Vitamin K and Calcium Chelation in Vascular Health.

The observation that the extent of artery calcification correlates with the degree of atherosclerosis was the background for the alternative treatment of cardiovascular disease with chelator ethylenediamine tetraacetate (EDTA). Recent studies have indicated that such chelation treatment has only marginal impact on the course of vascular disease. In contrast, endogenous calcium chelation with removal of calcium from the cardiovascular system paralleled by improved bone mineralization exerted, i.e., by matrix Gla protein (MGP) and osteocalcin, appears to significantly delay the development of cardiovascular diseases. After post-translational vitamin-K-dependent carboxylation of glutamic acid residues, MGP and other vitamin-K-dependent proteins (VKDPs) can chelate calcium through vicinal carboxyl groups. Dietary vitamin K is mainly provided in the form of phylloquinone from green leafy vegetables and as menaquinones from fermented foods. Here, we provide a review of clinical studies, addressing the role of vitamin K in cardiovascular diseases, and an overview of vitamin K kinetics and biological actions, including vitamin-K-dependent carboxylation and calcium chelation, as compared with the action of the exogenous (therapeutic) chelator EDTA. Consumption of vitamin-K-rich foods and/or use of vitamin K supplements appear to be a better preventive strategy than EDTA chelation for maintaining vascular health.

Effects of an Intervention with Selenium and Coenzyme Q10 on Five Selected Age-Related Biomarkers in Elderly Swedes Low in Selenium: Results That Point to an Anti-Ageing Effect-A Sub-Analysis of a Previous Prospective Double-Blind Placebo-Controlled Randomised Clinical Trial.

Background: Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related markers and the effects of selenium and coenzyme Q10 intervention to elucidate the mechanisms that may influence the course of ageing. Methods: This is a sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial that included 441 subjects low in selenium (mean age 77, 49% women). The active treatment group (n = 220) received 200 µg/day of selenium and 200 mg/day of coenzyme Q10, combined. Blood samples were collected at inclusion and after 48 months for measurements of the intercellular adhesion molecule (ICAM-1), adiponectin, leptin, stem cell factor (SCF) and osteoprotegerin (OPG), using ELISAs. Repeated measures of variance and ANCOVA evaluations were used to compare the two groups. In order to better understand and reduce the complexity of the relationship between the biomarkers and age, factor analyses and structural equation modelling (SEM) were performed, and a structural model is presented. Results: Correlation analyses of biomarker values at inclusion in relation to age, and relevant markers related to inflammation, endothelial dysfunction and fibrosis, demonstrated the biomarkers' association with these pathological processes; however, only ICAM1 and adiponectin were directly correlated with age. SEM analyses showed, however, that the biomarkers ICAM-1, adiponectin, SCF and OPG, but not leptin, all had significant associations with age and formed two independent structural factors, both significantly related to age. While no difference was observed at inclusion, the biomarkers were differently changed in the active treatment and placebo groups (decreasing and increasing levels, respectively) at 48 months (p ≤ 0.02 in all, adjusted), and in the SEM model, they showed an anti-ageing impact. Conclusions: Supplementation with selenium/Q10 influenced the analysed biomarkers in ways indicating an anti-ageing effect, and by applying SEM methodology, the interrelationships between two independent structural factors and age were validated.

Selenium and coenzyme Q10 improve the systemic redox status while reducing cardiovascular mortality in elderly population-based individuals.

