Determination of a Dose-dependent Effect of GOS on Iron Absorption, and Addition of Vitamin C (Fe_GOS_2)

The Effect of Prebiotics on Iron Absorption in Women With Low Iron Stores: Determination of a Dose-dependent Effect of Galacto-oligosaccharides on Iron Absorption, With and Without Addition of Ascorbic Acid

Iron deficiency is still the most common and widespread nutritional disorder in the world according to WHO.

In a recent iron absorption study in adult women with low iron stores in our lab (publication under review), we found that 15 g of GOS given with an iron supplement in the form of iron fumarate acutely increased iron absorption when given with water and a bread based meal. The dose of 15 g of GOS was tolerated well by the participants. As a follow up to the study mentioned above, we want to investigate: 1) if acute iron absorption is affected by lower doses of GOS; 2) whether this acute effect occurs for other commonly used iron compounds as well, such as iron sulphate and iron phosphate; and 3) if there are potential interactions on absorption with other enhancers of iron absorption, such as vitamin c.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency
• Intervention / Treatment: Dietary supplement: ferrous fumarate; Dietary supplement: ferrous sulphate; Dietary supplement: ferric pyrophosphate; Dietary supplement: ferrous fumarate + 3.5 g GOS; Dietary supplement: ferrous fumarate + 7 g GOS; Dietary supplement: ferrous sulphate + 15 g GOS; Dietary supplement: ferrous fumarate + Vitamin C; Dietary supplement: ferric pyrophosphate + 15 g GOS; Dietary supplement: ferrous fumarate + 7 g GOS + Vitamin C

Detailed Description

Iron is an important mineral in our body and fulfills essential functions such as for example oxygen transport from the lungs to the tissues. Iron deficiency is still the most common and widespread nutritional disorder in the world according to WHO. Common iron supplements all have their limitations in terms of availability and compatibility. Prebiotic fibers, such as galacto-oligosaccharides (GOS), selectively enhance growth of beneficial colonic bacteria. Prebiotics in general enhance the production of short-chain fatty acids (SCFAs) and thereby decrease luminal pH. Through the reduction in pH, prebiotics can enhance absorption of minerals such as calcium and magnesium and they have been proposed to potentially improve iron absorption.

In a recent iron absorption study in adult women with low iron stores in our lab (publication under review), we found that 15 g of GOS given with an iron supplement in the form of iron fumarate acutely increased iron absorption when given with water and a bread based meal. The dose of 15 g of GOS was tolerated well by the participants. As a follow up to the study mentioned above, we want to investigate: 1) if acute iron absorption is affected by lower doses of GOS; 2) whether this acute effect occurs for other commonly used iron compounds as well, such as iron sulphate and iron phosphate; and 3) if there are potential interactions on absorption with other enhancers of iron absorption, such as vitamin c.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female, 18 to 45 years old
• SF levels <30 µg/L
• Normal body Mass Index (18.5-24.9 kg/m2)
• Body weight <70 kg
• Signed informed consent

Exclusion Criteria:

• Severe anaemia (Hb < 80 g/L)
• Elevated CRP >10.0 mg/L
• 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, including pre- and-or probiotics supplements (excluding foods and beverages with life cultures such as yoghurt, raw milk cheese and kombucha)
• Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 4 months
• Difficulties with blood sampling
• Use of antibiotics over the past month
• Known hypersensitivity to iron supplements in the given amount, GOS, or lactose
• Women who are pregnant or breast feeding
• Women who intend become pregnant during the course of the study
• 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, inject-able, 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 (more than 2 drinks/day) abuse -
• Smokers (> 1 cigarette per week)
• Inability to follow the procedures of the study, e.g. due to language problems, self-- reported psychological disorders, etc. of the participant
• Enrollment 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: Crossover Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ferrous fumarate; labelled iron as ferrous fumarate	Dietary supplement: ferrous fumarate; nutritional iron (14 mg) supplement in form of ferrous fumarate
Experimental: ferrous sulphate; labelled iron as ferrous sulphate	Dietary supplement: ferrous sulphate; nutritional iron (14 mg) supplement in form of ferrous sulphate
Experimental: ferric pyrophosphate; labelled iron as ferric pyrophosphate	Dietary supplement: ferric pyrophosphate; nutritional iron (14 mg) supplement in form of ferric pyrophosphate
Experimental: ferrous fumarate + 3.5 g GOS; labelled iron as ferrous fumarate + prebiotics in the form of 3.5 g GOS	Dietary supplement: ferrous fumarate + 3.5 g GOS; nutritional iron (14 mg) supplement in form of ferrous fumarate with addition of prebiotics (3.5 g GOS)
Experimental: ferrous fumarate + 7 g GOS; labelled iron as ferrous fumarate + prebiotics in the form of 7 g GOS	Dietary supplement: ferrous fumarate + 7 g GOS; nutritional iron (14 mg) supplement in form of ferrous fumarate with addition of prebiotics (7 g GOS)
Experimental: ferrous sulphate + 15 g GOS; labelled iron as ferrous sulphate + prebiotics in the form of 15 g GOS	Dietary supplement: ferrous sulphate + 15 g GOS; nutritional iron (14 mg) supplement in form of ferrous sulphate with addition of prebiotics (15 g GOS)
Experimental: ferrous fumarate + Vitamin C; labelled iron as ferrous fumarate + Vitamin C	Dietary supplement: ferrous fumarate + Vitamin C; nutritional iron (14 mg) supplement in form of ferrous fumarate with addition of Vitamin C
Experimental: ferric pyrophosphate + 15 g GOS; labelled iron as ferric pyrophosphate + prebiotics in the form of 15 g GOS	Dietary supplement: ferric pyrophosphate + 15 g GOS; nutritional iron (14 mg) supplement in form of ferric pyrophosphate with addition of prebiotics (15 g GOS)
Experimental: ferrous fumarate + 7 g GOS + Vitamin C; labelled iron as ferrous fumarate + prebiotics in the form of 7 g GOS + Vitamin C	Dietary supplement: ferrous fumarate + 7 g GOS + Vitamin C; nutritional iron (14 mg) supplement in form of ferrous fumarate with addition of prebiotics (7 g GOS) and Vitamin C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fractional iron absorption	Fractional iron absorption will be calculated based on the shift of the iron isotope ratios in the collected blood samples after the administration of several isotopically labelled iron supplements.Fractional iron absorption will be measured as erythrocyte incorporation of the naturally occurring iron forms with different masses used to label the iron supplements.	2 months

Collaborators and Investigators

• Sponsor: Isabelle Herter-Aeberli
• Collaborators: Burgerstein Vitamine
• Investigators: Principal Investigator: Isabelle Herter-Aeberli, Dr., University of Zurich

Publications and helpful links

General Publications

• Jeroense FMD, Zeder C, Zimmermann MB, Herter-Aeberli I. Acute Consumption of Prebiotic Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate, but not from Ferrous Sulfate and Ferric Pyrophosphate: Stable Iron Isotope Studies in Iron-Depleted Young Women. J Nutr. 2020 Sep 1;150(9):2391-2397. doi: 10.1093/jn/nxaa199.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): June 11, 2019
• Study Completion (Actual): June 11, 2019

Study Registration Dates

• First Submitted: November 30, 2018
• First Submitted That Met QC Criteria: November 30, 2018
• First Posted (Actual): December 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 25, 2019
• Last Update Submitted That Met QC Criteria: July 24, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: prebiotics; iron-deficiency; galacto-oligosaccharides
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Trace Elements; Micronutrients; Antioxidants; Ferrous fumarate; Vitamins; Ascorbic Acid; Iron
• Other Study ID Numbers: Fe_GOS_2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No