TGI Friday! Our weekly round-up of recently published research abstracts | 25 April 204

April 25, 2014

From Biochimica et Biophysica Acta, Clinical, published online on 13 April 2014.

Association of mitochondrial dysfunction and fatigue: A review of the literature

Kristin Filler(a,c), Debra Lyon(b), James Bennett(a), Nancy McCain(a), Ronald Elswick(a), Nada Lukkahatai©, Leorey N. Saligan©.
a) Virginia Commonwealth University School of Nursing, 1100 East Leigh Street Richmond, VA 23298-0567, USA
b) University of Florida College of Nursing, PO Box 100197, Gainesville, FL 32610-0197, USA
c) National Institutes of Health, National Institute of Nursing Research, 3 Center Drive, Building 3, Room 5E26, Bethesda, MD, USA


• Etiologic mechanisms underlying the symptom of fatigue are not well understood.
• This review investigates the association of mitochondrial dysfunction with fatigue.
• Inconsistent associations observed between mitochondria dysfunction and fatigue.


Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue.

Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1220 articles.

After the application of inclusion and exclusion criteria, a total of 25 articles meeting
eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue.

Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter.

Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial
morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature.

From Fatigue: Biomedicine, Health & Behavior, published online 14 April 2014.

Feasibility of a home-based self-management program for chronic fatigue

Fred Friedberg(a,*), Man Chi Ngan(a) & Jeremy Chang(a)
a) Department of Psychiatry and Behavioral Sciences, Stony Brook University, Putnam Hall/South Campus, Stony Brook, New York, USA
* Corresponding author



This study evaluated the feasibility of a 12-week home-based self-management program for unexplained chronic fatigue (UCF) or chronic fatigue syndrome (CFS).


Self-report outcomes included measures of fatigue impact, physical function, depression, and global change. A web diary measured daily compliance with self-management activities.


Study withdrawals (20.8%) were due to time constraints, confidentiality concerns, or illness recovery. Subjects (N = 19) showed excellent compliance (62.3%) on the web diary. Participant feedback indicated high satisfaction. Effect sizes were large for fatigue severity, physical functioning, and depression.


A home-based self-management program for UCF and CFS may offer improved patient access to treatment that may be unavailable, inconvenient, or costly.

From Journal of Translational Medicine, 23 April 2014 (full text available).

Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO2peak indicates functional impairment

Betsy A Keller(1*), John Luke Pryor(2), Ludovic Giloteaux(3)
1) Department of Exercise & Sport Sciences, Ithaca College, School of Health Sciences & Human Performance, 318 Center for Health Sciences, Ithaca, NY 14850, USA
2) Department of Kinesiology, University of Connecticut, Neag School of Education, 2095 Hillside Rd, Unit 1110, Storrs, CT 06269-1110, USA
3) Department of Molecular Biology and Genetics, Cornell University, College of Agriculture and Life Sciences, 321 Biotechnology Building, Ithaca, NY 14853, USA
* Corresponding author Email:

Abstract (provisional)


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multi-system illness characterized, in part, by increased fatigue following minimal exertion, cognitive impairment, poor recovery to physical and other stressors, in addition to other symptoms.

Unlike healthy subjects and other diseased populations who reproduce objective physiological measures during repeat cardiopulmonary exercise tests (CPETs), ME/CFS patients have been reported to fail to reproduce results in a second CPET performed one
day after an initial CPET. If confirmed, a disparity between a first and second CPET could serve to identify individuals with ME/CFS, would be able to document their extent of disability, and could also providea physiological basis for prescribing physical activity as well as a metric of functional impairment.


22 subjects diagnosed with ME/CFS completed two repeat CPETs separated by 24 h. Measures of oxygen consumption (VO2), heart rate (HR), minute ventilation (Ve), workload (Work), and respiratory exchange ratio (RER) were made at maximal (peak) and ventilatory threshold (VT) intensities. Data were analyzed using ANOVA and Wilcoxon's Signed-Rank Test (for RER).


ME/CFS patients showed significant decreases from CPET1 to CPET2 in VO2peak (13.8%), HRpeak (9 bpm), Ve peak (14.7%), and Work@peak (12.5%). Decreases in VT measures included VO2@VT (15.8%), Ve@VT (7.4%), and Work@VT (21.3%).

Peak RER was high (>=1.1) and did not differ between tests, indicating maximum effort by participants during both CPETs. If data from only a single CPET test is used, a standard classification of functional impairment based on VO2peak or VO2@VT results in over-estimation of functional ability for 50% of ME/CFS participants in this study.


ME/CFS participants were unable to reproduce most physiological measures at both maximal and ventilatory threshold intensities during a CPET performed 24 hours after a prior maximal exercise test.

Our work confirms that repeated CPETs warrant consideration as a clinical indicator for diagnosing ME/CFS.

Furthermore, if based on only one CPET, functional impairment classification will be mis-identified in many ME/CFS participants.

From Fatigue: Biomedicine, Health and Behavior, published online on 23 April 2014.

Chronic fatigue syndrome: the current status and future potentials of emerging biomarkers

David B. Fischer(a), Arsani H. William(a), Adam C. Strauss (a.b), Elizabeth R. Unger©, Leonard A. Jason(d), Gailen D. Marshall Jr(e) & Jordan D. Dimitrakoff(f,g*)
a) New Pathway Program in Medical Education, Harvard Medical School, Boston, MA, USA
b) Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, USA
c) Division of High-Consequence Pathogens and Pathology (DHCPP), Centers for Disease Control and Prevention, Atlanta, GA, USA
d) DePaul University, Chicago, USA
e) Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
f) Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
g) Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA



Chronic fatigue syndrome (CFS) remains an incompletely characterized illness, in part due to controversy regarding its definition, biological basis, and diagnosis.


Biomarkers are objective measures that may lead to improvements in our understanding of CFS by providing a more coherent and consistent approach to study, diagnosis, and treatment of the illness. Such metrics may allow us to distinguish between CFS subtypes – each defined by characteristic biomarkers – currently conflated under the single, heterogeneous condition of CFS. These delineations, in turn, may guide more granular, focused, and targeted treatment strategies based on more precise characterizations of the illness.


Here, we review potential CFS biomarkers related to neurological and immunological components of the illness.


We discuss how these biomarkers may be used to move the field of CFS forward, emphasizing clinical utility and potential routes of future research.

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