Expression of concern.

The Editor in Chief would like to alert readers to the following three articles published in Biological Trace Element Research.

Lithium and other elements in scalp hair of residents of Tokyo Prefecture as investigational predictors of suicide risk.

The high suicide rates in Japan and several reports of inverse associations of suicide rates with the levels of lithium (Li) in drinking water prompted determinations of Li along with other elements in samples of scalp hair of 100 male and 100 female residents of Tokyo Prefecture. In more than half of the samples of both genders, Li levels were below the instrumental detection limit or below or the lower limit of the laboratory reference ranges. Among other elements, the concentrations namely of cobalt were also frequently below the laboratory reference range, suggesting that low circulating levels of vitamin B(12) were common in this study population. As vitamin B(12) deficiency is associated with depression and other psychiatric conditions, and there is evidence of interactions between Li and vitamin B(12), Li deficiency as well as suboptimal vitamin B(12) status must be considered as potential suicide risk factors. In view of its established positive effects on mood and brain function, an adequate supply of selenium (Se) is important as well. Although the analytical results suggested that the Se status of the subjects was generally adequate, as seafood was a major dietary source of Se, much of it was actually sequestered by mercury and only a fraction was bio-available. In addition, the hair samples were found to contain not insignificant levels of As, Cd, Ni, and Pb, arising from the adventitious presence of these elements in foods and the environment. As these elements also interact with Se in vivo and are known to adversely affect mood and behavior, in investigational studies, subjects at risk need to be evaluated also with respect to these elements.

Selenium and Alzheimer's disease: a systematic review.

Preventing Alzheimer's disease (AD) would require knowledge about its etiology to a degree of detail not yet available. The major hurdle in understanding the disease lies in teasing out the various causes and their complex interactions. Since considerable data have accrued showing that the essential trace element selenium (Se) might play different roles in the progression of AD, we conducted a systematic review of the literature regarding Se and AD. We identified 9 placebo-controlled studies (6 were multiple supplement trials including Se, 1 was ongoing), 4 prospective, 4 cross-sectional, 15 case control, 24 autopsy studies, as well studies in animals and cells. There is an absence of consistent clinical evidence as to whether supplementation of Se is beneficial in the treatment of AD and how Se levels are altered in brain, cerebrospinal fluid, and blood of patients with AD. Some longitudinal and cross-sectional studies, however, show an association of Se status and cognitive function. Findings from molecular biology reveal a decisive role of Se in the pathogenesis of AD. In summary, the current state of knowledge provides no evidence for a role of Se in the treatment of AD, but allows speculation on a potential preventive relevance. Large trials of long-term duration could provide definitive answers.

Lead exposure: a contributing cause of the current breast cancer epidemic in Nigerian women.

Breast cancer incidence in Nigerian women has significantly increased during the past three decades in parallel with the rapid industrialization of that country. This suggested that the associated widespread contamination of the soil and of the water supplies by lead (Pb) and other industrial metals was a major contributing cause. Because of its many domestic, industrial, and automotive uses, Pb is of particular concern as it has been shown to promote the development of mammary tumors in murine mammary tumor virus-infected female C3H mice at levels as low of 0.5 ppm Pb in the drinking water. Lead belongs to the group of selenium-antagonistic elements that interact with selenium (Se), abolishing its anti-carcinogenic effect. Lead on chronic, low-level exposure in addition also accelerates tumor growth rates. Higher levels of Pb were found in blood and head hair samples of newly diagnosed patients with breast cancer, all with infiltrating ductal carcinoma, the most common form of breast cancer in Nigeria, seen at Obafemi Awolowo University, than in cancer-free controls from the same area. Evidence for interactions between Pb and Se was obtained from blood, hair, and tumor biopsy tissue analyses. Furthermore, the Pb levels in hair samples of the patients were directly correlated with the volumes of their tumors, in accord with the tumor growth-promoting effects of Pb. Conversely, Se levels in hair and blood were inversely correlated with the tumor volumes, consistent with the anti-proliferative effects of Se. Several other elements, e.g., Cd, Hg, Cr, Sn, and As, were detected in the scalp hair of the patients and the controls, although at significantly lower levels than those of Pb. However, correlation calculations revealed them also to interact with Se, suggesting that only a fraction of the Se in organs and tissues is actually present in bioactive forms. In metal-exposed subjects, a state of latent Se deficiency may exist, resulting in depressed immune functions and increased cancer susceptibility. Evidence is presented to show that Pb and other metals also interact with iodine, another vitally important essential trace element believed to protect against breast cancer development. Public health programs aiming at lowering the breast cancer risk of Nigerian women thus will have to include effective measures to protect the population from exposures to Pb and other industrial metals that are presently contaminating the environment and the water supplies.

Selenium and cadmium levels and ratios in prostates, livers, and kidneys of nonsmokers and smokers.

