The present study did not find evidence that dietary iron content, either heme iron or nonheme iron, influences SF concentration in HFEC282Y homozygotes identified by screening primary care patients in North America.
In previous studies by other investigators, the absorption of heme and nonheme iron from an unfortified meal (16
) or nonheme iron from an oral iron test dose (17
) by hemochromatosis patients diagnosed in medical care was greater than would be predicted from the relationship between iron absorption and SF levels observed in normal volunteers. There was a significant inverse relationship of absorption of nonheme iron with increasing SF. In contrast, heme iron absorption was not significantly related to SF concentration (16
). In women in the United Kingdom, HFEC282Y
homozygotes had SF concentrations 2.4 times higher than women with wild-type HFE
genotype. The association between heme iron intake estimated using food frequency questionnaires and SF concentration was stronger in HFEC282Y
homozygotes than in subjects with other HFE
genotypes; nonheme iron intake had little effect on SF concentration (9
). In the Netherlands, women >50 years of age, HFEC282Y
homozygotes and HFEC282Y/H63D
compound heterozygotes had significantly higher SF concentrations than women with other HFE
homozygotes and HFEC282Y/H63D
compound heterozygotes who consumed relatively high amounts of heme iron had the highest SF concentration (20
). It has been proposed that the high rate of expression of iron overload and associated manifestations in hemochromatosis homozygotes diagnosed in medical care in Australia is attributable to the high national rate of meat consumption (21
). Red meat consumption was positively associated with higher SF concentrations among adults in Busselton, Australia, regardless of HFE
). Some persons with HFEC282Y
homozygosity may be especially susceptible to iron loading from diets in which a high proportion of available iron is present as heme, although they may also absorb increased fractions of nonheme iron.
Other studies have suggested that fortification of food with iron may increase the severity of iron overload in persons with hemochromatosis. In seven treated hemochromatosis patients, the absorption of nonheme iron from a test meal was measured using the extrinsic tag technique to simulate the effects of fortification (24
). Doubling of the iron dose produced a proportional increase similar to that in normal subjects (25
). In Sweden, fortification before 1995 accounted for 42% of the mean daily dietary iron content, although Swedish hemochromatosis homozygotes had lower iron burdens, on average, than those in Australia (26
). Decreased fortification in Sweden since 1995 is expected to decrease the rate of iron accumulation in persons with hemochromatosis (27
). It is similarly predicted that iron fortification of wheat flour at the current US levels would accelerate the initial rate of iron loading in persons with hemochromatosis, and that the accelerated evolution of clinical disease in susceptible individuals is directly proportional to the amount of fortification iron added (24
The iron phenotypes of HFEC282Y homozygotes diagnosed in screening are typically less severe than those of hemochromatosis patients diagnosed in medical care. This could account for some differences observed in the present and in previous studies. There are several other limitations to the present study. For example, SF concentration was measured at one point in time and did not address the effects of dietary therapy in a randomized trial. We did not use direct measures of body or liver iron. Dietary iron content in the present study was determined by recall questionnaire; the amounts are, therefore, approximations rather than precise amounts. The questionnaire may not have had sufficient sensitivity to fully reflect the variability in dietary iron content. Nevertheless, these results do not support recommending dietary iron restrictions to patients identified through screening programs.
Formulating an iron-restricted diet is difficult because iron is ubiquitous in fruits, vegetables and meat products and, in the US, all products that contain flour are fortified with iron. Regardless, the concept of dietary iron restriction for management of hemochromatosis and iron overload continues to hold appeal for patients and is often advocated by patient support groups as a way to limit iron accumulation. Dietary iron deficiency has been reported in developing countries; however, in these studies it is difficult to exclude the effects of enteric infections such as Helicobacter pylori
and parasitic infestations. Vegan diets have been associated with iron deficiency (29
). In persons with hemochromatosis diagnosed in medical care, iron absorption decreases as body iron stores increase (17
). Iron absorption can also be affected by other dietary factors such as tea consumption, alcohol consumption and the use of proton pump inhibitors that suppress gastric acid secretion (32
). Iron depletion by periodic phlebotomy removes iron efficiently, whereas dietary manipulation does not remove absorbed iron and has little effect on the rate of iron accumulation. It is likely that less emphasis on an iron-restricted diet could improve the quality of life of patients and simplify long-term management of hemochromatosis.