10 replies to this topic

[a3mlord]

What is the relationship between lactoferrin and ferritin?

 

My latest bloodwork is in. I have high ferritin (and normal-almost-low iron). I wonder if taking lactoferrin won't make things worse?

 

Thanks!

 

 

 

[Dorian Grey]

When ferritin is high but serum iron or iron saturation (transferrin saturation / TSAT) is low, this may be due more to inflammation than iron overload.  Transferrin Saturation is supposed to be the lab to watch for iron issues.  Ideally, you want TSAT in the middle third, and not the upper (or lower) third of the ranges.  

 

Here's an interesting take on ferritin elevations:  https://pubs.rsc.org...4/mt/c3mt00347g

 

Ferritin elevations most likely due to cell turnover?  The liver is the bodies primary storage site for ferritin bound iron, so liver inflammation would likely be the primary site for inflammation related ferritin elevations to originate from.  How are your ALT/AST liver enzymes?  

 

Iron homeostasis is my favorite hobby-horse for health & longevity.  https://www.longecit...isease-omnibus/

 

My favorite chelators are Curcumin, Quercetin, & IP6 (Inositol Hexaphosphate), but blood donation is the ultimate way to lower ferritin swiftly (if your hemoglobin/hematocrit is adequate for donation).

 

I looked into lactoferrin as a chelator.  Apparently there are two kinds, and you want "Apo-lactoferrin" if you wish to lower iron with this.  I noticed lactoferrin appears to dramatically stimulate immune response

 

https://www.ncbi.nlm...les/PMC4814036/

 

and this spooked me a bit as immune response and inflammation are closely related.  The liver is particularly susceptible to immune response to endotoxin from leaky gut and/or dysbiosis.  I chose to punt on the apo-lactoferrin and stick with bloodletting and the herbal / IP6 chelation.  

 

Don't know if you've got easy access to having labs done, but a bit of experimentation might be in order to see what will lower your ferritin without causing your hemoglobin to suffer.  Life Extension offers ferritin tests at the cheapest rate I've seen https://www.lifeexte...itin-Blood-Test

 

I'd stay on top of this and work on getting ferritin down by hook or crook, preferably out of triple digits.  Whether your elevation is iron related or caused by inflammation, ferritin elevation appears to be a substantial red flag for trouble (accelerated aging, chronic disease).  

Edited by Dorian Grey, 16 April 2019 - 04:57 AM.

[a3mlord]

Hi there.

 

Thank you so much for your answer.

 

I am aware of most of what you said.

 

Currently, I am chelating heavy metals with DMPS and ALA.

 

I have substantial liver problems (pain and symptoms that can be traced back to the liver/gb, such as dizziness and muscle - neck and back - stiffness).

 

However, all liver markers are on point. That is bilirrubin, AST, ALT, alkaline phosphatase.

 

So, as for iron, I will ask plasma tests for:

 

- Lactoferrin
- Iron
- Iron saturation
- UIBC
- TIBC
- Transferrin
- Transferrin saturation (TSAT)
- Ferritin

Could you perhaps help me interpreting the results?

 

Liver inflammation is a thing (it hurts and I can feel it). I would not be surprised if this is the first marker I find that is congruent with that. I am so surprised that I haven't found any so far (pretty much all my bloodwork is acceptable to optimal).

 

The reason why I am looking into lactoferrin is 1) to make iron more bioavaliable because it is low (this was before I knew ferritin was high), 2) increase immune activity, 3) use its antiviral activity and 4) deplete parasites from iron. Whether I should use apto- or bound- lactoferrin depends on clearing the ferritin marker (that is, being sure it is not high because of iron overload).

 

Thanks a lot!

[Dorian Grey]

Always happy to chat iron stuff with you a3.  

