Iron · The Ingredient Files

①

Evidence by effect

Evidence strength (A–D, color) and effect size (dots, fill) are shown separately. The two axes are independent.

Claimed effect

Evidence strength

Effect size

One-line summary · key source

Correcting iron-deficiency anemia (restoring hemoglobin and iron storesIron kept in reserve in organs such as the liver and spleen; gauged by ferritin.)Evidence type: Meta-analysis

A Strong

Large

Iron's established core use. Iron supplementation raises hemoglobin and replenishes iron storesIron kept in reserve in organs such as the liver and spleen; gauged by ferritin. (ferritinA protein reflecting the body's iron stores; a blood marker used to judge iron deficiency.) to correct iron-deficiency anemia. In a CochraneAn international network that rigorously reviews and synthesizes evidence. review of pregnant women (44 trials, 43,274 women), preventive iron reduced maternal anemia at term by 70% (relative risk 0.30) and iron-deficiency anemia as well (0.33), and women taking iron had higher hemoglobin at term and postpartum. In a meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of non-anemic iron-deficient adults, iron likewise significantly raised hemoglobin (mean difference +4.01 g/L) and ferritin. The direction of reversing anemia caused by a lack of iron is unmistakable. PMID: 26198451 · 29626044

Preventing maternal anemia and iron deficiency in pregnancyEvidence type: Meta-analysis

B Moderate

Moderate

Daily iron during pregnancy clearly reduces maternal anemia and iron deficiency, and the WHO recommends it in antenatal care. The CochraneAn international network that rigorously reviews and synthesizes evidence. review found a 70% reduction in maternal anemia at term (relative risk 0.30) and a 57% reduction in iron deficiency (0.43). However, the benefit for other birth outcomes such as low birth weight, preterm birthBirth before 37 weeks of pregnancy., and maternal mortality was not clear, and the GRADEAn international standard for rating the certainty of evidence from high to very low. certainty was rated low to moderate because of heterogeneity between trials. Confined to the goal of preventing anemia and iron deficiency, the evidence is consistent. PMID: 26198451

Easing fatigue in non-anemic iron deficiencyEvidence type: Meta-analysis

C Weak

Minimal

For fatigue in people who are not anemic but have low iron storesIron kept in reserve in organs such as the liver and spleen; gauged by ferritin., the evidence is mixed. In a meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of non-anemic iron-deficient adults (18 trials, 1,170 people), iron somewhat reduced subjective fatigue (standardized mean difference -0.38) but did not improve objective physical capacity such as maximal oxygen consumption. Moreover, in a randomized trial giving high-dose intravenous iron to blood donors with low iron stores (ferritinA protein reflecting the body's iron stores; a blood marker used to judge iron deficiency. 50 or below), ferritin and hemoglobin rose but fatigue scores did not differ (3.9 vs 4.0, p=0.819). Perceived fatigue may ease, but an actual improvement in performance is not confirmed. PMID: 29626044 · 32848185

Boosting energy in people who are not iron-deficient (a common belief)Evidence type: Meta-analysis

D Insufficient

None

The belief that iron gives you energy does not hold for people without actual iron deficiency. The benefit is confined to filling a deficiency, and even people with only low iron storesIron kept in reserve in organs such as the liver and spleen; gauged by ferritin. saw no fatigue improvement from intravenous iron. If anything, iron supplements (ferrous sulfate) more than doubled gastrointestinal side effects versus placeboAn inert dummy treatment used as the comparison baseline. (odds ratio 2.32, 43 trials, 6,831 people), with constipation and nausea being common. Because the body has no ready way to excrete excess iron, routine intake also carries a risk of accumulation and overload. Taking iron routinely without confirming a deficiency adds burden without benefit. PMID: 25700159 · 32848185

Evidence strength A Strong · B Moderate · C Weak · D Insufficient/refuted

Effect size Large → None

②

Who benefits / who should be cautious

The statements in this section are translated directly from institutional sources (NIH-ODS, etc.), not our own interpretation. Consult a professional before use.

