FINALLY found a scientific study that supports my theory about Brain Iron and Serum Iron. Finally!!!

First, the relevant quote from the article:

“The serum iron concentration was significantly higher in the RLS group than in the control group, but remained within normal ranges in both groups. In this study, there was a significant correlation between serum and CSF iron concentrations, both in the RLS group and in the control group. However, the slope of the regression line was markedly lower for the RLS group than for the control group. This might suggest that deficiencies in CNS iron levels could be at least partly corrected by oral iron supplementation.”

This quote too: “CSF iron concentrations did not differ significantly between the groups.”

So, clearly, the RLS brain has no problem sucking up iron from free circulating serum iron, just like the rest of the world. AND, more importantly, the higher the serum iron (not ferritin) the higher the brain iron (not brain ferritin). Sadly, if I’m reading this right, as serum iron drops, our CNS iron drops faster than controls.

What’s really odd to me is that not only do we have a larger reservoir of unprocessed dopamine than the average bear, but per the above quote, we also have a larger reservoir of serum iron? Any theorys out there? I have one, but I need to do more research. 💁‍♀️

The article further indicates that there’s little to no correlation between ferritin and having RLS. Just as many people with high ferritin, as those with low ferritin, have RLS. And RLSers with higher ferritin values are still very low on brain ferritin.

I thank the heavens just about everyday that our brains have no problem calling up iron from our plasma and that serum iron is relatively abundant in humans for 16 hours of the day. Otherwise we would have RLS 24/7/365.

I never get mad or curse the medical community for failing us. The worst I’ve said is they’re irrelevant and we have to do and discover every thing ourselves. Now I’m mad, because now it’s personal 😶. They make this life altering connection between serum iron and brain iron yet there’s no follow-up, no sirens go off, no shouting from the rooftops, no Nobel Prizes in Medicine are awarded??? You bet I’m mad 😡🤬⚡️☠️🔥

Here’s the one lousy article: onlinelibrary.wiley.com/doi...

EDIT: Wait, it gets crazzee-er still. The article cites Dr. Earley’s work, so I just went to the source. We don’t just have more serum iron than controls, we have A LOT more, nearly double.. On average, we with RLS actually have “higher” serum ferritin than controls. And, we’re not just equal in terms of brain iron to controls, we have significantly more - about 25% more. And yes, we’re silly low on brain ferritin compared to controls - 300% lower. Barely even in the ball park. See for yourselves - slides 8 & 9. Why is Dr. Earley ignoring these profound differences and just focusing on brain ferritin? Clearly, the focus should NOT really be on raising serum ferritin, but on maintaining a high level of serum iron, even at night. Timing of oral supplements is EVERYTHING. We need to maintain a high level of serum iron, even at night. Or, if your RLS is mild and intermittent, just take the oral iron on a bad night.

rls.org/file/member-publica...

[Hidden]

No matter what, that free circulating iron in our blood and in our brain plummets at night and we get RLS.

[Hidden]

Here’s what Dr. Early’s work indicates in terms of our serum iron, ferritin and transferrin as compared to controls.

Look at how much more serum iron we have.

[Hidden in reply to Hidden]

And here’s how our CSF/Brain iron, ferritin and transferrin compare to controls.

More brain iron, but way less brain ferritin

[Hidden in reply to Hidden]

The circles represent where individual participants are on the graph. Notice how many RLS participants are at or near zero CSF/brain ferritin. There appears to be 3 RLS participants that are right up there at normal??? Can we please talk to those three? How bad are their symptoms? Are they eating Captain Crunch for breakfast? What, what are they doing differently 😩

[VladimirF]

The role of the ferritine is quite interesting here. I have read that a high dopamine level can make ferritine lower: dopamin can transform ferritine into the iron. So there is direct connection between dopamine and ferritine and a negative feedback loop - it means that they are quite seriosly connected. My idea is following: at least part of people with RLS have some short but strong releases of dopamine because of some hormonal, genetic and so on issue. The brain is forced to protect itself from such releases because of the neurotoxicity of dopamine. And it restricts the ferritine level to decrease the speed of the dopamine releases.

[Hidden in reply to VladimirF]

Omg, you just pushed my bedtime back by an hour. I have to research this theory. So you’re saying our higher dopamine pool is forcing down our brain ferritin to protect from neurotoxicity. See you in the morning my friend.

