Iron Absorption from Bouillon Fortified with Iron-Enriched Aspergillus oryzae Is Higher Than That Fortified with Ferric Pyrophosphate in Young Women

Abstract

Background: Bouillon cubes are a potential vehicle for iron fortification. They are currently fortified with ferric pyrophosphate (FePP), which is known to be poorly absorbed. The objective of this study was to assess the iron absorption of Aspergillus oryzae grown in FePP (ASP-p) and compare it with FePP and ferrous sulfate (FeSO4)-fortified bouillon cubes.

Methods: In 2 single-blinded, crossover studies, healthy women with serum ferritin concentrations <40 μg/L were randomly assigned to consume a rice-vegetable meal with iron-fortified chicken bouillon. Subjects in study I (n = 17, 18-26 y) consumed iron from both iron sources as 57FePP and 58ASP-p (intrinsically labeled with 58FePP) with a meal containing 4.2 mg of total iron provided for 3 d. Study II (n = 18, 18-29 y) was similar except that subjects consumed 57FeSO4 and 58ASP-p. Whole-blood stable isotope enrichment after 14 d was used to measure fractional iron absorption. Hemoglobin, hematocrit, serum ferritin, hepcidin, and serum C-reactive protein were analyzed at baseline and at 14 d. A t test was used to compare the mean differences in fractional absorptions within each study and baseline characteristics between studies.

Results: Geometric mean (95% CI) fractional iron absorption of FePP [0.94% (0.63%, 1.40%)] was lower than ASP-p [2.20% (1.47%, 3.30%)] (P < 0.0001) in study I. In study II, ASP-p fractional absorption [2.98% (2.03%, 4.38%)] was lower than that of FeSO4 [9.88% (6.70%, 14.59%)] (P < 0.0001). Both ferritin (r = -0.41, P = 0.014) and hepcidin (r = -0.42, P = 0.01) concentrations were inversely correlated with ASP-p iron absorption. Fractional absorption of ASP-p was also positively correlated with FePP (r = 0.92, P < 0.0001) and FeSO4 (r = 0.52, P < 0.02) absorption.

Conclusions: ASP-p-fortified bouillon provided 2.3-fold higher absorbable iron than the currently used FePP. Bouillon fortified with ASP-p may contribute sufficient bioavailable iron to meet the daily iron requirements in young women only if consumed with other iron-fortified staple foods. This trial was registered at clinicaltrials.gov as NCT03586245.

Keywords: Aspergillus oryzae; bouillon cubes; ferric pyrophosphate; ferrous sulfate; iron absorption; iron fortification; stable iron isotope.

Copyright © The Author(s) 2020.

Figures

FIGURE 1

Study design and eligibility of women in studies I and II. *Participants were recruited based on eligibility from HSQ including BMI (kg/m2) of 18.5 to 25.0 and age >18 y. Test meals AB and BA were fed in a crossover design for both studies. Isotopes with meals were given to each subject over 3 test meals. One study I subject withdrew due to flu; a study II subject withdrew from an unfinished test meal. ASP-p, Aspergillus oryzae grown in ferric pyrophosphate; FePP, ferric pyrophosphate; HSQ, health screening questionnaire.

FIGURE 2

Study design for studies I and II in women who were provided meals A (57FePP), B1/B2 (58ASP-p), and C (57FeSO4) once a day for 3 consecutive days. ASP-p, Aspergillus oryzae grown in ferric pyrophosphate; FePP, ferric pyrophosphate.

FIGURE 3

Fractional iron absorption in women provided meals with 57FePP, 58ASP-p in study I (A; n = 17) and 58ASP-p and 57FeSO4 in study II (B; n = 18). *Different from FePP and FeSO4, P < 0.0001. ASP-p, Aspergillus oryzae grown in ferric pyrophosphate; FePP, ferric pyrophosphate.

FIGURE 4

Pearson's correlations of ASP-p fractional absorption with ferritin (A) and hepcidin (B) concentrations and with FePP (C) and FeSO4 (D) fractional absorptions in women provided test meals. Data from studies I and II were combined when the correlations were made with ASP-p absorption with hepcidin and ferritin. ASP-p, Aspergillus oryzae grown in ferric pyrophosphate; FePP, ferric pyrophosphate.