Benefit

In pregnancy, iron (with folic acid) has been the preferred intervention to build iron storesIron kept in reserve in organs such as the liver and spleen; gauged by ferritin. and prevent anemia, and the World Health Organization (WHO) recommends it in antenatal care. source↗

Original text

Iron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it is thought to improve other maternal and birth outcomes.
Caution

Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under six. Keep it out of reach of children, and in case of overdose contact a doctor or poison control center immediately. source↗

Original text

WARNING: Accidental overdose of iron containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children . In case of accidental overdose, call a doctor or Poison Control Center immediately.
Caution

Do not exceed the recommended dosage, and management of anemia should be under a doctor's advice and supervision. GI discomfort such as nausea can be reduced by taking iron with meals, and iron can also cause constipation or diarrhea. source↗

Original text

WARNINGS: Do not exceed recommended dosage. The treatment of any anemic condition should be under the advice and supervision of doctor. Occasional gastrointestinal discomfort (such as nausea) may be minimized by taking with meals. Iron-containing medication may occasionally cause constipation or diarrhea.
Caution

Oral iron interferes with the absorption of tetracycline antibiotics, so the two should be taken at least two hours apart. source↗

Original text

DRUG INTERACTION PRECAUTION Since oral iron products interfere with absorption of oral tetracycline antibiotics , these products should not be taken within two hours of each other.

③

Form & dosage evidence

Trial doses by effect

Preventing anemia and iron deficiency in pregnancy: Daily oral iron (with folic acid, in antenatal care) [26198451]

④

Balanced conclusion

Iron is not a tonic that is good for everyone; it is a nutrient for confirming and filling a deficiency. When iron-deficiency anemia is present, iron clearly reverses it by raising hemoglobin and replenishing iron storesIron kept in reserve in organs such as the liver and spleen; gauged by ferritin., and for preventing maternal anemia and iron deficiency in pregnancy the benefit reaches the level of a WHO recommendation. But for people who are not iron-deficient, the belief that iron is good for energy and fatigue does not hold. Even in non-anemic iron deficiency only subjective fatigue eased somewhat while actual physical capacity did not improve, and giving intravenous iron to donors with only low iron stores did not improve fatigue. Iron supplements commonly cause GI side effects such as constipation and nausea that do not ease much even at lower doses, and the body cannot easily excrete excess iron, so there is a risk of accumulation and overload. In particular, accidental overdose in children can be fatal, so storage demands special care. Rather than taking it vaguely, the principle is to confirm iron deficiency with a blood test and then fill it in those who need it.

Apply - Get it from food

Examples of foods rich in Iron. Amounts are shown for reference against the doses used in the trials.

Note: eating these foods does not guarantee immediate treatment or prevention of any disease.

Relative to the adult recommendation (8 mg a day for men, 18 mg for women of reproductive age), here is roughly how much each food contributes. Iron from red meat, liver, and shellfish (heme iron) is well absorbed, while plant iron (non-heme) from beans, spinach, and tofu is absorbed relatively less well and is helped by eating it with vitamin C-rich foods.

Beef liver, braised100 g ~6.5 mg (heme) [source]
Spinach, boiled100 g ~3.6 mg (non-heme) [source]
Lentils, boiled100 g ~3.3 mg (non-heme) [source]
Beef chuck, braised100 g ~3.1 mg (heme) [source]
Clams, cooked100 g ~2.8 mg (heme) [source]
Firm tofu100 g ~1.7 mg (non-heme) [source]

⑤

Sources

Each source shows its one-line summary and key summary up front. Expand the collapsed section to read the original abstract. Every citation is verified by re-resolving through the API.

PMID 26198451 Daily oral iron supplementation during pregnancy Meta-analysis (Cochrane) · Cochrane Database Syst Rev, 2015 44 trials, 43,274 women - iron in pregnancy cut maternal anemia at term by 70% (RR 0.30) and iron deficiency by 57%, raising hemoglobin.

