Prospective Biomarkers from Plasma Metabolomics of ME/CFS Implicate Redox Imbalance in Disease Symptomatology, 2018, Hanson et al

John Mac

John Mac

Senior Member (Voting Rights)
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease of enigmatic origin with no established cure. Its constellation of symptoms has silently ruined the lives of millions of people around the world.

A plethora of hypotheses have been vainly investigated over the past few decades, so that the biological basis of this debilitating condition remains a mystery.

In this study, we investigate whether there is a disturbance in homeostasis of metabolic networks in the plasma of a female 32-patient cohort compared to 19 healthy female controls.

Extensive analysis of the 832-metabolite dataset generated by Metabolon®, covering eight biological classes, generated important insight into metabolic disruptions that occur in ME/CFS.

We report on 14 metabolites with differences in abundance, allowing us to develop a theory of broad redox imbalance in ME/CFS patients, which is consistent with findings of prior work in the ME/CFS field.
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https://www.mdpi.com/2218-1989/8/4/90
 
In this study, we report on untargeted metabolomics profile of a relatively small cohort. Despite statistical challenges, we provide yet more evidence for a redox imbalance in ME/CFS patients. The rationale behind our theory is bolstered by parallels with our previous study and available datasets from other teams. The patient cohorts that have been used in our studies and others differ in geographical location, diet, treatment regimes, yet there are remarkable similarities among the findings. Thus, metabolomics may be revealing a fundamental feature of the disruption that occurs in victims of ME/CFS.
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Such consistency is rare in ME/CFS studies. Encouraging.

I also like how this study talks about "victims of ME/CFS" and "Its constellation of symptoms has silently ruined the lives of millions of people around the world."
 
The authors seem happy that the results of their work are consistent with the results from previous ME/CFS metabolomic studies. So that's good.

But the differences between patients and controls in the nine molecules that they have picked out from their very large survey (more than 800 molecules) look depressingly small to me. There's such a lot of overlap in the ranges.

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Is it possible that the variability in a single patients' metabolomics over time is so great that differences between patients and controls are going to be largely obscured? Do the patients actually need to be experiencing PEM in order to show clear differences?

Maybe we need metabolomics analyses done for these nine molecules on a set of patients every day for a month, with the first half of the month spent resting and the second half of the month spent being as active as possible, with the results correlated with symptoms.
 
I am probably being incredibly stupid, not having much biochemistry, but to me small differences are not the issue. Given the common nature of expression , surely in a system s condition it is not the individual difference s, but the cumulative effect of them that is as important?

How do these differences affect rate limited processes/ signalling when combined.
What is their impact on reactions downstream ?
 
Hutan said:
But the differences between patients and controls in the nine molecules that they have picked out from their very large survey (more than 800 molecules) look depressingly small to me. There's such a lot of overlap in the ranges.
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That was my feeling too. It doesn't seem realistic to talk of these metabolites as biomarkers when there is so much overlap with healthy controls, unless perhaps the pattern of all 9 metabolites taken together can clearly discriminate between groups. I would imagine that a next step would be to do a focused test of the 9 metabolites in much much bigger samples of pwME and healthy controls and people with other chronic health conditions.

Perhaps, rather than trying to call these potential biomarkers, it might be more useful to look closely at the biochemical pathways they are involved in and combine it with the genetic indications coming from other studies to try to home in on what exactly is going wrong so drugs can be targeted for treatments. I'm hoping some very clever biochemists are looking into this.
 
Noddy question about Biomarkers - based on metabolites is there actually going to be something that always distinguishes correctly between people that have ME and those who don’t. If it is something everyone should have in their blood isnt it likely there will be an overlap.
 
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I think with a lot of diseases there is a pattern of things wrong before they home in on a biomarker or diagnostic test. Even when I was pregnant in 1976, an elderly doctor said to me that if a woman thought she was pregnant there was a good chance she was. 20 years ago MS was diagnosed by a pattern of responses and symptoms and migraine still has no test.

Though I agree that the real value of these results is that they are a map to what is going wrong for us at a basic level.
 
If you wanted to convince a medical sceptic, which metabolomics paper would you use?
 
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