Dietary Heme Iron Research Articles

Cardiovascular diseases and red meat

Cardiovascular diseases and red meat

A cohort study of dietary iron and heme iron intake and risk of colorectal cancer in women

In a cohort study of 49 654 Canadian women, we assessed the association of colorectal cancer with total iron and heme iron intake, excluding iron supplements. Among women aged 40–59 years, followed for an average of 16.4 years, we identified 617 incident colorectal cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate red meat intake and intake of total dietary iron, iron from meat, and heme iron. Analyses were carried out for all cases and for the proximal colon, distal colon, and rectum, using Cox proportional hazards models. We found no association of intake of iron, heme iron, or iron from meat with risk of colorectal cancer overall or with any of the subsites, nor was there effect modification by alcohol consumption or hormonal replacement therapy.

Dietary Iron and Heme Iron Intake and Risk of Breast Cancer: A Prospective Cohort Study

Recent studies suggest that elevated body iron levels may contribute to breast carcinogenesis; however, epidemiologic evidence is lacking. We used data from a large cohort study of Canadian women to assess breast cancer in association with total iron and heme iron intake. Among 49,654 women ages 40 to 59 followed for an average of 16.4 years, we identified 2,545 incident breast cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate total dietary iron and heme iron intake. Using Cox proportional hazards models, we found no association of iron or heme iron intake with risk of breast cancer overall, in women consuming 30+ g of alcohol per day, or in women who had ever used hormone replacement therapy. The present study offers no support for an association of iron or heme iron intake with breast cancer risk or for a modification by iron of the effect of alcohol or estrogen. However, further cohort studies with repeated measurement of iron intake are warranted.

Dietary Iron, Alcohol Consumption and Serum Ferritin Concentrations in African Americans.

We investigated the relationship of dietary iron and alcohol consumption with serum ferritin concentration among 143 inner-city African-Americans from the community. Seventy-one of the participants reported consuming an average of more than four alcoholic drinks per day and 72 less than two alcoholic drinks per week. The mean age was 47 years for the high alcohol group and 49 years for the low alcohol group. Thirteen (18%) of the participants in the high alcohol group were women compared to 27 (38%) in the low alcohol group. Body mass index and rates of positivity for HIV and hepatitis C virus were similar. Typical daily dietary iron and alcohol consumption was calculated based on a dietary questionnaire that has been validated for use among various ethnic groups (University of Hawaii). The relationship of dietary iron content and alcohol consumption with log10 serum ferritin concentration and with log10 ratio of serum ferritin to AST (ferritin/AST) was examined in multivariate linear regression models that adjusted for age, sex, ferroportin Q248H status, caloric intake and serum concentrations of CRP and ALT. Ferritin/AST has been shown to correlate with hepatic iron concentration in the setting of alcoholic liver disease. Both average daily dietary iron from meat, poulty and fish (P = 0.013) and average daily alcohol consumption (P = 0.015) correlated positively with log10 serum ferritin, but average daily non-heme iron content did not (P = 0.9). Similar findings obtained for log10 ferritin:AST. According to this modeling and holding other variables constant, a 70 kg individual with serum ferritin of 100 ng/ml associated with dietary iron from meat, poultry and fish of 3.5 mg/day would have serum ferritin of 135 ng/ml (95% c.i. 107–172) associated with dietary iron from meat, poultry and fish of 7.0 mg/day. Similarly, a 70 kg individual with serum ferritin 100 ng/ml associated with no alcohol intake would have serum ferritin 124 ng/ml (105–148) associated with alcohol consumption of 56 g/day. Our results are consistent with the hypothesis that the amount of dietary heme iron and the degree of alcohol consumption influence the amount of storage iron in the body as reflected by serum ferritin concentration.

HFE genotypes and dietary heme iron: No evidence of strong gene–nutrient interaction on serum ferritin concentrations in middle-aged women

Background and aim Hereditary hemochromatosis (HH) is a disorder characterized by inappropriately high intestinal iron absorption. In populations of Northern European descent, HH is most commonly caused by mutations (C282Y/H63D) in the HFE gene. Methods and results We investigated the effects of dietary heme iron intake and HFE mutations on serum ferritin concentrations in a population-based random sample of 1611 women aged >50 years using analysis of covariance (ANCOVA). Higher heme iron intake was associated with significantly higher serum ferritin concentrations ( P trend < 0.001). Also, women with the compound or C282Y homozygous genotype had significantly higher serum ferritin concentrations (geometric mean 115.2 μg/L (95% CI 81.4–162.9 μg/L) than women carrying normal alleles (geometric mean 76.6 μg/L (95% CI 72.5–80.9 μg/L). We observed the highest serum ferritin concentrations among postmenopausal women who are compound heterozygous or C282Y homozygous, and who consume relatively high amounts of heme iron (geometric mean 183.9 μg/L (95% CI 97.2–347.8 μg/L). Conclusions Even when there are currently no clinical signs, women with the compound or C282Y homozygous genotype may still be at risk for developing iron overload sometime after menopause.

