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].

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Selenium and Coenzyme Q10 and heart protection

Healthy aging is the goal of us all. We want to remain physically active and mentally alert as long as we can. A study of the supplementation of elderly Swedish citizens has shown that daily supplementation with high-selenium yeast tablets and Coenzyme Q10 capsules significantly reduced the rate of death from heart disease. Depicted here: symptoms of heart attack.

Leading cardiologists in Sweden conducted a four-year study — the KiSel-10 study — of 443 of the elderly Swedish citizens and found that a prophylactic treatment with 200 micrograms of high-selenium yeast and 200 milligrams of Coenzyme Q10 daily reduces the risk of dying from heart disease by over 50 per cent.  This is an immensely interesting study result because heart disease is the number one killer in Western countries.

The KiSel-10 Study

The KiSel-10 clinical trial — a randomized, double-blind, placebo-controlled study–  investigated the effect of a combination of high-selenium yeast tablets and Coenzyme Q10 capsules, as compared with matching placebo capsules and tablets, on the following outcomes:

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Selenium in combination with Coenzyme Q10

Selenocysteine, C3H7NO2Se, is known as the 21st amino acid. It contains selenium as a component. It is a constituent part of the 25 known selenoproteins and selenoenzymes found in the human body. The selenoproteins, in turn, play an important role in the body’s defense against cancer, cardiovascular disease, and neurodegenerative disease.

Selenium is an essential micronutrient for us humans.  It is a component of the selenoproteins that we need for antioxidant protection and for good immune system function.  The selenoproteins glutathione peroxidase, thioredoxin reductase, and selenoprotein P are arguably the most important selenoproteins [Alehagen 2014].

Variability of selenium content and intakes

The soil content of selenium and, thus, the dietary intake of selenium varies considerably around the world.  Consequently, the need for selenium supplementation differs from region to region of the world.  Generally, selenium intakes are lower in Europe than in the United States; there is, however, also considerable variation within the United States.  The safest thing to do is to get a plasma or serum selenium concentration test done.

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Low serum selenium status and increased mortality

Too few studies have investigated the relationship between low serum selenium status and negative health effects. Professor Urban Alehagen from Linköping University in Sweden has published the results of a study showing that low serum selenium status is significantly associated with increased cardiovascular and all-cause mortality.

During an almost seven-year follow-up period, elderly healthy Swedish citizens with low serum selenium concentrations had significantly increased cardiovascular mortality and total mortality rates compared to contemporaries with higher serum selenium concentrations.  Specifically, there was a 56% increased risk for cardiovascular mortality and a 43% increased risk for all-cause mortality.  Accordingly, the Swedish researchers suggested that selenium supplementation should be recommended to all Swedish citizens with a serum selenium concentration below 57 micrograms per liter [Alehagen 2016].

In fact, Professor Urban Alehagen and his team of researchers at Linköping University pointed out that the average serum selenium concentrations observed in the study of elderly Swedish citizens – 67.1 micrograms per liter – is not sufficient to achieve optimal function of the important selenoproteins that require selenium as a component [Alehagen 2016]:

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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.

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Selenium and oral cancer

Because many cancers take so long to develop, research studies with cancer as the endpoint require a long period of observation and are very expensive. Focus on intermediate endpoints such as bio-markers for the development of cancer are useful for assessing the value of  selenium supplements for cancer prevention. Pictured here: a histo-pathologic image showing squamous cell carcinoma in a biopsy specimen.

When we test the efficacy of selenium supplementation in the prevention of cancer, we often look at the effect of the selenium supplementation on bio-markers for the development of cancer.  Bio-markers are substances whose presence in blood or tissue indicates the concurrent presence of a disease or an infection.

An Indian (sub-continent) research study has shown that supplementation with selenium, zinc, riboflavin, and vitamin A significantly inhibits the development of bio-markers for oral cancers [Prasad].

Okay, because the selenium was administered as one component in a micro-nutrient cocktail, we cannot attribute the outcome solely to the selenium supplementation.  But it is a good bet that the selenium – through its incorporation into antioxidant selenoproteins – was a major factor in the beneficial health effects.  There is support for the idea that antioxidant supplements are effective cancer chemopreventive agents [Prasad].

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Selenium and thyroid function

The thyroid system regulates and maintains many vital functions in the body.  To ensure its optimal functioning, the thyroid gland requires adequate levels of selenium and iodine.

Selenium is an essential micronutrient.  We need only small quantities of it, but we do need selenium as a component of the amino acid selenocysteine.  We need the selenocysteine, in turn, for the body’s synthesis of 25 identified selenoproteins that have a variety of biological functions [Bellinger].

