Contribute to NIH Research Strategy

“For the first time, NIH has requested public input into the future direction of ME/CFS research. This is a chance for researchers, organizations, advocates, and others to provide input directly to the Trans-NIH ME/CFS Working Group on the following questions:

  • Emerging needs and opportunities that should be considered as new ME/CFS research strategies are developed.
  • Challenges or barriers to progress in research on ME/CFS.
  • Gaps and opportunities across the research continuum from basic through clinical studies.

The deadline for response is June 24th, and responses to the RFI must be submitted via email to”

Jennie Spotila

Are you writing to the NIH? If you like you can copy your email into a comment below. My email was :


This will be less developed than I would like to make it due to my own health limitations. I have had ME since 1998. Currently I’m at housebound level. I read ME research as it is published and I am excited by the prospect of adequate funding for ME studies.

Emerging needs and opportunities that should be considered as new ME/CFS research strategies are developed:

I’m noticing greater collaboration and converging themes from international ME researchers. There’s an important opportunity to build on this. For example, multisite studies or replications. Themes seem to involve B cell issues (and related rituximab treatment and auto antibodies), the microbiome and metabolics. It would be useful to study all of these in the same well-defined patient group.

Challenges or barriers to progress in research on ME/CFS:

Previous research has been very hard to compare due to confused case definitions and methodological issues. For example, the recent systematic review of drug therapies (Collatz et al 2016) found that, although there were some significant outcomes, the results of the studies are limited to their respective cohorts and can’t be applied to other groups of people with ME (pwme). Depressingly for us this meant they could not recommend any treatment due to these problems with past research. They suggest this can be overcome by
1) using clearly defined, standardised diagnostic criteria such as ICC
2) standardising questionnaires and scales so that they are sensitive, specific and comparable in meta analysis
3) reaching consensus on how to measure the effectiveness of treatment in ME

I would add that objective measures should be included wherever possible, not just subjective scales which can be interpreted differently by different patients and researchers (this might include common technology such as a sports watch recording heart rate, sleep and steps).

Heated debate around the labels of ME and CFS causes problems for patients and researchers. These terms are used differently around the world. The label SEID doesn’t seem to work for most patients and hasn’t become popular. I wonder if it could help to drop the CFS term, take up a strict ICC criteria for research, but then also acknowledge those who don’t quite meet ICC as still physically ill but with Atypical ME (when working I saw this strategy used for other conditions)? Or a concerted effort to subgroup according to biomarkers could lead to specific, new labels which move away from negative past association with CFS.

Gaps and opportunities across the research continuum from basic through clinical studies.

There’s a lot of gaps in ME research, so I’m finding it hard to summarise here. A key starting point is people with Severe ME. Although Severe ME patients are hard to access the data will be much richer.

In addition to really getting to grips with aetiology and biomarkers longer term, we need some quick results on therapeutic interventions (even if the mechanism of action isn’t well understood). I am interested in Jared Younger’s current research into Gulf War Illness using 9 supplements which are easily available. Some quick turn around research like this into ME would be much appreciated. Some of us have been ill for decades with virtually no treatment. We don’t all have another 5 years to wait.

Also, once we are diagnosed with ME it is common for new symptoms to be dismissed as part of the ME and not treated. I recently had this experience with a 11 hour paralysis outside of my previous experience of 18 years with ME. I missed a comorbid POTS diagnosis and treatment for 16 years for this reason. Research to clarify which symptoms are exclusively ME and which associated (already treatable) co-morbidities could be valuable.

I contributed 2 research ideas to the Norwegian Research Council request for patient input when I was doing better. It will save me some energy to copy those here:

1) “Extended Family Extensive Medical History and Genome Analysis in Families with Multiple ME Patients

In what area do we need new research into CFS / ME ?