Identification of an Intestinal Heme Transporter

Dietary heme iron is an important nutritional source of iron in carnivores and omnivores that is more readily absorbed than non-heme iron derived from vegetables and grain. Most heme is absorbed in the proximal intestine, with absorptive capacity decreasing distally. We utilized a subtractive hybridization approach to isolate a heme transporter from duodenum by taking advantage of the intestinal gradient for heme absorption. Here we show a membrane protein named HCP 1 (heme carrier protein 1), with homology to bacterial metal-tetracycline transporters, mediates heme uptake by cells in a temperature-dependent and saturable manner. HCP 1 mRNA was highly expressed in duodenum and regulated by hypoxia. HCP 1 protein was iron regulated and localized to the brush-border membrane of duodenal enterocytes in iron deficiency. Our data indicate that HCP 1 is the long-sought intestinal heme transporter.

Interaction Among Heme Iron, Zinc, and Supplemental Vitamin C Intake on the Risk of Lung Cancer: Iowa Women's Health Study

: Redox-active iron present at physiological levels in the pulmonary epithelial lining fluid may lead to damage of lung tissue under some circumstances. For example, factors that increase potential for oxidative stress, such as higher intake of heme iron or higher intake of vitamin C in the presence of high intake of iron, might increase the risk of lung cancer, whereas higher intake of the antioxidant zinc might decrease that risk. During 16 yr of follow-up, 34,708 postmenopausal women, aged 55-69 yr at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for 700 incident lung cancers. When subjects were stratified by intake of vitamin C supplements, among women who took vitamin C supplements of >500 mg/day, after adjusting for age, total energy intake, cigarette smoking, alcohol consumption, and dietary zinc or dietary heme iron intake, relative risks across categories of dietary heme iron intake were 1.0, 0.85, 0.93, 1.32, 1.70, and 3.77 (P for trend = 0.05; P for interaction = 0.08), whereas corresponding figures for dietary zinc intake were 1.0, 1.15, 0.71, 0.84, 0.61, and 0.11 (P for trend = 0.12; P for interaction = 0.04). The strength of the associations of heme iron and zinc intake with lung cancer appeared to be stronger with increasing levels of vitamin C supplement intake. Our results suggest that high dietary heme iron intake may increase the risk of lung cancer, whereas high dietary zinc may decrease the risk of lung cancer among postmenopausal women who consume high-dose vitamin C supplements. This finding may be of particular importance to smokers, for whom vitamin C supplementation is a common recommendation.

Iron, zinc, and alcohol consumption and mortality from cardiovascular diseases: the Iowa Women’s Health Study

The relation between iron status and atherosclerosis has long been a topic of debate. We examined associations of cardiovascular disease (CVD) mortality with dietary intakes of iron (a possible prooxidant), zinc (a possible antioxidant), and alcohol (a disruptor of iron homeostasis). Postmenopausal women (n = 34 492) aged 55-69 y at baseline, who completed a food-frequency questionnaire, were followed for CVD mortality over 15 y. Among women who consumed >/=10 g alcohol/d, after adjustment for CVD risk factors in a model that contained dietary heme iron, nonheme iron, and zinc intakes, dietary heme iron showed a positive association, dietary nonheme iron showed a U-shaped association, and dietary zinc showed an inverse association with CVD mortality. For example, the relative risks (RRs) for categories of dietary heme iron were 1.0, 1.46, 1.52, 1.73, and 2.47 (P for trend = 0.04); corresponding RRs for dietary nonheme iron were 1.0, 0.93, 0.63, 0.83, and 1.20 (P for quadratic term = 0.02). The corresponding RRs for dietary zinc were 1.0, 0.61, 0.59, 0.57, and 0.37 (P for trend = 0.07). In an analysis restricted to those who consumed >/=30 g alcohol/d, the risk gradients strengthened. Our results suggest that a higher intake of heme iron might be harmful, whereas a higher intake of zinc might be beneficial in relation to CVD mortality in the presence of a trigger that can disturb iron homeostasis, such as alcohol consumption.

