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.

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Selenium and Longevity and Ageing

There are notable regional variations in the blood selenium concentrations in senior citizens. The differences range from 66 micrograms per liter in Brazil and Turkey to 126 micrograms per liter in Japan.  Below 85 micrograms per liter is poor selenium status.  The desirable range is thought to be 125-135 micrograms per liter.

We want, all of us, to stay as young and healthy as possible as late in life as possible.  Ageing is inevitable.  How can we delay the onset of ageing’s bio-chemical and physiological consequences?

  • Physical exercise?
  • Caloric restriction?
  • Ingestion of micronutrients?

Selenium Status and the Health of Senior Citizens

The authors of a 2019 review article have found that, overall, there is an inverse correlation between age and blood selenium levels. Higher age is associated with lower blood selenium concentrations [Robberecht 2019].

Inadequate dietary intakes of selenium and poor selenium status (< 85 micrograms per liter in blood) may increase the risk of following harmful health outcomes [Robberecht]:

  • oxidative stress (= imbalance of harmful free radicals and protective antioxidants)
  • destruction of nerve cells (neurons)
  • dementia

Selenium Status and Biological and Social Factors

A variety of factors must be taken into consideration when we investigate the relationship between ageing and selenium intake and status.  There are, first of all, considerable regional variations in the availability of selenium in the soil and in foodstuffs [Stoffaneller & Morse].

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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].

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Metabolic Changes After Supplementation with Selenium and Coenzyme Q10

Professor Urban Alehagen’s research has shown that there is a relatively high mortality risk in elderly Swedish subjects with low selenium intakes and low selenium status. Senior citizens in Sweden had, on average, serum selenium concentrations of 67.1 micrograms per liter. The same increased mortality risk seen in Sweden may be typical of other selenium-poor regions of the world as well.

There are clear differences in the metabolic profiles of elderly men who took 200 micrograms of selenium and 2 x 100 milligrams of Coenzyme Q10 daily for at least 18 months as compared with the metabolic profiles of elderly men who took matching placebos [Alehagen 2019].

Drawing on data from a sub-analysis of the KiSel-10 Study, Professor Urban Alehagen reported that the major differences were seen primarily in the following biological pathways [Alehagen 2019]:

  • pentose phosphate pathway (the pathway for the generation of nicotinamide adenine dinucleotide phosphate, which is a substance that reduces ubiquinone Coenzyme Q10)
  • mevalonate pathway (the pathway for the synthesis of cholesterol, Coenzyme Q10, and dolichol)
  • beta-oxidation pathway (the pathway for the breaking down of fatty acid molecules to produce energy and to produce acetyl-CoA, FADH2 and NADH, which are needed for the citric acid cycle [Krebs cycle]

There were other significant metabolic changes associated with the selenium and Coenzyme Q10 supplementation of senior citizens as well [Alehagen 2019].

Changes in Metabolic Profile After Supplementation with Selenium and Coenzyme Q10

In this study, Professor Alehagen and his team of researchers analyzed the metabolic patterns of 95 metabolites in the plasma of elderly men.

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Normal Serum Selenium Levels

Dr. Margaret P. Rayman, Professor of Nutritional Science, University of Surrey at Guildford, said in 2002: ” Se deficiency is defined by Baum et al (1997)  as  a  plasma  level  ≤ 85μg/liter,  a  level  not  attained  in many northern European countries.”

Selenium is an important trace element that is needed for the proper functioning of our cells.  It is needed in very small amounts, but it might be a good idea to have a blood test done to check the serum selenium level.

The Mayo Clinic Laboratories state that the normal concentration in adult human blood serum is 70 to 150 micrograms per liter (the same as 70 to 150 nanograms per milliliter). According to the Mayo Clinic, the US population mean value is 98 micrograms per liter [Mayo Clinic].

Variations in Serum Selenium Levels

Diet, geographic location, demographic factors, and environmental factors all influence serum selenium levels.

The following factors are independent predictors of higher selenium status in the United States [Park]:

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Selenium Supplementation: No Adverse Effect on Insulin Resistance

Researchers at the Arizona Cancer Center report study results that do not support any significant adverse effect of daily supplementation with 200 micrograms/day of selenized yeast on beta-cell function or insulin sensitivity. High-selenium yeast preparations contain more selenium species with more biological functions than the 100% selenomethionine preparations do.

Researchers at the University of Arizona Cancer Center in Tucson have reported interesting findings with respect to selenium supplementation [Jacobs 2019]:

  • Supplementation with 200 micrograms/day of a selenized yeast preparation for 2.9 years had no effect on insulin sensitivity or beta-cell function as compared with the placebo group.
  • Further stratification of the data by sex and age showed no effect modification in response to the selenium supplementation.

The Take-Home Message from this Selenium Research

  • The Arizona Cancer Center research does not support the idea of a major role for selenium in insulin sensitivity or beta-cell function.
  • The University of Arizona researchers write that their results provide key information for clinicians to convey to patients in the USA about the use of selenized yeast dietary supplements.

The Selenium Supplementation Research Design

The researchers analyzed the data from a subset of 400 individuals who were participating in the Selenium Trial, a randomized, double-blind, placebo-controlled trial of the effect of selenium supplementation at 200 micrograms per day on colorectal adenomatous polyps [Jacobs 2019].

The data included the fasting plasma glucose and insulin measured both before randomization and within 6 months of completing the intervention.

