+100%-

Check out Geoff’s Narrations

The GIST 

The Blog

 

Given how important exercise is to our long term health its no surprise that several exercise programs have been created. Simon Perikles is the latest one.

Given how important exercise is to our long term health, it’s no surprise that several exercise programs have been created. Simon Perikles’s is the latest one.

One of the more disturbing things from a long-term health perspective for people with diseases like chronic fatigue syndrome (ME/CFS) and long COVID is the difficulty and, oftentimes, inability to exercise. Given that, it’s not surprising many efforts have tried to find a way to do that.

THE GIST

  • One of the more disturbing things from a long-term health perspective for people with diseases like chronic fatigue syndrome (ME/CFS) and long COVID is the difficulty and, oftentimes, inability to exercise.
  • Given that, it’s not surprising several groups have tried to find a way to do that and we’ve come a long way from the blunt and unsophisticated graded exercise programs of the past. From Workwell’s precision oriented, heart rate-based approach to Putrino’s autonomic nervous system rehabilitation, we can now add an anaerobic exercise approach from Perikles Simon, a German exercise physiologist.
  • Simon came across his long-COVID patients when his lab was contacted by an insurance company that wanted to assess their ability to exercise and functional capacity. While Simon didn’t say so, the nature of their job and their early exposure to the full force of the coronavirus probably left them worse off than later ones. None of them were able to work.
    To say that he was impressed and shocked by his findings is probably to understate things. Simon reported that his group of long-COVID patients were “truly and severely physically affected” even 12 months later – despite being in “perfect organ health”.
  • Speaking about the “massive changes in the breathing physiology” he found in long COVID, he said, “we have never seen values like this before” and that their values of CO2 can get so low that you can’t produce them by purposefully hyperventilating – you would faint first.
  • Simon believes that the oxygenated arterial blood is not flowing correctly through the capillaries that provide blood to the muscles. This is-a situation that one typically begins to see in older people – and asserted that the people in his study had suddenly gone from middle-aged to 80. Once the breathing centers in the brain pick up the oxygen deficit, they cause the body to breathe more releasing too much CO2 and potentially causing many of the symptoms of ME/CFS.
  • The key theme of his anaerobic exercise plan is to exercise in very small chunks, and rest. When we exercise, our anaerobic exercise system kicks in first, and then after about 30 seconds, hands most of our energy production off to the aerobic energy system. It’s the anaerobic energy production that Perikles wants to focus on.
  • Simon suggests exercising for up to 30 seconds at a time – about the time the anaerobic energy system can supply energy without producing lactate. The idea is to exercise your muscles in ways that keep them from being oxygen-deprived, causing you to overbreathe and lose CO2. (He recommends the same for mental exertion. He believes too much stimuli, lights, sounds, mental activity can produce the same results.)
  • He often starts at 10-second intervals of standing – 10 seconds of sitting – and then adds 1 second a day. If you can get to 30 seconds without feeling breathless or that you are hyperventilating (taking deep rapid breaths), then you can try prodding your aerobic energy system a bit with 1 minute exercise then I minute rest, then 2 minutes – 2 minutes rest, then 4…
  • One key is to exercise different muscle groups. For instance, if you take dishes out of the washing machine – always use different muscles to do that – bend down (or pull up a chair) and take the dishes out for say, 30 seconds, then rest.
  • There are no hard and fast rules – just make sure that you get 30 seconds to a minute of rest in between sessions. (There’s no need to rest for more than a minute.) He noted that checking for increases in one’s pulse doesn’t always work because the pulse doesn’t rise for everyone.
  • Because overexertion can cause all sorts of symptoms, it’s helpful to keep a written journal of your symptoms so that you can tell when you go over. Most patients on the 30-second program notice a boost in cognitive functioning within 2 weeks. Noticeable physical improvement often takes months.
  • Simon acknowledged that his exercise program will only get many ME/CFS / long-COVID patients so far – but asserts it can help. He reported that at the beginning of the program, the nurse that had the capacity to work 0.5 hours a week had the capacity to work 5 hours a week at the end of it. That was not enough to resume her work but still a major improvement.
  • The Workwell Foundation uses exercise testing to determine the heart rates at which things go south (i.e. toxins start building up) during exercise. In this way, they can provide a more precision, tailored exercise program.
  • A case report found that a year of heart rate monitor use, deep breathing, flexibility and short-term endurance exercises, and consistent rest breaks one patient reported substantial improvements in general functioning and, importantly, some of her physiological measures notched upwards. She was not well but her long slide into disability had stopped and she had improved significantly.
  • David Putrino’s autonomic rehabilitation program emphasizes breathing, and a very slow ramp up of exercise using anaerobic exercise at first and, if the patient is able to tolerate them, eventually aerobic exercise activity. (See a Health Rising blog for more.)
  • While none of these programs promise a cure, it’s clear that they can improve fitness in some.
  • While we don’t know exactly what is causing these problems, it’s notable that problems with oxygen extraction and low CO2 levels have shown up repeatedly in the last five or so years in ME/CFS and now long COVID patients. They don’t affect everybody but do appear to affect a majority of patients and could play key roles in these diseases.

