Selenium Status and Risk of Non-Alcoholic Fatty Liver Disease

Data from an observational study done in the United States have shown the following relationships [Reja 2020]:

  • Upper right abdomen pain
    Liver pain is usually felt as a dull, throbbing pain in the upper right abdomen. NAFLD is the most common form of liver disease. It is characterized by the storing of too much fat in liver tissues, by inflammation, and by fibrosis. Liver fibrosis is a degenerative disease in which liver tissue is damaged and replaced by scar tissue.

    Higher serum selenium status is correlated with lower risk of advanced liver fibrosis.

  • This correlation is especially strong in liver disease patients who are elderly, who are non-Hispanic white, or who are female.
  • The patients with non-alcoholic fatty liver disease (NAFLD) who had higher serum selenium levels also had a 28% lower hazard ratio of death from all causes compared to the NAFLD patients with the lowest serum selenium levels.
Serum Selenium Levels and the Risk of Advanced Liver Fibrosis and All-Cause Mortality in NAFLD Patients
What was the study based on?

The data analyzed in the study came from 33,944 NAFLD patients identified in the Third National Health and Nutrition Examination Survey (NHANES).

What were the serum selenium levels in the study?

The researchers analyzed the severity of liver fibrosis in terms of the patients’ serum selenium levels divided into quartiles:

  • Quartile 1: less than 113 mcg/L
  • Quartile 2: 113 – 122 mcg/L
  • Quartile 3: 122 – 133 mcg/L
  • Quartile 4: greater than 133 mcg/L
What were the study outcomes?

NAFLD patients in the highest serum selenium quartile (greater than 133 mcg/L) had a 45 percent reduced risk of advanced liver fibrosis.

  • Women patients in the highest serum selenium quartile had a risk reduction of 68 percent.
  • Non-Hispanic white patients in the highest serum selenium quartile had a risk reduction of 59 percent.
  • Patients over 47 years of age in the highest serum selenium quartile had a risk reduction of 53 percent.
Take-Home Message: Selenium and Liver Disease

NAFLD patients with advanced liver fibrosis had lower levels of serum selenium.

  • Higher selenium intake and status play a role in the prevention of liver fibrosis in NAFLD patients.
  • Serum selenium levels are associated with a wide range of impacts on human health, in particular antioxidant effects and anti-inflammatory effects.
  • Selenium deficiency can have harmful effects including but not limited to advanced liver fibrosis and hepatocellular carcinoma [Reja 2020].
Additional Information About Selenium Status and Health
How do selenium levels in Europe and in the Middle East compare, generally, with selenium levels in the United States?

Serum selenium levels are generally considerably lower in much of Europe and the Middle East than in the much of the United States.

Data from the NHANES survey for 2003–2004 showed that the mean serum selenium concentration in U.S. adults aged 40 years or older is 136.7 mcg/L [Laclaustra 2010].

A review by Stoffaneller & Morse [2015] of 48 European/UK studies and 44 Middle East studies showed that suboptimal selenium status was widespread throughout Europe, the United Kingdom, and the Middle East. Suboptimal selenium status was defined as selenium levels below 90-100 mcg/L.

What is the healthy range for serum selenium levels?

Professor Margaret P. Rayman has suggested a U-shaped relationship between selenium status and health. In her graph, the beneficial range for serum selenium status is the range between 100 and 170 mcg/L [Rayman 2012, page 4, figure 3].

Hurst et al. [2010] report that serum Selenoprotein P levels have been identified as a functional biomarker for selenium status in several studies. Selenoprotein P is a plasma selenium transport protein with antioxidant activity.

The level of Selenoprotein P in the blood seems to plateau at a serum selenium level of greater than 125 mcg/L.

Thus, serum selenium levels of 125 mcg/L might be a useful target.

What levels of selenium supplementation are need to reach an optimal serum selenium status?

In a study of 119 healthy men and women aged 50–64 years living in the United Kingdom, Hurst et al. found the following relationships between selenium supplementation and steady-state selenium status:

In the KiSel-10 Study, Professor Urban Alehagen and a team of researchers administered 200 mcg/day of a selenium-enriched yeast preparation to elderly Swedish citizens (average age: 78 years) for four years.

  • The Swedish study participants had a mean selenium status of 67.1 mcg/L at the start of the study.
  • At the end of the 48-month supplementation period, the mean selenium status of the study participants had risen to 210.3 mcg/L [Alehagen 2020].
  • The daily supplementation of the Swedish senior citizens with a combination of 200 mcg of selenium and 200 mg of Coenzyme Q10 resulted in significant reductions in bio-markers of oxidative damage, systemic inflammation, and fibrosis [Alehagen 2018].
What form of selenium supplement gives the best results?

Richie et al. [2014] have shown that supplementation with a selenium-enriched yeast preparation results in a significant reduction in biomarkers of oxidative stress. Supplementation with equal quantities of 100% selenomethionine did not.

The study results suggest that the beneficial effects of the selenium supplementation vis-à-vis oxidative stress come from species of selenium other than selenomethionine.


Alehagen U, Aaseth J, Alexander J, Johansson P. (2020). Supplemental selenium and coenzyme Q10 reduce glycation along with cardiovascular mortality in an elderly population with low selenium status. Journal of Trace Elements in Medicine and Biology, 61: 126541.

Alehagen U, Aaseth J, Alexander J, Johansson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. PLoS One. 2018 Apr 11;13(4):e0193120.

Laclaustra M, Stranges S, Navas-Acien A, Ordovas JM, Guallar E. Serum selenium and serum lipids in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004. Atherosclerosis. 2010 Jun;210(2):643-8.

Rayman MP. Selenium and human health. Lancet. 2012;379(9822):1256–1268.

Reja M, Makar M, Visaria A, Marino D, Rustgi V. Increased serum selenium levels are associated with reduced risk of advanced liver fibrosis and all-cause mortality in NAFLD patients: National Health and Nutrition Examination Survey (NHANES) III. Ann Hepatol. 2020 Nov-Dec;19(6):635-640.

Richie JP Jr, Das A, Calcagnotto AM, Sinha R, Neidig W, Liao J, Lengerich EJ, Berg A, Hartman TJ, Ciccarella A, Baker A, Kaag MG, Goodin S, DiPaola RS, El-Bayoumy K. Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial. Cancer Prev Res (Phila). 2014 Aug;7(8):796-804.

Stoffaneller R, Morse NL. A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients. 2015 Feb 27;7(3):1494-537.

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

30 June 2021


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