Fatigue severity and serum leptin levels in chronic fatigue syndrome

In the very complicated world of medical research and science, the days of one chemical, one metabolite, or one gene driving and sustaining ill-health and particular diseases or conditions seem to be all but long past. Sure, there are conditions which on the surface seem to be driven by only one factor, but more often than not is the realisation that we humans are very complicated creatures indeed.

Leptin @ Wikipedia  

I was therefore interested to read the paper by Elizabeth Stringer and colleagues* (open-access) describing the results from a small cohort of women diagnosed with chronic fatigue syndrome (CFS) looking at potential biological correlates which might accompany day-to-day changes in the severity of fatigue experienced by participants.

Yes, I'm back with CFS to add to my ramblings about gut bacteria, mitochondrial disorder, amino acids. Bear with me...

The paper is open-access but a few pointers might be useful:

• It was an interesting methodology the authors adopted which saw 10 women diagnosed with CFS and 10 asymptomatic age- and BMI-matched controls asked to monitor their fatigue-related behaviours over the course of 25 days.
• This self-report was accompanied by a professionally taken daily blood draw (yes, 25 days of giving a blood sample!) which were subsequently analysed for various cytokines - 51 in all.
• The self-report data and pattern of cytokine levels were analysed, correlated and networked (using a machine learning algorithm).
• Results: "Six participants with CFS and one healthy control demonstrated significant positive correlations between fatigue and leptin". Leptin by the way is a hormone normally implicated in the in-and-out process of energy expenditure, so potentially relevant to a condition like CFS which is characterised by fatigue.
• Buoyed by their leptin results, the authors also report that with the help of that Weka’s LibLINEAR algorithm, they were able to use the suite of cytokine results to distinguish 'high' and 'low' fatigue days for the CFS group with 78.3% accuracy compared with just above chance level in the asymptomatic control group. "The CFS model correctly identified 77.8% of the low fatigue days and 78.9% of high fatigue days".
• Ergo cytokines and inflammation seem to be not only tied into CFS pathology but might actually be overlap with the ebb and flow of clinical symptoms on a day-to-day basis.

You can perhaps see how this study might be an important one for CFS. Given the connection between leptin (energy) and CFS, you might be saying to yourself that this sounds all very logical so why did no-one look at the possible connection before? Well, they did, or rather Cleare and colleagues** did and concluded: "we found no evidence of alterations in leptin levels in CFS" despite some potential effects from low dose hydrocortisone therapy on leptin levels under placebo-controlled conditions.

This is not by any means the first time that immune function has cropped up on the CFS research radar (see this post) and probably won't be the last either. I don't however want to speculate too much more on these results without them being subject to appropriate replication with a larger patient set and that all-important diagnostic criteria being standardised. The XMRV story (see here) still lingers in the mind, as do other controversies on the CFS landscape such as Ampligen and Rituximab.

To close, a song about a dirty old town.

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* Stringer EA. et al. Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity
in chronic fatigue syndrome: evidence of inflammatory pathology. Journal of Translational Medicine. 2013; 11: 93.

** Cleare AJ. et al. Plasma leptin in chronic fatigue syndrome and a placebo-controlled study of the effects of low-dose hydrocortisone on leptin secretion. Clin Endocrinol (Oxf). 2001; 55: 113-119.

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Stringer, E., Baker, K., Carroll, I., Montoya, J., Chu, L., Maecker, H., & Younger, J. (2013). Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology Journal of Translational Medicine, 11 (1) DOI: 10.1186/1479-5876-11-93