Adrenergic dysfunction in patients with [ME/CFS] and fibromyalgia: A systematic review and meta-analysis, 2024, Hendrix, Younger et al

Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis
Jolien Hendrix; Lara Fanning; Arne Wyns; Ishtiaq Ahmed; Madhura Shekhar Patil; Emma Richter; Jente Van Campenhout; Kelly Ickmans; Rembert Mertens; Jo Nijs; Lode Godderis; Andrea Polli

BACKGROUND
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms.

METHODS
A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software.

RESULTS
This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31–.67]; Z = 5.29, p < .01) and β1 adrenergic receptor expression (SMD = .79 [.06–1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18–.97]; Z = 2.85, p < .01), β2 AR (SMD = .41 [.02–.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03–.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [−.47 to −.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = −.79 [−1.27 to −.30]; Z = −3.14; p < .01).

CONCLUSIONS
This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.

Link | PDF (European Journal of Clinical Investigation)

 

Another study that should have used inactive, unhealthy controls. I would expect a difference in adrenaline functions between active an inactive people.

 

https://www.youtube.com/watch?v=mJqKbwE89rc

 

Doesn't high adrenaline slow down the thyroid? I have this issue since menopause started but not M.E.

 

The lead author has just written this:

Wanneer sporten je gezondheid in gevaar brengt
https://www.eoswetenschap.eu/psyche-brein/wanneer-sporten-je-gezondheid-gevaar-brengt

Automated English translation:
When exercise puts your health at risk
https://www-eoswetenschap-eu.transl...uto&_x_tr_tl=en&_x_tr_hl=en-US&_x_tr_pto=wapp

https://www-eoswetenschap-eu.transl...uto&_x_tr_tl=en&_x_tr_hl=en-US&_x_tr_pto=wapp
Jolien Hendrix
Jolien Hendrix is a PhD researcher at the Vrije Universiteit Brussel and KU Leuven. Her research focuses on the role of epigenetics and the autonomic nervous system in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia. She compares patients with healthy individuals to investigate which biological abnormalities could explain their symptoms. The research is supervised by professor Jo Nijs, professor Lode Godderis and dr. Andrea Polli and is funded by FWO.

 

https://www.youtube.com/watch?v=mJqKbwE89rc

Would anybody care to speculate upon why this was found? Also Jarred Younger Says ME & Fibromyalgia are different manifestations of the same illness, do we agree or disagree?

 

Yes.

I think he said they (him and his colleagues I guess) were tending to think of them as different manifestations of the same thing, rather than that they’d made a firm conclusion that this is the case. I think he did a video on this a while back?

I think at the milder end FM and ME present very differently, but people who’re severely affected by both have more overlap.

I’ve always thought of them as two overlapping circles and not two sides of the same coin or whatever.

But I think its complicated by the fact that the very worst people in UK BPSery and as well as all the doctors who call ME “your chronic fatigue” and use this as a reason not to investigate even unrelated symptoms and conditions because everything can be explained away via ‘chronic fatigue’ as if that were an explanation for and in itself. Failing this FM call explain all the troubling straggler symptoms also apparently as an explanation all to itself even though we don’t actually know what it is. So this well trodden path of conflation, as a tool of exclusion from medical treatment, both of these conditions are here considered no medical, does bias me against “Lumping”.

I don’t think we benefit people with either or both diagnosis and symptom patterns by assuming that they are one and the same from a research perspective.

I’m a “Splitter”.

I also think probably it’s too early to say either way.

 

I have been diagnosed with both FM and CFS, 28 years ago.

I find the words used for diagnosis (IOM 2015) are imprecise:

non-refreshing sleep, confusion, what exactly do these mean?

Since the etiology of either diagnosis is unknown, whether they are closely related is speculation.


The symptoms I do NOT have:

no headaches, no lymph node enlargement (during PEM).
No OI.
No extreme sleep disturbances (my sleep meds work for the most part)
no exacerbation of exhaustion to the point of needing days in bed

I DO have:

daily moderate-severe muscle pain in several body regions

delayed onset muscle soreness (DOMS) from innocuous or light, repetitive muscle use,

dizziness with gait problems when I've exceeded my limits (more than an hour at a time in public).

social and sensory intolerance, inability to concentrate, distracted

exhaustion from very light activities (one hour upright, in public; extended phone calls, walking 30 min x 2 days in a row)




.

 

Had a closer look at this review. The meta-analyses are presented in the supplementary material here:
https://onlinelibrary.wiley.com/act...i.14318&file=eci14318-sup-0001-AppendixS1.pdf

Here's an overview of the main results for the ME/CFS meta-analyses. Most of the findings did not show a significant result.

For adrenaline 3 out of 5 studies (78% of the weights) were from the Wyller group. The reviewers included 91 patients from the Kristiansen et al. 2019 study but those 91 were patients with chronic fatigue following EBV. Only a small minority of 19 met the Canadian criteria.
https://pubmed.ncbi.nlm.nih.gov/31039432/

The response to physical stressor studies sound interesting but I've checked and these are mainly the 3 studies by the Lights and the failed replication attempt by Lloyd et al. For those who don't remember Alan and Kathleen Wright were studying fatigue and reported gene expression changes in ME/CFS patients after exercise including in adrenergic receptors. These were popular studies for a while but when the group of Andrew Lloyd tried to replicate it, they failed to find the same results.
https://pubmed.ncbi.nlm.nih.gov/19647494/
https://pubmed.ncbi.nlm.nih.gov/21615807/
https://pubmed.ncbi.nlm.nih.gov/22210239/
https://pubmed.ncbi.nlm.nih.gov/27713703/

There is also one study, Krupp et al. 2003, that reported extreme effect sizes (SMD of -7.66 for example). Perhaps there is an error there than the authors reported an SE while the reviewers thought it was an SD. Anyway, it does not seem reliable and is best excluded I think.

 

I wonder why Lloyd didn't also test a2a.