Interaction of vitamin C and iron. Lynch S R,Cook J D Annals of the New York Academy of Sciences Food iron is absorbed by the intestinal mucosa from two separate pools of heme and nonheme iron. Heme iron, derived from hemoglobin and myoglobin, is well absorbed and relatively little affected by other foods eaten in the same meal. On the other hand, the absorption of nonheme iron, the major dietary pool, is greatly influenced by meal composition. Ascorbic acid is a powerful enhancer of nonheme iron absorption and can reverse the inhibiting effect of such substances as tea and calcium/phosphate. Its influence may be less pronounced in meals of high iron availability--those containing meat, fish, or poultry. The enhancement of iron absorption from vegetable meals is directly proportional to the quantity of ascorbic acid present. The absorption of soluble inorganic iron added to a meal increases in parallel with the absorption of nonheme iron, but ascorbic acid has a much smaller effect on insoluble iron compounds, such as ferric oxide or ferric hydroxide, which are common food contaminants. Ascorbic acid facilitates iron absorption by forming a chelate with ferric iron at acid pH that remains soluble at the alkaline pH of the duodenum. High cost and instability during food storage are the major obstacles to using ascorbic acid in programs designed to combat nutritional iron deficiency anemia. 10.1111/j.1749-6632.1980.tb21325.x

The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial. Li Nianyi,Zhao Guangjie,Wu Wanling,Zhang Mengxue,Liu Weiyang,Chen Qinfen,Wang Xiaoqin JAMA network open Importance:It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA). Objective:To compare the equivalence and assess the safety of oral iron supplements plus vitamin C or oral iron supplements alone in patients with IDA. Design, Setting, and Participants:This single-center, open-label, equivalence randomized clinical trial was conducted from January 1, 2016, to December 30, 2017, in Huashan Hospital, Fudan University. Adult patients with newly diagnosed IDA were enrolled. Participants were randomly assigned (1:1) to the oral iron supplements plus vitamin C group or the oral iron supplements-only group. Data analysis was performed from March to December 2018. Interventions:Patients were randomized to receive a 100-mg oral iron tablet plus 200 mg of vitamin C or a 100-mg iron tablet alone every 8 hours daily for 3 months. Main Outcomes and Measures:The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 weeks of treatment, the increase in hemoglobin level after 4 weeks of treatment, the increase in serum ferritin level after 8 weeks of treatment, and adverse events. Results:Among the 440 randomized patients (220 each in the oral iron supplements plus vitamin C group and iron-only group; 426 women [96.8%]; mean [SD] age, 38.3 [11.7] years), all were assessed for the primary outcome, and 432 (98.2%) completed the trial. From baseline to the 2-week follow-up, the mean (SD) change in hemoglobin level was 2.00 (1.08) g/dL in the oral iron supplements plus vitamin C group and 1.84 (0.97) g/dL in the oral iron supplements-only group (between-group difference, 0.16 g/dL; 95% CI, -0.03 to 0.35 g/dL), thus meeting the criteria for equivalence. The mean (SD) change in serum ferritin level from baseline to 8-week follow-up was 35.75 (11.52) ng/mL in the vitamin C plus iron group and 34.48 (9.50) ng/mL in the iron-only group (between-group difference, 1.27 ng/mL; 95% CI, -0.70 to 3.24 ng/mL; P = .21). There were no significant differences between the 2 groups regarding the rates of adverse events (46 [20.9%] vs 45 [20.5%]; difference, 0.4%; 95% CI, -6.7% to 8.5%; P = .82). No patient withdrew because of adverse events. Conclusions and Relevance:Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption. These findings suggest that on-demand vitamin C supplements are not essential to take along with oral iron supplements for patients with IDA. Trial Registration:ClinicalTrials.gov Identifier: NCT02631668. 10.1001/jamanetworkopen.2020.23644