Iron

AGA clinical practice guidance recommends oral ferrous sulfate once daily with vitamin C when tolerated, and IV iron when oral iron fails, is not absorbed, or faster repletion is needed.

A meta-analysis of 26 RCTs (4,365 pregnant women) found intermittent oral iron (~120 mg/day) raised hemoglobin similarly to daily 60 mg iron but caused less nausea, diarrhea, and constipation.

A meta-analysis of RCTs in low- and middle-income countries found iron therapy improved hemoglobin and ferritin in women of reproductive age, though heterogeneity across studies was high.

A meta-analysis of 129 pediatric iron trials (34,564 children) found frequent and intermittent regimens similarly reduced anemia; moderate-to-high doses improved hemoglobin and ferritin more than low doses.

A meta-analysis of 7 RCTs (905 anemic participants) found adding vitamin C or using ferrous ascorbate with oral iron did not significantly improve hemoglobin or ferritin versus iron alone.

British Society of Gastroenterology guidelines recommend investigating underlying causes of iron deficiency anemia and using oral or IV iron replacement tailored to tolerance, absorption, and comorbid conditions.

A meta-analysis of 8 pediatric RCTs (493 children) found ferrous sulfate was more effective than iron polymaltose complex for raising hemoglobin and ferritin in iron-deficiency anemia treatment.

In 120 children with iron-deficiency anemia, iron bisglycinate, iron polymaltose, and lactoferrin with iron improved iron stores more than lactoferrin alone, with more side effects in bisglycinate groups.

A network meta-analysis of 53 pregnancy trials (9,145 women) found IV iron sucrose and ferric carboxymaltose improved hemoglobin and ferritin more than oral ferrous sulfate for iron-deficiency anemia.

In 440 adults with iron-deficiency anemia, oral iron alone was equivalent to iron plus vitamin C for hemoglobin recovery at 2 weeks (mean rise 1.84 vs 2.00 g/dL), suggesting vitamin C co-supplementation is not essential.

A systematic review of 11 pregnancy iron prophylaxis trials found 30 mg/day maintained hemoglobin in global studies, while Indian data showed inconsistent results between 60 and 120 mg/day doses.

In Taiwanese adults with newly diagnosed iron-deficiency anemia, IDA was associated with 52% higher psychiatric disorder risk; iron supplementation in IDA patients lowered psychiatric and sleep disorder risk.

In 19 anemic women, alternate-day 200 mg ferrous sulfate produced roughly twice the fractional iron absorption of 100 mg given on consecutive days, likely due to lower hepcidin on non-consecutive dosing.

In 62 women with iron-deficiency anemia, twice-daily 60 mg iron raised hemoglobin ≥2 g/dL in more patients at 3 and 6 weeks than alternate-day 120 mg, though alternate-day dosing caused less nausea.

A Cochrane meta-analysis of 25 RCTs (10,996 menstruating women) found intermittent oral iron reduced anemia risk (RR 0.65) and improved hemoglobin (+5.2 g/L) and ferritin versus placebo or no treatment.

In iron-depleted women, alternate-day iron dosing increased fractional absorption versus consecutive daily dosing; single morning doses matched split doses for absorption with lower hepcidin elevation.

A Cochrane review of 67 RCTs (8,506 menstruating women) found daily iron reduced anemia risk (RR 0.39) and raised hemoglobin (+5.3 g/L) versus control, with more gastrointestinal side effects.

A systematic review of 15 trials in low birth weight or premature infants found iron supplementation improved hematologic iron markers and reduced iron-deficiency anemia prevalence, with insufficient evidence on growth or neurodevelopment.

AAP clinical guidance recommends screening and preventing iron deficiency and iron-deficiency anemia in infants and toddlers 0–3 years because deficiency may impair neurodevelopment even without anemia.

A meta-analysis of 7 trials found sodium iron EDTA (NaFeEDTA) significantly raised hemoglobin (+8.6 g/L) and serum ferritin in iron-deficient populations with good tolerability.

A clinical review notes iron-deficiency anemia affects up to 20% of reproductive-age women; serum ferritin is preferred for diagnosis and a 1–2 g/dL hemoglobin rise after 1 month of oral iron supports treatment response.

A systematic review of 55 pediatric iron RCTs found supplementation raised hemoglobin by 0.74 g/dL on average, with greater benefit in anemic children and smaller effects in malaria hyperendemic areas.

A meta-analysis of 6 adult trials (557 patients) found iron polymaltose complex achieved similar hemoglobin gains as ferrous sulfate for iron-deficiency anemia but with fewer gastrointestinal adverse events.

A review of 26 RCTs in young children found iron supplementation improved hematologic status and may aid development in deficient or anemic children, but benefits and risks vary by iron status and malaria endemicity.

