The extra iron in an iron supplement spills into the circulation. It’s DANGEROUS, so clearing it is a priority. Beta cells help but at a price.
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Unlocking the Hidden Dangers of Iron Supplements
The extra iron in an iron supplement spills into the circulation. It’s DANGEROUS, so clearing it is a priority. Beta cells help but at a price. Supplement wisely !
You’re taking an iron supplement, your reason :
- Maybe it’s because you are genuinely iron deficient. You’ve got the labs to prove it. Your hemoglobin and ferritin levels are low.
- Maybe it’s because you feel flat as a pancake and you’re hoping it will give you a bit of a lift.
- Maybe it’s an insurance policy. Iron supplementation is officially recommended for pregnant women and vegetarians
- You just want to be sure you’re covering ALL YOUR BASES i.e. it’s one of a host of supplements you take.
Whatever your reason – have you ever stopped to think about what happens when you take that supplement ?
Iron Overload and Beta Cells
Could there be unforeseen consequences for beta cells ? Iron overload has been implicated in bronze diabetes, this is the diabetes that strikes people with hemochromatosis.
So it’s a valid question and one that a team of Indian researchers decided to ask.
The chemistry of iron supplements
So let’s start with the basics, chemically speaking iron supplements are not equivalent to dietary iron. A variety of “chemicals” are used as iron sources in oral iron supplements. They always have the iron atom, which is identified as the ferrous atom and something else joined on. The something else varies and impacts the price.
So you get
- Ferrous sulphate
- Ferrous fumarate
- Ferrous glycerate
- Ferrous gluconate etc.
Sulphate is most often used, because it is significantly cheaper.
The iron is always a ferrous atom.
Dietary iron
Dietary iron comes in two forms :
Heme iron
This is the form iron is in, when you eat meat. Heme iron has it’s own unique biology, which is a story for another day.
Non-heme iron
This is the form of iron found in a variety of foods, most notably legumes. The iron atom is in the ferric form.
Ferric and ferrous are different.
The difference between them relates to the number of electrons the iron atom has lost. In the case of ferric iron, it has lost 3 electrons, which gives it a charge of plus 3 (Fe3+). In the case of ferrous, it has lost 2 two electrons (Fe2+), which means it still has an electron to play with.
Ferrous/ferric who cares ?
Chemically it matters……
Iron electrons DO biology
Iron MOVES electrons around : so that “spare” electron, in the ferrous form, is responsible for much of iron’s biology.
It facilitates lots of chemical reactions.
Good and NOT SO GOOD !
Making iron helpful and hurtful at the same time.
NOTE : There are multiple molecules working to keep iron atoms UNDER CONTROL, so they don’t unwittingly do harm.
The Importance of Iron Absorption
When it comes to biology the ferric/ferrous thing also matters, because it impacts iron absorption.
The ferrous form is what goes in.
This means dietary iron has to be CONVERTED.
Ferrireductase does the deed, but it’s not PERFECT i.e. not ALL the ferric iron becomes ferrous iron. When you consume ferrous iron……………
It’s ALL going in.
Iron’s Journey Through Enterocytes
Of course, going in does not mean getting in. When iron is absorbed it goes into the enterocytes (these are the cells that line your gut), but it often doesn’t come out. Enterocytes are sloughed off on a daily basis, so a lot of the time, they go to the “grave”, carrying the iron they picked up.
Hepcidin controls whether the iron is passed on.
As a rule, when you’re iron deficient, hepcidin is thin on the ground……..so more iron GETS IN.
Before we look at what happens next, I want to put things in perspective.
Hepcidin’s biology can be compromised
Hepcidin can be a NO SHOW, this is what happens in iron overload disorders e.g. hemochromatosis and blood transfusion therapies. But most of the time, when things go awry, the problem is hepcidin is being a problematic bully.
This happens when you’re insulin resistant and often happens when you suffering from a variety of chronic illnesses, including COVID. If you’re suffering from long COVID this might be an issue you want to explore for, watch this video to learn more.
So let’s get back to the iron.
Iron Transportation and Storage
Iron coming in, is transported to where it is needed. Every cell needs a little, but the biggest iron consumer are the cells responsible for making red blood cells. Because of the redox chemistry, the iron must be transported in specialized vehicles (transferrin) and any iron that is not being used, must be safely stored away (ferritin).
