Daily intakes of selenium

How much selenium from food and supplements do we need on a daily basis?  Which bio-markers of optimal selenium status seem to be most useful to answer this question?  Dr. Rachel Hurst and Dr. Susan J. Fairweather-Tait, Norwich Medical School, United Kingdom, and their colleagues set out to find answers.    The design of their study is very interesting.

They enrolled 119 healthy British men and women aged 50 – 64 years in a randomized, double-blind, placebo-controlled study that lasted 12 weeks [Hurst]. They excluded the following persons from the study:

• smokers
• overweight people
• people with already high plasma selenium status
• people with long-term illnesses
• people on various medications
• people unwilling to discontinue taking vitamins and herbal remedies at least one month prior to the start of the study

The 119 study participants received either placebo or one of the following treatments:

• selenium-enriched yeast tablets containing 50, 100, or 200 micrograms of a patented organic selenium (SelenoPrecise^® preparation delivered by Pharma Nord, Denmark)
• selenium-enriched onion meals that provided the equivalent of 50 micrograms of selenium per day
• unenriched onion meals that provided the equivalent of less than 4 micrograms of selenium per day

Measurements of selenium
Remember: Selenium is a trace element.  We measure its intake in micrograms per day, not milligrams.  We measure selenium status in plasma and serum in terms of micrograms per liter (or equivalently, in nanograms per milliliter).  Selenium in toenails or hair, then, we measure in micrograms per gram.

Results of the Hurst study of selenium status
The baseline plasma selenium concentrations of all the study participants had a mean of 95.7 micrograms per liter with a standard deviation of 11.5 micrograms per liter.  That means that roughly 68 percent of the study participants had plasma selenium concentrations that ranged between 84.2 and 107.2 micrograms per liter.  Roughly 95 percent of the study participants had plasma selenium concentrations that ranged between 72.7 and 118.7 micrograms per liter.

These are baseline plasma selenium concentrations that are somewhat higher than might be expected throughout the United Kingdom, which is generally known as a selenium-poor region of the world.

Please note: 95.7 micrograms per liter is the same concentration as 95.7 nanograms per milliliter (nanograms are micrograms divided by 1000; milliliters are liters divided by 1000).  You may see nanograms per milliliter when you read research reports.

After 10 weeks of supplementation, the Hurst study participants’ plasma selenium concentrations increased significantly from their baseline levels  to the following levels:

• 118.3 +/- 13.1 micrograms per liter for participants taking 50 micrograms of selenium daily
• 152.0 +/- 24.3 micrograms per liter for participants taking 100 micrograms of selenium daily
• 177.4 +/- 26.3 micrograms per liter for participants taking 200 micrograms of selenium daily

What happened after 10 weeks of selenium supplementation?
Plasma glutathione peroxidase activity did not change significantly.

Background note: The glutathione peroxidases (abbreviation: GPx) are selenoproteins.  They are enzymes whose primary biological function seems to be to serve as antioxidants and to prevent oxidative damage caused by harmful free radicals.

Actually, the researchers did not expect the plasma glutathione peroxidase levels to respond because the range in which plasma glutathione activity seems to reach optimal levels is thought to lie between 70 and 90 micrograms per liter. The study participants, most of them, were already at that level or above it when they started taking the selenium supplements.

Platelet glutathione peroxidase activity did not change significantly in response to any of the dosages or any of the forms of selenium supplementation of the diet.

Again, the researchers did not expect to see a significant response in platelet glutathione peroxidase activity – which is regarded as a more sensitive marker for selenium status than plasma glutathione peroxidase activity – because the mean baseline plasma selenium concentration of 95.7 micrograms per liter was within the assumed plateau for platelet glutathione peroxidase concentrations: 80 – 120 micrograms per liter.

Selenoprotein P levels did increase significantly in all of the organic high-selenium interventions.

The researchers’ conclusion: Plasma selenoprotein P is a more useful bio-marker of selenium status, at least in populations with relatively low selenium status (defined as less than 100 micrograms per liter) because selenoprotein P responds more sensitively to different dietary forms of selenium than the glutathione peroxidase does.

Background note: Supplemental selenium does not float around in the plasma or in the body tissues as a single element.  It is incorporated into the amino acids selenomethionine and selenocysteine.  The amino acid selenocysteine, then, is a vital constituent of the biologically active selenoproteins.

Selenoprotein P (abbreviation: SePP) is the most abundant selenoprotein in the blood in humans.  It makes up approximately 25-50 % of total plasma selenium.  The glutathione peroxidases are the second most abundant selenoproteins in the blood, typically comprising about 10-30 % of the total plasma selenium.  In addition to antioxidant function protecting cells against oxidative damage, selenoprotein P also has other important biological functions [Hurst]:

• reduces the risk of illness and death caused by infections
• reduces the risk of death from some cancers
• helps to maintain cell homeostasis

Selenium intakes and selenium status
Dr. Hurst and Dr. Fairweather-Tait and their colleagues estimated the common dietary intake of selenium in their study sample participants at approximately 55 micrograms per day.  Of course, there is considerable variation in dietary intakes of selenium in the general population.

But, assuming an average daily intake of 55 micrograms from food, then a minimum supplement of 50 – 100 micrograms per day would be necessary to optimize the plasma selenoprotein P concentration in people who are similar biochemically to the Hurst/Fairweather-Tait  study participants.

Needed selenium supplementation research
The Hurst/Fairweather-Tait study needs to be repeated in samples with the same characteristics and also in samples with different characteristics.  We need to see how much the increases in selenium status vary in accordance with different types of selenium supplements and with different study participant characteristics (including differences in the age and sex and ethnic background of the study participants).  We need more evidence to establish the association between plasma selenium status and the risk of cancer incidence and mortality, which is what interests us the most about selenium intakes.

Selenium supplements and cancer risk
We know from randomized controlled trials that supplementation with an organic high-selenium yeast preparation is associated with significant reductions of cancer risk [Blot, Clark, Yu].  Additionally, we know that supplementation with an organic selenomethionine supplement has been shown to reduce the risk of recurrent pre-cancerous adenomas in the colon [Bonelli].

Selenium supplements and risk of heart disease
Furthermore, supplementation with a combination of the same organic high selenium yeast preparation and a patented Coenzyme Q10 preparation reduced significantly the risk of death from heart disease [Alehagen].

Sources

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.

Blot, W.J., Li, J.Y., Taylor, P.R., Guo, W., Dawsey, S., Wang, G.Q., Yang, C.S., Zheng, S.F., Gail, M., Li, G.Y. (1993).  Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst, 85(18):1483-92.

Bonelli, L., Puntoni, M., Gatteschi, B., Massa, P., Missale, G., Munizzi, F., & Bruzzi, P. (2013). Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial. Journal of Gastroenterology, 48(6), 698-705.

Clark LC, Combs GF, Jr., Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 1996;276(24):1957-1963.

Hurst, R., Armah, C.N., Dainty J.R., Hart, D.J., Teucher, B., Goldson, A.J., Broadley, M.R., Motley, A.K., Fairweather-Tait, S.J.  (2010).  Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr, 91(4):923-31.

Reid ME, Duffield-Lillico AJ, Slate E, et al. The nutritional prevention of cancer: 400 μg per day selenium treatment. Nutr Cancer. 2008;60(2):155-163.

Yu SY, Zhu YJ, Li WG. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biol Trace Elem Res. 1997;56(1):117-124.