Tag: 2018

Low omega-3 index and polyunsaturated fatty acid status in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: Several studies have suggested that low levels of omega-3 fatty acids (n-3 PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with cardiovascular risk, major depression, sleep problems, inflammation and other health-related issues. So far, however, erythrocyte PUFA status in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) has not been established. This study aimed to determine whether n-3 PUFA content and omega-3 index are associated with measures in CFS/ME patients.

PATIENTS AND METHODS: PUFA levels and omega-3 index were measured in 31 Spanish CFS/ME patients using the HS-Omega-3 Index method. Demographic and clinical characteristics and self-reported outcome measures were also recorded.

RESULTS: A low mean omega-3 index (5.75%) was observed in 92.6% of the sample. Omega-3 index was inversely correlated with the AA/EPA ratio (p = 0.00002) and the BMI (p = 0.0106). In contrast, the AA/EPA ratio was positively associated with the BMI (p = 0.0038). No association for FIS-40 and PSQI measures was found (p > 0.05).

CONCLUSION: The low omega-3 index found in our CFS/ME patients may indicate increased risks for cardiovascular health, which should be further investigated. A low omega-3 index also suggests a pro-inflammatory state in these patients. Attempts should be made to increase the omega-3 index in CFS/ME patients, based on intervention trials assessing a potential therapeutic value.

Source: Castro-Marrero J, Zaragozá MC, Domingo JC, Martinez-Martinez A, Alegre J, von Schacky C. Low omega-3 index and polyunsaturated fatty acid status in patients with chronic fatigue syndrome/myalgic encephalomyelitis. Prostaglandins Leukot Essent Fatty Acids. 2018 Dec;139:20-24. doi: 10.1016/j.plefa.2018.11.006. Epub 2018 Nov 9. https://www.ncbi.nlm.nih.gov/pubmed/30471769

The role of mitochondria in ME/CFS: a perspective

Abstract:

Chronic fatigue syndrome (CFS) also known as Myalgic encephalomyelitis (ME) is a debilitating disease, characterized by the symptom of severe fatigue. ME/CFS is a heterogeneous condition in both clinical presentation and disease duration. A diagnosis of ME/CFS is based on the exclusion of other diseases due to a current lack of known biomarkers for the disease. Patients may be split into categories based on the severity of their illness – mild, moderate and severe. Here we consider some of the recent advances in the understanding of mitochondrial dysfunction and mitochondrial DNA (mtDNA) variation that may have relevance to ME/CFS.

Thus far, we have shown that ME/CFS patients do not harbor proven mtDNA mutations, another exclusion, albeit an important one. As such this group of patients do not fall within the category of patients with mitochondrial disorder. If ME/CFS patients have some form of mitochondrial dysfunction, the form and cause of this dysfunction is a matter of debate. The current data underlines the need to move from small studies to larger endeavors applying multiple methods to well-defined cohorts with samples taken longitudinally.

Source: Cara Tomas & Joanna L Elson (2019) The role of mitochondria in ME/CFS: a perspective, Fatigue: Biomedicine, Health & Behavior, 7:1, 52-58, DOI: 10.1080/21641846.2019.1580855 https://www.tandfonline.com/doi/abs/10.1080/21641846.2019.1580855  (Full text)

Oxidative Stress is a Convincing Contributor to Idiopathic Chronic Fatigue

Abstract:

The linkage between oxidative stress and idiopathic chronic fatigue (ICF) has not been explored in detail. This study thoroughly compared the serum levels of biomarkers for oxidative stress and antioxidants from 103 subjects with ICF (20 men and 83 women) to those of 82 healthy volunteers (27 men and 55 women).

Oxidative parameters, which included reactive oxygen species (ROS), malondialdehyde (MDA) and F2-isoprotan, and tumor necrosis factor-alpha (TNF-α) were significantly elevated, while antioxidant parameters, which included total antioxidant activity (TAC), catalase, superoxide dismutase, SOD and GSH activity, were decreased compared to those of healthy subjects (by approximately 1.2- to 2.3-fold, p < 0.05 or 0.01).

Our results confirmed that oxidative stress is a key contributor in the pathophysiology of ICF, and firstly explored the features of oxidative stress parameters in ICF subjects compared to a healthy population.

