Dietary iron and risk of myocardial infarction in the Rotterdam Study. (1/598)

Free iron has been implicated in lipid peroxidation and ischemic myocardial damage, and it has been suggested that iron is an independent risk factor for myocardial infarction. The authors investigated whether dietary iron is associated with an increased risk of fatal and nonfatal myocardial infarction in the Rotterdam Study, a community-based prospective cohort study of 7,983 elderly subjects in Rotterdam, the Netherlands. The study sample consisted of 4,802 participants who at baseline had no known history of myocardial infarction and for whom dietary data were available. From 1990 to 1996, 124 subjects had a myocardial infarction. No association was observed between total iron intake and risk of myocardial infarction after adjustment for age and sex (relative risk for the highest vs. the lowest tertile of intake = 0.89, 95% confidence interval (CI) 0.55-1.45, p for trend = 0.640). Heme iron intake was positively associated with risk of myocardial infarction (relative risk for the highest vs. the lowest tertile of intake = 1.83, 95% CI 1.16-2.91, p for trend = 0.008) after adjustment for age and sex, and this association persisted after multivariate adjustment (relative risk = 1.86, 95% CI 1.14-3.09, p for trend = 0.010). A distinction between fatal and nonfatal cases of myocardial infarction indicated that the association of heme iron with myocardial infarction was more pronounced in fatal cases. The results suggest that a high dietary heme iron intake is related to an increased risk of myocardial infarction and that it may specifically affect the rate of fatality from myocardial infarction.  (+info)

Iron-deficient diet reduces atherosclerotic lesions in apoE-deficient mice. (2/598)

BACKGROUND: Iron deposition is evident in human atherosclerotic lesions, suggesting that iron may play a role in the development of atherosclerosis. To test this idea, the correlation between the extent of iron deposition and the severity of atherosclerosis in apolipoprotein E (apoE)-deficient mice was investigated. Furthermore, the effect of a low-iron diet on the progression of atherosclerotic lesions in these animals was evaluated. METHODS AND RESULTS: Iron deposition in tissues of apoE-deficient mice was examined by Perls' staining method. The results clearly demonstrated that iron deposits are present in atherosclerotic lesions and tissue sections of heart and liver in an age-dependent manner. When the young mice received a low-iron diet for 3 months, the hematocrit, serum iron, hemoglobin, and cholesterol concentrations were not significantly altered compared with those of littermates placed on a chow diet. However, the serum ferritin level of animals in the iron-restricted group was 27% to 30% lower than that of the control group in either sex. Furthermore, the lipoproteins isolated from the iron-restricted group exhibited greater resistance to copper-induced oxidation. Histological examination revealed that atherosclerotic lesions developed in mice fed a low-iron diet were significantly smaller than those found in control littermates. Likewise, the iron deposition as well as tissue iron content was much less in aortic tissues of the iron-restricted animals. Circulating autoantibodies to oxidized LDL and immunostains for epitopes of malondialdehyde-modified LDL detected on lesions were also significantly lower in mice fed a low-iron diet. CONCLUSIONS: Iron deposition is closely associated with the progression of atherosclerosis in apoE-deficient mice. Restriction in dietary iron intake leads to significant inhibition of lesion formation in these animals. These results suggest that the beneficial effect of a low-iron diet may be mediated, at least in part, by the reduction of iron deposition as well as LDL oxidation in vascular lesions.  (+info)

Calcium intake is weakly but consistently negatively associated with iron status in girls and women in six European countries. (3/598)

