Capacity of the store‐regulator in maintaining iron balance

Background: Short-term measurements of iron absorption are substantially influenced by dietary bioavailability of iron, yet bioavailability negligibly affects serum ferritin in longer, controlled trials. Objective: Our objective was to test the hypothesis that in men fed diets with high or low iron bioavailability, iron absorption adapts to homeostatically maintain body iron stores. Design: Heme-and nonheme-iron absorption from whole diets were measured in 31 healthy men at 0 and 10 wk while the men consumed weighed, 2-d repeating diets with either high or low iron bioavailability for 12 wk. The diets with high and low iron bioavailability contained, respectively, 14.4 and 15.3 mg nonheme Fe/d and 1.8 and 0.1 mg heme Fe/d and had different contents of meat, ascorbic acid, whole grains, legumes, and tea. Results: Adaptation occurred with nonheme-but not with hemeiron absorption. Total iron absorption decreased from 0.96 to 0.69 mg/d (P < 0.05) and increased from 0.12 to 0.17 mg/d (P < 0.05) after 10 wk of the high-and low-bioavailability diets, respectively. This partial adaptation reduced the difference in iron bioavailability between the diets from 8-to 4-fold. Serum ferritin was insensitive to diet but fecal ferritin was substantially lower with the low-than the high-bioavailability diet. Erythrocyte incorporation of absorbed iron was inversely associated with serum ferritin. Conclusions: Iron-replete men partially adapted to dietary iron bioavailability and iron absorption from a high-bioavailability diet was reduced to Ϸ0.7 mg Fe/d. Short-term measurements of absorption overestimate differences in iron bioavailability between diets.Am J Clin Nutr 2000;71:94-102.

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“…This is consistent with theories that iron stores are regulated by adaptation of iron absorption to maintain individual set points (9,10).…”

Section: Introductionsupporting

confidence: 77%

Adaptation of iron absorption in men consuming diets with high or low iron bioavailability

Hunt

Roughead

2000

The American Journal of Clinical Nutrition

145

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“…Cellular iron homeostasis seems to be regulated at the level of iron uptake, which is dependent on TfR activity (11,36,37). In this study we show that HFE plays an essential role in modulating TfR activity, thus indirectly regulating the level of cellular iron uptake.…”

mentioning

confidence: 52%

Transferrin receptor is negatively modulated by the hemochromatosis protein HFE: Implications for cellular iron homeostasis

Salter–Cid

Brunmark

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

145

106

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Hereditary hemochromatosis is a common autosomal recessive disorder of iron metabolism. Recent demonstration of an association between transferrin receptor (TfR) and HFE, a major histocompatibility complex class I-like molecule that has been implicated to play a role in hereditary hemochromatosis, further strengthens the notion that HFE is involved in iron metabolism. Herein we show that TfR is required for and controls the assembly and the intracellular transport and surface expression of HFE. Because surface-expressed HFE and TfR remain firmly associated physically, only the fraction of TfR that is associated with HFE during biosynthesis is affected functionally. Moreover, we show that HFE binding reduces the number of functional transferrin binding sites and impairs TfR internalization, thus reducing the uptake of transferrin-bound iron. Thus, iron homeostasis is indirectly regulated by HFE, a negative modulator of TfR.

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“…In an iron forti®cation trial, 7.5 mg additional iron was consumed daily for 2 y leading to a signi®cant improvement of iron status in women but with no effect on SF in men (Ballot et al, 1989). In another study in an iron-replete man, 10 mg iron as ferrous sulphate was mixed into one of the main meals for 500 d with no signi®cant increase in SF (Sayers et al, 1994). Similarly, giving 1 g ascorbic acid twice daily with two main meals for two years, expected to increase dietary iron absorption, did not increase SF (Cook et al, 1984).…”

Section: The Inertia In Changes Of Iron Storesmentioning

confidence: 99%

Iron stores in man in relation to diet and iron requirements

1998

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Objective: To calculate iron stores in man and their rates of changes in relation to iron requirements and dietary iron intake and bioavailability. Method: Newly established relationships between iron absorption from whole diets and serum ferritin (SF) and between SF and iron stores allow calculations of amounts of stored iron under different conditions (diets, losses) at stationary states when absorption equals losses. Rate of growth of stores can also be calculated. All calculations are based on observations and require no model assumptions. Results: Present calculations of iron stores agree with previously observed phlebotomy values. Differences in intake and bioavailability of dietary iron and in iron requirements had marked effects on amounts of stored iron. A wide range of diets was studied, from a hypothetical high-meat diet typical for early man to diets in developing countries. A new equation is given for the translation of SF into iron stores. Analyses of growth rate of stores under different conditions showed a fast growth from zero iron stores during the ®rst year (reaching about 80% of ®nal amounts) followed by a much slower rate for 2±3 y. A marked inertia was seen in rate of changes in iron stores that was more marked the closer stores were to their stationary states making it dif®cult to use SF to estimate short term changes in iron absorption in iron replete subjects. Conclusions: Realistic Western-type diets with good bioavailability can cover iron requirements in most women and can restitute iron stores during lactation. The high prevalence of iron de®ciency in menstruating Western women is thus mainly related to a further low bioavailability of iron in present diets. Present analyses also demonstrated an effective control of iron absorption preventing development of iron overload in otherwise healthy subjects even if the diet is forti®ed with iron and even if meat intake is high.

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Capacity of the store‐regulator in maintaining iron balance

Cited by 40 publications

References 19 publications

Adaptation of iron absorption in men consuming diets with high or low iron bioavailability

Adaptation of iron absorption in men consuming diets with high or low iron bioavailability

Transferrin receptor is negatively modulated by the hemochromatosis protein HFE: Implications for cellular iron homeostasis

Iron stores in man in relation to diet and iron requirements

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