Category: Alternative Treatments

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)

Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications

Abstract:

Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions.
In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota’s link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body’s systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.
Source: Alenazy MF, Aljohar HI, Alruwaili AR, Daghestani MH, Alonazi MA, Labban RS, El-Ansary AK, Balto HA. Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications. Metabolites. 2022; 12(10):912. https://doi.org/10.3390/metabo12100912 (Full text)

Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

Objectives: This meta-analysis aimed to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treating chronic fatigue syndrome (CFS).

Methods: Nine electronic databases were searched from inception to May 2022. Two reviewers screened studies, extracted the data, and assessed the risk of bias independently. The meta-analysis was performed using the Stata 12.0 software.

Results: Eighty-four RCTs that explored the efficacy of 69 kinds of Chinese herbal formulas with various dosage forms (decoction, granule, oral liquid, pill, ointment, capsule, and herbal porridge), involving 6,944 participants were identified. This meta-analysis showed that the application of CHM for CFS can decrease Fatigue Scale scores (WMD: –1.77; 95%CI: –1.96 to –1.57; p < 0.001), Fatigue Assessment Instrument scores (WMD: –15.75; 95%CI: –26.89 to –4.61; p < 0.01), Self-Rating Scale of mental state scores (WMD: –9.72; 95%CI:–12.26 to –7.18; p < 0.001), Self-Rating Anxiety Scale scores (WMD: –7.07; 95%CI: –9.96 to –4.19; p < 0.001), Self-Rating Depression Scale scores (WMD: –5.45; 95%CI: –6.82 to –4.08; p < 0.001), and clinical symptom scores (WMD: –5.37; 95%CI: –6.13 to –4.60; p < 0.001) and improve IGA (WMD: 0.30; 95%CI: 0.20–0.41; p < 0.001), IGG (WMD: 1.74; 95%CI: 0.87–2.62; p < 0.001), IGM (WMD: 0.21; 95%CI: 0.14–0.29; p < 0.001), and the effective rate (RR = 1.41; 95%CI: 1.33–1.49; p < 0.001). However, natural killer cell levels did not change significantly. The included studies did not report any serious adverse events. In addition, the methodology quality of the included RCTs was generally not high.

Conclusion: Our study showed that CHM seems to be effective and safe in the treatment of CFS. However, given the poor quality of reports from these studies, the results should be interpreted cautiously. More international multi-centered, double-blinded, well-designed, randomized controlled trials are needed in future research.

Source: Zhang, Jin, Wei, Jin, Xie, Pan and Shen. Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis. Front. Pharmacol., 29 September 2022. Sec. Ethnopharmacology https://doi.org/10.3389/fphar.2022.958005 https://www.frontiersin.org/articles/10.3389/fphar.2022.958005/full (Full text)

Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review

Abstract:

Long COVID is an emergent, heterogeneous, and multisystemic condition with an increasingly important impact also on the pediatric population. Among long COVID symptoms, patients can experience chronic gastrointestinal symptoms such as abdominal pain, constipation, diarrhea, vomiting, nausea, and dysphagia.
Although there is no standard, agreed, and optimal diagnostic approach or treatment of long COVID in children, recently compounds containing multiple micronutrients and lactoferrin have been proposed as a possible treatment strategy, due to the long-standing experience gained from other gastrointestinal conditions. In particular, lactoferrin is a pleiotropic glycoprotein with antioxidant, anti-inflammatory, antithrombotic, and immunomodulatory activities. Moreover, it seems to have several physiological functions to protect the gastrointestinal tract.
In this regard, we described the resolution of symptoms after the start of therapy with high doses of oral lactoferrin in two patients referred to our post-COVID pediatric unit due to chronic gastrointestinal symptoms after SARS-CoV-2 infection.
Source: Morello R, De Rose C, Cardinali S, Valentini P, Buonsenso D. Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review. Children. 2022; 9(10):1446. https://doi.org/10.3390/children9101446 (Full text)

Polyphenols as possible alternative agents in chronic fatigue: a review

Abstract:

Chronic fatigue syndrome (CFS) is a pathological state of extreme tiredness that lasts more than six months and may possess an impact on the social, emotional, or occupational functioning of an individual. CFS is characterized by profound disabling fatigue associated with infectious, rheumatological, and neurological symptoms.

The current pharmacological treatment for CFS does not offer a complete cure for the disease, and none of the available treatments show promising results.

The exact mechanism of the pathogenesis of the disease is still unknown, with current suggestions indicating the overlapping roles of the immune system, central nervous system, and neuroendocrine system.

However, the pathological mechanism revolves around inflammatory and oxidative stress markers.

Polyphenols are the most abundant secondary metabolites of plant origin, with potent antioxidant and anti-inflammatory effects, and can exert protective activity against a whole range of disorders.

The current review is aimed at highlighting the emerging role of polyphenols in CFS from both preclinical and clinical studies. Numerous agents of this class have shown promising results in different in vitro and in vivo models of chronic fatigue/CFS, predominantly by counteracting oxidative stress and the inflammatory cascade.

The clinical data in this regard is still very limited and needs expanding through randomized, placebo-controlled studies to draw final conclusions on whether polyphenols may be a class of clinically effective nutraceuticals in patients with CFS.

