Regional, age, and sex differences in serum selenium status

Selenocysteine is the 21st amino acid. The trace element selenium plays its important biological roles in the body as a component of selenocysteine. Selenocysteine is found in at least 25 selenoproteins including selenoprotein P and the various glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases.

The results of clinical studies give us an estimate of what an individual’s optimal serum or plasma selenium status is.

  •  Plasma selenium status below 100 micrograms per liter  – also expressed as 100 nanograms per milliliter – is generally regarded as sub-optimal plasma selenium status [Hurst 2010].
  • Plasma selenium status of at least 110 – 118 micrograms per liter is considered necessary for the optimal expression of selenoprotein P [Hurst 2010]. 
  • Letsiou et al [2014] set the lower limit for optimal selenoprotein P activity at 120 micrograms per liter or higher.
  • Plasma selenium status of 120 up to 170 micrograms per liter is considered necessary for reducing the risk of prostate cancer [Hurst 2012].
  • Studies show that there are sex and age differences in the absorption and distribution of selenium taken in from the diet and from supplements [Letsiou 2014; Galan 2005].

Note: The Mayo Medical Laboratories report serum concentrations of 70 to 150 micrograms per liter as the adult reference range for residents of the United States.  The mean population serum concentration is 98 micrograms per liter [Mayo], but, remember, depending on the range and standard deviation of the data, the mean can be very little useful. The important thing about the United States is that there is regional variation in selenium intakes and status. See below.

Selenium intake and selenium status

The primary sources of selenium are the diet and supplements. The human body does not synthesize selenium.  It is difficult to calculate accurately how much selenium an individual gets from food.  It can also be difficult to know precisely how much selenium an individual absorbs from a supplement because of the variation in the form and formulation of the selenium supplements on the market.

Consequently, it is easier for researchers to test for associations between specific plasma (or serum) selenium concentrations and specific health outcomes.

High-selenium yeast supplements best

Individuals with low selenium status will want to choose a high-selenium yeast supplement – sometimes called a selenized yeast supplement – with a documented stable absorption rate of close to 90% and a documented stable retention rate of close to 75% [Bügel].  A comparative study has shown that a selenized yeast supplement reduces the levels of bio-markers for lipid peroxidation and oxidative damage to DNA while an exclusively selenomethionine supplement does not [Richie 2014].

Regional variation in selenium intakes and status

North America:

There are both high selenium and low selenium regions.  The following regions have low-selenium soils and, consequently, lower selenium levels in the food and forage crops grown there [National Research Council]:

  • the Pacific Northwest of the United States
  • the northeastern United States
  • the South Atlantic seaboard of the United States
  • the border region of Arizona and New Mexico
  • northern and eastern Canada


A systematic review published in 2015 concluded that sub-optimal selenium status is widespread throughout Europe, with people in Eastern European countries generally having even lower selenium intakes than people in Western European countries.  That conclusion about sub-optimal selenium intakes in Europe includes the people in the United Kingdom but excludes Finland where an extensive soil fertilization with selenium program has increased the daily intake of selenium [Stoffaneller & Morse 2015].

Middle East:

The 2015 systematic review shows that studies of selenium intakes and status in Middle Eastern countries give varying results – because of differences in food importation patterns and differences in eating habits – but generally reveal sub-optimal selenium status in the Middle East as well [Stoffaneller & Morse 2015].

The rest of the world:

Large regions of the rest of the world seem to have sub-optimal levels of selenium in their food production systems, but additional mapping is needed [Haug]:

  • China: in a belt running from north-east to south-central China
  • Africa: large regions of sub-Saharan Africa
  • Australia: both high-selenium and low-selenium regions
  • New Zealand: low-selenium regions
  • Asia and Latin America: sub-optimal selenium content in the food production systems of many countries similar to the situation in much of Europe [Haug 2007]

Age and sex may affect total selenium status

Total selenium status:

Researchers in a Greek study grouped the results from the study participants in tertiles of total selenium status. The selenium content of three important selenoproteins increased from the lowest to the highest tertile of total selenium status.

  • Glutathione peroxidase (GPx)
  • Selenoprotein (Sel-P)
  • Selenoalbumin (SeAlb)

However, there were sex-significant differences in selenium distribution in the lowest selenium status tertile: the sub-group with selenium status of less than 73 micrograms per liter.  In the middle and high tertiles, the distribution to the selenoproteins was similar for male and female study participants [Letsiou 2014].

Specifically, in the low tertile group, there was preferential distribution of selenium to GPx selenoproteins but only in males.  The researchers speculated that this sex-specific distribution might be attributed to the worse cardio-metabolic profile of males or to endocrinological differences between the sexes [Letsiou 2014].

It is not known why males prefer to distribute selenium to GPx selenoproteins and females prefer, slightly but significantly, to distribute selenium to the SeAlb selenoproteins.  The variations in the distribution of selenium may be caused by genetic differences or by biochemical and clinical differences [Letsiou 2014].


The Greek study showed a significant decline of total selenium status with increasing age.  The decline in total selenium status began to kick in at 35-45 years of age.

There was a sex-specific aspect to the relationship between age and selenium status.  In males, there was not a decline in GPx levels corresponding to the declines in total selenium status.  In females, there was a decline in GPx levels parallel to the declines in total selenium status.  For unexplained reasons, males but not females try to maintain adequate GPx levels even at declining levels of total selenium with increasing age [Letsiou 2014].

An Italian study showed that the age-related decline in selenium status is especially noticeable in men over 60 years [Morisi 1989].


