Inhibiting Dietary Iron Absorption in Subjects With Hereditary Hemochromatosis by a Natural Polyphenol Supplement

Testing the Efficacy of a Natural Polyphenol Supplement to Inhibit Dietary Iron Absorption in Subjects With Hereditary Hemochromatosis: a Stable Isotope Study

Polyphenolic compounds are very strong Inhibitors of non-heme iron absorption, as they form insoluble complexes with ferrous iron. Patients with hereditary hemochromatosis (HH) have an increased intestinal non-heme iron absorption due to a genetic mutation in the regulatory pathway, leading to excess iron in the body. This study investigates the inhibitory effect of a natural polyphenol Supplement in participants with HH.

Study Overview

• Status: Completed
• Conditions: Iron Metabolism Disorders; Iron Overload; Polyphenols
• Intervention / Treatment: Dietary supplement: meal matrix & NPPS; Dietary supplement: no-matrix & NPPS; Dietary supplement: meal matrix & CS; Dietary supplement: no-matrix & CS

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Porto, Portugal
    • Porto University Hospital Center
• Switzerland
  • Zurich, Switzerland
    • Laboratory of Human Nutrition ETH Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Homozygous for C282Y mutation in HFE (hemochromatosis) gene
• Written informed consent
• Age 18-65 y
• Not pregnant or lactating
• Body weight < 75 kg
• Body mass index (BMI) between 18.5 and 25 kg/m2
• No acute illness/infection (self-reported)
• No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported)
• No scheduled phlebotomy throughout the study period
• The last phlebotomy will be at least 4 weeks prior first test meal administration
• No use of medications affecting iron absorption or metabolism during the study
• No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study
• Participation in any other clinical study within the last 30 days
• Expected to comply with study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Meal & natural polyphenol supplement (NPPS); A meal, labelled with stable iron isotope as ferrous sulphate, consumed with the natural polyphenol supplement	Dietary supplement: meal matrix & NPPS; Test meal consumed with the natural polyphenol supplement
EXPERIMENTAL: Drink & natural polyphenol supplement; A drink, labelled with stable iron isotope as ferrous sulphate, consumed with the natural polyphenol supplement	Dietary supplement: no-matrix & NPPS; Test drink consumed with the natural polyphenol supplement
PLACEBO_COMPARATOR: Meal & control supplement (CS); A meal, labelled with stable iron isotope as ferrous sulphate, consumed with a control supplement	Dietary supplement: meal matrix & CS; Test meal consumed with the control supplement
PLACEBO_COMPARATOR: Drink & control supplement; A drink, labelled with stable iron isotope as ferrous sulphate, consumed with a control supplement	Dietary supplement: no-matrix & CS; Test drink consumed with the control supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline in the isotopic ratio of iron in blood at week 2	The change in the isotopic ratio of iron will be measured after administration of a test meal/drink including iron isotopes	baseline, 2 weeks
change from baseline in the isotopic ratio of iron in blood at week 4	The change in the isotopic ratio of iron will be measured after administration of a test meal/drink including iron isotopes	2 weeks, 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Ferritin concentration (µg/L)	to assess iron status	baseline, weeks 2, and 4
Serum iron concentration (µg/dL)	to assess iron status	baseline, weeks 2, and 4
Soluble transferrin receptor (mg/L)	to assess iron status	baseline, weeks 2, and 4
Transferrin saturation in %	to calculate percent of transferrin that has iron bound to it; Plasma iron and transferrin saturation will be combined to calculate transferrin saturation (ratio)	baseline, weeks 2, and 4
Hemoglobin (g/dL)	to assess blood volume based on weight, height, and Hb.	baseline, weeks 2, and 4
C-reactive Protein (mg/L)	identify acute inflammation	baseline, weeks 2, and 4
alpha-1-glycoprotein (g/L)	identify chronic inflammation	baseline, weeks 2, and 4
Serum Hepcidin (nM)	the major regulator of non-heme iron absorption	baseline, and weeks 2

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Collaborators: Instituto de Investigação em Imunologia

Publications and helpful links

General Publications

• Buerkli S, Salvioni L, Koller N, Zeder C, Teles MJ, Porto G, Habermann JH, Dubach IL, Vallelian F, Frey BM, Moretti D, Baumgartner J, Zimmermann MB. The effect of a natural polyphenol supplement on iron absorption in adults with hereditary hemochromatosis. Eur J Nutr. 2022 Sep;61(6):2967-2977. doi: 10.1007/s00394-022-02829-8. Epub 2022 Mar 23.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 20, 2019
• Primary Completion (ACTUAL): August 15, 2020
• Study Completion (ACTUAL): August 15, 2020

Study Registration Dates

• First Submitted: June 9, 2019
• First Submitted That Met QC Criteria: June 17, 2019
• First Posted (ACTUAL): June 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 26, 2021
• Last Update Submitted That Met QC Criteria: May 23, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Iron Overload; Metabolic Diseases; Hemochromatosis; Hemosiderosis; Iron Metabolism Disorders
• Other Study ID Numbers: FePPHH

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