Fe9.0

Iron Research

65 peer-reviewed studies · Evidence score: 9/10

Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency

Anker SD et al. • Nature medicine (2025)

This meta-analysis examined the effects of Iron.

All-cause mortality at 12 months and for the complete length of follow-up (HR = 0.82 (95% CI = 0.65-1.03)) and HR = 0.92 (95% CI = 0.80-1.07), respectively, indicated the overall safety of i.v. iron treatment.
These findings suggest that treating iron deficiency in patients with HF significantly reduces cardiovascular events and also suggests further investigation of optimal dosing of i.v. iron.
Treatment effects were greatest in the first year after randomization when the doses of i.v. iron provided are highest.

Meta-Analysisn=7,175

DOI

Optimal dose and duration of iron supplementation for treating iron deficiency anaemia in children and adolescents: A systematic review and meta-analysis

Rehman T et al. • PloS one (2025)

Low-dose iron supplementation (<5 mg/kg/day) combined with treatment durations of either less than 3 months or more than 6 months, is optimal for improving Hb levels in children and adolescents with IDA.

The pooled effect size for Hb improvement was 2.01 gm/dL (95% CI: 1.48-2.54, ).
Iron supplementation for less than 3 months showed the highest significant effect size (2.39 gm/dL, 95% CI: 0.72-4.07), followed by treatments exceeding 6 months (1.93 gm/dL, 95% CI: 0.09-3.77).
The lowest effect size was observed in treatments lasting 3-6 months (1.58 gm/dL, 95% CI: 0.93-2.23).

Meta-Analysisn=8,829

DOI

Intravenous iron therapy for heart failure and iron deficiency: An updated meta-analysis of randomized clinical trials

Ahmed M et al. • ESC heart failure (2025)

ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92).
Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death.
In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality.

Meta-Analysisn=6,651

DOI

Daily oral iron supplementation during pregnancy

Finkelstein JL et al. • The Cochrane database of systematic reviews (2024)

Daily oral iron supplementation during pregnancy may reduce maternal anaemia and iron deficiency at term.

There is probably little to no difference in maternal death (2 versus 4 events, RR 0.57, 95% CI 0.12 to 2.69; 3 trials, 14,060 women; moderate-certainty evidence).
Infant outcomes: Women taking iron supplements are probably less likely to have infants with low birthweight (5.2% versus 6.1%; RR 0.84, 95% CI 0.72 to 0.99; 12 trials, 18,290 infants; moderate-certainty evidence), compared to placebo or no iron supplementation.
However, the evidence is very uncertain for infant birthweight (MD 24.9 g, 95% CI -125.81 to 175.60; 16 trials, 18,554 infants; very low-certainty evidence).

Meta-Analysisn=48,971

DOI

Dietary iron and the risk of lung cancer

Mohammadzadeh M et al. • International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition (2024)

However, a positive association was observed between dietary heme iron and the risk of lung cancer in women, which may require further investigation.

Methods: We searched PubMed, Web of Science, Scopus and Google scholar for eligible articles published through May 2023 reporting the Relative Risk (RR), Hazard Ratio (HR) or Odds Ratio (OR) with 95% confidence interval (95% CI).
There were no significant associations between the highest dietary total iron (heme and non-heme) (RR: 1.09, 95% CI: 0.78 to 1.51) or heme iron (RR: 1.01, 95% CI: 0.73 to 1.38) intake compared to the lowest intake with lung cancer risk.
However, in the subgroup of women (cases n=5074), heme iron was associated with a 14% increase in the risk of lung cancer (RR: 1.14, 95% CI: 1.01 to 1.29).

Meta-Analysisn=21,943

DOI

Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis

Hansen R et al. • Acta obstetricia et gynecologica Scandinavica (2023)

Daily iron supplementation in iron replete non-anemic pregnant women probably reduces the risk of maternal iron deficiency anemia at term and low birthweight.

In addition, it may reduce iron deficiency at term (RR: 0.74, 95% CI: 0.60-0.92; 4 RCTs, 1663 women; I2 = 58%; low-certainty evidence) and the incidence of small for gestational age babies (RR: 0.39, 95% CI: 0.17-0.86; 1 RCT, 213 infants; I2 not estimable; low-certainty evidence).
Daily iron supplementation in iron replete non-anemic pregnant women probably reduces the risk of maternal iron deficiency anemia at term and low birthweight.
Further research warranted to confirm findings

Meta-Analysisn=2,822

DOI

A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose

Kennedy NA et al. • International journal of clinical pharmacy (2023)

HSR events were uncommon with both intravenous iron formulations; however, the present study showed a significantly lower incidence of HSRs with FDI relative to FCM.

