Donating Blood Effects

[Ihor]

The standard estimate is 30 ng/dl. It seems to vary a bit with starting ferrritin and other factors. If ferritin is really high, like say 900, it might drop significantly more than that from a single donation. Under 100, it might be less.

Thank you, a month ago I took tests and I had:
- iron: 11,7 μmol/l (ref: 11,6-31,3)
- TSAT: 18,0 % (ref: 15-50)
- ferritin: 44.99 ng/ml (ref: 25,0-350,0)

It's all on the background of a diet of low vitamin A with red meet (half a year) and low copper with ceruloplasmin (found out a year ago). A year ago my ferritin was 135 and I’m not sure that I know exactly why it dropped. Now I try to chelate iron and think to donate blood once, so as I suppose I have a hidden overload, but I'm not sure if my current ferritin is sufficient for this.

 

[tankasnowgod]

Thank you, a month ago I took tests and I had:
- iron: 11,7 μmol/l (ref: 11,6-31,3)
- TSAT: 18,0 % (ref: 15-50)
- ferritin: 44.99 ng/ml (ref: 25,0-350,0)

It's all on the background of a diet of low vitamin A with red meet (half a year) and low copper with ceruloplasmin (found out a year ago). And a year ago my ferritin was 135. Now I try to chelate iron and think to donate blood once, so as I suppose I have a hidden overload, but I'm not sure if my current ferritin is sufficient for this.

I don't think there is any "hidden overload," both TSAT and Ferritin look to be near deficiency. That's right within the target range of 25-75 ng/ml for Ferritin that most interested in iron reduction target. From my own experience, the 30 ng/ml estimate is too high for ferritin in this range, if you were thinking about donating blood.

 

[Ihor]

I don't think there is any "hidden overload," both TSAT and Ferritin look to be near deficiency. That's right within the target range of 25-75 ng/ml for Ferritin that most interested in iron reduction target. From my own experience, the 30 ng/ml estimate is too high for ferritin in this range, if you were thinking about donating blood.

I’m not sure, but I suppose that I accumulated a lot of iron and / or copper through low ceruloplasmin for a long time and they are in my tissues, liver, spleen, as I have no other explanation so far when I consume enough products with iron in over the course of a year, my ferritin fell, but I don’t know where this dietary iron went.
Now I think whether I should go for a blood donation to check whether it will remove the load from the body and improve my health if this “hidden overload” really exists or if I stop eating iron products (which I already did after the last tests), chelate and then take tests again and if ferritin rises, then donate blood. I'm just stuck here.

 

[tankasnowgod]

I’m not sure, but I suppose that I accumulated a lot of iron and / or copper through low ceruloplasmin for a long time and they are in my tissues, liver, spleen, as I have no other explanation so far when I consume enough products with iron in over the course of a year, my ferritin fell, but I don’t know where this dietary iron went.
Now I think whether I should go for a blood donation to check whether it will remove the load from the body and improve my health if this “hidden overload” really exists or if I stop eating iron products (which I already did after the last tests), chelate and then take tests again and if ferritin rises, then donate blood. I'm just stuck here.

I have no idea what you are basing this on. Ferritin is the best marker of overall iron stores. TSAT is pretty good, too. Both are on the low end of the lab range. It's more likely you didn't estimate your iron intake correctly. Plug a few days worth of eating into cronometer, see what it estimates your iron intake to be. Red Meat probably isn't as high as you think.

If you donated blood once and attempted to block or chelate iron with things like calcium, aspirin, IP6 or lactoferrin, that could easily explain the difference.

If you really think you have iron overload in your liver or other tissues, you could attempt to get a liver biopsy. Although that is risky and totally unnecessary. I don't think any doctor would recommend that with your iron panel numbers. If anything, they would likely want you to take an iron supplement.

 

[lampofred]

I’m not sure, but I suppose that I accumulated a lot of iron and / or copper through low ceruloplasmin for a long time and they are in my tissues, liver, spleen, as I have no other explanation so far when I consume enough products with iron in over the course of a year, my ferritin fell, but I don’t know where this dietary iron went.
Now I think whether I should go for a blood donation to check whether it will remove the load from the body and improve my health if this “hidden overload” really exists or if I stop eating iron products (which I already did after the last tests), chelate and then take tests again and if ferritin rises, then donate blood. I'm just stuck here.

