DYNAMICS OF SELENIUM NUTRITION OF ANIMALS IN RELATION TO HUMAN HEALTH

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1 DYNAMICS OF SELENIUM NUTRITION OF ANIMALS IN RELATION TO HUMAN HEALTH INTRODUCTION TO SELENIUM Steven A. Elliott PAS Alltech, Inc. Selenium, like the other trace minerals is necessary to sustain life and is essential for basic physiological functions in both animals and humans. While the daily requirement for these minerals is obviously small, their importance to and impact on the health and well being of livestock and humans are well documented in research. Fortunately, the difference between deficiency and toxicity with most of these trace minerals is believed to be fairly broad, allowing for the wide range of supplemental regimes that are used around the world. Unfortunately, selenium was recognized as a potentially toxic mineral long before it was identified as an essential nutrient, thus leading to unfortunate misunderstanding of this important trace mineral. This is one of the main reasons why federal regulations are in place to ensure that the animal feed industry is cognizant of the government s concerns. Before we go any further let us look at the definition of Se in a medical dictionary (Merriam-Webster, 1996): Selenium-a nonmetallic element that resembles sulfur and tellurium chemically, causes poisoning in range animals when ingested by eating some plants growing in soils in which it occurs in quantity, and occurs in allotropic forms of which a gray stable form varies in electrical conductivity with the intensity of its illumination and is used in electronic devices-symbol Se. Does anyone else find it disturbing that this definition only mentions toxicity while failing to mention deficiency? To further reaffirm the medical community s misunderstanding of this essential nutrient, one only needs to look up white muscle disease in this same dictionary and find that it is due only to an inadequate intake of vitamin E (versus also Se). These blatant misconceptions persist despite the fact that research has established that the areas of the world affected by Se deficiency are far larger and the consequences are more economically important, than those afflicted with Se toxicity concerns (McDowell 2003; Oldfield, 1999). SELENIUM CONCENTRATIONS IN SOIL AND FEED INGREDIENTS The concentration of Se in the soil and its availability to crops vary greatly from one geographic region to another. Therefore, it is not surprising that Se in crops grown on those 1

2 soils is also quite variable (Cantor, 1997). Early mapping (Kubota et al. 1967) showed a wide range of Se concentrations in forages and crops, and classified the various regions as high, moderate, or low in selenium. A map was put together by the National Research Council in 1983 to show the Se concentrations of the various areas in North America based on a 0.1- ppm scale (Figure 1). The map shows that many of the midwestern states, which are major corn and soybean producing areas, have low to variable Se content in their forages and grains even at the 0.1 ppm level. The soils in a major portion of the dairy regions in the United States, east of the Mississippi river and west of the Rocky mountains, are low in selenium resulting in lower Se levels in the grains and forages produced there (Figure 2). Combine the above mentioned situations with the fact that even in high soil Se areas, soil ph, moisture level, and aeration also contribute to plant Se levels, and it is easy to see why Se deficiencies have been documented in 44 states. Figure 1. Regional distribution of forages and grain containing low, variable, or adequate levels of selenium in the United States (National Research Council, 1983). Low: ~80% of forages/grains <0.1 ppm Se Variable: ~50% of forages/grains >0.1 ppm Se Adequate: 80% of forages/grains >0.1 ppm Se * Toxicity may be a problem. SELENIUM AND ITS IMPACT ON PRODUCTION Even though improvements in growth or milk production are rare, supplementing selenium to Se-deficient diets generally elicits a positive response in animal health (Weiss, 2003). Additionally, research with dairy and beef cattle has found that selenium 2

3 Figure 2. The state-by-state distribution of dairy cattle throughout the United States. supplementation to Se-deficient diets and/or Se-deficient areas can result in: 1. a reduction in milk somatic cell counts (Weiss et al., 1990); 2. a lower incidence and severity of clinical mastitis (Smith et al., 1997); 3. fewer retained placental membranes (Harrison et al., 1984); and 4. improved reproductive parameters (Arechiga et al., 1994). Each of these areas can have an important impact on the profitability of a dairy farm and by simply improving the selenium status of the animals, the economic value can be appreciated. SELENIUM AND MASTITIS Selenium status of lactating dairy cows is related to the incidence of mastitis and high somatic cell counts (SCC). A survey of Ohio dairy farms found a strong relationship between herd selenium and SCC (Figure 3). The herds with higher blood selenium concentrations had lower bulk tank SCC than herds with lower blood selenium levels (Weiss et al. 1990). The range of somatic cell counts in these farms was between 400,000 and 100,000, making them well within normal farm averages within the Ohio dairy region. This reduction in somatic cell count not only improves milk quality, but also can lead 3

4 Figure 3. Relationship Between Herd Serum Selenium and Bulk Tank Somatic Cell Count in Ohio Dairy Herds (Weiss, 1990). to additional milk production over the total lactation of a cow (Figure 4). The chart shows how researchers have calculated that a 50% reduction in bulk tank somatic cell count could result in up to 400 lbs. of additional milk/cow/year in second lactation animals. Figure 4. Relationship between somatic cell counts and lost milk production during the first and second lactation. Average Lactation Average Difference in Milk Yield SCC Score SCC Lactation 1 Lactation 2 cells/ml (lbs/305 Days) 2 50, , , , , Whole blood selenium is considered the best indicator of selenium status due to the incorporation of Se into developing red blood cells. A selenium level ranging between ng/ml has historically been considered to be the adequate range. Some research suggests 4

5 that higher blood selenium levels are beneficial for addressing specific mastitis pathogens (Jukola et al. 1996). It was determined that cows with blood selenium of 200 ng/ml or greater had 18% fewer mastitis infections than cows whose blood selenium levels were 150 ng/ml or less (Figure 5). Figure 5. Prevalence of infections of cows with high and low blood selenium levels. SELENIUM AND REPRODUCTION Successful reproductive performance is important to the profitability of every dairy operation and selenium status has been shown to be important in many reproductive functions. Selenium supplementation to Se-deficient dairy cows can improve reproductive performance (Arechiga et al., 1994). Improvements observed in this trial included fewer services per conception, improved pregnancy rates at first service, and fewer days to conception (Table 1). Table 1. Effect of selenium on post-partum reproduction in dairy cows Control Se P Retained Placentas 10/99 3/99.06 Pregnancy at 1 st Service 25% 41%.02 Services/Conception Days to Conception

6 MEETING THE SELENIUM REQUIREMENT OF DAIRY CATTLE The most recent edition of the National Research Council Nutritional Requirements of Dairy Cattle defines the selenium requirement for all classes of dairy cattle as 0.3 ppm (NRC, 2001). Moreover, the Food and Drug Administration has set the legal limit for supplemental selenium to dairy cattle at no greater than 0.3 ppm. However, continuing problems with dairy cows, like the mastitis and reproductive disorders mentioned above, suggest that current practices of selenium supplementation using sodium selenite may not be adequate. NRC recommendations are generally based on providing adequate trace mineral levels to prevent measurable deficiencies, not on adequate levels to optimize animal health. It is well documented that the currently available inorganic selenium sources, sodium selenite and sodium selenate, are poorly absorbed and utilized by ruminants. Inorganic selenium (selenite) is absorbed much less efficiently by ruminants than monogastrics (Gerloff, 1992). Absorption of selenite by ruminants has been reported at 29% (Van Saun, 1990) and between 17 and 50% (Harrison and Conrad, 1984). Poor absorption of inorganic selenium is likely due to the ruminal environment where oxidized selenite or selenate is in large part reduced by ruminal microbes to insoluble and unavailable elemental selenium which is excreted via the feces (Van Saun, 1990). Other dietary factors also influence the availability of inorganic selenium. Dietary concentrates alter the ruminal reduction capacity with high concentrate/low ph, presumably increasing the amount of inorganic selenium that the microbes would make unavailable to the animal (Gerloff, 1992). This variation in rumen acidity may be one reason why the response to a given amount of selenite can vary from farm to farm in the same region. Other minerals, including sulfur and iron, can also interfere with selenium absorption (Gerloff, 1992). IMPROVING THE SELENIUM STATUS OF DAIRY CATTLE Given the legal limits on supplemental selenium, what can we do to improve the selenium status of dairy cattle? One potential approach would be to use forages and grains with a higher selenium content. Plants, marine algae, and bacteria can convert inorganic selenium from the soil into organic selenoamino acids, like selenomethionine. These organic selenium sources are more available to the animal for absorption and utilization. However, this approach would require a consistent source of high selenium feedstuffs and monitoring of selenium content would be time-consuming and costly. One way that dairymen have been circumventing the selenium regulations is by strategically using selenium injections. These injectable forms of selenium avoid the problem of poor absorption due to the ruminal environment and are routinely administered to dairy cows during the dry period. This practice has been used for many years as a short-term therapy, but does very little to improve the long-term selenium status of the animal (Pavlata et al., 2001). A study that looked at various storage tissues, found that injectable selenium was no better at improving selenium stores than the no Se group. In fact, only the group that received the organic selenium source, Sel-Plex TM, showed significant improvements (Figure 6). 6

