In hemochromatosis, why would ferritin be low but transferrin saturation high?

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Question: In hemochromatosis, why would ferritin be low but transferrin saturation high?
Ferritin is your long-term iron storage. Transferrin is your short-term iron storage. The problem with hemochromatosis is that usually in a normal functioning system, there is a hormonal regulatory system that prevents you from absorbing iron from food when you have enough iron that when you have too much iron, shuttle the iron into ferritin which is protective both against pathogens eating the iron to grow and against oxidative stress, which free iron causes, which if you don't know the details about can be thought of as wear and tear on your tissues over time.
In hemochromatosis, normally the way you judge how much iron you have is in the circulating transferrin pool, which is your short-term storage. How full is it? The defect in hemochromatosis is that when the short-term storage, transferrin, starts getting fuller than usual, you don't notice it, so you don't stop absorbing iron from food that makes the transferrin saturation go up even further. But you don't shuttle the iron into ferritin. That makes ferritin lower.
What people get confused by is that historically, we have only paid attention to hemochromatosis when it's too late, when the person has been suffering for it from 30 or 40 years and they need organ transplants. What happens at that point is that the ferritin is very, very high. Why is the ferritin high? Not because you had too much iron. The person without hemochromatosis has the ferritin go up when they have too much iron. The defect in hemochromatosis is that you do not stop absorbing from food when you have enough, and you do not put the iron into ferritin when you have too much.
The reason that ferritin is high in someone who's had hemochromatosis for 30 or 40 years is not because they have too much iron. It is because they have oxidative stress and damage caused by that iron. Oxidative stress and damage cause ferritin to go up no matter how much iron you have. So does infection, no matter how much iron you have. Essentially, what you have is ferritin is not the fireman that he should be to put out the fire as it starts, and the smoke detectors go off. Ferritin hemochromatosis is the cleanup crew who got to the fire after the house burned down.
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DISCLAIMER: I have a PhD in Nutritional Sciences and my expertise is in performing and evaluating nutritional research. I am not a medical doctor and nothing herein is medical advice.

[@whitefreeman5798]

i have been watching videos on this subject for a couple days and this has been the best i have found on the subject.. thank you for sharing information

[@twiops]

Thank you for addressing a subject I requested. More information on iron overload and how to treat it would be appreciated.

[@someguy43210]

Blood donation or phlebotomy is the most effective. (doi: 10.1373/clinchem.2004.046847, PMC3096860) Improving ceruloplasmin status, which is the copper-containing enzyme crucial for the body's iron metabolism (PMC322742). Need to do a copper, iron and ceruloplasmin blood test to know for sure, then get recommendation from a knowledgeable doctor for safe approach. There are some ways to improve ceruloplasmin status, but balance is key. Both excess and inadequate copper and ceruloplasmin are a problem. (see articles: Self Hacked - Ceruloplasmin, Thyroid Nation - Balance Copper With Ceruloplasmin For Thyroid Health) -Zinc has to be balanced with copper (around 8:1 to 12:1 ratio). (doi: 10.1093/ajcn/61.3.621S) -Excess vitamin C supplementation reduces copper. (doi: 10.1093/ajcn/37.4.553) -Vitamin C increases iron absorption: PMC4931859, PMID: 15743017 PMID: 3464594 The study notes: "Ascorbate can be useful in enhancing the removal of iron by chelation therapy....must be balanced against the possibility of increased iron toxicity." So useful in proper chelation therapy, but otherwise can increase the absorption. -Patient with iron toxicity due to aceruloplasminemia is treated with copper. (doi: 10.1182/blood-2009-06-226175) -Free unbound iron and copper is a problem. (doi: 10.1021/tx900338d) There various iron chelators: -IP6 (phytic acid): sold as a supplement, taken on empty stomach to prevent interfering with nutrients update (PMC1134551) -Milk thistle: (human trials) doi: 10.1097/MCG.0b013e31815cff36, doi: 10.1111/j.1472-8206.2009.00681.x, PMC3308202) -Alpha Lipoic Acid (ALA): chelator for iron, mercury, and other heavy metals. Caution: short half-life in the body, can dump heavy metal into the blood for people with heavy metal toxicity, see Andy Cutler Chelation protocol. ALA unlike some other chelators will cross the blood brain barrier. (PMID: 15829111, PMC4172298) -Green tea (EGCG): PMID: 8424806, PMC4416964 -Quercetin: PMID: 21238582 Turmeric: PMC2614453, PMCID: PMC2615657, PMID: 16545682

[@twiops]

@@someguy43210 Thank you, Max. I am already well-versed with the supplements, but am grateful that you posted it all here for others to see. I will direct others to your post. Thank you!

[@twiops]

@@someguy43210 Great info on the ceruloplasmin, copper and Zinc... Still reading. 😀

[@CatS55587]

@@twiops If you are interested in treatment, I would also suggest looking into Dr. Eric Lewis at hemochromatosishelp.com He is very knowledgeable on the subject since he himself has it.

[@ChristineClifton]

I don't fully agree with what's being said here about why the ferritin is low in the situation mentioned. Ferritin can be low and Saturation can be high when the HH person has anemia caused by low stomach acid. I have HH (compound heterozygous) and also had this kind of anemia (though at the time I didn't know it was caused by low stomach acid). Low stomach acid can be caused by h.pylori infection - but it can also be caused by a chronic heightened stress response putting the body in fight/flight. One of the first systems to slow down during a high sympathetic nervous system state is the GI system. I was receiving iron infusions because of my dangerously low ferritin, even though I have HH. Once I researched and discovered the info re: stress response, I started focusing on stimulating my parasympathetic nervous system. Within a year, my ferritin stabilized and I didn't need infusions ever again.

