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Restless Legs Syndrome
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Ever wonder why those IV iron infusions didn't do a thing for your RLS? Note last paragraph of abstract..IV infusions BLOCK iron absorption!

Should we reconsider iron administration based on prevailing ferritin and hepcidin concentrations?

Takeshi Nakanishi,corresponding author Takahiro Kuragano, Shoji Kaibe, Yasuyuki Nagasawa, and Yukiko Hasuike

he discovery of hepcidin has profoundly changed our understanding of the place of FID in renal anemia therapy. Hepcidin reduces the abundance of iron transport proteins which facilitate iron absorption from the gut and iron mobilization from macrophages. Serum hepcidin is mainly modulated by iron stores, as is serum ferritin. High hepcidin or ferritin levels block intestinal iron absorption and iron recycling in macrophages and decrease iron availability for erythropoiesis, leading to FID. Iron administration, especially IVFe, increases hepcidin levels and concomitantly inhibits iron supply to erythroid cells. This in turn could lead to a vicious circle, exacerbating FID and increasing iron demand. Therefore, physicians should be cautious with unrestricted IVFe to chronic kidney disease patients with FID.


Recent studies on the mechanisms involved in iron metabolism have revealed that hepcidin is a master regulator of systemic iron availability [6, 7]. To maintain iron homeostasis, hepcidin tightly controls duodenal iron absorption and iron recycling from senescent erythrocytes by tissue macrophages. Hepcidin is the principal hormone responsible for the physiological regulation of iron balance as well as its control in a variety of pathologic conditions, including the anemia of chronic disease (ACD).

In this review, we address the mechanisms whereby pharmacological iron supplementation, especially via the IV route, may reduce the body’s capacity to absorb iron from the gut and to reutilize iron from endogenous sources [8], with particular focus on the importance of hepcidin in this process.

11 Replies

Could you please link to the article?


No, for some reason my puny brain is unable to comprehend how to do that. I can do that with emails but not this website? Google the title of the article and the author's name, I'm sure you will find it. Let me know.


What now Swedish?


I've asked someone who understand medicine english better than me to read and explain. I'll be back as soon as I got answer.


This has to do with patients with chronic kidney disease. Very interesting, and your link worked. ;) SOME people with kidney disease do develop RLS, or with renal (kidney) failure. But, certainly not all. It is a common issue with patients on dialysis, but again not all. :) Thanks, though. We all at least know we are dealing with a huge "mystery" with lots of theories.


I surmise that the people with renal failure who do NOT get RLS do not have the genetic variable that people with RLS have (I'm a guessin here remember). I think that RLSers are ultra sensitive to drops in iron (and hence dopamine) because of this genetic variable. So it seems that everyone's iron "availability" drops at night, and during times of infection, and during times of cancer, and during times of exercise, but WE, the chosen few, are so sensitive to this drop that our bodies go bonkers.


so some people with renal failure will notice the drops in iron and some won't notice

the drops in iron. Your big point is that while we are sleeping, our iron availability drops

for all people but only some will have symptoms of that happening.


Yes and no, now that you put it that way. I believe there is a genetic variable with an environmental trigger. It might not be so much a "sensitivity" as an over-reaction to infections and inflammation in our bodies. We REALLY withhold iron in the face of infection and inflammation. We produce more hepcidin than EVIAN has water. Add to that the drop at night and we get RLS. I bet if we were free of infection and inflammation and disease there would be no symptoms of RLS. There would just be this really defensive gene ready to strike at a moment's notice. If that notice never comes then the gene is silent and so are our legs.


I agree to the inflammation part, if we could stop inflammations in our body (cells?) we would be from WED/RLS. About the iron night drop, what about we who has pain 24/7?


Hi Lost in America, I seem to get delayed messages, some of these messages have been on here for a couple of days before I receive them, I only live in sunny England. Anyways I dont know if this info I am about to give will be of any use to anyone.

I have suffered from restless legs for many years and I have an inability to store iron/ ferritin. My ferritin levels have always been at 4.5, but since being diagnosed with RLS 2 years ago, the docs have had me on 305mg of iron aday, and now my levels are at 19. I recently communicated with someone on here about iron, as I have endometrial hyperplasia, so at 58 still have a menstrual cycle and the RLS is worse week before it is due. After researching from info on this forum, I tried taking Higher Nature true food iron,I tried it for a week and the RLS has been quite unbearable, starting as early as 11am, which on my docs iron it doesnt start until 4pm. On reading the natural iron info, I would have to take 75 capsules aday to get what I get with the docs one. I cannot take ferrous sulphate I take ferrous fumarate and that is what is in both tablets. So I would like to suggest that in my case I need lots of iron supplementation to keep the RLS away. I also take magnesium and calcium, I use the halcyon copper bracelets, and pramipexole. As for surgery, I had the best rest from RLS post surgery, I had a transthoracic T7/T8 discectomy and a ACDF of C4/5, and both times was on oxycodone, oxynorm, and cocodamol, and it was the best break ever from RLS, it didnt return until they weaned me off the pain killers. Hope this contributes in some way, Jimeka


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