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2 Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111; 3 Tufts University Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Boston, MA 02111; 4 National Cancer Institute, Bethesda, MD 20892; and 5 Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA 01003
* To whom correspondence should be addressed. E-mail: katherine.tucker{at}tufts.edu.
| ABSTRACT |
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| Introduction |
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In older adults, anemia is prevalent and is associated with increased morbidity and mortality (6,7). In one study, anemia was observed in 11% of individuals >65 y of age, and in >20% of those
85 y (8). Onset is insidious, so anemia can often go undetected (9). Approximately 80% of cases have a known etiology, with >34% linked to nutrition, and therefore modifiable (10,11). In contrast to younger age groups, the majority of cases in older adults are not typically due to iron deficiency (12). Rather, many cases are due to chronic infectious or inflammatory processes called "anemia of chronic disease." We previously reported that although 10% of elderly participants in the Framingham Heart Study cohort had anemia, the majority were due to anemia of chronic disease and not to iron deficiency (12). Furthermore, elevated serum ferritin concentrations were 4 times more prevalent than IDA (13).
Dietary composition is an important determinant of iron bioavailability and iron status (1317). Several studies demonstrated associations between heme iron from meat or iron supplements and serum ferritin (15,16). We previously reported associations between dietary factors and risk of elevated serum ferritin in the Framingham Heart Study (18). However, that population is almost exclusively non-Hispanic white, and results cannot be generalized to other ethnic groups with differing dietary patterns. The Hispanic population is the fastest-growing ethnic minority in the United States (19). A traditional Hispanic dietary pattern is more plant-based than the typical American diet (20,21), and plant-based diets are associated with low iron absorption and poor iron status.
Iron absorption occurs predominantly in the duodenum and upper jejunum (22) and absorption is influenced by the presence of gastric acid, which enhances iron uptake, along with dietary factors, such as ascorbate and citrate. However, iron absorption can also be inhibited by calcium, plant phytates, and tannins. Studies have evaluated iron bioavailability of foods from various Hispanic diets, but these do not provide information on the long-term effects of such dietary patterns on iron status (20,2325). The objectives of this study were, therefore, to describe the iron nutriture and status of Hispanic older adults and to identify dietary correlates associated with biological markers of iron status in this population.
| Methods |
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55 y of age were randomly sampled. Through door-to-door enumeration, both Hispanic and non-Hispanic white older adults were simultaneously located within the same census blocks. Of those invited, 83% of Hispanics (n = 779) and 54% of non-Hispanic whites (n = 251) participated (26). The non-Hispanic white group was randomly selected, from the same neighborhoods as Hispanic participants, to control for socioeconomic indicators representative of the Hispanic group (21). The final sample included 618 Puerto Ricans and Dominicans, and 161 "other Hispanics" comprised of Cubans, Mexicans, Central Americans, or South Americans. The "other Hispanic" group was excluded from this analysis due to their heterogeneity. Subjects lacking serum ferritin (n = 233) or with missing or implausible total energy intake (>16,736 kJ or <2510 kJ) (n = 31) were also excluded. Therefore, the current analysis included 604 subjects aged 5991 y; 451 Hispanic older adults from Puerto Rico and the Dominican Republic, and 153 non-Hispanic whites. All study procedures were approved by the Institutional Review Board of the Tufts New England Medical Center in Boston, MA.
Dietary intake. Dietary intake data were collected using a FFQ specifically designed and validated for Hispanic adults residing in the northeastern United States (13). Trained bilingual interviewers collected dietary information from study subjects using 3-dimensional models and measurement tools to aid in portion size estimation. Nutrient data were assessed with the Nutrient Data System, version 4.06 (NDS, University of Minnesota).
Biochemical measurements. Fasting blood samples were collected by venipuncture into evacuated EDTA-containing tubes during the home visit. All blood samples were taken to the Jean Mayer Human Nutrition Research Center on Aging (HNRCA), at Tufts University, in a cooler of ice, within 2 h of collection, and clinical chemistries were determined. White blood cell count (WBC), red blood cell count (RBC), and mean cell volume (MCV) were measured in whole blood specimens with a system 9000 Diff Model Automated Cell Counter (Serono-Baker Diagnostics). Hemoglobin was measured with the cyanmethemoglobin procedure. Hematocrit was calculated from the measured variables as (MCV) x (RBC)/10.
Physiologic iron stores were estimated on the basis of serum ferritin concentrations. Serum ferritin was measured using the Magic Ferritin 125I radioimmunoassay (Ciba Corning). As a means of quality control, we conducted the assay of the WHO International Ferritin Standard 80/578 with the Magic Ferritin radioimmunoassay. Mean ferritin values were within 510% of the stated concentration of this quality control. Plasma C-reactive protein (CRP), an inflammatory marker, was measured with a Behring Nephelometer (Behring Diagnostics). Inflammation was defined as plasma CRP
10 mg/L (27).
