“Question What is the preferred oral iron supplementation strategy in patients with iron deficiency anemia (IDA)?”
“Findings In this cohort study of 71 677 patients with IDA, improvement of hemoglobin and other iron indices were not different between patients who were prescribed daily or alternate day oral iron supplementation, although improvement happened at a slower pace than those who were prescribed multiple doses per day (≥2 times per day). Patients with chronic kidney disease showed similar trends but smaller magnitudes in changes compared with patients with normal kidney function.”
In general agreement with previous studies, our findings confirm that providing oral iron on alternate days rather than on consecutive days does not result in …Nov 3, 2023
If we really want to help people get to that magical ferritin number wherein their RLS will disappear or lessen (a number I do not believe exists) then we should advise them to take iron first thing in the morning with OJ, as it seems doctors these days advise, as well as this article. onlinelibrary.wiley.com/doi...
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DesertOasis
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Certainly taking iron first thing in the morning on an empty stomach is the recommendation from Professor Matthew Walker and Professor Toby Richards, which is why RLS-UK advise this. Hepcidin levels are lowest in the morning and the stomach is more likely to be acid.These studies certainly supercede the earlier studies on pregnant women which recommended double dose on alternate days. But the studies do say more research and more studies are needed.
The Lancet article states
"Alternate day dosing providing the same total dose of oral iron had comparable efficacy but triggered fewer gastrointestinal side effects".
I've been on a long journey with iron supplementation, and there's a lot to cover. Recently, I watched a fascinating video by Dr. Earley, where he discusses the Circadian Rhythm of Serum Iron and Cerebral Spinal Fluid. If you're interested, start at around the 26-minute mark, but I recommend watching the whole video. Dr. Earley is the only source I've found that discusses taking iron at night.
From my perspective, I received my lab results this week. Last year, I realized I wasn't taking enough Ferrous Bisglycinate. I was taking 45mg per day at night with Vitamin C, not necessarily on an empty stomach. This year, I decided to double my dose to 90mg of Ferrous Bisglycinate with Vitamin C at night. That was my only change. Additionally, I took 10,000 IU of Vitamin D daily, at least five days a week, with a fatty meal.
Unfortunately, my numbers were disappointing:
- **Ferritin:** 72 to 80
- **Serum Iron:** 134 to 90
I've been doing this for over eight years, and I still can't get my ferritin to a reasonable level. This means I'm going back to Liquid Ferrous Sulfate, 325mg (6.8ml) at night, because I know it worked in the past. For some reason, Ferrous Bisglycinate just doesn't do it for me.
Also, despite taking 10,000 IU of Vitamin D, my levels fell from 63 to 50! This experience has taught me a few things about iron stores and ferritin levels:
1. **Type of Iron:** Ferrous Bisglycinate is easier on the stomach, but Ferrous Sulfate absorbs more effectively.
2. **Timing:** The time of day is important. I tried twice a day but had gastric issues. My doctor advised doubling the dose and taking it once a day—yes, 650mg of Ferrous Sulfate in one dose.
3. **Absorption:** Iron absorption works better on an empty stomach. I need to ensure I don't eat two hours before or one hour after supplementation. My doctor mentioned that iron binds with proteins in the stomach.
4. **Vitamin D:** Vitamin D is a regulator of Hepcidin. If iron stores are low, chances are Vitamin D levels are low. Vitamin D blocks Hepcidin, and Hepcidin blocks iron absorption.
I absolutely believe that iron is my issue. That is why I am going back to liquid ferrous sulfate. I also intend to make sure I take it on an empty stomach.
Restless Legs Syndrome (RLS) is a complex condition with various causes, making it difficult to pinpoint a single treatment approach. For some, RLS may be genetic, while for others, it could be triggered by factors such as iron deficiency.
In my case, iron deficiency was the clear culprit. Despite taking oral iron supplements for a year and raising my ferritin levels from 7 to over 200, my RLS symptoms persisted. When I stopped the supplements, my ferritin levels dropped from 207 to 30 over 18 months. This led to the introduction of dopamine agonist (DA) drugs, which had a significant impact on my life, family, and business.
Eighteen months later, I received an iron infusion (iron sucrose, 200 mg*5), which was a turning point for me. The infusion not only alleviated my RLS but also addressed my iron deficiency without anemia. Ferritin levels provide a snapshot of current iron in the blood, while transferrin saturation percentage (TSP) is a better indicator of iron stores. As Dr. Early mentioned, TSP might be more crucial than ferritin levels.
To maintain normal iron levels, I now take 500% of the recommended daily allowance (RDA) of iron. Despite this, my ferritin levels only increased from 72 to 80 over a year, and my TSP dropped. My goal was once a ferritin level of 200, but now I aim for 100, which has been challenging to achieve. I really do not want another infusion.