The researchers compared changes in the homeostasis model assessment-beta cell function (HOMA2-%beta) and insulin sensitivity (HOMA2-%S) between the active selenium treatment group and the placebo control group.

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Selenium Intake and Status Related to Health

The quantity of selenium in foodstuffs may be inadequate in many parts of the world.  Sub-optimal selenium status is reported to be widespread throughout Europe, the UK, and the Middle East [Stoffaneller & Morse]. Coastal regions in the US tend to have selenium-poor soil. Vast regions in China, Korea, Siberia, Tibet, and New Zealand are low selenium regions. Low selenium status is associated with increased risk of cancer and cardiovascular disease and thyroid disorders [Tolonen].
The research evidence to date suggests that there is a U-shaped relationship between selenium intake and health.  According to a recent report by the long-time selenium researcher Professor Dr. Margaret P. Rayman, University of Surrey, UK, both selenium deficiency and selenium excess have been associated with adverse health effects.

Conditions Indicating a Need for Selenium Supplementation

Professor Rayman lists a number of conditions that have been associated in the research literature with selenium deficiency:

  • Keshan disease (a heart muscle disease caused by a selenium deficiency together with a strain of Coxsackie virus)
  • Kashin-Beck disease (a bone disease for which selenium deficiency is a factor)
  • Increased viral virulence
  • Increased mortality
  • Poorer immune function
  • Problematic fertility/reproduction
  • Thyroid autoimmune disease
  • Cognitive decline/dementia
  • Type-2 diabetes
  • Prostate cancer risk
  • Colo-rectal cancer risk (in women)
  • Increased risk of tuberculosis in HIV patients

Professor Rayman does not specify a plasma/serum selenium level for selenium deficiency

She does mention a US National Health and Nutrition Examination Survey that measured the serum selenium levels in 13,887 adult participants and then followed up for mortality for up to 18 years.  The mortality in that study showed a U-shaped association between serum selenium and death, with a serum selenium concentration of 135 micrograms per liter at the bottom of the U [Rayman 2019].

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Selenium and Autoimmune Diseases

Autoimmune diseases are conditions in which the person’s immune system mistakenly attacks parts of the person’s own body such as his or her joints or skin. There are as many as 14 common autoimmune diseases. Some attack only one organ; others attack the entire body. Through its role in the maintenance of thyroid function and its role in the antioxidant defense of cells and DNA, selenium may have a critical protective effect in the management of autoimmune diseases. More clinical research is needed.

Selenium is a micronutrient that plays an important role in the oxidative defense of cells and DNA against damage by harmful free radicals.  Selenium is the main component of the selenoproteins that play important roles in reproductive function, immune system modulation, and thyroid hormone synthesis [Sahebari].

Low Serum Selenium Levels and Autoimmune Diseases

Decreased serum selenium levels have been associated with increased incidence of some autoimmune diseases.  Furthermore, low levels of selenium may be a risk factor for systemic inflammation and for the initiation of some autoimmune diseases [Sahebari]:

  • Rheumatoid arthritis
  • Sjögren syndrome
  • Behcet’s diseases
  • Scleroderma (systemic sclerosis)

Selenium Supplementation and Autoimmune Diseases

Selenium supplementation has been shown to have beneficial effects in the management of rheumatoid arthritis and scleroderma [Sahebari].

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Selenium Supplementation for Premature Neonates

Preterm neonates are babies born more than three weeks before the normal term, i.e. born before the 37th week of gestation. Sepsis – the condition caused by harmful bacteria entering the blood circulation – is one of the complications associated with premature birth. Selenium supplementation can reduce the risk of late-onset sepsis in preterm neonates.

Selenium supplementation reduces the risk of sepsis in premature babies.

Three studies carried out in low-selenium countries – Australia, New Zealand, and India – have shown a positive effect of selenium supplementation in reducing the incidence of sepsis in premature babies [Daniels; Darlow; Aggarwal].

Selenium supplementation – both selenium fed orally and selenium fed parenterally – significantly improved the selenium status of premature babies and reduced the incidence of “late onset” sepsis [Darlow].

In none of the three clinical studies were there any adverse reactions to the selenium supplementation [Daniels; Darlow; Aggarwal].

Increased Risk of Sepsis in Premature Babies Without Selenium Supplementation

“Late onset” sepsis presents, typically, one week or more following birth and is caused by exposure to infection in the hospital.  A “late onset” sepsis occurs in about one out of five premature babies with a birth weight below 1500 grams (about 3 pounds and five ounces).

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Selenium Supplementation and HIV Infections

Selenium supplementation of HIV-infected patients can slow the progression of the virus, improve CD4 cell counts, and reduce the risk of mortality. The form and the dosage of the selenium supplementation needs to be researched further. At present, supplementation with 200 micrograms of high-selenium yeast daily seems most promising, but the dosage will vary according to regional variation in the selenium content in the soil and food.

Humans with low blood selenium concentrations are more likely to have impaired immune function and rapid mutation of benign variants of RNA viruses to virulent forms.  Low blood selenium concentrations are concentrations less than 1 micromol of selenium per liter of blood = less than 78 micrograms of selenium per liter of blood [Harthill].

If a virus-infected, selenium-deficient human host is supplemented with selenium, the mutation rate of the virus tends to decrease, and the immune function tends to improve [Harthill].

Thus, the selenium status of the human host can have a profound effect on the development of a virus infection In cases of selenium deficiency, a normally non-virulent virus can become virulent.  A virus can become pathogenic by replicating in a nutritionally deficient human host [Beck].

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