Selenium and Heart Failure Risk

Cardiologists at the University of Groningen in The Netherlands have published a comprehensive review of the current knowledge about selenium deficiency and the role of selenoproteins in heart failure patients [Al-Mubarak 2021].

Heart failure is a form of heart disease with high morbidity and mortality and with increasing prevalence. It is estimated that there are more than 26 million heart failure patients worldwide. Suboptimal selenium intakes and status adversely affect heart muscle function.

The key points in their review are as follows:

  • Selenium is an essential micronutrient. It is incorporated into 25 different selenoproteins that have many biological functions in the body.
  • Suboptimal selenium intakes and status lead to the impaired cellular synthesis of these selenoproteins and to the diminished function of selenoproteins, which may aggravate oxidative stress and inflammation, both of which are associated with greater severity of heart failure.
  • 70% of patients diagnosed with heart failure have suboptimal serum selenium levels (below 100 micrograms per liter).
  • The heart failure patients with suboptimal serum selenium concentrations have lower exercise capacity, lower quality of life, and a worse prognosis than heart failure patients with serum selenium concentrations above 100 mcg/L.
  • Clinical trials of the efficacy of selenium supplementation in patients with heart failure have shown improved clinical symptoms such as improvements in NYHA function class, in left ventricular ejection fraction, and in lipid profile.
Selenium Deficiency and Heart Failure
Observational Studies of Selenium Concentration and Heart Failure

Three meta-analyses have provided evidence of a relationship between selenium status and the risk of heart disease:

Studies of Selenium Supplementation – the KiSel-10 Study

The most interesting clinical study is the KiSel-10 study in which elderly community living citizens, average age 78 years, with low selenium status (mean baseline status: 67.1 mcg/L), were treated with a combination of 200 mcg of an organic high-selenium yeast preparation and 200 mg of Coenzyme Q10 daily for four years. read more

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

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

Effect of Selenium Supplementation on Heart Health

Chambers of the heart
The American Heart Association defines heart failure as a condition in which the heart muscle cannot pump enough blood out to the body to keep the tissues and organs sufficiently supplied with oxygen. Heart failure is a condition for which there is no known cure. Selenium deficiency is associated with worsening heart failure.

Selenium is an essential antioxidant trace element that is necessary for key activities in human metabolism [Djalalinia 2019]. Meta-analyses of randomized controlled trials of selenium supplementation reveal that selenium supplementation is a cost-effective and simple-to-use intervention that can play an important role in the prevention of heart disease risk factors [Hasani 2018; Hasani 2019; Mahdavi 2019; Tabrizi 2017].

These results from meta-analyses of randomized controlled trials reaffirm the outcomes in the Bomer multinational observational cohort study. In that study, heart failure patients with serum selenium concentrations below 70 micrograms per liter were more likely to have the following characteristics [Bomer 2019]: read more

Selenium and Coenzyme Q10 for Senior Citizens

Professor Urban Alehagen
Like a good detective inspector, Professor Urban Alehagen has investigated the biological mechanisms that could explain how combined selenium and Coenzyme Q10 supplementation reduces the risk of death from heart disease in senior citizens. Among the suspects that he has investigated are oxidative stress, systemic inflammation, fibrosis, and endothelial function.

Four years of daily supplementation with 200 micrograms of a patented high-selenium yeast and 200 milligrams of Coenzyme Q10 (in divided doses: 2 x 100 milligrams) has lowered the risk of dying from cardiovascular disease significantly by 54% (p=0.02) [Alehagen 2013].

The study participants were senior citizens aged 70-88 years (average age: 78 years) who were still able to live at home.

Professor Urban Alehagen and a team of researchers from Linköping University in Sweden randomly assigned the senior citizens to take the active treatment (selenium plus Coenzyme Q10) or matching placebos in a double-blind clinical study named the KiSel-10 Study [Alehagen 2013].

Improved Heart Function with Coenzyme Q10 and Selenium

Compared to the senior citizens in the placebo group, the senior citizens in the active treatment group had a significant improvement in heart function as measured on echocardiograms compared to placebo (p=0.03) and a significant improvement in a biochemical marker, NT-proBNP (p=0.014). NT-proBNP is a reliable indicator for heart disease; the heart muscle typically produces more of the NT-proBNP protein whenever the heart is exposed to stress or injury [Alehagen 2013]. read more

Selenium Status and Heart Failure

Heart failure patients with low serum selenium levels are much more likely to be re-hospitalized and/or to die than are heart failure patients with serum selenium levels above 100 micrograms per liter.

