Brain Blood Flows in ME/CFS and POTS

Memory-Loss-4352We’ve been looking at postural orthostatic tachycardia syndrome (POTS) lately. It’s clear that about fifty percent of POTS patients meet the criteria for ME/CFS and a much smaller percentage of ME/CFS patients probably meet the criteria for POTS.

The question is what do the two syndromes have in common? Two possibilities are low blood flows to the brain and low blood volume.

In this blog we cover several new studies on POTS while investigating the role brain-blood flows and low blood volume play in both disorders and conclude significant overlaps may exists between the two disorders.

Reduced blood flows to the brain sound pretty dire and the effects can be significant. Let’s see what research tells about blood flows to the brain in ME/CFS and POTS.


Natelson’s small but rigorous 2011 ME/CFS study found reduced absolute cerebral blood flows across nearly every region of the brain studied. Shungu found reduced blood flows in two areas on the brain in both ME/CFS patients and people with major depression. Other studies have had mixed findings but the improved technology used in the latest ME/CFS studies suggests the brain blood flow problem is a real one.

High rates of oxidative stress in the brain  and elsewhere may be one consequence of low blood volume

High rates of oxidative stress in the brain and elsewhere may be one consequence of low blood volume

Shungu’s findings of increased lactate and reduced glutathione in the brains of ME/CFS patients fit a scenario in which reduced blood flows (i.e. transient ischemia) to the brain causes increased oxidative stress which in turn knocks out the mitochondria. (Ischemia or low blood flows causes rapid increases in oxidative stress, which in turn can harm the mitochondria). Note that a similar explanation could apply to reduced oxygen delivery to the muscles in ME/CFS.

Postural Orthostatic Tachycardia Syndrome (POTS)

We may find a similar scenario in POTS.

A 2005 Mexican study and recently a Taiwanese study found that reduced blood flows to the brain were commonly associated with low blood volume and that greater reductions in blood volume were more likely to be found in people with POTS (excessive heart rate increases upon standing). This suggested that increased heart rates in orthostatic intolerance could be a function of low blood volume; i.e. the lower your blood volume is the more likely you are to have POTS.

People with POTS are unable to  recruit more oxygen to their brains  when  engaged in  cognitive tasks  while standing

People with POTS are unable to recruit more oxygen to their brains when engaged in cognitive tasks while standing

One might expect cognition to be affected by reduced brain blood flows and a study comparing POTS patients and healthy controls found just that. Just as exercise requires that more oxygen be sent to the muscles, thinking requires more oxygen (and blood flows) be sent to the brain.

Stewart’s inability to find any increase in cerebral blood flows in his ME/CFS/POTS patients when they were trying to think suggested their reduced cognitive functioning derived, at least in part, from the inability of the body to supply the brain with more blood when needed; his  POTS patients were going to have to do their cognitive tests without any increased oxygen.

The study suggested that problems with oxygen extraction were present, an intriguing finding given Vermoulen’s study suggesting that oxygen extraction in the muscles is limited in ME/CFS.

Exercise and Brain Blood Flows

We saw that POTS/ME/CFS patients failed to increase their brain blood flows during a thinking task (while tilted). A small 2008 study also found that oxygen delivery to the prefrontal cortex of ME/CFS patients brains was reduced but this time it occurred during exercise. The authors suggested this finding could help explain the exercise intolerance found in ME/CFS.

  • Conclusion:  Whether in POTS or ME/CFS studies are showing reduced blood flows to the brain are occurring during stressful situations (tilt table or exercise).

Low Blood Volume 

Now we look at the role low blood volume, whether in the brain, muscles or other parts of the body may play in POTS and ME/CFS.

A recent paper suggests that ischemic conditions at the carotid body may cause just about everything found those POTS patients who experience shortness of breath – a common symptom in ME/CFS.

Low blood  volume and oxygen levels  at the carotid  body could explain many  issues in POTS patients who  experience shortness of breath

Low blood volume and oxygen levels at the carotid body could explain many issues in POTS patients who experience shortness of breath

These researchers postulate that the CO2 driven breathing patterns, the sympathetic nervous system activation and the increased heart rate in these POTS patients are all triggered by low oxygen levels (i.e., low blood volume) at the carotid body. The carotid body consists of a collection of chemoreceptors in the arteries in the throat that assess gas levels in the blood.