[@chrismasterjohn]

Well if you are getting infusions that confounds everything, but why do you think HH plus low stomach acid would cause high transferrin saturation?

[@Ghost-oq8fw]

So is there a way to increase the iron going to ferritin? How do we reduce transferrin levels?

[@adama5239]

Please let me know if my results are OK: Ferritin: 130 .....38-380 range Iron Total: 114 ......50-180 range TIBC: 357% ......250-425 range Transferrin: 32% ......20-48 range

[@americankulak4596]

Hello Chris, I have been searching for information in regards to this for a very long time. Any suggestions on how to keep iron levels and saturation within limits? I present exactly what you describe here. I’m 41 y/o male with a saturation level consistently above 50% and free iron at or above upper range. Ferritin is consistently low (20), every physician I have presented has been stumped. I am very concerned, any advice would be greatly appreciated.

[@sofianebousnadji5233]

I have the same problem iron serum high low ferritin coefficient saturation high

[@friendcrow]

What effect would lactoferrin have in someone with high hemoglobin and hematocrit levels?

[@nicoc7024]

Do you think someone would have side effects of low ferritin if all other markers are normal?

[@09paritosh]

Iron Studies (Iron,TIBC, Transferrin saturation) 1 Iron Serum, Method: Ferene 81.69 50 - 170 µg/dL 2 TIBC Serum, Method: Ferene 481.19 250-450 µg/dL 3 Transferrin saturation Serum, Method: Calculated 16.98 20 - 50

[@captainplanet1260]

Excellent advice

[@hostapatch]

He mentioned another video on this topic, but I can’t find it. Anyone know where it is? Thanks

[@northernshore8327]

What if iron is normal, but very high ferritin and low transferrin? What about infections etc with this ?

[@nicoc7024]

So low ferritin with a high saturation means hemochromatosis if other things are ruled out? I have this but my hemochromatosis genetic test were negative.

[@justynajustyna7622]

Did you find out what is the reason?

[@jacoblas1371]

I am exactly like you. I am negative for hemochromatosis. Low ferritin, but high transferrin saturation.

[@EyeMags]

Unfortunately the simplifications in your description of Hemochromatosis are so over done what you say becomes mostly factually incorrect. Transferrin is a transporter moving iron from the blood to the organs. It's mostly the organs that suffer the oxidative stress when the organ ferritin levels in the organs become so high that the molecules leak iron and cause the damage. We measure serum ferritin (SF) (ferritin in the blood). The part you got right was that before we get iron overload the SF is low and TSAT% is high, but you did not mention that when treated with Phlebotomies the SF decreases and draws out the Ferritin from the organs (mostly the liver) using the Transferrin again but in the other direction,. So the patient again has low SF and still has high TSAT% at that point. Also your point about the age people overload for men and women is again a simplification such that its right in specific people but wrong overall. Patients (men and women) can be overloaded from 20s-70s dependent on the gene mutations they have of HFE, HAMP, and TF genes (in the common cases, others involved in the rarer forms). It's true that menstruation slows loading but you can say things like there is 30 years difference between men and women because the cases when it isn't are numerous.

[@CLRLY]

So if correcting iron overload and achieving a significant drop in serum ferritin, would you expect transferrin % saturation to increase in the short term as stored iron exits the liver (primarily)? How can you get transferrin % to drop in this situation outside of phlebotomy/what is the rate of excretion from transferrin?

[@pattytyndall1021]

Good question…I’m in the same dilemma. SF is below 50, SAT% is above 70%.

[@Datacorrupter234]

great content thank you

[@09paritosh]

I have HIGH TIBC but low saturation. Should this be alarming I'm 34

[@MsSarahRush]

So I have Hypothyroidism, was diagnosed at 194 TSH 3 years ago. This week, bloods came back with 55.22% transferrin saturation and and iron serum high. I’m a 36 yr old woman. Does this indicate Haemchromatosis?

[@chrismasterjohn]

It is suggestive.

[@gabriellakadar]

You can get DNA testing privately.

[@fredvorck6246]

Wait how does he not even define HH? Did I miss it? The medical definition of Hereditary Hemochromatosis is when the body does not make, or cannot use, hepcidin. (There are 4 major types though). Hepcidin degrades ferroportin which makes hepcidin a "cellular iron drain plug." (Without this peptide, iron slips out of cells, so ferritin can't go very high for the person's early life.) Oxidative stress is NOT the only reason ferritin goes up much later -- by later in life, HH patients have hepatocytes full of iron (from having high serum levels for **decades**). This is basic Ganz. See Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis, and Hepcidin and Iron in Health and Disease, and Hepcidin and iron homeostasis, etc etc all by Ganz and Nemeth.

[@chrismasterjohn]

I agree with most of what you wrote, but you don’t explain how the iron gets high in cells if it is slipping out. My contention is that if the hepcidin communication is impaired, and the relative stimulation of ferritin is decreased, then that gap is being met by the marginal increase in oxidative stress caused by the iron after it starts accumulating.

[@fredvorck6246]

@@chrismasterjohn The cellular iron goes up higher because serum iron has been high for decades. Ferroportin would let it out, but there's nowhere for it to go. Age 20, it could exit the cell to serum. Age 60, iron is everywhere and stays in the cell, ferroportin notwithstanding. Hepcidin (unused or not present) would be a drainplug but now at about age 60 the drain is clogged with iron. And indeed we can confirm these massive splenic and hepatic deposits with MRI.

[@rockclimber6766]

@@fredvorck6246 So should someone in this state still donate blood despite low ferritin to avoid organ damage?