Iron

What it is

Iron is a mineral the body needs to make haemoglobin, the oxygen-carrying protein in red blood cells, and for enzymes used in energy production [1]. Iron deficiency develops in stages, from low iron stores, to iron deficiency without anaemia, to iron-deficiency anaemia, usually defined as haemoglobin below 120 g/L in adults [1]. Oral supplements are mostly ferrous salts such as sulfate, fumarate, gluconate or glycine sulfate, and ferrous sulfate is the standard comparator in trials [2][3]. How much iron is absorbed from a meal depends on what else is eaten: tea, coffee, dairy products and whole grains reduce absorption [4][5]. Dietary iron comes from foods including meat, fish, pulses, whole grains and fortified cereals [5].

How it might work

Iron is needed for red-cell production and for oxidative enzymes in muscle, so low iron stores could limit oxygen use and contribute to tiredness; this proposed mechanism fits the rises in haemoglobin and ferritin seen in trials [1][6]. Why fatigue improves in iron-deficient people who are not anaemic is not fully explained, and some cross-sectional studies find no difference in fatigue between people with and without low iron [7]. One proposed brain mechanism is that iron is needed for energy metabolism and neurotransmitter synthesis in the brain; the measured effects depend on which symptom is studied [8].

What the research says

Iron-deficiency anaemia. In menstruating women, a Cochrane review of 67 randomised trials (8,506 women) found daily iron reduced the chance of anaemia at the end of treatment (risk ratio 0.39) and raised haemoglobin by about 5.3 g/L, with high-quality evidence for haemoglobin [9]. Pregnancy trials agree: a 2024 Cochrane review of 57 trials (48,971 women) found iron cut maternal anaemia (4.0% versus 7.4%; risk ratio 0.30) and iron-deficiency anaemia at term (5.0% versus 18.4%; risk ratio 0.41) [10]. Once anaemia is established, intravenous iron raises haemoglobin a little more than oral iron - about 0.6 g/dL across 29 trials (11,771 women) - and causes fewer mild side effects [11]; a network meta-analysis found intravenous iron sucrose beat oral ferrous sulfate by about 7 g/L at 4 weeks [12].

Prevention in pregnancy. Even when women start pregnancy with normal iron status, daily supplements cut anaemia risk. A 2025 meta-analysis of 23 studies (4,492 non-anaemic pregnant women) halved the risk of anaemia (risk ratio 0.50; number needed to treat 10) and raised haemoglobin by about 7 g/L [13]. A separate review of 8 trials (2,822 women) found less iron-deficiency anaemia at term (risk ratio 0.51) and fewer low-birthweight babies (risk ratio 0.30) [14].

Fatigue without anaemia. A systematic review of 18 trials in non-anaemic, iron-deficient adults found iron reduced self-reported fatigue (standardised mean difference -0.38; 4 trials, 714 people) and raised haemoglobin by about 4 g/L, but did not change objective physical capacity [6]. An earlier meta-analysis of 6 trials found a similar modest fatigue benefit (pooled effect size 0.33) [7]. A 2025 meta-analysis of 18 small studies (1,408 people) reported improvements in fatigue (d 0.34), anxiety (0.34), physical well-being (0.42), cognitive intelligence (0.46) and short-term memory (0.53), but not attention or depression, and effects were absent when people without iron deficiency were excluded [8].

Exercise. Benefits have been shown mainly in athletes who are iron deficient. A 2025 review of 23 studies (669 high-level female athletes) found iron deficiency lowered endurance performance by 3-4%, and treating it with about 100 mg of elemental iron a day improved endurance by 2-20%; most studies had 20 or fewer athletes [1]. In non-anaemic iron-deficient adults, iron did not improve maximal oxygen uptake or timed exercise tests [6], and in 219 female soldiers running time improved only in those who started with iron-deficiency anaemia [15]. For people who are not iron deficient, the trials summarised here show no objective performance gain [6][1].

