Tag: treatment

Microfluidic assessment of PO2-regulated RBC capillary velocity in ME/CFS

Key points:
1. PO2-regulated RBC capillary velocity is impaired in ME/CFS.
2. RBC velocity response to PO2 is a unique characteristic in ME/CFS.

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology that affects multiple organ systems. Although there is no established treatment or diagnostic test for ME/CFS yet, studies have consistently demonstrated impaired cerebral blood flow (CBF) and blood flow regulation in ME/CFS. In this study, we measured red blood cell (RBC) velocity in microfluidic capillaries at varied oxygen tensions (PO2) and showed that, compared to RBCs from heathy controls, RBCs from ME/CFS exhibit compromised capillary velocity in response to reduced PO2.
To examine whether such PO2-regulated RBC capillary velocity could be used to assess or diagnose ME/CFS, we conducted receiver operator characteristic (ROC) analysis and used machine learning (ML) to analyze various features of PO2-regulated RBC capillary velocity. We found that velocity slope-based classifiers were highly accurate, sensitive and specific (i.e., 77.8%, 76% and 90% respectively) in ME/CFS classification.
Furthermore, we demonstrated this RBC-based microfluidic approach can be used to evaluate potential drugs (i.e., salmeterol xinafoate and xanomeline) for improving RBC capillary velocity in ME/CFS. These findings highlight previously unrecognized roles of RBCs in the pathophysiology of ME/CFS and suggest a potential RBC-based test for ME/CFS diagnosis.
Source: Yaojun Guo, Sitong Zhou, Samuel Ren, Xin Liu, Mohsen Nemat-Gorgani, Mike Gresser, Ronald W. Davis, Jiandi Wan. Microfluidic assessment of PO2-regulated RBC capillary velocity in ME/CFS, Blood Red Cells & Iron, 2025, 100019. ISSN 3050-5984. https://doi.org/10.1016/j.brci.2025.100019. https://www.sciencedirect.com/science/article/pii/S3050598425000198 (Full text)

Effects of recumbent isometric yoga on the orthostatic cardiovascular response of patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Our previous studies demonstrated that the regular practice of recumbent isometric yoga reduced the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Some patients with ME/CFS have postural orthostatic tachycardia syndrome (POTS); however, the effects of recumbent isometric yoga on orthostatic cardiovascular responses and whether recumbent isometric yoga improves POTS remain unknown. This pilot study was done to investigate the effect of recumbent isometric yoga on the orthostatic cardiovascular response of patients with ME/CFS.

Main body: Ten adult female patients with ME/CFS performed recumbent isometric yoga for 12 weeks. Changes in their systolic blood pressure (SBP), diastolic blood pressure (DBP), and the pulse rate (PR) during an active standing test were compared before and after the 12-week regimen. Among the 10 patients, 8 manifested a normal orthostatic response and 2 manifested POTS before the yoga intervention. Patients who manifested a normal orthostatic response before yoga also manifested the normal orthostatic pattern after the yoga intervention. In contrast, the two patients who manifested POTS before the regimen showed a normal orthostatic response after completing the yoga intervention.

Conclusions: This study found that the patients who manifested POTS and performed recumbent isometric yoga for 12 weeks had a reduced increase in PR after standing up. This pilot study suggests that recumbent isometric yoga would be useful as an adjunctive nonpharmacological intervention for improving POTS in patients with ME/CFS. This finding should be confirmed in a larger number of cases.

Source: Oka T, Lkhagvasuren B. Effects of recumbent isometric yoga on the orthostatic cardiovascular response of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Biopsychosoc Med. 2025 Sep 1;19(1):16. doi: 10.1186/s13030-025-00336-w. PMID: 40890788. https://bpsmedicine.biomedcentral.com/articles/10.1186/s13030-025-00336-w (Full text)

Nutraceutical Supplementation Effects on Subjective Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition marked by severe, long-lasting fatigue and exhaustion that does not improve with rest. ME/CFS is reported in individuals of all ages and various racial, socioeconomic, and ethnic groups. This condition lacks standard treatment. Nutritional supplements and dietary interventions are often used to manage symptoms, but the efficacy of these interventions remains scarce in the current literature. This systematic review aims to evaluate and summarize recent evidence on nutrient supplementation and diet-based interventions in patients with ME/CFS sourced from clinical trial registries and article databases.