 

 

that, it’s not surprising several groups have tried to find a way to do that and we’ve come a long way from the blunt and unsophisticated graded exercise programs of the past. From Workwell’s precision oriented, heart rate-based approach to Putrino’s autonomic nervous system rehabilitation, we can now add an anaerobic exercise approach from Simon Perikles, a German exercise physiologist.

The Simon Approach 

(The material from the Simon section of the blog comes from Dr. Simon’s Vimeo presentation at 46:32 and the r/cfs superb overview on reddit)

Dr. Perikles Simon – About a year ago, Perikles Simon PhD, a well-published neurobiologist and exercise physiologist, and the head of the Division of Sports Medicine, Rehabilitation and Disease Prevention at the Johannes Gutenberg-University in Mainz, Germany, gave a talk at a long COVID at a conference put on by Mess Dusseldorf.

Most of Simon’s recent work has centered around professional athletes and he’s recently been exploring which blood-borne biomarkers could best explain an athlete’s training status. He came across his long-COVID patients when his lab was contacted by an insurance company that wanted to assess their ability to exercise and functional capacity. While Simon didn’t say so, the nature of their job and their early exposure to the full force of the coronavirus probably left them worse off than later ones. None of the patients in the cohort were able to work.

Strange Days

Dr. Simon is taking a different approach to long COVID than I’ve seen before. He’s focused on the levels of cell-free DNA (cfDNA) that gets released from cells when they are damaged (and from immune cells). Cell-free DNA levels explode in people with acute COVID (COVID-19). He believes they’re producing microclots that clog up the capillaries all over the body.

His research suggests that levels of cell-free DNA, while variable, correlate well with both COVID-19 severity, and with fatigue in healthy controls. His most recent study suggests that cell-free DNA (cfDNA) probably reflects the “primary muscle damage” that occurs during exercise rather than the secondary muscle damage that inflammation causes. Instead of inflammation, it appears to reflect a loss of muscle function. (Exercise always produce some damage – which our bodies are usually well-equipped to deal with.)

Exercise also increases the production of this factor dramatically but not nearly to the extent found in a COVID-19 infection. In healthy people, levels of cell-free DNA (cfDNA) rise 10-20 fold after exercise but typically fall within 90 minutes and then, interestingly, often drop below baseline. Exercise, as Dr. Perikles noted, is quite a stressor for the body, but in most people, it makes them stronger over time.

We are used to seeing chronic fatigue syndrome (ME/CFS) and long-COVID studies present bizarre and unexpected findings, and so it goes here: where we might have expected cfDNA  levels to explode after exercise in long COVID, smaller increases than normal were seen (!). Perikles didn’t explain that, but it perhaps it fits in with findings indicating that instead of producing a normal response to it, the bodies of people with ME/CFS just don’t respond much to it. Perikles did not explain what he thought was going on.

“We have never seen values like this before”

Simon next moved on to Inderjit Singh’s and David Systrom’s work at Yale and Harvard which showed that long-COVID patients had “decreased exercise capacity combined with exaggerated hyperventilatory response” during exercise. (Throughout the talk, Simon will note that similar findings show up in ME/CFS.)

