Managing Genetic Hemochromatosis: An Overview of Dietary Measures, Which May Reduce Intestinal Iron Absorption in Persons With Iron Overload

Abstract

Genetic hemochromatosis causes iron overload by excess absorption of dietary iron, due to a decreased expression of hepcidin. The objective was to elaborate dietary recommendations that can reduce intestinal iron absorption in hemochromatosis patients, based on our present knowledge of the iron contained in nutrients and the mechanisms of iron uptake. This is a narrative review. Literature search in PubMed and Google Scholar of papers dealing with iron absorption from the diet was conducted. Most important proposed dietary recommendations are: 1) Choose a varied vegetarian, semi-vegetarian or flexitarian diet. A "veggie-lacto-ovo-poultry-pescetarian" diet seems optimal. Avoid iron enriched foods and iron supplements. 2) Eat many vegetables and fruits, at least 600 g per day. Choose protein rich pulses and legumes (e.g., kidney-and soya beans). Fresh fruits should be eaten between meals. 3) Abstain from red meat from mammals and choose the lean, white meat from poultry. Avoid processed meat, offal and blood containing foods. Eat no more than 200 g meat from poultry per week. Choose fish, eggs, vegetables and protein rich legumes the other days. Eat fish two to four times a week as main course, 350 -500 g fish per week, of which half should be fat fish. 4) Choose whole grain products in cereals and bread. Avoid iron enriched grains. Choose nonsourdough, yeast-fermented bread with at least 50% whole grain. 5) Choose vegetable oils, and low-fat dairy products. 6) Eat less sugar and salt. Choose whole foods and foods with minimal processing and none or little added sugar or salt. 7) Quench your thirst in water. Drink green-or black tea, coffee, or low-fat milk with the meals, alternatively water or non-alcoholic beer. Fruit juices must be consumed between meals. Abstain from alcoholic beverages. Drink soft drinks, non-alcoholic beer, or non-alcoholic wine instead. These advices are close to the official Danish dietary recommendations in 2021. In the management of hemochromatosis, dietary modifications that lower iron intake and decrease iron bioavailability may provide additional measures to reduce iron uptake from the foods and reduce the number of phlebotomies. However, there is a need for large, prospective, randomized studies that specifically evaluate the effect of dietary interventions.

Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers

“…Iron is an essential element needed for many redox processes of the cell. Most iron in the diet is in the form of iron(III), weakly or more strongly bound to organic ligands present in the biological matrix [60]. During digestion, iron(III) is released, and because it is practically not absorbable, it must be reduced by intestinal oxidoreductase to iron(II) [61].…”

“…Iron(II) is then uptaken into intestinal mucosa cells by divalent metal transporter 1 (DMT1) [61]. Meat contains mainly heme-bound iron, which is the most bioavailable form of iron in the diet [60]. Heme-bound iron uptake is different; after digestion of protein part of the hemoproteins, heme is uptaken into intestinal mucosa cells by a dedicated heme transporter mechanism, and then iron is decomplexed intracellularly by oxidation with heme oxygenase [62,63].…”

“…Compounds in food that themselves reduce iron(III) to iron(II) (e.g., ascorbate or lactate) promote iron absorption [64,65], while compounds complexing iron (e.g., phytin or tannins; see below) [60] decrease its bioavailability. Dietary beta carotene significantly increases the bioavailability of iron [66,67] by means of a not yet fully understood process.…”

“…Higher iron losses may occur physiologically (due to menstrual bleeding or higher consumption during pregnancy of women) or generally due to any injury or pathological bleeding. It is very important that there are no regulated means of iron excretion, and therefore dietary iron absorption (primarily from duodenal enterocytes) is to be highly regulated [60]. Reticuloendothelial cells serve as the major hepcidin-regulated iron repository.…”

“…Orally administrable low-molecular-weight iron chelators, such as deferiprone (Ferriprox ® ) and deferasirox (Exjade ® ) (see Figure 2 for structures), are efficient, but they also have severe side effects, such as agranulocytosis, hepatic fibrosis and renal toxicity, because they are absorbed from the gastrointestinal tract [70,73,76]. Low-iron diets have been discussed [60]; nevertheless, the important issue is avoidance of alcohol to protect oxidatively damaged liver and maintaining a broadly healthy diet.…”