These results extend recently released estimates of toenail Se levels in American young adults including African Americans and Caucasians using data from the CARDIA Trace Element Study.(Xun et al., 2010b
) In this study, toenail Se levels were associated with gender, ethnicity, study center, smoking status and alcohol consumption. Men, African Americans, those in Birmingham, current smokers, and heavy drinkers were more likely to have low Se levels. In African American women, those who were relatively older were more likely to have low Se levels, while Se levels were lower in African American men with less education.
There is substantial evidence that Se measurement in toenails is an excellent indicator of long-term selenium intake (Hunter et al., 1990b
; Willett, 1987
) and has been used widely in clinical and epidemiological studies.(Guallar et al., 2002
; Yoshizawa et al., 2002
) Of note, this cohort included approximately equal percentages of African Americans (48.5%) and Caucasians, and men (45.3%) and women, which makes it unique. In contrast, other studies with available toenail data such as the Nurses' Health Study and the Health Professionals Follow-Up Study have only reported Se levels in small scale case-control studies (Michaud et al., 2005
; Yoshizawa et al., 2003
), and these studies do not include toenail Se data on both genders and/or on African Americans. Importantly, as Se levels may change over time, our findings will provide valuable information on Se status 20 years ago, which may serve as a baseline or a reference for future studies, and also allow for testing trends or changes in Se levels in relation to chronic disease development.
A few limitations of this study should be considered when interpreting the findings. First, toenail Se provides a long-term estimate of Se itself, but is not a real-time marker of Se status, as are glutathione peroxidase (GSH-Px) and selenoprotein P. However, toenail Se levels are highly correlated with Se levels in whole blood and other organs and with dietary intake, all of which are also highly correlated with functional markers such as selenoprotein P.(Hurst et al., 2010
) Second, CARDIA does not include a nationally representative sample, though sample selection was roughly balanced by gender and ethnicity, and every attempt was made to select a representative sample of young American adults from most of the selected metropolitan areas. Se status of CARDIA participants may be different from the general US population, and thus the generalizability of our findings may be limited.
This study showed that the median toenail Se level in CARDIA participants was 0.844 μg/g. This was slightly higher than the median of 0.82 μg/g in 181 healthy control subjects in a case-control sub-study based on the Health Professionals Follow-up Study.(Yoshizawa et al., 1998
) Our study also documented a wide range in levels, from a median of 0.691μg/g in the bottom quintile to 1.037μg/g in the top quintile. The difference in these two extreme quintiles is comparable to the range found in a sample of people living in the Boston area (0.74μg/g), a region with a relatively low soil Se concentration, and another sample of people living in South Dakota (1.17μg/g), an area with very high soil Se.(Morris et al., 1983
) The aforementioned studies all detected toenail Se levels with the same method in the same lab as our study; conversely, it is difficult to compare our results with Se levels reported in some other studies, such as NHANES, which were detected in different biological samples (i.e., serum) with different analytic methods. Further studies focusing on toenail Se levels in the general population are warranted.
In the present study, toenail Se levels varied geographically. Average toenail Se levels in these four cities were generally in accordance with regional distribution of Se in soil as indicated by the U. S. Geological Survey (Shacklette and Boerngen, 1984
), forage and grains (White and Zasoski, 1999
); this suggests that regional variations in toenail Se levels directly reflect changes in dietary Se intake by region, then variations in forage and grains, and ultimately, the concentration of Se in soil within the US. Geographic differences may also be explained by dietary factors that might limit food consumption from the national food distribution system.(Monsen, 2000
Although age has been reported to influence Se levels, our data fail to support any age-related pattern except in African American women, who had a net decrease of 0.01 μg/g in ln(Se) per 5 year increment in age. Our finding for this subgroup might be explained by the general fact that Se intake and absorption may decrease, and excretion increase, with increasing age.(Lloyd et al., 1983
) The gender heterogeneity observed for Se levels may be due to differences in Se intake and bioavailability between males and females. Although men generally consume more food than women and have higher Se intake as a result, their Se levels did not reflect greater exposure in this study sample; consistent with results from previous studies(Swanson et al., 1990
), this study documented higher Se levels among women than men. No evidence has been found to support that men absorb less Se than women. Higher Se levels in women relative to men might be partially explained by higher estrogen levels. A cross-sectional study of three generations (daughters, mothers and grandmothers) with mean age of 24, 50 and 75, respectively, reported that serum Se concentrations of mothers (135 ng/mL) were significantly greater than those of daughters (116ng/mL) and grandmothers (110 ng/mL), which indicated that Se status fluctuated during the female life cycle and was related to estrogen status.(Smith et al., 2000
Our data indicate an obvious racial difference in density of toenail Se within each gender subgroup. Racial variation in Se status has been reported previously.(Glauser et al., 1999
; Goodman et al., 2001
; Niskar et al., 2003
; Vogt et al., 2003
; Vogt et al., 2007
; Willett et al., 1983
) For example, the data from third National Health and Nutrition Examination Survey (NHANES) indicated that the Blacks had lower serum selenium concentrations relative to Whites.(Vogt et al., 2007
) However, most of these studies have been limited by the inclusion of relatively few African Americans. Although the mechanism for racial variation observed in this study is unclear, there are several potential explanations for our findings. First, Se intake was slightly higher among Caucasians than African Americans (Vogt et al., 2007
) and differential intake of Se-rich foods may play an important role in determining Se status. Second, genetic variation between ethnicities could affect the absorption, metabolism and excretion of Se and thus Se concentrations in the body.(Hu et al., 2001
; Rayman, 2005
) Third, although we adjusted for known potential confounders and included certain predictors in the model, we cannot rule out the possibility of unknown confounders explaining the variation observed.
In this study, smoking status remained an independent indicator of toenail Se levels across all ethnicity-gender subgroups. A European study documented that persons who currently smoked cigarettes had significantly lower toenail Se levels than ex-smokers and never smokers.(Kardinaal et al., 1997
) Similarly, toenail Se levels were found to be lower in smokers than non-smokers in other studies.(Ghadirian et al., 2000
; Krogh et al., 2003
; Swanson et al., 1990
) Although the dietary habits of smokers have not been adequately studied, there is published evidence that lower levels of Se can be attributed either to the nature of tobacco, which reduces Se absorption, or to smokers' reduced food intakes (Swanson et al., 1990
) or their selection of foods containing less Se.(Fehily et al., 1984
; Ghadirian et al., 2000
) Toenail Se levels were lower in African American men who consumed > 12ml/d of alcohol and in Caucasian men consuming >24 ml/d compared to non-drinkers. This finding is supported by other studies (Dhindsa et al., 1998
; Luty-Frackiewicz et al., 2002
), but potential mechanisms are unclear. Decreased Se intake among those consuming more alcohol and reduced hepatic storage resulting from alcohol consumption might be involved.(Dutta et al., 1983
In conclusion, using data from the CARDIA Trace Element Study, we observed that gender, ethnicity, study center, smoking status and alcohol consumption all influence toenail Se levels. Among these, alcohol consumption and smoking status are the most important indicators since they are two lifestyle habits for which we can promote some changes, e.g. cessation of smoking or control of alcohol use. Findings from this study might aid public health professionals in identifying people with relatively high or low Se levels, so that chronic disease prevention efforts can be directed toward these subgroups.