Several studies indicate that intake of calcium can inhibit iron absorption especially when taken simultaneously. In the CALEUR study, a cross-sectional study among girls (mean 13.5 y) and young women (mean 22.0 y) in six European countries, the association between calcium intake and iron status was studied. In 1,080 girls and 524 women, detailed information on calcium intake was collected by means of a 3-d food record, and serum ferritin, serum iron, serum transferrin and transferrin saturation were measured as indicators of iron status. The mean levels of serum iron, ferritin and transferrin were 15.8 +/- 6.1 mmol/L, 34.5 +/- 19.1 microg/L and 3. 47 +/- 0.47 g/L, respectively, in girls and 16.9 +/- 7.5 mmol/L, 40. 2 +/- 30.5 and microg/L, 3.59 +/- 0.60 g/L, respectively, in women. A consistent inverse association between calcium intake and serum ferritin was found, after adjusting the linear regression model for iron intake, age, menarche, protein, tea and vitamin C intake and country, irrespective of whether calcium was ingested simultaneously with iron. The adjusted overall regression coefficients for girls and women were -0.57 +/- 0.20 and -1.36 +/- 0.46 per 100 mg/d increase in calcium intake, respectively. Only in girls, transferrin saturation as a measure for short-term iron status was inversely associated with calcium intake (adjusted overall coefficient -0.18 +/- 0.08). However, analysis per country separately showed no consistency. We conclude that dietary calcium intake is weakly inversely associated with blood iron status, irrespective of whether calcium was ingested simultaneously with iron.  (+info)

Nonheme-iron absorption, fecal ferritin excretion, and blood indexes of iron status in women consuming controlled lactoovovegetarian diets for 8 wk. (4/598)

BACKGROUND: The characteristics of vegetarian diets suggest that these diets would have lower dietary iron bioavailability than nonvegetarian diets, but there is no evidence of iron deficiency in vegetarians. OBJECTIVE: We evaluated the responsiveness of serum and fecal ferritin to differences in iron absorption from controlled lactoovovegetarian and nonvegetarian diets. DESIGN: Twenty-one women aged 20-42 y with serum ferritin concentrations from 6 to 149 microg/L consumed lactoovovegetarian and nonvegetarian weighed diets for 8 wk each (crossover design). The diets differed substantially in meat and phytic acid contents. Nonheme-iron absorption was measured from the whole diets after 4 wk by using extrinsic 59Fe and whole-body counting. Ferritin in extracts of fecal composites and in serum was measured by enzyme-linked immunosorbent assay the last 2 wk of each diet. RESULTS: Nonheme-iron absorption was less from the lactoovovegetarian diet than from the nonvegetarian diet (1.1% compared with 3.8%; P < 0.01; n = 10). Diet did not affect hemoglobin, transferrin saturation, erythrocyte protoporphyrin, or serum ferritin. Substantially less fecal ferritin was excreted with the lactoovovegetarian diet than with the nonvegetarian diet (1.1 compared with 6.0 microg/d, respectively; P < 0.01; n = 21). CONCLUSIONS: This research indicates 1) 70% lower nonheme-iron absorption from a lactoovovegetarian diet than from a nonvegetarian diet; 2) an associated decrease in fecal ferritin excretion, suggesting partial physiologic adaptation to increase the efficiency of iron absorption; and 3) an insensitivity of blood iron indexes, including serum ferritin, to substantial differences in dietary iron absorption for 8 wk.  (+info)

Serum ferritin and risk of myocardial infarction in the elderly: the Rotterdam Study. (5/598)

BACKGROUND: Elevated body iron stores have been suggested to be a risk factor for ischemic heart disease. OBJECTIVE: We examined whether elevated serum ferritin concentrations, other indicators of iron status, and dietary iron affected the incidence of myocardial infarction (MI) in an elderly population. DESIGN: A nested, case-control study of 60 patients who had their first MI and 112 age- and sex-matched control subjects embedded in the population-based cohort of the Rotterdam Study. RESULTS: The age- and sex-adjusted risk of MI for subjects with serum ferritin concentrations > or = 200 microg/L was 1.82 (95% CI: 0.90, 3.69; P = 0.096). The odds ratio (OR) was 1.26 (95% CI: 0.98, 1.64; P = 0.078) for the highest tertile of serum ferritin and was only slightly altered in a multivariate model. Risk of MI associated with the highest tertile of ferritin was most evident in current or former smokers (OR: 1.68; 95% CI: 1.17, 2.47; P for trend = 0.008) and in subjects with hypercholesterolemia (OR: 1.43; 95% CI: 0.99, 2.11; P for trend = 0.056) or diabetes (OR: 2.41; 95% CI: 1.12, 7.67; P for trend = 0.027). No association with risk of MI was observed for tertiles of serum iron, serum transferrin, or total dietary iron. For dietary heme iron, risk of MI was significantly increased in a multivariate model in which dietary energy, fat, saturated fat, and cholesterol were adjusted for (OR: 4.01; 95% CI: 1.17, 15.87; P for trend = 0.031). CONCLUSION: In the presence of other risk factors, serum ferritin may adversely affect ischemic heart disease risk in the elderly.  (+info)

Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. (6/598)

Genetic studies in animal models of microcytic anemia and biochemical studies of transport have implicated the Nramp2 gene in iron transport. Nramp2 generates two alternatively spliced mRNAs that differ at their 3' untranslated region by the presence or absence of an iron-response element (IRE) and that encode two proteins with distinct carboxy termini. Antisera raised against Nramp2 fusion proteins containing either the carboxy or amino termini of Nramp2 and that can help distinguish between the two Nramp2 protein isoforms (IRE: isoform I; non-IRE: isoform II) were generated. These antibodies were used to identify the cellular and subcellular localization of Nramp2 in normal tissues and to study possible regulation by dietary iron deprivation. Immunoblotting experiments with membrane fractions from intact organs show that Nramp2 is expressed at low levels throughout the small intestine and to a higher extent in kidney. Dietary iron starvation results in a dramatic upregulation of the Nramp2 isoform I in the proximal portion of the duodenum only, whereas expression in the rest of the small intestine and in kidney remains largely unchanged in response to the lack of dietary iron. In proximal duodenum, immunostaining studies of tissue sections show that Nramp2 protein expression is abundant under iron deplete condition and limited to the villi and is absent in the crypts. In the villi, staining is limited to the columnar absorptive epithelium of the mucosa (enterocytes), with no expression in mucus-secreting goblet cells or in the lamina propria. Nramp2 expression is strongest in the apical two thirds of the villi and is very intense at the brush border of the apical pole of the enterocytes, whereas the basolateral membrane of these cells is negative for Nramp2. These results strongly suggest that Nramp2 is indeed responsible for transferrin-independent iron uptake in the duodenum. These findings are discussed in the context of overall mechanisms of iron acquisition by the body.  (+info)

Effects of high compared with low calcium intake on calcium absorption and incorporation of iron by red blood cells in small children. (7/598)

BACKGROUND: The potential benefits of increasing calcium intake in small children must be balanced with the potential risk to iron utilization from high calcium intakes. OBJECTIVE: This study was designed to evaluate the relation between calcium intake and calcium absorption and iron incorporation into red blood cells. DESIGN: We performed a multitracer, crossover study of the absorption of calcium and red blood cell incorporation of iron in 11 preschool children aged 3-5 y who had been adapted for 5 wk to low- (502 +/- 99 mg) and high- (1180 +/- 117 mg) calcium diets. Stable-isotope studies were performed by using 44Ca and 58Fe given orally with meals and 46Ca given intravenously. RESULTS: Iron incorporation into red blood cells 14 d postdosing was similar (6.9 +/- 4.2% compared with 7.9 +/- 5.5%; NS) with the low- and high-calcium diets, respectively. Total calcium absorption (181 +/- 50 compared with 277 +/- 91 mg/d; P = 0.002) was greater in children with the higher calcium intake. CONCLUSIONS: Our findings indicate that small children may benefit from calcium intakes similar to those recommended for older children without adverse effects on dietary iron utilization.  (+info)

Iron fortified follow on formula from 9 to 18 months improves iron status but not development or growth: a randomised trial. (8/598)

AIMS: Iron deficiency anaemia is associated, in observational studies, with developmental disadvantage. This study tested the hypothesis that feeding iron supplemented formula from 9 to 18 months of age would improve developmental performance. SUBJECTS AND METHODS: 493 healthy children aged 9 months being fed pasteurised cows' milk were recruited from three UK centres. They were randomised to: cows' milk as before, formula containing 0.9 mg/litre iron, or formula containing 1.2 mg/litre iron, until 18 months of age. Bayley mental and psychomotor developmental indices were measured at 18 months, as were growth and haematological indices. RESULTS: Children fed iron fortified formula had higher plasma ferritin concentrations, but there were no significant intergroup differences in development or growth. CONCLUSIONS: There are no developmental or growth advantages in children given iron supplemented formula, but a benefit for a minority who were anaemic, or the possibility that a benefit may emerge at a later age, cannot be excluded.  (+info)