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Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan
Address reprint requests to: Won O. Song, PhD, MPH, RD, Professor and Associate Dean, Dept. of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224. E-mail: Song{at}msu.edu
| ABSTRACT |
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Methods: Subjects (n = 4,394) were women (2049 years old) included in the most recent complete National Health and Nutritional Survey (NHANES III). Certain sociodemographic, lifestyle and nutritional determinants for BLL were identified.
Results: The BLL of reproductive age women was 1.78 µg/dL geometric mean, The BLL was inversely associated with poverty income ratio and education level, hematocrit, intake of thiamine, and serum levels of folate, and positively associated with ethnicity (Black, Hispanic), living in urban areas or the Northeast region, age, alcohol consumption, cigarette smoking, serum protoporphyrin, and intake of pyridoxine, iron, and folate. Subjects in the lowest decile for serum ascorbic acid had significantly higher BLLs than those in the 2nd through 8th deciles.
Conclusion: Infants born to women who smoke, drink and maintain poor nutritional status for selected nutrients are at a greater risk of lead toxicity than those born to other women. Nutritional manipulation of thiamine, ascorbic acid and folate may impact BLL in women.
Key words: lead, children, women, nutrition, smoking, alcohol, vitamin
Abbreviations: NHANES III = Third National Health and Nutrition Examination Survey BLL = blood lead level PIR = poverty income ratio ANCOVA = analyses of covariance DRIs = dietary reference intakes NCHS = National Center for Health Statistics CI = confidence interval
| INTRODUCTION |
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10.0 µg/dL had levels of 1014 µg/dL; 21.3% had levels of 1519 µg/dL; 9.2% had levels of 2024 µg/dL; 8.6% had levels of 2544 µg/dL; 1% had levels of 4569 µg/dL; and 0.2% had levels
70 µg/dL [5]. One of the important sources of lead exposure for the fetus and infant is maternal blood. Lead in the maternal blood readily crosses the placenta and mammary glands. The level of lead in umbilical cord blood and breast milk is closely associated with that in maternal blood [68]. Breast milk lead level is also dependent on the maternal body burden of lead [8]. It was reported that 45%70% of lead in the blood of reproductive age women originates from long-term tissue stores [9]. During pregnancy and lactation, the BLL increases by 15%20% due to altered mineral metabolism [6,10,11]. Together, these data suggest that the blood and tissue levels of lead in reproductive age women determine the body burden of lead in their offspring. The FDA reports that reproductive age women in the U.S. are exposed to lead through food (43%), dust (31%), water (22%), and air (4%) [12]. Accordingly, efforts should be made to reduce the BLL of reproductive age women to minimize transfer of maternal blood lead into the fetus and nursing infant.
Several studies [1316] reported that BLLs of young children and their mothers are affected by sociodemographic and nutritional factors even after controlling for environmental exposure. A body of knowledge exists that certain vitamins and dietary components chelate with lead to reduce the bodys burden. BLLs have been reported in pregnant and lactating women [9,1719] and infants [20] in various regions. To our best knowledge, little is known on the cycling of blood lead through generations and means to reduce the bodys lead burden of child bearing age women.
The objectives of this study were 1) to estimate the BLL of reproductive age women in the U.S., 2) to identify demographic, lifestyle and nutritional determinants for the BLL of reproductive age women in the U.S., and 3) to estimate the odds ratios of modifiable (nutritional and lifestyle) factors for elevated BLLs of reproductive age women. The subjects were a nationally representative sample of women selected for the National Health and Nutrition Examination Survey (198894) (NHANES III).
| MATERIALS AND METHODS |
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Data from reproductive age women (2049 years) who participated in NHANES III (phases I and II; 198894) were examined (n = 5,425). Those who were pregnant (n = 287) or lactating (n = 206), had unreliable dietary recall data (n = 16) or missing blood lead values (n = 515), or were examined at home (n = 7) were excluded. Of the remaining eligible women (n = 4,394), 3,716 had complete data for all variables investigated in this study.
