Iron

What it is

Iron is an essential mineral. It is a component of hemoglobin, the red blood cell protein that carries oxygen from the lungs to the tissues. Food contains heme iron (from meat and seafood) and nonheme iron (from plants).

What the research says

The evidence is strong that iron supplements correct iron deficiency and anaemia: a Cochrane review of 67 trials in menstruating women found less anaemia, higher haemoglobin, better exercise performance and less fatigue. The cost is gut side effects; a meta-analysis of 43 trials found ferrous sulfate roughly doubles the odds of GI symptoms. Absorption studies show each dose raises the iron-regulating hormone hepcidin for about 24 hours, which is why alternate-day dosing absorbs better per dose. Oral iron did not improve exercise capacity in heart failure. Iron can harm: accidental overdose is dangerous for young children, and in a large cohort of older women iron supplement use was associated with higher mortality. People with hereditary hemochromatosis, especially men, accumulate iron to the point of organ disease.

Evidence grade: Well established.

What goes wrong

Ferrous sulfate, the standard oral iron, significantly increased gastrointestinal side effects compared with placebo and with intravenous iron. (Source 1)

• Meta-analysis, Moderate certainty.
• Size: 6,831 adults in 43 RCTs.
• Who: Adults, including IBD patients and pregnant women.
• How long: Varied across trials.
• Result: OR 2.32 (95% CI 1.74-3.08) vs placebo; OR 3.05 (95% CI 2.07-4.48) vs IV iron; I2 53.6% and 41.6%.
• Funding: Independent (UK Medical Research Council)

Ferrous sulfate supplementation significantly increased risk of GI side-effects versus placebo with an odds ratio (OR) of 2.32 [95% CI 1.74–3.08, p<0.0001, I2 = 53.6%]

In a population cohort, iron-overload-related disease developed in about 28% of men homozygous for the HFE C282Y mutation but about 1% of women. (Source 2)

• Cohort study, Moderate certainty.
• Size: 31,192 genotyped; 203 C282Y homozygotes studied.
• Who: Adults aged 40-69 of northern European descent, Melbourne.
• How long: Average 12 years.
• Result: 28.4% (95% CI 18.8-40.2) of male vs 1.2% (0.03-6.5) of female C282Y homozygotes.
• Funding: Not stated in abstract.

The proportion of C282Y homozygotes with documented iron-overload-related disease was 28.4% (95% confidence interval [CI], 18.8 to 40.2) for men and 1.2% (95% CI, 0.03 to 6.5) for women.

Accidental ingestion of iron is most common in children under 6, and more than 60 mg/kg of elemental iron can cause severe toxicity and death. (Source 3)

• Case series, Moderate certainty.
• Size: Clinical review of poisoning literature.
• Who: Children and others ingesting iron.
• How long: Acute.
• Result: Under 20 mg/kg elemental iron non-toxic; over 60 mg/kg severe toxicity.
• Funding: Not applicable.

Ingestion of more than 60 mg/kg can result in severe toxicity and lead to severe morbidity and mortality.

NIH ODS (2025) states that at least 43 US children died from ingesting high-dose iron supplements between 1983 and 2000. (Source 4)

• Official position, Certainty not rated.
• Size: Not applicable.
• Who: US children.
• How long: 1983-2000.
• Result: At least 43 deaths.
• Funding: US government.

Between 1983 and 2000, at least 43 U.S. children died from ingesting supplements containing high doses of iron

What the evidence supports

Daily iron supplementation in menstruating women reduced anaemia and iron deficiency, raised haemoglobin, improved exercise performance and reduced fatigue, at the cost of more gastrointestinal side effects. (Source 5)

• Systematic review, Certainty not rated.
• Size: 8,506 women across 67 trials.
• Who: Menstruating women.
• How long: Varied across trials.
• Result: Anaemia RR 0.39; iron deficiency RR 0.62; haemoglobin MD 5.30 g/L (as summarised on the repository record); constipation RR 2.07.
• Funding: Not stated on the record read.