A multi-national cohort study has shown that selenium deficiency in heart failure patients is associated with impaired exercise tolerance and with a 50% higher mortality rate [Bomer].

In-vitro studies of cultured human heart muscle cells from the heart failure patients show that  low selenium levels in the heart muscle cells are associated with impaired mitochondrial function [Bomer].

Recent information shows that up to 50% of heart failure patients suffer from some form of micronutrient insufficiency, e.g. selenium, zinc, iron, or iodine [Bomer].

Selenium: An Essential Micronutrient

Selenium intakes and status vary considerably from geographical region to region according to the content of selenium in the soil and in the food.

Sufficient intakes of selenium are necessary for important biological functions: read more

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. read more

Selenium and Coenzyme Q10 for Senior Citizens

Professor Urban Alehagen, Linköping University, Sweden, was one of the key researchers on the Q-Symbio clinical trial and has been the lead researcher on the KiSel-10 clinical trial. He has shown that joint selenium and Coenzyme Q10 supplementation of senior citizens with low selenium status reduces the risk of cardiovascular mortality and improves heart function.

The Swedish KiSel-10 Study provides randomized controlled trial evidence that a daily combination of an organic high-selenium yeast supplement and a pharmaceutical-grade Coenzyme Q10 supplement can reduce cardiovascular mortality, improve heart function, and increase health-related quality of life in senior citizens [Alehagen 2013].

Low blood selenium concentrations and higher risk of heart disease

Professor Urban Alehagen and a team of researchers from Linköping University investigated the blood selenium levels in 688 Swedish senior citizens.  The mean blood selenium level was 67.1 micrograms per liter, which is quite low but not surprising, given that Sweden is a country with selenium-low soil and selenium-poor foodstuffs [Alehagen 2016].

When the researchers adjusted for gender, smoking, coronary artery disease, diabetes, chronic obstructive pulmonary disease, and impaired heart function, they found that the quartile of senior citizens with the lowest level of blood selenium had a 43% higher risk of all-cause mortality and a 56% higher risk of cardiovascular mortality [Alehagen 2016]. read more

Low serum selenium levels and increased cardiovascular mortality

A recent study has found a relatively high mortality risk in elderly Swedish subjects with low selenium status. Supplementation with a high-selenium yeast supplement and a Coenzyme Q10 supplement for four years resulted in significantly reduced risk of death from heart disease, better maintained heart function, and better quality of life for senior citizens. The beneficial effect of the supplementation has persisted through the 12th year of follow-up.

Low plasma/serum selenium concentrations are associated with increased risk of death from heart disease and increased risk of death from all causes.  Professor Urban Alehagen and a team of researchers at Linköping University in Sweden have investigated the relationship between low selenium levels and the risk of heart disease.

Selenium supplements suggested for adults with very low Se levels

The Swedish study shows that adults with a serum selenium concentration below 57 micrograms per liter are at significantly higher risk of death from all causes (43% increased risk) and death from heart disease (56% increased risk) [Alehagen 2016].
57 micrograms of selenium per liter of serum.  Wow!  That’s low.

These significant associations remained solid even after the researchers had adjusted for the effects of possibly modifying factors: read more

Long-term health protection of Selenium and Coenzyme Q10

The KiSel-10 study was done in Sweden, which is known to have selenium-poor soil and selenium-low foodstuffs. Consequently, daily supplementation with 200 micrograms of a high-selenium yeast preparations was appropriate. In geographical regions with higher levels of selenium in the soil and in the food, lesser selenium dosages may be needed. Selenium is an essential micro-nutrient, it has known antioxidant functions in the body, and it is associated with good thyroid health and good immune system defense.

Combining high-selenium yeast and Coenzyme Q10 supplements gives elderly people in low selenium regions good protection against heart disease.  That seems to be the take-home lesson from a 12-year follow-up analysis of the Swedish KiSel-10 study [Alehagen 2018].

Protective effects of selenium and CoQ10 persist 12 years

Originally, Professor Urban Alehagen and researchers at the University in Linköping enrolled 443 elderly Swedish citizens who were living in a community in which selenium intakes in the food were known to be low. They randomly assigned the study participants to take a combination of 200 micrograms of selenium in a high-selenium yeast tablet and 200 milligrams of Coenzyme Q10 daily or to take matching placebos.  The supplementation study lasted for four years [Alehagen 2013]. read more