Heme iron, zinc and upper digestive tract cancer: The Iowa Women's Health Study

We examined associations among dietary heme iron as a possible pro-oxidant, dietary zinc as a possible antioxidant, and the incidence of upper digestive tract cancer; 34,708 postmenopausal women, aged 55-69 years at baseline who completed a food frequency questionnaire, were followed 16 years. There were 75 upper digestive tract cancer cases (52 gastric cancer and 23 esophageal cancer). When heme iron and zinc were mutually adjusted, in dose-response manners, heme iron intake was positively associated with the risk of upper digestive tract cancer, while zinc intake was inversely associated with risk. After adjusting for age, total energy intake, cigarette smoking and alcohol consumption, relative risks for quintiles of heme iron intake were 1.0, 1.53, 2.15, 3.05 and 2.83 (p for trend = 0.06) and corresponding relative risks for zinc intake were 1.0, 0.86, 0.42, 0.37 and 0.13 (p for trend < 0.01). Additional adjustment for body mass index, physical activity, hormone replacement therapy, multivitamin intake and intake of saturated fat, vitamin C, vitamin E and folate did not change the results. Higher intake of heme iron is associated with higher risk, while higher intake of zinc is associated with lower, risk of upper digestive tract cancer.

Dietary haem iron and coronary heart disease in women

A role for iron in the risk of ischaemic heart disease has been supported by in vitro and in vivo studies. We investigated whether dietary haem iron intake is associated with coronary heart disease (CHD) risk in a large population-based cohort of middle-aged women. We used data of 16 136 women aged 49-70 years at recruitment between 1993 and 1997. Follow-up was complete until 1 January 2000 and 252 newly diagnosed CHD cases were documented. Cox proportional hazards analysis was used to estimate hazard ratios of CHD for quartiles of haem iron intake, adjusted for cardiovascular and nutritional risk factors. We stratified by the presence of additional cardiovascular risk factors, menstrual periods, and antioxidant intake to investigate the possibility of effect modification. High dietary haem iron intake was associated with a 65% increase in CHD risk [hazard ratio (HR)=1.65; 95% confidence interval (CI): 1.07-2.53], after adjustment for cardiovascular and nutritional risk factors. This risk was not modified by additional risk factors, menstruation, or antioxidant intake. The results indicate that middle-aged women with a relatively high haem iron intake have an increased risk of CHD.

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

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.

ReviewIs Serum Gamma Glutamyltransferase a Marker of Oxidative Stress?

The primary role of cellular gamma glutamyltransferase (GGT) is to metabolize extracellular reduced glutathione (GSH), allowing for precursor amino acids to be assimilated and reutilized for intracellular GSH synthesis. Paradoxically, recent experimental studies indicate that cellular GGT may also be involved in the generation of reactive oxygen species in the presence of iron or other transition metals. Although the relationship between cellular GGT and serum GGT is not known and serum GGT activity has been commonly used as a marker for excessive alcohol consumption or liver diseases, our series of epidemiological studies consistently suggest that serum GGT within its normal range might be an early and sensitive enzyme related to oxidative stress. For example, serum and dietary antioxidant vitamins had inverse, dose-response relations to serum GGT level within its normal range, whereas dietary heme iron was positively related to serum GGT level. More importantly, serum GGT level within its normal range positively predicted F2-isoprostanes, an oxidative damage product of arachidonic acid, and fibrinogen and C-reactive protein, markers of inflammation, which were measured 5 or 15 years later, in dose–response manners. These findings suggest that strong associations of serum GGT with many cardiovascular risk factors and/or events might be explained by a mechanism related to oxidative stress. Even though studies on serum and/or cellular GGT is at a beginning stage, our epidemiological findings suggest that serum GGT might be useful in studying oxidative stress-related issues in both epidemiological and clinical settings.

Association between serum γ-glutamyltransferase and dietary factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Diet may be involved in the strong dose-response relation of gamma-glutamyltransferase (GGT) concentration with incident diabetes. We examined dietary correlates of serum GGT activity. Study subjects were 3146 black and white men and women aged 17-35 y in 1985-1986. A diet history was taken at years 0 and 7. Food items were classified into alcohol; breaded, battered, or canned vegetables; fruit; fruit juice; refined grain; whole grain; dairy; legumes; meat; poultry; fish; fresh or frozen vegetables; nuts; and coffee. After adjustment for nondietary factors and other food groups, GGT was positively associated with alcohol consumption and meat intake. Geometric means of year 10 GGT across categories of alcohol consumption (0, 1-9, 10-19, 20-29, and > or = 30 g/d) were 17.7, 18.8, 20.4, 21.8, and 24.8 U/L (P for trend < 0.01); corresponding means across quintiles of meat intake were 19.2, 20.2, 20.5, 21.8, and 21.2 times/wk (P for trend < 0.01). GGT was inversely associated with fruit intake. Among possible meat constituents, dietary heme iron, but not saturated fat, was associated with GGT. Dietary constituents typical of plant foods showed an inverse association. In contrast, vitamin supplements were positively associated with GGT. Serum GGT activity increased in a dose-response manner as alcohol and meat consumption increased and fruit consumption decreased. Heme iron contained in meats and micronutrients contained in fruits may influence GGT metabolism. However, micronutrients taken as supplements had a positive association with GGT.