 

Iron saturation, transferrin saturation and TSAT are all one in the same.  Different doctors & labs use different terminology for this same test.  This is the most important indicator of iron loading when ferritin is elevated, & you really want to see this (saturation) in the middle third of its normal range.  When ferritin is elevated and saturation is in the upper third normal (or higher) this is the confirmation you're truly loaded with more iron than may be healthy and a ferritin elevation is not a false positive due to inflammation, infection or high rate of liver cell turnover (apoptosis).  

 

If you're not familiar with "hepcidin" yet, this is another piece to the puzzle.  Hepcidin is the bodies master iron regulating / transport hormone. It's an inverse acting hormone where low levels increase dietary iron absorption and transport within the body and high levels shut down both dietary iron absorption and importantly transport of iron within the body.  The body knows iron is highly inflammatory and can feed infections, so when inflammation is elevated or infection is present, hepcidin rises to put iron in "lock-down" mode.  This is only supposed to last until inflammation subsides or infection is resolved, but with chronic inflammation or infection, hepcidin remains chronically elevated, trapping stored iron in the liver & preventing transport to the bone marrow where red blood cells are made, which results in the "anemia of inflammation" often called "anemia of chronic disease".  

 

Ferritin, like hepcidin is an "acute phase reactant", & when inflammation is high or infection present, the body will pump out a lot of empty "apo-ferritin" in an attempt to mop-up any excess iron.  This type of ferritin elevation can cause a false positive for iron overload, which is why we like to look at saturation for clarification.  With chronic inflammation or infection both ferritin and hepcidin are chronically elevated and iron transport is locked-down.  This results in the anemia of inflammation or at lower levels can show high ferritin with low serum iron, which I gather is what you are seeing in your labs. 

 

It is also possible to have a liver that is overloaded with iron, but due to chronic inflammation, the iron is trapped by high hepcidin, preventing transport out of the liver.  This can result in an angry inflamed liver and a high rate of apoptosis (liver cell turnover).  Macrophages cleaning up the cellular debris from high cell turnover become loaded up with iron (from the liver cells) themselves, and when this happens, they start secreting cytokines (TNF / tumor necrosis factor), signaling the body "there is some nasty stuff in these dead cells".  This raises hepcidin & blood ferritin in a feedback loop of inflammation & crippled iron transport.  

 

If you're not anemic, a single whole blood donation can break this log-jam wonderfully well.  A significant blood loss causes hepcidin levels to plummet for up to a month, as the body, sensing low blood cell volume overrides all in an effort to rebuild red blood.  This opens the floodgates of iron transport and allows the body to shuttle iron around from where it is stored in the liver, to bone marrow for red cell production.  Macrophages also will cast off their excess iron for transport and stop giving off TNF cytokines, which breaks the cycle, restoring normal iron homeostasis.  

 

Iron chelation is not particularly effective at lowering hepcidin, as only a significant blood loss will override this hormone, though chelation can lower TNF, which can resolve minor acute phase iron issues.  If you're not eligible to donate blood & ferritin is high / out of normal range and saturation is also high, a referral to a hematologist would be helpful.  A hematologist can order a "therapeutic phlebotomy", which is the same as blood donation to resolve the issue.  

 

The key to a good donation experience is to go in well hydrated in the afternoon, a couple of hours after a good meal.  There are plenty of youtube videos on blood donation if you wish to see what the experience is like.  Millions around the world donate blood safely every year, so though this might seem an unusual therapy, it shouldn't hurt to try this provided you are not anemic.  Donate only "whole blood" and not plasma or platelets.  The iron is in the red cells, & plasma or platelet donations do not lower iron, ferritin or hepcidin.  

 

Hope this helps, & hope better health is in your future!  

Edited by Dorian Grey, 17 April 2019 - 05:11 PM.

[a3mlord]

Hey!

 

I was NOT aware of hepcidin, thanks a lot! The way I look at it (now reading a lot about it) is that it could also be an inflammation/infection marker, just like ferritin, as you wrote in your answer.

I've ordered a full iron panel. Still trying to know whether they can test hepcidin, but I've secured all the other markers. Should take a few weeks till I do the test and get the results, will post here later on OK?