Registries improve the quality, integrity, and transparency of clinical trials by providing a standardized platform for reporting study design and results and, thus, reducing the biases related to selective reporting practices. Systematic reviews using these registries, therefore, are an efficient pathway to acquire current medical evidence for use in clinical decision-making and the development of practice guidance in various fields. ClinicalTrials.gov, Medline, PubMed, Cochrane, and Web of Science were systematically searched for interventional studies in which patients suffering from ME/CFS supplemented or altered their diet.

The results of this review showed several supplements that suggest improvement in patients’ symptomatology, including nicotinamide adenine dinucleotide (NADH), coenzyme Q10 (CoQ10), wasabi, and probiotics. However, many of these registered clinical trials did not employ the U.S. National Institutes of Health (NIH)’s National Institute of Neurological Disorders and Stroke (NINDS) suggested common data elements (CDEs). These standardized outcome-measuring tools allow the generalization and true comparison of the patient-reported outcomes.

Source: Brito EM, Bonifanti L, Patel R, Jimenez J, Junco J, Rozenfeld IR, Renesca V, Cheema AK. Nutraceutical Supplementation Effects on Subjective Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review. Cureus. 2025 Jul 2;17(7):e87178. doi: 10.7759/cureus.87178. PMID: 40755709; PMCID: PMC12315604. https://pmc.ncbi.nlm.nih.gov/articles/PMC12315604/ (Full text)

Pyridostigmine and low-dose naltrexone for ME/CFS: study protocol for the Life Improvement Trial (LIFT), a randomized, double-blind, placebo-controlled clinical trial

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic disease with no FDA-approved treatments. This report describes a protocol for the Life Improvement Trial (LIFT), a randomized, double-blind, placebo-controlled clinical trial investigating the impact of low-dose naltrexone (LDN) and pyridostigmine (Mestinon) on physiological response, symptoms, and functionality of ME/CFS patients.

Methods: Participants (target n = 160) are recruited through clinics at Massachusetts General Hospital and Brigham and Women’s Hospital, and through Open Medicine Foundation’s StudyME registry. They are then randomized into one of four arms: LDN/pyridostigmine, LDN/placebo, placebo/pyridostigmine, placebo/placebo. Treatment is administered for 13 weeks after an initial screening period of up to 4 weeks. Primary outcomes are FUNCAP-55 score, peak oxygen utilization, heart rate recovery, and oxygen uptake efficiency slope. Secondary outcomes are scores from DSQ-PEM and PROMIS-29 surveys, DANA Brain Vital score, step count, heart rate, and heart rate variability.

Discussion: The results of this trial will provide novel insights into the efficacy of and predictors of response to LDN and pyridostigmine in ME/CFS. This may inform future treatment strategies for ME/CFS. The trial will also validate what primary and secondary outcomes to use in similar clinical trials.

Source: Danielle Meadows, Johanna Squires, Joshua Dibble et al. Pyridostigmine and low-dose naltrexone for ME/CFS: study protocol for the Life Improvement Trial (LIFT), a randomized, double-blind, placebo-controlled clinical trial, 04 March 2025, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-5626167/v1]

Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries

Abstract:

Purpose. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition with no single, uniformly effective pharmacologic therapy. Dysautonomic features like orthostatic intolerance and postural tachycardia syndrome are common features in ME/CFS, severely affecting the patient´s quality-of-life. Intermittent saline infusion may reduce symptoms associated with dysautonomia, but this has not been tested scientifically in patients with ME/CFS.

In this case-series, 22 patients with ME/CFS and signs of dysautonomia and/or hypovolemia were treated every third week over 9 weeks with intravenous saline (9 mg/mL NaCl), using standard aseptic technique. Symptoms were monitored throughout the treatment regime, and a follow-up evaluation was conducted.

Results. At treatment start, patients were predominantly female (95%), at mean age 46 ± 10 years, and with a mean body hydration percentage of 48 ± 6. Self-reported health status revealed an overall symptom score of 47 ± 13 on a 0-96 scale, a median POTS score of 64 (IQR 16) on a 0-120 scale, and poor measures of quality-of-life (median 25 IQR 25, on a 0-100 scale) and abilityto-work (median 0, IQR 26, on a 0-100 scale). Following 9 weeks of intermittent saline infusion (mean volume 1600 ± 360 mL), self-reported composite symptom score, quality-of-life and POTS-related symptoms improved significantly (all p<0.001), as did ability-to-work (p<0.05).