Diaphragmatic breathing

Perikles said he had never seen readings like he saw with his long-COVID patients. (From John Pierce CCO via Wikimedia Commons)

To say that he was impressed and shocked by his findings is probably to understate things. Simon reported that his group of long-COVID patients were “truly and severely physically affected” even 12 months later – despite being in “perfect organ health”.

Speaking about the “massive changes in the breathing physiology” he found in long COVID, he said, “we have never seen values like this before” and that their values of CO2 can get so low that you can’t produce them by purposefully hyperventilating – you would faint first.

Simon explained that the oxygenated arterial blood did not appear to be flowing correctly through the capillaries – a situation that one typically begins to see in older people – and asserted that the people in his study had suddenly gone from middle-aged to 80. He talked about a former nurse whose exercise study indicated she has the capacity to work about 20 hours a week in a sitting position and 0.5 hours a week as a nurse.

Once the breathing centers in the brain pick up the oxygen deficit, they cause the body to breathe more. Simon is attempting to develop better technology to measure this situation but is confident this is a major contributor to long COVID and ME/CFS.

Simon’s Anaerobic Energy Program

Simon – who has helped develop exercise programs for several other diseases – has developed one for long COVID and ME/CFS. His statement that, “Many are not aware of the situation they are in”, was so reminiscent of what Staci Stevens at the Workwell Foundation has been saying for years.

The goal is to restore the ability of the circulatory system to get blood to the tissues. The key theme of his anaerobic exercise plan is to exercise in very small chunks, and rest. When we exercise, our anaerobic exercise system kicks in first, and then after about 30 seconds, hands most of our energy production off to the aerobic energy system. It’s the anaerobic energy production that Simon wants to focus on.

Simon suggests exercising for up to 30 seconds at a time – about the time the anaerobic energy system can supply energy without producing lactate. The idea is to exercise your muscles in ways that keep them from being oxygen-deprived, causing you to overbreathe and lose CO2. (He recommends the same for mental exertion. He believes too much stimuli, lights, sounds, mental activity can produce the same results.)

muscles

Perikles suggests exerting different muscle groups.

He often starts at 10-second intervals of standing – 10 seconds of sitting – and then adds 1 second a day. If you can get to 30 seconds without feeling breathless or that you are hyperventilating (taking deep rapid breaths), then you can try prodding your aerobic energy system a bit with 1 minute exercise then I minute rest, then 2 minutes – 2 minutes rest, then 4…

People who have trouble standing should try to stand for 30 seconds (or until you feel unwell and/or start hyperventilating (breathing deeper and faster), and then rest and repeat.

One key is to exercise different muscle groups. For instance, if you take dishes out of the washing machine – always use different muscles to do that – bend down (or pull up a chair) and take the dishes out for say, 30 seconds, then rest. Stairs are particularly difficult. He recommends taking 3 steps and resting.

There are no hard and fast rules – just make sure that you get 30 seconds to a minute of rest in between sessions. (There’s no need to rest for more than a minute.) He noted that checking for increases in one’s pulse doesn’t always work because the pulse doesn’t rise for everyone.

Because overexertion can cause all sorts of symptoms, it’s helpful to keep a written journal of your symptoms so that you can tell when you go over. Most patients on the 30-second program notice a boost in cognitive functioning within 2 weeks. Noticeable physical improvement often takes months.

Simon acknowledged that his exercise program will only get many ME/CFS / long-COVID patients so far – but asserts it can help.

He reported that at the beginning of the program, the nurse that had the capacity to work 0.5 hours a week had the capacity to work 5 hours a week at the end of it. That was not enough to resume her work but still a major improvement. Her lactate accumulation and heartbeat also went down over time.

He did mention a professional athlete, though, with severe enough long COVID that he was experiencing rapid heartbeats even when lying down. Very disciplined, he started with lying in bed and raising 1 arm. When he could handle that, he did 2 arms, and so on. He was back to perfect health in 6 months.

Apheresis?

