Important Research Studies That Point to Hope for Chronic Fatigue

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Fourteen studies that give hope to Gulf War Veterans with Chronic Fatigue

Fourteen studies over a year that are helping to lead the way to answers for Chronic Fatigue and Gulf War Veterans are highlighted below.  Significant work is occurring on finding biomarkers, genetic markers, potentials for treatment, and future direction in this field of research.  The significant findings are underlined in the abstracts, to help guide the non medical person to the take away message.  Dr Klimas and Dr Baraniuk are in the lead here in the United States besides studies at Wayne State, Seattle, and Chicago but this is a significant list of research centers that is international with UK, Australia, Canada, India, and Belgium represented.

1. Allergy Asthma Proc. 2010 May-Jun;31(3):169-78.

Relationships among rhinitis, fibromyalgia, and chronic fatigue.
Baraniuk JN, Zheng Y.

Division of Rheumatology, Immunology and Allergy, Georgetown University, PHC Building, 3800 Reservoir Road, NW, Washington, DC 20007-2197, USA.

Abstract
New information about the pathophysiology of idiopathic nonallergic rhinopathy indicates a high prevalence in chronic fatigue syndrome (CFS). This article shows the relevance of CFS and allied disorders to allergy practice. CFS has significant overlap with systemic hyperalgesia (fibromyalgia), autonomic dysfunction (irritable bowel syndrome and migraine headaches), sensory hypersensitivity (dyspnea; congestion; rhinorrhea; and appreciation of visceral nociception in the esophagus, gastrointestinal tract, bladder, and other organs), and central nervous system maladaptations (central sensitization) recorded by functional magnetic resonance imaging (fMRI). Neurological dysfunction may account for the overlap of CFS with idiopathic nonallergic rhinopathy. Scientific advances are in fMRI, nociceptive sensor expression, and, potentially, infection with xenotropic murine leukemia-related virus provide additional insights to novel pathophysiological mechanisms of the “functional” complaints of these patients that are mistakenly interpreted as allergic syndromes. As allergists, we must accept the clinical challenges posed by these complex patients and provide proper diagnoses, assurance, and optimum care even though current treatment algorithms are lacking.

1 selected item: 20629967FormatSummarySummary (text)AbstractAbstract (text)MEDLINEXMLPMID

2. Pain Pract. 2010 Jan-Feb;10(1):54-9.

Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate.
Spitzer AR, Broadman M.

Neurology Department, Wayne State University School of Medicine, Detroit, Michigan, USA.

Abstract
This study investigates the response of the underlying sleep disorder associated with Chronic Fatigue Syndrome (CFS) and fibromyalgia (FM) to treatment. We retrospectively reviewed 118 cases clinically consistent with CFS or FM, treated in a neurology practice. Abnormal findings on sleep studies and associated human leukocyte antigen markers, and a clinical pattern suggestive of narcolepsy, are present in a high proportion of patients. When considered appropriate based on the clinical picture and test results, treatment with sodium oxybate was offered to these patients. Sixty percent of patients treated with oxybate experienced significant relief of pain, while 75% experienced significant relief of fatigue. We postulate that the response to oxybate in CFS and FM suggests a disturbance of sleep similar to narcolepsy. These findings support this novel approach to intervention and further research. The inability to distinguish CFS and FM by testing and response to treatment suggests that they may represent variations of the same disorder or may be closely related disorders.

PMID: 20629967 [PubMed – in process]

3. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Jul 4. [Epub ahead of print]

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.
Maes M.

Abstract
There is a significant ‘comorbidity’ between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy. This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2′-5′ oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS. Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways. Depression and ME/CFS are not ‘comorbid’ disorders, but should be regarded as ‘co-associated disorders’ that are clinical manifestations of shared pathways.

PMID: 20609377 [PubMed – as supplied by publisher]

4. Inflammopharmacology. 2010 Jul 3. [Epub ahead of print]

Potential role of pioglitazone, caffeic acid and their combination against fatigue syndrome-induced behavioural, biochemical and mitochondrial alterations in mice.
Kumar A, Vashist A, Kumar P.

Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, 160014, India

Abstract
Chronic fatigue is an illness characterised by persistent and relapsing fatigue, often accompanied by numerous neuropsychiatric problems, such as anxiety and depression. The aetiology of chronic fatigue remains unclear so far. However, recent studies suggested the involvement of oxidative stress in this chronic debilitating disease. Alternatively, antioxidants have also been reported to have beneficial effect against chronic fatigue-like conditions. Therefore, present study has been designed to explore the potential role of pioglitazone, caffeic acid and their combination against chronic fatigue-like condition in mice. In the experimental protocol, the mice were put on the running wheel apparatus for 6 min test session daily for 21 days which produced fatigue-like condition. The locomotor activity and anxiety levels were measured on 0, 8th, 15th and 22nd days. The brains were isolated on 22nd day immediately after the behavioural assessments, oxidative damage and mitochondrial enzyme complexes were then estimated subsequently. Three weeks pioglitazone (5 and 10 mg/kg) and caffeic acid (5 and 10 mg/kg) pretreatment significantly attenuated the chronic fatigue-like condition (restored running wheel activity, locomotor activity and reduced anxiety-like behaviour) as compared to that in control (chronic fatigue) animals. Further, pioglitazone (5 and 10 mg/kg) and caffeic acid (5 and 10 mg/kg) drug treatments for 3 weeks significantly attenuated oxidative damage (decreased lipid peroxidation, nitrite concentration, restored reduction in glutathione and catalase levels), altered mitochondrial enzymes complex (I, II and IV) activities and mitochondrial redox activity (MTT assay) when compared with control. Further, combination of lower dose of pioglitazone (5 mg/kg) and caffeic acid (5 mg/kg) showed significant synergism in their protective effect which was significant as compared to their effect per se. The present study highlights the potential role of pioglitazone, caffeic acid and their combination in the pathophysiology of chronic fatigue-like condition in mice.

PMID: 20602174 [PubMed – as supplied by publisher]

5. J Neuroimmunol. 2010 May 25. [Epub ahead of print]

Possible role of oxidative stress and immunological activation in mouse model of chronic fatigue syndrome and its attenuation by olive extract.
Gupta A, Vij G, Chopra K.

Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh 160014, India.

Abstract
Various putative theories involved in the development of chronic fatigue syndrome revolve around the role of stress, infection and oxidative stress. Scientific evidence highlighting the protective role of nutritional supplements in chronic fatigue syndrome is lacking. Based on these assumptions, the present study was designed to evaluate the effect of olive extract in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigen were used as immunogens. The assessment of chronic fatigue syndrome was based on immobility period during chronic water-immersion stress test for 10min daily. The stress-induced hyperalgesia was measured by tail withdrawal latency. Mice challenged with LPS or BA for 19days showed significant increase in the immobility time, hyperalgesia and oxidative stress on the 19th day. Serum tumor necrosis factor-alpha (TNF-alpha) levels were also markedly increased with LPS or BA challenge. Concurrent treatment with olive extract resulted in a significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as serum TNF-alpha levels. The results of the present study strongly indicate the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome and highlight the valuable role of olive extract in combating chronic fatigue syndrome.

PMID: 20537729 [PubMed – as supplied by publisher]

6. PLoS One. 2010 May 25;5(5):e10817.

Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26.
Fletcher MA, Zeng XR, Maher K, Levis S, Hurwitz B, Antoni M, Broderick G, Klimas NG.

Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.

Abstract
BACKGROUND: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others described decreased natural killer cell cytotoxicity (NKCC) and elevated proportion of lymphocytes expressing the activation marker, dipeptidyl peptidase IV (DPPIV) also known as CD26. However, neither these assays nor other laboratory tests are widely accepted for the diagnosis or prognosis of CFS. This study sought to determine if NKCC or DPPIV/CD26 have diagnostic accuracy for CFS.

