Margherita Bergomi

Adverse health effects of selenium in humans

Epidemiologic studies and case reports have shown that chronic exposure to selenium compounds is associated with several adverse health effects in humans. An early toxic effect of selenium is on endocrine function, particularly on the synthesis of thyroid hormones following dietary exposure of around 300 micrograms Se/d, and on the metabolism of growth hormone and insulin-like growth factor-1. Other adverse effects of selenium exposure can be the impairment of natural killer cells activity and at higher levels, hepatotoxicity and gastrointestinal disturbances. Dermatologic effects, such as nail and hair loss and dermatitis, occur after exposure to high levels of environmental selenium. Assessing the toxicity and morbidity after long-term exposure to environmental selenium is difficult: neurotoxicity, particularly the degeneration of motor neurons leading to increased risk of amyotrophic lateral sclerosis, might occur after chronic exposure to both organic and inorganic selenium compounds. The results of laboratory investigations and cohort studies suggest that selenium species exhibit a bivalent effect in cancer, either increasing or decreasing risk. Current environmental selenium exposure limits appear to be inadequate for averting adverse health effects.

Risk of Chronic Low-Dose Selenium Overexposure in Humans: Insights From Epidemiology and Biochemistry

The latest developments of epidemiologic and biochemical research suggest that current upper limits of intake for dietary selenium and for overall selenium exposure may be inadequate to protect human health. In particular, recent experimental and observational prospective studies indicate a diabetogenic effect of selenium at unexpectedly low levels of intake. Experimental evidence from laboratory studies and veterinary medicine appears to confirm previous epidemiologic observations that selenium overexposure is associated with an increased risk of amyotrophic lateral sclerosis, and a recent large trial indicated no beneficial effect in preventing prostate cancer. Moreover, the pro-oxidant properties of selenium species and the observation that the selenium-containing enzymes glutathione peroxidases are induced by oxidative stress imply that the increase in enzymatic activity induced by this metalloid may represent at least in part a compensatory response. Taken together, the data indicate that the upper safe limit of organic and inorganic selenium intake in humans may be lower than has been thought and that low-dose chronic overexposure to selenium may be considerably more widespread than supposed.

Relationship between lead exposure indicators and neuropsychological performance in children.

This study surveyed 237 schoolchildren in a lead‐polluted industrial area in northern Italy to assess the relationship between various biological indicators (lead in blood, hair and teeth, and delta‐aminolevulinic dehydratase [ALA‐D] activity) and some neuropsychological functions, assessed by a battery of five psychometric tests. The geometric means of lead measured in blood, hair and teeth were 10·99μg/dl, 6·79μg/g and 6·05/·g/g, respectively. Mean ALA‐D activity was 51mU/ml RBC. By analysis of covariance, after regressing out the variance accountable to confounding variables (age, sex, occupation/education of parents), Total and Verbal WISC‐R IQ and Toulouse Pieron test results were significantly affected by the levels of lead in teeth. ALA‐D values also appeared to be related to WISC‐R IQ results (Total, Verbal and Performance).

The epidemiology of selenium and human cancer.

Abstract The relation between selenium and cancer has been one of the most hotly debated topics in human health over the last decades. Early observational studies reported an inverse relation between selenium exposure and cancer risk. Subsequently, randomized controlled trials showed that selenium supplementation does not reduce the risk of cancer and may even increase it for some types, including advanced prostate cancer and skin cancer. An increased risk of diabetes has also been reported. These findings have been consistent in the most methodologically sound trials, suggesting that the early observational studies were misleading. Other studies have investigated selenium compounds as adjuvant therapy for cancer. Though there is currently insufficient evidence regarding the utility and safety of selenium compounds for such treatments, this issue is worthy of further investigation. The study of selenium and cancer is complicated by the existence of a diverse array of organic and inorganic selenium compounds, each with distinct biological properties, and this must be taken into consideration in the interpretation of both observational and experimental human studies.

Zinc and Copper Status and Blood Pressure

In order to elucidate the relationships between Zn and Cu and blood pressure, the present case-control study was carried out. Zn and Cu status was evaluated in 60 subjects, pharmacologically untreated, affected by mild stable hypertension and in 60 normotensives matched for sex, age and smoking habits. Different markers of Zn and Cu status, including serum, erythrocyte and urine levels of the two trace elements and activities of some Zn- or Cu-dependent enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase and lysyl oxidase) were evaluated. No significant difference between hypertensives and normotensives was observed in the mean levels of Zn and Cu as well as in Zn- or Cu-dependent enzymes, though higher levels of serum copper were associated with increased risk of hypertension. Interesting relationships between the biological parameters investigated were observed in the hypertensive subjects. Inverse correlations between blood pressures and serum Zn were observed. Furthermore, blood pressure was inversely related to lysyl oxidase activity. These findings give further support to the hypothesis that an imbalance of Zn and Cu bioavailability may be associated to hypertensive condition.

Biochemical and haemodynamic indicators of stress in truck drivers.

In order to investigate the extent of stress reaction during driving, this study was carried out on truck drivers engaged in long distance work. For each driver, epinephrine, norepinephrine, and cortisol were measured in urine, and dynamic ECG and blood pressure were monitored. The excretion rates of catecholamines showed great individual differences in the size of variations related to driving conditions. Epinephrine excretion rates were particularly high when weather and traffic conditions were more stressful. A relationship was found between epinephrine urinary levels and state-anxiety scores. Urinary excretion of norepinephrine was generally increased at the end of the working day and while driving in fog. The pattern of cortisol was not affected by the stress related to driving. The highest mean heart rates were monitored during difficult traffic and bad weather conditions.

