Category: Alternative Treatments

Autonomic Nervous System Regulation Effects of Epipharyngeal Abrasive Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Associated With Chronic Epipharyngitis

Abstract:

Objective: To evaluate the autonomic nerve stimulation effect of epipharyngeal abrasive therapy (EAT) on myalgic encephalomyelitis/chronic fatigue syndrome (CFS) associated with chronic epipharyngitis. Heart rate variability analysis was performed. The study was conducted by analyzing heart rate variability.

Subjects and methods: A total of 29 patients with chronic epipharyngitis who underwent EAT from July 2017 to April 2018 were classified into two groups: 11 patients in the CFS group and 18 patients in the control group without CFS. The patients were classified as phase 1 during bed rest, phase 2 during nasal endoscopy, phase 3 during nasal abrasion, and phase 4 during oral abrasion. Electrocardiographic recordings were made, and autonomic function was compared and evaluated by measuring heart rate, coefficient of variation on R-R interval (CVRR), coefficient of component variance high frequency (ccvHF), and low frequency/ccvHF ratio (L/H) for each of the four phases. The Shapiro-Wilk test was performed to confirm the normality of the two groups, and the parametric test was selected. A repeated measures analysis of variance was performed to assess changes over time between the four events in the two groups. Multiple comparisons were corrected by the Bonferroni method. Comparisons between resting data and three events within each group were performed by paired t-test.

Results: The CFS group had an increased baseline heart rate compared to the control group, and the CFS group had a greater increase in parasympathetic activity and a decrease in heart rate with nasal abrasion. Oral abrasion elicited a pharyngeal reflex and increased heart rate and both sympathetic and parasympathetic activity.

Conclusion: The CFS group was in a state of dysautonomia due to autonomic overstimulation, with an elevated baseline heart rate. The CFS group was considered to be in a state of impaired autonomic homeostasis, with an increased likelihood that overstimulation would induce a pathological vagal reflex and the Reilly phenomenon would develop. The direct effects of EAT on the autonomic nervous system were considered to be vagus nerve stimulation and the regulation of autonomic function by opposing stimulation input to sympathetic and parasympathetic nerves. As an indirect effect, bleeding from the epipharyngeal mucosa due to abrasion was thought to restore the function of the cerebral venous and lymphatic excretory systems and the autonomic nerve center.

Source: Hirobumi I. Autonomic Nervous System Regulation Effects of Epipharyngeal Abrasive Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Associated With Chronic Epipharyngitis. Cureus. 2023 Jan 14;15(1):e33777. doi: 10.7759/cureus.33777. PMID: 36655156; PMCID: PMC9840732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9840732/ (Full text)

The Role of Immunity and Inflammation in ME/ CFS and Post-COVID Syndrome: Implications for Treatment

Abstract:

Probably one in seven patients who have experienced acute COVID-19 continue having long-lasting complaints, called post-COVID syndrome or long-COVID, that are similar to those observed in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

There are good reasons to believe that common immunological, epigenetic and inflammatory mechanisms are involved in the pathogenesis both diseases.

To date, various therapeutic approaches have been recommended, but with moderate success. In the present opinion paper, the author weights his clinical experience against data from the literature, and suggests novel approaches.

In addition to general measures and paramedical approaches, food supplementation with a specific nutraceutical can be completed by oral administration of sodium dichloroacetate and Meldonium to optimize glucose metabolism and mitochondrial energy generation.

Alternatively, intravenous infusions with magnesium salt and multivitamins can be completed with glutathione, m-tranexamic acid, and cultured stem cells.

Preliminary results of an open-label, prospective, two-centre trial suggest more than four in five patients benefit from combined oral and infusion therapy with significantly diminished fatigue and improved well-being.

Monoclonal antibodies in “biologicals”, blocking the effects of cytokines, and “small molecules” with Janus kinase inhibiting activity may offer novel opportunities by focusing on both immunologic and inflammation targets. A pilot trial with, in particular, one of the Janus kinase inhibitors could be considered.

Source: Comhaire F. The Role of Immunity and Inflammation in ME/CFS and Post-COVID Syndrome: Implications for Treatment. MedLife Clinics 2022, Volume 4 (2), Article 1043 http://www.medtextpublications.com/open-access/the-role-of-immunity-and-inflammation-in-me-cfs-and-1254.pdf (Full text)

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline

Abstract:

The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy.

The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.

