The Two Faces of Selenium Deficiency and Toxicity are Similar in Animals and Man L.D. Koller and J.H. Exon* ABSTRACT minimum daily requirement for immune system has a role in preven- optimum biological performance. tion of cancer, these data would The purpose of this review article is Recognizing that humans in several suggest that those neoplasms which to demonstrate the close parallelism of countries do not meet the proposed are natural killer cell-sensitive could daily requirements, biological activity minimum daily requirement of 90 ,ig, be prevented and/or respondent to and minimum and maximum tolera- several compelling reasons are pres- selenium therapy while those which ble levels of selenium for animals and ented in deriving this minimal daily are natural killer cell-insensitive could man. In addition, the carcinogenic/ nutritional intake. be augmented by selenium treatment. anticarcinogenic properties of sele- Selenosis can occur in laboratory Further investigations are warranted nium are discussed and a postulate of animals, livestock, and humans to dispute or confirm this hypothesis. how these dichotomous effects may following long-term exposure to The intriguing feature of selenium occur in accordance with selenium- selenium concentrations as low as 5 nutrition is the remarkable interspe- induced immunomodulation is pres- mg selenium/kg of diet (5 ppm). The cies similarities of the action of this ented. A review of pertinent literature selenium-induced lesions for all element, especially between animals pertaining to the biological action of species are similar, which once again and man. With few exceptions, direct selenium in animals and man, includ- illustrates a positive corollary for extrapolations between species have a ing deficiency, toxicity, carcinogenic- selenium effects in both animals and high degree of correlation. We believe ity and effects on immunity, is man. From compilation of available that many of the long-term myths included to support these concepts. data, the maximum tolerable level for concerning selenium have been dis- The predominant biochemical selenium in man could be considered pelled and anticipate that recognition action of selenium in both animals and in the range of 1000 to 1500 ,ig/day. of the biological importance, as well as man is to serve as an antioxidant via This is in contrast to the currently limitations, of selenium nutrition will the selenium-dependent enzyme, recommended maximum human tol- unequivocally benefit human and glutathione peroxidase, and thus erable level of 500 ,ug/day. The animal health. protect cellular membranes and amount of selenium that can be organelles from peroxidative damage. tolerated, however, is dependent upon Key words: Selenium, deficiency, The signs and symptoms of selenium individual biological variation, nutri- toxicity, carcinogenicity, immunity, deficiency closely simulate each other tional status and general state of animals, man. for animals and man. Severe defi- health. Therefore, individuals who ciency is characterized by cardiomy- consume relatively large daily opathy while moderate deficiency amounts of selenium should periodi- RESUME results in less severe, myodegenerative cally have their blood concentrations syndromes such as muscular weakness monitored and closely observed for Cet article comporte une revue de la and pain as well as a variety of other symptoms of toxicity. litterature pertinente et vise a selenium-associated diseases. Clinical Selenium, once labeled as a carcino- demontrer le parallelisme etroit qui manifestations of many of these gen, is now thought to possess existe entre les besoins quotidiens, disorders require contributory factors, antineoplastic properties. Studies in I'activite biologique, ainsi que les such as stress, to precipitate symptoms our laboratory, investigating the quantites tolerables minimales et which are documented for animals effects of excess selenium on immun- maximales de selenium, pour les and implicated for humans. Current ity, could possibly provide a plausible animaux et l'homme. Les auteurs evidence suggests that a daily selenium explanation for these contrasting commentent en plus les proprietes consumption for man of approxi- data. Rats given selenium supple- carcinogenes et anticarcinogenes du mately 30 ,ug is necessary to prevent mented diets had suppressed humoral selenium et presentent un postulat sur the selenium-deficient syndrome, and cell-mediated immune responses la facon dont ces effets dichotomes Keshan disease, while approximately but markedly stimulated natural killer peuvent survenir, en accord avec une 90 ,ug/day/adult should be the cell cytotoxicity. Assuming the immunomodulation provoquee par le *Department of Veterinary Medicine, University of Idaho, Moscow, Idaho 83843. Present address of Dr. Koller: College of Veterinary Medicine, Oregon State University, Corvallis, Oregon 97331-4802. Submitted April 12, 1985. Can J Vet Res 1986; 50: 297-306. 