Efficacy and safety of Ma’s Bamboo-based medicinal moxibustion therapy for chronic fatigue syndrome

Abstract:

Background: Chronic fatigue syndrome (CFS) is a recurrent functional disease with an unknown pathogenesis. Modern treatment mainly focuses on symptomatic and supportive care, but no specific treatment has emerged. Ma’s Bamboo-based Medicinal Moxibustion therapy is a folk traditional Chinese medicine developed in Jinsha County, Guizhou Province. Over a long period of practice in the primary health care setting, it has been confirmed in folk medicine that the therapy can significantly improve the symptoms of patients with CFS, but there is no sufficient and scientific clinical evidence. Therefore, this randomised controlled pilot study was designed to preliminarily evaluate the efficacy and safety of Ma’s Bamboo-based Medicinal Moxibustion therapy.

Methods/design: This is a parallel, randomized, controlled, and exploratory study. Sixty patients with CFS admitted to the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine will be randomly assigned to the experimental or control group. The experimental group will receive Ma’s Bamboo-based Medicinal Moxibustion therapy, whereas the control group will undergo conventional acupuncture. Both groups will be treated once daily for 6 consecutive days as a course of treatment, and two courses separated by 1 day will be completed (12 total treatments). All patients will undergo follow-up after the end of treatment. The baseline period is 2 days. The Fatigue Assessment Instrument score as the primary efficacy measure and secondary efficacy measures, including the Clinical Symptom Score and Fatigue Scale-14, will be evaluated at baseline, after one and two courses of treatment, and during follow-up. Serum T lymphocyte subset counts (CD3+, CD4+, CD8+, CD4+/CD8+) and safety measures ((blood routine test, liver and kidney function and electrocardiogram) will be evaluated at baseline and after two courses of treatment. All adverse events occurring between baseline and the end of follow-up will be summarised at the end of the follow-up.

Discussion: The results of this trial will clarify whether Ma’s Bamboo-based Medicinal Moxibustion therapy can improve the symptoms of patients with CFS and provide preliminary evidence for the effectiveness and safety of Ma’s Bamboo-based Medicinal Moxibustion therapy for this indication.

Ethics approval: This study has been approved by the Ethics Review Committee of the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine (No.K2020–038).

Trial Registration:  Chinese Clinical Trial Registry, ChiCTR2000038860. Registered on 7 October 2020.

Source: Xue, Kaiyang MMa,b; Wang, Xianzhu MMa,b; Quan, Fei MMa,b; Tang, Jiaxuan MMa,b; Wang, Xin MMa; Lan, Lan MMa; Fu, Jing PhDa; Cui, Jin PhDa,∗ Efficacy and safety of Ma’s Bamboo-based medicinal moxibustion therapy for chronic fatigue syndrome, Medicine Case Reports and Study Protocols: January 2022 – Volume 3 – Issue 1 – p e0193
doi: 10.1097/MD9.0000000000000193 https://journals.lww.com/md-cases/Fulltext/2022/01000/Efficacy_and_safety_of_Ma_s_Bamboo_based_medicinal.6.aspx (Full text)

Letter: Could endothelial dysfunction and vascular damage contribute to pain, inflammation and post-exertional malaise in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)?

To the Editor,

In their hypothesis paper, Wirth, Scheibenbogen, and Paul describe how endothelial dysfunction could produce a wide range of neurological symptoms in people with ME/CFS [1]. As they and others work to refine their understanding of ME/CFS and the related Long COVID syndrome, I would encourage consideration of the possibility that endothelial dysfunction and vascular damage could also explain other symptoms, including widespread pain and inflammation and post-exertional malaise.

For the past four years, my wife and I have been caregivers for our teenage daughter, who has ME/CFS, hypermobile Ehlers-Danlos syndrome, craniocervical instability, Chiari malformation and several other comorbid conditions. Through observation and trial and error, I have developed a number of hypotheses on these matters that I offer here in the hope they might prompt formal research into how to effectively treat these conditions [2].