Heme iron, zinc, alcohol consumption, and colon cancer: Iowa Women's Health Study.

We examined associations among colon cancer incidence and dietary intake of heme iron, a possible prooxidant, zinc, a possible antioxidant, and alcohol, a disruptor of iron homeostasis. During 15 years of follow-up, 34 708 postmenopausal women, aged 55-69 years at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for incident colon cancer. After adjusting for each micronutrient, the relative risks for proximal colon cancer increased more than twofold across categories of heme iron intake (P(trend) =.01) and the corresponding relative risks decreased more than 50% across categories for zinc intake (P(trend) =.01). The positive association with heme iron and the inverse association with zinc intake were stronger among women who consumed alcohol than among those who did not. Zinc intake was also associated with a decreased risk of distal colon cancer (P(trend) =.03), regardless of alcohol or heme iron consumption. Our results suggest that intake of dietary heme iron is associated with an increased risk of proximal colon cancer, especially among women who drink, but that intake of dietary zinc is associated with a decreased risk of both proximal and distal colon cancer.

Dietary iron intake and Type 2 diabetes incidence in postmenopausal women: the Iowa Women's Health Study.

Recently, a clear biological link between iron metabolism and diabetes has emerged from epidemiological and experimental studies. We carried out a prospective study of dietary iron intake and incidence of Type 2 diabetes. 35,698 postmenopausal women initially aged 55 to 69 years were followed for 11 years. Diet was assessed with a food frequency questionnaire at baseline. Intake of heme iron showed a positive association with incident Type 2 diabetes; the relative risks were 1.0, 1.07, 1.12, 1.14, and 1.28 across quintiles of heme iron (p trend =0.02) after adjustment for non-dietary and dietary risk factors. Heme iron showed a weak positive association among non-drinkers, but the association appeared to be stronger among subjects who consumed more alcohol. For example, in a model restricted to those who drank alcohol at least 15 g/day, adjusted relative risks across quintiles of heme iron were 1.0, 2.26, 3.22, 1.92, and 4.42 (p trend =0.05); and consumers of 30 g/day of more of supplemental iron had an adjusted relative risk equal to 3.03 (95% CI, 1.29-7.12)], compared to those who took no iron supplement. Non-heme iron was inversely associated with incidence of Type 2 diabetes. Amongst non-drinkers adjusted relative risks were 1.0, 0.83, 0.87, 0.72, and 0.67 across quintiles (p trend <0.01). This inverse association was lost among drinkers, in whom there was no association of diabetes incidence with non-heme iron. Greater dietary heme-iron intake and/or supplemental iron were associated with an increased risk of Type 2 diabetes, especially amongst those who drink alcohol.

#80 Dietary iron and hemeiron as risk factors for myocardial infarction

Abstract PURPOSE: Several epidemiological and experimental studies have suggested a potential association between high levels of dietary iron/hemeiron and risk of acute myocardial infarction (AMI). Lean meat, a rich source of iron and hemeiron, is promoted because it is relatively low in fat and cholesterol. This leads to the concern that lean meat may increase risk for AMI and that we should reconsider its promotion. We investigated whether individuals who consume more iron and hemeiron were at increased risk for AMI. METHODS: We analyzed dietary intake of iron and hemeiron among 2198 participants in a nutrition survey in the province of Nova Scotia, Canada. Linkage with hospital discharge records, physicians' administrative records and vital statistics enabled us to analyze AMI during an eight-year follow up period. Using logistic regression, AMI cases were compared to those without AMI, while adjusting for differences in age, gender, smoking, body mass index, diabetes, socioeconomic background, dietary lipids, saturated fat, cholesterol and total energy intake. RESULTS: During the eight years following the survey, 94 (4.3%) participants had an AMI, of which 17 were fatal. Participants in the highest iron intake tertile had reduced risk of AMI, compared to those in the lowest tertile (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.34–1.05). Similarly, participants in the highest hemeiron intake tertile had reduced risk of AMI (OR, 0.65; 95% CI, 0.37–1.14). CONCLUSION: Based on the present results, showing no increased risk for AMI with high intake of iron and hemeiron, and results from the literature showing that Nova Scotians have a poorer diet, high obesity prevalence and among the highest cardiovascular disease and cancer rates in Canada, we conclude that there is no need for immediate reconsideration of promotion of lean meat in this province.

