Postural orthostatic tachycardia syndrome (POTS) has always been thought to be the big deal regarding orthostatic intolerance (increased symptoms while standing or sitting) in chronic fatigue syndrome (ME/CFS).

respiratory system chronic fatigue syndrome

Something is definitely off in the respiratory systems of quite a few people with ME/CFS.

That may be changing with a recent study, “Physiological assessment of orthostatic intolerance in chronic fatigue syndrome“, from Dr. Benjamin Natelson MD at the Icahn School of Medicine at Mount Sinai, and Elizabeth Unger of the Centers for Disease Control and Prevention (CDC). One had the feeling that Natelson – one of the first to uncover hypocapnia in ME/CFS – has been thinking the condition (low carbon dioxide levels in the breath) has not been given its proper due. If so, he’s probably right.

It’s not that it hasn’t been popping up – it has been. Systrom has found it in his invasive exercise studies, the Visser team found it during tilt table testing, and Naschitz also found it in his exciting run of ME/CFS/FM Israeli studies fifteen years ago. (Naschitz described it as “common” in fibromyalgia.). I imagine that name recognition is pretty low, though.

Hypocapnia has never been found in everyone with ME/CFS/FM, but it appears to be present in a substantial subset. Natelson and Mancini also found it during exercise testing, and Novak found it during tilt-table testing in people with long COVID.

The Study

The Natelson/Unger study brought something new to the game: unlike the Lee-Bateman study of two years ago, it also measured the incidence of hypocapnia.

These studies findings were boosted by the fact that Natelson tested each of the 63 ME/CFS patients in the study three times over a three-year period using the NASA Lean Test.

He measured respiration, heart rate, blood pressure, and carbon dioxide levels (eTCO2) twice while the person lay supine, and then once a minute at they remained standing while leaning against the wall.

Hypocapnia was defined as having an eTCO2≤ 32 mmHg. (Since normal eTCO2 is 40mmHg, that drop – 20% – is pretty severe.) Postural orthostatic tachycardia syndrome, or POTS, was defined as a heart rate increase ≥ 30 beats per minute (BPM) during the lean, and orthostatic hypotension (OH) was defined as a drop of systolic pressure ≥ 20 mmHg from baseline levels during the lean. Tachypnea was defined as a respiratory rate of 20 or higher breaths per minute—either while lying supine or while leaning.

A Critical Test

“We recommend that all ME/CFS and Fibromyalgia patients have a NASA 10-minute Lean Test to assess for orthostatic intolerance.” The Bateman Horne Center

The NASA Lean Test constitutes a potential breakthrough for ME/CFS, FM, POTS and long-COVID patients because it provides an easy way to diagnose orthostatic intolerance – something many doctors know little about – and quickly potentially provides a biological abnormality for the doctor.

No need to somehow find a tilt table near you – at its most basic, the test simply requires an exam table, a pulse oximeter (placed on one hand), a blood pressure cuff (placed on the opposite arm), and about 20 minutes.

First, the person rests lying down for 10 minutes, then she/he stands up, and with her/his heels 6-8 inches from the wall, and shoulder blades touching it, stays there for ten minutes (or until it’s clear they have OI). All the while, heart rate, blood pressure and symptoms are recorded.

The conclusions of the Lee-Bateman NASA Lean ME/CFS study were right in line with what we knew about the incidence of orthostatic intolerance in ME/CFS: it mostly occurred in the form of postural orthostatic tachycardia syndrome (POTS) (@40% of patients).

NASA Lean Test: An Easy Way to Diagnose Orthostatic Intolerance in ME/CFS, Fibromyalgia and POTS

A POSH (Postural Orthostatic Syndrome of Hypocapnia) Disease

As was noted earlier, the Natelson/Unger study was different in that it measured end-tidal CO2 and looked to see if low CO2 levels (hypocapnia) were present.

