Acupuncture in the treatment of chronic fatigue syndrome based on “interaction of brain and kidney” in TCM: a randomized controlled trial

Abstract:

OBJECTIVE: To observe the effects of acupuncture on the fatigue symptoms of chronic fatigue syndrome, the potential symptoms and cytokines on the base of the theory as “interaction of brain and kidney” and explore its clinical therapeutic effects and the potential mechanism.

METHODS: A total of 68 patients were randomized into an observation group and a control group, 34 cases in each one. In the control group, oryzanol and vitamin B1 were prescribed for oral administration and the patients were required to have a proper rest and physical exercise. In the observation group, on the base of the theory as “interaction of brain and kidney”, acupuncture was added to Baihui (BL 20), Fengchi (GB 20), Pishu (BL 20), Shenshu (BL 23), Sanyinjiao (SP 6) and Taixi (KI 3). The treatment was given once a day, 5 treatments a week, with 2 days break. The consecutive treatment for 4 weeks was required. Before and after treatment, the score of the fatigue scale-14 (FS-14), the score of the somatic and psychological health report (SPHERE) and the score of the Pittsburgh sleep quality index (PSQI) were observed in the patients of the two groups separately. The enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of serum interleukin-6 (IL-6) and interferon-γ (INF-γ) before and after treatment.

RESULTS: After treatment, FS-14 scores, SPHERE scores and PSQI scores were all reduced as compared with the scores before treatment in the two groups (P<0.05, P<0.01). After treatment, the levels of IL-6 and INF-γ in the serum in the observation group were reduced as compared with the levels before treatment (both P<0.01). After treatment, the scores of FS-14, SPHERE and PSQI as well as the levels of serum IL-6 and INF-γ in the observation group were all lower than the results in the control group (P<0.05, P<0.01).

CONCLUSION: On the base of the theory as “interaction of brain and kidney”, acupuncture therapy relieves the fatigue symptoms and the potential symptoms and improves the sleep quality in the patients of chronic fatigue syndrome. The effect mechanism is probably related to the decrease of the levels of IL-6 and INF-γ in serum.

Source: Xu YX, Luo HS, Sun D, Wang R, Cai J. Acupuncture in the treatment of chronic fatigue syndrome based on “interaction of brain and kidney” in TCM: a randomized controlled trial. Zhongguo Zhen Jiu. 2019 Feb 12;39(2):123-7. doi: 10.13703/j.0255-2930.2019.02.003. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/30942028

Artificial intelligence based discovery of the association between depression and chronic fatigue syndrome

Abstract:

BACKGROUND: Both of the modern medicine and the traditional Chinese medicine classify depressive disorder (DD) and chronic fatigue syndrome (CFS) to one type of disease. Unveiling the association between depressive and the fatigue diseases provides a great opportunity to bridge the modern medicine with the traditional Chinese medicine.

METHODS: In this work, 295 general participants were recruited to complete Zung Self-Rating Depression Scales and Chalder Fatigue Scales, and meanwhile, to donate plasma and urine samples for 1H NMR-metabolic profiling. Artificial intelligence methods was used to analysis the underlying association between DD and CFS. Principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyze the metabolic profiles with respect to gender and age. Variable importance in projection and t-test were employed in conjunction with the PLS-DA models to identify the metabolite biomarkers. Considering the asymmetry and complexity of the data, convolutional neural networks (CNN) model, an artificial intelligence method, was built to analyze the data characteristics between each groups.

RESULTS: The results showed the gender- and age-related differences for the candidate biomarkers of the DD and the CFS diseases, and indicated the same and different biomarkers of the two diseases. PCA analysis for the data characteristics reflected that DD and CFS was separated completely in plasma metabolite. However, DD and CFS was merged into one group.

LIMITATION: Lack of transcriptomic analysis limits the understanding of the association of the DD and the CFS diseases on gene level.

CONCLUSION: The unmasked candidate biomarkers provide reliable evidence to explore the commonality and differences of the depressive and the fatigue diseases, and thereby, bridge over the traditional Chinese medicine with the modern medicine.

Copyright © 2019 Elsevier B.V. All rights reserved.

