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

Study Overview
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Brief Summary
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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.

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

Conditions
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Iron Metabolism Disorders, Iron Overload, Polyphenols

Intervention / Treatment
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* Dietary Supplement: meal matrix & NPPS
* Dietary Supplement: meal matrix & CS
* Dietary Supplement: no-matrix & NPPS
* Dietary Supplement: no-matrix & CS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Meal & natural polyphenol supplement (NPPS)<br>A meal, labelled with stable iron isotope as ferrous sulphate, consumed with the natural polyphenol supplement | Dietary Supplement: meal matrix & NPPS<br>* Test meal consumed with the natural polyphenol supplement<br>|
| Experimental: Drink & natural polyphenol supplement<br>A drink, labelled with stable iron isotope as ferrous sulphate, consumed with the natural polyphenol supplement | Dietary Supplement: no-matrix & NPPS<br>* Test drink consumed with the natural polyphenol supplement<br>|
| Placebo Comparator: Meal & control supplement (CS)<br>A meal, labelled with stable iron isotope as ferrous sulphate, consumed with a control supplement | Dietary Supplement: meal matrix & CS<br>* Test meal consumed with the control supplement<br>|
| Placebo Comparator: Drink & control supplement<br>A drink, labelled with stable iron isotope as ferrous sulphate, consumed with a control supplement | Dietary Supplement: no-matrix & CS<br>* Test drink consumed with the control supplement<br>|

What is the study measuring?
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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 |