Exercise modifies glutamate and other metabolic biomarkers in cerebrospinal fluid from Gulf War Illness and Myalgic encephalomyelitis / Chronic Fatigue Syndrome

Abstract

Myalgic encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) share many symptoms of fatigue, pain, and cognitive dysfunction that are not relieved by rest. Patterns of serum metabolites in ME/CFS and GWI are different from control groups and suggest potential dysfunction of energy and lipid metabolism. The metabolomics of cerebrospinal fluid was contrasted between ME/CFS, GWI and sedentary controls in 2 sets of subjects who had lumbar punctures after either (a) rest or (b) submaximal exercise stress tests. Postexercise GWI and control subjects were subdivided according to acquired transient postexertional postural tachycardia. Banked cerebrospinal fluid specimens were assayed using Biocrates AbsoluteIDQ® p180 kits for quantitative targeted metabolomics studies of amino acids, amines, acylcarnitines, sphingolipids, lysophospholipids, alkyl and ether phosphocholines. Glutamate was significantly higher in the subgroup of postexercise GWI subjects who did not develop postural tachycardia after exercise compared to nonexercise and other postexercise groups. The only difference between nonexercise groups was higher lysoPC a C28:0 in GWI than ME/CFS suggesting this biochemical or phospholipase activities may have potential as a biomarker to distinguish between the 2 diseases. Exercise effects were suggested by elevation of short chain acylcarnitine C5-OH (C3-DC-M) in postexercise controls compared to nonexercise ME/CFS. Limitations include small subgroup sample sizes and absence of postexercise ME/CFS specimens. Mechanisms of glutamate neuroexcitotoxicity may contribute to neuropathology and “neuroinflammation” in the GWI subset who did not develop postural tachycardia after exercise. Dysfunctional lipid metabolism may distinguish the predominantly female ME/CFS group from predominantly male GWI subjects.

A case of post‐COVID‐19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post‐exertional malaise and low serum acylcarnitine level

“…A literature search for "('acylcarnitine'[tiab]) AND ('fatigue syndrome, chronic'[MeSH] OR 'chronic fatigue syndrome'[tiab] OR 'myalgic encephalomyelitis'[tiab] OR 'systemic exertion intolerance disease'[tiab])" on PubMed revealed 13 references, of which only four were from the last 20 years. 5,[13][14][15] Despite varied opinion in these references about the precise role of l-carnitine in fatty acid oxidation, there is common agreement that ME/CFS is associated with changes in acylcarnitine and l-carnitine homeostasis. 16 Viral infections are known to disrupt the mitochondrial fatty acid oxidation cascade, 17 thus potentially contributing to a decrease in serum acylcarnitine.…”

“… 4 ME/CFS causes various symptoms, such as morbid fatigue, pain, and mental disorders, that worsen after exertion; however, its pathogenesis and treatment remain unclear. 5 Thus, as many as 80% of patients struggle to receive a diagnosis of ME/CFS, and, in some cases, are forced to consult several specialists and medical facilities for a diagnosis. 6 …”

“…After recovery from COVID‐19, approximately 50% of patients reportedly experience sleep disturbance and chronic fatigue, 3 and approximately, 25% meet the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) 4 . ME/CFS causes various symptoms, such as morbid fatigue, pain, and mental disorders, that worsen after exertion; however, its pathogenesis and treatment remain unclear 5 . Thus, as many as 80% of patients struggle to receive a diagnosis of ME/CFS, and, in some cases, are forced to consult several specialists and medical facilities for a diagnosis 6 …”

A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level

“…The second factor that led to an accurate diagnosis of ME/CFS for our patient is serum acylcarnitine. A literature search for "("acylcarnitine"[tiab]) AND ("fatigue syndrome, chronic"[MeSH] OR "chronic fatigue syndrome"[tiab] OR "myalgic encephalomyelitis"[tiab] OR "systemic exertion intolerance disease"[tiab])" in PubMed revealed 13 references, of which only 4 were from the last 20 years (5,(13)(14)(15). Despite varied opinion in these references about the precise role of l-carnitine in fatty acid oxidation, there is widespread agreement that ME/CFS is associated with changes in acylcarnitine and l-carnitine homeostasis (16).…”

The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review

“…New information from ongoing studies of the consequences of COVID19 may indicate that the definition of ME/CFS will need to be refined to distinguish it from post-acute SARS-CoV-2 syndrome, even though a number of symptoms overlap. Notably, Gulf War Illness victims have symptoms that overlap with ME/CFS, but a number of studies are able to distinguish them from individuals with ME/CFS who did not participate in Gulf War era military activities (155)(156)(157)(158).…”