The liver carefully loads the iron coming in, onto the transferrin trucks.
Each transferrin truck can hold two irons. The number of trucks is finite, which can create a SITUATION. When there is more iron than trucks, the extra iron spills into the circulation. It’s referred to as NTBI (non-transferrin bound iron).
It’s DANGEROUS.
Cleaning up the excess iron
So cells that can clear the iron, step in and work hard to get this iron, out of the circulation as SOON as possible.
Clearing NTBI is primarily the job of liver cells.
They have a special transporter, the ZIP14 transporter, that grabs the “escaped iron” and brings it inside. Once it is inside, it gets shuttled to specialized iron storing molecules.
And everyone lives happily ever after.
Maybe…..
Sometimes the liver can get weighed under by the excessive load of iron. It doesn’t take a rocket scientist to work out, this is NOT HEALTHFUL. But, this is not the point of today’s story…..
All hands on deck
Since free floating iron constitutes a BIG RISK, when there is lots of NTBI circulating it’s a case of ALL HANDS ON DECK.
Any cell with a ZIP14 transporter helps clear the iron.
Beta Cells and Iron clearance
Beta cells are one of the cell types with a ZIP14 transporter. It’s there to transport zinc, not iron.
NOTE : Zinc is something that beta cells need LOTS OF, because zinc is co-secreted with insulin and plays a vital role in insulin signaling.
But, when the chips are down, the ZIP14 transporter brings iron into these pancreas cells.
Working as a team, NTBI levels don’t remain elevated for long, so there is nothing to worry about, right ? Well that is exactly what our team set about finding out.
Investigating the short term effects
A single dose of an iron supplement (120 mg ferrous sulphate) was given to healthy iron replete men. As expected serum iron levels and transferrin saturation increase after a single dose of an iron supplement.
Iron parameters during baseline and post?iron oral glucose tolerance test (OGTT). © 2022 The British Dietetic Association Ltd
What wasn’t expected was that glucose levels also rose. Remember, these guys were healthy. Anyone who was glucose intolerance was excluded from participating in the study. The difference is negligible, but significant.
Glucose concentration during baseline and post?iron oral glucose tolerance test (OGTT). © 2022 The British Dietetic Association Ltd
When the team probed a little further they established , the increase in glucose was most likely a reflection of changes in insulin kinetics.
Insulin concentration during baseline and post?iron oral glucose tolerance test (OGTT). © 2022 The British Dietetic Association Ltd
Oops. Too much of a good thing, became a liability, not just in theory, in reality !
Iron supplements hurt beta cells IN THE MOMENT.
It’s a short term effect. What about long term ?
Iron Supplements and Long-Term Implications
To date there are no studies that have directly linked iron supplements with type 2 diabetes. But, iron supplementation has been linked to gestational diabetes.
And removing iron, both physiologically (through blood letting) and chemically (using iron chelators) have been shown to be beneficial.
It’s food for thought !
Extra iron a liability
Taking “extra” nutrients and things, for insurance is something we’re encouraged to do – by health gurus and the media. BUT IRON is one of several supplements, you need to be weary of self-medicating with.
Iron supplements can be life saving, WHEN YOU NEED THEM, but can cause unexpected harm, when you don’t.
Supplement wisely.
Want a little help “scouting out” the supplements you’re taking ? Let me take a look at your supplement regimen and tell you what I think ! Are they helping or hurting your BODY CHEMISTRY ? Click here to book a call.
The association of iron status, supplement iron in the first-trimester pregnancy with gestational diabetes mellitus: A nested case-control study. J Obstet Gynaecol Res (2023) 49(2):597-605. Ying Lin, Chunli Wu, Rongjing An, Huixia Liu, Mengshi Chen, Hongzhuan Tan, Lizhang Chen, Jing Deng.
Further reading
Supplementing on iron biscuits ends up feeding the wrong kids
You only absorb the iron that YOU NEED. So, extra iron heads down south and the gut residents, get to feast on the leftovers. And feast they do…
When your iron deficiency is NOT an iron deficiency
If you’ve got iron issues……….but you do eat iron containing foods, odds are your problem is NOT too little iron, but too much hepcidin, thanks to too much insulin
The sting in the tail of a zinc supplement
Too much zinc deep inside the insulin secretory granules of beta cells, generates additional stress, especially if you’re insulin resistant. Supplement wisely !