SynthesisPloS one2015
Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.
Synthesis in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 11 registered trials, which are not on this map. Cited by 354 papers, 13 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Daily vs Alternate Day Iron Supplementation for Pregnant Women With Iron Deficiency Anemia: A Randomized Controlled
Daily vs. Intermittent Iron Therapy in Iron Deficient Pregnant Patients: A Randomized Noninferiority Trial
Doubling the Iron Dose VS Single Dose Iron Supplementation to Prevent Iron Deficiency Anemia (IDA) in Twin Pregnant Women: A Randomized Controlled Trial
The Postoperative Iron in Cardiac Surgery (PICS-) Trial: A Randomised Clinical Trial Comparing the Efficacy of Single-, High-dose Intravenous Iron and Oral Iron for the Treatment of Anaemia Following Cardiac Surgery
A Randomised, Double-blinded, Parallel Group Study to Demonstrate the Adherence and Efficacy of Different Doses of Iron Supplement in Subjects With or At-risk of Iron Deficiency With a History of Intolerance to Oral Iron
Intravenous Ferric Carboxymaltose Versus Oral Ferrous Sulfate Replacement in Anaemia Due to Acute Nonvariceal Gastrointestinal Bleeding (FIERCE): Protocol of a Multicentre Randomised Controlled Trial
Prevention of Iron Deficiency Anemia Post-delivery (PRIORITY Trial): A Randomized Controlled Trial of the Global Network for Women's and Children's Health Research
Randomized Open Comparative Trial of Oral Sucrosomial Iron (SiderAl Forte®) and Oral Iron Sulphate (Duroferon®) to Blood Donors.
A Stable Isotope Study in Young Iron-depleted Thai Women to Evaluate the Bioavailability of an Oat Protein-based Iron Delivery System
Improved Gastrointestinal Tolerance and Iron Status Via Probiotic Use in Iron Deficiency Anemia Patients Initiating Oral Iron Replacement
Co-supplementation of Ferrous Iron With Formulated Curcumin Reduces Hepcidin Response in Trained Individuals: a Cross-over, Double-blinded, Placebo-controlled Human Intervention Study
Who cites it
354 citing papers in PubMed, 13 syntheses or guidelines pooled it, 760 citations in OpenAlex.
- Caffeine Use in Sport: A Systematic Review and Meta-analysis of Acute Side Effects and Implications for Athlete Health and Safety.Sports medicine (Auckland, N.Z.) · 2026Pooled it
- Efficacy and safety of probiotics in the treatment of iron deficiency anemia in Chinese children: a systematic review and meta-analysis.Frontiers in nutrition · 2026Pooled it
- Effect of different Iron-Folic acid (IFA) formulations, doses, and frequencies on pregnancy and neonatal outcomes compared to multiple micronutrients (MMN) among pregnant women: a systematic review and meta-analysis.BMC pregnancy and childbirth · 2025Pooled it
- Management of paediatric ulcerative colitis, part 1: Ambulatory care-An updated evidence-based consensus guideline from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation.Journal of pediatric gastroenterology and nutrition · 2025Guideline
- The use of iron after surgery: a systematic review and meta-analysis.Anaesthesia · 2025Pooled it
- The benefits and harms of oral iron supplementation in non-anaemic pregnant women: a systematic review and meta-analysis.Family practice · 2025Pooled it
- Effectiveness and safety of Shengxuening for treatment of renal anemia: a comprehensive systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- A comparative analysis of heme vs non-heme iron administration: a systematic review and meta-analysis of randomized controlled trials.European journal of nutrition · 2024Pooled it
- Daily oral iron supplementation during pregnancy.The Cochrane database of systematic reviews · 2024Pooled it
- Effects of Oral Iron Supplementation on Blood Iron Status in Athletes: A Systematic Review, Meta-Analysis and Meta-Regression of Randomized Controlled Trials.Sports medicine (Auckland, N.Z.) · 2024Pooled it
- 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.Nutrition reviews · 2023Pooled it
- Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.BMJ global health · 2023Pooled it
- Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review.Systematic reviews · 2022Pooled it
- Safety and Efficacy of Oral Ferric Maltol and Ferrous Sulfate for Iron Deficiency Anemia in Infants, Children and Adolescents: A Multicenter Randomized Trial.Paediatric drugs · 2026Trial
- Bovine Lactoferrin Compared With Ferrous sulfate for Treating Iron-Deficiency Anemia in Bangladeshi Women-A Randomized Controlled Trial.The Journal of nutrition · 2026Trial
- Effect of a complementary feeding intervention based on iron- and zinc-biofortified pearl millet on the gut microbiota in 12-18-month-old children: a randomized trial.Nature communications · 2026Trial
- Clinical Trial: Predicting Response to Iron Therapy in Patients With Active Inflammatory Bowel Disease Using Hepcidin and Functional Iron Indices: A Multicentre Randomised Trial.Alimentary pharmacology & therapeutics · 2026Trial
- Energy restriction and iron supplementation improve iron status in women with obesity regardless of red meat consumption: a randomized controlled trial.Scientific reports · 2026Trial
- Dose-Dependent Alterations of the Human Gut Microbiome During Oral Iron Supplementation: A Randomized Study in Iron-Deficient Non-Anaemic Women.Nutrients · 2026Trial
- Pilot pragmatic clinical trial of iron therapy in children with anemia of chronic kidney disease (FeTCh-CKD).Pediatric nephrology (Berlin, Germany) · 2026Trial
294 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.
objectiveOur aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.
methodsSystematic 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. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I2 statistics.
resultsForty 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%]. Subgroup analysis in IBD patients showed a similar effect versus i.v. iron (OR = 3.14, 95% CI 1.34-7.36, p = 0.008, I2 = 0%). 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.
conclusionsOur 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.