Details of the survey procedures, handling of samples and analytical procedures are described elsewhere [21,22]. Briefly, blood samples in the survey were collected by venipuncture. The BLL was determined by graphite furnace atomic absorption spectrophotometry. The limit of detection for blood lead was 1 µg/dL. Values below the lower detection limit were replaced with a value equal to the detection limit divided by the square root of two (0.7 µg/dL). The survey obtained food consumption measurements for 1 d (24-h recall) along with dietary, nutritional and health status measurements. The information of dietary intakes included total energy intake, total fat, thiamine, pyridoxine, vitamin E, ascorbic acid, folate, calcium, phosphorus and iron. Hematocrit, RBC protoporphyrin and serum concentrations of ascorbic acid and folate were determined using conventional methods.
Description of Variables
Socioeconomic variables examined in the study are shown in Table 1. Participants were divided into the following race/ethnic categories: White (non-Hispanic); Black, (non-Hispanic); Mexican American; or Other. Rural-urban classification was based on the USDA rural-urban codes. "Urban" indicated central or fringe counties of metro areas with 1 million people or more and "Rural" encompassed all other areas. Regions were defined by the U.S. Bureau of the Census as Northeast, Midwest, South, and West. "Poverty income ratio" was the ratio of median family income over poverty threshold based on age of the family reference person and calendar year interviewed. "Education level" described the highest grade/year of regular school ever attended or grade/year finished. In this study, cigarette smoking indicated smoking habits at the time of interview. "Live birth" meant number of children born alive to mother. Breastfeeding history was judged by the response to the question regarding whether they breastfed more than one of their children. Bottled water was defined as the water which was commercially purchased in a bottle. "Year house built" included three categories: before 1946, 194673, and 1974 to present. Mobile homes were included in the third category.
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First, the association of BLL (log10) with each independent, continuous variable (alcohol consumption [g/day]; smoking [number of cigarettes/day]; number of live births; and all variables for nutritional status) was determined by the polynomial regression model using SAS. The final regression model included sociodemographic variables (race/ethnicity, age, degree of urbanization, region, poverty income ratio [PIR]); survey phase; alcohol consumption; number of cigarettes smoked per day; breastfeeding history; year house was built; daily intake of total fat, thiamine, pyridoxine, folate, calcium and iron; serum concentration of ascorbic acid and folate; hematocrit; and RBC protoporphyrin. The polynomial regression model up to the second order included the terms of PIR; education level; alcohol consumption; number of cigarettes smoked per day; intake of thiamine, calcium and iron; serum folate; and hematocrit.
Next, multiple polynomial regression analyses were performed (using WesVarPC) to analyze the relationship between BLL and the independent predictors. All independent variables (including the second order term of each continuous variable) were simultaneously pooled into the model to eliminate possible confounding effects. For this analysis, Fays replication method was used with a backward elimination model with p
0.1 as an elimination criterion. Subcategories with small sample sizes (i.e. "other" ethnic group) were not included in the multiple polynomial regression model as recommended by the Analytic and Reporting Guidelines of National Center for Health Statistics (NCHS)/CDC [22].
Finally, a logistic regression analysis was performed to determine the extent of association between BLL, and modifiable (lifestyle and nutritional) factors in women. The odds ratios for each significant modifiable factor were calculated to predict the BLLs at the highest versus the lowest deciles. Statistical analyses were conducted utilizing WesvarPC, taking sample weights and the survey design into account. Alcohol consumption and cigarette smoking were treated as dichotomous variables. Thiamine intake and serum ascorbic acid concentration were treated as continuous variables. The effect of confounding variables was controlled for by a method similar to the multiple polynomial regression analysis.
The relationship between BLL and deciles of thiamine intake and serum ascorbic acid and folate concentration were analyzed using analyses of covariance (ANCOVA). Effects of all confounding variables (including second order terms of continuous variables) were controlled for.
| RESULTS |
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2.5 µg/dL and
5 µg/dL, respectively and less than 1.0% of the women had a BLL
10 µg/dL.
