Vitamin C in the Management of Erythropoetin-resistant Anemia in Chronic Kidney Disease

A role for vitamin C in erythropoetin-hyporesponsive patients has been suggested, despite the lack of evidence to suggest a mechanism of action. A possible mechanism could be related to the antioxidant properties of vitamin C and to its effects on iron metabolism or endogenous erythropoetin synthesis.
The efficacy of vitamin D has been evaluated in clinical trials. A prospective, randomized, crossover study evaluated 27 hemodialysis patients with functional iron deficiency.[1] All patients who were administered 500 mg of intravenous vitamin C 3 times weekly for 3 months had significant increases in hemoglobin and transferrin saturation, and hemoglobin and transferrin saturation declined after cessation of vitamin C therapy. Sezer and colleagues[2] also reported a significant increase in hemoglobin concentration and a decrease in the dose of recombinant human erythropoetin (EPO) in 36 hemodialysis patients whose ferritin level was > 500 g/L after 8 weeks of treatment with vitamin C at a dosage of 1 g/wk.
More recently, this has been tested in a prospective, randomized, crossover study.[3] Approximately 65% of hemodialysis patients responded to treatment with 1500 mg/wk of intravenous vitamin C over a 6-month period with almost a 2 g/dL increase in hemoglobin concentration, together with a 2500 IU/wk (30%) reduction in EPO dose. Nevertheless, the K/DOQI Work Group for guideline 3.3.1 L stated: "in the opinion of the Work Group, there is insufficient evidence to recommend the use of vitamin C (ascorbate) in the management of anemia in patients with CKD." Furthermore, long-term high doses of vitamin C treatment might be a potential risk for the development of secondary oxalosis in patients with end-stage renal disease.