Academic journal article Environmental Health Perspectives

Lead Exposure, B Vitamins, and Plasma Homocysteine in Men 55 Years of Age and Older: The VA Normative Aging Study

Academic journal article Environmental Health Perspectives

Lead Exposure, B Vitamins, and Plasma Homocysteine in Men 55 Years of Age and Older: The VA Normative Aging Study

Article excerpt


Elevated homocysteine is a risk factor shared by neurodegenerative conditions, such as cognitive decline (Haan et al. 2007; Tucker et al. 2005) and Alzheimer's disease (Seshadri et al. 2002), and cardiovascular diseases (CVDs), such as ischemic heart disease and stroke (Homocysteine Studies Collaboration 2002; Wald et al. 2002). Increasing numbers of older adults are at risk for these conditions because of the unprecedented growth in the population of older adults worldwide. Thus, understanding and intervening in the determinants of elevated homocysteine concentrations may lessen the public health burden of these conditions.

Accumulating epidemiologic and experimental research has demonstrated that exposure to lead (Pb) increases the risk of hypertension (Navas-Acien et al. 2007), and recent research has provided strong evidence that Pb exposure is a risk factor for ischemic heart disease (Jain et al. 2007) and overall cardiovascular morbidity and mortality (Navas-Acien et al. 2007). More limited evidence suggests that exposure to Pb may increase plasma homocysteine concentration. This is an important consideration for the many older adults who have sustained long-term exposures to high levels of Pb earlier in their lives from occupational sources, Pb-based paint, and, especially, widespread combustion of leaded gasoline. Although regulatory actions have dramatically reduced these exposures over the last two decades, past exposures cannot be undone. Moreover, as bone turnover increases with age, Pb that has accrued in bone over decades may reenter the circulation, resulting in reexposure (Hu et al. 2007).

Schafer et al. (2005) proposed that Pb may increase homocysteine concentration by reacting with sulfhydryl groups on several proteins in the homocysteine-processing one-carbon metabolism cycle (Figure 1). Furthermore, in an in vitro study, methionine, an amino acid synthesized from the metabolism of homocysteine (in which folate and vitamin [B.sub.12] are cofactors) reduced oxidative stress and related physiological damage in Pb-exposed neuroblastoma cells (Chen et al. 2011). Previous epidemiologic studies have reported higher blood Pb concentration--an indicator of recent exposure to Pb (half-life of Pb in blood is approximately 30 days) (Hu et al. 1998)--in association with higher plasma homocysteine (Chia et al. 2007; Lee et al. 2012; Schafer et al. 2005; Yakub and Iqbal 2010). Little is known, however, about the potential influence of past and cumulative Pb exposures on homocysteine and changes in homocysteine over time. Further, to our knowledge, there have not been any longitudinal studies of the potential influence of the methyl donors--folate and B vitamins--on the association between Pb and plasma homocysteine. If diet can modify the association between Pb exposure and homocysteine, as suggested by findings from an analysis of cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES) (Lee et al. 2012), this could be a critical means for reducing deleterious effects of Pb exposure, even after exogenous exposure has ended.

Therefore, using an established longitudinal study of older men, we evaluated the association between Pb exposure and circulating levels of homocysteine, and the degree to which this association is modified by estimated intakes of methyl-donor nutrients/ cofactors (i.e., folic acid, vitamin [B.sub.12], and vitamin [B.sub.6]). We estimated the association between recent exposure to Pb, measured by blood Pb concentration, and concurrent homocysteine concentration. We compared associations of recent versus cumulative Pb exposures with homocysteine concentration using concentrations of Pb measured in blood and bone, respectively. Finally, we tested whether associations between Pb exposure and homocysteine were increased among participants whose diets were low in methyl-donor nutrients compared with other men.

Materials and Methods

Study population. …

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