Source: Lee JS, Kim HG, Lee DS, Son CG. Oxidative Stress is a Convincing Contributor to Idiopathic Chronic Fatigue. Sci Rep. 2018;8(1):12890. Published 2018 Aug 27. doi:10.1038/s41598-018-31270-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110864/ (Full article)

Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome

[Editor’s comment: Conspicuously absent from the reference section in this paper is the pioneering work of L. O. Simpson. In 1989 Dr. Leslie O. Simpson, a New Zealand pathologist, discovered that the blood of people with ME/CFS tends to have a higher proportion of cup-shaped red blood cells. (Simpson, L.O. “Nondiscocyte Erythrocytes in Myalgic Encephalomyelitis.” New Zealand Medical Journal 2(864):126-127,1989.) Cup-shaped cells are more difficult to squeeze through small capillaries than disc-shaped cells, making it harder for blood to oxygenate capillary-dependent tissues. In further investigations, Dr. Simpson also observed similar changes in red blood cell morphology in other diseases. He noted that red blood cell shape can change from minute to minute. A summary of Dr. Simpson’s work on red blood cell morphology in ME/CFS can be found HERE.]

Abstract:

BACKGROUND: Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood disease. Amongst others symptoms, the disease is associated with profound fatigue, cognitive dysfunction, sleep abnormalities, and other symptoms that are made worse by physical or mental exertion. While the etiology of the disease is still debated, evidence suggests oxidative damage to immune and hematological systems as one of the pathophysiological mechanisms of the disease. Since red blood cells (RBCs) are well-known scavengers of oxidative stress, and are critical in microvascular perfusion and tissue oxygenation, we hypothesized that RBC deformability is adversely affected in ME/CFS.

METHODS: We used a custom microfluidic platform and high-speed microscopy to assess the difference in deformability of RBCs obtained from ME/CFS patients and age-matched healthy controls.

RESULTS AND CONCLUSION: We observed from various measures of deformability that the RBCs isolated from ME/CFS patients were significantly stiffer than those from healthy controls. Our observations suggest that RBC transport through microcapillaries may explain, at least in part, the ME/CFS phenotype, and promises to be a novel first-pass diagnostic test

Source: Saha KA, Schmidt RB, Wilhelmy J, Nguyen V, Abugherir A, Do KJ, Nemat-Gorgani M, Davis WR, Ramasubramanian KA. Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome.Clin Hemorheol Microcirc. 2018 Dec 28. doi: 10.3233/CH-180469. [Epub ahead of print]  https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch180469 (Full article)

Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results

Abstract:

Introduction: Conflicting data have been published on the reduction of circulating blood volume in adults with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The aim of the present study was to compare blood volumes based on the presence or absence of orthostatic symptoms.

Methods and results: Twenty consecutive adults with ME/CFS participated in the study. All underwent dual isotope blood volume measurement and were evaluated for a clinical suspicion of orthostatic intolerance (OI). The mean age was 34 (10) years, and median duration of disease was 7.5 (6-10) years. The mean (SD) absolute blood volume was 59 (8) ml/kg, a value -11 (7) ml/kg below the reference blood volume. Of the 12 patients, 4 had no OI and 8 had a clinical suspicion of OI. In 8 patients with OI, absolute blood volumes were significantly lower than for the 4 without OI (56 [2] vs. 66 [5]; p < 0.05) as were the differences between the measured and the reference blood volume (-14 [2]; vs. -4 [3]; p < 0.02).

Conclusions: Adults with ME/CFS had a significantly lower blood volume if they had a clinical suspicion of OI compared to those without a clinical suspicion of OI, as well as a significantly lower blood volume compared to the expected value. The data suggest that accounting for symptoms of OI could enhance the detection of the subset with reduced blood volume.

Source: van Campen CLMC1, Rowe PC2, Visser FC1. Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results. Front Pediatr. 2018 Nov 15;6:352. doi: 10.3389/fped.2018.00352. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262290/ (Full article)

Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach

Abstract:

Chronic fatigue syndrome (CFS) is known as a multi-systemic and complex illness, which induces fatigue and long-term disability in educational, occupational, social, or personal activities. The diagnosis of this disease is difficult, due to lacking a proper and suited diagnostic laboratory test, besides to its multifaceted symptoms. Numerous factors, including environmental and immunological issues, and a large spectrum of CFS symptoms, have recently been reported.

