Advertisement

Vitamin E and Mortality: A Critical Perspective of the Conflicting Meta-analysis Outcomes

  • Wolfgang KöpckeEmail author
Chapter
Part of the Nutrition and Health book series (NH)

Abstract

The purpose of the present paper is to analyze the association of vitamin E supplementation and mortality by means of augmented data sources as well as additional methodological approaches. We performed a meta-analysis with 68 studies. The total numbers of study participants were 124,836 in the vitamin E group and 124,925 in the control group. Dosages of vitamin E supplementation ranged from 16.5 to 5000 IU/d. Additionally, the following covariables were part of the analysis: length of follow-up, mean age, and percent of males. We used different approaches of meta-analysis including fixed and random effect models, categorical dose-response models, models adjusted by covariates, and continuous dose-response models with linear splines. The above results show very clearly that with all different methods there is no effect of different dosages and no effect of possible covariables (length of study, mean age, percent of males). Thus on the basis of the published trials, there is no increase in all-cause mortality caused by vitamin E supplementation, and vitamin E supplementation is safe.

Keywords

Vitamin E supplementation All-cause mortality Meta-analysis Meta-regression 

References

Literary Sources Referred to in the Text

  1. 1.
    Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2004;142:37–46.PubMedCrossRefGoogle Scholar
  2. 2.
    Gerss J, Köpcke W. The questionable association of vitamin E supplementation and mortality—inconsistent results of different meta-analytic approaches. Cell Mol Biol (Noisy-le-Grand). 2009;55(Suppl):OL1111–20.Google Scholar
  3. 3.
    Abner EL, Schmitt FA, Mendiondo MS, Marcum JL, Kryscio RJ. Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci. 2011;4(2):158–70.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2008;2(2):CD007176.Google Scholar
  5. 5.
    Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2012;3:CD007176.Google Scholar
  6. 6.
    Oliver CJ, Myers SP. Validity of a cochrane systematic review and meta-analysis for determining the safety of vitamin E. BMC Complement Altern Med. 2017;17:408.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    The R Foundation for Statistical Computing Platform The statistical package R version 3.4.1. https://www.r-project.org – 2017.
  8. 8.
    EFSA Panel on Dietetic Products N, and Allergies. Scientific opinion on dietary reference values for vitamin E as α-tocopherol. EFSA J. 2015;13(7):4149.Google Scholar
  9. 9.
    IOM. Vitamin E. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academies Press (US); 2000. p. 186–283.Google Scholar
  10. 10.
    Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57.PubMedCrossRefGoogle Scholar
  11. 11.
    Hochberg I, Berinstein EM, Milman U, Shapira C, Levy AP. Interaction between the haptoglobin genotype and vitamin E on cardiovascular disease in diabetes. Curr Diab Rep. 2017;17(6):42.PubMedCrossRefGoogle Scholar
  12. 12.
    La Fata G, Weber P, Mohajeri MH. Effects of vitamin E on cognitive performance during ageing and in Alzheimer’s disease. Nutrients. 2014;6(12):5453–72.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Bjelakovic G, Nikolova D, Gluud C. Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? PLoS One. 2013;8(9):e74558.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Biesalski HK, Grune T, Tinz J, Zollner I, Blumberg JB. Reexamination of a meta-analysis of the effect of antioxidant supplementation on mortality and health in randomized trials. Nutrients. 2010;2(9):929–49.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Shekelle PG, Morton SC, Jungvig LK, Udani J, Spar M, Tu W, et al. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med. 2004;19(4):380–9.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Eidelman RS, Hollar D, Hebert PR, Lamas GA, Hennekens CH. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med. 2004;164(14):1552–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet. 2003;361(9374):2017–23.PubMedCrossRefGoogle Scholar
  18. 18.
    Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297(8):842–57.PubMedCrossRefGoogle Scholar
  19. 19.
    Bast A, Haenen GR. Ten misconceptions about antioxidants. Trends Pharmacol Sci. 2013;34(8):430–6.PubMedCrossRefGoogle Scholar

