The Effect of Lactoferrin and Dosing Regimen on Iron Absorption From a Maize-based Porridge in Kenyan Infants
Condition: Iron-deficiency
MeSH terms: Iron Deficiencies
Study type: Interventional

Summary: 
      The purpose of this study is to measure iron absorption from maize-based porridge fortified
      with either apo-lactoferrin, holo-lactoferrin or ferrous sulfate and to test whether there is
      an effect of these. Additionally, iron absorption from maize-based porridge containing 12 mg
      ferrous sulfate will be measured when consumed every other day versus every third day.
    

Detailed description: 
      Infants and young children in sub-Saharan Africa have high rates of iron deficiency anemia
      (IDA), which adversely affects their growth and cognitive development. In-home iron
      fortification of complementary foods using micronutrient powders (MNPs) reduces risk for IDA
      by ensuring that the iron needs of infants and young children are met without changing their
      traditional diet. Oral iron syrups, typically containing iron as ferrous sulfate, can also be
      given to prevent/correct IDA. However, iron absorption from MNPs and iron syrups,
      particularly when given with complementary foods high in inhibitors of iron absorption, is
      low. Thus, there is a need to find iron formulations with higher bioavailability for use in
      African infants. In a recent trial in Kenya, the investigators demonstrated that a prebiotic
      could improve iron bioavailability from an iron-containing MNP.

      In this study, the investigators plan to assess the human milk compound lactoferrin (Lf) as a
      possible enhancer of iron absorption. Lf is an important iron-binding protein in human milk,
      which has been thought to be responsible for the high bioavailability of breast-milk iron. It
      has many biological functions, including iron absorption, antimicrobial activity,
      immunomodulatory effects and stimulatory effect on cell proliferation. Lf has different iron
      binding statuses: the iron free form (apo-Lf) and the iron-saturated form (holo-Lf). One of
      the two main biological activities of Lf provided by the diet is the control of iron uptake,
      which is mediated by the Lf receptor (LFR) as undigested Lf can bind to LFR and facilitate
      the uptake of iron. Therefore, Lf may be a nutritional iron source and may enhance iron
      absorption in infants. To evaluate the possible role of Lf on the availability of iron, iron
      absorption will be measured from bovine Lf (bLf). BLf has GRAS (generally considered as safe)
      status by the US Food and Drug Administration.

      To optimize iron absorption, timing of supplementation might as well be important. Hepcidin,
      a key regulator of systemic iron balance and a single dose of iron can increase hepcidin
      levels and potentially inhibit iron absorption from a second dose, consumed close in time to
      the first dose. The investigators will conduct two studies, where 24 infants aged 3-14 months
      in Msambweni, Kenya, will be enrolled. In study 1, on three alternate mornings, these infants
      will consume maize porridge containing a low iron dose (1.5 mg) to compare iron absorption
      between meals with apo-Lf, holo-Lf and ferrous sulfate (FeSO4) as a reference; and whether
      the addition of either apo- or holo-Lf has a beneficial effect on iron absorption. The
      investigators hypothesize that iron absorption will be higher when holo-Lf is present in the
      meal compared to apo-Lf. In study 2, the investigators want to compare two different dosing
      regimens, in which they measure iron absorption after one-day washout period and after a
      two-day washout period, and hypothesize that absorption will be higher after 2 days of
      washout.

      The data from this project will provide valuable information towards the development of new,
      highly bioavailable iron formulations and dosing regimen that is most efficient.
    

Intervention name(s): apo-Lactoferrin; holo-Lactoferrin; FeSO4; 1. FeSO4; FeSO4 after 1 day break; FeSO4 after 2 day break
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 1.41 g of apo-Lactoferrin will be given together with 1.42 mg FeSO4 (0.08 mg of iron naturally in apo-Lf [total of 1.5 mg iron]) in a maize porridge (extrinsically labeled); 1.41 g of holo-Lactoferrin (intrinsically labeled with 1.5 mg 57Fe) will be given together in a maize porridge; 1.5 mg FeSO4 as 54Fe in a maize porridge; 10 mg 56Fe + 2 mg 54Fe Is the 1. FeSO4 meal in maize porridge; 10 mg 56Fe + 2 mg 57Fe Is the 2. FeSO4 in maize porridge with a 1 day washout period; 10 mg 56Fe + 2 mg 58Fe Is the 3. FeSO4 in maize porridge with a 2 day washout period
Intervention MeSH terms: Lactoferrin; Fesoterodine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment