Cause of RLS - another step

[RLSLearner]

Brain Iron Dysregulation in Iron Deficiency Anemia-Related Restless Leg Syndrome Revealed by Neuron-Derived Extracellular Vesicles: A Case–Control Study

Apostolos Manolopoulos, MD ,1 William York, BS,1 Krishna Ananthu Pucha, BS,1 Christopher J. Earley, MBBCh, PhD,2 and Dimitrios Kapogiannis, MD1

This is a bit complicated so I will cut and paste some excerpts from the paper. It does not give us much to go on as treatment but it is good to see they are looking for why RLS suffers have low brain iron. NDEV = Neuronal Derived Extracellular vesicles. Basically the nerves are spitting out the iron they have!

TfR = transferrin receptor, the primary cellular iron importer. So the nerves are not as good at getting the iron in.

Collectively, our findings suggest a pathogenic mechanism for intracellular iron depletion through secretion of NDEVs laden with H-ferritin.

the finding of lower NDEV TfR levels in RLS could be interpreted as evidence for diminished capacity of neurons to import iron. In the face of increased ferritin loss through EV secretion, decreased TfR on the cell surface would render neurons unable to mount a compensatory response to restore the intracellular iron levels. Taken together, our findings sug- gest that NDEV abnormalities are not incidental but reflect a coordinated perturbation of homeostatic mecha- nisms that regulate neuronal iron influx and efflux.

Our findings inform a more complete understanding of the role of iron homeostasis in RLS pathogen- esis and help dissociate it from peripheral ID. Future mechanistic studies are warranted to investigate how iron regulatory proteins in neuronal cells and secreted NDEVs may relate to each other and respond to iron changes.

So as we know, the brain iron level is dependent of the iron regulation in the rest of the body. I explain the benefit, to many, of oral/IV iron is that having more in you blood gives a better oportunity for it to get into the brain via its weaker than normal absorption ability. Dont make it harder by having low iron.

Good news that there is research getting done on the cause, it is really complicated!

[Joolsg]

This would explain why 30% of MS patients also have RLS. We lose neurons in the brain once the myelin is eaten away and destroyed.It could also explain why iron infusions do not make any improvement for 20% of patients.

[LanaCSR]

Thank you for sharing this information with us! It is very informative. 👍

[Flora-Rose in reply to LanaCSR]

Thanks indeed. I must keep taking the iron!

[DesertOasis]

Hi Learner, I don’t believe our brains have a problem absorbing iron from our body’s serum iron. If that were the case, wouldn’t we have RLS 24/7? I believe our brains have a problem storing iron (aka brain ferritin) for a rainy day, or should I say “night.”

healthunlocked.com/rlsuk/po...

As you can see, we have about 25% higher brain iron than control, but substantially lower brain ferritin than control. So what’s the solution? We take some highly bioavailable iron at night when serum iron plummets. Our brains readily suck it up and we get some relief ✨🌈💥

Edit: And I believe the reason we have higher brain iron than the average bear is for the same reason we have a larger dopamine pool. ..when your television reception is bad you crank up the volume. Then the darkness of night descends and serum iron, as well as that pool of dopamine, dramatically diminishes, in all us humans. The non-RLS world has plenty of brain “ferritin” to fall back on, as well as big, shiny, numerous D2/D3 dopamine receptors, to get them through the night without so much as a twitch. Not us 🫤

[Allyp69]

Wow..very complex. I had iron injections in the 70s for anaemia while pregnant but all the tablets I've tried since then make no difference to my RLS. I use herbal treatments and watch my diet ..but no cure.

[nocturne in reply to Allyp69]

What herbal treatments do you use ?

[Allyp69 in reply to nocturne]

Therapulse is the main treatment when I start to feel RLS ..plus Magnesium butter rubbed on legs and feet, magnesium spray, Passion Flower tablets for stress relief, Kalms, leg stretching, and Sweet Bee Honey last thing ...For a while garlic and root ginger paste helped but the taste is awful....🙄

[nocturne in reply to Allyp69]

Thank you so much!

[DicCarlson]

More puzzle pieces! Thank you!