7 Figure 6. Blood and tissue Se of calves: Injected Se vs. Sel-Plex TM Maas and coworkers (1993) found that after an animal was injected with inorganic selenium, Se peaked at 5 hours post-injection. By 28 days, blood selenium in cows was around 50 ng/ ml compared to the 100 ng/ml that was experienced during the first 24 hour period. So it appears that while injections may work as a short-term therapy, their effectiveness on body stores of selenium is very limited. Finally, injectable forms of selenium have been known to contribute to spontaneous abortions in the dry cow pen and are responsible for many injection site abscesses in the animals that receive them. The major advantage of an organic selenium source over inorganic selenium source is its improved absorption and retention in the body. Selenoamino acids incorporated into body proteins provide a reserve of stored selenium when demand for selenium is high, particularly during disease challenge and gestation (Gunter et al., 2003). Maternal transfer of selenium (through the placenta, colostrum and milk) improves the ability of the calf to survive and thrive (Table 2). Table 2. Sel-Plex Improves Se Status of Cows and Calves No Se NaSe Sel-Plex No Se vs. Se NaSe vs SP Whole Blood Se, ng/ml (cows) Probability of no effect At calving At 2 mo postpartum Whole Blood Se. ng/ml (Calves) At birth At 4 months

8 SUMMARY FOR PRODUCTION AGRICULTURE The modernization of dairy farms over the last few decades has led to many new stresses being placed on today s dairy animals. Increased demands for milk production and efficiency are forcing the scientific community to reconsider the nutrient requirements of dairy cattle on a frequent basis. The new NRC made several changes in vitamin and mineral recommendations, and yet federal regulations forced the committee to once again leave selenium at the original 0.3-ppm level. Recent discoveries and FDA approvals have now opened the door for another way to address our selenium dilemma. Research done over the last several years suggests a more practical approach to improving selenium status is through the supplementation of high selenium yeast. More than a decade ago, Alltech researchers began the process of developing an organic form of selenium as an alternative to inorganic sources. The result of this research program is Sel-Plex, an organic selenium source produced by yeast. Yeasts, as part of the plant kingdom, have the ability to convert inorganic selenium into selenoamino acids. These seleno-compounds are what animals need in order to build body reserves of selenium for times of need. Currently, Sel-Plex is the only selenium yeast that has undergone over 7 years of scrutiny by the FDA. It was this evaluation that was responsible for the approval of selenized yeast in ruminant diets in the United States on September 4 th, POTENTIAL IMPACT ON HUMAN HEALTH The ability of supplemental organic selenium to increase the selenium level in meat, milk and eggs is well documented (Richards 2004, Payne 2005). Work done in dairy cattle shows that milk selenium can only be effectively elevated with the use of an organic selenium source (Knowles1999, Pehrson 1999)). This could theoretically contribute a great deal of selenium to the human food chain if it were adopted by a large number of dairy producers around the world (Graph 4). OVERVIEW It has been over ten years since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then more than 30 new selenoproteins have been identified, of which almost 20 have been purified and characterized for their biological function. The long-term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognized universally. Interest in the role of selenium in human health gathered momentum in the late 1960 s, and investigations looked for human diseases similar to those of Se-responsive animal disorders (Combs, 1986). Although selenium was identified as essential to human nutrition 48 years ago, a universal marker of daily requirement remains a regionally debated 8

