ME Association April Summary of ME/CFS Published Research | 07 May 2018

May 7, 2018


ME Association Index of Published ME/CFS Research

The Index of Published ME/CFS Research has now been updated to take account of the studies that have been published during April. It is free to download and comes with an interactive contents table.

This is an A-Z index of all the most important research studies (and selected key documents and articles), listed by subject matter, that have been published on ME/CFS and is correct to 30th April 2018.

You can also find the index in the Research section of our website.

The following is a list of abstracts from those studies published in April 2018

Arring NM et al. 2018
Ginseng as a Treatment for Fatigue: A Systematic Review.
Journal of Alternative and Complimentary Medicine [Epub ahead of print].

Millions of people with chronic illness suffer from fatigue. Fatigue is a complex, multidimensional symptom with poorly understood causes, wide variations in severity among individuals, and negative effects on multiple domains of daily life.

Many patients with fatigue report the use of herbal remedies. Ginseng is one of the most widely used because it is believed to improve energy, physical and emotional health, and well-being.

To systematically review the published evidence to evaluate the safety and effectiveness of the two types of Panax ginseng (Asian [Panax ginseng] and American [Panax quinquefolius]) as treatments for fatigue.

PubMed, CINAHL (Cumulative Index to Nursing and Allied Health), Ovid MEDLINE, and EMBASE databases were searched using Medical Subject Heading and keyword terms, including ginseng, Panax, ginsenosides, ginsenoside* (wild card), fatigue, fatigue syndrome, cancer-related fatigue, and chronic fatigue.

Studies were included if participants had fatigue, had used one of the two Panax ginsengs as an intervention, and had scores from a self-report fatigue measure. Two reviewers independently assessed each article at each review phase and met to develop consensus on included studies. Risk of bias was assessed using version 5.3 of the Cochrane Collaboration Review Manager (RevMan), and results were synthesized in a narrative summary.

The search strategy resulted in 149 articles, with 1 additional article located through review of references. After titles, abstracts, and full text were reviewed, 139 articles did not meet inclusion criteria. For the 10 studies reviewed, there was a low risk of adverse events associated with the use of ginseng and modest evidence for its efficacy.

Ginseng is a promising treatment for fatigue. Both American and Asian ginseng may be viable treatments for fatigue in people with chronic illness. Because of ginseng's widespread use, a critical need exists for continued research that is methodologically stronger and that includes more diverse samples before ginseng is adopted as a standard treatment option for fatigue.


Brown AE et al. 2018
Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS.
Bioscience Reports [Epub ahead of print]


Skeletal muscle fatigue and post-exertional malaise are key symptoms of Myalgic Encephalomyelitis (ME/CFS).

We have previously shown that AMPK activation and glucose uptake are impaired in primary human skeletal muscle cell cultures derived from patients with ME/CFS in response to electrical pulse stimulation, a method which induces contraction of muscle cells in vitro.

The aim of this study was to assess if AMPK could be activated pharmacologically in ME/CFS.

Primary skeletal muscle cell cultures from patients with ME/CFS and healthy controls were treated with either metformin or 991. AMPK activation was assessed by Western blot and glucose uptake measured.

Both metformin and 991 treatment significantly increased AMPK activation and glucose uptake in muscle cell cultures from both controls and ME/CFS. Cellular ATP content was unaffected by treatment although ATP content was significantly decreased in ME/CFS compared to controls.

Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS.

This suggests that the failure of electrical pulse stimulation to activate AMPK in these muscle cultures is due to a defect proximal to AMPK.

Further work is required to delineate the defect and determine whether pharmacological activation of AMPK improves muscle function in patients with ME/CFS.


De Vega WC et al. 2018
Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome.
Epigenomics [Epub ahead of print].

To identify subtypes in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) based on DNA methylation profiles and health scores.

DNA methylome profiles in immune cells were integrated with symptomatology from 70 women with ME/CFS using similarity network fusion to identify subtypes.

We discovered four ME/CFS subtypes associated with DNA methylation modifications in 1939 CpG sites, three RAND-36 categories and five DePaul Symptom Questionnaire measures.

Methylation patterns of immune response genes and differences in physical functioning and postexertional malaise differentiated the subtypes.

ME/CFS subtypes are associated with specific DNA methylation differences and health symptomatology and provide additional evidence of the potential relevance of metabolic and immune differences in ME/CFS with respect to specific symptoms.


Maness C et al. 2018
Systemic exertion intolerance disease/chronic fatigue syndrome is common in sleep centre patients with hypersomnolence: A retrospective pilot study.
Journal of Sleep Research [ Epub ahead of print].

Symptoms of the central disorders of hypersomnolence extend beyond excessive daytime sleepiness to include non-restorative sleep, fatigue and cognitive dysfunction.

