Monday, 16 July 2012

Mitochondrial dysfunction and ME/CFS

I continue my interest in research examining chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME) in this post looking at what might turn out to be quite an important paper by Booth and colleagues* (full-text) on a potential role for mitochondrial dysfunction.


Where to start....

Mitochondria (plural) are not to be confused with the midi-chlorians of a Galaxy far, far away. A few associated words: organelleseukaryotic cell, the power plant of cells, cellular respiration (this link carries a really easy to understand description of this process). In short, mitochondria provide energy to the cell in the form of ATP. Cells like most thing need energy to function properly; where insufficient energy is produced... well, cells don't work as well as they should and the results can be serious and wide-ranging.

I've kinda eluded to mitochondrial function, or rather dysfunction, in posts like this one on lactate levels in autism although I dare say that as some point I will come back to the topic in more detail. Indeed elevations in lactate levels do seem to indicate some potential issue with mitochondrial dysfunction as per studies like this one from Magner and colleagues**.

I digress. Booth et al have previously reported on mitochondrial dysfunction in cases of CFS/ME in this paper*** (full-text); the current study being a sort of extension and elaboration effort. I might add that they are by no means the first to suggest that there may be some mitochondrial 'involvement' in cases of CFS/ME (see here and here). Low carnitine levels? Now where have I heard that before?

Their latest paper is full-text and contains quite a bit of data but a short summary is perhaps in order:

  • The ATP profile features quite strongly in the paper. This is described as containing among other things, ATP concentration in blood neutrophils (in the presence of excess magnesium, deficiencies of which have been linked to CFS) and is a part of a so-called mitochondrial energy score (MES). In their previous paper (***) the authors reported an impressive correlation between MES and CFS Ability as described using the Bell Ability Scale, a rough and ready measure of the level of disability as a consequence of the condition (see here)
  • It looks like there were a few elements to this paper including a reanalysis of the cohort reported in their previous paper - cohort 1 (minus 10 participants who were outside of the age range of controls, again taken from their original publication) and analysis of a new participant group - cohort 2 - made up of 138 participants aged between 18-65, mean age 41 years.
  • Similar to the last paper, the MES showed a pretty good correlation with CFS Ability (correlation coefficient = 0.80). I have to admit that quite a lot of the rest of the results are beyond the limits of my biochemistry as various measures of ATP inhibition, functionality of the translocator proteins (e.g. ANT) and efficiency of oxidative phosphorylation are tested ( I think!). The end result is that the mitochondrial dysfunction noted by the authors in this patient group seems to (a) frequent, very frequent and (b) particularly involves issues with the translocator protein (TL) regulating the passage of ATP and ADP across mitochondrial membranes (see here - no endorsement intended). Other preliminary studies of oxidative phosphorylation capacity in CFS for example, suggested that this is probably not the main reason for mitochondrial dysfunction**** (full-text).
  • The authors conclude: "Taken together, these measurements show that ME/CFS is a serious illness which may affect every cell in the body".

And relax. 

I should point out that my interpretation of the Booth results should not be taken as Gospel or anything like that. I do however believe that these results are important for CFS/ME and potentially represent at least one part of the puzzle that is this debilitating set of conditions. Independent replication of the Booth results is the next step.

I was drawn to the fact that other conditions presenting with a fatigue component such as fibromyalgia have also been suggested to be linked to issues with mitochondria as per this case study by Abdullah and colleagues***** (full-text). The 'solution' to their reported case was supplementation with various compounds including coenzyme Q10, creatine and carnitine among other things. Whilst I am not in a position to endorse anything like such a treatment protocol (please do speak to your healthcare provider first), I note that supplements like coenzyme Q10 have cropped up more than once in relation to CFS/ME as per articles like this one****** from a familiar name to this area of study, Michael Maes and colleagues.

ME/CFS are a heterogeneous set of conditions which, similar to the description of autism, probably include quite a few different paths to the development of symptoms. Whilst the area of mitochondrial dysfunction is an attractive potential marker showing involvement in cases - at least some cases - the question of whether this is a 'core' aspect of the conditions still remains to be seen alongside its connection with other pathways of interest


To finish, Kate Bush sings Wuthering Heights. A lesson in the art of dance and music (and its absolutely fantastic).

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* Booth NE. et alMitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). International Journal of Clinical & Experimental Medicine. 2012; 5: 208-220.


** Magner M. et al. Elevated CSF-lactate is a reliable marker of mitochondrial disorders in children even after brief seizures. European Journal of Paediatric Neurology. 2011; 15: 101-108.

*** Myhill S. et al. Chronic fatigue syndrome and mitochondrial dysfunction. International Journal of Clinical & Experimental Medicine. 2009; 2: 1-16.

**** Vermeulen RC. et al. Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. Journal of Translational Medicine. 2010; 8: 93.

***** Abdullah M. et al. Mitochondrial myopathy presenting as fibromyalgia: a case report. Journal of Medical Case Reports. 2012; 6: 55.

****** Maes M. et al. Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinology Letters. 2009; 30: 470-476.