Vitamin D and suppression of iron by Hepcidin

Hi jwrhn1951

Thanks so much on the info.

I took him to the hematologist this am, and he is going to send a fax to the nursing home doctor to do the iron panel.  I had to ask for it, because they were not going to do any blood test, as he saw all of Joe's blood tests from his recent hospital stay, due to hemoraging from duodenal ulcer.  He had 5 blood transfusions.  His hemoglobin is 94 now, so he has anemia.

If you scroll down to the 2nd paragraph, regarding vitamin D suppressing iron, it does refer to hemochromotosis.  I copied and pasted it for you

Patients with CKD require iron supplementation and erythropoiesis stimulating agents (ESAs) to correct disease-associated anemia.1 However, ESA hyporesponsiveness is common, with the iron homeostasis factor hepcidin (encoded by the HAMP gene) emerging as a possible culprit.2 Hepcidin post-translationally suppresses membrane expression of ferroportin, the only known exporter of intracellular iron.3 Elevated plasma hepcidin, common to patients with CKD4 or inflammation,5 causes intracellular sequestration of iron and increases risk of anemia. By contrast, patients with hemochromatosis or iron deficiency exhibit decreased hepcidin.6

unquote

So, if those with CKD need high dose vitamin D, then those with HH would need or low vitamin D, is what I understand.   I read in another post that someone was feeling more fatigue when they started vitamin D

I was wondering if anyone else had felt this way.

The hematologist said it was not a good idea to do anything considering Joe is 82 and very weak.....maybe phlebotomy if his HB goes up to over 120, but only once every few months, which would take years to go down.  He would not recommend it or chelation if it was his relative

thanks again for the info on how lowering ferritin not getting rid of iron stores

Emis Moderator comment: I have deleted the post below as the article is already linked in the initial post above if users wish to read in full.

Hi Sheryl

thanks so much for the info.  He was diagnosed with the C282Y gene.   The Naturopathic Doctor who also has HH, his mom, and gramma also have it.  His gramma died.  She also had diabetes.

The ND recommended no wheat and no dairy, or sugar.

He is also on a low/no salt diet due to the edema (swollen legs and ankles) from all the fluid he got when he was in the hospital.  His low hemoglobin is due to all the hemoraging from duodenal ulcer.  Yes, he has anemia as well as HH.  

He is also on lactulose for the ascites.

He had an iron panel done last Sep and was 90% saturated.  the blood test at the hospital a couple of weeks ago, after the 5 blood transfusions, was 100% saturated and the ferritin was down to 1121 from over 2300 before the transfusions.  I don't know how much of the ferritin was from inflammation and how much was from iron overload, though.  They were having problem getting blood, since he was swollen, so they did not do the iron panel.

I asked the hematologist to send a letter to the doctor at the nursing home for the iron panel and vitamin D blood test

For more info, please read my other replies to the others

From the article linked in first post.

I think that reducing or going off of vitamin D, will increase hepcidin in the liver, which will allow the stored iron to be released.

Thanks again for the info, Sheryl

Your friend's situation is easier to understand now that you have divulged all this information.

I am homozygous C282Y and my TS% is often 100% - one time is was 107%.  However my serum iron is always high as well as my Hb.

In my 20s I was found to have 6 duodenal ulcers and years later it was found that Helicobacter Pylori causes ulcers.  HP thrives on iron (as does cancer).  Mine often returns and yesterday had another positive test result.

If not already done so, ask for a HP test, and have that treated.  The ND is right in suggesting elimination of wheat and sugar.  And all starches which are sugars in disguise, i.e. potatoes, bread, pasta, rice, corn, and possibly all grains, etc.  We cannot tolerate them and they cause fatty liver  and inflammation which also raises ferritin iron levels.  Elimination will reduce this ferritin (without high iron) by the hundreds - well, in the experience of a couple of people with such a problem in my support group anyway.  There is also an 83 year old man in my group whose HH was only diagnosed after he called me to query it.  He has a venesection once a month because of his age.

Dairy not so much but if we are lactose intolerant then it is going to set up inflammation same as wheat, grains, sugars.

I wonder if his huge loss of blood has made him 'iron avid'.  Google that for more information.  Sometimes this can happen to us HHers if we over venesect.  Check IronDisorders org.

While orange juice is high in sugar, try vit C.  Read up on it first, to see if you think that would help your friend.  We generally avoid it so as to not promote the uptake of iron.  Conversely, calcium (including dairy), tea, coffee, red wine with meals helps reduce the uptake of iron.

