Iron, Rust and Immune Reactions
Updated: Dec 20, 2022
I've argued that the overconsumption of iron in enriched flours is the determining factor in the inflammation that results in Type I diabetes. Your liver, typically tasked with blood cell recycling and the site of the body's iron recycling system, stores iron in its own tissues in states of iron excess. But chronic states of iron excess means that the liver runs out of places to store it. So it begins to stash it in neighboring organs. Namely, the pancreas. Beta cells are particularly sensitive to iron because of the localization of the protein hepcidin which is responsible for a cell's iron uptake.
So there's iron in your beta cells. So what? What's the big deal with iron and, if the body ultimately needs iron and has proteins like hepcidin, why is it so toxic?
The first thing to clarify is that all of this only comes about because of iron excess. I'm not arguing against iron-containing foods. Iron is not a villain to be stricken from your diet. Meats, legumes and even unenriched flours have naturally occurring iron. After all, it's one of the most abundant elements on planet earth. So all of the mechanisms and reactions I'm about to talk about only come about when you get too much.
The next step is to define toxicity and understand what warrants inflammation to your body's natural immunity. Toxicity comes about in states of excess where the body's reactions and internal processes are skewed to an outcome without the ability to buffer or properly dispose of the byproducts of those processes. Inflammation results as the body identifies the accumulated byproducts as a threat to the body's survival and up-regulates its immune system to handle the threat. When we talk about iron the byproducts our immune system are concerned with are reactive oxygen species (ROS). The National Cancer Institute defines ROS as:
A type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell. A build up of reactive oxygen species in cells may cause damage to DNA, RNA, and proteins, and may cause cell death. Reactive oxygen species are free radicals. Also called oxygen radical.
Chemically speaking, ROS refer to any of three molecules: H2O2(hydrogen peroxide), O•−2 (superoxide radical), and OH• (hydroxyl radical). Hydrogen peroxide you know. That's the wound clearing liquid you use on cuts and burns, clearly reactive in its familiar bubbling that occurs when it reacts with a broken cell. O•−2, or superoxide radical, is an oxygen (O2) molecule that's missing an electron. OH•-1, or hydroxyl radical or hydroxide, is a constituent of water and is commonly known in caustic things like sodium hydroxide, or lye.
A step further would be to specify the exact type of iron that elicits such toxic behavior. Because iron is everywhere in your body, but not always wreaking all the havoc I'm talking about. Free iron, or unbound iron, is what we're talking about. Bound iron, like that found in the blood attached to heme, is not reactive because of it's being active with another compound. Think of it like a mischievous toddler. Give them something to do or they'll destroy your house.
In the context of the body, the excess iron that the liver is unable to recycle effectively is stored in the liver tissue (and eventually elsewhere). By being in the cell that free iron comes into contact with water (H2O) and oxygen (O2). You don't have to be a chemist or scientist to know what happens when iron meets oxygen and water. It rusts. But what is rust?
The processing of rusting happens in a sequence of steps. The first of which is the dissolution of iron into solution:
Fe(s) → Fe2+(aq) + 2e-
It's imperative to remember that liquid water (H2O) remains in a constant state of flow between water and it's constituents, hydrogen ion and hydroxide:
The 2 electrons from the dissolved iron react with the hydrogen (H+) and oxygen to form water.
4e- + 4H+(aq) + O2(aq) → 2H2O(l)
The above equations don't actually result in rust yet, but let's think about the implications thus far. Every dissolved iron molecule emits two electrons, which then reacts with an equal number of hydrogen to create water. Not terrible. But with those hydrogens (H+) getting tangled with the electrons, that leaves an abundance of hydroxide (OH-).
The iron molecule goes through 2 additional steps to reach it's final red, crusty state:
Fe3+(aq) + 3OH-(aq) → Fe(OH)3
Notice those 3 hydroxides. And the important thing to note about iron (III) hydroxide is that it is unstable at neutral pH. Human blood is neutral. So that means that the iron hydroxide will not remain whole for very long. It instead tends towards Fe3+ and OH- in solution.That's a lot of hydroxide to be floating around the cell.
Now, our cells aren't entirely unfamiliar with ROS. They play an important part in our natural ability to neutralize bacterial infections and have been shown to signal repair mechanisms in the cell. People with compromised abilities to generate ROS suffer far more bacterial infections than normal.
But, again, excess is the issue. Too many ROS and the immune system starts to interrupt the natural functions of the organs it's trying to protect. Imagine this: the beta cells have taken on free iron once the liver has become saturated. Oxidized iron emits hydroxide as it reacts with oxygen and water. Seeing an abundance of ROS, the immune system targets the beta cells to the point where they lose their function. Or maybe that the ROS have accumulated within the mitochondria of the cell to a level that alters the DNA, RNA or protein function of the beta cell. Insulin becomes an unintended victim of the immune reaction or is incorrectly coded for after the RNA that codes for it is altered.
Am I crazy for thinking this is VERY viable?
And why stop at diabetes? Iron overload doesn't just affect beta cells. Iron has also been tied to gastrointestinal issues as well. Iron contributes to the growth of proteobacteria in the gut, thus altering a healthy microbiota. Irritable bowel syndrome (IBS), celiac disease and Crohn's disease are on my list of suspected results of this iron condition.
The cosmetic industry will have you believing 1 of their 100000 creams and ointments is the cure to your wrinkles and liver spots. But did you know that oxidation and ROS are at the center of all signs of aging? That $120 night cream is like putting a band-aid on a bullet hole. You're wrinkling and balding from the inside, not the outside.
Fertility issues? PCOS? Ironic that these issues are coming about the same time as everything else. I'd put my money on it all being connected.