Selenium-enriched yeast as source for selenium added for nutritional purposes in foods for particular nutritional uses and foods (including food supplements) for the general population Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food

Following a request from the Commission, the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Foods (AFC Panel) was asked to deliver a scientific opinion on the safety and bioavailability of selenium-enriched yeast as a source for selenium when added for nutritional purposes in foods for particular nutritional uses and foods (including food supplements) for the general population. The Scientific Committee for Food (SCF) has previously given an opinion on the Tolerable Upper Intake Level of selenium and has also provided an opinion on selenium in relation to the essential requirements for infant formulae and follow-on formulae. The present opinion deals only with the safety and bioavailability of one particular source of selenium, selenium-enriched yeast, to be used in foods for particular nutritional uses and in foods (including food supplements) for the general population. The safety of selenium itself, in terms of amounts that may be consumed, is outside the remit of this Panel. Selenium in selenium-enriched yeast produced using sodium selenite as a source is typically in the form of the seleno-amino acid selenomethionine, accounting for approximately 60-85% of total selenium species in the selenium-enriched yeast product. Selenocysteine is the second most abundant identified species, approximating to 2-4% of total selenium species. Inorganic selenium (IV) ion is normally found at less than 1% of total, confirming that virtually all of the selenium present in the product is organically bound. The remaining proportion is the sum of minor species. The conclusions of the present opinion relate only to selenium-enriched yeasts in compliance with the following product characteristics: Selenium-enriched yeasts produced by culture in the presence of sodium selenite as selenium source and containing, in the dried form as marketed, not more than 2.5 mg selenium/g. The predominant organic selenium species present in the yeast is selenomethionine which constitutes between 60 and 85% of the total selenium in the product. The content of other organic selenium compounds including selenocysteine does not exceed 10%. While levels of inorganic selenium in selenium-enriched yeast normally do not exceed 1%, since inorganic selenium in the form of sodium selenite, sodium selenate and sodium hydrogen selenite has been reviewed by the SCF and has been also permitted in PARNUTS and fortified foods, inorganic selenium from a selenium-enriched yeast source is not a safety issue. Like other forms of selenium salts and organoselenium compounds, selenomethionine is readily absorbed from the gastrointestinal tract. In a number of studies in humans and animals, in particular those on selenium-deficient diets, the bioavailability of selenium from selenium-enriched yeasts and the bioavailability of selenomethionine has been shown to be approximately 1.5 to 2-fold higher than that of inorganic forms of selenium. Following absorption, selenomethionine is metabolised to other functional forms of selenium (e.g. selenocysteine) or diverted into pathways of methionine metabolism and stored as selenoproteins. The half-life of L-selenomethionine (252 days) is longer than that of inorganic selenite (102 days), indicating that once absorbed, selenomethionine is incorporated into a long term body pool. The steady-state is reached after 6-12 months of supplementation with selenium in the form of selenomethionine or selenium-enriched yeast. The selenium is incorporated into tissue proteins such as skeletal muscle, liver, erythrocytes and plasma albumin from which it can subsequently be released by catabolism to maintain increased selenium status, indicating that selenomethionine is extensively utilized and re-utilized. Recent data in human volunteers show that in response to an increase in dietary selenium intake from sources such as selenium-enriched yeast, plasma selenium concentration increases to a new steady-state level that is maintained for many years if the level of selenium intake is unchanged. Selenium is known to be chronically toxic and selenosis has been reported in humans and in food animals in seleniferous areas. Intakes in the range of 3200-6990 mu g/day (mean 4990 mu g/day) are associated with chronic selenosis, with no selenosis observed in the intake range of 240-1510 mu g /day (mean 750 mu g/day). Investigations into the health effects of high dietary intakes of selenium in populations living in the seleniferous areas of South Dakota, Venezuela and China have indicated that the highest long-term daily intake that can be ingested without the development of toxicity in most individuals is approximately 800 mu g while prolonged intakes of daily selenium doses of 1000 mu g or greater may cause adverse reactions. Data in lactating women supplemented with selenium or exposed to high dietary selenium levels suggest that the mother acts as a buffer, protecting the infant against excess intake of selenium. Even at a maternal selenium intake of 300 mu g/day (the recommended EC Tolerable Upper Intake Level) milk selenium concentration only rises to 60 mu g/l giving an infant intake of 39-47 mu g/day which is below the UL of 60 mu g/day for children aged 1-3 years recommended by the SCF and the UL of 45-60 mu g/day for infants aged 0 - 12 months recommended by the Food and Nutrition Board.. Despite the higher bioavailability of selenium from organic sources such as selenium-enriched yeast, the toxicity of these organic forms has been shown in a number of studies in experimental animals to be lower than that of inorganic selenite or selenate. This suggests that the increased bioavailability may be counterbalanced by lower