+100%-

This was a surprising study – not because of what was done – but because it hasn’t been done before. Since the two branches of the ANS (the sympathetic/parasympathetic) control the heart rate, heart rate variability (HRV) is a good way to assess at a basic level, the health of the ANS.

EKG

EKGs are used to measure HRV – which are low in ME/CFS, FM, and other diseases.

Low HRV – the kind typically found in fibromyalgia (FM) and chronic fatigue syndrome (ME/CFS) – suggests that the sympathetic nervous system (SNS) or fight/flight system has achieved dominance – leaving the parasympathetic nervous system (PNS) or rest/digest system in the dust.

The HRV test simply tracks a known pattern: our heart rate speeds up when we inhale and slows down when we exhale. The inhalation triggers SNS activation while the exhalation triggers the parasympathetic nervous system.

Since we both inhale and exhale more when we exercise, an exercise test provides a nice glimpse into how good our autonomic nervous system is at handling stress. A healthy, flexible cardiovascular system should be characterized by a heart that’s able to speed up and slow down rapidly during the long inhalations/exhalations done during exercise. While that test has been done in fibromyalgia, it hadn’t yet been done in ME/CFS.

The test’s simplicity can be deceiving. Low heart rate variability (HRV) – or overdominance of the sympathetic nervous system – has been associated with a host of negative outcomes, including an increased risk of early mortality and many types of cardiovascular disorders. The fact that low HRV has been found in so many disorders – from ME/CFS to FM to IBS to cardiovascular, respiratory, and gastrointestinal diseases and autoimmune conditions as well as anxiety and depression – suggests not being able to shift into the rest and digest stage is common in many chronic illnesses.

Quite a few different statistical assessments of heart rate variability (e.g., time domain, frequency domain, and non-linear analysis) can be made, and more are coming. The low-frequency LF/HF ratio is the most commonly used and is usually taken to reflect sympathetic/parasympathetic activity. (This isn’t completely accurate as the LF measure is affected by both sympathetic and parasympathetic activity – but appears to be good enough.)

Given the difficulty that people with ME/CFS have with exercise – and the role the autonomic nervous system (ANS) plays in delivering blood and oxygen to the muscles during exercise – one would think that an assessment of ANS functioning using HRV would have been one of the first studies run – but no, the 2021 Van Oosterwijck paper, “Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome“, from the Nijs group in Belgium is the first to focus on this issue.

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The Study

This 40-person (20 ME/CFS; 20 sedentary healthy controls) study put the participants through a submaximal exercise test that had the participants reach 75% of age-predicted maximum heart rate – a heart rate that is probably pushing ME/CFS patients’ hearts to the limit. The test, however, was quickly finished with the average time on the bike about 4 minutes. Heart rate, blood pressure, and various heart rate variability parameters were measured.

Results

The ME/CFS patients “demonstrate(d) a reduced functional capacity for exercise”. the authors

During Rest

As studies have often found, things were pretty normal at rest. Heart rate, blood pressure, and even HRV were all normal. One interesting exception occurred though. While LF/HF ratio (mostly sympathetic/parasympathetic) was normal – indicating that sympathetic dominance was not present – the values for each factor were lower than normal in the ME/CFS patients.

That suggested that the autonomic nervous system in the ME/CFS group might be underactive. While it might be responding in a balanced fashion, it may not have been responding enough. That, the authors asserted, potentially implicated something called the baroreflex.

The Baroreflex

This short exercise study suggested that the autonomic nervous system problems in ME/CFS really kick in during the post-exercise recovery period when the parasympathetic nervous system fails to kick in.

The baroreflex or baroreceptor reflex refers to a remarkable process whereby tiny receptors embedded in the major blood vessels of our hearts respond in fractions of a second to the artery wall as it changes shape (stretches) in response to very small changes in blood pressure. The baroreflex receptors respond by increasing the heart rate when blood pressure falls and decreasing it when it rises. This all happens in a fraction of a second.

Having these baroreceptors be a fraction off might not seem like a big deal, but in a rather dramatic demonstration of how interconnected everything is, it turns out that small problems with the baroreflex could cause a lot of mischief.

This is because the baroreflex is heavily tied into the stress response. Baroreceptor activation (which usually occurs when the blood pressure rises) inhibits the activity of the fight or flight, or sympathetic nervous system (SNS). It also appears to tamp down brain activity, and reduce pain levels and emotional volatility.

Studies suggest that having more sensitive cardiac baroreflex responses may result in increased pain inhibition, thus reducing pain. A less sensitive baroreflex – the kind that may have shown up in this study – could leave the stress response turned on – resulting in increased pain, central sensitization, etc. A 2017 exercise study by this same group, in fact, linked elevated blood pressure during the rest period to increased pain levels in ME/CFS. The authors concluded – as they did with this study – that parasympathetic “withdrawal” and baroreflex problems were present.