METHODS/RESULTS: Subjects included female and male CFS cases and healthy controls. NK cell function was measured with a bioassay, using K562 cells and (51)Cr release. Lymphocyte associated DPPIV/CD26 was assayed by qualitative and quantitative flow cytometry. Serum DPPIV/CD26 was measured by ELISA. Analysis by receiver operating characteristic (ROC) curve assessed biomarker potential. Cytotoxic function of NK cells for 176 CFS subjects was significantly lower than in the 230 controls. According to ROC analysis, NKCC was a good predictor of CFS status. There was no significant difference in NK cell counts between cases and controls. Percent CD2+ lymphocytes (T cells and NK cells) positive for DPPIV/C26 was elevated in CFS cases, but there was a decrease in the number of molecules (rMol) of DPPIV/C26 expressed on T cells and NK cells and a decrease in the soluble form of the enzyme in serum. Analyses by ROC curves indicated that all three measurements of DPPIV/CD26 demonstrated potential as biomarkers for CFS. None of the DPPIV/C26 assays were significantly correlated with NKCC.

CONCLUSIONS: By ROC analysis, NKCC and three methods of measuring DPPIV/C26 examined in this study had potential as biomarkers for CFS. Of these, NKCC, %CD2+CD26+ lymphocytes and rMol CD26/CD2+ lymphocyte, required flow cytometry, fresh blood and access to a high complexity laboratory. Soluble DPPIV/C26 in serum is done with a standard ELISA assay, or with other soluble factors in a multiplex type of ELISA. Dipeptidyl peptidase IV on lymphocytes or in serum was not predictive of NKCC suggesting that these should be considered as non-redundant biomarkers. Abnormalities in DPPIV/CD26 and in NK cell function have particular relevance to the possible role of infection in the initiation and/or the persistence of CFS.

PMID: 20520837 [PubMed – in process]PMCID: PMC2876037Free PMC Article

7. Brain Behav Immun. 2010 May 4. [Epub ahead of print]

A formal analysis of cytokine networks in Chronic Fatigue Syndrome.
Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Fletcher MA.

Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Abstract
Chronic Fatigue Syndrome (CFS) is a complex illness affecting 4 million Americans for which no characteristic lesion has been identified. Instead of searching for a deficiency in any single marker, we propose that CFS is associated with a profound imbalance in the regulation of immune function forcing a departure from standard pre-programmed responses. To identify these imbalances we apply network analysis to the co-expression of 16 cytokines in CFS subjects and healthy controls. Concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12, 13, 15, 17 and 23, IFN-gamma, lymphotoxin-alpha (LT-alpha) and TNF-alpha were measured in the plasma of 40 female CFS and 59 case-matched controls. Cytokine co-expression networks were constructed from the pair-wise mutual information (MI) patterns found within each subject group. These networks differed in topology significantly more than expected by chance with the CFS network being more hub-like in design. Analysis of local modularity isolated statistically distinct cytokine communities recognizable as pre-programmed immune functional components. These showed highly attenuated Th1 and Th17 immune responses in CFS. High Th2 marker expression but weak interaction patterns pointed to an established Th2 inflammatory milieu. Similarly, altered associations in CFS provided indirect evidence of diminished NK cell responsiveness to IL-12 and LT-alpha stimulus. These observations are consistent with several processes active in latent viral infection and would not have been uncovered by assessing marker expression alone. Furthermore this analysis identifies key sub-networks such as IL-2:IFN-gamma:TNF-alpha that might be targeted in restoring normal immune function.

PMID: 20447453 [PubMed – as supplied by publisher]

8. J Intern Med. 2010 Apr;267(4):394-401.

Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome.
Jones DE, Hollingsworth KG, Taylor R, Blamire AM, Newton JL.

Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.

Abstract
OBJECTIVES: To examine muscle acid handling following exercise in chronic fatigue syndrome (CFS/ME) and the relationship with autonomic dysfunction.

DESIGN: Observational study.

SETTING: Regional fatigue service. SUBJECTS &

INTERVENTIONS: Chronic fatigue syndrome (n = 16) and age and sex matched normal controls (n = 8) underwent phosphorus magnetic resonance spectroscopy (MRS) to evaluate pH handling during exercise. Subjects performed plantar flexion at fixed 35% load maximum voluntary contraction. Heart rate variability was performed during 10 min supine rest using digital photophlethysmography as a measure of autonomic function.

