The Effect of Different Prebiotics on Iron Absorption From High Dose Iron Supplements

January 20, 2021 updated by: Swiss Federal Institute of Technology

The Effect of Single Dose Oral Galacto-oligosaccharides, Fructo-oligosaccharides and Acacia Gum on Iron Absorption From Single 100 mg Oral Iron Doses Given as Ferrous Fumarate in Women Living in Switzerland

Iron deficiency (ID) remains the most common global nutrient deficiency, with young women at high risk. Iron supplements are first line treatment for ID but absorption is often low. Dietary components that could increase iron absorption would be valuable.

Prebiotics are among the potential enhancers of non-heme iron absorption. Galacto-oligosaccharides (GOS), fructo-oligosaccharides and acacia gum are safe and widely-used prebiotics.

To our knowledge, no studies have assessed the effect of acacia gum on iron absorption in human or animal models. Evidence exists about the enhancement of iron absorption when given in combination with FOS in rats. However, an iron stable isotope study in infants reported that 7.5 g of GOS improved iron absorption from 5 mg iron from a mixture of ferrous fumarate and sodium iron EDTA. In a recent iron absorption study in adult women with low iron stores in our lab we found that 15 g of GOS given with FeFum (14 mg of elemental iron) acutely increased iron absorption when given with water (+61%) and a meal (+28%).

For prevention of anemia among non-pregnant women, the WHO recommends intermittent (once, twice or three times a week) oral iron supplementation with 60 mg of elemental iron. This has been shown to be effective, safe and acceptable for improving hemoglobin concentrations in women and lowering their risk of anemia. If GOS improves iron absorption from a higher dose of iron, and if FOS and acacia gum might also enhance iron absorption from FeFum is unclear. With this study we therefore aim to investigate if consumption of a single oral dose of 15 g GOS, FOS or acacia gum increase iron absorption from single 100 mg oral iron doses, a common amount found in supplements on the market for treatment of iron deficiency, given as ferrous fumarate in otherwise healthy iron depleted women.

Study Overview

Detailed Description

Prebiotics are defined as "microbial food supplements that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon". Moreover, prebiotics are potential enhancers of iron absorption, via several mechanisms: a) increasing gastric residence time allowing for greater iron dissolution; b) stimulating enterocyte gene expression of proteins involved in iron absorption; c) stimulating enterocyte proliferation providing a greater surface for iron absorption; and d) stimulating SCFA production by gut commensal bacteria, decreasing distal gut luminal pH and increasing iron dissolution.

Galacto-oligosaccharides (GOS), a safe and widely-used prebiotic, are a mixture of glucose- and galactose-based di- and oligosaccharides of varying structure and may be more selectively utilized by Bifidobacterium spp. than other prebiotics. Fructo-oligosaccharides (FOS) are composed by 4 to 9 units of fructose alone or in combination with one unit of glucose. FOS are widely used as food ingredients/nutritional supplements due to their bifidogenic properties. Acacia gum is composed by highly branched galactan polymers with galactose and/or arabinose side chains, possibly terminated by rhamnose or glucuronic acid residues. Both in-vitro and in-vivo studies have shown that acacia gum supports bifidobacterial growth and short-chain fatty acids (SCFA) production in the large intestine.

GOS and FOS have received GRAS status in the USA. Acacia gum is extensively used in the food industry for various functions (emulsification, encapsulation, stabilization, etc.). It is affirmed as "GRAS" for use in various food items. Acacia gum in human subjects is well tolerated up to 50 g/day. The European Food Safety Authority stated that there is no safety concern for the use of Acacia Gum as a food supplement.

