Post-Exertional Malaise is associated with hypermetabolism, hypoacetylation and purine metabolism deregulation in ME/CFS cases, by Neil R McGregor, Christopher W Armstrong, Donald P Lewis and Paul R Gooley in Diagnostics 2019, 9(3), 70; [Published: 4 July 2019] https://doi.org/10.3390/diagnostics9030070
Research abstract:
Post-exertional malaise (PEM) is a cardinal predictive symptom in the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). If the cases overexert themselves they have what is termed “payback” resulting in a worsening of symptoms or relapse which can last for days, weeks or even months.
The aim was to assess the changes in biochemistry associated with the cases self-reported PEM scores over a 7-day period and the frequency of reporting over a 12-month period.
Forty-seven ME/CFS cases and age/sex-matched controls had a clinical examination, completed questionnaires; were subjected to standard serum biochemistry; had their serum and urine metabolomes analyzed in an observational study.
Thirty-five of the 46 ME/CFS cases reported PEM in the last 7-days and these were allocated to the PEM group. The principal biochemical change related to the 7-day severity of PEM was the fall in the purine metabolite, hypoxanthine. This decrease correlated with alterations in the glucose:lactate ratio highly suggestive of a glycolytic anomaly. Increased excretion of urine metabolites within the 7-day response period indicated a hypermetabolic event was occurring.
Increases in urine excretion of methylhistidine (muscle protein degradation), mannitol (intestinal barrier deregulation) and acetate were noted with the hypermetabolic event. These data indicate hypoacetylation was occurring, which may also be related to deregulation of multiple cytoplasmic enzymes and DNA histone regulation.
These findings suggest the primary events associated with PEM were due to hypoacetylation and metabolite loss during the acute PEM response.
Is this finding proving that GET really is harmful as long claimed being considered in the NICE review????
“The findings that the PEM is associated with a loss of metabolites, reduction in acetylation, deregulation of purine metabolism, increased contractile protein breakdown and bacteremia associated with exercise suggest that treatments such as graded exercise may be more detrimental than beneficial as claimed in some studies [39,40]. Until such time as these biological changes can be further investigated, the use of graded exercise as a therapy for those with severe forms of ME/CFS should be considered potentially harmful. In support of this, the use of graded exercise therapy has caused significant protest by ME/CFS sufferers as they see it as harmful [41,42].”
Yes Kara, one of the many research findings that highlight unhelpful changes in the way the ME body works. The important next step is to find a diagnostic test wo we can tell if this is happening in ‘our’ bodies. Jan