Selenium and cancer prevention: The Linxian Study

In the 1990s and before, the diets of the people in the Linxian province in China were poor in important micronutrients. Selenium status among the residents was notably low. Cancer rates were high. Supplementation with selenium and other antioxidants reduced cancer incidence and mortality.

The Nutrition Intervention Trials conducted in the Linxian province in China yielded some of the first promising results linking selenium supplementation to the reduction of cancer incidence and mortality.  The Linxian province at the time was characterized by a selenium-poor diet.

The treatment group that received selenium supplements was the group that showed significant health benefits of the supplementation:

  • Significantly lower total mortality
  • Significantly lower cancer mortality
  • Significantly lower stomach cancer mortality

The reduced mortality rates began to become apparent already after 1 – 2 years of supplementation.  The patterns for reductions in cancer incidence generally approximated the patterns for cancer mortality [Blot].

The Linxian study results were exciting because they were published in the Journal of the National Cancer Institute and because they appeared before the results of the Nutritional Prevention of Cancer study in the United States [Clark].

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We must not waste selenium

Selenium exists only in scarce quantities. Adequate dietary and supplemental intakes are vital for human health.  We need to use it carefully, and we need to begin to stockpile it for the use of future generations.

Selenium is a trace element.  It exists only in rare quantities in the world.  It is produced primarily as a by-product of the process of mining copper.  It is not recyclable.  It is very unevenly distributed in the soils of the earth.

Consequently, the availability of selenium in grasses and grains and, at the next stage of the food chain, in animals, varies considerably from region to region in the world. The human dietary intakes of selenium vary accordingly around the world.

Selenium a vital nutrient for humans
Selenium is a necessary micronutrient that our bodies do not produce.  We get our selenium primarily from our diets.  Selenium is important for good immune system function, good thyroid function, good reproductive function, and good protection of our cells’ DNA.

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Selenium supplements and breast cancer

Studies show that selenium intake and status are associated with breast cancer risk.  Low selenium status indicates an increased risk of breast cancer.

In many countries, breast cancer is the most commonly diagnosed and treated form of cancer.  A 2014 meta-analysis of 16 studies has shown that there is a statistically significant association between serum selenium status and risk of breast cancer.  The lower the serum selenium concentration, the greater the risk of breast cancer [Babaknejad].

What do we know about selenium and breast cancer?
Breast cancer is a frustrating topic for the selenium researcher.  There is not enough evidence to permit definitive statements about the effects of selenium supplementation on the prevention of breast cancer.

For example, the Nutritional Prevention of Cancer (NPC) study – a study that showed significant associations between selenium supplementation and reduced risk of colorectal, lung, prostate, and total cancer – did not enroll enough women for the effect of selenium supplementation on breast cancer to be studied [Clark].

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Selenium helps to avoid pregnancy complications

Adequate intakes of selenium can help to reduce the risk of some of the more serious complications of pregnancy. Studies done with an organic high-selenium yeast supplement have yielded encouraging results.

Women who have first-trimester miscarriages or recurrent miscarriages have been found to have significantly lower selenium status than women who do not miscarry.  Professor Margaret Rayman points out that blood selenium concentrations are typically lower during pregnancy, in part because there is an expansion of the volume of blood.  However, increased inflammation – implicated in miscarriages – could also be a cause of reduced circulating selenium [Rayman 2012].

For this article, I have searched the Medline database for results from randomized controlled studies involving selenium supplementation of low selenium status pregnant women.  There have been a number of interesting results.

Selenium and oxidative stress in pregnant women
Dr. Tara and a team of researchers did a simultaneous assay of pro-oxidant burden and antioxidant capacity in a total of 166 first-time-pregnant women.  In their first trimester, the women were randomly assigned to an active treatment group receiving 100 micrograms of a yeast-based selenium preparation (n=83) or placebo (n=83) per day until delivery.

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Selenium and heavy metals and childbirth

Studies show that higher concentrations of dangerous heavy metals — cadmium, mercury, and lead — in the blood of the mother are likely to be duplicated in the umbilical cord blood, in the blood of the fetus, in the breast milk, and in the blood of the newborn child, with potentially harmful long-term consequences for the child. There is evidence that selenium binds with cadmium and mercury and enables their elimination from the mothers’ bodies.

Early exposure to natural elements that are toxic – cadmium, mercury, and lead – can have long-term adverse health consequences.  Children exposed to these elements while still in the uterus and while breast-feeding may suffer lasting damage to the brain and nervous system and to the kidneys and liver.  The question is: to what extent can selenium supplementation reduce the risk of toxic damage?

Given the dangerous nature of these poisonous heavy metals – cadmium, mercury, and lead – both for the mother and for the fetus and the neonate, it is difficult to carry out randomized controlled studies.  Instead, the best evidence we have for the beneficial effects of selenium supplementation comes from studies that relate the degree of exposure and the selenium status of the mother and the child.