Daily iron supplementation effectively reduces the prevalence of anaemia and iron deficiency, raises haemoglobin and iron stores, improves exercise performance and reduces symptomatic fatigue.

In small stable-isotope absorption trials, an oral iron dose of 60 mg or more raised serum hepcidin 24 hours later and cut absorption of the next dose by 35-45%; twice-daily dosing did not add absorbed iron. (Source 6)

• Randomized trial, Low certainty.
• Size: 54 non-anaemic young women.
• Who: Iron-depleted women (ferritin 20 ug/L or less)
• How long: Single and consecutive-day doses.
• Result: Fractional absorption decreased 35% to 45% (P < .01) 24 h after doses of 60 mg or more.
• Funding: Not stated in abstract.

In studies 1 and 2, 24 hours after doses ≥60 mg, serum hepcidin was increased (P < .01) and fractional iron absorption was decreased by 35% to 45% (P < .01).

In women with iron-deficiency anaemia, fractional iron absorption from 100-200 mg doses was 40-50% higher on an alternate day than on the consecutive day, because hepcidin stayed raised for 24 hours. (Source 7)

• Randomized trial, Low certainty.
• Size: 19 women (cross-over: each woman received both dosing schedules)
• Who: Women with iron-deficiency anaemia (mean serum ferritin 10 ug/L)
• How long: Two 3-dose absorption periods separated by a 16-day incorporation period (about 4 weeks)
• Result: FIA on days 2 and 5 was 40-50% higher than on day 3 (P<0.001)
• Funding: Independent (ETH Zurich)

Limit of this finding: This was a small cross-over absorption study in 19 women that measured how much iron was absorbed, not a trial of health outcomes. The abstract text we recorded does not say the order of dosing was randomised, so treat it as trial-style evidence of limited strength.

Similarly, for both doses, fractional iron absorption (FIA) on days 2 and 5 was 40-50% higher than on day 3 (P<0.001)

What the evidence does not support

The same meta-analysis did not find that higher iron doses produced more gastrointestinal side effects. (Source 1)

• Meta-analysis, Low certainty.
• Size: 43 RCTs.
• Who: Adults.
• How long: Varied.
• Result: Meta-regression of study OR on iron dose not significant.
• Funding: Independent (UK Medical Research Council)

Meta-regression did not provide significant evidence of an association between the study OR and the iron dose.

High-dose oral iron did not improve peak exercise capacity in iron-deficient patients with heart failure with reduced ejection fraction. (Source 8)

• Randomized trial, Moderate certainty.
• Size: 225 randomised.
• Who: Adults with HFrEF and iron deficiency.
• How long: 16 weeks.
• Result: Peak VO2 difference 21 mL/min (95% CI -34 to +76); P = .46.
• Funding: Not stated in abstract (NIH-funded Heart Failure Network trial per public record; not verified here)

Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks.

Where the research disagrees

Whether oral iron helps iron-deficient people who have a disease beyond simple deficiency

• Low et al., Cochrane 2016, systematic review of 67 trials in menstruating women: "Daily iron supplementation effectively reduces the prevalence of anaemia and iron deficiency, raises haemoglobin and iron stores, improves exercise performance and reduces symptomatic fatigue." (Source 5)
• IRONOUT HF investigators, 2017, RCT, 225 patients with heart failure: "These results do not support use of oral iron supplementation in patients with HFrEF." (Source 8)

How much

• Reference intake: NIH ODS (fact sheet updated 2025, from the Food and Nutrition Board) lists an RDA of 18 mg/day for women aged 19-50 and 8 mg/day for men aged 19-50. (Source 4)
• Upper limit: NIH ODS (2025) lists a Tolerable Upper Intake Level of 45 mg/day for adults aged 19 and over. (Source 4)
• Studied: Moretti 2015: single doses of 40 to 240 mg iron as ferrous sulfate, and three 60 mg doses within 24 hours. (Source 6)
• Studied: Stoffel 2020: 100 or 200 mg iron as ferrous sulfate on consecutive versus alternate days. (Source 7)
• Studied: IRONOUT HF: iron polysaccharide 150 mg twice daily for 16 weeks. (Source 8)

A common belief, and what the research shows

The belief: Taking more iron, more often, gets iron levels up faster.