297 selenium. Ils ajoutent aussi, pour la quantite tolerable maximale de toxicite, effet carcinogene, immunite, supporter ces concepts, une revue de la selenium, chez l'homme, se situerait animaux, homme. litterature relative a l'action entre 1000 et 1500 ,g/jour. Une telle biologique du selenium, chez les conclusion contraste avec la recom- animaux et l'homme, y compris sa mandation courante de 50,tg/jour. La deficience, sa toxicite, ses proprietes quantite tolerable de selenium depend INTRODUCTION carcinogenes et ses effets sur toutefois des variations biologiques l'immunite. individuelles, de l'etat nutritionnel et Selenium (Se) has been recognized La principale action biochimique de l'etat general de la sante. Les for years as an essential trace element du selenium, tant chez les animaux individus qui consomment une quan- for animals (1), but until recently, it que chez l'homme, consiste 'a servir tite quotidienne relativement elevee de has not been recognized as an essential d'antioxydant, par le truchement de la selenium devraient donc en faire element for man. In the United States, glutathion-peroxydase, enzyme qui verifier periodiquement leur teneur the regions with the lowest amounts of depend du selenium, et a proteger ainsi sanguine et il faudrait les surveiller de Se in soils and plants are the les membranes et les organelles pres, afin de detecter les symptomes Northwest, Northeast, Southeast and cellulaires des dommages attribuables d'intoxication. areas of the Midwest which adjoin the au peroxyde. Les signes cliniques que On pense maintenant que le Great Lakes (2-4). The Plains States manifestent les animaux ressemblent selenium, deja identifie comme un and Southwest generally have ade- beaucoup aux symptomes qu'on agent carcinogene, possederait des quate Se in soils and plants. The observe chez l'homme, lors d'une proprietes antineoplasiques. Les majority of livestock raised in low Se deficience en selenium. Une deficience etudes relatives aux effets d'un exces regions generally do not receive marquee se caracterise par une de selenium sur l'immunite, realisees adequate dietary Se and thus are cardiomyopathie, tandis qu'une dans notre laboratoire, fourniraient deficient. Extreme Se deficiency in deficience moderee entraine des une explication plausible pour ces man has been more difficult to syndromes moins graves de donnees contradictoires-. Des rats demonstrate in the United States, degenerescence musculaire, tels que de auxquels on donnait des aliments primarily due to transportation of la faiblesse musculaire et de la enrichis de selenium manifesterent une consumable products from region to douleur, ainsi qu'une variete d'autres suppression de leur immunite humo- region. Nevertheless, Se deficiency in maladies reliees au selenium. Les rale et cellulaire, en meme temps man is well documented in China (5- manifestations cliniques de plusieurs qu'une stimulation marquee de la 10) while the extremely low Se content de ces conditions requierent des cytotoxicite naturelle de leurs phago- of New Zealand forages results in facteurs auxiliaires tels que le stress, cytes. Si on admet que le systeme relatively low Se concentrations in pour acceler l'apparition des immunitaire joue un role dans la both animal and human populations symptomes, qui sont documentes pour prevention du cancer, les constata- (1 1). les animaux et impliques chez tions precitees permettent de penser l'homme. L'evidence courante suggere qu'on pourrait prevenir les FUNCTION OF SELENIUM que les humains doivent consommer neoplasmes sensibles-aux phagocytes The biochemistry and mechanisms quotidiennement environ 30,ug de et/ou les amener "a repondre 'a une of action of Se have recently been selenium, pour prevenir la maladie de therapie a base de selenium, alors reviewed (12-14). Selenium is an Keshan, tandis que les adultes doivent qu'on pourrait stimuler les autres par important deterrent of lipid peroxida- en prendre au moins 90 ,ug/jour, pour cette therapie. II faudra realiser des tion, competes with sulfur in biochem- realiser une performance biologique experiences additionnelles, pour ical pathways, and is incorporated optimale. Tout en admettant que les infirmer ou confirmer cette hypothese. into the sulfur-containing amino habitants de plusieurs pays -fe con- Le point intriguant du metabolisme acids, cystine and methionine (15-17). somment pas cette dose quotidienne du selenium reside dans les ressem- Selenium is incorporated into minimale, on invoque plusieurs blances remarquables de son action enzymes which regulate normal body