Iron metabolism in RLS : iron transpo... - Restless Legs Syn...

Restless Legs Syndrome

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Iron metabolism in RLS : iron transporter ferroportin & Magnesium Malate

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Editing to preface: The important subject of iron metabolism deserves a much better post than this. I apologize for how confusing, messy, and inconsistent it is. Please disregard it or take it with a grain of salt. I would erase it but out of respect for the comments made, I wont. I cut and pasted it from my post on the PD forum and this made it worse as all paragraphs became one run on mess. I will revisit and revise it when not sleep deprived. Thank you for your patience.

hello, I’m new here. I posted this in the PD forum but am reposting here.

That is exactly why almost any doctor you see prescribes dopamine-stimulating drugs for restless legs.But this logic is flawed, and even they know this. Here’s why.The biggest problem with restless legs is the bulk of your receptors that are SUPPOSED to receive dopamine aren’t receiving it. [2] Restless Legs, Insomnia And Brain Chemistry: A Tangled Mystery Solved? Allen, Ph.D. 2013What these drugs will do is temporarily stimulate the receptors that ARE working, to work even harder. Until they eventually burn out.It’s kind of like replacing sleep with more caffeine. It may work for a while but you’re not fixing the root cause. So the real question becomes, why exactly aren’t dopamine-receptors functioning properly in those with restless legs?And recently, experts have discovered a very important clue – a severe lack of iron in the brains of over 85% of restless legs patients studied. [3] Causes of Restless Legs. Role of Iron in Restless Legs; Earley, Ph.D. 2018And iron is absolutely critical for the proper functioning of dopamine-receptors.”Iron levels are likely fine. Problem is with iron metabolism. I’m no longer a proponent of dopamine agonists. I think they are akin to flogging a tired old horse. I believe that Azilect, an MAOB inhibitor that increases available dopamine might be a cause of my having RLS. brain?“Inflammation – The Connecting Factor in Almost Every Restless Legs Case…”3. How Inflammation is at the very Heart of Restless LegsRestlessAdequate iron in the blood does not mean adequate amounts in the brain. What keeps it from crossing the BBB? Inflammation. (But my inflammation markers came back low-ish. Odd)(I no longer think MAOB inhibitors are Neuroprotective beyond the reduction in oxidative stress they cause. And there are many ways to reduce oxidative stress. And, I now think the dopamine agonists are prodding the tired dopamine receptors until they die instead of nurturing them back to health.) In fact, the most recent studies from 2016 and 2017 have linked low-dopamine activity AND low-iron levels in the brain directly to long term inflammation in restless legs patients(Maybe then the PWP who do not have RLS despite obviously having low levels of dopamine, have a functioning iron metabolism and therefore adequate iron in the brain whereas those with PD and RLS have dysfunctional iron metabolism and too little iron in their brain.)According to this research, inflammation causes a chain of events to happen in the body which first leads to poor iron metabolism and eventually, a malfunction of dopamine receptors in restless leg patients!!! Note: inflammation causes a malfunction of dopamine receptors During inflammation, your body releases immune cells called cytokines, which act like an army of troops for your immune system.And for reasons still unknown to scientists, these cytokine cells shut down something critical for allowing iron into the brain. [11] Restless legs. Theoretical roles of inflammatory and immune mechanisms; L. Weinstock, A. Walters. 2011It’s an iron-transporter called ferroportin.Ferroportin is critical, because it’s only job is to allow iron into your brain.But since most people with restless legs have constant, low-grade inflammation, this precious ferroportin becomes scarce over time.And the iron in your blood becomes stranded, unable to get to your brain(Cytokine storm due to inflammation causes the iron-transporter ferroportin to malfunction. Ferroportin is the iron transporter that enables iron to cross the BBB. ) Because of this constant state of inflammation, other immune cells are being released, which can alter the ability for dopamine-receptors to function.!!! Immune cells alter the ability for dopamine receptors to function. Autoimmunity! In fact, Michael Treadway, professor in Emory’s Department of Psychology, sums up the critical link between inflammation and dopamine by saying if your brain is overrun with inflammation, it simply can’t be calm.The body redirects its energy from producing “feel good” chemicals and instead makes immune and inflammatory chemicals, in order to fight more effectively.When your body is constantly inflamed, all of your extra energy is being used up by your immune system.This is because when your body is stuck in an un-ending loop of inflammation, there aren’t many resources for doing much else.And, as is the case for so many restless legs sufferers, their immune system never shuts off. It’s on “red alert” every second of the day.Note: IF YOUR BRAIN IS OVERRUN WITH INFLAMMATION IT SIMPLY CANT BE CALM!!!strain Lactobacillus plantarum 299 improves iron transport to the brain. helpers. The probiotic strain Lactobacillus plantarum 299, is especially efficient at breaking down iron so that can cross the blood-brain barrier – where it’s really neededMagnesium Malate – “A Spring Cleaning” for Your Dopamine Receptors 😍MAGNESIUM MALATE Once it gets absorbed, it magnetically binds with aluminum and other toxins that clog dopamine receptor sites, safely flushing these toxins from the body. [16] The Role of Magnesium in Neurological Disorders; A. Kirkland, G. Sarlo. 2018AndMagnesium Malate 😍 There is no other compound in the world which provides more inflammation reducing effects per ounce than curcumin.Curcumin is the active and beneficial ingredient found in the ancient herb Turmeric. It is quite literally one of the longest-used and most powerful, natural anti-inflammatory agents in the world.blakeleyfoundation.org/rest

