Category: Alternative Treatments

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

Abstract:

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown cause characterized by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and more recently post-COVID-19 condition (Long COVID).

To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders.

Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. Accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and Long COVID.

To address this issue, this article aimed to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Source: Mantle, D.; Hargreaves, I.P.; Domingo, J.C.; Castro-Marrero, J. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview. Preprints 2023, 2023111554. https://doi.org/10.20944/preprints202311.1554.v1 https://www.preprints.org/manuscript/202311.1554/v1 (Full text available as PDF file)

Effects of traditional Chinese mind-body exercises for patients with chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

Background: Chronic fatigue syndrome (CFS) is a global public health concern. We performed this systematic review of randomised controlled trials (RCTs) to evaluate the effects and safety of traditional Chinese mind-body exercises (TCME) for patients with CFS.

Methods: We comprehensively searched MEDLINE, Embase, Web of Science, PsycINFO, Cochrane Library, CNKI, VIP databases, and Wanfang Data from inception to October 2022 for eligible RCTs of TCME for CFS management. We used Cochran’s Q statistic and I2 to assess heterogeneity and conducted subgroup analyses based on different types of TCME, background therapy, and types of fatigue. We also assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.

Results: We included 13 studies (n = 1187) with a maximal follow-up of 12 weeks. TCME included Qigong and Tai Chi. At the end of the treatment, compared with passive control, TCME probably reduces the severity of fatigue (standardised mean differences (SMD) = 0.85; 95% confidence interval (CI) = 0.64, 1.07, moderate certainty), depression (SMD = 0.53; 95% CI = 0.34, 0.72, moderate certainty), anxiety (SMD = 0.29; 95% CI = 0.11, 0.48, moderate certainty), sleep quality (SMD = 0.34; 95% CI = 0.10, 0.57, low certainty) and mental functioning (SMD = 0.90; 95% CI = 0.50, 1.29, low certainty).

Compared with other active control therapies, TCME results in little to no difference in the severity of fatigue (SMD = 0.08; 95% CI = -0.18, 0.34, low certainty). For long-term outcomes, TCME may improve anxiety (SMD = 1.74; 95% CI = 0.44, 3.03, low certainty) compared to passive control. We did not identify TCME-related serious adverse events.

Conclusions: In patients with CFS, TCME probably reduces post-intervention fatigue, depression, and anxiety and may improve sleep quality and mental function compared with passive control, but has limited long-term effects. These findings will help health professionals and patients with better clinical decision-making.

Source: Kong L, Ren J, Fang S, Li Y, Wu Z, Zhou X, Hao Q, Fang M, Zhang YQ. Effects of traditional Chinese mind-body exercises for patients with chronic fatigue syndrome: A systematic review and meta-analysis. J Glob Health. 2023 Nov 24;13:04157. doi: 10.7189/jogh.13.04157. PMID: 37994837; PMCID: PMC10666566. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666566/ (Full text)

Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice

Abstract:

Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection, last for more than 2 months, and cannot be explained by other diagnoses. The most common symptoms include fatigue, dyspnea, coughing, and cognitive impairment.

The mechanisms of long COVID are not fully understood, but several hypotheses have been put forth. These include coagulation and fibrosis pathway activation, inflammatory and autoimmune manifestations, persistent virus presence, and Epstein-Barr virus reactivation.

Hyperbaric oxygen therapy (HBOT) is a therapeutic method in which a person inhales 100% oxygen under pressure greater than that of the atmosphere. HBOT has some therapeutic effects, including improvement of microcirculation, inhibition of cytokine release leading to a reduction in inflammatory responses, inhibition of autoimmune responses, and promotion of neurological repair.

Several clinical trials have been carried out using HBOT to treat long COVID. The results suggest that HBOT helps to improve symptom severity, reduce symptom duration, and enhance patients’ quality of life. It is believed that HBOT is an effective option for patients with long COVID, which is worth actively promoting.

