On the 9th of September, the Physiology Society has published a research study in Physiology Reports entitled ‘Total blood volume and red blood cell volume are not associated with orthostatic intolerance in adults with myalgic encephalomyelitis/chronic fatigue syndrome‘ (Yamazaki et al, 2026). Please see a summary and abstract of the study plus Dr Charles Shepherd, Honorary Medical Adviser's comments below.
AI Summary (checked by MEA)
- Aim: The study tested whether low blood volume (hypovolemia) or reduced red-blood-cell volume explains orthostatic intolerance (OI) in people with ME/CFS.
- Participants: 49 adults with ME/CFS underwent a 10-minute lean/standing test and quantitative blood-volume measurement.
- Blood volume varied considerably: 35% were hypovolemic, 43% had normal blood volume and 22% were hypervolemic; 49% had a reduced red-blood-cell volume
- OI was common (55%), but blood-volume status did not predict who developed an abnormal response. The most common abnormality was postural hypocapnia (POSH, 41%), while POTS occurred in 12%.
- Main conclusion: Static blood volume alone probably does not explain OI in ME/CFS. Other mechanisms—such as autonomic dysfunction, impaired blood-vessel constriction/venous pooling, abnormal breathing/CO₂ regulation, or reduced cerebral blood flow—may be more important.
Abstract
Orthostatic intolerance is common in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and may worsen daily functioning. Although hypovolemia has been proposed as a contributor, its relationship to objective orthostatic abnormalities remains uncertain.
We examined whether measured blood-volume abnormalities were associated with standardized lean-test outcomes. Adults meeting the 1994 ME/CFS criteria and reporting substantial post-exertional malaise underwent a 10-min lean test with capnography, followed 8 days later by total blood volume (TBV) measurement using the Daxor BVA-100. Supine hypocapnia was defined as baseline end-tidal CO2 (eTCO2) <34 mmHg; postural orthostatic syndrome of hypocapnia (POSH) as normal supine eTCO2with any leaning value <34 mmHg; and postural orthostatic tachycardia syndrome (POTS) as a heart-rate increase ≥30 beats/min or absolute heart rate ≥120 beats/min.
Among 49 participants, TBV was hypovolemic in 35%, normovolemic in 43%, and hypervolemic in 22%; red blood cell volume was deficient in 49%.
Overall, 55.1% had at least one lean-test abnormality, most commonly POSH (40.8%). Abnormalities did not differ by TBV or red blood cell volume category.
Static blood-volume categories were not associated with lean-test-defined orthostatic abnormalities in ME/CFS, suggesting contributions from autonomic, vascular, respiratory, or cerebrovascular mechanisms.
MEA Comment
Some interesting new research from Prof Ben Natelson (a US neurologist with a longstanding interest in ME/CFS) and colleagues into the possible role of low blood volume (hypovolaemia) in people with ME/CFS who have orthostatic intolerance (OI)
This research has failed to find any robust evidence of hypovolaemia and does therefore question the value of increasing fluid intake as self-help measure for more severe OI
As the authors point out, this suggests that autonomic nervous system dysfunction and the possibility of changes in cerebral (brain) blood flow are more likely to be the main causative factors
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