Widespread pain and inflammation

Discussion of endothelial dysfunction and vascular damage in ME/CFS and Long COVID generally focuses on how leakages from dysfunctional blood vessels lead to reduced blood flow, which has many consequences, including reduced oxygenation of muscles and reduced cerebral brain flow. As researchers study this phenomenon, I would encourage consideration of the additional possibility that the leaking fluid causes independent damage. Lipedema researchers have found that leakages from microangiopathic blood vessels cause an excess of interstitial fluid that stimulates the formation of subcutaneous adipose tissue [3], which generates hypoxic conditions and becomes fibrotic, contributing to pain and inflammation [4].

I hypothesize that a similar process happens when fluid leaks from faulty blood vessels in ME/CFS, possibly exacerbated by endothelial dysfunction in lymphatic vessels that inhibit the fluid’s removal, causing widespread pain and inflammation. This mechanism appears most pronounced among people with hypermobility or other connective tissue disorders, a common trait among people with both ME/CFS and lipedema.

My daughter experiences pain from fibrotic adipose tissue as well as what appears to be nerve compression from accumulated interstitial / lymphatic fluid. Manual lymphatic drainage, the squeezing of affected tissue, and the manual break-up of fibrotic adipose tissue have helped to ameliorate these symptoms.

In my daughter, I have also observed impaired drainage of fluid from the glymphatic system, both at the cribriform plate and down her spine. Could this be related to damaged lymphatic vessels or blockages from fibrotic adipose tissue?

Post-exertional malaise

Like many people with moderate or severe ME/CFS, my daughter struggles to recover from even small amounts of physical exertion. In addition to mitigating her pain, manual lymphatic drainage and the squeezing of affected tissue greatly accelerates this recovery process. We have observed a direct dose–response relationship: the more exercise, the more fluid is present in her tissues, and the more manual draining / squeezing is necessary for her to recover.

Based on this experience, I hypothesize that excess interstitial fluid resulting from dysfunctional blood and lymphatic vessels contributes to the experience of post-exertional malaise, with fluid literally drowning affected tissue, leading to hypoxic conditions and inflammation. Possible explanations for the increased interstitial fluid are increases in blood pressure during physical exertion, hypermobile joints going out of place, prompting localized increases in interstitial fluid, and increases in cortisol that generate an increase in fluid and blood volume. Increases in fluid leakage due to elevated cortisol levels may also explain why some people with ME/CFS feel worse when stressed or anxious. The role of cortisol (or another mediator with fluid retaining properties) may explain why cognitive exertion can also generate post-exertional malaise. When present, elevated estrogen levels may exacerbate leakage by increasing fluid volume.

I am not sure why there is typically a delay between physical exertion and the experience of the most acute symptoms of post-exertional malaise. One possibility is that it takes time for the tissue inundated with fluid to feel the full effects of the hypoxic conditions. Another possibility is that a biphasic reaction triggered during physical exertion leads to the release of a mediator that causes heightened endothelial dysfunction and fluid release.

Further research is needed into the causes of endothelial dysfunction and damage (in addition to initial infection and inflammatory overreaction, consider major “crashes,” mast cell activations, surgeries and microclots as additional contributors) and appropriate treatment.

References

1. Wirth KJ, Scheibenbogen C, Paul F. An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Transl Med. 2021;19:471. https://doi.org/10.1186/s12967-021-03143-3.

Article PubMed PubMed Central Google Scholar

2. For background, see Lubell, J. To speed progress in treating chronic conditions, engage patients and caregivers as research partners. 2021 Sept.20 In: BMJ Opinion. https://blogs.bmj.com/bmj/2021/09/20/to-speed-progress-in-treating-chronic-conditions-engage-patients-and-caregivers-as-research-partners/

3. Allen M, Schwartz M, Herbst KL. Interstitial Fluid in Lipedema and Control Skin. Womens Health Rep (New Rochelle). 2020;1(1):480–7. https://doi.org/10.1089/whr.2020.0086.PMID:33786515;PMCID:PMC7784769.

Article Google Scholar

4. Herbst KL. Subcutaneous Adipose Tissue Diseases: Dercum Disease, Lipedema, Familial Multiple Lipomatosis, and Madelung Disease. [Updated 2019 Dec 14]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. South Dartmouth (MA).