[Hidden in reply to VladimirF]

Vlad, are you a doctor or scientist? Hmmm? You have no history here. Yet you’re right on the money???

Schizophrenics, as very recently discovered, also have high brain iron, but low brain ferritin and excess dopamine (like us). The excess dopamine being a sort of hallmark of Schizophrenia. So, in this article, the researchers set out to see what their brain iron, brain ferritin status is like: nature.com/articles/s41380-...

I can accept that our brains are remarkably similar to schizophrenics.😅 And almost opposite of the low dopamine, high brain ferritin of PD patients. Yet we’re different from schizophrenics in that they have robust D2 receptors and robust dopamine release. And PD patients also have increased D2 receptors despite being opposite of schizophrenics (and us) in that they have low dopamine and high ferritin. I feel a sick headache coming on.

Moving on 🙄 ….how do we rectify this situation, my spooky smart friend?

I think there’s only one true solution and it doesn’t involve serum iron or ferritin, but I want to see what you have to say first?

[GaryHB]

Ok - really interesting. I have ordered some iron.

[ProudGreatNana in reply to GaryHB]

What actual iron supplement are you going to take? My RLS has been horrible. Almost 24/7. While walking the past two nights I must be falling asleep. Am walking into things. Have fallen. This is getting me angry but also scared.

[GaryHB in reply to ProudGreatNana]

So sorry to hear that. Why dont you ask for some advice from this forum? There may be better help available to you than iron tablets? There are some very knowledgeable people in this forum who could advise you?

[ProudGreatNana in reply to GaryHB]

Thanks Gary, I just may do that.

[GaryHB in reply to ProudGreatNana]

I really feel for you. You can't carry on like that. Why dont you put a post in this forum and list what medication you are taking and what your history with rls has been and ask for advice. You will get very good advice.

[SueJohnson in reply to ProudGreatNana]

See my reply to Brenda48 in the forum you just asked a question about Vitamins and magnesium making your RLS worse when taken at night. You need to have your ferritin checked first as I described to Brenda48

[Hidden in reply to ProudGreatNana]

Hi Proud, first off, be sure you’re not taking any SSRIs, HRT, melatonin, statins or calcium channel blockers for these will make the symptoms of RLS much worse. I believe that magnesium should not be taken at night and can potentially make symptoms worse after taking. In the long run it should help the symptoms.

I take 50mg of ferrous bisglycinate on an empty stomach about an hour before bed and it completely rids me of RLS for one night. Thus I must repeat every night.

[Hidden in reply to GaryHB]

Oh boy, can’t wait to hear your results - for better or for worse.

[Hidden in reply to GaryHB]

How did it go?

[SueJohnson]

Aren't you equating CSF to the brain? Something in the CSF hasn't crossed the brain barrier.

[Hidden in reply to SueJohnson]

I’m not equating anything. I’m regurgitating. It’s Earley and Allen that believe CSF is a good indicator of brain iron status.

[davchar23]

Dear Desert Oasis,

As you appear to be the main source of knowledge on iron (ferritin or serum) on the forum could I please ask for your advice on my RLS and iron.

As previously posted i am going through augmentation withdrawal from rotigotine and trying to do so with meds as follows:-

20mg/day oxy and 200 mg/day Pregabalin.

Separte from this my blood test reveal a ferritin level of only 42 and my GP has prescribed only ferrous sulphate (200mg tablet once per day). Should i be happy about that or try for more? Ferrous biglycinate has been mentioned by someone else on this forum?

Hope you can comment

Regards

davchar

[SueJohnson in reply to davchar23]

It has only 44 mg of elemental iron. You could take 2 of them. The only advantage to ferrous biglycinate is if you suffer from constipation or stomach problems on the ferrous sulfate.

[davchar23 in reply to SueJohnson]

Sue,

Thanks your comment. How long in your experience, with the average person, does it take to increase ferritin levels from say 40 to 100 using ferrous sulphate (2x 200 mg per day)?

Davchar

[SueJohnson in reply to davchar23]

It varies from individual to individual. Have a new test after 3 months. I may have mentioned this before but in case I didn't - when you have your test stop taking any iron supplements 48 hours before the test, don't eat a heavy meat meal the night before and fast after midnight. Have your test in the morning before 9 am if possible.