Gut side effects. A meta-analysis of 43 randomised trials (6,831 adults) found ferrous sulfate about doubled the odds of gastrointestinal side effects versus placebo (odds ratio 2.32) and tripled them versus intravenous iron (3.05), with no clear link to dose across studies [2]. The Cochrane review of menstruating women found more gastrointestinal side effects (risk ratio 1.99), constipation (2.07) and loose stools or diarrhoea (2.13), but no clear increase in nausea [9]. In a 2026 trial, 87% of women taking 100 mg daily reported gut side effects against 7% taking 6 mg twice daily [16], and across 111 studies side-effect rates ranged from about 4% to 47% depending on the iron salt [3].

Children and overdose. UK poison-centre data recorded 2,708 iron overdose referrals over 9.7 years, most often children under 6 (28%) and people aged 13-20 (37%); no deaths occurred in that cohort [17]. Serious cases still occur: in a South Indian case series, 2 of 5 children who swallowed tablets died of liver failure, and all had taken tablets belonging to their pregnant mothers [18]. Reported deaths in children under 6 in US poison-centre data fell from 29 to 1 after unit-dose packaging of iron supplements was required [19]. The dose that triggered serious toxicity in a Turkish study was 28 mg of elemental iron per kg of body weight [20], while an Australian case series of 54 children found most ingestions were mild and the swallowed dose was a poor predictor of symptoms [21].

Doses used in studies

Daily oral iron is the standard approach. The Cochrane review in menstruating women included any dose taken at least five days a week [9], and the 2024 pregnancy review pooled daily oral iron alone or with folic acid [10]. In a trial of 219 female soldiers, 100 mg of ferrous sulfate a day was given for 8 weeks [15], and a review of female athletes describes about 100 mg of elemental iron a day for up to 56 days [1]. A 2026 randomised study compared 100 mg once a day with 6 mg twice a day over 4 weeks [16]. The 2025 meta-analysis in non-anaemic people pooled small trials of widely varying doses and durations [8]. These are the doses the studies used, not recommendations.

Safety and interactions

Side effects: gut upset is the commonest problem [2][9], and it is more frequent at higher doses [16]. Serious iron poisoning in children has been reported from about 28 mg of elemental iron per kilogram of body weight [20], and activated charcoal is not useful for iron overdose [22]. Most unintentional ingestions in one case series were mild and the swallowed dose poorly predicted symptoms [21]. Poison-centre data show deaths in children under 6 fell from 29 to 1 after unit-dose packaging of iron supplements was required [19].

Upper limits and toxic doses: the trials above did not test an upper limit for long-term use; the clearest threshold in the data is the acute paediatric toxicity cut-off of about 28 mg/kg [20]. A trial found gut side effects in 87% of women taking 100 mg daily versus 7% on 6 mg twice daily [16].

Interactions: medicines that suppress stomach acid reduce iron absorption and are linked with iron deficiency [23]; calcium from dairy or supplements blocks some iron absorption when eaten at the same time, although long-term calcium supplementation did not change iron status in the studies reviewed [24]. Iron can also reduce absorption of levothyroxine, and a case report describes a hypothyroid patient needing higher thyroxine doses while taking ferrous sulfate, with thyroid tests suggested for people on both [25]; a primary-care study found levothyroxine users on tablets were more likely to need dose increases when medicines such as iron salts were started [26].

Pregnancy and breastfeeding: daily iron in pregnancy reduces anaemia and probably lowers the chance of a low-birthweight baby [10]. No studies of iron supplements in breastfeeding women specifically were identified; treatment trials after childbirth show oral iron raises haemoglobin, though less than intravenous iron [27].

Relevant conditions: people with genetic haemochromatosis are advised to avoid iron supplements and iron-enriched foods [5]. In children in malaria-endemic areas, iron did not increase malaria overall (high-certainty evidence), but where malaria prevention and management services are limited it may slightly increase clinical malaria (risk ratio 1.15, low-certainty evidence) [28].

Caveats and open questions

Most trials measured haemoglobin, ferritin, symptom scores or side effects rather than long-term disease; the pregnancy review found little difference in deaths but was uncertain [10], and its pooled haemoglobin and ferritin results had high heterogeneity [13]. Athlete evidence comes mostly from iron-deficient athletes in small studies [1], and the non-anaemic adult meta-analyses rely on small, short trials at unclear risk of bias [6]. High-dose iron has also been linked to changes in gut bacteria in small studies, with unknown health meaning [29][16]. Ongoing trials listed below are testing alternate-day dosing, better-tolerated iron forms and iron in female athletes.