“Bad Energy” is Core Problem in Fibromyalgia and CFS

Study Suggests “Bad Energy” is Core Problem in Fibromyalgia and Chronic Fatigue Syndrome (ME/CFS) – Health Rising – by Cort Johnson | May 31, 2017

Lactate has become a big deal in both chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM).  A by-product of anaerobic energy metabolism, lactate ordinarily gets pumped out of our cells in large amounts during exertion.

The lactate findings suggest that the energy needs of ME/CFS/FM patients are largely being addressed by glycolysis or anaerobic energy production.

Anaerobic energy production plays an important role in energy production, but when aerobic energy production is not available and it becomes the major source of energy it produces metabolites that produce the burning muscles, fatigue and other symptoms we associate with over-exercise. 

We mostly focus on lactate in the muscles and blood, but high lactate levels have also been found in the brains of people with chronic fatigue syndrome (ME/CFS).

Over the past ten years Dr. Shungu and Dr. Natelson have documented large lactate increases in the ventricles in the brains of ME/CFS patients.

They’ve also found large decreases in brain glutathione levels as well.  In their latest study, they went a step further and examined lactate levels in the brains of FM patients as well

Ventricular Lactate and the Cerebrospinal Fluid

When Shungu and Dr. Natelson refer to ventricular lactate, they’re also referring to the cerebral spinal fluid – a “tissue” that is becoming increasing important in ME/CFS and FM.

The ventricles are four cavities sitting at the bottom of the brain where the cerebral spinal fluid (CSF) is produced.

The CSF functions as a kind of cushion, a blood flow and neuro-endocrine-immune regulator and as an important waste removal outlet.

CSF studies are able to uncover several different kinds of pathologies associated with the brain including bleeding, infection, inflammation and autoimmunity. Protein analyses of CSF have identified unique protein signatures for multiple sclerosis, lupus and other diseases.

This study examined the makeup of CSF – aka the brain ventricles – in ME/CFS, FM, and healthy controls

The Study

Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia. Benjamin H.Natelsona, DianaVua, JeremyD.Coplanb, XianglingMaoc, MichelleBlatea, Guoxin Kangc, Eli Sotod*, Tolga Kapusuzd and Dikoma C. Shungu. FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR, 2017 http://dx.doi.org/10.1080/21641846.2017.1280114

Four studies have found increased lactate in fibromyalgia, and three studies have found it elevated in ME/CFS patients’ brains.

This means increased lactate levels may be one of the few abnormal findings present in both ME/CFS and FM.

In fact, the authors – two longtime ME/CFS/FM researchers – believe lactate elevations are likely to be a core part of both syndromes. Further study is needed, but this could be the tie that binds the two disorders together.

Those increased lactate levels are basically synonymous with mitochondrial dysfunction…

We have found elevated ventricular lactate in nearly every disorder in which mitochondrial dysfunction has been implicated.

These include primary mitochondrial disorders that I am still investigating with researchers at Columbia [Kaufmann et al 2004, Weiduschat et al 2014], Parkinson’s disease, lysosomal storage diseases, etc.  We also recently reported increased ventricular lactate in FM, as well.

With these preliminary data and new evidence, which consisted of a robust 36% deficit of cortical glutathione (GSH) – the most abundant and primary antioxidant in living tissue – in ME/CFS compared to controls, we competed for NIH funding and were awarded two grants, descriptively titled, “Specificity and Validity of Oxidative Stress Model of Chronic Fatigue Syndrome” (R01 MH100005) and “[N-acetylcysteine] NAC for Treatment of Oxidative Stress in Chronic Fatigue Syndrome” (R21 NR013650).

Oxidative Stress

Even though it was the similarity between mitochondrial disorders and ME/CFS that initially spurred his interest, Shungu has come to conclude that the primary problem in ME/CFS involves oxidative stress and that mitochondrial problems are secondary.

Rather than directly implicating mitochondrial dysfunction, the three studies culminated with strong evidence supporting oxidative stress and associated pathophysiological consequences as the most likely neurobiological underpinnings of the observed elevations of ventricular lactate in ME/CFS [Shungu et al 2012].

High levels of free radicals that can chew up and blast cells – and even affect blood vessel functioning – have been found several times in ME/CFS and FM.

Oxidative stress itself is a normal part of cellular functioning.

During the process of aerobic energy production, the mitochondria produce enormous amounts of free radicals, and immune cells use free radicals to kill pathogens as well.

Too much oxidative stress, however, can damage the mitochondria and impair cellular functioning.

Shungu’s finding of highly reduced levels of glutathione in the brains of ME/CFS patients suggested that the antioxidant systems that normally keep oxidative stress in the brain in check were not doing so any more.

High levels of isoprostanes in two (ME/CFS) studies, including one of Shungu’s (unpublished) provided an important early clue for Shungu. Isoprostanes are turning out to be major players in both cardiovascular and neurological diseases.

Shungu’s model – which builds on Martin Pall’s ME/CFS NO/ONOO model –  goes something like this:

An immunological trigger or pathogen triggers the production of pro-inflammatory cytokines and the potent free radical peroxynitrite.

Inadequate antioxidant reserves result in peroxynitrite reacting with lipids to form isoprostanes.

Isoprostanes – potent vasoconstrictors – compress the blood vessels, reducing blood flow, and producing an hypoxic or low oxygen environment.

That low oxygen environment: (a) results in increased anaerobic energy production (glycolysis); and (b) promotes the transformation of pyruvate into lactate – hence, the high lactate levels found in the brain.

Shungu believes mitochondrial dysfunction is present in ME/CFS; he just doesn’t believe it’s the driver of the disease.

It’s not that the mitochondria are not involved – they are – but they’re not getting whacked by a problem that they have. They’re getting whacked by the neuroinflammation and oxidative stress that’s present

Once the process starts, it can be hard to tell what is causing what as the mitochondrial and oxidative stress problems feed into each other:

Fibromyalgia – A Neuroinflammation Disorder?

At least three possible mechanisms could explain the increased lactate levels seen in FM:

  1. problems with anaerobic energy production/mitochondrial dysfunction,
  2. neuroinflammation and
  3. oxidative stress.

Again, note that none of them are exclusive of each other. Oxidative stress can whack the mitochondria and cause neuroninflammation. Neuroinflammation, on the other hand, is a really potent oxidative stress inducer. The question is where does it all begin?

One of his earlier studies found that Savella (milnacipran) significantly reduced FM patients’ pain as well as their ventricular lactate levels. Despite those reductions, the FM patients’ lactate and pain levels were still higher than in the healthy controls.


The most important takeaway from this study and from Shungu’s and Natelson work is that the same central finding – an overemphasis on anaerobic energy production- is showing up in both ME/CFS and FM, and it appears to be showing up across the body.


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