Are Oxygen Depleted Muscles Causing Problems in Fibromyalgia?

by Cort Johnson Mar 26, 2023

Fibromyalgia (FM) is so weird. Exercise studies are just going gangbusters. If

researchers devoted as much time and money to attempting to understand what’s
going on in FM as they do on exercise studies we might have some real answers.
The outcome has been that exercise is now considered the “foundation” of
fibromyalgia treatment. There’s no doubt that moderate exercise can be helpful. On
the other hand, studies keep also finding problems with exercise and energy
production, some of which echo similar findings in chronic fatigue syndrome
(ME/CFS) and long COVID. Energy assessments in ME/CFS tend to use
cardiopulmonary exercise tests, while those in FM tend to muscle function.
The result is that many more muscle studies have been done in FM than in ME/CFS
and the results almost always point to muscle issues. Other studies suggest that
something has gone wrong with the mitochondria in fibromyalgia (FM). CoQ10 levels
may be low, autophagy may be impaired, a genetic impairment may exist, carnitine
deficiencies have been found, peroxisomal problems may exist, AMPK activation is
reduced, decreased muscle ATP problems have shown up, and more.
These studies tend to be small, focus on different aspects of the mitochondria, and
the results have often not been subject to validation, but the results have consistently
pointed to problems in energy production. Still, no consensus exists as to the extent
and role of mitochondrial problems in FM. Hopefully, at some point, this subject will be
taken seriously and a large, organized effort will be undertaken to understand the role
the mitochondria play in FM.
For now, we have another study. The latest one, “The Behavior of Muscle Oxygen
Saturation, Oxy and Deoxy Hemoglobin during a Fatigue Test in Fibromyalgia”, comes
from a familiar place for fibromyalgia research – Spain.
The study didn’t mess around. Noting that if the mitochondria really are impaired in
FM, the authors asserted that that impairment should show up in an exercise test –
which, as was noted earlier, has rarely been done in FM. Specifically, since the
mitochondria use oxygen for energy, a mitochondrial impairment should show up as
reduced oxygen consumption during an exercise test. If the mitochondria aren’t doing
well, they simply won’t be able to take up as much oxygen.
If this was chronic fatigue syndrome (ME/CFS), we would probably see a bicycle test,
but this being FM, the researchers asked the participants to exercise the biggest
muscle in the body – the quadriceps muscle in the thigh – while they monitored
energy parameters (oxygen saturation (SmO2), total hemoglobin (THb),
deoxygenated hemoglobin (HHb) and oxygenated hemoglobin (O2Hb)) using a
portable near-infrared spectroscopy (NIRS) device.
For instance, during exercise, our muscle oxygen saturation should decrease as the
oxygen in the muscles is taken up by the mitochondria and converted into energy.
Since hemoglobin carries oxygen to the cells, it makes sense that the levels of
deoxygenated hemoglobin should increase as the hemoglobin transfer more and
more oxygen to the tissues during exercise.
Poorly functioning mitochondria, then, should result in increased oxygen saturation,
increased oxygenated hemoglobin, and decreased deoxygenated hemoglobin during
exercise. That’s what they found in the FM patients vs the healthy controls – before,
during, and after the exercise bout.
The authors concluded “These findings could suggest that people with FM had a
significant impairment in the consumption of muscle oxygen.”
The really weird finding, though, was that while these measures changed over time as
the exercise progressed in the healthy controls, they remained the same in the FM
patients. It was as if their muscles simply didn’t respond to the exercise.
This strange passivity was echoed in an autonomic nervous system exercise study
which found that the ANS of FM patients reacted much less than healthy controls did.
Since the ANS regulates blood vessel functioning this could result in reduced blood
flows (and oxygen) to the muscles.
An even more bizarre finding showed up in a metabolomics ME/CFS study which
found an explosion of metabolite changes during and after exercise in the healthy
controls – but little evidence of anything happening in the ME/CFS patients (!).
The mitochondrial deficiencies found in FM, thus far, should result in increased fatigue
and increased lactate production – both of which have been found in FM (and, of
course, ME/CFS). Other FM studies have found more evidence of mitochondrial and
muscle problems, including lower levels of phosphocreatine (a high energy reserve in
the brain and muscles) and ATP, and dramatic rapid drops in pH in the muscles during
exertion – a sign that the aerobic metabolism we rely on for clean energy was quickly
getting tapped out.
Some of these studies go way back. Back in 2007, David Katz proposed that the pain
in FM is caused by “vasomotor dysregulation (blood vessel problems), and
vasoconstriction in muscle, leading to low-level ischemia (hypoperfusion) and its
metabolic sequelae”. That study was preceded by a 2004 study which found fewer
capillaries, fewer dilated capillaries and reduced peripheral blood flows in FM. That
suggested that perhaps the muscles weren’t getting proper blood flows.
Interestingly, Katz proposed that “vasodilatory influences, including physical activity,
relieve the pain of FMS by increasing muscle perfusion”. My experience in my case of
ME/CFS/FM, which tends more to the FM side of the spectrum, is that that is true –
that exercise does temporarily tend to reduce muscle pain – but too much exercise
(and it doesn’t take a lot) causes payback.
Add that to recent studies showing problems with the microcirculation and the
autonomic nervous system, and you wonder why mitochondrial problems aren’t a
bigger thing in FM.

