Complementary and alternative medicine for patients with chronic fatigue syndrome: a systematic review

Abstract:

BACKGROUND: Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population.

METHODS: Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded.

RESULTS: A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium.

CONCLUSIONS: The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted.

© 2011 Alraek et al; licensee BioMed Central Ltd.

 

Source: Alraek T, Lee MS, Choi TY, Cao H, Liu J. Complementary and alternative medicine for patients with chronic fatigue syndrome: a systematic review. BMC Complement Altern Med. 2011 Oct 7;11:87. doi: 10.1186/1472-6882-11-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201900/ (Full article)

 

An Italian study on health-related quality of life and fatigue in patients with chronic fatigue syndrome and patients with chronic HCV virus infection: similarities and differences

Abstract:

Severe fatigue and a significantly reduced health-related quality of life (HRQoL) have been described in patients with chronic fatigue syndrome (CFS) in comparison with patients affected by chronic hepatitis C (CHC) and other chronic medical conditions. We examined 39 CFS and 49 CHC patients to explore whether fatigue and a poor HRQoL represent a greater medical and social problem in CFS than in CHC.

The severity of fatigue and the HRQoL were assessed using the Fatigue Impact Scale (FIS) and the Health Status Questionnaire Short Form-36 (SF-36), respectively. The statistical analysis showed both a higher score of fatigue and a lower HRQoL in CFS than in CHC patients. Furthermore, in CHC patients the FIS evaluation showed a significantly reduced score of the psychosocial domain in comparison with the other domains. Multivariate linear regression analysis revealed female gender as the most important positive variable in chronic hepatitis C patients for total score of FIS.

In conclusion, CFS was associated with a severe and disabling fatigue and an impaired HRQOL. In particular, both fatigue and all aspects of HRQOL perceived by CFS patients were significantly impaired compared to CHC patients. Consequently, management of fatigue should be considered a priority in order to improve HRQOL in CFS patients. In CHC patients the impact of fatigue on HRQoL was less significant than in CFS patients, even though the FIS evaluation showed a significant impairment of the psychosocial domain.

 

Source: Racciatti D, Gorgoretti V, Sepede G, Gambi F, Pizzigallo E. An Italian study on health-related quality of life and fatigue in patients with chronic fatigue syndrome and patients with chronic HCV virus infection: similarities and differences. Int J Immunopathol Pharmacol. 2011 Jul-Sep;24(3):673-81. https://www.ncbi.nlm.nih.gov/pubmed/21978699

 

Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin

Abstract:

BACKGROUND: There is evidence that inflammatory pathways and cell-mediated immunity (CMI) play an important role in the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Activation of inflammatory and CMI pathways, including increased levels of cytokines, is known to induce fatigue and somatic symptoms. Given the broad spectrum inflammatory state in ME/CFS, the aim of this study was to examine whether inflammatory and CMI biomarkers are increased in individuals with ME/CFS.

METHODS: In this study we therefore measured plasma interleukin-(IL)1, tumor necrosis factor (TNF)α, and PMN-elastase, and serum neopterin and lysozyme in 107 patients with ME/CFS, 37 patients with chronic fatigue (CF), and 20 normal controls. The severity of ME/CFS was measured with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: Serum IL-1, TNFα, neopterin and lysozyme are significantly higher in patients with ME/CFS than in controls and CF patients. Plasma PMN-elastase is significantly higher in patients with ME/CFS than in controls and CF patients and higher in the latter than in controls. Increased IL-1 and TNFα are significantly correlated with fatigue, sadness, autonomic symptoms, and a flu-like malaise; neopterin is correlated with fatigue, autonomic symptoms, and a flu-like malaise; and increased PMN-elastase is correlated with concentration difficulties, failing memory and a subjective experience of infection.

CONCLUSIONS: The findings show that ME/CFS is characterized by low-grade inflammation and activation of CMI. The results suggest that characteristic symptoms of ME/CFS, such as fatigue, autonomic symptoms and a flu-like malaise, may be caused by inflammatory mediators, e.g. IL-1 and TNFα.

Copyright © 2011 Elsevier B.V. All rights reserved.

 

Source: Maes M, Twisk FN, Kubera M, Ringel K. Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. J Affect Disord. 2012 Feb;136(3):933-9. doi: 10.1016/j.jad.2011.09.004. Epub 2011 Oct 4. https://www.ncbi.nlm.nih.gov/pubmed/21975140

 

Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome

Abstract:

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is accompanied by a) systemic IgA/IgM responses against the lipopolysaccharides (LPS) of commensal bacteria; b) inflammation, e.g. increased plasma interleukin-(IL)1 and tumor necrosis factor (TNF)α; and c) activation of cell-mediated immunity (CMI), as demonstrated by increased neopterin.

