Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.

<h4>Background</h4>The tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.<h4>Objective</h4>Our aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate....

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Main Authors: Zoe Tolkien, Lynne Stecher, Adrian P Mander, Dora I A Pereira, Jonathan J Powell
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0117383
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author Zoe Tolkien
Lynne Stecher
Adrian P Mander
Dora I A Pereira
Jonathan J Powell
author_facet Zoe Tolkien
Lynne Stecher
Adrian P Mander
Dora I A Pereira
Jonathan J Powell
author_sort Zoe Tolkien
collection DOAJ
description <h4>Background</h4>The tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.<h4>Objective</h4>Our aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.<h4>Methods</h4>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. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I2 statistics.<h4>Results</h4>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%]. 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.<h4>Conclusions</h4>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.
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spelling doaj-art-ab5e4ab93e7f4d1f8327a0d3c6f287ec2025-08-20T03:12:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011738310.1371/journal.pone.0117383Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.Zoe TolkienLynne StecherAdrian P ManderDora I A PereiraJonathan J Powell<h4>Background</h4>The tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.<h4>Objective</h4>Our aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.<h4>Methods</h4>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. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I2 statistics.<h4>Results</h4>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%]. 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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0117383
spellingShingle Zoe Tolkien
Lynne Stecher
Adrian P Mander
Dora I A Pereira
Jonathan J Powell
Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.
PLoS ONE
title Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.
title_full Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.
title_fullStr Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.
title_full_unstemmed Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.
title_short Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis.
title_sort ferrous sulfate supplementation causes significant gastrointestinal side effects in adults a systematic review and meta analysis
url https://doi.org/10.1371/journal.pone.0117383
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