Selenoprotein P – Selenium Transport Protein and Biomarker of Selenium Status

Selenium and selenoproteins are essential to human health [Rayman 2012]. However, selenium intakes from food vary considerably from region to region in the world, depending on how rich or poor the soil and the foodstuffs are.

Selenium researcher Professor Urban Alehagen
Professor Urban Alehagen realized that the low selenium content of the soil in Sweden and in much of Europe results in wide-spread low dietary selenium intake and selenium deficiency. In the Swedish KiSel-10 Study, the average serum selenium concentration was a quite low 67 mcg/L.

For example, widespread suboptimal selenium status has been reported throughout Europe, the UK, and the Middle East [Stoffaneller & Morse 2015]. In contrast, the soil and the foodstuffs in much of the United States and Canada have a much higher selenium content than is the case in Europe. Serum selenium levels of US citizens are generally above 120 mcg/L. In many European countries, the corresponding serum selenium levels are 90 mcg/L on average [Alehagen 2016].

  • The best estimate for serum selenium status that is sufficient for good health is around 125 mcg/L [Winther 2020, fig. 3].
  • Serum selenium levels below 70 mcg/L are indicative of selenium deficiency [Bomer 2020].
  • Serum selenium levels below 100 mcg/L are indicative of sub-optimal selenium status [Al-Mubarak 2021].
Selenoprotein P as the Major Selenium Transport Protein

Dietary selenium is incorporated into the amino acid selenocysteine, which becomes an integral component of 25 selenoproteins. The best known selenoproteins are the glutathione peroxidases, thioredoxin reductases, and
iodothyronine deiodinases [Schomburg 2019].

Selenoprotein P is the most prominent selenoprotein in the blood circulation. Selenoprotein P is synthesized in the liver. It mediates the transport of selenium to the organs that are most important for survival and reproduction, e.g., to the brain and the endocrine glands. In times of low selenium supply, these organs are preferentially supplied [Schomburg 2022].

Selenoprotein P as a Biomarker of Selenium Status

Selenoprotein P is also a functional bio-marker for testing selenium status, at least until selenoprotein P levels reach a plateau. Clinical studies have shown close associations between low circulating selenoprotein P concentrations and health risks [Schomburg 2022].

  • In the Swedish Malmö Preventive Project cohort study, researchers found that selenoprotein P deficiency predicted greater risk of cardiovascular disease and death [Schomburg 2019].
  • In the Swedish SCAN-B Study, three complementary serum selenium status biomarkers – total serum selenium, serum selenoprotein P, and serum glutathione peroxidase activity — correlated inversely with mortality and with recurrence in patients diagnosed with breast cancer. The prediction of mortality based on all three biomarkers outperformed prediction of mortality based on tumor size and characteristics and the number of affected lymph nodes [Demircan 2021].
  • In a German study, low total serum selenium levels and low serum selenoprotein P levels were significantly associated with mortality risk from COVID-19 [Moghaddam 2020].
  • In a Swedish acute heart failure cohort study, researchers measured plasma selenoprotein P concentrations. They found that each one standard deviation increase in plasma selenoprotein P was associated with a reduced risk of 1) poor health-related quality of life, 2) 30-day re-admission to hospital, and 3) mortality [Jujic 2019].

Note: The above-mentioned studies have been conducted in Sweden and Germany, countries with selenium-poor soils and insufficient selenium intakes [Alehagen 2016; Muecke 2018].

Testing for Selenium Status

Selenium researchers have suggested that a three-pronged approach to testing selenium status is preferable to testing only the total selenium concentration in serum.

These researchers go further and test for the concentration of selenoprotein P in serum and for the extent of glutathione peroxidase activity in serum. For example, in the SCAN-B Study, these three complementary serum selenium status biomarkers correlated inversely with mortality and with recurrence in patients diagnosed with breast cancer [Demircan 2021].

Conclusion: Selenoprotein P as a Biomarker for Low Selenium Status

Selenoprotein P is the primary transporter of selenium to the target organs in the body [Schomburg 2022].

Plasma or serum concentrations of selenoprotein P are a useful biomarker of selenium status in populations with relatively low selenium intakes because selenoprotein P responds to different dietary forms of selenium [Hurst 2010].

The plasma/serum total selenium concentration needed for selenoprotein P activity to reach a plateau is estimated to be somewhat greater than 125 mcg/L [Hurst 2010].