Cadmium (Cd) from cigarette smoke, environmental, and nutritional sources accumulates in the human prostate where it interacts with selenium (Se) in a manner suggesting the formation of a 1:1 Cd-Se-protein complex. At low Cd exposures and adequate Se status, this interaction may be beneficial as it results in the detoxification of Cd. At higher exposures, Cd may weaken or abolish the anticarcinogenic effects of Se and increase prostate cancer risk. In some older men and especially in smokers, Cd levels in prostates reach levels in stoichiometric excess over Se, which may be the reason why heavy smokers are at higher risk of developing lethal forms of prostate cancer. In the liver and the kidneys, Cd accumulates as well, but in these organs, Cd is efficiently sequestered through metallothionein formation. In the prostate, this mode of detoxification is not available or less efficient, causing Cd to interact with Se and to increase prostate cancer risk.

Selenium in human and animal nutrition: resolved and unresolved issues. A partly historical treatise in commemoration of the fiftieth anniversary of the discovery of the biological essentiality of selenium, dedicated to the memory of Klaus Schwarz (1914-1978) on the occasion of the thirtieth anniversary of his death.

Selenium (Se) is an essential trace element unevenly distributed on the Earth's crust with low selenium regions predominating. To prevent selenium-deficiency diseases in livestock, additions of selenium to animal feed are required and were approved for all species, but the chemical form of the element to be added was not specified. Presently, sodium selenite is still widely employed, although it is not a natural nutritional form of selenium. Its use creates ecological problems and affects human selenium nutriture in as much as the meat, milk, and eggs from animals maintained on selenite contain less selenium than from animals receiving it as selenomethionine, the chief natural nutritional form of the element present in grain crops grown in selenium-adequate regions, or from high-selenium yeast added to feedstock. Human dietary selenium intakes are sub-optimal in many countries but are considered to be adequate if they reach the currently adopted Recommended Dietary Allowances (RDAs). Their upward revision will be required if the health benefits of selenium are to be fully utilized.

Selenium/cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and nonsmokers, and relevance to the cancer protective effects of selenium.

Selenium (Se) in a large-scale human supplementation trial has been shown to significantly reduce the incidence of prostate cancer in elderly men. Because Se is known to interact with cadmium (Cd), it has been suggested that its cancer protective action could be attributable in part to its interaction with Cd, a toxic and suspected carcinogenic element, which is found in many foods, in drinking water, and in the environment. Cadmium is considered a significant prostate cancer risk factor as it stimulates the growth of prostate epithelial cells and promotes their malignant transformation. Accordingly, prostate cancer risk is determined not only by Se status, but also the degree of Cd exposure. Determinations of Se and Cd in 129 prostates of deceased men aged 15-99 yr revealed Cd to accumulate in the prostate. Whereas the atomic Se/Cd ratios of the prostates of young men were invariably >1, indicating a stoichiometric excess of Se over Cd, they were found to decline with age, approaching the 1:1 ratio in elderly nonsmokers, a fact suggestive of the formation of a 1:1 Cd-Se complex. The associated physiological inactivation of Se could account for the increase of the prostate cancer risk with advancing age. The Se/Cd ratios dropped more steeply and consistently with age in smokers than in nonsmokers. In the prostates of some smokers, Se/Cd ratios even reached values <1, indicating a stoichiometric excess of Cd over Se. The excessive accumulation of Cd in the prostates of smokers along with sub-optimal Se intakes could explain why smokers develop more aggressive and lethal forms of prostate cancer than nonsmokers.

Lithium: occurrence, dietary intakes, nutritional essentiality.

Lithium is found in variable amounts in foods; primary food sources are grains and vegetables; in some areas, the drinking water also provides significant amounts of the element. Human dietary lithium intakes depend on location and the type of foods consumed and vary over a wide range. Traces of lithium were detected in human organs and fetal tissues already in the late 19th century, leading to early suggestions as to possible specific functions in the organism. However, it took another century until evidence for the essentiality of lithium became available. In studies conducted from the 1970s to the 1990s, rats and goats maintained on low-lithium rations were shown to exhibit higher mortalities as well as reproductive and behavioral abnormalities. In humans defined lithium deficiency diseases have not been characterized, but low lithium intakes from water supplies were associated with increased rates of suicides, homicides and the arrest rates for drug use and other crimes. Lithium appears to play an especially important role during the early fetal development as evidenced by the high lithium contents of the embryo during the early gestational period. The biochemical mechanisms of action of lithium appear to be multifactorial and are intercorrelated with the functions of several enzymes, hormones and vitamins, as well as with growth and transforming factors. The available experimental evidence now appears to be sufficient to accept lithium as essential; a provisional RDA for a 70 kg adult of 1,000 microg/day is suggested.