The number of patients experiencing any serious or severe HSR event was 29/2683 (1.08%) with FCM versus 5/3474 with FDI (0.14%).
HSR events were uncommon with both intravenous iron formulations; however, the present study showed a significantly lower incidence of HSRs with FDI relative to FCM.
Further large-scale, head-to-head trials of the iron formulations would be required to confirm this finding.

Meta-Analysisn=10,467

DOI

Systematic review and meta-analysis of intravenous iron-carbohydrate complexes in HFrEF patients with iron deficiency

Sindone A et al. • ESC heart failure (2023)

ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose (FCM); 7.5% received iron sucrose and 1.6% received iron isomaltoside.
IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59-0.95); P = 0.016], but did not significantly impact all-cause mortality, compared with control.
IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control.

Meta-Analysisn=2,381

DOI

Alpha Lipoic Acid Supplementation and Iron Homeostasis: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Sharifi-Zahabi E et al. • International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition (2024)

ALA supplementation had no statistically significant effect on iron-related parameters.

In subgroup analysis, ALA significantly increased hemoglobin in patients with hematological disorders (WMD = 1.23 g/dL; 95% CI: 1.00, 1.45 g/dL; I2 = 96.6%, p < 0.001) and in studies with durations longer than 8 weeks (WMD = 1.03 g/dL; 95% CI: 0.82, 1.25 g/dL; I2 = 96.5%, p = 0.02).
ALA supplementation had no statistically significant effect on iron-related parameters.
Further research warranted to confirm findings

Meta-Analysisn=529

DOI

The Prevalence of Anemia among Pregnant Women in China: A Systematic Review and Meta-Analysis

Zhou Y et al. • Nutrients (2024)

It was found that dietary factors were one of the major causes of anemia, and iron-containing supplements and nutrition counseling could be effective interventions to reduce the prevalence of anemia, ID, and IDA among Chinese pregnant women.

The results showed that the prevalence of anemia, ID, and IDA among pregnant women in China were 30.7% (95% CI: 26.6%, 34.7%), 45.6% (95% CI: 37.0%, 54.2%), and 17.3% (95% CI: 13.9%, 20.7%), respectively.
Generally, lower prevalence was observed in the economically more advanced eastern region of the country, while the prevalence of ID was higher in the eastern region than that in the western region.
The prevalence of anemia and IDA in rural areas was higher than that in urban areas, but ID prevalence was higher in urban areas.

Meta-Analysisn=722

DOI

Treatment for women with postpartum iron deficiency anaemia

Jensen MCH et al. • The Cochrane database of systematic reviews (2024)

Intravenous iron probably reduces fatigue slightly in the early postpartum weeks (8 to 28 days) compared to oral iron tablets, but probably results in little to no difference after four weeks.

Intravenous iron versus oral iron supplementation The evidence is very uncertain about the effect of intravenous iron on mortality (risk ratio (RR) 2.95, 95% confidence interval (CI) 0.12 to 71.96; P = 0.51; I² = not applicable; 3 RCTs; 1 event; 572 women; very low-certainty evidence).
Intravenous iron probably results in a slight reduction in fatigue within 8 to 28 days (standardised mean difference -0.25, 95% CI -0.42 to -0.07; P = 0.006; I² = 47%; 2 RCTs; 515 women; moderate-certainty evidence).
Oral iron probably increases the risk of constipation compared to intravenous iron (RR 0.12, 95% CI 0.06 to 0.21; P < 0.001; I² = 0%; 10 RCTs; 1798 women; moderate-certainty evidence).

Meta-Analysisn=572

DOI

Serum or plasma ferritin concentration as an index of iron deficiency and overload

Garcia-Casal MN et al. • The Cochrane database of systematic reviews (2021)

At a threshold of 30 micrograms/L, there is low-certainty evidence that blood ferritin concentration is reasonably sensitive and a very specific test for iron deficiency in people presenting for medical care.

