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Metaanalyses

Selenium status and cardiovascular diseases: meta-analysis of prospective observational studies and randomized controlled trials

European Journal of Clinical Nutrition volume 70, pages 162–169 (2016)Cite this article

Subjects

Abstract

Background/Objectives:

Selenium was thought to have a role in cardiovascular disease (CVD) owing to its antioxidant properties; however, evidence from observational studies and randomized controlled trials (RCTs) has been inconsistent and controversial. We thus conducted a meta-analysis to assess the discrepancies between observational and randomized trial evidence.

Subjects/Methods:

We searched MEDLINE and EMBASE for eligible prospective studies regarding the relationship between selenium and CVD up to 15 December 2013 and finally included 16 prospective observational studies and 16 RCTs. Random effects model was used to estimate the pooled relative risk (RR). Generalized least-squares trend test and restricted cubic spline model were performed to assess a linear and a nonlinear dose–response relationship.

Results:

Our meta-analysis of prospective studies showed a nonlinear relationship of CVD risk with blood selenium concentrations across a range of 30–165 μg/l and a significant benefit of CVD within a narrow selenium range of 55–145 μg/l. Our meta-analyses of RCTs showed that oral selenium supplements (median dose: 200 μg/day) for 2 weeks to 144 months significantly raised the blood selenium concentrations by 56.4 μg/l (95% confidence interval (CI): 40.9, 72.0 μg/l), whereas oral selenium supplements (median: 100 μg/day) for 6 to 114 months caused no effect on CVD (RR=0.91; 95% CI: 0.74, 1.10).

Conclusions:

Our meta-analysis in prospective studies demonstrated a significant inverse association between selenium status and CVD risk within a narrow selenium range and a null effect of selenium supplementation on CVD was observed in RCTs. These findings indicate the importance of considering selenium status, dose and safety in health assessment and future study design.

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References

  1. Bleys J, Navas-Acien A, Guallar E . Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Arch Intern Med 2008; 168: 404–410.

    Article  CAS  Google Scholar 

  2. Steinbrenner H, Sies H . Protection against reactive oxygen species by selenoproteins. Biochim Biophys Acta 2009; 1790: 1478–1485.

    Article  CAS  Google Scholar 

  3. Rayman MP, Stranges S, Griffin BA, Pastor-Barriuso R, Guallar E . Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial. Ann Intern Med 2011; 154: 656–665.

    Article  Google Scholar 

  4. Murr C, Talasz H, Artner-Dworzak E, Schroecksnadel K, Fiegl M, Fuchs D et al. Inverse association between serum selenium concentrations and parameters of immune activation in patients with cardiac disorders. Clin Chem Lab Med 2007; 45: 1224–1228.

    Article  CAS  Google Scholar 

  5. Rayman MP . Selenium and human health. Lancet 2012; 379: 1256–1268.

    Article  CAS  Google Scholar 

  6. Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, Hesketh JE et al. Selenium in human health and disease. Antioxid Redox Signal 2011; 14: 1337–1383.

    Article  CAS  Google Scholar 

  7. Navarro-Alarcon M, Cabrera-Vique C . Selenium in food and the human body: a review. Sci Total Environ 2008; 400: 115–141.

    Article  CAS  Google Scholar 

  8. Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E . Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr 2006; 84: 762–773.

    Article  CAS  Google Scholar 

  9. Navarro-Alarcon M, Lopez-Martinez MC . Essentiality of selenium in the human body: relationship with different diseases. Sci Total Environ 2000; 249: 347–371.

    Article  CAS  Google Scholar 

  10. Eaton CB, Abdul BA, Waring ME, Roberts MB, 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.

    Article  CAS  Google Scholar 

  11. Xun P, Liu K, Morris JS, Daviglus ML, He K . Longitudinal association between toenail selenium levels and measures of subclinical atherosclerosis: the CARDIA trace element study. Atherosclerosis 2010; 210: 662–667.

    Article  CAS  Google Scholar 

  12. Lubos E, Sinning CR, Schnabel RB, Wild PS, Zeller T, Rupprecht HJ et al. Serum selenium and prognosis in cardiovascular disease: results from the AtheroGene study. Atherosclerosis 2010; 209: 271–277.

    Article  CAS  Google Scholar 

  13. Rajpathak S, Rimm E, Morris JS, Hu F . Toenail selenium and cardiovascular disease in men with diabetes. J Am Coll Nutr 2005; 24: 250–256.

    Article  CAS  Google Scholar 

  14. Rees K, Hartley L, Day C, Flowers N, Clarke A, Stranges S . Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; 1: D9671.

