The latest thinking from RLS research is that when we talk about iron ,we should be looking at Haemoglobin (hgb) rather than ferritin. This is from the latest magazine of the Restless legs Foundation ( Nightwalkers summer 2020). James R Connor PhD.
The thinking is that hgb levels are a better indication of iron transport to the brain than serum ferritin levels.
I'm sure @nightdancer will have more information on this.
The original research was published in Fluids Barriers CNS.
I don't know if it can be accessed by mere mortals.🤢
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I'll have a look soon. To the Nightwalkers report and shall try to access the original paper through my uni account. And give a readable summary. Remind me if I forget.
Hmm would like to know too more details on that. Wonder what Dr Early knows or doesnt know about it, or any of the other RLS experts that we know of . Do we have to change on what we always tell people, to get their ferritin level check. ? That has brought up alot of questions if they are correct in the findings, or is still just in the thinking stage.
Yes-- it will be interesting to see how this plays out among the experts.
They are all connected, between the organisation, and universities. Buchfuhrer, Early and Winkleman!!🤔
Raising hgb would be a lot easier than raising ferritin. But actual experience has shown definite responses to iron infusions. But, then, they may have raised hgb levels as collateral effect.
I'll get in a supply of vitB12 cobalthmin (???) Just in case! 👻👽💥
Interesting!
Some definitive answer to this would be good so we won't be mis-advising anybody.
I do admit to some scepticism about it based on the idea that's probably a limit to how high Hb levels can be due to various homeostatic mechanisms.
Hb is also an iron- globulin molecule only found in red blood cells (RBCs) , so the amount of Hb isn't just a matter of how much iron you have, it's also a matter of how many RBCs there are.
If that's the case then if, as is usually the case for me, my Hb is high normal then my brain iron levels must be normal?
Also bearing in mind the IRLSSG/EARLS RLS foundation guidelines evidence that somebody with RLS needs a ferritin level of 200 to have the same brain iron level as somebody who doesn't have RLS.
I suspect that it's some "form" of Hb that's involved here. For example the form of Hb known as "HbA1c" is now a standard blood test for diabetes. NOT blood glucose level. This is a better test for diabetes, since a blood glucose test only tells you what the level is at the time the blood is taken, which can fluctuate a lot. HbA1c however gives the average blood sugar level over the last 120 days, (the life span of a RBC).
The conclusion seems to be that iron transport - from blood to brain - correlates with plasma haemoglobin (Hb) NOT ferritin.
Having scanned this -
It's also a laboratory study, involved no humans (or anything alive) and hence nobody with RLS.
I will read on, but it's possible that this means that if you have LOW Hb, then you may have LOW brain iron. Conversely, NORMAL Hb may mean NORMAL brain iron levels - - - that is for normal people.
However it's known that with RLS you have lower brain iron than "normals" despite the absence of anaemia (low Hb) so it's still not clear how serum Hb relates to iron therapy for RLS.
How could Hb be raised ABOVE normal?
• in reply to
I think I know a wee bit about this and so the Haemoglobin story doesn't make sense. I'm a retired GP and my husband was a Haematologist. I have a naturally high Hb given the right conditions and so did my Mum but we both have/had severe RLS.
I think it used to be thought that there was a normal range for Hb and everyone had the same normal range but it doesn't seem to be that at all, but more that assuming there is plenty of Iron and other appropriate nutrients available, each individual has his/her own optimum Hb. Mine can easily be 15 ( or 150 ) - I am female so this is high.
But Iron is used needed for all sorts of other systems in the body apart from blood eg brain structures, muscles etc. I had decided that if your body preferentially used as much Iron as possible ( and Ferritin is just stored Iron ) for Hb then there is less available for the other systems which also need it, and you need a high Ferritin to force it into the right area of the brain.
No, you can't raise your Hb as far as I'm aware, higher than one's own natural maximum. I can have a Hb of 15 or 150 but a low/normal Ferritin.
So I don't see how Hb can be the answer.
I'll be interested to find out what the experts say, but the Ferritin story makes much more sense than the Hb idea
• in reply to
I agree
Some excerpts
absence of a relationship between serum ferritin and brain iron uptake in this model suggests that ferritin may not be the preferred biomarker for selecting patients for iron supplementation. ( for RLS).
Because -
end organs, including the brain, forgo their iron needs to maintain erythropoiesis and the blood’s oxygen carrying capacity (i.e. Hb)
Our data are also consistent with the report that RLS symptoms fail to respond to intravenous iron treatment in individuals with low hemoglobin levels
iron is redirected away from the brain when hemoglobin is low, and its uptake into the
brain is promoted as hemoglobin increases
Although the clinical implications of this cell culture study should be viewed with caution they are consistent with the lack of serum ferritin status to improve outcome in RLS and the absence of response to RLS symptoms in subjects with lower hemoglobin .