If beta-adrenergic or ACE-2 autoantibodies are the culprit, it’s been thought that apheresis that targets them and filters them out could help. Citing a partner at a hospital though, who said that five treatments were needed to produce what appeared to be pretty modest results, he said the thought the autoantibodies were probably buried too deeply in the tissues for the aptamer to reach most of them. Perhaps repeated infusions could get rid of them, but he didn’t sound excited about that treatment.

He didn’t seem that excited about the autoimmunity approach – stating that if autoimmunity was the primary cause, he would have expected to see more young people get the disease.

Other ME/CFS and Long COVID “Exercise” Programs

Other “exercise” programs have shown up in ME/CFS and long COVID over time.

Workwell’s Approach

The exercise physiologists and physical therapists at the Workwell Foundation – one of whom has ME/CFS – have been working on rehabilitation programs for ME/CFS for a long time. Workwell’s approach is unique in that its ability to physiologically improve things in ME/CFS was documented in a case report. Workwell uses exercise testing to determine the heart rates at which things go south (i.e. toxins start building up) during exercise. In this way, they can provide a more precision, tailored exercise program.

In this case, the 28 year-old was getting steadily worse and was having trouble doing her household chores. Every time her heart rate hit a preset number, she was to lie down. She was also provided with flexibility, resistance, and short-term endurance exercises. Because the muscles moving the lungs use up a lot of energy and can quickly become exhausted in ME/CFS, diaphragmatic breathing was encouraged and gentle upper body stretches were included to reduce pain levels. The resistance exercises were done while lying down. Yoga, meditation, and other disciplines that focus on breathing, as well, to slowly drop the heart rate, reduce stress, and reduce pain were recommended.

After a year of heart rate monitor use, deep breathing, flexibility and short-term endurance exercises, the patient reported substantial improvements in general functioning and, importantly, some of her physiological measures notched upwards.

Parts of her body began to respond more normally to exercise. During an exercise test, her respiratory rate (the number of breaths she took), the amount of oxygen she inhaled, her heart rate, and her blood pressure went up dramatically.

Her aerobic energy production system was still broken – but her ability to use her anaerobic energy production system to produce energy increased significantly. She was able to be active at a significantly higher level (about 20 heartbeats higher) without triggering a negative response. Even though she was still limited aerobically, it was as if her cardiovascular system had emerged from a state of partial hibernation.

Heart Rate Monitor Based Exercise Program Improves Heart Functioning in Chronic Fatigue Syndrome (ME/CFS)

The Workwell Foundation provides disability testing for ME/CFS and long COVID and provides many resources on exercise and rehabilitation.

Putrino’s Autonomic Nervous System Rehabilitation Program for Long COVID and ME/CFS

Putrino’s program is the only one put to the test in a study. Like Workwell, Putrino puts an emphasis on breathwork but to a greater extent – using the Stasis program to first get the breath under control. Similar to Perikles, Putrino limits exercise (done in the supine position) to 30 seconds with rest periods in between.

After 4-6 weeks – if the patient is able to – isometric exercises begin. If the patient is able to tolerate those, then aerobic exercises and walking begin at low levels. The goal is to be able to complete a 6-minute walk test (6MWT) without increased symptoms. If that goes well, then a 3-month-long progressive aerobic exercise program on a bicycle is next.

Breathing

Both Putrino’s and Workwell’s programs employ deep breathing techniques.

Forty percent of the people in the study were able to complete the full program. Overall, the participants went from feeling “very fatigued” to “moderately fatigued”.

Putrino’s Autonomic Rehabilitation Program for Long COVID: Does it Work?

Conclusion

None of these programs state they can cure ME/CFS, and all recognize that (with some exceptions) a substantial block to producing energy remains. Instead, they try to work within the limitations imposed by these diseases in hopes of increasing one’s tolerance of exertion. All three programs call for short exercise periods followed by rest. Perikles adds the interesting idea of being aware of exercising different muscle groups. Workwell and Putrino both include breathing exercises. Workwell – using the results from exercise tests – takes a more personalized approach. While these programs do not promise a cure, it’s clear that they can improve fitness in some.

Getting Closer? The Breathing / Oxygen Extraction Problem in ME/CFS and Long COVID

But what is causing these exercise problems? Two themes have cropped up recently: problems with extracting oxygen from the blood and getting it into the muscles; and breathing patterns that reduce CO2 levels.