In this review, we focus on the nutritional intervention in CFS, discussing the many immunological, environmental, and nutritional aspects currently investigated about this disease. Changes in immunoglobulin levels, cytokine profiles and B- and T- cell phenotype and declined cytotoxicity of natural killer cells, are commonly reported features of immune dysregulation in CFS. Also, some nutrient deficiencies (vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, l-carnitine, l-tryptophan, essential fatty acids, and coenzyme Q10) appear to be important in the severity and exacerbation of CFS symptoms. This review highlights a far-driven analysis of mineral and vitamin deficiencies among CFS patients.

Source: Bjørklund G, Dadar M, Pen JJ, Chirumbolo S, Aaseth J. Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach. Biomed Pharmacother. 2019 Jan;109:1000-1007. doi: 10.1016/j.biopha.2018.10.076. Epub 2018 Nov 5.  https://www.sciencedirect.com/science/article/pii/S0753332218342987?via%3Dihub (Full article)

Severe posterior hypometabolism but normal perfusion in a patient with CFS/ME

Abstract:

Chronic fatigue syndrome/myalgic encephalitis (CFS/ME) is a complex clinical condition defined by prolonged severe fatigue without medical or psychiatric causes, and by a subset of symptoms that mostly includes arthromyalgias, cognitive impairment, sleeping troubles, and unusual headaches [1]. Previous FDG-PET studies showed unspecific patterns of hypometabolism in the frontal and cingulate cortex in half of CFS patients compared to healthy controls [2].

We present 18F-FDG PET/MRI findings in a 21-year-old woman who fulfilled the criteria of CFS with a Fukuda score of 4. PET images (a) show severe and extensive hypometabolism in the posterior cortical regions (precuneus, parietal, temporal, and occipital), amygdalo-hippocampal complexes, and cerebellum. No structural abnormalities were found on T1 MPRAGE (b) or T2 FLAIR (c) MRI sequences. Interestingly, cerebral blood flow evaluated with Gadolinium first-pass method (d) was not decreased in these regions.

This peculiar pattern of hypometabolism was recently described in a large series of patients with aluminium-induced macrophagic myofasciitis (MMF) followed in our reference center [3]. However, the present patient had negative muscular biopsies for MMF. Neuropsychological testing showed severe impairment of short-term memory (immediate and working memory) in visual modality, and weakness of visual selective attention and executive functions, which are concordant with the pattern of hypometabolism. Finally, perfusion-metabolism uncoupling suggests that posterior hypometabolism may not be related to neuronal loss such as in degenerative diseases [4], but rather to an inflammatory or immunological process [5]. Further studies are warranted to investigate metabolism and perfusion using simultaneous PET/MRI in larger groups of patients with CFS/ME.

Source: S. Sahbai & P. Kauv & M. Abrivard & P. Blanc-Durand & M. Aoun-Sebati & B. Emsen & A. Luciani & J. Hodel & F-J. Authier & E. Itti. Severe posterior hypometabolism but normal perfusion in a patient with chronic fatigue syndrome/myalgic encephalomyelitis revealed by PET/MRI. Eur J Nucl Med Mol Imaging. 2018 Dec 14. doi: 10.1007/s00259-018-4229-3. [Epub ahead of print] https://forums.phoenixrising.me/index.php?threads/severe-posterior-hypometabolism-but-normal-perfusion-in-a-patient-with-cfs-me.62543/

Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis

Abstract:

To evaluate the magnitude of the difference in VO2peak between patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) and apparently healthy controls, 7 databases (Cochrane, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus, Medline) were searched for articles published up to March 2018. Search terms included “chronic fatigue syndrom*”AND (“peak” OR “maxim*” OR “max”) AND (“oxygen uptake” OR “oxygen consumption” OR “VO2peak” or “VO2max”.

Eligibility criteria were adults>18 y with clinically diagnosed CFS/ME, with VO2peak measured in a maximal test and compared against an apparently healthy control group. The methodological quality of included studies was assessed using a modified Systematic Appraisal of Quality for Observational Research critical appraisal framework. A random effects meta-analysis was conducted on 32 cross-sectional studies (effects).

Pooled mean VO2peak was 5.2 (95% CI: 3.8-6.6) ml.kg-1min-1 lower in CFS/ME patients vs. healthy controls. Between-study variability (Tau) was 3.4 (1.5-4.5) ml.kg-1min-1 indicating substantial heterogeneity. The 95% prediction interval was -1.9 to 12.2 ml.kg-1min-1. The probability that the effect in a future study would be>the minimum clinically important difference of 1.1 ml.kg-1min-1 (in favour of controls) was 0.88 – likely to be clinically relevant. Synthesis of the available evidence indicates that CFS/ME patients have a substantially reduced VO2peak compared to controls.

