Metabolomics and Chronic Fatigue Syndrome

There were lots of things I could have blogged about in this post. The recent EEG autism biomarkers study by Duffy and Als* (full-text) which seems to be generating lots and lots of interest, despite the fact that we've kinda been here before (see this post on the Dark Arts); the interesting case study reported by Sildorf and colleagues** on remission without insulin therapy following use of a gluten-free diet in a pediatric case of type-1 diabetes; or even the high prevalence of vitamin D deficiency in psychiatric in-patients reported by Menkes and colleagues*** (full-text). All noteworthy findings and very much within the remit of this blog and its previous posts.

But instead, I'm turning my attention to another paper by Armstrong and colleagues**** and their application of a field close to my research heart, turning the scientific eye of metabolomics to Chronic Fatigue Syndrome (CFS).

Aside from a metabolomics link and the use of some quite powerful analytical technology, NMR, which has been previously applied to both autism (here) and schizophrenia research (here), this study also caught my eye because of what they reported finding.

A very brief summary:

• Blood samples from a small patient group (n=11) diagnosed with CFS were analysed and compared with a small asymptomatic control group (n=10) via NMR. These participant groups are quite small but bear in mind the task ahead of the researchers given the number of potential compounds present in a blood sample (see this paper by Psychogios and colleagues***** on how many they found in human serum). I hasten to add that even in our lab we have found considerably more compounds to be present in other mediums like urine.
• Significant reductions in the amino acids glutamine and ornithine were detected in the CFS group compared with controls. These findings also correlated with other metabolites linked to glucogenic amino acids and metabolites of the urea cycle.
• I believe this to be only one of a handful of papers (that I can find) that discusses the application of techniques like NMR to CFS. On other occasions some interesting bacterial findings have been reported as per this paper by Sheedy and colleagues****** who I think might have been part of the same group (including Dr Henry Butt and the whole CFSUM1 and CFSUM2 episode).

My attention was immediately drawn to the reductions in glutamine which were present in this small participant group. Drawn because of the previously discussed 'possibility' of gut hyperpermeability in cases of CFS and the various suggestions that glutamine might play a role in intestinal permeability, or at least as an aid to improving such permeability in both animals (here) and humans (here). I might also add that lower levels of plasma glutamine have also cropped up in autism research too, bearing in mind that no direct connection between the conditions is intended. 

The literature on glutamine and CFS is still a little sparse. Aside from this paper looking at glutamine levels being related to something called 'overtraining syndrome' there's really not that much more to compare with. I note that exercise can induce changes to intestinal permeability (here) but wouldn't like to speculate on the mechanisms of this effect and any role for glutamine. I am on purpose also excluding the findings on glutamine related to ancillary conditions like fibromyalgia such as a raised glutamate/glutamine ratio (now where have I seen that before?)

I'm going to stop there with this interesting area of research which requires replication with much greater numbers. I've not really discussed the ornithine findings reported, simply because (a) there is even less research on this with CFS in mind, and (b) ornithine in relation to the urea cycle gets really, really complicated and my head is starting to hurt. Suffice to say that amino acid chemistry once again reveals itself as a possible correlate to another one of our heterogeneous medical syndromes without clues to causation. The question is: is the link with glutamine causation, association or just epiphenomenal?

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* Duffy FH. & Als H. A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study. BMC Medicine. June 2012.

** Sildorf SM. et al. Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus. BMJ Case Reports. June 2012

*** Menkes DB. et al. Vitamin D status of psychiatric inpatients in New Zealand's Waikato region. BMC Psychiatry. June 2012.

**** Armstrong CW. et al. NMR metabolic profiling of serum identifies amino acid disturbances in Chronic Fatigue Syndrome. Clinica Chimica Acta. June 2012.

***** Psychgios N. et al. The human serum metabolome. PLoS ONE. 2011; 6: e16957.

****** Sheedy JR. et al. Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo. 2009; 23: 621-628.