relative suggests "just build up your exercise," that guidance has been formally withdrawn by NICE. It's not a lack of willpower — pushing through can make things worse.

12 sources reviewed · see sources.csv, category "Pacing / energy envelope management"

Full status board

Every category we're tracking

Click a row to expand our working notes. Source counts and confidence grow as we work through the list — nothing here is final.

Possible Causes

Post-viral / post-infectious onset 12 sources Promising ▸
Best-evidenced trigger found so far — large matched-control studies (COVID and earlier viruses) consistently show a dose-related minority developing ME/CFS after infection, tied to how severe the initial illness was. Explains a subset of cases, not all of them; what happens biologically after the trigger is still unclear (immune dysregulation is the leading candidate).
Immune dysregulation / chronic immune activation 14 sources Inconclusive ▸
Reduced natural killer (NK) cell activity is well-replicated across multiple independent reviews — one of the more solid objective findings in the field. But general inflammation markers (cytokines) are inconsistent study to study, and the largest single study found cytokines track with how severe someone's illness is, not whether they have it at all. Autoimmune-antibody findings are real but only show up in a subset (roughly a quarter) of patients.
Autonomic nervous system dysfunction (POTS, orthostatic intolerance) 10 sources Inconclusive ▸
Genuinely common and clinically significant — heart rate, blood pressure, and even blood flow to the brain on standing are frequently abnormal. But the best-powered study comparing ME/CFS patients to other fatigued patients found no meaningful difference in how common POTS was between the two groups — suggesting this may be a common companion condition rather than a distinguishing cause. Testing methods also vary a lot between studies.
Mitochondrial / metabolic dysfunction 12 sources Inconclusive ▸
The body's response to exertion is measurably and reproducibly abnormal — this is essentially the physical signature of post-exertional malaise. But whether that's caused by broken mitochondria specifically, or something further upstream (like oxygen delivery), is unresolved. One well-designed study found normal mitochondrial function in cells despite clearly abnormal real-world exercise performance in the same patients.
Neuroinflammation / CNS sensitization Not started
HPA axis dysfunction (cortisol/stress response) Not started
Gut microbiome / gastrointestinal dysfunction Not started
Genetic / epigenetic predisposition Not started
Small fiber neuropathy Not started
Mast cell activation syndrome (comorbid) Not started
Sleep architecture abnormalities Not started
Psychological / psychiatric factors Not started

Possible Treatments

Pacing / energy envelope management 12 sources Promising ▸
Unanimously endorsed by NICE, the CDC, and the 2015 IOM report as safer and more appropriate than structured exercise. Meta-analyses show a moderate, consistent reduction in fatigue, and one 2025 review found pacing's benefits held up at 2.5-year follow-up where GET's did not. Caveat: no large multi-site trial exists yet, and in one survey around 14% of patients said pacing made things worse for them — individual variation matters.
Graded Exercise Therapy (GET) Not started · contested history
CBT Not started · contested history
Low-dose naltrexone (LDN) Not started
Antiviral therapy Not started
Supplements (CoQ10, D-ribose, carnitine, B vitamins, magnesium) 1 source In progress ▸
Only touched so far as a side note from the mitochondrial research: a 2021 review of 9 supplement studies found most reported some fatigue improvement, but judged the evidence too thin (small samples, short trials) to draw a real conclusion. Not yet properly reviewed as its own topic — treat this as a placeholder.
POTS-directed treatment Not started
Sleep management Not started
Antihistamines / mast cell stabilizers Not started
Immunomodulatory therapy (rituximab, IVIG) Not started
Dietary interventions Not started
Emerging / repurposed drug trials Not started

What's next

19 categories still untouched

Causes

  • Neuroinflammation / CNS sensitization
  • HPA axis dysfunction
  • Gut microbiome / GI dysfunction
  • Genetic / epigenetic predisposition
  • Small fiber neuropathy
  • Mast cell activation syndrome
  • Sleep architecture abnormalities
  • Psychological / psychiatric factors

Treatments

  • Graded Exercise Therapy (GET)
  • CBT
  • Low-dose naltrexone (LDN)
  • Antiviral therapy
  • Supplements (finish proper review)
  • POTS-directed treatment
  • Sleep management
  • Antihistamines / mast cell stabilizers
  • Immunomodulatory therapy
  • Dietary interventions
  • Emerging / repurposed drug trials