My comment : this makes sense, if Hb is low then it will be more difficult to get iron across the blood brain barrier.
efforts to provide iron to the brain could be impacted by hemoglobin levels, even if these are in normal range,
My comment : I don't see how the study results support this last statement.
Also, perhaps I'm missing something
Scenario - person with RLS (PIR) goes to see neurologist (NRT)
PIR : I have horrible sensations and feel I need to move.
NRT : You have RLS.
PIR : Oh no, what's causing it?
NRT : It's brain iron deficiency
PIR : Can you treat it?
NRT : Yes I think so.
PIR :What's the treatment
NRT : Let me test your Hb first.
PIR : OK - Ouch! (NRT is not very good with needles).
NRT : Oh dear!
PIR : What's the matter?
NRT : I was going to prescribe iron therapy for your RLS but it won't work.
Vit B12 will raise hgb. I ran into terrible problems with anemia when they were taking blood to get my ferritin down from 1400 after blood transfusions in spinal operation with complications.
Hgb would go down to 10 ( has to be at least 12.5 to allow phlebotomy) and I used to dose myself with vit B 12 oral spray to try and get the hgb up.
Anemia really makes a mess of the teeth and gums. I can't remember any effects on rls at the time-- but I was on opiates anyway, and probably wouldn't have had a difference.
I had daily B12 injections for ME/CFS and my RLS didn't improve that I recall (memory isn't great!) but I am now using B12 patches to see if that helps either illness.
It's 1.34am and it's one of those nights. I've given up on sleep. Two weeks until I see the marijuana doctor. Pick me, pick me!
First and foremost to remember, 1) you cannot raise hgb without first raising iron (doesn’t work the other way around). 2) You want to find out what is causing the low hgb. If it’s iron deficiency anemia you need to increase the iron but sometimes there’s a reason it’s iron deficiency anemia such as low vitamin B12 (that’s where my anemia comes from), not enough folic acid (also a B vitamin). You can keep replacing them but the ultimate answer is why what is helping you make iron (and subsequently your hgb) is continuously low? [As a registered nurse who worked in oncology, of course a persons hgb was of extreme importance but I’m not thinking in an iron or ferritin way but rather in that it transmits oxygen through your blood stream to all your organs, etc. If I had a patient with a low hgb it was reported to the doctor and often the only way when quite low of increasing your hemoglobin is through a blood transfusion, however, keep in mind and this was an oncology clinic and we were talking about dangerously low levels of hgb and the only rapid way is then a transfusion.]
But if it’s more like what you’re discussing and it is not critical here are 7 Natural ways to raise:
7 Natural Ways to Increase Hemoglobin
Eat Iron-Rich Foods. ...
Increase Vitamin C Intake. ...
Increase Folic Acid Intake. ...
An Apple (or Pomegranate) a Day Keeps The Doctor Away. ...
Drink Nettle Tea. ...
Avoid Iron Blockers. ...
Exercise.
This link gives you a better look at the anemia (keep in mind this is more from a cancer standpoint, but not worthless as it doesn’t just refer to blood transfusions, by any means: cancer.org/treatment/treatm...
This is from the Cleveland Clinic: my.clevelandclinic.org/heal... (This one gives you an awesome list of iron rich foods).
My big takeaway, I see iron/ferritin as important in relation to us with RLS much more than hemoglobin because iron is what affects the levels of you hemoglobin unless I suppose you had a massive blood loss but then you’re back to needing a transfusion.
Hopefully that makes some sense unfortunately I’m having insomnia and restless legs tonight 🙃
You are quite correct in that only iron will correct iron deficiency anaemia, (hypochromic anaemia). Also as you say it's important to ascertain WHY it's occurring, e.g. this could be indicative of a cancer. There are of course other reasons for low Hb.
Iron deficiency anaemia is a cause of secondary RLS. Primary RLS exists even in the absence of iron deficiency anaemia.
Low vitamin B12 as I previously wrote does NOT cause iron deficiency anaemia, it causes B12 deficiency anaemia (macrocytic anaemia). This is a differrent matter altogether. and there are different underlying causes.
