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Ferrous Sulfate

Evidence Level
Very Strong
4 Clinical Trials
5 Documented Benefits
5/5 Evidence Score

Ferrous sulfate is the reference oral iron salt, the form that most other iron supplements are compared against. It is 20 percent elemental iron by weight, so a 325 mg tablet supplies about 65 mg of iron. In placebo-controlled trials in non-anemic women with low iron stores, 80 mg of iron a day as ferrous sulfate reduced fatigue, and in iron-deficient teenage girls it improved a verbal learning test. Its main drawback is the gut: a pooled analysis of 20 placebo-controlled trials found it roughly doubled the odds of digestive side effects. Doses of 60 mg or more raise hepcidin, a hormone that limits absorption of the next day's dose, so the same doses taken every other day are absorbed better. Iron is only useful for low iron confirmed by a blood test.

Studied Dose 80 mg elemental iron a day in the fatigue trials (4 to 12 weeks); 60 mg doses in absorption studies, with alternate-day dosing absorbed best. These amounts are above the 45 mg/day adult upper limit and are for low iron confirmed by a blood test.
Active Compound Ferrous sulfate (FeSO4)

Benefits

Restores iron levels in women who run low

In a Cochrane review of 67 trials in 8506 menstruating women, daily oral iron cut the risk of anemia by about 60 percent and of iron deficiency by about 40 percent, and raised hemoglobin. The review pooled all oral iron forms rather than ferrous sulfate alone, and digestive side effects were more common on iron.

Supported by Trial 1, Trial 3

20 percent elemental iron by weight

Ferrous sulfate is 20 percent elemental iron by weight, compared with 33 percent for ferrous fumarate and 12 percent for ferrous gluconate. A 325 mg tablet supplies about 65 mg of iron, well above the 18 mg Daily Value. Supplement Facts panels list the elemental iron, so that is the number to compare.

Supported by Trial 2, Trial 3

Better absorption with alternate-day dosing

In iron-depleted women, doses of 60 mg or more raised the absorption-blocking hormone hepcidin for about a day and cut absorption from the next dose by 35 to 45 percent. Taking the same 14 doses of 60 mg every other day over 28 days delivered more iron (175 mg vs 131 mg absorbed) than taking them on 14 consecutive days.

Supported by Trial 2, Trial 3

Less fatigue when iron stores are low

In two placebo-controlled trials of this exact salt (80 mg elemental iron a day for 4 or 12 weeks), fatigue scores fell more on iron in non-anemic women: 29% vs 13% in 144 women, and 47.7% vs 28.8% in 198 women with ferritin below 50 ug/L. The gain was limited to women with low ferritin. A pooled analysis of 4 trials of iron by mouth or injection also found less self-reported fatigue, but no gain in measured physical capacity.

Supported by Trial 2, Trial 3

Attention and learning in iron-deficient teens and women

In a double-blind trial of 81 non-anemic, iron-deficient teenage girls, ferrous sulfate (650 mg twice daily for 8 weeks) improved a verbal learning and memory test versus placebo. A pooled analysis of 14 trials of oral iron in older children, teens and women found better attention and concentration but no memory gain, and called the trials small, short and weak. A later review in women judged the evidence uncertain.

Supported by Trial 4, Trial 2

Mechanism of action

1

Ferrous (Fe²⁺) Form

Iron exists as ferrous (Fe²⁺) or ferric (Fe³⁺) iron. The gut absorbs ferrous iron through the DMT1 transporter, while ferric iron must first be reduced. Because it is more soluble, ferrous iron in supplements is more bioavailable than ferric iron.

2

DMT1 Transport

DMT1 on the surface of duodenal cells takes up Fe²⁺. Inside the cell, iron is exported by ferroportin into the blood, where transferrin carries it to the bone marrow for red cell production, to the liver for storage as ferritin, and to other tissues.

3

Hepcidin Regulation

Hepcidin, a liver hormone, controls absorption by blocking ferroportin. It rises when iron status is high, during inflammation, and for about a day after an iron dose of 60 mg or more, which is why daily or split dosing absorbs less efficiently.

4

Stomach Acid Dependence

Stomach acid helps keep nonheme iron soluble for absorption, so acid-reducing drugs such as proton pump inhibitors can lower iron absorption. Vitamin C enhances absorption of nonheme iron.

Clinical trials

1
Ferrous Sulfate and Digestive Side Effects
PubMed

Systematic review and meta-analysis of 43 randomized trials in 6831 adults comparing ferrous sulfate with placebo or intravenous iron. (Tolkien et al. 2015, PLoS One)

Adults in 20 placebo-controlled trials (3168 people) and 23 trials against intravenous iron (3663 people), including pregnant women and people with inflammatory bowel disease.

