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

• ClinicalTrials.gov Identifier: NCT03762148
• Recruitment Status: Completed
• First Posted: December 3, 2018
• Last Update Posted: July 25, 2019
• Sponsor: Isabelle Herter-Aeberli
• Collaborator: Burgerstein Vitamine
• Information provided by (Responsible Party): Isabelle Herter-Aeberli, Swiss Federal Institute of Technology

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Iron-deficiency	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	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: April 1, 2019
• Actual Primary Completion Date: June 11, 2019
• Actual Study Completion Date: June 11, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. fractional iron absorption [ Time Frame: 2 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Only female participants are being studied
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Switzerland

Human Nutrition Laboratory, ETH Zurich

Zurich, Switzerland, 8092

Sponsors and Collaborators

Isabelle Herter-Aeberli

Burgerstein Vitamine

Investigators

• Principal Investigator: Isabelle Herter-Aeberli, Dr.; University of Zurich

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Isabelle Herter-Aeberli, PhD, Swiss Federal Institute of Technology
• ClinicalTrials.gov Identifier: NCT03762148
• Other Study ID Numbers: Fe_GOS_2
• First Posted: December 3, 2018
• Last Update Posted: July 25, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Isabelle Herter-Aeberli, Swiss Federal Institute of Technology:

iron-deficiency; prebiotics; galacto-oligosaccharides

Additional relevant MeSH terms:

Anemia, Iron-Deficiency; Anemia, Hypochromic; Anemia; Hematologic Diseases; Iron Metabolism Disorders; Metabolic Diseases; Vitamins; Ascorbic Acid; Ferrous fumarate; Iron; Micronutrients; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Trace Elements