RESULTS: Compared to normal controls, the CFS/ME group had significant suppression of proton efflux both immediately postexercise (CFS: 1.1 +/- 0.5 mmol L(-1) min(-1) vs. normal: 3.6 +/- 1.5 mmol L(-1) min(-1), P < 0.001) and maximally (CFS: 2.7 +/- 3.4 mmol L(-1) min(-1) vs. control: 3.8 +/- 1.6 mmol L(-1) min(-1), P < 0.05). Furthermore, the time taken to reach maximum proton efflux was significantly prolonged in patients (CFS: 25.6 +/- 36.1 s vs. normal: 3.8 +/- 5.2 s, P < 0.05). In controls the rate of maximum proton efflux showed a strong inverse correlation with nadir muscle pH following exercise (r(2) = 0.6; P < 0.01). In CFS patients, in contrast, this significant normal relationship was lost (r(2) = 0.003; P = ns). In normal individuals, the maximum proton efflux following exercise were closely correlated with total heart rate variability (r(2) = 0.7; P = 0.007) this relationship was lost in CFS/ME patients (r(2) < 0.001; P = ns).

CONCLUSION: Patients with CFS/ME have abnormalities in recovery of intramuscular pH following standardised exercise degree of which is related to autonomic dysfunction. This study identifies a novel biological abnormality in patients with CFS/ME which is potentially open to modification.

PMID: 20433583 [PubMed – indexed for MEDLINE]

9. J Altern Complement Med. 2010 Mar;16(3):235-49.

Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.
Porter NS, Jason LA, Boulton A, Bothne N, Coleman B.

Center for Community Research, DePaul University, Chicago, IL 60614, USA.

Abstract
BACKGROUND: There have been several systematic reviews attempting to evaluate the efficacy of possible treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). However, information regarding the efficacy of complementary and alternative medicine (CAM) has not been comprehensively or systematically covered in these reviews, despite its frequent use in the patient community.

PURPOSE: The purpose of this study was to systematically review and evaluate the current literature related to alternative and complementary treatments for ME/CFS and FM. It should be stressed that the treatments evaluated in this review do not reflect the clinical approach used by most practitioners to treat these illnesses, which include a mix of natural and unconventionally used medications and natural hormones tailored to each individual case. However, nearly all clinical research has focused on the utility of single CAM interventions, and thus is the primary focus of this review.

METHODS: Several databases (e.g., PubMed, MEDLINE,((R)) PsychInfo) were systematically searched for randomized and nonrandomized controlled trials of alternative treatments and nonpharmacological supplements. Included studies were checked for references and several experts were contacted for referred articles. Two leading subspecialty journals were also searched by hand. Data were then extracted from included studies and quality assessments were conducted using the Jadad scale.

RESULTS: Upon completion of the literature search and the exclusion of studies not meeting criterion, a total of 70 controlled clinical trials were included in the review. Sixty (60) of the 70 studies found at least one positive effect of the intervention (86%), and 52 studies also found improvement in an illness-specific symptom (74%). The methodological quality of reporting was generally poor.

CONCLUSIONS: Several types of alternative medicine have some potential for future clinical research. However, due to methodological inconsistencies across studies and the small body of evidence, no firm conclusions can be made at this time. Regarding alternative treatments, acupuncture and several types of meditative practice show the most promise for future scientific investigation. Likewise, magnesium, l-carnitine, and S-adenosylmethionine are nonpharmacological supplements with the most potential for further research. Individualized treatment plans that involve several pharmacological agents and natural remedies appear promising as well.

PMID: 20192908 [PubMed – indexed for MEDLINE]

10. J Affect Disord. 2010 Sep;125(1-3):287-294. Epub 2010 Jan 18.

Increased plasma peroxides and serum oxidized low density lipoprotein antibodies in major depression: Markers that further explain the higher incidence of neurodegeneration and coronary artery disease.
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E.

Maes Clinics, Belgium.

Abstract
BACKGROUND: Major depression is characterized by a decreased antioxidant status, an induction of the inflammatory and oxidative and nitrosative (IO&NS) pathways and inflammatory-neurodegenerative (I&ND) pathways. This study examines two markers of oxidative stress in depression, i.e. plasma peroxides and serum oxidized LDL (oxLDL) antibodies.