Source: Lubell J. Letter: Could endothelial dysfunction and vascular damage contribute to pain, inflammation and post-exertional malaise in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)? J Transl Med. 2022 Jan 24;20(1):40. doi: 10.1186/s12967-022-03244-7. PMID: 35073915. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03244-7

Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report

Abstract:

Background: Post-COVID-19 fatigue is a frequent symptom in COVID-19 survivors, which substantially limits patients to achieve full recovery and potentially restrains return to work. The previous literature has not yet reported the use of pulsed electromagnetic fields in this indication.

Methods: Over the course of 5 weeks, 10 sessions of pulsed electromagnetic field treatment with a high magnetic flux density were applied to a patient suffering from post-COVID-19 fatigue syndrome. Fatigue, work ability, quality of life as well as anxiety, depression, stress level, and resilience were evaluated using validated patient-reported outcome measures.

Results: Fatigue, work ability, quality of life, and psychological well-being improved clearly over the course of the treatment and showed stable results 6 weeks later.

Conclusion: The use of pulsed electromagnetic field therapy with a device that allows sufficient penetration of the body tissue might be a promising physical modality to manage post-COVID-19 fatigue syndrome, which could reduce clinical and economic health consequences. Clinical sham-controlled studies are needed to evaluate the effect of pulsed electromagnetic fields in this indication.

Source: Wagner B, Steiner M, Markovic L, Crevenna R. Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report. Wien Med Wochenschr. 2022 Jan 10:1–6. doi: 10.1007/s10354-021-00901-2. Epub ahead of print. PMID: 35006516; PMCID: PMC8743351. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743351/ (Full text)

Male vs. Female Differences in Responding to Oxygen-Ozone Autohemotherapy (O 2-O 3-AHT) in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a syndrome that has fatigue as its major symptom. Evidence suggests that ozone is able to relieve ME/CFS-related fatigue in affected patients.

Objective: To evaluate whether differences exist between males and females in ozone therapy outputs in ME/CFS. (3) Methods: In total, 200 patients previously diagnosed with ME/CFS (mean age 33 ± 13 SD years) underwent treatment with oxygen-ozone autohemotherapy (O2-O3-AHT). Fatigue was investigated via an FSS 7-scoring questionnaire before and following 1 month after treatment.

Results: The Mann-Whitney test (MW test) assessed the significance of this difference (H = 13.8041, p = 0.0002), and female patients showed better outcomes than males. This difference was particularly striking in the youngest age cohort (14-29 years), and a KW test resulted in H = 7.1609, p = 0.007 for the Δ = 28.3% (males = 3.8, females = 5.3).

Conclusions: When treated with O2-O3-AHT, females respond better than males.

Source: Chirumbolo S, Valdenassi L, Franzini M, Pandolfi S, Ricevuti G, Tirelli U. Male vs. Female Differences in Responding to Oxygen-Ozone Autohemotherapy (O2-O3-AHT) in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). J Clin Med. 2021 Dec 29;11(1):173. doi: 10.3390/jcm11010173. PMID: 35011914. https://pubmed.ncbi.nlm.nih.gov/35011914/

An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue

Chronic fatigue syndrome and fibromyalgia (CFS/FMS) affect 2.1% of the world’s population and ~10–25% of people who have had COVID-19. Previous clinical data suggested that a unique Panax ginseng (C.A. Meyer, family Araliaceae) root extract (HRG80™ Red Ginseng) often resulted in marked improvement. We aimed to study this hydroponic form of red ginseng root, containing high levels of rare ginsenosides, for improving energy, cognition, and stamina. This open-label prospective study included participants with severe CFS/FMS who took a daily supplement of HRG80 capsules (200–400 mg) or tablets (100–200 mg) for one month.
A total of 188 subject patients completed the one-month treatment trial. Of these, 60.1% rated themselves as improved, with 13.3% rating themselves as being much better. In this group, the mean composite score improved from 11.9 to 18.8 (p < 0.001), with a 67% average increase in energy, 44% average increase in overall well-being, 48% average improvement in mental clarity, 58% average composite improvement in the previous three measurements (primary outcome measure), 46% average improvement in sleep, 33% average decrease in pain, and 72% average increase in stamina. Our study showed that HRG80 red ginseng root powder resulted in a marked improvement in people with CFS and fibromyalgia. This included the subgroup with post-viral CFS/FMS.
Source: Teitelbaum J, Goudie S. An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue. Pharmaceuticals. 2022; 15(1):43. https://doi.org/10.3390/ph15010043 (Full text)

