“A Tale of TWO Irons & the HEPCIDIN peptide that regulates them & CAUSES Chaos, Confusion, Clinical Conditions, & thus Clinical Currency...”, by Morley Robbins

“People would rather believe a simple LIE, than the complex TRUTH…”
-- Lao Tzu (~600 BC)

For all intents & purposes, this Post on Iron Toxicity is a Modern-day Survival Guide in an Era when the ONLY clinical and robotic response to “Low Iron blood markers” is ignorance, apathy and MORE Iron…

Please KNOW, this Post = Complex TRUTH…
Your Doctor prescribing MORE Iron = Simple LIE…

Famous Chinese CURSE: “May you live in ‘interesting’ times…“ ;-)

Well Dorothy, we’re NOT in Kansas anymore, but we ARE living in MOST “I-ro-nteresting” times…

This Post will be among my last (Thank the Lord!...) to put to bed this ABSURD & ENTIRELY ENGINEERED CRISIS about Iron, Copper<>Iron metabolism and a COMPLICIT & TOTAL failure on the part of the Mainstream Medical System to sort out, and act on, the IRON TRUTH, as opposed to their IRON-ic & SIMPLE-MINDED TRAINING, which is simply INCOMPLETE…

I am APPALLED; and doctors – to a person – should be EMBARRASSED & THEN, ENRAGED!

These LAST 3 Posts will be in THREE Parts:
Part I: The Facts of Iron Anemia and what it REALLY stands for: “Low FUNCTIONAL Iron!”
Part II: Several KEY and SALIENT questions that YOU need to ask BEFORE taking Mo’ Iron!
Part III: The SPECIFIC blood tests that MUST be done BEFORE you take ANY action on your Iron!

Part I: The Facts of “Low FUNCTIONAL Iron”

Iron is a Janus-faced Mineral: It’s BOTH a Good guy AND a Bad guy…

Iron as “Good Guy”: “Iron forms the central cation of hemoglobin, other heme-containing proteins (such as myoglobin and cytochrome P450 enzymes including the mitochondrial electron transport chain), and iron-sulfur cluster-containing enzymes found in most cells [179, 180].” (Nairz et al, 2017)

Iron as “Bad Guy”: “Free labile forms of iron and heme, however, are potentially toxic and threaten tissue integrity due to their pro-oxidative properties which are largely based on the capacity of iron to non-enzymatically boost reactive oxygen species (ROS) production via Fenton chemistry [89, 119].” (Nairz et al, 2017)

(This TOXIC nature of Iron was 1st discovered in 1894 by H.J.H. Fenton, a British chemist at Cambridge University…)

It is worth noting that Iron is the #1 element on Planet Earth (36% of composition)…

It is worth noting that 80% of Iron – in the Human body -- is found in Hemoglobin protein…

It is worth noting that <10% of Iron – in the Human body -- is found in the Ferritin protein…

It is worth noting that Ferritin comes in TWO Forms: Heavy
form (with Ferroxidase function) & Light form…

It is worth noting that Ferritin has a transition relationship with Hemosiderin that relies on Ferroxidase enzyme function for optimal & healthy conversion between the two…

It is worth noting that the Ferritin protein is ONLY an INTRACELLULAR protein…

It is FURTHER worth noting that the Ferritin protein is NOT made in the serum, but is SECRETED into the serum, but NOTABLY under conditions of Liver Pathophysiology…

GIVEN ALL OF THE ABOVE ^^^^, it is WELL worth wondering WHY doctors ONLY measure Ferritin (but we have NO idea whether it’s the Heavy or the Light form…), and that from 1860-1972, ALL Clinicians & Scientists ONLY measured Hemoglobin (Hgb) to assess TRUE FUNCTIONAL Iron status. (Fox, 2003) When Hgb was LOW, these Clinicians & Scientists KNEW that this condition was a clinical sign of COPPER deficiency. (Please re-read that sentence, again, SLOOOOOOOWLY…)
I’m mildly curious, has your favorite M.ineral D.enialist EVER taught you ANY of these BASIC CLINICAL & IRON-ic FACTS?!?... And yet, when they claim – COMPLETELY INCORRECTLY, I might add – that "You’re Anemic!” – you respond like Lemmings to the Sea!... OMg!... Please MAG me with a spoon!... ;-)

