• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

New study may be relevant to stress intolerance. Osteocalcin blocks parasympathetic responses, a stress response blood factor from our bones.

kurt

Senior Member
Messages
1,186
Location
USA
Interesting new study that may be relevant to ME/CFS stress intolerance. In particular, related to overactive fight-flight response, adrenal insufficiency, or weak parasympathetic resonse. This is about osteocalcin.

Apparently adrenaline is not required for an acute stress response, but osteocalcin is a key factor that shuts down the parasympathetic response, allowing the fight-flight resonse to persist unchecked. Osteocalcin comes from the bones.

Could osteocalcin (or a close analog) be a blood factor in ME/CFS, maybe one of the mystery substances researchers are searching for? Anyone have these levels checked (in a parathyroid panel or in a test for osteoperosis perhaps)? Are they ever high in ME/CFS patients?

Somehow this seems important, I'm trying to work through the article now:

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30441-3

Mediation of the Acute Stress Response by the Skeleton

Abstract Highlights

- The ASR stimulates osteocalcin release from bone within minutes

- Glutamate uptake into osteoblasts is required for osteocalcin release during an ASR

- Osteocalcin inhibits the parasympathetic tone during an ASR

- In adrenal insufficiency, increased osteocalcin levels enablean ASR to occur

Authors
Julian Meyer Berger, Parminder Singh,Lori Khrimian, ..., Kamal Rahmouni, Xiao-Bing Gao, Gerard Karsenty

(Columbia University and others)

Full PDF: https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(19)30441-3
 
Last edited:

kurt

Senior Member
Messages
1,186
Location
USA
From the full abstract:

"We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a bone-derived signal is necessary to develop an acute stress response (ASR). Indeed, exposure to various types of stressors in mice, rats (rodents), and humans leads to a rapid and selective surge of circulating bioactive osteocalcin because stressors favor the uptake by osteoblasts of glutamate, which prevents inactivation of osteocalcin prior to its secretion. Osteocalcin permits manifestations of the ASR to unfold by signaling in post-synaptic parasympathetic neurons to inhibit their activity, thereby leaving the sympathetic tone unopposed. Like wild-type animals, adrenalectomized rodents and adrenal-insufficient patients can develop an ASR, and genetic studies suggest that this is due to their high circulating osteocalcin levels. We propose that osteocalcin defines a bony-vertebrate-specific endocrine mediation of the ASR. "
 

kurt

Senior Member
Messages
1,186
Location
USA
Graphical abstract:
fx1.jpg


Full size image:
https://marlin-prod.literatumonline...52f78-3d21-41cc-b528-2af5bf8dae29/fx1_lrg.jpg
 
Last edited:

ZeroGravitas

Senior Member
Messages
141
Location
UK
I also found this paper interesting, when I saw reports on it last year. Such a big change in understanding of this physiological response. :)

In adrenal insufficiency, increased osteocalcin levels enablean ASR to occur
Interesting, as (independantly) I've been starting to wonder if I should be looking into adrenal insufficiency for myself.

Also, I've been investigating (with NHS doctors) why my bone density appears to have plummeted over the last 6 years (since dietary and other changes). I searched up your post here because I also misspelt "osteoporosis", apparently, heh. Which I have, fairly badly, at the grand old age of 37 (with good serum calcium, magnesium and high vit-D, B-12 and testosterone). o_O

So, here, I'm wondering if osteocalcin release consumes calcium, depleting it from bones? Or if osteoblast activity in signalling detracts from their bone forming activities...?



I also just came across this article/study: https://www.gilmorehealth.com/mitoc...se-osteoporosis-according-to-study/#Reference

They found that (induced) dysfunction of mitochondrial energy production (something found in us pwME/CFS) causes stress signalling leading to osteoporosis. By increasing the conversion of phagocytes into osteoclasts (that naturally break down bone).
 
Last edited: