The Optimization of Bioavailability From Iron Supplements: Study 1

The Optimization of Bioavailability From Iron Supplements: Examinations of Different Supplementation Regimens Including Hepcidin Profiles

Iron deficiency (ID) with or without anaemia (IDA) is a major public health problem worldwide, especially in women of reproductive age and young children. Iron supplementation is an effective strategy to prevent and treat ID and IDA. There is a lack of data on iron bioavailability from different supplementation regimens and how to optimize bioavailability in a cost-effective and patient-friendly way. The present study will test whether the fractional and total iron absorption from iron supplements (60 mg) administered daily for 14 days differs from that of iron supplements (60 mg) administered every second day for 28 days. The prevailing serum hepcidin concentration (SHep) is the major determinant of iron absorption and erythrocyte iron utilization. Therefore we will monitor SHep during the whole supplementation period. We hypothesize that the fractional and total iron absorption from the daily administration of 60 mg is lower than that from the administration on every second day due to increased SHep levels when supplements are administered daily.

The study will provide important insights about the optimization of iron bioavailability from different supplementation regimens including the performance of SHep, a key regulator of human iron metabolism.

Study Overview

• Status: Completed
• Conditions: Anemia; Iron Deficiency Anemia; Iron Deficiency
• Intervention / Treatment: Dietary supplement: Daily administration of 60 mg iron in form of ferrous sulphate capsules for 14 consecutive days; Dietary supplement: Administrations of 60 mg iron in form of ferrous sulphate capsules on every second day for 28 days

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8092
    • Human Nutrition Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female, 18 to 45 years old,
• Serum ferritin levels </=25 µg/L,
• Normal body Mass Index (18.5-26.5 kg/m2),
• Body weight <80 kg,
• Signed informed consent

Exclusion Criteria:

• Anaemia (Hb < 8.0 g/dL),
• Elevated c-reactive protein or alpha1-glycoprotein concentrations >5.0 mg/L, >1.0 g/L, respectively,
• Any metabolic, gastrointestinal kidney or chronic disease such as diabetes, renal failure, hepatic dysfunction, hepatitis, hypertension, cancer or cardiovascular diseases (according to the participants own statement),
• Continuous/long-term use of medication during the whole studies (except for contraceptives),
• Consumption of mineral and vitamin supplements within 2 weeks prior to 1st supplement administration,
• Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 4 months,
• Earlier participation in a study using stable iron isotopes,
• Known hypersensitivity or allergy to iron supplements,
• Women who are pregnant or breast feeding,
• Intention to become pregnant during the course of the studies,
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the studies, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present studies,
• Enrolment of the investigator, his/her family members, employees and other dependent persons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral iron supplement every day for 14 days; Daily administration of 60 mg iron in form of ferrous sulphate capsules for 14 consecutive days	Dietary supplement: Daily administration of 60 mg iron in form of ferrous sulphate capsules for 14 consecutive days
Active Comparator: Oral iron supplement every second day for 28 days; Administrations of 60 mg iron in form of ferrous sulphate capsules on every second day for 28 days	Dietary supplement: Administrations of 60 mg iron in form of ferrous sulphate capsules on every second day for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Iron bio-availability from oral iron supplementation (%)	Iron bioavailability will be assessed with stable isotopic labels. The shift in the isotopic ratio in human whole blood will be measured with Inductively coupled plasma mass spectrometry (ICP-MS).	up to 4 weeks
Serum hepcidin concentrations		1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 19, 21, 23, 25 and 27 days

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Investigators: Principal Investigator: Diego Moretti, PhD, Human Nutrition Laboratory, ETH Zurich

Publications and helpful links

General Publications

• Lazrak M, El Kari K, Stoffel NU, Elammari L, Al-Jawaldeh A, Loechl CU, Yahyane A, Barkat A, Zimmermann MB, Aguenaou H. Tea Consumption Reduces Iron Bioavailability from NaFeEDTA in Nonanemic Women and Women with Iron Deficiency Anemia: Stable Iron Isotope Studies in Morocco. J Nutr. 2021 Sep 4;151(9):2714-2720. doi: 10.1093/jn/nxab159.
• Stoffel NU, Cercamondi CI, Brittenham G, Zeder C, Geurts-Moespot AJ, Swinkels DW, Moretti D, Zimmermann MB. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017 Nov;4(11):e524-e533. doi: 10.1016/S2352-3026(17)30182-5. Epub 2017 Oct 9.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: June 25, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimate): June 26, 2014

Study Record Updates

• Last Update Posted (Actual): November 7, 2017
• Last Update Submitted That Met QC Criteria: November 3, 2017
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Hepcidin; Iron absorption; Iron bio availability
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Physiological Effects of Drugs; Trace Elements; Micronutrients; Iron
• Other Study ID Numbers: FeSupp_Hep-1