Human Health Effects of Low-Level Methylmercury Exposure
Human Health Effects of Low-Level Methylmercury Exposure
For literature searches for MeHg and cardiovascular outcomes, we used the key words "mercury" or "methylmercury," "cardiovascular" or "coronary," or "hypertension." References cited in articles were also identified. The studies reviewed are summarized in Table 1 and Table 3 and in Supplemental Material, Table S3 (http://dx.doi.org/10.1289/ehp.1104494).
Although the developing brain is considered the critical target organ of MeHg toxicity for children, the cardiovascular system may be most sensitive for adults. In the studies we reviewed, the cardiovascular outcomes included myocardial infarction, blood pressure, heart rate variability, and atherosclerosis. Among the studies that met our definition of a low-level exposure, the studies carried out in Finland were the first to assess the association between MeHg and cardiovascular disease (CVD) (e.g., Salonen et al. 1995). A > 2-fold risk of acute myocardial infarction and mortality from coronary heart disease and CVD was associated with elevated hair mercury (> 2 µg/g). Inclusion of fatty acids had no appreciable effect on the relative risk estimates. As recently reviewed by Roman et al. (2011), subsequent studies have corroborated a potential link between MeHg and acute myocardial infarction. Mercury was associated with accelerated progression of carotid atherosclerosis, as determined by intima-media thickness (Salonen et al. 2000). The association remained significant after adjusting for fatty acids and selenium. Rissanen et al. (2000) reported that fish oil–derived fatty acids reduced the risk of acute coronary events. In a later study of Finnish men, Virtanen et al. (2005) reported that increased mercury exposure was associated with increased risk of acute coronary events and cardiovascular mortality, with adjustment for selenium and fatty acids. These two studies (Rissanen et al. 2000; Virtanen et al. 2005) concluded that mercury may attenuate the protective effects of fish on cardiovascular health. A large multicenter study from Europe showed an increased risk of CVD associated with toenail mercury concentrations after controlling for DHA (docosahexaenoic acid) (Guallar et al. 2002), whereas no association was found in the U.S. Health Professionals Study, with adjustment for DHA plus eicosapentaenoic acid (Yoshizawa et al. 2002). In a nested case–control study combining the U.S. male health professionals and the female registered nurses cohorts (Nurses' Health Study), Mozaffarian et al. (2011) found no adverse effects of mercury exposure on coronary heart disease, stroke, or total CVD. Findings were similar in additional analyses adjusted for DHA, eicosapentaenoic acid, and selenium. In a Swedish nested case–control study with low exposure, Wennberg et al. (2011) found no association between the risk of myocardial infarction and mercury concentration in erythrocytes with adjustment for DHA plus eicosapentaenoic acid. Another nested case–control study reported an inverse association between myocardial infarction and erythrocyte mercury (Hallgren et al. 2001); however, that study did not meet our definition of low-level exposure.
Several studies have found an association between increased mercury and increased blood pressure in adults, although only two met our low-dose exposure definition: Valera et al. (2009) adjusted for fish nutrients (DHA, eicosapentaenoic acid, and selenium), whereas Vupputuri et al. (2005) controlled for fish intake. In cross-sectional population data from the U.S. National Health and Nutrition Examination Survey (NHANES), associations were seen only among individuals who did not consume fish (Vupputuri et al. 2005). Among children more heavily exposed than criteria used in our review, an association between prenatal mercury exposure and childhood blood pressure has been observed in some (Sorensen et al. 1999; Thurston et al. 2007) but not all (Grandjean et al. 2004) studies; however, information on nutrients and fish consumption was not available in these studies.
MeHg may induce oxidative stress, an early biological response that can produce cell damage in several organs or systems including the cardiovascular system (Grotto et al. 2009). Experimental models suggest that oxidative stress plays an important role in the toxicodynamics of mercury (Grotto et al. 2010). A few recent studies have examined associations between mercury exposure and oxidative stress or antioxidant defense in populations exposed through fish consumption, although the findings have been inconclusive (Bélanger et al. 2008; Grotto et al. 2010; Pinheiro et al. 2008). These studies, however, have reported mercury concentrations that exceeded our definition of low-level exposure. Except for Grotto et al. (2010), information on fish intake was not available.
