Serum Selenium Status and Cancer Risk

On its Selenium: Fact Sheet for Health Professionals website, the US Office of Dietary Supplements, an agency of the National Institutes of Health, writes that selenium might play a role in the prevention of cancer for the following reasons:

  • selenium’s role in DNA repair
  • selenium’s role in apoptosis
  • selenium’s role in the endocrine and immune systems
  • the antioxidant properties of certain selenoproteins
Cancer prevention ribbons
It is not possible to draw any conclusions regarding a causal link between selenium exposure/status and the prevention of cancer. However, numerous observational studies show an inverse relationship between serum selenium status and the risk of cancer.
Different Selenium Compounds Have Different Effects on Cancer

The evidence from scientific research into the effect of selenium on cancer prevention can be confusing. Two observations about selenium supplementation may help to explain the confusing results from existing selenium and cancer studies:

1. Different selenium containing compounds differ widely in their ability to prevent cancer. Study results may vary according to the form of the selenium supplement tested.

2. Selenium supplementation may be more effective at cancer prevention in study participants with low baseline selenium status (below 100 mcg/L) and less effective in study participants with high baseline selenium status (above 135 mcg/L). read more

Selenium Supplementation and Prostate Cancer

New Zeland landscape
The New Zealand study results suggest that each of us needs to take personalized selenium supplement dosages based on our individual characteristics rather than have all of us take the same 200 microg/day tablet for prostate health benefits [Karunasinghe 2019].
Demographic, dietary, genetic, and life style factors influence the prostate health effects of selenium supplementation according to New Zealand researchers.

An inverse association between serum selenium concentrations and prostate-specific antigen levels was especially strong in the following sub-groups of study participants [Karunasinghe 2019]:

  • men below the age of 55 years
  • men who never smoked
  • men carrying the GPX1 rs1050450 T allele
  • men with dietary intakes above the recommended daily intake for zinc (11 mg)
  • men with dietary intakes below the recommended daily intake for vitamin B12 (15 mcg)

Moreover, the increase in serum selenium status and the resulting post-supplementation serum selenium status were significantly dependent upon baseline serum status [Karunasinghe 2019].

The overall gain in serum selenium levels from supplementation declined at a rate of 0.828 microg/L with each one microg/L increase in baseline serum selenium level [Karunasinghe 2019]. read more

Selenium Intakes and the Risk of Cancer: Two Meta-Analyses

Blue ribbon for prostate cancer
Despite the billions of dollars spent in the war on cancer, cancer in its various forms continues to be a leading cause of death worldwide. Treatment is expensive. The prognosis is often poor. Even so, the World Health Organization estimates that perhaps one third of all cancer cases could be prevented with changes in behavioral and dietary patterns. An inverse linear association has been found between increased selenium intake and reduced risk of all cancers. As the selenium intake increased, the overall risk of cancer incidence decreased [Kuria 2020].
A 2020 meta-analysis of population-based prospective studies shows that selenium supplementation is protective against cancer; however, the beneficial effects of the selenium supplementation vary with the different types of cancer. The differences in the effect of selenium intakes on the risk of various cancer forms has been attributed to differences in the pathophysiology of cancer [Kuria 2020].

Briefly, the data from the meta-analysis show that selenium decreases the risk of cancer at the highest daily intake levels of the included studies.

This outcome is consistent with the outcomes of a previous study showing a protective effect of selenium at high doses compared to low doses [Cai 2016]. A 2018 meta-analysis used different methods to assess selenium exposure and showed a null association between selenium at high doses compared to low doses [Vinceti 2018]. read more

Selenium Status and Prostate Cancer Risk

The light blue ribbon is the prostate cancer awareness ribbon. Along with skin cancer, prostate cancer is the most common cancer among American men. The American Cancer Society estimates that one man in nine will be diagnosed with prostate cancer during his lifetime. Research shows that blood selenium status within a specific range is associated with reduced risk of prostate cancer.

