How the gut absorbs iron and how hepcidin limits it

The body has no way to get rid of extra iron, so it controls iron at the gut.^[1] Cells lining the duodenum, the first part of the small intestine, absorb iron and pass it to the blood.^[2][3] Hepcidin, a hormone from the liver, lowers how much gets through.^[4] In young women with low iron stores, a dose of 60 mg or more raised hepcidin, and a dose 24 hours later was absorbed 35% to 45% less.^[5] In women with anemia from low iron, absorption of a dose 48 hours after the last one did not differ significantly from the first.^[6]

Where does the iron from a tablet go?

It follows this path:

1. The cells that line the duodenum take nonheme iron in through DMT1.^[4]
2. Ferroportin passes it to the blood, and transferrin carries it around the body.^[8]
3. The bone marrow, which makes red blood cells, has a particularly high need for iron.^[8]
4. Most of a dose is not absorbed. Of a 240 mg dose, 18.1 mg was absorbed.^[5]
5. The liver makes hepcidin, which lowers how much gets through.^[4]

An adult holds 3 to 4 g of iron, most of it in hemoglobin, the protein in red blood cells that carries oxygen. Much of the rest is stored as ferritin in the liver, spleen and bone marrow.^[10] The body loses only small amounts of iron in urine, stool, sweat and shed skin cells. Women lose more with menstrual bleeding.^[10] Because these losses are small, absorption decides how much iron the body holds.^[12]

Is iron every other day better than every day?

A larger share of each dose is absorbed every other day.^[9][6] But the main trial compared the same number of doses, not the same number of days.^[9] In trials mostly in people with anemia, hemoglobin was not significantly higher with daily doses than with alternate-day doses, but this evidence is very uncertain.^[13]

In the 2017 trial, 40 women aged 18 to 40 with low iron stores took 60 mg of iron at 8 in the morning. One group took 14 doses on 14 days in a row. The other group took the same 14 doses on alternate days, over 28 days. The daily group absorbed 16.3% of its iron, 131.0 mg in total. The alternate-day group absorbed 21.8%, 175.3 mg in total. Hepcidin was higher in the daily group during the first 14 days. The women knew which group they were in.^[9]

The daily group took its 14 doses in half the time. Over the same 28 days, the figure's model gives these totals for 60 mg on an empty stomach:

• every day: 28 doses, about 252 mg absorbed, 15% of 1,680 mg^[9]
• every other day: 14 doses, about 183 mg absorbed, 22% of 840 mg^[9]

These are model values, fitted to the 2017 trial. So in the model, every other day gives more iron per dose, and every day gives more iron in total over the same weeks.^[9] The authors of a 2020 trial write that, to give the same total on alternate days, the dose can be doubled. In 19 women with anemia, one 200 mg dose on an alternate day gave about twice the absorbed iron of one 100 mg dose on a day in a row.^[6]

A 2025 review pooled 11 randomized trials with 1,014 people, most of them with anemia. At the end, hemoglobin was 0.28 g/dL higher with daily doses, a difference that was not significant. The certainty of this result was very low. Side effects were about as common in both groups, but a metallic taste was more common with daily doses.^[13]

Does a bigger dose give more iron?

Yes, but not in proportion to the dose. In young women with low iron stores, a 6 times larger dose, from 40 to 240 mg, gave only about 3 times more absorbed iron, from 6.7 to 18.1 mg.^[5]

Splitting the dose did not help. Three doses of 60 mg within 24 hours, on two mornings and one afternoon, did not give significantly more absorbed iron than the two morning doses.^[5] In the 2017 trial, 120 mg once a day and 60 mg twice a day for 3 days gave about the same absorption: 11.8% against 13.1%. Hepcidin was higher with the split dose.^[9]

Most of these trial doses are above the US upper limit for adults, 45 mg a day, which was set because of side effects in the stomach and gut. Doctors sometimes prescribe more to people with iron deficiency anemia.^[10] Doses of 45 mg a day or more may cause nausea and constipation.^[10]

How long does hepcidin stay high after a dose?

About a day. In women with anemia from low iron, the liver makes little hepcidin. Even so, a dose of oral iron raised their hepcidin for 24 hours.^[6]

Hepcidin also rises with inflammation, through signals such as interleukin-6.^[12] In anemia of chronic disease, inflammation raises hepcidin, and iron moves from the blood into the stores.^[10] In a 2023 trial, hepcidin was higher in the afternoon than in the morning. An afternoon dose was absorbed 37% less, a difference that was not significant.^[14]

Too little hepcidin causes the opposite problem. In hemochromatosis, an inherited disease, the liver makes too little hepcidin, and the body takes in too much iron.^[8][2]

Does coffee or vitamin C change how much iron is absorbed?