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| DISCUSSION |
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The geometric mean BLL of reproductive age women in the U.S. was 1.78 µg/dL, and was higher in phase I than in phase II. The decrease in geometric mean BLL from phase I to II may have been due to reduced environmental exposure to lead, as use of lead in paint and gasoline was phased-out during the 1980s. Although the mean blood level of lead was below the level of concern for pregnant women and young children (10 µg/dL), four out of every thousand women had BLLs above this level. Recent studies on the blood lead levels in the NHANES III survey reported that at blood lead levels below the CDC level of concern (10 µg/dL), delayed puberty and sexual maturation were observed in U.S. girls [24,25], and that blood lead levels, even those below 10 µg/dL, were inversely associated with childrens IQ scores at 35 y and associated declines in IQ were greater at these levels than at higher levels [26].
All sociodemographic variables examined in this study were significant determinants for BLL. Reproductive age women who were Black or Hispanic, between 4049 years of age, were poor or had little education, or lived in urban areas or the Northeast region of the U.S. were most likely to have the highest BLLs. The direction and magnitude of these associations were consistent with a previous study conducted in men and women (2049 years of age) who participated in phase I of NHANES III [27].
Lifestyle variables such as alcohol consumption and cigarette smoking were positively associated with BLL, even after the differences in sociodemographic variables were controlled for. Other researchers have reported similar findings [2831]. Those who drank alcohol or smoked cigarettes were 5.6 or 4.5 times more likely to be in the highest decile than the lowest decile of BLL, respectively. Similar odds ratios for these variables have been found in women who live in southern Germany [29]. As hypothesized by Hense and colleagues [29], the effect of alcohol may be due to increased gastrointestinal lead absorption or lead contamination of foil capsules on wine bottles. Others have shown that smokers can inhale 15 g of lead by smoking 20 cigarettes [32]. Altogether, these studies support the public health efforts against alcohol and cigarette smoking in US women and children.
In agreement with results of others, we found that living in houses built before 1946 (when interior paints were as much as 50% lead by dry weight) was positively associated with BLL [33,34].
Researched on the underreporting of energy intake and its effect on the intake of other nutrients were carried out with the NHANES survey based on 1 d of intake estimated with use of 24-h recalls [35]. About 28% of the women were classified as under-reporters and underreporting of energy intake was highest in women and persons who were older, overweight, or trying to lose weight [35]. Therefore the fact that the daily intake of calories was much less than the DRI might be partly attributed to the underreporting.
Our regression model explained 29% of the variance of the BLL of reproductive age women in the U.S. In the multivariate regression analysis for the association of blood lead levels among a general population in Germany [29], the total percentage of variation explained by age, haematocrit, place of residence, BMI, cigarettes smoked, and alcohol consumption was 12% for men and 24% for women. On the other hand, in another study on the association of blood lead levels among 172 urban children, the percent of variation explained by environmental lead exposures, demographic characteristics and childrens behaviors was 44% for black children and 32% for white children [36]. Therefore, the percent of variation explained in the multivariate regression analysis depends on the subjects characteristics and variables included.
Although results of the multiple polynomial regression analysis suggested that ascorbic acid intake or serum ascorbic acid concentration was not related to BLL, further analyses indicated that subjects with very low serum ascorbic acid concentrations were more likely to have high BLLs than those with intermediate serum ascorbic acid levels. Houston and Johnson [37] also found that BLLs of NHANES III participants (aged 690) were inversely associated with serum (but not dietary) concentrations of ascorbic acid. Conversely, Dawson and colleagues [38] found that ingestion of ascorbic acid supplements (1000 mg/day) was associated with reductions in BLLs of men smokers. Altogether, these results suggest that further research into the relationship between dietary and serum levels of ascorbic acid, and their involvement in regulation of BLL in humans should be performed.
