Iron

Hepcidin, the switch almost nobody is told about

Hepcidin is a small hormone made by the liver, and it is the master control on iron in the body. Understand hepcidin and you understand iron. It explains more of what you will see on an iron panel than any of the markers do on their own.

It works through a single target. Every cell that releases iron does it through one exit protein called ferroportin, whether that is a gut lining cell, a storage cell in the liver, or a macrophage recycling old red cells. It is the only door. Hepcidin binds to that door and causes it to be pulled inside the cell and destroyed.

So hepcidin does not block iron from entering cells. It traps iron inside them. When hepcidin is high, iron absorbed from food stays stuck in the gut lining and is lost when those cells are shed a few days later, and iron held in storage cannot be released into circulation. When hepcidin is low, the doors stay open and iron flows.

Four things follow directly from that one mechanism, and they are usually explained separately as though they were unrelated.

Inflammation raises ferritin and lowers serum iron at the same time. Inflammatory signalling drives hepcidin up, which closes the doors. Iron is locked into storage, so ferritin rises, while the amount circulating falls. It looks contradictory on a report and it is one mechanism producing both halves.

It is also why a very high ferritin is not read as a lot of iron. Ferritin climbs with almost anything that inflames the body, so a mildly raised figure is usually unremarkable. Above roughly 1000 the list of explanations narrows to liver disease, heavy alcohol use, significant infection, some cancers, and genuine iron overload. Figures in the thousands or tens of thousands are a different category again and point at a small group of serious conditions rather than at iron at all. A ferritin in that range needs looking at quickly, whatever the rest of the panel says.

Testosterone drives iron consumption. Testosterone suppresses hepcidin, opening the doors and releasing iron into circulation, alongside a push on red cell production through erythropoietin, the kidney signal described in the section above. That is why a rising haematocrit is one of the most common adverse effects of testosterone therapy, and why ferritin often falls in people whose haematocrit is climbing.

Two things matter here if that is you. The first is that haematocrit is a concentration, not a count. Turn up dehydrated and it reads higher with no change whatsoever in the number of red cells you actually own. A lot of alarming haematocrit results are a dehydrated morning rather than a problem, which is the single best argument for drinking properly before any blood test.

The second is that clinicians commonly suggest giving blood, and it does work, because taking blood out takes the red cells and the iron inside them with it. It is not a fix for the cause, which is usually the dose. Donation has its own eligibility rules in the UK and they are worth checking with the blood service rather than assuming.

Reduced kidney function raises it. Hepcidin is cleared by the kidney, so as filtration falls it builds up and iron is held in storage. That is one of the two reasons anaemia and reduced kidney function travel together, and the Kidneys section covers the other.

Genetic iron overload is a hepcidin failure. In the inherited form of haemochromatosis, hepcidin stays inappropriately low. The doors never close, absorption never switches off, and iron accumulates over decades with no way to get rid of it.

Both too little and too much iron cause problems, which is why the profile looks at several angles rather than one number.

What the profile looks at

Iron is the amount circulating at the moment the sample was taken. It is the most volatile thing on the panel and on its own it says very little.

Total iron binding capacity and unsaturated iron binding capacity describe the carrying capacity available, which is how much transferrin is waiting empty. Transferrin is the protein that carries iron through the blood, and the body makes more of it when iron is short, so binding capacity tends to rise as stores fall, moving in the opposite direction to everything else. A high binding capacity therefore points towards low iron, not high.

Transferrin saturation puts those 2 together as a percentage, which is how full the transport system is. More stable than iron alone, and generally more informative. Around 20 to 45% is the usual range. Below roughly 20% points towards iron deficiency. UK gastroenterology guidance and the American haematology guidance published in 2026 both use that figure. Above 45% starts pointing the other way to iron overload, which is covered later.

Ferritin is the storage protein and the usual first stop for assessing stores. It is also an acute phase protein, so it rises during inflammation and infection regardless of what the stores are doing. Hepcidin is the reason. It locks iron into storage, which pushes ferritin up and serum iron down at the same moment. One mechanism, two movements that look contradictory.

That interaction is the reason to look at inflammation markers alongside iron rather than separately.

The order things fall in

Iron deficiency does not arrive all at once. It moves through stages, and the markers change in a predictable sequence. Knowing where you are in that sequence is what makes this profile readable.

