Iron Human Clinical Research: What the Evidence Shows

1. Executive evidence summary

Iron is an essential mineral. The body uses it to make hemoglobin, to store and carry oxygen in muscle, and to run enzymes involved in energy production, DNA synthesis and brain function. The body cannot make iron, and it loses iron through bleeding and shed cells, so low iron status is common worldwide, especially in menstruating women, pregnant women and young children. Human clinical research on iron is one of the largest bodies of evidence in the supplement field, but it is uneven. Some conclusions are very strong, while others are weak, mixed or negative.

This page reviews that research in a structured way. It summarizes randomized controlled trials, meta-analyses and systematic reviews in humans, explains how reliable each finding is, and states clearly where the evidence runs out. Animal, cell-culture and mechanistic studies are used only where they help explain a human result.

Key findings at a glance:

•      Anemia and iron deficiency: Strong and consistent evidence. Oral iron raises hemoglobin and ferritin and lowers the risk of anemia in people who are iron deficient or at high risk, including menstruating women, pregnant women and young children.

•      Pregnancy: A Cochrane review found that daily iron lowered the risk of anemia at term by roughly 70% and probably reduced low birth weight. Evidence for preterm birth and later child outcomes is less clear.

•      Fatigue without anemia: Moderate evidence. Two placebo-controlled trials in women with low ferritin found modest reductions in fatigue, but results are not identical across studies.

•      Exercise capacity: Moderate evidence of benefit in iron-deficient women. There is little evidence of benefit in people whose iron status is already normal.

•      Cognition: Mixed and low-certainty evidence.

•      Heart failure: In the largest oral iron trial, IRONOUT HF, oral iron did not improve exercise capacity, even though intravenous iron has helped in other trials.

•      Safety: Gastrointestinal side effects are common, iron can be harmful in people with iron overload, and children in malaria-endemic areas need special care. Iron overdose is dangerous for small children.

Bottom line: Iron works when iron is needed. The evidence supports targeted use guided by blood tests, not routine use in everyone.

2. Research question

This page is built around one primary question: in human participants, does iron supplementation improve outcomes that matter to health, and if so, for whom, at what dose and for how long? The question is broken into the standard PICO elements.

•      Population: Humans of any age, with a focus on groups where iron deficiency is common: menstruating women, pregnant women, infants and children, and patients with heart failure.

•      Intervention: Oral iron supplements, in any form, at any dose.

•      Comparison: Placebo, no treatment, or a different iron regimen (for example, alternate-day versus daily dosing).

•      Outcomes: Hemoglobin, ferritin, anemia, fatigue, exercise capacity, cognition, birth outcomes, hospitalization and adverse effects.

Three secondary questions shape the analysis. First, do the benefits depend on baseline iron status? Second, how does the dosing schedule affect absorption and tolerance? Third, what harms appear in the trials, and in which groups?

3. Search/inclusion methodology

This page is a narrative evidence review, not a new systematic review with its own database search. Studies were selected by working down a hierarchy of evidence. First priority went to systematic reviews and meta-analyses of randomized controlled trials, especially Cochrane reviews. Second came large or influential individual randomized trials. Third came guideline documents from bodies such as the World Health Organization and national hematology societies, which show how the evidence is interpreted in practice.

Inclusion criteria were: human participants; oral iron as the main intervention; a placebo, no-treatment or alternative-regimen comparison; and outcomes that were actually measured. Intravenous iron trials were considered only where they help explain an oral iron result. Food fortification trials, animal studies, in vitro work and purely observational studies were left out of the evidence grading, although observational findings are mentioned where they give useful context.

For each study, the review looked at design, sample size, baseline iron status, form and dose of iron, duration, primary endpoint, main result and funding source. These fields correspond to the sections that follow. Readers who need an exhaustive search should consult PubMed and the Cochrane Library directly, and the reference list at the end allows each claim to be traced to its source.

