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

[Murph]

Metabolomics. 2019 Nov 27;15(12):158. doi: 10.1007/s11306-019-1620-4.
A laboratory approach for characterizing chronic fatigue: what does metabolomics tell us?

Erasmus E1, Mason S2, van Reenen M2, Steffens FE3, Vorster BC2, Reinecke CJ2.
Author information
1Centre for Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University (Potchefstroom Campus), Private Bag X6001, Potchefstroom, South Africa. lardus.erasmus@nwu.ac.za.
2Centre for Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University (Potchefstroom Campus), Private Bag X6001, Potchefstroom, South Africa.
3Department of Consumer Science, University of Pretoria, Pretoria, South Africa.

Abstract

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.

KEYWORDS:
1H-NMR metabolomics; Chronic fatigue; Detoxification challenge test; Phase II biotransformation; Piper fatigue scale

PMID: 31776682 DOI: 10.1007/s11306-019-1620-4

 

[Murph]

This is a real weird one. A group I never heard of from a cuntry with not much prominence in ME/CFS, with a massive sample size, patients defined in an unknown way, doing interesting metabolomic work.

Hard to know what to make of it. I wonder how they got 570 people to do a detox!?

 

[Murph]

Some detail from the full paper on their sample selection and the detox methodology. Neither is anything I've seen before! I'm sure these people are promising but it'd be helpful if they'd use comparable methods to other researchers.

The full paper talks a lot about me/cfs (attached), but excludes people diagnosed with me/cfs!



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



More info on the bizarre choices they've made:


The selection of cases used for the laboratory assessment was made from 576 females identified by clinicians as suffering from chronic fatigue, supported by information from two known assessment scales. Based on exclusion criteria, the control (low fatigue) and patient (high fatigue) groups were selected from this cohort for the metabolomics study. Fatigue in our patient group was scored based on the Piper Fatigue Scale (PFS) (Piper et al. 1998) developed for fatigue prevailing in oncology patients. The information from the PFS was supplemented with that from a general Medical Symptoms Questionnaire (MSQ) used by the Departments of Medicine, Mercy Hospital and Maine Medical Center, Portland, for comprehensive profiling of patients with idi- opathic conditions.

The hepatic detoxification test probes the gut-liver function through a hepatic detoxification challenge with acetaminophen and acetylsalicylic acid (Cordts et al. 2001). The laboratory instrument used for the objective measurement of fatigue is based on the biotransformation profile derived from these hepatic challenge tests. The underlying physiological assumption is that fatigue is a symptom of energy depletion (e.g. as indicated by the PFS). Based on the presumed causal relationship between exogenous stimuli, biotransformation responses and fatigue, we speculated that the response to the highly energy dependent hepatic challenge test (that is, ATP required for the in vivo synthesis of biotransformation products) should be more pronounced in controls than in fatigue patients supposed to suffer from energy depletion.

 

[pattismith]

Well, I've not come deep into the study, but I don't understand it well.

Do they consider the acetaminophen (Paracetamol) + acetylsalicylic acid (Aspirin) challenge a liver detox challenge??

I would rather consider it as a "high xenobiotic load" ...

 

[Marylib]

This is a forgettable one, sadly, for patients in South Africa. Sounds like a study in chronic fatigue that has something to do with "detox." I see the word detox and I shut off. Not to mention 'chronic fatigue.'
Maybe xenobiotic could also refer to eating plastic.

 

[percyval577]

I don´t see the need of intoxination either, it might be accident though that detox works for so many ppl.

I think a proper question were: Why can beings feel fatiqued or exhausted?

And then: Where could which disturbance occur (I guess ME is that autonomous that detox is way too "normal")