Socio-demographic and health status. Information on age, education, income, physical activity, and alcohol and tobacco use, as well as medical history, was obtained by a questionnaire adapted from questions used in the Hispanic Health and Nutrition Examination Survey. All methods were pretested for clarity with subjects similar to those in the target population before the beginning of formal data collection. These factors represent nonnutritional determinants of serum ferritin and were analyzed for their possible confounding effects on body iron status.
Criteria for evaluating iron status. Ferritin is an acute-phase protein whose synthesis and secretion by hepatic cells is increased by inflammatory cytokines (12,13,2830). Thus, whereas serum ferritin typically reflects body iron stores (31,32), it is an unreliable indicator of iron status in the presence of various acute and/or chronic disease conditions such as inflammation, infection, liver disease, and malignancy as its concentration becomes disproportionately elevated relative to actual iron stores. We attempted to control for the possible confounding effects of these conditions by defining various disease conditions and adjusting for these in our models.
To evaluate the potential confounding effects of anemia of chronic disease the following guidelines were established. Plasma CRP concentrations
10.0 mg/L was used to define inflammation (n = 82, 18% of Hispanics; n = 21, 13% of non-Hispanic whites) (13,27). Infection status was based on sex-specific cutoff values for WBC count (13). Men with WBC concentrations <3.9 x 103 or >10.6 x 103/mm3 and women with concentrations <3.5 x 103 or >11.0 x 103/mm3 were categorized as having an infection. However, infection was not included in the final analysis, as it did not appear to affect serum ferritin. Diabetes and self-reported physician-diagnosed liver disease were also considered for their confounding effects. Subjects with one or more of the following were defined as having diabetes: fasting blood glucose >6.99 mmol/L, random (nonfasting) blood glucose >11.10 mmol/L, or pharmacological treatment for diabetes (diabetes related drugs or insulin). To increase comparability, we followed similar analysis procedures to those performed by Fleming et al. (13) in the Framingham Heart Study.
Hereditary hemochromatosis is an autosomal recessive disorder characterized by elevated iron absorption that affects
1 in 250 persons in populations of northern European descent and is characterized by pathologic elevations in blood ferritin concentrations (33). These elevations reflect actual increases in body iron stores. Given the probability that individuals within this study population may be homozygous for hemochromatosis is very small, we did not exclude subjects at risk for this mutation.
Iron stores. Generally acceptable cutoff points for iron status measures were selected. Given the age of our population and the evidence supporting a higher serum ferritin threshold for depleted iron stores in the elderly, we selected a conservative cutoff of <15 µg/L for evaluation of iron deficiency (34,35). Based on data from NHANES II (19), the 95th percentile values for serum ferritin concentration in women aged 1864 y and in men aged 1864 y were 193 and 299 µg/L, respectively. Therefore, we selected sexspecific cutoffs to define elevations of serum ferritin >200 µg/L for women and >300 µg/L for men, as used previously (12).
Definition of anemia. The WHO criteria for anemia are estimated on the basis of hemoglobin or hematocrit concentrations (12,36,37). Prevalence estimates of anemia are based on the NHANES III cutoff criteria for an abnormal hemoglobin concentration (<119 g/L for women and <124 g/L for men). We further evaluated the prevalence of suboptimal hemoglobin concentrations <125 g/L (in both sexes) in this population, as a preponderance of recent research indicates that current guidelines are not clinically optimal. Our evaluation of "suboptimal" hemoglobin concentrations allows us to evaluate iron status using cutoffs that may be functionally relevant (38,39). We also evaluated the prevalence of abnormally low hematocrit concentrations, using the WHO criteria (men <0.40; women <0.37).
We attempted to differentiate IDA from other types of anemia, after an evaluation of disease states. We defined IDA as serum ferritin concentrations <15 µg/L, or hemoglobin <119 g/L for women and <124 g/L for men, and MCV <80 µm3/cell (40).
Statistical analysis.
All statistical procedures were performed with SAS for Windows, version 8.1 (SAS Institute). Descriptive comparisons by ethnicity were examined by t test and chi-square analyses. Prevalence estimates for low hemoglobin concentrations, suboptimal hemoglobin, and anemia were obtained by sex and ethnic group. Serum ferritin values were assessed for both the total sample and the majority subset without inflammation (defined here as CRP
10 mg/L). Variable distributions were assessed and logarithmic transformations applied when necessary.