In 56 women after Roux-en-Y gastric bypass, prophylactic oral iron 320 mg twice daily for up to 2 years prevented iron deficiency but did not consistently prevent anemia versus placebo.

A meta-analysis found iron supplementation reduced breath-holding spell frequency and severity in children compared with placebo or no treatment.

In 42 children aged 6 months to 2 years with breath-holding spells, ferrous sulfate 6 mg/kg three times daily reduced spell frequency regardless of baseline anemia status.

A Cochrane meta-analysis of iron for breath-holding attacks in children found insufficient high-quality evidence to confirm benefit on frequency or severity.

In 504 Ethiopian schoolchildren, intermittent iron plus high-dose vitamin A for 5 months improved some cognitive test scores versus placebo in this 2×2 factorial RCT.

A meta-analysis in school-age children aged 6–12 years found iron supplementation improved some cognitive test scores, especially in iron-deficient or anemic children.

A meta-analysis of 1,196 children and adolescents in low- and middle-income countries found oral iron modestly improved intelligence and attention, with stronger effects in anemic participants.

A systematic review of 26 studies found mixed evidence linking iron status and iron interventions to cognitive and academic performance in adolescents.

Follow-up at age 16 of Chilean adolescents who received iron as nonanemic infants found no long-term neurocognitive differences between supplemented and unsupplemented groups.

In 200 Iranian high school girls, twice-weekly 50 mg iron for 16 weeks improved attention scores and hematologic measures versus placebo.

A meta-analysis in older children and adults found oral iron improved cognitive concentration and intelligence in anemic participants but not clearly in nonanemic iron-deficient subjects.

In 81 non-anaemic iron-deficient adolescent girls, ferrous sulfate 650 mg twice daily for 8 weeks improved verbal learning and memory versus placebo.

In 176 Indonesian children aged 3–6 years, 8 weeks of iron improved ferritin and cognitive scores in iron-deficient anemic children but not in nonanemic iron-deficient children.

A Taiwan cohort of 13,381 patients with newly diagnosed iron deficiency anemia had higher subsequent fibromyalgia risk than matched controls without IDA.

A systematic review and meta-analysis of 1,170 non-anaemic iron-deficient adults found iron therapy may reduce fatigue, though benefits on physical capacity were inconsistent across trials.

In 14 distance runners with low-normal ferritin, three IV ferric-carboxymaltose doses (100 mg) over 4 weeks improved fatigue and mood versus placebo but did not improve 3,000 m hemoglobin mass or main performance outcomes.

In 198 nonanemic menstruating women with ferritin below 50 µg/L, oral ferrous sulfate 80 mg/day for 12 weeks reduced fatigue scores by 47.7% versus 28.8% with placebo (p=0.02) and raised hemoglobin and ferritin.

In 144 nonanemic women with unexplained fatigue, oral ferrous sulfate 80 mg/day for 4 weeks reduced fatigue by 29% versus 13% with placebo (p=0.004), mainly in women with ferritin ≤50 µg/L.

A meta-analysis of 11 RCTs (6,511 heart failure patients with iron deficiency) found IV iron reduced heart failure hospitalizations by 21–28% but did not significantly lower all-cause mortality.

The 2023 ESC focused update provides updated recommendations for diagnosing and treating acute and chronic heart failure, including guidance on iron deficiency management.

In 539 Australian men aged 75+, each 1 mg/day increase in dietary haem iron over ~5 years was associated with higher major adverse cardiovascular events, mortality, heart failure, and revascularization.

A meta-analysis of 12 RCTs (3,492 HF patients with iron deficiency) found IV iron reduced HF hospitalization or cardiovascular mortality (RR 0.72) and HF hospitalization alone (RR 0.69) versus control.

A meta-analysis of 10 RCTs (3,373 HF patients with iron deficiency) found IV iron reduced recurrent HF hospitalization plus cardiovascular death (rate ratio 0.75) but mortality effects remained inconclusive.

A meta-analysis of IV ferric carboxymaltose/derisomaltose trials (3,258 patients) found reduced recurrent HF hospitalizations plus cardiovascular death (RR 0.77; NNT 6) with no clear effect on cardiovascular death alone.

A meta-analysis of RCTs in heart failure with reduced ejection fraction and iron deficiency found IV iron-carbohydrate complexes improved symptoms and reduced hospitalizations compared with standard care.

In the HEART-FID trial of 3,065 ambulatory HF patients with iron deficiency, repeated IV ferric carboxymaltose did not significantly improve the composite of death, HF hospitalization, or 6-minute walk distance versus placebo.

An individual patient data meta-analysis of 3 FCM trials (4,501 HF patients) found IV ferric carboxymaltose reduced cardiovascular hospitalizations (rate ratio 0.86) over 52 weeks without a clear mortality benefit.

The 2022 AHA/ACC/HFSA heart failure guideline provides updated evidence-based recommendations for prevention, diagnosis, and management of heart failure, including iron repletion in deficient patients.

