Haemochromatosis patients' research priorities: Towards an improved quality of life.

BACKGROUND: Chronic diseases are associated with a range of functional and psychosocial consequences that can adversely affect patients' quality of life (QoL). Haemochromatosis (HC) is a genetically heterogeneous disorder characterized by chronic iron overload that can ultimately lead to multiple organ dysfunction. Clinical diagnosis remains challenging due to the nonspecificity of symptoms and a lack of confirmatory genotyping in a substantial proportion of patients. Illness perception among HC patients has not been extensively investigated, lacking relevant information on how to improve their QoL. METHODS: We present the results of the first worldwide survey conducted in nearly 1500 HC respondents, in which we collected essential demographic information and identified the aspects that concern HC patients the most. RESULTS: Out of all the participants, 45.3% (n = 676) voiced their concern about physical and psychological consequences such as HC-related arthropathies, which can ultimately affect their social functioning. A similar proportion of patients (n = 635, 42.5%) also consider that better-informed doctors are key for improved HC disease management. Taking a patient-centred approach, we expose differences in patients' disease perspective by social and economic influences. CONCLUSIONS: We identify potential targets to improve patients' health-related QoL and reflect on strategic measures to foster gender equity in access to health resources. Finally, we make a call for a highly coordinated effort across a range of public policy areas to empower participants in the HC research process and design. PATIENT OR PUBLIC CONTRIBUTION: Nearly 1500 patients with hereditary HC responded to an anonymized online survey in which research and clinical priorities were addressed regarding this chronic and rare disease.

Correction to: Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect.

[This corrects the article DOI: 10.14740/gr1206.].

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

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 non-sourdough, 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.

A Review of Nutrients and Compounds, Which Promote or Inhibit Intestinal Iron Absorption: Making a Platform for Dietary Measures That Can Reduce Iron Uptake in Patients with Genetic Haemochromatosis.

OBJECTIVE: To provide an overview of nutrients and compounds, which influence human intestinal iron absorption, thereby making a platform for elaboration of dietary recommendations that can reduce iron uptake in patients with genetic haemochromatosis. DESIGN: Review. Setting. A literature search in PubMed and Google Scholar of papers dealing with iron absorption. RESULTS: The most important promoters of iron absorption in foods are ascorbic acid, lactic acid (produced by fermentation), meat factors in animal meat, the presence of heme iron, and alcohol which stimulate iron uptake by inhibition of hepcidin expression. The most important inhibitors of iron uptake are phytic acid/phytates, polyphenols/tannins, proteins from soya beans, milk, eggs, and calcium. Oxalic acid/oxalate does not seem to influence iron uptake. Turmeric/curcumin may stimulate iron uptake through a decrease in hepcidin expression and inhibit uptake by complex formation with iron, but the net effect has not been clarified. CONCLUSIONS: In haemochromatosis, iron absorption is enhanced due to a decreased expression of hepcidin. Dietary modifications that lower iron intake and decrease iron bioavailability may provide additional measures to reduce iron uptake from the foods. This could stimulate the patients' active cooperation in the treatment of their disorder and reduce the number of phlebotomies.

Dietary Iron Intakes in Men in Europe Are Distinctly Above the Recommendations: A Review of 39 National Studies From 20 Countries in the Period 1995 - 2016.

The objective of this review was to assess whether dietary iron intake in men in Europe is in symphony with the dietary recommendations. A literature search of national dietary surveys reporting the intake of iron using PubMed, Google Scholar, National Nutrient Databases and previous literature on dietary reviews was performed. The subjects were men aged 18 - 70 years. A total of 39 national dietary surveys in 20 European countries in the period 1995 - 2016 were included. There were considerable differences between median/mean iron dietary intake in the 20 countries. Seven countries/regions, UK-Northern Ireland, UK-Wales, Sweden, Belgium, UK-Scotland, UK-England and Serbia reported median/mean iron intake ranging from 10.5 to 11.6 mg/day. Ten countries, Norway, Finland, Lithuania, Italy, Hungary, Portugal, The Netherlands, Denmark, Iceland and Austria reported iron intake from 12.0 to 13.5 mg/day. France, Germany, Ireland and Spain reported iron intake from 14.8 to 16.0 mg/day, while Poland and Slovakia reported the highest intake of 17.2 and 22.7 mg/day. In surveys from France and The Netherlands, intake of heme iron constituted 11% of total dietary iron intake. Nutrient density for iron, reported in five countries, varied from median 11.6 mg iron/10 MJ in Denmark to 16.0 in France. In all countries, the majority of men had a dietary iron intake markedly above a recommended intake of 9 mg/day. In Europe, 75-87% of men have a dietary iron intake above 9 mg/day. A high iron intake together with relatively high intakes of meat and alcohol contributes to a high iron status and a high frequency of body iron overload in many men. We need consensus on common European standardized dietary methods, uniform dietary reference values and uniform statistical methods to perform inter-country comparisons.

Dietary Iron Intake in Pregnant Women in Europe: A Review of 24 Studies from 14 Countries in the Period 1991-2014.