blakeleyfoundation.org/rest...

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ChrisColumbus profile image
ChrisColumbus

I'm interested in the claims you've made for Mg malate.

The Kirkland & Sarlo paper on magnesium that you reference is certainly interesting:

ncbi.nlm.nih.gov/pmc/articl...

but it talks about magnesium in general and I'm not seeing anything in it referencing Mg malate specifically.

When I look up the 'spring cleaning your dopamine receptors' phrase that you used, that led me to a Seratame blog - produced and marketed by Pure Biogenics of California. You seem to have copied a large part of this blog piece (which I link below) word for word without crediting it, reference by reference, although it (currently) promotes Mg glycinate rather than Mg malate.

seratame.com/seratame/

Seratame's product packaging as shown on the Seratame site says that it contains magnesium *glycinate*, Passionflower, Turmeric Extract, Vitamin D3, Vitamin K2, Vitamin B6 and Lactobacillus plantarum: you've also mentioned both turmeric and lactobacillus plantarum.

Your sections about ferroportin also come from the Seratame piece.

On the other hand, if I go to the Pure Biogenics LLC site it says that Seratame contains Mg *malate* and a different probiotic - lactobacillus acidophilus. purebiogenics.com/rls-support/

I'm rather confused by all this: I don't think everything in your post has come from Seratame/Pure Biogenics but it's unclear which is your own research?; I would have been more comfortable if you'd mentioned that the source of much of your info is taken from a commercial supplement maker, and shown this; and why does that source (Seratame) seem to flip flop between malate and the more well known glycinate - when has it been reformulated and why?...

Little_apple profile image
Little_apple in reply to ChrisColumbus

Chris, I am sincerely sorry my post is basically such a mess. I meant to credit any sources sited and I sure don’t mean to flip flop and create general confusion. Everything you said is very valid and I will be much more careful in the future. I will edit my post to preface with an explanation until I have a clear enough mind to revise it as I should. I’m new to learning about RLS beyond the very basic “what is it.” It is so complex and nuanced that that particularly when sleep deprived, it’s an extreme learning curve. Thank you again for your input. I value it very much.

ChrisColumbus profile image
ChrisColumbus in reply to Little_apple

Transparency in detailing sources is important, but I understand the difficulties inherent in dealing with both/either RLS and/or PD.

I have written to Pure Biogenics asking about the ingredients in Seratame.

ChrisColumbus profile image
ChrisColumbus in reply to ChrisColumbus

I've had a reply from Pure Biogenics stating that Seratame contains magnesium glycinate. They didn't answer whether it had previously contained magnesium malate and - if it had - why they'd changed so I'm pressing them for an answer. At this point I'm unsure that they'll answer honestly: I hope to be proved wrong,

Little_apple profile image
Little_apple in reply to ChrisColumbus

Thank you for inquiring! I have a ton of learning to get caught up with what’s commonly known on this forum. The relationship of SIBO and RLS is interesting. Reduced stomach acid , common in SIBO, decreases iron absorption. Plant polyphenols a phytic acid reduce iron absorption.

Many Questions I’m trying to unravel! Example, excess iron in the brain is a proven cause of neurodegeneration but not enough causes RLS. Estrogen is Neuroprotective but excess causes RLS. So steps to protect the brain, cause RLS. This creates quite a challenge.

