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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Selenium as a single intervention for cancer prevention

In many regions of the world, low soil selenium levels result in the production of low-selenium wheat.  Then, the milling and processing of the wheat results in 14% less selenium in wheat flour than is found in the raw wheat.  The combined result is decreased intakes of dietary selenium and increased risk of cancer. Studies show that supplementation with high-selenium yeast preparations in low-selenium regions has a cancer preventive effect.

On this blog site, seleniumfacts.com, we focus on the health and nutritional benefits of selenium supplementation.  We look at the following types of studies:

  • human studies more so than lab studies or animal studies
  • intervention studies more so than observational studies
  • randomized controlled studies whenever possible

Cancer and Selenium as a single intervention agent

The best studies of selenium as a single intervention to prevent or treat cancer show significant results in regions with low selenium intakes and/or high cancer risk.

Professor Clark’s NPC study

The big breakthrough came when Professor Larry Clark published the results of the Nutritional Prevention of Cancer (NPC) study in the prestigious journal JAMA: The Journal of the American Medical Association.

The NPC study was a multi-center randomized, double-blind, placebo-controlled study carried out in a selenium-poor region of the southeastern United States.  The study participants who took 200 micrograms of a high selenium yeast preparation over an average 4.5-year period showed significant health benefits (as compared to placebo):

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Selenium and mercury and eating fish

Ocean fish – salmon, herring, mackerel, and sardines – are good sources of the omega-3 fatty acids EPA and DHA that have been associated with healthy fetal development, healthy cardiovascular function, and healthy ageing.  Whatever mercury there is in these fish has bound with the selenium in the fish.   This chemical binding has rendered the mercury harmless but has also depleted the amount of selenium available for absorption.

Too many of us are missing out on the health benefits of the omega-3 fatty acids available to us from eating certain types of fish a couple of times a week.  Why are we avoiding fish?  Because many of us are afraid of “eating mercury” in the fish.

It turns out, there is research to show that this is a misconception.  Professor Nick Ralston and his colleagues at the University of North Dakota’s Energy and Environmental Research Center have measured and evaluated the molar ratios of selenium in fish to the mercury in fish [Ralston 2007, 2016].

Their studies show that many of the edible ocean fish have an abundance of selenium in relation to mercury.  So, not only are we missing out on the omega-3 fatty acid benefits, we are also missing out on a good source of dietary selenium [Berry 2008].

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Selenium and Alzheimer’s disease and cognitive decline

Pictured: A healthy brain and a brain suffering from severe Alzheimer’s disease. The question: what is the role of the selenium-dependent antioxidant seleno-enzymes in the prevention of Alzheimer’s disease? Professors Aaseth and Alehagen offer an explanation.

There is no reliable method to prevent the development and progression of Alzheimer’s.  There is no known cure for Alzheimer’s.  The approaches that we have tried over the past 20-25 years have not prevented or inhibited the decline in cognitive function that is associated with Alzheimer’s.

Now, Professor Jan Aaseth (Norway) and Professor Urban Alehagen (Sweden) propose selenium supplementation as a prophylactic measure to inhibit the decline of cognitive function, especially in the selenium-poor regions of the world.  They hypothesize that the optimal functioning of the selenoproteins SEPP, GPx, and TrxR is necessary to protect against the cognitive decline associated with Alzheimer’s disease.

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Selenium and heart function in elderly males

Professor Urban Alehagen, Linköping University in Sweden: the changes in the expression of microRNAs — changes that are associated with serum selenium and Coenzyme Q10 concentrations — may be part of the mechanism by which selenium and Coenzyme Q10 contribute to improved heart health.

The randomized controlled clinical trial known as the KiSel-10 study documented that daily supplementation of healthy elderly adults (men and women aged 70 – 88 years) with 200 milligrams of Coenzyme Q10 and 200 micrograms of a high-selenium yeast preparation yields significant health benefits as compared with placebo supplementation:

  • reduced heart disease mortality
  • better heart function
  • fewer signs of chronic low-grade inflammation
  • fewer signs of oxidative stress (cell damage caused by harmful free radicals)

These research findings were/are encouraging for middle-aged adults and for senior citizens, no doubt about it.

The KiSel-10 study of selenium and Coenzyme Q10 treatment
Professor Alehagen and the team of bio-medical researchers in Linköping, Sweden, knew that selenium intakes and selenium status are low in Sweden generally.  They knew, moreover, that the human body’s bio-synthesis of Coenzyme Q10 declines with increasing age to the extent that, typically, an 80-year-old body produces about one half of the Coenzyme Q10 that a 25-year-old body produces.

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