In the general adult population, three studies reported sensitivities of 63% to 100% at the optimum cutoff for ferritin, with corresponding specificities of 92% to 98%, but the ferritin cutoffs varied between studies.
One study in healthy children reported a sensitivity of 74% and a specificity of 77%.
One study in pregnant women reported a sensitivity of 88% and a specificity of 100%.

Meta-Analysisn=6,059

DOI

Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis

Rogozińska E et al. • The Lancet. Haematology (2021)

Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose.

Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose.
Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment.
Further research warranted to confirm findings

Meta-Analysisn=9,145

DOI

Early Childhood Caries and Iron Deficiency Anaemia: A Systematic Review and Meta-Analysis

Easwaran HN et al. • Caries research (2022)

This meta-analysis examined the effects of Iron.

In comparison with children not affected by ECC, those affected had an increased likelihood of IDA (OR = 6.07 [3.61, 10.21]).
The meta-analysis showed no statistical difference when comparing blood parameters (Hb, MCV, and serum ferritin) in children with and without ECC.
This systematic review demonstrates an association between ECC and increased odds of IDA rather than it being the cause for IDA.

Meta-Analysisn=1,434

DOI

Iron deficiency, supplementation, and sports performance in female athletes: A systematic review

Burden RJ et al. • European Journal of Sport Science (2024)

Endurance performance improved by 2-20% in iron-deficient athletes with supplementation.

23 studies with 669 athletes analyzed
Iron deficiency reduces performance by 3-4%
100mg/day elemental iron effective for 56 days

Systematic Reviewn=669

DOI

Risk of Infection Associated With Administration of Intravenous Iron: A Systematic Review and Meta-analysis

Shah AA et al. • JAMA network open (2021)

In this large systematic review and meta-analysis, intravenous iron was associated with an increased risk of infection.

Intravenous iron was associated with an increased risk of infection when compared with oral iron or no iron (RR, 1.17; 95% CI, 1.04-1.31; I2 = 37%; moderate certainty of evidence).
In this large systematic review and meta-analysis, intravenous iron was associated with an increased risk of infection.
Well-designed studies, using standardized definitions of infection, are required to understand the balance between this risk and the potential benefits.

Meta-Analysisn=920

DOI

Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Oh C et al. • Nutrients (2020)

In addition, they further contribute to the ongoing discourse of choosing antenatal MMN over IFA as the standard of care in LMICs.

IFA supplementation showed notable improvement in maternal anemia and the reduction in low birthweight, whereas LNS supplementation had no apparent effect on outcomes; further research that compares LNS and MMN supplementation could help understand differences with these commodities.
For single micronutrient supplementation, improvements were noted in only a few outcomes, mainly pre-eclampsia/eclampsia (calcium), maternal anemia (iron), preterm births (vitamin D), and maternal serum zinc concentration (zinc).
These findings highlight that micronutrient-specific supplementation should be tailored to specific groups or needs for maximum benefit.

Meta-Analysisn=451,723

DOI

Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD)

Ruospo M et al. • The Cochrane database of systematic reviews (2018)

In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification.

The effects of binders on patient-important outcomes compared to placebo are uncertain.
In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.
Further research warranted to confirm findings

Meta-Analysisn=1,467

DOI

Daily iron supplementation for improving anaemia, iron status and health in menstruating women

Low MS et al. • The Cochrane database of systematic reviews (2016)

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

Women receiving iron had a higher haemoglobin concentration at the end of intervention compared to women receiving control (mean difference (MD) 5.30, 95% CI 4.14 to 6.45, 51 studies, 6861 women, high quality evidence).
Women receiving iron had a reduced risk of iron deficiency compared to women receiving control (RR 0.62, 95% CI 0.50 to 0.76, 7 studies, 1088 women, moderate quality evidence).
Seven trials recruiting 901 women reported on 'any side effect' and did not identify an overall increased prevalence of side effects from iron supplements (RR 2.14, 95% CI 0.94 to 4.86, low quality evidence).

Meta-Analysisn=8,506

DOI

Effects of Oral Iron Supplementation on Blood Iron Status in Athletes: A Systematic Review, Meta-Analysis and Meta-Regression

Mielgo-Ayuso J et al. • Sports Medicine (2024)

Oral iron supplementation effectively improves blood iron parameters in athletes.

449 participants across included studies
Significant improvements in ferritin levels
Primarily studied in female athletes

Meta-Analysisn=449

DOI

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