Simon is only the latest researcher to glom onto the problem that low CO2 level and problems getting oxygen into the tissues may be playing a major role in these diseases. Note in the review below that no one finding can explain what’s going on in every ME/CFS and long-COVID patient – a mixture of problems exist. That said, low CO2 levels and problems with oxygen extraction are showing up again and again in a significant proportion of people with these diseases.

The first person to study low CO2 levels in ME/CFS, Benjamin Natelson was way ahead of the crowd when, in 2006, he found evidence of hypocapnia in 21% of people with ME/CFS. It took the field years to catch up, but eventually it did. In a 2022 follow-up study, Natelson found that 60% of people with ME/CFS exhibited hypocapnia and hyperpnea – deeper than normal breathing upon standing – and called the condition POSH (postural orthostatic syndrome of hypocapnia).

Move Over POTS – Hypocapnia May be a Bigger Deal in ME/CFS

  • Check out two simple at-home tests to see if you are hyperventilating or if you have “POSH”: postural orthostatic hypocapnia syndrome; i.e. low CO2 levels upon standing.

Systrom’s invasive exercise studies found that 45% of patients had low oxygen extraction that was probably produced by hyperventilation and/or mitochondrial issues. Another large group demonstrated hyperventilation without problems with oxygen extraction. Fifteen percent of the group were simply mysteries.

Poor Oxygen Extraction is Contributing to Exercise Intolerance in Chronic Fatigue Syndrome (ME/CFS)

 

In a large study Vermeulen reported that low oxygen uptake by muscle cells caused exercise intolerance in a majority of ME/CFS patients. In a very large study, Van Campen et Al. found evidence of hypocapnia during a tilt table test in 80% of ME/CFS patients but concluded that it did not play a role in the reduced blood flows to the brain that the group has repeatedly found. (They believed the poor oxygen extraction did.)

The largest exercise study done to date (n=413) – the Cook/CDC study, which did the deepest dive into breathing yet in ME/CFS – found that people with ME/CFS were breathing more deeply and slowly during exercise, presumably in an attempt to get more oxygen into the muscles. Cook did not find increased lactate levels. Cook believed that oxygen extraction problems were probably key, though, and said he’d wished he could have done every mitochondrial test possible.

A Gas Exchange Disease? Huge CDC Exercise Study Puts New Slant on ME/CFS

Natelson recently showed up again (with Mancini) in a long-COVID study of people with shortness of breath. Almost 90% exhibited, in one form or another, strange breathing patterns (dysfunctional breathing) that got worse as the exercise session went on. Mancini and Natelson commonly found hypocapnia (low CO2 levels), and/or an excessive ventilatory response to exercise (elevated VE/VCO2 slope). In both cases, they were moving more air than was necessary.

Uneasy Breaths: Strange Breathing Patterns in Long COVID May Contribute to Exercise Intolerance

 

Wust’s recent muscle biopsy long-COVID study also found evidence of oxygen extraction issues and hypocapnia. Those features were paired with multiple findings indicating that the people with long COVID were depending more on anaerobic energy production. A recent fibromyalgia study found evidence of hypocapnia in about a third of FM patients.

Exercise Causes Muscle Damage and Energy Depletion in Long COVID

Problems with oxygen extraction (i.e. problems getting oxygen from the blood into the tissues) has become a key theme. Why that’s happening is unclear but could include microclots that block the flow of blood, small fiber neuropathies that shunt blood away from the capillaries, mitochondrial problems that prevent the oxygen uptake from the blood, damage to the microcirculation, and probably others.

The promising thing is that these problems are showing up consistently. What we above all want in these fields are consistent findings that researcher then dig more deeply into thus getting us closer to answers.

 

A BIG thanks to the 320 people who helped make Health Rising's fundraising drive a success!

Stay Up to Date with ME/CFS, Long COVID and Fibromyalgia News

Get Health Rising's free blogs featuring the latest findings and treatment options for the ME/CFS, long COVID, fibromyalgia and complex chronic disease communities. 

Thanks for subscribing! :)

Pin It on Pinterest

Share This