Selenium and Selenoprotein P and Mortality

Higher all-cause mortality and higher mortality due to cancer, cardiovascular disease, gastrointestinal diseases, and respiratory disorders are associated with lower serum selenoprotein P concentrations in older German adults [Schöttker 2024].

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Death from all causes and death specifically caused by cancer, cardiovascular disease, gastrointestinal diseases, and respiratory disorders are strongly associated with low serum concentrations of the selenium-dependent selenoprotein P.

In plain English, lower blood concentrations of the selenium-dependent selenoprotein P are significantly associated with a higher risk of degenerative disease progression and with dying. Moreover, the data from the German study show that the risk of dying associated with low blood Selenoprotein P levels was more than double in men compared to women [Schöttker 2024].

In the Esther Study, German researchers assessed the association of measurements of serum Selenoprotein P concentrations with all-cause and cause-specific mortality data. They measured serum Selenoprotein P at baseline and again at a 5-year follow-up in 7,186 and 4,164 participants, respectively [Schöttker 2024].

Strong Association of Serum Selenoprotein P with Mortality

The study participants were part of a population-based cohort aged 50-74 years at baseline. At the start of the study, the mean age of the study participants was 62.3 years. Nearly half of the participants were male (45%) [Schöttker 2024].

During 17.3 years of follow-up, 2,126 study participants (30%) died. The relationship of serum Selenoprotein P concentration with all-cause mortality was L-shaped. By L-shaped, the researchers mean that the graph of the all-cause mortality (y-axis) is falling as the serum selenoprotein P level (x-axis) is rising from 2.0 to 5.0 mg/L. Then, at concentrations of 5.0 mg/L and above, the all-cause mortality rate levels off [Schöttker 2024].

  • Mortality was significantly higher, 35% higher, at Selenoprotein P concentrations less than 4.2 mg/L.
  • All-cause mortality of study participants in the bottom Selenoprotein P tertile was significantly increased compared to study participants in the top tertile.
  • Study participants in the bottom Selenoprotein P tertile were at risk of increased cardiovascular mortality, increased cancer mortality, increased gastrointestinal disease mortality, and increased respiratory disease mortality.
  • The increased risk of all-cause mortality for study participants in the bottom Selenoprotein P tertile was more than twice as strong in men as in women.
Why Is Selenoprotein P Important for Good Health and Longevity?

Selenoprotein P is synthesized in the liver. It is the most prominent selenoprotein in the blood. It is the primary carrier of selenium to the cells and tissues. In times of inadequate selenium intake, it mediates selenium transport to essential tissues such as the endocrine glands (especially the testes) and the brain, which have privileged status in the selenium need hierarchy in the human body. Note that organs that are important for survival and for reproduction have a higher priority for selenium [Schomburg 2022].

Many clinical studies point to close links between low circulating Selenoprotein P levels and disease risks. Accordingly, serum Selenoprotein P concentrations serve as a valid functional biomarker of selenium supply, at least up to the achievement of saturated status at which Selenoprotein P levels reach a plateau [Schomburg 2022].

Selenium Unevenly Distributed Around the World

Selenium is an essential trace element. Humans cannot synthesize it. It must come from the diet. Unfortunately, the dietary intake of selenium varies considerably around the world. As a consequence, many people are at risk of inadequate selenium intakes and at risk of disease related to selenium deficiency [Schomburg 2022].

Available evidence indicates that serum selenium concentrations should be in the range 120-130 mcg/L in order to optimize the concentration of Selenoprotein P in the blood. A combined dietary and supplemental selenium intake of at least 100 mcg per day is needed to raise serum selenium concentrations to this desired level [Kipp 2015; Winther 2020].

Note that, by comparison, the mean serum selenium concentration was 68  mcg/L in the Lipid Analytic Cologne cohort in Germany [Berthold 2012].
Factors associated with low circulating Selenoprotein P status include the following [Schöttker 2024]:

  • older age
  • male sex
  • higher BMI
  • lower physical activity level
  • no or very high alcohol consumption
  • current smoker
  • chronic systemic inflammation
  • vitamin D deficiency or insufficiency
Selenium and Disease and Possible Reverse Causality?

Question: Do low levels of selenoprotein P cause disease development and progression and eventually death, as we think? Or, could it be that the progression of disease is the real cause of death and the low selenoprotein P concentrations are not involved? Could it be that the disease is causing both death and reduced concentrations of selenoprotein P?

In the Esther study, the researchers conducted separate analyses of the data to address this question of a possible reverse causality. For example, they excluded disease events that occurred in the first nine years of follow-up. These disease events could have been caused by already existing (and not diagnosed) diseases at baseline. The results of the analysis of the data after nine months showed that the strong relationship between selenoprotein P concentration and all-cause mortality was unchanged. The results for cancer mortality were stronger than in the main analysis [Schöttker 2023].

Conclusion: Selenium and Selenoprotein P and Mortality

In the Esther Study of older German adults, researchers found a strong association between serum levels of Selenoprotein P and all-cause and cause-specific mortality [Schøttker 2024].

  • Study participants in the lowest tertile of serum Selenoprotein P concentrations – below 4.2 mg/L – were at significantly higher risk of dangerous disease progression and death [Schøttker 2024].
  • At baseline, the Esther Study participants had a mean serum Selenoprotein P concentration of 4.8 mg/L. Five years into the study, they had a mean serum Selenoprotein P concentration that had fallen to 3.9 mg/L [Schöttker 2024]. These serum Selenoprotein P concentrations are roughly equivalent to serum selenium concentrations of 90 mcg/L and 72 mcg/L, respectively, well below that 120-130 mcg/L selenium concentrations needed for optimal Selenoprotein P activity.

Berthold H.K., Michalke B., Krone W., Guallar E., Gouni-Berthold I. Influence of serum selenium concentrations on hypertension: The Lipid Analytic Cologne cross-sectional study. J. Hypertens. 2012;30:1328–1335.

Kipp AP, Strohm D, Brigelius-Flohe R, Schomburg L, Bechthold A, Leschik-Bonnet E, Heseker H. Revised reference values for selenium intake. Journal of Trace Elements in Medicine and Biology. 2015;32:195-9.

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

Schöttker B, Holleczek B, Hybsier S, Köhrle J, Schomburg L, Brenner H. Strong associations of serum selenoprotein P with all-cause mortality and mortality due to cancer, cardiovascular, respiratory and gastrointestinal diseases in older German adults. Eur J Epidemiol. 2024 Jan 10. doi: 10.1007/s10654-023-01091-4. Epub ahead of print.

Winther KH, Rayman MP, Bonnema SJ, Hegedus L. Selenium in thyroid disorders – essential knowledge for clinicians. Nature Reviews Endocrinology. 2020;16:165-76.

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

30 January 2024

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