One of the big challenges in selenium research is the optimizing of the daily selenium intake to reduce the risk of prostate cancer. We need more research results to answer the following questions about the use of selenium supplements to reduce the risk of prostate cancer [Waters & Chiang 2017]:

  • What is the optimal formulation of the selenium supplement?
  • What is the correct daily dosage?
  • What is the range of baseline blood selenium concentrations that indicates a need for selenium supplementation?
  • What is the blood selenium level above which selenium supplementation will not reduce the risk of prostate cancer further?

The idea that selenium intakes and selenium status are an important determinant of prostate cancer risk began to receive considerable attention after University of Arizona Professor Larry Clark published the results of the Nutritional Prevention of Cancer Trial in JAMA in December 1996 [Clark 1996].

High-Selenium Yeast Supplements in the Nutritional Prevention of Cancer Trial

The Nutritional Prevention of Cancer Trial (NPCT) was a supplementation trial using 200 micrograms of a selenized yeast preparation or placebo for an average duration of 4.5 years.  The study participants were 1312 men and women with an average age 63 years. read more

Selenium For Cancer Treatment

Pre-clinical studies suggest that selenium supplementation in the right formulation and the right dosage may enhance the effects of chemotherapy for certain forms of cancer. Selenium may help to protect normal cells and tissues against the toxicities of chemotherapy drugs.  Selenium may enable the administration of higher than normal doses of the chemotherapy drugs.

Chemotherapy and radiation continue to be the major forms of treatment for many types of cancer. The considerable toxicity of these treatments to normal cells is a problem in cancer treatment and management.

Selenium’s Role in Cancer Prevention

Selenium supplementation has already been associated with statistically significant reductions in the risk of various cancers and pre-cancerous conditions:

Possible Role for Selenium in Cancer Treatment

Selenium supplementation may be valuable in the treatment of cancer as well as in the prevention of cancer.  Selenium has the ability to protect against the formation and progression of some cancer cells and also the ability to selectively target some existing cancer cells.

Moreover, it may be that selenium can work in synergy with conventional cancer therapies.  Pre-clinical research data suggest that selenium may in some instances protect normal cells and tissues against the toxic effects of conventional cancer treatments on the cells [Evans 2017]. read more

Blood selenium concentrations and high-grade prostate cancer

A 2012 meta-analysis and systematic review has shown an inverse association between plasma/serum selenium levels and prostate cancer advanced prostate cancer in particular. Denmark is in a low-selenium region of the world, and the Danish population as a whole has low selenium intakes and sub-optimal blood selenium levels. Danish researchers have, accordingly, investigated the association between pre-diagnostic selenium levels and the risk of total, advanced, and high-grade prostate cancer. Pictured here: the Dannebrog, Denmark’s national flag.

Higher blood selenium concentrations and higher blood selenoprotein P concentrations are significantly associated with reduced risk of high-grade prostate cancer [Outzen].

The researchers defined “advanced” prostate cancer as ≥T3 or with a Gleason-score ≥7.  They defined “high-grade prostate cancer” as cancers having a Gleason score equal to or greater than 8.

Furthermore, in survival analyses, a higher pre-diagnostic level of plasma selenium is significantly associated with a lower risk of all-cause mortality in prostate cancer patients [Outzen].

Selenium and prostate cancer in the “Diet, Cancer, and Health” cohort

These are the conclusions from an analysis of the data from the Danish “Diet, Cancer, and Health” cohort.  The cohort consists of 27,179 men living in the greater metropolitan areas of Copenhagen and Aarhus who were recruited into the study.  They were aged 50 – 64 years and had no previous record of cancer at the time of recruitment [Outzen]. read more

Selenium and prostate cancer: the toenail evidence

Meta-analyses have shown an inverse association between plasma/serum selenium concentrations and the risk of prostate cancer. The same inverse association has also been seen in three high-quality studies of toenail selenium concentrations and the risk of prostate cancer. The data from the Netherlands Cohort Study clearly show that higher toenail selenium is associated with significantly reduced risk of prostate cancer.

Analysis of data from the Netherlands Cohort Study shows that higher toenail selenium concentrations are associated with a substantial reduction in the risk of advanced prostate cancer.  Men in the highest quintile of toenail selenium had a statistically significant (p=0.001) 63% reduced risk of advanced (stage III-IV) prostate cancer compared to men in the lowest quintile of toenail selenium [Geybels].

