MAG-pie and MAG-net Alert!
Iron Toxicity Post #56: “You are NOT Anemic!”, at least NOT Anemic from “Iron Deficiency!”
Yes, I’ve said this before, but I’m gradually assembling the research that is making it PATENTLY OBVIOUS that this ubiquitous “D”eclaration that MANY, MANY, MANY MAG-pies & MAG-nets are terrorized with re their Iron status is an absolute case of MYTH-TAKEN Identity…
Your LOW Ferritin is NOT a sign of “Anemia of Iron Deficiency.” (Please RE-READ that sentence again, take a tug on your seat-belt, and settle in for some VERY unsettling TRUTH about what is REALLY going on…)
But what you MOST likely have is what is deemed as “Anemia of Chronic Inflammation” (and it is ALSO called “Anemia of Chronic Disease,” which phrase I elect NOT use, as I seem to “D”etest words that start with & Vitamins that end with the letter: “D!”… 😉 )
So, here’s what I learned this am while waking up to my daily Cup of Joe and reading this short but VERY IMPORTANT article by Fiorelli et al, 2007 (link noted below):
- In “Anemia of Chronic Inflammation” (ACI): serum Ferritin can be normal or increased & serum Transferrin Saturation (% Sat) are USUALLY associated with LOW Hemoglobin levels and RBCs that are either normal (normocytic) or small (microcytic) – when did you LAST measure Hgb?…
- There is a Pathophysiological mechanism with ACI – which will NOT show on ANY typical blood test – that results in INCREASED uptake & retention of Iron in Active Macrophages…
- This uptake & retention of Iron – that, again, does NOT show on blood tests – is linked to Increased Pro-Inflammatory and Increased Anti-Inflammatory Cytokines (esp. IL-6…)
- This uptake & retention of Iron – that, again, does NOT show… — is responsible for DECREASED availability of Iron for cells to make new RBCs (aka, Erythroid Progenitors)
- There is an Increased expression of Hepcidin – IN RESPONSE TO INFLAMMATORY STIMULI – that CAUSES the retention of Iron in these cells… (that is a MAJOR BIG DEAL, folks!…)
- The Hepcidin peptide (a 25 Amino Acid peptide considered to be the “Iron Regulatory Hormone”) may be cytokine-regulated, which CAUSES impaired Iron acquisition, by restricting the release of Iron from Macrophages… (because of Hepcidin’s impact on Ferroportin…)Fiorelli, 2007, serum Ferritin & Transferrin Saturation in Anemia of Chronic Inflammation.. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581906/
OK… that’s A LOT of blah-blah-blah and a bunch of metabolic switchbacks, but It’s Scientific GOLD, as it lays out the rationale and the reality of this HIGHLY prevalent condition of “deficiency” that many, many, many folks are afflicted with… And please understand, this condition of ACI is CAUSED by a LACK of Bioavailable Copper, that has profound impacts on downstream metabolic events involving Iron, as we have explored and discussed on numerous occasions…
Furthermore, Fiorelli added EVEN GREATER value by referencing the DEFINITIVE study, in NEJM no less, that explains how ALL of this ACI chaos happens. I want EACH & EVERY ONE OF YOU to take a moment and read this important article by Weiss & Goodnough (btw, don’t you just LOVE those names: “Wise” & “Good-enough”?!?… 😉 )
Please read this article SLOOOOOOOOOOWLY… It may be one of the MOST important articles referenced in this series of Posts on Iron Toxicity.
Weiss & Goodnough, 2005, Anemia of Chronic Disease: https://www.med.unc.edu/medselect/files/anemia2.pdf
Figure 1 (Below…) comes from this KEY study by Weiss & Goodnough.
So here’s my question: “Do you HONESTLY believe that the outrageous complexity that is implied in this Picture is ACCURATELY or COMPLETELY captured by the simple, & single myth-leading blood marker called, Ferritin?!?…
I mean, REALLY?!?…
I would go so far as to suggest that ANYONE being informed by their favorite M.ineral D.enialist that they are “Anemic!” should be REQUIRED to read this 2005 article from NEJM, and then EXPLAIN HOW the intracellular protein, Ferritin, covers ALL of those bases & sites of metabolic action… And please keep in mind that our Iron-hero, Sir Douglas B. Kell, PhD, world renowned EXPERT on Ferritin, not only thinks, but has documented that Ferritin is found INSIDE the cell, and that the serum level of Ferritin should, for a fact, be ZERO!…
Hmmmmmmmmm… Who else is feeling a bit queezy right about now?…
So, it turns out that this dynamic between Iron and the Inflammatory process is REALLY important and has been the subject of MUCH research. For those that want to REALLY dig in, please explore the compelling research & writings of Marianne Wessling-Ressnick:
Wessling-Ressnick, 2010, Iron Homeostasis and the Inflammatory Response
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108097/pdf/nihms294977.pdf
My favorite comment from her study: “The evidence that supplemental iron can PROMOTE BOTH [emphasis added] Infectous and chronic Inflammatory disease is clear…” Certainly, your doctor has brought this KNOWN fact about how IRON FEEDS PATHOGENS to your attention, right?…
And continuing down this rabbit hole of IRON-IC TRUTH are the compelling articles by Nancy Andrews, MD, PhD. She seems to have a knack for simplifying what, at times, can be a most daunting topic. I simply LOVE her diagram of the process of Iron Recycling, presented as Figure 2, which highlights the dynamic and fluid aspects of Iron metabolism.