One fibromyalgia study found all three branches of the baroreflex response were inhibited – both at rest and when stressed. The results jived with a 2017 study which found that a reduced baroreflex response was associated with reduced quality of life in FM. Reduced baroreflex responses have also been found in adolescents and adults with ME/CFS and/or postural orthostatic tachycardia syndrome (POTS).

Are Balky Baroreceptors Causing Pain, Fatigue and Poor Sleep in Fibromyalgia, ME/CFS and POTS?

The fact that the signals the baroreceptors emit go through the brainstem (possible factor in ME/CFS/FM), activate motor neurons associated with the vagal nerve (another possible factor), and inhibit sympathetic nervous system neurons in the spinal cord (another possible factor) makes the whole process of baroreceptor activation all that more interesting. Could the baroreceptors have gotten whacked by something? Or is the signal not getting through?

During Exercise

A host of problems have been found during exercise in ME/CFS, but this study found few. Heart rate and blood pressure were normal and sympathetic nervous system domination – a typical finding since the SNS exists in part to enhance our ability to exercise – was found in both groups.

The baroreflex – which uses stretch receptors in the big blood vessels leading to the heart to adjust the heart rate – has been implicated in increased pain and other symptoms. Baroreflex problems have shown up in ME/CFS and in spades in fibromyalgia. (Image by Darrel Francis from Wikimedia Commons).

This wasn’t entirely unexpected. One-day exercise studies don’t pick up as many abnormalities as two-day exercise studies and the exercise period in this study was short and it didn’t measure the factors (VO2 max, anaerobic threshold, etc.) that are often abnormal in comprehensive exercise studies.

One finding did suggest that the sympathetic nervous system might not have kicked in in the ME/CFS patients as much as it did in the healthy controls. That could make sense. We know that when the heart is put under load during longer exercise tests, in a process called chronotropic incompetence, it appears to fade. The system then seems hyperactive and underpowered at the same time. It’s “on” much of the time, but when put under stress it quickly bottoms out.

After Exercise

It was in the 10-minute period after exercise that the autonomic nervous system abnormalities really appeared. Once the exercise has stopped, the parasympathetic nervous system should quickly put the brakes on the sympathetic nervous system and return the heart rate to normal.

Note what happened during the entire test period in ME/CFS. The heart rates of the ME/CFS patients were essentially the same as the healthy controls at rest, were a bit low (but not significantly low) during the exercise period, but were higher at the end of the recovery period.

In fact, by the end of the 10-minute recovery period, the heart rates of the healthy controls had returned to baseline but the heart rates of the ME/CFS patients remained significantly increased (p< .020) compared to baseline: they had still not recovered. That might seem an obvious result to anyone with ME/CFS who had attempted to exercise, or indeed anyone who has exerted too much in other ways. Long periods of apparently increased – or at least very noticeable – heartbeats can easily ensue.

A similar finding was also found in a recent fibromyalgia study which also found reduced HR recovery; i.e. abnormally increased heart rates at 30, 120, 180, 300, and 600 seconds after exercise. The increased heart rates after exercise provided an interesting contrast to the reduced heart rates the researchers found during exercise. Once again, we see a system that seems to be turned on but then bottoms out when stressed.

The study only assessed heart rate after the completion of exercise for ten minutes, but it turns out that a quick return to normal after exercise may be quite important. A 1999 study that followed almost 2,500 people found that a delayed decrease in the heart rate during the first minute after exercise was, surprise, surprise “a powerful predictor of overall mortality”.

The relative risk of dying in the participants (average age 57) doubled over the next six years in those with delayed heart rate recoveries. This didn’t mean they were likely to die, but their risk of dying had certainly increased. Since then, several studies have shown that quick heart rate recovery after exercise is a function of a healthy and responsive parasympathetic nervous system.

The authors of this study suggested that future ME/CFS studies examine the extent of the heart rate drop during the first minute after exercise in particular.

Heart rate variability (i.e. the sympathetic/parasympathetic ratio (fight-flight/rest-digest)) returned to normal in the ME/CFS patients during the ten-minute recovery period, but abnormalities suggested that all was not well.

The strange inhibited autonomic nervous system response occurred. While the HRV returned to normal, the reduced magnitude of both the SNS and PNS response suggested that a blunting of the autonomic nervous system had occurred.  Plus, it took longer for the ME/CFS patients’ HRV to return to normal (@ 8 minutes), and the sympathetic nervous system was more activated. All in all, the authors stated the results “demonstrate(d) a reduced functional capacity for exercise”.

