E2 ModeratePreliminaryPEM unclearCase-ControlPeer-reviewedMachine draft
Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome.
De Lorenzo, F, Hargreaves, J, Kakkar, V V · Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 1997 · DOI
Quick Summary
Some ME/CFS patients experience dizziness or fainting when standing up, a condition called orthostatic hypotension. This study tested whether salt supplements could help 22 ME/CFS patients with this symptom. After 8 weeks, salt helped 11 patients feel better, but 10 patients' symptoms returned—and those 10 had lower levels of a hormone called renin that helps regulate blood pressure.
Why It Matters
Orthostatic symptoms are common and disabling in ME/CFS. This study suggests that sodium chloride may help some patients but not others, and identifies a potential biomarker (low renin activity) that could predict treatment response and point toward distinct disease mechanisms within the ME/CFS population.
Observed Findings
- 22 of 78 ME/CFS patients (28%) showed abnormal responses to upright tilt-table testing at baseline.
- After 8 weeks of sodium chloride therapy, 11 of 22 patients with orthostatic abnormalities showed normalized tilt responses and improved CFS symptoms.
- 10 of 22 treated patients redeveloped orthostatic hypotension despite sodium chloride therapy.
- Non-responders to sodium chloride had significantly lower plasma renin activity (0.79 pmol/ml per h) than responders (1.0 pmol/ml per h) and healthy controls (1.29 pmol/ml per h).
Inferred Conclusions
- Sodium chloride supplementation is effective for approximately 50% of ME/CFS patients with orthostatic abnormalities.
- Low plasma renin activity may identify ME/CFS patients who will not respond to salt therapy and may reflect dysfunction of the renin-angiotensin-aldosterone system.
- Distinct pathogenic subtypes of orthostatic dysfunction may exist within the ME/CFS population, differentiated by renin-aldosterone axis function.
Remaining Questions
- What is the long-term durability of sodium chloride response in the 11 responders beyond 8 weeks?
- How should clinicians manage the 10 non-responders with low renin activity—what alternative therapies might target renin-aldosterone dysfunction?
What This Study Does Not Prove
This study does not prove that renin deficiency causes orthostatic hypotension in ME/CFS, only that an association exists in non-responders. The findings are correlational and come from a single center with modest sample size; results require replication before clinical practice changes. The study also does not establish whether low renin is a primary cause or a secondary consequence of ME/CFS pathology.
Tags
Symptom:Orthostatic IntoleranceFatigue
Biomarker:Blood Biomarker
Method Flag:Small SampleExploratory Only
Metadata
- DOI
- 10.1007/BF02267980
- PMID
- 9292244
- Review status
- Machine draft
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 8 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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