Does Ferrous Sulfate Cause Constipation?
Yes, ferrous sulfate significantly increases the risk of gastrointestinal side effects including constipation compared to placebo, with an odds ratio of 2.32 (95% CI 1.74-3.08). 1
Evidence for Gastrointestinal Side Effects
The British Society of Gastroenterology guidelines explicitly state that GI adverse effects (such as nausea, diarrhea, constipation) are much commoner with oral preparations, and ferrous sulfate specifically causes significantly more GI side effects than both placebo and parenteral iron. 1
- Ferrous sulfate increases GI side effects with an odds ratio of 2.32 versus placebo and 3.05 versus intravenous iron. 1
- A systematic review of 43 trials comprising 6,831 adult participants confirmed that ferrous sulfate supplementation significantly increases the risk of all gastrointestinal side effects, including constipation. 2
- In clinical trials, 75% of participants reporting one or more GI symptoms in the first week were in the ferrous sulfate group versus placebo. 3
Specific Constipation Risk
Constipation is one of the most common and discriminating side effects of ferrous sulfate therapy. 1
- Higher doses (80 mg elemental iron daily) are associated with significantly higher frequencies of constipation and increased use of laxatives compared to lower doses. 1
- Constipation was specifically listed among the gastrointestinal symptoms commonly reported with oral ferrous iron salts in controlled trials. 3
- In healthy volunteers taking ferrous sulfate 325 mg three times daily, significant nausea and diarrhea were noted, though constipation was also documented as a common complaint. 4
Important Clinical Context
Despite the high prevalence of GI side effects including constipation, discontinuation rates in clinical trials are relatively low (0-24%), though real-world discontinuation rates can reach up to 40%. 1
- There is no dose-effect relationship for GI side effects over the range of 50-400 mg elemental iron per day, meaning higher doses do not necessarily cause proportionally more constipation. 1
- Low-dose prophylactic iron supplementation (25-50 mg elemental iron daily) in pregnancy is not associated with clinically significant GI complaints, suggesting dose matters for symptom severity. 5
Strategies to Minimize Constipation
If constipation becomes problematic, switch to alternate-day dosing (every other day) with 100-200 mg elemental iron, which markedly improves fractional absorption and reduces GI side effects while preserving efficacy. 6, 7
- Once-daily dosing of 50-100 mg elemental iron causes fewer GI side effects than multiple daily doses because doses ≥60 mg trigger hepcidin elevation lasting ~24 hours. 6, 8
- Taking iron with food can reduce GI side effects including constipation, though this decreases absorption. 6
- Do not switch between different ferrous salts (ferrous fumarate, ferrous gluconate) expecting better tolerability regarding constipation, as evidence does not support this practice. 6
When to Consider Alternatives
If constipation remains intolerable despite dosing adjustments, consider switching to intravenous iron, which has significantly fewer GI side effects (OR 0.33 compared to oral ferrous sulfate). 1
- Ferric maltol (30 mg twice daily) may be considered for patients with prior intolerance to ferrous sulfate, as GI adverse events are comparable to placebo, though it is substantially more expensive. 6, 7
- Intravenous iron produces a clinically meaningful hemoglobin response within one week and avoids all oral GI side effects including constipation. 6, 7