In individuals with low to moderate selenium status, i.e., less than 100 mcg/L, the serum selenoprotein P levels tightly correlate with selenium intake and selenium status. However, when individuals reach a replete selenium status, the linear correlation between serum selenium status and serum selenoprotein P levels ceases. A saturated selenoprotein P expression plateau extends over selenium intake levels from approximately 100 to 300 mcg/day [Schomburg 2022, fig. 6].

Note that EFSA has set the tolerable upper limit for selenium intakes at 255 mcg/day [EFSA 2023].

A supplemental selenium intake of 50 mcg/day from a selenium yeast preparation optimized the plasma selenoprotein P concentrations in healthy British men and women aged 50-64 years. The study participants had an average daily intake of 55 mcg of selenium from food and a pre-supplementation total serum selenium level of 95 mcg/L [Hurst 2010].

Sources

Al-Mubarak AA, van der Meer P, Bomer N. Selenium, Selenoproteins, and Heart Failure: Current Knowledge and Future Perspective. Curr Heart Fail Rep. 2021 Jun;18(3):122-131.

Alehagen U, Johansson P, Björnstedt M, Rosén A, Post C, Aaseth J. Relatively high mortality risk in elderly Swedish subjects with low selenium status. Eur J Clin Nutr. 2016 Jan;70(1):91-6.

Bomer N, Grote Beverborg N, Hoes MF, Streng KW, Vermeer M, Dokter MM, IJmker J, Anker SD, Cleland JGF, Hillege HL, Lang CC, Ng LL, Samani NJ, Tromp J, van Veldhuisen DJ, Touw DJ, Voors AA, van der Meer P. Selenium and outcome in heart failure. Eur J Heart Fail. 2020 Aug;22(8):1415-1423.

Demircan K, Bengtsson Y, Sun Q, Brange A, Vallon-Christersson J, Rijntjes E, Malmberg M, Saal LH, Rydén L, Borg Å, Manjer J, Schomburg L. Serum selenium, selenoprotein P and glutathione peroxidase 3 as predictors of mortality and recurrence following breast cancer diagnosis: A multicentre cohort study. Redox Biol. 2021 Nov;47:102145.

EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA); Turck D, Bohn T, Castenmiller J, de Henauw S, Hirsch-Ernst KI, Knutsen HK, Maciuk A, Mangelsdorf I, McArdle HJ, Peláez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Aggett P, Crous Bou M, Cubadda F, Ciccolallo L, de Sesmaisons Lecarré A, Fabiani L, Titz A, Naska A. Scientific opinion on the tolerable upper intake level for selenium. EFSA J. 2023 Jan 20;21(1):e07704.

Hurst R, Armah CN, Dainty JR, Hart DJ, Teucher B, Goldson AJ, Broadley MR, Motley AK, Fairweather-Tait SJ. Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2010 Apr;91(4):923-31.

Jujić A, Melander O, Bergmann A, Hartmann O, Nilsson PM, Bachus E, Struck J, Magnusson M. Selenoprotein P Deficiency and Risk of Mortality and Rehospitalization in Acute Heart Failure. J Am Coll Cardiol. 2019 Aug 20;74(7):1009-1011.

Moghaddam A, Heller RA, Sun Q, Seelig J, Cherkezov A, Seibert L, Hackler J, Seemann P, Diegmann J, Pilz M, Bachmann M, Minich WB, Schomburg L. Selenium deficiency is associated with mortality risk from COVID-19. Nutrients. 2020 Jul 16;12(7):2098.

Muecke R, Micke O, Schomburg L, Buentzel J, Kisters K, Adamietz IA; AKTE. Selenium in radiation oncology-15 years of experiences in Germany. Nutrients. 2018 Apr 13;10(4):483.

Rayman MP. Selenium and human health. Lancet. 2012 Mar 31;379(9822):1256-68.

Schomburg L. Selenoprotein P – Selenium transport protein, enzyme and biomarker of selenium status. Free Radic Biol Med. 2022 Oct;191:150-163.

Schomburg L, Orho-Melander M, Struck J, Bergmann A, Melander O. Selenoprotein-P Deficiency Predicts Cardiovascular Disease and Death. Nutrients. 2019 Aug 9;11(8):1852.

Stoffaneller R, Morse NL. A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients. 2015 Feb 27;7(3):1494-537.

Winther KH, Rayman MP, Bonnema SJ, Hegedüs L. Selenium in thyroid disorders – essential knowledge for clinicians. Nat Rev Endocrinol. 2020 Mar;16(3):165-176.

The information presented in this review article is not intended as medical advice and should not be used as such.

15 April 2023

Leave a Reply

Your email address will not be published. Required fields are marked *