Source: Pan JQ, Tian ZM, Xue LB. Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice. Curr Med Sci. 2023 Nov 4. doi: 10.1007/s11596-023-2799-1. Epub ahead of print. PMID: 37924387. https://pubmed.ncbi.nlm.nih.gov/37924387/

Therapeutic Potential of Indian Medicinal Herbs and Current Therapeutic Approach used to Mitigate the Symptoms of Chronic Fatigue Syndrome: A Review

Abstract:

Chronic fatigue syndrome (CFS) is a complex condition marked by severe exhaustion that lasts at least 6 months. The global prevalence of CFS ranging between 0.4% and 2.5% is growing. Women are affected by CFS more often than men. It is considered a common condition in developed countries. There is no approved treatment for CFS but symptoms can be managed and controlled persistent exhaustion causes significant impairment in daily routine activities. Lowered ATP synthesis, mitochondrial impairment, decreased oxidative phosphorylation, disruption of the hypothalamic–pituitary–adrenal (HPA) axis, and an imbalance of brain neurotransmitters play a major role in the pathophysiology of CFS.

The purpose of the present study is to figure out the several plants that are used as a source of medication in chronic fatigue syndrome (CFS) and its current therapeutic approach. The Indian medicinal herbs described in this article are very efficacious in the management of chronic fatigue syndrome symptoms due to the presence of phytochemicals.

This review article also covers the current therapeutic approach for chronic fatigue syndrome in a concise form that comprises CBT (Cognitive based therapy), GET (Graded exercise therapy), usage of immunoglobins, psychodynamic counseling, and yoga therapy that includes isometric yoga and yoga nidra are very beneficial in alleviating the symptoms of chronic fatigue syndrome. Antidepressants, immunomodulatory agents, and corticosteroids come under conventional medication for CFS.

This article explores different Indian medicinal herbs, their pharmacological properties, and their potential role and current treatments for reducing the severity of symptoms of chronic fatigue syndrome.

Source: Singh, Nisha; Sharma, Rahul K.; Kushwah, Ajay Singh; Kumar, Manish. Therapeutic Potential of Indian Medicinal Herbs and Current Therapeutic Approach used to Mitigate the Symptoms of Chronic Fatigue Syndrome: A Review. Current Traditional Medicine, Volume 10, Number 4, 2024, pp. 115-128(14). https://www.ingentaconnect.com/content/ben/ctm/2024/00000010/00000004/art00013

Integrated ‘omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome

Abstract:

Objective: To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome (CFS) and explore the effects on gut microbiota and metabolic profiles.

Methods: Forty-eight male Sprague-Dawley rats were randomly assigned to control group (Con), CFS model group (Mod, established by multiple chronic stress for 35 d), MoxA group (CFS model with moxibustion Shenque (CV8) and Guanyuan (CV4), 10 min/d, 28 d) and MoxB group (CFS model with moxibustion Zusanli (ST36), 10 min/d, 28 d).

Open-field test (OFT) and Morris-water-maze test (MWMT) were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer (LC-MS) based fecal metabolomics were executed, as well as Spearman correlation analysis, was utilized to uncover the functional relevance between the potential metabolites and gut microbiota.

Results: The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT. Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition, including increases in pro-inflammatory species (such as Proteobacteria) and decreases in anti-inflammatory species (such as Bacteroides, Lactobacillus, Ruminococcus, and Prevotella). Moxibustion partially normalized these changes in the gut microbiota.

Furthermore, CFS was associated with metabolic disorders, which were effectively ameliorated by moxibustion. This was demonstrated by the normalization of 33 microbiota-related metabolites, including mannose (P = 0.001), aspartic acid (P = 0.009), alanine (P = 0.007), serine (P = 0.000), threonine (P = 0.027), methionine (P = 0.023), 5-hydroxytryptamine (P = 0.008), alpha-linolenic acid (P = 0.003), eicosapentaenoic acid (P = 0.006), hypoxanthine (P = 0.000), vitamin B6 (P = 0.000), cholic acid (P = 0.013), and taurocholate (P = 0.002).

Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels, with a notable negative relationship between LCA and Bacteroides.

Conclusions: In this study, we demonstrated that moxibustion has an antifatigue-like effect. The results from the 16S rRNA gene sequencing and metabolomics analysis suggest that the therapeutic effects of moxibustion on CFS are related to the regulation of gut microorganisms and their metabolites. The increase in Bacteroides and decrease in LCA may be key targets for the moxibustion treatment of CFS.