As I have an aggressive form of HH and a lot of complications from a very late diagnosis, I am forever searching for answers to reduce the severity of this problems.  I could not read in that study that eliminating Vit D was helpful for HH.  I only read it as affecting those who do not have HH.  I understand though that you are not looking at the HH angle.  But because our hepcidin just does not switch on to turn the iron absorption off like 'normal' people, the study sounds irrelevent to us.

Somewhere, some researchers are trying to replicate hepcidin or a medication to switch our hepcidin on.

My best result so far is from taking 100mg of aspirin a day.  Not recommended for your friend though.

Perhaps check what they do for thallasemia.  People with thallasemia have transfusions, then end up with high ferritin iron, but cannot be venesected because their HB is generally too low.

Perhaps the gastroenterologist should refer him to a cardiologist instead of just saying he may have heart failure.  If your friend is able to afford it, an MRI of the heart is available to check on iron deposits in the heart.

Also check on Vit B12 and folate.  If Vit B12 is low, injections are best.  This was a problem for my husband who is homozygous H63D and ended up with Hodgkins Lymphoma.  After chemo and radiumtherapy, his iron level was very low and he has not needed another venesection since.  Not a good way to cure HH though, LOL!

Another bit of interesting info, when I had surgery to replace my hips (caused by HH), I had a couple of bags of blood taken for autonomous transfusion.  Surgeon gave me one bag.  I ended up with chest pains (same as I had for a year prior to HH diagnosis).  My heart did not like that transfusion one little bit - even my own blood.

For the second surgery, even though I had a couple of bags of blood ready, I told surgeon not to give it to me unless I really, really needed it.  He didn't and though I felt rather weak for a while, I did not have chest pains again.  Really I would have been better off not having the blood taken before hand.

 

Reading the above again, maybe I am misreading what you are saying, but it sounds like you believe that your friend was 90% saturated with ferritin iron, and 100% another time.

Transferring saturation % indicates, that e.g., 90% of the serum iron is available to be absorbed into organs.  And if is serum iron is minimal, then 90% of a minimal quantity is not to be worried about.  Usually ferritin iron does not go everywhere, it usually picks the path of least resistence, more often than not, to the liver.

My liver is fine, the pathway picked on a couple of other parts of the body, i.e. hips (osteo necrosis), heart, skin, hypothalamus, pituitary gland, to name the obvious.  HP can cause anaemia too because of the bleeding it can cause even without hemorrhage.  Although I have HP, I have never been anaemic.  Everyone is so different.

How long has your friend known he has HH?  And for how many years has he been venesected?  Or has he just found out?  If he has known for years, and has been venesected for year, then he was probably "deironed".  But the duodenal ulcers has caused serious inflammation, causing high ferritin again.

At one time, my ferritin iron sky rocketed from low to 813 just because I had a cold or flu, but the haemotologist did not know that this is what happens.  So I was back on to frequent venesections, and suddenly I am down to 6.  No one seems to know what they are doing.

Anyway, if that is what you are thinking, perhaps this information will ease your worries a bit.

 

Hi Sheryl

Thanks so much for the explanation.  I am anxious to see the test results to see what the serum iron is.  

He just found out he had HH in Feb 2014.  I've read that one can carry the gene and not get it, but he never went to the doctor for years, but he never needed to, until he became dehydrated and fell.  The ambulance had to take him to the hospital.  That is when they discovered the cirrhosis because of his ascites infection (swollen stomach).  He never started any phlebotomies, only 14 chelation treatments.  After the 1st 4 treatments, his ferritin fell 700 points, but i don't know how much was from inflammation and how much from iron.  After another 10 treatments, it plateaued.  The doctor recommended 5000 IU vitamin D in Feb, which is when he started to plateau, so, after reading about how vitamin D regulates hepcidin levels, I thought that most likely is why he plateaued.  I've reduced him to 1000 iu vitamin D, and will monitor

You're right about "no one seems to know what they're doing".  I read  that alot of people do not get diagnosed with HH for years and after a few doctors.  They are told they have CFS or Fibromyalgia, and don't get the proper blood test done to see if they have the HH gene.  

Some of them die of various liver diseases, or kidney or heart failure, but they never discovered it was caused by HH, from what I've been reading.

 

I see that your earlier response to me still has not been released by the moderator.  It usually only takes about 24 hours.  It happens when the post contains an url address or naughty words!

Honestly, for HH being the most common genetic disorder among westerners, (one in 200 have two genes, one in 7 have one gene, and among those with Irish heritage it is one in 80 for two genes), drs prefer to remain ignorant.  Keeps business going, I suppose.

When not diagnosed and treated early, It does kill or disable a lot of people costing us and the health system millions of dollars.  A simple Iron Study test (A$27.95) then a genetic test if two of the markers are high (A$35.95) would diagnose.  Everyone should be screened by their gp.