4. Evidence by health outcome

4.1 Anemia and iron stores

The most reliable finding in iron research is also the least surprising: giving iron to people who are iron deficient raises hemoglobin and rebuilds stores. A Cochrane review of daily iron in menstruating women pooled 67 trials with more than 8,000 participants. Iron reduced the risk of anemia by about 60% and raised hemoglobin by roughly 5 g/L on average, with a lower risk of iron deficiency as well. The same pattern appears in pregnancy and in young children.

Hemoglobin usually begins to rise within a few weeks, while ferritin, the marker of stored iron, often takes two to three months of treatment to recover. Trials that enrolled people with normal iron status show little change in hemoglobin. This matches physiology: the hormone hepcidin tightly regulates absorption, so people with full stores absorb much less.

4.2 Fatigue in people with low ferritin but no anemia

Two well-known double-blind trials tested iron in women who felt tired, had normal hemoglobin and had ferritin of 50 µg/L or lower. In the earlier Swiss-French trial of 144 women, four weeks of 80 mg ferrous sulfate daily reduced fatigue scores by about 29%, compared with about 13% on placebo. In a later trial of 198 women, 12 weeks of 80 mg elemental iron daily produced a larger fall in self-rated fatigue than placebo, about 48% versus 29%.

A systematic review of trials in non-anemic, iron-deficient adults concluded that iron probably reduces fatigue, although the size of the effect varies and the trials are small. Because fatigue is self-reported and iron can change stool color and cause stomach upset, some participants may have guessed their treatment, which could inflate the result.

4.3 Physical performance and exercise

A meta-analysis of trials in women of reproductive age found that iron supplementation improved maximal oxygen uptake and endurance, with the clearest effect in women who were iron deficient or anemic. Evidence in athletes who already have adequate iron stores is thin, and there is no convincing evidence that extra iron improves performance when stores are normal. Athletes with heavy training loads, heavy periods or restrictive diets are the group most likely to benefit, and testing first is sensible.

4.4 Cognition and mental performance

A meta-analysis of randomized trials found that iron supplementation improved attention and concentration in some age groups, but results for memory, intelligence and academic performance were inconsistent. In infants and toddlers, trials of iron on motor and language development have produced mixed results. The overall picture is plausible but not firmly proven: iron deficiency is clearly harmful to the developing brain, yet supplementation does not always reverse the damage, and the timing of treatment appears to matter.

4.5 Pregnancy and birth outcomes

The Cochrane review of daily oral iron in pregnancy included 61 trials and more than 43,000 women. Compared with no iron or placebo, daily iron lowered the risk of anemia at term by about 70% and the risk of iron deficiency at term by more than half. Low birth weight was also less likely, by roughly one fifth. No clear effect was seen on preterm birth or on most other newborn outcomes, and the trials used many different doses.

Guidelines translate this into practice. The World Health Organization recommends 30 to 60 mg of elemental iron daily during pregnancy where anemia is common, while UK hematology guidance supports treating confirmed deficiency with lower daily doses or alternate-day dosing. Intermittent regimens can reduce side effects, although the evidence on clinical outcomes is thinner than for daily dosing.

4.6 Infants and children

A meta-analysis of trials in children aged 4 to 23 months found that daily iron improved hemoglobin and reduced anemia and iron deficiency. The evidence on development was less consistent. Safety is the central issue in this age group. A large trial on the island of Pemba, in a high-malaria setting, was stopped early after children given iron with folic acid had about 12% more deaths or hospital admissions. A later Cochrane review concluded that iron does not increase clinical malaria when malaria prevention and treatment services are in place. Context therefore decides the risk-benefit balance.

4.7 Heart failure

Iron deficiency is common in people with heart failure and is linked to worse symptoms. Intravenous iron has improved symptoms and exercise capacity in several trials, such as FAIR-HF. Oral iron did not. In IRONOUT HF, 225 patients with reduced ejection fraction and iron deficiency took 150 mg of iron polysaccharide twice daily for 16 weeks, and peak oxygen uptake did not differ from placebo. One plausible explanation is that inflammation raises hepcidin and limits oral absorption in these patients. The result is a useful reminder that benefits seen with one route of administration cannot be assumed for another.