Source: Chaoran LI, Yan Y, Chuwen F, Heng LI, Yuanyuan QU, Yulin W, Delong W, Qingyong W, Jing G, Tianyu S, Xiaowei S, Xue W, Yunlong H, Zhongren S, Tiansong Y. Integrated ‘omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome. J Tradit Chin Med. 2023 Oct;43(6):1176-1189. doi: 10.19852/j.cnki.jtcm.20231018.004. PMID: 37946480; PMCID: PMC10623263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623263/ (Full text)

Yeast Beta-Glucan Supplementation with Multivitamins Attenuates Cognitive Impairments in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract:

This research aimed to examine the potential alleviative effects of beta-glucan administration on fatigue, unrefreshing sleep, anxiety/depression symptoms and health-related quality of life in ME/CFS. A 36-week unicenter, randomized, double-blind, placebo-controlled trial was conducted in 65 ME/CFS patients, who were randomly allocated to one of two arms to receive four capsules each one of 250 mg beta-glucan, 3.75 µg vitamin D3, 1.05 mg vitamin B6, and 7.5 mg zinc (n = 35), or matching placebo including only microcrystalline cellulose as an excipient (n = 30) once daily.

The findings showed that the beta-glucan supplementation significantly improved cognitive fatigue (assessed with FIS-40 scores) after the 36-week treatment compared to the baseline (p = 0.0338). Taken together, this study presents the novel finding that yeast-derived beta-glucan may alleviate cognitive fatigue symptoms in ME/CFS. Thus, it offers valuable scientific insights into the potential use of yeast beta-glucan as a nutritional supplement and/or functional food to prevent or reduce cognitive dysfunction in patients with ME/CFS. Further interventions are warranted to validate these findings and also to delve deeper into the possible immunometabolic pathomechanisms of beta-glucans in ME/CFS.

Source: Lacasa M, Alegre-Martin J, Sentañes RS, Varela-Sende L, Jurek J, Castro-Marrero J. Yeast Beta-Glucan Supplementation with Multivitamins Attenuates Cognitive Impairments in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2023 Oct 24;15(21):4504. doi: 10.3390/nu15214504. PMID: 37960157. https://www.mdpi.com/2072-6643/15/21/4504 (Full text)

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Abstract:

Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) is linked to severe neurological manifestations. Senescent cells contribute to brain aging, but the impact of virus-induced senescence on neuropathologies is unknown. Here we show that senescent cells accumulate in aged human brain organoids and that senolytics reduce age-related inflammation and rejuvenate transcriptomic aging clocks.

In postmortem brains of patients with severe COVID-19 we observed increased senescent cell accumulation compared with age-matched controls. Exposure of human brain organoids to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced cellular senescence, and transcriptomic analysis revealed a unique SARS-CoV-2 inflammatory signature. Senolytic treatment of infected brain organoids blocked viral replication and prevented senescence in distinct neuronal populations. In human-ACE2-overexpressing mice, senolytics improved COVID-19 clinical outcomes, promoted dopaminergic neuron survival and alleviated viral and proinflammatory gene expression.

Collectively our results demonstrate an important role for cellular senescence in driving brain aging and SARS-CoV-2-induced neuropathology, and a therapeutic benefit of senolytic treatments.

Source:Aguado, J., Amarilla, A.A., Taherian Fard, A. et al. Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology. Nat Aging (2023). https://doi.org/10.1038/s43587-023-00519-6 https://www.nature.com/articles/s43587-023-00519-6 (Full text)

Senolytic drugs: from discovery to translation

Abstract:

Senolytics are a class of drugs that selectively clear senescent cells (SC). The first senolytic drugs Dasatinib, Quercetin, Fisetin and Navitoclax were discovered using a hypothesis-driven approach.

SC accumulate with ageing and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality and health expenditures. The most deleterious SC are resistant to apoptosis and have up-regulation of anti-apoptotic pathways which defend SC against their own inflammatory senescence-associated secretory phenotype (SASP), allowing them to survive, despite killing neighbouring cells. Senolytics transiently disable these SCAPs, causing apoptosis of those SC with a tissue-destructive SASP.

Because SC take weeks to reaccumulate, senolytics can be administered intermittently – a ‘hit-and-run’ approach. In preclinical models, senolytics delay, prevent or alleviate frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment.

As anticipated for agents targeting the fundamental ageing mechanisms that are ‘root cause’ contributors to multiple disorders, potential uses of senolytics are protean, potentially alleviating over 40 conditions in preclinical studies, opening a new route for treating age-related dysfunction and diseases. Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans.

Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer’s disease, COVID-19, osteoarthritis, osteoporosis, eye diseases and bone marrow transplant and childhood cancer survivors are underway or beginning. Until such studies are done, it is too early for senolytics to be used outside of clinical trials.