9 Graph 4. The influence of dietary selenium as selenium yeast or sodium selenite on the concentration of selenium in the milk subject. Research has extended our knowledge of the essential functional roles attributed to selenium, which have both short-, and long-term public health implications. BACKGROUND Even though Selenium (Se) was known to be nutritionally essential since 1957 (Schwarz and Foltz, 1957), in the mid 1960s it was still officially listed as an environmental carcinogen. Selenium thus could not be legally added to animal feed, making it impossible to prevent outbreaks of Se deficiency diseases in farm animals, which at that time annually caused losses in the millions of dollars. To find out whether Se was indeed an environmental carcinogen, which had never been conclusively demonstrated, Shamberger and Frost in 1969 compared the human cancer mortalities in regions of the US with the Se contents of locally grown forage crops. When fewer cancer deaths were shown to occur in the high-se regions than in the low-se areas, the notion of Se as an environmental carcinogen became untenable and led to the recognition of Se as an environmental anticarcinogenic agent. HEALTH CONDITIONS ASSOCIATED WITH SELENIUM DEFICIENCY Recognition of the important role of the above mentioned selenoproteins in metabo- 9

10 lism helps to explain the adverse consequences of selenium deficiency in human and animal health. Selenium can enter the food chain through either plants, which take it up from the soil, or animal protein like meat milk, and eggs. Selenium deficiency has therefore been identified in parts of the world notable for their low soil content of selenium, which in turn results in low tissue selenium of the local livestock. Acid soils and moisture also reduce the uptake of selenium by plants, as is the case in many parts of the developed world. Animal deficiency diseases have been identified since the 1950s on a wide scale in livestock in countries that have such soil conditions, examples being reproductive impairment, growth depression (ill-thrift), and white-muscle disease. These disorders have had such serious economic consequences that measures to increase selenium intake (applying selenized fertilizers, selenium fortified mineral mixes, boluses, drenches, and injections) are now being used to prevent their occurrence. Human dietary intakes also range from high to low according to geography. Human selenium-deficiency diseases have been recognized in some regions: Keshan disease, an endemic cardiomyopathy, and Kashin-Beck disease, a deforming arthritis, were first identified in an area of China where the soil is extremely low in selenium. Both these conditions are believed to have other causative cofactors. SE-ANTICANCER HYPOTHESIS This hypothesis has been tested by means of ecological and correlation studies. These showed that human cancer mortalities were influenced by regional variation in dietary Se intake, leading to the prediction that the mortalities from major forms of cancer would decline significantly if the dietary Se intakes were increased to approximately twice the current average US dietary Se intakes, corresponding to about µg/day (Schrauzer et al., 1977). It has also been shown that blood Se levels are proportional to dietary Se intake (Schrauzer and White, 1978). In animal trials, higher blood selenium status has been linked to an improved immune response to specific pathogens (Jukola, 1996). In many countries, Se intakes have declined during the past 20 years due to the increased use of low-se cereals and advancements in cropping techniques (i.e., irrigation, fertilization, and decreased days to harvest). When looking at international blood Se and dietary Se intake data, statistically significant inverse associations are obtained for cancers at all sites: colon, rectum, prostate, breast, ovary, leukemia, lung, pancreas, skin, bladder and urinary organs. As an example of the results obtained, a plot of the age-corrected prostate cancer mortalities in 13 countries against the blood Se concentrations of healthy subjects in the respective countries is given in Graph 1. From these data it can be seen that prostate cancer mortalities decline with increasing Se intake and become very low at blood Se concentrations of 0.25 to 0.30 µg/ml. Blood Se levels of this magnitude are reached by adults of average weight at dietary Se intakes of µg/day, which corresponds to approximately twice the amount of Se obtained by an adult consuming a typical American diet, and 4-5 times the adult Daily Reference Intake (DRI) set in the year 2000 by the Panel on Dietary Antioxidants 10

