TBARS – American ME and CFS Society

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome

Abstract:

BACKGROUND: In myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), altered membrane excitability often occurs in exercising muscles demonstrating muscle dysfunction regardless of any psychiatric disorder. Increased oxidative stress is also present in many ME/CFS patients and could affect the membrane excitability of resting muscles.

METHODS: Seventy-two patients were examined at rest, during an incremental cycling exercise and during a 10-min post-exercise recovery period. All patients had at least four criteria leading to a diagnosis of ME/CFS. To explore muscle membrane excitability, M-waves were recorded during exercise (rectus femoris (RF) muscle) and at rest (flexor digitorum longus (FDL) muscle). Two plasma markers of oxidative stress (thiobarbituric acid reactive substance (TBARS) and oxidation-reduction potential (ORP)) were measured. Plasma potassium (K+) concentration was also measured at rest and at the end of exercise to explore K+ outflow.

RESULTS: Thirty-nine patients had marked M-wave alterations in both the RF and FDL muscles during and after exercise while the resting values of plasma TBARS and ORP were increased and exercise-induced K+ outflow was decreased. In contrast, 33 other patients with a diagnosis of ME/CFS had no M-wave alterations and had lower baseline levels of TBARS and ORP. M-wave changes were inversely proportional to TBARS and ORP levels.

CONCLUSIONS: Resting muscles of ME/CFS patients have altered muscle membrane excitability. However, our data reveal heterogeneity in some major biomarkers in ME/CFS patients. Measurement of ORP may help to improve the diagnosis of ME/CFS.

Trial registration Ethics Committee “Ouest II” of Angers (May 17, 2019) RCB ID: number 2019-A00611-56.

Source: Jammes Y, Adjriou N, Kipson N, Criado C, Charpin C, Rebaudet S, Stavris C, Guieu R, Fenouillet E, Retornaz F. Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome. J Transl Med. 2020 Apr 19;18(1):173. doi: 10.1186/s12967-020-02341-9. https://www.ncbi.nlm.nih.gov/pubmed/32306967

Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study and in Patients and Healthy Subjects

Abstract:

PURPOSE: Oxidative stress has been proposed as a contributor to pain in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). During incremental exercise in patients with ME/CFS, oxidative stress enhances sooner and antioxidant response is delayed. We explored whether oxidative stress is associated with pain symptoms or pain changes following exercise, and the possible relationships between oxidative stress and parasympathetic vagal nerve activity in patients with ME/CFS versus healthy, inactive controls.

METHODS: The present study reports secondary outcomes from a previous work. Data from 36 participants were studied (women with ME/CFS and healthy controls). Subjects performed a submaximal exercise test with continuous cardiorespiratory monitoring. Levels of thiobarbituric acid-reactive substances (TBARSs) were used as a measure of oxidative stress, and heart rate variability was used to assess vagal activity. Before and after the exercise, subjects were asked to rate their pain using a visual analogic scale.

FINDINGS: Significant between-group differences in pain at both baseline and following exercise were found (both, P < 0.007). In healthy controls, pain was significantly improved following exercise (P = 0.002). No change in oxidative stress level after exercise was found. Significant correlation between TBARS levels and pain was found at baseline (r = 0.540; P = 0.021) and after exercise (r = 0.524; P = 0.024) in patients only. No significant correlation between TBARS and heart rate variability at baseline or following exercise was found in either group. However, a significant correlation was found between exercise-induced changes in HRV and TBARS in healthy controls (r = -0.720; P = 0.001).

IMPLICATIONS: Oxidative stress showed an association with pain symptoms in people with ME/CFS, but no exercise-induced changes in oxidative stress were found. In addition, the change in parasympathetic activity following exercise partially accounted for the change in oxidative stress in healthy controls. More research is required to further explore this link.

Source: Polli A, Van Oosterwijck J, Nijs J, Marusic U, De Wandele I5Paul L, Meeus M, Moorkens G, Lambrecht L, Ickmans K. Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study and in Patients and Healthy Subjects. Clin Ther. 2019 Jan 18. pii: S0149-2918(18)30611-8. doi: 10.1016/j.clinthera.2018.12.012. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30665828

Activity in Chronic Fatigue Syndrome: An Observational Study and in Patients and Healthy Subjects

Abstract:

Source: Polli A, Van Oosterwijck J, Nijs J, Marusic U, De Wandele I, Paul L, Meeus M, Moorkens G, Lambrecht L, Ickmans K. Activity in Chronic Fatigue Syndrome: An Observational Study and in Patients and Healthy Subjects. Clin Ther. 2019 Jan 18. pii: S0149-2918(18)30611-8. doi: 10.1016/j.clinthera.2018.12.012. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30665828

Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients

Abstract:

BACKGROUND: Myalgic encephalomyelitis chronic fatigue syndrome (ME/CFS) is a common debilitating disorder associated with an intense fatigue, a reduced physical activity, and an impaired quality of life. There are no established biological markerof the syndrome. The etiology is unknown and its pathogenesis appears to be multifactorial. Various stressors, including intense physical activity, severe infection, and emotional stress are reported in the medical history of ME/CFS patients which raises the question whether any physiological and biological abnormalities usually found in these patients could be indicative of the etiology and/or the quality-of-life impairment.

METHODS: Thirty-six patients and 11 age-matched healthy controls were recruited. The following variables that appear to address common symptoms of ME/CFS were studied here: (1) muscle fatigue during exercise has been investigated by monitoring the compound muscle action potential (M-wave); (2) the excessive oxidative stress response to exercise was measured via two plasma markers (thiobarbituric acid reactive substances: TBARS; reduced ascorbic-acid: RAA); (3) a potential inflammatory component was addressed via expression of CD26 on peripheral blood mononuclear cells; (4) quality-of-life impairment was assessed using the London Handicap Scale (LHS) and the Medical Outcome Study Short Form-36 (SF-36). The medical history of each patient, including the presence of stressors such as intense sports practice, severe acute infection and/or severe emotional stress was documented.

RESULTS: We observed that: (1) there were striking differences between cases and controls with regard to three biological variables: post-exercise M-wave, TBARS variations and CD26-expression at rest; (2) each of these three variables correlated with the other two; (3) abnormalities in the biomarkers associated with health-related quality of life: the LHS score was negatively correlated with the exercise-induced TBARS increase and positively correlated with CD26-expression while the pain component of SF-36 was negatively correlated with CD26-expression; (4) the TBARS increase and the M-wave decrease were the highest, and the CD26-expression level the lowest in patients who had been submitted to infectious stressors.

CONCLUSION: In ME/CFS patients, severe alterations of the muscle excitability, the redox status, as well as the CD26-expression level are correlated with a marked impairment of the quality-of-life. They are particularly significant when infectious stressors are reported in the medical history.

Source: Fenouillet E, Vigouroux A, Steinberg JG, Chagvardieff A, Retornaz F, Guieu R, Jammes Y. Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients. J Transl Med. 2016 Aug 31;14:251. doi: 10.1186/s12967-016-1010-x. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006431/ (Full article)