Source: Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020 Nov;288(5):518-536. doi: 10.1111/joim.13141. Epub 2020 Aug 4. PMID: 32686219; PMCID: PMC7405395. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405395/ (Full text)

Patient perspectives of recovery from myalgic encephalomyelitis/chronic fatigue syndrome: An interpretive description study

Abstract:

Aims and objectives: Myalgic encephalomyelitis (ME), also called chronic fatigue syndrome (CFS), is characterised by persistent fatigue, postexertional malaise, and cognitive dysfunction. It is a complex, long-term, and debilitating illness without widely effective treatments. This study describes the treatment choices and experiences of ME/CFS patients who have experienced variable levels of recovery.

Method: Interpretive description study consisting of semi-structured qualitative interviews with 33 people who met the US Centers for Disease Control (2015) diagnostic criteria for ME/CFS and report recovery or symptom improvement.

Results: Twenty-six participants endorsed partial recovery, and seven reported full recovery from ME/CFS. Participants reported expending significant time and energy to identify, implement, and adapt therapeutic interventions, often without the guidance of a medical practitioner. They formulated individualised treatment plans reflecting their understanding of their illness and personal resources. Most fully recovered participants attributed their success to mind-body approaches.

Conclusion: Patients with ME/CFS describe independently constructing and managing treatment plans, due to a lack of health system support. Stigmatised and dismissive responses from clinicians precipitated disengagement from the medical system and prompted use of other forms of treatment.

Source: Hasan Z, Kuyvenhoven C, Chowdhury M, Amoudi L, Zeraatkar D, Busse JW, Sadik M, Vanstone M. Patient perspectives of recovery from myalgic encephalomyelitis/chronic fatigue syndrome: An interpretive description study. J Eval Clin Pract. 2023 Nov 6. doi: 10.1111/jep.13938. Epub ahead of print. PMID: 37927138. https://onlinelibrary.wiley.com/doi/10.1111/jep.13938 (Full text)

Repetitive Transcranial Magnetic Stimulation Ameliorates Symptoms in Patients with Myalgic Encephalomyelitis (Chronic Fatigue Syndrome)

Highlights:

• Repetitive transcranial magnetic stimulation (rTMS) was applied to the brain in patients with myalgic encephalomyelitis.
• After therapy, the restriction of activity of daily living was ameliorated in most patients.
• rTMS alleviated various symptoms, especially orthostatic intolerance and disequilibrium.

Abstract:

Background: Central nervous system dysfunction has been postulated to cause debilitating symptoms in patients with myalgic encephalomyelitis (ME) (originally called “chronic fatigue syndrome”). Repetitive transcranial magnetic stimulation (rTMS) is a newly developed neuromodulatory procedure and has been suggested to facilitate the cortical neural activity.

Methods: This study enrolled 30 patients with ME (7 men and 23 women) with a mean age of 39±12 years, who received rTMS treatment of both the left dorsolateral prefrontal cortex and the left primary motor area in the brain. The performance status score (0–9) for restricting activities of daily living, orthostatic intolerance (OI) during a 10-min standing test, neurologic disequilibrium diagnosed as unstable standing with their feet together and eyes closed, neuropathic pain or fibromyalgia, and muscle weakness were compared before and after treatment.

Results: After therapy, favorable effects were observed with a decrease in performance status score or index for restriction of activities of daily living of ≥2 points in 20 patients (67%). OI with the inability to complete the 10-min standing test was resolved in 10 (83%) out of 12 patients, and disequilibrium was resolved in 15 (88%) out of 17 patients. Neuropathic pain or fibromyalgia was attenuated in seven (70%) out of 10 patients. Muscle weakness with grip power of <10 kg was resolved in two (50%) out of four patients. No untoward effects were encountered in all the study patients.

Conclusion: The treatment with rTMS is effective in alleviating various symptoms, especially OI and disequilibrium, and in improving the activities of daily living in patients with ME.

Source: Kunihisa Miwa, Yukichi Inoue. Repetitive Transcranial Magnetic Stimulation Ameliorates Symptoms in Patients with Myalgic Encephalomyelitis (Chronic Fatigue Syndrome). Published: October 30, 2023 DOI:https://doi.org/10.1016/j.ibneur.2023.10.008 https://www.sciencedirect.com/science/article/pii/S2667242123022777 (Full text)