Source: Zhang F, Wu C, Jia C, Gao K, Wang J, Zhao H, Wang W, Chen J. Artificial intelligence based discovery of the association between depression and chronic fatigue syndrome. J Affect Disord. 2019 Mar 8;250:380-390. doi: 10.1016/j.jad.2019.03.011. [Epub ahead of print]

Jin’s three-needle acupuncture technique for chronic fatigue syndrome: a study protocol for a multicentre, randomized, controlled trial

Abstract:

BACKGROUND: With an unclear pathomechanism, no confirmed treatment regimen has been established for chronic fatigue syndrome (CFS). Acupuncture is applied as an alternative therapy for CFS. As a kind of acupuncture therapy, Jin’s three-needle acupuncture (JTN) has been applied to treat CFS. However, few large-sample randomised controlled trials on JTN treatment for CFS have been reported. We designed this study to evaluate the efficacy and safety of JTN treatment for CFS.

METHOD/DESIGN: This study is a multicentre, single-blind, randomised controlled trial. Patients who meet the inclusion criteria will be recruited and randomly assigned to either the JTN treatment group or the basic acupuncture group. Both interventions will be conducted for five consecutive days per week and last for 2 weeks. The primary outcome is the effective rate based on the 14-item Fatigue Scale (FS-14) score. Other outcome measures include the Fatigue Assessment Scale (FAI), the Depression Status Inventory (DSI), and the Self-rating Anxiety Scale (SAS). Plasma adrenocorticotropic hormone (ACTH), plasma cortisol, and serum levels of IL-2 and IFN-γ will also be measured in this study. Adverse events will be observed and recorded for the safety evaluation.

DISCUSSION: This study may help to identify the efficacy and safety of JTN acupuncture treatment for CFS.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17011009 . Registered on 29 March 2017.

Source: Lin W, Chen XL, Chen Q, Wen J, Chen X. Jin’s three-needle acupuncture technique for chronic fatigue syndrome: a study protocol for a multicentre, randomized, controlled trial. Trials. 2019 Mar 4;20(1):155. doi: 10.1186/s13063-019-3243-5. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3243-5 (Full article)

WITHDRAWN: Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue is increasingly common. Conventional medical care is limited in treating chronic fatigue, leading some patients to use traditional Chinese medicine therapies, including herbal medicine.

OBJECTIVES: To assess the effectiveness of traditional Chinese medicine herbal products in treating idiopathic chronic fatigue and chronic fatigue syndrome.

SEARCH METHODS: The following databases were searched for terms related to traditional Chinese medicine, chronic fatigue, and clinical trials: CCDAN Controlled Trials Register (July 2009), MEDLINE (1966-2008), EMBASE (1980-2008), AMED (1985-2008), CINAHL (1982-2008), PSYCHINFO (1985-2008), CENTRAL (Issue 2 2008), the Chalmers Research Group PedCAM Database (2004), VIP Information (1989-2008), CNKI (1976-2008), OCLC Proceedings First (1992-2008), Conference Papers Index (1982-2008), and Dissertation Abstracts (1980-2008). Reference lists of included studies and review articles were examined and experts in the field were contacted for knowledge of additional studies.

SELECTION CRITERIA: Selection criteria included published or unpublished randomized controlled trials (RCTs) of participants diagnosed with idiopathic chronic fatigue or chronic fatigue syndrome comparing traditional Chinese medicinal herbs with placebo, conventional standard of care (SOC), or no treatment/wait lists. The outcome of interest was fatigue.

DATA COLLECTION AND ANALYSIS: 13 databases were searched for RCTs investigating TCM herbal products for the treatment of chronic fatigue. Over 2400 references were located. Studies were screened and assessed for inclusion criteria by two authors.

MAIN RESULTS: No studies that met all inclusion criteria were identified.

AUTHORS’ CONCLUSIONS: Although studies examining the use of TCM herbal products for chronic fatigue were located, methodologic limitations resulted in the exclusion of all studies. Of note, many of the studies labelled as RCTs and conducted in China did not utilize rigorous randomization procedures. Improvements in methodology in future studies is required for meaningful synthesis of data.

