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.

muscles fibromyalgia

Muscle studies have often found problems with the mitochondria and other factors in FM.

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.

mitochondria fibromyalgia

Higher oxygen levels in the muscles of FM patients during exercise meant their mitochondria weren’t taking up as much oxygen (and were producing less energy).

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 (!).

Could Core Issues in ME/CFS Be Cropping Up? Report from the IACFS/ME Conference #4

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.

Low Energy Production and Pain in Fibromyalgia – Is Your Microcirculation To Blame?

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

Mitochondrial Enhancers for Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Pt. I: D-Ribose, CoQ10 and PQQ

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.

Mitochondrial Enhancers for ME/CFS and Fibromyalgia Pt II: L-carnitine and Acetylcarnitine

The Gist

  • Exercise clinical trials now permeate fibromyalgia research and they indicate that moderate exercise is,  by and large, helpful. The other side of the coin, though, are muscle and mitochondrial studies that have wracked up a pretty impressive list of problems as well. 
  • The latest study made a very simple assertion – if mitochondria problems are indeed present in FM, then problems with oxygen delivery should show up as well. The mitochondria – the energy centers of the cells – rely on oxygen to produce energy. If they aren’t working well, then oxygen delivery should drop. 
  • The Spanish researchers examined the oxygen and hemoglobin levels in FM patients and healthy controls as they exercised their quadriceps muscle. As their mitochondria used up more oxygen, their muscle oxygen levels should drop, and the number of hemoglobin molecules – which carry oxygen to the muscles – should rise, as they pump more and more oxygen into the muscles.
  • In a clear sign that their mitochondria weren’t working as well and weren’t taking in as much oxygen as the healthy controls, the FM patients’ levels of muscle tissue oxygen weren’t as depleted, nor did they have as many oxygen-depleted hemoglobin cells as the healthy controls. 
  • Even more interesting, despite the fact that their muscles had undergone a considerable amount of stress, their oxygen levels, etc. simply didn’t change that much.  
  • A similar finding regarding the autonomic nervous system showed up in a fibromyalgia exercise study – it simply didn’t respond much. Plus, despite finding that exercise induced massive changes in metabolites in healthy controls, the metabolites in ME/CFS hardly responded at all. It’s as if the proper response to exercise has been shut off. 
  • Several studies that have found that energy-enhancing supplements such as CoQ10 and acetyl-carnitine may be as helpful as Lyrica and Cymbalta.
  • Interestingly, fatty acid problems – which play a key role in energy production – have recently shown up in FM, ME/CFS and long COVID. 
  • Still, exercise studies have generally been helpful in FM. How to parse those findings, and these, will be the subject of an upcoming blog. 

A recent review, while noting that larger studies involving hundreds of patients are needed, reported that a “positive causal relationship between the amount of CoQ10 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.


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