To our knowledge, no studies have assessed the effect of acacia gum on iron absorption in human or animal models. Evidence exists about the enhancement of iron absorption when given in combination with FOS in rats. In humans, studies so far have failed in showing an effect of FOS on iron absorption. However, an iron stable isotope study in infants reported that 7.5 g of GOS improved iron absorption from 5 mg iron from a mixture of ferrous fumarate and sodium iron EDTA. Moreover, in a recent iron absorption study in adult women with low iron stores in our lab we found that 15 g of GOS given with FeFum (14 mg of elemental iron) acutely increased iron absorption when given with water (+61%) and a meal (+28%). In another study in our lab (unpublished data) we found that 7 g of GOS given with FeFum (14 mg of elemental iron) acutely increased iron absorption when given with water (+26%), in iron depleted women. These effects were found to be iron compound specific and could not be shown for ferrous sulfate, the iron compound used in the existing human studies with FOS.

For prevention of anemia among non-pregnant women, the WHO recommends intermittent (once, twice or three times a week) oral iron supplementation with 60 mg of elemental iron. This has been shown to be effective, safe and acceptable for improving hemoglobin concentrations in women and lowering their risk of anemia.

If GOS improves iron absorption from a higher dose of iron, and if FOS and acacia gum might also enhance iron absorption from FeFum is unclear. With this study we therefore aim to investigate if consumption of a single oral dose of 15 g GOS, FOS or acacia gum increase iron absorption from single 100 mg oral iron doses, a common amount found in supplements on the market for treatment of iron deficiency, given as ferrous fumarate in otherwise healthy iron depleted women.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female, 18 to 45 years old
  • SF concentrations ≤ 25 µg/L
  • Normal body Mass Index (18.5-24.9 kg/m2)
  • Body weight <70 kg
  • Signed informed consent

Exclusion Criteria:

  • Anaemia (Hb < 11,7g/dL)
  • 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 study (except for contraceptives),
  • Consumption of mineral and vitamin supplements within 2 weeks prior to 1st supplement administration, including pre- and/or probiotic 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
  • Known 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 to 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, 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 (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
  • Enrolment of the investigator, his/her family members, employees and other dependent persons

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ferrous fumarate
labelled iron as ferrous fumarate
iron (100 mg) supplement in form of ferrous fumarate
Experimental: ferrous fumarate + 15 g GOS
labelled iron as ferrous fumarate + prebiotics in the form of 15 g GOS
iron (100 mg) supplement in form of ferrous fumarate with addition of prebiotics (15 g GOS)
Experimental: ferrous fumarate + 15 g FOS
labelled iron as ferrous fumarate + prebiotics in the form of 15 g FOS
iron (100 mg) supplement in form of ferrous fumarate with addition of prebiotics (15 g FOS)
Experimental: ferrous fumarate + 15 g acacia gum
labelled iron as ferrous fumarate + prebiotics in the form of 15 g acacia gum
iron (100 mg) supplement in form of ferrous fumarate with addition of prebiotics (15 g acacia gum)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
fractional iron absorption
Time Frame: 43 days
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.
43 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Hemoglobin (Hb)
Time Frame: Baseline, 43 days
Baseline, 43 days
Serum ferritin
Time Frame: Baseline, 43 days
Baseline, 43 days
soluble transferrin receptor
Time Frame: Baseline, 43 days
Baseline, 43 days
serum iron
Time Frame: Baseline, 43 days
Baseline, 43 days
alpha-1-acid glycoprotein (AGP)
Time Frame: Baseline, 43 days
Baseline, 43 days
C-reactive protein (CRP)
Time Frame: Baseline, 43 days
Baseline, 43 days
Retinol binding protein (RBP)
Time Frame: Baseline, 43 days
Baseline, 43 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Isabelle Herter-Aeberli, PhD, Laboratory of Human Nutrition ETH Zürich

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 20, 2020

Primary Completion (Actual)

October 6, 2020

Study Completion (Actual)

October 6, 2020

Study Registration Dates

First Submitted

December 9, 2019

First Submitted That Met QC Criteria

December 9, 2019

First Posted (Actual)

December 11, 2019

Study Record Updates

Last Update Posted (Actual)

January 22, 2021

Last Update Submitted That Met QC Criteria

January 20, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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