Iron Supplements That Minimize Constipation
For patients prone to constipation, start with standard ferrous salts (ferrous sulfate, ferrous fumarate, or ferrous gluconate) at 50-100 mg elemental iron taken once daily or every other day, as no oral iron formulation has proven superior in reducing gastrointestinal side effects, but alternate-day dosing significantly reduces constipation while maintaining efficacy. 1, 2
Optimal Dosing Strategy to Minimize Constipation
Take iron once daily rather than multiple times per day, as increased dosing frequency elevates hepcidin for 24 hours, blocking subsequent iron absorption while increasing side effects including constipation (which occurs in 12% of patients on standard dosing). 1, 2
Consider alternate-day (every-other-day) dosing as the preferred strategy if constipation is problematic, as this significantly increases fractional iron absorption and reduces gastrointestinal symptoms while maintaining therapeutic efficacy. 1, 2
Start with one 200 mg ferrous sulfate tablet (containing 65 mg elemental iron) or one 324 mg ferrous fumarate tablet (containing 106 mg elemental iron) once daily in the morning. 2
Timing and Administration to Improve Tolerance
Take iron in the morning on an empty stomach (1-2 hours before meals), as serum hepcidin increases during the day and reduces absorption, and morning dosing is superior to afternoon or evening administration. 2, 3
Co-administer with 500 mg vitamin C (ascorbic acid) to enhance absorption, especially if you need to take iron with small amounts of food for tolerability. 1, 2
If constipation is severe with daily dosing, take iron with a small amount of food or at bedtime to improve tolerance, though this reduces absorption by up to 50%. 1, 4
What to Avoid
Do not consume tea or coffee within 1 hour after taking iron, as these are powerful inhibitors reducing absorption by up to 54%. 2, 4
Avoid taking iron with calcium-containing foods or supplements, fiber-rich foods, or antacids, as these significantly reduce iron absorption. 1, 2, 4
Do not take iron with proton pump inhibitors or H2-blockers when possible, as these reduce gastric acid needed for iron absorption. 4
Alternative Formulations (If Standard Ferrous Salts Fail)
Ferrous bisglycinate chelate may be better tolerated in some patients, though no clinical trials demonstrate superiority over standard ferrous salts in reducing constipation. 1, 5, 6
Ferric maltol has gastrointestinal side effects comparable to placebo but is significantly more expensive and has slower iron loading. 2
Enteric-coated formulations may improve tolerability but decrease absorption and are generally not recommended. 2
Monitoring Response
Check hemoglobin at 4 weeks to assess response; expect a rise of at least 10 g/L within 2 weeks if oral iron is being absorbed. 2, 4
Continue treatment for approximately 3 months after hemoglobin normalizes to adequately replenish iron stores, not just correct anemia. 2, 4
When to Switch to Intravenous Iron
Consider IV iron if oral iron causes intolerable constipation despite dosing adjustments (switching to alternate-day dosing, taking with food, or trying different formulations). 1, 2
Switch to IV iron if hemoglobin fails to rise after 2-4 weeks of adherent oral therapy, indicating treatment failure. 2, 4
IV iron is preferred for patients with malabsorption conditions (celiac disease, inflammatory bowel disease, prior gastric surgery, chronic kidney disease) where oral iron absorption is significantly impaired. 1, 2, 4
Common Pitfalls to Avoid
Do not take iron more than once daily (unless using alternate-day dosing), as this increases constipation and other side effects without improving absorption due to hepcidin elevation. 1, 2
Do not discontinue therapy prematurely when hemoglobin normalizes—continue for 3 months to replenish iron stores. 2, 4
Do not assume all gastrointestinal symptoms are due to iron; persistent constipation warrants evaluation for other causes. 2