First, ferritin falls. Stores begin to empty in order to keep circulating iron at a steady level. At this stage everything else on the panel is normal, and so is the full blood count.

Then transferrin saturation falls. Stores are completely emptied, so the transport system starts running emptier. The body makes more transferrin to compensate, which is why binding capacity rises while saturation drops. Still no anaemia.

Haemoglobin falls last. Only when supply can no longer keep up with red cell production does the blood count finally change.

Two consequences matter. You can be genuinely iron deficient with a completely normal full blood count. In fact that is the usual picture, because the blood count is the last thing to go. And ferritin is the early warning precisely because it is the first to move, which is why it is one of the most important markers in the profile.

The sequence also explains why the size of the drop tells you very little. Somebody can have a haemoglobin sitting barely below the bottom of the range while the rest of the blood count is clearly abnormal and their ferritin is down at 8. Haemoglobin is the last domino, so by the time it moves at all the shortage behind it has usually been building for a long time. How far it has fallen is a poor guide to how depleted somebody actually is.

There is one number on the full blood count that moves earlier than the rest. Red cell distribution width, or RDW on your report. It is the spread of cell sizes, and it widens while the average is still normal.

Recovery runs the same sequence backwards, which is why ferritin takes months to rebuild after haemoglobin has already normalised. Stopping treatment when the blood count looks fine leaves the stores empty and the problem returns.

Low iron is a sign of something, not the answer

This is the part most often skipped. Iron deficiency always has a cause, and taking iron treats the number rather than the reason the number moved.

In a woman who is still menstruating, heavy periods are by far the most common explanation and often can be the whole story. In a man, or in a woman past the menopause, there is no routine way of losing iron at all. So unexplained deficiency in those groups means something is taking it, and the source needs finding. The usual suspects sit in the gut: coeliac disease, which is more common than most people think, or slow bleeding from somewhere in the bowel that is invisible to the eye.

The reason this is taken seriously is bowel cancer. Unexplained iron deficiency anaemia is one of the recognised warning signs, because a tumour in the bowel can bleed slowly for a very long time without ever being visible. It is not the likeliest cause and most people investigated will not have it. But it is the one to rule out first, and national guidance treats unexplained iron deficiency anaemia in a man of any age, or in a woman past the menopause, as grounds for urgent investigation rather than a trial of iron tablets.

Neither of those tests is something we sell, and you should know about both. Coeliac serology is a simple blood test any GP can arrange and it is sold privately too. A faecal immunochemical test, usually called FIT, looks for blood in a stool sample at concentrations you would never see, costs very little, and is now the front door to bowel investigation in the NHS.

Bowel screening starts in your 50s in England, Scotland and Wales, and at 60 in Northern Ireland, but those are population screening ages rather than a rule about who is allowed the test. A GP will usually arrange a FIT at a much younger age for someone with symptoms or with unexplained iron deficiency. Ask for it. Do not assume you are too young.

The reason to emphasise the point is that iron tablets will raise the number either way. If the cause was worth finding, raising the number is exactly what stops anybody looking for it.

What hepcidin means for taking iron

This is general physiology rather than advice about your own treatment, and anything you take should be discussed with whoever prescribed it. But it is well established, it follows directly from the mechanism above, and it is not yet what most people are told.

An oral iron dose raises hepcidin within about 6 to 8 hours. That rise persists for roughly 24 hours and has returned to baseline by 48. Which means a second dose given the same day, or the next morning, arrives while the doors are still being closed by the first one, so a much smaller amount of it gets through.

The effect is substantial. Alternate-day single doses produce around a third more absorption than the same amount given daily. A 200 mg dose on alternate days delivers roughly twice the total absorbed iron of 100 mg on consecutive days. And splitting a daily dose into morning and evening, which sounds gentler, does not improve absorption at all. The same total taken in one go is absorbed just as well, and splitting it pushes hepcidin higher, so there is nothing to gain from it.

At equal total iron, alternate-day dosing matches daily dosing for raising ferritin, and is better tolerated, with fewer effects on the gut.

Most guidelines and most textbooks still describe daily dosing. UK prescribing guidance has moved a bit with the BNF dropping divided doses for once daily in 2023. It states alternate-day dosing as the fallback where daily is not tolerated. Plenty of practice has not caught up which is why doing your own research can help a lot. That gap between what is established and what gets said in a ten-minute appointment is one of the reasons this guide exists.