BACKGROUND: Serum sulfhydryl groups (R-SH, free thiols) reflect the systemic redox status in health and disease, and may be amenable to therapeutic modulation. Since R-SH are readily oxidized by reactive species, oxidative stress is characterized by reduced serum R-SH levels. Selenium and coenzyme Q10 supplementation may improve the systemic redox status. This study aimed to evaluate the effect of supplementation with selenium and coenzyme Q10 on serum free thiols and to study associations with the risk of cardiovascular mortality in elderly community-dwelling individuals. METHODS: In this randomized, double-blind, placebo-controlled trial, serum R-SH were measured colorimetrically and adjusted for albumin in 434 individuals at baseline and after 48 months of intervention. Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) or placebo were provided as dietary supplements. RESULTS: After 48 months of intervention, participants receiving combined selenium and coenzyme Q10 supplementation demonstrated increased levels of serum R-SH compared to placebo (P = 0.002). In prospective association analysis, the highest rate of cardiovascular mortality after a median follow-up of 10 years (IQR: 6.8-10.5) was observed in the lowest quartile (Q1) of R-SH levels. Baseline albumin-adjusted serum R-SH were significantly associated with the risk of cardiovascular mortality, even after adjustment for potential confounding factors (hazard ratio [HR] 1.98 per SD, 95% CI: 1.34-2.91, P < 0.001). CONCLUSION: Supplementation with selenium and coenzyme Q10 to an elderly community-dwelling population low on the two substances, significantly improved serum R-SH levels, supporting a reduction in systemic oxidative stress. Low serum R-SH levels were significantly associated with an increased risk of cardiovascular mortality in elderly individuals.

Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality-Sub-Study of a Randomized Clinical Trial.

Short telomeres have been associated with ageing and cardiovascular disease. The influence on leukocyte telomere length (LTL) of long-term intervention with combined selenium and coenzyme Q10 is unknown. Our aim was to determine whether 42 months of selenium and coenzyme Q10 supplementation prevented telomere attrition and further cardiovascular mortality. The investigation is an explorative sub-study of a double-blind, placebo-controlled, randomized trial. Swedish citizens low in selenium (n = 118), aged 70−80 years, were included. Intervention time was 4 years, with 10 years' follow-up time. LTL was relatively quantified with PCR at baseline and after 42 months. At baseline, LTL (SD) was 0.954 (0.260) in the active treatment group and 1.018 (0.317) in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared with placebo (+0.019 vs. −0.129, respectively, p = 0.02), with a significant difference in change basing the analysis on individual changes in LTL (p < 0.001). Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors [0.791 (0.190) vs. 0.941 (0.279), p = 0.01], with a significant difference in change of LTL according to cardiovascular mortality and survival (p = 0.03). To conclude, preservation of LTL after selenium and coenzyme Q10 supplementation associated with reduced cardiovascular mortality.

Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in Sweden.

PURPOSE: Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers. METHODS: Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780. RESULTS: In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (ß = 0.74; p < 0.001) and myocardium (ß = 0.65; p < 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality. CONCLUSION: Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10.

Decreased Concentration of Fibroblast Growth Factor 23 (FGF-23) as a Result of Supplementation with Selenium and Coenzyme Q10 in an Elderly Swedish Population: A Sub-Analysis.

There is a reduced intake of selenium in many countries due to low levels of selenium in the soil. This results in an increased cardiovascular risk. Fibroblast growth factor 23 (FGF-23) is active mainly in the metabolism of vitamin D and phosphorus. However, there are indications that FGF-23 may also provide information both on cardiovascular function and prognosis. The aim of the study was to evaluate the effect of supplementation with selenium and coenzyme Q10 on the FGF-23 concentration in an elderly population with low concentrations of both selenium and coenzyme Q10 and in which the supplementation improved cardiac function and mortality. In a randomised double-blind placebo-controlled trial, FGF-23 was measured in 219 individuals at the start and after 48 months. Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 118) or placebo (n = 101) were given as a dietary supplement. The intervention time was 48 months. t-Tests, repeated measures of variance, and ANCOVA analyses were used to evaluate the differences in FGF-23 concentration. Following supplementation with selenium and coenzyme Q10, a significantly lower level of FGF-23 could be seen (p = 0.01). Applying 10 years of follow-up, those who later died a cardiovascular death had a significantly higher FGF-23 concentration after 48 months compared with those who survived (p = 0.036), and a significantly lower FGF-23 concentration could be seen in those with a normal renal function compared to those with an impaired renal function (p = 0.027). Supplementation with selenium and coenzyme Q10 to an elderly community-living population low in both substances prevented an increase of FGF-23 and also provided a reduced cardiovascular risk.

Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review.

Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1-3), glutathione peroxidases (GPX1-4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1-4 and TXNRD1-3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.

The Aging Kidney-As Influenced by Heavy Metal Exposure and Selenium Supplementation.

The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50-60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance.

