Picking a Selenium Form for Enriching Infant Formula

  • The FDA requires that infant formulas be fortified with selenium, a micronutrient essential for infant health and development, but it doesn’t recommend a particular form of selenium for the fortification.
  • A recent review article suggests that organic forms of selenium—particularly selenium-enriched yeast—are more bioavailable, better absorbed and retained, and may have improved biological activity compared with inorganic forms.
  • Most studies of selenium fortification of infant formula have used inorganic selenium, and the review recommends additional studies evaluating the safety and health outcomes of fortification with organic selenium.

 

When thinking about infant nutrition, selenium isn’t necessarily the first thing that comes to mind. But it’s been known for more than 50 years that selenium is a crucial micronutrient. This trace mineral can’t be synthesized in the human body, and is required for a variety of functions including antioxidant defense, modulation of the inflammatory response, and production of thyroid hormones [1,2]. It acts in conjunction with many proteins, and about 25 genes encoding these “selenoproteins” have been identified in humans [3–5]. Selenoprotein deficiency has been associated with an increased risk for cardiovascular disease and stroke [2].

Selenium is particularly important for infant health and development. Infants are born with some selenium reserves, and infants born at term usually have larger selenium stores than pre-term infants [6]. Selenium concentrations in preterm infants are considerably lower than those of both formula-fed and breastfed term infants. Preterm infants are at risk for selenium deficiency [7]. Supplementation with trace minerals, including selenium, is particularly important in these infants [8]. But even for infants born at term, selenium stores are quickly depleted as the infants grow, and dietary sources of selenium become increasingly important.

Breastfed infants generally receive sufficient selenium from human milk, which typically contains higher concentrations of the nutrient than unfortified cow’s milk-based formula. The selenium concentration in the blood of breastfed infants generally increases from birth until the age of six months and then remains stable in the long term [9].

However, infants fed unfortified formulas have consistently lower selenium levels compared with breastfed infants, and their selenium levels decrease several months after birth, suggesting that that their selenium intake may be too low to support their rapid growth [4]. Researchers have thus suggested that infant formula should be supplemented with selenium levels similar to those in human milk [10].

After considering the evidence about the importance of selenium in infant nutrition, in June 2015 the United States Food and Drug Administration (FDA) added it to the list of required nutrients in infant formulas, and required that they contain selenium at levels between 2.0 and 7.0 μg per 100 kilocalories [11].

However, selenium exists in both organic and inorganic forms, and the FDA did not recommend a particular form for fortification. Infant formula has so far been supplemented with inorganic forms of selenium such as sodium selenite or sodium selenate. Human milk doesn’t contain inorganic forms of selenium, and it is instead secreted as part of organic compounds.

In a new review article, distinguished professor emeritus Bo Lönnerdal from the University of California at Davis and colleagues suggest that organic forms of selenium may have some benefits over inorganic forms for fortifying formula [12].

Most trials of selenium fortification in infants have used selenite, an inorganic form of selenium. Clinical trials have demonstrated that infants receiving formula fortified with inorganic selenium have improved selenium levels compared with infants receiving non-fortified formula [13–15]. However, the recent review suggests that organically bound forms of selenium—such as selenomethionine and selenium-enriched yeast—are better absorbed and retained than inorganic forms, and fortification with selenium-enriched yeast may be particularly beneficial compared with other organic forms.

Evidence from preclinical studies suggest that inorganic forms of selenium may be more acutely toxic than organic forms, although studies on selenium-fortified infant formulas have reported few adverse effects [13-15]. Several studies have also shown that organic selenium is more efficiently incorporated into milk proteins than inorganic forms, and is more rapidly and extensively absorbed by the body [8,16–20]. In addition, selenium from selenium-enriched yeast may be 1.5–2 times more bioavailable than inorganic selenium, and may also have increased biological activity and be retained longer in the body [20–22].

There may also be differences between various organic forms of selenium. Studies have shown that different forms may have different levels of antioxidant activity, and selenium-enriched yeast may be particularly beneficial [23]. Selenium-enriched yeast is also expected to be safe for use; it is used in inactive form and in tiny quantities, and is closely related to another form of yeast that has been used as a probiotic in children since the 1950s. In addition, a standardized formulation of selenium-enriched yeast in which selenium levels are entirely bound to organic compounds, with no free inorganic selenium present, has been shown to be safe and well tolerated in growing infants and older individuals [21,22,24].

The review concludes that organically bound forms of selenium, and particularly selenium-enriched yeast, are safe and may be preferred for use in infant formulas compared with inorganic forms. However, most studies of selenium fortification in infant formula have so far used inorganic selenium, and the researchers suggest that more studies are needed to evaluate the safety and potential health benefits of enriching formula with organic selenium, and in particular with standardized selenium-enriched yeast.