They share much in common with myalgic encephalomyelitis/chronic fatigue syndrome, recently renamed systemic exertion intolerance disease, whose additional features include post-exertional malaise and orthostatic intolerance.

We sought to determine the frequency and correlates of systemic exertion intolerance disease in a hypersomnolent population.

One-hundred and eighty-seven hypersomnolent patients completed questionnaires regarding sleepiness and fatigue; questionnaires and clinical records were used to assess for systemic exertion intolerance disease.

Sleep studies, hypocretin and cataplexy were additionally used to assign diagnoses of hypersomnolence disorders or sleep apnea.

Included diagnoses were idiopathic hypersomnia (n = 63), narcolepsy type 2 (n = 25), persistent sleepiness after obstructive sleep apnea treatment (n = 25), short habitual sleep duration (n = 41), and sleepiness with normal sleep study (n = 33).

Twenty-one percent met systemic exertion intolerance disease criteria, and the frequency of systemic exertion intolerance disease was not different across sleep diagnoses (p = .37). Patients with systemic exertion intolerance disease were no different from those without this diagnosis by gender, age, Epworth Sleepiness Scale, depressive symptoms, or sleep study parameters.

The whole cohort reported substantial fatigue on questionnaires, but the systemic exertion intolerance disease group exhibited more profound fatigue and was less likely to respond to traditional wake-promoting agents (88.6% versus 67.7%, p = .01).

Systemic exertion intolerance disease appears to be a common co-morbidity in patients with hypersomnolence, which is not specific to hypersomnolence subtype but may portend a poorer prognosis for treatment response.


Njølstad BW et al. 2018
‘It's like being a slave to your own body in a way': a qualitative study of adolescents with chronic fatigue syndrome.
Scandanavian Journal of Occupational Therapy 1-10. [Epub ahead of print].

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a relatively common disabling illness in adolescents that may limit participation in daily life.

This study explored interactions between the illness experiences of adolescents with CFS/ME, their occupational lives and expectations for the future.

Seven adolescents with CFS/ME were interviewed. The interviews were analyzed using thematic analysis.

Three themes were developed:

  • ‘Being ruled by an unfamiliar and inexplicable body', which illustrated that altered and strange bodies seemed to separate and disrupt the participants from their former occupational lives.
  • ‘On the sideline of life with peers', which demonstrated that the informants spent time at home, doing undemanding activities instead of participating in activities with peers.
  • ‘A coherent connection between present and future life', which was reflected by how the participants eventually accepted their situation and rebuilt a meaningful occupational life and value of self.

CFS/ME made the body unfamiliar and disconnected informants from participating in their usual daily occupations. A coherent interaction between body, occupational life and social self was achieved by taking their new body into account and adjusting their occupations accordingly. This practice enabled the participants to hope for a better future life.


Oka T et al. 2018
Changes in fatigue, autonomic functions, and blood biomarkers due to sitting isometric yoga in patients with chronic fatigue syndrome.
Biopsychosocial Medicine 12: 3.

Background: In a previous randomized controlled trial, we found that sitting isometric yoga improves fatigue in patients with chronic fatigue syndrome (CFS) who are resistant to conventional therapy.

The aim of this study was to investigate possible mechanisms behind this finding, focusing on the short-term fatigue-relieving effect, by comparing autonomic nervous function and blood biomarkers before and after a session of isometric yoga.

Fifteen patients with CFS who remained symptomatic despite at least 6 months of conventional therapy practiced sitting isometric yoga (biweekly 20 min practice with a yoga instructor and daily home practice) for eight weeks.

Acute effects of sitting isometric yoga on fatigue, autonomic function, and blood biomarkers were investigated after the final session with an instructor. The effect of a single session of sitting isometric yoga on fatigue was assessed by the Profile of Mood Status (POMS) questionnaire immediately before and after the session.

Autonomic nervous function (heart rate (HR) variability) and blood biomarkers (cortisol, DHEA-S, TNF-α, IL-6, IFN-γ, IFN-α, prolactin, carnitine, TGF-β1, BDNF, MHPG, and HVA) were compared before and after the session.

Sitting isometric yoga significantly reduced the POMS fatigue score (p < 0.01) and increased the vigor score (p < 0.01). It also reduced HR (p < 0.05) and increased the high frequency power (p < 0.05) of HR variability.

Sitting isometric yoga increased serum levels of DHEA-S (p < 0.05), reduced levels of cortisol (p < 0.05) and TNF-α (p < 0.05) and had a tendency to reduce serum levels of prolactin (p < 0.1).

Decreases in fatigue scores correlated with changes in plasma levels of TGF-β1 and BDNF. In contrast, increased vigor positively correlated with HVA.