It is quite commonly believed that the word "anaemia" equates with iron deficiency anaemia, but this is a misconception. Anaemia refers to a problem with red blood cells (RBCs) leading to a lack of oxygen carrying capacity for whatever reason. This includes
- Iron deficiency anaemia : lack of iron = lack of haemiglobin = pale cells (hypochromic)
- Vitamin Deficiency anaemia ; lack of B12 folate = immature/badly formed RBCs = macrocytic.
- Anaemia of inflammation.
- Aplastic anaemia.
- Anaemias associated with bone marrow disease. .
- Haemolytic anaemias.
- Sickle cell anaemia.
ONLY iron deficiency aneamia is due to a lack of iron and in the other cases iron is not necessarily an appropriate treatment.
E.g iron will not treat B12 anaemia and B12 will not treat iron anaemia.
What this post is about and what the article I gave a link to is about, is the suggestion that the current method for estimating brain iron levels in people with RLS i.e. serum ferritin is not a good indicator.
You can read many references to ferritin in relation to RLS e.g.
- Raising ferritin to 100ug/L will benefit 50% of people with RLS
- For somebody with RLS to have the same brain iron levels as somebody who doesn't have RLS their ferritin must be at least 200ug/L
- Experts saying that people with RLS should have a ferritin level of at least 300ug/L
and so on.
The linked article would appear to imply is that none of these statements may be accurate and haemoglobin level is a better indicator of brain iron levels.
My own view on this, which perhaps wasn't made that clearly is that while a low Hb level might indicate low brain iron level, a "high" Hb level doesn't necessarily mean a high brain iron level as Hb levels are limited. This the conclusion of the article appears illogical.
I hope that clarifies it.
Sorry to say, vit B12 won't raise Hb.
Low Hb is a cause of "iron deficiency anaemia" also known as "hypochromic" meaning not enough colour. - the treatment for this is iron.
Low B12 is a cause of "B12 deficency anaemia" also known as "macrocytic anaemia" meaning BIG cells. - the treatment for this is B12.
There are many forms of anaemia which generally means "lack of oxygen carrying capacity"
You can of course have both hypochromic AND macrocytic anaemia at the same time, but only iron will raise the Hb level and only B12 will ensure that red blood cells mature properly (they're small!)
I not only have RLS but myleoproliferative neoplasms - a blood cancer where I over produce red cells, white cells and plasma - thus my hb levels had been extremely high (although now under control with a daily chemotherapy drug). I have not had any change in my rls symptoms throughout which makes me question the results of this study from the perspective of my own experiences.
That makes sense Hb is the form of iron found in red blood cells i.e. in the circulatory system. The other form of iron found in the circulatory system (and some organs e.g. the liver), is ferritin.
The issue with RLS is the level of iron in the BRAIN. This is a separate "compartment" because there is a barrier between the circulatory system and the brain, (the BBB). If sufficient iron is to get to the brain it has to get through the BBB.
What studies like the one I gave a link to show is that the bodys' systems "favour" the blood in terms of iron levels. Therefore when there is a greater demand for iron in the blood, then the transfer of iron across the BBB is limited i.e. the brain is starved of iron.
In your case, because of the excessive amount of blood cells formed (known as polycythaemia) there will be a greater demand for iron in the blood hence the transfer across the BBB may be limited. In that case your Hb level may not be a good indicator of your brain iron level and despite a high Hb you still have RLS.
However, this would be neither practical nor economic.
As far as I'm aware the main ways of determining brain iron levels directy are
- Specialised scans e.g. specific MRI scans (not the "normal" ones)
- Extracting CSF (cerebro spinal fluid) e.g. lumbar puncture and its inherent risks.
- Post-mortem brain dissection, not for the living!
Hence there is a need for a means of assessing brain iron levels indirectly, easily and economically and the current accepted way of doing this is serum ferritin.
There is evidence that there is a "positive correlation" between serum ferritin and brain iron levels i.e. if one goes up then the other goes up.
The study under discussion here seems to contradict that.
Yes that’s helpful to know. I have had my ferritin monitored but the GP seems happy with levels of 74 (I was at 43) and the discussion seems to suggest much higher is beneficial. I’ll have a further discussion with them.
If your ferritin is 74, then despite the study being discussed here and according to the current accepted guidelines then it's not really necessary to discuss this with your doctor.
Firstly, if you can persuade your doctor that 74 is too low then I imagine they will prescribe a strong oral iron supplement with the instruction to take it every day.
The chances are that in this case the main effects will be constipation, stomach upset and black poo! Possibly very little effect on your ferritin.
As your ferritin is below 75 then you may benefit from taking an oral iron supplement which might be successful in raising it to 100. There is evidence that a ferritin level of 100 will benefit 50% of people with RLS. There is further evidence that 200 or more would be better, but this is hard to achieve by taking an oral iron supplement. 100 is the best you can expect really.