    Google Scholar 

  15. Salonen JT, Alfthan G, Huttunen JK, 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.

    Article  CAS  Google Scholar 

  16. Salonen JT, Salonen R, Penttila I, Herranen J, Jauhiainen M, Kantola M et al. Serum fatty acids, apolipoproteins, selenium and vitamin antioxidants and the risk of death from coronary artery disease. Am J Cardiol 1985; 56: 226–231.

    Article  CAS  Google Scholar 

  17. Miettinen TA, Alfthan G, Huttunen JK, Pikkarainen J, Naukkarinen V, Mattila S et al. Serum selenium concentration related to myocardial infarction and fatty acid content of serum lipids. Br Med J (Clin Res Ed) 1983; 287: 517–519.

    Article  CAS  Google Scholar 

  18. Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 2004; 164: 2335–2342.

    Article  CAS  Google Scholar 

  19. Zureik M, Galan P, Bertrais S, Mennen L, Czernichow S, Blacher J et al. Effects of long-term daily low-dose supplementation with antioxidant vitamins and minerals on structure and function of large arteries. Arterioscler Thromb Vasc Biol 2004; 24: 1485–1491.

    Article  CAS  Google Scholar 

  20. Kilander L, Berglund L, Boberg M, Vessby B, Lithell H . Education, lifestyle factors and mortality from cardiovascular disease and cancer. A 25-year follow-up of Swedish 50-year-old men. Int J Epidemiol 2001; 30: 1119–1126.

    Article  CAS  Google Scholar 

  21. Koyama H, Abdulah R, Ohkubo T, Imai Y, Satoh H, Nagai K . Depressed serum selenoprotein P: possible new predicator of increased risk for cerebrovascular events. Nutr Res 2009; 29: 94–99.

    Article  CAS  Google Scholar 

  22. DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.

    Article  CAS  Google Scholar 

  23. Begg CB, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088–1101.

    Article  CAS  Google Scholar 

  24. Matthias E, George DS, Martin S, Christoph M . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

    Article  Google Scholar 

  25. Greenland S, Longnecker MP . Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 1992; 135: 1301–1309.

    Article  CAS  Google Scholar 

  26. Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D . Meta-Analysis for Linear and Nonlinear Dose-Response Relations: Examples, an Evaluation of Approximations, and Software. Am J Epidemiol 2012; 175: 66–73.

    Article  Google Scholar 

  27. Berlin JA, Longnecker MP, Greenland S . Meta-analysis of epidemiologic dose-response data. Epidemiology 1993; 4: 218–228.

    Article  CAS  Google Scholar 

  28. Yoshizawa K, Ascherio A, Morris JS, Stampfer MJ, Giovannucci E, Baskett CK et al. Prospective study of selenium levels in toenails and risk of coronary heart disease in men. Am J Epidemiol 2003; 158: 852–860.

    Article  Google Scholar 

  29. Salvini S, Hennekens CH, Morris JS, Willett WC, Stampfer MJ . Plasma levels of the antioxidant selenium and risk of myocardial infarction among U.S. physicians. Am J Cardiol 1995; 76: 1218–1221.

    Article  CAS  Google Scholar 

  30. Wennberg M, Bergdahl IA, Hallmans G, Norberg M, Lundh T, Skerfving S et al. Fish consumption and myocardial infarction: a second prospective biomarker study from northern Sweden. Am J Clin Nutr 2011; 93: 27–36.

    Article  CAS  Google Scholar 

  31. Kuklinski B, Weissenbacher E, Fahnrich A . Coenzyme Q10 and antioxidants in acute myocardial infarction. Mol Aspects Med 1994; 15: s143–s147.

    Article  Google Scholar 

  32. Hawkes WC, Laslett LJ . Selenium supplementation does not improve vascular responsiveness in healthy North American men. Am J Physiol Heart Circ Physiol 2009; 296: H256–H262.

    Article  CAS  Google Scholar 

  33. Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG et al. Effect of selenium and vitamin e on risk of prostate cancer and other cancers: The selenium and vitamin e cancer prevention trial (select). JAMA 2009; 301: 39–51.

    Article  CAS  Google Scholar 

  34. Miller JC, Thomson CD, Williams SM, van Havre N, Wilkins GT, Morison IM et al. Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response of glutathione peroxidase activity to selenium supplementation: a randomized controlled trial. Am J Clin Nutr 2012; 96: 923–931.

    Article  CAS  Google Scholar 

  35. Marshall JR, Tangen CM, Sakr WA, Wood DP, Berry DL, Klein EA et al. Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia: SWOG S9917. Cancer Prev Res 2011; 4: 1761–1769.

    Article  CAS  Google Scholar 

  36. Ravn-Haren G, Bugel S, Krath BN, Hoac T, Stagsted J, Jorgensen K et al. A short-term intervention trial with selenate, selenium-enriched yeast and selenium-enriched milk: effects on oxidative defence regulation. Br J Nutr 2008; 99: 883–892.

