Bamboo-based medicinal moxibustion for chronic fatigue syndrome: a randomized controlled trial

Abstract:

Objective: To observe the clinical efficacy of bamboo-based medicinal moxibustion for chronic fatigue syndrome (CFS), and to preliminarily explore its action mechanism.

Methods: Sixty-four patients with CFS were randomly divided into a moxibustion group (32 cases, 1 case dropped off, 1 case excluded) and an acupuncture group (32 cases, 2 cases dropped off). The patients in the moxibustion group were treated with bamboo-based medicinal moxibustion, while the patients in the acupuncture group were treated with routine acupuncture. Both groups were treated once a day, 6 days as a course of treatment with 1 day interval, for a total of 2 courses of treatment. Before treatment, 1 and 2 courses into treatment and in the follow-up of 14 days after treatment, the fatigue scale-14 (FS-14) and somatic and psychological health report (SPHERE) scores were observed in the two groups. Before and after treatment, the contents of CD+3, CD+4, CD+8 of peripheral blood T lymphocyte subsets were measured and CD+4/CD+8 ratio was calculated; the clinical efficacy of the two groups was compared.

Results: Compared before treatment, the FS-14 and SPHERE scores in the two groups were decreased 1 and 2 courses into treatment and in the follow-up (P<0.01), and the FS-14 and SPHERE scores in the moxibustion group were lower than those in the acupuncture group (P<0.01, P<0.05). Compared before treatment, the contents of CD+3, CD+4 and CD+4/CD+8 ratio in the moxibustion group were increased after treatment (P<0.01). There was no significant difference of CD+3, CD+4, CD+8 and CD+4/CD+8 ratio between before and after treatment in the acupuncture group (P>0.05). After treatment, the contents of CD+3 and CD+4 in the moxibustion group were higher than those in the acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the moxibustion group, which was higher than 73.3% (22/30) in the acupuncture group (P<0.05).

Conclusion: Bamboo-based medicinal moxibustion could improve the physical and mental fatigue symptoms and psychological status in patients with CFS. Its effect may be related to regulating the contents of CD+3, CD+4 of peripheral blood T lymphocyte subsets and CD+4/CD+8 ratio.

Source: Xue KY, Quan F, Tang JX, Xiao CH, Lu CX, Cui J. [Bamboo-based medicinal moxibustion for chronic fatigue syndrome: a randomized controlled trial]. Zhongguo Zhen Jiu. 2023 May 12;43(5):493-8. Chinese. PMID: 37161800. https://pubmed.ncbi.nlm.nih.gov/37161800/

Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating disease with no symptomatic treatment. Astragalus polysaccharide (APS), a component derived from the traditional Chinese medicine A. membranaceus, has significant anti-fatigue activity. However, the mechanisms underlying the potential beneficial effects of APS on CFS remain poorly understood.

A CFS model of 6-week-old C57BL/6 male mice was established using the multiple-factor method. These mice underwent examinations for behavior, oxidative stress and inflammatory indicators in brain and intestinal tissues, and ileum histomorphology. 16 S rDNA sequencing analysis indicated that APS regulated the abundance of gut microbiota and increased production of short chain fatty acids (SCFAs) and anti-inflammatory bacteria.

In addition, APS reversed the abnormal expression of Nrf2, NF-κB, and their downstream factors in the brain-gut axis and alleviated the reduction in SCFAs in the cecal content caused by CFS. Further, APS modulated the changes in serum metabolic pathways induced by CFS.

Finally, it was verified that butyrate exerted antioxidant and anti-inflammatory effects in neuronal cells. In conclusion, APS could increase the SCFAs content by regulating the gut microbiota, and SCFAs (especially butyrate) can further regulate the oxidative stress and inflammation in the brain, thus alleviating CFS.

This study explored the efficacy and mechanism of APS for CFS from the perspective of gut-brain axis and provides a reference to further explore the efficacy of APS and the role of SCFAs in the central nervous system.

Source: Wei X, Xin J, Chen W, Wang J, Lv Y, Wei Y, Li Z, Ding Q, Shen Y, Xu X, Zhang X, Zhang W, Zu X. Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice. Biomed Pharmacother. 2023 May 9;163:114862. doi: 10.1016/j.biopha.2023.114862. Epub ahead of print. PMID: 37167729. https://www.sciencedirect.com/science/article/pii/S0753332223006522?via%3Dihub (Full study)

Whole-body cryotherapy as a treatment for chronic medical conditions?

Abstract:

Introduction: Whole-body cryotherapy (WBC) is a controlled exposure of the whole body to cold to gain health benefits. In recent years, data on potential applications of WBC in multiple clinical settings have emerged.

Sources of data: PubMed, EBSCO and Clinical Key search using keywords including terms ‘whole body’, ‘cryotherapy’ and ‘cryostimulation’.

