Advertisement
Research Article| Volume 167, ISSUE 5, P1860-1866, September 01, 2013

Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

  • Urban Alehagen
    Correspondence
    Corresponding author at: Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Heart Center, Linköping University, SE-581 85 Linköping, Sweden. Tel.: +46 10 103 0000.
    Affiliations
    Division of Cardiovascular Medicine, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden

    Department of Cardiology UHL, County Council of Östergötland, Linköping, Sweden
    Search for articles by this author
  • Peter Johansson
    Affiliations
    Division of Cardiovascular Medicine, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden

    Department of Cardiology UHL, County Council of Östergötland, Linköping, Sweden
    Search for articles by this author
  • Mikael Björnstedt
    Affiliations
    Division of Pathology, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Search for articles by this author
  • Anders Rosén
    Affiliations
    Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping University, Linköping, Sweden
    Search for articles by this author
  • Ulf Dahlström
    Affiliations
    Division of Cardiovascular Medicine, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden

    Department of Cardiology UHL, County Council of Östergötland, Linköping, Sweden
    Search for articles by this author

      Abstract

      Background

      Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking.

      Methods

      A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention.
      The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan–Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied.

      Results

      During a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P=0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P=0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P=0.03).

      Conclusion

      Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to International Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Rayman M.P.
        The importance of selenium to human health.
        Lancet. 2000; 356: 233-241
        • Selenius M.
        • Rundlöf A.K.
        • Olm E.
        • Fernandes A.P.
        • Björnstedt M.
        Selenium and the selenoprotein thioredoxin reductase in the prevention, treatment and diagnostics of cancer.
        Antioxid Redox Signal. 2010; 12: 867-880
        • Fairweather-Tait S.J.
        • Bao Y.
        • Broadley M.R.
        • et al.
        Selenium in human health and disease.
        Antioxid Redox Signal. 2011; 14: 1337-1383
        • Goldson A.J.
        • Fairweather-Tait S.J.
        • Armah C.N.
        • et al.
        Effects of selenium supplementation on selenoprotein gene expression and response to influenza vaccine challenge: a randomised controlled trial.
        PLoS One. 2011; 6: e14771
        • Rayman M.P.
        Selenium in cancer prevention: a review of the evidence and mechanism of action.
        Proc Nutr Soc. 2005; 64: 527-542
        • Cheng Y.Y.
        • Qian P.C.
        The effect of selenium-fortified table salt in the prevention of Keshan disease on a population of 1.05 million.
        Biomed Environ Sci. 1990; 3: 422-428
        • Clark L.C.
        • Combs Jr., G.F.
        • Turnbull B.W.
        • et al.
        Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.
        JAMA. 1996; 276: 1957-1963
        • Bleys J.
        • Navas-Acien A.
        • Laclaustra M.
        • et al.
        Serum selenium and peripheral arterial disease: results from the national health and nutrition examination survey, 2003–2004.
        Am J Epidemiol. 2009; 169: 996-1003
        • Eaton C.B.
        • Abdul Baki A.R.
        • Waring M.E.
        • Roberts M.B.
        • Lu B.
        The association of low selenium and renal insufficiency with coronary heart disease and all-cause mortality: NHANES III follow-up study.
        Atherosclerosis. 2010; 212: 689-694
        • Stranges S.
        • Marshall J.R.
        • Trevisan M.
        • et al.
        Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial.
        Am J Epidemiol. 2006; 163: 694-699
        • Salonen J.T.
        • Alfthan G.
        • Huttunen J.K.
        • Pikkarainen J.
        • Puska P.
        Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study.
        Lancet. 1982; 2: 175-179
        • Venardos K.M.
        • Perkins A.
        • Headrick J.
        • Kaye D.M.
        Myocardial ischemia–reperfusion injury, antioxidant enzyme systems, and selenium: a review.
        Curr Med Chem. 2007; 14: 1539-1549
        • Moosmann B.
        • Behl C.
        Selenoproteins, cholesterol-lowering drugs, and the consequences: revisiting of the mevalonate pathway.
