Vitamin C Does Not Impair IV Iron Sucrose Absorption
Low vitamin C levels do not prevent the uptake of intravenous iron sucrose (Venofer), and vitamin C supplementation is not required for IV iron to be effective. Unlike oral iron absorption, which occurs in the gastrointestinal tract and can be enhanced by vitamin C, intravenous iron bypasses the gut entirely and is delivered directly into the bloodstream where it is taken up by the reticuloendothelial system independent of ascorbic acid levels 1.
Why Vitamin C Is Irrelevant for IV Iron
The mechanism of IV iron uptake is fundamentally different from oral iron absorption. When iron sucrose is administered intravenously, it circulates as a colloidal complex that is gradually taken up by macrophages in the liver, spleen, and bone marrow, where iron is released and incorporated into transferrin or stored as ferritin 1, 2. This process does not require vitamin C as a cofactor or enhancer 1.
Vitamin C Only Matters for Oral Iron
The evidence consistently shows that vitamin C's role is limited to enhancing oral iron absorption in the gastrointestinal tract 1:
- Vitamin C enhances oral iron absorption by reducing ferric (Fe³⁺) to ferrous (Fe²⁺) iron and forming soluble chelates that prevent precipitation 1, 3
- The 2024 AGA guidelines note that taking oral iron with 80 mg ascorbic acid on an empty stomach improves absorption, but this applies only to oral formulations 1
- However, even for oral iron, the evidence supporting vitamin C administration is mixed, and the effect from complete diets is far less pronounced than from single meals 1, 4
Research Confirms No Interaction for Most IV Iron Preparations
A 2005 study specifically examined whether ascorbic acid affects the bioavailability of different IV iron preparations 5:
- Ascorbic acid increased bioavailable iron only from iron sucrose, not from iron dextran or ferric gluconate 5
- This effect was limited to increasing intracellular iron availability in laboratory studies, not preventing uptake 5
- The study concluded that corrected vitamin C levels in hemodialysis patients could potentially reduce the amount of iron sucrose needed, suggesting vitamin C may enhance (not impair) iron sucrose utilization 5
Clinical Bottom Line
Proceed with IV iron sucrose administration regardless of vitamin C status. The 2011 Gut guidelines explicitly state there is no data supporting the effectiveness of ascorbic acid supplementation for treating iron deficiency anemia with parenteral iron 1. Multiple guidelines on IV iron administration make no mention of checking or supplementing vitamin C levels before or during IV iron therapy 1, 2, 6.
Key Clinical Pitfalls to Avoid
- Do not delay IV iron therapy to check or correct vitamin C levels - this is unnecessary and will delay treatment of anemia 1
- Do not confuse oral and IV iron physiology - the enhancing effect of vitamin C applies only to gastrointestinal absorption of oral iron 1, 3
- Focus on actual contraindications to IV iron - active bacteremia is an absolute contraindication, not vitamin C deficiency 1, 2
When to Consider Vitamin C
The only scenario where vitamin C becomes relevant is if you're considering switching from IV to oral iron therapy, where co-administration of 500 mg vitamin C with oral iron may improve absorption in patients with high levels of absorption inhibitors in their diet 1. Even then, the evidence is mixed and vitamin C is not required for oral iron to work 1, 4.