Category: Alternative Treatments

Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, and multi-faceted illness. Heterogenous onset and clinical presentation with additional comorbidities make it difficult to diagnose, characterize, and successfully treat. Current treatment guidelines focus on symptom management, but with no clear target or causative mechanism, remission rates are low, and fewer than 5% of patients return to their pre-morbid activity levels. Therefore, there is an urgent need to undertake robust clinical trials to identify effective treatments.
This review synthesizes insights from clinical trials exploring pharmacological interventions and dietary supplements targeting immunological, metabolic, gastrointestinal, neurological, and neuroendocrine dysfunction in ME/CFS patients which require further exploration. Additionally, the trialling of alternative interventions in ME/CFS based on reported efficacy in the treatment of illnesses with overlapping symptomology is also discussed. Finally, we provide important considerations and make recommendations, focusing on outcome measures, to ensure the execution of future high-quality clinical trials to establish clinical efficacy of evidence-based interventions that are needed for adoption in clinical practice.
Source: Seton KA, Espejo-Oltra JA, Giménez-Orenga K, Haagmans R, Ramadan DJ, Mehlsen J on behalf of the European ME Research Group for Early Career Researchers (Young EMERG). Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives. Journal of Clinical Medicine. 2024; 13(2):325. https://doi.org/10.3390/jcm13020325 https://www.mdpi.com/2077-0383/13/2/325 (Full text)

Nutrition and Chronobiology as Key Components of Multidisciplinary Therapeutic Interventions for Fibromyalgia and Associated Chronic Fatigue Syndrome: A Narrative and Critical Review

Abstract:

Fibromyalgia (FM) is often accompanied by chronic fatigue syndrome (CFS). It is a poorly understood disorder that mainly affects women and leads to chronic pain, fatigue, and insomnia, among other symptoms, which decrease quality of life. Due to the inefficiency of current pharmacological treatments, increasing interest is being directed towards non-pharmacological multicomponent therapies. However, nutrition and chronobiology are often overlooked when developing multicomponent therapies.

This narrative and critical review explore the relevance of nutritional and chronobiological strategies in the therapeutic management of FM and the often-associated CFS. Reviewed literature offers scientific evidence for the association of dietary habits, nutrient levels, body composition, gut microbiota imbalance, chronobiological alterations, and their interrelation with the development and severity of symptoms. This review highlights the key role of nutrition and chronobiology as relevant and indispensable components in a multidisciplinary approach to FM and CFS.

Source: Carrasco-Querol N, Cabricano-Canga L, Bueno Hernández N, Gonçalves AQ, Caballol Angelats R, Pozo Ariza M, Martín-Borràs C, Montesó-Curto P, Castro Blanco E, Dalmau Llorca MR, et al. Nutrition and Chronobiology as Key Components of Multidisciplinary Therapeutic Interventions for Fibromyalgia and Associated Chronic Fatigue Syndrome: A Narrative and Critical Review. Nutrients. 2024; 16(2):182. https://doi.org/10.3390/nu16020182 https://www.mdpi.com/2072-6643/16/2/182 (Full text)

Dermatologic Changes in Experimental Model of Long-COVID

Abstract:

The COVID-19 pandemic, declared in early 2020, is an unprecedented global health crisis, causing over 7.0 million deaths and ongoing challenges. While the pharmaceutical industry expedited vaccine development, mutant SARS-CoV-2 strains remain a major fear. Moreover, concerns regarding the long-term health repercussions of COVID-19-affected individuals persist since individuals affected by mild and moderate to severe SARS-CoV-2 infection experience long-term cardiovascular complications, liver dysfunction, pulmonary afflictions, kidney impairments, and most importantly neurocognitive deficits.
In recent studies, we documented pathophysiological changes in various organs following the post-acute infection of mice with murine hepatitis virus-1 (MHV-1), a coronavirus, at both 7 days and 12 months after infection. One part of the body that can be drastically affected by SARS-CoV-2 is the skin. Studies have shown major changes in the skin post-acute SARS CoV-2 infection in humans. However, long-term dermatologic changes post-COVID have never been explored.
For the first time, we show several cutaneous findings both at the acute stages and long-term post-infection of mice with MHV-1 coronavirus (a promising experimental model to study acute and long-COVID). Precisely, we found destruction of the epidermal layer, an increase in the number of hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of the sebaceous glands at the acute stages, along with thinning of the panniculus carnosus, as well as the adventitial layer, which corresponds well with studies in humans.
In contrast, the cutaneous investigation in the long-COVID phase shows the absence of hair follicles from both the epidermal and dermal layers, the destruction of adipose tissues, and the devastation of the epidermal layer. Further, treatment of these mice with a 15 amino acid synthetic peptide, SPIKENET (SPK), which was effective in preventing Spike glycoprotein-1 binding with host receptors, as well as has a potent anti-inflammatory response to severe inflammatory stimulus) restored the loss of hair follicles and re-architected the epidermal and dermal layers.
Additionally, destruction in fatty tissue in the infected mice was successfully restored post-treatment with SPK. These findings suggest that SARS-CoV-2 initiates the changes early post-infection, leading to devastating skin alterations in the long term which can be prevented by our newly identified peptide drug SPK.
Source: Hussain, H.; Paidas, M.J.; Rajalakshmi, R.; Fadel, A.; Ali, M.; Chen, P.; Jayakumar, A.R. Dermatologic Changes in Experimental Model of Long-COVID. Preprints 2023, 2023122339. https://doi.org/10.20944/preprints202312.2339.v1 https://www.preprints.org/manuscript/202312.2339/v1 (Full text available as PDF file)

Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19—A Scoping Review

Abstract:

Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute “long” COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations.
This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection. Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm. Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite. While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.
Source: Scott C, Hall S, Zhou J, Lehmann C. Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19—A Scoping Review. Journal of Clinical Medicine. 2024; 13(1):227. https://doi.org/10.3390/jcm13010227 https://www.mdpi.com/2077-0383/13/1/227 (Full text)

Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach

Abstract:

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin.

