Using Stable Iron Isotopic Techniques and Serum Hepcidin Profiles to Optimize Iron Supplementation
Condition: Iron Deficiency; Anemia; Iron Deficiency Anemia
MeSH terms: Anemia; Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional

Summary: 
      Oral iron supplementation (OIS) is a widely-used strategy to treat iron deficiency anemia.
      However, absorption of OIS is often low and response is variable. To overcome this, large
      doses are given but this may reduce compliance due to gastric irritation. Thus, OIS doses
      should be low, while maximizing absorption. The prevailing serum hepcidin concentration
      (SHep) is the major determinant of iron absorption and erythrocyte iron utilization. Based on
      limited data in humans, SHep can be increased by a single OIS dose but the duration of the
      increase is uncertain: it may be in the range of 24 to 96 hr. Also, there are few data on how
      the increase in SHep determines the absorption of further doses of oral iron. Is there a
      threshold SHep at which subsequent iron absorption is sharply reduced? Better understanding
      of this relationship would be valuable to design more effective and safer OIS regimens.

      Objectives: 1) Determine the duration and magnitude of the Fe induced Hepcidin rise form a
      single iron dose while determining its bioavailability and 2) Compare the bioavailability of
      a single dose to iron supplements consumed one after the other (two dosages).
    

Detailed description: 
      Background: Oral iron supplementation (OIS) is a widely-used strategy to treat iron
      deficiency anemia. However, absorption of OIS is often low and response is variable. To
      overcome this, large doses are given but this may reduce compliance due to gastric
      irritation. Thus, OIS doses should be low, while maximizing absorption. The prevailing serum
      hepcidin concentration (SHep) is the major determinant of iron absorption and erythrocyte
      iron utilization. Based on limited data in humans, SHep can be increased by a single OIS dose
      but the duration of the increase is uncertain: it may be in the range of 24 to 96 hr. Also,
      there are few data on how the increase in SHep determines the absorption of further doses of
      oral iron. Is there a threshold SHep at which subsequent iron absorption is sharply reduced?
      Better understanding of this relationship would be valuable to design more effective and
      safer OIS regimens.

      Objectives: 1) Determine the duration and magnitude of the Fe induced Hepcidin rise form a
      single iron dose while determining its bioavailability and 2) Compare the bioavailability of
      a single dose to iron supplements consumed one after the other (two dosages).
      Methods/Subjects: Healthy female subjects will be screened for low iron status. Anemic
      subjects will be excluded from the study. Thirty two subjects will be included with serum
      ferritin <20 µg/L, C-reactive protein <5 mg/L and Hemoglobin >117 g/L. Subjects will be
      randomized in two groups and their Hepcidin (sHep) and iron status markers monitored at day 1
      (baseline). Subjects will receive iron supplement dosages of 40, 80, 160 and 240 mg in either
      single or as two consecutive dosages with stable iron isotopes 54Fe, 57Fe, 58Fe in form of 4
      mg of iron sulfate (FeSO4). Prior administration blood samples will be collected at 8:00,
      12:00 and 16:00 to monitor sHep and iron status markers, these measurements will be repeated
      on the days of supplement administration. On the following days, sHep will be measured at
      8:00 to quantify the duration of the iron induced hepcidin rise. In the second week, subjects
      receiving a single Fe dose on week 1 will receive two consecutive dosages and vice versa,
      while the same sampling scheme as in week one will be applied. On day 23, a last blood sample
      will be collected and iron incorporation of stable isotopic labels will be measured from the
      different dosages administered.

      Outcome: The combined use of stable iron isotopes and a sensitive SHep assay will allow for
      better understanding of the iron-hepcidin relationship and this may enable design of more
      effective OIS regimens.
    

Intervention name(s): Iron Supplement (Ferrous Sulfate Dried)
Intervention type(s): Dietary Supplement
Intervention description(s): Iron supplements of varying concentration will be administered to the four groups in the study. Iron bioavailability from the supplements will be assessed.
Other intervention name(s): Ferrous Sulfate (dried)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Iron bio availability; Hepcidin; Iron absorption