Noting that it’s unclear how to use exercise to return the autonomic nervous system to normal in people with a “dysfunctional stress system”, they suggested that an HRV-informed training regimen be tried in ME/CFS. Decreased morning parasympathetic activity would indicate that more recovery time is needed. Increased parasympathetic activity, on the other hand, would suggest it’s time to get a bit more exercise.

exhaustion after exercise chronic fatigue syndrome

The healthy controls were able to recover quickly. The people with ME/CFS did not.

Conclusion

This Belgium study filled in a hole in the exercise saga in ME/CFS when it assessed what’s happening with the autonomic nervous system (heart rate, heart rate variability, and blood pressure) during and after exercise. The low heart rate variability found in MECFS, FM, and other diseases has been associated with the dominance of the fight/flight or sympathetic nervous system, and a withdrawal of the rest/digest or parasympathetic nervous system.

The Gist

  • This study, for the first time, assessed autonomic nervous system functioning measures such as heart rate variability (HRV) in ME/CFS before, during, and after a short submaximal exercise stressor.
  • Nothing abnormal was found during rest -before the short exercise period. During exercise, the autonomic nervous system measures assessed were mostly normal. However, the magnitude of the ME/CFS patients’ autonomic nervous system response appeared to be limited – something the authors proposed could be due to an impaired baroreflex.
  • The baroreflex refers to a reflex triggered by stretch receptors in the arterial walls of the blood vessels leading to the heart. Increased or decreased blood pressure that causes the arterial walls to stretch triggers the baroreflex to adjust the heart rate.
  • Because the baroreflex also inhibits the activity of the fight or flight, or sympathetic nervous system (SNS), regulates some brain activities and affects pain levels and emotional volatility, a balky baroreflex response could be quite problematic. Problems with the baroreflex have been found in spades in fibromyalgia and in postural orthostatic tachycardia syndrome (POTS) as well.
  • The major finding was that while the heart rates of the healthy controls returned to baseline during the 10-minute recovery period, they remained elevated in the ME/CFS patients. It also took longer for the sympathetic nervous system to calm down in the ME/CFS patients, and their autonomic nervous systems displayed the same kind of inhibition that was seen during the exercise period.
  • Some similar findings that have been found in fibromyalgia suggest that dysautonomia is common in that disease as well.
  • The authors reported that their results “demonstrate(d) a reduced functional capacity for exercise”.
  • This and other study’s results suggest that parasympathetic withdrawal is allowing the sympathetic nervous system or fight/flight system to remain active longer than normal in ME/CFS and fibromyalgia.

 

This study used a short submaximal exercise stressor in people with milder ME/CFS to probe these issues. As often happens, nothing abnormal was found at baseline. Even during exercise, the autonomic nervous system measures assessed were normal, with one exception: the magnitude of the autonomic nervous system response appeared to be limited – something the authors proposed could be due to an impaired baroreflex.

The baroreflex refers to a reflex triggered by stretch receptors in the arterial walls of the blood vessels leading to the heart. Increased or decreased blood pressure that causes the arterial walls to stretch triggers the baroreflex to adjust the heart rate.

Because the baroreflex also inhibits the activity of the fight or flight, or sympathetic nervous system (SNS), regulates some brain activities, and affects pain levels and emotional volatility, a balky baroreflex response could be quite problematic, and problems with the baroreflex have been found in spades in fibromyalgia.

The major finding in this study showed up in the 10-minute rest period. While the heart rates of the healthy controls returned to baseline, they remained elevated in the ME/CFS patients. It also took longer for the sympathetic nervous system dominance that accompanies exercise to calm down in the ME/CFS patients, and their autonomic nervous systems displayed the same kind of inhibition seen during exercise. Very short-term delays (within 1-minute) in heart rate recovery have been associated with an increased risk of mortality, and need to be assessed in ME/CFS and FM.

With the authors reporting that their results “demonstrate(d) a reduced functional capacity for exercise” in ME/CFS, we can add heart rate variability and autonomic nervous system tests to the invasive and non-invasive cardiopulmonary tests that have found the same in ME/CFS. Meanwhile, similar findings that have shown up in FM suggest that similar problems with autonomic nervous system functioning during exercise are present as well.

Once again, we see a withdrawal of the “rest and digest” or parasympathetic nervous system that allows the fight/flight or sympathetic nervous system to remain activated. Future blogs will search for ways to boost the rest and digest system.

While this study did not measure them it should be noted that very short-term (<1 min) reductions in heart rate recovery have been associated with increased mortality overall.  Those studies, though, remain to be done in these diseases.

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