Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating condition, probably of multifactorial etiology. No effective approved drugs are currently available for its treatment. Several studies have proposed symptomatic treatment with melatonin and zinc supplementation in chronic illnesses; however, little is known about the synergistic effect of this treatment on fatigue-related symptoms in ME/CFS. The primary endpoint of the study was to assess the effect of oral melatonin plus zinc supplementation on fatigue in ME/CFS. Secondary measures included participants’ sleep disturbances, anxiety/depression and health-related quality of life.

A proof-of-concept, 16-week, randomized, placebo-controlled, double-blind trial was conducted in 50 ME/CFS patients assigned to receive either oral melatonin (1 mg) plus zinc (10 mg) supplementation (n = 24) or matching placebo (n = 26) once daily. Endpoint outcomes were evaluated at baseline, and then reassessed at 8 and 16 weeks of treatment and 4 weeks after treatment cessation, using self-reported outcome measures. The most relevant results were the significant reduction in the perception of physical fatigue in the Mel-Zinc group at the final treatment follow-up versus placebo (p < 0.05), and the significant improvement in the physical component summary at all follow-up visits in the experimental group. Urinary 6-sulfatoxymelatonin levels were significantly elevated though the treatment in experimental group vs. placebo (p < 0.0001); however, no significantly differences were observed for zinc concentration among participants. Our findings suggest that oral melatonin plus zinc supplementation for 16 weeks is safe and potentially effective in reducing fatigue and improving the quality of life in ME/CFS.

This clinical study was registered on ClinicalTrials.gov (NCT03000777).

Source: Castro-Marrero J, Zaragozá MC, López-Vílchez I, Galmés JL, Cordobilla B, Maurel S, Domingo JC, Alegre-Martín J. Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Antioxidants (Basel). 2021 Jun 23;10(7):1010. doi: 10.3390/antiox10071010. PMID: 34201806. https://pubmed.ncbi.nlm.nih.gov/34201806/

Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?

Abstract:

As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called “post-COVID syndrome” or “long-COVID” [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups.

Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.

Source: Bornstein SR, Voit-Bak K, Donate T, Rodionov RN, Gainetdinov RR, Tselmin S, Kanczkowski W, Müller GM, Achleitner M, Wang J, Licinio J, Bauer M, Young AH, Thuret S, Bechmann N, Straube R. Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis? Mol Psychiatry. 2021 Jun 17. doi: 10.1038/s41380-021-01148-4. Epub ahead of print. PMID: 34140635. https://pubmed.ncbi.nlm.nih.gov/34140635/

A proprietary herbal drug Young Yum Pill ameliorates chronic fatigue syndrome in mice

Abstract:

Background: Chronic fatigue syndrome (CFS) is a complex disease with few effective and safe therapies. Young Yum Pill (YYP), a proprietary herbal drug, has been used to relieve CFS-like symptoms. The pharmacological basis of this application of YYP is unknown.

Purpose: This study aimed to investigate the pharmacological effects and mechanisms of action of YYP in a mouse model of CFS.

Study design and methods: A food restriction and exhaustive swimming-induced mouse CFS model was used to evaluate the effects of YYP. Lymphocyte proliferation was assessed by MTT assays. T-lymphocyte subsets were analyzed by flow cytometry. Serum biochemical parameters were determined using commercial kits. Protein levels were measured by immunoblotting.

Results: Intragastric administration of YYP (2.85, 5.70, 11.40 g/kg) daily for 21 consecutive days significantly prolonged swimming time and diminished body weight loss of CFS mice. Mechanistic investigations revealed that YYP increased thymus and spleen indices of CFS mice, enhanced proliferation of lipopolysaccharide- or concanavalin A-stimulated spleen lymphocytes, and increased CD3+CD4+ and CD3+CD8+ T-cells in the spleen. YYP increased glycogen content in gastrocnemius muscle and liver, and lowered levels of triglyceride, lactic acid and urea nitrogen in sera of CFS mice. YYP suppressed the elevation of serum level of malondialdehyde, the increase of activities of lactic dehydrogenase and creatine phosphokinase, and the decrease of activity of the serum antioxidant enzyme superoxide dismutase in CFS mice. Moreover, YYP upregulated protein level of activated AMPK in gastrocnemius muscle and liver of CFS mice.