I think OJ, coffee, raising metabolism in general pulls iron from tissues. Taking Vitamin D might not be good if you suspect you have excess iron in your tissues (if you are taking it).

 

[Ihor]

I have no idea what you are basing this on. Ferritin is the best marker of overall iron stores. TSAT is pretty good, too. Both are on the low end of the lab range. It's more likely you didn't estimate your iron intake correctly. Plug a few days worth of eating into cronometer, see what it estimates your iron intake to be. Red Meat probably isn't as high as you think.

If you donated blood once and attempted to block or chelate iron with things like calcium, aspirin, IP6 or lactoferrin, that could easily explain the difference.

If you really think you have iron overload in your liver or other tissues, you could attempt to get a liver biopsy. Although that is risky and totally unnecessary. I don't think any doctor would recommend that with your iron panel numbers. If anything, they would likely want you to take an iron supplement.

There is a direct link, and transferrin and ferritin can bound only Fe (III), which was oxidized from the state Fe (II) with the help of feroxidase, and ceruloplasmin is the main feroxidase. And this mechanism is importantnot only in the absorption of dietary iron, this is one of many processes where copper controls iron, it also takes part in the redox process iron in the cell, is responsible for the release of iron from the cell through ferroportin, participates in the synthesis of hemoglobin, and many other things related to iron metabolism. Interpretation levels of ferritin, transferrin and TSAT are no guarantee that they bound with all iron that is present in the body.
According to the chronometer, there was an average of 15-20 mg of iron per day. Well, I ate 200-300 grams of beef per day, in fact, red meat makes me tired. Of these things, there was always only coffee and calcium from milk, I doubt that they would cause iron deficiency. I started chelating only after the last blood test and have not donated yet. In fact, I remember that somewhere around 3 years ago my hemoglobin was as much as 180 and now it worries me a little.
I think so, because of everything that I have learned so far, it seems to me the most logical. A biopsy would not be bad, but in my case it seems too radical.

 

[Ihor]

I think OJ, coffee, raising metabolism in general pulls iron from tissues. Taking Vitamin D might not be good if you suspect you have excess iron in your tissues (if you are taking it).

I tried them for quite a long time, unfortunately I did not achieve noticeable improvements. I used to take a little vitamin D for a while, about 5,000 IU not every day and magnesium, but quit later, it did nothing for me. Why vit. D is bad in this case of iron excess?
This iron metabolism is quite complex, every time my mind starts to think freely that it understands the mechanism of action, I just realize that this is another rationalization, in fact, only one of the known variables that is controlled by a large system of many other unknown variables and feedback loops.

 

[tankasnowgod]

There is a direct link, and transferrin and ferritin can bound only Fe (III), which was oxidized from the state Fe (II) with the help of feroxidase, and ceruloplasmin is the main feroxidase. And this mechanism is importantnot only in the absorption of dietary iron, this is one of many processes where copper controls iron, it also takes part in the redox process iron in the cell, is responsible for the release of iron from the cell through ferroportin, participates in the synthesis of hemoglobin, and many other things related to iron metabolism. Interpretation levels of ferritin, transferrin and TSAT are no guarantee that they bound with all iron that is present in the body.
According to the chronometer, there was an average of 15-20 mg of iron per day. Well, I ate 200-300 grams of beef per day, in fact, red meat makes me tired. Of these things, there was always only coffee and calcium from milk, I doubt that they would cause iron deficiency. I started chelating only after the last blood test and have not donated yet. In fact, I remember that somewhere around 3 years ago my hemoglobin was as much as 180 and now it worries me a little.
I think so, because of everything that I have learned so far, it seems to me the most logical. A biopsy would not be bad, but in my case it seems too radical.

What you say about transferrin and ferritin is irrelevant, as you tested serum iron as well, and it was also on the low end of the range. Again, from your iron panel numbers, there is nothing at all to suggest any sort of iron overload.

