Why take ferrous sulfate (iron supplement) every other day instead of daily?

Why Take Ferrous Sulfate Every Other Day Instead of Daily

Taking ferrous sulfate every other day instead of daily maximizes iron absorption while reducing gastrointestinal side effects, because oral iron triggers a rise in hepcidin that blocks further iron absorption for up to 48 hours. 1

The Physiological Rationale

When you take oral iron, your body responds by increasing serum hepcidin levels, which remain elevated for up to 48 hours and actively block further iron absorption during this period. 1 This means that taking iron more frequently than once daily will not improve absorption but will increase side effects due to this hepcidin-mediated regulatory mechanism. 1

In iron-depleted women, alternate-day dosing leads to significantly increased fractional iron absorption compared with daily dosing. 1 A landmark randomized controlled trial demonstrated that cumulative fractional iron absorption was 21.8% with alternate-day dosing versus only 16.3% with consecutive-day dosing (p=0.0013), and total iron absorption was 175.3 mg versus 131.0 mg respectively (p=0.0010). 2

Evidence-Based Dosing Recommendations

Optimal Dosing Strategy

• Once-daily dosing of 50-100 mg elemental iron is recommended rather than multiple daily doses. 1
• The dose should be taken in the morning, as hepcidin levels are lower at this time, optimizing absorption. 3
• Taking iron on an empty stomach maximizes absorption, though this may increase gastrointestinal side effects. 1

Alternate-Day Dosing as a Preferred Option

• Alternate-day dosing may be equally effective with better tolerability compared to daily dosing. 4
• A clinical trial in women with iron deficiency anemia showed that 270 mg ferrous sulfate (80 mg elemental iron) given every other day produced similar hemoglobin increases to daily dosing, but with significantly fewer gastrointestinal side effects. 5
• The increase in hemoglobin levels was similar among daily and alternate-day groups (p=0.09), but gastrointestinal side effects were significantly lower with alternate-day dosing. 5

Enhancing Absorption

• Taking iron with vitamin C (250-500 mg) enhances absorption by forming a chelate with iron. 1
• This vitamin C co-administration is recommended as Best Practice Advice by the American Gastroenterological Association based on vitamin C's well-established role as the most potent enhancer of non-heme iron absorption. 3
• Avoid taking iron with tea or coffee, which inhibit absorption. 1, 4

Monitoring Treatment Response

• Expect hemoglobin to increase by approximately 1 g/dL within 2 weeks in patients responding to therapy. 1, 4
• The absence of a hemoglobin rise of at least 10 g/L after 2 weeks of daily oral iron therapy strongly predicts subsequent treatment failure (sensitivity 90.1%, specificity 79.3%). 1
• Treatment should continue for approximately 3 months after hemoglobin normalizes to ensure adequate repletion of marrow iron stores. 1

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses of iron, as this increases side effects without improving absorption due to hepcidin elevation. 1, 4
• Avoid modified-release preparations, which are indicated as "less suitable for prescribing" according to the British National Formulary. 1
• Do not take iron with calcium-containing foods or medications, which can significantly reduce absorption. 1

When to Consider Intravenous Iron

Intravenous iron should be considered when: 1, 4

• Oral iron is not tolerated despite modifications to dosing schedule
• Ferritin levels do not improve with oral iron trial
• Patient has conditions where oral iron absorption is impaired (e.g., inflammatory bowel disease, post-bariatric surgery)
• Rapid correction of anemia is needed, as parenteral iron can produce a clinically meaningful hemoglobin response within a week 1