Iron Scientific References and Clinical Study Library

This page is a working bibliography for iron, an essential mineral. It collects peer-reviewed studies that a reader, writer or clinician can open and check, and it groups them by study type so the strength of each source is visible at a glance. Every entry lists its design, population and iron dose or exposure, and every entry links to a DOI and a PubMed record. The page makes no health claims of its own. It points to the evidence and describes what each study actually found.

1. How This Library Is Organized

Entries are arranged from the types of human evidence most useful for answering clinical questions, through observational and pharmacokinetic work, to laboratory studies that explain mechanisms. Each study has a short ID such as MA1 or RCT2. The same IDs appear in the study table in section 10 and the link table in section 11.

•       Sections 2 to 4 cover systematic reviews, meta-analyses and randomized controlled trials.

•       Sections 5 to 7 cover observational studies, pharmacokinetic studies and safety or toxicology sources.

•       Sections 8 and 9 cover mechanistic and preclinical studies.

•       Sections 10 to 12 give the master table, the identifier table and the update log.

Three reading rules apply throughout. First, all doses are elemental iron unless stated, because tablet labels often list the iron salt weight, which is larger. Second, the category of a study is not a quality score. A large trial can be flawed and a small mechanistic study can be rigorous. Third, a study sits in one category but may inform several topics, so cross-references are given where relevant.

Inclusion was limited to sources whose identifiers could be checked against PubMed, publisher or institutional records on the review date. The library is deliberately selective rather than exhaustive. It is a starting set of anchor studies, not a full literature search.

2. Systematic Reviews

Systematic reviews collect studies using a defined search and selection method. They are only as reliable as the studies they include, but they show the overall picture.

SR1. Cancelo-Hidalgo et al., 2013: tolerability of oral iron

This review analysed 111 clinical or observational studies covering 10,695 patients to compare adverse effects across oral iron products. The authors concluded that extended-release ferrous sulfate with mucoproteose appeared best tolerated. They also warned that study designs varied widely, which limits direct comparison between products.

SR2. Fonseca-Nunes et al., 2014: iron and cancer risk

This review examined 59 epidemiologic studies published between 1995 and 2012. For every extra 1 mg per day of heme iron intake, the pooled relative risk was 1.08 for colorectal cancer (95% CI 1.00 to 1.17) and 1.12 for colon cancer (1.03 to 1.22). Breast and lung estimates were not clearly different from no effect. The authors described a tendency toward a positive association with heme iron and called for more prospective work. Because the data are observational, the findings show association, not cause.

3. Meta-Analyses

Meta-analyses pool numerical results from several studies. The four below address tolerability, benefit, pregnancy and long-term disease associations.

MA1. Tolkien et al., 2015: ferrous sulfate and gastrointestinal effects

Pooling 43 randomized trials with 6,831 adults, this analysis found higher odds of gastrointestinal side effects with ferrous sulfate than placebo (odds ratio 2.32, 95% CI 1.74 to 3.08). In seven pregnancy trials the odds ratio was 3.33, with wide uncertainty. The meta-regression did not find a relationship between dose and side effects, a result that is easy to overstate in either direction because the included trials differed in design.

MA2. Low et al., 2016: daily iron in menstruating women

This Cochrane review included 67 studies and 8,506 participants. Daily iron reduced anaemia and iron deficiency, raised haemoglobin and iron stores, improved exercise performance and reduced symptomatic fatigue. Doses ranged from about 1 mg to about 300 mg daily and durations from one to 24 weeks. The evidence on cognition was uncertain and no mortality data were available.

MA3. Peña-Rosas et al., 2015: daily iron in pregnancy

In 44 trials with 43,274 women contributing data, daily oral iron reduced the risk of maternal anaemia and iron deficiency in pregnancy, while benefits for other maternal and infant outcomes were less clear. The review found no evidence that iron increases placental malaria. Cochrane has since issued a newer version of this review, so readers should check the current edition.

MA4. Bao et al., 2012: iron and type 2 diabetes

Eleven prospective studies were included. Highest versus lowest heme iron intake carried a pooled relative risk of 1.33 (95% CI 1.19 to 1.48), and body iron stores measured by ferritin were also associated with risk. Total dietary iron, non-heme iron and supplemental iron were not significantly associated. This distinction matters because it separates food-pattern and iron-store signals from supplement use.

4. Randomized Controlled Trials

Randomized trials give the strongest evidence of cause and effect for a specific intervention, within the population and dose studied.

RCT1. Sazawal et al., 2006: iron and folic acid in a malaria setting

This community trial on Pemba Island, Tanzania randomized about 24,000 preschool children to iron plus folic acid, iron, folic acid and zinc, or placebo. Iron dosing was 12.5 mg daily, with half the dose for infants aged 1 to 11 months. The iron-containing arms were stopped early on the advice of the safety monitoring board. The authors concluded that routine supplementation of children who are not iron deficient could be harmful where malaria transmission is high, while deficient children could benefit when malaria is actively detected and treated.