METHODS: Blood was sampled in 54 patients with major depression (mean+/-SD age=43.5+/-11.6years) and 37 normal volunteers (43.6+/-11.1years). The severity of illness was measured by means of the Hamilton Depression Rating Scale. The Fibromyalgia and Chronic Fatigue Syndrome Rating Scale was used to measure severity of “psychosomatic” symptoms in depression.

RESULTS: We found significantly higher plasma peroxides (p=0.002) and serum oxLDL antibodies (p=0.0002) in depressed patients as compared to normal controls. There was no significant correlation between both markers and both independently from each other predicted major depression. There were significant correlations between the oxLDL antibodies and the scores on two items of the FF scale, i.e. gastro-intestinal symptoms and headache.

DISCUSSION: The results show that major depression is accompanied by increased oxidative stress and lipid peroxidation. These results further extend the IO&NS pathophysiology of major depression. Since increased peroxides and oxLDL antibodies are predictors of coronary artery disease (CAD) and neurodegeneration, our findings suggest that IO&NS pathways are involved in the increased incidence of both CAD and neurodegeneration in depression.

PMID: 20083310 [PubMed – as supplied by publisher]

11. J Transl Med. 2010 Jan 11;8:1.

Immune and hemorheological changes in chronic fatigue syndrome.
Brenu EW, Staines DR, Baskurt OK, Ashton KJ, Ramos SB, Christy RM, Marshall-Gradisnik SM.

Faculty of Health Science and Medicine, Population Health and Neuroimmunology Unit, Bond University, Robina, Queensland, Australia.

Abstract
BACKGROUND: Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients.

METHODS: Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56(dim)CD16(+) and CD56(bright)CD16(-)) and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed.

RESULTS: CFS patients (n = 10) had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56(bright)CD16(-) NK phenotypes in comparison to healthy controls (n = 10). However, hemorheological characteristic, aggregation, deformability, fibrinogen, lymphocyte numbers and CD56(dim)CD16(+) NK cells were similar between the two groups.

CONCLUSION: These results indicate immune dysfunction as potential contributors to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes may be important diagnostic markers for CFS. The absence of rheological changes may indicate no abnormalities in erythrocytes of CFS patients.

PMID: 20064266 [PubMed – indexed for MEDLINE]PMCID: PMC2829521Free PMC Article

12. Am J Med. 2009 Dec;122(12 Suppl):S44-55.

Further strategies for treating fibromyalgia: the role of serotonin and norepinephrine reuptake inhibitors.
Mease PJ.

Seattle Rheumatology Associates, Swedish Medical Center, Seattle, Washington, USA.

Abstract
Fibromyalgia and associated conditions such as irritable bowel syndrome and temporomandibular disorder involve dysfunctions in central sensitization and pain modulation. Central nervous system dysfunction may also contribute to other symptoms characteristic of fibromyalgia, such as fatigue and sleep disturbance. Two key neurotransmitters in the pain modulation pathway are serotonin and norepinephrine. Preclinical studies using animal models of chronic pain have shown that pharmacologic agents that combine serotonergic and noradrenergic reuptake inhibition, thus augmenting the function of these neurotransmitters, have stronger analgesic effects than agents that inhibit reuptake of either neurotransmitter alone. Although tricyclic antidepressants (TCAs) inhibit reuptake of both serotonin and norepinephrine and have shown efficacy for the treatment of fibromyalgia, long-term use of these drugs is limited owing to poor tolerability. Unlike TCAs, the newer dual reuptake inhibitors of serotonin and norepinephrine, such as the drugs approved by the US Food and Drug Administration (FDA) for fibromyalgia, milnacipran and duloxetine, do not possess significant affinity for other neurotransmitter systems, resulting in diminished side effects and enhanced tolerability. Both duloxetine and milnacipran have shown efficacy in clinical trials by improving pain and other symptoms associated with fibromyalgia. Both compounds inhibit the serotonin and norepinephrine transporters; however, there is a difference in their affinities and selectivity for these transporters. Although duloxetine has affinity for both receptors, it is somewhat more selective for the serotonin transporter. In contrast, milnacipran is somewhat more selective for norepinephrine than serotonin reuptake inhibition. Pharmacologic agents that specifically target serotonin and norepinephrine reuptake may prove to be valuable tools in the treatment of fibromyalgia.