Source: Franklin JD, Atkinson 1, Atkinson JM, Batterham AM. Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis. Int J Sports Med. 2018 Dec 17. doi: 10.1055/a-0802-9175. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30557887

A systematic review of enteric dysbiosis in chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is an illness characterised by profound and pervasive fatigue in addition to a heterogeneous constellation of symptoms. The aetiology of this condition remains unknown; however, it has been previously suggested that enteric dysbiosis is implicated in the pathogenesis of CFS/ME. This review examines the evidence currently available for the presence of abnormal microbial ecology in CFS/ME in comparison to healthy controls, with one exception being probiotic-supplemented CFS/ME patients, and whether the composition of the microbiome plays a role in symptom causation.

METHODS: EMBASE, Medline (via EBSCOhost), Pubmed and Scopus were systematically searched from 1994 to March 2018. All studies that investigated the gut microbiome composition of CFS/ME patients were initially included prior to the application of specific exclusion criteria. The association between these findings and patient-centred outcomes (fatigue, quality of life, gastrointestinal symptoms, psychological wellbeing) are also reported.

RESULTS: Seven studies that met the inclusion criteria were included in the review. The microbiome composition of CFS/ME patients was compared with healthy controls, with the exception of one study that compared to probiotic-supplemented CFS/ME patients. Differences were reported in each study; however, only three were considered statistically significant, and the findings across all studies were inconsistent. The quality of the studies included in this review scored between poor (< 54%), fair (54-72%) and good (94-100%) using the Downs and Black checklist.

CONCLUSIONS: There is currently insufficient evidence for enteric dysbiosis playing a significant role in the pathomechanism of CFS/ME. Recommendations for future research in this field include the use of consistent criteria for the diagnosis of CFS/ME, reduction of confounding variables by controlling factors that influence microbiome composition prior to sample collection and including more severe cases of CFS/ME.

Source: Du Preez S, Corbitt M, Cabanas H, Eaton N, Staines D, Marshall-Gradisnik S. A systematic review of enteric dysbiosis in chronic fatigue syndrome/myalgic encephalomyelitis. Syst Rev. 2018 Dec 20;7(1):241. doi: 10.1186/s13643-018-0909-0. https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-018-0909-0 (Full article)

The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology

Abstract:

PURPOSE: Idiopathic intracranial hypertension (IICH) is a condition characterized by raised intracranial pressure (ICP), and its diagnosis is established when the opening pressure measured during a lumbar puncture is elevated >20 cm H2O in nonobese patients or >25 cm H2O in obese patients. Papilledema is caused by forced filling of the optic nerve sheath with cerebrospinal fluid (CSF). Other common but underappreciated symptoms of IICH are neck pain, back pain, and radicular pain in the arms and legs resulting from associated increased spinal pressure and forced filling of the spinal nerves with CSF. Widespread pain and also several other characteristics of IICH share notable similarities with characteristics of fibromyalgia (FM) and chronic fatigue syndrome (CFS), two overlapping chronic pain conditions. The aim of this review was to compare literature data regarding the characteristics of IICH, FM, and CFS and to link the shared data to an apparent underlying physiopathology, that is, increased ICP.

METHODS: Data in the literature regarding these three conditions were compared and linked to the hypothesis of the shared underlying physiopathology of increased cerebrospinal pressure.

RESULTS: The shared characteristics of IICH, FM, and CFS that can be caused by increased ICP include headaches, fatigue, cognitive impairment, loss of gray matter, involvement of cranial nerves, and overload of the lymphatic olfactory pathway. Increased pressure in the spinal canal and in peripheral nerve root sheaths causes widespread pain, weakness in the arms and legs, walking difficulties (ataxia), and bladder, bowel, and sphincter symptoms. Additionally, IICH, FM, and CFS are frequently associated with sympathetic overactivity symptoms and obesity. These conditions share a strong female predominance and are frequently associated with Ehlers-Danlos syndrome.

CONCLUSION: IICH, FM, and CFS share a large variety of symptoms that might all be explained by the same pathophysiology of increased cerebrospinal pressure.

Source: Hulens M, Rasschaert R, Vansant G, Stalmans I, Bruyninckx F, Dankaerts. The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology. J Pain Res. 2018 Dec 10;11:3129-3140. doi: 10.2147/JPR.S186878. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292399/ (Full article)