toxicity. A number of recent clinical studies carried out with selenium-enriched yeast show no evidence of toxicity following selenium intakes up to 343 mu g/day, and whole-blood levels of 441 selenium mu g/l, for a period of over 4 years. The Panel thus concludes that the reservations expressed by the SCF in 1999, when the Committee initially considered selenium-enriched yeasts for use in foods for particular nutritional purpose (PARNUTS), namely that there was uncertainty about the range of selenium-enriched yeast preparations which could be used and the range of selenium compounds they may contain, and differences in the way in which the body handles organic compared with inorganic forms, have been addressed via the additional data considered in this opinion. These data include (i) the general product characteristics for the majority of the selenium-enriched yeast products covered by this opinion, (ii) the additional data that have become available on the identity and speciation of the organo-selenium compounds contained in the yeast, (iii) the available information indicating that on repeated supplementation/exposure to a selenium-rich source such as yeast, levels of selenium reach a steady-state within 2-4 months, rather than increasing indefinitely in plasma and in tissues such as muscle, (iv) the results of recent clinical trials with selenium enriched yeast. The quantity of selenium-enriched yeast to be added to food supplements is in the range of 30200 mg of enriched yeast, providing 50-200 mu g selenium per day, although the majority of products identified by the petitioners would provide 100 mu g selenium or less per day. Limited information was provided on use levels in foods for particular nutritional purposes, although one petitioner indicated that levels to be added to food would provide an intake of less than 50 mu g selenium/day. Average dietary intake of selenium by the European population has been estimated to lie in the range of 27-70 mu g/day, with higher intakes seen in Finland, where selenium is added to agricultural fertilizers. Assuming a mean dietary selenium intake in the range of 30-70 mu g/day, consumption of an additional food supplement containing 100 mu g Se would result in a total daily Se intake of 130-170 mu g/day in an adult at an average level of dietary exposure. Intake from the proposed use of supplements containing selenium-enriched yeast would thus be approximately 2-3 times the average dietary intake from food. In the case of a food supplement containing 200 mu g Se, the total daily Se intake would be between 230-270 mu g/day in an adult at an average level of dietary exposure, with higher intakes being anticipated in individuals from selenium-rich areas where consumption of selenium-rich cereals may contribute to a higher intake. For these individuals, the Tolerable Upper Intake Level for selenium established by the SCF in 2000 could be exceeded. Assuming a use level of selenium-enriched yeast in foods for particular nutritional uses and for fortification purposes that would provide an intake of less than 50 mu g selenium/day, the total daily selenium intake of an adult exposed at the average level of dietary exposure from these sources plus dietary sources would lie in the range of 80-120 mu g/day. Having considered the general product characteristics for the selenium-enriched yeast products covered by this opinion, and the additional data that have become available on the identity and speciation of the organo-selenium compounds contained in the yeast, the Panel concludes that five of the selenium-enriched yeasts included in this opinion are sufficiently well characterised in terms of the selenium content and the nature of the selenium compounds contained therein, enabling the broad product characteristics for the product outlined above to be defined. For the two remaining products: biotransformed yeast produced using selenium dioxide as a source and selenium-enriched yeast produced using selenium-aminoate, the Panel considered that insufficient information was provided on the selenium species likely to be present in these products. The Panel also noted that in the case of the products from these two petitioners, the selenium source used in the manufacturing process was not sodium selenite. The Panel considered therefore that it was not possible to conclude that the profile of the selenium species in these two selenium-enriched yeast products is likely to be similar to those reported for the other five products, with selenomethionine accounting for approximately 60 - 85% of the total selenium. Due to deficiencies in the bioavailability and safety data provided on the selenium species likely to be present in these products, the Panel was unable to evaluate their safety. The Panel notes that the quantity of yeast ingested as a result of the use of supplements containing selenium-enriched yeast will be small (up to 200 mg daily) and that the cellular constituents of the yeast are anticipated to be endogenous in the human body. The Panel also concludes that the quantity of yeast ingested as a result of the use of supplements containing selenium-enriched yeast is unlikely to present an allergenic risk, and that individuals with yeast sensitivity will be alerted to the presence of yeast protein via the labelling of these products. On the basis of the data provided by the petitioners and information in the literature on the bioavailability, metabolism and toxicity of selenium-enriched yeast and selenomethionine, from dietary sources and in the form of dietary supplements, the Panel concludes that the use of selenium-enriched yeast, complying with the general product characteristics outlined above, as a source of selenium when used in foods for particular nutritional uses and in foods (including food supplements) for the general population does not present a safety concern at the proposed intake levels.