For the Hispanics only, the logged ferritin variable was regressed onto dietary intake variables, adjusting for age, sex, BMI, total energy intake, and additional potential confounders. In addition to age, sex, and BMI, nondietary factors previously shown to be associated with serum ferritin include age, sex, BMI, smoking status, and aspirin use (13). Total energy intake was included in the regression analyses to adjust for differences in energy intakes and for possible systematic over- or underreporting of dietary intake (13,41). Alcohol intake (no intake, moderate, or heavy) was also included, as it is known to be positively associated with serum ferritin (42). Moderate intake was defined as
13.2 g/d for women and
26.4 g/d for men and heavy intake was defined as >13.2 g/d and >26.4 g/d for women and men, respectively. Use of medications, including aspirin, nonsteroidal anti-inflammatory agents, antiplatelet medications, antiulcer medications, and anticoagulants, were examined for possible confounding effects but were excluded from the regression analysis when the variables did not appear to affect serum ferritin concentrations in this sample. We also adjusted for presence of inflammation (CRP
10 mg/L, yes/no), diabetes (yes/no), and liver disease (yes/no) as these may confound the diet-ferritin associations. Repeating the analyses excluding those with inflammation did not alter the results, therefore the full sample is presented. Values presented in the text are means ± SD.
The 1st set of dietary factors included total intake of iron, vitamin C, calcium, dietary fiber, and caffeine (from all sources). To examine the impact of various nutrient intakes on iron status, the 2nd set of dietary factors divided total nutrient intakes into their dietary and supplement components. Dietary iron was further separated into heme and nonheme iron. Because white meat has considerably less heme iron, we examined heme iron from red meat and heme iron from white meat separately. Nonheme iron was defined as the difference between total dietary iron and heme iron. Supplemental intake of iron, vitamin C, and calcium were entered as categorical (yes/no) variables.
The 3rd set of dietary factors included general food and beverage groups composed of items collapsed from the FFQ. Food groups were created by first combining total daily intake (g) of specific foods. The total was then divided by a median-defined portion size and then multiplied by 7 to reach the total servings per week. Food groups included milk (skim, low fat, or whole), fruit (including all fruit and fruit juices), starchy vegetables (including plantains, potatoes, and other root crops), and all other vegetables (including tomatoes). The legumes group included dried beans and peas. White meats included chicken, turkey, and fish. The red meat group was composed of liver, beef, pork, and all processed meats. Fortified and refined grain products were classified as different groups based on the form of iron used for fortification, i.e., the bread and pasta group, which consisted of items fortified primarily with iron sulfate, and the sweet baked goods group, which consisted of items fortified with elemental iron powder produced by hydrogen reduction (i.e., reduced iron). Breads were white or wheat, corn bread, corn tortillas, and sweet baked goods. Cold breakfast cereals were divided into refined or whole-grain cereals on the basis of the content of whole grain or bran.
| Results |
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10 mg/L), BMI, or total energy intake between Hispanics and non-Hispanic whites did not differ.
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Biological markers of iron status.
Hispanic older adults had lower mean hemoglobin concentrations (P < 0.01), and higher prevalence of suboptimal hemoglobin concentrations (P < 0.05) than non-Hispanic whites (Table 4). When examined by sex, these differences appeared to be due mainly to particularly low hemoglobin status in Hispanic women. Greater than 28% of Hispanic women had suboptimal hemoglobin compared with 12% of men. Microcytosis (MCV <80 µm3) was
10 times more prevalent in the Hispanic group than in the non-Hispanic whites (P < 0.001). Again, this was more apparent among Hispanic women. More than 11% of Hispanic women had microcytosis compared with <1% of non-Hispanic white women. Macrocytosis (MCV >90µm3), an indicator of folate or vitamin B-12 deficiency, was not present in either group. The geometric mean serum ferritin concentration in Hispanics was significantly lower than that of non-Hispanic whites; however, the prevalence of elevated serum ferritin did not differ significantly between groups. Results for serum ferritin were similar when we excluded subjects with inflammation [geometric mean 73.6 µg/L in Hispanics (n = 366) vs. 95.5 µg/L in non-Hispanic whites (n = 132); P < 0.05] and prevalence of elevated ferritin (8.3% in Hispanics vs. 12.1% in non-Hispanic whites; P > 0.05). There was a trend toward higher prevalence of IDA in Hispanics than in non-Hispanic whites (P = 0.08). This was significant (P < 0.05) for Hispanic women, >7% of whom had IDA, compared with 2% of non-Hispanic white women.
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After controlling for age, sex, BMI, alcohol intake, smoking status, energy intake, inflammation, diabetes, and liver disease, neither total iron intake nor intake of other nutrients tested were significantly associated with serum ferritin among Hispanics (Table 5). However, when total iron, vitamin C, and calcium were expanded into their component dietary sources, intakes of heme iron derived from red meat and caffeine were positively associated, and dietary calcium negatively associated with serum ferritin. Each mg of heme iron consumed from red meat was associated with a 46% greater log serum ferritin concentration (P < 0.02). Every 100 mg of caffeine consumed was associated with a 5% greater log serum ferritin (P < 0.04), and each 100 mg of dietary calcium consumed was associated with a 4% lower log serum ferritin concentration (P < 0.01).