We found that intake of thiamine had a strong, inverse, and curvilinear association with BLL (Fig. 1). Those in the lowest decile of thiamine intake had the highest BLL. In addition, the odds of having a high BLL were greater for those with lower thiamine intake. Thiamine has been reported to inhibit the lead uptake in Chinese hamster peritoneal cells, and to reduce lead toxicity [39]. Flora and colleagues [40] identified thiamine and pyridoxine as inhibitors of lead intoxication. Thiamine enhanced the efficacy of chelating agents in mobilizing tissue lead and induced its excretion in lead-exposed animals [41]. The thiol group of thiamine may complex with lead by conformational transformation in vivo resulting into thiazole open-ring conformation [42,43]. Furthermore, rats injected subcutaneously with lead acetate increased lead excretion in feces via bile when thiamine was given [44]. In addition to the therapeutic effects against lead toxicity in animals [3941], results from a cross-sectional human study showed that the BLL of men occupationally exposed to lead was negatively correlated with the daily dietary intake of fiber, iron and thiamine [45]. Our observational study results, along with animal studies, support the preventive effect of thiamine intake.
The present study analyzed the diet datasets of NHANES III collected by a 24-h dietary recall between 19981994. We acknowledge one weakness in the study is the reliability of the dietary measures. The nutrient intakes were based on a single days intake, done by recall rather than direct measurement. In addition, there was no information on the subjects dietary patterns after the baseline measurement.
Our findings of a positive relationship between folate intake and BLL and an inverse relationship between serum folate and BLL are somewhat puzzling. This suggests that folate in blood may enhance lead excretion, while dietary folate in the GI system may facilitate lead absorption. Tandon and colleagues [46] reported that the supplementation of folic acid through gastric gavage enhanced the urinary excretion of lead, mobilized tissue lead and restored lead induced biological alteration in lead intoxicated rats. We have to notice that, however, the folate intake of subjects in our study was only 58% of DRI, which might induce a different metabolism in vivo.
In our study, we found a positive association between blood lead and intake of iron (when curvilinear data were square transformed) or pyridoxine. In contrast, smaller studies involving urban preschool children (n = 299), pregnant women (n = 831), and middle-aged and older men (n = 747), have shown negative associations between blood lead and dietary iron intake [15,28,47]. The results on pyridoxine also show discordance with a study by Fischer and colleagues [39] which demonstrated that the B vitamins, pyridoxine and thiamine had a protective effect against lead uptake and toxicity in mammalian cells. Tandon and colleagues [48] reported that lead intoxication could be prevented by the application of vitamin B complex and different parameters of lead poisoning were aggravated by vitamin B deficiency. The authors also treated lead poisoned rats with vitamin B, alone and in combination with CaNa2-EDTA, and found that pyridoxine as well as folic acid might be factors responsible for the favorable effects [46]. However, there is no human research, and the metabolic interactions between pyridoxine and BLLs cannot be explained with the existing body of knowledge.
As expected, we found a strong positive association between erythrocyte protoporphyrin and BLL. It is well recognized that elevated erythrocyte protoporphyrin is a marker for lead exposure. Our finding of a weak inverse association between hematocrit and BLL also was somewhat expected given that lead inhibits heme synthesis and shortens the life span of erythrocytes [49]. Low hematocrits have been found in children and adults who have been exposed to lead [50,51].
In this study, we did not find a relationship between BLL and dietary fat, calcium or phosphorus. In contrast, Lucas and colleagues [14] found that total fat intake enhanced the absorption of lead in preschool children. The lack of an inverse effect of calcium intake on BLL also is inconsistent with findings of previous smaller-scale studies [7,18,28,47]. Our observation can partly be explained by the lower calcium intake by our study population (718.6 ± 12.3 mg/day) than those in other studies. Although the effect of vitamin D on blood lead was not measured in our study, others have shown that calcium has no effect on blood lead if vitamin D is controlled for [47].
This cross-sectional study may be limited to detecting delayed response to repeated exposure.
| CONCLUSION |
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| ACKNOWLEDGMENTS |
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Received October 23, 2003. Accepted March 26, 2004.
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