Effect of Low-dose Versus Standard-dose Iron Supplementation on the Gut Microbiome

Single Center Clinical Trial to Evaluate the Effect of Low-dose Versus Standard-dose Iron Supplementation on the Gut Microbiome in Non-anemic Iron-deficient Females

Iron deficiency is a common problem that is often treated with the administration of oral iron.

Most of the iron is not absorbed and remains in the intestine, where it influences the balance of gut bacteria.

This influence is usually undesirable and should be kept as small as possible. With lower iron doses, the amount of unabsorbed iron is smaller and therefore a smaller change in the intestinal bacteria composition is to be expected.

Study Overview

• Status: Completed
• Conditions: Iron Deficiency (Without Anemia)
• Intervention / Treatment: Dietary supplement: Iron

Detailed Description

Iron deficiency affects about one in five premenopausal women. The first line treatment for patients with iron deficiency is an oral therapy with iron-supplements, another option is the intravenous iron supplementation.

The oral supplementation causes side-effects such as nausea, vomiting, abdominal pain and many more in a lot of patients. There is a positive correlation between the appearance of gastrointestinal side-effects and the applicated iron dose.

Only a low fraction of orally taken iron is actually absorbed, even in patients with iron-deficiency. Since only a fraction of the orally administered iron is actually absorbed, the toxicity of high concentrations of iron in the gastrointestinal tract and the altered selection advantages of the bacteria presumably leads to microbiome changes.

The unabsorbed iron is potentially changing the microbiome, which leads to undesirable side effects.

With low-dose iron-supplementation the amount of unabsorbed iron is smaller, therefore a dosage dependent microbiome change would be expected.

The aim of the study is to determine the magnitude of the microbiome response to daily iron substitution with 12mg and 100mg.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • Universitatsspital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Informed Consent as documented by signature
• Female gender
• Premenopausal
• Age > 18 years
• Regular menstrual cycle
• BMI in normal range (18-25kg/m2)
• Serum-ferritin ≤30ng/ml
• No anemia (hemoglobin ≥117g/l)
• No intake of dietary supplements for at least 4 weeks

Exclusion Criteria:

• Pregnancy
• Hypermenorrhea (more than 5 unties/tampons per day)
• Chronic inflammatory disease, psychiatric disorders
• Hypersensitivity to iron supplements
• chronic kidney disease (creatinine >80 µmol/l)
• Liver disease (ALT >35 U/l)
• Hypo- or Hyperthyroidism (TSH not between 0.16-4.25 mU/l)
• Intake of medicines that interact with oral iron supplementation (e.g. PPI)*

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard-dose; The standard-dose arm takes one 100mg of iron per day together with a meal, no matter breakfast, lunch or dinner - one tablet a day.	Dietary supplement: Iron; 4 weeks of daily oral iron therapy. The subjects administer the therapy themselves.
Experimental: Low-dose; The low-dose arm 12mg of iron a day. The first 6mg tablet in the morning on an empty stomach and the second 6mg tablet in the evening either one hour before or after eating - two tablets a day.	Dietary supplement: Iron; 4 weeks of daily oral iron therapy. The subjects administer the therapy themselves.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome diversity and oral iron therapy	The microbiome is analyzed using stool samples. A stool sample is taken before and after the 4 weeks period. The low-dose arm is expected to have a smaller decrease compared to the standard-dose arm. The microbiome composition is measured using 16S rDNA gene amplicon sequencing. The results are analysed using the Shannon-Index to include diversity as well as abundance.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side-effects of treatment	Adverse events will be assessed on a report form after 4 weeks	4 weeks

Collaborators and Investigators

• Sponsor: University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2023
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: July 5, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Microbiome; Iron; Gut Bacteria
• Additional Relevant MeSH Terms: Metabolic Diseases; Iron Metabolism Disorders; Iron Deficiencies
• Other Study ID Numbers: IronGutMicrobiome

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