Source: Ullah, H., Khan, A., Riccioni, C. et al. Polyphenols as possible alternative agents in chronic fatigue: a review. Phytochem Rev (2022). https://doi.org/10.1007/s11101-022-09838-9 (Full text)

Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis

Abstract:

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID.

Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically.

The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

Source: Nishi K, Yoshimoto S, Nishi S, Nishi T, Nishi R, Tanaka T, Tsunoda T, Imai K, Tanaka H, Hotta O, Tanaka A, Hiromatsu K, Shirasawa S, Nakagawa T, Yamano T. Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis. Int J Mol Sci. 2022 Aug 16;23(16):9205. doi: 10.3390/ijms23169205. PMID: 36012469; PMCID: PMC9409341. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409341/ (Full text)

Long Covid and Apheresis – Where are we Standing?

Abstract:

A continual increase in cases of Long 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 suggests that up to 20% of people with confirmed with SARS-CoV-2 suffer from clinically relevant symptoms of Long 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 Long 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 Long 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, Babir M, Khan TZ, Puhan MA, Straube R, Hohenstein B, Bornstein SR, Rodionov R. Long Covid and Apheresis – Where are we Standing? Horm Metab Res. 2022 Sep 16. doi: 10.1055/a-1945-9694. Epub ahead of print. PMID: 36113501.  https://pubmed.ncbi.nlm.nih.gov/36113501/

Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function

Summary:

Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.

Aim: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vitamins, and plant extracts (Apportal®) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.

Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal® for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one-minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS).

Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low-flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at t1 as compared to t0. A trend, although not significant, in reduction of ferritin levels was found after nutritional supplementation (94.4 vs. 84.3, respectively; p = 0.01). The self-rated health status increased by at least 13 points (t0, mean 57.6 ± 5.86; t1, mean 71.4 ± 6.73; p < 0.05).

Conclusion: After 28 days of nutritional supplementation with Apportal® in COVID-19 survivors affected by fatigue with reduced tolerance to exercise, we found a significant improvement in means of muscle strength and physical performance, associated with enhancement of self-rated health status between t0 and t1.

Source: Vincenzo Galluzzo, Maria Beatrice Zazzara, Francesca Ciciarello, Giulia Savera, Cristina Pais, Riccardo Calvani, Anna Picca, Emanuele Marzetti, Francesco Landi, Matteo Tosato, Steering Committee, Francesco Landi, Elisa Gremese, Coordination, Roberto Bernabei, Massimo Fantoni, Antonio Gasbarrini, Field investigators, Gastroenterology team, Serena Porcari, Carlo Romano Settanni, Geriatric team, Francesca Benvenuto, Giulia Bramato, Vincenzo Brandi, Angelo Carfì, Francesca Ciciarello, Sofia Fabrizi, Vincenzo Galluzzo, Maria Rita Lo Monaco, Anna Maria Martone, Emanuele Marzetti, Carmen Napolitano, Francesco Cosimo Pagano, Cristina Pais, Sara Rocchi, Elisabetta Rota, Andrea Salerno, Matteo Tosato, Marcello Tritto, Maria Beatrice Zazzara, Riccardo Calvani, Lucio Catalano, Anna Picca, Giulia Savera, Francesco Paolo Damiano, Alessandra Rocconi, Alessandro Galliani, Giovanni Spaziani, Salvatore Tupputi, Camilla Cocchi, Flavia Pirone, Federica D’Ignazio, Stefano Cacciatore, Infectious disease team, Roberto Cauda, Enrica Tamburrini, A. Borghetti, Simona Di Gianbenedetto, Rita Murri, Antonella Cingolani, Giulio Ventura, E. Taddei, D. Moschese, A. Ciccullo, A. Dusina, Internal Medicine team, Leonardo Stella, Giovanni Addolorato, Francesco Franceschi, Gertrude Mingrone, M.A. Zocco, Microbiology team, Maurizio Sanguinetti, Paola Cattani, Simona Marchetti, Brunella Posteraro, M. Sali, Neurology team, Alessandra Bizzarro, Alessandra Lauria, Ophthalmology team, Stanislao Rizzo, Maria Cristina Savastano, G. Gambini, G.M. Cozzupoli, C. Culiersi, Otolaryngology team, Giulio Cesare Passali, Gaetano Paludetti, Jacopo Galli, F. Crudo, G. Di Cintio, Y. Longobardi, L. Tricarico, M. Santantonio, Pediatric team, Danilo Buonsenso, P. Valentini, D. Pata, D. Sinatti, C. De Rose, Pneumology team, Luca Richeldi, Francesco Lombardi, A. Calabrese, Paolo Maria Leone, Maria Rosaria Calvello, Enrica Intini, Giuliano Montemurro, Psychiatric team, Gabriele Sani, Delfina Janiri, Alessio Simonetti, G. Giuseppin, M. Molinaro, M. odica, Radiology team, Luigi Natale, Anna Rita Larici, Riccardo Marano, Rheumatology team, Annamaria Paglionico, Luca Petricca, Luca Gigante, G. Natalello, A.L. Fedele, M.M. Lizzio, B. Tolusso, Clara Di Mario, S. Alivernini, Vascular team, Angelo Santoliquido, Luca Santoro, Angela Di Giorgio, Antonio Nesci, V. Popolla, Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function, Clinical Nutrition ESPEN, 2022, ISSN 2405-4577, https://doi.org/10.1016/j.clnesp.2022.08.029. (Full text)