Newly uncovered biochemical and functional aspects of ferritin, 2023, Yanatori et al.

Newly uncovered biochemical and functional aspects of ferritin
Izumi Yanatori; Sohji Nishina; Fumio Kishi; Keisuke Hino

Iron homeostasis is strictly regulated at both the systemic and cellular levels by complex mechanisms because of its indispensability and toxicity. Among the various iron-regulatory proteins, ferritin is the earliest discovered regulator of iron metabolism and is a molecule that safely retains excess intracellular iron in the cores of its shells. Two types of ferritin, cytosolic ferritin and mitochondrial ferritin (FTMT), have been identified in a range of organisms from plants to humans.

FTMT was identified approximately 60 years after the discovery of cytosolic ferritin. Cytosolic ferritin expression is regulated in an iron-responsive manner.
Recently, the molecular mechanisms of iron-dependent degradation of cytosolic ferritin or its secretion into serum have been clarified. FTMT, which shares a high degree of sequence homology with cytosolic ferritin, has distinct functions and is regulated in different ways from cytosolic ferritin. Although knowledge of the physiological role of FTMT is still incomplete, recent studies have shed light on the function and regulation of FTMT. The accumulating biological evidence of both ferritins has made it possible to deepen our knowledge about iron metabolism and its significance in diseases.

In this review, we discuss the biological properties of both ferritins, focusing on their newly uncovered behaviors.

Link | PDF (The FASEB Journal)

 

Do you know why people with low iron can raise their ferritin (with iron supplements) to be well in range, then they stop supplementing and their ferritin level immediately starts dropping very quickly? And that can happen over and over again?

 

Others may have a better idea, but this old abstract might offer one explanatory scenario. If there's ongoing blood loss, eg from gut or uterus, and iron supplementation is more than can be used in the production of red blood cells. I don't know if that could apply if there was a problem with normal dietary absorption of iron, rather than blood loss.

From Effect of iron therapy on serum ferritin levels in iron-deficiency anemia (1980, Blood) —

 

My doctor couldn't understand why this occurred either. His response was "where does it go?"

Low ferritin started after getting M.E.

 

I'd love to know that too.

 

I expect part of the explanation may be that iron is not simply there to allow oxygen transport in red blood cells — it's needed in cells, including within mitochondria. If mitochondrial function is impaired then that would likely affect the requirements for and handling of iron. Ferritin that's measurable in the serum may no longer be directly correlating with body (intracellular) ferritin and/or iron levels.

From Chemistry and biology of ferritin (2021, Metallomics) —

Perhaps ME changes the activity of those receptors, leading to a reduction in measurable serum ferritin.

Perhaps ME upsets macrophage function and affects this.

 

Likewise: low ferritin started after developing ME. I wonder what percentage of pwME have this same timing.

 

I was first treated for anaemia around the age of 10 or 11. I was tested for it because I got a mouthful of really huge mouth ulcers that turned out to have a secondary, bacterial infection - I couldn't eat or speak and I drooled because I couldn't swallow. The anaemia was found about a year after I'd had two operations just six weeks apart. I don't think I was suffering from ME at that time.

Anaemia is a problem that afflicts multiple people in my extended family, mostly female.

But my poor health and energy has been a lifelong issue, and iron problems have been bound up with that. I don't have a diagnosis of ME, although I think I probably have it. If I do have it it probably wasn't triggered by a virus, I would suspect a genetic iron absorption problem and a pituitary problem.

 

In the analysis of DecodeME questionnaire answers from 2022, 14% of participants reported a co-occuring diagnosis of anaemia.

 

I wonder how many of those people thought doctors took their anaemia seriously and treated it for long enough to allow for the patient's levels to become similar to those of healthy people and stay there?

According to this (old - 2010) link each molecule of ferritin holds 4,500 atoms of iron.

https://web.archive.org/web/2013112...files/Content/828895/ST ferritin NOV 2010.pdf

I'm fantasising in the next bit...

If ferritin can exist and not be "full" of iron atoms then perhaps the answer to my earlier question (post #3 above) is that the ferritin test is measuring ferritin that is in any state from "full" to empty". Perhaps something (stopping taking iron supplements?) triggers destruction of the empty ferritin molecules and so the level of ferritin drops.

 

My understanding is that low ferritin is the cause of iron deficiency anaemia, but not the cause of anaemia.

 

Thank you @Andy.

That's interesting.


According to Statistics Canada, 3% of the population has anemia (low hemoglobin):

https://www150.statcan.gc.ca/n1/pub/82-003-x/2012004/article/11742-eng.htm#:~:text=Approximately 3% of Canadians had,iron, but by%



NICE has the exact same statistic:

https://www.nice.org.uk/cks-uk-only#:~:text=In the UK, it is,women have iron deficiency anaemia.


Over 30 years ago, someone I know was very iron deficient, fatigued, couldn't stay awake in the early evenings, was exertion intolerant, had muscle pain, and was out of breath with exertion.

This person was, and is very fit, and healthy.

Their hemoglobin was fine, as was the rest of the iron panel that was done, however, when the patient's request for a ferritin test was followed up on, the result was in the single digits. Iron supplementation and eating MORE beef did the trick.

Low ferritin is where my iron issue shows up; the rest of the iron panels are always fine to quite good, including hemoglobin.

 

A useful summary, but I'm certain it is not complete and there are other forms of anaemia:

How do I know if I'm anemic?

@DokaGirl - I can't read your second link, even though I'm in the UK. Is there any other way of getting to the same info?

 

Hi @Arnie Pye

I went back to this site, and it says it's only accessible in the UK, and other "properties".

So bouncing it from the UK to me, and back to the Forum didn't work.

To initially find info on this I googled something like what percentage of people in the UK are anemic?



This site below told me this info is not available outside the UK and its "properties":

https://www.nice.org.uk/cks-uk-only#:~:text=In the UK, it is,due to iron deficiency anaemia

Hope this helps.

 

Yes, I got that comment as well, but I am in the UK. I live here! I'll try googling what you did and see what happens.

 

@DokaGirl I found this :

Source : https://cks.nice.org.uk/topics/anaemia-iron-deficiency/background-information/prevalence/
Last revised : April 2023

 

My carer aunt has high ferritin and anaemia .
Iron supplementation has made a huge difference to her health which she notices almost immediately when she stops .

ETA anaemia is recent . Previous iron panel was ok .