Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here, we explore muscle bioenergetic function in response to three bouts of exercise.

METHODS: A total of 18 CFS (CDC 1994) patients and 12 sedentary controls underwent assessment of maximal voluntary contraction (MVC), repeat exercise with magnetic resonance spectroscopy and cardio-respiratory fitness test to determine anaerobic threshold.

RESULT: Chronic fatigue syndrome patients undertaking MVC fell into two distinct groups: 8 (45%) showed normal PCr depletion in response to exercise at 35% of MVC (PCr depletion >33%; lower 95% CI for controls); 10 CFS patients had low PCr depletion (generating abnormally low MVC values). The CFS whole group exhibited significantly reduced anaerobic threshold, heart rate, VO(2) , VO(2) peak and peak work compared to controls. Resting muscle pH was similar in controls and both CFS patient groups. However, the CFS group achieving normal PCr depletion values showed increased intramuscular acidosis compared to controls after similar work after each of the three exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects. This CFS group also exhibited significant prolongation (almost 4-fold) of the time taken for pH to recover to baseline.

CONCLUSION: When exercising to comparable levels to normal controls, CFS patients exhibit profound abnormality in bioenergetic function and response to it. Although exercise intervention is the logical treatment for patients showing acidosis, any trial must exclude subjects who do not initiate exercise as they will not benefit. This potentially explains previous mixed results in CFS exercise trials.

© 2011 The Authors. European Journal of Clinical Investigation

© 2011 Stichting European Society for Clinical Investigation Journal Foundation.

 

Source: Jones DE, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MI, Newton JL. Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study. Eur J Clin Invest. 2012 Feb;42(2):186-94. doi: 10.1111/j.1365-2362.2011.02567.x. Epub 2011 Jul 12. https://www.ncbi.nlm.nih.gov/pubmed/21749371

 

Psycho-physiological impact on women with chronic fatigue syndrome in the context of their couple relationship

Abstract:

The quality of dyadic adjustment is likely to play an important role in patients’ relational problems and may also be associated with the clinical presentation of chronic fatigue syndrome (CFS) symptoms. The objective of this study was (1) to determine whether CFS patients and their partners have similar perceptions of their dyadic adjustment and (2) to evaluate whether the influence of dyadic satisfaction in women with CFS, as well as common psychological parameters such as anxiety, may correlate with physiological responses at rest and/or when performing very low intensity exercise.

Forty females with CFS and their partners completed the Dyadic Adjustment Scale, the State-Trait Anxiety Inventory, and the Hospital Anxiety and Depression scale. The cardiovascular adaptation of patients was evaluated during resting conditions and on a precalibrated cycle ergometer while performing very low intensity exercise. Patients and partners had similar perceptions of their marital relationship.

Both at rest and during very low workload, various physiological parameters in the patient group showed statistical correlations with certain psychological parameters. Several psychological variables, such as anxiety and dyadic adjustment, were associated with the cardioventilatory response monitored at rest and during very low intensity exercise. Further studies are needed to determine the nature of this association.

 

Source: Blazquez A, Guillamó E, Alegre J, Ruiz E, Javierre C. Psycho-physiological impact on women with chronic fatigue syndrome in the context of their couple relationship. Psychol Health Med. 2012;17(2):150-63. doi: 10.1080/13548506.2011.582124. Epub 2011 Jul 11. https://www.ncbi.nlm.nih.gov/pubmed/21745025

 

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome

Abstract:

OBJECTIVES: To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise.

DESIGN: Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate). Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments.

RESULTS: No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor’s transcription was decreased at all time-points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.

CONCLUSIONS: At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A. FM-only patients can be identified by baseline increases in three genes. Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.

© 2011 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome. J Intern Med. 2012 Jan;271(1):64-81. doi: 10.1111/j.1365-2796.2011.02405.x. Epub 2011 Jul 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175315/ (Full article)

 

Graded exercise therapy can have harmful effects

In journal no. 3/2011 claims Larun & Malterud that individualized graded exercise has positive health effects of chronic fatigue syndrome and the research does not provide evidence that such therapy is associated with side effects, for example. in the form of more pain ( 1 ).

The claim that graded exercise therapy is effective treatment for chronic fatigue syndrome is not durable. White and colleagues ( 2 ) found in a recent study that only 28% of those with “chronic fatigue” achieved average (mean ± 1 SD) scores for fatigue and physical function after graded exercise therapy, compared with 15% of those who received standard medical treatment. The placebo effect of behavioral intervention is 14%.

You can read the rest of this comment here: http://tidsskriftet.no/2011/05/brev-til-redaktoren/gradert-treningsterapi-kan-ha-skadelige-effekter

Comment on: Exercise therapy for patients with chronic fatigue syndrome.  Tidsskr Nor Laegeforen. 2011

 

Source: Twisk FN, Maes M, Festvåg L. Graded exercise therapy can have harmful effects. Tidsskr Nor Laegeforen. 2011 May 6;131(8):803. doi: 10.4045/tidsskr.11.0244. [Article in Norwegian] http://tidsskriftet.no/2011/05/brev-til-redaktoren/gradert-treningsterapi-kan-ha-skadelige-effekter (Full article)

 

Diagnostic accuracy of symptoms characterising chronic fatigue syndrome

Abstract:

PURPOSE: To determine the diagnostic accuracy for single symptoms and clusters of symptoms to distinguish between individuals with and without chronic fatigue syndrome (CFS).