Coenzyme Q10 supplementation - In ageing and disease.

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial electron transport chain. It is also an antioxidant in cellular membranes and lipoproteins. All cells produce CoQ10 by a specialized cytoplasmatic-mitochondrial pathway. CoQ10 deficiency can result from genetic failure or ageing. Some drugs including statins, widely used by inter alia elderly, may inhibit endogenous CoQ10 synthesis. There are also chronic diseases with lower levels of CoQ10 in tissues and organs. High doses of CoQ10 may increase both circulating and intracellular levels, but there are conflicting results regarding bioavailability. Here, we review the current knowledge of CoQ10 biosynthesis and primary and acquired CoQ10 deficiency, and results from clinical trials based on CoQ10 supplementation. There are indications that supplementation positively affects mitochondrial deficiency syndrome and some of the symptoms of ageing. Cardiovascular disease and inflammation appear to be alleviated by the antioxidant effect of CoQ10. There is a need for further studies and well-designed clinical trials, with CoQ10 in a formulation of proven bioavailability, involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ10 treatment in neurodegenerative disorders, as well as in metabolic syndrome and its complications.

Dietary Supplementation with Selenium and Coenzyme Q10 Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population.

A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q10. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q10 on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 µg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q10 in a group of elderly low in selenium and coenzyme Q10 prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.

Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium: Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial.

A low selenium intake is found in European countries, and is associated with increased cardiovascular mortality. There is an association between selenium level and the severity of kidney disease. An association between inflammation and selenium intake is also reported. The coenzyme Q10 level is decreased in kidney disease. The aim of this study was to examine a possible association between selenium and renal function in an elderly population low in selenium and coenzyme Q10, and the impact of intervention with selenium and coenzyme Q10 on the renal function. The association between selenium status and creatinine was studied in 589 elderly persons. In 215 of these (mean age 71 years) a randomised double-blind placebo-controlled prospective trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 117) or placebo (n = 98) was conducted. Renal function was determined using measures of glomerular function at the start and after 48 months. The follow-up time was 5.1 years. All individuals were low on selenium (mean 67 µg/L (SD 16.8)). The changes in renal function were evaluated by measurement of creatinine, cystatin-C, and the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm, and by the use of T-tests, repeated measures of variance and ANCOVA analyses. An association between low selenium status and impaired renal function was observed. Intervention causes a significantly lower serum creatinine, and cystatin-C concentration in the active treatment group compared with those on placebo (p = 0.0002 and p = 0.001 resp.). The evaluation with CKD-EPI based on both creatinine and cystatin-C showed a corresponding significant difference (p < 0.0001). All validations showed corresponding significant differences. In individuals with a deficiency of selenium and coenzyme Q10, low selenium status is related to impaired renal function, and thus supplementation with selenium and coenzyme Q10 results in significantly improved renal function as seen from creatinine and cystatin-C and through the CKD-EPI algorithm. The explanation could be related to positive effects on inflammation and oxidative stress as a result of the supplementation.

Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19.

OBJECTIVES: The novel coronavirus infection (COVID-19) conveys a serious threat globally to health and economy because of a lack of vaccines and specific treatments. A common factor for conditions that predispose for serious progress is a low-grade inflammation, e.g., as seen in metabolic syndrome, diabetes, and heart failure, to which micronutrient deficiencies may contribute. The aim of the present article was to explore the usefulness of early micronutrient intervention, with focus on zinc, selenium, and vitamin D, to relieve escalation of COVID-19. METHODS: We conducted an online search for articles published in the period 2010-2020 on zinc, selenium, and vitamin D, and corona and related virus infections. RESULTS: There were a few studies providing direct evidence on associations between zinc, selenium, and vitamin D, and COVID-19. Adequate supply of zinc, selenium, and vitamin D is essential for resistance to other viral infections, immune function, and reduced inflammation. Hence, it is suggested that nutrition intervention securing an adequate status might protect against the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - coronavirus-2) and mitigate the course of COVID-19. CONCLUSION: We recommended initiation of adequate supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority as regards this nutritive adjuvant therapy, which should be started prior to administration of specific and supportive medical measures.