This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

Source: Chambers, P.W.; Chambers, S.E. Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach. Preprints 2023, 2023121881. https://doi.org/10.20944/preprints202312.1881.v2 https://www.preprints.org/manuscript/202312.1881/v2 (Full text available as PDF file)

Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review

Abstract:

Post-acute sequelae of COVID-19 can present as multi-organ pathology, with neuropsychiatric symptoms being the most common symptom complex, characterizing long COVID as a syndrome with a significant disease burden for affected individuals. Several typical symptoms of long COVID, such as fatigue, depressive symptoms and cognitive impairment, are also key features of other psychiatric disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and major depressive disorder (MDD). However, clinically successful treatment strategies are still lacking and are often inspired by treatment options for diseases with similar clinical presentations, such as ME/CFS.

Acetylcarnitine, the shortest metabolite of a class of fatty acid metabolites called acylcarnitines and one of the most abundant blood metabolites in humans can be used as a dietary/nutritional supplement with proven clinical efficacy in the treatment of MDD, ME/CFS and other neuropsychiatric disorders. Basic research in recent decades has established acylcarnitines in general, and acetylcarnitine in particular, as important regulators and indicators of mitochondrial function and other physiological processes such as neuroinflammation and energy production pathways.

In this review, we will compare the clinical basis of neuropsychiatric long COVID with other fatigue-associated diseases. We will also review common molecular disease mechanisms associated with altered acetylcarnitine metabolism and the potential of acetylcarnitine to interfere with these as a therapeutic agent. Finally, we will review the current evidence for acetylcarnitine as a supplement in the treatment of fatigue-associated diseases and propose future research strategies to investigate the potential of acetylcarnitine as a treatment option for long COVID.

Source: Helbing DL, Dommaschk EM, Danyeli LV, Liepinsh E, Refisch A, Sen ZD, Zvejniece L, Rocktäschel T, Stabenow LK, Schiöth HB, Walter M, Dambrova M, Besteher B. Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review. Eur Arch Psychiatry Clin Neurosci. 2024 Jan 3. doi: 10.1007/s00406-023-01734-3. Epub ahead of print. PMID: 38172332. https://link.springer.com/article/10.1007/s00406-023-01734-3 (Full text)

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 causes characterised 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. The 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 aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims 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 IP, Domingo JC, Castro-Marrero J. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview. International Journal of Molecular Sciences. 2024; 25(1):574. https://doi.org/10.3390/ijms25010574 https://www.mdpi.com/1422-0067/25/1/574 (Full text)

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial

Abstract:

Background: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms.

Methods: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803.

Findings: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036).

Interpretation: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions.

Source: Lau RI, Su Q, Lau ISF, Ching JYL, Wong MCS, Lau LHS, Tun HM, Mok CKP, Chau SWH, Tse YK, Cheung CP, Li MKT, Yeung GTY, Cheong PK, Chan FKL, Ng SC. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2023 Dec 7:S1473-3099(23)00685-0. doi: 10.1016/S1473-3099(23)00685-0. Epub ahead of print. PMID: 38071990. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00685-0/fulltext (Full text)

An international survey of experiences and attitudes towards transcutaneous auricular vagus nerve stimulation for people with Myalgic Encephalomyelitis/chronic fatigue syndrome

Abstract:

Background and objectives: Myalgic encephalomyelitis (ME) is a complex, multi-system neurological condition. Dysfunction of the autonomic nervous system is a primary feature in diagnostic criteria, and management may include attempts to stimulate the parasympathetic nervous system. Transcutaneous auricular vagus nerve stimulation is an intervention that has been researched in neurological disorders, e.g. epilepsy, depression. While little evidence exists for its use in ME, this survey aims to explore the experiences and attitudes of people with ME to this intervention.

Methods: A 31-question online survey was devised and released on ME websites, Twitter and Facebook pages. People with ME read the information sheet and followed an online link to the survey. The survey was open for four weeks and all answers were anonymous.

Results: 116 responses were received. 56% of respondents reported favourable effects. Benefits of transcutaneous auricular vagus nerve stimulation were identified in relation to post exertional malaise, pain, gut problems, urinary problems, mental health, and the ability to leave the house. 67.2% of respondents would recommend the intervention to other people with ME. However, 4.3% would not recommend it and 6% reported it made them worse. 8.6% received support in setting up the device from healthcare workers.

Conclusion: The survey highlights that many people with ME experience significant benefits from using transcutaneous auricular vagus nerve stimulation; however due to potential negative effects there is the need for formal intervention studies to clearly identify safe parameters.

Source: Karen Leslie, Nicola Clague-Baker, Mohammad Abdelfattah Atallah Madi, Dawn Wiley, Andrea Parker, Michelle Bull & Natalie Hilliard. (2023) An international survey of experiences and attitudes towards transcutaneous auricular vagus nerve stimulation for people with Myalgic Encephalomyelitis/chronic fatigue syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2286029 https://www.tandfonline.com/doi/abs/10.1080/21641846.2023.2286029

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)