 

If you don't mind, here are a few questions:

 

 

The way I look at it is (please tell me whether you agree):

1 - If ferritin is high but TSAT is OK, then ferritin is an inflammation marker and it is fine to take hololactoferrin.

2 - If ferritin and hepcidin are high but TSAT is OK, there is a chance they are markers of inflammation/infection but it could also be iron overload (although inflammation could come from the liver due to stuck iron) it is NOT OK to take hololactoferrin because there is a risk I am overloaded with iron. Taking apolactoferrin should not hurt.

Q: this is right even if iron is low, because apolactoferrin is not a true chelator; it does chelate but iron is even more bioavaliable.

3 - If ferritin is high, iron is low or normal and hepcidin is normal, then it is a very strange pattern. The way i look to it is that hepcidin cannot be normal if any of the other parameters are wrong, both due to iron overload and inflammation.

4 - If iron is low and ferritin and hepcidin are high then I should downregulate hepcidin, even at the cost of more inflammation. It should relieve the liver and decrease the chances of anemia.

BTW, in this case ferritin could be truly elevated meaning iron overload in the liver. 

BTW 2, this is a truly fucked up scenario! I bet this can cause liver cancer.

5 - If iron overload, I will donate whole blood and market it as not usable. If it is inflammation, then I it should be OK to take hololactoferrin even if ferritin is high.

Anything wrong? I am obviously trying to predict scenarios just to put my knowledge to the limit. Of course that UIBC and TIBC can help and I am ignoring them for academic purposes.

I think iron is causing a lot of problems in my liver...

 

 

 

Either way and in summary: If inflammation/infection is present and I can rule out iron overload, then I should supplement with lactoferrin and investigate more about the origin of the inflammation. If I am overloaded with iron, I should probably supplement with apo-lactoferrin and consider blood donation / discharge. Right?

 

thanks a lot!

Edited by a3mlord, 18 April 2019 - 04:18 PM.

[Dorian Grey]

"1 - If ferritin is high but TSAT is OK, then ferritin is an inflammation marker and it is fine to take hololactoferrin". 

TSAT really should be in the middle third of normal range,& not up near the top.  As long as TSAT is middle third, you should not have a substantial iron overload.  

 

I'm really not well read on lactoferrin, particularly hololactoferrin vs apo-lactoferrin.  I assume both are safe (but then I really don't know).  From what I gather, the immune modulation from lactoferrin is supposed to be beneficial, but I get a bit spooked about modulating my immune system when it seems to be doing fine as it is.  I know IP6 is supposed to increase natural killer cells, & I guess curcumin & quercetin have some immunomodulatory effects too.  I just couldn't understand the immune effects of lactoferrin when I tried to dig into the weeds, so I punted and stick with the more well known chelators (Curcumin, Quercetin & IP6)

 

Regarding question #2: again TSAT middle third of normal range is OK, upper (or lower) third not so much.  As long as there is no distinct advantage to hololactoferrin, I'd say why not simply go with the apo-lactoferrin.  As you note, "it shouldn't hurt"; and if you do have an iron issue, it should help.  

 

For question #3: I agree, it probably would be unusual to see normal hepcidin & iron with high ferritin, but then I really don't know as hepcidin is an expensive test (I've never heard of it actually being done).  I believe inflammation/infection related ferritin and hepcidin probably should rise in lock-step, but then I really don't know.  

 

#4: Ferritin & hepcidin should be high for a reason if they are elevated.  If there is no obvious reason for these elevations, yes, I would want to try and break the log-jam and let my body shuttle iron around normally.  BTW, yes, high hepatic iron, particularly iron staining on biopsy is strongly associated with HCC (liver cancer).  

 

#5: A single blood donation should produce significant results if iron related inflammation is what's causing ferritin elevation.  I've seen reports of ferritin dropping over 100 points with a single donation, when typically you'd only see a 30-50 point drop.  The other 50 must have been inflammation related.  If you see impressive results like this, then yes, I believe hololactoferrin should be fine.  You might wish to drop another pint of blood 3 to 6 months down the road.  