300 grams of beef would have about 6mg of iron. Not a huge amount. Also, any blood test will lower body iron stores a little.

And if chronometer is suggesting 15-20mg of iron a day, that is right in line with most "official" recommendations for daily iron intake, which is 18mg.

I didn't suggest you have deficiency, either, just only that you are near deficiency, which is where most people who are interested in lowering iron aim to be.

If you want to think that you have some sort of "hidden iron overload" despite the fact that every tested iron marker is suggesting it is near deficiency, well then, go ahead. But I don't know why you would even do an iron panel in the first place if you just plan to ignore what the results are telling you.

I'd suggest reading some of E.D. Weinberg's work, like "Exposing the Hidden Dangers of Iron," and finding a doctor knowledgeable about iron.

 

[Ihor]

What you say about transferrin and ferritin is irrelevant, as you tested serum iron as well, and it was also on the low end of the range. Again, from your iron panel numbers, there is nothing at all to suggest any sort of iron overload.

300 grams of beef would have about 6mg of iron. Not a huge amount. Also, any blood test will lower body iron stores a little.

And if chronometer is suggesting 15-20mg of iron a day, that is right in line with most "official" recommendations for daily iron intake, which is 18mg.

I didn't suggest you have deficiency, either, just only that you are near deficiency, which is where most people who are interested in lowering iron aim to be.

If you want to think that you have some sort of "hidden iron overload" despite the fact that every tested iron marker is suggesting it is near deficiency, well then, go ahead. But I don't know why you would even do an iron panel in the first place if you just plan to ignore what the results are telling you.

I'd suggest reading some of E.D. Weinberg's work, like "Exposing the Hidden Dangers of Iron," and finding a doctor knowledgeable about iron.

I don’t really want to argue, I just don’t understand why you are discarding the case when, in the context of low ceruloplasmin, the iron on transferrin and ferritin cannot be low and, especially, can't be low in blood serum. The body precisely controls the concentration of serum most tightly, which prevents the body from simply releasing it into tissues, such as the liver, if there is no ability to absorb it? There are many studies where low ceruloplasmin causes latent iron overload and I agree with them.

I’m just not trying to believe in what I like or think as it is more convenient, but I try to look at things rationally. My dietary iron was always sufficient, I did not lose blood, did not chelate, did not suppress absorption. It is believed that the body loses only 1-2 mg of iron per day, the rest is recycled, in this case, especially in men, it should either accumulate / remain normal, and less likely to decrease. Tests were made for this reason and I don’t ignore their results, I just don’t know what to do with them since their direct interpretation does not seem logical to me.

Thanks for the book, I will look at it, it seems interesting.

 

[tankasnowgod]

I don’t really want to argue, I just don’t understand why you are discarding the case when, in the context of low ceruloplasmin, the iron on transferrin and ferritin cannot be low and, especially, can't be low in blood serum.

Well, even if that's true, you are comparing a year old ceruloplasmin test with a more recent iron panel. Why would you be giving more weight to older tests?

I also don't understand why you put more faith in a non-iron related marker to tell you about whole body iron stores, than actual iron related markers. This is no different than endos who exclusively use the pituitary hormone TSH to diagnose hypothyroidism, ignoring any actual thyroid hormones.

 

[tankasnowgod]

There are many studies where low ceruloplasmin causes latent iron overload and I agree with them.

What studies are you referring to? How did those studies measure iron overload? And also, how did they conclude that low ceruloplasmin was causal?

 

[Ihor]

Well, even if that's true, you are comparing a year old ceruloplasmin test with a more recent iron panel. Why would you be giving more weight to older tests?

I also don't understand why you put more faith in a non-iron related marker to tell you about whole body iron stores, than actual iron related markers. This is no different than endos who exclusively use the pituitary hormone TSH to diagnose hypothyroidism, ignoring any actual thyroid hormones.

Because presumably since the low ceruloplasmin registered by me since last year, unbound copper and iron began to accumulate, possibly even earlier, and at the same time my systemic metabolism of other things, for example, the same iron binding, deteriorated, this is just my vision.