Key summary

A CochraneAn international network that rigorously reviews and synthesizes evidence. review of daily iron in pregnancy (61 trials included; 44 contributing data, 43,274 women). Preventive iron reduced maternal anemia at term by 70% (relative risk 0.30) and also reduced iron-deficiency anemia at term (0.33) and iron deficiency (0.43). Women on iron had higher hemoglobin at term and postpartum, but more often had hemoglobin above 130 g/L during pregnancy. Benefits for other outcomes such as low birth weight, preterm birthBirth before 37 weeks of pregnancy., and maternal mortality were not clear, with low to moderate certainty. The conclusion: anemia and iron deficiency are clearly reduced, but the positive effect on other maternal and infant outcomes is less clear.

Show original abstract

BACKGROUND: Iron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it is thought to improve other maternal and birth outcomes. OBJECTIVES: To assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention in antenatal care. MAIN RESULTS: We included 61 trials. Forty-four trials, involving 43,274 women, contributed data and compared the effects of daily oral supplements containing iron versus no iron or placebo. Preventive iron supplementation reduced maternal anaemia at term by 70% (risk ratio (RR) 0.30; 95% confidence interval (CI) 0.19 to 0.46, 14 trials, 2199 women, low quality evidence), iron-deficiency anaemia at term (RR 0.33; 95% CI 0.16 to 0.69, six trials, 1088 women), and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to 0.66, seven trials, 1256 women, low quality evidence). Women receiving iron were on average more likely to have higher haemoglobin (Hb) concentrations at term and in the postpartum period, but were at increased risk of Hb concentrations greater than 130 g/L during pregnancy, and at term. AUTHORS' CONCLUSIONS: Supplementation reduces the risk of maternal anaemia and iron deficiency in pregnancy but the positive effect on other maternal and infant outcomes is less clear. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

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PMID 29626044 Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials Meta-analysis · BMJ Open, 2018 18 trials, 1,170 people - in non-anemic iron deficiency, iron reduced subjective fatigue (SMD -0.38) but not objective physical capacity.

Key summary

A systematic review of iron in non-anemic iron-deficient (IDNA) adults (18 trials, 1,170 people). Iron reduced self-reported fatigue (standardized mean difference -0.38) but made no difference to objective physical capacity such as maximal oxygen consumption. Hemoglobin (+4.01 g/L) and ferritinA protein reflecting the body's iron stores; a blood marker used to judge iron deficiency. rose significantly. The authors noted that even without anemia one could consider iron-rich foods or supplementation to improve fatigue symptoms, while objective performance improvements were not confirmed.

Show original abstract

OBJECTIVE: Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). PARTICIPANTS: Adults (>/=18 years) who were iron deficient but non-anaemic. RESULTS: From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients. Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) -0.38; 95% CI -0.52 to -0.23; I2 0%; 4 trials; 714 participants) but was not associated with differences in objective measures of physical capacity, including maximal oxygen consumption (SMD 0.11; 95% CI -0.15 to 0.37; I2 0%; 9 trials; 235 participants) and timed methods of exercise testing. Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I2 48%; 12 trials; 298 participants) and serum ferritin (MD 9.23 umol/L; 95% CI 6.48 to 11.97; I2 58%; 14 trials; 616 participants). CONCLUSION: In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

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PMID 32848185 The effects of intravenous iron supplementation on fatigue and general health in non-anemic blood donors with iron deficiency: a randomized placebo-controlled superiority trial Randomized controlled trial · Sci Rep, 2020 405-person RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects. - IV iron in donors with low stores raised ferritinA protein reflecting the body's iron stores; a blood marker used to judge iron deficiency. and hemoglobin but did not improve fatigue (3.9 vs 4.0, p=0.819).