 

ALSO...  I'm not a doctor, so always wise to pester your own doc about anything you are considering, be it bloodletting or supplements.  If you're marginally anemic or might have anemia of inflammation, donating blood might be unwise.  It may help lower inflammation and break the homeostasis log-jam, but I assume it's also possible it may not, and if iron is low you might have trouble rebuilding red cells if you've got something else going on we haven't considered.  

 

A medical opinion from a real MD is always wise before you embark on any type of alternative quest for better health.  

[a3mlord]

Hi!

 

Thanks so much for your answer!

 

Let me ask additional questions, please:

 

TSAT really should be in the middle third of normal range,& not up near the top.  As long as TSAT is middle third, you should not have a substantial iron overload.

 

Is this true regardless of all other parameters? Meaning, if TSAT is in the middle third of normal range then there is no iron overload regardless of other parameters?

 

I'm really not well read on lactoferrin, particularly hololactoferrin vs apo-lactoferrin.  I assume both are safe (but then I really don't know).  From what I gather, the immune modulation from lactoferrin is supposed to be beneficial, but I get a bit spooked about modulating my immune system when it seems to be doing fine as it is.

 

Setting aside the immune modulating effect, the way I look at is: holo- is the equivalent to supplement with iron + the effects of lactoferrin itself (should not be used in iron overload cases), whereas apo- is a chelator of iron, that could (and probably should) be used in iron overload cases. Don't you agree? I understand you're concerned about messing up with the immune system if you're not 100% sure about the impact, though.

 

 

Regarding question #2: again TSAT middle third of normal range is OK, upper (or lower) third not so much.  As long as there is no distinct advantage to hololactoferrin, I'd say why not simply go with the apo-lactoferrin.  As you note, "it shouldn't hurt"; and if you do have an iron issue, it should help.  

I'm really not well read on lactoferrin, particularly hololactoferrin vs apo-lactoferrin.  I assume both are safe (but then I really don't know).  From what I gather, the immune modulation from lactoferrin is supposed to be beneficial, but I get a bit spooked about modulating my immune system when it seems to be doing fine as it is.

 

My point with the question was that even if TSAT is perfect (middle third), there could be an iron overload problem, if ferritin is high and hepcidin is high, but this COULD ALSO mean inflammation, and therefore other markers should be looked at. You agree?

 

Well, I think that if you are iron anemic (or with low iron in general), apo-lactoferrin MAY be a problem, as it will chelate some iron out (althouth the bound iron is more bioavailable, which is a weird thing). Do you agree? 

 

For question #3: I agree, it probably would be unusual to see normal hepcidin & iron with high ferritin, but then I really don't know as hepcidin is an expensive test (I've never heard of it actually being done).  I believe inflammation/infection related ferritin and hepcidin probably should rise in lock-step, but then I really don't know.  

 

 

Great we agree.  I live in Portugal, the lab just returned my email. It will cost me 40 euros (about $50). As I am asking for the entire iron panel, this could make sense (however it costs 40 euros to get ALL the other markers). Lactoferrin costs 60 euros, which is too much (and does not provide too much value, I think).

 

#4: Ferritin & hepcidin should be high for a reason if they are elevated.  If there is no obvious reason for these elevations, yes, I would want to try and break the log-jam and let my body shuttle iron around normally.  BTW, yes, high hepatic iron, particularly iron staining on biopsy is strongly associated with HCC (liver cancer).  

 

 

Absolutely agree. I think the body is way cleaver than we are. Sometimes it just gets stuck with the nasty things we do to it, and then it needs our help. But very rarely things go crazy for no reason.

 

The point of my question is that, when ferritin and hepcidin are elevated, it MAY be beneficial to lower hepcidin even at the cost of higher inflammation because this will help release some iron stored in the liver (in theory decreasing liver inflammation and chances of cancer) and reduce the chances of anemia. Of course, this may cause other problems - the problems the body is trying to prevent/mitigate by increasing hepcidin. Do you agree?