Source: Adams D, Wu T, Yang X, Tai S, Vohra S. WITHDRAWN: Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome. Cochrane Database Syst Rev. 2018 Oct 15;10:CD006348. doi: 10.1002/14651858.CD006348.pub3. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30321452

The effects of warm water immersion on blood pressure, heart rate and heart rate variability in people with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a central sensitisation syndrome with abnormalities in autonomic regulation of blood pressure (BP), heart rate (HR) and heart rate variability (HRV). Prior to exploring the effects of hydrotherapy as a treatment for this population, changes in BP, HR and HRV during warm water immersion need to be established.

OBJECTIVES: The study aimed to determine the effects of warm water immersion on BP, HR and HRV in adults with CFS compared to matched-pair healthy adults.

METHOD: A quasi-experimental, single-blinded study design was used with nine CFS participants and nine matched controls. Participants’ BP, HR and HRV were measured before, after 5 minutes and post warm water immersion at the depth of the fourth intercostal space, using the Ithlete® System and Dräger BP monitor.

RESULTS: There was a significant difference between groups in HRV prior to immersion (control group: 73 [55-74] vs. chronic fatigue syndrome group: 63 [50-70]; p = 0.04). There was no difference in HRV post-immersion. A significant difference in HR after immersion was recorded with the control group having a lower HR than those with CFS (78 [60-86] vs. 86 [65-112]; p = 0.03). The low HRV present in the CFS group prior to immersion suggests autonomic dysregulation. Individuals with CFS may have reduced vagal nerve activation post-immersion. During immersion, HRV of the CFS participants improved similar to that of the healthy controls.

CONCLUSION: Prior to immersion, differences were present in the HRV of the participants with CFS compared to healthy controls. These differences were no longer present post-immersion.

CLINICAL IMPLICATIONS: Warm water immersion appears safe and may be beneficial in the management of individuals with CFS.

Source: Parker R, Higgins Z, Mlombile ZNP, Mohr MJ, Wagner TL. The effects of warm water immersion on blood pressure, heart rate and heart rate variability in people with chronic fatigue syndrome. S Afr J Physiother. 2018 Aug 28;74(1):442. doi: 10.4102/sajp.v74i1.442. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131699/ (Full article)

Effects of a short-term aquatic exercise intervention on symptoms and exercise capacity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a pilot study

Abstract:

PURPOSE: This pilot pre-and post-intervention study investigated the effects of a short-term aquatic exercise programme on physiological outcomes, symptoms and exercise capacity in women with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

METHODS: Eleven women (54.8 ± 12.4 year) volunteered for the 5-week program; an initial 20-min aquatic exercise session then two self-paced 20-min sessions per week for 4 weeks. Pre- and post-intervention outcomes were physiological measures, 6 min Walk Test (6MWT), perceived exertion (RPE), hand grip strength, Sit-to-Stand, Sit-Reach test, Apley’s shoulder test, FACIT questionnaire, and 24-h post-test tiredness and pain scores (0-10 visual analogue scale). Heart rates, RPE, 24- and 48-h post-session tiredness/pain scores were recorded each session.

RESULTS: 6MWT distance increased by 60.8 m (p = 0.006), left hand grip strength by 6 kg (p = 0.038), Sit-Reach test by 4.0 cm (p = 0.017), right shoulder flexibility by 2.9 cm (p = 0.026), FACIT scores by 8.2 (p = 0.041); 24-h post-test tiredness and pain decreased by 1.5 and 1.6, respectively (p = 0.002). There were significant post-intervention increases in exercising heart rates (6MWT 4- and 6-min time points), oxygen saturation at 2-min, and reduced RPE at 4-min. Weekly resting and exercising heart rates increased significantly during the study but RPE decreased; immediately post- and 24-h post-session tiredness decreased significantly. There were no reports of symptom exacerbation.

CONCLUSIONS: Five weeks of low-moderate intensity aquatic exercise significantly improved exercise capacity, RPE and fatigue. This exercise mode may potentially be a manageable and safe physical activity for CFS/ME patients.

Source: Broadbent S , Coetzee S , Beavers R. Effects of a short-term aquatic exercise intervention on symptoms and exercise capacity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a pilot study. Eur J Appl Physiol. 2018 Jun 19. doi: 10.1007/s00421-018-3913-0. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29923110

Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review

Abstract:

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 patient, 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.