List of Publications of All Trials Included in the Meta Analysis

  1. Age Related Macular Degeneration Study Group. Multicenter ophthalmic and nutritional age related macular degeneration study—part 2: antioxidant intervention and conclusions. J Am Optom Assoc. 1996;67:30–49.Google Scholar
  2. Antoniadi G, Eleftheriadis T, Liakopoulos V, Kakasi E, Kartsios C, Passadakis P, Vargemezis V. Effect of one-year oral á-tocopherol administration on hemodialysis patients. Ther Apher Dial. 2008;12:237–42.PubMedCrossRefGoogle Scholar
  3. AREDS Research Group. Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the age-related eye disease study. AREDS report no 13. Arch Ophthalmol. 2004;122:716–26.PubMedCentralCrossRefPubMedGoogle Scholar
  4. Avenell A, Campbell MK, Cook JA, Hannaford PC, Kilonzo MM, McNeill G, et al. Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, randomized, double blind, placebo controlled, trial. Br Med J. 2005;331:324–9.CrossRefGoogle Scholar
  5. Bairati I, Meyer F, Jobin E, Gelinas M, Fortin A, Nabid A, et al. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int J Cancer. 2006;119:2221–4.PubMedCrossRefGoogle Scholar
  6. Belch J, MacCuish A, Campbell I. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomized placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:1030–3.CrossRefGoogle Scholar
  7. Blot WJ, Li J, Taylor PR, Guo W, Dawsey S, Wang G, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst. 1993;85:1483–92.PubMedCrossRefGoogle Scholar
  8. Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo controlled trial. Lancet. 2000;356:1213–8.PubMedCrossRefGoogle Scholar
  9. Bonelli L, Camoriano A, Ravelli P, Missale G, Bruzzi P, Aste H. Reduction of the incidence of metachronous adenomas of the large bowel by means of antioxidants. Proceedings of International Selenium Tellurium Development Association. Brussels, Belgium: Se-Te Press, 1998:91–94.Google Scholar
  10. 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. NEJM. 2001;345:1583–92.PubMedCrossRefGoogle Scholar
  11. Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005;100:1082–90.CrossRefGoogle Scholar
  12. Bukin YV, Draudlin-Krylenko VA, Kuvshinov YP, Poddubniy BK, Shabanov MA. Decrease of ornithine decarboxylase activity in premalignant gastric mucosa and regression of small intestinal metaplasia in patients supplemented with high doses of vitamin E. Cancer Epidemiol Biomark Prev. 1997;6:543–6.Google Scholar
  13. Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet. 1992;340:1124–7.PubMedCrossRefGoogle Scholar
  14. Chylack LT, Brown NP, Bron A, Hurst M, Kopcke W, Thien U, Schalch W. The Roche European American cataract trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract. Opthalmic Epidemiol. 2002;9:49–80.CrossRefGoogle Scholar
  15. Clinical Trial of Nutritional Supplements and Age-Related Cataract Study Group. A randomized, double-masked, placebo-controlled trial of multivitamin supplementation for age-related lens opacities. Ophthalmology. 2008;115:599–607.CrossRefGoogle Scholar
  16. Collins EG, Edwin Langbein W, Orebaugh C, Bammert C, Hanson K, Reda D, et al. PoleStriding exercise and vitamin E for management of peripheral vascular disease. Med Sci Sports Exerc. 2003;35(3):384–93.PubMedCrossRefGoogle Scholar
  17. Cook NR, Albert CM, Gaziano JM, Zaharris E, MacFayden J, Danielson E, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the women’s antioxidant cardiovascular study. Arch Intern Med. 2007;167(15):1610–8.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Critical Leg Ischaemia Prevention (CLIPS) Group. Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial. J Intern Med. 2006;261:276–84.CrossRefGoogle Scholar
  19. de la Maza MP, Petermeann M, Bunout D, Hirsch S. Effects of long-term vitamin E supplementation in alcoholic cirrhotics. J Am Coll Nutr. 1995;14:192–6.PubMedCrossRefGoogle Scholar
  20. de Waart FG, Kok FJ, Smilde TJ, Hijmans A, Wollershein H, Stalenhoef AF. Effect of glutathione S-transferase M1 genotype on progression of atherosclerosis in lifelong male smokers. Atherosclerosis. 2001;158:227–31.PubMedCrossRefGoogle Scholar
  21. Desnuelle C, Dib M, Garrel C, Favier A. A double-blind, placebo-controlled randomized clinical trial of a-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol study group. ALS Motor Neur Dis. 2001;2:9–18.Google Scholar
  22. Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311(1):33–44.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M, Behrendt D, et al. Effect of vitamins C and E on progression of transplant-associated atherosclerosis: a randomized trial. Lancet. 2002;359:1108–13.PubMedCrossRefGoogle Scholar
