Selenium and human health

Abstract

The review by Margaret Rayman (July 15, p 233)1Rayman MP The importance of selenium to human health.Lancet. 2000; 356: 233-241Summary Full Text Full Text PDF PubMed Scopus (3091) Google Scholar focused primarily on the encouraging effects of selenium in cancer trials and describes current and planned selenium supplementation in cancer research. This review and the increasing attention on the possible roles of growth hormone (GH), especially insulin-like growth factor I (IGF-I), in cancer pathogenesis made us recollect a small series of studies (the latest being Gronbask and co-workers2Gronbaek H Frystyk J Ørskov H Flyvbjerg A Effect of sodium selenite on growth, insulin-like growth factor-binding proteins and insulin-like growth factor-I in rats.J Endocrinol. 1995; 145: 105-112Crossref PubMed Scopus (39) Google Scholar) of the impact in rats of selenium administration (3 mg/L in drinking water) on body growth, GH, and IGF-I secretion. Rayman emphasises that although selenium is an important trace element, it is also toxic, with a narrow therapeutic window, and some individuals are more sensitive than others. Selenium intoxication has been extensively studied in animals for more than 60 years, was termed alkali disease already in 1860, and includes, in severe cases, liver necrosis and involvement of the central nervous system. The most striking symptom in young animals is, however, growth retardation, and the American National Research Council concluded in 1976 that growth inhibition might be the best indicator of toxic effects from selenium. Selenium accumulated in the anterior pituitary, especially in the secretory granules of the somatotroph, and in the liver.3Thorlacius-Ussing O Flyvbjerg A Esmann J Evidence that selenium induces growth retardation through reduced growth hormone and somatomedin C production.Endocrinology. 1987; 120: 659-663Crossref PubMed Scopus (32) Google Scholar Infant rats exposed to selenium intake from age 25 days to 46 days (after weaning) had a 36% lower bodyweight gain during the 3 weeks of exposure than controls (46 g vs 72 g). Serum IGF-I increased from 151 μg/L to 500 μg/L in the control rats, but no increase was seen in selenium-treated rats.4Thorlacius-Ussing O Flyvbjerg A Jorgensen KD Ørskov H Growth hormone restores normal growth in selenium-treated rats without increase in circulating somatomedin C.Acta Endocrinol. 1988; 117: 65-72PubMed Google Scholar GH response to a stimulation test with GH releasing hormone was severely lowered (by 75%).3Thorlacius-Ussing O Flyvbjerg A Esmann J Evidence that selenium induces growth retardation through reduced growth hormone and somatomedin C production.Endocrinology. 1987; 120: 659-663Crossref PubMed Scopus (32) Google Scholar We found that concomitant GH administration restored normal growth without inducing increase in serum IGF-I, which suggests a GH-independent lesion in the liver IGF-I producing system.4Thorlacius-Ussing O Flyvbjerg A Jorgensen KD Ørskov H Growth hormone restores normal growth in selenium-treated rats without increase in circulating somatomedin C.Acta Endocrinol. 1988; 117: 65-72PubMed Google Scholar Withdrawal of selenium resulted in recovery of GH secretion within 2 weeks, but low circulating serum IGF-I concentrations and growth retardation persisted for much longer. We therefore wish to further stress Rayman's warnings against high selenium intake, especially in children, because of the risk of stunting their growth. We also underscore the possibility that some of the beneficial effects of selenium in cancer are mediated by the substantial suppressive action on the GH and IGF-I system. The growing evidence of the importance of IGFs for tumourigenesis and neoplastic growth has been reviewed.5Khandwala HM McCutcheon IE Flyvbjerg A Friend KE The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.Endocr Rev. 2000; 21: 215-244Crossref PubMed Scopus (683) Google Scholar We suggest that measurements of serum GH, and especially IGFs and their binding proteins, be included in continuing and future studies.