It appears that an initial reduction in blood volume during standing in POTS induces these chemoreceptors to trigger breathing patterns which produce ischemia (reduced blood flows) in the brain). The brain ischemia then triggers the SNS to reduce blood vessel diameter – further impairing blood flows – and the tachycardia present in POTS.

Sympathetic Nervous System Trigger

Another study suggested that brain blood flow patterns may trigger SNS activity in POTS as well. The two sides of the brain should receive similar levels of oxygen but a Japanese study found that the left frontal cortex (LFC) of the brains of POTS patients received significantly less oxygen than the right frontal cortex.

To put it another way the Japanese researchers believe that the significant decrease in oxygenation found in the left frontal side of the brain has left the brain unbalanced, giving the right frontal cortex more say in how the body functions.

The greater activation of the right frontal cortex (RFC) was intriguing given its involvement in sympathetic nervous system functioning. The authors suggested that a relative over-activation of the RFC compared to the LFC could play a role in the increased heart rates found in POTS. (A similar type of unbalance is found in heart rate variability studies in ME/CFS).

It’s not clear if a similar problem occurs in ME/CFS but the evidence of increased sympathetic nervous system is clear and consistent. Note, though, that the parasympathetic nervous system, which is directed by the vagus nerve, is responsible for keeping the SNS under control.

Has the SNS gone crazy on its own or has a damaged vagus nerve simply failed to step up to the plate and check it? Some researchers believe all this sympathetic nervous system activity is more a sign of a damaged vagus nerve than any SNS dysfunction.

  • Conclusion – we have evidence that reduced blood flows up on standing could trigger chemoreceptor activity which begins a cascade which produces all the symptoms in some POTS patients, and evidence that decreased blood flows to one region of the brain could trigger the SNS activity that is apparently so damaging in this disorder.

 Chronic Fatigue Syndrome

Of course people with Chronic Fatigue Syndrome are frequently described as being a quart or so low in blood volume and blood volume enhancers are often helpful. Studies suggest the low blood volume found in ME/CFS is real.

Stewart asserted that low blood volume plays a key role in producing the reduced cardiac output seen in severely afflicted ME/CFS patients and Hurwitz’s large study agreed with that.

A 2002 study found that blood volumes were mildly lowered but were still significantly correlated with the reduced peak oxygen consumption found during exercise. It suggested that even mildly reduced blood volumes may have an exaggerated effect on exercise in ME/CFS. (Could the reduced oxygen extraction found in the muscles or the increased vasoconstriction found in POTS in the brain be causing this?)

Newton’s Apple – The Low Cerebral Blood Flows Begin in the Muscles

Although conventionally CFS has been considered to be a disease with primary CNS pathologies and secondary peripheral consequences, our results point to possible alternative disease mechanisms.It is possible that CFS is driven by a primary peripheral abnormality … where a compromised skeletal muscle cellular membrane function underpins the observed abnormalities. “ He et al. 2013

Newton, in fact, believes the muscles are the key. A recent Newton study found decreased cerebral blood flows and prolonged blood vessel constriction in the brain were associated with increased muscle pH.

The He-Newton paper suggested that muscle oxidation problems may be driving the low blood flow problems in the brain. In this scenario compromised muscle cell membranes that produce increased blood pH levels cause chemoreceptors to induce people with ME/CFS to hyperventilate. The hyperventilation drives blood oxygen concentrations up and causes the cerebral (brain) blood vessels to vasoconstrict (become smaller) thus reducing blood flows to the brain.


Low blood volume and low blood delivery to the brain appear to be common in both POT and ME/CFS.

 Researchers in both POTS and ME/CFS propose that chemoreceptor activation in response to altered blood gases is driving the reduced brain blood flows found in both disorders. Newton believes the problem starts in the muscles. Stewart et. al. If I’m reading them right believe low blood volume at the carotid body is the key.

It may be that your next bout of transient ischemia, which can show up as pain, pallor, tingling and other symptoms is simply the next part of your body you put under stress. Ischemia may be occurring in your muscles when you exercise, in your brain when you think hard and if  the Workwell researchers are right, in your lung muscles when you breathe hard.

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