Charlotte Stephens, Research Correspondent, ME Association.
In addition to the following report on this week's failed attempt to replicate the commercial mitochondria test, we have comments below from Dr Charles Shepherd and the lead researchers, Prof. Julia Newton and Dr Cara Tomas of Newcastle University.
The long-awaited first independent assessment of Dr Myhill’s mitochondrial function test was published on Wednesday in Scientific Reports – an online, open access journal from the publishers of Nature.
The study was a joint effort by leading scientists in the field of ME/CFS from Oxford and Newcastle Universities; Dr. Cara Tomas, Dr. Tiffany Lodge, Dr. Michelle Potter, Dr Joanna Elson, Prof. Julia Newton and Dr. Karl Morten.
The study, funded by the ME Association’s Ramsay Research Fund, concluded that the mitochondrial energy score (MES) protocol is unreliable:
|“The MES test does not have the reliability and reproducibility required of a diagnostic test and therefore should not currently be offered as a diagnostic test for CFS/ME.” |
Tomas et al. (2019), Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test, Scientific Reports.
Comment from Dr. Charles Shepherd, Hon. Medical Adviser, ME Association:
“Members of the ME Association will already be aware that the MEA Ramsay Research Fund has been funding several studies of mitochondrial function involving researchers with expertise in muscle and mitochondrial disease at the Universities of Oxford and Newcastle.
“This latest study was designed to assess the reliability and reproducibility of a commercial blood test that is claimed to assess mitochondrial energy production in ME/CFS.
“We have been concerned for some time about the way in which people with the condition have been spending a considerable amount of money on an unvalidated blood test.
“It is not a test that is recognised by NHS clinicians who specialise in muscle and mitochondrial disease and is often therefore dismissed as not being of any practical value in the assessment of mitochondrial function in people with ME/CFS.
“This new study has taken a considerable period of time to organise and complete – because everyone involved felt that it had to be as thorough as possible and involve several experts in two different university centres.
“The researchers have now published the results and reached a very clear conclusion: The commercial test does not have the reliability and reproducibility required of a diagnostic test and therefore should not currently be offered for ME/CFS.
“The differences observed by the Myhill group may be down to differences in sample processing time between cohorts.
“The mitochondrial energy score test is not a laboratory investigation that the ME Association has ever recommended.
“Neither do we endorse the commercial supplements that are supposed to improve mitochondrial function and may be sold in conjunction with the test results.
“Following publication of these findings our position remains exactly the same.”
Mitochondria are key players in energy production in our cells and there have been several studies looking into the role of mitochondrial dysfunction in ME/CFS.
- The ME Association recently published a summary review of the role of mitochondria in ME/CFS.
The possibility of mitochondria playing a role in the pathology of ME/CFS led to the development of a commercial blood test, often referred to as the ‘ATP profiling test’ or ‘Acumen Test’ by Dr. Sarah Myhill, Prof. Norman Booth and Dr John McLaren-Howard.
The test claimed to determine how well a person’s mitochondria were functioning and how much energy they were producing, and it was considered an objective test for ME/CFS by the original authors.
Subsequently, some people with ME/CFS have paid a lot of money to have this commercial blood test carried out and then purchased the suggested supplements or special dietary plan, based on the results.
However, neither the test, the supplements or the diet have been validated or have robust scientific evidence behind them, nor are they recommended or used by the NHS to treat any mitochondrial dysfunction.
Independent validation by other research groups is important for checking the reliability and validity of any test. This is especially important for commercial tests where patients are investing their own money and in the belief that any treatments based upon them will prove beneficial. This is why we chose to fund this study through the Ramsay Research Fund.
This newly published study set out to replicate the Mitochondrial Energy Score (MES) protocol, developed by the Myhill group, in order to assess its reliability and reproducibility and determine whether it can be used as the basis for a diagnostic test.
Contrary to the results of the original study published by the Myhill group, this latest study found no differences in any of the parameters measured in the protocol between ME/CFS patients and controls.
|“Experiments using the established protocol showed no differences between CFS/ME patients and healthy controls in any of the components of the MES.”|
“While this study used relatively small samples sizes compared with the original study, abnormalities in CFS/ME patients should be reproducible even in small sample sizes given the current use of this test for diagnostic purposes.”
Tomas et al. (2019)
Delays in Sample Processing
The researchers from Newcastle and Oxford attributed the differences in mitochondrial function found in the original paper to relate to differences in sample processing time.
The patient samples in the Myhill studies had been collected at least 24 hrs (even up to 72 hours) prior to processing and sent for analysis via the postal service. Whereas control samples were fresh from the lab.