It may take up to 3 months to raise ferritin this way.
Here's a link to some guidelines on iron therapy for RLS.
Over the counter (no doctor needed) "Gentle" iron (ferrous bisglycinate) is quite a popular supplement for RLS as it has less dire consequences for the digestive system than "prescription" supplements. My GP actually advised me of this.
There is more recent evidence about the factors that prevent or promote oral iron absorption (not identified in the above guidelines). It can be that less than 2% of any oral iron swallowed is absorbed. The following can increase that amount and hence be more effective
1) take the iron in the evening 30 mins before or 2 hours after eating.
2) drink a glass of orange or take a vitamin C tablet at the same time.
3) take it every OTHER day NOT every day as instructions may state. Taking it every day prevents it being absorbed.
I did just check my old blood tests - Raging RLS with Ferritin at 49, % Saturation at 23% and Hgb - right in the middle of normal range. Iron supplements ELIMINATED the severe RLS almost immediately. As Manerva suggests this is a cell culture study. Here is another interesting article on iron, inflammation, and anemia... blog.insidetracker.com/how-...
Like Manerva,I had/am having a look at the original paper.The study used a cell culture trying to mimic iron transport by transferrin across the blood-brain barrier (BBB). In the cells representing the brain they used cerebrospinal fluid (CSF, fluid from the spinal chord) to study the influence of CSF on iron transport across the BBB. Although they obtainedCSF and blood smaples (for hemoglobin and ferritin values) from 350 people with excessive daytime sleepiness or central disorder of hypersomnolence and 4 people with RLS, they show results from 9-10 people with RLS and 11-12 people without RLS. Not very large sample sizes. The authors'main finding is "[a] positive correlation between iron transport and hemoglobin concentrations". However, the range of iron uptake values (roughly 8-13) with low-avergae hemoglobin was hardly different from the iron uptake range (roughly 9-14) with average to high hemoglobin. There was no relation with ferritin concentrations.
As Manerva already explained, they write that when hemoglobin (the oxygen-carrying protein inred blood cells) is low, iron may first go to increase hemoglobin and thus oxygen-carrying capacity of the blood, instead of iron going to other organs, including the brain. Thus, they imply that when hemoglobin is relatively low, extra iron is used first and formemost to increase hemoglobinand thus may hinder uptake by the brain. "Low" blood value of hemoglobin is just above the lowest value of the normal range (Dutch range values).
I think the study is too small and the results too weak (see the large overlap in range) to draw any conclusions. And I would definitely not conclude that hemoglobin is a better indicator than ferritin. Interestingly, the authors did not look at how the combination of hemoglobin and ferritin values affected ironuptake; I suspect/assume because there were not enough samples to do so.
But the study is definitely interesting enough not to focus on ferritin only.
I looked at my own data. Unfortunately, I did not always have hemoglobin assessed. With oral iron, Ihad been able to increase my ferritin values to just above 100 ng/l, but hemoglobin remained between 12.5 and 13 g/dl. After my iron infusion, ferritin increased to above 350, but I have only one hemoglobin value of 13.5 g/dl 8 month post-infusion. If anything, it seems that my hemoglobin is fairly resistant to getting it increased. That is consistent with me as a child always being close to anemic, and even as a young adult blood donor most of the time having too low hemoglobin to be allowed to donate blood. My RLS dates back at least to my early twenties.
If someone is willing to share her/his iron blood values and iron suppletion history with me, please PM me. If I get enough data of both people whose RLS reacted positively to oral or IV iron and of people with no effect on their RLS (about 10 in each group?), it may be enough to write a paper - only with everybody's consent, of course.
My ferritin is 240 and my hemoglobin is 15. 7 and I just got back my 23 and me DNA and I have the marker for the iron overload disease. My dr doesn’t want to see me for 6 weeks and I’m worried it’s going to hurt my liver. Is there anything I can do to help my liver in the meantime. I do not drink alcohol
Some of this does now make sense to me. I think what they are saying is that each individual needs their Hb to be got into his own maximum level before raising ferritin helps force it into the brain ie the body gives 1st choice to Oxygen carrying capacity.
The mention of Ferritin maybe not being the ideal biomarker also makes sense as it can be affected by eg inflammation.
Maybe one of the other less used markers of Iron status would be better??
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The link between Iron and RLS
What form of iron?
Which iron supplement is the best and what dose?
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!
IRON PANEL test, what exactly?
