Targeting mitochondrial dysfunction in ME/CFS?

Consider this post a bit of a follow-up to a previous one based on some interesting observations by Booth and colleagues looking at mitochondrial dysfunction in cases of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).

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Same authorship group but this time around presenting the results of an audit of patients who underwent examination based on the ATP profile (no endorsement given) and what they did about it published by Sarah Myhill and colleagues* (open-access).

I will at this point just reiterate my caveat about not giving advice, medical or otherwise, on this blog and hence not advocating anything based on discussions about the Myhill paper. I'm just talking, nothing else.

So here goes:

• The paper is based on the same 138 participants diagnosed with ME/CFS as described on their previous paper and how, when a multi-faceted intervention regime was put in place, some of the participants fared in terms of their mitochondrial profiles and presented symptoms.
• I say that this paper describes some of the original cohort; in essence this boils down 34 of them who had more than one ATP profile "separated by some months" of which 30 followed the intervention regime with vigour and 4 participants who were a little more lax. Bear in mind this was reported as an audit not a clinical trial.
• What was the treatment regime? Well, (a) a stone age diet which I assume is similar to a Paleolithic diet(?), (b) a good sleeping routine, (c) a supplemental vitamin/mineral/other regime and (d) assuming an appropriate work-rest balance; pacing but not PACE.
• Elements of these interventions were specifically tailored for participants based on their mitochondrial and other tests of nutritional status. Interestingly the authors report on some familiar issues as per often finding "deficiencies in glutathione (GSH) and glutathione peroxidase (GSH-PX) which are needed  to protect cells from oxidative damage and to detoxify xenobiotics". Other elements that turned up on the various testing panels were slightly more contentious as per the suggestion that "High levels of heavy metals can be tackled using selective chelation therapy".
• Results: there are some case histories reported and quite a bit of data per participant per testing occasion. I'll let you draw your own conclusions from what is described but in essence, the authors observed that there was some degree of responsiveness to the interventions shown on the repeat testing profiles for some of the participants. The caveat being that there was as expected, some degree of variability in response potentially affected by lots of variables, not least because individuals are individuals, and also probably due to the intervention regime itself.
• The authors report that "All 30 of the multiple test patients who followed the treatment protocol have increases in the major parameters of mitochondrial function and in the Mitochondrial Energy Score".
• The co-factors involved in ATP production - niacinamde, L-carnitine, coenzyme Q10 - also saw some interesting changes between baseline and post-intervention testing as a function of "% within normal range" though not presented in absolute mean values (pre- and post).
• All that being said, there is little in the way of formalised description as to the presentation of symptoms, and whether and how these overlapped with such changes (perhaps reiterating the audit nature of this paper).

For those who might be rather sceptical of this area of functional medicine, mitochondria being involved in ME/CFS or even members of the authorship group themselves, it would be easy to dismiss this paper as being nothing more than an advert for the clinical services of the authors. It is not a formal study of mitochondrial function being assessed or 'modified' in cases of ME/CFS, it focuses on individuals not groups, and there are plenty of scientific holes in how and what results have been presented (or not).

But step back a little and consider a few things. ME/CFS is probably in an even worse clinical position that autism for example, is at the moment. Whereas autism (mostly) enjoys the recognition of being a biologically-based neurodevelopmental condition, ME/CFS is still, in some quarters, thought to be a purely psychiatric condition, where sufferers - yes, people do suffer from ME/CFS - are thought to be either mentally ill or perhaps just as bad, to be hypochondriacs. Labels such as yuppie flu didn't really help matters either.

The next hurdle to be faced is the fact that the presentation of ME/CFS is heterogeneous. Even the diagnostic criteria for the condition has not been fully agreed upon, or at least as a condition with universal diagnostic consensus. That even before we start talking about comorbidity and the like.

When taking these factors into account, it does start to make a little more sense as to why initial, preliminary investigations should reflect these factors. So that mitochondrial issues might be part and parcel of ME/CFS or at least some cases, that reporting and correcting mitochondrial dysfunction might involve different strategies for different people, and that sticking to an intervention regime is not always possible in an intention-to-treat analysis manner, particularly when you are dealing with a condition which impacts so centrally on a person. Don't get me wrong, I'm not standing up for the use of audits over clinical trials - randomised, controlled clinical trials - but do consider this paper, and the previous publications from the authors, to be a good first step of where further investigation should be carried out.

Of course I would very much like to see more formal study not just on what happened to biochemistry as a result of the interventions discussed by Myhill and colleagues but also on overt signs and symptoms and importantly overall quality of life (QoL) outside of just clinical measures. Dietary changes such as those discussed are no laughing matter and can, on occasion, negatively impact on QoL as a consequence of their restrictiveness. Indeed as per other mentions of diet and ME/CFS on this blog, one wonders whether there may be either certain elements of the Stone Age diet which might be more usefully connected to cases, or indeed whether underlying clinical comorbidity such as coeliac disease or non-coeliac gluten sensitivity might be important to symptoms and outcomes.

Whatever your views on this area of research or more generally the definition of what ME/CFS is or isn't, this is peer-reviewed research and therefore represents an addition to the scientific literature and a challenge to the scientific community to undertake further independent replication save any repeat of XMRV...

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* Myhill S. et al. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit. Int J Clin Exp Med 2013;6 : 1-15.

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Myhill S,, Booth NE,, & McLaren-Howard J (2013). Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit International Journal of Clinical & Experimental Medicine, 6 (1), 1-15