Areas of agreement: WBC could be applied as adjuvant therapy in multiple conditions involving chronic inflammation because of its potent anti-inflammatory effects. Those might include systemic inflammation as in rheumatoid arthritis. In addition, WBC could serve as adjuvant therapy for chronic inflammation in some patients with obesity.

Areas of controversy: WBC probably might be applied as an adjuvant treatment in patients with chronic brain disorders including mild cognitive impairment and general anxiety disorder and in patients with depressive episodes and neuroinflammation reduction as in multiple sclerosis. WBC effects in metabolic disorder treatment are yet to be determined. WBC presumably exerts pleiotropic effects and therefore might serve as adjuvant therapy in multi-systemic disorders, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Growing points: The quality of studies on the effects of WBC in the clinical setting is in general low; hence, randomized controlled trials with adequate sample size and longer follow-up periods are needed.

Areas are timely for developing research: Further studies should examine the mechanism underlying the clinical efficacy of WBC. Multiple conditions might involve chronic inflammation, which in turn could be a potential target of WBC. Further research on the application of WBC in neurodegenerative disorders, neuropsychiatric disorders and ME/CFS should be conducted.

Source: Tabisz H, Modlinska A, Kujawski S, Słomko J, Zalewski P. Whole-body cryotherapy as a treatment for chronic medical conditions? Br Med Bull. 2023 May 12:ldad007. doi: 10.1093/bmb/ldad007. Epub ahead of print. PMID: 37170956. https://pubmed.ncbi.nlm.nih.gov/37170956/

Can we Reduce the Symptoms of Chronic Fatigue Syndrome by Regulating Micronutrients? A Review

Abstract:

Introduction: Deficiencies of some micronutrients have been observed in chronic fatigue syndrome patients, but the underlying cause has not been fully understood. The aim of this study was to investigate whether there is a relationship between CFS and micronutrients.

Methods: Related articles searched the combinations of the following terms which were used for the search in the Web of Science database: “Chronic Fatigue Syndrome” OR “Chronic Fatigue- Fibromyalgia Syndrome” OR “Postviral Fatigue Syndrome” AND “vitamins” OR “minerals” OR “micronutrients”. Articles that met the inclusion criteria were included.

Results: The initial search resulted in 225 studies, with 11 studies fully meeting the inclusion criteria. In these studies, it has been shown that micronutrients may play a role in the etiology of CFS, and that supplemented micronutrients can positively affect the symptoms of CFS.

Conclusion: Although there seems to be a close relationship between CFS-related syndromes and nutritional status, the literature on this subject remains limited. The results of the studies were not compatible with each other due to differences in the studies. Therefore, new studies are needed to fully explain the relationship between CFS and micronutrients.

Source: Akduman, GUl; Kurtbeyoglu, Emine; Gunes, Fatma E. Can we Reduce the Symptoms of Chronic Fatigue Syndrome by Regulating Micronutrients? A Review. Current Nutrition & Food Science, Volume 19, Number 5, 2023, pp. 509-518(10). https://www.ingentaconnect.com/content/ben/cnf/2023/00000019/00000005/art00005

Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study

Abstract:

Fatigue is one of the most frequent and disabling symptoms of the post-COVID syndrome. In this study, we aimed to assess the effects of transcranial direct current stimulation on fatigue severity in a group of patients with post-COVID syndrome and chronic fatigue.

We conducted a double-blind, parallel-group, sham-controlled study to evaluate the short-term effects of anodal transcranial direct current stimulation (2 mA, 20 min/day) on the left dorsolateral prefrontal cortex. The modified fatigue impact scale score was used as the primary endpoint. Secondary endpoints included cognition (Stroop test), depressive symptoms (Beck depression inventory) and quality of life (EuroQol-5D).

Patients received eight sessions of transcranial direct current stimulation and were evaluated at baseline, immediately after the last session, and one month later. Forty-seven patients were enrolled (23 in the active treatment group and 24 in the sham treatment group); the mean age was 45.66 ± 9.49 years, and 37 (78.72%) were women. The mean progression time since the acute infection was 20.68 ± 6.34 months.

Active transcranial direct current stimulation was associated with a statistically significant improvement in physical fatigue at the end of treatment and 1 month as compared with sham stimulation. No significant effect was detected for cognitive fatigue.

In terms of secondary outcomes, active transcranial direct current stimulation was associated with an improvement in depressive symptoms at the end of treatment. The treatment had no effects on the quality of life. All the adverse events reported were mild and transient, with no differences between the active stimulation and sham stimulation groups.

In conclusion, our results suggest that transcranial direct current stimulation on the dorsolateral prefrontal cortex may improve physical fatigue. Further studies are needed to confirm these findings and optimize stimulation protocols.