11 and Related Compounds. This prediction has since been essentially confirmed by The Nutritional Prevention of Cancer (or NPC) Trial (Clark et al., 1996). Graph 1. Plot of age -corrected prostate cancer mortalities in 13 countries versus the blood Se concentrations of healthy subjects. Y= x R^2=0.888 THE CLARK STUDY The Nutritional Prevention of Cancer (or NPC) Trial was carried out in low selenium areas of the United States in cooperation with dermatology clinics in several states. In this fully randomized, placebo-controlled trial, a total of 1312 subjects were enrolled from 1983 to Seventy-five percent of the subjects were male and their average age on enrollment was 63±10 years. All subjects had previously received treatment for non-melanoma skin cancer (Clark et al., 1996). To show whether supplemental Se could prevent skin cancer recurrence, study subjects received either a placebo or 200 µg of Se in form of high-se yeast. While supplemental Se had no effect on skin cancer recurrence, the incidence and mortality from cancers in other organs were significantly reduced. Seventy non-epithelial cancers occurred in the Se group vs. 117 in the placebo group, corresponding to a RR, (Relative Risk), of 0.58, and overall cancer mortality was reduced by 56%. The incidence of prostate cancer was reduced by 63%, colorectal and lung cancer by 58% and 46%, respectively 11

12 (Graph 2). The observed trend of reduced incidence of prostate, colorectal and lung cancer appears to be related to the ages (Waterhouse, 1974) at which these cancers maximally occur (72.9, 66.1 and 62.3 years). For cancer at other sites (melanoma, esophagus, bladder, brain, breast, etc.), case numbers were too small to reach statistical significance. Graph 2. The clinical response to Se-Yeast supplementation versus placebo on cancer incidence and mortality. 46% 58% 63% p<0.001 p<0.04 p<0.03 p<0.002 DETERMINING ADEQUATE SELENIUM STATUS Analysis of treatment effect in the NPC trial by initial plasma selenium status showed that the strongest effect was seen in people in the lowest tertile of plasma selenium, i.e., those whose plasma selenium level was below 106 ( ug/l) at entry to the trial (Table 3). Table 3. Total cancers by plasma selenium level at baseline Baseline Plasma Selenium (ug/l) Selenium Cases Placebo Cases Relative Risk 95% C I P < >

13 Selenium supplementation reduced the risk of cancer in this tertile by 48%. The NPC trial was carried out in regions where dietary selenium intake is generally 90 µg per day or less, low in US terms, but already near the level needed to optimize selenoenzyme activity. The upper level of the bottom tertile is still well above the average plasma Se level in many countries around the world (Graph 3). Consequently, it might be predicted that a repeat of the NPC trial in these countries would show a large treatment effect. Graph 3. Average blood selenium of European countries as it relates to optimal GSH-Px activity and the NPC trial. Level required to optimize GSH-Px activity Bottom tertile in NPC trial While this observation does not preclude a role for the selenoenzymes in cancer prevention, it may suggest the operation of additional important mechanisms. Thus the anticancer effect of selenium may relate more closely to its ability to enhance the immune response or, more likely, to its ability to produce anti-tumorigenic metabolites that can perturb tumour-cell metabolism, inhibit angiogenesis, and induce apoptosis of cancer cells. In this context, there is considerable interest in defining the species of selenium present in selenium yeast (of which the major proportion is believed to be SeMet) with a view to identifying the most active anticarcinogenic component. SUGGESTED DAILY RECOMMENDED INTAKE The adult Daily Reference Intake (DRI) was set in the year 2000 by the Panel on Dietary Antioxidants and Related Compounds. The DRIs were derived largely from the estimated Se intake needed to maximize plasma glutathione peroxidase (GSH-Px) activity, 13