Which iron, and what to take with it

Three things come up constantly, and on all three the evidence is not what people assume.

Ferrous bisglycinate. Iron chelated to two glycine molecules, sold as the gentle one. The claim usually made for it is better absorption. That is not really what the evidence shows.

What it does show is that bisglycinate matches ferrous sulfate for raising haemoglobin and ferritin at a lower elemental dose, with far fewer gut side effects. It can be taken with food without losing much, and it is much less bothered by the things that block ordinary iron, like tea, coffee, calcium and the phytates in grains.

That still counts for a lot. Side effects are the main reason people stop taking iron, and iron you stopped taking absorbs nothing at all. So bisglycinate is not magic. It is just far easier to keep taking, and that is most of the battle. It costs 3 to 5 times more, and that is the trade.

Vitamin C. Everyone says take it with iron. The mechanism is real. Vitamin C holds iron in the form the gut can absorb, and in lab work it clearly improves absorption from a single meal.

Then somebody ran the trial. Adults with iron deficiency anaemia, iron alone against iron plus vitamin C. At 8 weeks the haemoglobin and the ferritin had moved by the same amount in both groups. Side effects were the same too. American gastroenterology guidance published in 2024 still says to add vitamin C. The one proper trial says it makes no difference.

It is cheap and it is harmless, so this is not worth arguing about. Just know it is a habit rather than a finding.

Lactoferrin. The iron-binding protein in milk, and in your own tears and saliva. It has been tested against ferrous sulfate in a number of trials, mostly in pregnancy, and pooled together it comes out ahead on haemoglobin and iron levels with fewer side effects.

Why it works is not the obvious reason. Lactoferrin does not seem to improve iron absorption much at all. The likeliest explanation is that it lowers inflammation, lower inflammation means lower hepcidin, and lower hepcidin opens the doors. If that holds, lactoferrin is not really an iron supplement. It is a hepcidin supplement that happens to carry iron.

Those trials are smaller and patchier than the dosing work above, so it sits a step below. It is still an option to consider, particularly if you cannot tolerate tablets at all.

When tablets are not the answer

All of the above assumes tablets work. For a lot of people they do not, either because the gut will not tolerate them or because absorption cannot keep up with what is being lost.

The alternative is an iron infusion, and most people have no idea it exists. A single infusion can deliver in under an hour what months of tablets would struggle to, because it goes straight into the blood and bypasses both the gut and hepcidin entirely. The preparation used across the NHS is ferric carboxymaltose, and it is the same one used privately.

On the NHS it needs a referral to haematology or gastroenterology, and waits vary enormously by region. Privately it is available on self-referral at a number of clinics for several hundred pounds depending on the dose. If you go that way, check that the clinic uses ferric carboxymaltose or an equivalent, and that a full iron panel has been done first, because the dose is calculated from your results and your weight rather than picked off a shelf.

It is not a first step and it should not be. But if you have spent 6 months on tablets and your ferritin has barely moved, that is information in itself, and the answer is not always more tablets.

What changes when iron is low or high

Falling iron tends to produce tiredness out of proportion to activity, breathlessness on exertion, pallor, brittle nails, hair shedding, poor concentration, and in some people restless legs. As the sequence above explains, stores are usually depleted well before haemoglobin falls, so the full blood count can look entirely ordinary while iron is running down.

Iron overload is less common and is often inherited. It tends to present with joint pain, fatigue, and effects on the liver, heart and pancreas as iron deposits in them. Because there is no way to excrete iron, the standard treatment is still the oldest one in medicine, which is removing blood.

This profile is already the screening test for it. A high transferrin saturation is the earliest abnormality in inherited iron overload. It appears before ferritin moves, and long before anything is felt.

UK practice treats a transferrin saturation above 45%, together with a ferritin above roughly 300 in men or 200 in women and no other explanation for either, as the trigger for genetic testing. Some labs set the saturation threshold at 50% in men. The genetic test looks for 2 variants in a gene called HFE, it is available on the NHS through the national genomic testing service when those criteria are met, and it is sold privately as well. The variants are most common in people of northern European background, particularly Celtic, and where someone is confirmed to carry them their first-degree relatives can be tested too.

This one matters because inherited iron overload is one of the few conditions where the damage is entirely preventable if it is caught early, and where the treatment costs nothing but time.