Treatment efficacy of vitamin C or ascorbate given as co-intervention with iron for anemia – A systematic review and meta-analysis of experimental studies

Iron deficiency anemia (IDA) is one of the leading causes of anemia, globally. Oral vitamin C enhances iron absorption and is commonly prescribed with iron for anemia patients. Considering the lack of evidence to support this practice, we conducted this systematic review and meta-analysis to determine the treatment efficacy of experimental studies where oral vitamin C or ascorbate was given as co-intervention with iron compared to providing only iron among participants with anemia of all ages.A comprehensive strategy was used to search literature from PubMed, Cochrane and Google Scholar. Experimental studies conducted among participants with lab-confirmed anemia at baseline, with "oral ascorbic acid or vitamin C given as co-intervention with iron" as intervention and "only oral iron" as the comparator, and reported the outcomes hemoglobin or ferritin, were selected. Random-effects model was used to estimate standardized mean differences or odds ratio of outcomes, and sensitivity analyses were done. Sub-group and meta-regression analyses were conducted to evaluate the reasons for heterogeneity (PROSPERO number: CRD42022306612).Of the total nine studies included in the review, seven studies with 905 participants were included for meta-analysis. The pooled estimate for standardized mean difference (SMD) of hemoglobin (g/dL) and Serum Ferritin (mcg/L) for intervention-type ferrous ascorbate were 0.44 (95% C.I.: -0.30, 1.26) and 0.03 (95% C.I.: -0.68, 0.73) respectively, and were not statistically significant. The pooled estimate for SMD of hemoglobin (g/dL) and Serum Ferritin (mcg/L) for intervention type 'oral iron and vitamin C' was 0.11 (95% C.I.: -0.05, 0.28) and -0.90 (95% C.I.: -1.09, -0.72) respectively, and were not statistically significant.The SMD of hemoglobin or serum ferritin between the intervention group were not significantly favouring the intervention when the intervention group was ferrous ascorbate or oral iron and vitamin C, and the methodological quality of evidence of these effect measures was very low. This necessitates studying the treatment efficacy of oral vitamin C or ascorbate when given with oral iron for participants with anemia in future clinical trials.