Source: Melrose J, Smith MM. Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline. Front Biosci (Elite Ed). 2022 Oct 9;14(4):27. doi: 10.31083/j.fbe1404027. PMID: 36575843.  https://www.imrpress.com/journal/FBE/14/4/10.31083/j.fbe1404027/htm (Full text)

Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics

Abstract:

Symptom treatments for Coronavirus disease 2019 (COVID-19) infection and Long COVID are one of the most critical issues of the pandemic era. In light of the lack of standardized medications for treating COVID-19 symptoms, traditional Chinese medicine (TCM) has emerged as a potentially viable strategy based on numerous studies and clinical manifestations. Taiwan Chingguan Yihau (NRICM101), a TCM designed based on a medicinal formula with a long history of almost 500 years, has demonstrated its antiviral properties through clinical studies, yet the pharmacogenomic knowledge for this formula remains unclear. The molecular mechanism of NRICM101 was systematically analyzed by using exploratory bioinformatics and pharmacodynamics (PD) approaches.

Results showed that there were 434 common interactions found between NRICM101 and COVID-19 related genes/proteins. For the network pharmacology of the NRICM101, the 434 common interacting genes/proteins had the highest associations with the interleukin (IL)-17 signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, the tumor necrosis factor (TNF) was found to have the highest association with the 30 most frequently curated NRICM101 chemicals.

Disease analyses also revealed that the most relevant diseases with COVID-19 infections were pathology, followed by cancer, digestive system disease, and cardiovascular disease. The 30 most frequently curated human genes and 2 microRNAs identified in this study could also be used as molecular biomarkers or therapeutic options for COVID-19 treatments.

In addition, dose-response profiles of NRICM101 doses and IL-6 or TNF-α expressions in cell cultures of murine alveolar macrophages were constructed to provide pharmacodynamic (PD) information of NRICM101. The prevalent use of NRICM101 for standardized treatments to attenuate common residual syndromes or chronic sequelae of COVID-19 were also revealed for post-pandemic future.

Source: Singh S, Yang YF. Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics. Int J Mol Sci. 2022 Dec 6;23(23):15385. doi: 10.3390/ijms232315385. PMID: 36499711; PMCID: PMC9740625. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740625/ (Full text)

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial

Abstract:

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis.

A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence.

Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03).

The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

Source: Tosato M, Calvani R, Picca A, Ciciarello F, Galluzzo V, Coelho-Júnior HJ, Di Giorgio A, Di Mario C, Gervasoni J, Gremese E, Leone PM, Nesci A, Paglionico AM, Santoliquido A, Santoro L, Santucci L, Tolusso B, Urbani A, Marini F, Marzetti E, Landi F; Gemelli against COVID-19 Post-Acute Care Team. Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial. Nutrients. 2022 Nov 23;14(23):4984. doi: 10.3390/nu14234984. PMID: 36501014; PMCID: PMC9738241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738241/ (Full text)

Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial

Abstract:

Background: Wasabi (Eutrema japonicum) is a common pungent spice used in Japan. 6-Methylsulfinylhexyl isothiocyanate (6-MSITC) found in the rhizome of wasabi has been shown to have anti-inflammatory and antioxidant effects, as well as improve neuroinflammation and memory. Therefore, we hypothesized that these effects would be beneficial for treating myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The present study was conducted to investigate the effectiveness of wasabi extract containing 6-MSITC on ME/CFS in an open-label trial.

Methods: Fifteen patients (3 males, 12 females, 20-58 years old) were orally administered wasabi extract (9.6 mg of 6-MSITC/day) for 12 weeks. The following parameters and test results were compared pre- and post-treatment: performance status (PS), self-rating questionnaires, pressure pain threshold (PPT) on the occiput, Trail Making test-A (TMT-A), and hemodynamic patterns determined by an active standing test.

Results: After treatment with 6-MSITC, PS improved significantly (p = 0.001). Although the scores on the 11-item Chalder Fatigue scale (CFS-11) and numerical rating scale (NRS) of fatigue did not show significant changes, subjective symptoms improved significantly, including headache frequency (4.1 to 3.0 times/week, p = 0.001) and myalgia (4.1 to 2.4 times/week, p = 0.019), NRS brain fog scores (5.7 to 4.5, p = 0.011), difficulty finding appropriate words (4.8 to 3.7, p = 0.015), photophobia (4.8 to 3.5, p = 0.008), and the Profile of Mood Status vigor score (46.9 to 50.0, p = 0.045). The PPT of the right occiput (17.3 to 21.3 kPa, p = 0.01) and TMT-A scores (53.0 to 38.1 s, p = 0.007) also changed, suggesting reduced pain sensitivity, and improved cognitive function, respectively. Orthostatic patterns determined by a standing test did not show remarkable changes. There were no serious adverse reactions.