A meta-analysis of 4 RCTs (582 HF patients with iron deficiency) found oral iron modestly improved LVEF (+1.52%) and ferritin but did not improve 6-minute walk distance, NT-proBNP, or hemoglobin.

A network meta-analysis of 16 HF trials found IV iron improved 6-minute walk distance and quality of life and reduced HF hospitalization after 12+ weeks; oral iron reduced hospitalization and all-cause death but not exercise capacity.

In 41 HF patients with iron-deficiency anemia, oral ferrous sulfate 200 mg three times daily for 12 weeks improved 6-minute walk distance by 46 m versus a 14 m decline with placebo (p<0.001).

A meta-analysis of 7 RCTs (2,166 HF patients with iron deficiency) found IV iron reduced first HF hospitalization or cardiovascular mortality (OR 0.73) and HF hospitalization (OR 0.67) with uncertain mortality benefit.

Post-hoc analysis of IRONOUT-HF (98 HFrEF patients) found only 24% responded to oral iron polysaccharide 150 mg twice daily for 16 weeks, with no link between iron response and functional or biomarker improvement.

A meta-analysis of 4 RCTs (594 chronic HF patients) found IV iron improved quality of life, reduced hospitalizations, increased 6-minute walk distance and ejection fraction, with acceptable safety.

In 459 chronic HF patients with iron deficiency, IV ferric carboxymaltose improved symptoms, NYHA class, 6-minute walk distance, and quality of life at 24 weeks versus placebo with similar adverse event rates.

In 28,209 Chinese mother-infant pairs, maternal iron supplementation during pregnancy was associated with higher newborn birth weight, especially among anemic mothers and lower birth-weight percentiles.

A meta-analysis of 23 trials (4,492 nonanemic pregnant women) found prophylactic oral iron reduced anemia risk (NNT 10) and raised hemoglobin and ferritin without clear effects on birth weight or preterm birth.

A meta-analysis of 22 trials comparing intermittent versus daily iron-folic acid in pregnancy found similar anemia incidence but lower gastric side effects and better adherence with intermittent dosing.

A meta-analysis of 34 pregnancy trials (13,909 women) found IV iron raised hemoglobin faster, reduced maternal adverse events (OR 0.39 vs oral iron), but neonatal outcomes did not differ significantly.

A Cochrane review of 13 RCTs (3,939 pregnant women with anemia) found IV iron likely increased antenatal and postpartum hemoglobin and reduced anemia versus oral iron, with uncertain effects on postpartum hemorrhage.

An updated meta-analysis of 14 cardiac surgery RCTs (1,955 patients) found perioperative IV iron reduced red blood cell transfusion risk (RR 0.77) and improved postoperative hemoglobin and iron status.

A meta-analysis of 8 RCTs (2,822 iron-replete nonanemic pregnant women) found daily oral iron probably reduced iron-deficiency anemia at term (RR 0.51) and low birthweight (RR 0.30).

In 119 Danish pregnant women, ferrous fumarate 66 mg/day from mid-pregnancy through 8 weeks postpartum reduced iron deficiency and anemia versus placebo and improved newborn cord ferritin.

In 120 pregnant women with iron-deficiency anemia, ferrous sulfate, fumarate, ascorbate, and carbonyl iron at 200 mg/day elemental iron were equally effective for correcting anemia over the study period.

A Cochrane meta-analysis of 21 pregnancy trials (5,490 women) found intermittent versus daily iron caused fewer side effects and less high hemoglobin, with similar effects on maternal anemia and infant outcomes.

A Cochrane review of 49 pregnancy trials found daily or intermittent iron with or without folic acid prevented anemia and iron deficiency but did not clearly reduce low birthweight, preterm birth, or postpartum hemorrhage.

A Cochrane review of 17 pregnancy anemia trials (2,578 women) found oral iron improved hematologic indices with frequent GI adverse effects; parenteral iron improved hematology but lacked robust clinical outcome data.

A meta-analysis of prenatal iron trials in developing countries found iron supplementation raises maternal hemoglobin in a dose- and baseline-dependent manner, though clinical benefits remain uncertain.

In 70 RLS patients with iron-deficiency anemia, IV ferumoxytol and oral ferrous sulfate both markedly improved RLS symptoms over 6 weeks with no significant difference between routes and no serious adverse events.

A meta-analysis of 10 RLS trials found iron therapy reduced IRLS scores by 3.55 points (oral or IV) versus control, supporting iron as effective RLS treatment despite increased non-severe adverse events.

AAN guidelines recommend considering pramipexole, rotigotine, or gabapentin enacarbil for moderate-severe primary RLS; IV ferric carboxymaltose has moderate evidence, and ferrous sulfate plus vitamin C may help when ferritin ≤75 µg/L.

