Effect of High Dietary Iron and Ascorbic Acid on Copper and Iron Utilization during Copper Deficiency

1988 ◽  
pp. 545-546 ◽  
Author(s):  
Mary Ann Johnson ◽  
Cynthia Lee Murphy
Keyword(s):  
Ascorbic Acid ◽  
Copper Deficiency ◽  
Dietary Iron ◽  
Iron Utilization

The Effect of Dietary Factors on Hemochromatosis Disease Expression in C282Y Homozygotes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3680-3680
Author(s):  
Pradyumna D. Phatak ◽  
Brain Bundy ◽  
Caroline Andrews ◽  
Laura Braggins ◽  
Ronald L. Sham
Keyword(s):  
Ascorbic Acid ◽  
Hereditary Hemochromatosis ◽  
Rank Correlation ◽  
Dry Weight ◽  
Heme Iron ◽  
Dietary Factors ◽  
Hfe Gene ◽  
Dietary Iron ◽  
Liver Iron ◽  
Disease Expression

Abstract Background. Hereditary hemochromatosis (HHC) is a common inherited disorder and the vast majority of cases are associated with HFE gene mutations; about 80% are homozygous for the C282Y HFE mutation. Although homozygosity for C282Y is relatively common among individuals of northern European descent, the penetrance, as measured by clinically relevant iron overload, is low. Both environmental and genetic factors have been implicated in modulating disease expression. Most clinicians and patients attribute at least some of the observed variation to differences in dietary patterns. Methods: 28 C282Y homozygous subjects who had completed de-ironing therapy at our center, and were on stable maintenance phlebotomy treatments, participated in a previously validated dietary survey. We examined the influence of dietary iron, heme iron, fiber, ascorbic acid and alcohol intake on disease expression as measured by liver iron, phlebotomy-mobilized iron and maintenance phlebotomy requirement. Results. We developed a maintenance iron score (Maint Fe) which was the iron in milligrams removed per month by phlebotomy treatments in order to maintain serum ferritin in the 25–75 μG/L range. Maint Fe ranged from 36.8–203 mg/month in our patients (87.8 ± 37.7). Liver iron ranged from 30.5 to 505.4 micromoles per gram dry weight (192.7 ± 123). Phlebotomy-mobilized iron ranged from 2.35–18.03 G (6.43 ± 4.08). The Spearman’s Rank Correlation was used to compare dietary parameters with each of the above measures of disease expression. No significant correlation was found. Conclusions. Disease expression varied considerably in our C282Y homozygous subjects as measured by liver iron, phlebotomy-mobilized iron and Maint Fe. The observed variation is not explained by variations in dietary iron, fiber, ascorbic acid or ethanol intake. Our data suggests that other unknown environmental variables or alternatively, modifier genes, may play a role in modulating disease expression in these patients. Contrary to popular belief, dietary variation does not appear to play a major role.

scholarly journals Consumption of a high-iron diet disrupts homeostatic regulation of intestinal copper absorption in adolescent mice

2017 ◽  
Vol 313 (4) ◽  
pp. G353-G360 ◽  
Author(s):  
Jung-Heun Ha ◽  
Caglar Doguer ◽  
James F. Collins
Keyword(s):  
Iron Overload ◽  
Copper Deficiency ◽  
Copper Homeostasis ◽  
Dietary Iron ◽  
Iron Loading ◽  
Homeostatic Regulation ◽  
Dietary Copper ◽  
Copper Absorption ◽  
High Iron ◽  
Copper Depletion

High-iron feeding of rodents has been commonly used to model human iron-overload disorders. We recently noted that high-iron consumption impaired growth and caused severe systemic copper deficiency in growing rats, but the mechanism by which this occurred could not be determined due to technical limitations. In the current investigation, we thus utilized mice; first to determine if the same phenomenon occurred in another mammalian species, and second since we could assess in vivo copper absorption in mice. We hypothesized that excessive dietary iron impaired intestinal copper absorption. Weanling, male mice were thus fed AIN-93G-based diets containing high (HFe) (~8,800 ppm) or adequate (AdFe) (~80 ppm) iron in combination with low (~0.9 ppm), adequate (~9 ppm), or high (~180 ppm) copper for several weeks. Iron and copper homeostasis was subsequently assessed. Mice consuming the HFe diets grew slower, were anemic, and had lower hepatic copper levels and serum ceruloplasmin activity. These physiological perturbations were all prevented by higher dietary copper, demonstrating that copper depletion was the underlying cause. Furthermore, homeostatic regulation of copper absorption was noted in the mice consuming the AdFe diets, with absorption increasing as dietary copper decreased. HFe-fed mice did not have impaired copper absorption (disproving our hypothesis), but homeostatic control of absorption was disrupted. There were also noted perturbations in the tissue distribution of copper in the HFe-fed mice, suggesting that altered storage and thus bioavailability contributed to the noted copper deficiency. Dietary iron loading thus antagonizes copper homeostasis leading to pathological symptoms of severe copper depletion. NEW & NOTEWORTHY High-iron feeding is a common experimental method to model human iron-overload disorders in rodents. Here, we show that dietary iron loading causes severe copper deficiency due to perturbations in the homeostatic regulation of intestinal copper absorption and tissue distribution, which may decrease the bioavailability of copper for use in cuproenzyme synthesis. Whether high-dose iron supplementation in humans antagonizes copper homeostasis is worthy of consideration.

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