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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Serum selenium level and heart disease

Dietary selenium intakes in the Nordic countries are generally quite low.  In Finland, the situation is different because, there, the government implemented a policy of selenium fertilization of the soil.  As a result, Finns have a much higher selenium intake than their Nordic neighbors. Unfortunately, there is not enough selenium available for every selenium-poor region in the world to use soil fertilization as a solution. Supplementation is the more efficient option.

Daily supplementation for four years with a high-selenium yeast tablet and two Coenzyme Q10 capsules reduced the risk of death from heart disease in elderly men and women aged 70-80 years at the time of enrollment into the KiSel-10 randomized controlled trial.  The effective dosages were 200 micrograms of selenium and 200 milligrams of Coenzyme Q10 (100 milligrams twice a day) [Alehagen 2013].

The daily supplementation also maintained good heart function as documented on echocardiograms and reduced the concentrations of bio-markers for oxidative damage and low-grade inflammation.  Best of all, the beneficial health effects of the selenium and Coenzyme Q10 persisted for up to ten years after the four-year supplementation [Alehagen 2015].

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Selenium and liver cancer: the Qidong study results

China is a country with many selenium-poor regions. The people living in these regions have paid the price with high rates of heart disease, bone disease, and various forms of cancer. Selenium supplementation has proven beneficial in China.

Some 50 years ago now, Chinese researchers began to understand the health risks associated with low selenium status.  Cross-sectional studies showed an association between low selenium concentrations in cereal grains, the low selenium status of local citizens, and the incidence of Keshan disease, a heart disease with high death rates.  The administration of selenium supplements in intervention studies resulted in significant reductions in the incidence of Keshan disease [Chen 2012].  Selenium status is one of the main factors contributing to the development of Keshan disease.

Selenium and Kashin-Beck disease
Not long afterwards, Chinese researchers realized that Kashin-Beck disease, a disease of the bone, is prevalent in regions of China and Tibet that are poor in selenium.  The researchers saw that a deficiency of selenium and iodine was a common factor Kashin-Beck disease regions [Yao 2011].

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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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