My gp took 9 years to diagnose me after I had a hysterectomy (at age 38) and stopped menstruating, and started loading iron.  I knew when 6 weeks after the surgery I started feeling worse and worse that something was wrong.  I was so fatigued I was staggering and slurring, wanted to lie on the ground/floor/razor edge/anywhere and sleep, my whole body ached, one hip in particular.  I could sleep deeply and wake up like I have been hit by a truck.  I had left side chest pain for a whole year before diagnosis.  Google did not exist back then for me to find my own answers.

It was not till my hip broke up and the radiologist knew what caused it.  My gp said I did not look like I had it, i.e. yellow needing a liver transplant, or grey because of diabetes.  She was looking for end result, not beginning symptoms.

It has stuffed up my life and health quite a bit (I have to not say completely because cancer patients are worse - but then hopefully they get better - I am getting worse as all the organ damage starts coming to the fore).  I have had two cancerous tumours removed, luckily that was possible, and now have an MRI every 3 months to monitor.  I had to give up work long ago.

Anyway, we have to try to spread awareness, not only to make people aware and ask to be tested, but get drs aware too.  HH assocs are compaigning governments to have screening done.  Maybe you can help spread some brochures around.  Medical centres, pathologies, nursing homes, libraries - anywhere where you are allowed.

Have you got in touch with your country's assoc and spoken to them?  They will send you some info on it, talk to them about your friend's problem.  Quite often there are local support groups and we learn from each other.  There was none in my whole state, so I started one.  My haemotologist has told me that there had been a huge rise in people being diagnosed in my city since my campaigns.  I have even spoken to medical students about it at the local university.

I tell you if not taking vit D would switch on our hepcidin on to switch off the absorption of iron, it would be a HUGE deal in the HH world.  Most of us HHers seem to have very low Vit D.  Maybe it is just generally across the board for everyone anyway.  I live in the dry tropics and the sun is a killer here and it is hard to avoid, so my vit D should be high.

So while I had low vit D for years and not taking a supplement, it was not helping me one iota in preventing the uptake of iron.

Chelation can be quite unpleasant too.  It is not problem free.  He probably needs lots of antioxidents to get well again.  So the poor guy does not have to take so many tablets, try Vit D3 oral drops.  One drop on back on hand and licked = 1000iu is much more effective.

 

Hi Sheryl

Thanks for your response

He is getting 1000 iu now as part of Ultra Balance III multi vitamin and anti oxidant (3 tablets in the am and 3 at bedtime, crushed and put in apple sauce)

There is a facebook group for HH, which I've posted on, asking about coconut oil, but no one responded, but, you're right about educating people, especially doctors.  I will see if there is a doctors group on Facebook.

Did you have low vitamin D before your hysterectemy or did you check it at the time?

Linda

Hi Linda, just a quick one - on way out.

I don't remember that vit D was an issue before my hysterectomy.  I don't think the medical people thought it was important back then.

Coconut oil - I eat as much as I can find a way to for its benefits, in the beginning for its cholesterol balancing - I have low good chol.  Cholesterol is also a basis for oestrogen manufacturing too - which I am always short of.  Then there is the antibacterial, anti fungal, anti worms benefits.  I use it on my hair ends before washing, any dry skin patches, healing wounds, etc etc.

But I have not found any connection with iron, so I guess no one could answer your question on the HH facebook.

Sheryl

Hi Sheryl

Thanks for your email.

I read that coconut oil is not good for advanced cirrhosis from the book by Dr Mary Newport, whose husband had Alzheimers.

Thanks

Linda

Hi Gillian

Thanks so much for the link and info.  I will go read it.

He has to C282Y gene per the blood test done in Feb 2014 from the liver specialist.

See my reply to another post above for more info on him

Thanks Gillian

Hi Strathroy,

Here’s what I understand so far about what’s happened to Joe (age 82) – did I get it right?

Feb 2014 – cirrhosis, ascites, diagnosed as having hereditary HFE haemochromatosis (C282Y gene). 

Feb 2014 – given deferoxamine mesylate (Desferal) x 14, with initial drop in ferritin of 700 ug/L after the first 4 treatments. 

Feb 2014 – started 5000 IU vitamin D

March-May? 2014 – no further drop in ferritin after 10 more treatments with deferoxamine

Sept 2014 – iron panel done, transferrin saturation 90%

May? 2015 – ferritin 2300 ug/L

June? 2015 – massive bleeding from duodenal ulcer, given 5 blood transfusions

-          After transfusions, transferrin saturation 100%, ferritin 1121 ug/L, hemoglobin too low for phlebotomy

July 2015 – hemoglobin still too low for phlebotomy and iron panel will be done / has been done?

