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3 Environmental Health Department, Harvard School of Public Health, Boston, MA; 4 Department of Nutritional Sciences, University of California, Davis, CA; and 5 Division of Nutritional Sciences, Cornell University, Ithaca, NY
* To whom correspondence should be addressed. E-mail: kkordas{at}hsph.harvard.edu.
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ABSTRACT |
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 TOP ABSTRACT IntroductionLITERATURE CITED |
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Introduction |
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TOPABSTRACTIntroductionLITERATURE CITED |
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Accumulating evidence suggests that the connections among nutritional status, nutrients, and environmental toxicants are not trivial, but the extent of these interactions has not been fully investigated. There are several ways in which nutrition and environmental chemicals are interconnected. This symposium focuses on heavy metals because they have been most thoroughly studied, but other substances may be equally harmful. For example, pesticides are designed to be poisonous. It is also worth noting that most individuals are not exposed to a single toxicant, and the impact of multiple exposures on human health is largely unknown. Because of the number of toxicants and the range of manifestations of malnutrition (across multiple nutrients and from under- to overnutrition), the relation between environmental exposures and nutritional status/nutrients is multifaceted and complex. In addition, essential metals can be toxic in their own right. The symposium on "Heavy Metal Exposure in Women and Children, the Role of Nutrients" considers the implications of nutrient-toxicant interactions for the health of women and children. The overall aim of both the symposium and the proceedings is to encourage nutritionists to consider the importance of environmental exposures to their study populations and their research questions. Furthermore, it is to encourage the involvement of nutritionists in the design of high-quality, rigorous studies of nutritional assessment and interventions in populations exposed to environmental chemicals. As a growing field, the intersection between nutritional science and toxicology would benefit from the expertise of nutritionists. This introductory article highlights a few examples of nutrient-toxicant interactions and serves as background for the more focused papers that follow.
We consider 3 main ways in which toxicants and nutrition are connected (Fig. 1), with the understanding that these connections are highly nuanced. We also recognize there may be other determinants of health and disease that are not depicted here but that may interact with toxicants, nutrients, or both. As to our specific model, first, food may be the vehicle for delivering toxicants and may increase an individual's exposure and toxicant body burden. Second, as a toxicant is absorbed by the human body, it may interact with an individual's nutritional status to affect the amount of toxicant that is retained and bioavailable to do harm. It is also possible that toxicants may affect nutrient absorption and stores. Third, once inside the body, nutrients and nutrient metabolism may also interact with the toxicant in affecting a specific health outcome. Other factors, such as gender and age, need to be considered in this model because they affect both nutritional status (child-feeding practices) and toxicant exposure (hand-to-mouth behavior is common in young children). The examples that follow illustrate the interactions between heavy metals and nutrients outlined in this model.
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Toxic chemicals can be introduced into food while it is being grown. Processing and storage may also increase hazardous chemical content of food. For example, in some Chinese rural communities, drying or smoking food over coal-burning stoves increases food arsenic content (5). Perhaps the best known example of food as a source of toxicant exposure is fish and seafood for methylmercury (6). Inorganic mercury is released into the air, settles in water, undergoes methylation, is accumulated in fatty tissues of fish, and is particularly high in fish at the top of the predatory food chain (7).
Two prospective cohort studies in the Faroe Islands and New Zealand have shown that prenatal and early postnatal exposure from seafood is associated with cognitive deficits in children, including attention, perceptual deficits, select language, and general cognitive deficits (8,9). This claim has been controversial, based on the evidence of limited adverse effects found in a fish-eating population in the Republic of the Seychelles (10,11).
The potential harm from prenatal methylmercury exposure has caused concern among pregnant women. Current recommendations in the United States call for reduced consumption of seafood during pregnancy (12). In low-income countries such advisories may not exist, and if they do, fish-consuming communities may be economically constrained from changing their diets. However, advisories have also created a dilemma because fish and seafood are a rich source of fatty acids that promote brain development and heart health (13). Current scientific discussion is focused on disentangling the benefits of fish consumption from the harmful effects of mercury (14). In these symposium proceedings, Myers, Davidson, and Strain describe the Seychelles cohort and suggest the potential protective role of fish nutrients, such as polyunsaturated fatty acids, on neurodevelopment of mercury-exposed children (15).
Nutritional deficiencies may influence the level of pollutant exposure and toxicity
Lead exposure occurs most frequently among disadvantaged populations and is associated with cognitive deficits in children at levels previously thought not to produce harm (16,17). Many lead-exposed populations are also at risk for nutritional deficiencies. Evidence exists for interactions between lead and micronutrients at the level of intestinal absorption, brain neurochemistry, and cognitive function. Iron and lead share a common intestinal transporter, the divalent metal transporter 1 (18), and it is thought that iron deficiency contributes to increased lead absorption (19–21).