 

#5: A single blood donation should produce significant results if iron related inflammation is what's causing ferritin elevation.

 

 

 

 

I just remembered of a very interesting point. So if inflammation is there because of iron (and this is not necessarily captured or reflected through TSAT and the other markers, such as hepcidin), then holo-lactoferrin may not be beneficial, because it will increase iron even more.

 

I understand that you're not an MD but sadly I see no benefit in talking with one. Being severely ill for 6 years now, I learned that MDs are very little educated about these topics and tend to discard everything if lab values are not way too of the ranges. I may talk with a functional medicine doctor that specializes in metabolism, I would benefit a lot from that, I think.

 

Thanks a lot for your help. You're very knowledgeable and you surely helped me a lot!

[Dorian Grey]

The Iron Disorders Institute has a lot of reference material that may be helpful.  

 

http://www.irondisorders.org/

 

The site is a bit difficult to navigate, but their library page is here: http://www.irondisor...g/iron-library1

 

And there are a lot of good charts here: http://www.irondisor...OA ALL 2011.pdf

 

I don't really know for sure if inflammation related hepcidin elevation might push TSAT down, but TSAT is supposed to be the go-to lab when ferritin is elevated that should confirm or rule out iron overload or inflammation related ferritin.  Notice the normal range for TSAT from the Iron Disorders Institute is set narrower than many lab ranges @ 25-35.  Many labs put the upper end of normal higher at 40 or even 45, so 25 to 35 is what I call the "middle third" where you want to see TSAT.  I don't really know of any other good way to gauge iron loading other than this.  

 

Is your hemoglobin/hematocrit normal?  This is an important part of the puzzle too.

 

I really don't know all that much about the lactoferrin, but I'd be very weary of supplementing iron if ferritin is elevated.  The results from your iron labs should clarify what's actually going on. I'm very interested in your case, so hope you can share them.  Hope you get good numbers and we get clarification rather than more confusion!  

Edited by Dorian Grey, 19 April 2019 - 09:06 PM.

[a3mlord]

Hi Dorian

 

I am definitely posting my results once I get them! Thank you so much for the valuable info and help bud!

 

 

 

I don't really know for sure if inflammation related hepcidin elevation might push TSAT down, but TSAT is supposed to be the go-to lab when ferritin is elevated that should confirm or rule out iron overload or inflammation related ferritin.  Notice the normal range for TSAT from the Iron Disorders Institute is set narrower than many lab ranges @ 25-35.  Many labs put the upper end of normal higher at 40 or even 45, so 25 to 35 is what I call the "middle third" where you want to see TSAT.  I don't really know of any other good way to gauge iron loading other than this.  

 

If hepcidin is high, there will be less iron in the blood (due to ferroportin inhibition), but transferrin will be constant (unless I got it wrong)*. Therefore, TSAT will be lower.

 

*Are you aware of any transferrin - hepcidin relationship?

 

I get it that TSAT is the GO-TO after ferriting being high.

 

I also get it how you look at it in terms of "middle third". I learned to use quarters and work on the higher quarters when it is a good parameter and the lower quarter when it is a bad one. Ferritin could be good and bad, but mostly bad I guess (both because of higher iron and inflammation). Therefore, with a lab range of 25 - 40, we'd have Q1 = 25 - 28.75. This is where it should be according to this logic. If we use thirds, with an upper limit of 40, the ideal range would be 25 - 30 if we wanted 1T. For 2T it would be 30-35.

 

Hope all this makes sense and you agree. :D

 

Thanks! 