The following outcomes are some of the health benefits associated with adequate selenium intake and status [Ventura]:

  • Reduction of the risk of cancer
  • Enhancement of thyroid function
  • Protection against oxidative damage
  • Enhancement of immune system function
  • Detoxification and elimination of mercury
  • Slower progression of HIV infections to AIDS and death
  • More resistance to opportunistic infections

Selenium and thyroid function

The thyroid is the small butterfly-shaped gland at the base of our necks, just above our breastbones.  For such a small gland, the thyroid gland is very important.  When it is healthy, it produces the hormones that regulate many bodily functions:

  • the body’s metabolism rate
  • the body’s heart function
  • the functioning of the digestive system
  • the body’s muscle control
  • the brain’s development
  • the maintenance of good bone health

Diseases inhibiting thyroid gland function

The most prevalent diseases of the thyroid gland are the following [Iddah]:

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Properties of a high-selenium yeast preparation

The element selenium is seldom found alone and unbound. In the body, it forms a part of the amino acids selenomethionine and selenocysteine and functions as a component of some 25 selenoproteins. The high-selenium yeast used in nutritional supplements is produced by enriching Saccharomyces cerevisiae yeast (also known as baker’s yeast or brewer’s yeast) with selenium. As the yeast grows, it absorbs the selenium. The result is an organic high-selenium yeast that has a relatively good absorption and bio-availability. It provides several species of selenium that are necessary for many cellular functions in the body. The yeast in the high-selenium yeast tablets is dead. It cannot cause yeast infections.

The evidence from clinical studies shows that high-selenium yeast preparations give the best health outcomes [Alehagen; Blot; Clark; Yu].

Today, I want to look at the documented properties of the high-selenium yeast preparation that was developed for use in the PRECISE studies.  PRECISE is the acronym for PREvention of Cancer by Intervention with SElenium.  The PRECISE studies were designed to test the effectiveness of selenium supplementation at preventing cancer.

The preparation is also the high-selenium yeast preparation used in the KiSel-10 study of combined selenium and Coenzyme Q10 supplementation of healthy elderly citizens to protect against heart disease.  Professor Urban Alehagen and the researchers at Linköping University in Sweden have written about the special interrelationship between selenium and Coenzyme Q10: our cells need adequate selenium status to obtain optimal concentrations of Coenzyme Q10, and our cells need adequate Coenzyme Q10 status to realize optimal selenoprotein function [Alehagen].

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Serum/plasma selenium status and protection against cancer

In cancer prevention, there seems to be a U-shaped response to selenium supplementation. The threat of adversity is greater at the lower and higher levels of serum/plasma selenium. For example, Emily Chiang and her colleagues posit that the optimal serum selenium level for the reduction of prostate cancer risk is between 119 and 137 micrograms per liter. (Graph for illustration purposes only)

The documentation in various systematic reviews and meta-analyses of selenium and cancer studies shows a significant inverse association between selenium intake and/or plasma/serum selenium status and cancer [Lee; Hurst; Cai].

There is some evidence of a U-shaped relationship between plasma/serum selenium status and protection against cancer [Hurst; Rayman].  Low plasma/serum selenium status clearly correlates with higher risk of cancer.  High plasma/serum selenium status correlates with no increased protective effect against cancer.  The key is to find the supplement doses and subsequent plasma/serum status that give the best protection in between the two extremes.

Evaluating the evidence from published studies is complicated.  We need to remember that the following factors affect the relationship between selenium status and/or intake and cancer risk:

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Selenium and antioxidants in combination against cancer

Nothing is clear-cut, it seems.  Yes, we want to eat fruits and berries for their antioxidant content.  But, fruits and berries are full of the sugar called fructose.  So, like everything else, we need to eat fruits and berries in moderation.  In this report, I focus on studies of selenium and antioxidant combinations to prevent cancer.

On the topic of cancer and selenium as a cancer chemo-preventive agent, we know some basic facts from published research:

  • selenium prevents or delays tumor development in animals [Schrauzer]
  • regions with low selenium intakes are regions with higher incidence of cancer [Schrauzer]
  • greater exposure to selenium is associated with lower incidence of cancer [Cai]
  • single interventions with high-selenium yeast preparations reduce the incidence of cancer [Clark; Yu; Li]

What do randomized controlled studies reveal about the efficacy of selenium and antioxidant combinations against the development of cancerous tumors, I wondered.

The first studies to come to mind were the Linxian Nutritional Intervention Studies, which are probably just as important in the history of selenium and cancer research as Professor Larry Clark’s Nutritional Prevention of Cancer study is.

Professor Blot’s Linxian Nutrition Intervention Studies in China

The Linxian studies were a very big research undertaking.  The researchers enrolled 29,584 study participants aged 40 to 69 years from four Linxian County municipalities.  The study participants lived in a region of China characterized by constantly low intakes of selenium and by high cancer mortality rates.

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