Effects of Enhancers and Inhibitors on Absorption From Iron Supplements

Sponsor

Swiss Federal Institute of Technology (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05414474

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

17.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Iron deficiency (ID) is a major public health problem worldwide and oral iron supplementation can be an effective strategy to treat and prevent ID. To maximize iron bioavailability form oral iron supplements the simultaneous intake of the iron absorption enhancer ascorbic acid (AA) is recommended, and the simultaneous intake of coffee or tea containing the iron absorption inhibitors polyphenols should be avoided. Also, oral iron supplements are recommended to be taken on an empty stomach in the morning and without a meal to avoid any interaction with phytic acid, another iron absorption inhibitor present in many foods. However, the effects of these iron absorption enhancers and inhibitors have only been shown on iron absorption from dietary iron (up to 10mg). Also, the effect of the diurnal hepcidin increase on absorption from an iron supplement given in the afternoon without a preceding morning dose is unclear. Whether AA also increases iron bioavailability from a supplemental iron dose and whether a cup of coffee, a breakfast or iron administration in the afternoon decreases iron bioavailability from a supplemental dose is uncertain.

Condition or Disease	Intervention/Treatment	Phase
Iron-deficiency Iron Deficiency Anemia	Other: Reference Other: Ascorbic acid (AA) 500 mg Other: Ascorbic acid (AA) 80 mg Other: Coffee Other: Breakfast Other: Afternoon	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effects of Nutritional Iron Absorption Enhancers and Inhibitors and Daytime on Absorption From Oral Iron Supplements

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Reference Ferrum Hausmann 100 mg is consumed with 200 mL nanopure water with labelled ferrous fumarate (3 mg 54Fe).	Other: Reference Ferrum Hausmann 100 mg + 200 mL nanopure water with 3 mg 54Fe isotopes
Experimental: Ascorbic acid (AA) 500 mg Ferrum Hausmann 100 mg is consumed with 200 mL nanopure water with labelled ferrous fumarate (3 mg 57Fe) and 500 mg AA.	Other: Ascorbic acid (AA) 500 mg Ferrum Hausmann 100 mg + 200 mL nanopure water with 3 mg 57Fe isotopes + 500 mg AA
Experimental: Ascorbic acid (AA) 80 mg Ferrum Hausmann 100 mg is consumed with 200 mL nanopure water with labelled ferrous fumarate (3 mg 58Fe) and 80 mg AA.	Other: Ascorbic acid (AA) 80 mg Ferrum Hausmann 100 mg + 200 mL nanopure water with 3 mg 58Fe + 80 mg AA
Experimental: Coffee Ferrum Hausmann 100 mg is consumed with 200 mL nanopure water with labelled ferrous fumarate (3 mg 54Fe) and 150 mL coffee.	Other: Coffee Ferrum Hausmann 100 mg + 200 mL nanopure water with 3 mg 54Fe isotopes + 150 mL coffee
Experimental: Breakfast Ferrum Hausmann 100 mg is consumed with 200 mL nanopure water with labelled ferrous fumarate (3 mg 57Fe) and 1 bread roll (~100 g) with butter and honey, 1 cup of plain yoghurt (180 mL), 1 cup of coffee (150 mL) and 1 glass of orange juice (250 mL).	Other: Breakfast Ferrum Hausmann 100 mg + 200 mL nanopure water with 3 mg 57Fe isotopes + 1 bread roll (~100 g) with butter and honey + 1 cup of plain yoghurt (180 mL) + 1 cup of coffee (150 mL) + 1 glass of orange juice (250 mL)
Experimental: Afternoon Ferrum Hausmann 100 mg is consumed with 200 mL nanopure water with labelled ferrous fumarate (3 mg 58Fe) in the afternoon .	Other: Afternoon Ferrum Hausmann 100 mg + 200 mL nanopure water with 3 mg 58Fe isotopes administered in the afternoon

Outcome Measures

Primary Outcome Measures

Fractional iron absorption [percent] [Day 22]
Fractional iron absorption will be calculated based on the shift of the iron isotope ratios in the collected blood samples after the administration of the intervention products. Fractional iron absorption will be measured as erythrocyte incorporation of the naturally occurring iron forms with different masses used to label the iron supplements.
Fractional iron absorption [percent] [Day 43]
Fractional iron absorption will be calculated based on the shift of the iron isotope ratios in the collected blood samples after the administration of the intervention products. Fractional iron absorption will be measured as erythrocyte incorporation of the naturally occurring iron forms with different masses used to label the iron supplements.
Total iron absorption [mg] [Day 22]
Total iron absorption will be calculated based on the shift of the iron isotope ratios in the collected blood samples after the administration of the intervention products. Total iron absorption will be measured as erythrocyte incorporation of the naturally occurring iron forms with different masses used to label the iron supplements.
Total iron absorption [mg] [Day 43]
Total iron absorption will be calculated based on the shift of the iron isotope ratios in the collected blood samples after the administration of the intervention products. Total iron absorption will be measured as erythrocyte incorporation of the naturally occurring iron forms with different masses used to label the iron supplements.

Secondary Outcome Measures

Hemoglobin (Hb) [Day 1, 22, 26 and 43]
Iron status marker
Serum ferritin (SF) [Day 1, 22, 26 and 43]
Iron status marker
Serum transferrin receptor (sTfR) [Day 1, 22, 26 and 43]
Iron status marker
Serum iron (SFe) [Day 1, 22, 26 and 43]
Iron status marker
Total iron binding capacity (TIBC) [Day 1, 22, 26 and 43]
Iron status marker
Hepcidin [Day 1, 22 and 26]
Iron regulatory protein
C-reactive protein (CRP) [Day 1, 22, 26 and 43]
Inflammation marker
Alpha-1-acid-glycoprotein (AGP) [Day 1, 22, 26 and 43]
Inflammation marker

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Female, 18 to 45 years old,
SF levels <30 μg/L,
Body weight < 70 kg
Normal Body Mass Index (18.5-25 kg/m2),
Signed informed consent.

Exclusion Criteria:

Anemia (Hb < 12 g/dL)
Elevated CRP > 5 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) affecting iron metabolism,
Continuous/long-term use of medication during the whole study, which may interfere with iron absorption, gut physiology and iron metabolism,
Consumption of mineral and vitamin supplements since screening and over the study period until last blood sample collection,
Difficulties with blood sampling,
Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 6 months,
Known hypersensitivity or allergy to iron capsules in the given amount (ferrous fumarate, brilliant blue FCF (E133), titandioxide (E171) and sodium lauryl sulfate)
Pregnancy, breastfeeding
Women who intend to become pregnant during the course of the study,
Known or suspected non-compliance, drug or alcohol (more than 2 drinks/day) abuse,
Smokers (> 1 cigarette per week),
Participant is likely to be absent on one the study appointments,
Inability to follow the procedures of the study, e.g. due to language problems, self-reported psychological disorders, etc. of the participant.