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| Discussion |
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125 g/L were as much as 1.5 times as likely to have difficulty performing daily tasks, whereas women with higher hemoglobin concentrations performed significantly better on tests of mobility (38,43). This notion is further supported by the Women's Health and Aging Studies I and II that demonstrated the prevalence of mobility difficulties was inversely related to hemoglobin concentration even within a hemoglobin range considered normal. In contrast to the present findings in Hispanic older adults, we previously showed that IDA was uncommon (1.2% prevalence) in a free-living, white, elderly Framingham Heart Study cohort (12). Interestingly, although significantly lower than the Hispanic population (6.5%), the prevalence of anemia for our generally low-income non-Hispanic white comparison population (3.3%) was also higher than that of the Framingham older adults. The reason for these ethnic and socio-economic level differences in iron status is unknown, but may reflect, at least in part, differences in iron intake and the contribution of dietary factors that are known to influence iron bioavailability.
We found significant ethnic differences in nutrient intake and intake of specific food items. Despite living in the same neighborhoods, these Caribbean Hispanics differed from non-Hispanic whites in both demographics and dietary intake patterns. Bartholomew et al. (44) showed that ethnicity and therefore ethnically related food choices may affect the health status of a population. We have previously reported that the intake of heme, supplemental iron, dietary vitamin C, and ethanol were significant positive predictors of iron stores (serum ferritin) in white, elderly persons in the Framingham Heart Study cohort (13). We also found that heme intake was positively associated with serum ferritin among these elderly Hispanics. The relation of heme iron and meat, specifically red meat, has consistently been observed in studies across varying populations (13,45,46). The association of meat with serum ferritin has been attributed to the high concentration of highly bioavailable heme iron found exclusively in animal products (13). In addition, the presence of red meat in the diet may enhance dietary iron absorption from nonheme sources. A study examining iron absorption from Latin American diets indicated that variation in both heme and nonheme iron absorption among Hispanics was due in large part to a variation in meat intake (23). Hallberg et al. (24) showed that the addition of meat to a typical cereal-based Latin American meal effectively elevated rates of iron absorption. Our current findings of elderly Hispanics living in Massachusetts support the importance of red meat intake as an important determinant of body iron stores (47). Vitamin C can promote the absorption of iron and we have previously reported that dietary vitamin C intake was positively associated with iron stores in the elderly Framingham Heart Study cohort (13). Total vitamin C intake was about one-third lower in our Hispanic compared with non-Hispanic older adults and may have been an additional factor that contributed to lower iron stores in this group.
Ethanol consumption is associated with higher serum ferritin concentrations in the elderly (18). Hispanics in our study were much less likely to consume significant amounts of alcohol, which may have influenced their iron stores. On the other hand, some dietary factors have an inhibitory effect on iron bioavailability. It has been shown that calcium given in the form of cheese, milk, and calcium chloride reduces iron absorption (47,48). Calcium can interfere with absorption of both heme and nonheme iron (47,49), although the negative influence of calcium can be less significant in mixed diets (48,50). We found that dietary calcium intake and milk intake had a negative association with serum ferritin, supporting the potential practical effect of habitual dietary calcium on iron bioavailability and iron status. The higher milk intake noted in Hispanics compared with non-Hispanic whites may contribute to lower body iron stores in this group.
This study examined dietary intake and iron status in a representative group of Hispanic older adults residing in Massachusetts and in a non-Hispanic white neighborhood comparison group. Unlike other regions of the country where Mexican Americans are more prevalent, Puerto Ricans and Dominicans make up the majority of the Hispanic population in the Northeast. The differing cultural backgrounds and dietary patterns of these Hispanic groups may lead to group-specific effects on iron status. Therefore, these results may not be generalized to Mexican Americans or other Hispanic groups.
Our results demonstrate that Hispanic older adults in Massachusetts, particularly Hispanic women, are more likely than their non-Hispanic white neighbors to suffer from IDA. The cause of the relatively high rates of IDA in this Hispanic elderly population is uncertain. However, differences in dietary patterns are evident and may play an important role in the determination of iron status and the increased risk for anemia in these Hispanic older adults. Such dietary patterns could be modified to help alleviate ethnic differences in nutritional status.
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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6 Abbreviations used: CRP, C-reactive protein; IDA, iron deficiency anemia; MCV, mean cell volume; WBC, white blood cell count. ![]()
Manuscript received 6 September 2006. Initial review completed 26 September 2006. Revision accepted 26 November 2006.
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