Serum selenium level and heart disease

Dietary selenium intakes in the Nordic countries are generally quite low.  In Finland, the situation is different because, there, the government implemented a policy of selenium fertilization of the soil.  As a result, Finns have a much higher selenium intake than their Nordic neighbors. Unfortunately, there is not enough selenium available for every selenium-poor region in the world to use soil fertilization as a solution. Supplementation is the more efficient option.

Daily supplementation for four years with a high-selenium yeast tablet and two Coenzyme Q10 capsules reduced the risk of death from heart disease in elderly men and women aged 70-80 years at the time of enrollment into the KiSel-10 randomized controlled trial.  The effective dosages were 200 micrograms of selenium and 200 milligrams of Coenzyme Q10 (100 milligrams twice a day) [Alehagen 2013].

The daily supplementation also maintained good heart function as documented on echocardiograms and reduced the concentrations of bio-markers for oxidative damage and low-grade inflammation.  Best of all, the beneficial health effects of the selenium and Coenzyme Q10 persisted for up to ten years after the four-year supplementation [Alehagen 2015].

The KiSel-10 study results document the effect of the combined action of selenium and Coenzyme Q10 to protect heart muscle cells against the damage caused by harmful free radicals [Xia 2003].

Protection against heart disease and selenium status
Professor Urban Alehagen and a team of researchers at Linköping University in Sweden designed and carried out the KiSel-10 study.  More recently, they have gone back to do a secondary analysis of the study data.

Specifically, they have asked the question: are the beneficial heart health outcomes of the study dependent on the baseline selenium status of the elderly participants in the study? [Alehagen 2016]

What the Swedish researchers’ secondary analysis has revealed is interesting.

First: Documenting the generally low selenium status of the elderly people
First of all, the researchers documented that the selenium status in elderly Swedish citizens is generally low.  Selenium status sufficient to optimize the activity of the important selenoprotein SEPP1 is regarded as a good measure of sufficient selenium status.

In their study of healthy British men and women aged 50 – 64 years, Dr. Hurst et al documented that plasma selenoprotein SEPP1 concentrations start to plateau in the range 110 – 118 micrograms per liter [Hurst 2010].

By contrast, 90% of the KiSel-10 study participants had serum selenium levels below 85 micrograms per liter.  Nearly half, 45%, of the study participants had serum selenium levels below 65 micrograms per liter.

Only 1.6% of the participants in the KiSel-10 study had serum selenium concentrations adequate enough to optimize the activity of the SEPP1 selenoproteins [Alehagen 2016].

Remember: sufficient concentrations of selenium are needed not only to optimize the activity of the antioxidant selenoproteins glutathione peroxidase, thioredoxin reductase, and SEPP1.  Sufficient concentrations of selenium are also required to reduce the ubiquinone form of Coenzyme Q10 and to regenerate the ubiquinol form of Coenzyme Q10, thereby providing protection against the peroxidation of lipids and proteins [Xia 2003].  Coenzyme Q10 supplementation improved symptoms and survival of chronic heart failure patients in the Q-Symbio study.

Second: Classifying the baseline selenium levels in the KiSel-10 study
Professor Alehagen and the Swedish researchers divided the data from the supplemented group into three sub-groups based on the serum selenium concentrations of the participants at the start of the study:

  • Low: less than 65 micrograms per liter (45% of the group)
  • Medium: between 65 and 85 micrograms per liter (45% of the group)
  • High: above 85 micrograms per liter (only 10% of the group)

Note: High is a relative concept.  A serum selenium status of 85 micrograms per liter is high only in the context of the Swedish participants with generally low selenium status. Normally, we might think of 110-120 micrograms per liter and higher as being “high” selenium status.

Third: Raising the serum selenium concentrations via supplementation
Four years of daily supplementation with 200 micrograms of a high-selenium yeast SelenoPrecise® preparation resulted in almost all participants’ reaching more or less the same serum selenium status, regardless of the individual participants’ baseline level.

The post-treatment levels ranged from 185 to 245 micrograms of selenium per liter of serum [Alehagen 2016].

Fourth: Documenting significant heart health benefits in the lower two tertiles
Using the data from 98 of the study participants who had been in the supplemented group, the researchers showed that statistically significant reductions in the risk of dying from heart disease occurred in the lowest two sub-groups:

  • the below 65 micrograms per liter sub-group
  • the between 65 and 85 micrograms per liter sub-group

There was also a reduction in the risk of dying from heart disease in the high sub-group, the participants with a baseline serum selenium concentration above 85 micrograms per liter.  However, the reduction in risk did not reach the level of statistical significance.

There are a couple of possible explanations why the risk reduction in this sub-group did not achieve statistical significance:

  • the sample size was very small
  • the number of deaths in the high sub-group was low [Alehagen 2016]

The small sample size and the small number of events made it much more difficult to detect true population differences if true population differences exist at levels above 85 micrograms per liter.

Fifth: documenting the effect of selenium supplementation in low selenium status individuals
The greater the individual’s need for selenium supplementation was, i.e. the lower his or her baseline selenium status was in the KiSel-10 study, the greater and more pronounced was the effect of the selenium supplementation on heart health [Alehagen 2016].

If this sounds self-evident, perhaps it was and is.  But it is good to have scientific results from a well-designed study to back up the supposition.  We need more research into the question of when – at what levels of plasma or serum selenium concentration – the beneficial health effects of selenium supplementation begin to plateau.

Summing up the main points from the KiSel-10 study

  • The KiSel-10 study was a well-designed and well-run study that has yielded valuable scientific information about the heart health benefits of supplementation with selenium and Coenzyme Q10.
  • Daily supplementation raises serum selenium and Coenzyme Q10 concentrations to effective levels.
  • Daily supplementation reduces the risk of heart disease and the risk of death from heart disease.
  • Selenium and Coenzyme Q10 work together.

In the words of Professor Alehagen, individuals with sub-optimal levels of either Coenzyme Q10, selenium, or both will be at a higher risk of an adverse cardiovascular event.

Sources

Alehagen, U., Johansson, P., Björnstedt, M., Rosén, A., & Dahlström, U. (2013). Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. International Journal of Cardiology, 167(5), 1860-1866. doi:10.1016/j.ijcard.2012.04.156

Alehagen, U., Aaseth, J., & Johansson, P. (2015).  Reduced cardiovascular mortality 10 years after supplementation with selenium and coenzyme q10 for four years: follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly citizens. PLoS ONE 10(12): e0141641. doi:10.1371/journal.pone.0141641

Alehagen, U., Alexander, J., & Aaseth, J. (2016). Supplementation with selenium and Coenzyme Q10 reduces cardiovascular mortality in elderly with low selenium status. a secondary analysis of a randomised clinical trial. PLoS ONE 11(7):
e0157541. doi:10.1371/journal.pone.0157541

Alehagen, U., Johansson, P., Aaseth, J., Alexander, J., Wågsäter, D. (2017). Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.
PLoS ONE 12(4): e0174880. https://doi.org/10.1371/journal.pone.0174880

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.

Xia, L., Nordman, T., Olsson, J. M., Damdimopoulos, A., Björkhem-Bergman, L., Nalvarte, I., & Björnstedt, M. (2003). The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress. The Journal of Biological Chemistry, 278(4), 2141-2146.

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

Leave a Reply

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