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Sex Differences in Selenium Metabolism and Selenoproteins

Couple on the beach
Males and females are different in ways that go beyond the morphology of their sex organs. This sexual dimorphism affects critical aspects of the selenium metabolism in animals and humans. Here Seale et al. review the available information on the influence of biological sex parameters on selenium metabolism and the effect of selenium and selenoproteins on sex hormones.

One thing that the Covid-19 infections have taught us is that biological sex differences affect the way we respond to the virus. The Johns Hopkins University biologist Dr. Sabra Klein says that men are more likely to die from Covid-19 and more likely to be hospitalized with severe cases of the disease.

This seems to hold true even though women are just as likely to be infected and even when researchers control for the effect of factors such as age and region.

Women seem to have a stronger immune response to pathogens – bacteria, viruses, parasites – and to have a higher antibody production after vaccination. On the other hand, women are at greater risk for the development of auto-immune diseases. read more

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Selenium Deficiency A Big Risk Factor for Heart Disease

Ash tray with cigarette butts
In the Italian study (Giacconi et al. 2021), only smoking ranked above selenium deficiency as a risk factor for heart disease. Age, BMI, cholesterol and triglyceride levels, and gender all ranked lower than selenium deficiency as risk factors for heart disease.

Results from an Italian study have added to the evidence that adequate selenium status is necessary to prevent heart disease, especially in elderly individuals.

The Italian study data showed that study participants with plasma selenium concentrations below 60 micrograms per liter were 1.9 times more likely to suffer from cardiovascular disease compared to study participants with higher selenium status [Giacconi 2021].

Reduced plasma selenium status was associated with elevated levels of biomarkers of inflammation, increased expression of cytokines, and down-regulation of sirtuins in peripheral blood mononuclear cells [Giacconi 2021].

Selenium Status and Risk of Cardiovascular Disease

The KiSel-10 Study Results

In a clinical trial with combined selenium and Coenzyme Q supplementation of elderly citizens, average age: 78 years, with low selenium status (mean: 67.1 micrograms per liter), for 48 months, researchers found reduced cardiovascular mortality after 10 and 12 years of follow-up [Alehagen 2018, 2015). read more

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Selenium as a Nutritional and Preventive Medicine Substance

Berlin Brandenburger Tor
Professor Dr. Lutz Schomburg, affiliated with the Charité Institute of Experimental Endocrinology and with both the Humboldt University and the Free University in Berlin, has analyzed the research literature on selenium supplementation. He concludes that current data show that selenium supplementation does not cause diabetes.

The long-time selenium researcher Professor Dr. Lutz Schomburg has reviewed the nutritional and preventive medicine aspects of selenium supplementation. In his mind, a selenium deficiency in and of itself constitutes a health risk that should be corrected by dietary measures or by supplemental selenium intake [Schomburg 2020].

He interprets the available evidence for positive health effects of selenium supplement as the outcome of correcting a deficiency or insufficiency of selenium.

His review of the research literature indicates that selenium supplement does not cause diabetes. Instead, the current evidence suggests that the development of type 2 diabetes with low insulin levels and high glucose levels may be causing increases in selenium levels; hence, the perceived association between the incidence of diabetes and the higher selenium status [Schomburg 2020]. read more

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Plasma Selenium Levels and the Risk of a First Stroke

A Chinese study has shown that there is a significant negative association between plasma selenium concentrations and the risk of a first stroke in males but not in females. This is not the first time that sex differences have been reported relative to selenium metabolism. More on that later.

Picture of the brain
Typically, there were many more cases of first ischemic stroke, usually caused by a blood clot, than there are cases of first hemorrhagic stroke, usually caused when a blood vessel leaks or breaks open). Adequate selenium supply to the brain may protect against the risk of stroke.

Plasma Selenium Levels and the Risk of a First Stroke

The Chinese researchers analyzed the results from a nested case-control study with 1255 first stroke cases and 1255 matched controls [Hu 2021].

N.B. In this study,  there were many more cases of first ischemic stroke (n=1079) than there are cases of first hemorrhagic stroke (n=171). Five cases were of uncertain origin.

Evidence from Other Studies of Selenium Level and Stroke Risk

The results from studies of selenium level and stroke risk have been somewhat confusing to date: read more

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Selenium and Antioxidants to Prevent Heart Disease

Heart trouble
Selenium deficiency (< 70 mcg/L) and low selenium status (70 – 100 mcg/L) are associated with reduced exercise capacity and higher risk of death in heart failure patients [Bomer 2019].
Canadian researchers have concluded that the addition of selenium should be considered for antioxidant supplements if the antioxidant mixtures are to be associated with reductions in the risk of heart disease and all-cause mortality [Jenkins 2020].

How did they arrive at this conclusion? First, they did a preliminary analysis of the available research literature and found that antioxidant supplements seemed to reduce incidence of all-cause death when the supplements included selenium [Jenkins 2020].

Systematic Review of Supplements With and Without Selenium

Next, they did a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of selenium supplementation alone and the effect of antioxidant mixtures with or without selenium on the risk of heart disease and all-cause mortality [Jenkins 2020]. read more

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Selenium Supplementation and Rheumatoid Arthritis

Arthritic hands
Rheumatoid arthritis patients typically have lower serum selenium status than healthy individuals do. Some studies show that selenium supplementation is associated with reduced swelling and stiffness of the joints and with less severe pain in rheumatoid arthritis patients.