RCT2. Stoffel et al., 2017: alternate-day versus daily dosing

In two open-label trials in iron-depleted women, 60 mg doses given on alternate days produced higher cumulative fractional absorption than consecutive days (21.8% versus 16.3%). Splitting a 120 mg dose into two 60 mg doses did not improve absorption. These trials measured absorption in small groups, not clinical outcomes.

RCT3. Wolf et al., 2020: intravenous iron and low phosphate

Two randomized trials with 245 adults compared intravenous iron isomaltoside with ferric carboxymaltose in iron-deficiency anaemia. Hypophosphatemia occurred in 7.9% and 8.1% of the isomaltoside groups versus 75.0% and 73.7% of the carboxymaltose groups over 35 days. The authors noted that the clinical importance needs further study.

5. Observational Human Studies

Observational studies follow people without assigning treatment. They suggest associations and reveal natural history but cannot prove cause. Most large observational findings on iron reach this library through the reviews above (SR2 and MA4).

OBS1. Allen et al., 2008: iron overload in HFE hemochromatosis

Researchers genotyped 31,192 northern Europeans aged 40 to 69 in the Melbourne Collaborative Cohort Study and examined a stratified sample including all 203 C282Y homozygotes, followed for about 12 years. Iron-overload-related disease occurred in 28.4% of male and 1.2% of female homozygotes. This study underpins the standard caution that people with genetic iron overload should avoid unsupervised iron supplements.

6. Pharmacokinetic Studies

Standard drug measures such as blood concentration over time do not suit iron, because the body already holds iron and tightly recycles it. Absorption studies using isotopes and hormone measures are therefore the main tools.

PK1. Moretti et al., 2015: hepcidin and absorption

In iron-depleted young women, doses of 60 mg or more raised hepcidin and cut fractional absorption by 35% to 45% twenty-four hours later. A sixfold dose increase from 40 to 240 mg produced only a threefold increase in iron absorbed, from 6.7 to 18.1 mg. The authors suggested that lower doses of 40 to 80 mg and avoiding twice-daily dosing maximize fractional absorption, and that longer-term effects of such schedules need study.

PK2. Geisser and Burckhardt, 2011: pharmacokinetics of iron preparations

This review explains why serum concentration and area-under-the-curve methods are of limited use for iron, and why intravenous complexes differ in stability. It notes that high oral doses, or rapid release from intravenous preparations, can saturate the iron transport system and cause oxidative stress. RCT2 also belongs in this category as an absorption study.

7. Safety and Toxicology Studies

Safety evidence is spread across categories. The sources here are the most direct for poisoning and reference limits, and other safety findings appear under MA1, RCT1 and RCT3.

TOX1. Manoguerra et al., 2005: iron ingestion guideline

This evidence-based consensus guideline is for poison-centre triage. It reports that from 1983 to 1991 iron caused over 30% of deaths from accidental drug ingestion in children. It advises referral to a healthcare facility for known ingestions of 40 mg per kg or more of elemental iron, or for severe or persistent symptoms.

Reference intake limits

The National Institutes of Health sets the adult upper intake level at 45 mg per day from all sources. It notes that a doctor may prescribe more for a limited time to treat deficiency. The fact sheet is listed in section 11.

8. Mechanistic Studies

Mechanistic studies explain how iron behaves in cells and tissues. They support biological plausibility and do not by themselves show effects of supplements in people.

MECH1. Nemeth et al., 2004: hepcidin and ferroportin

In cell culture, hepcidin bound the iron exporter ferroportin and caused it to be internalized and degraded, reducing iron export. This work explains the absorption pattern seen in PK1 and RCT2, where one dose temporarily lowers absorption of the next.

MECH2. Dixon et al., 2012: ferroptosis

This study described ferroptosis, an iron-dependent form of cell death driven by oxidative damage, using cancer cell lines and rat brain slices. It is foundational for iron biology but does not assess dietary or supplemental iron in humans.

9. Preclinical Studies

Animal studies allow tests that would be unethical in people, yet results often fail to transfer.

PRE1. Werner et al., 2011: luminal iron and ileitis in mice

In a mouse model of Crohn’s disease-like ileitis, an iron-sulfate-free diet combined with systemic iron repletion prevented chronic ileitis and altered the gut microbiota. The authors suggested oral iron sulfate may promote inflammation in this model. This is a hypothesis for human research, not a clinical finding. Preclinical coverage in this library is currently limited to this one verified entry.

10. Study Table: Year, Design, Population and Dose

The table summarizes every study above using the facts reported in the abstracts. Doses are as reported by each study.