Hi again. I’m not convinced that inflammation is at the root of RLS. Excess inflammation certainly can’t be good for RLS. If inflammation played a significant role then we would have RLS 24/7/365. I think the main trigger is the fact that serum iron, not ferritin, plummets at night. We with RLS rely very heavily on serum iron since our brains can’t seem to store some for a rainy day. When it plummets (with a nadir of 12am) we get RLS. I take 25mg of ferrous bisglycinate about an hour before bed and it stops the RLS completely, for one night. So must be repeated every night.

If the inflammation is crazy bad and the body senses it’s under attack then a hormone called hepcidin will be released in ever greater amounts and will sequester that precious iron out of our bloodstream. So it can’t hurt to keep inflammation at bay.

A while back I took a hard look at PD because a friend’s mother had it. I swung at every possible cause and treatment and nothing made sense except for mercury (environmental trigger) and of course a genetic predisposition. There was an article and analysis and they found that people with PD who had similar exposure to mercury as controls had an unusual tendency for certain regions of their brains to take up that mercury and deposit it whereas controls had it more localized in the body. I will try to find that article. Also if you look at countries and even States with the highest prevalence they tend to be seaside ones with mercury laden fish and fish consumption. So naturally Qatar and Kuwait, which are practically floating in the Persian Gulf, have VERY high rates. So does Norway and the Northeast States with Vermont having the highest prevalence. Vermont is also the “whitest” state in the Union so there’s that. But then there’s also Indiana and Illinois. Indiana had/has the most coal generated power plants. This is all surmise and conjecture on my part but thought I would share. Oh, and supposedly the Atlantic has more mercury than the Pacific.

EDIT: Here it be: pubmed.ncbi.nlm.nih.gov/350...

BocaMom profile image
BocaMom in reply to

This is completely anecdotal and I’m not even sure there is a connection, but I had all the mercury amalgams removed from my teeth in 2021 (with a dentist who specializes in removal - extremely important or you can do even more damage).

My RLS is not gone, but I’m off all my RLS meds except 200 mgs of Gabapentin at night. Trying to taper off that.

Iron supplementation seems to help my RLS.

That being said, I’m still not sure there’s a connection with amalgams. My mother in law died a horrible death from Parkinson’s and I read some of the same research suggesting a connection to amalgams. She also had bad RLS for years. So for me, I felt it was worth a shot getting my fillings removed.

It’s an expensive and somewhat scary process though I’m not sorry I did it.

in reply to BocaMom

How many amalgam fillings did you have? I read too that they can be problematic but like most things in life it depends on number and even size of fillings. I want to say the crossover threshold is either 3 or 6. The important thing is your RLS is dramatically better. Remember, with iron, timing and type is everything.

BocaMom profile image
BocaMom in reply to

I had 4-5 of them and a couple were fairly big.

Little_apple profile image
Little_apple in reply to

Your explanation about inflammation not being a cause but a contributor is so interesting. That makes so much sense to my (sleepy) mind. Mercury has definitely been said to be a trigger or cause of PD. Fascinating association with PD prevalence and proximity to water sources. Interestingly, ALS has been shown to be caused by an algae bloom. PD and neurodegeneration in general, are definitely caused by and made worse by glyphosate. Dr. Ray Dorsey elaborates upon this in his book Ending Parkinson’s.

DicCarlson profile image
DicCarlson

Whew! That's it in a nutshell!

From Wikipedia: "Ferroportin is the only known iron exporter. After dietary iron is absorbed into the cells of the small intestine, ferroportin allows that iron to be transported out of those cells and into the bloodstream."

en.wikipedia.org/wiki/Ferro...

This could explain my severe RLS - 10 months after a head injury while skiing. My Ferritin was 49. There is also the Small Intestine Bacterial Overgrowth (SIBO) connection with RLS, which I am sure I also had.

Injury induces inflammation. So, connecting the dots - inflammation increases Glutamate over GABA (increasing excitability - awake - over relaxing - sleep). Inflammation decreases iron. And SIBO further decreases absorption of iron from the small intestine. RLS is directly associated with low iron in the brain.

BTW - iron supplements (Ferrous Bisglycinate Chelate) completely eliminated the severe RLS in 3 months. Sleep, not so much - years later still challenged with sleep issues.

Reducing inflammation is a worthy goal to reduce RLS. Diet (reducing simple carbohydrates and sugar), supplements include Curcumin, Fish Oil, Vitamin C and others.

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