There is some evidence that adult women (21) and children (22) who consume higher amounts of dietary calcium have lower blood lead concentrations (BPb). Placental transfer of lead was shown to be lower in women who consume diets rich in iron (23) and in those who have higher hemoglobin levels (24). Various nutritional interventions have attempted to reduce lead absorption in children and women. Although primary prevention of lead exposure is optimal, it may not be feasible when exposure is ubiquitous or when it involves sources not under the control of the caregiver or community. In such circumstances nutrient supplements may play a mitigating role. In children, several studies examined the efficacy of supplemental calcium (25,26), iron alone (27,28), and iron with zinc (29) in lowering BPb. Iron and calcium supplementation has had some positive impact, but additional trials are needed to identify groups most likely to benefit. Some authors have cautioned against relying on calcium as the sole treatment for lead toxicity (30).
In adults, nutritional interventions have also been scarce. During the symposium, Dr. Ettinger from the Harvard School of Public Health presented evidence on calcium supplementation as a means of reducing bone resorption and BPb in pregnant and lactating women as well as the impact of supplemental calcium on breast milk lead concentrations. This overview was based on a series of ongoing cohort and intervention studies conducted in Mexico City (31,32). The Mexican interventions constitute the bulk of existing data on the efficacy of calcium supplementation in reducing maternal lead burdens. Ettinger et al. (33) have recently published an article on this topic.
Cadmium exposure is associated most critically with renal tubular toxicity, but there is increasing evidence of effects on bone (decreased bone density, and increased bone turnover and fractures) even at low-level environmental exposures (34,35). Cadmium-related health effects are more common in women than men (36). Besides tobacco smoke, diet is the main source of environmental cadmium exposure. Shellfish, leafy vegetables, rice, cereals, and legumes may contain relatively high levels of cadmium (37,38). The mechanism of cadmium absorption is similar to that of iron, calcium, and zinc. There is evidence that low iron stores and intake are associated with higher body cadmium burdens (38). Cadmium and iron are both absorbed into small intestine by the divalent metal transporter 1 (39). Once inside enterocytes, cadmium (and lead) is likely shuffled into the bloodstream via calcium transporters (40) in addition to ferroportin (41). There is some speculation that the absorption of cadmium may increase at very early stages of iron deficiency, even before increased iron absorption is observed (40).
Nutrient deficiencies and toxicants affect similar outcomes
Excess arsenic exposure may occur from ground water, as in some regions of India and Bangladesh (42). Exposure from drinking water is also common in other areas, including Mexico, Argentina, and Vietnam, with an estimated 100 million people exposed at levels above 100 g/L (42,43), the WHO drinking water standard (44). Other sources of arsenic, such as coal-burning stoves and contaminated food, are also common. Arsenic is associated with increased likelihood of lung and bladder cancers as well as skin lesions, even at moderate exposures (45). It is also thought to be associated with diabetes mellitus and hypertension (45,46), particularly in populations with high exposures (47). In children, arsenic is negatively associated with IQ scores, memory, and attention (48–52). Fetal and infant death (53–56) and a modest drop in birth weight (57) have also been documented in exposed populations. An interaction between arsenic and nutrient status and metabolism (folate) on health outcomes has been proposed. In these proceedings, Vahter (58) describes the evidence for the association among nutrients, 1-carbon metabolism, and arsenic toxicity in Bangladeshi women.
Malnourished individuals, especially women of reproductive age and young children, may be more vulnerable to adverse health effects of chemical exposures. The very nature of children's growth and development creates windows of vulnerability to both nutritional deficiencies and toxicant exposures (59). A recent article suggests that neurodevelopmental disorders caused by chemical exposures constitute a modern "silent pandemic" (1). With a double burden of nutrient deficiencies and environmental exposures, a substantial portion of the world's children may never realize their right to optimal health and development.
Women of reproductive age are also vulnerable to nutritional deficiencies. This is especially true during pregnancy, when maternal and fetal growth create high nutrient demands. Environmental exposures in women of reproductive age are especially precarious because women may become sources of exposure to their fetuses and infants through placental exchange and breast milk. Finally, with a connection between toxicants and chronic diseases, environmental exposures may contribute to the development and course of diseases in adulthood, particularly neurodegenerative diseases (1), beyond the effects of suboptimal nutritional status. Wright and Baccarelli (60), in this symposium, propose that early life exposures to metals program later disease and adverse outcomes through epigenetic processes.
In conclusion, the fraction of disease attributable to environmental (i.e., low-level, nonoccupational) exposures may be small, but 3 considerations speak to the importance of toxicants in affecting health. First, even relatively small risk factors make a notable contribution to disease when a large population is exposed. Second, toxicants are present at all stages of development, potentially accumulating to cause a lifetime of ill health. Third, if chemical exposures interact with poor nutrition, the result may be high costs to health and well-being of resource-poor individuals and communities who are least able to cope with those costs. Better understanding of the interactions between nutrition and environmental exposures is needed to guide action from governments and individuals. Future nutrition studies need to consider exposures to environmental pollutants in their study populations and investigate the effects of nutritional interventions as an approach to preventing or reducing toxicity.
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FOOTNOTES |
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2 Author disclosures: K. Kordas, B. Lönnerdal, and R. J. Stoltzfus, no conflicts of interest.
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LITERATURE CITED |
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TOPABSTRACTIntroductionLITERATURE CITED |
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