METHODS: To study the relationships between the IgA/IgM responses to the LPS of microbiota, inflammation, CMI and the symptoms of ME/CFS we measured the IgA/IgM responses to the LPS of 6 different enterobacteria, serum IL-1, TNFα, neopterin, and elastase in 128 patients with ME/CFS and chronic fatigue (CF). Severity of symptoms was assessed by the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: Serum IL-1, TNFα, neopterin and elastase are significantly higher in patients with ME/CFS than in CF patients. There are significant and positive associations between the IgA responses to LPS and serum IL-1, TNFα, neopterin and elastase. Patients with an abnormally high IgA response show increased serum IL-1, TNFα and neopterin levels, and higher ratings on irritable bowel syndrome (IBS) than subjects with a normal IgA response. Serum IL-1, TNFα and neopterin are significantly related to fatigue, a flu-like malaise, autonomic symptoms, neurocognitive disorders, sadness and irritability.

CONCLUSIONS: The findings show that increased IgA responses to commensal bacteria in ME/CFS are associated with inflammation and CMI activation, which are associated with symptom severity. It is concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.

Copyright © 2011 Elsevier B.V. All rights reserved.

 

Source: Maes M, Twisk FN, Kubera M, Ringel K, Leunis JC, Geffard M. Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome. J Affect Disord. 2012 Feb;136(3):909-17. doi: 10.1016/j.jad.2011.09.010. Epub 2011 Oct 2. https://www.ncbi.nlm.nih.gov/pubmed/21967891

 

Fatigue Scales and Chronic Fatigue Syndrome: Issues of Sensitivity and Specificity

Abstract:

Few studies have explored issues of sensitivity and specificity for using the fatigue construct to identify patients meeting chronic fatigue syndrome (CFS) criteria. In this article, we examine the sensitivity and specificity of several fatigue scales that have attempted to define severe fatigue within CFS. Using Receiver Operating Characteristic (ROC) curve analysis, we found most scales and sub-scales had either significant specificity and/or sensitivity problems.

However, the post-exertional subscale of the ME/CFS Fatigue Types Questionnaire (Jason, Jessen, et al., 2009) was the most promising in terms of specificity and sensitivity. Among the more traditional fatigue scales, Krupp, LaRocca, Muir-Nash, and Steinberg’s (1989) Fatigue Severity Scale had the best ability to differentiate CFS from healthy controls. Selecting questions, scales and cut off points to measure fatigue must be done with extreme care in order to successfully identify CFS cases.

 

Source: Jason LA, Evans M, Brown M, Porter N, Brown A, Hunnell J, Anderson V, Lerch A. Fatigue Scales and Chronic Fatigue Syndrome: Issues of Sensitivity and Specificity. Disabil Stud Q. 2011 Winter;31(1). Pii: 1375. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181109/ (Full article)

 

Role of infection and neurologic dysfunction in chronic fatigue syndrome

Abstract:

Chronic fatiguing illnesses following well-documented infections and acute “infectious-like” illnesses of uncertain cause have been reported for many decades. Chronic fatigue syndrome (CFS) was first formally defined in 1988. There is considerable evidence that CFS is associated with abnormalities of the central and autonomic nervous systems. There also is evidence linking several infectious agents with CFS, although no agent has been proven to be a cause of the illness.

Most of the infectious agents that have been linked to CFS are able to produce a persistent, often life-long, infection and thus are a constant incitement to the immune system. Most also have been shown to be neuropathogens. The evidence is consistent with the hypothesis that CFS, in some cases, can be triggered and perpetuated by several chronic infections that directly or indirectly affect the nervous system, and that symptoms are a reflection of the immune response to the infection.

© Thieme Medical Publishers.

 

Source: Komaroff AL, Cho TA. Role of infection and neurologic dysfunction in chronic fatigue syndrome. Semin Neurol. 2011 Jul;31(3):325-37. doi: http://dx.doi.org/10.1055/s-0031-1287654. Epub 2011 Sep 30. https://www.ncbi.nlm.nih.gov/pubmed/21964849

 

Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections

Abstract:

BACKGROUND: Several infections trigger postinfective fatigue syndromes, which share key illness characteristics with each other and with chronic fatigue syndrome (CFS). Previous cross-sectional case-control studies of CFS have suggested that unique gene expression signatures are evident in peripheral blood samples.

METHODS: Peripheral blood transcriptomes in samples collected longitudinally, in 18 subjects with a fatigue syndrome lasting ≥ 6 months after acute infection due to Epstein-Barr virus, Ross River virus, or Coxiella burnetii (Q fever), and 18 matched control subjects who had recovered promptly, were studied by microarray (n = 127) and confirmatory quantitative polymerase chain reaction (PCR). Gene expression patterns associated with CFS were sought by univariate statistics and regression modeling.