ID	Study / year	Design	Population	Dose / exposure
SR1	Cancelo-Hidalgo, 2013	Systematic review of clinical and observational studies	111 studies; 10,695 patients	Various oral iron products; tolerability outcomes
SR2	Fonseca-Nunes, 2014	Systematic review and meta-analysis of epidemiologic studies	59 studies (1995–2012); general populations	Dietary, heme and total iron; biomarkers; per +1 mg/day heme iron
MA1	Tolkien, 2015	Meta-analysis of RCTs	43 trials; 6,831 adults	Ferrous sulfate versus placebo or IV iron
MA2	Low, 2016	Cochrane review and meta-analysis	67 studies; 8,506 menstruating women	Oral iron, about 1 to about 300 mg/day; 1–24 weeks
MA3	Peña-Rosas, 2015	Cochrane review and meta-analysis	Pregnant women; 44 trials, 43,274 women contributing data	Daily oral iron alone or with folic acid or other nutrients
MA4	Bao, 2012	Systematic review and meta-analysis of prospective studies	11 prospective studies; type 2 diabetes risk	Dietary heme and total iron; ferritin and related markers
RCT1	Sazawal, 2006	Community-based randomized placebo-controlled trial	About 24,000 preschool children; Pemba, Tanzania	12.5 mg iron + 50 µg folic acid daily (half dose at 1–11 months)
RCT2	Stoffel, 2017	Two open-label randomized trials (isotope absorption)	Iron-depleted women; study 1 n = 40	60 mg daily for 14 days vs alternate days for 28 days; 120 mg once vs 60 mg twice daily
RCT3	Wolf, 2020	Two randomized trials of intravenous iron	245 adults with iron-deficiency anaemia	Iron isomaltoside 1,000 mg vs ferric carboxymaltose 750 mg on days 0 and 7; 35 days
OBS1	Allen, 2008	Population cohort with genotype-stratified sample	31,192 northern Europeans aged 40–69; 203 C282Y homozygotes	Genetic iron overload; about 12 years follow-up
PK1	Moretti, 2015	Isotope absorption studies (three studies)	Iron-depleted young women	Oral iron 40–240 mg; once vs twice daily
PK2	Geisser, 2011	Narrative review	Not applicable	Oral iron(II) salts, iron(III) complexes, IV complexes
TOX1	Manoguerra, 2005	Evidence-based consensus guideline	Adults and children; poison-centre triage	Referral at ≥40 mg/kg elemental iron
MECH1	Nemeth, 2004	Cell-culture mechanistic study	Tissue culture cells	Hepcidin–ferroportin interaction (no supplement dose)
MECH2	Dixon, 2012	Cell and tissue-slice mechanistic study	Cancer cell lines; rat brain slices	Erastin-induced iron-dependent cell death
PRE1	Werner, 2011	Mouse model of Crohn’s disease-like ileitis	Mice (TNFΔARE model)	Iron-sulfate-free diet with systemic iron repletion vs standard diet

 

11. DOI, PubMed and Official Links

Each identifier below was checked against a PubMed, publisher or institutional record. For PK1 and PK2 a confirmed PubMed ID was not retrieved, so the PubMed link runs a search on the DOI, which opens the matching record.

ID	Study	DOI	PubMed
SR1	Cancelo-Hidalgo 2013	10.1185/03007995.2012.761599	PMID 23252877
SR2	Fonseca-Nunes 2014	10.1158/1055-9965.EPI-13-0733	PMID 24243555
MA1	Tolkien 2015	10.1371/journal.pone.0117383	PMID 25700159
MA2	Low 2016	10.1002/14651858.CD009747.pub2	PMID 27087396
MA3	Peña-Rosas 2015	10.1002/14651858.CD004736.pub5	PMID 26198451
MA4	Bao 2012	10.1186/1741-7015-10-119	PMID 23046549
RCT1	Sazawal 2006	10.1016/S0140-6736(06)67962-2	PMID 16413877
RCT2	Stoffel 2017	10.1016/S2352-3026(17)30182-5	PMID 29032957
RCT3	Wolf 2020	10.1001/jama.2019.22450	PMID 32016310
OBS1	Allen 2008	10.1056/NEJMoa073286	PMID 18199861
PK1	Moretti 2015	10.1182/blood-2015-05-642223	PubMed search by DOI
PK2	Geisser 2011	10.3390/pharmaceutics3010012	PubMed search by DOI
TOX1	Manoguerra 2005	10.1081/CLT-200068842	PMID 16255338
MECH1	Nemeth 2004	10.1126/science.1104742	PMID 15514116
MECH2	Dixon 2012	10.1016/j.cell.2012.03.042	PMID 22632970
PRE1	Werner 2011	10.1136/gut.2010.216929	PMID 21076126

 

Official sources

•       NIH Office of Dietary Supplements, Iron: Health Professional Fact Sheet — https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

•       NIH Office of Dietary Supplements, Iron: Fact Sheet for Consumers — https://ods.od.nih.gov/factsheets/Iron-Consumer/

•       Cochrane Library (for current versions of MA2 and MA3) — https://www.cochranelibrary.com

12. Update Log and Last Reviewed

Last reviewed: October 13, 2026

Next review due: April 2027

Date	Change
2026-10-13	First release with 16 studies across eight categories. DOI and PubMed identifiers checked against public records.
2026-10-13	Known gaps recorded: WHO supplementation guidelines, intravenous iron hypersensitivity studies, infant and child trials beyond RCT1, and additional animal studies.
Planned	Check whether newer versions of the Cochrane reviews MA2 and MA3 are available and update the summaries.

 

Readers who spot an error or a newer version of a listed study are encouraged to report it so the log can be updated. This library is educational and is not medical advice.