My Story and Dilemma

[wacomme]

I'm trying to get my head around the mechanism for iron infusions and why they work. Basically, iron absorption from the gut is body regulated, so ingested iron is limited with its absorption into the blood. Conversely, iron infusions add iron directly to the blood stream, and the hope is that with the higher blood concentration of iron, an adequate supply will migrate into the brain. Is this correct?

Is there a problem with the high blood iron after an iron infusion? If the body regulates iron blood absorption from the gut, adding extra iron directly into the blood stream seems problematic. We need it for our poor blood/brain iron transfer, but what maladies will come due to high blood iron? Is this a problem?

Also, since iron infusions happen about once a year, where is the iron stored? Does the brain store it? Does it just circulate in the bloodstream? And if it's stored elsewhere, why can't we inject iron directly to that organ?

Michael

[stjohnh]

I'm trying to get my head around the mechanism for iron infusions and why they work. Basically, iron absorption from the gut is body regulated, so ingested iron is limited with its absorption into the blood. Conversely, iron infusions add iron directly to the blood stream, and the hope is that with the higher blood concentration of iron, an adequate supply will migrate into the brain. Is this correct?

Is there a problem with the high blood iron after an iron infusion? If the body regulates iron blood absorption from the gut, adding extra iron directly into the blood stream seems problematic. We need it for our poor blood/brain iron transfer, but what maladies will come due to high blood iron? Is this a problem?

Also, since iron infusions happen about once a year, where is the iron stored? Does the brain store it? Does it just circulate in the bloodstream? And if it's stored elsewhere, why can't we inject iron directly to that organ?

Michael

Yes, oral iron absorption by the intestine is regulated by hepcidin, and hepcidin has a feedback loop with ferritin. More-or-less, hepcidin cuts off intestinal iron absorption when the ferritin is in the 100 range, which is why oral iron only helps those RLS patients that are total body iron deficient. Getting brain iron levels up for RLS patients (not normal people) requires lots of iron in the blood. There is a (currently unknown) transport mechanism that moves iron from the blood across the blood-brain barrier. There is speculation that the reason for BID (Brain Iron Deficiency) is malfunction of this transport mechanism. High total body iron is dangerous (hemochromatosis) and the gut regulating system is there to prevent iron overload in people with a high iron diet (eat lots of bloody meat).

Free iron in the blood can be dangerous, which is why there are many types of IV Iron available. The older preparations had a high fatality rate, and newer IV Iron preparations are made so that they slowly release the iron into the blood to avoid extremely high blood levels. People who need repeat IV iron (like me and other RLS patients) get a blood test before each IV infusion to make sure iron levels are not too high.

The iron is stored as ferritin. Ferritin is a protein that can bind iron (keep free iron levels in the blood in the safe range) and release the iron when the blood level is low. Ferritin is stored in all body tissues, but the majority is in the liquid blood, the bone marrow, the liver and the spleen. The actual mechanism is more complicated than I have outlined, but the above will get a reasonable approximation of how the body handles iron.

The area that needs iron is the brain. So far, there hasn't been a way of injecting iron into the brain. I've considered putting nails in my ears to see if that would help, but haven't tried that yet, LOL. I suppose iron could be injected directly into the bone marrow, or liver, or spleen. However, I personally prefer an IV rather than (likely painful) injections into my liver, spleen or bone marrow.

The reason that only 1/2 of people getting IV Iron have relief from RLS symptoms is unknown. The IV iron prepartions that work the best (Injectafer) probably do so by slowly releasing iron at a level that crosses the blood-brain barrier without using the assumed transport mechanism (faulty in most RLS patients). The exact level that this occurs at is unknown. It is quite possible that as a future (hopefully soon) result of further research, that iron can be administered in a way that is both safe and provides a high enough iron level to get accross the blood brain barrier of all RLS patients. Remember that some people with RLS have it because of total body iron deficency, rather than blood-brain barrier iron transport malfunction. Renal failure patients also have RLS, I don't think the reason is known.

Drugs that interfere with hepcidin allowing iron to be absorbed from the gut even if the ferritin is high, are being explored, and would make possible treatment with oral iron more successful. Ultimately the "cure" for RLS is splicing some gene into our DNA that allows the blood brain transport system to work correctly. That however is likely decades in the future.

See this Wikipedia article for more details on iron metabolism: https://en.wikipedia.org/wiki/Human_iron_metabolism

[wacomme]

Holland,

Thank you for the thorough explanation.

Is iron infusion the first-line treatment for RLS? I ask because I'm trying to justify the cost if my insurance doesn't cover the expense (likely).

Michael

[wacomme]

Another perplexing issue for me is inflammation and ferrous blood concentration. From what I've read the more inflammation one has ferrous levels rise. This makes me wonder if my "natural" ferrous levels are very low. The last measured ferrous was 87. However, this was measured hours after eating breakfast and taking 325mg of ferrous sulfate. It was also two weeks after undergoing significant hand and food surgeries that were osteoarthritic related. I had a lot of inflammation in my body. And still, my ferrous levels were relatively low; under the circumstances they should me much higher.

Since inflammation increases ferrous levels, does inflammation "help" RLS symptoms? I have significant osteoarthritis throughout the body, particularly in my cervical and lumber spine.

My neurologist suggested that the stenosis in my cervical spine might be contributing to my RLS (via my peripheral neuropathy?). I don't understand this connection. Thoughts? Research?

Thanks. Michael

[stjohnh]

Another perplexing issue for me is inflammation and ferrous blood concentration. From what I've read the more inflammation one has ferrous levels rise. This makes me wonder if my "natural" ferrous levels are very low. The last measured ferrous was 87. However, this was measured hours after eating breakfast and taking 325mg of ferrous sulfate. It was also two weeks after undergoing significant hand and food surgeries that were osteoarthritic related. I had a lot of inflammation in my body. And still, my ferrous levels were relatively low; under the circumstances they should me much higher.