RESULTS: There were 23 genes with modest differential expression (0.6-2.3-fold change) in within-subject comparisons of early, symptomatic time points with late, recovered time points. There were modest differences found in 63 genes, either in cross-sectional comparison of cases and controls at 6 months after infection onset or in the regression model. There were 223 genes significantly correlated with individual symptom domains. Quantitative PCR confirmed 33 (73%) of 45 genes-none were consistent across cohorts.

CONCLUSIONS: Although the illness characteristics of patients with postinfective fatigue syndromes have more similarities than differences, no reliable peripheral blood gene expression correlate is evident.

 

Source: Galbraith S, Cameron B, Li H, Lau D, Vollmer-Conna U, Lloyd AR. Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections. J Infect Dis. 2011 Nov 15;204(10):1632-40. doi: 10.1093/infdis/jir612. Epub 2011 Sep 29. http://jid.oxfordjournals.org/content/204/10/1632.long (Full article)

 

Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome

Abstract:

The weight of current evidence supports the presence of the following factors related to hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS): mild hypocortisolism; attenuated diurnal variation of cortisol; enhanced negative feedback to the HPA axis; and blunted HPA axis responsiveness. Furthermore, HPA axis changes seem clinically relevant, as they are associated with worse symptoms and/or disability and with poorer outcomes to standard treatments for CFS.

Regarding etiology, women with CFS are more likely to have reduced cortisol levels. Studies published in the past 8 years provide further support for a multifactorial model in which several factors interact to moderate HPA axis changes. In particular, low activity levels, depression and early-life stress appear to reduce cortisol levels, whereas the use of psychotropic medication can increase cortisol. Addressing these factors-for example, with cognitive behavioral therapy-can increase cortisol levels and is probably the first-line approach for correcting HPA axis dysfunction at present, as steroid replacement is not recommended.

Given what is now a fairly consistent pattern of findings for the type of HPA axis changes found in CFS, we recommend that future work focuses on improving our understanding of the cause and relevance of these observed changes.

Comment in: Neuroendocrine correlates of childhood trauma in CFS. [Nat Rev Endocrinol. 2012]

 

Source: Papadopoulos AS, Cleare AJ. Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. 2011 Sep 27;8(1):22-32. doi: 10.1038/nrendo.2011.153. https://www.ncbi.nlm.nih.gov/pubmed/21946893

 

Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression

Abstract:

BACKGROUND: Depression is characterized by activation of cell-mediated immunity (CMI), including increased neopterin levels, and increased pro-inflammatory cytokines (PICs), such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). These PICs may induce depressive, melancholic and chronic fatigue (CF) symptoms.

METHODS: We examined serum neopterin and plasma PIC levels in depressive subgroups in relation to the depressive subtypes and the melancholic and CF symptoms of depression. Participants were 85 patients with depression and in 26 normal controls. Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of CF with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: Serum neopterin was significantly higher in depressed patients and in particular in those with melancholia. There were positive correlations between serum neopterin, the plasma PICs and the number of previous depressive episodes. Neopterin and TNFα were associated with melancholia, while both PICs were associated with CF. Melancholia-group membership was predicted by the HDRS and neopterin, and CF group membership by age, the FF score and serum TNFα.

DISCUSSION: Depression and melancholia are accompanied by CMI activation, suggesting that neopterin plays a role in their pathophysiology, e.g. through activation of oxidative and nitrosative stress and apoptosis pathways. The intertwined CMI and inflammatory responses are potentially associated with the onset of depression and with the melancholic and CF symptoms of depression. Exposure to previous depressive episodes may magnify the size of CMI and PIC responses, possibly increasing the likelihood of new depressive episodes. CMI activation and inflammation may contribute to the staging or recurrence of depression.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Maes M, Mihaylova I, Kubera M, Ringel K. Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jan 10;36(1):169-75. doi: 10.1016/j.pnpbp.2011.09.006. Epub 2011 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/21945535

 

Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue syndrome: a multi-laboratory study

Abstract:

Murine leukemia viruses (MLVs), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled coded replicate samples of blood from 15 subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15 healthy donors previously determined to be negative for the viruses. These samples were distributed in a blinded fashion to nine laboratories, which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody. Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disagreement, and reactivity was similar among CFS subjects and negative controls. These results indicate that current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening is not warranted.

 

Source: Simmons G, Glynn SA, Komaroff AL, Mikovits JA, Tobler LH, Hackett J Jr, Tang N, Switzer WM, Heneine W, Hewlett IK, Zhao J, Lo SC, Alter HJ, Linnen JM, Gao K, Coffin JM, Kearney MF, Ruscetti FW, Pfost MA, Bethel J, Kleinman S, Holmberg JA, Busch MP; Blood XMRV Scientific Research Working Group (SRWG). Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue syndrome: a multi-laboratory study. Science. 2011 Nov 11;334(6057):814-7. doi: 10.1126/science.1213841. Epub 2011 Sep 22. Collaborators (25) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299483/ (Full article)