Assessment of Acute Serum, Non-Transferrin Bound Iron and Gastrointestinal Symptoms with 3-Week Consumption with Iron-Enriched Aspergillus Oryzae Compared to Ferrous Sulfate

Abstract

Abstract Background Iron deficiency anemia (IDA) is a widespread nutritional deficiency and iron supplementation, especially with ferrous sulfate (FeSO4) is the most common strategy to treat IDA; however, compliance is often poor with daily FeSO4 due to negative side effects. In a previous study, iron from iron-enriched A. oryzae (Ultimine, ULT) was similarly absorbed as FeSO4. The main objective of this study was to assess the safety of consuming ULT in terms of increasing non-transferrin bound iron (NTBI) and gastrointestinal distress. Methods Young female participants (n = 16) with serum ferritin <40 μg/L were randomized to a double-blind, 9-wk cross-over study with a 3-wk placebo/washout period between treatments. Oral FeSO4 and ULT supplements containing 65 mg Fe was administered daily, for 21 consecutive days. On day one, serum iron, % transferrin saturation (%TS) and NTBI were measured for 8 h on the first day of iron consumption. Change in biochemical indicators were evaluated following 3-wk consumption. Side effects questionnaires were completed weekly on two randomly selected weekdays and one weekend day for the entire study. Results Serum iron, TS and NTBI were all markedly higher from hours 2–8 (P < 0.001) with FeSO4, compared to ULT. Oxidative stress, inflammatory, kidney and liver function markers remained unchanged with both supplementations compared to placebo. Changes in iron status markers were not significantly different among three treatments. Individual or global side effects were not significantly different among all treatments. Even when common side effects of nausea, constipation and diarrhea were combined, only at week 3 FeSO4 treatment had significantly higher effect than ULT (P = 0.04) and placebo (P = 0.004) but the difference was not significant between ULT and placebo. Conclusions Low NTBI production, and less of common gastrointestinal side effects with ULT suggest that it is a safe oral iron supplement to treat IDA. This trial was registered at ClinicalTrails.gov as NCT04018300.