Energy Enhancements Can Help

A rather startling randomized, placebo-controlled trial found that CoQ10
supplementation (300 mg/day) was more effective than Lyrica in reducing pain and
anxiety, as well as mitochondrial oxidative stress, and inflammation. Plus, it increased
antioxidant levels (glutathione levels superoxide dismutase (SOD)).
Another randomized, double-blind, placebo-controlled trial study found that 300
mg/day CoQ10 produced a reduction in pain, fatigue, and morning tiredness and
helped to recover antioxidant enzyme levels as well as mitochondrial productivity and
the all-important AMPK activity. Other studies have been done.
A recent review, while noting that larger studies involving hundreds of patients are
needed, reported that a “positive causal relationship between the amount of CoQ 10
supplementation and the relief of FM symptoms, the first and foremost being the
feeling of fatigue” was found.

Problems with carnitine metabolism – a key part of energy production involving fatty
acids – have also come to the fore in some case reports and studies. Acetyl-
carnitine’s analgesic or pain-relieving properties have lead some to suggest it may be
helpful in FM.  A 2007 study suggested that 1500 mg/day of acetyl-carnitine taken for
10 weeks might be helpful in reducing pain. Similarly, 1500 mg/day acetyl-carnitine
was found to be as effective as Cymbalta in reducing pain.
I don’t think anybody believes supplements like these are THE answer to FM or
ME/CFS or long COVID. They may help some people but if energy productions play a
role in these diseases more refined treatments are clearly needed.

Not Just Fibromyalgia

It’s notable, though, how some of these problems seem to pervade the
ME/CFS/FM/long COVID class of illnesses. Fatty acid and carnitine problems have
recently come to light in both long COVID and ME/CFS metabolomic studies.  A
recent long COVID study called for treatments focused on “restoring mitochondrial fat-
burning capacity”. 
While peroxisomes – the organelles involved in fatty acid metabolism – have recently
become a big deal in ME/CFS, it should be noted that peroxisomes were first
identified as a possible target in FM three years before they popped up in ME/CFS
and that two years ago a peroxisomal enhancer called pioglitazone significantly
relieved fatigue, improved muscle performance, reduced inflammatory cytokines and
enhanced antioxidant’s activity in an FM mouse model. Clearly more and more study
in energy production is needed in these diseases.
A strange yin/yang situation is occurring in FM. On the one hand, studies suggest that
energy production is impaired and mitochondrial and muscle problems are present.
On the other hand, exercise studies consistently show that exercise can be helpful.
Quality of life, physical functioning – even pain levels – have been improved.
An attempt to parse those two findings will be the subject of a future blog.

https://www.healthrising.org/blog/2023/03/26/oxygen-muscles-fibromyalgia/