Cardiovascular Outcomes
For literature searches for MeHg and cardiovascular outcomes, we used the key words "mercury" or "methylmercury," "cardiovascular" or "coronary," or "hypertension." References cited in articles were also identified. The studies reviewed are summarized in Table 1 and Table 3 and in Supplemental Material, Table S3 (http://dx.doi.org/10.1289/ehp.1104494).
Although the developing brain is considered the critical target organ of MeHg toxicity for children, the cardiovascular system may be most sensitive for adults. In the studies we reviewed, the cardiovascular outcomes included myocardial infarction, blood pressure, heart rate variability, and atherosclerosis. Among the studies that met our definition of a low-level exposure, the studies carried out in Finland were the first to assess the association between MeHg and cardiovascular disease (CVD) (e.g., Salonen et al. 1995). A > 2-fold risk of acute myocardial infarction and mortality from coronary heart disease and CVD was associated with elevated hair mercury (> 2 µg/g). Inclusion of fatty acids had no appreciable effect on the relative risk estimates. As recently reviewed by Roman et al. (2011), subsequent studies have corroborated a potential link between MeHg and acute myocardial infarction. Mercury was associated with accelerated progression of carotid atherosclerosis, as determined by intima-media thickness (Salonen et al. 2000). The association remained significant after adjusting for fatty acids and selenium. Rissanen et al. (2000) reported that fish oil–derived fatty acids reduced the risk of acute coronary events. In a later study of Finnish men, Virtanen et al. (2005) reported that increased mercury exposure was associated with increased risk of acute coronary events and cardiovascular mortality, with adjustment for selenium and fatty acids. These two studies (Rissanen et al. 2000; Virtanen et al. 2005) concluded that mercury may attenuate the protective effects of fish on cardiovascular health. A large multicenter study from Europe showed an increased risk of CVD associated with toenail mercury concentrations after controlling for DHA (docosahexaenoic acid) (Guallar et al. 2002), whereas no association was found in the U.S. Health Professionals Study, with adjustment for DHA plus eicosapentaenoic acid (Yoshizawa et al. 2002). In a nested case–control study combining the U.S. male health professionals and the female registered nurses cohorts (Nurses' Health Study), Mozaffarian et al. (2011) found no adverse effects of mercury exposure on coronary heart disease, stroke, or total CVD. Findings were similar in additional analyses adjusted for DHA, eicosapentaenoic acid, and selenium. In a Swedish nested case–control study with low exposure, Wennberg et al. (2011) found no association between the risk of myocardial infarction and mercury concentration in erythrocytes with adjustment for DHA plus eicosapentaenoic acid. Another nested case–control study reported an inverse association between myocardial infarction and erythrocyte mercury (Hallgren et al. 2001); however, that study did not meet our definition of low-level exposure.
Several studies have found an association between increased mercury and increased blood pressure in adults, although only two met our low-dose exposure definition: Valera et al. (2009) adjusted for fish nutrients (DHA, eicosapentaenoic acid, and selenium), whereas Vupputuri et al. (2005) controlled for fish intake. In cross-sectional population data from the U.S. National Health and Nutrition Examination Survey (NHANES), associations were seen only among individuals who did not consume fish (Vupputuri et al. 2005). Among children more heavily exposed than criteria used in our review, an association between prenatal mercury exposure and childhood blood pressure has been observed in some (Sorensen et al. 1999; Thurston et al. 2007) but not all (Grandjean et al. 2004) studies; however, information on nutrients and fish consumption was not available in these studies.
MeHg may induce oxidative stress, an early biological response that can produce cell damage in several organs or systems including the cardiovascular system (Grotto et al. 2009). Experimental models suggest that oxidative stress plays an important role in the toxicodynamics of mercury (Grotto et al. 2010). A few recent studies have examined associations between mercury exposure and oxidative stress or antioxidant defense in populations exposed through fish consumption, although the findings have been inconclusive (Bélanger et al. 2008; Grotto et al. 2010; Pinheiro et al. 2008). These studies, however, have reported mercury concentrations that exceeded our definition of low-level exposure. Except for Grotto et al. (2010), information on fish intake was not available.