A single session of sitting isometric yoga reduced fatigue and increased vigor in patients with CFS. Yoga also increased vagal nerve function and changed blood biomarkers in a pattern that suggested anti-stress and anti-inflammatory effects.

These changes appear to be related to the short-term fatigue-relieving effect of sitting isometric yoga in patients with CFS. Furthermore, dopaminergic nervous system activation might account for sitting isometric yoga-induced increases in energy in this patient population.


Pajediene E et al. (2018)
Sleep patterns among patients with chronic fatigue: A polysomnography-based study.
The Clinical Respiratory Journal 12 (4): 1389-1397.

The purpose of this study was to detect treatable sleep disorders among patients complaining of chronic fatigue by using sleep questionnaires and polysomnography.

Patients were referred to hospital for investigations and rehabilitation because of a suspected diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

The criteria for further referral to full-night polysomnography (PSG) were symptoms of excessive daytime sleepiness and/or tiredness in the questionnaires.

Of a total of 381 patients, 78 (20.5%) patients underwent PSG: 66 women and 12 men, mean age 48.6 years, standard deviation ±9.9 years.

On the basis of the PSG, 31 (40.3%) patients were diagnosed with obstructive sleep apnoea, 7 (8.9%) patients with periodic limb movement disorder, 32 (41.0%) patients with restless legs syndrome and 54 (69.3%) patients had one or more other sleep disorder.

All patients were grouped into those who fulfilled the diagnostic criteria for ME/CFS (n = 55, 70.5%) and those who did not (n = 23, 29.5%). The latter group had significantly higher respiratory (P = .01) and total arousal (P = .009) indexes and a higher oxygen desaturation index (P = .009).

More than half of these chronic fatigue patients, who also have excessive daytime sleepiness and/or tiredness, were diagnosed with sleep disorders such as obstructive sleep apnoea, periodic limb movement disorder and/or restless legs syndrome.

Patients with such complaints should undergo polysomnography, fill in questionnaires and be offered treatment for sleep disorders before the diagnose ME/CFS is set.


Rasouli O et al. 2018
Lower regulatory frequency for postural control in patients with fibromyalgia and chronic fatigue syndrome.
PLoS One 13 (4): e0195111.

As many similar symptoms are reported in fibromyalgia (FM) and chronic fatigue syndrome(CFS), underlying deficits may potentially also be similar. Postural disequilibrium reported in both conditions may thus be explained by similar deviations in postural control strategies.

75 females (25/group FM, CFS and control, age 19-49 years) performed 60 s of quiet standing on a force platform in each of three conditions: 1) firm surface with vision, 2) firm surface without vision and, 3) compliant surface with vision.

Migration of center of pressure was decomposed into a slow and a fast component denoting postural sway and lateral forces controlling postural sway, analyzed in the time and frequency domains.

Main effects of group for the antero-posterior (AP) and medio-lateral (ML) directions showed that patients displayed larger amplitudes (AP, p = 0.002; ML, p = 0.021) and lower frequencies (AP, p < 0.001; ML, p < 0.001) for the slow component, as well as for the fast component (amplitudes: AP, p = 0.010; ML, p = 0.001 and frequencies: AP, p = 0.001; ML, p = 0.029) compared to controls.

Post hoc analyses showed no significant differences between patient groups.

In conclusion, both the CFS- and the FM-group differed from the control group. Larger postural sway and insufficient control was found in patients compared to controls, with no significant differences between the two patient groups.


Richardson AM et al. 2018
Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection.
Journal of Translational Medicine 16 (1): 97.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is clinically defined and characterised by persistent disabling tiredness and exertional malaise, leading to functional impairment.

This study introduces the weighted standing time (WST) as a proxy for ME/CFS severity and investigates its behaviour in an Australian cohort.

WST was calculated from standing time and subjective standing difficulty data, collected via orthostatic intolerance assessments. The distribution of WST for healthy controls and ME/CFS patients was correlated with the clinical criteria, as well as pathology and cytokine markers.

Included in the WST cytokine analyses were activins A and B, cytokines causally linked to inflammation, and previously demonstrated to separate ME/CFS from healthy controls.

Forty-five ME/CFS patients were recruited from the CFS Discovery Clinic (Victoria) between 2011 and 2013. Seventeen healthy controls were recruited concurrently and identically assessed.

WST distribution was significantly different between ME/CFS participants and controls, with six diagnostic criteria, five analytes and one cytokine also significantly different when comparing severity via WST.

On direct comparison of ME/CFS to study controls, only serum activin B was significantly elevated, with no significant variation observed for a broad range of serum and urine markers, or other serum cytokines.