Supplemental selenium and coenzyme Q10 reduce glycation along with cardiovascular mortality in an elderly population with low selenium status - A four-year, prospective, randomised, double-blind placebo-controlled trial.

BACKGROUND: A low intake of selenium has been shown to increase the risk of cardiovascular mortality, and supplementation of selenium and coenzyme Q10 influences this. The mechanism behind is unclear although effects on inflammation, oxidative stress and microRNA expression have been reported. Fructosamine, a marker of long-term glycaemic control, is also a marker of increased risk of heart disease and death, even in non-diabetics. OBJECTIVE: To analyse the impact of selenium and coenzyme Q10 supplementation on the concentration of fructosamine. Also, the relation between pre-intervention serum selenium concentration and the effect on fructosamine of the intervention was studied. METHODS: Fructosamine plasma concentration was determined in 219 participants after six and 42 months of intervention with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/ day) (n = 118 of which 20 had diabetes at inclusion), or placebo (n = 101 of which 18 had diabetes at inclusion). Pre-intervention, the serum selenium levels were 67 µg/L (active treatment group: 66.6 µg/L; placebo group: 67.4 µg/L), corresponding to an estimated intake of 35 µg/day. Changes in concentrations of fructosamine following intervention were assessed by the use of T-tests, repeated measures of variance, and ANCOVA analyses. RESULTS: Post-intervention selenium concentrations were 210 µg/L in the active group and 72 µg/L in the placebo group. A lower concentration of fructosamine could be seen as a result of the intervention in the total population (P = 0.001) in both the males (P = 0.04) and in the females (P = 0.01) in the non-diabetic population (P = 0.002), and in both the younger (<76 years) (P = 0.01) and the older (≥76 years) participants (P = 0.03). No difference could be demonstrated in fructosamine concentration in the diabetic patients, but the total sample was small (n = 38). In subjects with a low pre-intervention level of serum selenium the intervention gave a more pronounced decrease in fructosamine compared with those with a higher baseline selenium level. CONCLUSION: A significantly lower concentration of fructosamine was observed in the elderly community-living participants supplemented with selenium and coenzyme Q10 for 42 months compared to those on the placebo. As oxidative mechanisms are involved in the glycation of proteins, less glycoxidation could be a result of the supplementation of selenium and coenzyme Q10, which could have contributed to lower cardiac mortality and less inflammation, as has earlier been reported. This study was registered at Clinicaltrials.gov, and has the identifier NCT01443780.

Significant decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and coenzyme Q10 to an elderly population with a low selenium status.

PURPOSE: Endothelial dysfunction and inflammation are conditions which fuel atherosclerosis and ischaemic heart disease. We have previously reported reduced cardiovascular (CV) mortality following supplementation with selenium and coenzyme Q10 to 443 elderly individuals with low selenium status (mean 67 µg/L) for 4 years. Here, we wanted to evaluate a possible association between the supplementation and the plasma concentrations of the von Willebrand factor (vWf), and the plasminogen activator inhibitor-1 (PAI-1), as they, besides other functions, are also strongly associated with endothelial function. METHODS: In this sub-study, 308 individuals (active substance: 157, placebo: 151) were included. Blood samples were drawn after 6 and 36 months and vWf and PAI-1 were determined in plasma by ELISA. Changes in concentrations of the biomarkers were evaluated by the use of T tests, repeated measures of variance, and ANCOVA analyses. RESULTS: The active treatment group presented a lower level of vWf after 36 months compared with the placebo group (1.08 U/mL vs. 5.10 U/mL; p = 0.0007). The results were validated through the repeated measures of variance evaluation. The PAI-1 levels showed an equally significant decrease in the active group (26.2 ng/mL vs. 49.2 ng/mL; p = 0.0002) and were also validated through repeated measures of variance evaluation. CONCLUSION: In this sub-study on elderly receiving selenium and coenzyme Q10, or placebo we found significantly lower levels of vWf and PAI-1 in the active treatment group as compared to the placebo group. We interpret this as a better endothelial function because of the intervention, which accords with a previous finding of reduced CV mortality.

Significant Changes in Metabolic Profiles after Intervention with Selenium and Coenzyme Q10 in an Elderly Population.