PMID: 19962496 [PubMed – indexed for MEDLINE]

13. Neuro Endocrinol Lett. 2009;30(4):470-6.

Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder.
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E.

Maes Clinics, Antwerp, Belgium.

Abstract
INTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medical illness characterized by disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways.

METHODS: This paper examines the role of Coenzyme Q10 (CoQ10), a mitochondrial nutrient which acts as an essential cofactor for the production of ATP in mitochondria and which displays significant antioxidant activities. Plasma CoQ10 has been assayed in 58 patients with ME/CFS and in 22 normal controls; the relationships between CoQ10 and the severity of ME/CFS as measured by means of the FibroFatigue (FF) scale were measured.

RESULTS: Plasma CoQ10 was significantly (p=0.00001) lower in ME/CFS patients than in normal controls. Up to 44.8% of patients with ME/CFS had values beneath the lowest plasma CoQ10 value detected in the normal controls, i.e. 490 microg/L. In ME/CFS, there were significant and inverse relationships between CoQ10 and the total score on the FF scale, fatigue and autonomic symptoms. Patients with very low CoQ10 (<390 microg/L) suffered significantly more from concentration and memory disturbances.

DISCUSSION: The results show that lowered levels of CoQ10 play a role in the pathophysiology of ME/CFS and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion. Our results suggest that patients with ME/CFS would benefit from CoQ10 supplementation in order to normalize the low CoQ10 syndrome and the IO&NS disorders. The findings that lower CoQ10 is an independent predictor of chronic heart failure (CHF) and mortality due to CHF may explain previous reports that the mean age of ME/CFS patients dying from CHF is 25 years younger than the age of those dying from CHF in the general population. Since statins significantly decrease plasma CoQ10, ME/CFS should be regarded as a relative contraindication for treatment with statins without CoQ10 supplementation.

PMID: 20010505 [PubMed – indexed for MEDLINE]

14. J Clin Pathol. 2010 Feb;63(2):156-64. Epub 2009 Dec 2.

Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis.
Zhang L, Gough J, Christmas D, Mattey DL, Richards SC, Main J, Enlander D, Honeybourne D, Ayres JG, Nutt DJ, Kerr JR.

Department of Cellular & Molecular Medicine, St George’s University of London, London, UK.

Abstract
BACKGROUND: The authors have previously reported genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) based on expression of 88 human genes.

AIM: To attempt to reproduce these findings, determine the specificity of this signature to CFS/ME, and test for associations between CFS/ME subtype and infection.

METHODS: Expression levels of 88 human genes were determined in blood of 62 new patients with idiopathic CFS/ME (according to Fukuda criteria), six patients with Q-fever-associated CFS/ME from the Birmingham Q-fever outbreak (according to Fukuda criteria), 14 patients with endogenous depression (according to DSM-IV criteria) and 29 normal blood donors.

RESULTS: In patients with CFS/ME, differential expression was confirmed for all 88 genes. Q-CFS/ME had similar patterns of gene expression to idiopathic CFS/ME. Gene expression in patients with endogenous depression was similar to that in the normal controls, except for upregulation of five genes (APP, CREBBP, GNAS, PDCD2 and PDCD6). Clustering of combined gene data in CFS/ME patients for this and the authors’ previous study (117 CFS/ME patients) revealed genomic subtypes with distinct differences in SF36 scores, clinical phenotypes, severity and geographical distribution. Antibody testing for Epstein-Barr virus, enterovirus, Coxiella burnetii and parvovirus B19 revealed evidence of subtype-specific relationships for Epstein-Barr virus and enterovirus, the two most common infectious triggers of CFS/ME.

CONCLUSIONS: This study confirms the involvement of these genes in CFS/ME.

PMID: 19955554 [PubMed – indexed for MEDLINE]Free Article

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