 

[Ihor]

The role of ceruloplasmin in iron metabolism​

Abstract
The importance of ceruloplasmin in iron metabolism was studied in swine made hypoceruloplasminemic by copper deprivation. When the plasma ceruloplasmin level fell below 1% of normal, cell-to-plasma iron flow became sufficiently impaired to cause hypoferremia, even though total body iron stores were normal. When ceruloplasmin was administered to such animals, plasma iron increased immediately and continued to rise at a rate proportional to the logarithm of the ceruloplasmin dose. The administration of inorganic copper induced increases in plasma iron only after ceruloplasmin appeared in the circulation. Thus, ceruloplasmin appeared to be essential to the normal movement of iron from cells to plasma.

Studies designed to define the mechanism of action of ceruloplasmin were based on the in vitro observation that ceruloplasmin behaves as an enzyme (ferroxidase) that catalyzes oxidation of ferrous iron. Retention of injected ferrous iron in the plasma of ceruloplasmin-deficient swine was significantly less than that of ferric iron, reflecting impaired transferrin iron binding. Rat ceruloplasmin, which has little ferroxidase activity, was much less effective than porcine or human ceruloplasmin in inducing increases in plasma iron. These observations suggest that ceruloplasmin acts by virtue of its ferroxidase activity.

Eight patients with Wilson's disease were evaluated in order to investigate iron metabolism in a disorder characterized by reduced ceruloplasmin levels. Evidence of iron deficiency was found in six of these, and in five of the six, plasma ceruloplasmin was less than 5% of normal. In comparison, the two patients without evidence of iron deficiency had ceruloplasmin levels of 11 and 18% of normal. It is suggested that iron deficiency tends to occur in those patients with Wilson's disease who have the severest degrees of hypoceruloplasminemia, possibly because of defective transfer of iron from intestinal mucosal cells to plasma.

The role of ceruloplasmin in iron metabolism

 

[Ihor]

Hepatic iron overload or cirrhosis may occur in acquired copper deficiency and is likely mediated by hypoceruloplasminemia.​

Abstract
BACKGROUND: The metabolic fates of copper and iron are closely linked through ceruloplasmin and hephaestin. Ceruloplasmin is the principal copper carrying protein and decreases in acquired copper deficiency. Congenital absence of ceruloplasmin (aceruloplasminemia) results in tissue iron overload. Animal studies suggest hypoceruloplasminemia and impaired hephaestin function result in tissue iron accumulation.

OBJECTIVES: There are no data on hepatic function, pathology, and iron status in patients with acquired copper deficiency. This report studies these issues in 4 patients with acquired copper deficiency.

STUDY: This is a retrospective review of hepatic status (imaging, liver function tests, liver biopsy) in 4 patients with neurologic and hematologic manifestations of acquired copper deficiency who also had imaging and/or pathologic evidence of hepatic dysfunction.

RESULTS: Two patients (cases 1 and 2) showed imaging evidence of cirrhosis and pathologic evidence of cirrhosis or advanced fibrosis. Two patients (cases 3 and 4) had pathologic evidence of hepatic iron overload. All patients had some evidence of abnormality on liver function tests.

CONCLUSIONS: Acquired copper deficiency causes a secondary ceruloplasmin deficiency which can result in hepatic iron overload and/or cirrhosis.

Hepatic iron overload or cirrhosis may occur in acquired copper deficiency and is likely mediated by hypoceruloplasminemia. - PubMed - NCBI

 

[Ihor]

Hepatic iron overload associated with a decreased serum ceruloplasmin level in a novel clinical type of aceruloplasminemia.​

Abstract
BACKGROUND & AIMS: Aceruloplasminemia is a novel hereditary iron overload disease caused by a mutation in the ceruloplasmin gene and characterized by a complete deficiency of serum ceruloplasmin and iron accumulation in the liver and brain.