4.8 Tolerability and safety

A meta-analysis of placebo-controlled trials of ferrous sulfate found that gastrointestinal side effects were more than twice as likely as with placebo. Nausea, constipation, abdominal pain and dark stools are the most common complaints, and they are a major reason people stop taking iron. Gastrointestinal effects appear to be dose related, which is one reason lower and alternate-day regimens are of interest.

Iron is not suitable for everyone. People with hemochromatosis or other iron-overload conditions should not take supplemental iron unless a clinician directs it. The US tolerable upper intake level for adults is 45 mg of iron per day from all supplement sources. Accidental iron overdose in small children can be fatal, which is why iron products carry specific warnings and should be stored out of reach.

5. Human studies table

The table below lists the main human studies and reviews discussed on this page. Percentages and effect sizes are approximate and are rounded for readability; see the references for exact values.

Study (design)	Participants	Dose/form and duration	Primary endpoint	Main result
Low 2016 (Cochrane review)	67 trials, about 8,500 menstruating women	Daily oral iron, various doses; weeks to months	Hemoglobin, anemia, iron deficiency	Hemoglobin up about 5 g/L; anemia risk about 60% lower
Peña-Rosas 2015 (Cochrane review)	61 trials, about 43,000 pregnant women	Daily oral iron versus none or placebo; to term	Anemia at term, birth outcomes	Anemia at term about 70% lower; fewer low-birth-weight infants; no clear effect on preterm birth
Verdon 2003 (double-blind RCT)	144 non-anemic women with unexplained fatigue, ferritin 50 µg/L or lower	80 mg ferrous sulfate daily; 4 weeks	Fatigue score	Fatigue down about 29% versus about 13% with placebo
Vaucher 2012 (double-blind RCT)	198 menstruating women with fatigue, ferritin 50 µg/L or lower	80 mg elemental iron daily; 12 weeks	Self-rated fatigue	Fatigue down about 48% versus about 29% with placebo
Pasricha 2014 (meta-analysis)	Women of reproductive age	Oral iron, various; various durations	Aerobic capacity, endurance	Improved aerobic capacity and endurance, mainly in deficiency
Houston 2018 (systematic review)	Non-anemic iron-deficient adults	Oral iron, various; various durations	Fatigue, physical capacity	Fatigue reduced; physical capacity mixed
Moretti 2015 (isotope studies)	Iron-depleted young women	Single versus split daily doses, labeled iron	Fractional iron absorption, hepcidin	Hepcidin rose after a dose and absorption of later doses fell
Stoffel 2017 (RCT, isotope)	Iron-depleted young women	Alternate-day versus consecutive-day dosing; about 2 weeks	Fractional iron absorption	Higher absorption with alternate days (about 22% versus 16%)
Pasricha 2013 (meta-analysis)	Children aged 4 to 23 months	Daily oral iron; months	Hemoglobin, anemia, development	Better hemoglobin, less anemia; development results inconsistent
Sazawal 2006 (RCT)	About 32,000 preschool children in a high-malaria setting	Iron with folic acid (with or without zinc); stopped early	Hospital admission or death	About 12% more events with iron and folic acid
IRONOUT HF 2017 (RCT)	225 patients with heart failure and iron deficiency	150 mg iron polysaccharide twice daily; 16 weeks	Peak oxygen uptake	No significant difference from placebo
Tolkien 2015 (meta-analysis)	Adults in placebo-controlled trials	Ferrous sulfate, various doses	Gastrointestinal side effects	More than twice the odds of side effects

 

6. Study design quality

Most of the strongest iron evidence comes from randomized controlled trials and systematic reviews of them, which is the best design available for testing a supplement. Even so, design quality varies across the field.

