Glial cells and plasmalogens – do they have a role in ME/CFS?

Several disease mechanisms have been proposed to explain the symptoms of ME/CFS, including immune abnormalities, inflammation of the central nervous system, and alterations in the mitochondria. However, it is still not clear whether and how these mechanisms may be connected.

Glial cells

An article published in 2022 proposed one theory that might provide a link. This theory suggests that glial cells – which are part of the central nervous system and are found in the brain – may have an abnormal response to stress in the body (for example, as a result of infection, or physical, mental or emotional exertion).

The article then goes on to say that this abnormal stress response might:

  • explain the key features of ME/CFS, including post exertional malaise and autonomic dysfunction; and
  • join together other proposed disease mechanisms for ME/CFS, specifically immune, metabolic and mitochondrial dysfunction.

This is not the first time glial cells have been highlighted as a potential mechanism in chronic illness. For example, a review funded by ME Research UK found that stress and poor sleep may lead to chronic pain through glial cell activation and inflammation in the brain.

Of particular interest, therefore, is a newly published article which builds on the existing theory of glial cell dysfunction by discussing the role of specific fat molecules called plasmalogens in ME/CFS, and how they could provide a potential treatment for symptoms.

What is a plasmalogen?

Plasmalogens are a type of fat molecule (phospholipid) in the body. They are structural components of cell membranes, act as antioxidants, and are involved in inflammatory and immune processes.  They are thought to protect cell membranes from damage through oxidative stress, where harmful molecules called free radicals can cause damage to the cells of the body.

Plasmalogens are thought to play a role in maintaining health across multiple levels in the body: body systems, cells of the body, and organelles within cells of the body (including mitochondria).

How could plasmalogens be involved in ME/CFS?

Reduced levels of plasmalogens have been seen in people with ME/CFS, and are thought to be associated with glial cell dysfunction and inflammation in the brain – as is the case for conditions such as Alzheimer’s disease.

Authors of the new article suggest that plasmalogen levels may be reduced in people with ME/CFS due to an increased state of oxidative stress causing damage to the plasmalogens themselves, and disrupting the cells that make them, called peroxisomes.

In addition to plasmalogen production, peroxisomes interact with mitochondria and play an important role in maintaining energy levels in the body. It is thought that disruption of peroxisome function may lead to fatigue, cognitive dysfunction and immune system exhaustion, all of which are key symptoms of ME/CFS.

Plasmalogen replacement therapy

The new article suggests that reduced plasmalogen levels may be an underlying biological feature of ME/CFS. A novel approach called plasmalogen replacement therapy – which works to restore plasmalogen levels in the hope of improving health outcomes – is therefore discussed.

As plasmalogen replacement therapy is new, there is very limited research available looking at the success of the technique. While there is some evidence suggesting that plasmalogen replacement therapy may improve health outcomes in both animal models (for example, mouse models of Alzheimer’s disease) and using human cell samples analysed in the laboratory (in vitro), there is very limited research in humans.


This new article discusses how glial cell dysfunction and inflammation in the brain may explain the symptoms seen in ME/CFS, and how they may be explained by reduced plasmalogen levels, and considers the potential for plasmalogen replacement therapy as a treatment for ME/CFS.

These are all potentially exciting ideas, but it is important to remember that they are still theories, rather than evidence from robust scientific tests. While the authors do discuss the theories in detail, and consider them alongside existing evidence, they are yet to be confirmed using thorough research methods.

There is no current research investigating the use of plasmalogen replacement therapy in ME/CFS, and much more work is needed to assess the validity, safety and usefulness of this therapy in humans. However, the article does raise the possibility that plasmalogen replacement therapy could be a valuable tool for treating the ME/CFS in the future.

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