        Trends Cardiovasc Med. 2004; 14: 273-281
        • Kalén A.
        • Appelkvist E.L.
        • Dallner G.
        Age-related changes in the lipid compositions of rat and human tissues.
        Lipids. 1989; 24: 579-584
        • Folkers K.
        • Vadhanavikit S.
        • Mortensen S.A.
        Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10.
        Proc Natl Acad Sci U S A. 1985; 82: 901-904
        • Senes M.
        • Erbay A.R.
        • Yilmaz F.M.
        • et al.
        Coenzyme Q10 and high-sensitivity C-reactive protein in ischemic and idiopathic dilated cardiomyopathy.
        Clin Chem Lab Med. 2008; 46: 382-386
        • Molyneux S.L.
        • Florkowski C.M.
        • George P.M.
        • et al.
        Coenzyme Q10: an independent predictor of mortality in chronic heart failure.
        J Am Coll Cardiol. 2008; 52: 1435-1441
        • Witte K.K.
        • Nikitin N.P.
        • Parker A.C.
        • et al.
        The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure.
        Eur Heart J. 2005; 26: 2238-2244
        • Sander S.
        • Coleman C.I.
        • Patel A.A.
        • Klüger J.
        • White C.M.
        The impact of coenzyme Q10 on systolic function in patients with chronic heart failure.
        J Card Fail. 2006; 12: 464-472
        • Mortensen S.A.
        Coenzyme Q10 as an adjunctive therapy in patients with congestive heart failure.
        J Am Coll Cardiol. 2000; 36: 304-305
        • de Lorgeril M.
        • Salen P.
        Selenium and antioxidant defenses as major mediators in the development of chronic heart failure.
        Heart Fail Rev. 2006; 11: 13-17
        • Jensen-Urstad K.
        • Bouvier F.
        • Hojer J.
        • et al.
        Comparison of different echocardiographic methods with radionuclide imaging for measuring left ventricular ejection fraction during acute myocardial infarction treated by thrombolytic therapy.
        Am J Cardiol. 1998; 81: 538-544
        • van Royen N.
        • Jaffe C.C.
        • Krumholz H.M.
        • et al.
        Comparison and reproducibility of visual echocardiographic and quantitative radionuclide left ventricular ejection fractions.
        Am J Cardiol. 1996; 77: 843-850
        • Larsen E.H.
        • Sloth J.J.
        • Hansen M.
        • Moesgaard S.
        Selenium speciation and isotope composition in 77Se-enriched yeast using gradient elution HPLC separation and ICP-dynamic reaction cell-MS.
        J Anal At Spectrom. 2003; 18: 310-316
        • Larsen E.H.
        • Hansen M.
        • Paulin H.
        • Moesgaard S.
        • Reid M.
        • Rayman M.
        Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies.
        J AOAC Int. 2004; 87: 225-232
        • Bugel S.
        • Larsen E.H.
        • Sloth J.J.
        • et al.
        Absorption, excretion, and retention of selenium from a high selenium yeast in men with a high intake of selenium.
        Food Nutr Res. 2008; 52
        • Weis M.
        • Mortensen S.A.
        • Rassing M.R.
        • Moller-Sonnergaard J.
        • Poulsen G.
        • Rasmussen S.N.
        Bioavailability of four oral coenzyme Q10 formulations in healthy volunteers.
        Mol Aspects Med. 1994; 15 ([Suppl.]): s273-s280
        • Folkers K.
        • Moesgaard S.
        • Morita M.
        A one year bioavailability study of coenzyme Q10 with 3 months withdrawal period.
        Mol Aspects Med. 1994; 15 ([Suppl.]): s281-s285
        • Xia L.
        • Nordman T.
        • Olsson J.M.
        • et al.
        The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress.
        J Biol Chem. 2003; 278: 2141-2146
        • Kuklinski B.
        • Weissenbacher E.
        • Fahnrich A.
        Coenzyme Q10 and antioxidants in acute myocardial infarction.
        Mol Aspects Med. 1994; 15 ([Suppl.]): s143-s147
        • Fumagalli S.
        • Fattirolli F.
        • Guarducci L.
        • et al.
        Coenzyme Q10 terclatrate and creatine in chronic heart failure: a randomized, placebo-controlled, double-blind study.
        Clin Cardiol. 2011; 34: 211-217
        • Lubos E.
        • Sinning C.R.
        • Schnabel R.B.
        • et al.
        Serum selenium and prognosis in cardiovascular disease: results from the AtheroGene study.
        Atherosclerosis. 2010; 209: 271-277
        • Lymbury R.S.
        • Marino M.J.
        • Perkins A.V.
        Effect of dietary selenium on the progression of heart failure in the ageing spontaneously hypertensive rat.
        Mol Nutr Food Res. Oct 2010; 54: 1436-1444
        • Jekell A.
        • Hossain A.
        • Alehagen U.
        • Dahlström U.
        • Rosén A.
        Elevated circulating levels of thioredoxin and stress in chronic heart failure.
        Eur J Heart Fail. 2004; 6: 883-890