Assuming you mean ferritin rather than ferrous: Ferritin is called an acute phase reactant, that is roughly akin to what we call inflammation, but not exactly. Ferritin levels increase with certain diseases and changes in the body's reactions to "inflammation." While your surgery and osteoartritis are inflammatory from your point of view, they don't usually cause the ferritin to increase.

Since inflammation increases ferrous levels, does inflammation "help" RLS symptoms? I have significant osteoarthritis throughout the body, particularly in my cervical and lumber spine.

No. The exact mechanism that causes the urge-to-move and insomnia of RLS is unknown, but is definitely NOT caused by low ferritin levels. Low ferritin levels are correlated with low iron levels. Low iron affects the body in many ways. It is thought to cause changes in adenosine and glutamate metabolism which may lead to the symptoms we have. There is a disease called hemochromatosis in which iron accumulates in the body tissues and causes problems, those people have ferritin levels over 1000. Some of them ALSO have RLS, and in spite of having too much iron in their body, they still have BID (Brain Iron Deficiency). More research is needed.

My neurologist suggested that the stenosis in my cervical spine might be contributing to my RLS (via my peripheral neuropathy?). I don't understand this connection. Thoughts? Research?

As far as I know, there is no direct correlation between RLS and cervical spinal stenosis, though there are tantalizing bits of research data implicating peripheral nerve and spinal cord abnormalities with RLS. The common peripheral neuropathies (repetative strain injury, diabetes, Vitamin B12 deficiency, post-herpetic neuralgia, compression neuropaties) are not associated with an increase in RLS symptoms. Chronic renal failure (kidney failure) is associated with RLS and peripheral neuropathy, but I think this is just an association with the multiple severe metabolic abnormalies that occur with kidney failure.

A side note: The word ending "-itis" as in osteoarthritis, conjunctivitis, etc. is used to mean inflammation in a medical sense. Osteoarthritis was named before fully understanding the disease. There is no actual inflammation (in a medical sense) in osteoarthritis, and there has been a movement to rename the disease Degenerative Joint Disease (DJD) because it more accurately describes the disease process. Rheumatoid arthritis is a true inflammatory disease, osteoarthritis is not.

[wacomme]

Thanks again Holland.

My new neurologist suggested my neck pain (stenosis and lots of degeneration, though cannot yet pinpoint the source of the pain) may contribute to the RLS - seems contradictory to what you're saying with common peripheral neuropathies.

Michael

[wacomme]

Now I seem to have a new problem - constipation. I've been on ferrous sulfate (325mg) for 4 months now. Could I just now be getting constipated because of it? Until now, I have very regular bowel movements. All I eat are fruits, vegetables, and lean meats. I drink plenty of water. I know opioids give me constipation, but I've been off of them for a couple of weeks post-surgery. The only thing I can think of that's causing me constipation is my iron supplement. Dang! BTW - do iron infusions create the same constipation problem?

I hate constipation, more than most anything. And stool softeners are not something I want to take on a regular basis. So, do I stop taking oral iron? I'm tempted to do so, at least temporarily, to at least determine if the oral iron is causing my constipation. So frustrating . . .

Michael

[wacomme]

BTW - I take Feosol as my ferrous sulfate supplement. Are there oral iron supplements that do NOT cause constipation?

Michael

[Yankiwi]

Constipation is awful.
Try Benefiber and/or Metamucil. They are plants, not drugs. I prefer Benefiber because it can go in any beverage, hot or cold and has no taste. It also mixes in with yoghurt, custard—almost anything. Maybe once or twice a week I also take a Coloxyl (laxsol) tablet if I feel really stopped up.
Pears have more fiber than apples, kiwifruit is high in fiber as are avocadoes. We really need to concentrate on keeping constipation at bay.

[ViewsAskew]

I also find that walking really helps (and seems necessary for me).

[Yankiwi]

I walk seven k or more every day possible (weather permitting, I live in a high rainfall area). I don't know how bad it would be if I didn't walk.

[wacomme]

Lack of exercise may be what's keeping me constipated from the iron, and why I'm not realizing it until 4 months after starting iron. I had hand and foot surgeries three weeks ago, and I'm non-weight bearing for seven weeks. Both hands are compromised as well as my left foot since I had thumb surgery on my right hand 11 weeks ago and the same surgery on by dominant left hand three weeks ago. I'm relegated to a knee scooter and an iWalk - both are quite limiting in terms of exercise. I crawl around on the floor a lot, and I head to the garage daily for about an hour's worth of stretching, core work, and now some upper body work thanks to resistance bands and wrist straps. However, as an amateur bicycle racer, someone who spends 12-15 hours/week training, this is not "much" exercise. I'm quite compromised for another 4-5 weeks.

I'm going to stop taking oral iron and see what happens. If my RLS gets worse I will have to reconsider my options.

Do iron infusions create the same constipation effect as oral iron?

Michael

[stjohnh]

Do iron infusions create the same constipation effect as oral iron?

Michael

No, but then constipation with iron tablets is not universal, and constipation with ferrous iron is less common than with ferric iron preparations.

[wacomme]

Wow! I tried 5mg of THC edibles right before bedtime last night. Once I got past my leg jerking and fell asleep, I don't think I woke or even moved for 7 hours. Amazing. That never happens. So sweet!!!

[wacomme]

Yippee! I'm scheduled for two rounds of Injectafer iron infusions August 9 & 16. And apparently the infusions are covered through my medical insurance (I'll be checking this next week). Surprised and amazed. I now hope I'm in the 50% of the population that responds positively to the infusions.