Ferrous sulfate raised the odds of digestive side effects against placebo (odds ratio 2.32) and against intravenous iron (odds ratio 3.05). The analysis found no significant link between iron dose and side-effect risk. Two authors hold a patent on an alternative iron compound.

2
Iron for Unexplained Fatigue in Non-Anemic Women
PubMed

Double-blind, randomized, placebo-controlled trial of ferrous sulfate (80 mg elemental iron a day) for 4 weeks. (Verdon et al. 2003, BMJ)

144 women aged 18 to 55 with unexplained fatigue and no anemia, from Swiss primary care; 136 completed.

Fatigue fell 29 percent on iron against 13 percent on placebo (p = 0.004). In subgroup analysis only women with ferritin at or below 50 ug/L improved.

3
Iron for Fatigue in Women with Low Ferritin
PubMed

Multicentre, closed-label, observer-blinded, placebo-controlled randomized trial of ferrous sulfate (80 mg elemental iron a day) for 12 weeks. (Vaucher et al. 2012, CMAJ)

198 menstruating women aged 18 to 53 in France with fatigue, ferritin below 50 ug/L and hemoglobin above 12.0 g/dL.

Fatigue scores fell 47.7 percent on iron against 28.8 percent on placebo (p = 0.02). There was no effect on quality of life, depression or anxiety. Hemoglobin rose 0.32 g/dL and ferritin 11.4 ug/L more than on placebo.

4
Iron and Verbal Learning in Iron-Deficient Teenage Girls
PubMed

Double-blind, placebo-controlled randomized trial of ferrous sulfate 650 mg twice daily for 8 weeks, using four tests of attention and memory. (Bruner et al. 1996, Lancet)

81 non-anemic, iron-deficient girls (ferritin 12 ug/L or less) from four Baltimore high schools; 73 in the per-protocol analysis.

Ferritin ended at 27.3 against 12.1 ug/L on placebo. Girls given iron scored better on a test of verbal learning and memory (p < 0.02); only this test is reported as showing a significant difference.

Side effects and drug interactions

Common Potential side effects

Digestive side effects: in a pooled analysis of 20 placebo-controlled trials, ferrous sulfate roughly doubled the odds of digestive complaints.
Constipation and loose stools: in a Cochrane review of menstruating women, daily iron about doubled the rate of each.
Dark or black stools are expected with iron.
Taking iron with food can reduce stomach upset.
The adult upper limit is 45 mg of iron a day, and supplements with 25 mg or more can reduce zinc absorption.
Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep iron out of reach of children, and in case of overdose call a doctor or poison control center immediately.

Important Drug interactions

Quinolone and tetracycline antibiotics: iron binds them; ferrous sulfate cut ciprofloxacin absorption by 57 percent in one study. Follow the antibiotic label on spacing.
Levothyroxine: iron reduces its absorption; labels advise not taking levothyroxine within 4 hours of iron.
Bisphosphonates such as alendronate: take them with plain water at least 30 minutes before any other food, drink or medicine, as their labels direct.
Methyldopa: ferrous sulfate sharply cut its absorption and raised blood pressure in people taking it.
Levodopa: iron supplements may reduce how much levodopa the body absorbs.
Mycophenolate: one small volunteer study found a large drop in absorption, but later controlled studies, including one in kidney transplant recipients, found no interaction. Ask the prescriber.
Calcium: may reduce iron absorption; take calcium and iron supplements at different times.
Proton pump inhibitors: by lowering stomach acid they can reduce iron absorption.
Coffee and tea: polyphenol-rich drinks strongly reduce absorption of iron from a meal (black tea by 79 to 94 percent in one study).
Vitamin C: enhances absorption of nonheme iron.

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Frequently asked questions about Ferrous Sulfate

What is ferrous sulfate used for?

Ferrous sulfate is a widely used iron supplement for raising low iron levels. It provides a well-absorbed form of iron, though it often causes digestive side effects.

How much ferrous sulfate should I take?

A standard 325 mg ferrous sulfate tablet provides about 65 mg of elemental iron. In iron-depleted women, 60 mg doses taken every other day were absorbed better than the same doses taken on consecutive days. Only take iron to correct a confirmed deficiency, under medical guidance.

Why does ferrous sulfate upset my stomach?

