Selenium neurotoxicity in humans: Bridging laboratory and epidemiologic studies

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Published on Tuesday, 12 November 2013 16:52

Vinceti M, Mandrioli J, Borella P, Michalke B, Tsatsakis A, Finkelstein Y.

Toxicol Lett. 2014 Oct 15;230(2):295-303. PMID: 24269718

Abstract

Selenium is a metalloid of considerable interest in the human from both a toxicological and a nutritional perspective, with a very narrow safe range of intake. Acute selenium intoxication is followed by adverse effects on the nervous system with special clinical relevance, while the neurotoxicity of long-term overexposure is less characterized and recognized. We aimed to address this issue from a public health perspective, focusing on both laboratory studies and the few epidemiologic human studies available, with emphasis on their methodological strengths and limitations. The frequently overlooked differences in toxicity and biological activity of selenium compounds are also outlined. In addition to lethargy, dizziness, motor weakness and paresthesias, an excess risk of amyotrophic lateral sclerosis is the effect on the nervous system which has been more consistently associated with chronic low-level selenium overexposure, particularly to its inorganic compounds. Additional research efforts are needed to better elucidate the neurotoxic effects exerted by selenium overexposure.

Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

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Published on Wednesday, 30 October 2013 16:52

Vinceti M, Crespi CM, Malagoli C, Del Giovane C, Krogh V.

J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2013;31(4):305-41. PMID: 24171437

Abstract

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders.

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Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite

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Published on Monday, 30 September 2013 16:52

Vinceti M, Solovyev N, Mandrioli J, Crespi CM, Bonvicini F, Arcolin E, Georgoulopoulou E, Michalke B.
Neurotoxicology. 2013 Sep;38:25-32 PMID: 23732511

Abstract

Exposure to selenium, and particularly to its inorganic forms, has been hypothesized as a risk factor for amyotrophic lateral sclerosis (ALS), a fast progressing motor neuron disease with poorly understood etiology. However, no information is known about levels of inorganic and some organic selenium species in the central nervous system of ALS patients, and recent observations suggest that peripheral biomarkers of exposure are unable to predict these levels for several Se species including the inorganic forms. Using a hospital-referred case-control series and advanced selenium speciation methods, we compared the chemical species of selenium in cerebrospinal fluid from 38 ALS patients to those of 38 reference neurological patients matched on age and gender. We found that higher concentrations of inorganic selenium in the form of selenite and of human serum albumin-bound selenium were associated with increased ALS risk (relative risks 3.9 (95% confidence interval 1.2-11.0) and 1.7 (1.0-2.9) for 0.1μg/L increase). Conversely, lower concentrations of selenoprotein P-bound selenium were associated with increased risk (relative risk 0.2 for 1μg/L increase, 95% confidence interval 0.04-0.8). The associations were stronger among cases age 50 years or older, who are postulated to have lower rates of genetic disease origin. These results suggest that excess selenite and human serum albumin bound-selenium and low levels of selenoprotein P-bound selenium in the central nervous system, which may be related, may play a role in ALS etiology.

Serum Fatty acids and risk of cutaneous melanoma: a population-based case-control study

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Published on Friday, 30 August 2013 16:53

Vinceti M, Malagoli C, Iacuzio L, Crespi CM, Sieri S, Krogh V, Marmiroli S, Pellacani G, Venturelli E.
Dermatol Res Pract. 2013;2013:659394 PMID: 23431289

Abstract

Background. Some observational studies have suggested that excess dietary intake of polyunsaturated fatty acids such as linoleic acid increases cutaneous melanoma risk. We aimed at examining the association between serum fatty acids and melanoma risk by conducting a population-based case-control study in a northern Italy community. Methods. The percentage composition of 12 fatty acids was determined in 51 newly diagnosed melanoma patients and 51 age- and sex-matched population controls by extracting total lipids from serum samples using thin layer and gas chromatography. Conditional logistic regression was used to estimate the relative risk of melanoma associated with tertiles of percentage composition of each fatty acid as well as groupings including saturated, monounsaturated, and polyunsaturated fatty acids. Results. We found a slightly increased melanoma risk for stearic and arachidic acids proportion, with and without adjustment for potential confounders. For an n-3 polyunsaturated fatty acid, docosapentaenoic acid, we found a male-specific direct association with melanoma risk. No other associations emerged for the other saturated, monounsaturated, and polyunsaturated fatty acids, individually or grouped by type. Conclusions. These findings do not suggest a major role of fatty acids, including linoleic acid, on risk of cutaneous melanoma, though their evaluation is limited by the small sample size.

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Inquinamento da traffico e rischio di malformazioni congenite: considerazioni metodologiche sull'uso di differenti modellistiche espositive

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Published on Sunday, 30 June 2013 12:00

Vinceti M, Malagoli C, Rodolfi R, Cherubini A, Maffeis G, Greco S, Fabbi S, Signorelli C, Storani S, Iacuzio L, Fraulini A, Teggi S, Bergomi M, Astolfi G, Calzolari E, Nicolini F.

Annali di Igiene 2013;25 (Suppl. 1): 509-514

Abstract

The relation between air pollution from road traffic and teratogenic risk is an issue of considerable interest in epidemiological research. We examined the risk of birth defects associated with exposure to benzene and paticulate matter (PM10) emitted by motorized traffic in an Italian community, using a validated dispersion model (CALINE4) of these contaminants and two different methodological approaches for exposure assessment within a Geographical Information System. The study population included 228 cases of congenital malformation diagnosed at birth and the same number of matched controls. The results showed that estimates of individual exposure to benzene and PM10 and associated relative risks were substantially affected by the different approaches for exposure assessment.