[Dorian Grey]

Regarding the TSAT, the Iron Disorders Institute's range of 25--35 is actually quite a reasonable "middle thirdish / optimal range" compared to what we find in Wikipedia, 

 

https://en.wikipedia...rrin_saturation

 

where they opine: "15–50% (males), 12–45% (females)" is a "normal range".  Precision isn't required, but TSAT under 20% or over 35-40% would be less than optimal in my humble opinion.  If I had ferritin up around 200 or more and TSAT of 40-45, I'd consider this a strong indication of excessive iron on board, even though this would be well within normal ranges for both, set by many labs.  

 

My personal sweet spot for ferritin is 50-80 and when I keep my ferritin within this range, my TSAT hangs right around 30.  I always check my iron labs 2-3 months after donating blood, so my TSAT of 30 would be my personal high end.  I do eat a lot of red meat & food in the USA is fortified with iron.  I also drink a bit of alcohol daily, which increases absorption of dietary iron, so I need to donate blood around 3 times a year to keep my iron labs where I want them.  

 

For a male who doesn't donate blood, TSAT of 35 wouldn't be unusual or alarming, but if ferritin is up over 200 and TSAT is closer to 40 than 35, I'd consider trying a donation or two (provided you are healthy enough to donate!), just to see if my symptoms improved.  Very little risk, and any possible reward would be priceless if this fixed you up.  Always best to ask your doc if he thinks donation would be safe for you if you have any chronic health issues going on.  

 

I really don't know about the hepcidin/TSAT relationship, but it would seem to make sense that if iron is in lock-down from high hepcidin, this might push TSAT lower and possibly mask an iron overload (but then I really don't know).  Let's look into how iron labs typically appear with the anemia of inflammation / anemia of chronic disease, and see if we can find what effect this usually has on TSAT.  I'll see what I can find.  

 

 

[Dorian Grey]

Ah!  https://www.med-ed.v...rcd/chronic.cfm

 

Looks like the anemia of inflammation / chronic disease DOES push TSAT lower along with serum iron, while ferritin often shows up high.  Looks like hematocrit also typically shows up on the puny side (30-40).  Don't know where this leaves us on trying to decide if your ferritin elevation indicates a true iron surplus or not.  About Ferritin...  The Iron Disorders Institute opines: 

 

http://www.irondisor...org/iron-tests/

 

Under Serum Ferritin (SF): "Serum ferritin measurements range from about 15–200 ng/ml for women and 20–300 ng/ml for men.  Although laboratory ranges vary, most are close to these values.  Approximately 95% of the population will fall within “normal” population range simply because ranges are calculated using standard statistical methodology.  Except for the lower ends of these ranges, which can predict anemia or iron deficiency anemia, the ranges per se do not define optimal or even healthy iron levels.  Optimal SF ranges for men and women are 25 – 75 ng/ml.  Individuals with risk factors for diabetes, cardiovascular diseases, stoke, liver diseases and cancer face amplified risks proportional to the amount of stored body iron over and above the optimal range.

 

Numerous medical research studies have demonstrated that serum ferritin above 100 ng/ml has been associated with decreased cardio vascular fitness and increased incidences of: atherosclerosis, type 2 diabetes, cancer gout and accelerated aging including osteoporosis and sarcopenia (muscle wasting) due to oxidative stress.  Fortunately this does not pertain to everyone; ferritin levels and stored iron can remain safely contained, even when ferritin exceeds 150 ng/ml, if the body’s natural antioxidant defenses are working properly (see section on GGT)."

 

--------------------------

 

The WHO (World Health Organization) opines: https://www.who.int/...um_ferritin.pdf

 

"Severe Risk of Iron Overload" in adults: anything over 200 for males, and a safe upper limit for females set at 150."

 

And lastly, the Mayo Clinic: https://www.mayoclin...ut/pac-20384928

 

"20 - 500 for males and 20 - 200 for females".  Ferritin of 500 in males normal?  Oh my!  

 

This is all very confusing, but what I gather from this is, ferritin elevations have become so common that many labs consider substantial elevations to be "normal".  Normal and Optimal are apparently very different things though!  

Edited by Dorian Grey, 23 April 2019 - 01:16 AM.