Low serum selenium status and increased mortality

Too few studies have investigated the relationship between low serum selenium status and negative health effects. Professor Urban Alehagen from Linköping University in Sweden has published the results of a study showing that low serum selenium status is significantly associated with increased cardiovascular and all-cause mortality.

During an almost seven-year follow-up period, elderly healthy Swedish citizens with low serum selenium concentrations had significantly increased cardiovascular mortality and total mortality rates compared to contemporaries with higher serum selenium concentrations.  Specifically, there was a 56% increased risk for cardiovascular mortality and a 43% increased risk for all-cause mortality.  Accordingly, the Swedish researchers suggested that selenium supplementation should be recommended to all Swedish citizens with a serum selenium concentration below 57 micrograms per liter [Alehagen 2016].

In fact, Professor Urban Alehagen and his team of researchers at Linköping University pointed out that the average serum selenium concentrations observed in the study of elderly Swedish citizens – 67.1 micrograms per liter – is not sufficient to achieve optimal function of the important selenoproteins that require selenium as a component [Alehagen 2016]:

  • the glutathione peroxidases
  • the thioredoxin reductases
  • the selenoproteins P (SEPP1)

These selenoproteins protect tissues from the harmful effects of oxidative stress and protect endothelial functions [Rayman 2012].

Supplementation with selenium and Coenzyme Q10 combination

In the KiSel-10 study, the Swedish researchers randomly assigned the study participants to an active treatment group receiving 200 micrograms of a high-selenium yeast preparation and 200 milligrams of a pharmaceutical-grade Coenzyme Q10 preparation.  The study participants in the active treatment group had significantly better health outcomes compared to study participants in the placebo group.  The beneficial effects persisted through a ten-year period [Alehagen 2015]:

  • reduced risk of death from heart disease
  • improved heart function as monitored on echocardiograms
  • reduced levels of a bio-marker for heart failure

Daily selenium intakes and optimal SEPP1 activity

Hurst et al [2010] in the United Kingdom have estimated that a total selenium intake of approximately 105 micrograms per day is required to achieve optimal SEPP1 activity.  In the UK, that would translate to approximately 55 micrograms from food and 50 micrograms from a selenium supplement.  In their work, Hurst et al concluded that the beneficial range for the concentration of selenium in plasma is the range between 120 and 150 micrograms per liter [Hurst 2010].

It is important to remember that the soil content of selenium and thus the food intake of selenium varies considerably in various regions of the world.  It is a good idea to have a serum selenium test done to see whether one needs 50 or 100 micrograms per day from supplements.

Selenium levels and oxidative stress

Oxidative stress is the bio-medical term for the potential damage to cells, lipids, proteins, and DNA caused by free radicals whenever the number of free radicals greatly exceeds the number of neutralizing antioxidants.

Thus, one possible explanation for the significant association between low serum selenium concentrations and increased cardiovascular and total mortality is the known increased oxidative stress in patients with ischemic heart disease and heart failure.  Insufficient levels of selenoproteins will result in a less than optimal anti-oxidative defense against free radicals, which could explain the increased mortality rates in elderly people with low serum selenium levels [Alehagen 2016].

The explanation involving sub-optimal selenoprotein activity as it relates to inadequate anti-oxidative defense seems especially plausible because the Swedish researchers adjusted for the modifying effects of other known clinical conditions associated with increased risk of mortality.  For example, the researchers measured the levels of two bio-markers for inflammation across the four quartiles of study participants and did not find significant differences between the lowest serum selenium quartile and the higher serum selenium quartiles [Alehagen 2016]:

  • high-sensitivity C-reactive protein levels
  • soluble P-selectin protein levels

Serum selenium concentrations and smoking

Current smokers in the study did have lower serum selenium levels than non-smokers, but the difference was not statistically significant.  Professor Alehagen thought that the lack of a significant difference might be attributed to the low number of smokers in the study (only 9% of all participants).  Some studies have found decreased selenium levels in smokers; other studies have failed to find an association between smoking and selenium level [Alehagen 2016].

Serum selenium concentrations and cancer mortality

In this Swedish study, there was no significant difference in cancer mortality between the lowest selenium concentration quartile and the quartiles with somewhat higher selenium concentrations [Alehagen 2016].

Association of serum selenium levels and heart disease

Earlier studies have also shown a significant association between low serum selenium status and increased risk of cardiovascular disease:

  • A Danish study of more than 3000 males showed that serum selenium concentrations below 60 micrograms per liter are associated with increased risk of ischemic heart disease [Suadicani 1992].
  • A Finnish case-control study showed that serum selenium levels of less than 45 micrograms per liter are associated with an increased risk of fatal and non-fatal heart attacks [Salonen 1982].
  • A French study, a nine-year longitudinal study, showed an association between low plasma selenium levels and increased mortality [Akbaraly 2005].

Conclusion

We need more studies of the effect of selenium status and selenium supplementation on positive health outcomes.  The studies we do have indicate that adequate serum selenium status plays a role in the maintenance of good health in elderly individuals.

The research data from the KiSel-10 study show that the supplementation of low selenium status individuals with a combination of selenium-enriched yeast and Coenzyme Q10 improves mortality and quality of life [Alehagen 2015].

Sources

Akbaraly, N. T., Arnaud, J., Hininger-Favier, I., Gourlet, V., Roussel, A., & Berr, C. (2005). Selenium and mortality in the elderly: results from the EVA study. Clinical Chemistry, 51(11), 2117-2123.

Alehagen, U., Johansson, P., Björnstedt, M., Rosén, A., Post, C., & Aaseth, J. (2016). Relatively high mortality risk in elderly Swedish subjects with low selenium status. European Journal of Clinical Nutrition, 70(1), 91-96. doi:10.1038/ejcn.2015.92

Hurst, R., Armah, C. N., Dainty, J. R., Hart, D. J., Teucher, B., Goldson, A. J., & Fairweather-Tait, S. J. (2010). Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. The American Journal of Clinical Nutrition, 91(4), 923-931.

Rayman, M.P. (2012). Selenium and human health.  Lancet, 379, 1256-1268.

Salonen, J. T., Alfthan, G., Huttunen, J. K., Pikkarainen, J., & Puska, P. (1982). Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet (London, England), 2(8291), 175-179.

Suadicani, P., Hein, H. O., & Gyntelberg, F. (1992). Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males. Atherosclerosis, 96(1), 33-42.

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

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