Blinding is a recurring problem. Iron changes stool color and often causes gastrointestinal effects, so participants may be able to guess whether they received iron or placebo. This matters most for subjective endpoints such as fatigue and mood. Objective endpoints such as hemoglobin and ferritin are not affected in the same way.

Sample size and attrition are further concerns. Many trials in non-anemic adults enrolled fewer than 200 people and ran for only a few weeks. Dropouts caused by side effects can bias results if they are not handled carefully. Cochrane reviewers frequently rated individual trials as having unclear risk of bias because randomization or allocation concealment was poorly described.

Finally, many of the mechanistic findings, such as the effect of hepcidin on absorption, come from small stable-isotope studies. These are excellent for understanding how iron is absorbed, but they measure absorption, not health outcomes, and they should not be treated as proof of clinical benefit.

7. Participant characteristics

The participants in iron trials are not a cross-section of the population. Most trials enrolled young or middle-aged women, pregnant women or young children, because these are the groups at highest risk of deficiency. Men, older adults, people with chronic disease and people from a wide range of ethnic backgrounds are under-represented.

Baseline iron status also differs between trials, and this has a large influence on results. The World Health Organization defines iron deficiency in healthy adults as ferritin below 15 µg/L, while the fatigue trials above used a much higher cut-off of 50 µg/L or lower. A trial that enrolls people with mild depletion will usually show smaller effects than one enrolling people with overt deficiency or anemia. Pooled results should therefore be read as the average effect for the group studied, not as a promise for every individual.

Special populations deserve their own mention. Patients with heart failure, inflammatory bowel disease or chronic kidney disease often have inflammation that disrupts iron handling, so findings from healthy women do not transfer directly to them.

8. Dose/form used

Trials have used many iron salts and complexes. Ferrous sulfate is by far the most common, followed by ferrous fumarate and ferrous gluconate. Polysaccharide-iron complexes, as in IRONOUT HF, and amino-acid chelates such as iron bisglycinate appear less often. Ferrous sulfate is the usual comparator because it is inexpensive and well understood. Evidence that newer forms are better absorbed or better tolerated exists, but it comes mostly from smaller studies, and few large trials compare forms head to head on clinical outcomes.

Doses are usually reported as milligrams of elemental iron, and the number matters because iron salts contain different amounts of iron by weight. The fatigue trials used about 80 mg of elemental iron daily. Pregnancy trials ranged from about 30 mg to more than 100 mg. The adult recommended dietary allowance is 8 mg for men and 18 mg for women aged 19 to 50, and 27 mg in pregnancy, so therapeutic doses in trials are far higher than dietary needs. These are doses meant to correct deficiency, not to maintain normal status.

Absorption research has changed how dosing is understood. Stable-isotope studies in iron-depleted women show that a dose of iron raises hepcidin for about a day, which reduces absorption of the next dose. Giving iron on alternate days produced higher fractional absorption, about 22% versus 16% in one study, than giving it on consecutive days. Splitting a dose into two daily portions did not improve absorption. Whether alternate-day dosing produces equal or better hemoglobin responses in long trials is still being tested, and results so far are encouraging but not conclusive.

Practical factors also influence absorption. Vitamin C taken with iron improves absorption of non-heme iron in meals, while tea, coffee, calcium and some medicines reduce it. These effects are well documented in meal studies, but their size in long-term supplement trials is less certain.

9. Duration

Iron trial durations match the biology of recovery. Fatigue trials lasted four to twelve weeks. Trials in menstruating women commonly ran for one to three months. Pregnancy trials continued until delivery, so they lasted several months. Pediatric trials usually lasted two to twelve months, and IRONOUT HF lasted 16 weeks.

Hemoglobin typically rises noticeably within two to four weeks in deficient people, but replenishing ferritin stores often takes three months or longer after hemoglobin normalizes. Short trials can therefore show a hemoglobin benefit while saying little about whether stores are truly restored.