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Greatly Improved Fatigue Symptoms When Treated with Oxygen-Ozone Autohemotherapy

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic syndrome characterized by fatigue as its major and most outstanding symptom. Previous evidence has supported the ability of ozone to relief ME/CFS related fatigue in affected patients.
Methods: A number of 200 ME/CFS previously diagnosed patients, (mean age 33 ± 13 SD years) were consecutively treated with oxygen-ozone autohemotherapy (O2-O3-AHT). Fatigue was evaluated via an FSS 7-scoring questionnaire before and following 30 days after treatment.
Results: Almost half (43.5%) of the treated patients evolved their FSS scale from the worst (7) to the best (1) score, assessing the highest improvement from being treated with O2-O3-AHT. Furthermore 77.5% of patients experienced significant ameliorations of fatigue, of 4–6 delta score. No patient showed side effects, yet experienced long lasting fatigue disappearance, by three months follow up.
Conclusions: Treatment with O2-O3-AHT greatly improves ME/CFS related fatigue, aside from sex and age distribution.
Source: Tirelli U, Franzini M, Valdenassi L, Pandolfi S, Berretta M, Ricevuti G, Chirumbolo S. Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Greatly Improved Fatigue Symptoms When Treated with Oxygen-Ozone Autohemotherapy. Journal of Clinical Medicine. 2022; 11(1):29. https://doi.org/10.3390/jcm11010029  https://www.mdpi.com/2077-0383/11/1/29/htm (Full text)

Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats

Abstract:

Recent studies have reported that plasma levels of tricarboxylic acid (TCA) cycle metabolites and TCA cycle-related metabolite change in patients with chronic fatigue syndrome (CFS) and in healthy humans after exercise. Exogenous dietary citric acid has been reported to alleviate fatigue during daily activities and after exercise. However, it is unknown whether dietary citric acid affects the plasma levels of these metabolites. Therefore, the present study aimed to investigate the effects of exogenously administered citric acid on TCA cycle metabolites and TCA cycle-related metabolites in plasma.

Sprague-Dawley rats were divided into control and citric acid groups. We evaluated the effect of exogenous dietary citric acid on the plasma TCA cycle and TCA cycle-related metabolites by metabolome analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). TCA cycle metabolites, including plasma citrate, cis-aconitate, and isocitrate, were significantly elevated after exogenous administration of citric acid. Anaplerotic amino acids, which are converted to TCA cycle metabolites, such as serine, glycine, tryptophan, lysine, leucine, histidine, glutamine, arginine, isoleucine, methionine, valine, and phenylalanine, also showed significantly elevated levels.

Citric acid administration significantly increased the levels of initial TCA cycle metabolites in the plasma. This increase after administration of citric acid was shown to be opposite to the metabolic changes observed in patients with CFS. These results contribute novel insight into the fatigue alleviation mechanism of citric acid.

Source: Hara Y, Kume S, Kataoka Y, Watanabe N. Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats. Heliyon. 2021 Dec 4;7(12):e08501. doi: 10.1016/j.heliyon.2021.e08501. PMID: 34934832; PMCID: PMC8654791. https://pubmed.ncbi.nlm.nih.gov/34934832/

Can l-carnitine reduce post-COVID-19 fatigue?

Abstract:

A significant number of patients infected with the new coronavirus suffer from chronic fatigue syndrome after COVID-19, and their symptoms may persist for months after the infection. Nevertheless, no particular treatment for post-disease fatigue has been found. At the same time, many clinical trials have shown the effectiveness of l-carnitine in relieving fatigue caused by the treatment of diseases such as cancer, MS, and many other diseases. Therefore, it can be considered as a potential option to eliminate the effects of fatigue caused by COVID-19, and its consumption is recommended in future clinical trials to evaluate its effectiveness and safety.