Ferrous sulfate commonly causes constipation, nausea and stomach upset; in pooled trials it roughly doubled the odds of digestive complaints. Taking it with a little food can help. Dark or black stools are common: in one study of pregnant women, 31 percent taking 50 mg of iron a day as ferrous sulphate reported them.

How can I absorb ferrous sulfate better?

Take it with vitamin C (such as orange juice) and away from coffee and tea, which can sharply cut iron absorption, and from calcium, which may lower it. If it upsets your stomach, taking it with food can help.

What is Ferrous Sulfate?

Ferrous sulfate is the reference oral iron salt, the form that most other iron supplements are compared against. It is 20 percent elemental iron by weight, so a 325 mg tablet supplies about 65 mg of iron.

What is the recommended dosage of Ferrous Sulfate?

The clinically studied dose is 80 mg elemental iron a day in the fatigue trials (4 to 12 weeks); 60 mg doses in absorption studies, with alternate-day dosing absorbed best. These amounts are above the 45 mg/day adult upper limit and are for low iron confirmed by a blood test. Always follow the product label and check with a healthcare provider for personal advice.

Is Ferrous Sulfate safe, and does it have side effects?

For most healthy adults, Ferrous Sulfate is well tolerated at studied doses. Reported effects can include: Digestive side effects: in a pooled analysis of 20 placebo-controlled trials, ferrous sulfate roughly doubled the odds of digestive complaints. Constipation and loose stools: in a Cochrane review of menstruating women, daily iron about doubled the rate of each. It may also interact with some medications. Ferrous Sulfate is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Ferrous Sulfate interact with any medications?

Possible interactions include: Quinolone and tetracycline antibiotics: iron binds them; ferrous sulfate cut ciprofloxacin absorption by 57 percent in one study. Follow the antibiotic label on spacing. Levothyroxine: iron reduces its absorption; labels advise not taking levothyroxine within 4 hours of iron. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Ferrous Sulfate?