Key summary

A randomized placeboAn inert dummy treatment used as the comparison baseline.-controlled trial of intravenous iron (a single 800 mg dose of iron-carboxymaltose) in non-anemic repeat blood donors with low iron storesIron kept in reserve in organs such as the liver and spleen; gauged by ferritin. (ferritinA protein reflecting the body's iron stores; a blood marker used to judge iron deficiency. 50 or below). At 6 to 8 weeks, self-rated fatigue was 3.9 in the iron group and 4.0 in the placebo group with no difference (p=0.819), and prespecified subgroups (gender, ferritin under 25, fatigue 4 or more) showed no difference either. Ferritin (+114.2) and hemoglobin (+5.7 g/L) rose significantly. The numbers improved, but there was no effect on fatigue or general well-being.

Show original abstract

We investigated whether intravenous iron supplementation improves fatigue and general health in non-anemic repeat adult blood donors with iron deficiency (ferritin </= 50 ug/L). Of 1,487 potentially eligible participants, 203 were randomly assigned to a single intravenous dose of 800 mg iron-carboxymaltose and 202 to placebo; 393 participants completed the trial. At 6 to 8 weeks after intervention, self-rated mean fatigue scores (numeric rating scale from 1-10, primary outcome) were 3.9 +/- 1.8 in the iron supplementation group and 4.0 +/- 2.2 in the placebo group, showing no group difference (p = 0.819). Pre-specified subgroup analyses of gender, ferritin < 25 ug/L and fatigue >/= 4 points, as well as exploratory analyses of lower ferritin cut-offs did not reveal any between-group differences. In terms of secondary outcomes, the mean differences were 114.2 ug/L for ferritin (95% CI 103.1-125.3) and 5.7 g/L for hemoglobin (95% CI 4.3-7.2) with significantly higher values in the iron supplementation group. No group differences were observed for different measures of general well-being and other clinical and safety outcomes. Intravenous iron supplementation compared with placebo resulted in increase of ferritin and hemoglobin levels in repeat blood donors with low iron stores, yet had no effect on fatigue and general well-being. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

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PMID 25700159 Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis Meta-analysis · PLoS One, 2015 43 trials, 6,831 adults - ferrous sulfate more than doubled GI side effects vs placeboAn inert dummy treatment used as the comparison baseline. (odds ratio 2.32), independent of dose.

Key summary

A systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. quantifying gastrointestinal side effects of oral iron (ferrous sulfate) (43 trials, 6,831 adults). Ferrous sulfate more than doubled the risk of GI side effects versus placeboAn inert dummy treatment used as the comparison baseline. (odds ratio 2.32) and was three times higher than intravenous iron (3.05). Subgroups of inflammatory bowel disease patients and pregnant women showed the same direction. Side effects had no clear relationship with dose, suggesting they are hard to reduce by lowering the dose. The conclusion is that standard oral iron significantly increases GI-specific side effects.

Show original abstract

BACKGROUND: The tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed. OBJECTIVE: Our aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GI side-effects that included ferrous sulfate and a comparator that was either placebo or intravenous (i.v.) iron. RESULTS: Forty three trials comprising 6831 adult participants were included. Twenty trials (n = 3168) had a placebo arm and twenty three trials (n = 3663) had an active comparator arm of i.v. iron. 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%] and versus i.v. iron with an OR of 3.05 [95% CI 2.07-4.48, p<0.0001, I2 = 41.6%]. Likewise, subgroup analysis of pooled data from 7 RCTs in pregnant women (n = 1028) showed a statistically significant increased risk of GI side-effects for ferrous sulfate although there was marked heterogeneity in the data (OR = 3.33, 95% CI 1.19-9.28, p = 0.02, I2 = 66.1%). Meta-regression did not provide significant evidence of an association between the study OR and the iron dose. CONCLUSIONS: Our meta-analysis confirms that ferrous sulfate is associated with a significant increase in gastrointestinal-specific side-effects but does not find a relationship with dose. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

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FDA (openFDA) Ferrous sulfate (oral) - drug label (pediatric overdose, dosage, GI, and drug-interaction warnings)

This is an institutional information source. Verify directly in the original below.

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USDA FoodData Central Beef, variety meats and by-products, liver, cooked, braised (FDC 168626)