There is already good evidence of a genetic predisposition to ME, with a hereditability estimate of around 50% (2nd World Conf ). There is also evidence of mitochondria dysfunction, cardiovascular and autonomic impairments (which can have a hereditability element). It would be useful to do in-depth medical history and extended pedigree research on case study families where more than one person has had ME, taking a broad view of different health conditions. Depending on resources, this would include Genome Wide Association or a focus on areas such as mitochondrial DNA, immune function, MTHFR gene mutation and conditions related to dysautonomia such as Ehlers-Danos Syndrome. How do family members’ symptoms of other illnesses relate to recent genetic ME research? For example, hablogroup H has been associated with Post Exertional Malaise; J with joint pain and U with less bloating in ME (Billing-Ross et al 2016). Do family members experience these symptoms in the absence of meeting ME diagnosis criteria?

What specific issues should be investigated further ?

It would be interesting to find out if genetic variations related to ME can be expressed as different conditions in other family members, or as variations which would not be severe enough for diagnosis. This idea is inspired by a paper posthumously analysing the medical history of Charles Darwin’s family (Hayman, 2013). Many of his relatives suffered chronic illness but in different forms (including the appearance of ME/CFS). This paper speculates a specific A3243G mtDNA mutation caused the different symptoms. What is more interesting for ME research is that “the detailed, lifetime history of his illness and those of family members shows us the range of symptoms that may occur with the one mtDNA abnormality”.

Any research on participants with ME should also include careful recording of length of illness, apparent triggers, severity, the nature of symptoms and other co-morbidities for use as further comparison or subgrouping.

Why is this important for this population ?

This could be an important element of identifying hereditary causal factors, which in turn could identify effective treatment. It may also be possible to identify differences in relation to triggers. In relatives who have similar mutations, but do not develop ME, what life experiences have been different for these individuals? In particular, what has their experience of infectious disease been? Does anything appear to be protective against ME, despite having a genetic predisposition? This could be useful for younger relatives who are at risk of ME.

If the families do not demonstrate clean Mendelian segregation patterns, does this suggest the possibility of multiple underlying genes requiring further research?

Why is this important and useful for therapists ( health ) ?

If family members have genetic mutations in common, but different expressions of illness, it may be that existing treatments for their other conditions are beneficial to ME patients with this specific variation. Information about patient reaction to drugs may also come out of this research (for example the families may be more often poor metabolizers). There may be useful preventative precautions for other family members, or treatment that could be taken early if relatives show initial symptoms.

It could lead to useful subgrouping, as patients with different mutations are likely to need different treatment. For future patients, with the same mutation as those studied, it would not be necessary to analyse their extended family tree to get the relevant information.


Hayman, J. (2013). Charles Darwin’s Mitochondria. Genetics, 194(1), 21–25.

Billing-Ross (2016) Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2016 Jan 20;14(1):19. doi: 10.1186/s12967-016-0771-6. Billing-Ross P1, Germain A2, Ye K3, Keinan A4, Gu Z5, Hanson MR6.

Jason, L. A., Zinn, M. L., & Zinn, M. A. (2015). Myalgic Encephalomyelitis: Symptoms and Biomarkers. Current Neuropharmacology, 13(5), 701–734.

Bhattacharjee, M., Rajeevan, M. S., & Sillanpää, M. J. (2015). Prediction of complex human diseases from pathway-focused candidate markers by joint estimation of marker effects: case of chronic fatigue syndrome. Human Genomics, 9(1), 8.

International Consensus Primer (2012) primer.pdf

2)Glucose Metabolism Dysfunction and Personalised Nutrition in ME
In what area do we need new research into CFS / ME ?

Anecdotally many people with ME complain of issues to do with sugar, but are not usually diabetic. Some people cut down portions of carbohydrates and others cut out refined sugar. One study found that a low sugar diet was not significantly different from a healthy eating control diet, contrary to patient perception (Hobday et al, 2008).

However, in a recent study people with CFS were shown to have elevated glucose levels, there appeared to be an inhibition of glycolysis (Armstrong, 2015). Another recent study, found striking biochemical differences in skeletal muscle cultures, including a lack of increase in glucose uptake following 16 hours of stimulation (in contrast to control cultures) despite remaining responsive to insulin (Brown et al, 2015).