  24. Garbagnati F, Cairella G, De Martino A, Multari M, Scognamiglio U, Venturiero V, et al. Is antioxidant and n-3 supplementation able to improve functional status in poststroke patients? Results from the Nutristroke trial. Cerebrovasc Dis. 2009;27(4):375–83.PubMedCrossRefGoogle Scholar
  25. Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget A, Arnaud J, et al. Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Ann Nutr Metab. 1997;41:98–107.PubMedCrossRefGoogle Scholar
  26. Girodon F, Galan P, Monget A, Boutron-Ruault M, Brunet-Lecomte P, Preziosi P, et al. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients. Arch Intern Med. 1999;159:748–54.PubMedCrossRefGoogle Scholar
  27. Graat JM, Schouten EG, Kok FJ. Effect of multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons. A randomized controlled trial. JAMA. 2002;288:715–21.PubMedCrossRefGoogle Scholar
  28. Graf M, Ecker D, Horowski B, Kramer B, Riederer P, Gerlach M, et al. High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo controlled double-blind study. J Neural Transm. 2005;112:649–60.PubMedCrossRefGoogle Scholar
  29. Greenberg ER, Baron JA, Tosteson TD, Freeman DH Jr, Beck GJ, Bond JH, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N Engl J Med. 1994;331:141–7.PubMedCrossRefGoogle Scholar
  30. Gruppos Italiano per lo Studio della Sopravvivenza nell’Infarto miocardio. (GISSI). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354:447–55.CrossRefGoogle Scholar
  31. 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;164:2335–42.PubMedCrossRefGoogle Scholar
  32. Hodis HN, Mack WJ, LaBree L, Mahrer PR, Sevanian A, Liu C, et al. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis. The vitamin E atherosclerosis prevention study (VEAPS). Circulation. 2002;106:1453–9.PubMedCrossRefGoogle Scholar
  33. Lee I, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer. The women’s health study: a randomized controlled trial. JAMA. 2005;294:56–65.PubMedCrossRefGoogle Scholar
  34. Li J, Taylor PR, Li B, Dawsey S, Wang G, Ershow AG, et al. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J Natl Cancer Inst. 1993;85:1492–8.PubMedCrossRefGoogle Scholar
  35. 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. 2008;301(1):39–51.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Liu BA, McGeer A, McArthur MA, Simor AE, Aghdassi E, Davis L, et al. Effect of multivitamin and mineral supplementation on episodes of infection in nursing home residents: a randomized, placebo-controlled study. J Am Geriatr Soc. 2007;55(1):35–42.PubMedCrossRefGoogle Scholar
  37. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JMO, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer. A randomized controlled trial. The HOPE and HOPE-TOO investigators. JAMA. 2005;293:1338–47.PubMedCrossRefGoogle Scholar
  38. Magliano D, McNeil J, Branley P, Shiel L, Demos L, Wolfe R, et al. The Melbourne atherosclerosis vitamin E trial (MAVET): a study of high dose vitamin E in smokers. Eur J Cardiovasc Prev Rehabil. 2006;113:241–7.Google Scholar
  39. Manuel-Y-Keenoy B, Vinckx M, Vertommen J, GaalL V. De Leeuw I. impact of vitamin E supplementation on lipoprotein peroxidation and composition in type 1 diabetic patients treated with atorvastatin. Atherosclerosis. 2004;175(2):369–76.PubMedCrossRefGoogle Scholar
  40. Marras C, Oakes D, Tanner CM, Fahn S. Vitamin E supplementation was not associated with mortality in the DATATOP cohort. Ann Intern Med. 2005;143:152–3.PubMedCrossRefGoogle Scholar
  41. McKeown-Eyssen G, Holloway C, Jazmaji V, Bright-See E, Dion P, Bruce WR. A randomized trial of vitamins C and E in the prevention of recurrence of colorectal polyps. Cancer Res. 1988;48:4701–5.PubMedGoogle Scholar
  42. McNeil JJ, Robman L, Tikellis G, Sinclair MI, McCarty CA, Taylor HR. Vitamin E supplementation and cataract: randomized controlled trial. Opthalmol. 2004;111:75–84.CrossRefGoogle Scholar
  43. Meydani SN, Leka LS, Fine BC, Dallal GE, Keusch GT, Singh MF, Hamer DH. Vitamin E and respiratory tract infections in elderly nursing home residents. A randomized controlled trial. JAMA. 2004;292:828–36.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Mezey E, Potter JJ, Rennie-Tankersley L, Caballeria J, Pares A. A randomized placebo controlled trial of vitamin E for alcoholic hepatitis. J Hepatol. 2004;40:40–6.PubMedCrossRefGoogle Scholar
