Vitamin C Dosing with Oral Iron Supplementation

Co-administer 100–500 mg of vitamin C (ascorbic acid) with each dose of oral ferrous sulfate to maximize non-heme iron absorption. 1

Optimal Vitamin C Dose Range

The American Gastroenterological Association recommends approximately 100–500 mg vitamin C taken together with each iron dose, with 500 mg representing the upper practical limit for routine supplementation. 1
A minimum of 80–100 mg vitamin C is sufficient to significantly enhance iron absorption, which can be provided by a small glass of unsweetened orange juice or a vitamin C tablet. 1
For patients with severe iron deficiency (hemoglobin ≈7 g/dL, ferritin <20 ng/mL, transferrin saturation <5%), the higher end of the range (500 mg) is recommended to maximize absorption when rapid repletion is needed. 1

One glass of orange juice (providing approximately 100 mg vitamin C) taken with the iron tablet is a cost-effective and practical alternative to vitamin C tablets. 1
Vitamin C tablets of 250–500 mg should be taken simultaneously with the iron dose, not separately, to ensure the chelating and reducing effects occur in the gastrointestinal lumen. 1, 2
The molar ratio of vitamin C to iron should be at least 2:1 (e.g., 20 mg vitamin C per 3 mg elemental iron) for meals with low to moderate iron absorption inhibitors, and may need to exceed 4:1 in the presence of high levels of inhibitors such as phytates or polyphenols. 2

Vitamin C enhances non-heme iron absorption by forming a soluble chelate with iron that prevents formation of insoluble iron compounds and by reducing ferric (Fe³⁺) to ferrous (Fe²⁺) iron, the more readily absorbed form. 1, 2
The enhancing effect is strongly dose-related and is particularly important when transferrin saturation is markedly low (<20%), as in severe iron deficiency. 1, 3
Vitamin C is the most potent enhancer of non-heme iron absorption, far more effective than other organic acids such as citric acid, which would require molar ratios exceeding 100:1 (≥1 g citric acid per 3 mg iron) to achieve comparable effects. 2

Patients with hemochromatosis or iron overload conditions must completely avoid vitamin C supplements with iron, as vitamin C accelerates iron mobilization and can saturate transferrin, potentially causing cardiac arrhythmias, cardiomyopathy, and sudden death. 1
For hemochromatosis patients who require vitamin C for other medical reasons, supplementation should be limited to 500 mg daily and only after physician discussion, and never during the iron depletion/induction phase of phlebotomy therapy. 1
The American Association for the Study of Liver Diseases explicitly states that supplemental vitamin C should be avoided by iron-loaded patients, particularly those undergoing phlebotomy. 1

Take iron with vitamin C in the morning on an empty stomach (1–2 hours before or after meals) to maximize absorption, which can be reduced by up to 50% when food is consumed within 2 hours. 1, 4
Avoid coffee, tea, or calcium-containing foods for at least 1–2 hours after taking iron with vitamin C, as these are powerful inhibitors that can negate the enhancing effect. 1, 5
If gastrointestinal intolerance necessitates taking iron with food, vitamin C becomes even more important because it allows iron absorption even when calcium, fiber, or other inhibitors are present in the meal. 1

Guidelines recommend 100 mg vitamin C three times daily (total 300 mg/day) or 500 mg daily for one month when treating iron deficiency in post-bariatric surgery patients. 1

Limit total elemental iron to ≤100 mg per day in patients with inactive IBD, and co-administer with 250–500 mg vitamin C to optimize absorption from the lower iron dose. 1, 4
During active IBD flares, oral iron should be avoided entirely; intravenous iron is required regardless of vitamin C supplementation. 1, 4

In non-dialysis CKD patients requiring oral iron, vitamin C 100–500 mg with each dose remains appropriate, but iron-related therapy should be managed according to nephrology-specific protocols once dialysis is initiated. 4

Do not assume that dietary vitamin C from meals consumed hours before or after the iron dose will enhance absorption—vitamin C must be present simultaneously with iron in the gastrointestinal lumen. 2
Do not use enteric-coated vitamin C preparations, as they release vitamin C beyond the duodenum, the primary site of iron absorption, negating the enhancing effect. 4
Do not exceed 500 mg vitamin C daily in patients with any degree of iron overload (ferritin >300 ng/mL in men, >200 ng/mL in women, or transferrin saturation >50%), as this may accelerate iron deposition. 1
Do not rely on vitamin C alone to overcome severe malabsorption—if hemoglobin fails to rise by ≥10 g/L after 2 weeks despite optimal oral iron plus vitamin C, escalate to intravenous iron. 1, 4