Please know, chances are 99.9 out of 100 that you have LOW Ferritin because you have HIGH Iron in your tissue -- that does NOT show up in the Blood tests -- and is, for a fact, being CAUSED by an Inflammatory process – NOT an Iron deficiency state.

Inflammatory Chemicals, called Cytokines (esp. IL-6), CAUSE the uptick of Hepcidin synthesis, the very Iron regulatory peptide (hormone) that CAUSES Iron Storage during a state of Inflammation. I'm quite confident that you do NOT know your Hepcidin status, and the fact that you ONLY know your Ferritin status, and NOT EVEN your Hemoglobin status, is WHY you are soooo confused and yet, soooo Iron TOXIC, and are likely suffering from one or more of the 30+ Autoimmune conditions that are CAUSED by excess, stored Iron... Iron-ic, eh?!?...

OK, so let’s lay out these arguments with compelling clinical literature that YOU can use to educate YOUR doctor to the TRUTH of Iron, the TRUTH of Copper<>Iron metabolism, as well as the DANGERS of Iron supplementation:

1) Here is a very thoughtful and helpful overview of HOW the body responds to infection and what the metal dynamics are in response to THAT ubiquitous state: (Porcheron et al, 2014)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852070/

What I found particularly important in this study by Porcheron (2014) was the following:
- In response to infection, a cascade of host signals leads to increased sequestration [STORAGE] of Iron.
- Production of Interleukin-6 (IL-6) by immune effector cells is triggered, leading to binding of proinflammatory cytokines to Hepatocyte receptors [in the Liver] and to increased expression of Acute Phase Proteins (APP) involved in nutritional immunity.
- Among these,
o HEPCIDIN reduces release of iron into the circulation,
o FERRITIN promotes intracellular iron storage, and
o HAPTOGLOBIN binds free hemoglobin (Parrow et al., 2013)

2A) Here is a very recent and very understandable overview of Iron metabolism and the role of KEY proteins to manage this Janus mineral: (Nairz et al, 2017) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362662/
What is particularly important with regard to THIS ^^^^ study is the following:

“The presence of Fpn1 [Ferroportin] in the absorptive epithelium [tissue that absorbs…] is under negative control of HEPCIDIN, which is mainly secreted by Hepatocytes [Liver cells] in response to high circulating and tissue amounts of iron OR upon stimulation by inflammatory mediators [171, 229].”

Please NOTE, IL-6 – noted in the Porcheron, 2014 study -- is the grand-daddy of ALL Inflammatory mediators… The fact that your doctor has NEVER considered, NOR tested for, Inflammation should send a *CHILL* down your spine… And it’s worth noting that Iron, acting alone, can cause a RISE in IL-6…

2B) And please know that this is NOT new information that Inflammation causes LOW Iron levels in the blood, known formally & clinically as “Hypoferremia.” It has been a mainstream medical FACT for at least the past 30+ years… (Beaumier et al, 1984)
http://iai.asm.org/content/46/2/489.full.pdf

3) Now, next to understanding the importance of the role that Inflammation plays in these Iron dynamics is understanding the PROFOUND role of Iron Recycling, which I have termed “R.E.cycling,” to properly acknowledge the role of the Recticulo-Endothelial System, aka RES, which relies on Macrophages [cellular Pac-men] to gobble up the dying Red Blood Cells (RBCs), and ideally, release the Iron consumed in this process into making NEW RBCs… Two excellent articles that explain these amazing dynamics are noted here:
- Kong et al, 2008: http://www.sciencedirect.com/…/article/pii/S1002007108002384
- Soares et al, 2016: http://www.cell.com/immunity/pdf/S1074-7613(16)30054-1.pdf

I will assert that if AFTER reading & studying -- JUST THE DIAGRAMS -- in the Soares article, and you STILL think that a lame, Ferritin-ONLY blood test, from the Serum, properly captures the ENTIRETY & PROFOUND complexity of Copper<>Iron Metabolism -- INSIDE THE CELL, then you simply DESERVE to be called "Anemic!..."

