The “Virtual Hypoxia” Hypothesis in ME/CFS

Researchers from the University of Vienna, in collaboration with the Karolinska University Hospital in Stockholm, Sweden, recently proposed that the brains of ME/CFS patients behave as if they are chronically oxygen-starved, even when oxygen is readily available.

They refer to this hypothesis as the “virtual hypoxia (low oxygen)” hypothesis.

We must first understand the relationship between energy production and oxygen levels before learning about their hypothesis in detail.

The cellular demand for oxygen is highest in the brain, which is only 2% of the body’s total mass yet consumes 20% of the body’s energy.

In general, this occurs using:

1. Glucose (dietary sugar)

2. Oxygen (O₂)

3. Mitochondria

These three ingredients enable your cells to efficiently produce adenosine triphosphate (ATP), the energy currency your enzymes use to supercharge catalytic reactions.

What happens when one of these ingredients is missing, like oxygen or the mitochondria?

Well, ATP is still produced in the absence of oxygen. It can also be made without functional mitochondria. However, this form of sugar metabolism is a very inefficient way of making ATP and results in the production of a metabolic waste product called lactate.

Okay, back to the “virtual hypoxia (low oxygen)” hypothesis.

If there is one buzzword every ME patient has heard along their patient journey, it’s the term mitochondrial dysfunction. This is (partly) what sparked the “virtual hypoxia (low oxygen)” hypothesis, which is the knowledge that:

1. The brain’s mitochondria consume a large amount of oxygen relative to other tissues in order to efficiently make energy.

2. The mitochondria in those with ME/CFS are dysfunctional.

Thus, the ME/CFS brain should behave as if they are chronically oxygen-starved, even when oxygen is readily available, due in part to mitochondrial dysfunction.

We mentioned that converting sugar into energy without oxygen is not only highly inefficient (producing less ATP) but also produces lactate as a metabolic byproduct.

In healthy people, spikes in lactate are transient and occur only during exercise due to the increased oxygen demand from the muscles. However, in those with ME, blood lactate levels correlate with the severity of post-exertional malaise (PEM) even at rest.

This increase in lactate occurs when ample oxygen and glucose are present, suggesting the culprit is mitochondrial dysfunction. However, it’s unknown where in the brain metabolism is dysregulated, if at all. Therefore, the purpose of this featured study is to determine:

1. Is it also true in the brains of ME patients at rest?

2. If so, what brain regions are most affected?

Okay, now we can move on to the study.