Conclusions: YYP ameliorates CFS by reversing metabolic changes, reducing oxidative damage, and improving some immune function parameters in mice. This study provides pharmacological justifications for the use of YYP in treating fatigue, including CFS.

Source: Yin C, Fu X, Chou J, Li J, Chen Y, Bai J, Wu J, Wu Y, Wang X, Yu ZL. A proprietary herbal drug Young Yum Pill ameliorates chronic fatigue syndrome in mice. Phytomedicine. 2021 May 25;88:153602. doi: 10.1016/j.phymed.2021.153602. Epub ahead of print. PMID: 34102522. https://pubmed.ncbi.nlm.nih.gov/34102522/

The efficacy and safety of moxibustion for chronic fatigue syndrome: A protocol for systematic review and meta-analysis

Abstract:

Background: The pathogenesis of chronic fatigue syndrome (CFS) is not clear. The main purpose of treatment is to improve autoimmune function and relieve fatigue symptoms. Moxibustion is often used to treat diseases caused by low autoimmunity, especially in relieving fatigue symptoms. It is a superior therapy for CFS in traditional Chinese medicine. At present, there is a lack of the high level clinical evidence to support the moxibustion in the treatment of CFS, so this study will systematically review and analyze the currently available randomized controlled trials to evaluate the efficacy and safety of moxibustion in the treatment of CFS.

Methods: We will systematically search PubMed, EMBASE, Cochrane library, Sinomed, CNKI, VIP, and Wanfang Database, ClinicalTrials.gov and Chinese Clinical Trial Registry will also be searched. The time range for the search will be from database activation to March 31, 2021. The randomized controlled trials (RCTs) associated with moxibustion for CFS will be included, regardless of language.We will use the standard proposed in Cochrane Handbook 5.1.0 to assess the bias risk of a single RCT. The main outcome index of the study is Fatigue Assessment Instrument (FAI), secondary outcome indexes will include Fatigue Scale -14 (FS-14), Fatigue Severity Scale (FSS), Pittsburgh sleep quality index (PSQI), natural killer (NK) cells, interleukin- 2 (IL-2), T lymphocyte subsets (CD4+, CD8+), cure rate, total efficiency and adverse reactions. The random effect model meta was used to analyze the effect data of a single RCT. Heterogeneity will be measured by Cochran Q test and I-squared statistics. We will use 2 subgroup analyses to explore the source of heterogeneity. RCTs with high bias risk was excluded and adjustment effect model was used for sensitivity analysis to test the robustness of the meta-analysis results. The publication bias included in RCTs will be assessed by funnel plot and Egger test.

Results: This study will objectively and comprehensively evaluate the efficacy and safety of randomized controlled trials of moxibustion in the treatment of chronic fatigue syndrome, and the results will be submitted to peer-reviewed journals for publication.

Conclusion: This systematic review will provide clinicians with the latest high-quality evidence for the use of moxibustion in the treatment of chronic fatigue syndrome.

Source: Xue K, Wang Y, Wang X, Chen P, Xiao C, Fu J, Cui J. The efficacy and safety of moxibustion for chronic fatigue syndrome: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021 May 7;100(18):e25742. doi: 10.1097/MD.0000000000025742. PMID: 33950958. https://pubmed.ncbi.nlm.nih.gov/33950958/ 

The Health-Promoting Properties and Clinical Applications of Rice Bran Arabinoxylan Modified with Shiitake Mushroom Enzyme-A Narrative Review

Abstract:

Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran hydrolyzed with Lentinus edodes mycelial enzyme. It has been marketed as a functional food and a nutraceutical with health-promoting properties. Some research has demonstrated this rice bran derivative to be a potent immunomodulator, which also possesses anti-inflammatory, antioxidant, and anti-angiogenic properties. To date, research on RBAC has predominantly focused on its immunomodulatory action and application as a complementary therapy for cancer. Nonetheless, the clinical applications of RBAC can extend beyond cancer therapy.

This article is a narrative review of the research on the potential benefits of RBAC for cancer and other health conditions based on the available literature. RBAC research has shown it to be useful as a complementary treatment for cancer and human immunodeficiency virus infection. It can positively modulate serum glucose, lipid and protein metabolism in diabetic patients. Additionally, RBAC has been shown to ameliorate irritable bowel syndrome and protect against liver injury caused by hepatitis or nonalcoholic fatty liver disease. It can potentially ease symptoms in chronic fatigue syndrome and prevent the common cold. RBAC is safe to consume and has no known side effects at the typical dosage of 2-3 g/day. Nevertheless, further research in both basic studies and human clinical trials are required to investigate the clinical applications, mechanisms, and effects of RBAC.