OBJECTIVE: Assessment of dietary iron intake in pregnant women in Europe. DESIGN: Review. Setting. Literature search of dietary surveys reporting the intake of dietary iron using the PubMed and Google Scholar databases covering the years 1990-2019. SUBJECTS: Healthy pregnant women. RESULTS: 24 dietary surveys/studies in 14 European countries were included. Nine studies (38%) used Food Frequency Questionnaires, which yielded significantly higher iron intake than studies using Dietary Records. Results from Dietary Record studies in 11 countries showed that iron intake varied between 8.3-15.4 mg/day with an estimated "median" value of 10-11 mg/day. Spain, Bosnia, and Poland reported an intake of 8.3-10.1 mg/day, Croatia, England, Norway, and Finland an intake of 10.2-11.4 mg/day, and Germany, Portugal, Czech Republic, and Greece an intake of 12.2-15.4 mg/day. The recommended iron intake in the various countries varied from 14.8-30 mg/day. In all studies, 60-100% of the women had a dietary iron intake below the recommended intake. CONCLUSIONS: In Europe, the majority of pregnant women have a dietary iron intake, which is markedly below the recommended intake. This contributes to a low iron status in many pregnant women. Most guidelines do not advice routine iron supplements, while two guidelines (World Health Organization and Nordic Nutrition Recommendations) recommend routine iron supplementation during pregnancy. Within the European community, we need to reach consensus on the various guidelines and on the issue of iron supplementation. We should establish common European standardized dietary methods, uniform Dietary Reference Values, and uniform statistical methods in order to perform more reliable comparisons between studies in different countries.

Dietary Iron Intake in Women of Reproductive Age in Europe: A Review of 49 Studies from 29 Countries in the Period 1993-2015.

OBJECTIVE: Assessment of dietary iron intake in women of reproductive age in Europe. DESIGN: Review. SETTING: Literature search of dietary surveys reporting intake of iron using PubMed, Internet browsers, and national nutrient databases in the period 1993-2015. SUBJECTS: Women of reproductive age. RESULTS: 49 dietary surveys/studies in 29 European countries were included. Belgium, Bosnia, Denmark, Hungary, Italy, Northern Ireland, Serbia, Scotland, Sweden, Switzerland, United Kingdom/England, and Wales reported a median/mean iron intake of 7.6-9.9 mg/day. Finland, Iceland, Ireland, the Netherlands, Norway, Poland, and Spain reported an intake of 10.0-10.7 mg/day. Austria, Estonia, France, and Russia reported an intake of 11.0-11.9 mg/day. Latvia and Germany reported an intake of 12.0-12.2 mg/day. Croatia, Lithuania, Portugal, and Slovakia reported an intake of 15.9-19.0 mg/day. The percentage of dietary iron consisting of heme iron, reported in 7 studies, varied from 4.3% in United Kingdom to 25% in Spain. Nutrient density for iron (mg iron/10 MJ, median/mean) varied from 11.8 in Sweden to 23.0 in Lithuania. The correlation between nutrient density and dietary iron was significant (p=0.0006). In most countries, the majority of women had a dietary iron intake below 15 mg/day. In Belgium, Denmark, Hungary, and Sweden, 91-95% of women had an intake below 15 mg/day. In Ireland and Germany, 61-78% had an intake below 15 mg/day. CONCLUSIONS: In Europe, 61-97% of women have a dietary iron intake below 15 mg/day. This contributes to a low iron status in many women. We need common European standardized dietary methods, uniform dietary reference values, and uniform statistical methods to perform intercountry comparisons.

Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect.

This paper outlines the Danish aspects of HFE-hemochromatosis, which is the most frequent genetic predisposition to iron overload in the five million ethnic Danes; more than 20,000 people are homozygous for the C282Y mutation and more than 500,000 people are compound heterozygous or heterozygous for the HFE-mutations. The disorder has a long preclinical stage with gradually increasing body iron overload and eventually 30% of men will develop clinically overt disease, presenting with symptoms of fatigue, arthralgias, reduced libido, erectile dysfunction, cardiac disease and diabetes. Subsequently the disease may progress into irreversible arthritis, liver cirrhosis, cardiomyopathy, pancreatic fibrosis and osteoporosis. The effective standard treatment is repeated phlebotomies, which in the preclinical and early clinical stages ensures a normal survival rate. Early detection of the genetic predisposition to the disorder is therefore important to reduce the overall burden of clinical disease. Population screening seems to be cost-effective and should be considered.

[Diagnosis and treatment of genetic haemochromatosis]. / Diagnostik og behandling af genetisk hæmokromatose.

Genetic haemochromatosis is a complex disorder/disease, which can be caused by a multiplicity of mutations in genes involved in iron metabolism being located on different chromosomes. In Caucasians, mutations in the HFE-gene account for the most common form of haemochromatosis (type 1). Non-HFE-haemochromatoses are less frequent and consist of juvenile haemochromatosis (type 2A and 2B) and TRF2-related haemochromatosis (type 3), which all respond to phlebotomies. The others comprise ferroportin disease (type 4A) atypical ferroportin disease (type 4B), acoeruloplasminaemia, atransferrinaemia and DMT1-associated haemochromatosis.

[Juvenile haemochromatosis caused by a homozygous Gly320Val mutation in the haemojuvelin gene]. / Juvenil hæmokromatose forårsaget af homozygot Gly320Val-mutation på hæmojuvelingenet.

Juvenile haemochromatosis caused by a homozygous Gly320Val mutation in the haemojuvelin (HJV) gene was diagnosed in a 12-year-old Danish girl and her 10-year-old sister. Both appeared healthy without clinical or biochemical signs of organ damage. They had iron overload (plasma transferrin saturation 81 and 80%, plasma ferritin 3,671 and 1,356 microgram/l, liver iron content of 375 and 361 micromol/g dry weight, normal myocardial iron content. Their parents were both HJV heterozygous with normal iron status. The girls began phlebotomy treatment with favourable effect.