Evidence explainerIron (ferrous sulfate vs bisglycinate vs other forms)

Iron Pills Without the Stomach Upset? The Case for Every-Other-Day Dosing

Iron works, but ferrous sulfate roughly doubles the odds of stomach trouble. Two Swiss trials suggest a simple schedule change helps. Here is what they found and who they studied.

By Kymata Health editorial teamPublished October 9, 2026Last reviewed October 9, 2026

Medical review pending. Written by our editorial team from the studies cited below; a credentialed clinician has not reviewed it yet. Educational only, not medical advice.

Key takeaways

  • In menstruating women, daily iron raised hemoglobin by 5.30 g/L and lowered the risk of anemia (RR 0.39) in a Cochrane review [1].
  • Ferrous sulfate raised the odds of stomach and bowel side effects versus placebo (odds ratio 2.32) across 20 trials [2].
  • In iron-depleted young women, alternate-day iron was absorbed better than consecutive-day iron (21.8% vs 16.3%) [3].
  • At the same total dose over 6 months, alternate-day iron matched daily iron on ferritin with fewer gut side effects [4].
  • Check iron status with a clinician first; men and postmenopausal women need much less iron, and the adult upper limit is 45 mg/day [5].

The evidence, graded

Pulled from our monograph evidence tables. Grades follow our evidence-grading policy.

  • Grade AImprovedHemoglobin and iron status in menstruating womenIron (ferrous sulfate vs bisglycinate vs other forms) · Meta-analysis · n=6,861 · 2016 · PMID 27087396Hemoglobin was 5.30 g/L higher with iron (high-quality evidence). Iron also lowered the risk of anaemia (RR 0.39; 3273 women) and iron deficiency (RR 0.62; 1088 women), moderate-quality evidence.
  • Grade AImprovedStomach and bowel side effects with ferrous sulfateIron (ferrous sulfate vs bisglycinate vs other forms) · Meta-analysis · n=3,168 · 2015 · PMID 25700159Ferrous sulfate raised the odds of gastrointestinal side effects versus placebo (OR 2.32; 95% CI 1.74-3.08). Meta-regression found no clear link with the iron amount.
  • Grade DImprovedIron absorption: alternate-day vs consecutive-dayIron (ferrous sulfate vs bisglycinate vs other forms) · RCT · n=40 · 2017 · PMID 29032957Cumulative fractional absorption was 21.8% on alternate days vs 16.3% on consecutive days, and total absorbed iron 175.3 vs 131.0 mg. In a second study (n=20), splitting 120 mg into two daily doses did not raise absorption.
  • Grade CMixedIron stores and side effects: alternate-day vs dailyIron (ferrous sulfate vs bisglycinate vs other forms) · RCT · n=150 · 2023 · PMID 38021373Ferritin did not differ (43.8 vs 44.8 μg/L). Daily dosing had more gastrointestinal side effects on iron days (LPR 1.56), and iron deficiency at 6 months was 11.4% with daily vs 3.0% with alternate-day dosing.

Iron works, and it bothers the gut

The Cochrane review of daily iron in menstruating women pooled 51 trials with 6,861 women for hemoglobin, which rose 5.30 g/L with iron (high-quality evidence) [1]. Anemia and iron deficiency were also less common [1]. Loose and hard stools were each about twice as common with iron [1].

A separate meta-analysis of 20 placebo-controlled trials found ferrous sulfate raised the odds of gastrointestinal side effects (odds ratio 2.32), with no clear link to the amount of iron [2].

Why every other day might work better

In a 2017 Swiss study, 40 iron-depleted women aged 18 to 40 took 60 mg of isotope-labelled iron each morning, either on consecutive days for 14 days or on alternate days for 28 days [3]. Cumulative absorption was 21.8% on alternate days versus 16.3% on consecutive days, and total iron absorbed was 175.3 versus 131.0 mg [3]. Splitting 120 mg into two doses a day did not help absorption [3].

A 2023 double-masked trial then gave 150 young women 100 mg of iron either daily for 90 days or on alternate days for 180 days, keeping the total equal [4]. Ferritin ended up the same (43.8 vs 44.8 µg/L), daily dosing caused more gut side effects, and iron deficiency at 6 months was 11.4% with daily versus 3.0% with alternate-day dosing [4].

These are small trials in young Swiss women, so we grade them D and C [3][4]. Whether they apply to other groups is not known.

Forms and the elemental number

US labels list elemental iron. By weight, ferrous fumarate is about 33% iron, ferrous sulfate about 20% and ferrous gluconate about 12% [5]. Ferrous salts are more bioavailable than ferric salts [5]. In pregnant women, ferrous bisglycinate was linked to fewer reported gut side effects than other iron supplements in one meta-analysis [6]. NIH notes that having iron with food can lessen side effects [5].

Cautions before you start

Iron and zinc compete too: iron supplements of 25 mg or more can reduce zinc absorption [5]; see zinc forms and safe limits. Full details are on the iron monograph.

  • Test first: low iron has many causes, and men and women over 50 need only 8 mg/day [5].
  • Levothyroxine and levodopa: iron reduces their absorption; some levothyroxine labels advise a 4-hour gap [5].
  • Calcium might interfere with iron absorption; experts suggest taking them at different times [5].
  • Keep iron away from children: accidental overdose has caused child deaths [5].
  • Hereditary hemochromatosis: avoid iron and vitamin C supplements, per liver specialists cited by NIH [5].

Quick answers

Should I take iron with vitamin C?

Vitamin C increases nonheme iron absorption, which is not a concern for most healthy people but matters in hemochromatosis [7].

Is iron bisglycinate gentler?

In pregnant women, a meta-analysis found fewer reported gut side effects with ferrous bisglycinate than other iron supplements [6].

Keep reading

Full monographs

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References

  1. [1]Daily iron supplementation for improving anaemia, iron status and health in menstruating women. Cochrane Database Syst Rev, 2016. PMID 27087396
  2. [2]Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One, 2015. PMID 25700159
  3. [3]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. PMID 29032957
  4. [4]Alternate day versus consecutive day oral iron supplementation in iron-depleted women: a randomized double-blind placebo-controlled study. EClinicalMedicine, 2023. PMID 38021373
  5. [5]Iron: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements, 2025.
  6. [6]The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev, 2023. PMID 36728680
  7. [7]Vitamin C: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements, 2025.

Iron (ferrous sulfate vs bisglycinate vs other forms) and other dietary supplements are not intended to diagnose, treat, cure or prevent any disease, and these statements have not been evaluated by the FDA. Talk to your clinician or pharmacist before starting a supplement, especially if you take prescription medicines. This page has no product or affiliate links.

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