 

1. Carver J.D. Advances in nutritional modifications of infant formulas. Am J Clin Nutr. 2003 Jun;77(6):1550S-54S.
2. Fairweather-Tait S.J., Bao Y., Broadley M.R., Collings R., Ford D., Hesketh J.E., Hurst R. Selenium in human health and disease. Antioxid Redox Signal. 2011 Apr 1;14(7):1337-83.
3. Méplan C. Selenium and chronic diseases: a nutritional genomics perspective. Nutrients. 2015 May 15;7(5):3621-51.
4. Reeves M.A., Hoffmann P.R. The human selenoproteome: recent insights into functions and regulation. Cell Mol Life Sci. 2009 Aug;66(15):2457-78.
5. Kryukov G.V., Castellano S., Novoselov S.V., Lobanov A.V., Zehtab O., Guigó R., Gladyshev V.N. Characterization of mammalian selenoproteomes. Science. 2003 May 30;300(5624):1439-43.
6. Dorea J.G. Selenium and breast-feeding. Br J Nutr. 2002 Nov;88(5):443-61.
7. Sievers E., Arpe T., Schleyerbach U., Garbe-Schönberg D., Schaub J. Plasma selenium in preterm and term infants during the first 12 months of life. J Trace Elem Med Biol. 2001 Apr;14(4):218-22.
8. Finch C.W. Review of trace mineral requirements for preterm infants: what are the current recommendations for clinical practice? Nutr Clin Pract. 2015 Feb;30(1):44-58.
9. Victora C.G., Bahl R., Barros A.J., França G.V., Horton S., Krasevec J., Murch S., Sankar M.J., Walker N., Rollins N.C.; Lancet Breastfeeding Series Group. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet. 2016 Jan 30;387(10017):475-90.
10. He M.J., Zhang S.Q., Mu W., Huang Z.W. Selenium in infant formula milk. Asia Pac J Clin Nutr. 2018;27(2):284-92.
11. Food and Drug Administration, HHS. Infant formula: The addition of minimum and maximum levels of selenium to infant formula and related labeling requirements. Fed Regist. 2015, Jun 23;80(120):35834–41.
12. Lönnerdal B., Vargas-Fernández E., Whitacre M. Selenium fortification of infant formulas: does selenium form matter? Food Funct. 2017 Nov 15;8(11):3856-68.
13. Darlow B.A., Inder T.E., Sluis K.B., Nuthall G., Mogridge N., Winterbourn C.C. Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula. J Paediatr Child Health. 1995 Aug;31(4):339-44.
14. Tyrala E.E., Borschel M.W., Jacobs J.R. Selenate fortification of infant formulas improves the selenium status of preterm infants. Am J Clin Nutr. 1996 Dec;64(6):860-5.
15. Smith A.M., Chen L.W., Thomas M.R. Selenate fortification improves selenium status of term infants fed soy formula. Am J Clin Nutr. 1995 Jan;61(1):44-7.
16. European Food Safety Authority. Scientific Opinion on dietary reference values for selenium. EFSA J. 2014 Oct;12(10):3846.
17. Ortman K., Andersson R., Holst H. The influence of supplements of selenite, selenate and selenium yeast on the selenium status of dairy heifers. Acta Vet Scand. 1999;40(1):23-34.
18. Burk R.F., Norsworthy B.K., Hill K.E., Motley A.K., Byrne D.W. Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial. Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):804-10.
19. Thomson C.D., Burton C.E., Robinson M.F. On supplementing the selenium intake of New Zealanders. 1. Short experiments with large doses of selenite or selenomethionine. Br J Nutr. 1978 May;39(3):579-87.
20. Alfthan G., Aro A., Arvilommi H., Huttunen J.K. Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate. Am J Clin Nutr. 1991 Jan;53(1):120-5.
21. Rayman M.P. The use of high-selenium yeast to raise selenium status: how does it measure up? Br J Nutr. 2004 Oct;92(4):557-73.
22. Bogye G., Alfthan G., Machay T., Zubovics L. Enteral yeast-selenium supplementation in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1998 May;78(3):F225-6.
23. Richie J.P. Jr., Das A., Calcagnotto A.M., Sinha R., Neidig W., Liao J., Lengerich E.J., Berg A., Hartman T.J., Ciccarella A., Baker A., Kaag M.G., Goodin S., DiPaola R.S., El-Bayoumy K. Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial. Cancer Prev Res (Phila). 2014 Aug;7(8):796-804.
24. Uden P.C., Boakye H.T., Kahakachchi C., Turner J. Element selective characterization of stability and reactivity of selenium species in selenized yeast. J. Anal. At. Spectrom. 2004 Jan:19(1):65–73.

Contributed by
Dr. Sandeep Ravindran
Freelance Science Writer
Sandeepr.com