NutraSmarts rates the evidence for Ferrous Sulfate as Very Strong (5 out of 5). It is backed by 4 clinical trials and 18 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(18 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Stoffel NU, Cercamondi CI, Brittenham G, Zeder C, Geurts-Moespot AJ, Swinkels DW, Moretti D, Zimmermann MB. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017;4(11):e524-e533. doi: 10.1016/S2352-3026(17)30182-5.PubMedUsed to support: Two open-label randomized trials with isotope-labelled ferrous sulfate in iron-depleted Swiss women. In 40 women, 60 mg given on alternate days for 28 days gave higher cumulative fractional absorption (21.8 vs 16.3 percent) and more total iron absorbed (175.3 vs 131.0 mg) than the same 14 doses on consecutive days, with lower hepcidin. In 20 women, splitting 120 mg into two daily doses raised hepcidin without increasing absorption.
  2. Moretti D, Goede JS, Zeder C, Jiskra M, Chatzinakou V, Tjalsma H, Melse-Boonstra A, Brittenham G, Swinkels DW, Zimmermann MB. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015;126(17):1981-9. doi: 10.1182/blood-2015-05-642223.PubMedUsed to support: Stable-isotope studies in 54 non-anaemic young women with ferritin of 20 ug/L or less. Twenty-four hours after ferrous sulfate doses of 60 mg or more, serum hepcidin was raised and fractional absorption of the next dose fell by 35 to 45 percent. A sixfold rise in dose (40 to 240 mg) gave only a threefold rise in iron absorbed. The authors conclude that 40 to 80 mg doses and avoiding twice-daily dosing maximize fractional absorption.
  3. Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015;10(2):e0117383. doi: 10.1371/journal.pone.0117383.PubMedUsed to support: Meta-analysis of 43 randomized trials in 6831 adults. Ferrous sulfate raised the odds of gastrointestinal side effects against placebo (OR 2.32; 20 trials, 3168 people) and against intravenous iron (OR 3.05; 23 trials, 3663 people), with no significant link to dose. Two authors hold a patent on an alternative iron compound.
  4. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron deficiency anaemia. Lancet. 2016;387(10021):907-16. doi: 10.1016/S0140-6736(15)60865-0.PubMedUsed to support: Lancet seminar on iron deficiency anaemia. Anaemia affects roughly a third of the world's population and about half of cases are due to iron deficiency. Oral iron is usually recommended as first-line therapy, while newer intravenous iron formulations replenish stores safely and effectively.
  5. Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, Bischoff T, de Vevey M, Studer JP, Herzig L, Chapuis C, Tissot J, Pécoud A, Favrat B. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003;326(7399):1124. doi: 10.1136/bmj.326.7399.1124.PubMedUsed to support: Double-blind randomized trial in 144 Swiss women aged 18 to 55 with unexplained fatigue and no anaemia. Ferrous sulphate (80 mg elemental iron a day) for 4 weeks lowered fatigue by 29 percent against 13 percent on placebo (p = 0.004). In subgroup analysis only women with ferritin at or below 50 ug/L improved.
  6. Vaucher P, Druais PL, Waldvogel S, Favrat B. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ. 2012;184(11):1247-54. doi: 10.1503/cmaj.110950.PubMedUsed to support: Multicentre, closed-label, observer-blinded randomized trial in 198 French women aged 18 to 53 with fatigue, ferritin below 50 ug/L and haemoglobin above 12.0 g/dL. Oral ferrous sulfate (80 mg elemental iron a day) for 12 weeks lowered fatigue scores by 47.7 percent against 28.8 percent on placebo (p = 0.02), with no effect on quality of life, depression or anxiety. Haemoglobin rose 0.32 g/dL and ferritin 11.4 ug/L more than on placebo.
  7. Houston BL, Hurrie D, Graham J, Perija B, Rimmer E, Rabbani R, Bernstein CN, Turgeon AF, Fergusson DA, Houston DS, Abou-Setta AM, Zarychanski R. Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials. BMJ Open. 2018;8(4):e019240. doi: 10.1136/bmjopen-2017-019240.PubMedUsed to support: Systematic review and meta-analysis of 18 randomized trials (1170 people) of oral, intramuscular or intravenous iron in non-anaemic, iron-deficient adults. Iron reduced self-reported fatigue (SMD -0.38; 4 trials, 714 participants) but did not change objective physical capacity such as maximal oxygen consumption (9 trials, 235 participants) or timed exercise tests. Haemoglobin and ferritin rose.
  8. Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet. 1996;348(9033):992-6. doi: 10.1016/S0140-6736(96)02341-0.PubMedUsed to support: Double-blind placebo-controlled trial in 81 non-anaemic, iron-deficient girls (ferritin 12 ug/L or less) from four Baltimore high schools. Ferrous sulphate 650 mg twice daily for 8 weeks raised ferritin (27.3 vs 12.1 ug/L) and improved scores on a test of verbal learning and memory against placebo (p < 0.02).
  9. Falkingham M, Abdelhamid A, Curtis P, Fairweather-Tait S, Dye L, Hooper L. The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis. Nutr J. 2010;9:4. doi: 10.1186/1475-2891-9-4.PubMedUsed to support: Meta-analysis of 14 randomized trials of oral iron in children aged 6 and over, adolescents and women (no trials in men or older people). Iron improved attention and concentration regardless of baseline iron status (SMD 0.59) and raised IQ by 2.5 points in anaemic groups only, with no effect on memory, psychomotor skills or school achievement. The trials were generally small, short and methodologically weak, with signs of publication bias.