METHODS: We herein studied a novel clinical type of aceruloplasminemia in which a low amount of ceruloplasmin was detected in the serum of a patient. The patient presented with an asymptomatic hepatic iron overload, retinal degeneration, and diabetes mellitus. Magnetic resonance imaging of the liver and basal ganglia showed T2-hypointensity signals associated with parenchymal iron accumulation because of an absence of the ferroxidase activity in ceruloplasmin.

RESULTS: A gene analysis showed a novel G969S mutation in the ceruloplasmin gene. A biochemical analysis of the patients' serum and a biogenesis study of G969S mutant ceruloplasmin using mammalian cell culture system resulted in the synthesis and secretion of only apoceruloplasmin without any ferroxidase activity.

CONCLUSIONS: This novel clinical type of aceruloplasminemia should therefore be considered in the differential diagnosis of unexplained hemochromatosis, which is associated with a decrease in the serum ceruloplasmin level.

Hepatic iron overload associated with a decreased serum ceruloplasmin level in a novel clinical type of aceruloplasminemia. - PubMed - NCBI

 

[Ihor]

Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations.​

Abstract
Aceruloplasminemia is a recessive disorder characterized by anemia, iron overload, and neurodegeneration, caused by the absence of ceruloplasmin (Cp), a multicopper oxidase important for iron export. Few patients homozygous for loss of function mutations of the Cp gene have been reported. We describe a 62-year-old white woman with heavy liver iron overload, diabetes, anemia, and neurologic symptoms. She was compound heterozygote for 2 novel mutations that result in the absence of hepatocyte Cp: an adenine insertion at nucleotide 2917 causing a truncated protein and a C-G transversion causing a glutamine-->glutamic acid substitution at position 146. Although rare in whites, aceruloplasminemia should be considered in the differential diagnosis of unexplained anemia associated with iron overload, because these features anticipate progressive neurologic symptoms. We propose that anemia, secondary to the impaired macrophage iron release, plays a major role in hepatic iron overload through increased absorption mediated by the erythroid regulator.

Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations. - PubMed - NCBI

 

[Ihor]

Identification and in silico characterization of a novel compound heterozygosity associated with hereditary aceruloplasminemia.​

Abstract
BACKGROUND: Hereditary aceruloplasminemia is an adult-onset autosomal recessive disease characterized by increased iron overload in the liver, pancreas, retina, and central nervous system. So far, 45 families with cases of aceruloplasminemia have been reported world-wide and mainly missense and nonsense mutations in the ceruloplasmin gene were detected.

MATERIAL AND METHODS: Here, we report the identification, clinical characterization, and in silico analysis of a novel compound heterozygosity in the ceruloplasmin gene of a 31-year-old man with iron overload.

RESULTS: Increased serum ferritin levels, elevated iron saturation, as well as results of iron quantification in the liver and magnetic resonance imaging-based measurement of T2 relaxation times of the substantia nigra consistently suggested iron overload. By sequencing the ceruloplasmin gene, so far unknown nucleotide replacements G229C, and C2131A were detected in exons 2 and 12, respectively. In silico analyses showed that the resulting amino acid changes Asp58His and Gln692Lys are located at highly conserved positions. The Asp58His mutation is located on the surface of the protein, alters polarity, and may interfere with copper incorporation or ceruloplasmin trafficking. The Gln692Lys mutation is mapped to a beta-strand of domain 4 and may lead to conformational change of the cupredoxin fold.

CONCLUSIONS: As causative for aceruloplasminemia, a formerly unknown compound heterozygosity in the ceruloplasmin gene was identified. In silico characterization suggests an impact on ceruloplasmin conformation and function.

