Carnitine conjugation profiling in a selected cohort of patients with chronic fatigue syndrome, 2019, Du Plessis

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Source: North West University Date: July 2019, Online February 14, 2020 URL: https://repository.nwu.ac.za/handle/10394/34126

https://repository.nwu.ac.za/bitstream/handle/10394/34126/Du Plessis L 21648859.pdf

Carnitine conjugation profiling in a selected cohort of patients with chronic fatigue syndrome ---------------------------------------------------------------- Liana Du Plessis - Faculty of Health Sciences, North West University, Potchefstroom Campus, South Africa

Abstract

Chronic fatigue syndrome (CFS) is classified by the World Health Organisation (WHO) as a non-communicable disease. Fatigue is a symptom commonly experienced by many individuals and is also a symptom associated with a wide variety of diseases, but once this fatigue becomes long lasting, persistent and debilitating, a case of CFS is considered. Research of CFS dates back to the nineteen hundreds, but unfortunately, no definite underlying cause or one single positive treatment has been identified. Diagnosis also poses a difficult task due to different criteria available, but also because of the lack in confidence of diagnosing doctors in making a positive diagnosis, because this disease is still poorly understood.

Recent studies and research found promising evidence that mitochondrial dysfunction may be considered as a possible underlying cause of CFS. Because mitochondria are responsible for the release of energy in cells, the connection between mitochondrial dysfunction and the underlying energy deficiency in CFS patients may indicate a good starting point for further investigation. L-carnitine plays an important role in energy metabolism and could possibly be used as potential biomarkers for energy related diseases such as CFS.

The first part of the study focused on method development and validation. A pre-existing high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method coupled with electrospray ionisation (ESI) was further developed and validated to simultaneously quantify carnitine and acylcarnitines in human urine samples.

The second part of the study included application of the developed and validated method to urine samples of controls and possible CFS patients. All carnitines of interest could be detected and identified with this method, although the longer chain aclylcarnitines posed some difficulty. The aim of this study was to identify altered acylcarnitine profiles associated with possible CFS patients compared to control samples. At the end, principal component analysis (PCA) statistical analysis could not differentiate between the two groups, but two acylcarnitines were identified by the Mann Whitney test to have significant p-values, namely octanoylcarnitine (C8) and decanoylcarnitine (C10).

Although the method can be applied for acylcarnitine identification in urine samples, it is advised to pay attention to detecting the long chain acylcarnitines more efficiently in order to get the whole profile for comparison.

Key words: chronic fatigue syndrome; HPLC-MS/MS; carnitine; acylcarnitines; urine; mitochondria.

-------- (c) 2019 North-West University
 
When I got some analysis of my cortisol/cortisone levels done, it involved a collection of urine for 24 hours.
A bit easier for men than women.
Thankfully I was housebound, so it wasn't a huge inconvenience.

One time my mother had to go in for an extra container due to the volume I had excreted.
 
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When I got some analysis of my cortisol/cortisone levels done, it involved a collection of urine for 24 hours.
A bit easier for men than women.
Thankfully I was housebound, so it wasn't a huge inconvenience.

One time my mother had to go in for an extra container due to the volume I had excreted.
So did I - I used a well-rinsed lemonade bottle or similar. At the time I was very polyuric, having no desmopressin, so I must have urinated more than 20 times in the 24 hours.

It didn't do me any good. I was rejected as being 'normal'!
 
The trouble with urine samples is that (many?) people with ME may have widely varying levels of various things in urine due to polyuria (production of large amounts of urine).

Forty years ago they used early morning urine samples to test for pregnancy as there was time overnight for the hormone to gather. Mine was negative as no one took into account how often I had to get up during the night.

It makes me wonder how often our negative tests are due to the fact our ME biochemistry is different from normal.
 
The trouble with urine samples is that (many?) people with ME may have widely varying levels of various things in urine due to polyuria (production of large amounts of urine).

Not necessarily insurmountable or easy to address. Chris Armstrong (2015 paper 2016 webinar) found that creatinine, i.e. the compound normally used to correct for urine dilution, couldn't be used in ME. Chris reckoned that creatinine levels were altered owing to the switch to using amino acids for cellular energy production.

This (carnitine) study was based on mass spectrometry; it is very sensitive, so you may be able to find a compound (detectable along with carnitine) which can be used to correct for urine dilution.

Only looked at this briefly but the authors have identified potential ways to progress this research - section titled "CONCLUSION AND FUTURE PROSPECTS" (pages 80 & 81).

I just wonder if a GWAS study might pick up an association between carnitine and ME. Chris Ponting has submitted an application for funding for a GWAS study in ME. @Simon M

@Michiel Tack @Giada Da Ros A potential biomarker in ME?
 
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