Source: Oliver-Mas S, Delgado-Alonso C, Delgado-Álvarez A, Díez-Cirarda M, Cuevas C, Fernández-Romero L, Matias-Guiu A, Valles-Salgado M, Gil-Martínez L, Gil-Moreno MJ, Yus M, Matias-Guiu J, Matias-Guiu JA. Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study. Brain Commun. 2023 Apr 10;5(2):fcad117. doi: 10.1093/braincomms/fcad117. PMID: 37091591; PMCID: PMC10116605. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116605/ (Full text)

Ginsenoside Rg1 can reverse fatigue behavior in CFS rats by regulating EGFR and affecting Taurine and Mannose 6-phosphate metabolism

Abstract:

Background: Chronic fatigue syndrome (CFS) is characterized by significant and persistent fatigue. Ginseng is a traditional anti-fatigue Chinese medicine with a long history in Asia, as demonstrated by clinical and experimental studies. Ginsenoside Rg1 is mainly derived from ginseng, and its anti-fatigue metabolic mechanism has not been thoroughly explored.

Methods: We performed non-targeted metabolomics of rat serum using LC-MS and multivariate data analysis to identify potential biomarkers and metabolic pathways. In addition, we implemented network pharmacological analysis to reveal the potential target of ginsenoside Rg1 in CFS rats. The expression levels of target proteins were measured by PCR and Western blotting.

Results: Metabolomics analysis confirmed metabolic disorders in the serum of CFS rats. Ginsenoside Rg1 can regulate metabolic pathways to reverse metabolic biases in CFS rats. We found a total of 34 biomarkers, including key markers Taurine and Mannose 6-phosphate. AKT1, VEGFA and EGFR were identified as anti-fatigue targets of ginsenoside Rg1 using network pharmacological analysis. Finally, biological analysis showed that ginsenoside Rg1 was able to down-regulate the expression of EGFR.

Conclusion: Our results suggest ginsenoside Rg1 has an anti-fatigue effect, impacting the metabolism of Taurine and Mannose 6-phosphate through EGFR regulation. This demonstrates ginsenoside Rg1 is a promising alternative treatment for patients presenting with chronic fatigue syndrome.

Source: Lei C, Chen J, Huang Z, Men Y, Qian Y, Yu M, Xu X, Li L, Zhao X, Jiang Y, Liu Y. Ginsenoside Rg1 can reverse fatigue behavior in CFS rats by regulating EGFR and affecting Taurine and Mannose 6-phosphate metabolism. Front Pharmacol. 2023 Apr 10;14:1163638. doi: 10.3389/fphar.2023.1163638. PMID: 37101547; PMCID: PMC10123289. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123289/ (Full text)

Exploring the Genetic Contribution to Oxidative Stress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

OBJECTIVES/GOALS: Strong evidence has implicated oxidative stress (OS) as a disease mechanism in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The study aim was to assess whether a C>T single nucleotide polymorphism (SNP) (rs1800668), which reduces the activity of glutathione peroxidase 1 (GPX1), is associated with brain OS in patients with ME/CFS.

METHODS/STUDY POPULATION: Study population: The study enrolled 20 patients with ME/CFS diagnosed according to Canadian Consensus Criteria, and 11 healthy control (HC) subjects. Genotyping: DNA was extracted from whole blood samples, amplified by PCR, and purified. Sanger sequencing was used for genotyping. 1H MRS: Proton magnetic resonance spectroscopy (1H MRS) was used to measure levels of glutathione (GSH) a primary tissue antioxidant and OS marker in a 3x3x2 cm3 occipital cortex (OCC) voxel. GSH spectra were recorded in 15 minutes with the standard J-editing technique. The resulting GSH peak area was normalized to tissue water level in the voxel. Statistical Analysis: T-tests were used to compare OCC GSH levels between ME/CFS and HC groups, and between the study’s genotype groups (group 1: CC, group 2: combined TC and TT).

RESULTS/ANTICIPATED RESULTS: Clinical characteristics: ME/CFS and HC groups were comparable on age and BMI but not on sex (p = 0.038). Genotype frequencies: Genotype frequencies in the ME/CFS group were 0.55 (CC), 0.25 (TC) and 0.2 (TT); and 0.636 (CC), 0.364 (TC), and 0 (TT) in the HC group. GSH levels: There was a trend-level lower mean OCC GSH in ME/CFS than in HC (0.0015 vs 0.0017; p = 0.076). GSH levels by genotype group interaction: Within the ME/CFS group but not in the combined ME/CFS and HC group or HC group alone, GSH levels were lower in the TC and TT genotypes than in CC genotypes (0.00143 vs 0.00164; p = 0.018).

DISCUSSION/SIGNIFICANCE: This study found that the presence of a C>T SNP in GPX1 is associated with lower mean GSH levels and, hence, brain oxidative stress, in ME/CFS patients. If validated in a larger cohort, this finding may support targeted antioxidant therapy based on their genotype as a potentially effective treatment for patients with ME/CFS.