  45. Milman U, Blum S, Shapira C, Aronson D, Miller-Lotan R, Anbinder Y, et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial. Arterioscler Thromb Vasc Biol. 2008;28(2):341–7.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Mooney LA, Madsen AM, Tang D, Orjuela MA, Tsai W, Garduno ER, Perera FP. Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers. Cancer Epidemiol Biomark Prev. 2005;14:237–42.Google Scholar
  47. MRC/BHF. Heart protection study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23–33.CrossRefGoogle Scholar
  48. Pathak AK, Bhutani M, Guleria R, Bal S, Mohan A, Mohanti BK, et al. Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer. J Am Coll Nutr. 2005;24:16–21.PubMedCrossRefGoogle Scholar
  49. Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. NEJM. 2005;352:1–10.CrossRefGoogle Scholar
  50. Pike J, Chandra RK. Effect of vitamin and trace element supplementation on immune indices in healthy elderly. Int J Vitam Nutr Res. 1995;65:117–20.PubMedGoogle Scholar
  51. Plummer M, Vivas J, Lopez G, Bravo JC, Peraza S, Carillo E, et al. Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. J Natl Cancer Inst. 2007;99:137–46.PubMedCrossRefGoogle Scholar
  52. Richer S, Stiles W, Statkuke L, Pulido J, Frankowski J, Rudy D, et al. Double-masked, placebo controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the veterans LAST study (lutein antioxidant supplementation trial). Optometry. 2004;75:216–30.PubMedCrossRefGoogle Scholar
  53. Roncaglioni MC. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet. 2001;357:89–95.CrossRefGoogle Scholar
  54. Salonen RM, Nyyssonen K, Kaikkonnen J, Porkkala-Sarataho E, Voutilained S, Rissanen TH, et al. Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression. The antioxidant supplementation in atherosclerosis prevention (ASAP) Study. Circulation. 2003;107:947–53.PubMedCrossRefGoogle Scholar
  55. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. NEJM. 1997;336:1216–22.PubMedCrossRefGoogle Scholar
  56. Sano M, Aisen PS, Andrews HF, Tsai WY, Lai F, Dalton AJ. Vitamin E in aging persons with down syndrome A randomized, placebo-controlled clinical trial. Neurology. 2016;86(22):2071–6.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Sanyal AD, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. NEJM. 2010;362:1675–85.PubMedCrossRefGoogle Scholar
  58. Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFayden J, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the physicians’ health study II randomized controlled trial. JAMA. 2008;300(18):2123–33.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Singh U, Otvos J, Dasgupta A, de Lemos JA, Devaraj S, Jialal I. High-dose a-tocopherol therapy does not affect HDL subfractions in patients with coronary artery disease on statin therapy. Clin Chem. 2007;53:525–8.PubMedCrossRefGoogle Scholar
  60. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchison MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge heart antioxidant study (CHAOS). Lancet. 1996;347:781–9.PubMedCrossRefGoogle Scholar
  61. Stevic Z, Nikolic A, Blagojevic DP, Saicic ZS, Kocev NI, Apostolski SA, Spasic MB. A controlled trial of combination of methionine and antioxidants in ALS patients. Jugoslav Med Biohem. 2001;20:223–8.Google Scholar
  62. Takagi H, Kakizaki S, Sohara N, Sato K, Tsukioka G, Tago Y, et al. Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis. Int J Vitam Nutr Res. 2003;73:411–5.PubMedCrossRefGoogle Scholar
  63. Takamatsu S, Takamatsu M, Satoh K, Imaizumi T, Yoshida H, Hiramoto M, et al. Effects on health of dietary supplementation with 100 mg d-a-tocopheryl acetate, daily for 6 years. J Int Med Res. 1995;23:342–57.PubMedCrossRefGoogle Scholar
  64. Tam LS, Li EK, Leung VY, Griffith JF, Benzie IF, Lim PL, et al. Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: a double blind, placebo controlled pilot study. J Rheumatol. 2005;32:275–82.PubMedGoogle Scholar
  65. Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA. 2002;288:2432–40.PubMedCrossRefGoogle Scholar
  66. Wluka AE, Stuckey S, Brand C, Cicuttini F. Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2-year double blind randomized placebo controlled study. J Rheumatol. 2002;29:2585–91.PubMedGoogle Scholar
  67. Wright ME, Lawson KA, Weinstein SJ, Pietinen P, Taylor PR, Virtamo J, Albanes D. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the alpha-tocopherol, beta-carotene cancer prevention study. Am J Clin Nutr. 2006;84:1200–7.PubMedCrossRefGoogle Scholar
  68. 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;10:257–63.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institute of Biostatistics and Clinical ResearchUniversity Clinic MünsterMünsterGermany

Personalised recommendations