Why is ferrous sulfate (iron supplement) better given with vitamin C (ascorbic acid)?

Why Ferrous Sulfate Is Better Given with Vitamin C

Vitamin C should be added to ferrous sulfate supplementation to improve iron absorption by forming a chelate with iron that prevents insoluble iron compounds and by reducing ferric to ferrous iron, enhancing overall absorption and effectiveness. 1

Mechanism of Action

Vitamin C (ascorbic acid) enhances iron absorption through two primary mechanisms:

1. Chelation effect: Vitamin C forms a chelate with iron that prevents the formation of insoluble iron compounds 1
2. Reduction action: Vitamin C reduces ferric (Fe³⁺) iron to ferrous (Fe²⁺) iron, which is more readily absorbed in the intestine 1

These mechanisms are particularly important when:

• Iron is taken with meals containing absorption inhibitors like calcium or fiber
• The patient has conditions that impair iron absorption

Dosage Recommendations

The American Gastroenterological Association (AGA) recommends:

• 500 mg of vitamin C when taking iron with meals that contain calcium or fiber 1
• A recent iron isotope study showed that taking iron with just 80 mg of ascorbic acid on an empty stomach improves iron absorption 1

Earlier guidelines from 2011 suggested 250-500 mg of vitamin C twice daily with iron preparations 1

Clinical Benefits

Adding vitamin C to ferrous sulfate provides several advantages:

• Enhanced absorption: Particularly important in meals containing inhibitors of iron absorption 2
• Improved effectiveness: For meals with low to medium levels of inhibitors, a molar ratio of 2:1 (vitamin C:iron) is recommended (e.g., 20 mg vitamin C to 3 mg iron) 2
• Counteracts absorption inhibitors: Tea and coffee are powerful inhibitors of iron absorption and should not be consumed within an hour of taking iron 1

Practical Considerations

When prescribing ferrous sulfate with vitamin C:

• Timing: Iron is best absorbed when taken on an empty stomach, though some patients tolerate it better with meals 1
• Frequency: Once-daily dosing is sufficient; more frequent dosing increases side effects without improving absorption due to hepcidin response 1
• Formulation: Ferrous sulfate is the preferred iron formulation as it's the least expensive with similar effectiveness to other preparations 1

Important Caveats

• Mixed evidence: While the AGA recommends vitamin C supplementation with iron (Best Practice Advice 3), they note that evidence supporting this practice is mixed and further study is needed 1
• Not for everyone: Patients with hemochromatosis or iron overload conditions should avoid vitamin C supplementation with iron as it may enhance iron absorption and worsen their condition 3
• Limited benefit in certain contexts: A 2023 systematic review found that the standardized mean difference in hemoglobin levels between iron plus vitamin C versus iron alone was not statistically significant 4

Monitoring Response

• Hemoglobin should increase by approximately 1 g/dL within 2 weeks of starting iron supplementation 1
• Ferritin levels should increase within a month in adherent patients 1
• If these parameters are not met despite adherence, intravenous iron may be needed 1

By combining ferrous sulfate with vitamin C, you can optimize iron absorption and improve outcomes in patients with iron deficiency anemia, particularly those with dietary factors that might inhibit iron absorption.