Selenium and coenzyme Q10 (SeQ10) are important for normal cellular function. Low selenium intake leads to increased cardiovascular mortality. Intervention with these substances with healthy elderly persons over a period of four years in a double-blind, randomised placebo-controlled prospective study showed reduced cardiovascular mortality, increased cardiac function, and a lower level of NT-proBNP. Therefore, we wanted to evaluate changes in biochemical pathways as a result of the intervention with SeQ10 using metabolic profiling. From a population of 443 healthy elderly individuals that were given 200 µg selenium and 200 mg coenzyme Q10, or placebo daily for four years, we selected nine males on active intervention and nine males on placebo for metabolic profiling in the main study. To confirm the results, two validation studies (study 1 n = 60 males, study 2 n = 37 males) were conducted. Principal component analyses were used on clinical and demographic data to select representative sets of samples for analysis and to divide the samples into batches for analysis. Gas chromatography time-of-flight mass spectrometry-based metabolomics was applied. The metabolite data were evaluated using univariate and multivariate approaches, mainly T-tests and orthogonal projections to latent structures (OPLS) analyses. Out of 95 identified metabolites, 19 were significantly decreased due to the intervention after 18 months of intervention. Significant changes could be seen in the pentose phosphate, the mevalonate, the beta-oxidation and the xanthine oxidase pathways. The intervention also resulted in changes in the urea cycle, and increases in the levels of the precursors to neurotransmitters of the brain. This adds information to previous published results reporting decreased oxidative stress and inflammation. This is the first-time metabolic profiling has been applied to elucidate the mechanisms behind an intervention with SeQ10. The study is small and should be regarded as hypothesis-generating; however, the results are interesting and, therefore, further research in the area is needed. This study was registered at Clinicaltrials.gov, with the identifier NCT01443780.

Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK.

BACKGROUND: Inflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation. METHODS: Osteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42 months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200 µg/day) and coenzyme Q10 (200 mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates. RESULTS: Significantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences. CONCLUSION: In this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group . TRIAL REGISTRATION: The intervention study was registered at Clinicaltrials.gov, and has the identifier NCT01443780 and registered on 09/30/2011.

Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly.

BACKGROUND: Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. METHODS: From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. FINDINGS: After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95%CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. CONCLUSIONS: This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating. TRIAL REGISTRATION: Clinicaltrials.gov NCT01443780.

Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10-A mechanism behind reduced cardiovascular mortality?

BACKGROUND: In an intervention study where 221 healthy elderly persons received selenium and coenzyme Q10 as a dietary supplement, and 222 received placebo for 4 years we observed improved cardiac function and reduced cardiovascular mortality. As fibrosis is central in the aging process, we investigated the effect of the intervention on biomarkers of fibrogenic activity in a subanalysis of this intervention study. MATERIAL AND METHODS: In the present subanalysis 122 actively treated individuals and 101 controls, the effect of the treatment on eight biomarkers of fibrogenic activity were assessed. These biomarkers were: Cathepsin S, Endostatin, Galectin 3, Growth Differentiation Factor-15 (GDF-15), Matrix Metalloproteinases 1 and 9, Tissue Inhibitor of Metalloproteinases 1 (TIMP 1) and Suppression of Tumorigenicity 2 (ST-2). Blood concentrations of these biomarkers after 6 and 42 months were analyzed by the use of T-tests, repeated measures of variance, and factor analyses. RESULTS: Compared with placebo, in those receiving supplementation with selenium and coenzyme Q10, all biomarkers except ST2 showed significant decreased concentrations in blood. The changes in concentrations, that is, effects sizes as given by partial eta2 caused by the intervention were considered small to medium. CONCLUSION: The significantly decreased biomarker concentrations in those on active treatment with selenium and coenzyme Q10 compared with those on placebo after 36 months of intervention presumably reflect less fibrogenic activity as a result of the intervention. These observations might indicate that reduced fibrosis precedes the reported improvement in cardiac function, thereby explaining some of the positive clinical effects caused by the intervention. © 2017 BioFactors, 44(2):137-147, 2018.

Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.

BACKGROUND: Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. METHODS: 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. FINDINGS: After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; P<0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. CONCLUSION: Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.