METHODS: A cohort study was conducted in an exercise physiology laboratory in an academic setting. Thirty subjects participated in this study (n = 16 individuals with CFS; n = 14 non-disabled sedentary matched control subjects). An open-ended symptom questionnaire was administered 1 week following the second of two maximal cardiopulmonary exercise tests administered 24 h apart.

RESULTS: Receiver operating characteristics (ROC) curve analysis was significant for failure to recover within 1 day (area under the curve  =  0.864, 95% confidence interval [CI]: 0.706-1.00, p = 0.001) but not within 7 days. Clinimetric properties of failure to recover within 1 day to predict membership in the CFS cohort were sensitivity 0.80, specificity 0.93, positive predictive value 0.92, negative predictive value 0.81, positive likelihood ratio 11.4, and negative likelihood ratio 0.22. Fatigue demonstrated high sensitivity and modest specificity to distinguish between cohorts, while neuroendocrine dysfunction, immune dysfunction, pain, and sleep disturbance demonstrated high specificity and modest sensitivity. ROC analysis suggested cut-point of three associated symptoms (0.871, 95% CI: 0.717-1.00, p < 0.001). A significant binary logistic regression model (p < 0.001) revealed immune abnormalities, sleep disturbance and pain accurately classified 92% of individuals with CFS and 88% of control subjects.

CONCLUSIONS: A cluster of associated symptoms distinguishes between individuals with and without CFS. Fewer associated symptoms may be necessary to establish a diagnosis of CFS than currently described.

 

Source: Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011;33(19-20):1768-75. doi: 10.3109/09638288.2010.546936. Epub 2011 Jan 6. https://www.ncbi.nlm.nih.gov/pubmed/21208154

 

Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome

Abstract:

A systematic review was undertaken to examine whether patients with chronic fatigue syndrome (CFS) differ from healthy sedentary controls in physiological exercise capacity, physical activity level and muscle strength. From the available literature, it can be concluded that patients with CFS perform less physical activity during daily life, and have less peak isometric muscle strength compared to healthy sedentary control subjects. Conflicting data in relation to physiological exercise capacity of patients with CFS have been reported, but the weighted available evidence points towards a reduced physiological exercise capacity in CFS. Future studies should use a wash-out period for medication use, blinded assessments, a priori power calculation and a sedentary control group comparable for age, gender, body weight, body length and current physical activity level.

 

Source: Nijs J, Aelbrecht S, Meeus M, Van Oosterwijck J, Zinzen E, Clarys P. Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome. Disabil Rehabil. 2011;33(17-18):1493-500. doi: 10.3109/09638288.2010.541543. Epub 2010 Dec 20. https://www.ncbi.nlm.nih.gov/pubmed/21166613

 

Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity

Abstract:

BACKGROUND: The aim of this study was to investigate the possibility that a decreased mitochondrial ATP synthesis causes muscular and mental fatigue and plays a role in the pathophysiology of the chronic fatigue syndrome (CFS/ME).

METHODS: Female patients (n = 15) and controls (n = 15) performed a cardiopulmonary exercise test (CPET) by cycling at a continuously increased work rate till maximal exertion. The CPET was repeated 24 h later. Before the tests, blood was taken for the isolation of peripheral blood mononuclear cells (PBMC), which were processed in a special way to preserve their oxidative phosphorylation, which was tested later in the presence of ADP and phosphate in permeabilized cells with glutamate, malate and malonate plus or minus the complex I inhibitor rotenone, and succinate with rotenone plus or minus the complex II inhibitor malonate in order to measure the ATP production via Complex I and II, respectively. Plasma CK was determined as a surrogate measure of a decreased oxidative phosphorylation in muscle, since the previous finding that in a group of patients with external ophthalmoplegia the oxygen consumption by isolated muscle mitochondria correlated negatively with plasma creatine kinase, 24 h after exercise.

RESULTS: At both exercise tests the patients reached the anaerobic threshold and the maximal exercise at a much lower oxygen consumption than the controls and this worsened in the second test. This implies an increase of lactate, the product of anaerobic glycolysis, and a decrease of the mitochondrial ATP production in the patients. In the past this was also found in patients with defects in the mitochondrial oxidative phosphorylation. However the oxidative phosphorylation in PBMC was similar in CFS/ME patients and controls. The plasma creatine kinase levels before and 24 h after exercise were low in patients and controls, suggesting normality of the muscular mitochondrial oxidative phosphorylation.

CONCLUSION: The decrease in mitochondrial ATP synthesis in the CFS/ME patients is not caused by a defect in the enzyme complexes catalyzing oxidative phosphorylation, but in another factor.

TRIAL REGISTRATION: CLINICAL TRIALS REGISTRATION NUMBER: NL16031.040.07.