Identification and in silico characterization of a novel compound heterozygosity associated with hereditary aceruloplasminemia. - PubMed - NCBI

 

[Ihor]

A case of ceruloplasmin deficiency which showed dementia, ataxia and iron deposition in the brain.​

Abstract
A 55-year-old female with progressed dementia, cerebellar ataxia was reported. There was no family history of the same symptoms although her brothers, sisters and a son showed hypoceruloplasminemia and decrease of the serum copper content. On physical examination, anemia, dementia, dysarthria, torticollis, choreic involuntary movement of respiratory muscles, hyperreflexia in extremities and cerebellar ataxia were noted. Blood analysis revealed microcytic hypochromic anemia, diabetes mellitus, decrease of copper content of the serum and urine. Serum ferritin concentration was increased. Serum ceruloplasmin could not be detected. Biopsy of the liver showed that copper content in the liver was slightly increased and iron content was remarkably increased. On MRI study, dentate nucleus of the cerebellum, the thalamus, the putamen and the caudate nucleus and the liver showed low intensity in both T1 and T2 weighted images. Based on increased iron content in the liver, the radiological findings of the brain suggested deposition of iron in the brain. This deposition was considered as caused by deficiency of function of ceruloplasmin as ferroxidase. This disorder is suggested as a new disease due to ceruloplasmin deficiency different from Wilson's disease.

[A case of ceruloplasmin deficiency which showed dementia, ataxia and iron deposition in the brain]. - PubMed - NCBI

 

[Ihor]

Hepatic but not brain iron is rapidly chelated by deferasirox in aceruloplasminemia due to a novel gene mutation.
​

Abstract
BACKGROUND & AIMS: Aceruloplasminemia is a rare autosomal recessive neurodegenerative disease associated with brain and liver iron accumulation which typically presents with movement disorders, retinal degeneration, and diabetes mellitus. Ceruloplasmin is a multi-copper ferroxidase that is secreted into plasma and facilitates cellular iron export and iron binding to transferrin.

RESULTS: A novel homozygous ceruloplasmin gene mutation, c.2554+1G>T, was identified as the cause of aceruloplasminemia in three affected siblings. Two siblings presented with movement disorders and diabetes. Complementary DNA sequencing showed that this mutation causes skipping of exon 14 and deletion of amino acids 809-852 while preserving the open reading frame. Western blotting of liver extracts and sera of affected patients showed retention of the abnormal protein in the liver. Aceruloplasminemia was associated with severe brain and liver iron overload, where hepatic mRNA expression of the iron hormone hepcidin was increased, corresponding to the degree of iron overload. Hepatic iron concentration normalized after 3 and 5months of iron chelation therapy with deferasirox, which was also associated with reduced insulin demands. During short term treatment there was no clinical or imaging evidence for significant effects on brain iron overload.

CONCLUSIONS: Aceruloplasminemia can show an incomplete clinical penetrance but is invariably associated with iron accumulation in the liver and in the brain. Iron accumulation in aceruloplasminemia is a result of defective cellular iron export, where hepcidin regulation is appropriate for the degree of iron overload. Iron chelation with deferasirox was effective in mobilizing hepatic iron but has no effect on brain iron.

Hepatic but not brain iron is rapidly chelated by deferasirox in aceruloplasminemia due to a novel gene mutation. - PubMed - NCBI

 

[Ihor]

Aceruloplasminemia.
​

Abstract
Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains greater than 95% of the copper present in human plasma. It is synthesized mainly in the liver. Aceruloplasminemia is an autosomal recessive disorder affecting iron metabolism, originally called familial apoceruloplasmin deficiency, which manifests late-onset blepharospasm and retinal degeneration. Subsequent investigations have found patients with late adult onset of ataxia and diabetes mellitus. Our patients have also shown diabetes. Clinically, aceruloplasminemia is a triad consisting of neurologic disease, retinal degeneration, and diabetes. This disease is characterized by mutations in the ceruloplasmin gene and iron accumulation in the retina and basal ganglia as well as in parenchymal tissues caused by a complete deficiency of ceruloplasmin ferroxidase activity. The neurological symptoms in affected patients include involuntary movements, ataxia, and dementia reflecting the sites of iron deposition detected by MRI as well as the regions of neurodegeneration observed at autopsy. Consistent with this observation, ceruloplasmin gene expression is detected in the retina and basal ganglia revealing that this protein is essential for iron homeostasis neuron survival in the central nervous system. The unique involvement of the central nervous system distinguishes aceruloplasminemia from other inherited and acquired iron storage disorders.

[Aceruloplasminemia]. - PubMed - NCBI