Very few randomized trials follow people beyond one year. Long-term effects of continued iron use in people with normal status, including possible effects on infection risk, gut microbiota and oxidative stress, are not well studied in humans. This is an important gap, and it is one reason supplemental iron is best used for a defined purpose and period, with follow-up testing.

10. Primary endpoints

The primary endpoints in iron research fall into three groups. Laboratory endpoints include hemoglobin, ferritin and transferrin saturation. Clinical event endpoints include the incidence of anemia, low birth weight, preterm birth, hospitalization and death. Function and symptom endpoints include fatigue scales, peak oxygen uptake, cognitive tests and developmental scores.

Laboratory endpoints dominate the literature because they respond quickly and are cheap to measure. They are valid and important, since anemia has real consequences, but they are surrogate markers. A higher hemoglobin does not automatically mean a person feels or functions better, which is why trials such as the fatigue studies and IRONOUT HF matter. In IRONOUT HF, iron improved laboratory markers modestly but did not improve the functional endpoint that patients care about.

Patient-reported endpoints bring their own problem: scales differ between trials, so results cannot always be pooled. Meta-analysts often convert them to standardized effect sizes, which are harder for general readers to interpret.

11. Results

Bringing the findings together, the results can be summarized by size and certainty.

•      Hemoglobin: An average gain of about 5 g/L in menstruating women taking daily oral iron, with larger gains in people who start with anemia.

•      Anemia: Risk lower by about 60% in menstruating women and about 70% at term in pregnancy.

•      Iron deficiency: Risk lower by roughly one third to one half across groups, depending on dose and baseline status.

•      Fatigue: Moderate reductions in non-anemic women with low ferritin, with a difference of roughly 15 to 20 percentage points between iron and placebo in the two main trials.

•      Exercise: Improved aerobic capacity and endurance in iron-deficient women; no clear benefit when iron status is normal.

•      Birth outcomes: Lower risk of low birth weight; no clear effect on preterm birth.

•      Heart failure: No improvement in peak oxygen uptake with oral iron in IRONOUT HF.

•      Harms: More than twice the odds of gastrointestinal side effects; excess deaths or hospital admissions in one large trial in a high-malaria setting.

12. Clinical significance

A statistically significant result is not always a clinically meaningful one. A hemoglobin rise of 5 g/L is modest on its own, but in someone with anemia it can be the difference between being below and above the diagnostic threshold, and larger gains are seen in more severe deficiency. For pregnancy, preventing anemia at term lowers the chance of transfusion and related complications, so the clinical significance is high.

For fatigue, a reduction of about 15 to 20 percentage points compared with placebo is meaningful to many individuals, but it is an average. Some women improve substantially and others do not at all, and iron does not treat fatigue from other causes such as poor sleep, thyroid disease, depression or infection. That is why unexplained fatigue should be evaluated, not simply treated with iron.

Clinical significance also depends on cost and burden. Side effects occur in a sizeable minority of users, and a treatment that people cannot tolerate will not help them. Where side effects lead to stopping, a lower dose, alternate-day schedule or different formulation may do more good than a higher dose taken inconsistently.

13. Conflicts of interest/funding

Funding sources in the iron literature vary widely. The Cochrane reviews cited here are produced under strict conflict-of-interest policies. Some large trials are publicly funded: IRONOUT HF was funded by the US National Heart, Lung, and Blood Institute. Trials of intravenous iron products are more often industry sponsored; for example, FAIR-HF was sponsored by the manufacturer of the product tested, Vifor Pharma.

Industry funding does not make a trial invalid, but it raises the importance of pre-registration, independent analysis and transparent reporting. Small trials of branded oral iron formulations are sometimes sponsored by the manufacturer, and positive results from them should be read with extra care until replicated. Publication bias is another risk, because trials with null results are less likely to be published.

Readers should check the funding and conflict statements in each original paper. This page does not rely on any single sponsored study for its main conclusions.