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Selenium: protection against the accumulation of mercury in the body

Even relatively low exposure to mercury during pregnancy can impair the development of the baby’s brain and nervous system. Fortunately, supplementation with a high-selenium yeast preparation has been shown to reduce significantly the accumulation of mercury in the tissues in the body.

Mercury.  In the form of methylmercury, it is a very harmful biological toxin.  It is a threat to our brains and nervous systems and our livers and our kidneys.  Too much exposure to methylmercury is likely to cause brain damage and nerve damage.

Fortunately, selenium supplements can help.  And they do help.  The relationship of mercury and selenium is a story with an ironic twist.  To the extent that selenium binds with mercury in the body and de-toxifies the mercury – a very good thing for us – to that extent the body is robbed of selenium that could be used for the production of beneficial selenoproteins with other important biological functions.

Protecting us against the toxic effects of mercury means fewer selenoproteins to act as antioxidants neutralizing harmful free radicals, fewer selenoproteins to strengthen immune system function and thyroid function, and fewer selenoproteins to help reduce the risk of cancer.

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Selenium and Coenzyme Q10 and heart health

There seems to be a special biological inter-relationship between selenium and Coenzyme Q10 such that, taken in combination, they can provide significant heart health benefits.

In my mind, I keep coming back to the question of heart health and the role that selenium supplements play in heart health.  That may surprise many of you because we tend to think of selenium supplements primarily for the prevention of cancer and for the prevention of thyroid disorders and for protection against the toxic effects of heavy metals like mercury and cadmium.  We know that our immune system needs adequate intakes of selenium if it is to function optimally.  That’s correct, isn’t it?

Selenium supplements and good heart health
But, what about the relationship between selenium intakes and status and heart health?  Writing in the medical journal, The Lancet, Professor Margaret P. Rayman, University of Surrey, in Guildford, United Kingdom, has listed and documented the following ways that adequate selenium status and optimal levels of selenoproteins can potentially benefit the heart [Rayman 2012]:

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Selenium and glucose metabolism

In our thinking about our diet and our fitness, scientific research must be our highest authority.  The results from randomized controlled studies are the best evidence for the possible existence of a cause-effect relationship between treatment with a selenium (or Coenzyme Q10) supplement and beneficial health outcomes.

Recently, I did a search of the Medline database on the subject of selenium supplementation and its effect or non-effect on glucose metabolism, insulin resistance, glycemic control, etc.  I limited my search to reports of data from randomized, controlled trials.

Altogether, the Medline search yielded 48 hits.  Reading through the abstracts of the 48 journal articles, I was able to eliminate 30 references from consideration.  These 30 eliminated studies were studies that included all of my search terms but did not actually measure the effect of an intervention with selenium on some aspect of glucose metabolism.

18 good selenium supplementation studies
I was left with 18 good intervention studies that met my search criteria.  I read these studies and separated them into three distinct categories related to the effect of selenium supplementation on glucose metabolism and insulin sensitivity:

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Selenium intakes and type-2 diabetes

In many regions of the world, it may not be possible to get an optimal amount of selenium from meals. The content of selenium in our food depends on the availability of selenium in the soil. Known selenium-poor areas are found in much of Europe and the Middle East, China, Korea, Japan, and New Zealand. In the United States, the coastal areas tend to have lower selenium content than the middle of the country does.

In 2013, Dr. Margaret Rayman, University of Surrey, United Kingdom, reviewed the published reports of randomized controlled trials in which a selenium supplement had been used as a single-agent treatment option and in which there had been a follow-up or sub-group analysis of the effect of the selenium supplementation on the risk of type-2 diabetes.

Dr. Rayman found 5 such studies.  I want to summarize Dr. Rayman’s review, and then I want to see what studies have been done since 2013.

Selenium and diabetes studies
Nutritional Prevention of Cancer (NPC) study
In 2007, Dr. Saverio Stranges published the results of a post hoc analysis of the data from the Nutritional Prevention of Cancer study.  In the NPC study, supplementation for an average of 4.5 years with 200 micrograms of a high selenium yeast preparation resulted in significant reductions in the risk of lung cancer, colon cancer, and prostate cancer [Clark 1996].  The age of most participants in the study was 63 years, plus or minus 10 years.

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Selenium and HIV and opportunistic infections

Individuals infected by the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) commonly have low selenium status. Selenium supplementation can prevent or delay the decline of immune system function and can protect against opportunistic infections.

Selenium supplements – especially selenium supplements as a component of a multi-micronutrient cocktail – can help to delay the decline of the immune system and can reduce the risk of death in HIV-infected patients.  Most of the data that we have comes from randomized controlled studies carried out in African countries, but the results are relevant to the United States and Europe.  Moreover, the results from studies of HIV-infected patients speak to the issue of the anti-microbial protection and antioxidant protection that comes with adequate selenium status.

Selenium and HIV and CD4 counts
CD4 cells are white blood cells that are part of the immune system.  Specifically, the CD4 cells fight infections in the body.  The HIV virus kills CD4 cells.  When a person has fewer CD4 cells, he or she is at greater risk of contracting an infection.

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