What is the optimal timing for taking ferrous sulfate (iron supplement) in adults, particularly those with a history of gastrointestinal disorders such as celiac disease or Crohn's disease?

Optimal Timing for Ferrous Sulfate Administration

Take ferrous sulfate once daily in the morning on an empty stomach (at least 1-2 hours before or after meals) with vitamin C (approximately 500 mg) or citrus juice, and avoid coffee, tea, or calcium-containing foods for at least 1-2 hours. 1, 2, 3

Dosing Frequency and Timing

Once-daily dosing is superior to multiple daily doses because iron doses ≥60 mg stimulate hepcidin elevation that persists for 24 hours, reducing absorption of subsequent doses by 35-45%. 1, 2, 4 This contradicts the traditional FDA labeling recommendation of 2-3 times daily dosing, but recent high-quality evidence clearly demonstrates that split dosing actually decreases overall iron absorption. 5, 4

• Morning administration is optimal because serum hepcidin increases throughout the day, reducing iron absorption when taken in the afternoon or evening. 2, 3

• Alternate-day dosing (every other day) significantly increases fractional iron absorption and may reduce gastrointestinal side effects while maintaining efficacy, making it an excellent option if daily dosing causes intolerable symptoms. 1, 2, 4

Optimal Dose for Initial Treatment

Start with one 200 mg ferrous sulfate tablet daily (containing 65 mg elemental iron), which falls within the recommended 50-100 mg elemental iron range. 1, 6, 2 Higher doses do not improve absorption and increase side effects. 1

Administration Guidelines to Maximize Absorption

Take on an empty stomach (1-2 hours before or after meals) whenever possible, as food can reduce iron absorption by up to 50%. 2, 3

Co-administer with vitamin C (approximately 500 mg) or citrus juice to enhance absorption, especially important if you must take it with food due to GI intolerance. 7, 2, 3

Avoid these absorption inhibitors for at least 1-2 hours:

• Coffee and tea (powerful iron absorption inhibitors) 1, 2, 3
• Calcium-containing foods or supplements 2, 3
• Antacids, H2 blockers, or proton pump inhibitors 2, 3
• High-fiber foods, cereals, and grains 3

Take with a full glass of liquid and remain upright for 30-60 minutes to reduce the risk of pill esophagitis. 3

Special Considerations for Celiac Disease and Crohn's Disease

Patients with active inflammatory bowel disease (including active celiac disease or Crohn's disease) absorb oral iron poorly due to intestinal inflammation and hepcidin elevation. 1, 8 In these patients:

• No more than 100 mg elemental iron should be taken daily in the setting of active inflammation. 1

• Consider intravenous iron first-line if disease is active and anemia is moderate to severe (Hb <100 g/L), as oral iron absorption is significantly impaired. 1, 2, 8

• Once on a gluten-free diet (for celiac disease) or in remission (for Crohn's disease), oral iron absorption improves, but normalization can take 6 months to 2 years. 9, 8

Managing Gastrointestinal Side Effects

If once-daily dosing causes intolerable GI upset:

• Switch to alternate-day dosing (every other day), which maintains effectiveness while reducing side effects. 1, 7, 2

• Consider taking with a small amount of food, though this reduces absorption. 7, 2

• Try alternative formulations (ferrous fumarate or ferrous gluconate), though evidence for improved tolerability is limited. 1, 7

• Ferric maltol has GI side effects comparable to placebo but is significantly more expensive and has slower iron loading. 1

• Avoid modified-release or enteric-coated preparations, as they have reduced efficacy despite higher cost. 7, 10

Monitoring Response

Check hemoglobin at 4 weeks to assess response to therapy. 1, 7, 2 The absence of a hemoglobin rise of at least 10 g/L after 2 weeks strongly predicts treatment failure (sensitivity 90.1%, specificity 79.3%). 1, 2

Continue treatment for approximately 3 months after hemoglobin normalizes to adequately replenish iron stores, not just correct anemia. 1, 7, 2

Monitor blood counts every 6 months initially after completing therapy to detect recurrent iron deficiency. 1, 2

When to Switch to Intravenous Iron

Consider IV iron if:

• Oral iron causes intolerable side effects despite dosing adjustments 1, 7, 2
• Hemoglobin fails to rise after 2-4 weeks of adherent oral therapy 1, 2
• Active inflammatory bowel disease with moderate to severe anemia (Hb <100 g/L) 1, 2
• History of gastric surgery, malabsorption syndromes, or chronic kidney disease 2

Common Pitfalls to Avoid

Do not take iron more than once daily unless specifically using alternate-day dosing, as multiple daily doses increase side effects without improving absorption. 1, 2, 4

Do not assume enteric-coated or modified-release preparations are better tolerated—they have reduced bioavailability (AUC less than 30% of standard preparations) and are not recommended. 7, 10

Do not discontinue therapy prematurely when hemoglobin normalizes—continue for 3 months to replenish iron stores. 1, 7, 2

In patients with celiac disease or Crohn's disease, verify disease activity status before relying on oral iron, as active inflammation severely impairs absorption. 1, 9, 8