    Article  CAS  Google Scholar 

  37. Schnabel R, Lubos E, Messow CM, Sinning CR, Zeller T, Wild PS et al. Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease The SElenium Therapy in Coronary Artery disease Patients (SETCAP) Study. Am Heart J 2008; 156: 1201.

    Article  Google Scholar 

  38. Yu SY, Mao BL, Xiao P, Yu WP, Wang YL, Huang CZ et al. Intervention trial with selenium for the prevention of lung cancer among tin miners in Yunnan, China. A pilot study. Biol Trace Elem Res 1990; 24: 105–108.

    Article  CAS  Google Scholar 

  39. Brown BG, Zhao X, Chait A, Fisher LD, Cheung MC, Morse JS et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001; 345: 1583–1592.

    Article  CAS  Google Scholar 

  40. Stranges S, Galletti F, Farinaro E, D'Elia L, Russo O, Iacone R et al. Associations of selenium status with cardiometabolic risk factors: an 8-year follow-up analysis of the Olivetti Heart study. Atherosclerosis 2011; 217: 274–278.

    Article  CAS  Google Scholar 

  41. You WC, Chang YS, Heinrich J, Ma JL, Liu WD, Zhang L et al. An intervention trial to inhibit the progression of precancerous gastric lesions: compliance, serum micronutrients and S-allyl cysteine levels, and toxicity. Eur J Cancer Prev 2001; 10: 257–263.

    Article  CAS  Google Scholar 

  42. Gail MH, You WC, Chang YS, Zhang L, Blot WJ, Brown LM et al. Factorial trial of three interventions to reduce the progression of precancerous gastric lesions in Shandong, China: design issues and initial data. Control Clin Trials 1998; 19: 352–369.

    Article  CAS  Google Scholar 

  43. Lloyd B, Lloyd RS, Clayton BE . Effect of smoking, alcohol, and other factors on the selenium status of a healthy population. J Epidemiol Community Health 1983; 37: 213–217.

    Article  CAS  Google Scholar 

  44. Luty-Frackiewicz A, Jethon Z, Januszewska L . Effect of smoking and alcohol consumption on the serum selenium level of Lower Silesian population. Sci Total Environ 2002; 285: 89–95.

    Article  CAS  Google Scholar 

  45. Laclaustra M, Navas-Acien A, Stranges S, Ordovas JM, Guallar E . Serum selenium concentrations and hypertension in the US Population. Circ Cardiovasc Qual Outcomes 2009; 2: 369–376.

    Article  Google Scholar 

  46. Stewart RD, Griffiths NM, Thomson CD, Robinson MF . Quantitative selenium metabolism in normal New Zealand women. Br J Nutr 1978; 40: 45–54.

    Article  CAS  Google Scholar 

  47. Fairweather-Tait SJ . Bioavailability of selenium. Eur J Clin Nutr 1997; 51: S20–S23.

    Article  Google Scholar 

  48. Thomson CD . Selenium speciation in human body fluids. Analyst 1998; 123: 827–831.

    Article  CAS  Google Scholar 

  49. Bleys J, Navas-Acien A, Guallar E . Serum selenium and diabetes in U.S. sdults. Diabetes Care 2007; 30: 829–834.

    Article  CAS  Google Scholar 

  50. Bleys J, Navas-Acien A, Stranges S, Menke A, Miller ER, Guallar E . Serum selenium and serum lipids in US adults. Am J Clin Nutr 2008; 88: 416–423.

    Article  CAS  Google Scholar 

  51. Spallholz JE, Palace VP, Reid TW . Methioninase and selenomethionine but not Se-methylselenocysteine generate methylselenol and superoxide in an in vitro chemiluminescent assay: implications for the nutritional carcinostatic activity of selenoamino acids. Biochem Pharmacol 2004; 67: 547–554.

    Article  CAS  Google Scholar 

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Acknowledgements

The study was supported by the Indiana University Health–Indiana University School of Medicine Strategic Research Initiative Grant (Drs XZ and YS). We are thankful for the excellent advice and guidance from Dr Wanzhu Tu, from the Department of Biostatistics at the Indiana University School of Medicine, who served as statistical consultant for this study.

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Author notes

  1. X Zhang and C Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA

    X Zhang & Y Song

  2. Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    C Liu

  3. Centre for the Youth Sport Research and Development, China Institute of Sport Science, Beijing, China

    J Guo

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  1. X Zhang
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Correspondence to Y Song.

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Zhang, X., Liu, C., Guo, J. et al. Selenium status and cardiovascular diseases: meta-analysis of prospective observational studies and randomized controlled trials. Eur J Clin Nutr 70, 162–169 (2016). https://doi.org/10.1038/ejcn.2015.78

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