Conclusion: This study suggests that 6-MSITC improves PS as well as subjective symptoms such as pain and cognitive dysfunction, and psychological vitality of patients with ME/CFS. It also improved cognitive performance and increased pain thresholds in these patients. 6-MSITC may be a promising therapeutic option especially for improving cognitive dysfunction associated with ME/CFS.

Source: Oka T, Yamada Y, Lkhagvasuren B, Nakao M, Nakajima R, Kanou M, Hiramatsu R, Nabeshima YI. Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial. Biopsychosoc Med. 2022 Dec 12;16(1):26. doi: 10.1186/s13030-022-00255-0. PMID: 36510244. https://bpsmedicine.biomedcentral.com/articles/10.1186/s13030-022-00255-0 (Full text)

Post COVID and Apheresis – Where are we Standing?

Abstract:

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis.

However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

Source: Steenblock C, Walther R, Tselmin S, Jarzebska N, Voit-Bak K, Toepfner N, Siepmann T, Passauer J, Hugo C, Wintermann G, Julius U, Barbir M, Khan TZ, Puhan MA, Straube R, Hohenstein B, Bornstein SR, Rodionov RN. Post COVID and Apheresis – Where are we Standing? Horm Metab Res. 2022 Nov;54(11):715-720. doi: 10.1055/a-1945-9694. Epub 2022 Sep 16. PMID: 36113501. https://www.thieme-connect.de/products/ejournals/html/10.1055/a-1945-9694 (Full text)

Transcutaneous Vagus Nerve Stimulation in the Treatment of Long Covid-Chronic Fatigue Syndrome

Abstract:

Many patients do not recover following Covid infection. The resulting illness is called Long Covid. Because there is no agreed upon treatment for this ailment, we decided to do an open label pilot study using non-invasive, transcutaneous stimulation of the auricular branch of the vagus nerve. Inclusion criteria required the patient to fulfill criteria for having chronic fatigue syndrome. Fourteen patients provided evaluable data. Eight of these fulfilled our requirements for treatment success. Since our criterion for a successful study was that at least a third of patients had to show a positive response to treatment, this was a successful pilot that warrants a follow up study that is appropriately sham controlled.

Source: Benjamin H Natelson, Michelle Blate, Tiffany Soto. Transcutaneous Vagus Nerve Stimulation in the Treatment of Long Covid-Chronic Fatigue Syndrome. medRxiv 2022.11.08.22281807; doi: https://doi.org/10.1101/2022.11.08.22281807 https://www.medrxiv.org/content/10.1101/2022.11.08.22281807v1.full-text (Full text)

Effect of herbal cake-separated moxibustion on behavioral stress reactions and blood lactic acid level and muscular AMPK/PGC-1α signaling in rats with chronic fatigue syndrome

Abstract:

in English, Chinese

Objective: To observe the effect of herbal cake-separated moxibustion (HCSM) on serum lactic acid (BLA) level and AMPK/PGC-1α signaling pathway in the quadriceps femoris in chronic fatigue syndrome (CFS) rats, so as to explore its mechanisms underlying improvement of CFS.

Methods: According to the random number table, 50 SD rats were divided into blank control, model, HCSM, sham HCSM and medication (herbal medicine gavage) groups, with 10 rats in each group. The CFS model was established by using chronic restraint and exhaustive swimming, alternately, once daily for 21 days. The herbal cake was made of Xiaoyao Powder (Mental Ease Powder, composed of [Danggui (Radix Angelicae Sinensis), Baishao (Radix Paeoniae Alba), Chaihu (Radix Bupleuri), Fuling (Poria), Baizhu (Rhizoma Atractylodis, Macrocephalae), etc.]. The HCSM was applied to “Shenque” (CV8), “Guanyuan “(CV4), bilateral “Zusanli” (ST36) and “Qimen” (LR14), 5 moxa-cones for each acupoint, once daily for 10 days. For sham HCSM, the excipient was instead of herbal cake, and the same 5 moxa-cones was given as the HCSM group. Rats of the medication group received gavage of Xiaoyao Powder suspension (60 mg·kg-1), once daily for 10 days. The open field test and tail suspension test were conducted for determining the animals’ locomotor activity. The blood sample was taken from the abdominal aorta under anesthesia for assaying the levels of serum BLA, chemokine ligand CXCL9 and β-endorphin (EP) by ELISA. Bilateral quadriceps femoris were sampled for observing histopathological changes after staining with conventional H.E. technique, and for detecting the expression levels of phosphorylated AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by using immunohistochemistry.