14 and with-out taking into account protective functions of Se. In addition, the chemical form of Se was not specified. The latter omission could have potentially serious consequences, as the bioavailability of Se compounds in foods varies tremendously. Additionally, inorganic selenium sources, like sodium selenite, are not effectively stored in the body of animals and are therefore limited in their ability to contribute to the selenium status of humans The committee also established an Upper Tolerable Intake Limit (UL) for Se of 400 µg/day for adults 19 years or older. The UL defines the Se intake that is tolerable without posing a risk of adverse health effects to almost all individuals in the general population and which is half of the No-Observed-Adverse-Effect-Level (NOAEL) intake of 800 µg/day. The Se intake for cancer prevention as determined from the correlational and ecological studies lies below the UL and is safe for indefinite periods. SUMMARY Since Se must be supplemented for extended periods to have cancer-protective effects, the question as to the appropriate dosage and supplemental form of Se must be addressed. As to dosage, there is probably general agreement that a daily supplemental Se intake of 200 µg will suffice to provide adequate protection. As to the chemical form of Se, it should ideally be supplemented in the same form or forms in which it occurs naturally in foods. Sources such as Se yeast, are suitable for human and animal Se supplementation (Schrauzer, 2001). Yeasts, as part of the plant kingdom, have the ability to convert inorganic selenium into organic selenium compounds for storage. These seleno-compounds are what humans and animals need in order to build body reserves of selenium for times of need. Researchers continue to identify these organic selenium compounds and determine what individual contributions they have on the various protective mechanisms in the body of man and animals. CONCLUSION Blood selenium concentration data does reflect dietary intake but tells us nothing of its functional significance, particularly in antioxidant defense and the immune response. It is also evident from clinical studies that increasing Se intake decreases the incidences of certain cancers. These biological requirements mean there is an urgent need to establish valid biomarkers in terms of functional requirement and adequacy of intake. Scientists have recommended minimum and maximum daily Se intakes, but they have not proposed an optimal intake at this point. While ongoing research will further deepen our understanding of the modes of protective action of Se, the available evidence already indicates that a daily extra-dietary supplement of 200 µg Se reduces cancer risk and increases our immune status. In Se-adequate regions, the desired Se intakes of 200 to 300 µg Se/day may be attained through prudent diet choices alone. On the other hand, in most regions around the 14

15 world, the supplementation of our diet with organic selenium sources, such as selenium yeast or selenium enriched foods, may be needed to address our selenium needs. REFERENCES Arechiga, C.F., O. Ortiz, and P.J. Hanson Effect of prepartum injection of vitamin E and selenium on postpartum reproductive function of dairy cattle. Theriogenology 41:1251. Awadeh, F.T., M.M. Abdelrahman, R.L. Kincaid and J.W. Finley Effect of selenium supplements on the distribution of selenium among serum proteins in cattle. J. Dairy Sci. 81:1089. Cantor, A.H The role of selenium in poultry nutrition. In: Biotechnology in the Feed Industry, Proceedings of the 13th Annual Symposium. (T.P. Lyons and K.A. Jacques, eds) Nottingham University Press, Nottingham, UK. Clark LC, Combs Jr GF, Turnbill BW, et al, Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. JAMA 1996; 276(24): Combs SB, Combs GF. The role of selenium in Nutrition. New York: Academic Press Inc, Food and Drug Administration. Federal Register: September 3, 2003 (Volume 68, Number 170)][Rules and Regulations][Page ] Gerloff, B.J Effect of selenium supplementation on dairy cattle. J. Anim. Sci. 70: Gunter, S.A., P.A. Beck, and J.M. Phillips Effects of supplementary selenium source on the performance and blood parameters in beef cows and their calves. Sel-Plex Technical Report 189, Alltech, Inc., Nicholasville, KY Harrison, J.H., and H.R. Conrad Effect of selenium intake on selenium utilization by the nonlactating dairy cow. J. Dairy Sci. 67:219. Jukola, E., J. Hakkarainen, J. Soloniemi, and S. Sankari. Effect of selenium fertilization on selenium in feedstuffs and selenium, vitamin E, and beta-carotene concentrations in blood of cattle. J. Dairy Sci. 79:

16 Knowles, S.O., N.D. Grace, K. Wurms and J. Lee Significance of Amount and form of dietary selenium on blood, milk and casein selenium concentrations in grazing cows. J. Dairy Sci. 82: Kubota, J. W.H. Allaway, D.L. Carter, E.E. Cary and VA. Lazar Selenium in crops in the United States in relation to selenium-responsive diseases of animals. J. Agric. Food Chem. 15:448. Maas, J., J.R. Peanroi, T. Tonjes, J. Karlonas, F.D. Galey, and B. Han Intramuscular selenium administration in selenium deficient cattle. J. Vet. Intern. Med. 7: McDowell, L.R Minerals in Animal and Human Nutrition. 2nd ed. Elsevier Science, Amsterdam. Merriam-Webster Merriam-Webster s Medical Desk Dictionary. Merriam- Webster, incorporated, Springfield, MA National Research Council, Nutrient Requirements of Dairy Cattle. Seventh Revised Edition. National Academy Press, Washington, DC. Oldfield, J.E Selenium World Atlas. Selenium-Tellurium Development Association. Grimbergen, Belgium. Ortman, K. and B. Pehrsen Selenite and selenium yeast as feed supplements for dairy cows. J. Vet Medicine A 44: Pavlata, L., J. Illek, and A. Pechova Blood and tissue selenium concentrations in calves treated with inorganic or organic selenium compounds A comparison. Acta Vet. Brno 70: Payne, R.L., Lavergne, T.K., and Southern, L.L. Effect of inorganic versus organic selenium on hen production and egg selenium concentration. Poult. Sci. 84: Pehrson, B., K. Ortman, N. Madjid, and U. Trafikowska The influence of dietary selenium as selenium yeast or sodium selenite on the concentration of selenium in the milk of suckler cows and on the selenium status of their calves. J. Anim. Sci. 77: Richards, C. J. et al. Selenium in tissues of calves supplemented with selenium yeast. J.Anim. Sci. 82 (Suppl. 1): 269 Schrauzer, G.N Nutritional selenium supplements: product types, quality and safety. J. Am. Coll. Nutr. 20(1):

17 Schrauzer, G.N. and D.A. White Selenium in human nutrition: Dietary intakes and effects of supplementation. Bioinorg. Chem. 8(4): Schrauzer, G.N., D.A. White and C.J. Schneider Cancer mortality correlation studies-iii: Statistical associations with dietary selenium intakes. Bioinorg. Chem. 7(1): Schwarz, K. and C.M. Foltz Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. J. Am. Chem. Soc. 79: Shamberger, R.J. and D.V. Frost Possible protective effect of selenium against human cancer. Can. Med. Assoc. J. 100(14): 682. Smith, K.L., J.S. Hogan and W.P. Weiss Dietary vitamin E and selenium affect mastitis and milk quality. J. Anim. Sci. 75: Spears, J.W., R.W. Harvey and E.C. Segerson Effects of marginal selenium deficiency and winter protein supplementation on growth, reproduction and selenium status of beef cows. J. Anim. Sci. 63: Van Saun, R. J. 1990: Rational approach to selenium supplementation essential. Feedstuffs (Jan 15): Waterhouse, J.A.H Cancer Handbook of Epidemiology and Prognosis. Churchill Livingstone, Edinburgh and London. Weiss, W.P., J. S. Hogan, K.S. Smith, and K.H. Hoblet Relationships among selenium, vitamin E, and mammary gland health in commercial dairy herds. J. Dairy Sci. 73:381. Weiss, W. P Selenium nutrition of dairy cows: comparing responses to organic and inorganic selenium forms. In: Biotechnology in the Feed Industry: Proceeding from Alltech s 19 th Annual Symposium (T.P. Lyons and K.A.Jacques, eds), Nottingham Press University, Nottingham, UK, pp