Assuming I have this right, I can think of two main possibilities for Joe’s hemoglobin not coming back up:

1.       The amount of bleeding from the duodenal ulcer was huge, the same amount as so many phlebotomies all at once, that Joe is for now not iron overloaded any more, and that is why his hemoglobin isn’t coming back up.

OR

2.       Joe has lot of (too much) iron still, but his body isn’t able to make it into red blood cells very well, and that is why his hemoglobin isn’t coming back up.

If  #1 is the case, then you’d expect the iron panel to show low iron indices, and if #2 is the case, then you’d expect the iron panel to show normal or high iron indices.

If #1 is the case, then Joe would want to talk to his doctors about continuing to monitor his hemoglobin and iron.  When his hemoglobin is back to normal and his iron indices show that he is starting to get iron overloaded again, then he can be treated with phlebotomy.  If his hemoglobin and iron don’t go up, you’d wonder if he was continuing to bleed from his ulcer and losing red cells and iron from his body that way.

If #2 is the case, then Joe would want to ask his doctor about getting checked for other things that might stop his body from making red blood cells.  For example, two common reasons why some older people can’t make red blood cells very well is being low in B12 or folic acid.  If you don’t absorb B12 very well, you need either to take high doses by mouth or – if you can’t absorb it at all – get B12 shots.  Or, some people have a tea-and-toast type diet that is low in folic acid (good sources of folic acid are chickpeas and other dried beans, and leafy greens) and being low in folic acid can also cause problems making enough red blood cells.

I found a couple of articles that talk about treatment of C282Y hemochromatosis that may be helpful? – I’ll post them separately so I can include the links.

BTW, deferoxamine works by binding (chelating) iron from ferritin and hemosiderin (but not so much from transferrin).  When iron is bound to deferoxamine, it can pass out of the body in the urine, plus a bit goes out in the stool via the bile as well.

And, you have to watch out with ferritin.  There are three reasons for ferritin to be high:  a) too much iron on board, b) inflammation of some sort, including inflammation from liver disease, and c) both.  So somebody with inflammation could have a high ferritin with normal or even low iron levels.

I hope some of this might be helpful -

Here we go with the articles I mentioned -

http://www.researchgate.net/profile/Trond_Flaten/publication/224917461_Iron_mobilization_using_chelation_and_phlebotomy/links/0fcfd50f510da715b5000000.pdf

http://repository.ubn.ru.nl/dspace31xmlui/bitstream/handle/2066/95805/95805.pdf?sequence=1

Emis Moderator comment: I have removed the articles that were pasted here as it may breach other website's copyright and users can use the links to read the articles. Please do not paste articles in posts. You can add a link to it and this will be approved as long as it complies with rules for posting links.

Hi Gillian

Thanks for all the info.  I have copied and pasted your info and corrected a few dates (see bolded changes)

Feb 2014 – cirrhosis, ascites, diagnosed as having hereditary HFE haemochromatosis (C282Y gene). 

Sept 2014 – iron panel done, transferrin saturation 90%

Jan  2015 – given deferoxamine mesylate (Desferal) x 14, with initial drop in ferritin of 700 ug/L after the first 4 treatments. 

early Feb 2015 – started 5000 IU vitamin D

early Feb - mid Apr 2015 – no further drop in ferritin after 10 more treatments with deferoxamine

May 2015 – ferritin 2300 ug/L

June 9, 2015 – massive bleeding from duodenal ulcer, given 5 blood transfusions

-          After transfusions, transferrin saturation 100%, ferritin 1121 ug/L, hemoglobin too low for phlebotomy

July 2015 – hemoglobin still too low for phlebotomy and iron panel will be done.  The CBC and electrolytes were done, yesterday because he nursing home doctor ordered this on Monday.  The Hematologist did not send the fax request in yet, so the iron panel hasn't been done yet. 

His B12 was over 1400 while in the hospital, last month, but i don't know if Folic acid was tested.  Is there a blood test for this?  I will check the test results, as i have copies of all from all doctors and clinics, hospitals since Jan 2014.

He definitely had inflammation but we don't know how much of the ferritin is from inflammation and how much from iron overload.  Maybe the desferral got the iron down, but it also took out other vitamins/minerals, because he got weaker and was not able to get out of bed, let alone walk starting the beginning of March.  The chelation clinic doctor prescribed Ultra Balance III, (vitamins, minerals, anti oxidants), and he was talking that from the 2nd week in January, but, apparently, it wasn't enough.  

I will look for your links.

thanks again Gillian

Linda