  10. Low MS, Speedy J, Styles CE, De-Regil LM, Pasricha SR. Daily iron supplementation for improving anaemia, iron status and health in menstruating women. Cochrane Database Syst Rev. 2016;4(4):CD009747. doi: 10.1002/14651858.CD009747.pub2.PubMedUsed to support: Cochrane review of 67 trials in 8506 menstruating women. Daily oral iron lowered the risk of anaemia (RR 0.39, moderate-quality evidence) and iron deficiency (RR 0.62), raised haemoglobin, improved maximal and submaximal exercise performance and appeared to reduce symptomatic fatigue. Gastrointestinal side effects were more common, including hard stools or constipation (RR 2.07, 8 trials, 1036 women) and loose stools (RR 2.13). Evidence on cognitive performance was uncertain. The review pooled all forms of oral iron.
  11. Hurrell RF, Reddy M, Cook JD. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br J Nutr. 1999;81(4):289-95..PubMedUsed to support: Radio-iron absorption study in adults eating a bread meal. Coffee, black tea, cocoa and several herb teas all reduced non-haem iron absorption in proportion to their polyphenol content; black tea cut absorption by 79 to 94 percent, and adding milk made little difference.
  12. Lehto P, Kivistö KT, Neuvonen PJ. The effect of ferrous sulphate on the absorption of norfloxacin, ciprofloxacin and ofloxacin. Br J Clin Pharmacol. 1994;37(1):82-5. doi: 10.1111/j.1365-2125.1994.tb04245.x.PubMedUsed to support: Three crossover studies in 8 healthy volunteers each. Ferrous sulphate (100 mg elemental iron) taken with the antibiotic cut absorption of norfloxacin by 73 percent, ciprofloxacin by 57 percent and ofloxacin by 25 percent.
  13. Campbell N, Paddock V, Sundaram R. Alteration of methyldopa absorption, metabolism, and blood pressure control caused by ferrous sulfate and ferrous gluconate. Clin Pharmacol Ther. 1988;43(4):381-6. doi: 10.1038/clpt.1988.47.PubMedUsed to support: Crossover study in 12 healthy people: ferrous sulfate taken with methyldopa cut the share of methyldopa absorbed from 29.1 to 7.9 percent, and ferrous gluconate had a similar effect. In 5 people on long-term methyldopa, 2 weeks of ferrous sulfate raised blood pressure in 4.
  14. Morii M, Ueno K, Ogawa A, Kato R, Yoshimura H, Wada K, Hashimoto H, Takada M, Tanaka K, Nakatani T, Shibakawa M. Impairment of mycophenolate mofetil absorption by iron ion. Clin Pharmacol Ther. 2000;68(6):613-6. doi: 10.1067/mcp.2000.111480.PubMedUsed to support: Randomized crossover study in healthy volunteers: taking an iron preparation with 1.0 g of mycophenolate mofetil sharply lowered blood levels of its active form, mycophenolic acid (12-hour exposure 2.92 vs 32.9 ug.h/mL).
  15. Mudge DW, Atcheson B, Taylor PJ, Sturtevant JM, Hawley CM, Campbell SB, Isbel NM, Nicol DL, Pillans PI, Johnson DW. The effect of oral iron admiinistration on mycophenolate mofetil absorption in renal transplant recipients: a randomized, controlled trial. Transplantation. 2004;77(2):206-9. doi: 10.1097/01.TP.0000100446.44001.00.PubMedUsed to support: Open-label randomized trial in 40 new kidney transplant recipients given iron with mycophenolate mofetil, iron 4 hours later, or no iron. Exposure to mycophenolic acid did not differ between groups (p = 0.82), nor did rejection or side effects. The paper notes an earlier study in seven healthy volunteers that found a 91 percent fall in absorption.
  16. NIH Office of Dietary Supplements. Iron: Fact Sheet for Health Professionals. National Institutes of Health. 2025;Online fact sheet, updated September 4, 2025..SourceUsed to support: Not PubMed-indexed (official NIH fact sheet). Gives the iron RDAs (8 mg a day for men and for women over 50, 18 mg for women 19 to 50, 27 mg in pregnancy) and the adult Tolerable Upper Intake Level of 45 mg a day; notes that supplements with 25 mg or more can reduce zinc absorption, that ferrous fumarate is 33 percent, ferrous sulfate 20 percent and ferrous gluconate 12 percent elemental iron, and that the WHO estimates about half of the 1.62 billion cases of anemia worldwide are due to iron deficiency. Lists interactions with levodopa, levothyroxine (labels advise a 4-hour gap) and proton pump inhibitors, advises taking calcium and iron supplements at different times, and quotes the required US warning that accidental iron overdose is a leading cause of fatal poisoning in children under 6.
  17. Ducray PS, Banken L, Gerber M, Boutouyrie B, Zandt H. Absence of an interaction between iron and mycophenolate mofetil absorption. Br J Clin Pharmacol. 2006;62(4):492-5. doi: 10.1111/j.1365-2125.2005.02541.x.PubMedUsed to support: Open-label randomized crossover trial in 16 healthy fasting men. Mycophenolic acid exposure over 24 hours was similar whether mycophenolate mofetil was taken alone or together with an iron supplement (42.5 vs 44.7 ug.h/mL), so no interaction was found.
  18. Milman NT, Bergholt T. Low-Dose Prophylactic Oral Iron Supplementation (Ferrous Fumarate, Ferrous Bisglycinate, and Ferrous Sulphate) in Pregnancy Is Not Associated With Clinically Significant Gastrointestinal Complaints: Results From Two Randomized Studies. J Pregnancy. 2024;2024:1716798. doi: 10.1155/2024/1716798.PubMedUsed to support: Two randomized double-blind studies in 482 healthy pregnant women taking low-dose iron as ferrous fumarate (20 to 80 mg a day), ferrous bisglycinate (25 mg) or ferrous sulphate (50 mg). Digestive complaints did not rise with dose between 20 and 60 mg of fumarate, but 80 mg brought more constipation and laxative use. Black stools became more frequent with dose and were reported by 8 percent on bisglycinate 25 mg, 22 percent on fumarate 40 mg and 31 percent on sulphate 50 mg. No woman needed to change or stop her iron.