Again, Iron is MEANT to be in constant circulation… The process of Iron inside the Human Body is an elegant Square Dance where movement & motion are derigeur…
WHY, OH WHY, are we using an INTRACELLULAR IRON-STORAGE protein, i.e. Ferritn, to assess the complexicity, importance and elegance of Copper<>Iron metabolism?!?… And again, Ferritin is NOT supposed to be in the serum — in the 1st place!
For those that take the time to read this, please enjoy the short Bio on Nancy C. Andrews, MD, PhD, now Dean of Duke University School of Medicine – she is one of the GREATS of the field of Hematology…
Andrews, NC “The Golden Age of Iron Biology” http://www.bloodjournal.org/content/bloodjournal/112/2/219.full.pdf?sso-checked=true
And an even better, crisper and shorter article by Dr. Andrews is one where she draws the KNOWN link between the Inflammatory Cytokines and their notable impact on the expression of Hepcidin, that THEN affects the RETENTION OF IRON INSIDE THE MACROPHAGE… What I especially LOVE about this article is the VERY SIMPLE, but PROFOUND diagram of:
– HOW Inflammation affects the Macrophage,
– which CAUSES the release of the Inflammatory Cytokine, IL-6,
– which STIMULATES the synthesis & expression of Hepcidin
– that then BLOCKS Macrophage Iron Release AND BLOCKS Intestinal Iron absorption.
This is depicted at Figure 3 below…
An important question for those who are STILL taking Iron supplements, yet are experiencing NO CHANGE in their Iron status: “Has your doctor explained HOW Iron supplements CAUSE Inflammation that then TRIGGERS the actions depicted in this diagram?!?… Here’s the link to Dr. Andrews insights about this Cytokine<>Hepcidin dynamic:
Andrews, NC “Anemia of Inflammation: the Cytokine-Hepcidin Link” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC398435/pdf/JCI0421441.pdf
For those that are NEVER satisfied with enough, here’s are some BONUS reads that will shed important light on these IRON-IC dynamics, particularly as it relates to the dampening affect that Inflammation has on the accessibility of Iron in the human body:
Karolnek, et al, 2016, “Iron Trafficking at Birth & Death of RBCs” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424413/
Nairz et al, 2016, “Iron deficiency or Anemia of Inflammation?” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065583/
OK, enough of that… Now let’s get down to some BRASS TACKS… (Brass is made of Copper, right?…)
What’s REALLY going on here?!?… Where’s Copper/Cp in ALL of these diagrams?!?… I thought Ceruloplasmin, esp. via it’s Ferroxidase function, was CRITICAL to these Iron issues?!?…
Patience, Grasshopper, you are absolutely RIGHT! And we’re just about to point that out!
We have discussed this several times before, but the UBER-gifted Italian researcher, Giovanni Musci, has CLEARLY demonstrated how Ceruloplasmin is ESSENTIAL for the proper functioning of Ferroportin to ALLOW PROPER & NATURAL IRON RELEASE from cells, and macrophages, in particular. This is pointed out in Figure 4, and please pay particular attention to Diagrams A, and note in Diagram D HOW Hepcidin’s presence KILLS the Iron-egress function of Ferroportin and also disempowers the supporting role of Ceruloplasmin in these critical dynamics to move Iron out of the cell.
Again, that is the GIFT of the Ferroxidase function of Ceruloplasmin – it ENSURES proper Iron mobilization and circulation in the body. If you haven’t already done so, please enjoy reading this seminal study by Dr. Musci:
Musci et al, 2014, “Ceruloplasmin <> Ferroportin System https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050113/
To me, Figure 3 absolutely SUMS IT UP. The ONLY word missing in that simple diagram is the word: IRON. It is, indeed, the pivotal agent to CAUSE Inflammation… Please KNOW that.
So, what to do?… Here are some suggestions.
- STOP thinking that you have a deficiency of Iron…
- START thinking that you LIKELY have “Anemia of Chronic Inflammation,” a condition that is caused by a LACK of Bioavailable Copper, AND excess, unbound Iron sequestered in the tissues…
- START understanding the complexity & elegance of Copper<>Iron metabolism…
- In the event you are told you are “Anemic,” do NOT panic! Simply ask the Doctor to:
- Read the NEJM Article by Weiss & Goodnough…
- Ask the Doctor to explain HOW the Intracellular storage protein, Ferritin, is related to & regulates ALL facets of the Iron dynamics shown in that Article (our Fig 1 below…)
- Request the FULL Monty Iron panel…
- Be sure to ADD a marker for Hemoglobin, esp. given that this accounts for 70% of the Iron in your body, as opposed to the ~10% that is represented in Ferritin…
- Please get these additional blood tests PROPERLY interpreted before taking any action…
- START the Root Cause Protocol, particularly in the event you have Copper<>Iron dysregulation
- START donating blood on a regular basis
- 2 times/year for menstruating women
- 4-6 times/year for menopausal women or men
- Have faith that your body will return to homeostasis, as well as proper metabolic balance…
- START to share these TRUTHS & ACTIONS with your loved ones…
And that’s ALL folks!
We are engaged in a wholesale “re-wiring” of the mind and our understanding of what factors are genuinely important to assess our Copper<>Iron metabolism. Again, these two critical metals – that SHAPE the function of the Liver – are joined at the Hip of Ferroxidase enzyme function of Ceruloplasmin. It is VITALLY important that you internalize that and be sure to teach that to your doctor or health practitioner that you might be working with.
I truly hope you find this latest treatise on Copper<>Iron dynamics helpful and healthful!
As always, I will look forward to your comments, your questions, your insights and most of all, your SHARES!…
Have a blessed weekend!
A votre sante!
Morley Robbins