4) What we learned recently (Iron Toxicity Post #56) was that these Macrophages can AND DO GET OVERWHELMED with too much Iron. The lack of Bioavailable Copper via Ceruloplasmin Oxidase, aka Ferroxidase, prevents the PROPER release of Macrophage-held Iron. And when that happens, they perform very differently, and these Iron-laden Macrophages create Immune System Mayhem and CAUSE a break-down in Iron R.E.cycling: (Weiss & Goodnough, 2005)
https://www.med.unc.edu/medselect/files/anemia2.pdf

5) What we’ve also learned – in several Iron Toxicity Posts – is the FOUNDATIONAL importance of having Ceruloplasmin Oxidase, aka FERROXIDASE enzyme function, to ALLOW proper Iron egress [release] from the cells, esp. the Macrophages: (Musci et al, 2014)
https://www.ncbi.nlm.nih.gov/…/PMC4050113/pdf/wjbc-5-204.pdf

6) And then these Iron-Ic concepts and regulatory conditions took a RADICAL turn when we learned that Iron, in and of itself, ACTIVATES what is called the Inflammasome via stimulation of the NLRP3 protein! This is otherwise known as the cellular “DANGER” sensor, that triggers the Inflammatory cascade of Cytokines, Chemokines and other Acute Phase Proteins (APPs). Again, IRON ACTIVATES THE CELLULAR DANGER SIGNAL! This then creates the very conditions to ensure a CHRONIC INFLAMMATORY STATE. Please read about this Iron-induced mechanism here: (Nakamura et al, 2015)
http://www.exphem.org/article/S0301-472X(15)00730-4/pdf

7) And finally, It is worth knowing that Iron supplements, in and of themselves, CAUSE an INCREASE in HEPCIDIN synthesis and release from the Liver cells, aka Hepatocytes. In a way, I wish I were making up this mind-bending reality, but the fact of the matter is, the VERY ACT of IRON SUPPLEMENTATION CREATES MORE IRON STORAGE… I, too, was STUNNED to learn this Iron-ic reality over the weekend!... (Moretti et al, 2015)
http://www.bloodjournal.org/…/bloodjou…/126/17/1981.full.pdf

There you have it folks, two SOLID years of research boiled down to 8 scientific articles, from hundreds that I read, that say the following:

o STOP thinking that you’re dealing with “Anemia of Iron Deficiency”…
o START knowing that you’re dealing with “Anemia of Chronic Inflammation,” which means TOO MUCH Iron…
o STOP beLIEving in the “accuracy” or the RELEVANCE of the Ferritin-ONLY blood test!...
o START understanding that Iron-laden Macrophages are the CAUSE of ALL Autoimmune conditions…
o STOP taking Iron Supplements – they are ONLY CAUSING MORE IRON STORAGE & thus MORE INFLAMMATION!...
o START demanding BETTER & MORE RELEVANT blood tests to find out your TRUE Copper<>Iron metabolic status…
So in my NEXT Post on Iron Toxicity, I will DRILL INTO the proper questions to ask and then the proper tests and testing panels to use that will get you out of this Iron-ic state of confusion & clinical chaos…

A votre sante!

P.S. The lone graphic comes by way of an Important Iron-focused presentation by Marc J. Kahn, MD, MBA, entitled “Iron – Too Much, Too Little, Too Late” (pg 37 of 61)

Source: https://www.facebook.com/groups/MagnesiumAdvocacy/permalink/1366914676709931/