Source: Roman P, Carrillo-Trabalón F, Sánchez-Labraca N, Cañadas F, Estévez AF, Cardona D. Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review.  Benef Microbes. 2018 Apr 26:1-10. doi: 10.3920/BM2017.0125. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29695180

KPAX002 as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a prospective, randomized trial

Abstract:

Mitochondrial dysfunction and a hypometabolic state are present in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). KPAX002 consists of low-dose methylphenidate hydrochloride to treat a hypometabolic state combined with key micronutrients intended to broadly support mitochondrial function.

The objective of this study was to evaluate KPAX002 as a treatment for fatigue and concentration disturbance symptoms in ME/CFS subjects. This phase 2 randomized, double-blinded, placebo-controlled trial was conducted at 4 sites in the United States. A total of 135 subjects with ME/CFS were randomly assigned to either KPAX002 (n=67) or placebo (n=68) for 12 weeks of treatment. The primary endpoint was change in the Checklist Individual Strength (CIS) total score from baseline to Week 12. Secondary measurements included visual analog scales for fatigue and concentration disturbance symptoms.

In the intent-to-treat population, the mean reduction in the CIS total score from baseline to week 12 for the KPAX002 and placebo groups was -16.9 (± 23.52) and -13.8 (± 22.15), respectively (95% confidence interval, -11.1, 4.0; P=0.359). On the visual analog scale for fatigue, the mean reduction from baseline to week 12 was -18.2 mm (± 25.05) and -11.1 mm (± 22.08) for the KPAX002 and placebo groups, respectively (95% confidence interval, -11.5, 2.3; P=0.189). The two groups demonstrating the most robust response to KPAX002 were subjects with more severe ME/CFS symptoms at baseline (P=0.086) and subjects suffering from both fatigue and pain (P=0.057). The incidence of adverse events was not statistically different between the two groups.

Treatment with KPAX002 resulted in a reduction in fatigue and concentration disturbance symptoms in multiple analyses. Two key subgroups of patients whose response approached statistical significance were identified.

Source: Jose G Montoya, Jill N Anderson, Danya L Adolphs, Lucinda Bateman, Nancy Klimas, Susan M Levine, Donn W Garvert, Jon D Kaiser. KPAX002 as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a prospective, randomized trial. Int J Clin Exp Med 2018;11(3):2890-2900 www.ijcem.com /ISSN:1940-5901/IJCEM0065685 (Full article)

Changes in fatigue, autonomic functions, and blood biomarkers due to sitting isometric yoga in patients with chronic fatigue syndrome

Abstract:

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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN CTR) UMIN000009646. Registered Dec 27, 2012.

Source: Oka T, Tanahashi T, Sudo N, Lkhagvasuren B, Yamada Y. Changes in fatigue, autonomic functions, and blood biomarkers due to sitting isometric yoga in patients with chronic fatigue syndrome. Biopsychosoc Med. 2018 Apr 10;12:3. doi: 10.1186/s13030-018-0123-2. eCollection 2018. https://www.ncbi.nlm.nih.gov/pubmed/29643935

Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial

Abstract:

Twenty-two consecutive patients suffering from refractory myalgic encephalitis/chronic fatigue syndrome (ME/CFS) were treated with an innovative nutriceutical containing sodium dichloroacetate in a proof-of-principle, pilot, open-label prospective cohort trial. Ten patients experienced significant improvement of their health condition with reduction to almost half of their score in the fatigue severity scale. In twelve patients treatment failed to exert any beneficial effect. In the latter patients several other diseases have commonly been revealed by extensive biological and imaging investigations. These preliminary findings sustain the hypothetical role of mitochondrial hypo-metabolism due to inhibition of the activity of the pyruvate dehydrogenase in the pathogenesis of primary ME/CFS, and suggest a possible benefit of nutriceutical treatment by sodium dichloroacetate.

Source: Comhaire F. Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial. Med Hypotheses. 2018 May;114:45-48. doi: 10.1016/j.mehy.2018.03.002. Epub 2018 Mar 5.   https://www.ncbi.nlm.nih.gov/pubmed/29602463