Source: Vaziri-Harami R, Delkash P. Can l-carnitine reduce post-COVID-19 fatigue? Ann Med Surg (Lond). 2022 Jan;73:103145. doi: 10.1016/j.amsu.2021.103145. Epub 2021 Dec 13. PMID: 34925826; PMCID: PMC8667465. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667465/ (Full text)

Proposal of a food supplement for the management of post-COVID syndrome

Abstract:

A vast majority of COVID-19 patients experience fatigue, extreme tiredness and symptoms that persist beyond the active phase of the disease. This condition is called post-COVID syndrome. The mechanisms by which the virus causes prolonged illness are still unclear. The aim of this review is to gather information regarding post-COVID syndrome so as to highlight its etiological basis and the nutritional regimes and supplements that can mitigate, alleviate or relieve the associated chronic fatigue, gastrointestinal disorders and continuing inflammatory reactions. Naturally-occurring food supplements, such as acetyl L-carnitine, hydroxytyrosol and vitamins B, C and D hold significant promise in the management of post-COVID syndrome. In this pilot observational study, we evaluated the effect of a food supplement containing hydroxytyrosol, acetyl L-carnitine and vitamins B, C and D in improving perceived fatigue in patients who recovered from COVID-19 but had post-COVID syndrome characterized by chronic fatigue. The results suggest that the food supplement could proceed to clinical trials of its efficacy in aiding the recovery of patients with long COVID.

Source: Naureen Z, Dautaj A, Nodari S, Fioretti F, Dhuli K, Anpilogov K, Lorusso L, Paolacci S, Michelini S, Guda T, Kallazi M, Bertelli M. Proposal of a food supplement for the management of post-COVID syndrome. Eur Rev Med Pharmacol Sci. 2021 Dec;25(1 Suppl):67-73. doi: 10.26355/eurrev_202112_27335. PMID: 34890036. https://www.europeanreview.org/article/27335 (Full article as PDF file)

A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study

Abstract:

Dietary therapy may be beneficial in alleviating symptoms of chronic fatigue syndrome (CFS), a disorder that is characterized by extreme fatigue and other symptoms, but the cause of which remains unclear. The aim of this study was to evaluate the protective effect of a botanical product containing cistanche (Cistanche tubulosa [Schenk] Wight) and ginkgo (Ginkgo biloba L.) extracts on adults with CFS in a randomized, double-blind, placebo-controlled clinical trial.

A total of 190 subjects (35-60 years old, non-obese) with CFS were randomized to receive one tablet of a low dose (120-mg ginkgo and 300-mg cistanche), a high dose (180-mg ginkgo and 450-mg cistanche) or a placebo once daily for 60 days. Blood samples and responses on the Chalder fatigue scale (CFQ 11), the World Health Organization’s quality of life questionnaire (WHOQOL), and the sexual life quality questionnaire (SLQQ) were collected at baseline and post-intervention.

CFS symptoms of impaired memory or concentration, physical fatigue, unrefreshing sleep, and post-exertional malaise were significantly improved (p < 0.001) in both of the treatment groups. The botanical intervention significantly decreased physical and mental fatigue scores of CFQ 11 and improved WHOQOL and SLQQ scores of the subjects (p < 0.01). Levels of blood ammonia and lactic acid in the treatment groups were significantly lower than those of the placebo group (low-dose: p < 0.05; high-dose: p < 0.01). In addition, the change in lactic acid concentration was negatively associated with the severity of CFS symptoms (p = 0.0108) and was correlated with the change in total physical fatigue score of the CFQ (p = 0.0302). Considering the trivial effect size, the results may lack clinical significance.

In conclusion, this botanical product showed promising effects in ameliorating the symptoms of CFS. Clinical trials with improved assessment tools, an expanded sample size, and an extended follow-up period are warranted to further validate the findings.

Clinical Trial Registration: https://clinicaltrials.gov/, identifier: NCT02807649.

Source: Kan J, Cheng J, Hu C, Chen L, Liu S, Venzon D, Murray M, Li S, Du J. A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study. Front Nutr. 2021 Nov 26;8:658630. doi: 10.3389/fnut.2021.658630. PMID: 34901100; PMCID: PMC8662561.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662561/ (Full study)