Heme and Nonheme Iron Content of Animal Products Commonly Consumed in Thailand

When estimating the iron bioavailability of a meal, the amount and type of meat consumed should be considered; therefore, animal products commonly consumed in Thailand were analyzed for iron attached to hemoglobin (heme iron) and other iron compounds (nonheme iron). Conventional household cooking methods, i.e., blanch- ing, boiling and steaming, were used for sample preparation. The results showed that cooked chicken breast and drumsticks contained small amounts of heme iron (0.1 and 0.3 mg/100 g) and nonheme iron (0.3 and 0.6 mg/100 g). Heme and nonheme iron in cooked beef loin was found to be 1.1 and 1.3 mg/100 g, respectively. Liver is a good source of iron, particularly pork liver (12.6 mg/100 g), with approximately 2.3 mg/100 g of heme iron. Cooked blood curds from pork and chicken were the best sources of heme iron; the average was 9.2 and 15.4 mg/100 g, respectively. Cooked meatballs and sausage products contained only small amounts of heme and nonheme iron, ranging from trace to 0.3 and 0.2 to 0.5 mg/100 g, respectively. A good source of total and heme iron was also found in cooked shellfish, especially steamed green mussels and blanched cockle with approximately 14.7 and 17.7 mg/100 g for total iron, and 4.0–9.1 mg/100 g for heme iron, respectively. Of the animal products analyzed in this study and commonly eaten by Thai people, cooked blood curds were determined to be the richest source of dietary heme iron.

Iron absorption and transport-an update.

Iron is vital for all living organisms. However, excess iron is hazardous because it produces free radical formation. Therefore, iron absorption is carefully regulated to maintain an equilibrium between absorption and body loss of iron. In countries where heme is a significant part of the diet, most body iron is derived from dietary heme iron because heme binds few of the luminal intestinal iron chelators that inhibit absorption of non-heme iron. Uptake of luminal heme into enterocytes occurs as a metalloporphyrin. Intracellularly, iron is released from heme by heme oxygenase so that iron leaves the enterocyte to enter the plasma as non-heme iron. Ferric iron is absorbed via a beta(3) integrin and mobilferrin (IMP) pathway that is not shared with other nutritional metals. Ferrous iron uptake is facilitated by DMT-1 (Nramp-2, DCT-1) in a pathway shared with manganese. Other proteins were recently described which are believed to play a role in iron absorption. SFT (Stimulator of Iron Transport) is postulated to facilitate both ferric and ferrous iron uptake, and Hephaestin is thought to be important in transfer of iron from enterocytes into the plasma. The iron concentration within enterocytes reflects the total body iron and either upregulates or satiates iron-binding sites on regulatory proteins. Enterocytes of hemochromatotics are iron-depleted similarly to the absorptive cells of iron-deficient subjects. Iron depletion, hemolysis, and hypoxia each can stimulate iron absorption. In non-intestinal cells most iron uptake occurs via either the classical clathrin-coated pathway utilizing transferrin receptors or the poorly defined transferrin receptor independent pathway. Non-intestinal cells possess the IMP and DMT-1 pathways though their role in the absence of iron overload is unclear. This suggests that these pathways have intracellular functions in addition to facilitating iron uptake.

Iron status and dietary levels of iron affect the bioavailability of haem and nonhaem iron in Atlantic salmonSalmo salar

The absorption of haem iron and nonhaem iron in 155-g Atlantic salmon Salmo salar was studied by simultaneous labelling of the two forms of iron with 59Fe or 55Fe, respectively. Iron absorption was measured after incorporation of this element into blood and tissue 2 days after oral administration. Fish with a low iron status showed a significantly greater absorption of both haem and nonhaem iron than iron-loaded fish. The low-iron group distributed a larger proportion of the iron to kidney and spleen than the iron-loaded or control fish. Absorption of both forms of iron increased with higher doses administered, but absorption relative to dose administered decreased. There was a trend suggesting that increased levels of dietary haem iron resulted in the reduced uptake of nonhaem iron, but not vice versa. The results of the present study suggest that factors affecting bioavailability of haem and nonhaem iron in Atlantic salmon are similar to those of other vertebrates.

Serum ferritin and risk of myocardial infarction in the elderly: the Rotterdam Study

Elevated body iron stores have been suggested to be a risk factor for ischemic heart disease. 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. 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. 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). In the presence of other risk factors, serum ferritin may adversely affect ischemic heart disease risk in the elderly.