Our data derived from a non-controlled case-series indicate health benefits from volume loading with intermittent infusion of saline among patients with ME/CFS, which may stimulate further studies on various forms of intravenous volume loading to patients with ME/CFS and dysautonomia.

Source: Per Sjogren, Helena Huhmar, Bo Christer Bertilson, Björn A Bragée, Olli Polo. Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries. Front. Neurol., Sec. Autonomic Disorders, Volume 16 – 2025 | doi: 10.3389/fneur.2025.1601599 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1601599/abstract

Medication use and symptomology in North American women with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: There are no known curative treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and current therapeutic regimens often yield inconsistent results. Despite the profound physical and mental burden experienced by those living with ME/CFS, patients often face a trial-and-error process in finding medications that offer some relief.

Method: The current study surveyed 135 North American women diagnosed with ME/CFS to characterize medication use in relation to disease features, symptomology, and function. Medications were classified into 9 categories according to their primary mechanism of action and therapeutic use.

Results: Participants were primarily middle-aged (47.1 ± 15.3 years) and were diagnosed for a mean duration of 8.4 ± 9.5 years (mean ± SD). Responses showed 68.6% of participants reported taking medications specifically for ME/CFS. Of those taking ME/CFS-related symptom medications, the average use was 3.0 medications per patient, with higher use in US compared to Canadian participants. Analgesic medications (31.7%) were the most frequently used, followed by psychotropic (26.4%), and immune-related medications (10.6%). These trends persisted across different symptom profiles, apart from gastrointestinal associated medication use replacing immune-related medications in those with gastrointestinal, neurological, and psychiatric symptoms. There was no significant correlation found between the number of medications used with disease duration, age, or age at diagnosis. However, a U-shaped relationship between ME/CFS-related symptom medication use and functional capacity as assessed by self-reported physical movement (hours/week) was evident.

Conclusion: Our study highlights the diverse and complex patterns in pharmacological treatment regimens for ME/CFS in women, while also underscoring the need for more tailored and evidence-based therapeutic strategies to address the varied symptom profiles.

Source: Pochakom A, MacNevin G, Madden RF, Moss AC, Martin JM, Lalonde-Bester S, Parnell JA, Stein E, Shearer J. Medication use and symptomology in North American women with myalgic encephalomyelitis/chronic fatigue syndrome. Front Med (Lausanne). 2025 Jun 6;12:1543158. doi: 10.3389/fmed.2025.1543158. PMID: 40547918; PMCID: PMC12179203. https://pmc.ncbi.nlm.nih.gov/articles/PMC12179203/ (Full text)

Low Dose Rapamycin Alleviates Clinical Symptoms of Fatigue and PEM in ME/CFS Patients via Improvement of Autophagy

Abstract:

Background: mTOR activation is associated with chronic inflammation in ME/CFS. Previous studies have shown that sustained mTOR activation can cause chronic muscle fatigue by inhibiting ATG13-mediated autophagy. This highlights the pivotal role of mTOR in the pathogenesis of ME/CFS.

Methods: We conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy. Low-dose rapamycin (6 mg/week) was administered, and core ME/CFS symptoms were assessed on days 30 (T1), 60 (T2), and 90 (T3). Plasma levels of autophagy metabolites, such as pSer258-ATG13 and BECLIN-1, were measured and correlated with clinical outcomes, specifically MFI.

Results: Rapamycin (6 mg/week) was tolerated without any SAEs. Of the 40 patients, 29 (72.5%) showed strong recovery in PEM, fatigue, and OI, along with improvements in MFI fatigue domains and SF-36 aspects. High levels of BECLIN-1 were detected in T3. Plasma pSer258-ATG13 levels were strongly downregulated at T1. Spearman’s correlation analysis indicated an association between autophagy impairment and reduced activity.

Conclusions: Low-dose rapamycin effectively reduced PEM and other key symptoms in patients with ME/CFS, as measured by BAS, SSS, MFI, and SF-36.  Future studies should encompass dose optimization and develop a diagnostic tool to identify responders with mTOR-mediated autophagy disruption.