 

Source: Vermeulen RC, Kurk RM, Visser FC, Sluiter W, Scholte HR. Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. J Transl Med. 2010 Oct 11;8:93. doi: 10.1186/1479-5876-8-93. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964609/ (Full article)

 

Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study

Abstract:

OBJECTIVE: The aims of this study were to examine: (i) baseline pressure pain thresholds in patients with chronic fatigue syndrome and those with chronic low back pain compared with healthy subjects; (ii) the change in mean pain threshold in response to exercise; and (iii) associations with exercise-induced increase in nitric oxide.

PARTICIPANTS: Twenty-six patients with chronic fatigue syndrome suffering of chronic pain, 21 patients with chronic low back pain and 31 healthy subjects.

METHODS: Participants underwent a submaximal aerobic exercise protocol on a bicycle ergometer, preceded and followed by venous blood sampling (nitric oxide) and algometry (hand, arm, calf, low back).

RESULTS: Patients with chronic fatigue syndrome presented overall lower pain thresholds compared with healthy subjects and patients with chronic low back pain (p < 0.05). No significant differences were found between healthy subjects and patients with chronic low back pain. After submaximal aerobic exercise, mean pain thresholds decreased in patients with chronic fatigue syndrome, and increased in the others (p < 0.01). At baseline, nitric oxide levels were significantly higher in the chronic low back pain group. After controlling for body mass index, no significant differences were seen between the groups at baseline or in response to exercise. Nitric oxide was not related to pain thresholds in either group.

CONCLUSION: The results suggest hyperalgesia and abnormal central pain processing during submaximal aerobic exercise in chronic fatigue syndrome, but not in chronic low back pain. Nitric oxide appeared to be unrelated to pain processing.

 

Source: Meeus M, Roussel NA, Truijen S, Nijs J. Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study. J Rehabil Med. 2010 Oct;42(9):884-90. Doi: 10.2340/16501977-0595. https://www.medicaljournals.se/jrm/content/html/10.2340/16501977-0595 (Full article)

 

Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To explore contexts of experiences of physical activity perceived as beneficial or harmful for CFS patients.

METHODS: A qualitative study with empirical data from two focus groups with purposive sampling. Mean age was 50, two of ten participants were male, and social demographics varied. Participants were invited to share stories of good as well as bad experiences concerning physical activity. Data were analysed with systematic text condensation.

RESULTS: Participants were not averse to physical activity, but specific preconditions would determine how the activity was perceived. Physical activity was experienced as helpful and enjoyable, especially related to leisure activities where flexible and individual adaptation was feasible. Non-customized activity may precipitate set-backs giving patients the impression of losing control and being betrayed by their bodies. Strategies to review energy usage in daily life could adjust expectations, diminish stress load and assist in approaching a more appropriate priority and balance.

CONCLUSION: Self-management, body awareness and physical activity of choice combined with facilitation and advice from health care professionals is essential to achieve a positive outcome.

PRACTICE IMPLICATIONS: Exercise programmes should be adapted, paced, and self-managed in accordance with personal preferences and activity levels to be beneficial and empowering for CFS patients.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

 

Source: Larun L, Malterud K. Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome. Patient Educ Couns. 2011 May;83(2):222-6. doi: 10.1016/j.pec.2010.05.027. Epub 2010 Jun 26. https://www.ncbi.nlm.nih.gov/pubmed/20580520

 

Nitric oxide metabolite production during exercise in chronic fatigue syndrome: a case-control study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of unknown etiology that is characterized by fatigue associated with a reduced ability to work, lasting for more than 6 months, and accompanied by a specific set of symptoms. The diagnosis remains difficult because of the absence of laboratory tests and is, therefore, made largely on the basis of the symptoms reported by the patient. The aim of this study was to analyze differences in blood nitrate levels in CFS patients and a matched control group after a physical exercise test.

METHODS: Forty-four consecutive female patients with CFS and 25 healthy women performed an exercise test using a cycle ergometer with monitoring of cardiopulmonary response. Blood samples were obtained for biochemical analyses of glucose, lactate, and nitrates at the beginning (under resting conditions) and after the maximal and supramaximal tests.

RESULTS: Plasma nitrates differed between the groups, with higher values in the CFS group (F = 6.93, p = 0.003). Nitrate concentration increased in relation to workload and reached higher values in the CFS group, the maximum difference with respect to the control group being 295% (t = 4.88, p < 0.001).

CONCLUSIONS: The main result of the present study is that nitric oxide (NO) metabolites (nitrates) showed a much higher increase after a maximal physical test in CFS patients than in a group of matched subjects. This combination (exercise plus NO response evaluation) may be useful in the assessment of CFS.

 

Source: Suárez A, Guillamó E, Roig T, Blázquez A, Alegre J, Bermúdez J, Ventura JL, García-Quintana AM, Comella A, Segura R, Javierre C. Nitric oxide metabolite production during exercise in chronic fatigue syndrome: a case-control study. J Womens Health (Larchmt). 2010 Jun;19(6):1073-7. doi: 10.1089/jwh.2008.1255. https://www.ncbi.nlm.nih.gov/pubmed/20469961