About 60% of the group had at least one abnormality, and 80% of the time that abnormality was POSH. Eleven people even exhibited POSH while lying down. POSH is often associated with fast breathing (tachypnea) or fast and deep breathing (hyperventilation), but this was not the case in this study. Instead, Natelson found his patients experienced hyperpnea, or deeper than normal breathing. (Other studies have found hyperventilation.)

Hyperpnea often occurs in a response to increased metabolic demand; i.e. during exercise, when our cells need more oxygen. Systrom has found that people with ME/CFS hyperventilate (breathe deeply/rapidly) – perhaps in an attempt to get more oxygen into their mitochondria – during exercise.

Although the authors didn’t mention it, one wonders if an oxygen deficit in the mitochondria, even at rest, could be triggering deeper breaths in some people with ME/CFS.

Low CO2 levels hypocapnia

CO2 is often thought of as a toxic byproduct of energy production, but low levels of CO2 can cause problems.

The sympathetic nervous system activation we see in ME/CFS/FM and long COVID could also potentially be contributing to the hyperpnea and/or hyperventilation found in ME/CFS. Conversely, because it appears that overbreathing can trigger sympathetic nervous system activation, achieving a healthier breathing pattern might be able to help tamp down the fight/flight system.

Overbreathing/hyperpnea/hyperventilation (all cause similar symptoms, and all produce low CO2 levels or hypocapnia) can produce symptoms such as dizziness or lightheadedness, shortness of breath, abdominal bloating and belching, fatigue, feeling weak, cognitive and sleep problems, numbness and tingling sensations, muscle spasms, chest pain, and palpitations.

Interestingly, a sudden onset of the illness, probably an infectious event, was significantly more common among the patients who demonstrated some abnormality.


Hypocapnia refers to low CO2 levels in the breath/blood caused by overbreathing e.g. hyperpnea (deepened breathing), tachypnea (rapid breathing), or hyperventilation (deep and rapid breathing).

Normal breathing is actually “small and light” and is barely perceptible. Compare the 10-12 breaths/min in normal breathing to the over 18 breaths/min in a person with hypocapnia. People with hypocapnia often move 2/3rds more breath in and out of their lungs than people normally do (10 L/min to 6 L/min).

Whatever the problem (hyperpnea – deeper than normal breaths; tachypnea – more rapid than normal breaths, or both) the problem is the excessive movement of air out of the body. (This is presumably why  the slow and deep breathing found in some yoga practices does not appear to be a problem.)

Doctors are generally taught that hypocapnia in an otherwise healthy person is a sign of anxiety, but the Generalized Anxiety Disorder 7-item questionnaire given didn’t indicate that the patients with hypocapnia were more anxious than the patients without it.

New Forms of Orthostatic Intolerance Popping Up

Peter Novak MD PhD

Peter Novak, MD, PhD, has been making the invisible visible.

Peter Novak, a board-certified neurologist, and autonomic nervous system specialist at Brigham and Women’s Hospital in Harvard, is right in the middle of the ME/CFS/POTS/Lyme/Long-COVID soup. He’s become something of a specialist in making the invisible visible and uncovering new forms of orthostatic intolerance.

After linking hypocapnia to reduced blood flows to the brain in his own strange group of patients, he called the new condition “hypocapnic cerebral hypoperfusion”. Like his colleague David Systrom, Novak was being handed patients who just didn’t fit the mold. In Novak’s case, he was getting patients who had all the symptoms of POTS but who didn’t experience heart racing upon standing.

Novak had a long list of possible causes (baroreceptor problems interfering with “respiratory drive”, compensation for metabolic acidosis, orthostatic ventilation-perfusion mismatch, problems with the respiratory centers in the brain), and is digging deeper into this condition.

