Efficacy of vitamin C with Fe supplementation in patients with iron deficiency anemia: a systematic review and meta-analysis

Oral iron (Fe) supplementation is one of the mainstays of treatment for iron deficiency anemia (IDA). However, its therapeutic effects are limited when there is poor absorption from the gastrointestinal tract. Vitamin C is hypothesized to improve uptake when combined as an adjunct agent. We aimed to determine the difference in hematologic outcomes in patients with IDA receiving oral iron, with or without vitamin C. MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched from database inception to July 2023 for studies investigating the use of oral iron supplements with vitamin C in patients with IDA. The primary outcome was the change in serum hemoglobin (Hb). Secondary outcomes include change in serum ferritin, reticulocyte percentage, and incidence of adverse events. A total of 2231 studies were retrieved; 10 randomized control trials (n = 1782), and 1 prospective cohort study (n = 148) comprising 1930 patients were included. Vitamin C supplementation was associated with a significant increase in serum Hb level (mean differences [MDs], 0.14 g/dL; 95% confidence interval [CI], 0.08-0.20; P < .01; 10 studies, 1490 patients) and serum ferritin levels (MD, 3.23 μg/L; 95% CI, 1.63-4.84; P < .01; 9 studies, 1682 patients) in the iron plus vitamin C group compared with the iron-only group. The addition of vitamin C to iron supplementation was associated with a small and likely clinically insignificant increase in serum Hb. The results of this study do not support routine supplementation of oral iron therapy with vitamin C in the treatment of IDA.