Additionally, I suspect that my iron deficiency might indicate other vitamin or mineral deficiencies. Raising my vitamin D levels has been as challenging as increasing my ferritin. I diligently take 10,000 IU of vitamin D3 daily.
In summary, I think we are all trying to understand RLS from our own unique perspective.
I've had good and bad nights. I went through a phase where I was taking dipyridamole on an as needed basis. That lasted for a couple months. Now. I take it nightly again. Dipyridamole still takes away the RLS and lessons PLMD.
I am doing good but would hate to be without dipyridamole.
Widebody, feel like taking a walk on the wild side 😈? Stop the iron for 2 to 3 days. Then start up again, but only take one to two capsules a night (25 to 50mg). Always take the iron before the dipyridamole. If after 3 to 4 weeks you still need dipyridamole then go back to Plan A. I’m going to do this as well - lower the amount of iron I take. You gotta scroll down and read Jerry57’s post that I attached here.
I think he is 100% correct. I think these huge amounts of nightly iron you’re taking are also triggering huge amounts of hepcidin and making the RLS worse - especially since all three of us don’t put a day in -between (Sue, are you grinning right now and saying mwahaha?). Your ferritin isn’t going up and you’re not getting “immediate” relief and your symptoms are worsening. This tells me you’re absorbing very little of that nightly iron and the reason might be that you have elevated hepcidin, which stops that iron from entering the bloodstream from the GI tract. Supposedly, it is much harder for hepcidin to stop heme iron, but that’s another topic for another day. This is all wild speculation, but it only requires a 3 to 4 week harmless trial. If you were anemic I would never suggest this. And if you’re not off the dipyridamole by the end of the trial, then feel free to come back on here and call me names 🤡
I think Jerry’s ferritin is very good, between 100 and 200? That might be due to the fact that slow and steady wins the race. That great ferritin doesn’t do a thing for his RLS - he still needs nightly iron, otherwise he suffers. Here ya go, words of wisdom?:
Jerry57 profile imageJerry57Minijackrussell
2 days ago
I'm certain Sue is correct, but like DesertOasis, my brain/body needs iron every night. I tried alternating, and every night I skipped iron, my RLS flared up and woke me between 3-5AM. After months of experimentation, I now alternate between one and two iron tablets. Taking less than that, I get RLS at night. Taking more than that seems to trigger hepcidin production, which flares my RLS for days. It feels like a delicate balance.
The Nature article only measured ferritin at 4 weeks and we know it takes up to 3 months to raise ferritin.
It also said "the inflammatory status of participants was not assessed at baseline or follow up using markers like C-reactive protein. Thus, the baseline ferritin as well as subsequent changes in ferritin levels could have been affected by inflammation ... Further, serum ferritin levels could be affected by recent iron intake; therefore, ferritin values could have acutely increased if the test was done within 1–3 days after the iron dose."
The Lancelet article contradicted a previous Lancelet article thelancet.com/journals/lanh... but it also said "At equal total iron doses, compared to consecutive day dosing of iron, alternate day dosing did not result in higher serum ferritin but reduced iron deficiency at 6 months and triggered fewer gastrointestinal side effects."
The Veteran article was confusing. They talked about the ADD group and the MDD group but did not define them. they said "no significant difference in the improvement of hemoglobin and iron indices between daily and ADD groups, but quickest improvement was observed in the MDD group." It said "In comparison with a daily regimen, an MDD regimen was associated with a significantly steeper increase in ferritin"
It allowed people with taking PPIs which lower the absorption of iron and didn't control for this.
And I don't see any allowance for the different amounts of elemental iron in what they took.
Nor whether they took blood thinners or took vitamin C with the iron nor whether they took it an hour before or 2 hours after meals or coffee or whether they took magnesium , calcium or zinc, at least 2 hours apart since they interfere with the absorption of iron. Also antacids taken at least 4 hours before the iron or at least 2 hours after. Of course the other articles didn't either.
Two of the articles referred to a previous article that said "alternate-day iron dosing showed 34% higher rate of iron absorption."
An aside: Iron is absorbed less the higher the dose, so twice the amount of iron on alternative days is not the equivalent on the iron taken every day.
And one of the advantages of alternate day doses is to reduce the side effects.
