Effects of Polyphenols on Iron Absorption in Iron Overload Disorders.

Iron overload diseases are highly prevalent. Dysmetabolic iron overload syndrome involves 15% of men with metabolic syndrome X. Genetic hemochromatosis is the most common genetic disease in Northern Europe. Both are due to a lack of regulation in iron absorption. To date, there is no nutritional study for those patients.

Polyphenols, particularly flavanols, have shown as good iron-chelating abilities as pharmacological chelators. However, no human study in iron-overload disease have been so far conducted.

The aim of POLYFER-study is to demonstrate that oral polyphenol intake reduces iron absorption in patients with genetic or metabolic iron-overload diseases.

POLYFER is a cross-over randomized controlled trial comparing the effect of polyphenol supplementation versus placebo on iron absorption after loading dose of iron given through a rich-iron meal. Iron absorption will be studied by the area under the curve of serum iron after the meal. Serum iron will be collected after the meal à 0 minute, 30 minutes, 1 hour, 2 hours, 3 hours et 4 hours.

Because of the nycthemeral variations of serum iron, it is essential to obtain a collection of serum iron data in the basal state (after fasting), allowing the calculation for each subject of a "relative" AUC after iron-rich meal with placebo and after iron-rich meal with polyphenols. The endpoint will be the difference between "relative" AUC after meal rich in iron alone and after polyphenols.

In order to improve the underlying mechanism of atherosclerosis which is highly prevalent in those diseases, we will conduct an ancillary study. Recent studies showed interesting results linking some oxylipins levels and inflammation. Investigator will study basal oxylipin level and post-prandial oxylipin level by lipidomic analysis in both diseases.

Inclusion criteria

• 18 years old and over
• Written consent.
• For DIOS Group : at least one criteria of the metabolic syndrome as defined by the International Diabetes Federation, associated with hepatic iron overload measured by MRI (at least 50 µmol/g) or by hepatic biopsy.
• For Genetic Haemochromatosis type 1 Group: homozygosity mutation C282Y in HFE gene ; patients undergoing therapeutic phlebotomies.

Exclusion criteria

• Persons under guardianship
• Body-weight less than 45 kg
• Hemoglobin less than 9 g/dL.
• Intestinal malabsorption of any cause
• Current use or previous use during the last 2 months of iron supplement.
• Current use or previous use during the last 2 months of treatment interacting with iron absorption (increasing like C vitamin or decreasing like iron chelators)
• Other causes of hyperferritinemia : chronic inflammatory syndrome, porphyria, hyperferritinemia-cataract-syndrome, chronic alcohol consumption, chronic hemolysis.