Men in the highest quintile of toenail selenium concentrations had a toenail selenium level higher than 0.617 micrograms of selenium per gram of toenail.  Men in the lowest quintile of toenail selenium concentrations has a toenail selenium level lower than 0.469 micrograms of selenium per gram of toenail [Geybels]. read more

Selenium and the prevention of prostate cancer: meta-analysis

There are many risk factors associated with the development of prostate cancer: age, family history, geographic region, insulin growth factor, nationality, and race. One risk factor that merits investigation is the relationship between blood selenium concentrations and prostate cancer risk.

Quote: “Selenium most probably has a protective role against the development of prostate cancer and its progression to advanced stages. Therefore, selenium supplementation can be proposed for prevention of prostate cancer.”

These words are taken from the conclusion of a 2018 systematic review and meta-analysis of studies of the association between selenium and prostate cancer [Sayehmiri].

The meta-analysis is based on the data from 38 journal medical articles that included 36,419 prostate cancer cases and 105,293 healthy controls. There were 22 case-control studies, 6 cohort studies, and 10 randomized controlled trials included in the meta-analysis [Sayehmiri].

Selenium levels associated with risk of prostate cancer

The pooled relative risk from the 38 studies of the association of selenium concentration and prostate cancer risk showed a statistically significant 14% risk reduction with higher levels of blood selenium or toe nail selenium. read more

Selenium for preventing cancer

A Cochrane review is a systematic review of research results in a field of human health care or health policy. The review’s authors summarize and analyze the evidence from observational studies and randomized controlled studies. Observational studies are studies in which the predictor variable (the study participants’ exposure to selenium) is not under the control of the researchers. In randomized controlled studies, the predictor variable (supplementation of some of the participants with selenium) is under the control of the researchers even though they are commonly blinded until the end of the study from knowing which study participants are receiving the active substance instead of the placebo substance.

Observational studies show predominantly and consistently an inverse association between selenium exposure and the risk of some cancer types [Vinceti 2018; Cai 2016].  The evidence from some 70 observational studies indicates that higher levels of exposure to selenium are associated with lower levels of cancer incidence and mortality [Vinceti 2018]. What the observational studies haven’t shown thus far is a systematic pattern suggesting specific dose-response relationships.   [Vinceti 2018].

The evidence from observational studies also indicates that there may be a U-shaped form to the relationship between selenium exposure and disease risk. For example, one study suggests that the best serum selenium range for protection against prostate cancer is between 119 and 137 micrograms per liter [Chiang 2010]. A second study shows that the risk of prostate cancer decreases gradually as the selenium concentrations increase in the range from 60 micrograms of selenium per liter of plasma up to 170 micrograms per liter.  Above 170 micrograms per liter, the protection ceases [Hurst 2012]. read more

Selenium supplementation in the Su.Vi.Max. study

Depicted above (A): apoptosis in normal cell division with a damaged cell (2) and programmed cell death (1). Depicted below (B): cancer cell division with uninhibited cell production and increasingly more dangerous cell mutations. Selenium supplementation can help normal healthy adults who have low selenium status with cancer chemo-prevention benefits, thyroid function benefits, and cognitive function benefits.

The Su.Vi.Max. study —  SUpplementation en VItamines et Minéraux AntioXydants — was a big randomized, double-blind, placebo-controlled study carried out with typical French efficiency.  Even though I have written the name of the study in French, there are so many English cognates that I am sure you can read the full name of the study.

The study was designed to test the health benefits of daily supplementation with a number of vitamins and minerals at nutritional dosages (roughly, one to three times the daily recommended dietary intakes) [Hercberg 1998]:

  • selenium, 100 micrograms
  • vitamin C, 120 mg
  • vitamin E, 30 mg
  • beta-carotene, 6 mg
  • zinc, 20 mg

In particular, the French researchers wanted to see the effect of the daily supplementation over a long period, approximately 7.5 years, from 1994 to 2002, on the prevention of cancer and cardiovascular disease, both of which have been linked to oxidative stress and oxidative damage and might, therefore, be affected by supplementation with antioxidants. read more