What is the recommended dose of ascorbic acid (Vitamin C) when initiating ferrous sulfate for the treatment of iron deficiency anemia in adults?

Recommended Dose of Ascorbic Acid with Ferrous Sulfate

When initiating ferrous sulfate for iron deficiency anemia, add 250-500 mg of ascorbic acid (vitamin C) with each iron dose to enhance absorption. 1

Optimal Dosing Strategy

Primary Recommendation

• Take ferrous sulfate 200 mg (65 mg elemental iron) once daily in the morning with 250-500 mg ascorbic acid. 1, 2
• The American Gastroenterological Association recognizes vitamin C as the most potent enhancer of non-heme iron absorption and recommends it as Best Practice Advice. 1
• Practical options include taking iron with orange juice (which provides natural vitamin C) or a 250-500 mg ascorbic acid supplement. 1

Why Vitamin C Matters

• Vitamin C forms a chelate with iron that prevents formation of insoluble iron compounds and reduces ferric to ferrous iron, significantly improving absorption. 3
• This enhancement is particularly critical when iron saturation is severely low (as absorption is already compromised). 1, 3
• For plant-based diets where non-heme iron predominates, vitamin C supplementation becomes even more essential. 1, 3

Timing and Administration

Optimal Timing

• Take iron in the morning when hepcidin levels (which inhibit iron absorption) are lowest. 1
• Iron should be taken on an empty stomach for maximum absorption, though taking with small amounts of food is acceptable if gastrointestinal side effects occur. 1
• Separate iron from calcium supplements by 1-2 hours, as calcium inhibits iron absorption. 1

Dosing Frequency

• Once-daily dosing is superior to multiple daily doses because oral iron doses ≥60 mg stimulate hepcidin elevation that persists for 24 hours, blocking subsequent iron absorption. 4, 5
• Consider alternate-day dosing (giving twice the daily dose every other day) if daily dosing causes intolerable side effects, as this may be equally effective with better tolerability. 1, 5

Expected Response and Duration

Monitoring

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment. 4, 2
• If no response occurs within 4 weeks, reassess for non-adherence, malabsorption, or ongoing blood loss. 2

Treatment Duration

• Continue iron therapy for 3 months after hemoglobin normalizes to fully replenish iron stores. 4, 1, 2
• Monitor hemoglobin and ferritin every 3 months for the first year, then again after another year. 1, 2

Managing Side Effects

If Gastrointestinal Side Effects Occur

• Take iron with small amounts of food (accepting reduced absorption for improved adherence). 1
• Start with lower doses and gradually increase to target dose. 1
• Try taking iron at bedtime. 1
• Consider alternative formulations like ferrous gluconate or ferrous fumarate if ferrous sulfate is intolerable. 4, 1

Critical Contraindication

Hemochromatosis and Iron Overload

• Patients with hemochromatosis or iron overload must completely avoid vitamin C supplements. 3
• Vitamin C accelerates iron mobilization and can saturate transferrin, potentially causing cardiac arrhythmias, cardiomyopathy, and sudden death. 3
• If vitamin C is required for other medical reasons in iron-loaded patients, limit to 500 mg daily only after physician discussion. 1, 3

Evidence Quality Considerations

The British Society of Gastroenterology guidelines note that ferrous sulfate with ascorbic acid formulations are available, though they are listed as modified-release preparations that are "less suitable for prescribing" due to reduced bioavailability. 4 However, immediate-release ferrous sulfate taken with separate vitamin C supplementation avoids this issue while maintaining the absorption-enhancing benefit. 1

Recent research shows mixed results on vitamin C's efficacy when given with iron—a 2023 meta-analysis found no statistically significant benefit. 6 However, this conflicts with the well-established physiological mechanism and guideline recommendations. The discrepancy likely reflects methodological limitations in the studies analyzed, as the American Gastroenterological Association continues to recommend vitamin C based on its established role as the most potent enhancer of non-heme iron absorption. 1

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses of iron—this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade. 1, 5
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores. 1, 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal. 1, 2
• Do not give vitamin C to patients with known or suspected hemochromatosis. 3