Smoking was associated with lower total selenium status, lower selenium-GPx ratios, and lower selenium-Sel-P ratios but only in male study participants.  In the Greek study, male smokers and male non-smokers had the same diets.  Smokers had higher levels of low-grade systemic inflammation [Letsiou 2014].

Similarly, in the French Su.Vi.Max. study, smoking was associated with lower serum selenium levels [Galan 2005].

Physical activity:

There was also a sex-specific difference in the association between selenium status and physical activity.  Sedentary males had small but significant – about 10% — decreases in selenium status compared to physically active males.

Sedentary and physically active females, on the other hand, showed similar selenium profiles.

There remains the question of whether age and/or menopausal status might complicate the association between physical activity and selenium status [Letsiou 2014].

Body mass index:

The results of the Greek study show that, in males only, there is a sex-specific inverse association between body mass index and selenium status.  This inverse relationship persists even when the researchers control for such variables as age and high blood pressure and high blood sugar [Letsiou 2014].


Education level has not been studied much, possibly because education level itself can be associated with effect modification variables such as diet, physical activity, and social-economic status.


The effect of diet is difficult to assess because the data are based on study participants’ self-reports; furthermore, selenium content in foodstuffs varies from region to region and from season to season. Males eat more than females, but their total selenium status does not increase accordingly [Letsiou 2014].

Alcohol consumption:

In the French Su.Vi.Max. study, alcohol consumption was associated with higher serum selenium concentrations [Galan 2005].


  • The level of serum or plasma selenium is dependent upon diet and supplementation.
  • The distribution of selenium to selenoproteins is variable depending on the levels of total selenium and on age and sex.
  • The ratio of total selenium to specific selenoproteins, in turn, may be relevant to the understanding of the association between selenium status and various diseases [Letsiou 2014].
  • The results of the Nutritional Prevention of Cancer (NPC) study show that sex has a strong effect modification of selenium supplementation on cancer incidence.  For example, the Hazard Ratio for all cancers associated with selenium supplementation was a significant negative 0.67 in men and a positive 1.20 women.  That is to say, the 33% fewer men and 20% more women on selenium supplements got cancer compared to men and women on placebo supplements [Vinceti 2018].
    Remember: three-fourths of the study participants enrolled in the NPC study were men.

Randomized assignment of study participants to the selenium supplementation group or to the placebo control group together with the drawing of large enough samples is intended to reduce the risk of confounding or effect modification.  However, such variables as age, sex, physical activity, smoking, and alcohol use can conceivably magnify or reduce the effect size.

There are always the nagging questions:

  • Is there too much heterogeneity in the sample of study participants being tested?
  • Could age, sex, physical activity, etc. be affecting the outcome?
  • If the study is done using primarily men, can the results be generalized to women?
  • If the study is done using primarily middle-aged individuals, can the results be generalized to elderly individuals?

The best thing to do – if funding permits – is to draw large enough samples that the study will have power to examine the associations in sub-groups characterized by age, gender, physical activity, etc.


Bügel, S., Larsen, E. H., Sloth, J. J., Flytlie, K., Overvad, K., Steenberg, L. C., & Moesgaard, S. (2008). Absorption, excretion, and retention of selenium from a high selenium yeast in men with a high intake of selenium. Food & Nutrition Research, 52doi:10.3402/fnr.v52i0.1642

Galan, P., Viteri, F. E., Bertrais, S., Czernichow, S., Faure, H., Arnaud, J., & … Hercberg, S. (2005). Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population. European Journal of Clinical Nutrition, 59(10), 1181-1190.

Haug, A., Graham, R. D., Christophersen, O.A., & Lyons, G.H. (2007). How to use the world’s scarce selenium resources efficiently to increase the selenium concentration in food. Microb Ecol Health Dis., 19(4): 209–228. Published online 2007 Nov 27. doi:  10.1080/08910600701698986

Letsiou, S., Nomikos, T., Panagiotakos, D. B., Pergantis, S. A., Fragopoulou, E., Pitsavos, C., & … Antonopoulou, S. (2014). Gender-specific distribution of selenium to serum selenoproteins: associations with total selenium levels, age, smoking, body mass index, and physical activity. Biofactors (Oxford, England), 40(5), 524-535. doi:10.1002/biof.1176

Mayo Medical Laboratories. (2018).  Test ID: Selenium, Serum.  Mayo Clinic.  Retrieved from

Morisi G, Patriarca M, Marano G, Giampaoli S, Taggi F. Age and sex specific reference serum selenium levels estimated for the Italian population. Annali Dell’istituto Superiore Di Sanita [serial online]. 1989;25(3):393-403. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed March 5, 2018.

National Research Council. (1983). Selenium in Nutrition: Revised Edition. Washington, DC: The National Academies Press.

Richie, J. J., Das, A., Calcagnotto, A. M., Sinha, R., Neidig, W., Liao, J., & … El-Bayoumy, K. (2014). Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial. Cancer Prevention Research (Philadelphia, Pa.), 7(8), 796-804. doi:10.1158/1940-6207.CAPR-14-0042

Stoffaneller, R. & Morse, N. (2015). A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients, 7(3): 1494–1537.

Vinceti, M., Filippini, T., Del Giovane, C., Dennert, G., Zwahlen, M., Brinkman, M., & … Crespi, C. M. (2018). Selenium for preventing cancer. The Cochrane Database Of Systematic Reviews, 1CD005195. doi:10.1002/14651858.CD005195.pub4

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

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