Source: Hampilos, N., Germain, A., Mao, X., Hanson, M., & Shungu, D. (2023). 474 Exploring the Genetic Contribution to Oxidative Stress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Clinical and Translational Science, 7(S1), 137-138. doi:10.1017/cts.2023.488. DOI: https://doi.org/10.1017/cts.2023.488

Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?

Abstract:

Following a SARS-CoV-2 infection, many individuals suffer from post-COVID-19 syndrome. It makes them unable to proceed with common everyday activities due to weakness, memory lapses, pain, dyspnea and other unspecific physical complaints. Several investigators could demonstrate that the SARS-CoV-2 related spike glycoprotein (SGP) attaches not only to ACE-2 receptors but also shows DNA sections highly affine to nicotinic acetylcholine receptors (nAChRs).

The nAChR is the principal structure of cholinergic neuromodulation and is responsible for coordinated neuronal network interaction. Non-intrinsic viral nAChR attachment compromises integrative interneuronal communication substantially. This explains the cognitive, neuromuscular and mood impairment, as well as the vegetative symptoms, characterizing post-COVID-19 syndrome. The agonist ligand nicotine shows an up to 30-fold higher affinity to nACHRs than acetylcholine (ACh).

We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.

Source: Leitzke, M. Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?. Bioelectron Med 9, 2 (2023). https://doi.org/10.1186/s42234-023-00104-7 (Full text)

Synbiotic Supplementation Improves Quality of Life and Inmunoneuroendocrine Response in Patients with Fibromyalgia: Influence of Codiagnosis with Chronic Fatigue Syndrome

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are two medical conditions in which pain, fatigue, immune/inflammatory dysregulation, as well as various mental health disorders predominate in the diagnosis, without evidence of a clear consensus on the treatment of FM and CFS.
The main aim of this research was to analyse the possible effects of a synbiotic (Synbiotic, Gasteel Plus® (Heel España S.A.U.), through the study of pro-inflammatory/anti-inflammatory cytokines (IL-8/IL-10) and neuroendocrine biomarkers (cortisol and DHEA), in order to evaluate the interaction between inflammatory and stress responses mediated by the cytokine-HPA (hypothalamic-pituitary-adrenal) axis, as well as mental and physical health using body composition analysis, accelerometry and previously validated questionnaires.
The participants were women diagnosed with FM with or without a diagnostic of CFS. Each participant was evaluated at baseline and after the intervention, which lasted one month. Synbiotic intervention decreased levels of perceived stress, anxiety and depression, as well as improved quality of life during daily activities. In addition, the synbiotic generated an activation of HPA axis (physiological cortisol release) that can compensate the increased inflammatory status (elevated IL-8) observed at baseline in FM patients. There were no detrimental changes in body composition or sleep parameters, as well as in the most of the activity/sedentarism-related parameters studied by accelerometry.
It is concluded that synbiotic nutritional supplements can improve the dysregulated immunoneuroendocrine interaction involving inflammatory and stress responses in women diagnosed with FM, particularly in those without a previous CFS diagnostic; as well as their perceived of levels stress, anxiety, depression and quality of life.
Source: Hinchado MD, Quero-Calero CD, Otero E, Gálvez I, Ortega E. Synbiotic Supplementation Improves Quality of Life and Inmunoneuroendocrine Response in Patients with Fibromyalgia: Influence of Codiagnosis with Chronic Fatigue Syndrome. Nutrients. 2023; 15(7):1591. https://doi.org/10.3390/nu15071591 https://www.mdpi.com/2072-6643/15/7/1591 (Full text)

An Orthomolecular Protocol for Long COVID

Abstract:

A significant number of COVID-19 patients suffer from SARS-CoV-2 post-acute chronic sequelae, also known as post-COVID syndrome or long COVID. These patients report a broad range of persistent and debilitating symptoms such as fatigue, brain fog, pain, breathlessness, and dysrhythmias. These chronic symptoms are believed to be a consequence of excessive production of reactive oxygen species (ROS), inflammation, tissue damage, and mitochondrial dysfunction. Patients at higher risk of long-term sequelae are those who experienced severe COVID-19 infection, are immunocompromised and likely have depleted reserves of biological factors and micronutrients necessary for prompt recovery.

Based on biochemical principles and studies in conditions that share common traits with long COVID patients such as chronic fatigue syndrome and fibromyalgia, symptom relief and sustained recovery can be expected by administering an orthomolecular protocol consisting of a combination of precursors, cofactors, and biological response modifiers.

Source: Gonzalez MJ et al. (2023) An Orthomolecular Protocol for Long-COVID. J Orthomol Med. 38(1) https://www.researchgate.net/publication/369328211_An_Orthomolecular_Protocol_for_Long_COVID (Full text)