14. Consistency across trials

Consistency is highest for the basic effect on hemoglobin and anemia. Trials in different countries, ages and settings point in the same direction, even though the size of the effect varies with dose, duration and baseline iron status. Meta-analyses often report high statistical heterogeneity for hemoglobin because baseline deficiency differs so much between studies, but the direction of effect is rarely in doubt.

Consistency is lower for fatigue and cognition. Fatigue trials mostly agree on a modest benefit, yet some trials in women with less severe deficiency find little difference from placebo. Cognitive trials use many different tests and age groups, which makes pooling difficult and results patchy.

The heart failure data are the clearest example of inconsistency by route. Intravenous iron shows benefits across several trials, while the large oral trial was neutral. Pediatric safety results are consistent with a context effect: concern about malaria arises in high-transmission settings without malaria control, while trials with prevention services show no increase in clinical malaria.

15. Meta-analyses/systematic reviews

The main synthesized evidence on iron in humans comes from the following reviews.

•      Daily iron in menstruating women (Cochrane, 2016): 67 trials. Lower anemia and iron deficiency risk, higher hemoglobin, with evidence of improved physical performance.

•      Daily iron in pregnancy (Cochrane, 2015): 61 trials. Lower risk of anemia and iron deficiency at term and probable reduction in low birth weight.

•      Iron and physical performance in women (J Nutr, 2014): Improved aerobic capacity and endurance, largest in women with deficiency.

•      Iron in non-anemic iron deficiency (BMJ Open, 2018): Evidence of reduced fatigue; mixed results for physical capacity.

•      Iron and cognition (Nutr J, 2010): Some benefit for attention and concentration; inconsistent elsewhere.

•      Iron in infants and young children (Lancet Glob Health, 2013): Improved hemoglobin and reduced anemia and deficiency; inconsistent developmental effects.

•      Iron in malaria-endemic areas (Cochrane, 2016): No increase in clinical malaria when malaria prevention or management is provided.

•      Ferrous sulfate side effects (PLoS One, 2015): Gastrointestinal adverse events more than twice as likely as with placebo.

These reviews are generally well conducted, but they inherit the weaknesses of their component trials, including short duration and variable dose and form.

16. Evidence grading

The ratings below are an editorial assessment inspired by the GRADE approach, which considers study design, risk of bias, consistency, directness and precision. They are a reader's guide, not formal GRADE judgments.

Outcome	Population	Certainty	Main reason
Raises hemoglobin and ferritin, lowers anemia	Iron-deficient adults, pregnant women, children	High	Many consistent RCTs and Cochrane reviews
Lower anemia at term	Pregnant women	High	Large Cochrane review with consistent direction
Lower low birth weight	Pregnant women	Moderate	Benefit seen but trial quality and dosing vary
Reduced fatigue	Non-anemic women with low ferritin	Moderate	Few trials, subjective endpoint, possible unblinding
Improved aerobic capacity	Iron-deficient women	Moderate	Meta-analysis with limited trial size
Improved cognition	Children and adults	Low	Inconsistent tests, ages and results
Improved exercise capacity with oral iron	Heart failure	Moderate (no benefit)	One large neutral RCT
Alternate-day dosing improves clinical outcomes	Iron-deficient women	Low	Absorption data stronger than clinical outcome data
Safety in malaria-endemic areas	Young children	Moderate	Harm in one large trial; no excess when malaria control exists
Benefit in people with normal iron status	General adults	Very low	Little direct evidence and no long-term trials

 

High certainty means further research is unlikely to change the conclusion. Moderate means the conclusion is likely correct but could change. Low means the conclusion is uncertain.

17. Limitations

No evidence review is complete, and this one has specific limits. It is a narrative review, so some relevant studies may be missing, and the numerical results are rounded and approximate. Readers should confirm exact values in the original papers.

•      Most evidence is for ferrous salts. Results may not apply to other forms or to combination products.

•      Many trials are short and use self-reported outcomes that are vulnerable to unblinding.

•      Long-term outcomes of iron use in people with normal iron status are largely unstudied.