Yes. Coffee cut absorption from a supplement by 54%, and 80 mg of vitamin C raised it by 30%.^[14] In this 2023 trial, 34 women with low iron stores took 100 mg of iron six times, each time in a different way.^[14]

Compared with the dose with water in the morning:

• with 80 mg of vitamin C, 30% more was absorbed^[14]
• with 500 mg of vitamin C, absorption rose no further^[14]
• with coffee, 54% less^[14]
• with a breakfast with coffee and orange juice, 66% less, although the juice held about 90 mg of vitamin C^[14]
• with water in the afternoon, 37% less, a difference that was not significant^[14]

The authors suggest taking ferrous iron supplements in the morning, away from meals and coffee, with a food or drink rich in vitamin C. Their aim is to absorb the most iron.^[14] Food has a second side: taking iron with food can reduce side effects such as nausea and stomach upset.^[10]

In a 3-month trial, iron with vitamin C raised hemoglobin about as much as iron alone. 440 adults with iron deficiency anemia took a 100 mg iron tablet every 8 hours, with or without 200 mg of vitamin C. After 2 weeks, hemoglobin had risen by 2.00 g/dL with vitamin C and by 1.84 g/dL without it. The trial counted the two results as equivalent.^[15]

What about tea, grains and calcium?

They lower the absorption of iron from a meal. These numbers come from studies of single meals with iron from bread, not from a supplement:

• Drinks with polyphenols, plant compounds in tea, coffee and cocoa, cut absorption by 50% to 90%. Black tea cut it by 79% to 94%. Milk in the tea or coffee made little difference.^[16]
• Phytate, found in grains and beans, cut absorption from a wheat roll by 18% at the smallest amount tested and by 82% at the largest. Vitamin C counteracted this.^[17][10]
• 165 mg of calcium, as milk, cheese or a calcium salt, cut absorption by 50% to 60%.^[18]

Over many meals the effect is smaller. In studies with a varied diet, the effect of each single dietary factor was more modest than in single meals.^[1] Studies in which people took much more calcium for long periods found no change in their iron status.^[19] The NIH Office of Dietary Supplements says the calcium effect is not definitively established, and that experts suggest taking calcium and iron supplements at different times of day.^[10]

How much iron a person already has generally matters more than what they eat with it.^[1] During iron deficiency, hepcidin falls, so more iron can pass to the blood.^[2]

In short

• The duodenum absorbs iron. DMT1 takes it into the lining cells, and ferroportin passes it to the blood.^[4]
• Hepcidin from the liver acts on ferroportin and lowers absorption.^[4]
• In women with low iron stores, after a dose of 60 mg or more, a dose 24 hours later was absorbed 35% to 45% less.^[5]
• 21.8% of 14 doses of 60 mg on alternate days was absorbed, and 16.3% of the same doses on days in a row.^[9]
• In the model, 28 days of 60 mg give about 252 mg of absorbed iron every day and about 183 mg every other day.^[9]
• In 11 trials, hemoglobin did not rise significantly more with daily or with alternate-day doses.^[13]
• Compared with water, 80 mg of vitamin C raised absorption by 30%, coffee cut it by 54% and breakfast by 66%.^[14]

What this figure leaves out

The small intestine comes from the Human Reference Atlas: Small Intestine, Female, v1.2, shared under the CC BY 4.0 licence.^[20] The atlas gives the outer surface only. The 2 mm wall and its lining in the cut view are a typical thickness added for the figure, not measured. The atlas has no folds, no villi (the tiny projections of the lining) and no blood vessels, and the figure has no stomach or liver. The rust dots and the glow are signs, not single atoms.^[20]

The motion and the numbers come from a small model. It is for women with low iron stores who take ferrous sulfate in the morning on an empty stomach. It is fitted to four trials in women with low iron. The first measured how absorption grows with the dose and drops 24 hours later.^[5] The second compared 14 doses daily or on alternate days.^[9] The third measured hepcidin and absorption again 48 hours later.^[6] The fourth measured the effect of vitamin C, coffee and breakfast.^[14] The hepcidin curve has no units. Its height is set from the drop in absorption, and its shape between doses is modelled, not measured. Only its effect on absorption comes from trials.^[5][6]

The model leaves out people with full iron stores. They absorb less, because their hepcidin is higher.^[8] It also leaves out anemia and inflammation. Inflammation raises hepcidin.^[12] Heme iron from meat and fish is left out too. It is absorbed better than nonheme iron.^[10] The model does not show how fast hemoglobin rises. For education; not for diagnosis.^[10]