The enhanced understanding of standing test behaviour to reflect orthostatic intolerance as a ME/CFS symptom, and the subsequent calculation of WST, will encourage the greater implementation of this simple test as a measure of ME/CFS diagnosis, and symptom severity, to the benefit of improved diagnosis and guidance for potential treatments.


Roman P et al. 2018
Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review.
Beneficial Microbes [Epub ahead of print].

Evidence suggests that the gut microbiota might play an important role in fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). Our goal is to systematically review the reported effect of probiotic treatments in patients diagnosed with FMS or CFS.

A systematic review was carried out using 14 databases (PubMed, Cochrane Library, Scopus, PsycINFO, and others) in February 2016 to search for randomised controlled trials (RCTs) and pilot studies of CFS or FMS patients published in the last ten years (from 2006 to 2016). The Jadad scale was used to asseverate the quality of the clinical trials considered.

Two studies (n=83) met the inclusion criteria, which were performed in CFS patients and both studies were considered as a ‘High range of quality score'. The administration of Lactobacillus casei strain Shirota in CFS patients, over the course of 8 weeks, reduced anxiety scores.

Likewise, this probiotic changed the faecal composition following 8 weeks of treatment. Additionally, the treatment with Bifidobacterium infantis 35624 in CFS patients, during the same period, reduced inflammatory biomarkers.

The evidence about the usefulness of probiotics in CFS and FMS patients remains limited. The studied strains of probiotics have demonstrated a significant effect on modulating the anxiety and inflammatory processes in CFS patients. However, more experimental research, focusing mainly on the symptoms of the pathologies studied, is needed.


Sotzny F et al. 2018
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease.
Autoimmune Reviews [Epub ahead of print]

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality.

The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS.

Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups.

Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS.

Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.


Tomas C and Newton J. 2018
Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review.
Biochemical Society Transactions. [Epub ahead of print]

Chronic fatigue syndrome (CFS), commonly known as myalgic encephalomyelitis (ME), is a debilitating disease of unknown etiology. CFS/ME is a heterogeneous disease associated with a myriad of symptoms but with severe, prolonged fatigue as the core symptom associated with the disease.

There are currently no known biomarkers for the disease, largely due to the lack of knowledge surrounding the eitopathogenesis of CFS/ME. Numerous studies have been conducted in an attempt to identify potential biomarkers for the disease.

This mini-review offers a brief summary of current research into the identification of metabolic abnormalities in CFS/ME which may represent potential biomarkers for the disease.

The progress of research into key areas including immune dysregulation, mitochondrial dysfunction, 5′-adenosine monophosphate-activated protein kinase activation, skeletal muscle cell acidosis, and metabolomics are presented here.

Studies outlined in this mini-review show many potential causes for the pathogenesis of CFS/ME and identify many potential metabolic biomarkers for the disease from the aforementioned research areas.

The future of CFS/ME research should focus on building on the potential biomarkers for the disease using multi-disciplinary techniques at multiple research sites in order to produce robust data sets.

Whether the metabolic changes identified in this mini-review occur as a cause or a consequence of the disease must also be established.


Van der Schaaf ME et al. 2018
Fatigue Is Associated with Altered Monitoring and Preparation of Physical Effort in Patients with Chronic Fatigue Syndrome.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging 3 (4): 392-404.

Chronic fatigue syndrome (CFS) is characterized by disabling fatigue, which is suggested to be maintained by dysfunctional beliefs.

Fatigue and its maintenance are recently conceptualized as arising from abnormally precise expectations about bodily inputs and from beliefs of diminished control over bodily states, respectively.

This study used functional neuroimaging to identify the neural correlates of fatigue and its maintenance by beliefs during a physical effort task.

We isolated behavioral adjustments and cerebral activity during feedback processing and motor preparation, in the context of a task in which patients with CFS (n = 85) and healthy control subjects (n = 29) produced 30%, 50%, and 70% of their right-hand maximal voluntary contraction, and received directional feedback on performance (e.g., too little force).

Patients with CFS showed an effort-dependent behavioral bias toward less effort investment in response to directional feedback for the highest effort level as compared with healthy control subjects. This bias was associated with reduced feedback-related activity in the dorsolateral prefrontal cortex.

These effects were proportional to state-related fatigue and prior beliefs about CFS patients' ability to perform the task. Patients with CFS also showed higher activity in the supplementary motor area, proportional to their state-related fatigue, and reduced connectivity between the supplementary motor area and sensorimotor cortex during motor preparation as compared with control subjects.

These findings link fatigue symptoms to alterations in behavioral choices on effort investment, prefrontal functioning, and supplementary motor area connectivity, with the dorsolateral prefrontal cortex being associated with prior beliefs about physical abilities.



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