In 30 RLS patients with low-normal ferritin, oral iron and pramipexole for 12 weeks similarly reduced IRLS scores, with response rates of 46.7% in each group.

In a 12-week double-blind RCT, oral iron reduced IRLS scores more than placebo in RLS patients with low-normal ferritin (10.3 vs 1.1 point decrease; p=0.01) and raised ferritin.

A meta-analysis in women of reproductive age found iron supplementation improved exercise performance measures compared with control, supporting benefit in iron-deficient WRA.

A systematic review of 3 RCTs in children aged 0–18 years found insufficient evidence that iron supplementation improves heart rate, endurance time, lactate, or oxygen consumption.

A meta-analysis through February 2010 found iron interventions had little overall effect on height, weight, head circumference, or birth weight across gestation, infancy, childhood, and adolescence.

Meta-analyses of micronutrient trials in children under 5 found multimicronutrient interventions improved growth more than single-nutrient supplements, with iron alone showing smaller effects.

A meta-analysis of 25 pediatric iron supplementation trials found no significant pooled effect on physical growth anthropometry.

Three meta-analyses found multimicronutrient supplementation improved child height and weight, whereas vitamin A or iron alone did not significantly enhance growth.

In 427,939 UK Biobank adults, habitual iron supplementation was associated with higher chronic kidney disease risk among users of antihypertensive medication after multivariable adjustment.

In 478 nulliparous Burkinabé women, weekly periconceptional iron plus folic acid was associated with lower birthweight (−111 g) and higher preterm birth risk (27.5% vs 13.9%) in a malaria-endemic setting.

Analysis of the Burkina Faso iron trial proposed dual inflammatory pathways linking long-term iron supplementation, raised hepcidin, and increased preterm birth risk in malaria-endemic first pregnancies.

A systematic review and meta-analysis of 7 trials in children with neurodevelopmental disorders found limited, low-quality evidence that iron supplementation improves behavioral or cognitive outcomes.

In 104 exclusively or predominantly breastfed infants given 1 mg/kg/day iron from 4 to 9 months, supplementation did not improve psychomotor development at 12 months versus placebo.

In 875 Chilean children, infant iron deficiency or anemia predicted lower verbal ability at follow-up, partly mediated by reduced caregiver stimulation and child engagement.

A meta-analysis of RCTs in healthy exclusively breastfed infants found daily iron improved hematologic status but did not consistently improve growth or cognitive outcomes.

A meta-analysis of low-dose iron and zinc interventions from conception to age 2 years found modest benefits for some micronutrient status markers but inconsistent effects on child development.

In 544 Nepali infants and toddlers, daily zinc, iron-folic acid, or combined supplementation for 1 year did not improve motor or language milestone scores versus placebo.

A systematic review of 561 participants across 5 RCTs found no individual trial showed iron supplementation in nonanemic pregnant women or young children improved children's mental development index.

A meta-analysis of RCTs found iron supplementation improved mental development scores in anemic children but not consistently in nonanemic children.

In 490,593 NIH-AARP participants followed 11 years, multivitamin or single vitamin/mineral supplement use was not associated with altered risk of upper gastrointestinal cancers.

In 172 Cambodian women of reproductive age, 12 weeks of ferrous sulfate or ferrous bisglycinate did not change gut microbial diversity but increased Enterobacteriaceae abundance and EPEC virulence genes with ferrous sulfate.

In 83 adults with hair loss on standard drug therapy, adding a collagen/amino acid/iron/selenium supplement for 12 weeks improved global assessment scores versus drugs alone (GAS 1.67 vs 0.66; p<0.001).

A meta-analysis of 154 RCTs (32,920 participants) found IV iron increased infection risk (RR 1.17) versus oral iron or no iron, while raising hemoglobin and reducing transfusion need.

A meta-analysis of 12 case-control studies found children with early childhood caries had higher odds of iron deficiency (OR 2.63) and iron-deficiency anemia (OR 2.74) than caries-free children.

A meta-analysis of 8 trials (1,093 preterm or low birth weight infants) found enteral iron improved linear growth and reduced anemia without clear effects on infection, necrotizing enterocolitis, or cognition.

Post-hoc analysis of 692 extremely preterm infants found higher cumulative enteral iron dose at 60 days was associated with better Bayley cognitive scores, especially among erythropoietin-treated infants.

A dose-response meta-analysis of 11 cohorts (323,788 participants) found each 1 mg/day increase in dietary heme iron was associated with 16% higher type 2 diabetes risk; total or non-heme iron showed no association.

A review of vegan children found normal growth when diets were well planned, but cobalamin, calcium, and vitamin D deficiencies were common risks without supplementation and careful planning.

In 146 healthy adults, replacing 70% of animal protein with plant protein for 12 weeks lowered vitamin B-12 and iodine intake and status without changing iron biomarkers.