Ascorbic acid may be effective in managing anemia in hemodialysis (HD) patients, according to a recent meta-analysis by Canadian investigators.

Brenda R. Hemmelgarn, MD, PhD, of Foothills Medical Centre in Calgary, Alberta, and collaborators conducted a meta-analysis of six randomized clinical trials of ascorbic acid use in addition to standard anemia management. These trials included a total of 326 patients. The duration of the studies ranged from two to six months.

Three trials included 125 patients subjects with baseline mean hemoglobin (Hb) levels below 11 g/dL and three included subjects with baseline mean Hb levels of 11 g/dL or higher. Ascorbic acid dosages ranged from 500 mg IV once weekly to 500 mg IV three times weekly. All studies used recombinant human erythropoietin (rHuEPO) therapy with baseline doses ranging from 47-477 U/kg/wk.

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Combining the three trials whose participants’ baseline Hb levels were below 11 g/dL, the researchers found that ascorbic acid use resulted in a mean 0.9 g/dL increase in Hb level compared with controls, Dr. Hemmelgarn’s group reported in the American Journal of Kidney Diseases (2009; published online ahead of print).

The effect of ascorbic acid on erythropoietin dose was evaluated in five trials that included a total of 303 patients. Compared with standard care, ascorbic acid use was associated with a significant 17.1 U/kg/wk decrease in erythropoietin dose.

Five trials with a total of 266 participants examined ascorbic acid use on ferritin concentrations. Pooled results showed small nonsignificant decrease in serum ferritin  in ascorbic acid recipients compared with controls.

In addition, five trials (173 patients) looked at the effect of ascorbic acid on transferrin saturation. Pooled results revealed a significant 7.9% increase in transferrin saturation for ascorbic acid compared with controls.

Although reporting of adverse events (AEs) was poor, the authors noted, AEs did not appear to be increased in patients receiving ascorbic acid.

The researchers acknowledged various study limitations, such as the small number of studies, the heterogeneity between study populations, and short study durations.

“Despite these limitations, this meta-analysis suggests potential short-term efficacy of ascorbic acid in improving Hb concentrations and transferrin saturations and decreasing rHuEPO doses in hemodialysis patients,” the authors concluded.

The researchers noted that ascorbic acid has been shown to stabilize degradation of the soluble intracellular ferritin fraction to the insoluble hemosiderin fraction, resulting in an increase in the cytosolic pool of iron stores in the reticuloendothelial system. “This increased labile iron pool is available for release to transferrin, which then transports it to the erythroid marrow, where it is used in erythropoiesis,” they explained. In the marrow, ascorbic acid also maintains iron in the reduced, or ferrous, state, the form required for incorporation into protoporphyrin for heme synthesis.

“Our findings are consistent with these mechanisms in hemodialysis patients, in whom we observed a significant increase in transferrin saturation with ascorbic acid treatment,” the investigators wrote.