Project Number: 5450-51000-035-13
Project Type: Trust

Start Date: Jul 01, 2002
End Date: Sep 30, 2006

Objective:
Objective 1: To determine the efficacy of fortifying food with elemental iron powders, relative to equivalent amounts of ferrous sulfate, or of supplementing with a limited amount of iron in the heme form, on serum ferritin in women with low iron stores. As supporting objectives, we will assess the effect of these iron sources on: absorption of nonheme iron from other dietary sources, oxidative stress in the lower intestine, plasma zinc, attention, and affect (mood). Objective 2: To determine the absorption of irradiated electrolytic iron powder, relative to ferrous sulfate, as affected by dose and by interactions with ascorbic acid and phytic acid.

Approach:
The efficacy of two elemental iron powders (objective 1) will be assessed in a human study of premenopausal women with low iron stores. In a 17 week study, healthy premenopausal women, admitted with moderate to low iron stores (serum ferritin <30 ug /L), will have their iron stores reduced to low using individualized phlebotomy schedules for 5 weeks. Then for 12 weeks, one of the following 5 iron sources or placebo will be added to their diets: ferrous sulfate monohydrate (a positive control), electrolytic iron powder, reduced iron powder (each providing 50 mg iron daily), heme iron (providing 5 mg iron daily), or placebo. Serum ferritin, an indicator of body iron stores, will be the primary outcome variable. Other blood measurements will include additional iron status variables and plasma zinc. Stool indices of oxidative stress, psychological tests of affect and attention, and nonheme iron absorption from foods will be measured at the beginning and end of the 12-week period of iron treatment. The absorption of irradiated electrolytic iron powder, relative to ferrous sulfate (Objective 2), will be determined using radiolabeled meals consumed by healthy adults. Absorption of a commercially available electrolytic iron powder labeled with Fe-55 isotope by previous neutron activation will be compared with absorption of ferrous sulfate radiolabeled with Fe-59. A series of three radiolabeled meal studies will be used to assess the effects of the iron source and of one of the dietary modifiers (ascorbic acid, phytic acid, or dose), in a 2X2 factorial design. Each experiment will last for 29 days, with 4 different radiolabeled meals served on days 1, 2, 15, and 16. Erythrocyte isotope incorporation will be measured 2 weeks after each set of 2 meals. Experiment 1 will compare the absorption of electrolytic iron and ferrous sulfate, and assess the effects of ascorbic acid. A farina test meal will be fortified with 3 mg of iron as either ferrous sulfate (labeled with Fe-59) or electrolytic iron (labeled with Fe-55), and these two sources will be tested with and without orange juice to provide approximately 100 mg ascorbic acid to increase nonheme iron absorption by two-fold, or 100%. Experiment 2 will compare the absorption of the same two forms of iron with and without wheat bran, a source of phytic acid. Approximately 300 mg phytic acid will reduce nonheme iron absorption from a meal by 75%. This amount of phytic acid is contained in 10 g of wheat bran, which will be added to the farina meal. Experiment 3 will compare the absorption of the two forms of iron as affected by the iron dose, tested at doses of 1 and 20 mg. The latter amount is comparable to the amount of iron in some highly fortified breakfast cereals on the US market. This increase in the iron dose is predicted to reduce percent iron absorption from ferrous sulfate by one-half (the absolute amount of iron absorbed will be increased at the higher dose).