Hypocapnic Cerebral Hypoperfusion: New Kind of Orthostatic Intolerance Points to Key Factor in ME/CFS and Others

The Gist

  • This is the first of a series of blogs on breathing and ME/CFS/FM and long COVID.
  • Dr. Natelson did the NASA Lean Test on people with ME/CFS three times over three years. He tested heart rate, blood pressure, and CO2 levels.
  • Contrary to perceived wisdom, Natelson found that hypocapnia (low CO2 levels) was the most prevalent orthostatic abnormality found. It was far more prevalent, for instance, than postural orthostatic tachycardia syndrome (POTS). Hypocapnia was even found in some people when they were lying down.
  • Hypocapnia is often a result of hyperventilation, which is characterized by rapid and deep breathing. Natelson found little evidence of rapid breathing; instead, he consistently found deeper than normal breathing. Natelson et al. called the condition POSH (postural orthostatic syndrome of hypocapnia).
  • We breathe more rapidly and deeply to get more oxygen to our muscles, and to remove CO2 from our blood, when we exercise. Exercise, however, was not a factor in this study.
  • Normal breathing is light breathing; it’s barely perceptible.
  • Other forms of orthostatic intolerance have recently been uncovered by Peter Novak MD, PhD of Harvard. Novak found hypocapnia was linked to low brain blood flows in a condition he called hypocapnic cerebral hypoperfusion.
  • Novak also uncovered a condition similar to what the Visser team has found in ME/CFS. In orthostatic cerebral  hypoperfusion syndrome (OCHOS), low brain blood flows are found in the absence of increased hearts rates or drops in blood pressure.
  • A long list of possible causes (baroreceptor problems interfering with “respiratory drive”, compensation for metabolic acidosis, orthostatic ventilation-perfusion mismatch, problems with the respiratory centers in the brain) may be responsible for these conditions.

Novak was also the first to identify something called orthostatic cerebral hypoperfusion syndrome (OCHOS). OCHOS is potentially particularly significant for ME/CFS because it may be the most common orthostatic disorder found in the disease.

OCHOS occurs when someone has reduced blood flows to the brain in the absence of any other identifying characteristics; i.e. no increased heart rates (POTS), no decreases in blood pressure (orthostatic hypotension), no heart issues – just dizziness upon standing – which has surely got many of us of a psych label.

Novak’s findings seem very similar to what the Visser/Van Campen/Rowe team found when they used a new, more accurate technique to assess blood flows in ME/CFS.

Novak believes that a reduction of blood flows to the brain is a core characteristic of all forms of orthostatic intolerance. Given the Visser team’s finding that everyone with ME/CFS also exhibits reduced blood flows to the brain, ME/CFS must be considered, among other things, an orthostatic intolerance disorder.

Novak also found that orthostatic intolerance, dysautonomia, and small fiber neuropathy were common in long COVID, and was the first one to identify small fiber neuropathy in post-treatment Lyme disease. In short, we’re lucky to have this skilled and respected (he’s the chief of the Division of Autonomic Neurology at Brigham) researcher focused on these areas of concern in ME/CFS/FM/POTS and long COVID.

Treatment Possibilities

Treatment Takeaways

Treatment possibilities include:

  • Increasing blood volume by using oral rehydration salts, and compression hose
  • Having respiratory therapists use biofeedback techniques to try to reduce the depth of breathing.
  • Abdominal breathing (done slowly), breathing through pursed lips, meditation, mindfulness, relaxation exercises are recommended. We’ll check out more breathing options in this series.
  • Check out how to do an in-home test for hypocapnic hyperventilation –  A Home Postural Hypocapnic Hyperventilation Test for Chronic Fatigue Syndrome and Fibromyalgia

The authors of this paper suggested that hypovolemia, or low blood volume, could be responsible for altering the ratio between ventilation/perfusion. They suggested increasing blood volume by using oral rehydration salts, and compression hose could help.

The authors also suggested having respiratory therapists use biofeedback techniques to try to reduce the depth of breathing.

Deep breathing exercises are not suggested in hypocapnia unless they’re done slowly (Pranayama). Otherwise, abdominal breathing, breathing through pursed lips, meditation, mindfulness, relaxation exercises are recommended. We’ll check out more breathing exercises in this series.

The Natelson Files:


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