•      Men, older adults and diverse ethnic groups are under-represented.

•      Baseline iron status differs between studies, so pooled effects blur differences between mild and severe deficiency.

•      Absorption studies in small groups of women do not prove clinical benefit.

•      Genetic differences affecting iron metabolism, and interactions with medicines and inflammation, are rarely addressed.

18. Bottom-line interpretation

The human evidence on iron is clear on its central point. Iron supplementation corrects iron deficiency and anemia, and it prevents anemia in groups where the risk is high, most notably pregnant women. This conclusion rests on many randomized trials and Cochrane-level reviews and is graded high certainty.

Beyond that, benefit depends on need. Women with low ferritin and unexplained fatigue may feel better on iron, and iron-deficient women may improve aerobic capacity, but these effects are moderate in size and certainty. Evidence for cognition is mixed, and oral iron did not help patients with heart failure in the largest trial. There is no strong evidence that taking iron when stores are normal improves health, and there are plausible reasons for caution, including side effects, interactions and the risk of overload in susceptible people.

Practical takeaways drawn from the evidence:

•      Test before supplementing. Hemoglobin and ferritin, interpreted by a clinician, show whether iron is likely to help.

•      Look for the cause. Iron deficiency in a man or in a postmenopausal woman should prompt a search for blood loss.

•      Use a defined dose and period, then retest, typically after two to three months.

•      Consider lower or alternate-day dosing if side effects are a problem.

•      Do not exceed the 45 mg tolerable upper intake level for adults unless a clinician prescribes it.

•      Avoid iron if you have an iron-overload condition, and keep all iron products away from children.

This page is educational and is not medical advice. Anyone considering iron supplementation should speak with a qualified health professional.

19. References

1.      Low MS, Speedy J, Styles CE, De-Regil LM, Pasricha SR. Daily iron supplementation for improving anaemia, iron status and health in menstruating women. Cochrane Database Syst Rev. 2016;4:CD009747.

2.      Peña-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T. Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015;(7):CD004736.

3.      Verdon F, Burnand B, Stubi CL, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003;326:1124.

4.      Vaucher P, Druais PL, Waldvogel S, Favrat B. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ. 2012;184:1247-1254.

5.      Pasricha SR, Low M, Thompson J, Farrell A, De-Regil LM. Iron supplementation benefits physical performance in women of reproductive age: a systematic review and meta-analysis. J Nutr. 2014;144:906-914.

6.      Houston BL, Hurrie D, Graham J, et al. Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials. BMJ Open. 2018;8:e019240.

7.      Falkingham M, Abdelhamid A, Curtis P, et al. The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis. Nutr J. 2010;9:4.

8.      Moretti D, Goede JS, Zeder C, et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015;126:1981-1989.

9.      Stoffel NU, Cercamondi CI, Brittenham G, et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017;4:e524-e533.

10.   Pasricha SR, Hayes E, Kalumba K, Biggs BA. Effect of daily iron supplementation on health in children aged 4-23 months: a systematic review and meta-analysis of randomised controlled trials. Lancet Glob Health. 2013;1:e77-e86.

11.   Sazawal S, Black RE, Ramsan M, et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet. 2006;367:133-143.

12.   Neuberger A, Okebe J, Yahav D, Paul M. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2016;2:CD006589.

13.   Lewis GD, Malhotra R, Hernandez AF, et al. 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. JAMA. 2017;317:1958-1966.

14.   Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361:2436-2448.

15.   Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015;10:e0117383.

16.   Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet. 2021;397:233-248.

17.   Pavord S, Daru J, Prasannan N, et al. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2020;188:819-830.

18.   World Health Organization. Guideline on use of ferritin concentrations to assess iron status in individuals and populations. Geneva: WHO; 2020.

19.   World Health Organization. Daily iron and folic acid supplementation during pregnancy. Geneva: WHO; 2016 (guideline and e-Library of Evidence for Nutrition Actions).

20.   Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academies Press; 2001.