A meta-analysis shows a significant association between low serum selenium status and rheumatoid arthritis (RA) [Yu 2016].

-The researchers examined the data from 14 case-control studies involving 716 subjects.

-The analysis of the pooled data indicated that patients with rheumatoid arthritis had lower serum levels of selenium than the healthy controls.

-The rheumatoid arthritis patients had significantly lower serum selenium levels than healthy controls did in studies in Europe and in Asia but not in studies in the USA.

Selenium and Rheumatoid Arthritis Studies

Sahebari et al [2019] reported on 13 studies that assessed selenium status in rheumatoid arthritis patients.

Adequate Selenium for Rheumatoid Arthritis Patients

Rheumatoid arthritis is a chronic inflammatory disease that affects the joints of the hands and feet and leads to disability. read more

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Low Selenium Status and At-Risk Pregnancies

Pregnant woman
Low serum selenium status (defined as below 80 micrograms per liter) during pregnancy is associated with increased risk of miscarriage, pre-eclampsia, pre-term births, and other adverse outcomes.

A recent review article presents the evidence that low selenium status in pregnant women may be implicated in the following complications [Duntas 2020]:

  • miscarriage
  • preeclampsia
  • pre-term birth
  • retarded fetus intrauterine growth
  • post-partum hypothyroidism and auto-immune thyroiditis

To ensure an optimal pregnancy outcome, Dr. Leonidas Duntas recommends that physicians take an individualized approach and prescribe dietary and supplemental selenium intakes that are tailored to the pregnant woman’s needs.

Why is Adequate Selenium Important for Pregnant Women?

Selenium is an essential trace element. Its intake and status in the blood plasma can vary considerably according to a number of factors [Duntas 2020]:

  • differences in diet and nutrition
  • differences in soil and plant selenium content
  • ethnic differences
  • genetic differences

Without a blood selenium test, it is not possible to know whether women planning a pregnancy have sufficient circulating selenium. The Mayo Clinic reports that the normal selenium concentration in adult human blood serum in the United States is 70 to 150 micrograms per liter with a population mean value of 98 micrograms per liter. read more

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IV Selenium Supplementation for Critically Ill Patients

Critically ill patient
Increased generation of harmful free radicals and increased systemic inflammation seem to play a direct role in cell death, increased morbidity, and higher mortality in critically ill patients. Selenium is a trace element that has cell regulatory, immunologic, and antioxidant and anti-inflammatory functions. Early selenium supplementation is a promising adjunctive therapy for critically ill patients.

Selenium supplementation – especially intravenous selenium supplementation – seems to be a promising adjuvant treatment for critically ill patients.

The aggregated results of a meta-analysis of the clinical outcomes of selenium supplementation on critically ill patients shows that intravenous selenium supplements as a single therapy can decrease the total mortality and can shorten the length of stay in hospital [Zhao 2019].

Furthermore, the results from the meta-analysis showed that the selenium supplementation did not increase the incidence of drug-induced side effects compared with the control group [Zhao 2019].

Selenium Supplementation for Critically Ill Patients – The Evidence

The researchers reviewed 19 randomized controlled trials enrolling 3341 critically ill patients. There were 1694 critically ill patients in the selenium supplementation group and 1647 critically ill patients in the control group. read more

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Selenium Supplementation and HIV Infections: A Review

Symptoms of AIDS
The six selenium and HIV infection studies show a beneficial effect of daily supplementation with 200 micrograms of selenium on immune function, in particular on CD4 white blood cell counts. The same beneficial effect on the immune system may be protective against other forms of infection, including against Covid-19 infections.

Six randomized controlled studies show that providing daily selenium supplementation to HIV-infected adults increases CD4 cell counts, reduces the risk of diarrhea morbidity, and lowers hospital admission rates for HIV-related conditions and opportunistic infection in HIV-infected adults [Kayode 2020].

Alexander et al [2020] have recognized the importance of selenium to immune system function and have recommended the initiation of adequate selenium supplementation in high-risk Covid-19 areas and as soon as possible after a suspected Covid-19 infection.

Richie et al [2014] have shown that selenium supplementation in the form of selenium-enriched yeast provides significantly greater protection against oxidative stress than supplementation with exclusively selenomethionine does. read more

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Selenium Supplementation and Blood Sugar Levels

Testing blood sugar
The results of randomized controlled trials of selenium supplementation show beneficial effects or no effect on blood sugar levels and insulin sensitivity values. In this review, we summarize the study results.

The effect of selenium supplementation on blood sugar levels and on the risk of diabetes is still an open question. However, the data from randomized controlled studies show that selenium supplementation is associated with either a beneficial effect or no effect at all on blood sugar levels, insulin sensitivity, and glucose tolerance [Jablonska 2016].

Study Participants with Type-2 Diabetes

Beneficial effect. In a 2019 study, the participants were 72 male and 22 female patients aged 48 to 64 years old with diabetes mellitus type 2. They were smokers, all of them, and they all followed a Mediterranean diet.

The researchers administered selenium 200 microg/day once daily on an empty stomach. The study data showed a statistically significant reduction in the blood levels of glucose and in HbA1c values at both three months and six months after the beginning of the treatment. The administration of selenium to type-2 diabetic patients seemed to improve the patients’ glycemic profile [Karalis 2019]. read more