A laboratory approach for characterizing chronic fatigue: what does metabolomics tell us?, 2019, Erasmus et al

[Andy]

Introduction
Manifestations of fatigue range from chronic fatigue up to a severe syndrome and myalgic encephalomyelitis. Fatigue grossly affects the functional status and quality of life of affected individuals, prompting the World Health Organization to recognize it as a chronic non-communicable condition.

Objectives
Here, we explore the potential of urinary metabolite information to complement clinical criteria of fatigue, providing an avenue towards an objective measure of fatigue in patients presenting with the full spectrum of fatigue levels.

Methods
The experimental group consisted of 578 chronic fatigue female patients. The measurement design was composed of (1) existing clinical fatigue scales, (2) a hepatic detoxification challenge test, and (3) untargeted proton nuclear magnetic resonance (1H-NMR) procedure to generate metabolomics data. Data analysed via an in-house Matlab script that combines functions from a Statistics and a PLS Toolbox.

Results
Multivariate analysis of the original 459 profiled 1H-NMR bins for the low (control) and high (patient) fatigue groups indicated complete separation following the detoxification experimental challenge. Important bins identified from the 1H-NMR spectra provided quantitative metabolite information on the detoxification challenge for the fatigue groups.

Conclusions
Untargeted 1H-NMR metabolomics proved its applicability as a global profiling tool to reveal the impact of toxicological interventions in chronic fatigue patients. No clear potential biomarker emerged from this study, but the quantitative profile of the phase II biotransformation products provide a practical visible effect directing to up-regulation of crucial phase II enzyme systems in the high fatigue group in response to a high xenobiotic-load.

Paywall, https://link.springer.com/article/10.1007/s11306-019-1620-4
Scihub, https://sci-hub.se/10.1007/s11306-019-1620-4

 

[Hutan]

Patients suffering from fatigue emanating from well- defined clinical conditions such as cancer and CFS/ME or other known conditions such as diabetes or hypertension were excluded from the study.

 

[rogerblack]

I do wish people would use terms less casually. I note for example NICE used 'abstract review' in one round of summarising the field, and using CFS/ME in this manner is reprehensible in abstract if they are excluded.

It annoyed me enough in the end I wrote the corresponding author asking:

I write (as a patient with CFS) with some questions and comments about your paper.
in the abstract, there is no mention at all of the passage in the text "Patients suffering from fatigue emanating
from well-defined clinical conditions such as cancer and CFS/ME or other known conditions such as diabetes or
hypertension were excluded from the study."

It is unfortunate that you do not clarify in the abstract that you are not considering CFS, when you specifically
mention it, and do not clarify that you are using "chronic fatigue" in a looser sense.


To the main point.

You note you exclude patients with CFS/ME.
In your paper "The diagnostic criteria indicative of CFS/ME specify: (1) a substantial reduction or impairment in the ability to engage in pre-illness levels of activity (occupational, educational, social or personal life); (2) symptoms that present for more than 6 months; (3) episodes of profound fatigue; (4) symptoms of new onset and not resulting from on-going or unusual excessive exertion; and (5) symptoms that are nor substan-tially alleviated by rest."

However, this is a partial quote.
It misses the required "AND Postexertional malaisea AND Unrefreshing sleep"

To the main point.
The patient questionaires do not appear to capture PEM, and the supplementary information(1) does not describe how you excluded patients with CFS/ME. Is this exclusion solely based on patient reports of prior diagnosis?

1) ( https://static-content.springer.com.../MediaObjects/11306_2019_1620_MOESM1_ESM.docx )

 

[rvallee]

Patients suffering from fatigue emanating from well- defined clinical conditions such as cancer and CFS/ME or other known conditions such as diabetes or hypertension were excluded from the study.

Well that's a puzzling decision. That fatigue is no more explained than any other group other than there being a label for it. Completely arbitrary choice based on superficial characteristics that does not inspire confidence in the results.

At least it's consistent in studying idiopathic fatigue but the distinction is without much difference. Knowing that something causes another thing is not an explanation for how that thing works.