Source: Brian T. Ruan, Sarojini Bulbule, Amy Reyes et al. Low Dose Rapamycin Alleviates Clinical Symptoms of Fatigue and PEM in ME/CFS Patients via Improvement of Autophagy, 03 June 2025, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-6596158/v1] https://www.researchsquare.com/article/rs-6596158/v1 (Full text)

The Effect on Quality of Life of Therapeutic Plasmapheresis and Intravenous Immunoglobulins on a Population of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies—A Pilot Study

Abstract:

Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with not fully understood causes, though evidence points to immune system involvement and possible autoimmunity. ME/CFS could be triggered by various infectious pathogens, like SARS-CoV-2; furthermore, a subset of the post-COVID-19 condition (PCC) patients fulfill the diagnostic criteria of ME/CFS. According to the Canadian Consensus Criteria (CCC), the presence of specific symptoms such as fatigue, post-exertional malaise, sleep dysfunction, pain, neurological/cognitive manifestations, and symptoms from at least two of the following categories lead to the diagnosis of ME/CFS: autonomic, neuroendocrine, and immune manifestation. In this study, the patient selection was based on the identification of ME/CFS patients with elevated autoantibodies, regardless of the triggering factor of their condition.
Methods: The aim of this study was to identify ME/CFS patients among long COVID patients with elevated autoantibodies. In seven cases, plasmapheresis (PE) and intravenous immunoglobulins (IVIGs) with repetitive autoantibody measurements were applied: four PE sessions on days 1, 5, 30, and 60, and a low-dose IVIG therapy after each treatment. Antibodies were measured before the first PE and two weeks after the last PE session. To monitor clinical outcomes, the following somatic and psychometric follow-up assessments were conducted before the first PE, 2 weeks after the second, and 2 weeks after the last PE: the Schellong test, ISI (insomnia), FSS (fatigue), HADS (depression and anxiety), and EQ-5D-5L (quality of life) questionnaires.
Results: There was a negative association between both the β2-adrenergic and M3-muscarinic receptor autoantibody concentration and the quality of life measurements assessed with the EQ-5D-5L questionnaire. Per 1 U/mL increase in the concentration levels of β2-adrenergic receptor antibodies or M3-muscarinic acetylcholine receptor antibodies, the EQ-5D-5L index score [−0.59 to 1] decreased by 0.01 (0.63%) or 0.02 (1.26%), respectively. There were no significant associations between the ISI, HADS, and FSS questionnaires and the β1-adrenergic and M4-muscarinic receptor antibodies titers.
Conclusions: After a thorough selection of patients with present autoantibodies, this pilot study found negative associations concerning autoantibody concentration and somatic, as well as psychological wellbeing. To validate these promising feasibility study results—indicating the potential therapeutic potential of antibody-lowering methods—further investigation with larger sample sizes is needed.
Source: Oesch-Régeni B, Germann N, Hafer G, Schmid D, Arn N. The Effect on Quality of Life of Therapeutic Plasmapheresis and Intravenous Immunoglobulins on a Population of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies—A Pilot Study. Journal of Clinical Medicine. 2025; 14(11):3802. https://doi.org/10.3390/jcm14113802 https://www.mdpi.com/2077-0383/14/11/3802 (Full text)

HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab

Abstract:

This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments.

Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient’s blood supportive of an altered immune system.

Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered.

Source: Martín-Martínez E, Gil-Perotin S, Giménez-Orenga K, Barea-Moya L, Oltra E. HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab. Int J Mol Sci. 2025 May 20;26(10):4885. doi: 10.3390/ijms26104885. PMID: 40430026; PMCID: PMC12111851. https://pmc.ncbi.nlm.nih.gov/articles/PMC12111851/ (Full text)

The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS.

Methods: The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including “ME/CFS,” “Gut-Brain Axis,” “Gut Health,” “Intestinal Dysbiosis,” “Microbiome Dysbiosis,” “Pathophysiology,” and “Therapeutic Approaches.” Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings.

Results: The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration.

Conclusions: Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.

Source: Hsu CY, Ahmad I, Maya RW, Abass MA, Gupta J, Singh A, Joshi KK, Premkumar J, Sahoo S, Khosravi M. The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review. J Transl Med. 2025 May 11;23(1):530. doi: 10.1186/s12967-025-06527-x. PMID: 40350437. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06527-x (Full text)