Source: Ooi SL, Pak SC, Micalos PS, Schupfer E, Lockley C, Park MH, Hwang SJ. The Health-Promoting Properties and Clinical Applications of Rice Bran Arabinoxylan Modified with Shiitake Mushroom Enzyme-A Narrative Review. Molecules. 2021 Apr 27;26(9):2539. doi: 10.3390/molecules26092539. PMID: 33925340. https://pubmed.ncbi.nlm.nih.gov/33925340/ (Full text)

Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue

Abstract:

COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

Source: Theoharides TC, Cholevas C, Polyzoidis K, Politis A. Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue. Biofactors. 2021 Apr 12. doi: 10.1002/biof.1726. Epub ahead of print. PMID: 33847020. https://pubmed.ncbi.nlm.nih.gov/33847020/

Acupuncture therapy on chronic fatigue syndrome based on radar plot: A protocol for an overview of systematic reviews

Abstract:

Background: Chronic fatigue syndrome (CFS) is a debilitating chronic disease of unknown etiology that is recognized by the World Health Organization (WHO) and the United States Center for Disease Control and Prevention (US CDC) as a disorder of the brain. CFS affects 1% (17-24 million people) of the world’s population and is a major and costly public health problem. In traditional Chinese medicine (TCM), acupuncture can achieve a certain effect in the treatment of chronic fatigue syndrome, but evidence-based medicine is controversial. This protocol aims to multi-evaluate the literature quality and evidence quality of the current systematic reviews (SRs)/meta-analyses (MAs) of acupuncture treatment for chronic fatigue syndrome, and provide intuitive and reliable evidence synthesis and decision-making basis for clinical treatment.

Methods: Eight databases will be searched from their inception to 1 June, 2020: the Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed, and Cochrane Library. Published systematic reviews that were reported in Chinese or English, and the included studies were randomized controlled clinical trials (RCTs) for acupuncture in people with CFS will be included. Reviews selection, data extraction and management, and assessment of the study quality will be completed independently by 2 or more reviewers. The quality of evidence, methodological quality, and reporting quality will be evaluated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), A Measurement Tool to Assessment of Multiple Systematic Reviews-2 (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Adobe Illustrator Creative Cloud (Adobe Illustrator CC) will be used to draw and optimize the radar plot.

Results: The article in this overview will be submitted for publication in a peer-reviewed journal.

Conclusion: We hope to collect evidence from accessible and useful systematic reviews of acupuncture treatment for chronic fatigue syndrome, to provide visual and scientific decision-making methods for more clinical practice and medical research.

Source: Tang L, Jiang T, ZHu FY, Liu Z, Wu X. Acupuncture therapy on chronic fatigue syndrome based on radar plot: A protocol for an overview of systematic reviews. Medicine (Baltimore). 2021 Apr 9;100(14):e24572. doi: 10.1097/MD.0000000000024572. PMID: 33832063. https://pubmed.ncbi.nlm.nih.gov/33832063/

Ginger-separated moxibustion for chronic fatigue syndrome and its effect on intestinal flora

Abstract:

Objective: To observe the effect of ginger-separated moxibustion on fatigue state and intestinal flora in patients with chronic fatigue syndrome (CFS).

Methods: A total of 62 patients with CFS were randomly divided into an observation group (31 cases, 3 cases dropped off) and a control group (31 cases, 2 cases dropped off). The patients in the control group were treated with normal diet and moderate exercise; on the basis of the control group, the patients in the observation group were treated with ginger-separated moxibustion at Zhongwan (CV 12), Shenque (CV 8) and Guanyuan (CV 4), 30 min each time, once every other day, three times a week. Both groups were intervened for 4 weeks. Before and after treatment, the fatigue scale-14 (FS-14) was used to observe the improvement of fatigue state, and 16S rRNA detection technology was used to detect the distribution of intestinal flora.