What the research shows: Absorption studies found the opposite for fractional absorption: "Providing lower dosages (40-80 mg Fe) and avoiding twice-daily dosing maximize fractional absorption." These were short, small absorption studies, not long-term outcome trials.

Questions and answers

What is it?

Iron is an essential mineral. Its best-known job is as part of hemoglobin, the protein in red blood cells that carries oxygen. (Source 4)

What does it do in the body?

Iron lets red blood cells carry oxygen. The body controls how much it absorbs with a hormone called hepcidin, which rises after an iron dose and lowers absorption of the next dose for about a day. (Source 6)

Is it good or bad for you?

Both, depending on the person. For people who are iron deficient, supplements reliably correct anaemia and reduce fatigue, but they commonly upset the stomach. For people who are not deficient, especially men with the HFE C282Y gene and older women, the literature shows iron overload disease and an association with higher mortality. Accidental overdose is dangerous for young children. (Source 5)

How do you get more of it?

Food provides heme iron (meat, seafood) and nonheme iron (nuts, beans, vegetables). In trials, iron was given as ferrous sulfate tablets; small absorption studies found alternate-day doses were absorbed better per dose than consecutive-day doses. (Source 7)

If it is harmful, what reduces it?

For acute iron poisoning, the chelating drug deferoxamine is used in hospital to remove iron from tissues and plasma. The sources we read did not describe treatment of hereditary hemochromatosis. (Source 3)

Why might someone be low in it or missing it?

Low iron is most common in groups with higher needs or losses: infants, young children, teenage girls, pregnant women and premenopausal women (menstrual loss). Other causes such as blood loss or poor absorption are not covered by the quotes we collected. (Source 4)

Which whole foods contain it or feed it?

Lean meat and seafood are the richest sources of heme iron; nuts, beans, vegetables and fortified grain products supply nonheme iron. (Source 4)

What happens if you do not have it?

Iron deficiency leads to anaemia, lower exercise capacity and fatigue; the Cochrane review found correcting it improved these. (Source 5)

How can you test for it?

A blood test for serum ferritin, which reflects the body's iron stores, is described by NIH ODS as the most efficient and cost-effective test for iron deficiency. Genetic testing for the HFE C282Y mutation identifies hereditary hemochromatosis risk, though most women with it do not develop disease. (Source 4)

References

1. PLOS ONE. Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis. 2015. PMID 25700159, DOI 10.1371/journal.pone.0117383. Read the source
2. New England Journal of Medicine (record in UWA Research Repository). Iron-Overload-Related Disease in HFE Hereditary Hemochromatosis. 2008. DOI 10.1056/NEJMoa073286. Read the source
3. StatPearls Publishing, NCBI Bookshelf. Iron Toxicity (StatPearls, archived). 2023. Read the source
4. NIH Office of Dietary Supplements. Iron: Fact Sheet for Health Professionals (updated September 4, 2025). 2025. Read the source
5. Cochrane Database of Systematic Reviews (record in Monash Health repository). Daily iron supplementation for improving anaemia, iron status and health in menstruating women. 2016. PMID 27087396, DOI 10.1002/14651858.CD009747.pub2. Read the source
6. Blood. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. 2015. PMID 26289639, DOI 10.1182/blood-2015-05-642223. Read the source
7. Haematologica. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. 2020. DOI 10.3324/haematol.2019.220830. Read the source
8. JAMA (record in WashU Medicine Research Profiles). Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial. 2017. PMID 28510680, DOI 10.1001/jama.2017.5427. Read the source