Results: Compared with the blank control group, the number of rearing and horizontal grid-crossing times, struggling times of tail suspension test were significantly decreased (P<0.05), and the immobility time was obviously prolonged (P<0.05) in the model group. Compared with the model group, both HCSM and medication groups had a significant increase of rearing, horizontal grid-crossing times and struggling times (P<0.05), and the immobility time had a significant decrease (P<0.05). But there were no significant differences in the total movement distance among the 5 groups (P>0.05), and in the 5 indexes of behavioral measurements between the HCSM and medication groups (P>0.05). The sham HCSM could also evidently increase the struggling times and reduce the immobility time (P<0.05). The contents of serum BLA, CXCL9 and β-EP were obviously higher in the model group than in the blank control group (P<0.05), as well as remarkably lower in the HCSM and medication groups than in the model group (P<0.05). Whereas the expression levels of muscular p-AMPK and PGC-1α were considerably lower in the model group than in the blank control group (P<0.05), and significantly increased in both HCSM and medication groups relevant to the model group (P<0.05). Compared with the sham HCSM group, the contents of BLA, CXCL9 and β-EP in serum of the HCSM group and contents of CXCL9, β-EP in medication group were significantly decreased (P<0.05), and the protein expressions of p-AMPK and PGC-1α in quadriceps femoris in both HCSM and medication groups were significantly increased (P<0.05). H.E. staining showed smaller intercellular space, uneven cytoplasmic staining in some muscle fibers, nucleus pyknosis and condensation, and inflammatory cell infiltration in the model group, which was milder in both HCSM and medication groups.

Conclusion: HCSM can mitigate the stress behavioral state in CFS rats, which may be related with its functions in lowering the levels of serum BLA, CXCL9 and β-EP, and activating AMPK/PGC-1α signaling pathway (balancing energy metabolism) in the quadriceps femoris.

Source: Xu XS, Ma W, Xiong LJ, Zhai CT, Li W, Tian YF. [Effect of herbal cake-separated moxibustion on behavioral stress reactions and blood lactic acid level and muscular AMPK/PGC-1α signaling in rats with chronic fatigue syndrome]. Zhen Ci Yan Jiu. 2022 Oct 25;47(10):878-84. Chinese. doi: 10.13702/j.1000-0607.20220017. PMID: 36301164. https://pubmed.ncbi.nlm.nih.gov/36301164/

Combination of whole-body cryotherapy with static stretching exercises reduces fatigue and improves functioning of the autonomic nervous system in Chronic Fatigue Syndrome

Abstract:

Background: The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective autonomic nervous system functioning in those with Chronic Fatigue Syndrome (CFS) compared to a control population.

Methods: Thirty-two CFS and eighteen healthy controls (HC) participated in 2 weeks of a SS + WBC programme. This programme was composed of five sessions per week, 10 sessions in total.

Results: A significant decrease in fatigue was noted in the CFS group in response to SS + WBC. Some domains of cognitive functioning (speed of processing visual information and set-shifting) also improved in response to SS + WBC in both CFS and HC groups. Our study has confirmed that WBC is well tolerated by those with CFS and leads to symptomatic improvements associated with changes in cardiovascular and autonomic function.

Conclusions: Given the preliminary data showing the beneficial effect of cryotherapy, its relative ease of application, good tolerability, and proven safety, therapy with cold exposure appears to be an approach worth attention. Further studies of cryotherapy as a potential treatment in CFS is important in the light of the lack of effective therapeutic options for these common and often disabling symptoms.

Source: Kujawski S, Słomko J, Godlewska BR, Cudnoch-Jędrzejewska A, Murovska M, Newton JL, Sokołowski Ł, Zalewski P. Combination of whole body cryotherapy with static stretching exercises reduces fatigue and improves functioning of the autonomic nervous system in Chronic Fatigue Syndrome. J Transl Med. 2022 Jun 17;20(1):273. doi: 10.1186/s12967-022-03460-1. PMID: 35715857; PMCID: PMC9204866.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204866/ (Full text)