Research conclusion: “The 20% with lowest SELENOP concentrations in a N orth European population without history of cardiovascular disease have markedly increased risk of cardiovascular morbidity and mortality” [Schomburg 2019].
This is the conclusion from the Malmö Preventive Project, a population-based prospective cohort study in southern Sweden, that examined the relationship between plasma selenoprotein P status and 1) risk of all-cause mortality, 2) risk of cardiovascular mortality, and 3) risk of a first cardiovascular event in 4366 study participants.
Note that this was a study done with study participants who had no history of cardiovascular disease. It was truly a study of the relationship between selenium status and the risk of heart disease.
The researchers used the study participants’ personal identification number to track the three endpoints in the Swedish Hospital Discharge Register, the Swedish Cause of Death Register, the Stroke in Malmö Register, and the
Swedish Coronary Angiography and Angioplasty Registry.
Selenoprotein P and Risk of Cardiovascular Disease
The Malmö Preventive Project had a median follow-up time of 9.3 years with an interquartile range of 8.3 years to 11 years follow-up time.
- For data analysis purposes, the researchers divided the study participants into quintiles by plasma selenoprotein P status with quintile 1 being the study participants with the lowest plasma selenoprotein P levels and quintile 5 being the study participants with the highest plasma selenoprotein P levels.
- The study participants in quintiles 2 through 5 had significantly lower risk than the study participants in quintile 1 in all three endpoints: 1) all-cause mortality, 2) cardiovascular mortality, and 3) a first cardiovascular event.
- The risk for all three endpoints decreased gradually with the lowest risk reached in quintile 4.
- In quintile 4, compared to quintile 1, the risk of all-cause mortality was 43% reduced, the risk of cardiovascular mortality was 48% reduced, and the risk of a first cardiovascular event was 44% reduced.
- The lower risk of a first cardiovascular event in quintiles 2–5 as compared to quintile 1 was significant for both coronary artery disease and stroke.
Selenium and Selenoproteins
- Selenium is an essential trace element that we cannot synthesize in our cells. We need an adequate intake from our food.
- Selenium intakes and status vary considerably from region to region in the world, depending upon the content of selenium in the soil and in foodstuffs. Schomburg [2019] regards most of Europe, Africa, and Asia as insufficiently supplied with selenium in contrast to much of the United States and Canada.
- In humans, a small group of 25 proteins contains selenium in the form of the amino acid selenocysteine. These selenoproteins include the glutathione peroxidases, thioredoxin reductases, iodothyronine deiodinases, selenoprotein P, and others [Schomburg 2019].
- Low selenium intake results in insufficient expression of selenoproteins, in low selenium concentrations in the blood circulation and in tissues, and in an increased risk for certain diseases including colorectal cancer, autoimmune thyroid disease, and sub-responsive immune function [Schomburg 2019].
- Selenoprotein P is produced in the liver and serves as the primary transport protein for the delivery of selenium from the liver to tissues. Moreover, selenoprotein P is capable of enzymatic activity and is thought to protect vascular endothelial cells from damage by harmful free radicals [Schomburg 2019].
Why Selenoprotein P as a Bio-Marker of Selenium Status?
- The full expression of selenoprotein P requires higher selenium intakes than are required for the saturation of the glutathione peroxidase-1 and glutathione peroxidase-3 seleno-enzymes; consequently, selenoprotein P saturation is considered the most suitable protein-based biomarker of selenium status.
- Selenoprotein P becomes maximally expressed at serum or plasma selenium concentrations of 125 mcg/L.
- A total serum selenium concentration in the range of 70 mcg/L and lower indicates a sub-optimal expression of the circulating selenoproteins glutathione peroxidase and selenoprotein P.
- The low at-risk quintile (Quintile 1) in the Malmö Preventive Project had serum selenoprotein P concentrations below 4.3 mg/L, corresponding to serum selenium concentrations of less than 70 mcg/L.
The KiSel-10 Study of Selenium and Coenzyme Q10 Supplementation
In a study of healthy elderly Swedish citizens, Professor Urban Alehagen et al reported two important results:
- The study participants had a low mean serum selenium concentration, 67 mcg/L, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations < 65 mcg/L than in the subgroup with a serum selenium concentration > 85 mcg/L.
- Supplementation with selenium and Coenzyme Q10 was cardio-protective in those with a low selenium concentration, ≤ 85 mcg/L at inclusion.
BIOSTAT-CHF Study of Selenium Status in Heart Failure Patients
In a multinational, observational cohort study that enrolled patients with worsening heart failure, Bomer et al. [2019] found that heart failure patients with serum selenium concentrations below 70 mcg/L had worse New York Heart Association functional class, had more severe signs and symptoms of heart failure, had poorer exercise capacity (6-min walking test), and poorer quality of life. The researchers found that heart failure patients with serum selenium concentrations below 100 mcg/L had symptoms nearly as bad as the patients under 70 mcg/L, suggesting that the true start of sub-optimal levels of selenium in the blood start when individuals drop below 90-100 mcg/L.
Kuria Meta-Analysis of Selenium Status and Heart Disease
In a 2020 meta-analysis of five cohort studies, Kuria et al. concluded that high selenium status significantly reduced cardiovascular mortality and incidence of cardiovascular disease, compared to low selenium status.
Conclusion: Serum Selenium and Risk of Heart Disease
The above evidence leads to one conclusion: Individuals living in regions with low selenium intake should be tested for selenoprotein P deficiency and advised about the potential heart health benefits of taking natural selenium-rich products or supplements.
Anyone with a serum selenium concentration below 70 mcg/L or, as a precaution, below 90-100 mcg/L, may want to consult a physician about taking a selenium supplement.
Sources
Alehagen U, Alexander J, Aaseth J. Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial. PLoS One. 2016 Jul 1;11(7):e0157541.
Bomer N, Grote Beverborg N, Hoes MF, Streng KW, Vermeer M, Dokter MM, IJmker J, Anker SD, Cleland JGF, Hillege HL, Lang CC, Ng LL, Samani NJ, Tromp J, van Veldhuisen DJ, Touw DJ, Voors AA, van der Meer P. Selenium and outcome in heart failure. Eur J Heart Fail. 2020 Aug;22(8):1415-1423.
Kuria A, Tian H, Li M, Wang Y, Aaseth JO, Zang J, et al. Selenium status in the body and cardiovascular disease: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2020;1–10.
Schomburg L, Orho-Melander M, Struck J, Bergmann A, Melander O. Selenoprotein-P deficiency predicts cardiovascular disease and death. Nutrients. 2019 Aug 9;11(8):1852.
The information presented in this review article is not intended as medical advice and should not be used as such.
30 October 2021