HYPERMOBILITY & FATIGUE: THE HIDDEN ENERGY TAX

There is a quiet assumption built into the phrase mitochondria are the powerhouse of the cell.

It suggests something steady, reliable, almost automatic.

Feed the system. Make the energy. Move on.

Yet biology is rarely that simple.

Energy production is dynamic, responsive, and, in some bodies, far more complicated than expected.

Imagine the cell as a city, with mitochondria acting as its factories, converting incoming nutrients into ATP, the currency that funds nearly every action. In most cases, supply and demand stay in balance. Energy is produced, cellular byproducts are managed, and the city keeps moving.

Now shift the lens slightly.

In a hypermobile body, there may be another piece worth considering:

How much energy does it take just to maintain normal function?

Connective tissue, including collagen-rich structures like ligaments and tendons, contributes to the structural framework that helps stabilize our joints. When joints have more available movement, stability may require more active muscular control.

Posture may require constant, subtle adjustments.

Standing requires muscular control.

Sitting upright requires muscular control.

Moving through space requires the nervous system and muscles to continually coordinate where a joint is and where it is going next.

All of that requires energy.

This is what we like to think of as the energy tax.

To be clear, research has not demonstrated a specific mitochondrial “energy tax” in people with hypermobility. We use the term as a framework for thinking about something our patients describe often: when stability requires more active work, the baseline cost of moving through the world may feel higher.

And that brings us back to the mitochondria.

Energy production has a cost.

ATP production is not a perfectly clean process.

Mitochondrial energy metabolism is closely connected with the production and management of reactive oxygen species. In a balanced system, antioxidant defenses help keep these reactive molecules under control.

When that balance is disrupted, oxidative stress can occur.

Researchers have been interested in mitochondrial dysfunction as one potential contributor to fatigue for years. A review of the literature found associations between several markers of mitochondrial function and fatigue, while also emphasizing that the evidence is inconsistent and that fatigue itself is biologically complex.¹

Translation?

Fatigue is not simply a matter of “running out of energy.”

How energy is produced, utilized, and regulated may matter too.

And in hypermobility, we have another question to add:

What happens when the body may already be spending more energy on stability, autonomic regulation, pain, movement, and recovery?

That is where the energy tax becomes interesting.

Then there is folate

Another emerging piece of the hypermobility conversation involves folate metabolism.

Researchers have proposed a relationship between MTHFR gene variants, folate metabolism, and extracellular matrix function in hypermobility.

In a 2024 retrospective study of 157 patients evaluated in a U.S. hypermobility clinic, approximately 85% had at least one of two commonly studied MTHFR variants, C677T or A1298C.⁵

That finding is interesting.

It is not the same as saying MTHFR causes hypermobility.

These variants are common in the general population, the study examined patients from a single specialty clinic, and it did not include a matched control group. The researchers themselves describe folate-dependent hypermobility as a proposed mechanism requiring further investigation.

Their earlier work proposed that altered folate metabolism could influence methylation and extracellular matrix regulation.⁶

That opens another door.

Not an answer.

A door.

Because nutrient intake is only one part of cellular biology. Nutrients also have to be absorbed, metabolized, converted, and used within pathways that interact with cellular repair and tissue maintenance.

How much that contributes to fatigue in hypermobility?

We do not know yet.

But the intersection between metabolism and connective tissue biology is becoming increasingly interesting.

Now bring it back to the floppy body.

Connective tissue does not exist separately from metabolism.

Neither does the nervous system.

Neither does the cardiovascular system.

Neither do muscles.

This is where looking at fatigue through only one lens starts to fall apart.

A person with symptomatic hypermobility may be managing joint instability, increased muscular demand, pain, disrupted sleep, dysautonomia, gastrointestinal dysfunction, and other physiological stressors at the same time.

POTS and chronic fatigue, for example, are well-recognized alongside hypermobility disorders.⁴

So when a floppy friend says,

“I am exhausted, and I barely did anything today,”

the visible activity may not tell us very much about the actual physiological workload.

The body may have been working all day.

Stabilizing.

Compensating.

Regulating blood flow.

Processing sensory information.

Managing pain.

Maintaining posture.

Recovering.

That does not prove the mitochondria are failing.

It tells us that fatigue deserves a more interesting question than:

What did you do today?

Maybe the better question is:

What did your body have to do today?

This is why we like the idea of an energy tax.

Not as a diagnosis.

Not as a proven biochemical pathway.

And definitely not as another explanation that gets applied to every floppy body.

It is a framework.

A way of recognizing that the amount of work we can see from the outside may be very different from the amount of work happening underneath.

The phrase mitochondria are the powerhouse of the cell remains true.

It is just incomplete.

It tells us where much of our usable cellular energy comes from.

It does not tell us how complicated the demand side of the equation can become.

And in a hypermobile body, that may be one of the most important questions:

How much energy is being spent just keeping everything together?

Want to go down the rabbit hole?

1. Filler, K., Lyon, D., Bennett, J., McCain, N., Elswick, R., Lukkahatai, N., & Saligan, L. N. (2014). Association of mitochondrial dysfunction and fatigue: A review of the literature. BBA Clinical, 1, 12–23. https://doi.org/10.1016/j.bbacli.2014.04.001

2. Ngo, S. T., Steyn, F. J., & McCombe, P. A. (2022). Mitochondrial dysfunction in neurological disorders and fatigue. Frontiers in Neurology, 13, 860789. https://doi.org/10.3389/fneur.2022.860789

3. Malfait, F., Castori, M., Francomano, C. A., et al. (2020). The Ehlers-Danlos syndromes. Nature Reviews Disease Primers, 6(1), 64. https://doi.org/10.1038/s41572-020-0194-9

4. Roma, M., Marden, C. L., De Wandele, I., et al. (2021). Postural tachycardia syndrome and chronic fatigue in hypermobility disorders. Autonomic Neuroscience, 235, 102828.

5. Courseault, J., Umar, M., Bordnick, P., Simons, J., Volic, M., Stock, A., & Bix, G. (2024). Prevalence of MTHFR polymorphisms in patients with hypermobile Ehlers-Danlos syndrome and hypermobile spectrum disorders in a US hypermobility clinic. ACR Open Rheumatology, 6(7), 399–402. https://doi.org/10.1002/acr2.11667

6. Courseault, J., Kingry, C., Morrison, V., et al. (2023). Folate-dependent hypermobility syndrome: A proposed mechanism and diagnosis. Heliyon, 9(4), e15387. https://doi.org/10.1016/j.heliyon.2023.e15387

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About the Author

Allyson Barnes, PT, DPT is the founder of BAR Therapies and BAR Institute. She is a physical therapist specializing in the evaluation and treatment of symptomatic hypermobility and related connective tissue disorders. Through The Floppy Files, Allyson translates complex research into practical, evidence-informed education that helps patients, families, and healthcare professionals better understand hypermobility and participate more fully in everyday life. Learn more about Allyson, explore more articles in The Floppy Files, or browse continuing education courses through BAR Institute.

This content is intended for educational purposes only and is not medical advice. It is not a substitute for individualized evaluation, diagnosis, or treatment. Always consult your qualified healthcare provider regarding your specific health concerns.