[CFS-L] Myalgic encephalopathy associated with cellular energy strain

[Dr. Marc-Alexander Fluks]

Source: Medical Xpress / University of Bergen
Date: August 23, 2021
URL:
https://medicalxpress.com/news/2021-08-myalgic-encephalopathy-cellular-energy-strain.html
Ref: https://www.jci.org/articles/view/150377


Myalgic encephalopathy associated with cellular energy strain
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Professor Karl Johan Tronstad at the University of Bergen has supervised
a study which found biochemical changes in the blood of ME patients. The
results support the hypothesis that the disease involves impaired
cellular energy metabolism.

ME (Myalgic Encephalopathy), also known as Chronic Fatigue Syndrome
(CFS), can be a debilitating disease. It frequently presents after an
infection, and key features are long-lasting fatigue and worsening of
symptoms after exertion. Symptoms include flu-like malaise, muscle and
joint pains, headaches, and cognitive problems.

One hypothesis suggests that ME is caused by an irregularity in the
patients' immune system. This assumption was supported by the
observations of oncologists Olav Mella and Oystein Fluge at Haukeland
University Hospital, who found that some cancer patients who also
suffered from ME, experienced an improvement in ME symptoms when they
were given immunosuppressive cancer treatment.

This gave Tronstad's group at the Department of biomedicine a basis to
explore the mechanistic connections in more detail, in close
collaboration with the clinical research group. At first, they found
evidence suggesting reduced function of a central enzyme in the cell's
energy metabolism called pyruvate dehydrogenase (PDH). They have now
performed a comprehensive study of the biochemical composition of the
blood. 'We compared blood samples from 83 patients and 35 healthy
controls, and measured over 1700 different compounds', says the
professor. 'We found significant differences in the levels of over 300
different substances, many of which were related to amino acid and lipid
metabolism.'


A defect in cellular energy supply

A common trait of the ME patients' blood samples was changes in energy
metabolites (molecules associated with cellular energy metabolism) which
would typically occur when the body is subjected to exertion or a
limited energy supply. Furthermore, the levels of certain metabolites
varied between subgroups of ME patients:'Changes that are common within
the patient group may be associated with a common disease mechanism. We
also identified metabolic signatures that point to different kinds of
metabolic adaptations among the patients, some of which appeared to
relate to the severity of the disease. Part of our work consisted of
grouping the patients based on the metabolic differences to explore
associations with clinical patient data', says Tronstad.

The findings by Tronstad and colleagues support a theory that ME is
associated with a persistent disturbance in the cells' ability to
satisfy energy needs.

According to Tronstad, some changes are expressed differently in
different patients because the body has distinct ways of dealing with
threatening situations. By ways of example, he mentions the body's
response to fasting: When you fast, you limit the normal supply of
nutrition to the cells, and the body will respond by supplying the cells
with alternative sources of energy via the blood. Such metabolic
compensatory mechanisms can be triggered by illness and may vary from
individual to individual. 'Among the ME patients, we found
characteristic features of two types of metabolic adaptations, one of
which was associated with a more severe symptomatology. Possible
contributing factors include diets, drugs, genetics, and lack of
physical activity', says Tronstad


Hypothesis: An autoimmune mechanism blocks the oxygen supply to the
cells during exertion

The findings are also compatible with the fact that symptoms often
intensify during and after physical activity. During physical activity,
the demand for energy supply to the cells increases. If the energy
supply is not working properly, it increases the strain on the cells.

The assumption that the changes in energy supply are caused by a flaw in
the immune system is only a hypothesis, but this too agrees with the
present findings: 'To be specific, an autoimmune mechanism could be
affecting the blood supply during exertion. When we are physically
active, our blood flow is adjusted to enable activity, but in ME
patients this autoregulation may be impaired', says Tronstad. 'As a
consequence, the cells receive too little oxygen. Our metabolic findings
are compatible with this kind of changes', says Tronstad, emphasizing
that this is a hypothesis that requires further research. Tronstad,
Fluge and Mella have recently published an article where they describe
their hypothesis in further detail:
https://www.jci.org/articles/view/150377


An indication of where to look for the mechanisms behind ME

Similar studies have been done before, but never of the scope and size
of this study; the scientist explains: 'Several, somewhat smaller
studies have shown singular differences between patients and healthy
controls. In this study, however, we observed a system in the metabolic
changes, which tells us more about the processes that may relate to key
ME symptoms'.

In other words, the scope of the study has enabled the researchers to
make assumptions on which changes may be associated with the trigger
mechanism, and which may be so-called 'secondary' consequences: 'For
those suffering from ME, this means that we now have a somewhat better
understanding of the disease, and the study provides possible
explanations for the differences in patient responses to various types
of symptomatic treatments or dietary changes,' says Tronstad.

In the long term, he also hopes that these findings can make it easier
to find biomarkers for the disease, and to find effective treatments and
eventually a cure. 'Today we have no established treatment for ME, and
we want to understand more of what happens in the bodies of ME patients.
If we know that the autoregulation of blood flow is involved in the
disease, we can search for markers and autoimmune mechanisms that are
specifically connected with the blood supply', says the professor.

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