[Hidden in reply to davchar23]

The iron should provide that night relief. Because your receptors are somewhat down-regulated fro baseline you may not notice much improvement. Ferrous bisglycinate is far superior to sulfate. More is absorbed quicker because the bisglycinate is very bioavailable. Sulfate is not even in the same ball park. I believe the bisglycinate, even before digestion, is already in a form that can cross the blood brain barrier. That’s what you want. The old guard on here are slow to accept the dawn of a new era.

[Hidden in reply to davchar23]

I don’t like ferrous sulfate. I recommend ferrous bisglycinate. I take around 50mg on an empty stomach about an hour before bed. Should help that very first night. You can try the ferrous sulfate with some ascorbic acid as long as you have it but take it two hours before bed. If you don’t feel a nice improvement come back to me and I’ll hit you with another idea.

[SueJohnson]

Can you show me where in the article you come to the conclusion that " the higher the serum iron (not ferritin) the higher the brain iron (not brain ferritin)" as I can't find it. None of the charts show brain iron.

[WideBody]

You know that video I always post about Iron? You should watch it starting at 8:45

youtube.com/watch?v=VVlQKOO...(Not working as expected?)

You will recognize some charts plus get all the information you were looking for to support your hypothesis.

[WideBody]

I don't think RLS experts are ignoring elevated serum and CSF, I think they are more concerned with how well our bodies are utilizing the iron.

Transferrin saturation provides additional information about the efficiency of iron transport and utilization. While serum iron and ferritin offer insights into iron levels and storage, transferrin saturation helps assess how well transferrin is carrying iron. Low transferrin saturation may indicate inadequate iron supply to tissues, despite normal or high iron stores, while high transferrin saturation could suggest excess iron availability.

[Hidden in reply to WideBody]

I don’t think they connected the dots as Vladimir did. It’s all part of this strange syndrome, seen also in schizophrenics, whereby excess dopamine leads to increased brain iron and decreased brain ferritin. Thus, I think the best solution is short-acting dopamine antagonists like berberine and to a much weaker extent magnesium and possibly B6.

[707twitcher]

I don’t profess to understand this, but wouldn’t an explanation for RLS sufferers having higher serum and CSF iron but low CSF ferritin be that the iron isn’t being converted to ferritin? Maybe that’s caused by high dopamine?

[Hidden in reply to 707twitcher]

Yes, that is the running theory. And, we with RLS, have an abundance of dopamine possibly as a bodily response mechanism to our pathetic dopamine receptors. Then, as you stated, our body tightly regulates brain ferritin as protective measure because of that excess dopamine. I need to research that more. Finally, because of low brain ferritin I feel that an all points bulletin is put out to allow in and scavenge up some of that unbound serum iron. Thank heavens for serum iron. I believe that even though the researchers don’t mention this fact, it’s clear (to me) that our brains have no problem letting in iron, just storing it. I’ve read articles wherein RLS experts float this notion that the RLS blood brain barrier doesn’t allow in much iron. Haven’t they seen this study. Bottom line, we on here have to do our own analysis and come up with solutions ourselves.

[Hidden]

Our brains are literally drowning in in serum iron. Controls on average have 5 to 10mcg while we with RLS have 20 to 20mcg. Back in 2000 when the measured various parameters in the CSF of RLS patients they found elevated transferrin, low ferritin protein (special emphasis on H Ferritin and low transferrin receptor activity. As far as I can tell they didn’t measure serum iron. They were confounded because normally in the face of iron deficiency transferrin receptors are up -regulated. Yet here we were with down-regulated ones. I would like to scream at them it’s because our brains have iron overload but are VERY low on that H ferritin storage protein. The way it works is iron ion will bind to transferrin then get picked up by the transferrin receptor and distributed to cells in the brain. This process more or less works in the RLS brain, especially by day. In a non-RLS brain some of this post receptor bound iron will couple with H ferritin and get stored. Not us - were H ferritin deprived. So once again I don’t understand the mechanism whereby infusions or oral iron taken in the morning helps us or raising bodily ferritin. H -ferritin isn’t produced in the blood - in the body or the brain. Cytoplasm? Anyways, if there was someway of prompting our brains to produce more H ferritin it would probably be a good thing. We would likely still have lousy dopamine receptors but at least we would be able to store some iron for night time and negate the need for the iron at night trick.