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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Iron-deficiency

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron-deficiency, prebiotics, galacto-oligosaccharides