The Confounding Impact of Post Exertional Malaise Part III - genes, mitchondria, autoimmunity, oh my!

Note: This is a Part Three of a blog about Post Exertional Malaise (PEM).  Read parts one and two to catch up. 

In the first two posts of this series, I wrote about my personal experience with Post Exertional Malaise and what was known about it.  Since then, a lot more information is available thanks to increased visibility, research studies, and healthcare system support.  This post is a deeper dive on mechanisms of Post Exertional Malaise, and the next post will be what the heck to do about it. 

To review, Post Exertional Malaise (PEM), according to the CDC is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks.

Yes, after exercise most normal people will feel tired, sore, lightheaded, or foggy, and then recover within a day or so.  People with PEM do not recover so quickly, and remain unwell for days, weeks, or months.  People with PEM will also have symptom severity which supersedes the precipitating event -- even small amounts of exercise can cause it. Instead of exercise helping a person build fitness, it results in the person relapsing to below their current fitness baseline.  

ON TOP OF THAT,  is it's not just physical exertion either -- Social, cognitive, or emotional efforts will also trigger PEM.  So if a person with PEM is trying to balance work, family life, and fitness, it often results in catastrophic failure with bed bound days or even hospital visits.  If you are a person with PEM, you are often frustrated and scared of your own body or any type of challenge.  It's a very tough way to live:  

The  exact causes of Post Exertional Malaise are unknown. It is associated with Chronic Fatigue/Myalgic Encaphilitis, Long COVID, Multiple Sclerosis, Fibromyalgia, Irritable Bowel Syndrome, and more.  There are several theories researchers are currently studying: 

Autoimmune: Often Post Exertional Malaise occurs in people with post viral illness or other autoimmune issues.  A theory of PEM gaining wide acceptance is this is another type of autoimmune dysfunction.  Most people, once recovered from an illness, have an "all clear" signal from their immune system and they return to a relatively non-reactive baseline.  However for some people, their immune systems continue to be on guard and produce a variety of antibodies for protection.  Some of these antibodies are known to target enzymes responsible for energy production.  This means the body becomes more sensitive to stress (it triggers more antibody release) and also doesn't recover well from stress when it occurs (the obstruction of energy production in the body). 

**Side note -- For people with Long COVID the presence of viral remnants in areas such as the GI, meninges, and bone marrow is well established.  The presence of these remnants is plausible enough to trigger these autoimmune responses. 

Decreased metabolism of oxygen:  Our bodies have trillions of cells, and within each little cell are numerous engines called the mitochondria.  They take oxygen and turn it into energy for our body.  Studies of people with Long COVID and ME/CFS show higher amounts of lactic acid in their bloodstream with exertion than a normal person.  Because mitochondria use lactic acid (in part), this is a sign they are not able to do their job of turning oxygen into energy.  This dysfunction would have a profound effect on all organ systems, especially the musculoskeletal, cardiovascular, and brain/nervous systems. 

Genetic Phenotype: Some people may be born with a propensity to developing PEM.  These are the same folks with histories of orthostatic intolerance, pain conditions, digestive dysfunction, sensory disorders, and fatigue.  Perhaps the propensity toward developing PEM has always been there, and then a viral illness or major life event triggers its full blown expression.  I personally relate quite a bit to this explanation.  And you may find this resonates with my blog post about women being predisposed to autoimmune conditions.

If you have a science based mind, you probably concluded from the above the cause of PEM is likely a combination of all three theories.  And if you are thinking that, I absolutely agree with you and so do many clinicians and researchers!

Phew!  I know I need a brain break after typing that out.  Full disclosure, to manage my own PEM this blog post has taken me over a week to do in small bits of time, resting when needed.  Please stay tuned for what to do about this confounding condition! 

Nerdy research articles you can read about PEM, which informed this blog post: 

Chronic Fatigue Exhibits Heterogeneous Autoimmunity Characteristics Which Reflect Etiology https://pmc.ncbi.nlm.nih.gov/articles/PMC9231045/ 

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome
https://www.nature.com/articles/s41598-019-55473-4

Epidemiological and clinical factors associated with post-exertional malaise severity in patients with myalgic encephalomyelitis/chronic fatigue syndrome
https://rdcu.be/d0MmJ

Chronic fatigue syndrome and mitochondrial dysfunction
https://pmc.ncbi.nlm.nih.gov/articles/PMC2680051/

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00229/full

Post-Exertional Malaise May Be Related to Central Blood Pressure, Sympathetic Activity and Mental Fatigue in Chronic Fatigue Syndrome Patients
https://pmc.ncbi.nlm.nih.gov/articles/PMC8198768/

What is Post-Exertional Malaise and how can it best be managed? 
https://meassociation.org.uk/medical-matters/items/symptoms-post-exertional-malaise-pem/