Results: Compared before treatment, the FS-14 score was reduced after treatment in the observation group (P<0.01), and the reduction in the observation group was larger than that in the control group (P<0.01). The relative abundance of intestinal flora was similar between the observation group and control group at the phylum and genus level before treatment. After treatment, there was no significant change of intestinal flora in the control group. However, the enterobacteriaceae, corynebacterium, erysipelothrix, actinomycetes were increased in the observation group (P<0.05), and actinomycetes, ruminococcus, lactarius had obvious flora advantages compared with the control group (P<0.05).

Conclusion: The ginger-separated moxibustion could significantly improve the fatigue state in CFS patients, which may be related to the regulation of intestinal flora structure and the repair of intestinal barrier.

Source: Lin YF, Jin XQ, Zhu JF, Chen YD, Sheng JL, He JJ, Jin YY. [Ginger-separated moxibustion for chronic fatigue syndrome and its effect on intestinal flora]. Zhongguo Zhen Jiu. 2021 Mar 12;41(3):269-74. Chinese. doi: 10.13703/j.0255-2930.20200210-k0001. PMID: 33798308. https://pubmed.ncbi.nlm.nih.gov/33798308/

A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness, characterised by persistent fatigue that is unrelieved by rest, in combination with a range of other disabling symptoms. There is no diagnostic test nor targeted treatment available for this illness. The pathomechanism also remains unclear. Mitochondrial dysfunctions have been considered a possible underlying pathology based on reported differences including structural and functional changes in ME/CFS patients compared to healthy controls. Due to the potential role that mitochondria may play in ME/CFS, mitochondrial-targeting nutraceutical interventions have been used to potentially assist in improving patient outcomes such as fatigue. The aim of this systematic review is to appraise literature assessing these nutraceuticals as a possible intervention for treating ME/CFS.

Methods: A systematic search of Pubmed, Embase, Medline (EBSCO host) and Web of Science (via Clarivate Analytics) for journal articles published between January 1995 and 10th November 2020 was conducted. Articles assessing nutraceutical interventions and ME/CFS patient outcomes were retrieved. Using specific inclusion and exclusion criteria, the list of articles was further refined. Quality was measured using the Rosendal scale.

Results: Nine intervention studies were included in this review. The studies investigated patient symptom severity changes such as altered fatigue levels in response to mitochondrial-targeting nutraceuticals. Improvements in fatigue levels were observed in six of the nine studies. Secondary outcomes assessed include biochemical, psychological, and quality of life parameters.

Conclusion: There is insufficient evidence on the effectiveness of mitochondria- targeting nutraceuticals in ME/CFS patients. Future well-designed studies are required to elucidate both the involvement of mitochondria in the pathomechanism of ME/CFS and the effect of mitochondrial-modifying agents on illness severity.

Source: Maksoud R, Balinas C, Holden S, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2021 Feb 17;19(1):81. doi: 10.1186/s12967-021-02742-4. PMID: 33596913; PMCID: PMC7890871. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02742-4  (Full text)

Effect of acupoint catgut embedding in chronic fatigue syndrome patients: A protocol for systematic review and meta-analysis

Abstract:

Background: Chronic fatigue syndrome (CFS) is a relatively complex and disabling illness with a substantial economic burden and functional impairment. Until now, many CFS patients lack appropriate healthcare. Acupoint catgut embedding is an effective and emerging alternative therapy for CFE. With this research, we endeavor to investigate the effect and safety of ACE for CFS.

Methods: Eight databases will be searched from inception to December 2020: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chong-Qing VIP database, and Wan-fang database. We regard studies as eligible for inclusion if they were RCTs done in CFS patients, compare acupoint catgut embedding to another treatment strategy, and report fatigue changes at the end of the intervention period. Two independent reviewers complete the study selection, data extraction, and the risk of bias assessment. We assess pooled data using a random-effects model through Revman software (v.5.3) and Stata (version 15.0).

Ethics and dissemination: Ethics approval is not required because the individual patient data will not be involved, with no privacy concerns. This systematic review and meta-analysis will provide a reference for CFS patients and clinicians on the non-drug interventions. We will publish and disseminate the results of this review in a peer-reviewed journal or relevant conference.

Source: Zhang ML, Fu HJ, Tang Y, Luo ZG, Li JY, Li R. Effect of acupoint catgut embedding in chronic fatigue syndrome patients: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021 Feb 5;100(5):e23946. doi: 10.1097/MD.0000000000023946. PMID: 33592847; PMCID: PMC7870242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870242/ (Full text)