Great observations! You know my position, however. Much adieu about nothing. We give people false hope and send them down rabbit holes. At least my rabbit hole is one level and one night. I look at posts about once a week and every time I do I see people wasting weeks, if not months, trying to get a ferritin test. Inevitably presenting with ferritin lower than we have ordained proper for someone with RLS. Raising ferritin has about the same, if not a lower success rate, than magnesium glycinate. We’ve had two to three people throw away the Gabapentin and rely solely on magnesium. I’ve never read of anyone raising their ferritin and throwing away their RLS med. Over the years we’ve seen people come on here with severe RLS that have ferritin in the low teens all the way to hundreds, yet it makes no difference. If this bizarre theory that higher ferritin helps RLS then people in the hundreds should at least only have mild RLS. So remind me why we think telling people to raise their ferritin will help? And we don’t mention it like we do magnesium, we really push this idea that they must get a ferritin test, they must stop iron for days before the test, and finally, they must raise their ferritin. Especially with people who are in augmentation and haven’t slept in a week we probably shouldn’t put all their focus (and hopes) on a frickin ferritin test. They need to demand an opiate, try ferrous bisglycinate one night, and then when they’re feeling better then let’s look at some other option like raising ferritin if they’re very low. I feel like we’re counting ants (fractions of fractions of iron absorption) while the elephants are flying over our heads.
Except that there are people who throw away RLS meds, or better still never need to start them, after having raised their ferritin (or at least one or all of their iron count). Particular populations that really seem to benefit are pregnant women and pediatrics. I benefited more from an iron infusion (minor benefit) than iron every night (nil benefit).
90% saw little or no benefit. No one threw their meds away and we’re talking about people who got their ferritin between 400 and 800. The same is true for raising ferritin with oral supplements from what I have seen on here. If low body ferritin was a major (or even a moderate) player, in this nightmare we call RLS, then those with low ferritin would have RLS 24/7/365. Not just at night. And most people who got their ferritin up into the 100s should see significant improvement. Alas, very few do.
If you know members on here who had significant (or even moderate) benefit from raising ferritin, please share their stories here, in this post. Thank you!
As I’ve said a 1000 times before, it’s not so much ferritin, as it is serum iron, which drops precipitously at night. And even serum iron is just part of the equation. Bodily ferritin is not part of the equation, unless we’re talking about IDA
Thanks for the articles. My personal experience is that taking oral iron had a limited effectiveness at raising my ferritin level and when I did get the ferritin level raised it didn't seem to do much for my PLM. I think I've had PLM for most of my adult life but it never bothered me until I gave blood in 2019. I went to the doc and found out my ferritin was 12 ng/mL. All of my other iron parameters were normal (I had what we call a full iron profile). Over the course of 3 years of oral iron I was able to raise the ferritin level to about 100 ng/mL but still suffered from PLM. I was able to get an iron infusion after I shared some publications with my doc and this raised my ferritin level to a peak of 450 ng/mL. Unfortunately, this made no noticeable difference in the PLM symptoms. Based on the reading I've done it seems that some are helped by increasing the ferritin levels and some are not.
I have no idea where my PLMD has come from. My family doesn't have any so genetics is unlikely unless it was a random mutation. I was diagnosed when I had a sleep study in 2013. This was a surprise. I did the sleep study because I thought i had sleep apnea. I think I've had PLMD at least since the 1980's because people told my I twitched in my sleep. It never bothered me (like keeping me from falling asleep or waking me up). The doc prescribed ropinerol which thankfully I didn't take because my PLM didn't bother me so why take meds. After I gave blood in 2019 my PLM really started to bother me. Perhaps this was coincidence but I did find out my ferritin was very low (12 ng/mL). This might indicate that low ferritin was the issue but I've now raised my ferritin to over 300 ng/mL with no noticeable change to my PLMD. I was on ropinerol for a few months until I got a new doc and he switched me to gabapentin and then pregabalin. I think the fancy medical term for what causes my PLM is ideopathic (we have no effing idea).
It's still possible it is genetic. No one in my extended family had RLS but when I tested my genes I had the ones associated with RLS. Of course it doesn't really matter.
PLMD does have a strong genetic component. My son had a 50% chance of inheriting the condition (which he did). However, my identical twin sister doesn't appear to have it (and sleeps extremely well). And in my extremely large family of origin and extended family, it has only been observed in one other family member.
Looking back, it appears that my dad had mild narcolepsy (which has an association with PLMD).
I only discovered that i had PLMD when i had a sleep study just over a decade ago. I first noticed RLS when i took an SSRI some decades ago. It seemed to wax and wane but was never severe enough to really stop me from going to sleep.
In looking up how heritable it is, i came across this interesting article. You've probably read most of it before, however the comments on heritability and age of onset are interesting.
Tanker, I don’t know what time of day you take iron but you really should try to take it about an hour before bed on an empty stomach - on the outside chance you are an immediate responder.
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