Zinc, copper, and zinc- or copper-dependent enzymes in human hypertension

Imbalance of zinc and copper status has been hypothesized in human hypertension. A case-control study was carried out to elucidate the possible relationship between zinc and copper status and essential hypertension. Thirty-one subjects affected by mild stable hypertension, pharmacologically untreated, were investigated together with 31 normotensive controls individually matched for sex, age, and smoking habits. Zinc and copper in serum and urine were measured, and serum activities of alkaline phosphatase (AP), lactic dehydrogenase (LDH), copper-zinc superoxide dismutase (Cu−Zn SOD), lysyl oxidase (LOX), and monoamine oxidase (MAO) were evaluated. No significant difference in serum and urine zinc and copper content as far as in serum activity of zinc (AP and LDH) or copper (Cu−Zn SOD, LOX, and MAO)-dependent enzymes was found between hypertensives and normotensives. Positive relationships were found in normotensives between serum and urine levels of zinc (r=0.577;p=0.001) and copper (r=0.394;p=0.028), and between serum copper and Cu−Zn SOD (r=0.534;p=0.002). In normotensives, diastolic blood pressure and serum zinc were positively related (r=0.370;p=0.041). In hypertensives, inverse correlations were observed between diastolic blood pressure and AP (r=−0.498;p=0.004) and Cu−Zn SOD (r=−0.452;p=0.011), and between systolic blood pressure and LOX (r=−0.385;p=0.033). Diastolic blood pressure was related to LDH inversely in hypertensives (r=−0.357;p=0.049) and positively in normotensives (r=0.457;p=0.010). In normotensives, diastolic blood pressure was inversely related with MAO (r=−0.360;p=0.046). These findings support the hypothesis that an imbalance of zinc and copper status might be involved in human hypertension.

Mortality in a population with long-term exposure to inorganic selenium via drinking water

We analyzed the 1986-1997 mortality in a cohort of 2065 residents of an Italian municipality which had been exposed to drinking water with a high content of inorganic selenium over a long period of time, and compared it with mortality in the remainder of the municipal population. Mortality from malignant neoplasms increased [standardized mortality ratio (SMR) 1.17, 95% confidence interval (CI) 0.96-1.42], mainly due to an excess mortality from melanoma and colorectal cancer in both sexes, kidney cancer in men, and lymphoid malignancies in women. Overall cardiovascular mortality changed little (SMR 1.05, 95% CI 0.89-1.23), despite the higher cerebrovascular mortality (SMR 1.43, 95% CI 1.03-1.93). Coronary disease mortality slightly decreased (SMR 0.87, 95% CI 0.63-1.16), due to a low mortality among women. We also noted an excess mortality from Parkinsons disease in men and from motor neuron disease in women. Evaluation of these findings is, however, hampered by the lack of information about potential lifestyle confounders, the fact that the exposure could only be characterized by a simple dichotomization, and the inconsistencies of most estimates between the two sexes.

Risk of birth defects in a population exposed to environmental lead pollution.

To investigate the relation between environmental lead and risk of birth defects in humans, we examined the prevalence at birth of congenital anomalies in an industrial area of northern Italy heavily polluted with lead. Through a population-based registry of birth defects, we identified anomalies diagnosed during three consecutive periods characterized by decreasing environmental lead exposure, 1982-1986, 1987-1990 and 1991-1995. In the lead-polluted area, we observed an excess risk of cardiovascular defects which decreased from 2.59 [95% confidence interval (CI) 1.68-3.82] in the first period to 1.18 (95% CI 0.62-2.06) and 0.97 (95% CI 0.57-1.54) in the subsequent periods. We also found an excess risk of oral clefts and musculoskeletal anomalies, with decreasing trends over time. We could not identify homogeneous patterns of temporal variation for other congenital anomalies, neither did we detect cases of neural tube defects. These results appear to support an association between severe parental lead exposure and specific birth defects.

Adverse pregnancy outcomes in a population exposed to the emissions of a municipal waste incinerator

Some contaminants emitted by municipal waste incinerators are believed to adversely affect reproductive health in the exposed populations; yet only limited and conflicting epidemiologic evidence on this issue has been provided so far. In this study we analyzed rates of spontaneous abortion and prevalence at birth of congenital anomalies in women residing or working near the municipal solid waste incinerator of Modena, northern Italy, during the 2003--2006 period and who experienced higher levels of exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans, compared to the remaining municipal population. In women residing in two areas close to the incinerator plant with increasing exposure to dioxins, we did not detect an excess risk of miscarriage (relative risk [RR] 1.00, 95% confidence interval [CI] 0.65-1.48) and of birth defects (RR 0.64, 95% CI 0.20-1.55), nor did any indication of dose-response relation emerge. Among female workers employed in the factories located in the exposed areas, we did not observe a higher risk of spontaneous abortion (RR 1.04, 95% CI 0.38-2.30); however, an increase in prevalence of birth defects was noted (RR 2.26), although this risk estimate was statistically very unstable (95% CI 0.57-6.14). Overall, the study results provide little evidence of an excess risk of adverse pregnancy outcomes in women exposed to emissions from a modern municipal solid waste incinerator.