The current study tested cells that had been processed within 24 hours of collection and compared with those collected over 24 hours and found that this had a significant effect on the cells and the results of the test.
|“Having taken into account a 24-hour delay between blood collection and cell isolation, we have shown decreases in ATP parameters in control cells similar to those seen by the Myhill group in the CFS/ME patients.” |
“We suggest that it is potentially the delay between sample collection and cell isolation that is causing the decrease in mitochondrial function previously reported in CFS/ME patients.”
Tomas et al. (2019)
What does this mean?
The results from this study do not exclude mitochondrial dysfunction or ATP production as being involved in the pathology of ME/CFS. However, it shows that the technique used by the Myhill group should not be used as an objective or diagnostic test, nor should the results of such testing be used as the basis for treatment recommendations.
The authors warn:
|“Clinicians approached by patients with results from the MES test should be advised to interpret the results with caution, while patients considering paying for the test should be advised of the lack of supporting scientific evidence.” |
“The test in its current form does not have the reliability or reproducibility required of a diagnostic test and therefore should not be offered by the NHS or private clinics as a diagnostic test for CFS/ME.”
Tomas et al. (2019)
Comments from Professor Julia Newton:
“This is an important study for people with M.E. Frequently people who come into the clinic ask about tests and whether they are helpful in their management. Often people have paid for these tests and struggle to understand why they aren't available on the NHS.”
“The ME Association very kindly supported a project to validate one currently available test in Newcastle. During our experiments it became clear that the test wasn't necessarily measuring what it claimed.
“Under these kind of scientific circumstances, it's important to replicate the experiments, so initially we did that with a second researcher in Newcastle and subsequently with a second group of scientists with Karl Morten’s group in Oxford. Both of which confirmed the initial findings.”
“It's really important with any test that it conforms with a set of specific principles. It needs to measure what it says it measures, that it is reliable, valid and robust. We definitely need such tests in M.E. but sadly remain someway away from that.”
Comments from Dr. Cara Tomas:
“Our study offers the first independent assessment of the suitability of the mitochondrial energy score (MES) test, used as a diagnostic test for ME/CFS by the Myhill group. This work was conducted in order to give patients more information regarding the suitability of the test for the diagnosis of ME/CFS.”
“The test calculates a number of different parameters of the production of ATP, the energy currency of the cell. The Myhill group found that ME/CFS patients have significantly reduced ATP production in neutrophils, a type of white blood cell that helps to protect against infection.”
“Diagnostic tests need to be reproducible in multiple laboratories to show that they are accurate enough to make a confident diagnosis.”
“We investigated the reliability and reproducibility of the test in two laboratories (University of Oxford and Newcastle University) using a protocol provided by the Myhill group.”
“Experiments used to calculate different aspect of the test score found no significant differences between ME/CFS and healthy control cohorts, implying that the results published by the Myhill group were not reproducible by independent research groups.”
“This study also looked at the effect of delayed sample processing on the parameters used to calculate the test score, something we thought may be responsible for the differences between the patient and controls groups. This is a major problem where sample processing using the Myhill protocol can be delayed by up to 72hrs for patients but control cells are processed within 24 hours.”
“In this study we found that sample processing time may account for the differences between the ME/CFS and healthy control cohorts reported by the Myhill group as a delay in sample processing in control cells showed similar results to the ME/CFS patient cells reported by the Myhill group.”
“Our study shows that the test does not have the reliability and reproducibility required of a diagnostic test, given that the results could not be independently replicated, and therefore should not be offered as a diagnostic test for ME/CFS by either private clinics or the NHS.”
“Patients pay large sums of money for this test and the interpretation of results and are often offered treatment in the form of supplements (at an additional cost) despite there being no published evidence that the treatment is effective.”
“The dissemination of this study among patients and their healthcare teams will allow patients to have the information to make an informed decision about the quality of the information they are likely to receive from this provider when paying for the MES test.”
- See also: Establishing Protocols to Assess Mitochondrial Function in ME/CFS by Dr Karl Morten | 21 August 2019
Myhill Group Publications
- Myhill S., Booth N. E. & McLaren-Howard J. (2009) Chronic fatigue syndrome and mitochondrial dysfunction. International Journal of Clinical and Experimental Medicine 2: 1–16.
- Booth N. E., Myhill S. & McLaren-Howard J. (2012) Mitochondrial dysfunction and the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). International Journal of Clinical and Experimental Medicine 5: 208–220.
- Myhill S., Booth N. E. & McLaren-Howard, J. (2013) Targeting mitochondrial dysfunction in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) – A clinical audit. International Journal of Clinical and Experimental Medicine 6: 1–15.
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