Is there an unusual metabolic problem with glucose in ME? For example, greater fluctuation than normally seen, apart from in diabetics? Can this be managed with any efficiency at the diet level or is it a more fundamental metabolic problem?

What specific issues should be investigated further ?

A study similar in design to the Zeevi general population study in Israel that had nearly 1000 participants could be useful (Zeevi et al, 2015). That study had 2 phases. Firstly they constantly measured blood glucose levels via a glucometer placed under the skin and recorded sleep and activity using an activity wristband (eg a fitbit). Participants recorded further information in real time about their food, mood and exercise regimes on an app. Obviously a ME study would add in symptom scales into this too and detailed information on activity would be essential. They also took a stool sample for microbiome information.

The Israeli team then created ‘good’ diets that prevented blood sugar spikes based on data from the 1st phase of the study (results were surprisingly individual). They found that not only did blood sugar respond as predicted but that the ‘good’ diet was associated with positive microbiome changes too. Can this diet information be applied in ME too and used as a 2nd phase?

Why is this important for this population ?

Energy metabolism dysfunction is a likely problem in ME and deserves further investigation. The 1st phase of this research can contribute valuable data about glucose metabolism in ME. The 2nd phase may provide an evidence informed approach to managing diet. Even if diet changes are not substantial enough to correct potential problems at the level of ATP production, is it beneficial for patients to keep glucose levels more consistent? In the absence of substantial research, patients find it hard to interpret information about diet and information is shared at an anecdotal level.

In the Zeevi study they found surprising levels of individual difference in blood sugar reaction to food. For example, some people have a healthy reaction if foods include fat whereas for others this makes no difference. People’s response to food was also linked to their gut bacteria composition. There was a benefit to individualising diet advice. Can this general population data be useful for people with ME?

Why is this important and useful for therapists ( health ) ?

Further information about patients’ glucose metabolism would be useful for medics. At the moment glucose issues in ME are rarely acknowledged in primary care, once diabetes has been ruled out. It maybe, depending on results, that treatment for other conditions could be used once the nature of the problem is known. This approach is also very likely to steer nutritionists to improved dietary advice for patients.


Armstrong (2015) Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients. Metabolomics. 2015 May 30. doi: 10.1007/s11306-015-0816-5. Armstrong CW, McGregor NR, Lewis DP, Butt HL, Gooley PR.

A. E. Brown, D. E. Jones, M. Walker, and J. L. Newton (2015), “Abnormalities of AMPK activation and glucose uptake in Chronic Fatigue Syndrome,” PLoS ONE, vol. 10, no. 4, Article ID e0122982, 2015.

Hobday, R. A., Thomas, S., O’Donovan, A., Murphy, M. and Pinching, A. J. (2008), Dietary intervention in chronic fatigue syndrome. Journal of Human Nutrition and Dietetics, 21: 141–149. doi: 10.1111/j.1365-277X.2008.00857.x

Zeevi et al., 2015, Personalized Nutrition by Prediction of Glycemic Responses. Cell 163, 1079–1094, November 19, 2015

Thank you for investing in ME research I believe that this can be solved.

Best wishes

If you like this post you might like:

Post about glucose

Post about paradoxical research funding

Post about whether it is more important not to get worse 



6 thoughts on “Contribute to NIH Research Strategy

  1. Energins needs:

    1) Multiply the biomedical research by a 100 times to find a cure please! We want to be active and useful again! Waited too long.

    2) Diastolic dysfunction and reduced cardiac output found by Dr Cheney and others must be looked at.
    Many ME-patients feel the basic problem is very connected to an inflammation in their heart area.

    3) How reduced is the blood volume?
    How does the reduced blood volume and circulation affect different organs?
    Do the ME sufferer need a higher concentration of minerals and vitamins in the blood to support the organs?

    5) Different sub groups. How is ME changing over time. Risk of relapses. This will clear up a lot of misunderstandings of ME.

    Liked by 1 person

  2. Pingback: A patient responds to NIH request for input – Shoutout About ME

  3. Pingback: Persuasion Savvy Advocacy Challenge | Tips for ME

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